Applied Evidence

Mohs micrographic surgery (MMS) is a unique dermatologic surgery technique that allows the dermatologist to fill the concomitant roles of surgeon and pathologist. It is utilized for the extirpation of skin malignancy, with an emphasis on tissue preservation and immediate surgical margin evaluation. In MMS, the Mohs surgeon acts as the surgeon for physical removal of the lesion and the pathologist during evaluation of frozen section margins.¹

Primary care providers (PCPs) are on the frontlines of management of cutaneous malignancy. Whether referring to Dermatology for biopsy or performing a biopsy themselves, PCPs can assure optimal treatment outcomes by guiding patients to ­evidence-based treatments, while still respecting the patient’s wishes. In this evidence-based review of the advantages, improved outcomes, and safety of Mohs surgery for the treatment of common and rare skin neoplasms, we provide our primary care colleagues with information on the indications, process (the order in which steps of the procedure are performed), and techniques used for treating cutaneous malignancies with Mohs surgery.

When is Mohs surgery appropriate?

MMS has typically been reserved for treatment of cutaneous malignancy in cosmetically sensitive areas where tissue preservation is key. In 2012, Connolly et al released appropriate use criteria (AUC) for MMS.² (See “An app that helps clinicians apply the criteria for Mohs surgery.”) Within the AUC, there are 4 major qualitative and quantitative categories when considering referral for MMS:

• area of the body in which the lesion manifests
• the patient’s medical characteristics
• tumor characteristics
• the size of the lesion to be treated.²

Areas of the body are divided into 3 categories by the AUC according to how challenging tumor extirpation is expected to be and how critical tissue preservation is. Areas termed “H” receive the highest score for appropriate Mohs usage, followed by areas “M” and “L.”

Patient medical characteristics that should be taken into account when referring for Mohs surgery are the patient’s immune status, genetic syndromes that may predispose the patient to cutaneous malignancies (eg, xeroderma pigmentosa), history of radiation to the area of involvement, and the patient’s history of aggressive cutaneous malignancies.

Tumor characteristics. The most common malignancies treated with MMS include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are further delineated through histologic evaluation by a pathologist or dermatopathologist. Aggressive features of a BCC on any area of the body that warrant referral to a Mohs surgeon include morpheaform/fibrosing/sclerosing histologic findings, as well as micronodular architecture and perineural invasion. Concerning histologic SCC findings that warrant Mohs surgery through the AUC include sclerosing, basosquamous, and small cell histology, as well as poorly differentiated and/or undifferentiated SCC.

The procedure’s emphasis on evaluating 100% of tissue margins and tissue preservation give it many inherent advantages over wide local excisions.

Melanoma in situ and lentigo maligna, which are variants of melanoma limited to the epidermis without invasion into the underlying dermis, are included within the AUC for MMS. For invasive melanoma (melanoma that has invaded into the dermis or subcutaneous tissue), MMS has been shown to have marginal benefit but currently is not included within the AUC.³

Continue to: Due to excellent margin control...

Due to excellent margin control via immediate microscopic evaluation of surgical margins, MMS is an appropriate treatment choice and indicated for many more uncommon cutaneous malignancies, including sebaceous and mucinous carcinoma, microcystic adnexal carcinoma, Merkel cell carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, angiosarcoma, and other more rarely encountered clinical malignancies.²

Tumor size. When considering a referral to MMS for cancer extirpation, the size of the tumor does play a role; however, size depends on the type of tumor as well as the location on the body. In general, most skin cancers of any size on the face, perianal area, genitalia, nipples, hands, feet and ankles, or pretibial surface are appropriate for Mohs surgery. Skin cancers on the trunk and extremities are also appropriate if they are above a certain size specified by the AUC. Tumor type and whether they are recurrences also factor into the equation.

Who will do the procedure?

A recent review showed that PCPs were more likely to refer patients to plastic surgery rather than Mohs surgery for skin cancer removal, especially among younger female patients.⁴ This is likely because of the perception that plastic surgeons do more complex closures and have more experience removing difficult cancers. Interestingly, this same study showed that Mohs surgeons may actually be doing several-fold more complex closures (flaps and grafts) on the nose and ears than plastic surgeons at similar practice settings.⁴

Aside from Mohs surgeons doing more closures, perhaps the biggest difference between Mohs surgeons and plastic surgeons is the pathology training of the Mohs surgeon. Mohs surgeons evaluate 100% of the tissue margins at the time of the procedure to both ensure complete tumor removal and to preserve as much tumor-free skin as possible, ultimately resulting in decreased recurrences and smaller scars. In contrast, the plastic surgeon’s rigorous training typically does not include extensive dermatopathology training, particularly the pathology of cutaneous neoplasms. Plastic surgeons will often send pathologic specimens for evaluation, meaning patients have to wait for outside histologic confirmation before their wounds can be closed. Additionally, the histologic evaluation is often not a full-margin assessment, as not all labs are equipped for this technique.

Consider early consultation with a Mohs surgeon for tumor extirpation to keep the defect size as small as possible, as MMS does not require taking margins of healthy surrounding tissue, in contrast to wide local excisions (WLEs; FIGURE 1). A smaller initial incision will result in a smaller scar, which is likely to have better cosmetic outcomes and decreased risk for wound infection.

Continue to: Before consultation...

Before consultation, include a picture of the surgical site with the patient’s referral documentation or have the patient present a photo from his or her phone to the Mohs surgeon. (If a camera or cell phone is not available, triangulation of the site’s location using cosmetic landmarks can be documented in the patient’s chart.)

What the patient can expect during preop visits

During an initial consultation, patients can expect an evaluation by the surgeon that will include more photo taking, a discussion of the surgery, and possibly, performance of an in-clinic biopsy of suspicious lesions. Many practices, including the authors’, use a photo capturing add-on for the EMR in the office.^5-7

During the consent process, MMS is described to the patient using lay language and, often, pictorial depictions of the procedure. While explaining that the procedure helps preserve healthy tissue and limit the size of the resulting scar, the surgeon will typically manage the expectations of the patient prior to the first incision. Many clinically small lesions can have significant subclinical extension adjacent to, or on top of, cosmetic landmarks, requiring a flap or graft to close the surgical defect with acceptable cosmetic outcomes.⁸

One more time. Immediately before surgery, the surgeon will again review the procedure with the patient, using photos of the biopsy site taken during the initial consult, in conjunction with patient verification of the biopsy site, to verify the surgical site and confirm that the patient understands and agrees to the surgery.

A look at how Mohs surgery is performed

MMS typically is performed in the outpatient setting but can also be performed in an operating room or outpatient surgical center. MMS can be performed in a nonsterile procedure room with surgeons and assistants typically utilizing clean, nonsterile gloves, although many Mohs surgeons prefer to perform part, or all, of the technique using sterile gloves.⁹ A recent systematic review and large meta-analysis showed no significant difference in postsurgical site infections when comparing the use of sterile vs nonsterile gloves.¹⁰

Continue to: Prior to initial incision...

Prior to initial incision, the site is marked with a surgical pen and given 1-mm margins around the clinically visualized lesion. The site is then cleansed with an antiseptic, typically a chlorhexidine solution. Local anesthesia is employed, most commonly with a 1:100,000 lidocaine and epinephrine injection. Marking of the tumor prior to numbing is imperative, as the boundaries of the tumor are typically obscured when the local cutaneous vasculature constricts and causes visualized blanching of adjacent skin. Many Mohs surgeons perform a brief curettage of the lesion with a nondisposable, dull curette to better define the tumor edges and to debulk any obvious exophytic tumor noted by the naked eye.

Prior to the first incision, the surgical site is scored in a variety of ways in order to properly orient the tissue after it has been removed from the patient. Mohs surgeons have differing opinions on how to score and/or mark the tissue, but a common practice is to make a nick at the 12 o’clock position. Following removal of the first stage, the nick will be visible on both the extirpated tissue and the tissue just above the surgical defect. This prevents potential confusion regarding orientation during tissue processing.

The majority of all WLEs are performed utilizing the scalpel blade at an angle 90° perpendicular to the plane of the skin. In MMS, a signature 45° angle with the tip of the scalpel pointing toward, and the handle pointing away from, the lesion is commonly used in order to bevel the tissue being excised (FIGURE 2). Once the tissue is excised, hemostasis is obtained using electrodessication/electrofulguration or electrocoagulation.

Tissue processing and microscopic evaluation

The technique of beveling allows the epidermis, dermis, and subcutaneous tissue to lie flat on the tissue block, so the Mohs surgeon can evaluate 100% of the excised tissue’s margins. The tissue is transported to a nearby lab for staining and processing. Even if near-perfect beveling is achieved, many stages will require bisecting, quadrissecting, or relaxing cuts in order to allow the margins to lie flat on the tissue block.

Using the scoring system made prior to incision, the tissue is oriented and stained with colored ink. Subsequently, a map is made with sections highlighting the colors used to stain designated areas of the tissue. This step is imperative for orientation during microscopic evaluation. Additionally, the map serves as a guide and log, should a section of the specimen have an involved margin and require another stage.

Continue to: Once fixed to the block...

Once fixed to the block, the tissue is engulfed in appropriate embedding medium and placed within the cryostat. The block is slowly cut to produce several micron-thin wafers of tissue that are then mounted on glass slides and processed with hematoxylin and eosin (H&E) or various stains. The first wafers of tissue that come from the tissue block are those that are closest to the margin that was excised. Thus, 100% of the epidermis and deep margin can be visualized. “Deeper sections” are those that come from deeper cuts within the tissue and are more likely to show the malignant neoplasm.

Mohs surgery is the standard of care for treating cutaneous malignancy in light of its high cure rates and maximal conservation of tissue in sensitive locations.

The evaluation of immediate margins at the very edge of the tissue is in contrast to the technique of “bread-loafing,” which is the standard of evaluating margins after a WLE.¹¹ With this process, the pathologist examines sections that are cut 2- to 4-mm apart. This process only allows the pathologist to examine roughly 1% of the total tissue that was excised, and large variability in cutaneous representation can occur depending on the individual who cuts and processes the tissue.¹¹

Closing the defect

Once the site is deemed clear of residual tumor, the Mohs surgeon approaches the defect and determines the most appropriate way to close the surgical wound. Mohs surgeons are trained to close wounds using a variety of methods, including complex linear closures, flaps, and full-thickness skin grafts. Thoughtful consideration of local anatomy, cosmetic landmarks that may be affected by the closure method, and local tissue laxity are evaluated.

Depending on the location, a secondary intention closure may prove to be just as effective and cosmetically satisfying as a primary intention closure. In light of the many methods of closure, a complex or large surface area defect may better be suited for evaluation and closure by another specialist such as an ENT physician, ophthalmologist, or plastic surgeon.¹²

Lower recurrence rates for patients who undergo Mohs surgery

As noted earlier, the cutaneous malignancies most commonly treated with MMS are BCCs, followed by SCCs.¹³ Comparison studies between WLE and MMS show clinically significant differences in terms of recurrence rates between the 2 procedures.

Continue to: For BCCs

For BCCs, recurrence rates for excisions vs MMS are 10% and 1%, respectively.^14-16 A randomized trial reviewing 10-year recurrence of primary BCCs on the face showed recurrence rates for MMS of 4.4% compared to 12.2% for WLE.¹⁷ This study also showed recurrence rates for recurrent facial BCCs treated with MMS to be 3.9% vs 13.5% for standard WLE.¹⁷

SCC. The evidence similarly supports the efficacy of MMS for SCCs. A recent study showed primary T2a tumors had a 1.2% local recurrence rate with Mohs vs a 4% recurrence rate with WLE at an average follow-up of 2.8 years.¹⁸ Another study showed that primary tumors that were < 2 cm in diameter had a 5-year cure rate of 99% with Mohs surgery.¹¹

Melanoma in situ. A few studies have shown no clinically significant benefit of MMS compared to WLE when it comes to melanoma in situ.^19,20 However, a more recent article by Etzkom et al noted the ability to potentially upstage melanoma in situ and invasive melanoma after reviewing peripheral and deep margins during MMS.²¹ In this study, the authors uniquely delayed wound closure if upstaging was established and the need for a sentinel lymph node biopsy was warranted. This approach to MMS with delayed closure ultimately paved the way for very low recurrence rates.

CORRESPONDENCE
Andres Garcia, MD, 2612 112th Street, Lubbock, TX 79423; [email protected]

Mohs micrographic surgery (MMS) is a unique dermatologic surgery technique that allows the dermatologist to fill the concomitant roles of surgeon and pathologist. It is utilized for the extirpation of skin malignancy, with an emphasis on tissue preservation and immediate surgical margin evaluation. In MMS, the Mohs surgeon acts as the surgeon for physical removal of the lesion and the pathologist during evaluation of frozen section margins.¹

Primary care providers (PCPs) are on the frontlines of management of cutaneous malignancy. Whether referring to Dermatology for biopsy or performing a biopsy themselves, PCPs can assure optimal treatment outcomes by guiding patients to ­evidence-based treatments, while still respecting the patient’s wishes. In this evidence-based review of the advantages, improved outcomes, and safety of Mohs surgery for the treatment of common and rare skin neoplasms, we provide our primary care colleagues with information on the indications, process (the order in which steps of the procedure are performed), and techniques used for treating cutaneous malignancies with Mohs surgery.

When is Mohs surgery appropriate?

MMS has typically been reserved for treatment of cutaneous malignancy in cosmetically sensitive areas where tissue preservation is key. In 2012, Connolly et al released appropriate use criteria (AUC) for MMS.² (See “An app that helps clinicians apply the criteria for Mohs surgery.”) Within the AUC, there are 4 major qualitative and quantitative categories when considering referral for MMS:

• area of the body in which the lesion manifests
• the patient’s medical characteristics
• tumor characteristics
• the size of the lesion to be treated.²

Areas of the body are divided into 3 categories by the AUC according to how challenging tumor extirpation is expected to be and how critical tissue preservation is. Areas termed “H” receive the highest score for appropriate Mohs usage, followed by areas “M” and “L.”

Patient medical characteristics that should be taken into account when referring for Mohs surgery are the patient’s immune status, genetic syndromes that may predispose the patient to cutaneous malignancies (eg, xeroderma pigmentosa), history of radiation to the area of involvement, and the patient’s history of aggressive cutaneous malignancies.

Tumor characteristics. The most common malignancies treated with MMS include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are further delineated through histologic evaluation by a pathologist or dermatopathologist. Aggressive features of a BCC on any area of the body that warrant referral to a Mohs surgeon include morpheaform/fibrosing/sclerosing histologic findings, as well as micronodular architecture and perineural invasion. Concerning histologic SCC findings that warrant Mohs surgery through the AUC include sclerosing, basosquamous, and small cell histology, as well as poorly differentiated and/or undifferentiated SCC.

The procedure’s emphasis on evaluating 100% of tissue margins and tissue preservation give it many inherent advantages over wide local excisions.

Melanoma in situ and lentigo maligna, which are variants of melanoma limited to the epidermis without invasion into the underlying dermis, are included within the AUC for MMS. For invasive melanoma (melanoma that has invaded into the dermis or subcutaneous tissue), MMS has been shown to have marginal benefit but currently is not included within the AUC.³

Continue to: Due to excellent margin control...

Due to excellent margin control via immediate microscopic evaluation of surgical margins, MMS is an appropriate treatment choice and indicated for many more uncommon cutaneous malignancies, including sebaceous and mucinous carcinoma, microcystic adnexal carcinoma, Merkel cell carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, angiosarcoma, and other more rarely encountered clinical malignancies.²

Tumor size. When considering a referral to MMS for cancer extirpation, the size of the tumor does play a role; however, size depends on the type of tumor as well as the location on the body. In general, most skin cancers of any size on the face, perianal area, genitalia, nipples, hands, feet and ankles, or pretibial surface are appropriate for Mohs surgery. Skin cancers on the trunk and extremities are also appropriate if they are above a certain size specified by the AUC. Tumor type and whether they are recurrences also factor into the equation.

Who will do the procedure?

A recent review showed that PCPs were more likely to refer patients to plastic surgery rather than Mohs surgery for skin cancer removal, especially among younger female patients.⁴ This is likely because of the perception that plastic surgeons do more complex closures and have more experience removing difficult cancers. Interestingly, this same study showed that Mohs surgeons may actually be doing several-fold more complex closures (flaps and grafts) on the nose and ears than plastic surgeons at similar practice settings.⁴

Aside from Mohs surgeons doing more closures, perhaps the biggest difference between Mohs surgeons and plastic surgeons is the pathology training of the Mohs surgeon. Mohs surgeons evaluate 100% of the tissue margins at the time of the procedure to both ensure complete tumor removal and to preserve as much tumor-free skin as possible, ultimately resulting in decreased recurrences and smaller scars. In contrast, the plastic surgeon’s rigorous training typically does not include extensive dermatopathology training, particularly the pathology of cutaneous neoplasms. Plastic surgeons will often send pathologic specimens for evaluation, meaning patients have to wait for outside histologic confirmation before their wounds can be closed. Additionally, the histologic evaluation is often not a full-margin assessment, as not all labs are equipped for this technique.

Consider early consultation with a Mohs surgeon for tumor extirpation to keep the defect size as small as possible, as MMS does not require taking margins of healthy surrounding tissue, in contrast to wide local excisions (WLEs; FIGURE 1). A smaller initial incision will result in a smaller scar, which is likely to have better cosmetic outcomes and decreased risk for wound infection.

Continue to: Before consultation...

Before consultation, include a picture of the surgical site with the patient’s referral documentation or have the patient present a photo from his or her phone to the Mohs surgeon. (If a camera or cell phone is not available, triangulation of the site’s location using cosmetic landmarks can be documented in the patient’s chart.)

What the patient can expect during preop visits

During an initial consultation, patients can expect an evaluation by the surgeon that will include more photo taking, a discussion of the surgery, and possibly, performance of an in-clinic biopsy of suspicious lesions. Many practices, including the authors’, use a photo capturing add-on for the EMR in the office.^5-7

During the consent process, MMS is described to the patient using lay language and, often, pictorial depictions of the procedure. While explaining that the procedure helps preserve healthy tissue and limit the size of the resulting scar, the surgeon will typically manage the expectations of the patient prior to the first incision. Many clinically small lesions can have significant subclinical extension adjacent to, or on top of, cosmetic landmarks, requiring a flap or graft to close the surgical defect with acceptable cosmetic outcomes.⁸

One more time. Immediately before surgery, the surgeon will again review the procedure with the patient, using photos of the biopsy site taken during the initial consult, in conjunction with patient verification of the biopsy site, to verify the surgical site and confirm that the patient understands and agrees to the surgery.

A look at how Mohs surgery is performed

MMS typically is performed in the outpatient setting but can also be performed in an operating room or outpatient surgical center. MMS can be performed in a nonsterile procedure room with surgeons and assistants typically utilizing clean, nonsterile gloves, although many Mohs surgeons prefer to perform part, or all, of the technique using sterile gloves.⁹ A recent systematic review and large meta-analysis showed no significant difference in postsurgical site infections when comparing the use of sterile vs nonsterile gloves.¹⁰

Continue to: Prior to initial incision...

Prior to initial incision, the site is marked with a surgical pen and given 1-mm margins around the clinically visualized lesion. The site is then cleansed with an antiseptic, typically a chlorhexidine solution. Local anesthesia is employed, most commonly with a 1:100,000 lidocaine and epinephrine injection. Marking of the tumor prior to numbing is imperative, as the boundaries of the tumor are typically obscured when the local cutaneous vasculature constricts and causes visualized blanching of adjacent skin. Many Mohs surgeons perform a brief curettage of the lesion with a nondisposable, dull curette to better define the tumor edges and to debulk any obvious exophytic tumor noted by the naked eye.

Prior to the first incision, the surgical site is scored in a variety of ways in order to properly orient the tissue after it has been removed from the patient. Mohs surgeons have differing opinions on how to score and/or mark the tissue, but a common practice is to make a nick at the 12 o’clock position. Following removal of the first stage, the nick will be visible on both the extirpated tissue and the tissue just above the surgical defect. This prevents potential confusion regarding orientation during tissue processing.

The majority of all WLEs are performed utilizing the scalpel blade at an angle 90° perpendicular to the plane of the skin. In MMS, a signature 45° angle with the tip of the scalpel pointing toward, and the handle pointing away from, the lesion is commonly used in order to bevel the tissue being excised (FIGURE 2). Once the tissue is excised, hemostasis is obtained using electrodessication/electrofulguration or electrocoagulation.

Tissue processing and microscopic evaluation

The technique of beveling allows the epidermis, dermis, and subcutaneous tissue to lie flat on the tissue block, so the Mohs surgeon can evaluate 100% of the excised tissue’s margins. The tissue is transported to a nearby lab for staining and processing. Even if near-perfect beveling is achieved, many stages will require bisecting, quadrissecting, or relaxing cuts in order to allow the margins to lie flat on the tissue block.

Using the scoring system made prior to incision, the tissue is oriented and stained with colored ink. Subsequently, a map is made with sections highlighting the colors used to stain designated areas of the tissue. This step is imperative for orientation during microscopic evaluation. Additionally, the map serves as a guide and log, should a section of the specimen have an involved margin and require another stage.

Continue to: Once fixed to the block...

Once fixed to the block, the tissue is engulfed in appropriate embedding medium and placed within the cryostat. The block is slowly cut to produce several micron-thin wafers of tissue that are then mounted on glass slides and processed with hematoxylin and eosin (H&E) or various stains. The first wafers of tissue that come from the tissue block are those that are closest to the margin that was excised. Thus, 100% of the epidermis and deep margin can be visualized. “Deeper sections” are those that come from deeper cuts within the tissue and are more likely to show the malignant neoplasm.

Mohs surgery is the standard of care for treating cutaneous malignancy in light of its high cure rates and maximal conservation of tissue in sensitive locations.

The evaluation of immediate margins at the very edge of the tissue is in contrast to the technique of “bread-loafing,” which is the standard of evaluating margins after a WLE.¹¹ With this process, the pathologist examines sections that are cut 2- to 4-mm apart. This process only allows the pathologist to examine roughly 1% of the total tissue that was excised, and large variability in cutaneous representation can occur depending on the individual who cuts and processes the tissue.¹¹

Closing the defect

Once the site is deemed clear of residual tumor, the Mohs surgeon approaches the defect and determines the most appropriate way to close the surgical wound. Mohs surgeons are trained to close wounds using a variety of methods, including complex linear closures, flaps, and full-thickness skin grafts. Thoughtful consideration of local anatomy, cosmetic landmarks that may be affected by the closure method, and local tissue laxity are evaluated.

Depending on the location, a secondary intention closure may prove to be just as effective and cosmetically satisfying as a primary intention closure. In light of the many methods of closure, a complex or large surface area defect may better be suited for evaluation and closure by another specialist such as an ENT physician, ophthalmologist, or plastic surgeon.¹²

Lower recurrence rates for patients who undergo Mohs surgery

As noted earlier, the cutaneous malignancies most commonly treated with MMS are BCCs, followed by SCCs.¹³ Comparison studies between WLE and MMS show clinically significant differences in terms of recurrence rates between the 2 procedures.

Continue to: For BCCs

For BCCs, recurrence rates for excisions vs MMS are 10% and 1%, respectively.^14-16 A randomized trial reviewing 10-year recurrence of primary BCCs on the face showed recurrence rates for MMS of 4.4% compared to 12.2% for WLE.¹⁷ This study also showed recurrence rates for recurrent facial BCCs treated with MMS to be 3.9% vs 13.5% for standard WLE.¹⁷

SCC. The evidence similarly supports the efficacy of MMS for SCCs. A recent study showed primary T2a tumors had a 1.2% local recurrence rate with Mohs vs a 4% recurrence rate with WLE at an average follow-up of 2.8 years.¹⁸ Another study showed that primary tumors that were < 2 cm in diameter had a 5-year cure rate of 99% with Mohs surgery.¹¹

Melanoma in situ. A few studies have shown no clinically significant benefit of MMS compared to WLE when it comes to melanoma in situ.^19,20 However, a more recent article by Etzkom et al noted the ability to potentially upstage melanoma in situ and invasive melanoma after reviewing peripheral and deep margins during MMS.²¹ In this study, the authors uniquely delayed wound closure if upstaging was established and the need for a sentinel lymph node biopsy was warranted. This approach to MMS with delayed closure ultimately paved the way for very low recurrence rates.

CORRESPONDENCE
Andres Garcia, MD, 2612 112th Street, Lubbock, TX 79423; [email protected]

Mohs micrographic surgery (MMS) is a unique dermatologic surgery technique that allows the dermatologist to fill the concomitant roles of surgeon and pathologist. It is utilized for the extirpation of skin malignancy, with an emphasis on tissue preservation and immediate surgical margin evaluation. In MMS, the Mohs surgeon acts as the surgeon for physical removal of the lesion and the pathologist during evaluation of frozen section margins.¹

Primary care providers (PCPs) are on the frontlines of management of cutaneous malignancy. Whether referring to Dermatology for biopsy or performing a biopsy themselves, PCPs can assure optimal treatment outcomes by guiding patients to ­evidence-based treatments, while still respecting the patient’s wishes. In this evidence-based review of the advantages, improved outcomes, and safety of Mohs surgery for the treatment of common and rare skin neoplasms, we provide our primary care colleagues with information on the indications, process (the order in which steps of the procedure are performed), and techniques used for treating cutaneous malignancies with Mohs surgery.

When is Mohs surgery appropriate?

MMS has typically been reserved for treatment of cutaneous malignancy in cosmetically sensitive areas where tissue preservation is key. In 2012, Connolly et al released appropriate use criteria (AUC) for MMS.² (See “An app that helps clinicians apply the criteria for Mohs surgery.”) Within the AUC, there are 4 major qualitative and quantitative categories when considering referral for MMS:

• area of the body in which the lesion manifests
• the patient’s medical characteristics
• tumor characteristics
• the size of the lesion to be treated.²

Areas of the body are divided into 3 categories by the AUC according to how challenging tumor extirpation is expected to be and how critical tissue preservation is. Areas termed “H” receive the highest score for appropriate Mohs usage, followed by areas “M” and “L.”

Patient medical characteristics that should be taken into account when referring for Mohs surgery are the patient’s immune status, genetic syndromes that may predispose the patient to cutaneous malignancies (eg, xeroderma pigmentosa), history of radiation to the area of involvement, and the patient’s history of aggressive cutaneous malignancies.

Tumor characteristics. The most common malignancies treated with MMS include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are further delineated through histologic evaluation by a pathologist or dermatopathologist. Aggressive features of a BCC on any area of the body that warrant referral to a Mohs surgeon include morpheaform/fibrosing/sclerosing histologic findings, as well as micronodular architecture and perineural invasion. Concerning histologic SCC findings that warrant Mohs surgery through the AUC include sclerosing, basosquamous, and small cell histology, as well as poorly differentiated and/or undifferentiated SCC.

The procedure’s emphasis on evaluating 100% of tissue margins and tissue preservation give it many inherent advantages over wide local excisions.

Melanoma in situ and lentigo maligna, which are variants of melanoma limited to the epidermis without invasion into the underlying dermis, are included within the AUC for MMS. For invasive melanoma (melanoma that has invaded into the dermis or subcutaneous tissue), MMS has been shown to have marginal benefit but currently is not included within the AUC.³

Continue to: Due to excellent margin control...

Due to excellent margin control via immediate microscopic evaluation of surgical margins, MMS is an appropriate treatment choice and indicated for many more uncommon cutaneous malignancies, including sebaceous and mucinous carcinoma, microcystic adnexal carcinoma, Merkel cell carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, angiosarcoma, and other more rarely encountered clinical malignancies.²

Tumor size. When considering a referral to MMS for cancer extirpation, the size of the tumor does play a role; however, size depends on the type of tumor as well as the location on the body. In general, most skin cancers of any size on the face, perianal area, genitalia, nipples, hands, feet and ankles, or pretibial surface are appropriate for Mohs surgery. Skin cancers on the trunk and extremities are also appropriate if they are above a certain size specified by the AUC. Tumor type and whether they are recurrences also factor into the equation.

Who will do the procedure?

A recent review showed that PCPs were more likely to refer patients to plastic surgery rather than Mohs surgery for skin cancer removal, especially among younger female patients.⁴ This is likely because of the perception that plastic surgeons do more complex closures and have more experience removing difficult cancers. Interestingly, this same study showed that Mohs surgeons may actually be doing several-fold more complex closures (flaps and grafts) on the nose and ears than plastic surgeons at similar practice settings.⁴

Aside from Mohs surgeons doing more closures, perhaps the biggest difference between Mohs surgeons and plastic surgeons is the pathology training of the Mohs surgeon. Mohs surgeons evaluate 100% of the tissue margins at the time of the procedure to both ensure complete tumor removal and to preserve as much tumor-free skin as possible, ultimately resulting in decreased recurrences and smaller scars. In contrast, the plastic surgeon’s rigorous training typically does not include extensive dermatopathology training, particularly the pathology of cutaneous neoplasms. Plastic surgeons will often send pathologic specimens for evaluation, meaning patients have to wait for outside histologic confirmation before their wounds can be closed. Additionally, the histologic evaluation is often not a full-margin assessment, as not all labs are equipped for this technique.

Consider early consultation with a Mohs surgeon for tumor extirpation to keep the defect size as small as possible, as MMS does not require taking margins of healthy surrounding tissue, in contrast to wide local excisions (WLEs; FIGURE 1). A smaller initial incision will result in a smaller scar, which is likely to have better cosmetic outcomes and decreased risk for wound infection.

Continue to: Before consultation...

Before consultation, include a picture of the surgical site with the patient’s referral documentation or have the patient present a photo from his or her phone to the Mohs surgeon. (If a camera or cell phone is not available, triangulation of the site’s location using cosmetic landmarks can be documented in the patient’s chart.)

What the patient can expect during preop visits

During an initial consultation, patients can expect an evaluation by the surgeon that will include more photo taking, a discussion of the surgery, and possibly, performance of an in-clinic biopsy of suspicious lesions. Many practices, including the authors’, use a photo capturing add-on for the EMR in the office.^5-7

During the consent process, MMS is described to the patient using lay language and, often, pictorial depictions of the procedure. While explaining that the procedure helps preserve healthy tissue and limit the size of the resulting scar, the surgeon will typically manage the expectations of the patient prior to the first incision. Many clinically small lesions can have significant subclinical extension adjacent to, or on top of, cosmetic landmarks, requiring a flap or graft to close the surgical defect with acceptable cosmetic outcomes.⁸

One more time. Immediately before surgery, the surgeon will again review the procedure with the patient, using photos of the biopsy site taken during the initial consult, in conjunction with patient verification of the biopsy site, to verify the surgical site and confirm that the patient understands and agrees to the surgery.

A look at how Mohs surgery is performed

MMS typically is performed in the outpatient setting but can also be performed in an operating room or outpatient surgical center. MMS can be performed in a nonsterile procedure room with surgeons and assistants typically utilizing clean, nonsterile gloves, although many Mohs surgeons prefer to perform part, or all, of the technique using sterile gloves.⁹ A recent systematic review and large meta-analysis showed no significant difference in postsurgical site infections when comparing the use of sterile vs nonsterile gloves.¹⁰

Continue to: Prior to initial incision...

Prior to initial incision, the site is marked with a surgical pen and given 1-mm margins around the clinically visualized lesion. The site is then cleansed with an antiseptic, typically a chlorhexidine solution. Local anesthesia is employed, most commonly with a 1:100,000 lidocaine and epinephrine injection. Marking of the tumor prior to numbing is imperative, as the boundaries of the tumor are typically obscured when the local cutaneous vasculature constricts and causes visualized blanching of adjacent skin. Many Mohs surgeons perform a brief curettage of the lesion with a nondisposable, dull curette to better define the tumor edges and to debulk any obvious exophytic tumor noted by the naked eye.

Prior to the first incision, the surgical site is scored in a variety of ways in order to properly orient the tissue after it has been removed from the patient. Mohs surgeons have differing opinions on how to score and/or mark the tissue, but a common practice is to make a nick at the 12 o’clock position. Following removal of the first stage, the nick will be visible on both the extirpated tissue and the tissue just above the surgical defect. This prevents potential confusion regarding orientation during tissue processing.

The majority of all WLEs are performed utilizing the scalpel blade at an angle 90° perpendicular to the plane of the skin. In MMS, a signature 45° angle with the tip of the scalpel pointing toward, and the handle pointing away from, the lesion is commonly used in order to bevel the tissue being excised (FIGURE 2). Once the tissue is excised, hemostasis is obtained using electrodessication/electrofulguration or electrocoagulation.

Tissue processing and microscopic evaluation

The technique of beveling allows the epidermis, dermis, and subcutaneous tissue to lie flat on the tissue block, so the Mohs surgeon can evaluate 100% of the excised tissue’s margins. The tissue is transported to a nearby lab for staining and processing. Even if near-perfect beveling is achieved, many stages will require bisecting, quadrissecting, or relaxing cuts in order to allow the margins to lie flat on the tissue block.

Using the scoring system made prior to incision, the tissue is oriented and stained with colored ink. Subsequently, a map is made with sections highlighting the colors used to stain designated areas of the tissue. This step is imperative for orientation during microscopic evaluation. Additionally, the map serves as a guide and log, should a section of the specimen have an involved margin and require another stage.

Continue to: Once fixed to the block...

Once fixed to the block, the tissue is engulfed in appropriate embedding medium and placed within the cryostat. The block is slowly cut to produce several micron-thin wafers of tissue that are then mounted on glass slides and processed with hematoxylin and eosin (H&E) or various stains. The first wafers of tissue that come from the tissue block are those that are closest to the margin that was excised. Thus, 100% of the epidermis and deep margin can be visualized. “Deeper sections” are those that come from deeper cuts within the tissue and are more likely to show the malignant neoplasm.

Mohs surgery is the standard of care for treating cutaneous malignancy in light of its high cure rates and maximal conservation of tissue in sensitive locations.

