Diagnosis: Porokeratotic eccrine ostial and dermal duct nevus (PEODDN)

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare, benign adnexal hamartoma first reported by Marsden et al. in 1979 as “comedo nevus of the palm” (Br J Dermatol. 1979 Dec;101[6]:717-22).

To date, 77 cases of PEODDN have been reported in the literature, with 53% having congenital onset. The average age of onset for the acquired lesions was 6 years. PEODDN affects males and females equally. Acral location is the most common (94%), but lesions have been reported less commonly on the trunk and face. A review of the literature found that most cases of PEODDN were independent, not associated with other conditions. Rarely, Bowen’s disease and squamous cell carcinoma have been reported to arise within PEODDN. Interestingly, two cases have been associated with keratitis-ichthyosis-deafness syndrome (KID).

Common differential diagnoses for PEODDN include porokeratosis of Mibelli, linear psoriasis, and linear epidermal nevus. Linear porokeratosis and porokeratosis of Mibelli are characterized by sharply demarcated hyperkeratotic annular lesions with distinct keratotic edges but do not have eccrine gland involvement on histopathology. Linear psoriasis, a rare form of psoriasis, is characterized by late onset linear psoriatic lesions along Blaschko lines. Linear epidermal nevus is a disease characterized by pruritic, erythematous scaly lesions following Blaschko lines that occurs in the first months of life and is slowly progressive. Histopathological features of PEODDN are diagnostic and distinguish it from these other clinical entities. A prominent parakeratotic column within an epidermal invagination that displays loss of the granular layer is found overlaying an eccrine duct with a dilated acrosyringium. Vacuolated and dyskeratotic keratinocytes are also typically present within the epidermal invagination.

The treatment for PEODDN remains elusive. Topical keratolytics, topical retinoids, topical steroids, topical calcipotriol, cryosurgery, phototherapy, and anthralin have been used to treat PEODDN unsuccessfully. Thus far, the most efficacious treatments include CO₂ laser and surgical excision for small lesions. Given the young age of this patient, emollient therapy was chosen as treatment until the patient reaches an age at which the lesion is cosmetically more disturbing and other therapies may be safely attempted.

In conclusion, this patient represents a classic case of the rare entity, PEODDN, and draws attention to recent discoveries that a genetic mutation in GJB2 is causative. Because PEODDN shares its pathogenic mutation with KID syndrome, clinicians should be aware that, if the same mutation also affects germline cells, offspring have the potential to express manifestations of KID syndrome.

This case and photo are courtesy of Molly B. Hirt, a medical student at Indiana University, Indianapolis; Carrie L. Davis, MD, of the Dermatology Center of Southern Indiana and Indiana University, Bloomington; and Anita N. Haggstrom, MD, of the departments of dermatology and pediatrics, Indiana University, Indianapolis.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

Diagnosis: Porokeratotic eccrine ostial and dermal duct nevus (PEODDN)

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare, benign adnexal hamartoma first reported by Marsden et al. in 1979 as “comedo nevus of the palm” (Br J Dermatol. 1979 Dec;101[6]:717-22).

To date, 77 cases of PEODDN have been reported in the literature, with 53% having congenital onset. The average age of onset for the acquired lesions was 6 years. PEODDN affects males and females equally. Acral location is the most common (94%), but lesions have been reported less commonly on the trunk and face. A review of the literature found that most cases of PEODDN were independent, not associated with other conditions. Rarely, Bowen’s disease and squamous cell carcinoma have been reported to arise within PEODDN. Interestingly, two cases have been associated with keratitis-ichthyosis-deafness syndrome (KID).

Common differential diagnoses for PEODDN include porokeratosis of Mibelli, linear psoriasis, and linear epidermal nevus. Linear porokeratosis and porokeratosis of Mibelli are characterized by sharply demarcated hyperkeratotic annular lesions with distinct keratotic edges but do not have eccrine gland involvement on histopathology. Linear psoriasis, a rare form of psoriasis, is characterized by late onset linear psoriatic lesions along Blaschko lines. Linear epidermal nevus is a disease characterized by pruritic, erythematous scaly lesions following Blaschko lines that occurs in the first months of life and is slowly progressive. Histopathological features of PEODDN are diagnostic and distinguish it from these other clinical entities. A prominent parakeratotic column within an epidermal invagination that displays loss of the granular layer is found overlaying an eccrine duct with a dilated acrosyringium. Vacuolated and dyskeratotic keratinocytes are also typically present within the epidermal invagination.

The treatment for PEODDN remains elusive. Topical keratolytics, topical retinoids, topical steroids, topical calcipotriol, cryosurgery, phototherapy, and anthralin have been used to treat PEODDN unsuccessfully. Thus far, the most efficacious treatments include CO₂ laser and surgical excision for small lesions. Given the young age of this patient, emollient therapy was chosen as treatment until the patient reaches an age at which the lesion is cosmetically more disturbing and other therapies may be safely attempted.

In conclusion, this patient represents a classic case of the rare entity, PEODDN, and draws attention to recent discoveries that a genetic mutation in GJB2 is causative. Because PEODDN shares its pathogenic mutation with KID syndrome, clinicians should be aware that, if the same mutation also affects germline cells, offspring have the potential to express manifestations of KID syndrome.

This case and photo are courtesy of Molly B. Hirt, a medical student at Indiana University, Indianapolis; Carrie L. Davis, MD, of the Dermatology Center of Southern Indiana and Indiana University, Bloomington; and Anita N. Haggstrom, MD, of the departments of dermatology and pediatrics, Indiana University, Indianapolis.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

Diagnosis: Porokeratotic eccrine ostial and dermal duct nevus (PEODDN)

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare, benign adnexal hamartoma first reported by Marsden et al. in 1979 as “comedo nevus of the palm” (Br J Dermatol. 1979 Dec;101[6]:717-22).

To date, 77 cases of PEODDN have been reported in the literature, with 53% having congenital onset. The average age of onset for the acquired lesions was 6 years. PEODDN affects males and females equally. Acral location is the most common (94%), but lesions have been reported less commonly on the trunk and face. A review of the literature found that most cases of PEODDN were independent, not associated with other conditions. Rarely, Bowen’s disease and squamous cell carcinoma have been reported to arise within PEODDN. Interestingly, two cases have been associated with keratitis-ichthyosis-deafness syndrome (KID).

Common differential diagnoses for PEODDN include porokeratosis of Mibelli, linear psoriasis, and linear epidermal nevus. Linear porokeratosis and porokeratosis of Mibelli are characterized by sharply demarcated hyperkeratotic annular lesions with distinct keratotic edges but do not have eccrine gland involvement on histopathology. Linear psoriasis, a rare form of psoriasis, is characterized by late onset linear psoriatic lesions along Blaschko lines. Linear epidermal nevus is a disease characterized by pruritic, erythematous scaly lesions following Blaschko lines that occurs in the first months of life and is slowly progressive. Histopathological features of PEODDN are diagnostic and distinguish it from these other clinical entities. A prominent parakeratotic column within