The evaluation of immediate margins at the very edge of the tissue is in contrast to the technique of “bread-loafing,” which is the standard of evaluating margins after a WLE.¹¹ With this process, the pathologist examines sections that are cut 2- to 4-mm apart. This process only allows the pathologist to examine roughly 1% of the total tissue that was excised, and large variability in cutaneous representation can occur depending on the individual who cuts and processes the tissue.¹¹

Closing the defect

Once the site is deemed clear of residual tumor, the Mohs surgeon approaches the defect and determines the most appropriate way to close the surgical wound. Mohs surgeons are trained to close wounds using a variety of methods, including complex linear closures, flaps, and full-thickness skin grafts. Thoughtful consideration of local anatomy, cosmetic landmarks that may be affected by the closure method, and local tissue laxity are evaluated.

Depending on the location, a secondary intention closure may prove to be just as effective and cosmetically satisfying as a primary intention closure. In light of the many methods of closure, a complex or large surface area defect may better be suited for evaluation and closure by another specialist such as an ENT physician, ophthalmologist, or plastic surgeon.¹²

Lower recurrence rates for patients who undergo Mohs surgery

As noted earlier, the cutaneous malignancies most commonly treated with MMS are BCCs, followed by SCCs.¹³ Comparison studies between WLE and MMS show clinically significant differences in terms of recurrence rates between the 2 procedures.

Continue to: For BCCs

For BCCs, recurrence rates for excisions vs MMS are 10% and 1%, respectively.^14-16 A randomized trial reviewing 10-year recurrence of primary BCCs on the face showed recurrence rates for MMS of 4.4% compared to 12.2% for WLE.¹⁷ This study also showed recurrence rates for recurrent facial BCCs treated with MMS to be 3.9% vs 13.5% for standard WLE.¹⁷

SCC. The evidence similarly supports the efficacy of MMS for SCCs. A recent study showed primary T2a tumors had a 1.2% local recurrence rate with Mohs vs a 4% recurrence rate with WLE at an average follow-up of 2.8 years.¹⁸ Another study showed that primary tumors that were < 2 cm in diameter had a 5-year cure rate of 99% with Mohs surgery.¹¹

Melanoma in situ. A few studies have shown no clinically significant benefit of MMS compared to WLE when it comes to melanoma in situ.^19,20 However, a more recent article by Etzkom et al noted the ability to potentially upstage melanoma in situ and invasive melanoma after reviewing peripheral and deep margins during MMS.²¹ In this study, the authors uniquely delayed wound closure if upstaging was established and the need for a sentinel lymph node biopsy was warranted. This approach to MMS with delayed closure ultimately paved the way for very low recurrence rates.

CORRESPONDENCE
Andres Garcia, MD, 2612 112th Street, Lubbock, TX 79423; [email protected]

All clinicians who have patients who are employed play an essential role in work disability programs—whether or not those clinicians have received formal training in occupational health. A study found that primary care clinicians are asked to provide guidance about work activities in nearly 10% of their patient encounters; however, 25% of those clinicians thought they had little influence over work disability outcomes.¹

In this article, we explain why it is important for family physicians to better manage work disability at the point of care, to help patients return to their pre-injury or pre-illness level of activity.

Why managing the duration of work disability matters

Each year, millions of American workers leave their jobs—temporarily or permanently—because of illness, injury, or the effects of a chronic condition.² It is estimated that 893 million workdays are lost annually due to a new medical problem; an additional 527 million workdays are lost due to the impact of chronic health conditions on the ability to perform at work.³ The great majority of these lost workdays are the result of personal health conditions, not work-related problems; patients must therefore cope with the accompanying disruption of life and work.

Significant injury and illness can create a life crisis, especially when there is uncertainty about future livelihood, such as an income shortfall during a lengthy recovery. Only 40% of the US workforce is covered by a short-term disability insurance program; only 10% of low-wage and low-skill workers have this type of coverage.⁴ Benefits rarely replace loss of income entirely, and worker compensation insurance programs provide only partial wage replacement.

In short, work disability is destabilizing and can threaten overall well-being.⁵

Furthermore, the longer a person remains on temporary disability, the more likely that person is to move to a publicly funded disability program or leave the workforce entirely—thus, potentially losing future earnings and self-identity related to being a working member of society.^6-8

Most of the annual cost of poor health for US employers derives from medical and wage benefits ($226 billion) and impaired or reduced employee performance ($223 billion).³ In addition, temporarily disabled workers likely account for a disproportionate share of health care costs: A study found that one-half of medical and pharmacy payments were paid out to the one-quarter of employees requiring disability benefits.⁹

Continue to: Benefits of staying on the job

Benefits of staying on the job. Research shows that there are physical and mental health benefits to remaining at, or returning to, work after an injury or illness.^10,11 For example, in a longitudinal cohort of people with low back pain, immediate or early return to work (in 1-7 days) was associated with reduced pain and improved functioning at 3 months.¹² Physicians who can guide patients safely back to normal activities, including work, minimize the physical and mental health impact of the injury or illness and avoid chronicity.¹³

Emphasizing the importance of health, not disease or injury

Health researchers have found that diagnosis, cause, and extent of morbidity do not adequately explain observed variability in the impact of health conditions, utilization of resources, or need for services. A wider view of the functional implications of an injury or illness is therefore required for physicians to effectively recommend disability duration.

Consider that your patient’s prolonged work disability and consequent loss of livelihood are very poor outcomes of a medical or health condition.

The World Health Organization recommends a shift toward a more holistic view of health, impairment, and disability, including an emphasis on functional ability, intrinsic capacity, and environmental context.¹⁴ The American Medical Association, American College of Occupational and Environmental Medicine, and Canadian Medical Association emphasize that prolonged absence from one’s normal role can be detrimental to mental, physical, and social well-being.⁸ These advisory groups recommend that physicians encourage patients who are unable to work to (1) focus on restoring the rhythm of their everyday life in a stepwise fashion and (2) resume their usual responsibilities as soon as possible.

Advising a patient to focus on “what you can do,” not “what you can’t do,” might make all the difference in their return to productivity. Keeping the patient’s—as well as your own—attention focused on the positive process of recovery and documenting evidence of functional progress is an important addition to (or substitute for) detailed inquiries about pain and dysfunction.

Why does duration of disability vary so much from case to case?

Disability duration is influenced by the individual patient, employer, physician, jurisdiction, insurer or benefits structure, and access to care.¹⁵ For you to effectively manage a patient who is out of work for a medical reason, it is important to understand how nonmedical variables often influence the pace of recovery and the timing of return to work (FIGURE).

Continue to: Deficient communication

Deficient communication. Often, employers, insurers, third-party administrators, and clinicians—each a key stakeholder in disability care—are disconnected from one another, resulting in poor communication with the injured worker. Such fragmented communication can delay treatment and recovery.¹⁶ Data systems are not designed to measure the duration of disability or provide proactive notification for key stakeholders who might intervene to facilitate a patient’s recovery.

Alternatively, a collaborative approach to disability management has been shown to improve outcomes.^17,18 Communication among the various professionals involved can be coordinated and expedited by a case manager or disability manager hired by the medical practice, the employer, or the insurance company.

Psychosocial and economic influences can radically affect the time it takes to return to pre-injury or pre-illness functional status. Demographic variables (age, sex, income, education, and support system) influence how a person responds to a debilitating injury or illness.¹⁹ Fear of re-injury, anxiety over the intensity of pain upon movement, worry over dependency on others, and resiliency play an important role when a patient is attempting to return to full activity.^20,21

Job satisfaction has been identified as the most significant variable associated with prompt return to work.¹⁵ Work has many health-enhancing aspects, including socioeconomic status, psychosocial support, and self-identity²²; however, not everyone wants, or feels ready, to go back to work even once they are physically able. Workplace variables, such as the patient–employee’s dislike of the position, coworkers, or manager, have been cited by physicians as leading barriers to returning to work at an appropriate time.^23,24

Other external variables. Physicians should formulate activity prescriptions and medical restrictions based on the impact the medical condition has on the usual ability to function, as well as the anticipated impact of specific activities on the body’s natural healing process. However, Rainville and colleagues found that external variables—patient requests, employer characteristics, and jurisdiction issues—considerably influence physicians’ recommendations.²⁰ For example, benefit structure might influence how long a patient wants to remain out of work—thus altering the requests they make to their physician. Jurisdictional characteristics, such as health care systems, state workers’ compensation departments, and payer systems, all influence a patient’s recovery timeline and time away from work.²⁵

Continue to: What does your patient need so that they can recover?

What does your patient need so that they can recover? Individual and systemic factors must be appropriately addressed to minimize the impact that recovery from a disability has on a person’s life. Successful functional recovery enables the person to self-manage symptoms, reduce disruption-associated stress, preserve mental health, and maintain healthy relationships at home and work. An example is the patient who has successfully coped with the entire predicament that their medical condition posed and resumed their usual daily routine and responsibilities at home and at work—albeit sometimes with temporary or permanent modification necessitated by their specific condition.

Strategies that help patients stay at, or return to, their job

Physicians who anticipate, monitor, and actively manage the duration of a work disability can improve patient outcomes by minimizing life disruption, avoiding unnecessary medical care, and shortening the period of absence from work.

Key strategy: Set expectations for functional recovery early in the episode, including a forecast of how long it will take to get life and work back to normal.^26,27 This is similar to discussing expectations about pain before surgery, which has been shown to decrease subsequent requests for opioids.²⁸ It is crucial to educate the patient about timelines, define functional outcomes, and encourage them to set goals for recovery.²⁹

Devise an evidence-based treatment plan. A fundamental way to reduce disability duration is to (1) devise a treatment plan that is evidence based and (2) take the most effective route to recovery. Given the pace with which medical research changes the understanding of diseases and treatments, it is essential to rely on up-to-date, comprehensive, independent, and authoritative resources to support your care decisions.

Aligning clinical practice with evidence-based medicine (EBM) is a good way to accomplish that goal. By definition, EBM practice guidelines recommend the safest and most effective treatments after unbiased assessment of the best available research. Increasingly, EBM is adopted to improve clinical and functional outcomes, establish national standards of care, and set criteria to evaluate clinical performance.³⁰

Continue to: Utilize established guidelines

Utilize established guidelines. A tactic that can make it easier to discuss return to work with patients is to rely on an independent and authoritative reference set of codified disability duration guidelines, which, typically, can be searched by diagnosis, procedure, or presenting symptoms. Such guidelines provide a condition-specific expected duration of work disability in the form of number of days, with shortest, typical, and maximum durations for different levels of job demands. If necessary, you can then adjust the guideline’s estimated duration to account for the patient’s age, underlying state of health, comorbidities, and so forth. 

The use of disability duration guidelines at the point of care can facilitate the process of setting early and appropriate expectations for a patient’s recovery. If a patient is confrontational in response to your recommendation on the duration of work disability, guidelines can be used to address specific objections and facilitate understanding of functional recovery.

Consider the employer’s needs. To support return-to-work efforts, your guidance about work should consider the employer’s business needs. Employers require that the patient’s abilities, restrictions, and limitations be described in concrete terms because they must decide which specific tasks are unsafe and which ones they can reasonably expect the recovering worker to perform. However, employers often fail to send information to the physician about the patient’s job tasks—such that the clinician must rely on patient self-reporting, which might be inaccurate, incomplete, or biased.¹⁵ When a patient needs protection against foreseeable harm, highlight specific activities that are currently unsafe on the recovery timeline.

Employers rely on the physician to (1) estimate what the patient can do and (2) describe work ability in clear, objective terms that both patient and employer can interpret (TABLE). For example, “no heavy lifting” might be hard for an employer to interpret; “may lift 10 pounds from the floor to the waist as many as 12 times an hour” might be applied in a more practical manner to help a patient return to work safely.³¹ Including specific numbers, rates, and metrics in activity restrictions can also help demonstrate improvement over the course of treatment.

Be clear and specific on work restrictions. During recovery, it is important to tell the patient which temporary work restrictions are intended to prevent further injury or recurrence (prophylactic work restrictions) and which are an estimate of what they are able to do safely at work (capacity-based restrictions). Your written work restrictions form should be kept separate from private medical information because those restrictions will be the basis of subsequent conversations between patient and employer, who should be invited to give feedback if the guidance needs revision or clarification.

Continue to: Employer programs

Employer programs, such as modified duty, transitional duty, or early return to work programs, have been found to resolve claims faster and improve recovery outcomes.^10,12 Such programs might also reduce occupational stress and improve productivity when an employee realizes that their functional abilities are matched to realistic job expectations during recovery.¹⁶ You can play an important role in empowering your patients to seek out these support programs.

What’s ahead for managing disability durations?

Work disability duration is influenced by the complex mix of biological, psychosocial, and economic variables that we have touched on here. All stakeholders involved in the recovery process should support the patient’s ability to live life with as few restrictions as possible; you play a key role in their recovery by focusing on ability, highlighting remaining capabilities, emphasizing activities that are safe to perform, and encouraging acceptance of, and adaptation to, any irrevocable losses.

This is a holistic approach that might help patients overcome the stress and anxiety associated with major life events arising from illness or injury that trigger disability benefits. Open communication and establishing a shared goal, among all involved, of the best possible outcome increases the likelihood that working patients will return to their familiar life or find another positive path forward.

Keep the patient’s attention on the positive process of recovery, and document evidence of functional progress.

Using EBM and disability duration guidelines can help decrease the length of life–work disruption by ensuring that patients are given a diagnosis, treated, and managed appropriately.^32,33 Although these practices have been adopted by some physicians, health care systems, and insurers, they are not being implemented systematically and are unlikely to become ubiquitous unless they are mandated by payers or by law.

Family physicians are front-line providers for America’s workforce. They are distinctly situated to help patients achieve their best life at home and work. Improving the timeliness and quality of work guidance provided by the physician is an important way to minimize the impact of health problems on working people’s lives and livelihoods—and to help them stay employed.

CORRESPONDENCE
Kerri Wizner, MPH, 10355 Westmoor Drive, Westminster, CO 80021; [email protected].

All clinicians who have patients who are employed play an essential role in work disability programs—whether or not those clinicians have received formal training in occupational health. A study found that primary care clinicians are asked to provide guidance about work activities in nearly 10% of their patient encounters; however, 25% of those clinicians thought they had little influence over work disability outcomes.¹

In this article, we explain why it is important for family physicians to better manage work disability at the point of care, to help patients return to their pre-injury or pre-illness level of activity.

Why managing the duration of work disability matters

Each year, millions of American workers leave their jobs—temporarily or permanently—because of illness, injury, or the effects of a chronic condition.² It is estimated that 893 million workdays are lost annually due to a new medical problem; an additional 527 million workdays are lost due to the impact of chronic health conditions on the ability to perform at work.³ The great majority of these lost workdays are the result of personal health conditions, not work-related problems; patients must therefore cope with the accompanying disruption of life and work.

Significant injury and illness can create a life crisis, especially when there is uncertainty about future livelihood, such as an income shortfall during a lengthy recovery. Only 40% of the US workforce is covered by a short-term disability insurance program; only 10% of low-wage and low-skill workers have this type of coverage.⁴ Benefits rarely replace loss of income entirely, and worker compensation insurance programs provide only partial wage replacement.

In short, work disability is destabilizing and can threaten overall well-being.⁵

Furthermore, the longer a person remains on temporary disability, the more likely that person is to move to a publicly funded disability program or leave the workforce entirely—thus, potentially losing future earnings and self-identity related to being a working member of society.^6-8

Most of the annual cost of poor health for US employers derives from medical and wage benefits ($226 billion) and impaired or reduced employee performance ($223 billion).³ In addition, temporarily disabled workers likely account for a disproportionate share of health care costs: A study found that one-half of medical and pharmacy payments were paid out to the one-quarter of employees requiring disability benefits.⁹

Continue to: Benefits of staying on the job

Benefits of staying on the job. Research shows that there are physical and mental health benefits to remaining at, or returning to, work after an injury or illness.^10,11 For example, in a longitudinal cohort of people with low back pain, immediate or early return to work (in 1-7 days) was associated with reduced pain and improved functioning at 3 months.¹² Physicians who can guide patients safely back to normal activities, including work, minimize the physical and mental health impact of the injury or illness and avoid chronicity.¹³

Emphasizing the importance of health, not disease or injury

Health researchers have found that diagnosis, cause, and extent of morbidity do not adequately explain observed variability in the impact of health conditions, utilization of resources, or need for services. A wider view of the functional implications of an injury or illness is therefore required for physicians to effectively recommend disability duration.

Consider that your patient’s prolonged work disability and consequent loss of livelihood are very poor outcomes of a medical or health condition.

The World Health Organization recommends a shift toward a more holistic view of health, impairment, and disability, including an emphasis on functional ability, intrinsic capacity, and environmental context.¹⁴ The American Medical Association, American College of Occupational and Environmental Medicine, and Canadian Medical Association emphasize that prolonged absence from one’s normal role can be detrimental to mental, physical, and social well-being.⁸ These advisory groups recommend that physicians encourage patients who are unable to work to (1) focus on restoring the rhythm of their everyday life in a stepwise fashion and (2) resume their usual responsibilities as soon as possible.

Advising a patient to focus on “what you can do,” not “what you can’t do,” might make all the difference in their return to productivity. Keeping the patient’s—as well as your own—attention focused on the positive process of recovery and documenting evidence of functional progress is an important addition to (or substitute for) detailed inquiries about pain and dysfunction.

Why does duration of disability vary so much from case to case?

Disability duration is influenced by the individual patient, employer, physician, jurisdiction, insurer or benefits structure, and access to care.¹⁵ For you to effectively manage a patient who is out of work for a medical reason, it is important to understand how nonmedical variables often influence the pace of recovery and the timing of return to work (FIGURE).

Continue to: Deficient communication

Deficient communication. Often, employers, insurers, third-party administrators, and clinicians—each a key stakeholder in disability care—are disconnected from one another, resulting in poor communication with the injured worker. Such fragmented communication can delay treatment and recovery.¹⁶ Data systems are not designed to measure the duration of disability or provide proactive notification for key stakeholders who might intervene to facilitate a patient’s recovery.

Alternatively, a collaborative approach to disability management has been shown to improve outcomes.^17,18 Communication among the various professionals involved can be coordinated and expedited by a case manager or disability manager hired by the medical practice, the employer, or the insurance company.

Psychosocial and economic influences can radically affect the time it takes to return to pre-injury or pre-illness functional status. Demographic variables (age, sex, income, education, and support system) influence how a person responds to a debilitating injury or illness.¹⁹ Fear of re-injury, anxiety over the intensity of pain upon movement, worry over dependency on others, and resiliency play an important role when a patient is attempting to return to full activity.^20,21

Job satisfaction has been identified as the most significant variable associated with prompt return to work.¹⁵ Work has many health-enhancing aspects, including socioeconomic status, psychosocial support, and self-identity²²; however, not everyone wants, or feels ready, to go back to work even once they are physically able. Workplace variables, such as the patient–employee’s dislike of the position, coworkers, or manager, have been cited by physicians as leading barriers to returning to work at an appropriate time.^23,24

Other external variables. Physicians should formulate activity prescriptions and medical restrictions based on the impact the medical condition has on the usual ability to function, as well as the anticipated impact of specific activities on the body’s natural healing process. However, Rainville and colleagues found that external variables—patient requests, employer characteristics, and jurisdiction issues—considerably influence physicians’ recommendations.²⁰ For example, benefit structure might influence how long a patient wants to remain out of work—thus altering the requests they make to their physician. Jurisdictional characteristics, such as health care systems, state workers’ compensation departments, and payer systems, all influence a patient’s recovery timeline and time away from work.²⁵

Continue to: What does your patient need so that they can recover?

What does your patient need so that they can recover? Individual and systemic factors must be appropriately addressed to minimize the impact that recovery from a disability has on a person’s life. Successful functional recovery enables the person to self-manage symptoms, reduce disruption-associated stress, preserve mental health, and maintain healthy relationships at home and work. An example is the patient who has successfully coped with the entire predicament that their medical condition posed and resumed their usual daily routine and responsibilities at home and at work—albeit sometimes with temporary or permanent modification necessitated by their specific condition.

Strategies that help patients stay at, or return to, their job

Physicians who anticipate, monitor, and actively manage the duration of a work disability can improve patient outcomes by minimizing life disruption, avoiding unnecessary medical care, and shortening the period of absence from work.

Key strategy: Set expectations for functional recovery early in the episode, including a forecast of how long it will take to get life and work back to normal.^26,27 This is similar to discussing expectations about pain before surgery, which has been shown to decrease subsequent requests for opioids.²⁸ It is crucial to educate the patient about timelines, define functional outcomes, and encourage them to set goals for recovery.²⁹

Devise an evidence-based treatment plan. A fundamental way to reduce disability duration is to (1) devise a treatment plan that is evidence based and (2) take the most effective route to recovery. Given the pace with which medical research changes the understanding of diseases and treatments, it is essential to rely on up-to-date, comprehensive, independent, and authoritative resources to support your care decisions.

Aligning clinical practice with evidence-based medicine (EBM) is a good way to accomplish that goal. By definition, EBM practice guidelines recommend the safest and most effective treatments after unbiased assessment of the best available research. Increasingly, EBM is adopted to improve clinical and functional outcomes, establish national standards of care, and set criteria to evaluate clinical performance.³⁰

Continue to: Utilize established guidelines

Utilize established guidelines. A tactic that can make it easier to discuss return to work with patients is to rely on an independent and authoritative reference set of codified disability duration guidelines, which, typically, can be searched by diagnosis, procedure, or presenting symptoms. Such guidelines provide a condition-specific expected duration of work disability in the form of number of days, with shortest, typical, and maximum durations for different levels of job demands. If necessary, you can then adjust the guideline’s estimated duration to account for the patient’s age, underlying state of health, comorbidities, and so forth. 

The use of disability duration guidelines at the point of care can facilitate the process of setting early and appropriate expectations for a patient’s recovery. If a patient is confrontational in response to your recommendation on the duration of work disability, guidelines can be used to address specific objections and facilitate understanding of functional recovery.

Consider the employer’s needs. To support return-to-work efforts, your guidance about work should consider the employer’s business needs. Employers require that the patient’s abilities, restrictions, and limitations be described in concrete terms because they must decide which specific tasks are unsafe and which ones they can reasonably expect the recovering worker to perform. However, employers often fail to send information to the physician about the patient’s job tasks—such that the clinician must rely on patient self-reporting, which might be inaccurate, incomplete, or biased.¹⁵ When a patient needs protection against foreseeable harm, highlight specific activities that are currently unsafe on the recovery timeline.

Employers rely on the physician to (1) estimate what the patient can do and (2) describe work ability in clear, objective terms that both patient and employer can interpret (TABLE). For example, “no heavy lifting” might be hard for an employer to interpret; “may lift 10 pounds from the floor to the waist as many as 12 times an hour” might be applied in a more practical manner to help a patient return to work safely.³¹ Including specific numbers, rates, and metrics in activity restrictions can also help demonstrate improvement over the course of treatment.

Be clear and specific on work restrictions. During recovery, it is important to tell the patient which temporary work restrictions are intended to prevent further injury or recurrence (prophylactic work restrictions) and which are an estimate of what they are able to do safely at work (capacity-based restrictions). Your written work restrictions form should be kept separate from private medical information because those restrictions will be the basis of subsequent conversations between patient and employer, who should be invited to give feedback if the guidance needs revision or clarification.

Continue to: Employer programs

Employer programs, such as modified duty, transitional duty, or early return to work programs, have been found to resolve claims faster and improve recovery outcomes.^10,12 Such programs might also reduce occupational stress and improve productivity when an employee realizes that their functional abilities are matched to realistic job expectations during recovery.¹⁶ You can play an important role in empowering your patients to seek out these support programs.

What’s ahead for managing disability durations?

Work disability duration is influenced by the complex mix of biological, psychosocial, and economic variables that we have touched on here. All stakeholders involved in the recovery process should support the patient’s ability to live life with as few restrictions as possible; you play a key role in their recovery by focusing on ability, highlighting remaining capabilities, emphasizing activities that are safe to perform, and encouraging acceptance of, and adaptation to, any irrevocable losses.

This is a holistic approach that might help patients overcome the stress and anxiety associated with major life events arising from illness or injury that trigger disability benefits. Open communication and establishing a shared goal, among all involved, of the best possible outcome increases the likelihood that working patients will return to their familiar life or find another positive path forward.

Keep the patient’s attention on the positive process of recovery, and document evidence of functional progress.

Using EBM and disability duration guidelines can help decrease the length of life–work disruption by ensuring that patients are given a diagnosis, treated, and managed appropriately.^32,33 Although these practices have been adopted by some physicians, health care systems, and insurers, they are not being implemented systematically and are unlikely to become ubiquitous unless they are mandated by payers or by law.

Family physicians are front-line providers for America’s workforce. They are distinctly situated to help patients achieve their best life at home and work. Improving the timeliness and quality of work guidance provided by the physician is an important way to minimize the impact of health problems on working people’s lives and livelihoods—and to help them stay employed.

CORRESPONDENCE
Kerri Wizner, MPH, 10355 Westmoor Drive, Westminster, CO 80021; [email protected].

All clinicians who have patients who are employed play an essential role in work disability programs—whether or not those clinicians have received formal training in occupational health. A study found that primary care clinicians are asked to provide guidance about work activities in nearly 10% of their patient encounters; however, 25% of those clinicians thought they had little influence over work disability outcomes.¹

In this article, we explain why it is important for family physicians to better manage work disability at the point of care, to help patients return to their pre-injury or pre-illness level of activity.

Why managing the duration of work disability matters

Each year, millions of American workers leave their jobs—temporarily or permanently—because of illness, injury, or the effects of a chronic condition.² It is estimated that 893 million workdays are lost annually due to a new medical problem; an additional 527 million workdays are lost due to the impact of chronic health conditions on the ability to perform at work.³ The great majority of these lost workdays are the result of personal health conditions, not work-related problems; patients must therefore cope with the accompanying disruption of life and work.

Significant injury and illness can create a life crisis, especially when there is uncertainty about future livelihood, such as an income shortfall during a lengthy recovery. Only 40% of the US workforce is covered by a short-term disability insurance program; only 10% of low-wage and low-skill workers have this type of coverage.⁴ Benefits rarely replace loss of income entirely, and worker compensation insurance programs provide only partial wage replacement.

In short, work disability is destabilizing and can threaten overall well-being.⁵

Furthermore, the longer a person remains on temporary disability, the more likely that person is to move to a publicly funded disability program or leave the workforce entirely—thus, potentially losing future earnings and self-identity related to being a working member of society.^6-8

Most of the annual cost of poor health for US employers derives from medical and wage benefits ($226 billion) and impaired or reduced employee performance ($223 billion).³ In addition, temporarily disabled workers likely account for a disproportionate share of health care costs: A study found that one-half of medical and pharmacy payments were paid out to the one-quarter of employees requiring disability benefits.⁹

Continue to: Benefits of staying on the job

Benefits of staying on the job. Research shows that there are physical and mental health benefits to remaining at, or returning to, work after an injury or illness.^10,11 For example, in a longitudinal cohort of people with low back pain, immediate or early return to work (in 1-7 days) was associated with reduced pain and improved functioning at 3 months.¹² Physicians who can guide patients safely back to normal activities, including work, minimize the physical and mental health impact of the injury or illness and avoid chronicity.¹³

Emphasizing the importance of health, not disease or injury

Health researchers have found that diagnosis, cause, and extent of morbidity do not adequately explain observed variability in the impact of health conditions, utilization of resources, or need for services. A wider view of the functional implications of an injury or illness is therefore required for physicians to effectively recommend disability duration.

Consider that your patient’s prolonged work disability and consequent loss of livelihood are very poor outcomes of a medical or health condition.

The World Health Organization recommends a shift toward a more holistic view of health, impairment, and disability, including an emphasis on functional ability, intrinsic capacity, and environmental context.¹⁴ The American Medical Association, American College of Occupational and Environmental Medicine, and Canadian Medical Association emphasize that prolonged absence from one’s normal role can be detrimental to mental, physical, and social well-being.⁸ These advisory groups recommend that physicians encourage patients who are unable to work to (1) focus on restoring the rhythm of their everyday life in a stepwise fashion and (2) resume their usual responsibilities as soon as possible.

Advising a patient to focus on “what you can do,” not “what you can’t do,” might make all the difference in their return to productivity. Keeping the patient’s—as well as your own—attention focused on the positive process of recovery and documenting evidence of functional progress is an important addition to (or substitute for) detailed inquiries about pain and dysfunction.

Why does duration of disability vary so much from case to case?

Disability duration is influenced by the individual patient, employer, physician, jurisdiction, insurer or benefits structure, and access to care.¹⁵ For you to effectively manage a patient who is out of work for a medical reason, it is important to understand how nonmedical variables often influence the pace of recovery and the timing of return to work (FIGURE).

Continue to: Deficient communication

Deficient communication. Often, employers, insurers, third-party administrators, and clinicians—each a key stakeholder in disability care—are disconnected from one another, resulting in poor communication with the injured worker. Such fragmented communication can delay treatment and recovery.¹⁶ Data systems are not designed to measure the duration of disability or provide proactive notification for key stakeholders who might intervene to facilitate a patient’s recovery.

Alternatively, a collaborative approach to disability management has been shown to improve outcomes.^17,18 Communication among the various professionals involved can be coordinated and expedited by a case manager or disability manager hired by the medical practice, the employer, or the insurance company.

Psychosocial and economic influences can radically affect the time it takes to return to pre-injury or pre-illness functional status. Demographic variables (age, sex, income, education, and support system) influence how a person responds to a debilitating injury or illness.¹⁹ Fear of re-injury, anxiety over the intensity of pain upon movement, worry over dependency on others, and resiliency play an important role when a patient is attempting to return to full activity.^20,21

Job satisfaction has been identified as the most significant variable associated with prompt return to work.¹⁵ Work has many health-enhancing aspects, including socioeconomic status, psychosocial support, and self-identity²²; however, not everyone wants, or feels ready, to go back to work even once they are physically able. Workplace variables, such as the patient–employee’s dislike of the position, coworkers, or manager, have been cited by physicians as leading barriers to returning to work at an appropriate time.^23,24

Other external variables. Physicians should formulate activity prescriptions and medical restrictions based on the impact the medical condition has on the usual ability to function, as well as the anticipated impact of specific activities on the body’s natural healing process. However, Rainville and colleagues found that external variables—patient requests, employer characteristics, and jurisdiction issues—considerably influence physicians’ recommendations.²⁰ For example, benefit structure might influence how long a patient wants to remain out of work—thus altering the requests they make to their physician. Jurisdictional characteristics, such as health care systems, state workers’ compensation departments, and payer systems, all influence a patient’s recovery timeline and time away from work.²⁵

Continue to: What does your patient need so that they can recover?

What does your patient need so that they can recover? Individual and systemic factors must be appropriately addressed to minimize the impact that recovery from a disability has on a person’s life. Successful functional recovery enables the person to self-manage symptoms, reduce disruption-associated stress, preserve mental health, and maintain healthy relationships at home and work. An example is the patient who has successfully coped with the entire predicament that their medical condition posed and resumed their usual daily routine and responsibilities at home and at work—albeit sometimes with temporary or permanent modification necessitated by their specific condition.

Strategies that help patients stay at, or return to, their job

Physicians who anticipate, monitor, and actively manage the duration of a work disability can improve patient outcomes by minimizing life disruption, avoiding unnecessary medical care, and shortening the period of absence from work.

Key strategy: Set expectations for functional recovery early in the episode, including a forecast of how long it will take to get life and work back to normal.^26,27 This is similar to discussing expectations about pain before surgery, which has been shown to decrease subsequent requests for opioids.²⁸ It is crucial to educate the patient about timelines, define functional outcomes, and encourage them to set goals for recovery.²⁹

Devise an evidence-based treatment plan. A fundamental way to reduce disability duration is to (1) devise a treatment plan that is evidence based and (2) take the most effective route to recovery. Given the pace with which medical research changes the understanding of diseases and treatments, it is essential to rely on up-to-date, comprehensive, independent, and authoritative resources to support your care decisions.

Aligning clinical practice with evidence-based medicine (EBM) is a good way to accomplish that goal. By definition, EBM practice guidelines recommend the safest and most effective treatments after unbiased assessment of the best available research. Increasingly, EBM is adopted to improve clinical and functional outcomes, establish national standards of care, and set criteria to evaluate clinical performance.³⁰

Continue to: Utilize established guidelines

Utilize established guidelines. A tactic that can make it easier to discuss return to work with patients is to rely on an independent and authoritative reference set of codified disability duration guidelines, which, typically, can be searched by diagnosis, procedure, or presenting symptoms. Such guidelines provide a condition-specific expected duration of work disability in the form of number of days, with shortest, typical, and maximum durations for different levels of job demands. If necessary, you can then adjust the guideline’s estimated duration to account for the patient’s age, underlying state of health, comorbidities, and so forth. 

The use of disability duration guidelines at the point of care can facilitate the process of setting early and appropriate expectations for a patient’s recovery. If a patient is confrontational in response to your recommendation on the duration of work disability, guidelines can be used to address specific objections and facilitate understanding of functional recovery.

Consider the employer’s needs. To support return-to-work efforts, your guidance about work should consider the employer’s business needs. Employers require that the patient’s abilities, restrictions, and limitations be described in concrete terms because they must decide which specific tasks are unsafe and which ones they can reasonably expect the recovering worker to perform. However, employers often fail to send information to the physician about the patient’s job tasks—such that the clinician must rely on patient self-reporting, which might be inaccurate, incomplete, or biased.¹⁵ When a patient needs protection against foreseeable harm, highlight specific activities that are currently unsafe on the recovery timeline.

Employers rely on the physician to (1) estimate what the patient can do and (2) describe work ability in clear, objective terms that both patient and employer can interpret (TABLE). For example, “no heavy lifting” might be hard for an employer to interpret; “may lift 10 pounds from the floor to the waist as many as 12 times an hour” might be applied in a more practical manner to help a patient return to work safely.³¹ Including specific numbers, rates, and metrics in activity restrictions can also help demonstrate improvement over the course of treatment.

Be clear and specific on work restrictions. During recovery, it is important to tell the patient which temporary work restrictions are intended to prevent further injury or recurrence (prophylactic work restrictions) and which are an estimate of what they are able to do safely at work (capacity-based restrictions). Your written work restrictions form should be kept separate from private medical information because those restrictions will be the basis of subsequent conversations between patient and employer, who should be invited to give feedback if the guidance needs revision or clarification.

Continue to: Employer programs

Employer programs, such as modified duty, transitional duty, or early return to work programs, have been found to resolve claims faster and improve recovery outcomes.^10,12 Such programs might also reduce occupational stress and improve productivity when an employee realizes that their functional abilities are matched to realistic job expectations during recovery.¹⁶ You can play an important role in empowering your patients to seek out these support programs.

What’s ahead for managing disability durations?

Work disability duration is influenced by the complex mix of biological, psychosocial, and economic variables that we have touched on here. All stakeholders involved in the recovery process should support the patient’s ability to live life with as few restrictions as possible; you play a key role in their recovery by focusing on ability, highlighting remaining capabilities, emphasizing activities that are safe to perform, and encouraging acceptance of, and adaptation to, any irrevocable losses.

This is a holistic approach that might help patients overcome the stress and anxiety associated with major life events arising from illness or injury that trigger disability benefits. Open communication and establishing a shared goal, among all involved, of the best possible outcome increases the likelihood that working patients will return to their familiar life or find another positive path forward.

Keep the patient’s attention on the positive process of recovery, and document evidence of functional progress.

Using EBM and disability duration guidelines can help decrease the length of life–work disruption by ensuring that patients are given a diagnosis, treated, and managed appropriately.^32,33 Although these practices have been adopted by some physicians, health care systems, and insurers, they are not being implemented systematically and are unlikely to become ubiquitous unless they are mandated by payers or by law.

Family physicians are front-line providers for America’s workforce. They are distinctly situated to help patients achieve their best life at home and work. Improving the timeliness and quality of work guidance provided by the physician is an important way to minimize the impact of health problems on working people’s lives and livelihoods—and to help them stay employed.

CORRESPONDENCE
Kerri Wizner, MPH, 10355 Westmoor Drive, Westminster, CO 80021; [email protected].

CASE

A 48-year-old man comes to your clinic with a dark nevus on his right upper arm that appeared 2 months earlier. He says that the lesion has continued to grow and has bled (he thought because he initially picked at it). On exam, there is a 7-mm brown papule with 2 black dots and slightly asymmetric borders.

How would you proceed with this patient?

Melanoma is the fifth leading cause of new cancer cases annually, with > 96,000 new cases in 2019.¹ Overall, melanoma is more common in men and in Whites, with 48% diagnosed in people ages 55 to 74.¹ The past 2 decades have seen numerous developments in the diagnosis, treatment, and surveillance of melanoma. This article covers recommendations, controversies, and issues that require future study. It does not cover uveal or mucosal melanoma.

Evaluating a patient with a new or changing nevus

Known risk factors for melanoma include a changing nevus, indoor tanning, older age, many melanocytic nevi, history of a dysplastic nevus or of blistering sunburns during teen years, red or blonde hair, large congenital nevus, Fitzpatrick skin type I or II, high socioeconomic status, personal or family history of melanoma, and intermittent high-intensity sun exposure.^2-3 Presence of 1 or more of these risk factors should lower the threshold for biopsy.

Worrisome physical exam features (FIGURE) are nevus asymmetry, irregular borders, variegated color, and a diameter > 6 mm (the size of a pencil eraser). Inquire as to whether the nevus’ appearance has evolved and if it has bled without trauma. In a patient with multiple nevi, 1 nevus that looks different than the rest (the so-called “ugly duckling”) is concerning. Accuracy of diagnosis is enhanced with dermoscopy. A Cochrane review showed that skilled use of dermoscopy, in addition to inspection with the naked eye, considerably increases the sensitivity and specificity of diagnosing melanoma.⁴ Yet a 2017 study of 705 US primary care practitioners showed that only 8.3% of them used dermoscopy to evaluate pigmented lesions.⁵

Several published algorithms and checklists can aid clinicians in identifying lesions suggestive of melanoma—eg, ABCDE, CASH, Menzies method, “chaos and clues,” and 2-step and 3- and 7-point checklists.^6-10 A simple 3-step algorithm, the TADA (triage amalgamated dermoscopic algorithm) method is available to novice dermoscopy users.¹¹ Experts in pigmented lesions prefer to use pattern analysis, which requires simultaneously assessing multiple lesion patterns that vary according to body site.^12,13

Dermoscopic features suggesting melanoma are atypical pigment networks, pseudopods, radial streaking, irregular dots or globules, blue-whitish veil, and granularity or peppering.¹⁴ Appropriate and effective use of dermoscopy requires training.^15,16 Available methods for learning dermoscopy include online and in-person courses, mentoring by experienced dermoscopists, books and articles, and free apps and online resources.¹⁷

Continue to: Perform a skin biopsy, but do this first

Skin biopsy is the definitive way to diagnose melanoma. Prior to biopsy, take photographs to document the exact location of the lesion and to ensure that the correct area is removed in wide excision (WE). A complete biopsy should include the full depth and breadth of the lesion to ensure there are clinically negative margins. This can be achieved with an elliptical excision (for larger lesions), punch excision (for small lesions), or saucerization (deep shave with 1- to 2-mm peripheral margins, used for intermediate-size lesions).¹⁸ Saucerization is distinctly different from a superficial shave biopsy, which is not recommended for lesions with features of melanoma.¹⁹

A decision to perform a biopsy on a part of the lesion (partial biopsy) depends on the size of the lesion and its anatomic location, and is best made in agreement with the patient. If the lesion cannot be removed in its entirety and a partial biopsy is necessary, take the sample from the most atypical appearing area and communicate this decision to the pathologist on the biopsy order. There is no evidence that performing a partial biopsy increases the risk of spreading melanoma.^20,21

If you are untrained or uncomfortable performing the biopsy, contact a dermatologist immediately. In many communities, such referrals are subject to long delays, which further supports the advisability of family physicians doing their own biopsies after photographing the suspicious lesion. Many resources are available to help family physicians learn to do biopsies proficiently (www.mdedge.com/familymedicine/article/164358/oncology/biopsies-skin-cancer-detection-dispelling-myths).¹⁹

What to communicate to the pathologist. At a minimum, the biopsy request form should include patient age, sex, biopsy type (punch, excisional, or scoop shave), intention (complete or partial sample), exact site of the biopsy with laterality, and clinical details. These details should include the lesion size and clinical description, the suspected diagnosis, and clinical information, such as whether there is a history of bleeding or changing color, size, or symmetry. In standard biopsy specimens, the pathologist is only examining a portion of the lesion. Communicating clearly to the pathologist may lead to a request for deeper or additional sections or special stains.

Complete biopsy of a concerning pigmented lesion is the standard. If, however, a partial biopsy is necessary, sample the most atypical area.

If the biopsy results do not match the clinical impression, a phone call to the pathologist is warranted. In addition, evaluation by a dermatopathologist may be merited as pathologic diagnosis of melanoma can be quite challenging. Newer molecular tests, such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), can assist in the histologic evaluation of complex pigmented lesions.

Continue to: CASE

CASE

You perform an elliptical excisional biopsy on your patient. The biopsy report comes back as a nodular malignant melanoma, Breslow depth 2.5 mm without ulceration, and no evidence of lymphovascular invasion or microsatellitosis. The report states that the biopsy margins appear clear of tumor involvement.

Further evaluation when the biopsy result is positive

Key steps in initial patient care include relaying pathology results to the patient, conducting (as needed) a more extensive evaluation, and obtaining appropriate consultation.

Clearly explain the diagnosis and convey an accurate reading of the pathology report. The vital pieces of information in the biopsy report are the Breslow depth and presence of ulceration, as evidence shows these 2 factors to be important independent predictors of outcome.^22,23 Also important are the presence of microsatellitosis (essential for staging purposes), pathologic stage, and the status of the peripheral and deep biopsy margins. Review Breslow depth with the patient as this largely dictates treatment options and prognosis.

Evaluate for possible metastatic disease. Obtain a complete history from every patient with cutaneous melanoma, looking for any positive review of systems as a harbinger of metastatic disease. A full-body skin and lymph node exam is vital, given that melanoma can arise anywhere including on the scalp, in the gluteal cleft, and beneath nails. If the lymph node exam is worrisome, conduct an ultrasound exam, even while referring to specialty care. Treating a patient with melanoma requires a multidisciplinary approach that may include dermatologists, surgeons, and oncologists based on the stage of disease. A challenge for family physicians is knowing which consultation to prioritize and how to counsel the patient to schedule these for the most cost-effective and timely evaluation.

Expedite a dermatology consultation. If the melanoma is deep or appears advanced based on size or palpable lymph nodes, contact the dermatologist immediately by phone to set up a rapid referral. Delays in the definitive management of thick melanomas can negatively affect outcome. Paper, facsimile, or electronic referrals can get lost in the system and are not reliable methods for referring patients for a melanoma consultation. One benefit of the family physician performing the initial biopsy is that a confirmed melanoma diagnosis will almost certainly get an expedited dermatology appointment.

Continue to: Wide excision and sentinel node biopsy

Wide excision and sentinel node biopsy

Wide excision of a primary melanoma is standard practice, with evidence favoring the following surgical margins: 0.5 to 1 cm for melanoma in situ, 1 cm for tumors up to 1 mm in thickness, 1 to 2 cm for tumors > 1 to 2 mm thick, and 2 cm for tumors > 2 mm thick.¹⁸ WE is often performed by dermatologists for nonulcerated tumors < 0.8 mm thick (T1a) without adverse features. If trained in cutaneous surgery, you can also choose to excise these thin melanomas in your office. Otherwise refer all patients with biopsy-proven melanoma to dermatologists to perform an adequate WE.

Refer patients who have tumors ≥ 0.8 mm thick to the appropriate surgical specialty (surgical oncology, if available) for consultation on sentinel lymph node biopsy. SLNB, when indicated, should be performed prior to WE of the primary tumor, and whenever possible in the same surgical setting, to maximize lymphatic drainage mapping techniques.¹⁸ Medical oncology referral, if needed, is usually made after WE.

SLNB remains the standard for lymph node staging. It is controversial mainly in its use for very thin or very thick lesions. Randomized controlled trials, including the Multicenter Selective Lymphadenectomy Trial,²⁴ have shown no difference in melanoma-­specific survival for patients with intermediate-thickness melanomas who had undergone SLNB.²⁴However, a subgroup analysis did find a significant increase in melanoma survival among patients with positive early SLNB results and immediate lymphadenectomy compared with patients who were observed and subsequently underwent lymphadenectomy only as metastases developed.²⁴

Many professional organizations consider SLNB to be the most significant prognostic indicator of disease recurrence. With a negative SLNB result, the risk of regional node recurrence is 5% or lower.^18,25 In addition, sentinel lymph node status is a critical determinant for systemic adjuvant therapy consideration and clinical trial eligibility. For patients who have primary cutaneous melanoma without clinical lymphadenopathy, an online tool is available for patients to use with their physician in predicting the likelihood of SLNB positivity.²⁶

Recommendations for SLNB, supported by multidisciplinary consensus:¹⁸

• Do not pursue SLNB for melanoma in situ or most cutaneous melanomas < 0.8 mm without ulceration (T1a). (See TABLE 1²⁷)
• Discuss SLNB with patients who have T1a melanoma and additional adverse features: young age, high mitotic rate, lymphovascular invasion, and nevus depth close to 0.8 mm with positive deep biopsy margins.
• Discuss SLNB with patients who have T1b disease (< 0.8 mm with ulceration, or 0.8-1 mm), although rates of SLNB positivity are low.
• Offer SLNB to patients with T2a and higher disease (> 1 mm).¹⁸

Continue to: Patients who have...

Patients who have clinical Stage I or II disease (TABLE 1²⁷) and a negative review of systems and lymph node exam do not require baseline laboratory or radiology tests.^18,28-31 Ultrasonography of the lymph node basin is recommended for any Stage I or II patient with an equivocal lymph node exam.^27,32 Stage III disease warrants computed tomography of the chest, abdomen, and pelvis, and possibly magnetic resonance imaging (MRI) of the brain. For Stage IV, brain MRI is recommended in all patients. Patients with higher risk disease (IIB - IV) will need consultation with Medical Oncology. The surgery and oncology team will make decisions regarding SLNB, genetic testing, and chemotherapy.

Melanoma in women: Considerations to keep in mind

Hormonal influences of pregnancy, lactation, contraception, and menopause introduce special considerations regarding melanoma, which is the most common cancer occurring during pregnancy, accounting for 31% of new malignancies.³³ Risk of melanoma lessens, however, for women who first give birth at a younger age or who have had > 5 live births.^18,34,35 There is no evidence that nevi darken during pregnancy, although nevi on the breast and abdomen may seem to enlarge due to skin stretching.¹⁸ All changing nevi in pregnancy warrant an examination, preferably with dermoscopy, and patients should be offered biopsy if there are any nevus characteristics associated with melanoma.¹⁸

One benefit of the family physician performing the initial biopsy is that a confirmed melanoma diagnosis will almost certainly get an expedited dermatology appointment.

The effect of pregnancy on an existing melanoma is not fully understood, but evidence from controlled studies shows no negative effect. Recent working group guidelines advise WE with local anesthesia without delay in pregnant patients.¹⁸ Definitive treatment after melanoma diagnosis should take a multidisciplinary approach involving obstetric care coordinated with Dermatology, Surgery, and Medical Oncology.¹⁸

Most recommendations on the timing of pregnancy following a melanoma diagnosis have limited evidence. One meta-­analysis concluded that pregnancy occurring after successful treatment of melanoma did not change a woman’s prognosis.³⁶ Current guidelines do not recommend delaying future pregnancy if a woman had an early-stage melanoma. For melanomas deemed higher risk, a woman could consider a 2- to 3-year delay in the next planned pregnancy, owing to current data on recurrence rates.¹⁸

A systematic review of women who used hormonal contraception or postmenopausal hormone replacement therapy (HRT) showed no associated increased risk of melanoma.³⁵ An additional randomized trial showed no effect of HRT on melanoma risk.³⁷

Continue to: Systemic melanoma treatment and common adverse effects

Multiple systemic therapies have been approved for the treatment of advanced or unresectable cutaneous melanomas. While these treatments are managed primarily by Oncology in concert with Dermatology, an awareness of the medications’ common dermatologic toxicities is important for the primary care provider. The 2 broad categories of FDA-approved systemic medications for advanced melanoma are mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors, each having its own set of adverse cutaneous effects.

MAPK pathway–targeting drugs include the B-Raf proto-oncogene serine/threonine-kinase inhibitors (BRAFIs) vemurafenib and dabrafenib, and the MAPK inhibitors (MEKIs) trametinib and cobimetinib. The most common adverse skin effects in MAPK pathway–targeting drugs are severe ultraviolet photosensitivity, cutaneous epidermal neoplasms (particularly squamous cell carcinoma, keratoacanthoma-type), thick actinic keratosis, wart-like keratosis, painful palmoplantar keratosis, and dry skin.³⁸ These effects are most commonly seen with BRAFI monotherapy and can be abated with the addition of a MEKI. MEKI therapy can cause acneiform eruptions and paronychia.³⁹ Additional adverse effects include diarrhea, pyrexia, arthralgias, and fatigue for BRAFIs and diarrhea, fatigue, and peripheral edema for MEKIs.⁴⁰

Immune checkpoint inhibitors include anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab and nivolumab), and anti-PDL-1 (atezolizumab). Adverse skin effects include morbilliform rash with or without an associated itch, itch with or without an associated rash, vitiligo, and lichenoid skin rashes. PD-1 and PDL-1 inhibitors have been associated with flares or unmasking of atopic dermatitis, psoriasis, sarcoidosis, and autoimmune bullous disease.¹⁸ Diarrhea, colitis, hepatitis, elevated liver enzymes, hypophysitis, and thyroiditis are some of the more common noncutaneous adverse effects reported with CTLA-4 inhibitors, while fatigue, diarrhea, nausea, pneumonitis, and thyroid disease are seen with anti-PD-1/PDL-1 therapy.³

A look at the prognosis

For patients diagnosed with primary cutaneous melanoma between 2011 and 2017, the 5-year survival rate for localized disease (Stages I-II) was 99%.¹ For regional (Stage III) and distant (Stage IV) disease, the 5-year survival rates were 68% and 30%, respectively.¹ With the advent of adjuvant systemic therapy, 5-year overall survival rates for metastatic melanoma have markedly improved from < 10% to up to 40% to 50%.⁴¹ The 3-year survival rate for patients with high tumor burden, brain metastasis, and elevated lactate dehydrogenase remains at < 10%.⁴² Relative survival decreases with increased age, although survival is higher in women than in men.⁴³ Risk of melanoma recurrence after surgical excision is high in patients with stage IIB, IIC, III and IV (resectable) disease. The most important risk factor for recurrence is primary tumor thickness.⁴⁴ The most common site of first recurrence in stage I-II disease is regional lymph node metastasis (42.8%), closely followed by distant metastasis (37.6%).⁴⁴

Long-term follow-up and surveillance

Recommendations for long-term care of patients with melanoma have evolved with advances in treatment, prognostication, and imaging. Caring for these patients requires a multidisciplinary approach wherein the family physician provides frontline care and team coordination. Since most recurrences are discovered by the patient or the patient’s family, patient education and self-examination are the cost-effective foundation for recurrence screening. In a trial of patients and partners, a 30-minute structured session on skin examination followed by physician reminders every 4 months increased the detection of melanoma recurrence without significant increases in patient visits.⁴⁵

Continue to: Patient education should include sun safety...

Patient education should include sun safety (wearing sun-protective clothing, using broad-spectrum sunscreen, and avoiding sun exposure during peak times of the day). The US Preventive Services Task Force (USPSTF) says the level of evidence is insufficient to support routine skin cancer screening in adults.⁴⁶ However, the USPSTF recommends discussing efforts to minimize UV radiation exposure to prevent skin cancer in fair-skinned individuals 10 to 24 years of age.

Current National Comprehensive Cancer Network (NCCN) guidelines have outlined the follow-up frequency for all melanoma patients. TABLE 2³² outlines those recommendations in addition to self-examination and patient education.

Melanoma epidemic or overdiagnosis?

Over the past 2 decades, a marked rise in the incidence of melanoma has been reported in developed countries worldwide, although melanoma mortality rates have not increased as rapidly, with melanoma-specific survival stable in most groups.^47-50 Due to conflicting evidence, significant disagreement exists as to whether this is an actual epidemic caused by a true rise in disease burden or is merely an artifact stemming from overdiagnosis.⁴⁷

Evidence supporting a true melanoma epidemic includes population-based studies demonstrating greater UV radiation–induced carcinogenesis (from the sun and tanning bed use), a larger aging population, and increased incidence regardless of socioeconomic status.⁴⁷ Those challenging the validity of an epidemic instead attribute the rising incidence to early-detection public awareness campaigns, expanded screenings, improved diagnostic modalities, and increased biopsies. They also credit lower pathologic thresholds that help identify thinner tumors with little to no metastatic potential.⁴⁸ Additionally, multiple studies report an increased incidence in melanomas of all histologic subtypes and thicknesses, not just thinner, more curable tumors.^49,51,52 Although increased screening and biopsies are effective, they alone cannot account for the sharp rise in melanoma cases.⁴⁷ This “melanoma paradox” of increasing incidence without a parallel increase in mortality remains unsettled.⁴⁷

CASE

Your patient had Stage IIA disease and a WE was performed with 1-cm margins. Ultrasound of the axilla identified an enlarged node, which was removed and found not to be diseased. He has now returned to have you look at another lesion identified by his spouse. His review of symptoms is negative. His initial melanoma was removed 2 years earlier, and his last dermatology skin exam was 5 months prior. You look at the lesion using a dermatoscope and do not note any worrisome features. You recommend that the patient photograph the area for reexamination and follow-up with his dermatologist next month for a 6-month follow-up.

CORRESPONDENCE
Jessica Servey, MD, 4301 Jones Bridge Road, Bethesda, MD 20814; [email protected]

CASE

A 48-year-old man comes to your clinic with a dark nevus on his right upper arm that appeared 2 months earlier. He says that the lesion has continued to grow and has bled (he thought because he initially picked at it). On exam, there is a 7-mm brown papule with 2 black dots and slightly asymmetric borders.

How would you proceed with this patient?

Melanoma is the fifth leading cause of new cancer cases annually, with > 96,000 new cases in 2019.¹ Overall, melanoma is more common in men and in Whites, with 48% diagnosed in people ages 55 to 74.¹ The past 2 decades have seen numerous developments in the diagnosis, treatment, and surveillance of melanoma. This article covers recommendations, controversies, and issues that require future study. It does not cover uveal or mucosal melanoma.

Evaluating a patient with a new or changing nevus

Known risk factors for melanoma include a changing nevus, indoor tanning, older age, many melanocytic nevi, history of a dysplastic nevus or of blistering sunburns during teen years, red or blonde hair, large congenital nevus, Fitzpatrick skin type I or II, high socioeconomic status, personal or family history of melanoma, and intermittent high-intensity sun exposure.^2-3 Presence of 1 or more of these risk factors should lower the threshold for biopsy.

Worrisome physical exam features (FIGURE) are nevus asymmetry, irregular borders, variegated color, and a diameter > 6 mm (the size of a pencil eraser). Inquire as to whether the nevus’ appearance has evolved and if it has bled without trauma. In a patient with multiple nevi, 1 nevus that looks different than the rest (the so-called “ugly duckling”) is concerning. Accuracy of diagnosis is enhanced with dermoscopy. A Cochrane review showed that skilled use of dermoscopy, in addition to inspection with the naked eye, considerably increases the sensitivity and specificity of diagnosing melanoma.⁴ Yet a 2017 study of 705 US primary care practitioners showed that only 8.3% of them used dermoscopy to evaluate pigmented lesions.⁵

Several published algorithms and checklists can aid clinicians in identifying lesions suggestive of melanoma—eg, ABCDE, CASH, Menzies method, “chaos and clues,” and 2-step and 3- and 7-point checklists.^6-10 A simple 3-step algorithm, the TADA (triage amalgamated dermoscopic algorithm) method is available to novice dermoscopy users.¹¹ Experts in pigmented lesions prefer to use pattern analysis, which requires simultaneously assessing multiple lesion patterns that vary according to body site.^12,13

Dermoscopic features suggesting melanoma are atypical pigment networks, pseudopods, radial streaking, irregular dots or globules, blue-whitish veil, and granularity or peppering.¹⁴ Appropriate and effective use of dermoscopy requires training.^15,16 Available methods for learning dermoscopy include online and in-person courses, mentoring by experienced dermoscopists, books and articles, and free apps and online resources.¹⁷

Continue to: Perform a skin biopsy, but do this first

Skin biopsy is the definitive way to diagnose melanoma. Prior to biopsy, take photographs to document the exact location of the lesion and to ensure that the correct area is removed in wide excision (WE). A complete biopsy should include the full depth and breadth of the lesion to ensure there are clinically negative margins. This can be achieved with an elliptical excision (for larger lesions), punch excision (for small lesions), or saucerization (deep shave with 1- to 2-mm peripheral margins, used for intermediate-size lesions).¹⁸ Saucerization is distinctly different from a superficial shave biopsy, which is not recommended for lesions with features of melanoma.¹⁹

A decision to perform a biopsy on a part of the lesion (partial biopsy) depends on the size of the lesion and its anatomic location, and is best made in agreement with the patient. If the lesion cannot be removed in its entirety and a partial biopsy is necessary, take the sample from the most atypical appearing area and communicate this decision to the pathologist on the biopsy order. There is no evidence that performing a partial biopsy increases the risk of spreading melanoma.^20,21

If you are untrained or uncomfortable performing the biopsy, contact a dermatologist immediately. In many communities, such referrals are subject to long delays, which further supports the advisability of family physicians doing their own biopsies after photographing the suspicious lesion. Many resources are available to help family physicians learn to do biopsies proficiently (www.mdedge.com/familymedicine/article/164358/oncology/biopsies-skin-cancer-detection-dispelling-myths).¹⁹

What to communicate to the pathologist. At a minimum, the biopsy request form should include patient age, sex, biopsy type (punch, excisional, or scoop shave), intention (complete or partial sample), exact site of the biopsy with laterality, and clinical details. These details should include the lesion size and clinical description, the suspected diagnosis, and clinical information, such as whether there is a history of bleeding or changing color, size, or symmetry. In standard biopsy specimens, the pathologist is only examining a portion of the lesion. Communicating clearly to the pathologist may lead to a request for deeper or additional sections or special stains.

Complete biopsy of a concerning pigmented lesion is the standard. If, however, a partial biopsy is necessary, sample the most atypical area.

If the biopsy results do not match the clinical impression, a phone call to the pathologist is warranted. In addition, evaluation by a dermatopathologist may be merited as pathologic diagnosis of melanoma can be quite challenging. Newer molecular tests, such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), can assist in the histologic evaluation of complex pigmented lesions.

Continue to: CASE

CASE

You perform an elliptical excisional biopsy on your patient. The biopsy report comes back as a nodular malignant melanoma, Breslow depth 2.5 mm without ulceration, and no evidence of lymphovascular invasion or microsatellitosis. The report states that the biopsy margins appear clear of tumor involvement.

Further evaluation when the biopsy result is positive

Key steps in initial patient care include relaying pathology results to the patient, conducting (as needed) a more extensive evaluation, and obtaining appropriate consultation.

Clearly explain the diagnosis and convey an accurate reading of the pathology report. The vital pieces of information in the biopsy report are the Breslow depth and presence of ulceration, as evidence shows these 2 factors to be important independent predictors of outcome.^22,23 Also important are the presence of microsatellitosis (essential for staging purposes), pathologic stage, and the status of the peripheral and deep biopsy margins. Review Breslow depth with the patient as this largely dictates treatment options and prognosis.

Evaluate for possible metastatic disease. Obtain a complete history from every patient with cutaneous melanoma, looking for any positive review of systems as a harbinger of metastatic disease. A full-body skin and lymph node exam is vital, given that melanoma can arise anywhere including on the scalp, in the gluteal cleft, and beneath nails. If the lymph node exam is worrisome, conduct an ultrasound exam, even while referring to specialty care. Treating a patient with melanoma requires a multidisciplinary approach that may include dermatologists, surgeons, and oncologists based on the stage of disease. A challenge for family physicians is knowing which consultation to prioritize and how to counsel the patient to schedule these for the most cost-effective and timely evaluation.

Expedite a dermatology consultation. If the melanoma is deep or appears advanced based on size or palpable lymph nodes, contact the dermatologist immediately by phone to set up a rapid referral. Delays in the definitive management of thick melanomas can negatively affect outcome. Paper, facsimile, or electronic referrals can get lost in the system and are not reliable methods for referring patients for a melanoma consultation. One benefit of the family physician performing the initial biopsy is that a confirmed melanoma diagnosis will almost certainly get an expedited dermatology appointment.

Continue to: Wide excision and sentinel node biopsy

Wide excision and sentinel node biopsy

Wide excision of a primary melanoma is standard practice, with evidence favoring the following surgical margins: 0.5 to 1 cm for melanoma in situ, 1 cm for tumors up to 1 mm in thickness, 1 to 2 cm for tumors > 1 to 2 mm thick, and 2 cm for tumors > 2 mm thick.¹⁸ WE is often performed by dermatologists for nonulcerated tumors < 0.8 mm thick (T1a) without adverse features. If trained in cutaneous surgery, you can also choose to excise these thin melanomas in your office. Otherwise refer all patients with biopsy-proven melanoma to dermatologists to perform an adequate WE.

Refer patients who have tumors ≥ 0.8 mm thick to the appropriate surgical specialty (surgical oncology, if available) for consultation on sentinel lymph node biopsy. SLNB, when indicated, should be performed prior to WE of the primary tumor, and whenever possible in the same surgical setting, to maximize lymphatic drainage mapping techniques.¹⁸ Medical oncology referral, if needed, is usually made after WE.

SLNB remains the standard for lymph node staging. It is controversial mainly in its use for very thin or very thick lesions. Randomized controlled trials, including the Multicenter Selective Lymphadenectomy Trial,²⁴ have shown no difference in melanoma-­specific survival for patients with intermediate-thickness melanomas who had undergone SLNB.²⁴However, a subgroup analysis did find a significant increase in melanoma survival among patients with positive early SLNB results and immediate lymphadenectomy compared with patients who were observed and subsequently underwent lymphadenectomy only as metastases developed.²⁴

Many professional organizations consider SLNB to be the most significant prognostic indicator of disease recurrence. With a negative SLNB result, the risk of regional node recurrence is 5% or lower.^18,25 In addition, sentinel lymph node status is a critical determinant for systemic adjuvant therapy consideration and clinical trial eligibility. For patients who have primary cutaneous melanoma without clinical lymphadenopathy, an online tool is available for patients to use with their physician in predicting the likelihood of SLNB positivity.²⁶

Recommendations for SLNB, supported by multidisciplinary consensus:¹⁸

• Do not pursue SLNB for melanoma in situ or most cutaneous melanomas < 0.8 mm without ulceration (T1a). (See TABLE 1²⁷)
• Discuss SLNB with patients who have T1a melanoma and additional adverse features: young age, high mitotic rate, lymphovascular invasion, and nevus depth close to 0.8 mm with positive deep biopsy margins.
• Discuss SLNB with patients who have T1b disease (< 0.8 mm with ulceration, or 0.8-1 mm), although rates of SLNB positivity are low.
• Offer SLNB to patients with T2a and higher disease (> 1 mm).¹⁸

Continue to: Patients who have...

Patients who have clinical Stage I or II disease (TABLE 1²⁷) and a negative review of systems and lymph node exam do not require baseline laboratory or radiology tests.^18,28-31 Ultrasonography of the lymph node basin is recommended for any Stage I or II patient with an equivocal lymph node exam.^27,32 Stage III disease warrants computed tomography of the chest, abdomen, and pelvis, and possibly magnetic resonance imaging (MRI) of the brain. For Stage IV, brain MRI is recommended in all patients. Patients with higher risk disease (IIB - IV) will need consultation with Medical Oncology. The surgery and oncology team will make decisions regarding SLNB, genetic testing, and chemotherapy.

Melanoma in women: Considerations to keep in mind

Hormonal influences of pregnancy, lactation, contraception, and menopause introduce special considerations regarding melanoma, which is the most common cancer occurring during pregnancy, accounting for 31% of new malignancies.³³ Risk of melanoma lessens, however, for women who first give birth at a younger age or who have had > 5 live births.^18,34,35 There is no evidence that nevi darken during pregnancy, although nevi on the breast and abdomen may seem to enlarge due to skin stretching.¹⁸ All changing nevi in pregnancy warrant an examination, preferably with dermoscopy, and patients should be offered biopsy if there are any nevus characteristics associated with melanoma.¹⁸

One benefit of the family physician performing the initial biopsy is that a confirmed melanoma diagnosis will almost certainly get an expedited dermatology appointment.

The effect of pregnancy on an existing melanoma is not fully understood, but evidence from controlled studies shows no negative effect. Recent working group guidelines advise WE with local anesthesia without delay in pregnant patients.¹⁸ Definitive treatment after melanoma diagnosis should take a multidisciplinary approach involving obstetric care coordinated with Dermatology, Surgery, and Medical Oncology.¹⁸

Most recommendations on the timing of pregnancy following a melanoma diagnosis have limited evidence. One meta-­analysis concluded that pregnancy occurring after successful treatment of melanoma did not change a woman’s prognosis.³⁶ Current guidelines do not recommend delaying future pregnancy if a woman had an early-stage melanoma. For melanomas deemed higher risk, a woman could consider a 2- to 3-year delay in the next planned pregnancy, owing to current data on recurrence rates.¹⁸

A systematic review of women who used hormonal contraception or postmenopausal hormone replacement therapy (HRT) showed no associated increased risk of melanoma.³⁵ An additional randomized trial showed no effect of HRT on melanoma risk.³⁷

Continue to: Systemic melanoma treatment and common adverse effects

Multiple systemic therapies have been approved for the treatment of advanced or unresectable cutaneous melanomas. While these treatments are managed primarily by Oncology in concert with Dermatology, an awareness of the medications’ common dermatologic toxicities is important for the primary care provider. The 2 broad categories of FDA-approved systemic medications for advanced melanoma are mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors, each having its own set of adverse cutaneous effects.

MAPK pathway–targeting drugs include the B-Raf proto-oncogene serine/threonine-kinase inhibitors (BRAFIs) vemurafenib and dabrafenib, and the MAPK inhibitors (MEKIs) trametinib and cobimetinib. The most common adverse skin effects in MAPK pathway–targeting drugs are severe ultraviolet photosensitivity, cutaneous epidermal neoplasms (particularly squamous cell carcinoma, keratoacanthoma-type), thick actinic keratosis, wart-like keratosis, painful palmoplantar keratosis, and dry skin.³⁸ These effects are most commonly seen with BRAFI monotherapy and can be abated with the addition of a MEKI. MEKI therapy can cause acneiform eruptions and paronychia.³⁹ Additional adverse effects include diarrhea, pyrexia, arthralgias, and fatigue for BRAFIs and diarrhea, fatigue, and peripheral edema for MEKIs.⁴⁰

Immune checkpoint inhibitors include anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab and nivolumab), and anti-PDL-1 (atezolizumab). Adverse skin effects include morbilliform rash with or without an associated itch, itch with or without an associated rash, vitiligo, and lichenoid skin rashes. PD-1 and PDL-1 inhibitors have been associated with flares or unmasking of atopic dermatitis, psoriasis, sarcoidosis, and autoimmune bullous disease.¹⁸ Diarrhea, colitis, hepatitis, elevated liver enzymes, hypophysitis, and thyroiditis are some of the more common noncutaneous adverse effects reported with CTLA-4 inhibitors, while fatigue, diarrhea, nausea, pneumonitis, and thyroid disease are seen with anti-PD-1/PDL-1 therapy.³

A look at the prognosis

For patients diagnosed with primary cutaneous melanoma between 2011 and 2017, the 5-year survival rate for localized disease (Stages I-II) was 99%.¹ For regional (Stage III) and distant (Stage IV) disease, the 5-year survival rates were 68% and 30%, respectively.¹ With the advent of adjuvant systemic therapy, 5-year overall survival rates for metastatic melanoma have markedly improved from < 10% to up to 40% to 50%.⁴¹ The 3-year survival rate for patients with high tumor burden, brain metastasis, and elevated lactate dehydrogenase remains at < 10%.⁴² Relative survival decreases with increased age, although survival is higher in women than in men.⁴³ Risk of melanoma recurrence after surgical excision is high in patients with stage IIB, IIC, III and IV (resectable) disease. The most important risk factor for recurrence is primary tumor thickness.⁴⁴ The most common site of first recurrence in stage I-II disease is regional lymph node metastasis (42.8%), closely followed by distant metastasis (37.6%).⁴⁴

Long-term follow-up and surveillance

Recommendations for long-term care of patients with melanoma have evolved with advances in treatment, prognostication, and imaging. Caring for these patients requires a multidisciplinary approach wherein the family physician provides frontline care and team coordination. Since most recurrences are discovered by the patient or the patient’s family, patient education and self-examination are the cost-effective foundation for recurrence screening. In a trial of patients and partners, a 30-minute structured session on skin examination followed by physician reminders every 4 months increased the detection of melanoma recurrence without significant increases in patient visits.⁴⁵

Continue to: Patient education should include sun safety...

Patient education should include sun safety (wearing sun-protective clothing, using broad-spectrum sunscreen, and avoiding sun exposure during peak times of the day). The US Preventive Services Task Force (USPSTF) says the level of evidence is insufficient to support routine skin cancer screening in adults.⁴⁶ However, the USPSTF recommends discussing efforts to minimize UV radiation exposure to prevent skin cancer in fair-skinned individuals 10 to 24 years of age.

Current National Comprehensive Cancer Network (NCCN) guidelines have outlined the follow-up frequency for all melanoma patients. TABLE 2³² outlines those recommendations in addition to self-examination and patient education.

Melanoma epidemic or overdiagnosis?

Over the past 2 decades, a marked rise in the incidence of melanoma has been reported in developed countries worldwide, although melanoma mortality rates have not increased as rapidly, with melanoma-specific survival stable in most groups.^47-50 Due to conflicting evidence, significant disagreement exists as to whether this is an actual epidemic caused by a true rise in disease burden or is merely an artifact stemming from overdiagnosis.⁴⁷

Evidence supporting a true melanoma epidemic includes population-based studies demonstrating greater UV radiation–induced carcinogenesis (from the sun and tanning bed use), a larger aging population, and increased incidence regardless of socioeconomic status.⁴⁷ Those challenging the validity of an epidemic instead attribute the rising incidence to early-detection public awareness campaigns, expanded screenings, improved diagnostic modalities, and increased biopsies. They also credit lower pathologic thresholds that help identify thinner tumors with little to no metastatic potential.⁴⁸ Additionally, multiple studies report an increased incidence in melanomas of all histologic subtypes and thicknesses, not just thinner, more curable tumors.^49,51,52 Although increased screening and biopsies are effective, they alone cannot account for the sharp rise in melanoma cases.⁴⁷ This “melanoma paradox” of increasing incidence without a parallel increase in mortality remains unsettled.⁴⁷

CASE

Your patient had Stage IIA disease and a WE was performed with 1-cm margins. Ultrasound of the axilla identified an enlarged node, which was removed and found not to be diseased. He has now returned to have you look at another lesion identified by his spouse. His review of symptoms is negative. His initial melanoma was removed 2 years earlier, and his last dermatology skin exam was 5 months prior. You look at the lesion using a dermatoscope and do not note any worrisome features. You recommend that the patient photograph the area for reexamination and follow-up with his dermatologist next month for a 6-month follow-up.

CORRESPONDENCE
Jessica Servey, MD, 4301 Jones Bridge Road, Bethesda, MD 20814; [email protected]

CASE

A 48-year-old man comes to your clinic with a dark nevus on his right upper arm that appeared 2 months earlier. He says that the lesion has continued to grow and has bled (he thought because he initially picked at it). On exam, there is a 7-mm brown papule with 2 black dots and slightly asymmetric borders.

How would you proceed with this patient?

Melanoma is the fifth leading cause of new cancer cases annually, with > 96,000 new cases in 2019.¹ Overall, melanoma is more common in men and in Whites, with 48% diagnosed in people ages 55 to 74.¹ The past 2 decades have seen numerous developments in the diagnosis, treatment, and surveillance of melanoma. This article covers recommendations, controversies, and issues that require future study. It does not cover uveal or mucosal melanoma.

Evaluating a patient with a new or changing nevus

Known risk factors for melanoma include a changing nevus, indoor tanning, older age, many melanocytic nevi, history of a dysplastic nevus or of blistering sunburns during teen years, red or blonde hair, large congenital nevus, Fitzpatrick skin type I or II, high socioeconomic status, personal or family history of melanoma, and intermittent high-intensity sun exposure.^2-3 Presence of 1 or more of these risk factors should lower the threshold for biopsy.

Worrisome physical exam features (FIGURE) are nevus asymmetry, irregular borders, variegated color, and a diameter > 6 mm (the size of a pencil eraser). Inquire as to whether the nevus’ appearance has evolved and if it has bled without trauma. In a patient with multiple nevi, 1 nevus that looks different than the rest (the so-called “ugly duckling”) is concerning. Accuracy of diagnosis is enhanced with dermoscopy. A Cochrane review showed that skilled use of dermoscopy, in addition to inspection with the naked eye, considerably increases the sensitivity and specificity of diagnosing melanoma.⁴ Yet a 2017 study of 705 US primary care practitioners showed that only 8.3% of them used dermoscopy to evaluate pigmented lesions.⁵

Several published algorithms and checklists can aid clinicians in identifying lesions suggestive of melanoma—eg, ABCDE, CASH, Menzies method, “chaos and clues,” and 2-step and 3- and 7-point checklists.^6-10 A simple 3-step algorithm, the TADA (triage amalgamated dermoscopic algorithm) method is available to novice dermoscopy users.¹¹ Experts in pigmented lesions prefer to use pattern analysis, which requires simultaneously assessing multiple lesion patterns that vary according to body site.^12,13

Dermoscopic features suggesting melanoma are atypical pigment networks, pseudopods, radial streaking, irregular dots or globules, blue-whitish veil, and granularity or peppering.¹⁴ Appropriate and effective use of dermoscopy requires training.^15,16 Available methods for learning dermoscopy include online and in-person courses, mentoring by experienced dermoscopists, books and articles, and free apps and online resources.¹⁷

Continue to: Perform a skin biopsy, but do this first

Skin biopsy is the definitive way to diagnose melanoma. Prior to biopsy, take photographs to document the exact location of the lesion and to ensure that the correct area is removed in wide excision (WE). A complete biopsy should include the full depth and breadth of the lesion to ensure there are clinically negative margins. This can be achieved with an elliptical excision (for larger lesions), punch excision (for small lesions), or saucerization (deep shave with 1- to 2-mm peripheral margins, used for intermediate-size lesions).¹⁸ Saucerization is distinctly different from a superficial shave biopsy, which is not recommended for lesions with features of melanoma.¹⁹

A decision to perform a biopsy on a part of the lesion (partial biopsy) depends on the size of the lesion and its anatomic location, and is best made in agreement with the patient. If the lesion cannot be removed in its entirety and a partial biopsy is necessary, take the sample from the most atypical appearing area and communicate this decision to the pathologist on the biopsy order. There is no evidence that performing a partial biopsy increases the risk of spreading melanoma.^20,21

If you are untrained or uncomfortable performing the biopsy, contact a dermatologist immediately. In many communities, such referrals are subject to long delays, which further supports the advisability of family physicians doing their own biopsies after photographing the suspicious lesion. Many resources are available to help family physicians learn to do biopsies proficiently (www.mdedge.com/familymedicine/article/164358/oncology/biopsies-skin-cancer-detection-dispelling-myths).¹⁹

What to communicate to the pathologist. At a minimum, the biopsy request form should include patient age, sex, biopsy type (punch, excisional, or scoop shave), intention (complete or partial sample), exact site of the biopsy with laterality, and clinical details. These details should include the lesion size and clinical description, the suspected diagnosis, and clinical information, such as whether there is a history of bleeding or changing color, size, or symmetry. In standard biopsy specimens, the pathologist is only examining a portion of the lesion. Communicating clearly to the pathologist may lead to a request for deeper or additional sections or special stains.

Complete biopsy of a concerning pigmented lesion is the standard. If, however, a partial biopsy is necessary, sample the most atypical area.

If the biopsy results do not match the clinical impression, a phone call to the pathologist is warranted. In addition, evaluation by a dermatopathologist may be merited as pathologic diagnosis of melanoma can be quite challenging. Newer molecular tests, such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), can assist in the histologic evaluation of complex pigmented lesions.

Continue to: CASE

CASE

You perform an elliptical excisional biopsy on your patient. The biopsy report comes back as a nodular malignant melanoma, Breslow depth 2.5 mm without ulceration, and no evidence of lymphovascular invasion or microsatellitosis. The report states that the biopsy margins appear clear of tumor involvement.

Further evaluation when the biopsy result is positive

Key steps in initial patient care include relaying pathology results to the patient, conducting (as needed) a more extensive evaluation, and obtaining appropriate consultation.

Clearly explain the diagnosis and convey an accurate reading of the pathology report. The vital pieces of information in the biopsy report are the Breslow depth and presence of ulceration, as evidence shows these 2 factors to be important independent predictors of outcome.^22,23 Also important are the presence of microsatellitosis (essential for staging purposes), pathologic stage, and the status of the peripheral and deep biopsy margins. Review Breslow depth with the patient as this largely dictates treatment options and prognosis.

Evaluate for possible metastatic disease. Obtain a complete history from every patient with cutaneous melanoma, looking for any positive review of systems as a harbinger of metastatic disease. A full-body skin and lymph node exam is vital, given that melanoma can arise anywhere including on the scalp, in the gluteal cleft, and beneath nails. If the lymph node exam is worrisome, conduct an ultrasound exam, even while referring to specialty care. Treating a patient with melanoma requires a multidisciplinary approach that may include dermatologists, surgeons, and oncologists based on the stage of disease. A challenge for family physicians is knowing which consultation to prioritize and how to counsel the patient to schedule these for the most cost-effective and timely evaluation.

Expedite a dermatology consultation. If the melanoma is deep or appears advanced based on size or palpable lymph nodes, contact the dermatologist immediately by phone to set up a rapid referral. Delays in the definitive management of thick melanomas can negatively affect outcome. Paper, facsimile, or electronic referrals can get lost in the system and are not reliable methods for referring patients for a melanoma consultation. One benefit of the family physician performing the initial biopsy is that a confirmed melanoma diagnosis will almost certainly get an expedited dermatology appointment.

Continue to: Wide excision and sentinel node biopsy

Wide excision and sentinel node biopsy

Wide excision of a primary melanoma is standard practice, with evidence favoring the following surgical margins: 0.5 to 1 cm for melanoma in situ, 1 cm for tumors up to 1 mm in thickness, 1 to 2 cm for tumors > 1 to 2 mm thick, and 2 cm for tumors > 2 mm thick.¹⁸ WE is often performed by dermatologists for nonulcerated tumors < 0.8 mm thick (T1a) without adverse features. If trained in cutaneous surgery, you can also choose to excise these thin melanomas in your office. Otherwise refer all patients with biopsy-proven melanoma to dermatologists to perform an adequate WE.

Refer patients who have tumors ≥ 0.8 mm thick to the appropriate surgical specialty (surgical oncology, if available) for consultation on sentinel lymph node biopsy. SLNB, when indicated, should be performed prior to WE of the primary tumor, and whenever possible in the same surgical setting, to maximize lymphatic drainage mapping techniques.¹⁸ Medical oncology referral, if needed, is usually made after WE.

SLNB remains the standard for lymph node staging. It is controversial mainly in its use for very thin or very thick lesions. Randomized controlled trials, including the Multicenter Selective Lymphadenectomy Trial,²⁴ have shown no difference in melanoma-­specific survival for patients with intermediate-thickness melanomas who had undergone SLNB.²⁴However, a subgroup analysis did find a significant increase in melanoma survival among patients with positive early SLNB results and immediate lymphadenectomy compared with patients who were observed and subsequently underwent lymphadenectomy only as metastases developed.²⁴

Many professional organizations consider SLNB to be the most significant prognostic indicator of disease recurrence. With a negative SLNB result, the risk of regional node recurrence is 5% or lower.^18,25 In addition, sentinel lymph node status is a critical determinant for systemic adjuvant therapy consideration and clinical trial eligibility. For patients who have primary cutaneous melanoma without clinical lymphadenopathy, an online tool is available for patients to use with their physician in predicting the likelihood of SLNB positivity.²⁶

Recommendations for SLNB, supported by multidisciplinary consensus:¹⁸

• Do not pursue SLNB for melanoma in situ or most cutaneous melanomas < 0.8 mm without ulceration (T1a). (See TABLE 1²⁷)
• Discuss SLNB with patients who have T1a melanoma and additional adverse features: young age, high mitotic rate, lymphovascular invasion, and nevus depth close to 0.8 mm with positive deep biopsy margins.
• Discuss SLNB with patients who have T1b disease (< 0.8 mm with ulceration, or 0.8-1 mm), although rates of SLNB positivity are low.
• Offer SLNB to patients with T2a and higher disease (> 1 mm).¹⁸

Continue to: Patients who have...

Patients who have clinical Stage I or II disease (TABLE 1²⁷) and a negative review of systems and lymph node exam do not require baseline laboratory or radiology tests.^18,28-31 Ultrasonography of the lymph node basin is recommended for any Stage I or II patient with an equivocal lymph node exam.^27,32 Stage III disease warrants computed tomography of the chest, abdomen, and pelvis, and possibly magnetic resonance imaging (MRI) of the brain. For Stage IV, brain MRI is recommended in all patients. Patients with higher risk disease (IIB - IV) will need consultation with Medical Oncology. The surgery and oncology team will make decisions regarding SLNB, genetic testing, and chemotherapy.

Melanoma in women: Considerations to keep in mind

Hormonal influences of pregnancy, lactation, contraception, and menopause introduce special considerations regarding melanoma, which is the most common cancer occurring during pregnancy, accounting for 31% of new malignancies.³³ Risk of melanoma lessens, however, for women who first give birth at a younger age or who have had > 5 live births.^18,34,35 There is no evidence that nevi darken during pregnancy, although nevi on the breast and abdomen may seem to enlarge due to skin stretching.¹⁸ All changing nevi in pregnancy warrant an examination, preferably with dermoscopy, and patients should be offered biopsy if there are any nevus characteristics associated with melanoma.¹⁸

One benefit of the family physician performing the initial biopsy is that a confirmed melanoma diagnosis will almost certainly get an expedited dermatology appointment.

The effect of pregnancy on an existing melanoma is not fully understood, but evidence from controlled studies shows no negative effect. Recent working group guidelines advise WE with local anesthesia without delay in pregnant patients.¹⁸ Definitive treatment after melanoma diagnosis should take a multidisciplinary approach involving obstetric care coordinated with Dermatology, Surgery, and Medical Oncology.¹⁸

Most recommendations on the timing of pregnancy following a melanoma diagnosis have limited evidence. One meta-­analysis concluded that pregnancy occurring after successful treatment of melanoma did not change a woman’s prognosis.³⁶ Current guidelines do not recommend delaying future pregnancy if a woman had an early-stage melanoma. For melanomas deemed higher risk, a woman could consider a 2- to 3-year delay in the next planned pregnancy, owing to current data on recurrence rates.¹⁸

A systematic review of women who used hormonal contraception or postmenopausal hormone replacement therapy (HRT) showed no associated increased risk of melanoma.³⁵ An additional randomized trial showed no effect of HRT on melanoma risk.³⁷

Continue to: Systemic melanoma treatment and common adverse effects

Multiple systemic therapies have been approved for the treatment of advanced or unresectable cutaneous melanomas. While these treatments are managed primarily by Oncology in concert with Dermatology, an awareness of the medications’ common dermatologic toxicities is important for the primary care provider. The 2 broad categories of FDA-approved systemic medications for advanced melanoma are mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors, each having its own set of adverse cutaneous effects.

MAPK pathway–targeting drugs include the B-Raf proto-oncogene serine/threonine-kinase inhibitors (BRAFIs) vemurafenib and dabrafenib, and the MAPK inhibitors (MEKIs) trametinib and cobimetinib. The most common adverse skin effects in MAPK pathway–targeting drugs are severe ultraviolet photosensitivity, cutaneous epidermal neoplasms (particularly squamous cell carcinoma, keratoacanthoma-type), thick actinic keratosis, wart-like keratosis, painful palmoplantar keratosis, and dry skin.³⁸ These effects are most commonly seen with BRAFI monotherapy and can be abated with the addition of a MEKI. MEKI therapy can cause acneiform eruptions and paronychia.³⁹ Additional adverse effects include diarrhea, pyrexia, arthralgias, and fatigue for BRAFIs and diarrhea, fatigue, and peripheral edema for MEKIs.⁴⁰

Immune checkpoint inhibitors include anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab and nivolumab), and anti-PDL-1 (atezolizumab). Adverse skin effects include morbilliform rash with or without an associated itch, itch with or without an associated rash, vitiligo, and lichenoid skin rashes. PD-1 and PDL-1 inhibitors have been associated with flares or unmasking of atopic dermatitis, psoriasis, sarcoidosis, and autoimmune bullous disease.¹⁸ Diarrhea, colitis, hepatitis, elevated liver enzymes, hypophysitis, and thyroiditis are some of the more common noncutaneous adverse effects reported with CTLA-4 inhibitors, while fatigue, diarrhea, nausea, pneumonitis, and thyroid disease are seen with anti-PD-1/PDL-1 therapy.³

A look at the prognosis

For patients diagnosed with primary cutaneous melanoma between 2011 and 2017, the 5-year survival rate for localized disease (Stages I-II) was 99%.¹ For regional (Stage III) and distant (Stage IV) disease, the 5-year survival rates were 68% and 30%, respectively.¹ With the advent of adjuvant systemic therapy, 5-year overall survival rates for metastatic melanoma have markedly improved from < 10% to up to 40% to 50%.⁴¹ The 3-year survival rate for patients with high tumor burden, brain metastasis, and elevated lactate dehydrogenase remains at < 10%.⁴² Relative survival decreases with increased age, although survival is higher in women than in men.⁴³ Risk of melanoma recurrence after surgical excision is high in patients with stage IIB, IIC, III and IV (resectable) disease. The most important risk factor for recurrence is primary tumor thickness.⁴⁴ The most common site of first recurrence in stage I-II disease is regional lymph node metastasis (42.8%), closely followed by distant metastasis (37.6%).⁴⁴

Long-term follow-up and surveillance

Recommendations for long-term care of patients with melanoma have evolved with advances in treatment, prognostication, and imaging. Caring for these patients requires a multidisciplinary approach wherein the family physician provides frontline care and team coordination. Since most recurrences are discovered by the patient or the patient’s family, patient education and self-examination are the cost-effective foundation for recurrence screening. In a trial of patients and partners, a 30-minute structured session on skin examination followed by physician reminders every 4 months increased the detection of melanoma recurrence without significant increases in patient visits.⁴⁵

Continue to: Patient education should include sun safety...

Patient education should include sun safety (wearing sun-protective clothing, using broad-spectrum sunscreen, and avoiding sun exposure during peak times of the day). The US Preventive Services Task Force (USPSTF) says the level of evidence is insufficient to support routine skin cancer screening in adults.⁴⁶ However, the USPSTF recommends discussing efforts to minimize UV radiation exposure to prevent skin cancer in fair-skinned individuals 10 to 24 years of age.

Current National Comprehensive Cancer Network (NCCN) guidelines have outlined the follow-up frequency for all melanoma patients. TABLE 2³² outlines those recommendations in addition to self-examination and patient education.

Melanoma epidemic or overdiagnosis?

Over the past 2 decades, a marked rise in the incidence of melanoma has been reported in developed countries worldwide, although melanoma mortality rates have not increased as rapidly, with melanoma-specific survival stable in most groups.^47-50 Due to conflicting evidence, significant disagreement exists as to whether this is an actual epidemic caused by a true rise in disease burden or is merely an artifact stemming from overdiagnosis.⁴⁷

Evidence supporting a true melanoma epidemic includes population-based studies demonstrating greater UV radiation–induced carcinogenesis (from the sun and tanning bed use), a larger aging population, and increased incidence regardless of socioeconomic status.⁴⁷ Those challenging the validity of an epidemic instead attribute the rising incidence to early-detection public awareness campaigns, expanded screenings, improved diagnostic modalities, and increased biopsies. They also credit lower pathologic thresholds that help identify thinner tumors with little to no metastatic potential.⁴⁸ Additionally, multiple studies report an increased incidence in melanomas of all histologic subtypes and thicknesses, not just thinner, more curable tumors.^49,51,52 Although increased screening and biopsies are effective, they alone cannot account for the sharp rise in melanoma cases.⁴⁷ This “melanoma paradox” of increasing incidence without a parallel increase in mortality remains unsettled.⁴⁷

CASE

Your patient had Stage IIA disease and a WE was performed with 1-cm margins. Ultrasound of the axilla identified an enlarged node, which was removed and found not to be diseased. He has now returned to have you look at another lesion identified by his spouse. His review of symptoms is negative. His initial melanoma was removed 2 years earlier, and his last dermatology skin exam was 5 months prior. You look at the lesion using a dermatoscope and do not note any worrisome features. You recommend that the patient photograph the area for reexamination and follow-up with his dermatologist next month for a 6-month follow-up.

CORRESPONDENCE
Jessica Servey, MD, 4301 Jones Bridge Road, Bethesda, MD 20814; [email protected]

Some adults who have an intellectual or other developmental disability (IDD) require extensive subspecialty care; many, however, depend primarily on their family physician for the bulk of their health care. With that reliance in mind, this article provides (1) an overview of important services that family physicians can provide for their adult patients with IDD and (2) pragmatic clinical suggestions for tailoring that care. Note: We highlight only some high-impact areas of clinical focus; refer to the 2018 Canadian consensus guidelines for a comprehensive approach to optimizing primary care for this population.¹

CASE

Laura S, a 24-year-old woman with Down syndrome, is visiting your clinic with her mother to establish care. Ms. S has several medical comorbidities, including type 2 diabetes, hyperlipidemia, repaired congenital heart disease, schizoaffective disorder, and hypothyroidism. She is under the care of multiple specialists, including a cardiologist and an endocrinologist. Her medications include the atypical antipsychotic risperidone, which was prescribed for her through the services of a community mental health center.

Ms. S is due for multiple preventive health screenings. She indicates that she feels nervous today talking about these screenings with a new physician.

First step in care: Proficiency in the lexicon of IDD

Three core concepts of IDD are impairment, disability, and handicap. According to the World Health Organization²:

• impairment “is any loss or abnormality of psychological, physiological, or anatomical structure or function.”
• disability “is any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.”
• handicap therefore “represents socialization of an impairment or disability, and as such it reflects the consequences for the individual—cultural, social, economic, and environmental—that stem from the presence of impairment and disability.”

Essential transition: Pediatric to adult health care

Health care transition (HCT) is the planned process of transferring care from a pediatric to an adult-based health care setting,³ comprising 3 phases:

• preparation
• transfer from pediatric to adult care
• integration into adult-based care.

Two critical components of a smooth HCT include initiating the transition early in adolescence and providing transition-support resources, which are often lacking, even in large, integrated health systems.⁴ Got Transition, created by the National Alliance to Advance Adolescent Health, outlines core elements of an organized HCT process (www.gottransition.org) specific to young adults with IDD, including young adults with autism spectrum disorder.^5,6 

Even young people who are served by a family physician and who intend to remain in that family practice as they age into adulthood require HCT services that include⁶:

• assessment of readiness to transition to adult care
• update of the medical history
• assessment and promotion of self-care skills
• consent discussions and optimized participation in decision-making
• transition of specialty care from pediatric to adult specialists.

Continue to: For an ideal HCT...

For an ideal health care transition, full engagement of the patient, the medical home, and the patient’s family (including the primary caregiver or guardian) is critical.

For an ideal HCT, full engagement of the patient, the medical home (physicians, nursing staff, and care coordinators), and the patient’s family (including the primary caregiver or guardian) is critical. In addition to preventive care visits and management of chronic disease, additional domains that require explicit attention in transitioning young people with IDD include health insurance, transportation, employment, and postsecondary education.

Young people who have special health care needs and receive high-quality HCT demonstrate improvements in adherence to care, disease-specific measures, quality of life, self-care skills, satisfaction with care, and health care utilization.⁷TABLE 1³ lists resources identified by Berens and colleagues that are helpful in facilitating the transition.

Teach and practice disability etiquette

Societal prejudice harms people with IDD—leading to self-deprecation, alienation from the larger community, and isolation from others with IDD.⁸ To promote acceptance and inclusivity in residential communities, the workplace, recreational venues, and clinical settings, disability etiquette should be utilized—a set of guidelines on how to interact with patients with IDD. These include speaking to the patient directly, using clear language in an adult voice, and avoiding stereotypes about people with disabilities.⁹ The entire health care team, including all front-facing staff (receptionists and care and financial coordinators) and clinical staff (physicians, nurses, medical assistants), need to be educated in, and practice, disability etiquette.

Preparing for in-person visits. Pre-­visit preparation, ideally by means of dialogue between health care staff and the patient or caregiver (or both), typically by telephone and in advance of the scheduled visit, is often critical for a successful first face-to-face encounter. (See “Pre-visit telephone questionnaire and script for a new adult patient with IDD,” page 287, which we developed for use in our office practice.) Outcomes of the pre-visit preparation should include identifying:

• words or actions that can trigger anxiety or panic
• de-escalation techniques, such as specific calming words and actions
• strategies for optimal communication, physical access, and physical examination.

Initial appointments should focus on building trust and rapport with the health care team and desensitizing the patient to the clinical environment.¹⁰ Examination techniques used with pediatric patients can be applied to this population: for example, demonstrating an examination maneuver first on the parent or caregiver; beginning the examination with the least invasive or anxiety-­provoking components; and stating what you plan to do next—before you do it.

Continue to: Systematic health checks provide great value

A health check is a systematic and comprehensive health assessment that is provided annually to adults with IDD, and includes:

• specific review of signs and symptoms of health conditions that often co-­occur in adults with IDD (TABLE 2Calibri¹¹)
• screening for changes in adaptive functioning and secondary disability
• lifestyle counseling
• medication review and counseling
• immunization update
• discussion of caregiver concerns.

Successful implementation of preventive health screening tests for a patient with IDD often requires ingenuity and creativity to allay fears and anxieties.

Regarding the last point: Many caregivers are the aging parents of the adult patient with IDD—people who have their own emerging health and support needs. You should initiate conversations about advanced planning for the needs of patients, which often involves engaging siblings and other family members to assume a greater role in caregiving.¹²

Benefits of the health check. A systematic review of 38 studies, comprising more than 5000 patients with IDD, found that health checks increased the detection of serious conditions, improved screening for sensory impairments, and increased the immunization rate.¹³ Although many patients with IDD generally understand the need for a periodic health examination, you can enhance their experience by better explaining the rationale for the health check; scheduling sufficient time for the appointment, based on the individual clinical situation; and discussing the value of laboratory testing and referrals to specialists.¹⁴

Tailoring preventive care

Many of the preventive services recommendations typically utilized by family physicians, such as guidelines from the US Preventive Services Task Force, have been developed for the general population at average risk of conditions of interest.¹⁵ Adults with IDD, depending on the cause of their developmental disability and their behavioral risk profile, might be at significantly higher (or lower) risk of cancer, heart disease, or other conditions than the general population. To address these differences, preventive care guidelines tailored to patients with certain developmental disabilities have been created, including guidelines specific to adults with Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, and 22q11.2 deletion (DiGeorge) syndrome.¹⁶

Clarifying the molecular genetic etiology of many developmental disabilities has led to more precise understandings about physical and behavioral health issues associated with specific developmental disabilities. For that reason, patients without a known cause for their IDD might benefit from referral to a geneticist—even in early or middle adulthood. Variables generally associated with a higher likelihood of an abnormal genetic test result include¹⁷:

• a family history of developmental disability
• a congenital malformation or dysmorphic features
• a dual diagnosis of developmental disability and co-occurring mental illness
• hypotonia
• severe or profound IDD.

Continue to: Successful implementation of preventive health screening tests...

Successful implementation of preventive health screening tests often requires ingenuity and the collective creativity of the patient, family members, staff, and family physician to allay fears and anxieties. Examples: Women who have been advised to undergo screening mammography might feel less anxious by undergoing tandem screening with their sister or mother, and colorectal cancer screening might be more easily accomplished using a fecal DNA test rather than by colonoscopy. Procedural desensitization strategies and preventive care instructional materials targeting people with IDD are posted on YouTube (for example, the “DD CARES Best Practices” series [see www.youtube.com/watch?v=EPJy4zvg4io]) and other websites.

Management of chronic disease

Evidence of health disparities in patients with IDD includes suboptimal management of chronic diseases, such as diabetes¹⁸ and hypertension,¹⁹ despite contact with a primary care physician. Nonadherence to a medication regimen might be more common in patients who live with their family or in a residential setting where there is a lower degree of supervision—that is, compared to a residence that maintains 24-hour staffing with daily nursing care and supervision. For a patient who is not so closely supervised, reviewing the medication refill history with the pharmacy, or using the so-called brown-bag technique of counting pill bottles brought to appointments, can ensure medication adherence.

CASE

As you interview Ms. S, you note that she is shy, avoids eye contact, and appears generally anxious. You calm her by noticing and complimenting her jewelry and fingernail polish. Ms. S smiles and talks about her favorite polish colors.

Evaluation of suspected mental and behavioral health issues begins with assessment for medical conditions that might be causing pain and distress or stereotypies.

Her mother reports that, when Ms. S is stressed, she talks to herself alone in her bedroom. However, you do not observe evidence of schizoaffective disorder, and begin to wonder whether she needs to be taking risperidone.

Essentials of mental health care

It is estimated that one-third of adults with IDD have significant mental and behavioral health care needs.²⁰ Patients with IDD suffer the same psychiatric disorders as the general population; some also engage in problematic behaviors, such as self-injurious actions, physical or verbal aggression (or both), property destruction, and resistance to caregiving assistance.

Continue to: Mental and behavioral health problems...

Mental and behavioral health problems can have a profound impact on the quality of life of patients with IDD, their peers, and their family and other caregivers. If untreated, these problems can lead to premature institutionalization, loss of employment or desired program participation, fractured social relationships, and caregiver withdrawal and burnout.

Initial evaluation of suspected mental and behavioral health problems begins with careful assessment for medical conditions that might be causing pain and distress, stereotypies, and other problematic behaviors. Common sources of pain and discomfort include dental and other oral disease, dysphagia, gastroesophageal reflux disease, gastritis, constipation, allergic disease, headache, musculoskeletal pathology, lower urinary tract disease, and gynecologic disorders.¹¹ Identification and optimal treatment of medical conditions might not eliminate problematic behaviors but often decrease their frequency and intensity.

Psychoactive medications are prescribed for many patients with IDD. Many have behavioral adverse effects, such as akathisia, aggression, and disinhibition—leading to a prescribing cascade of psychoactive medication polypharmacy and escalating dosages.²¹ Antipsychotic medications are often initiated without a careful diagnosis, explicit outcome targets, or adequate clinical monitoring for effectiveness; in addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.²¹ Even a family physician who is not the prescriber can perform an important advocacy role by critically reviewing psychoactive medications, documenting adverse effects, insisting on a clear therapeutic target, and calling for discontinuation of medications that appear to be ineffective.

Evaluation of mental and behavioral health problems requires a developmental perspective to interpret specific, observable behaviors with a proper clinical lens. For example, many patients with IDD engage in self-talk (soliloquizing) as a means of processing the world around them. This practice might escalate during a time of physical or psychological stress, and the unwary clinician might misinterpret this behavior as psychotic, leading to inappropriate prescribing of antipsychotic medication. Other psychotoform behaviors that, superficially, mimic but are typically not truly psychotic, include talk with or about imaginary friends and repetitive retelling of sometimes elaborate or grandiose tales or assertions. The failure of clinicians to recognize developmentally determined expressions of distress often leads to a misdiagnosis of schizophrenia or other psychotic illness and, consequently, inappropriate psychopharmacotherapy. 

Family physicians, familiar with the use of psychiatric scales for diagnosis and treatment monitoring, should use similar scales that have been developed specifically for patients with IDD (TABLE 3¹¹). In addition, a psychiatric diagnosis manual, the Diagnostic Manual—Intellectual Disability 2, specific to people with IDD (and analogous to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) provides modification of diagnostic criteria to account for patients who have difficulty articulating their internal emotional state and inner thoughts.²²

Continue to: Problematic behaviors

Problematic behaviors that are not features of a bona fide psychiatric disorder are often best understood through functional behavioral analysis, which examines antecedents and consequences of problematic behaviors and identifies their predictable outcomes, such as gaining attention, avoiding a task, or securing a desired item. Rather than being given a prescription for psychoactive medication, many adult patients with IDD and problematic behaviors might be best served by having you order consultation with a certified behavior analyst. The analyst will conduct an evaluation and, along with family or residential staff and the patient, craft a behavioral support plan to address core drivers of the undesired behavior. Behavioral support plans might be enriched by multidisciplinary input from a speech and language pathologist, habilitation professionals, occupational and physical therapists, a neuropsychologist, and others.²³

Antipsychotic medications are often initiated without a careful diagnosis. In addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.

Resources to help you address the physical, mental, and behavioral health problems of these patients are available online through Vanderbilt Kennedy Center’s “Toolkit for primary care providers” (https://iddtoolkit.vkcsites.org).

CASE

During your examination, you review Ms. S’s vital signs, including body mass index (BMI). You calculate that she is morbidly obese—BMI, 37—in the setting of a known comorbidity, diabetes.

Ms. S tells you that she is interested in having a healthy lifestyle, but feels frustrated because she does not know how to make the necessary changes. You discuss with her how some medications, including risperidone, can promote weight gain, and that it is important for her mental health provider to carefully reassess whether she needs to continue the drug.

Weight management in a patient population that tends to be sedentary

Patients with IDD are more likely to live a sedentary lifestyle. Compared to adults who do not have IDD, adults with IDD—especially women and patients with Down syndrome—are reported to have a higher prevalence of obesity.²⁴

Continue to: As in the general population...

Similarly, undesired weight loss demands careful evaluation and management because such loss can reflect a medically significant condition, such as gastroesophageal reflux, constipation, dysphagia, neglect, and cancer.²⁷

Boosting the amount and effectiveness of physical activity

Young people with IDD participate in physical activity less often than their neurotypical peers; as a result, they tend to be less fit and have a higher prevalence of obesity.²⁸ Based on a meta-analysis, interventions that focus on sport and movement skills training, such as soccer, basketball, and ball-throwing programs, might be more effective than general physical activity programs.²⁸ In addition to year-round sports training and athletic competitions, Special Olympics conducts vital health screenings of athletes and supports community-based initiatives that address bias against patients with IDD, promote inclusion, and foster social relationships (www.specialolympics.org/our-work/inclusive-health?locale=en).

Success in weight management involves multidisciplinary treatment, including nutritional support, physical activity, behavioral changes, and close follow-up.

Emphasize regular activity. In adulthood, fewer than 10% of patients with IDD exercise regularly.²¹ According to the second edition of Physical Activity Guidelines for Americans,²⁹ “all adults, with or without a disability, should get at least 150 minutes of aerobic physical activity a week. Activities can be broken down into smaller amounts, such as about 25 minutes a day every day.”³⁰ Supplementation with muscle-strengthening activities (eg, yoga, weight training, and resistance-band training) provides further health benefit, such as improvement in posture and prevention of future injury.³¹ An ideal exercise program proposed by Tyler and Baker is based on a daily, “3-2-1” schedule (ie, of every hour of activity, 30 minutes should be of aerobic exercise; 20 minutes, of strength building; and 10 minutes, of flexibility).¹¹ By participating in any type of physical activity, there is potential for considerable health benefit in reducing psychosocial stressors, improving mental health, counteracting metabolic syndromes, and, ultimately, reducing morbidity and mortality related to physical inactivity.

CASE

With permission from Ms. S, you send your progress notes by fax to her mental health provider at the community mental health center and request a call to discuss her case—in particular, to examine potential alternatives to risperidone. With Ms. S’s input, you also co-create an exercise prescription that includes a daily 20-minute walking program with her mother.

At the follow-up visit that is scheduled in 3 months, you anticipate adding a resistance component and balance activity to the exercise prescription to enrich Ms. S’s physical activity regimen.

CORRESPONDENCE
Carl V. Tyler Jr., MD, 14601 Detroit Avenue, Lakewood, OH, 44107; [email protected]

Some adults who have an intellectual or other developmental disability (IDD) require extensive subspecialty care; many, however, depend primarily on their family physician for the bulk of their health care. With that reliance in mind, this article provides (1) an overview of important services that family physicians can provide for their adult patients with IDD and (2) pragmatic clinical suggestions for tailoring that care. Note: We highlight only some high-impact areas of clinical focus; refer to the 2018 Canadian consensus guidelines for a comprehensive approach to optimizing primary care for this population.¹

CASE

Laura S, a 24-year-old woman with Down syndrome, is visiting your clinic with her mother to establish care. Ms. S has several medical comorbidities, including type 2 diabetes, hyperlipidemia, repaired congenital heart disease, schizoaffective disorder, and hypothyroidism. She is under the care of multiple specialists, including a cardiologist and an endocrinologist. Her medications include the atypical antipsychotic risperidone, which was prescribed for her through the services of a community mental health center.

Ms. S is due for multiple preventive health screenings. She indicates that she feels nervous today talking about these screenings with a new physician.

First step in care: Proficiency in the lexicon of IDD

Three core concepts of IDD are impairment, disability, and handicap. According to the World Health Organization²:

• impairment “is any loss or abnormality of psychological, physiological, or anatomical structure or function.”
• disability “is any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.”
• handicap therefore “represents socialization of an impairment or disability, and as such it reflects the consequences for the individual—cultural, social, economic, and environmental—that stem from the presence of impairment and disability.”

Essential transition: Pediatric to adult health care

Health care transition (HCT) is the planned process of transferring care from a pediatric to an adult-based health care setting,³ comprising 3 phases:

• preparation
• transfer from pediatric to adult care
• integration into adult-based care.

Two critical components of a smooth HCT include initiating the transition early in adolescence and providing transition-support resources, which are often lacking, even in large, integrated health systems.⁴ Got Transition, created by the National Alliance to Advance Adolescent Health, outlines core elements of an organized HCT process (www.gottransition.org) specific to young adults with IDD, including young adults with autism spectrum disorder.^5,6 

Even young people who are served by a family physician and who intend to remain in that family practice as they age into adulthood require HCT services that include⁶:

• assessment of readiness to transition to adult care
• update of the medical history
• assessment and promotion of self-care skills
• consent discussions and optimized participation in decision-making
• transition of specialty care from pediatric to adult specialists.

Continue to: For an ideal HCT...

For an ideal health care transition, full engagement of the patient, the medical home, and the patient’s family (including the primary caregiver or guardian) is critical.

For an ideal HCT, full engagement of the patient, the medical home (physicians, nursing staff, and care coordinators), and the patient’s family (including the primary caregiver or guardian) is critical. In addition to preventive care visits and management of chronic disease, additional domains that require explicit attention in transitioning young people with IDD include health insurance, transportation, employment, and postsecondary education.

Young people who have special health care needs and receive high-quality HCT demonstrate improvements in adherence to care, disease-specific measures, quality of life, self-care skills, satisfaction with care, and health care utilization.⁷TABLE 1³ lists resources identified by Berens and colleagues that are helpful in facilitating the transition.

Teach and practice disability etiquette

Societal prejudice harms people with IDD—leading to self-deprecation, alienation from the larger community, and isolation from others with IDD.⁸ To promote acceptance and inclusivity in residential communities, the workplace, recreational venues, and clinical settings, disability etiquette should be utilized—a set of guidelines on how to interact with patients with IDD. These include speaking to the patient directly, using clear language in an adult voice, and avoiding stereotypes about people with disabilities.⁹ The entire health care team, including all front-facing staff (receptionists and care and financial coordinators) and clinical staff (physicians, nurses, medical assistants), need to be educated in, and practice, disability etiquette.

Preparing for in-person visits. Pre-­visit preparation, ideally by means of dialogue between health care staff and the patient or caregiver (or both), typically by telephone and in advance of the scheduled visit, is often critical for a successful first face-to-face encounter. (See “Pre-visit telephone questionnaire and script for a new adult patient with IDD,” page 287, which we developed for use in our office practice.) Outcomes of the pre-visit preparation should include identifying:

• words or actions that can trigger anxiety or panic
• de-escalation techniques, such as specific calming words and actions
• strategies for optimal communication, physical access, and physical examination.

Initial appointments should focus on building trust and rapport with the health care team and desensitizing the patient to the clinical environment.¹⁰ Examination techniques used with pediatric patients can be applied to this population: for example, demonstrating an examination maneuver first on the parent or caregiver; beginning the examination with the least invasive or anxiety-­provoking components; and stating what you plan to do next—before you do it.

Continue to: Systematic health checks provide great value

A health check is a systematic and comprehensive health assessment that is provided annually to adults with IDD, and includes:

• specific review of signs and symptoms of health conditions that often co-­occur in adults with IDD (TABLE 2Calibri¹¹)
• screening for changes in adaptive functioning and secondary disability
• lifestyle counseling
• medication review and counseling
• immunization update
• discussion of caregiver concerns.

Successful implementation of preventive health screening tests for a patient with IDD often requires ingenuity and creativity to allay fears and anxieties.

Regarding the last point: Many caregivers are the aging parents of the adult patient with IDD—people who have their own emerging health and support needs. You should initiate conversations about advanced planning for the needs of patients, which often involves engaging siblings and other family members to assume a greater role in caregiving.¹²

Benefits of the health check. A systematic review of 38 studies, comprising more than 5000 patients with IDD, found that health checks increased the detection of serious conditions, improved screening for sensory impairments, and increased the immunization rate.¹³ Although many patients with IDD generally understand the need for a periodic health examination, you can enhance their experience by better explaining the rationale for the health check; scheduling sufficient time for the appointment, based on the individual clinical situation; and discussing the value of laboratory testing and referrals to specialists.¹⁴

Tailoring preventive care

Many of the preventive services recommendations typically utilized by family physicians, such as guidelines from the US Preventive Services Task Force, have been developed for the general population at average risk of conditions of interest.¹⁵ Adults with IDD, depending on the cause of their developmental disability and their behavioral risk profile, might be at significantly higher (or lower) risk of cancer, heart disease, or other conditions than the general population. To address these differences, preventive care guidelines tailored to patients with certain developmental disabilities have been created, including guidelines specific to adults with Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, and 22q11.2 deletion (DiGeorge) syndrome.¹⁶

Clarifying the molecular genetic etiology of many developmental disabilities has led to more precise understandings about physical and behavioral health issues associated with specific developmental disabilities. For that reason, patients without a known cause for their IDD might benefit from referral to a geneticist—even in early or middle adulthood. Variables generally associated with a higher likelihood of an abnormal genetic test result include¹⁷:

• a family history of developmental disability
• a congenital malformation or dysmorphic features
• a dual diagnosis of developmental disability and co-occurring mental illness
• hypotonia
• severe or profound IDD.

Continue to: Successful implementation of preventive health screening tests...

Successful implementation of preventive health screening tests often requires ingenuity and the collective creativity of the patient, family members, staff, and family physician to allay fears and anxieties. Examples: Women who have been advised to undergo screening mammography might feel less anxious by undergoing tandem screening with their sister or mother, and colorectal cancer screening might be more easily accomplished using a fecal DNA test rather than by colonoscopy. Procedural desensitization strategies and preventive care instructional materials targeting people with IDD are posted on YouTube (for example, the “DD CARES Best Practices” series [see www.youtube.com/watch?v=EPJy4zvg4io]) and other websites.

Management of chronic disease

Evidence of health disparities in patients with IDD includes suboptimal management of chronic diseases, such as diabetes¹⁸ and hypertension,¹⁹ despite contact with a primary care physician. Nonadherence to a medication regimen might be more common in patients who live with their family or in a residential setting where there is a lower degree of supervision—that is, compared to a residence that maintains 24-hour staffing with daily nursing care and supervision. For a patient who is not so closely supervised, reviewing the medication refill history with the pharmacy, or using the so-called brown-bag technique of counting pill bottles brought to appointments, can ensure medication adherence.

CASE

As you interview Ms. S, you note that she is shy, avoids eye contact, and appears generally anxious. You calm her by noticing and complimenting her jewelry and fingernail polish. Ms. S smiles and talks about her favorite polish colors.

Evaluation of suspected mental and behavioral health issues begins with assessment for medical conditions that might be causing pain and distress or stereotypies.

Her mother reports that, when Ms. S is stressed, she talks to herself alone in her bedroom. However, you do not observe evidence of schizoaffective disorder, and begin to wonder whether she needs to be taking risperidone.

Essentials of mental health care

It is estimated that one-third of adults with IDD have significant mental and behavioral health care needs.²⁰ Patients with IDD suffer the same psychiatric disorders as the general population; some also engage in problematic behaviors, such as self-injurious actions, physical or verbal aggression (or both), property destruction, and resistance to caregiving assistance.

Continue to: Mental and behavioral health problems...

Mental and behavioral health problems can have a profound impact on the quality of life of patients with IDD, their peers, and their family and other caregivers. If untreated, these problems can lead to premature institutionalization, loss of employment or desired program participation, fractured social relationships, and caregiver withdrawal and burnout.

Initial evaluation of suspected mental and behavioral health problems begins with careful assessment for medical conditions that might be causing pain and distress, stereotypies, and other problematic behaviors. Common sources of pain and discomfort include dental and other oral disease, dysphagia, gastroesophageal reflux disease, gastritis, constipation, allergic disease, headache, musculoskeletal pathology, lower urinary tract disease, and gynecologic disorders.¹¹ Identification and optimal treatment of medical conditions might not eliminate problematic behaviors but often decrease their frequency and intensity.

Psychoactive medications are prescribed for many patients with IDD. Many have behavioral adverse effects, such as akathisia, aggression, and disinhibition—leading to a prescribing cascade of psychoactive medication polypharmacy and escalating dosages.²¹ Antipsychotic medications are often initiated without a careful diagnosis, explicit outcome targets, or adequate clinical monitoring for effectiveness; in addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.²¹ Even a family physician who is not the prescriber can perform an important advocacy role by critically reviewing psychoactive medications, documenting adverse effects, insisting on a clear therapeutic target, and calling for discontinuation of medications that appear to be ineffective.

Evaluation of mental and behavioral health problems requires a developmental perspective to interpret specific, observable behaviors with a proper clinical lens. For example, many patients with IDD engage in self-talk (soliloquizing) as a means of processing the world around them. This practice might escalate during a time of physical or psychological stress, and the unwary clinician might misinterpret this behavior as psychotic, leading to inappropriate prescribing of antipsychotic medication. Other psychotoform behaviors that, superficially, mimic but are typically not truly psychotic, include talk with or about imaginary friends and repetitive retelling of sometimes elaborate or grandiose tales or assertions. The failure of clinicians to recognize developmentally determined expressions of distress often leads to a misdiagnosis of schizophrenia or other psychotic illness and, consequently, inappropriate psychopharmacotherapy. 

Family physicians, familiar with the use of psychiatric scales for diagnosis and treatment monitoring, should use similar scales that have been developed specifically for patients with IDD (TABLE 3¹¹). In addition, a psychiatric diagnosis manual, the Diagnostic Manual—Intellectual Disability 2, specific to people with IDD (and analogous to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) provides modification of diagnostic criteria to account for patients who have difficulty articulating their internal emotional state and inner thoughts.²²

Continue to: Problematic behaviors

Problematic behaviors that are not features of a bona fide psychiatric disorder are often best understood through functional behavioral analysis, which examines antecedents and consequences of problematic behaviors and identifies their predictable outcomes, such as gaining attention, avoiding a task, or securing a desired item. Rather than being given a prescription for psychoactive medication, many adult patients with IDD and problematic behaviors might be best served by having you order consultation with a certified behavior analyst. The analyst will conduct an evaluation and, along with family or residential staff and the patient, craft a behavioral support plan to address core drivers of the undesired behavior. Behavioral support plans might be enriched by multidisciplinary input from a speech and language pathologist, habilitation professionals, occupational and physical therapists, a neuropsychologist, and others.²³

Antipsychotic medications are often initiated without a careful diagnosis. In addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.

Resources to help you address the physical, mental, and behavioral health problems of these patients are available online through Vanderbilt Kennedy Center’s “Toolkit for primary care providers” (https://iddtoolkit.vkcsites.org).

CASE

During your examination, you review Ms. S’s vital signs, including body mass index (BMI). You calculate that she is morbidly obese—BMI, 37—in the setting of a known comorbidity, diabetes.

Ms. S tells you that she is interested in having a healthy lifestyle, but feels frustrated because she does not know how to make the necessary changes. You discuss with her how some medications, including risperidone, can promote weight gain, and that it is important for her mental health provider to carefully reassess whether she needs to continue the drug.

Weight management in a patient population that tends to be sedentary

Patients with IDD are more likely to live a sedentary lifestyle. Compared to adults who do not have IDD, adults with IDD—especially women and patients with Down syndrome—are reported to have a higher prevalence of obesity.²⁴

Continue to: As in the general population...

Similarly, undesired weight loss demands careful evaluation and management because such loss can reflect a medically significant condition, such as gastroesophageal reflux, constipation, dysphagia, neglect, and cancer.²⁷

Boosting the amount and effectiveness of physical activity

Young people with IDD participate in physical activity less often than their neurotypical peers; as a result, they tend to be less fit and have a higher prevalence of obesity.²⁸ Based on a meta-analysis, interventions that focus on sport and movement skills training, such as soccer, basketball, and ball-throwing programs, might be more effective than general physical activity programs.²⁸ In addition to year-round sports training and athletic competitions, Special Olympics conducts vital health screenings of athletes and supports community-based initiatives that address bias against patients with IDD, promote inclusion, and foster social relationships (www.specialolympics.org/our-work/inclusive-health?locale=en).

Success in weight management involves multidisciplinary treatment, including nutritional support, physical activity, behavioral changes, and close follow-up.

Emphasize regular activity. In adulthood, fewer than 10% of patients with IDD exercise regularly.²¹ According to the second edition of Physical Activity Guidelines for Americans,²⁹ “all adults, with or without a disability, should get at least 150 minutes of aerobic physical activity a week. Activities can be broken down into smaller amounts, such as about 25 minutes a day every day.”³⁰ Supplementation with muscle-strengthening activities (eg, yoga, weight training, and resistance-band training) provides further health benefit, such as improvement in posture and prevention of future injury.³¹ An ideal exercise program proposed by Tyler and Baker is based on a daily, “3-2-1” schedule (ie, of every hour of activity, 30 minutes should be of aerobic exercise; 20 minutes, of strength building; and 10 minutes, of flexibility).¹¹ By participating in any type of physical activity, there is potential for considerable health benefit in reducing psychosocial stressors, improving mental health, counteracting metabolic syndromes, and, ultimately, reducing morbidity and mortality related to physical inactivity.

CASE

With permission from Ms. S, you send your progress notes by fax to her mental health provider at the community mental health center and request a call to discuss her case—in particular, to examine potential alternatives to risperidone. With Ms. S’s input, you also co-create an exercise prescription that includes a daily 20-minute walking program with her mother.

At the follow-up visit that is scheduled in 3 months, you anticipate adding a resistance component and balance activity to the exercise prescription to enrich Ms. S’s physical activity regimen.

CORRESPONDENCE
Carl V. Tyler Jr., MD, 14601 Detroit Avenue, Lakewood, OH, 44107; [email protected]

Some adults who have an intellectual or other developmental disability (IDD) require extensive subspecialty care; many, however, depend primarily on their family physician for the bulk of their health care. With that reliance in mind, this article provides (1) an overview of important services that family physicians can provide for their adult patients with IDD and (2) pragmatic clinical suggestions for tailoring that care. Note: We highlight only some high-impact areas of clinical focus; refer to the 2018 Canadian consensus guidelines for a comprehensive approach to optimizing primary care for this population.¹

CASE

Laura S, a 24-year-old woman with Down syndrome, is visiting your clinic with her mother to establish care. Ms. S has several medical comorbidities, including type 2 diabetes, hyperlipidemia, repaired congenital heart disease, schizoaffective disorder, and hypothyroidism. She is under the care of multiple specialists, including a cardiologist and an endocrinologist. Her medications include the atypical antipsychotic risperidone, which was prescribed for her through the services of a community mental health center.

Ms. S is due for multiple preventive health screenings. She indicates that she feels nervous today talking about these screenings with a new physician.

First step in care: Proficiency in the lexicon of IDD

Three core concepts of IDD are impairment, disability, and handicap. According to the World Health Organization²:

• impairment “is any loss or abnormality of psychological, physiological, or anatomical structure or function.”
• disability “is any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.”
• handicap therefore “represents socialization of an impairment or disability, and as such it reflects the consequences for the individual—cultural, social, economic, and environmental—that stem from the presence of impairment and disability.”

Essential transition: Pediatric to adult health care

Health care transition (HCT) is the planned process of transferring care from a pediatric to an adult-based health care setting,³ comprising 3 phases:

• preparation
• transfer from pediatric to adult care
• integration into adult-based care.

Two critical components of a smooth HCT include initiating the transition early in adolescence and providing transition-support resources, which are often lacking, even in large, integrated health systems.⁴ Got Transition, created by the National Alliance to Advance Adolescent Health, outlines core elements of an organized HCT process (www.gottransition.org) specific to young adults with IDD, including young adults with autism spectrum disorder.^5,6 

Even young people who are served by a family physician and who intend to remain in that family practice as they age into adulthood require HCT services that include⁶:

• assessment of readiness to transition to adult care
• update of the medical history
• assessment and promotion of self-care skills
• consent discussions and optimized participation in decision-making
• transition of specialty care from pediatric to adult specialists.

Continue to: For an ideal HCT...

For an ideal health care transition, full engagement of the patient, the medical home, and the patient’s family (including the primary caregiver or guardian) is critical.

For an ideal HCT, full engagement of the patient, the medical home (physicians, nursing staff, and care coordinators), and the patient’s family (including the primary caregiver or guardian) is critical. In addition to preventive care visits and management of chronic disease, additional domains that require explicit attention in transitioning young people with IDD include health insurance, transportation, employment, and postsecondary education.

Young people who have special health care needs and receive high-quality HCT demonstrate improvements in adherence to care, disease-specific measures, quality of life, self-care skills, satisfaction with care, and health care utilization.⁷TABLE 1³ lists resources identified by Berens and colleagues that are helpful in facilitating the transition.

Teach and practice disability etiquette

Societal prejudice harms people with IDD—leading to self-deprecation, alienation from the larger community, and isolation from others with IDD.⁸ To promote acceptance and inclusivity in residential communities, the workplace, recreational venues, and clinical settings, disability etiquette should be utilized—a set of guidelines on how to interact with patients with IDD. These include speaking to the patient directly, using clear language in an adult voice, and avoiding stereotypes about people with disabilities.⁹ The entire health care team, including all front-facing staff (receptionists and care and financial coordinators) and clinical staff (physicians, nurses, medical assistants), need to be educated in, and practice, disability etiquette.

Preparing for in-person visits. Pre-­visit preparation, ideally by means of dialogue between health care staff and the patient or caregiver (or both), typically by telephone and in advance of the scheduled visit, is often critical for a successful first face-to-face encounter. (See “Pre-visit telephone questionnaire and script for a new adult patient with IDD,” page 287, which we developed for use in our office practice.) Outcomes of the pre-visit preparation should include identifying:

• words or actions that can trigger anxiety or panic
• de-escalation techniques, such as specific calming words and actions
• strategies for optimal communication, physical access, and physical examination.

Initial appointments should focus on building trust and rapport with the health care team and desensitizing the patient to the clinical environment.¹⁰ Examination techniques used with pediatric patients can be applied to this population: for example, demonstrating an examination maneuver first on the parent or caregiver; beginning the examination with the least invasive or anxiety-­provoking components; and stating what you plan to do next—before you do it.

Continue to: Systematic health checks provide great value

A health check is a systematic and comprehensive health assessment that is provided annually to adults with IDD, and includes:

• specific review of signs and symptoms of health conditions that often co-­occur in adults with IDD (TABLE 2Calibri¹¹)
• screening for changes in adaptive functioning and secondary disability
• lifestyle counseling
• medication review and counseling
• immunization update
• discussion of caregiver concerns.

Successful implementation of preventive health screening tests for a patient with IDD often requires ingenuity and creativity to allay fears and anxieties.

Regarding the last point: Many caregivers are the aging parents of the adult patient with IDD—people who have their own emerging health and support needs. You should initiate conversations about advanced planning for the needs of patients, which often involves engaging siblings and other family members to assume a greater role in caregiving.¹²

Benefits of the health check. A systematic review of 38 studies, comprising more than 5000 patients with IDD, found that health checks increased the detection of serious conditions, improved screening for sensory impairments, and increased the immunization rate.¹³ Although many patients with IDD generally understand the need for a periodic health examination, you can enhance their experience by better explaining the rationale for the health check; scheduling sufficient time for the appointment, based on the individual clinical situation; and discussing the value of laboratory testing and referrals to specialists.¹⁴

Tailoring preventive care

Many of the preventive services recommendations typically utilized by family physicians, such as guidelines from the US Preventive Services Task Force, have been developed for the general population at average risk of conditions of interest.¹⁵ Adults with IDD, depending on the cause of their developmental disability and their behavioral risk profile, might be at significantly higher (or lower) risk of cancer, heart disease, or other conditions than the general population. To address these differences, preventive care guidelines tailored to patients with certain developmental disabilities have been created, including guidelines specific to adults with Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, and 22q11.2 deletion (DiGeorge) syndrome.¹⁶

Clarifying the molecular genetic etiology of many developmental disabilities has led to more precise understandings about physical and behavioral health issues associated with specific developmental disabilities. For that reason, patients without a known cause for their IDD might benefit from referral to a geneticist—even in early or middle adulthood. Variables generally associated with a higher likelihood of an abnormal genetic test result include¹⁷:

• a family history of developmental disability
• a congenital malformation or dysmorphic features
• a dual diagnosis of developmental disability and co-occurring mental illness
• hypotonia
• severe or profound IDD.

Continue to: Successful implementation of preventive health screening tests...

Successful implementation of preventive health screening tests often requires ingenuity and the collective creativity of the patient, family members, staff, and family physician to allay fears and anxieties. Examples: Women who have been advised to undergo screening mammography might feel less anxious by undergoing tandem screening with their sister or mother, and colorectal cancer screening might be more easily accomplished using a fecal DNA test rather than by colonoscopy. Procedural desensitization strategies and preventive care instructional materials targeting people with IDD are posted on YouTube (for example, the “DD CARES Best Practices” series [see www.youtube.com/watch?v=EPJy4zvg4io]) and other websites.

Management of chronic disease

Evidence of health disparities in patients with IDD includes suboptimal management of chronic diseases, such as diabetes¹⁸ and hypertension,¹⁹ despite contact with a primary care physician. Nonadherence to a medication regimen might be more common in patients who live with their family or in a residential setting where there is a lower degree of supervision—that is, compared to a residence that maintains 24-hour staffing with daily nursing care and supervision. For a patient who is not so closely supervised, reviewing the medication refill history with the pharmacy, or using the so-called brown-bag technique of counting pill bottles brought to appointments, can ensure medication adherence.

CASE

As you interview Ms. S, you note that she is shy, avoids eye contact, and appears generally anxious. You calm her by noticing and complimenting her jewelry and fingernail polish. Ms. S smiles and talks about her favorite polish colors.

Evaluation of suspected mental and behavioral health issues begins with assessment for medical conditions that might be causing pain and distress or stereotypies.

Her mother reports that, when Ms. S is stressed, she talks to herself alone in her bedroom. However, you do not observe evidence of schizoaffective disorder, and begin to wonder whether she needs to be taking risperidone.

Essentials of mental health care

It is estimated that one-third of adults with IDD have significant mental and behavioral health care needs.²⁰ Patients with IDD suffer the same psychiatric disorders as the general population; some also engage in problematic behaviors, such as self-injurious actions, physical or verbal aggression (or both), property destruction, and resistance to caregiving assistance.

Continue to: Mental and behavioral health problems...

Mental and behavioral health problems can have a profound impact on the quality of life of patients with IDD, their peers, and their family and other caregivers. If untreated, these problems can lead to premature institutionalization, loss of employment or desired program participation, fractured social relationships, and caregiver withdrawal and burnout.

Initial evaluation of suspected mental and behavioral health problems begins with careful assessment for medical conditions that might be causing pain and distress, stereotypies, and other problematic behaviors. Common sources of pain and discomfort include dental and other oral disease, dysphagia, gastroesophageal reflux disease, gastritis, constipation, allergic disease, headache, musculoskeletal pathology, lower urinary tract disease, and gynecologic disorders.¹¹ Identification and optimal treatment of medical conditions might not eliminate problematic behaviors but often decrease their frequency and intensity.

Psychoactive medications are prescribed for many patients with IDD. Many have behavioral adverse effects, such as akathisia, aggression, and disinhibition—leading to a prescribing cascade of psychoactive medication polypharmacy and escalating dosages.²¹ Antipsychotic medications are often initiated without a careful diagnosis, explicit outcome targets, or adequate clinical monitoring for effectiveness; in addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.²¹ Even a family physician who is not the prescriber can perform an important advocacy role by critically reviewing psychoactive medications, documenting adverse effects, insisting on a clear therapeutic target, and calling for discontinuation of medications that appear to be ineffective.

Evaluation of mental and behavioral health problems requires a developmental perspective to interpret specific, observable behaviors with a proper clinical lens. For example, many patients with IDD engage in self-talk (soliloquizing) as a means of processing the world around them. This practice might escalate during a time of physical or psychological stress, and the unwary clinician might misinterpret this behavior as psychotic, leading to inappropriate prescribing of antipsychotic medication. Other psychotoform behaviors that, superficially, mimic but are typically not truly psychotic, include talk with or about imaginary friends and repetitive retelling of sometimes elaborate or grandiose tales or assertions. The failure of clinicians to recognize developmentally determined expressions of distress often leads to a misdiagnosis of schizophrenia or other psychotic illness and, consequently, inappropriate psychopharmacotherapy. 

Family physicians, familiar with the use of psychiatric scales for diagnosis and treatment monitoring, should use similar scales that have been developed specifically for patients with IDD (TABLE 3¹¹). In addition, a psychiatric diagnosis manual, the Diagnostic Manual—Intellectual Disability 2, specific to people with IDD (and analogous to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) provides modification of diagnostic criteria to account for patients who have difficulty articulating their internal emotional state and inner thoughts.²²

Continue to: Problematic behaviors

Problematic behaviors that are not features of a bona fide psychiatric disorder are often best understood through functional behavioral analysis, which examines antecedents and consequences of problematic behaviors and identifies their predictable outcomes, such as gaining attention, avoiding a task, or securing a desired item. Rather than being given a prescription for psychoactive medication, many adult patients with IDD and problematic behaviors might be best served by having you order consultation with a certified behavior analyst. The analyst will conduct an evaluation and, along with family or residential staff and the patient, craft a behavioral support plan to address core drivers of the undesired behavior. Behavioral support plans might be enriched by multidisciplinary input from a speech and language pathologist, habilitation professionals, occupational and physical therapists, a neuropsychologist, and others.²³

Antipsychotic medications are often initiated without a careful diagnosis. In addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.

Resources to help you address the physical, mental, and behavioral health problems of these patients are available online through Vanderbilt Kennedy Center’s “Toolkit for primary care providers” (https://iddtoolkit.vkcsites.org).

CASE

During your examination, you review Ms. S’s vital signs, including body mass index (BMI). You calculate that she is morbidly obese—BMI, 37—in the setting of a known comorbidity, diabetes.

Ms. S tells you that she is interested in having a healthy lifestyle, but feels frustrated because she does not know how to make the necessary changes. You discuss with her how some medications, including risperidone, can promote weight gain, and that it is important for her mental health provider to carefully reassess whether she needs to continue the drug.

Weight management in a patient population that tends to be sedentary

Patients with IDD are more likely to live a sedentary lifestyle. Compared to adults who do not have IDD, adults with IDD—especially women and patients with Down syndrome—are reported to have a higher prevalence of obesity.²⁴

Continue to: As in the general population...

Similarly, undesired weight loss demands careful evaluation and management because such loss can reflect a medically significant condition, such as gastroesophageal reflux, constipation, dysphagia, neglect, and cancer.²⁷

Boosting the amount and effectiveness of physical activity

Young people with IDD participate in physical activity less often than their neurotypical peers; as a result, they tend to be less fit and have a higher prevalence of obesity.²⁸ Based on a meta-analysis, interventions that focus on sport and movement skills training, such as soccer, basketball, and ball-throwing programs, might be more effective than general physical activity programs.²⁸ In addition to year-round sports training and athletic competitions, Special Olympics conducts vital health screenings of athletes and supports community-based initiatives that address bias against patients with IDD, promote inclusion, and foster social relationships (www.specialolympics.org/our-work/inclusive-health?locale=en).

Success in weight management involves multidisciplinary treatment, including nutritional support, physical activity, behavioral changes, and close follow-up.

Emphasize regular activity. In adulthood, fewer than 10% of patients with IDD exercise regularly.²¹ According to the second edition of Physical Activity Guidelines for Americans,²⁹ “all adults, with or without a disability, should get at least 150 minutes of aerobic physical activity a week. Activities can be broken down into smaller amounts, such as about 25 minutes a day every day.”³⁰ Supplementation with muscle-strengthening activities (eg, yoga, weight training, and resistance-band training) provides further health benefit, such as improvement in posture and prevention of future injury.³¹ An ideal exercise program proposed by Tyler and Baker is based on a daily, “3-2-1” schedule (ie, of every hour of activity, 30 minutes should be of aerobic exercise; 20 minutes, of strength building; and 10 minutes, of flexibility).¹¹ By participating in any type of physical activity, there is potential for considerable health benefit in reducing psychosocial stressors, improving mental health, counteracting metabolic syndromes, and, ultimately, reducing morbidity and mortality related to physical inactivity.

CASE

With permission from Ms. S, you send your progress notes by fax to her mental health provider at the community mental health center and request a call to discuss her case—in particular, to examine potential alternatives to risperidone. With Ms. S’s input, you also co-create an exercise prescription that includes a daily 20-minute walking program with her mother.

At the follow-up visit that is scheduled in 3 months, you anticipate adding a resistance component and balance activity to the exercise prescription to enrich Ms. S’s physical activity regimen.

CORRESPONDENCE
Carl V. Tyler Jr., MD, 14601 Detroit Avenue, Lakewood, OH, 44107; [email protected]

As the population of older adults rises, primary osteoporosis has become a problem of public health significance, resulting in more than 2 million fractures and $19 billion in related costs annually in the United States.¹ Despite the availability of effective primary and secondary preventive measures, many older adults do not receive adequate information on bone health from their primary care provider.² Initiation of osteoporosis treatment is low even among patients who have had an osteoporotic fracture: Fewer than one-­quarter of older adults with hip fracture have begun taking osteoporosis medication within 12 months of hospital discharge.³

In this overview of osteoporosis care, we provide information on how to evaluate and manage older adults in primary care settings who are at risk of, or have been given a diagnosis of, primary osteoporosis. The guidance that we offer reflects the most recent updates and recommendations by relevant professional societies.^1,4-7

The nature and scope of an urgent problem

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture.⁸ Operationally, it is defined by the World Health Organization as a bone mineral density (BMD) score below 2.5 SD from the mean value for a young White woman (ie, T-score ≤ –2.5).⁹ Primary osteoporosis is age related and occurs mostly in postmenopausal women and older men, affecting 25% of women and 5% of men ≥ 65 years.¹⁰

An osteoporotic fracture is particularly devastating in an older adult because it can cause pain, reduced mobility, depression, and social isolation and can increase the risk of related mortality.¹ The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.¹ Therefore, it is of paramount importance to identify patients who are at increased risk of fracture and intervene early.

The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.

Clinical manifestations

Osteoporosis does not have a primary presentation; rather, disease manifests clinically when a patient develops complications. Often, a fragility fracture is the first sign in an older person.¹¹

A fracture is the most important complication of osteoporosis and can result from low-trauma injury or a fall from standing height—thus, the term “fragility fracture.” Osteoporotic fractures commonly involve the vertebra, hip, and wrist. Hip and extremity fractures can result in limited or lost mobility and depression. Vertebral fractures can be asymptomatic or result in kyphosis and loss of height. Fractures can give rise to pain.

Age and female sexare risk factors

TABLE 1^1,6,10 lists risk factors associated with osteoporosis. Age is the most important; prevalence of osteoporosis increases with age. Other nonmodifiable risk factors include female sex (the disease appears earlier in women who enter menopause prematurely), family history of osteoporosis, and race and ethnicity. Twenty percent of Asian and non-Hispanic White women > 50 years have osteoporosis.¹ A study showed that Mexican Americans are at higher risk of osteoporosis than non-Hispanic Whites; non-Hispanic Blacks are least affected.¹⁰

Other risk factors include low body weight (< 127 lb) and a history of fractures after age 50. Behavioral risk factors include smoking, excessive alcohol intake (> 3 drinks/d), poor nutrition, and a sedentary lifestyle.^1,6

Continue to: Who should be screened?...

Who should be screened?

Screening is generally performed with a clinical evaluation and a dual-energy x-ray absorptiometry (DXA) scan of BMD. Measurement of BMD is generally recommended for screening all women ≥ 65 years and those < 65 years whose 10-year risk of fracture is equivalent to that of a 65-year-old White woman (see “Assessment of fracture risk” later in the article). For men, the US Preventive Services Task Force recommends screening those with a prior fracture or a secondary risk factor for disease.⁵ However, the National Osteoporosis Foundation recommends screening all men ≥ 70 years and those 50 to 69 years whose risk profile shows heightened risk.^1,4

DXA of the spine and hip is preferred; the distal one-third of the radius (termed “33% radius”) of the nondominant arm can be used when spine and hip BMD cannot be interpreted because of bone changes from the disease process or artifacts, or in certain diseases in which the wrist region shows the earliest change (eg, primary hyperparathyroidism).^6,7

Clinical evaluation includes a detailed history, physical examination, laboratory screening, and assessment for risk of fracture.

❚ History. Explore the presence of risk factors, including fractures in adulthood, falls, medication use, alcohol and tobacco use, family history of osteoporosis, and chronic disease.^6,7

❚ Physical exam. Assess height, including any loss (> 1.5 in) since the patient’s second or third decade of life; kyphosis; frailty; and balance and mobility problems.^4,6,7

❚  Laboratory and imaging studies. Perform basic laboratory testing when DXA is abnormal, including thyroid function, serum calcium, and renal function.^6,12 Radiography of the lateral spine might be necessary, especially when there is kyphosis or loss of height. Assess for vertebral fracture, using lateral spine radiography, when vertebral involvement is suspected.^6,7

❚ Assessment of fracture risk. Fracture risk can be assessed with any of a number of tools, including:

• Simplified Calculated Osteoporosis Risk Estimation (SCORE): www.medicalalgorithms.com/simplified-calculated-osteoporosis-risk-estimation-tool
• Osteoporosis Risk Assessment Instrument (ORAI): www.physio-pedia.com/The_Osteoporosis_Risk_Assessment_Instrument_(ORAI)

• Osteoporosis Index of Risk (OSIRIS): https://www.tandfonline.com/doi/abs/10.1080/gye.16.3.245.250?journalCode=igye20
• Osteoporosis Self-Assessment Tool (OST): www.ncbi.nlm.nih.gov/books/NBK45516/figure/ch10.f2/
• FRAX tool⁵: www.sheffield.ac.uk/FRAX.

The FRAX tool is widely used. It assesses a patient’s 10-year risk of fracture.

Diagnosis is based on these criteria

Diagnosis of osteoporosis is based on any 1 or more of the following criteria⁶:

• a history of fragility fracture not explained by metabolic bone disease
• T-score ≤ –2.5 (lumbar, hip, femoral neck, or 33% radius)
• a nation-specific FRAX score (in the absence of access to DXA).

❚ Secondary disease. Patients in whom secondary osteoporosis is suspected should undergo laboratory investigation to ascertain the cause; treatment of the underlying pathology might then be required. Evaluation for a secondary cause might include a complete blood count, comprehensive metabolic panel, protein electrophoresis and urinary protein electrophoresis (to rule out myeloproliferative and hematologic diseases), and tests of serum 25-hydroxyvitamin D, parathyroid hormone, serum calcium, alkaline phosphatase, 24-hour urinary calcium, sodium, and creatinine.^6,7 Specialized testing for biochemical markers of bone turnover—so-called bone-turnover markers—can be considered as part of the initial evaluation and follow-up, although the tests are not recommended by the US Preventive Services Task Force (see “Monitoring the efficacy of treatment,” later in the article, for more information about these markers).⁶

Although BMD by DXA remains the gold standard in screening for and diagnosing osteoporosis, a high rate of fracture is seen in patients with certain diseases, such as type 2 diabetes and ankylosing spondylitis, who have a nonosteoporotic low T-score. This raises concerns about the usefulness of BMD for diagnosing osteoporosis in patients who have one of these diseases.^13-16

❚ Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when risk of fracture is high. Oral bisphosphonates can be used as initial treatment.

❚ Trabecular bone score (TBS), a surrogate bone-quality measure that is calculated based on the spine DXA image, has recently been introduced in clinical practice, and can be used to predict fracture risk in conjunction with BMD assessment by DXA and the FRAX score.¹⁷ TBS provides an indirect index of the trabecular microarchitecture using pixel gray-level variation in lumbar spine DXA images.¹⁸ Three categories of TBS (≤ 1.200, degraded microarchitecture; 1.200-1.350, partially degraded microarchitecture; and > 1.350, normal microarchitecture) have been reported to correspond with a T-score of, respectively, ≤ −2.5; −2.5 to −1.0; and > −1.0.¹⁸ TBS can be used only in patients with a body mass index of 15 to 37.5.^19,20

There is no recommendation for monitoring bone quality using TBS after osteoporosis treatment. Such monitoring is at the clinician’s discretion for appropriate patients who might not show a risk of fracture, based on BMD measurement.

Continue to: Putting preventive measures into practice...

Putting preventive measures into practice

Measures to prevent osteoporosis and preserve bone health (TABLE 2^1,6) are best started in childhood but can be initiated at any age and maintained through the lifespan. Encourage older adults to adopt dietary and behavioral strategies to improve their bone health and prevent fracture. We recommend the following strategies; take each patient’s individual situation into consideration when electing to adopt any of these measures.

❚ Vitamin D. Consider checking the serum 25-hydroxyvitamin D level and providing supplementation (800-1000 IU daily, the National Osteoporosis Foundation recommends¹) as necessary to maintain the level at 30-50 ng/mL.⁶

❚ Calcium. Encourage a daily dietary calcium intake of 1000-1200 mg. Supplement calcium if you determine that diet does not provide an adequate amount.

❚ Alcohol. Advise patients to limit consumption to < 3 drinks a day.

❚ Tobacco. Advise smoking cessation.

❚ Activity. Encourage an active lifestyle, including regular weight-bearing and balance exercises and resistance exercises such as Pilates, weightlifting, and tai chi. The regimen should be tailored to the patient’s individual situation.

❚ Medical therapy for concomitant illness. When possible, prescribe medications for chronic comorbidities that can also benefit bone health. For example, long-term use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics for hypertension are associated with a slower decline in BMD in some populations.^21-23

Tailor treatment to patient’s circumstances

TABLE 3^4,6,24 describes indications for pharmacotherapy in osteoporosis. Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when fracture risk is high.²⁴

Generally, you should undertake a discussion with the patient of the relative risks and benefits of treatment, taking into account their values and preferences, to come to a shared decision. Tailoring treatment, based on the patient’s distinctive circumstances, through shared decision-making is key to compliance.²⁵

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.²⁶ Women with a very high BMD might not need to be retested with DXA any sooner than every 10 to 15 years.

There are 3 main classes of first-line pharmacotherapeutic agents for osteoporosis in older adults (TABLE 4^4,6,7,26-41): antiresorptives (bisphosphonates and denosumab), anabolics (teriparatide and abaloparatide), and a monoclonal sclerostin antibody (romosozumab). (TABLE 4^4,6,7,26-41 and the discussion in this section also remark on the selective estrogen-receptor modulator raloxifene, which is used in special clinical circumstances but has been removed from the first line of osteoporosis pharmacotherapy.)

Continue to: Influence of chronic...

Influence of chronic diseaseon bone health

Chronic diseases—hypertension, type 2 diabetes, hyperthyroidism, rheumatoid arthritis, ankylosing spondylitis, and gastroenterologic disorders such as celiac disease and ulcerative colitis—are known to affect bone loss that can hasten osteoporosis.^16,18,21 Furthermore, medications used to treat chronic diseases are known to affect bone health: Some, such as statins, ACE inhibitors, and hydrochlorothiazide, are bone protective; others, such as steroids, pioglitazone, and selective serotonin reuptake inhibitors, accelerate bone loss.^1,14,42,43 It is important to be aware of the effect of a patient’s chronic diseases, and treatments for those diseases, on bone health, to help develop an individualized osteoporosis prevention plan.

Monitoring the efficacy of treatment

Treatment of osteoporosis should not be initiated without baseline measurement of BMD of the spine and hip. Subsequent to establishing that baseline, serial measurement of BMD can be used to (1) determine when treatment needs to be initiated for an untreated patient and (2) assess response in a treated patient. There is no consensus on the interval at which DXA should be repeated for the purpose of monitoring treatment response; frequency depends on the individual’s circumstances and the medication used. Notably, many physicians repeat DXA after 2 years of treatment⁸; however, the American College of Physicians recommends against repeating DXA within the first 5 years of pharmacotherapy in women.²⁴

Patients with suspected vertebral fracture or those with loss of height > 1.5 inches require lateral radiographs of the thoracic and lumbar spine to assess the status of fractures.^4,6

❚ Bone-turnover markers measured in serum can be used to assess treatment efficacy and patient adherence. The formation marker procollagen type I N-terminal propeptide (P1NP) and the resorption marker beta C-terminal cross-linking telopeptide of type 1 collagen (bCTX) are preferred for evaluating bone turnover in the clinical setting. Assessing P1NP and bCTX at baseline and after 3 months of treatment might be effective in monitoring adherence, particularly in patients taking a bisphosphonate.⁴⁴

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.

Be sure to address fall prevention

It is important to address falls, and how to prevent them, in patients with osteoporosis. Falls can precipitate fracture in older adults with reduced BMD, and fractures are the most common and debilitating manifestation of osteoporosis. Your discussion of falls with patients should include⁴⁵:

• consequences of falls
• cautions about medications that can cloud mental alertness
• use of appropriate footwear
• home safety, such as adequate lighting, removal of floor clutter, and installation of handrails in the bathroom and stairwells and on outside steps.
• having an annual comprehensive eye exam.

Osteoporosis is avoidable and treatable

Earlier research reported various expressions of number needed to treat for medical management of osteoporosis—making it difficult to follow a single number as a reference for gauging the effectiveness of pharmacotherapy.^46,47 However, for older adults of different ethnic and racial backgrounds with multiple comorbidities and polypharmacy, it might be more pragmatic in primary care to establish a model of goal-oriented, individualized care. By focusing on prevention of bone loss, and being mindful that the risk of fracture almost doubles with a decrease of 1 SD in BMD, you can translate numbers to goals of care.⁴⁸

In the United States, approximately one-half of osteoporosis cases in adults ≥ 50 years are managed by primary care providers. As a chronic disease, osteoporosis requires that you, first, provide regular monitoring and assessment, because risk can vary with comorbidities,⁴⁹ and, second, discuss and initiate screening and treatment as appropriate, which can be done annually during a well-care visit.

CORRESPONDENCE

Nahid Rianon, MD, DrPH, Department of Family and Community Medicine, UTHealth McGovern Medical School, 6431 Fannin Street #JJL 324C, Houston, TX, 77030; [email protected]

As the population of older adults rises, primary osteoporosis has become a problem of public health significance, resulting in more than 2 million fractures and $19 billion in related costs annually in the United States.¹ Despite the availability of effective primary and secondary preventive measures, many older adults do not receive adequate information on bone health from their primary care provider.² Initiation of osteoporosis treatment is low even among patients who have had an osteoporotic fracture: Fewer than one-­quarter of older adults with hip fracture have begun taking osteoporosis medication within 12 months of hospital discharge.³

In this overview of osteoporosis care, we provide information on how to evaluate and manage older adults in primary care settings who are at risk of, or have been given a diagnosis of, primary osteoporosis. The guidance that we offer reflects the most recent updates and recommendations by relevant professional societies.^1,4-7

The nature and scope of an urgent problem

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture.⁸ Operationally, it is defined by the World Health Organization as a bone mineral density (BMD) score below 2.5 SD from the mean value for a young White woman (ie, T-score ≤ –2.5).⁹ Primary osteoporosis is age related and occurs mostly in postmenopausal women and older men, affecting 25% of women and 5% of men ≥ 65 years.¹⁰

An osteoporotic fracture is particularly devastating in an older adult because it can cause pain, reduced mobility, depression, and social isolation and can increase the risk of related mortality.¹ The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.¹ Therefore, it is of paramount importance to identify patients who are at increased risk of fracture and intervene early.

The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.

Clinical manifestations

Osteoporosis does not have a primary presentation; rather, disease manifests clinically when a patient develops complications. Often, a fragility fracture is the first sign in an older person.¹¹

A fracture is the most important complication of osteoporosis and can result from low-trauma injury or a fall from standing height—thus, the term “fragility fracture.” Osteoporotic fractures commonly involve the vertebra, hip, and wrist. Hip and extremity fractures can result in limited or lost mobility and depression. Vertebral fractures can be asymptomatic or result in kyphosis and loss of height. Fractures can give rise to pain.

Age and female sexare risk factors

TABLE 1^1,6,10 lists risk factors associated with osteoporosis. Age is the most important; prevalence of osteoporosis increases with age. Other nonmodifiable risk factors include female sex (the disease appears earlier in women who enter menopause prematurely), family history of osteoporosis, and race and ethnicity. Twenty percent of Asian and non-Hispanic White women > 50 years have osteoporosis.¹ A study showed that Mexican Americans are at higher risk of osteoporosis than non-Hispanic Whites; non-Hispanic Blacks are least affected.¹⁰

Other risk factors include low body weight (< 127 lb) and a history of fractures after age 50. Behavioral risk factors include smoking, excessive alcohol intake (> 3 drinks/d), poor nutrition, and a sedentary lifestyle.^1,6

Continue to: Who should be screened?...

Who should be screened?

Screening is generally performed with a clinical evaluation and a dual-energy x-ray absorptiometry (DXA) scan of BMD. Measurement of BMD is generally recommended for screening all women ≥ 65 years and those < 65 years whose 10-year risk of fracture is equivalent to that of a 65-year-old White woman (see “Assessment of fracture risk” later in the article). For men, the US Preventive Services Task Force recommends screening those with a prior fracture or a secondary risk factor for disease.⁵ However, the National Osteoporosis Foundation recommends screening all men ≥ 70 years and those 50 to 69 years whose risk profile shows heightened risk.^1,4

DXA of the spine and hip is preferred; the distal one-third of the radius (termed “33% radius”) of the nondominant arm can be used when spine and hip BMD cannot be interpreted because of bone changes from the disease process or artifacts, or in certain diseases in which the wrist region shows the earliest change (eg, primary hyperparathyroidism).^6,7

Clinical evaluation includes a detailed history, physical examination, laboratory screening, and assessment for risk of fracture.

❚ History. Explore the presence of risk factors, including fractures in adulthood, falls, medication use, alcohol and tobacco use, family history of osteoporosis, and chronic disease.^6,7

❚ Physical exam. Assess height, including any loss (> 1.5 in) since the patient’s second or third decade of life; kyphosis; frailty; and balance and mobility problems.^4,6,7

❚  Laboratory and imaging studies. Perform basic laboratory testing when DXA is abnormal, including thyroid function, serum calcium, and renal function.^6,12 Radiography of the lateral spine might be necessary, especially when there is kyphosis or loss of height. Assess for vertebral fracture, using lateral spine radiography, when vertebral involvement is suspected.^6,7

❚ Assessment of fracture risk. Fracture risk can be assessed with any of a number of tools, including:

• Simplified Calculated Osteoporosis Risk Estimation (SCORE): www.medicalalgorithms.com/simplified-calculated-osteoporosis-risk-estimation-tool
• Osteoporosis Risk Assessment Instrument (ORAI): www.physio-pedia.com/The_Osteoporosis_Risk_Assessment_Instrument_(ORAI)

• Osteoporosis Index of Risk (OSIRIS): https://www.tandfonline.com/doi/abs/10.1080/gye.16.3.245.250?journalCode=igye20
• Osteoporosis Self-Assessment Tool (OST): www.ncbi.nlm.nih.gov/books/NBK45516/figure/ch10.f2/
• FRAX tool⁵: www.sheffield.ac.uk/FRAX.

The FRAX tool is widely used. It assesses a patient’s 10-year risk of fracture.

Diagnosis is based on these criteria

Diagnosis of osteoporosis is based on any 1 or more of the following criteria⁶:

• a history of fragility fracture not explained by metabolic bone disease
• T-score ≤ –2.5 (lumbar, hip, femoral neck, or 33% radius)
• a nation-specific FRAX score (in the absence of access to DXA).

❚ Secondary disease. Patients in whom secondary osteoporosis is suspected should undergo laboratory investigation to ascertain the cause; treatment of the underlying pathology might then be required. Evaluation for a secondary cause might include a complete blood count, comprehensive metabolic panel, protein electrophoresis and urinary protein electrophoresis (to rule out myeloproliferative and hematologic diseases), and tests of serum 25-hydroxyvitamin D, parathyroid hormone, serum calcium, alkaline phosphatase, 24-hour urinary calcium, sodium, and creatinine.^6,7 Specialized testing for biochemical markers of bone turnover—so-called bone-turnover markers—can be considered as part of the initial evaluation and follow-up, although the tests are not recommended by the US Preventive Services Task Force (see “Monitoring the efficacy of treatment,” later in the article, for more information about these markers).⁶

Although BMD by DXA remains the gold standard in screening for and diagnosing osteoporosis, a high rate of fracture is seen in patients with certain diseases, such as type 2 diabetes and ankylosing spondylitis, who have a nonosteoporotic low T-score. This raises concerns about the usefulness of BMD for diagnosing osteoporosis in patients who have one of these diseases.^13-16

❚ Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when risk of fracture is high. Oral bisphosphonates can be used as initial treatment.

❚ Trabecular bone score (TBS), a surrogate bone-quality measure that is calculated based on the spine DXA image, has recently been introduced in clinical practice, and can be used to predict fracture risk in conjunction with BMD assessment by DXA and the FRAX score.¹⁷ TBS provides an indirect index of the trabecular microarchitecture using pixel gray-level variation in lumbar spine DXA images.¹⁸ Three categories of TBS (≤ 1.200, degraded microarchitecture; 1.200-1.350, partially degraded microarchitecture; and > 1.350, normal microarchitecture) have been reported to correspond with a T-score of, respectively, ≤ −2.5; −2.5 to −1.0; and > −1.0.¹⁸ TBS can be used only in patients with a body mass index of 15 to 37.5.^19,20

There is no recommendation for monitoring bone quality using TBS after osteoporosis treatment. Such monitoring is at the clinician’s discretion for appropriate patients who might not show a risk of fracture, based on BMD measurement.

Continue to: Putting preventive measures into practice...

Putting preventive measures into practice

Measures to prevent osteoporosis and preserve bone health (TABLE 2^1,6) are best started in childhood but can be initiated at any age and maintained through the lifespan. Encourage older adults to adopt dietary and behavioral strategies to improve their bone health and prevent fracture. We recommend the following strategies; take each patient’s individual situation into consideration when electing to adopt any of these measures.

❚ Vitamin D. Consider checking the serum 25-hydroxyvitamin D level and providing supplementation (800-1000 IU daily, the National Osteoporosis Foundation recommends¹) as necessary to maintain the level at 30-50 ng/mL.⁶

❚ Calcium. Encourage a daily dietary calcium intake of 1000-1200 mg. Supplement calcium if you determine that diet does not provide an adequate amount.

❚ Alcohol. Advise patients to limit consumption to < 3 drinks a day.

❚ Tobacco. Advise smoking cessation.

❚ Activity. Encourage an active lifestyle, including regular weight-bearing and balance exercises and resistance exercises such as Pilates, weightlifting, and tai chi. The regimen should be tailored to the patient’s individual situation.

❚ Medical therapy for concomitant illness. When possible, prescribe medications for chronic comorbidities that can also benefit bone health. For example, long-term use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics for hypertension are associated with a slower decline in BMD in some populations.^21-23

Tailor treatment to patient’s circumstances

TABLE 3^4,6,24 describes indications for pharmacotherapy in osteoporosis. Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when fracture risk is high.²⁴

Generally, you should undertake a discussion with the patient of the relative risks and benefits of treatment, taking into account their values and preferences, to come to a shared decision. Tailoring treatment, based on the patient’s distinctive circumstances, through shared decision-making is key to compliance.²⁵

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.²⁶ Women with a very high BMD might not need to be retested with DXA any sooner than every 10 to 15 years.

There are 3 main classes of first-line pharmacotherapeutic agents for osteoporosis in older adults (TABLE 4^4,6,7,26-41): antiresorptives (bisphosphonates and denosumab), anabolics (teriparatide and abaloparatide), and a monoclonal sclerostin antibody (romosozumab). (TABLE 4^4,6,7,26-41 and the discussion in this section also remark on the selective estrogen-receptor modulator raloxifene, which is used in special clinical circumstances but has been removed from the first line of osteoporosis pharmacotherapy.)

Continue to: Influence of chronic...

Influence of chronic diseaseon bone health

Chronic diseases—hypertension, type 2 diabetes, hyperthyroidism, rheumatoid arthritis, ankylosing spondylitis, and gastroenterologic disorders such as celiac disease and ulcerative colitis—are known to affect bone loss that can hasten osteoporosis.^16,18,21 Furthermore, medications used to treat chronic diseases are known to affect bone health: Some, such as statins, ACE inhibitors, and hydrochlorothiazide, are bone protective; others, such as steroids, pioglitazone, and selective serotonin reuptake inhibitors, accelerate bone loss.^1,14,42,43 It is important to be aware of the effect of a patient’s chronic diseases, and treatments for those diseases, on bone health, to help develop an individualized osteoporosis prevention plan.

Monitoring the efficacy of treatment

Treatment of osteoporosis should not be initiated without baseline measurement of BMD of the spine and hip. Subsequent to establishing that baseline, serial measurement of BMD can be used to (1) determine when treatment needs to be initiated for an untreated patient and (2) assess response in a treated patient. There is no consensus on the interval at which DXA should be repeated for the purpose of monitoring treatment response; frequency depends on the individual’s circumstances and the medication used. Notably, many physicians repeat DXA after 2 years of treatment⁸; however, the American College of Physicians recommends against repeating DXA within the first 5 years of pharmacotherapy in women.²⁴

Patients with suspected vertebral fracture or those with loss of height > 1.5 inches require lateral radiographs of the thoracic and lumbar spine to assess the status of fractures.^4,6

❚ Bone-turnover markers measured in serum can be used to assess treatment efficacy and patient adherence. The formation marker procollagen type I N-terminal propeptide (P1NP) and the resorption marker beta C-terminal cross-linking telopeptide of type 1 collagen (bCTX) are preferred for evaluating bone turnover in the clinical setting. Assessing P1NP and bCTX at baseline and after 3 months of treatment might be effective in monitoring adherence, particularly in patients taking a bisphosphonate.⁴⁴

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.

Be sure to address fall prevention

It is important to address falls, and how to prevent them, in patients with osteoporosis. Falls can precipitate fracture in older adults with reduced BMD, and fractures are the most common and debilitating manifestation of osteoporosis. Your discussion of falls with patients should include⁴⁵:

• consequences of falls
• cautions about medications that can cloud mental alertness
• use of appropriate footwear
• home safety, such as adequate lighting, removal of floor clutter, and installation of handrails in the bathroom and stairwells and on outside steps.
• having an annual comprehensive eye exam.

Osteoporosis is avoidable and treatable

Earlier research reported various expressions of number needed to treat for medical management of osteoporosis—making it difficult to follow a single number as a reference for gauging the effectiveness of pharmacotherapy.^46,47 However, for older adults of different ethnic and racial backgrounds with multiple comorbidities and polypharmacy, it might be more pragmatic in primary care to establish a model of goal-oriented, individualized care. By focusing on prevention of bone loss, and being mindful that the risk of fracture almost doubles with a decrease of 1 SD in BMD, you can translate numbers to goals of care.⁴⁸

In the United States, approximately one-half of osteoporosis cases in adults ≥ 50 years are managed by primary care providers. As a chronic disease, osteoporosis requires that you, first, provide regular monitoring and assessment, because risk can vary with comorbidities,⁴⁹ and, second, discuss and initiate screening and treatment as appropriate, which can be done annually during a well-care visit.

CORRESPONDENCE

Nahid Rianon, MD, DrPH, Department of Family and Community Medicine, UTHealth McGovern Medical School, 6431 Fannin Street #JJL 324C, Houston, TX, 77030; [email protected]

As the population of older adults rises, primary osteoporosis has become a problem of public health significance, resulting in more than 2 million fractures and $19 billion in related costs annually in the United States.¹ Despite the availability of effective primary and secondary preventive measures, many older adults do not receive adequate information on bone health from their primary care provider.² Initiation of osteoporosis treatment is low even among patients who have had an osteoporotic fracture: Fewer than one-­quarter of older adults with hip fracture have begun taking osteoporosis medication within 12 months of hospital discharge.³

In this overview of osteoporosis care, we provide information on how to evaluate and manage older adults in primary care settings who are at risk of, or have been given a diagnosis of, primary osteoporosis. The guidance that we offer reflects the most recent updates and recommendations by relevant professional societies.^1,4-7

The nature and scope of an urgent problem

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture.⁸ Operationally, it is defined by the World Health Organization as a bone mineral density (BMD) score below 2.5 SD from the mean value for a young White woman (ie, T-score ≤ –2.5).⁹ Primary osteoporosis is age related and occurs mostly in postmenopausal women and older men, affecting 25% of women and 5% of men ≥ 65 years.¹⁰

An osteoporotic fracture is particularly devastating in an older adult because it can cause pain, reduced mobility, depression, and social isolation and can increase the risk of related mortality.¹ The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.¹ Therefore, it is of paramount importance to identify patients who are at increased risk of fracture and intervene early.

The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.

Clinical manifestations

Osteoporosis does not have a primary presentation; rather, disease manifests clinically when a patient develops complications. Often, a fragility fracture is the first sign in an older person.¹¹

A fracture is the most important complication of osteoporosis and can result from low-trauma injury or a fall from standing height—thus, the term “fragility fracture.” Osteoporotic fractures commonly involve the vertebra, hip, and wrist. Hip and extremity fractures can result in limited or lost mobility and depression. Vertebral fractures can be asymptomatic or result in kyphosis and loss of height. Fractures can give rise to pain.

Age and female sexare risk factors

TABLE 1^1,6,10 lists risk factors associated with osteoporosis. Age is the most important; prevalence of osteoporosis increases with age. Other nonmodifiable risk factors include female sex (the disease appears earlier in women who enter menopause prematurely), family history of osteoporosis, and race and ethnicity. Twenty percent of Asian and non-Hispanic White women > 50 years have osteoporosis.¹ A study showed that Mexican Americans are at higher risk of osteoporosis than non-Hispanic Whites; non-Hispanic Blacks are least affected.¹⁰

Other risk factors include low body weight (< 127 lb) and a history of fractures after age 50. Behavioral risk factors include smoking, excessive alcohol intake (> 3 drinks/d), poor nutrition, and a sedentary lifestyle.^1,6

Continue to: Who should be screened?...

Who should be screened?

Screening is generally performed with a clinical evaluation and a dual-energy x-ray absorptiometry (DXA) scan of BMD. Measurement of BMD is generally recommended for screening all women ≥ 65 years and those < 65 years whose 10-year risk of fracture is equivalent to that of a 65-year-old White woman (see “Assessment of fracture risk” later in the article). For men, the US Preventive Services Task Force recommends screening those with a prior fracture or a secondary risk factor for disease.⁵ However, the National Osteoporosis Foundation recommends screening all men ≥ 70 years and those 50 to 69 years whose risk profile shows heightened risk.^1,4

DXA of the spine and hip is preferred; the distal one-third of the radius (termed “33% radius”) of the nondominant arm can be used when spine and hip BMD cannot be interpreted because of bone changes from the disease process or artifacts, or in certain diseases in which the wrist region shows the earliest change (eg, primary hyperparathyroidism).^6,7

Clinical evaluation includes a detailed history, physical examination, laboratory screening, and assessment for risk of fracture.

❚ History. Explore the presence of risk factors, including fractures in adulthood, falls, medication use, alcohol and tobacco use, family history of osteoporosis, and chronic disease.^6,7

❚ Physical exam. Assess height, including any loss (> 1.5 in) since the patient’s second or third decade of life; kyphosis; frailty; and balance and mobility problems.^4,6,7

❚  Laboratory and imaging studies. Perform basic laboratory testing when DXA is abnormal, including thyroid function, serum calcium, and renal function.^6,12 Radiography of the lateral spine might be necessary, especially when there is kyphosis or loss of height. Assess for vertebral fracture, using lateral spine radiography, when vertebral involvement is suspected.^6,7

❚ Assessment of fracture risk. Fracture risk can be assessed with any of a number of tools, including:

• Simplified Calculated Osteoporosis Risk Estimation (SCORE): www.medicalalgorithms.com/simplified-calculated-osteoporosis-risk-estimation-tool
• Osteoporosis Risk Assessment Instrument (ORAI): www.physio-pedia.com/The_Osteoporosis_Risk_Assessment_Instrument_(ORAI)

• Osteoporosis Index of Risk (OSIRIS): https://www.tandfonline.com/doi/abs/10.1080/gye.16.3.245.250?journalCode=igye20
• Osteoporosis Self-Assessment Tool (OST): www.ncbi.nlm.nih.gov/books/NBK45516/figure/ch10.f2/
• FRAX tool⁵: www.sheffield.ac.uk/FRAX.

The FRAX tool is widely used. It assesses a patient’s 10-year risk of fracture.

Diagnosis is based on these criteria

Diagnosis of osteoporosis is based on any 1 or more of the following criteria⁶:

• a history of fragility fracture not explained by metabolic bone disease
• T-score ≤ –2.5 (lumbar, hip, femoral neck, or 33% radius)
• a nation-specific FRAX score (in the absence of access to DXA).

❚ Secondary disease. Patients in whom secondary osteoporosis is suspected should undergo laboratory investigation to ascertain the cause; treatment of the underlying pathology might then be required. Evaluation for a secondary cause might include a complete blood count, comprehensive metabolic panel, protein electrophoresis and urinary protein electrophoresis (to rule out myeloproliferative and hematologic diseases), and tests of serum 25-hydroxyvitamin D, parathyroid hormone, serum calcium, alkaline phosphatase, 24-hour urinary calcium, sodium, and creatinine.^6,7 Specialized testing for biochemical markers of bone turnover—so-called bone-turnover markers—can be considered as part of the initial evaluation and follow-up, although the tests are not recommended by the US Preventive Services Task Force (see “Monitoring the efficacy of treatment,” later in the article, for more information about these markers).⁶

Although BMD by DXA remains the gold standard in screening for and diagnosing osteoporosis, a high rate of fracture is seen in patients with certain diseases, such as type 2 diabetes and ankylosing spondylitis, who have a nonosteoporotic low T-score. This raises concerns about the usefulness of BMD for diagnosing osteoporosis in patients who have one of these diseases.^13-16

❚ Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when risk of fracture is high. Oral bisphosphonates can be used as initial treatment.

❚ Trabecular bone score (TBS), a surrogate bone-quality measure that is calculated based on the spine DXA image, has recently been introduced in clinical practice, and can be used to predict fracture risk in conjunction with BMD assessment by DXA and the FRAX score.¹⁷ TBS provides an indirect index of the trabecular microarchitecture using pixel gray-level variation in lumbar spine DXA images.¹⁸ Three categories of TBS (≤ 1.200, degraded microarchitecture; 1.200-1.350, partially degraded microarchitecture; and > 1.350, normal microarchitecture) have been reported to correspond with a T-score of, respectively, ≤ −2.5; −2.5 to −1.0; and > −1.0.¹⁸ TBS can be used only in patients with a body mass index of 15 to 37.5.^19,20

There is no recommendation for monitoring bone quality using TBS after osteoporosis treatment. Such monitoring is at the clinician’s discretion for appropriate patients who might not show a risk of fracture, based on BMD measurement.

Continue to: Putting preventive measures into practice...

Putting preventive measures into practice

Measures to prevent osteoporosis and preserve bone health (TABLE 2^1,6) are best started in childhood but can be initiated at any age and maintained through the lifespan. Encourage older adults to adopt dietary and behavioral strategies to improve their bone health and prevent fracture. We recommend the following strategies; take each patient’s individual situation into consideration when electing to adopt any of these measures.

❚ Vitamin D. Consider checking the serum 25-hydroxyvitamin D level and providing supplementation (800-1000 IU daily, the National Osteoporosis Foundation recommends¹) as necessary to maintain the level at 30-50 ng/mL.⁶

❚ Calcium. Encourage a daily dietary calcium intake of 1000-1200 mg. Supplement calcium if you determine that diet does not provide an adequate amount.

❚ Alcohol. Advise patients to limit consumption to < 3 drinks a day.

❚ Tobacco. Advise smoking cessation.

❚ Activity. Encourage an active lifestyle, including regular weight-bearing and balance exercises and resistance exercises such as Pilates, weightlifting, and tai chi. The regimen should be tailored to the patient’s individual situation.

❚ Medical therapy for concomitant illness. When possible, prescribe medications for chronic comorbidities that can also benefit bone health. For example, long-term use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics for hypertension are associated with a slower decline in BMD in some populations.^21-23

Tailor treatment to patient’s circumstances

TABLE 3^4,6,24 describes indications for pharmacotherapy in osteoporosis. Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when fracture risk is high.²⁴

Generally, you should undertake a discussion with the patient of the relative risks and benefits of treatment, taking into account their values and preferences, to come to a shared decision. Tailoring treatment, based on the patient’s distinctive circumstances, through shared decision-making is key to compliance.²⁵

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.²⁶ Women with a very high BMD might not need to be retested with DXA any sooner than every 10 to 15 years.

There are 3 main classes of first-line pharmacotherapeutic agents for osteoporosis in older adults (TABLE 4^4,6,7,26-41): antiresorptives (bisphosphonates and denosumab), anabolics (teriparatide and abaloparatide), and a monoclonal sclerostin antibody (romosozumab). (TABLE 4^4,6,7,26-41 and the discussion in this section also remark on the selective estrogen-receptor modulator raloxifene, which is used in special clinical circumstances but has been removed from the first line of osteoporosis pharmacotherapy.)

Continue to: Influence of chronic...

Influence of chronic diseaseon bone health

Chronic diseases—hypertension, type 2 diabetes, hyperthyroidism, rheumatoid arthritis, ankylosing spondylitis, and gastroenterologic disorders such as celiac disease and ulcerative colitis—are known to affect bone loss that can hasten osteoporosis.^16,18,21 Furthermore, medications used to treat chronic diseases are known to affect bone health: Some, such as statins, ACE inhibitors, and hydrochlorothiazide, are bone protective; others, such as steroids, pioglitazone, and selective serotonin reuptake inhibitors, accelerate bone loss.^1,14,42,43 It is important to be aware of the effect of a patient’s chronic diseases, and treatments for those diseases, on bone health, to help develop an individualized osteoporosis prevention plan.

Monitoring the efficacy of treatment

Treatment of osteoporosis should not be initiated without baseline measurement of BMD of the spine and hip. Subsequent to establishing that baseline, serial measurement of BMD can be used to (1) determine when treatment needs to be initiated for an untreated patient and (2) assess response in a treated patient. There is no consensus on the interval at which DXA should be repeated for the purpose of monitoring treatment response; frequency depends on the individual’s circumstances and the medication used. Notably, many physicians repeat DXA after 2 years of treatment⁸; however, the American College of Physicians recommends against repeating DXA within the first 5 years of pharmacotherapy in women.²⁴

Patients with suspected vertebral fracture or those with loss of height > 1.5 inches require lateral radiographs of the thoracic and lumbar spine to assess the status of fractures.^4,6

❚ Bone-turnover markers measured in serum can be used to assess treatment efficacy and patient adherence. The formation marker procollagen type I N-terminal propeptide (P1NP) and the resorption marker beta C-terminal cross-linking telopeptide of type 1 collagen (bCTX) are preferred for evaluating bone turnover in the clinical setting. Assessing P1NP and bCTX at baseline and after 3 months of treatment might be effective in monitoring adherence, particularly in patients taking a bisphosphonate.⁴⁴

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.

Be sure to address fall prevention

It is important to address falls, and how to prevent them, in patients with osteoporosis. Falls can precipitate fracture in older adults with reduced BMD, and fractures are the most common and debilitating manifestation of osteoporosis. Your discussion of falls with patients should include⁴⁵:

• consequences of falls
• cautions about medications that can cloud mental alertness
• use of appropriate footwear
• home safety, such as adequate lighting, removal of floor clutter, and installation of handrails in the bathroom and stairwells and on outside steps.
• having an annual comprehensive eye exam.

Osteoporosis is avoidable and treatable

Earlier research reported various expressions of number needed to treat for medical management of osteoporosis—making it difficult to follow a single number as a reference for gauging the effectiveness of pharmacotherapy.^46,47 However, for older adults of different ethnic and racial backgrounds with multiple comorbidities and polypharmacy, it might be more pragmatic in primary care to establish a model of goal-oriented, individualized care. By focusing on prevention of bone loss, and being mindful that the risk of fracture almost doubles with a decrease of 1 SD in BMD, you can translate numbers to goals of care.⁴⁸

In the United States, approximately one-half of osteoporosis cases in adults ≥ 50 years are managed by primary care providers. As a chronic disease, osteoporosis requires that you, first, provide regular monitoring and assessment, because risk can vary with comorbidities,⁴⁹ and, second, discuss and initiate screening and treatment as appropriate, which can be done annually during a well-care visit.

CORRESPONDENCE

Nahid Rianon, MD, DrPH, Department of Family and Community Medicine, UTHealth McGovern Medical School, 6431 Fannin Street #JJL 324C, Houston, TX, 77030; [email protected]

Skin and soft-tissue infections, frequently encountered in primary care, range from the uncomplicated erysipelas to the life-threatening necrotizing fasciitis. This review draws from the latest evidence and guidelines to help guide the care you provide to patients with cellulitis, orbital cellulitis, erysipelas, folliculitis, furuncles, carbuncles, abscesses, and necrotizing fasciitis.

Cellulitis

Cellulitis, an infection of the deep dermal and subcutaneous layers of the skin, has become increasingly common in recent years, with both incidence and hospitalization rates rising.¹ Cellulitis occurs when pathogens enter the dermis through breaks in the skin barrier due to cutaneous fungal infections, trauma, pressure sores, venous stasis, or inflammation. The diagnosis is often made clinically based on characteristic skin findings—classically an acute, poorly demarcated area of erythema, warmth, swelling, and tenderness. Lymphangitic streaking and local lymphadenopathy may also be present. Infection often occurs on an extremity (although it can be found on other areas of the body) and is usually unilateral. Fever may or may not be present.²

Likely responsible microorganisms. Staphylococcus aureus and Group A streptococci (often Streptococcus pyogenes) are common culprits. One systematic review that examined cultures taken of intact skin in cellulitis patients found S aureus to be about twice as common as S pyogenes, with both bacteria accounting for a little more than 70% of cases. Of the remaining positive cultures, the most common organisms were alpha-­hemolytic streptococcus, group B streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli, Pasteurella multocida, and Proteus mirabilis.³ Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S aureus was responsible for just 14%), with the remainder of cases caused by gram-negative organisms such as E coli and P aeruginosa.⁴

Treatment considerations. Strict treatment guidelines for cellulitis are lacking, but general consensus encourages the use of antibiotics and occasionally surgery. For mild and moderate cases of cellulitis, prescribe oral and parenteral antibiotics to cover for streptococci and methicillin-susceptible S aureus, respectively. Expand coverage to include vancomycin if nasal colonization shows methicillin-resistant S aureus (MRSA) or if you otherwise suspect prior MRSA exposure. Expanded coverage will also be needed if there is severe nonpurulent infection associated with penetrating trauma or a history of intravenous drug use, or the patient meets criteria for systemic inflammatory response syndrome. If patients are severely compromised (eg, neutropenic), it is reasonable to further add broad-spectrum coverage (eg, intravenous piperacillin-­tazobactam or carbapenem). Typical duration of treatment is 5 to 7 days, although this should be extended if there is no clinical improvement.

For orbital cellulitis, choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.

Generally, cellulitis can be managed in the outpatient setting, although hospitalization is recommended if there are concerns for deep or necrotizing infection, if patients are nonadherent to therapy or are immunocompromised, or if outpatient therapy has failed.⁵ Furthermore, in an observational study of 606 adult patients, prior episodes of cellulitis, venous insufficiency, and immunosuppression were all independently associated with poorer clinical outcomes.² Also treat underlying predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities such as fissures, scaling, or maceration.⁵ Consider the use of prophylactic antibiotics for patients who have had 3 to 4 episodes of cellulitis despite attempts to treat predisposing conditions. Prophylactic antibiotic regimens include penicillin or erythromycin orally and penicillin G benzathine intramuscularly.⁵ Antibiotic regimens are summarized in the TABLE.⁵

Orbital cellulitis

Orbital cellulitis is an infection of the tissues posterior to the orbital septum.^6,7 Periorbital, or preseptal, cellulitis occurs anterior to the orbital septum and is the more common of the 2 infections—84% compared with 16% for orbital cellulitis.⁶ However, orbital cellulitis, which affects mainly children at a median age of 7 years,⁶ must be detected and treated early due to the potential for serious complications such as cavernous sinus thrombosis, meningitis, intracranial abscess, and vision loss.⁷ Chemosis (conjunctival edema) and diplopia are more commonly associated with orbital cellulitis and are seldom seen with preseptal cellulitis.

Predominant causative organisms are S pneumoniae, Moraxella catarrhalis, non-typeable Haemophilus influenzae, and group A streptococcus. The most common mechanism of infection is tracking from periorbital structures (eg, paranasal and ethmoid sinusitis). Other causes include orbital trauma/fracture, periorbital surgery, and bacterial endocarditis. Clinically, patients present with limited ocular motility and proptosis associated with inflamed conjunctiva, orbital pain, headache, malaise, fever, eyelid edema, and possible decrease in visual acuity. The diagnosis is often made clinically and confirmed with orbital computed tomography (CT) with contrast, which can assist in ruling out intracranial involvement such as abscess.

Continue to: Antibiotic therapy

Antibiotic therapy, generally administered intravenously, is recommended for at least 3 days or until orbital symptoms begin to resolve. Choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.⁸ For instance, a regimen may include vancomycin for MRSA coverage, a third-generation cephalosporin, or metronidazole for anaerobic coverage if there is concern about intracranial involvement. Surgical intervention is often reserved for patients with inadequate response to antibiotic therapy, necessitating biopsy for pathogen identification, as well as drainage of large abscesses refractory to antibiotics.

Erysipelas

Erysipelas, a related yet distinct form of cellulitis, is a bacterial infection of the superficial dermis and hypodermis and is commonly caused by group A streptococcus.^5,9 Other less common organisms include S aureus, P aeruginosa, and enterobacteria. Erysipelas predominantly affects the lower extremities unilaterally (~90%); the arms and the face are the next most common locations. In addition to the rapid onset of well-demarcated erythema, pain, and swelling, patients may have fever and regional lymphadenopathy. Risk factors include portal of entry (eg, tinea pedis, ulceration), lymphedema, and diabetes. Complications of erysipelas include bullae from edema, abscess formation, and, rarely, bacteremia.

When clinical exam alone is inconclusive when evaluating skin and softtissue infections in children and adolescents, consider using ultrasound to improve diagnostic accuracy.

Antibiotic treatment regimens include penicillin G, macrolides (reserved for those with penicillin allergies), fluoroquinolones, and cephalosporins, with duration of treatment ranging from 10 to 14 days depending on infection severity. Fever, pain, and erythema generally improve within 48 to 72 hours of antibiotic therapy. If there is no improvement, consider alternative diagnoses, such as necrotizing fasciitis. Recurrence rates following the initial episode of erysipelas are estimated at 10% of patients at 6 months and 30% at 3 years.¹⁰

Folliculitis

Inflammation of hair follicles is characterized by superficial inflammation with the development of perifollicular papules or pustules on an erythematous base.^11,12 Folliculitis most commonly affects the face, scalp, thighs, buttocks, axillae, and inguinal areas.¹³ It may be caused by infection, an inflammatory reaction, or physical injury. Diagnosis is typically based on the patient’s history and physical examination.

Bacteria are the most common cause of infection, although fungi, viruses, and other entities can cause folliculitis. S aureus (methicillin sensitive or methicillin resistant) is the most common pathogen; in the past, superficial pustular folliculitis attributed to S aureus was referred to as Bockhart impetigo. Folliculitis secondary to P aeruginosa, often seen after exposure to contaminated water or hot tubs, is frequently referred to as “hot tub folliculitis.” Malassezia, a reported cause of fungal folliculitis, tends to occur in adolescents of either sex and men with high sebum production, is common in tropical climates, and can be associated with HIV or immunosuppression.^11,12,14

Continue to: Differential diagnosis...

Differential diagnosis of folliculitis includes pseudofolliculitis barbae, eosinophilic folliculitis, keratosis pilaris, acne vulgaris, candidiasis, contact dermatitis, impetigo, and miliaria.¹³ Pseudofolliculitis barbae is an inflammatory reaction to shaving, more commonly seen in darkly pigmented skin. Pseudofolliculitis develops when the hair shaft penetrates the wall of the follicle or directly enters the epidermis.

Initial treatment for mild disease includes the elimination of predisposing factors such as occlusion, moisture, and abrasion. The area should be kept clean and dry, avoiding friction. For localized disease, prescribe topical clindamycin, mupirocin ointment, or benzoyl peroxide. If symptoms fail to respond, prescribe a 7-day course of antibiotic that targets methicillin-sensitive S aureus—eg, cephalexin or dicloxacillin. Also consider doxycycline, which has anti-inflammatory effects and is effective against MRSA. For refractory lesions, ­trimethoprim-sulfamethoxazole, clindamycin, or minocycline may be useful. If you suspect pseudomonas, consider giving ciprofloxacin for 10 to 14 days for persistent lesions or if the patient is immunocompromised.^13,15 Consider obtaining bacterial, fungal, or viral cultures for lesions that fail to respond to initial treatment.

Do not routinely order cultures or prescribe antibiotics for uncomplicated abscesses.

Furuncles/carbuncles/abscesses

A furuncle, commonly referred to as a boil, is an infected hair follicle that becomes enclosed, creating a collection of pus. A carbuncle is a collection of furuncles that converge and drain through a single opening. An abscess is a localized collection of pus arising from within the dermis that can extend within deeper tissues.⁵ Furuncles, carbuncles, and abscesses are managed similarly with drainage and consideration for MRSA risk factors.

S aureus is the most common cause of these infections; 59% of skin abscesses are due to community-acquired MRSA.¹⁶ Anaerobes may contribute to the polymicrobial flora of skin abscesses.¹⁷ Risk factors for MRSA infection include a history of previous MRSA infection, diabetes, dialysis or renal failure, placement of an indwelling catheter or medical device, injection drug use, incarceration, close contact with a person with known MRSA infection or colonization, long-term care residence, hospitalization or surgery within the past 12 months, and high prevalence of MRSA in the community.⁵

Ultrasound improves diagnostic accuracy. One study showed that when a clinical exam alone was inconclusive in evaluating skin and soft-tissue infections in children and adolescents, an ultrasound-assisted examination improved diagnostic accuracy.¹⁸ Sensitivity of the clinical examination was 43.7%, compared with 77.6% for the clinical examination plus ultrasound.¹⁸

Continue to: Incision and drainage first

Incision and drainage first. Ultrasound-guided needle aspiration, however, has not improved treatment efficacy compared with incision and drainage,¹⁹ the mainstay approach for abscesses.¹⁷ The procedure to drain a furuncle, carbuncle, or abscess should include the expression of all purulent material and the removal of all loculations if possible. Wound culture is recommended during incision and drainage per current guidelines.⁵ Simple dry dressings are convenient and effective, although some wounds may require packing. Tap water (that is potable) is suitable for wound cleansing. However, there is no strong evidence that irrigating wounds increases healing or reduces infection.²⁰

Routine use of antibiotics is not recommended for simple cutaneous abscesses.^5,17,21 Evidence has been conflicting regarding empiric antibiotic coverage of MRSA following incision and drainage.^22-25 Guidelines recommend considering the initiation of antibiotics if there are multiple abscesses, gangrene, surrounding cellulitis, or systemic signs of infection, or if the host is immunocompromised.⁵

If MRSA is suspected, recommended antibiotic coverage includes trimethoprim-­sulfamethoxazole, clindamycin, doxycycline, or minocycline.⁵ If MRSA is identified, treatment options include dicloxacillin or cephalexin. For severe infections persisting after incision and drainage, in addition to oral antibiotic therapy, consider intravenous antibiotic options for MRSA: cefazolin, clindamycin, linezolid, nafcillin, telavancin, or vancomycin.⁵

Necrotizing fasciitis

Necrotizing fasciitis is a rare but potentially deadly infection of the skin and soft tissue. It progresses rapidly and spreads along fascial planes, leading to the necrosis of the superficial fascia. The infection often is more extensive than is indicated by superficial signs. Prompt diagnosis is imperative as necrotizing fasciitis is a surgical emergency.^5,26 In the United States, 500 to 1500 cases of necrotizing fasciitis occur each year.²⁷ Risk factors for necrotizing fasciitis include diabetes, peripheral vascular disease, malignancy, obesity, cirrhosis, renal failure, injection drug use, chronic corticosteroid therapy, alcohol abuse, malnutrition, and iatrogenic immunosuppression.^26,28

Monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.

Necrotizing fasciitis may be polymicrobial or monomicrobial. Polymicrobial infection, also referred to as type I, is often due to multiple bacteria that originate from the bowel flora, typically including a mix of anaerobic and aerobic organisms. On average, there can be 5 infecting organisms identified per wound, although in some cases up to 15 organisms have been identified in a single wound.⁵ Type I infection is often associated with tissue injury, abscess, or abdominal surgery. The majority of cases of necrotizing fasciitis are polymicrobial.^27,28

Continue to: Monomicrobial infection...

Monomicrobial infection, also referred to as type II, is often due to group A streptococcus, S aureus, vibrio spp, Aeromonas hyrophilio, or an anaerobic streptococci like peptostreptococcus spp. Typically monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.^5,26,29,30

Clinical presentation. In the early stages of disease, patients commonly complain of flu-like symptoms and extreme pain that is out of proportion to findings on the exam. Additional warning signs include fevers and other symptoms of toxicity such as tachycardia, hypotension, nausea, vomiting, and diarrhea. Later in the course, symptoms may localize to the affected area and include erythema, tense swelling, development of blisters or bullae, blackish blue discoloration of the skin, severe pain, and loss of sensation. In some cases involving gas-forming bacteria, tissue crepitus may be noted on exam.^5,27-31

Rely on clinical judgment to hasten surgical intervention. Laboratory or imaging findings may augment clinical judgment. But if you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery. Blood tests that may aid in the diagnosis of necrotizing fasciitis include a complete blood count with differential; coagulation studies; a comprehensive metabolic panel; assays of lactate, C-reactive protein (CRP), and creatinine kinase; and blood cultures. Most often, patients with necrotizing fasciitis will have leukocytosis or leukopenia, evidence of hemolysis, thrombocytopenia, acute renal failure, and significantly elevated CRP.

If you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery.

On any imaging modality, indications of necrotizing fasciitis are inflammatory infiltration of the deep fascia on the affected side that is absent on the contralateral side, and the presence of subcutaneous air (which is a specific but rare finding). Imaging modalities may include CT or magnetic resonance imaging. A definitive diagnosis can only be made with surgical exploration of the involved area. Definitive microbiologic diagnosis will require culture of organisms from affected tissue or blood.^5,26,30,31

First address any hemodynamic instability (hypotension is frequently encountered), followed by urgent surgical exploration, debridement of the wound, and antimicrobial therapy. Antibiotic treatment should align with probable pathogens and treatment should be continued until repeated surgical debridement is no longer necessary, clinical improvement is evident, and 48 to 72 hours have passed since defervescence. A reasonable initial empiric regimen in adults would include an agent that is effective against group A streptococcus, gram-negative pathogens, and anaerobes, such as a carbapenem or a beta-lactam-­beta-lactamase inhibitor such as piperacillin-­tazobactam. Additionally, include an agent that targets MRSA, such as vancomycin, linezolid, or clindamycin.⁵

CORRESPONDENCE
Karl T. Clebak, MD, Department of Family and Community Medicine Residency Program, Penn State Health M.S. Hershey Medical Center, 500 University Drive, H154/C1613, Hershey, PA 17033; [email protected]

Skin and soft-tissue infections, frequently encountered in primary care, range from the uncomplicated erysipelas to the life-threatening necrotizing fasciitis. This review draws from the latest evidence and guidelines to help guide the care you provide to patients with cellulitis, orbital cellulitis, erysipelas, folliculitis, furuncles, carbuncles, abscesses, and necrotizing fasciitis.

Cellulitis

Cellulitis, an infection of the deep dermal and subcutaneous layers of the skin, has become increasingly common in recent years, with both incidence and hospitalization rates rising.¹ Cellulitis occurs when pathogens enter the dermis through breaks in the skin barrier due to cutaneous fungal infections, trauma, pressure sores, venous stasis, or inflammation. The diagnosis is often made clinically based on characteristic skin findings—classically an acute, poorly demarcated area of erythema, warmth, swelling, and tenderness. Lymphangitic streaking and local lymphadenopathy may also be present. Infection often occurs on an extremity (although it can be found on other areas of the body) and is usually unilateral. Fever may or may not be present.²

Likely responsible microorganisms. Staphylococcus aureus and Group A streptococci (often Streptococcus pyogenes) are common culprits. One systematic review that examined cultures taken of intact skin in cellulitis patients found S aureus to be about twice as common as S pyogenes, with both bacteria accounting for a little more than 70% of cases. Of the remaining positive cultures, the most common organisms were alpha-­hemolytic streptococcus, group B streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli, Pasteurella multocida, and Proteus mirabilis.³ Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S aureus was responsible for just 14%), with the remainder of cases caused by gram-negative organisms such as E coli and P aeruginosa.⁴

Treatment considerations. Strict treatment guidelines for cellulitis are lacking, but general consensus encourages the use of antibiotics and occasionally surgery. For mild and moderate cases of cellulitis, prescribe oral and parenteral antibiotics to cover for streptococci and methicillin-susceptible S aureus, respectively. Expand coverage to include vancomycin if nasal colonization shows methicillin-resistant S aureus (MRSA) or if you otherwise suspect prior MRSA exposure. Expanded coverage will also be needed if there is severe nonpurulent infection associated with penetrating trauma or a history of intravenous drug use, or the patient meets criteria for systemic inflammatory response syndrome. If patients are severely compromised (eg, neutropenic), it is reasonable to further add broad-spectrum coverage (eg, intravenous piperacillin-­tazobactam or carbapenem). Typical duration of treatment is 5 to 7 days, although this should be extended if there is no clinical improvement.

For orbital cellulitis, choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.

Generally, cellulitis can be managed in the outpatient setting, although hospitalization is recommended if there are concerns for deep or necrotizing infection, if patients are nonadherent to therapy or are immunocompromised, or if outpatient therapy has failed.⁵ Furthermore, in an observational study of 606 adult patients, prior episodes of cellulitis, venous insufficiency, and immunosuppression were all independently associated with poorer clinical outcomes.² Also treat underlying predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities such as fissures, scaling, or maceration.⁵ Consider the use of prophylactic antibiotics for patients who have had 3 to 4 episodes of cellulitis despite attempts to treat predisposing conditions. Prophylactic antibiotic regimens include penicillin or erythromycin orally and penicillin G benzathine intramuscularly.⁵ Antibiotic regimens are summarized in the TABLE.⁵

Orbital cellulitis

Orbital cellulitis is an infection of the tissues posterior to the orbital septum.^6,7 Periorbital, or preseptal, cellulitis occurs anterior to the orbital septum and is the more common of the 2 infections—84% compared with 16% for orbital cellulitis.⁶ However, orbital cellulitis, which affects mainly children at a median age of 7 years,⁶ must be detected and treated early due to the potential for serious complications such as cavernous sinus thrombosis, meningitis, intracranial abscess, and vision loss.⁷ Chemosis (conjunctival edema) and diplopia are more commonly associated with orbital cellulitis and are seldom seen with preseptal cellulitis.

Predominant causative organisms are S pneumoniae, Moraxella catarrhalis, non-typeable Haemophilus influenzae, and group A streptococcus. The most common mechanism of infection is tracking from periorbital structures (eg, paranasal and ethmoid sinusitis). Other causes include orbital trauma/fracture, periorbital surgery, and bacterial endocarditis. Clinically, patients present with limited ocular motility and proptosis associated with inflamed conjunctiva, orbital pain, headache, malaise, fever, eyelid edema, and possible decrease in visual acuity. The diagnosis is often made clinically and confirmed with orbital computed tomography (CT) with contrast, which can assist in ruling out intracranial involvement such as abscess.

Continue to: Antibiotic therapy

Antibiotic therapy, generally administered intravenously, is recommended for at least 3 days or until orbital symptoms begin to resolve. Choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.⁸ For instance, a regimen may include vancomycin for MRSA coverage, a third-generation cephalosporin, or metronidazole for anaerobic coverage if there is concern about intracranial involvement. Surgical intervention is often reserved for patients with inadequate response to antibiotic therapy, necessitating biopsy for pathogen identification, as well as drainage of large abscesses refractory to antibiotics.

Erysipelas

Erysipelas, a related yet distinct form of cellulitis, is a bacterial infection of the superficial dermis and hypodermis and is commonly caused by group A streptococcus.^5,9 Other less common organisms include S aureus, P aeruginosa, and enterobacteria. Erysipelas predominantly affects the lower extremities unilaterally (~90%); the arms and the face are the next most common locations. In addition to the rapid onset of well-demarcated erythema, pain, and swelling, patients may have fever and regional lymphadenopathy. Risk factors include portal of entry (eg, tinea pedis, ulceration), lymphedema, and diabetes. Complications of erysipelas include bullae from edema, abscess formation, and, rarely, bacteremia.

When clinical exam alone is inconclusive when evaluating skin and softtissue infections in children and adolescents, consider using ultrasound to improve diagnostic accuracy.

Antibiotic treatment regimens include penicillin G, macrolides (reserved for those with penicillin allergies), fluoroquinolones, and cephalosporins, with duration of treatment ranging from 10 to 14 days depending on infection severity. Fever, pain, and erythema generally improve within 48 to 72 hours of antibiotic therapy. If there is no improvement, consider alternative diagnoses, such as necrotizing fasciitis. Recurrence rates following the initial episode of erysipelas are estimated at 10% of patients at 6 months and 30% at 3 years.¹⁰

Folliculitis

Inflammation of hair follicles is characterized by superficial inflammation with the development of perifollicular papules or pustules on an erythematous base.^11,12 Folliculitis most commonly affects the face, scalp, thighs, buttocks, axillae, and inguinal areas.¹³ It may be caused by infection, an inflammatory reaction, or physical injury. Diagnosis is typically based on the patient’s history and physical examination.

Bacteria are the most common cause of infection, although fungi, viruses, and other entities can cause folliculitis. S aureus (methicillin sensitive or methicillin resistant) is the most common pathogen; in the past, superficial pustular folliculitis attributed to S aureus was referred to as Bockhart impetigo. Folliculitis secondary to P aeruginosa, often seen after exposure to contaminated water or hot tubs, is frequently referred to as “hot tub folliculitis.” Malassezia, a reported cause of fungal folliculitis, tends to occur in adolescents of either sex and men with high sebum production, is common in tropical climates, and can be associated with HIV or immunosuppression.^11,12,14

Continue to: Differential diagnosis...

Differential diagnosis of folliculitis includes pseudofolliculitis barbae, eosinophilic folliculitis, keratosis pilaris, acne vulgaris, candidiasis, contact dermatitis, impetigo, and miliaria.¹³ Pseudofolliculitis barbae is an inflammatory reaction to shaving, more commonly seen in darkly pigmented skin. Pseudofolliculitis develops when the hair shaft penetrates the wall of the follicle or directly enters the epidermis.

Initial treatment for mild disease includes the elimination of predisposing factors such as occlusion, moisture, and abrasion. The area should be kept clean and dry, avoiding friction. For localized disease, prescribe topical clindamycin, mupirocin ointment, or benzoyl peroxide. If symptoms fail to respond, prescribe a 7-day course of antibiotic that targets methicillin-sensitive S aureus—eg, cephalexin or dicloxacillin. Also consider doxycycline, which has anti-inflammatory effects and is effective against MRSA. For refractory lesions, ­trimethoprim-sulfamethoxazole, clindamycin, or minocycline may be useful. If you suspect pseudomonas, consider giving ciprofloxacin for 10 to 14 days for persistent lesions or if the patient is immunocompromised.^13,15 Consider obtaining bacterial, fungal, or viral cultures for lesions that fail to respond to initial treatment.

Do not routinely order cultures or prescribe antibiotics for uncomplicated abscesses.

Furuncles/carbuncles/abscesses

A furuncle, commonly referred to as a boil, is an infected hair follicle that becomes enclosed, creating a collection of pus. A carbuncle is a collection of furuncles that converge and drain through a single opening. An abscess is a localized collection of pus arising from within the dermis that can extend within deeper tissues.⁵ Furuncles, carbuncles, and abscesses are managed similarly with drainage and consideration for MRSA risk factors.

S aureus is the most common cause of these infections; 59% of skin abscesses are due to community-acquired MRSA.¹⁶ Anaerobes may contribute to the polymicrobial flora of skin abscesses.¹⁷ Risk factors for MRSA infection include a history of previous MRSA infection, diabetes, dialysis or renal failure, placement of an indwelling catheter or medical device, injection drug use, incarceration, close contact with a person with known MRSA infection or colonization, long-term care residence, hospitalization or surgery within the past 12 months, and high prevalence of MRSA in the community.⁵

Ultrasound improves diagnostic accuracy. One study showed that when a clinical exam alone was inconclusive in evaluating skin and soft-tissue infections in children and adolescents, an ultrasound-assisted examination improved diagnostic accuracy.¹⁸ Sensitivity of the clinical examination was 43.7%, compared with 77.6% for the clinical examination plus ultrasound.¹⁸

Continue to: Incision and drainage first

Incision and drainage first. Ultrasound-guided needle aspiration, however, has not improved treatment efficacy compared with incision and drainage,¹⁹ the mainstay approach for abscesses.¹⁷ The procedure to drain a furuncle, carbuncle, or abscess should include the expression of all purulent material and the removal of all loculations if possible. Wound culture is recommended during incision and drainage per current guidelines.⁵ Simple dry dressings are convenient and effective, although some wounds may require packing. Tap water (that is potable) is suitable for wound cleansing. However, there is no strong evidence that irrigating wounds increases healing or reduces infection.²⁰

Routine use of antibiotics is not recommended for simple cutaneous abscesses.^5,17,21 Evidence has been conflicting regarding empiric antibiotic coverage of MRSA following incision and drainage.^22-25 Guidelines recommend considering the initiation of antibiotics if there are multiple abscesses, gangrene, surrounding cellulitis, or systemic signs of infection, or if the host is immunocompromised.⁵

If MRSA is suspected, recommended antibiotic coverage includes trimethoprim-­sulfamethoxazole, clindamycin, doxycycline, or minocycline.⁵ If MRSA is identified, treatment options include dicloxacillin or cephalexin. For severe infections persisting after incision and drainage, in addition to oral antibiotic therapy, consider intravenous antibiotic options for MRSA: cefazolin, clindamycin, linezolid, nafcillin, telavancin, or vancomycin.⁵

Necrotizing fasciitis

Necrotizing fasciitis is a rare but potentially deadly infection of the skin and soft tissue. It progresses rapidly and spreads along fascial planes, leading to the necrosis of the superficial fascia. The infection often is more extensive than is indicated by superficial signs. Prompt diagnosis is imperative as necrotizing fasciitis is a surgical emergency.^5,26 In the United States, 500 to 1500 cases of necrotizing fasciitis occur each year.²⁷ Risk factors for necrotizing fasciitis include diabetes, peripheral vascular disease, malignancy, obesity, cirrhosis, renal failure, injection drug use, chronic corticosteroid therapy, alcohol abuse, malnutrition, and iatrogenic immunosuppression.^26,28

Monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.

Necrotizing fasciitis may be polymicrobial or monomicrobial. Polymicrobial infection, also referred to as type I, is often due to multiple bacteria that originate from the bowel flora, typically including a mix of anaerobic and aerobic organisms. On average, there can be 5 infecting organisms identified per wound, although in some cases up to 15 organisms have been identified in a single wound.⁵ Type I infection is often associated with tissue injury, abscess, or abdominal surgery. The majority of cases of necrotizing fasciitis are polymicrobial.^27,28

Continue to: Monomicrobial infection...

Monomicrobial infection, also referred to as type II, is often due to group A streptococcus, S aureus, vibrio spp, Aeromonas hyrophilio, or an anaerobic streptococci like peptostreptococcus spp. Typically monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.^5,26,29,30

Clinical presentation. In the early stages of disease, patients commonly complain of flu-like symptoms and extreme pain that is out of proportion to findings on the exam. Additional warning signs include fevers and other symptoms of toxicity such as tachycardia, hypotension, nausea, vomiting, and diarrhea. Later in the course, symptoms may localize to the affected area and include erythema, tense swelling, development of blisters or bullae, blackish blue discoloration of the skin, severe pain, and loss of sensation. In some cases involving gas-forming bacteria, tissue crepitus may be noted on exam.^5,27-31

Rely on clinical judgment to hasten surgical intervention. Laboratory or imaging findings may augment clinical judgment. But if you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery. Blood tests that may aid in the diagnosis of necrotizing fasciitis include a complete blood count with differential; coagulation studies; a comprehensive metabolic panel; assays of lactate, C-reactive protein (CRP), and creatinine kinase; and blood cultures. Most often, patients with necrotizing fasciitis will have leukocytosis or leukopenia, evidence of hemolysis, thrombocytopenia, acute renal failure, and significantly elevated CRP.

If you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery.

On any imaging modality, indications of necrotizing fasciitis are inflammatory infiltration of the deep fascia on the affected side that is absent on the contralateral side, and the presence of subcutaneous air (which is a specific but rare finding). Imaging modalities may include CT or magnetic resonance imaging. A definitive diagnosis can only be made with surgical exploration of the involved area. Definitive microbiologic diagnosis will require culture of organisms from affected tissue or blood.^5,26,30,31

First address any hemodynamic instability (hypotension is frequently encountered), followed by urgent surgical exploration, debridement of the wound, and antimicrobial therapy. Antibiotic treatment should align with probable pathogens and treatment should be continued until repeated surgical debridement is no longer necessary, clinical improvement is evident, and 48 to 72 hours have passed since defervescence. A reasonable initial empiric regimen in adults would include an agent that is effective against group A streptococcus, gram-negative pathogens, and anaerobes, such as a carbapenem or a beta-lactam-­beta-lactamase inhibitor such as piperacillin-­tazobactam. Additionally, include an agent that targets MRSA, such as vancomycin, linezolid, or clindamycin.⁵

CORRESPONDENCE
Karl T. Clebak, MD, Department of Family and Community Medicine Residency Program, Penn State Health M.S. Hershey Medical Center, 500 University Drive, H154/C1613, Hershey, PA 17033; [email protected]

Skin and soft-tissue infections, frequently encountered in primary care, range from the uncomplicated erysipelas to the life-threatening necrotizing fasciitis. This review draws from the latest evidence and guidelines to help guide the care you provide to patients with cellulitis, orbital cellulitis, erysipelas, folliculitis, furuncles, carbuncles, abscesses, and necrotizing fasciitis.

Cellulitis

Cellulitis, an infection of the deep dermal and subcutaneous layers of the skin, has become increasingly common in recent years, with both incidence and hospitalization rates rising.¹ Cellulitis occurs when pathogens enter the dermis through breaks in the skin barrier due to cutaneous fungal infections, trauma, pressure sores, venous stasis, or inflammation. The diagnosis is often made clinically based on characteristic skin findings—classically an acute, poorly demarcated area of erythema, warmth, swelling, and tenderness. Lymphangitic streaking and local lymphadenopathy may also be present. Infection often occurs on an extremity (although it can be found on other areas of the body) and is usually unilateral. Fever may or may not be present.²

Likely responsible microorganisms. Staphylococcus aureus and Group A streptococci (often Streptococcus pyogenes) are common culprits. One systematic review that examined cultures taken of intact skin in cellulitis patients found S aureus to be about twice as common as S pyogenes, with both bacteria accounting for a little more than 70% of cases. Of the remaining positive cultures, the most common organisms were alpha-­hemolytic streptococcus, group B streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli, Pasteurella multocida, and Proteus mirabilis.³ Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S aureus was responsible for just 14%), with the remainder of cases caused by gram-negative organisms such as E coli and P aeruginosa.⁴

Treatment considerations. Strict treatment guidelines for cellulitis are lacking, but general consensus encourages the use of antibiotics and occasionally surgery. For mild and moderate cases of cellulitis, prescribe oral and parenteral antibiotics to cover for streptococci and methicillin-susceptible S aureus, respectively. Expand coverage to include vancomycin if nasal colonization shows methicillin-resistant S aureus (MRSA) or if you otherwise suspect prior MRSA exposure. Expanded coverage will also be needed if there is severe nonpurulent infection associated with penetrating trauma or a history of intravenous drug use, or the patient meets criteria for systemic inflammatory response syndrome. If patients are severely compromised (eg, neutropenic), it is reasonable to further add broad-spectrum coverage (eg, intravenous piperacillin-­tazobactam or carbapenem). Typical duration of treatment is 5 to 7 days, although this should be extended if there is no clinical improvement.

For orbital cellulitis, choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.

Generally, cellulitis can be managed in the outpatient setting, although hospitalization is recommended if there are concerns for deep or necrotizing infection, if patients are nonadherent to therapy or are immunocompromised, or if outpatient therapy has failed.⁵ Furthermore, in an observational study of 606 adult patients, prior episodes of cellulitis, venous insufficiency, and immunosuppression were all independently associated with poorer clinical outcomes.² Also treat underlying predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities such as fissures, scaling, or maceration.⁵ Consider the use of prophylactic antibiotics for patients who have had 3 to 4 episodes of cellulitis despite attempts to treat predisposing conditions. Prophylactic antibiotic regimens include penicillin or erythromycin orally and penicillin G benzathine intramuscularly.⁵ Antibiotic regimens are summarized in the TABLE.⁵

Orbital cellulitis

Orbital cellulitis is an infection of the tissues posterior to the orbital septum.^6,7 Periorbital, or preseptal, cellulitis occurs anterior to the orbital septum and is the more common of the 2 infections—84% compared with 16% for orbital cellulitis.⁶ However, orbital cellulitis, which affects mainly children at a median age of 7 years,⁶ must be detected and treated early due to the potential for serious complications such as cavernous sinus thrombosis, meningitis, intracranial abscess, and vision loss.⁷ Chemosis (conjunctival edema) and diplopia are more commonly associated with orbital cellulitis and are seldom seen with preseptal cellulitis.

Predominant causative organisms are S pneumoniae, Moraxella catarrhalis, non-typeable Haemophilus influenzae, and group A streptococcus. The most common mechanism of infection is tracking from periorbital structures (eg, paranasal and ethmoid sinusitis). Other causes include orbital trauma/fracture, periorbital surgery, and bacterial endocarditis. Clinically, patients present with limited ocular motility and proptosis associated with inflamed conjunctiva, orbital pain, headache, malaise, fever, eyelid edema, and possible decrease in visual acuity. The diagnosis is often made clinically and confirmed with orbital computed tomography (CT) with contrast, which can assist in ruling out intracranial involvement such as abscess.

Continue to: Antibiotic therapy

Antibiotic therapy, generally administered intravenously, is recommended for at least 3 days or until orbital symptoms begin to resolve. Choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.⁸ For instance, a regimen may include vancomycin for MRSA coverage, a third-generation cephalosporin, or metronidazole for anaerobic coverage if there is concern about intracranial involvement. Surgical intervention is often reserved for patients with inadequate response to antibiotic therapy, necessitating biopsy for pathogen identification, as well as drainage of large abscesses refractory to antibiotics.

Erysipelas

Erysipelas, a related yet distinct form of cellulitis, is a bacterial infection of the superficial dermis and hypodermis and is commonly caused by group A streptococcus.^5,9 Other less common organisms include S aureus, P aeruginosa, and enterobacteria. Erysipelas predominantly affects the lower extremities unilaterally (~90%); the arms and the face are the next most common locations. In addition to the rapid onset of well-demarcated erythema, pain, and swelling, patients may have fever and regional lymphadenopathy. Risk factors include portal of entry (eg, tinea pedis, ulceration), lymphedema, and diabetes. Complications of erysipelas include bullae from edema, abscess formation, and, rarely, bacteremia.

When clinical exam alone is inconclusive when evaluating skin and softtissue infections in children and adolescents, consider using ultrasound to improve diagnostic accuracy.

Antibiotic treatment regimens include penicillin G, macrolides (reserved for those with penicillin allergies), fluoroquinolones, and cephalosporins, with duration of treatment ranging from 10 to 14 days depending on infection severity. Fever, pain, and erythema generally improve within 48 to 72 hours of antibiotic therapy. If there is no improvement, consider alternative diagnoses, such as necrotizing fasciitis. Recurrence rates following the initial episode of erysipelas are estimated at 10% of patients at 6 months and 30% at 3 years.¹⁰

Folliculitis

Inflammation of hair follicles is characterized by superficial inflammation with the development of perifollicular papules or pustules on an erythematous base.^11,12 Folliculitis most commonly affects the face, scalp, thighs, buttocks, axillae, and inguinal areas.¹³ It may be caused by infection, an inflammatory reaction, or physical injury. Diagnosis is typically based on the patient’s history and physical examination.

Bacteria are the most common cause of infection, although fungi, viruses, and other entities can cause folliculitis. S aureus (methicillin sensitive or methicillin resistant) is the most common pathogen; in the past, superficial pustular folliculitis attributed to S aureus was referred to as Bockhart impetigo. Folliculitis secondary to P aeruginosa, often seen after exposure to contaminated water or hot tubs, is frequently referred to as “hot tub folliculitis.” Malassezia, a reported cause of fungal folliculitis, tends to occur in adolescents of either sex and men with high sebum production, is common in tropical climates, and can be associated with HIV or immunosuppression.^11,12,14

Continue to: Differential diagnosis...

Differential diagnosis of folliculitis includes pseudofolliculitis barbae, eosinophilic folliculitis, keratosis pilaris, acne vulgaris, candidiasis, contact dermatitis, impetigo, and miliaria.¹³ Pseudofolliculitis barbae is an inflammatory reaction to shaving, more commonly seen in darkly pigmented skin. Pseudofolliculitis develops when the hair shaft penetrates the wall of the follicle or directly enters the epidermis.

Initial treatment for mild disease includes the elimination of predisposing factors such as occlusion, moisture, and abrasion. The area should be kept clean and dry, avoiding friction. For localized disease, prescribe topical clindamycin, mupirocin ointment, or benzoyl peroxide. If symptoms fail to respond, prescribe a 7-day course of antibiotic that targets methicillin-sensitive S aureus—eg, cephalexin or dicloxacillin. Also consider doxycycline, which has anti-inflammatory effects and is effective against MRSA. For refractory lesions, ­trimethoprim-sulfamethoxazole, clindamycin, or minocycline may be useful. If you suspect pseudomonas, consider giving ciprofloxacin for 10 to 14 days for persistent lesions or if the patient is immunocompromised.^13,15 Consider obtaining bacterial, fungal, or viral cultures for lesions that fail to respond to initial treatment.

Do not routinely order cultures or prescribe antibiotics for uncomplicated abscesses.

Furuncles/carbuncles/abscesses

A furuncle, commonly referred to as a boil, is an infected hair follicle that becomes enclosed, creating a collection of pus. A carbuncle is a collection of furuncles that converge and drain through a single opening. An abscess is a localized collection of pus arising from within the dermis that can extend within deeper tissues.⁵ Furuncles, carbuncles, and abscesses are managed similarly with drainage and consideration for MRSA risk factors.

S aureus is the most common cause of these infections; 59% of skin abscesses are due to community-acquired MRSA.¹⁶ Anaerobes may contribute to the polymicrobial flora of skin abscesses.¹⁷ Risk factors for MRSA infection include a history of previous MRSA infection, diabetes, dialysis or renal failure, placement of an indwelling catheter or medical device, injection drug use, incarceration, close contact with a person with known MRSA infection or colonization, long-term care residence, hospitalization or surgery within the past 12 months, and high prevalence of MRSA in the community.⁵

Ultrasound improves diagnostic accuracy. One study showed that when a clinical exam alone was inconclusive in evaluating skin and soft-tissue infections in children and adolescents, an ultrasound-assisted examination improved diagnostic accuracy.¹⁸ Sensitivity of the clinical examination was 43.7%, compared with 77.6% for the clinical examination plus ultrasound.¹⁸

Continue to: Incision and drainage first

Incision and drainage first. Ultrasound-guided needle aspiration, however, has not improved treatment efficacy compared with incision and drainage,¹⁹ the mainstay approach for abscesses.¹⁷ The procedure to drain a furuncle, carbuncle, or abscess should include the expression of all purulent material and the removal of all loculations if possible. Wound culture is recommended during incision and drainage per current guidelines.⁵ Simple dry dressings are convenient and effective, although some wounds may require packing. Tap water (that is potable) is suitable for wound cleansing. However, there is no strong evidence that irrigating wounds increases healing or reduces infection.²⁰

Routine use of antibiotics is not recommended for simple cutaneous abscesses.^5,17,21 Evidence has been conflicting regarding empiric antibiotic coverage of MRSA following incision and drainage.^22-25 Guidelines recommend considering the initiation of antibiotics if there are multiple abscesses, gangrene, surrounding cellulitis, or systemic signs of infection, or if the host is immunocompromised.⁵

If MRSA is suspected, recommended antibiotic coverage includes trimethoprim-­sulfamethoxazole, clindamycin, doxycycline, or minocycline.⁵ If MRSA is identified, treatment options include dicloxacillin or cephalexin. For severe infections persisting after incision and drainage, in addition to oral antibiotic therapy, consider intravenous antibiotic options for MRSA: cefazolin, clindamycin, linezolid, nafcillin, telavancin, or vancomycin.⁵

Necrotizing fasciitis

Necrotizing fasciitis is a rare but potentially deadly infection of the skin and soft tissue. It progresses rapidly and spreads along fascial planes, leading to the necrosis of the superficial fascia. The infection often is more extensive than is indicated by superficial signs. Prompt diagnosis is imperative as necrotizing fasciitis is a surgical emergency.^5,26 In the United States, 500 to 1500 cases of necrotizing fasciitis occur each year.²⁷ Risk factors for necrotizing fasciitis include diabetes, peripheral vascular disease, malignancy, obesity, cirrhosis, renal failure, injection drug use, chronic corticosteroid therapy, alcohol abuse, malnutrition, and iatrogenic immunosuppression.^26,28

Monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.

Necrotizing fasciitis may be polymicrobial or monomicrobial. Polymicrobial infection, also referred to as type I, is often due to multiple bacteria that originate from the bowel flora, typically including a mix of anaerobic and aerobic organisms. On average, there can be 5 infecting organisms identified per wound, although in some cases up to 15 organisms have been identified in a single wound.⁵ Type I infection is often associated with tissue injury, abscess, or abdominal surgery. The majority of cases of necrotizing fasciitis are polymicrobial.^27,28

Continue to: Monomicrobial infection...

Monomicrobial infection, also referred to as type II, is often due to group A streptococcus, S aureus, vibrio spp, Aeromonas hyrophilio, or an anaerobic streptococci like peptostreptococcus spp. Typically monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.^5,26,29,30

Clinical presentation. In the early stages of disease, patients commonly complain of flu-like symptoms and extreme pain that is out of proportion to findings on the exam. Additional warning signs include fevers and other symptoms of toxicity such as tachycardia, hypotension, nausea, vomiting, and diarrhea. Later in the course, symptoms may localize to the affected area and include erythema, tense swelling, development of blisters or bullae, blackish blue discoloration of the skin, severe pain, and loss of sensation. In some cases involving gas-forming bacteria, tissue crepitus may be noted on exam.^5,27-31

Rely on clinical judgment to hasten surgical intervention. Laboratory or imaging findings may augment clinical judgment. But if you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery. Blood tests that may aid in the diagnosis of necrotizing fasciitis include a complete blood count with differential; coagulation studies; a comprehensive metabolic panel; assays of lactate, C-reactive protein (CRP), and creatinine kinase; and blood cultures. Most often, patients with necrotizing fasciitis will have leukocytosis or leukopenia, evidence of hemolysis, thrombocytopenia, acute renal failure, and significantly elevated CRP.

If you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery.

On any imaging modality, indications of necrotizing fasciitis are inflammatory infiltration of the deep fascia on the affected side that is absent on the contralateral side, and the presence of subcutaneous air (which is a specific but rare finding). Imaging modalities may include CT or magnetic resonance imaging. A definitive diagnosis can only be made with surgical exploration of the involved area. Definitive microbiologic diagnosis will require culture of organisms from affected tissue or blood.^5,26,30,31

First address any hemodynamic instability (hypotension is frequently encountered), followed by urgent surgical exploration, debridement of the wound, and antimicrobial therapy. Antibiotic treatment should align with probable pathogens and treatment should be continued until repeated surgical debridement is no longer necessary, clinical improvement is evident, and 48 to 72 hours have passed since defervescence. A reasonable initial empiric regimen in adults would include an agent that is effective against group A streptococcus, gram-negative pathogens, and anaerobes, such as a carbapenem or a beta-lactam-­beta-lactamase inhibitor such as piperacillin-­tazobactam. Additionally, include an agent that targets MRSA, such as vancomycin, linezolid, or clindamycin.⁵

CORRESPONDENCE
Karl T. Clebak, MD, Department of Family and Community Medicine Residency Program, Penn State Health M.S. Hershey Medical Center, 500 University Drive, H154/C1613, Hershey, PA 17033; [email protected]

Hypertension and elevated blood pressure (BP) in children and adolescents correlate to hypertension in adults, insofar as complications and medical therapy increase with age.^1,2 Untreated, hypertension in children and adolescents can result in multiple harmful physiologic changes, including left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, arterial stiffening, endothelial dysfunction, and neurocognitive deficits.^3-5

In 2017, the American Academy of Pediatrics (AAP) published clinical practice guidelines for the diagnosis and management of elevated BP and hypertension in children and adolescents^a (TABLE 1⁶). Applying the definition of elevated BP set out in these guidelines yielded a 13% prevalence of hypertension in a cohort of subjects 10 to 18 years of age with comorbid obesity and diabetes mellitus (DM). AAP guideline definitions also improved the sensitivity for identifying hypertensive end-organ damage.⁷

The American Academy of Pediatrics recommends measuring BP annually in all children ≥ 3 years of age and at every encounter in patients with specific comorbid conditions and in those taking a medication known to increase BP

As the prevalence of hypertension increases, screening for and accurate diagnosis of this condition in children are becoming more important. Recognition and management remain a vital part of primary care. In this article, we review the updated guidance on diagnosis and treatment, including lifestyle modification and pharmacotherapy.

First step: Identifying hypertension

Risk factors

Risk factors for pediatric hypertension are similar to those in adults. These include obesity (body mass index ≥ 95th percentile for age), types 1 and 2 DM, elevated sodium intake, sleep-disordered breathing, and chronic kidney disease (CKD). Some risk factors, such as premature birth and coarctation of the aorta, are specific to the pediatric population.^8-14 Pediatric obesity strongly correlates with both pediatric and adult hypertension, and accelerated weight gain might increase the risk of elevated BP in adulthood.^15,16

Intervening early to mitigate or eliminate some of these modifiable risk factors can prevent or treat hypertension.¹⁷ Alternatively, having been breastfed as an infant has been reliably shown to reduce the risk of elevated BP in children.¹³

Recommendations for screening and measuring BP

The optimal age to start measuring BP is not clearly defined. AAP recommends measurement:

• annually in all children ≥ 3 years of age
• at every encounter in patients who have a specific comorbid condition, including obesity, DM, renal disease, and aortic-arch abnormalities (obstruction and coarctation) and in those who are taking medication known to increase BP.⁶

Protocol. Measure BP in the right arm for consistency and comparison with reference values. The width of the cuff bladder should be at least 40%, and the length, 80% to 100%, of arm circumference. Position the cuff bladder midway between the olecranon and acromion. Obtain the measurement in a quiet and comfortable environment after the patient has rested for 3 to 5 minutes. The patient should be seated, preferably with feet on the floor; elbows should be supported at the level of the heart.

Continue to: When an initial reading...

When an initial reading is elevated, whether by oscillometric or auscultatory measurement, 2 more auscultatory BP measurements should be taken during the same visit; these measurements are averaged to determine the BP category.¹⁸

TABLE 1⁶ defines BP categories based on age, sex, and height. We recommend using the free resource MD Calc (www.mdcalc.com/aap-pediatric-hypertension-guidelines) to assist in calculating the BP category.

TABLE 2⁶ describes the timing of follow-up based on the initial BP reading and diagnosis.

Ambulatory BP monitoring (ABPM) is a validated device that measures BP every 20 to 30 minutes throughout the day and night. ABPM should be performed initially in all patients with persistently elevated BP and routinely in children and adolescents with a high-risk comorbidity (TABLE 2⁶). Note: Insurance coverage of ABPM is limited.

Children older than 10 years who have been given a diagnosis of hypertension should be asked about smoking, alcohol, and other substance use.

ABPM is also used to diagnose so-called white-coat hypertension, defined as BP ≥ 95th percentile for age, sex, and height in the clinic setting but < 95th percentile during ABPM. This phenomenon can be challenging to diagnose.

Continue to: Home monitoring

Home monitoring. Do not use home BP monitoring to establish a diagnosis of hypertension, although one of these devices can be used as an adjunct to office and ambulatory BP monitoring after the diagnosis has been made.⁶

Evaluating hypertension in children and adolescents

Once a diagnosis of hypertension has been made, undertake a thorough history, physical examination, and diagnostic testing to evaluate for possible causes, comorbidities, and any evidence of end-organ damage.

Comprehensive history. Pertinent aspects include perinatal, nutritional, physical activity, psychosocial, family, medication—and of course, medical—histories.⁶

Maternal elevated BP or hypertension is related to an offspring’s elevated BP in childhood and adolescence.¹⁹ Other pertinent aspects of the perinatal history include complications of pregnancy, gestational age, birth weight, and neonatal complications.⁶

Nutritional and physical activity histories can highlight contributing factors in the development of hypertension and can be a guide to recommending lifestyle modifications.⁶ Sodium intake, which influences BP, should be part of the nutritional history.²⁰

Continue to: Important aspects...

The family history should include notation of first- and second-degree relatives with hypertension.⁶

Inquire about medications that can raise BP, including oral contraceptives, which are commonly prescribed in this population.^21,22

The physical exam should include measured height and weight, with calculation of the body mass index percentile for age; of note, obesity is strongly associated with hypertension, and poor growth might signal underlying chronic disease. Once elevated BP has been confirmed, the exam should include measurement of BP in both arms and in a leg (TABLE 2⁶). BP that is lower in the leg than in the arms (in any given patient, BP readings in the legs are usually higher than in the arms), or weak or absent femoral pulses, suggest coarctation of the aorta.⁶

Focus the balance of the physical exam on physical findings that suggest secondary causes of hypertension or evidence of end-organ damage.

Continue to: Testing

Testing. TABLE 3^6,23 summarizes the diagnostic testing recommended for all children and for specific populations; TABLE 2⁶ indicates when to obtain diagnostic testing. Patients 6 years and older who are overweight or obese and have a family history of hypertension likely have primary hypertension; they do not require an extensive work-up for secondary hypertension unless findings of the comprehensive history and physical examination lead in that direction.^6,23

TABLE 4^2,12,13,24 outlines the basis of primary and of secondary hypertension and common historical and physical findings that suggest a secondary cause.

Mapping out the treatment plan

Pediatric hypertension should be treated in patients with stage 1 or higher hypertension.⁶ This threshold for therapy is based on evidence that reducing BP below a goal of (1) the 90th percentile (calculated based on age, sex, and height) in children up to 12 years of age or (2) of < 130/80 mm Hg for children ≥ 13 years reduces short- and long-term morbidity and mortality.^5,6,25

Ambulatory BP monitoring should be performed initially in all patients with persistently elevated BP and routinely in children and adolescents with a high-risk comorbidity.

Choice of initial treatment depends on the severity of BP elevation and the presence of comorbidities (FIGURE^6,20,25-28). The initial, fundamental treatment recommendation is lifestyle modification,^6,29 including regular physical exercise, a change in nutritional habits, weight loss (because obesity is a common comorbid condition), elimination of tobacco and substance use, and stress reduction.^25,26 Medications can be used as well, along with other treatments for specific causes of secondary hypertension.

Referral to a specialist can be considered if consultation for assistance with treatment is preferred (TABLE 2⁶) or if the patient has:

• treatment-resistant hypertension
• stage 2 hypertension that is not quickly responsive to initial treatment
• an identified secondary cause of ­hypertension.

Continue to: Lifestyle modification can make a big difference

Exercise. “Regular” physical exercise for children to reduce BP is defined as ≥ 30 to 60 minutes of active play daily.^6,29 Studies have shown significant improvement not only in BP but also in other cardiovascular disease risk parameters with regular physical exercise.²⁷ A study found that the reduction in systolic BP is, on average, approximately 6 mm Hg with physical activity alone.³⁰

Nutrition. DASH—Dietary Approaches to Stop Hypertension—is an evidence-based program to reduce BP. This nutritional guideline focuses on a diet rich in natural foods, including fruits, vegetables, minimally processed carbohydrates and whole grains, and low-fat dairy and meats. It also emphasizes the importance of avoiding foods high in processed sugars and reducing sodium intake.³¹ Higher-than-recommended sodium intake, based on age and sex (and established as part of dietary recommendations for children on the US Department of Health and Human Services’ website health.gov) directly correlates with the risk of prehypertension and hypertension—especially in overweight and obese children.^20,32 DASH has been shown to reliably reduce the incidence of hypertension in children; other studies have supported increased intake of fruits, vegetables, and legumes as strategies to reduce BP.^33,34

The family history should include notation of first- and second-degree relatives with hypertension. Inquire about medications that can raise BP, including oral contraceptives.

Other interventions. Techniques to improve adherence to exercise and nutritional modifications for children include motivational interviewing, community programs and education, and family counseling.^27,35 A recent study showed that a community-based lifestyle modification program that is focused on weight loss in obese children resulted in a significant reduction in BP values at higher stages of obesity.³⁶ There is evidence that techniques such as controlled breathing and meditation can reduce BP.³⁷ Last, screening and counseling to encourage tobacco and substance use discontinuation are recommended for children and adolescents to improve health outcomes.²⁵

Proceed with pharmacotherapy when these criteria are met

Medical therapy is recommended when certain criteria are met, although this decision should be individualized and made in agreement by the treating physician, patient, and family. These criteria (FIGURE^6,20,25-28) are^6,29:

• once a diagnosis of stage 1 hypertension has been established, failure to meet a BP goal after 3 to 6 months of attempting lifestyle modifications
• stage 2 hypertension without a modifiable risk factor, such as obesity

• any stage of hypertension with comorbid CKD, DM, or proteinuria
• target-organ damage, such as left ventricular hypertrophy

• symptomatic hypertension.^6,29

There are circumstances in which one or another specific antihypertensive agent is recommended for children; however, for most patients with primary hypertension, the following classes are recommended for first-line use^6,22:

• angiotensin-converting enzyme (ACE) inhibitors
• angiotensin receptor blockers (ARBs)
• calcium-channel blockers (CCBs)
• thiazide diuretics.

Continue to: For a child with known CKD...

For a child with known CKD, DM, or proteinuria, an ACE inhibitor or ARB is beneficial as first-line therapy.³⁸ Because ACE inhibitors and ARBs have teratogenic effects, however, a thorough review of fertility status is recommended for female patients before any of these agents are started. CCBs and thiazides are typically recommended as first-line agents for Black patients.^6,28 Beta-blockers are typically avoided in the first line because of their adverse effect profile.

Most antihypertensive medications can be titrated every 1 or 2 weeks; the patient’s BP can be monitored with a home BP cuff to track the effect of titration. In general, the patient should be seen for follow-up every 4 to 6 weeks for a BP recheck and review of medication tolerance and adverse effects. Once the treatment goal is achieved, it is reasonable to have the patient return every 3 to 6 months to reassess the treatment plan.

The initial, fundamental treatment recommendation is lifestyle modification, including regular physical exercise, a change in nutritional habits, and weight loss.

If the BP goal is difficult to achieve despite titration of medication and lifestyle changes, consider repeat ABPM assessment, a specialty referral, or both. It is reasonable for children who have been started on medication and have adhered to lifestyle modifications to practice a “step-down” approach to discontinuing medication; this approach can also be considered once any secondary cause has been corrected. Any target-organ abnormalities identified at diagnosis (eg, proteinuria, CKD, left ventricular hypertrophy) need to be reexamined at follow-up.⁶

Restrict activities—or not?

There is evidence that a child with stage 1 or well-controlled stage 2 hypertension without evidence of end-organ damage should not have restrictions on sports or activity. However, in uncontrolled stage 2 hypertension or when evidence of target end-organ damage is present, you should advise against participation in highly competitive sports and highly static sports (eg, weightlifting, wrestling), based on expert opinion^6,25 (FIGURE^6,20,25-28).

^aAAP guidelines on the management of pediatric hypertension vary from those of the US Preventive Services Task Force. See the Practice Alert, “A review of the latest USPSTF recommendations,” in the May 2021 issue.

CORRESPONDENCE
Dustin K. Smith, MD, Family Medicine Department, 2080 Child Street, Jacksonville, FL, 32214; [email protected]

Hypertension and elevated blood pressure (BP) in children and adolescents correlate to hypertension in adults, insofar as complications and medical therapy increase with age.^1,2 Untreated, hypertension in children and adolescents can result in multiple harmful physiologic changes, including left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, arterial stiffening, endothelial dysfunction, and neurocognitive deficits.^3-5

In 2017, the American Academy of Pediatrics (AAP) published clinical practice guidelines for the diagnosis and management of elevated BP and hypertension in children and adolescents^a (TABLE 1⁶). Applying the definition of elevated BP set out in these guidelines yielded a 13% prevalence of hypertension in a cohort of subjects 10 to 18 years of age with comorbid obesity and diabetes mellitus (DM). AAP guideline definitions also improved the sensitivity for identifying hypertensive end-organ damage.⁷

The American Academy of Pediatrics recommends measuring BP annually in all children ≥ 3 years of age and at every encounter in patients with specific comorbid conditions and in those taking a medication known to increase BP

As the prevalence of hypertension increases, screening for and accurate diagnosis of this condition in children are becoming more important. Recognition and management remain a vital part of primary care. In this article, we review the updated guidance on diagnosis and treatment, including lifestyle modification and pharmacotherapy.

First step: Identifying hypertension

Risk factors

Risk factors for pediatric hypertension are similar to those in adults. These include obesity (body mass index ≥ 95th percentile for age), types 1 and 2 DM, elevated sodium intake, sleep-disordered breathing, and chronic kidney disease (CKD). Some risk factors, such as premature birth and coarctation of the aorta, are specific to the pediatric population.^8-14 Pediatric obesity strongly correlates with both pediatric and adult hypertension, and accelerated weight gain might increase the risk of elevated BP in adulthood.^15,16

Intervening early to mitigate or eliminate some of these modifiable risk factors can prevent or treat hypertension.¹⁷ Alternatively, having been breastfed as an infant has been reliably shown to reduce the risk of elevated BP in children.¹³

Recommendations for screening and measuring BP

The optimal age to start measuring BP is not clearly defined. AAP recommends measurement:

• annually in all children ≥ 3 years of age
• at every encounter in patients who have a specific comorbid condition, including obesity, DM, renal disease, and aortic-arch abnormalities (obstruction and coarctation) and in those who are taking medication known to increase BP.⁶

Protocol. Measure BP in the right arm for consistency and comparison with reference values. The width of the cuff bladder should be at least 40%, and the length, 80% to 100%, of arm circumference. Position the cuff bladder midway between the olecranon and acromion. Obtain the measurement in a quiet and comfortable environment after the patient has rested for 3 to 5 minutes. The patient should be seated, preferably with feet on the floor; elbows should be supported at the level of the heart.

Continue to: When an initial reading...

When an initial reading is elevated, whether by oscillometric or auscultatory measurement, 2 more auscultatory BP measurements should be taken during the same visit; these measurements are averaged to determine the BP category.¹⁸

TABLE 1⁶ defines BP categories based on age, sex, and height. We recommend using the free resource MD Calc (www.mdcalc.com/aap-pediatric-hypertension-guidelines) to assist in calculating the BP category.

TABLE 2⁶ describes the timing of follow-up based on the initial BP reading and diagnosis.

Ambulatory BP monitoring (ABPM) is a validated device that measures BP every 20 to 30 minutes throughout the day and night. ABPM should be performed initially in all patients with persistently elevated BP and routinely in children and adolescents with a high-risk comorbidity (TABLE 2⁶). Note: Insurance coverage of ABPM is limited.

Children older than 10 years who have been given a diagnosis of hypertension should be asked about smoking, alcohol, and other substance use.

ABPM is also used to diagnose so-called white-coat hypertension, defined as BP ≥ 95th percentile for age, sex, and height in the clinic setting but < 95th percentile during ABPM. This phenomenon can be challenging to diagnose.

Continue to: Home monitoring

Home monitoring. Do not use home BP monitoring to establish a diagnosis of hypertension, although one of these devices can be used as an adjunct to office and ambulatory BP monitoring after the diagnosis has been made.⁶

Evaluating hypertension in children and adolescents

Once a diagnosis of hypertension has been made, undertake a thorough history, physical examination, and diagnostic testing to evaluate for possible causes, comorbidities, and any evidence of end-organ damage.

Comprehensive history. Pertinent aspects include perinatal, nutritional, physical activity, psychosocial, family, medication—and of course, medical—histories.⁶

Maternal elevated BP or hypertension is related to an offspring’s elevated BP in childhood and adolescence.¹⁹ Other pertinent aspects of the perinatal history include complications of pregnancy, gestational age, birth weight, and neonatal complications.⁶

Nutritional and physical activity histories can highlight contributing factors in the development of hypertension and can be a guide to recommending lifestyle modifications.⁶ Sodium intake, which influences BP, should be part of the nutritional history.²⁰

Continue to: Important aspects...

The family history should include notation of first- and second-degree relatives with hypertension.⁶

Inquire about medications that can raise BP, including oral contraceptives, which are commonly prescribed in this population.^21,22

The physical exam should include measured height and weight, with calculation of the body mass index percentile for age; of note, obesity is strongly associated with hypertension, and poor growth might signal underlying chronic disease. Once elevated BP has been confirmed, the exam should include measurement of BP in both arms and in a leg (TABLE 2⁶). BP that is lower in the leg than in the arms (in any given patient, BP readings in the legs are usually higher than in the arms), or weak or absent femoral pulses, suggest coarctation of the aorta.⁶

Focus the balance of the physical exam on physical findings that suggest secondary causes of hypertension or evidence of end-organ damage.

Continue to: Testing

Testing. TABLE 3^6,23 summarizes the diagnostic testing recommended for all children and for specific populations; TABLE 2⁶ indicates when to obtain diagnostic testing. Patients 6 years and older who are overweight or obese and have a family history of hypertension likely have primary hypertension; they do not require an extensive work-up for secondary hypertension unless findings of the comprehensive history and physical examination lead in that direction.^6,23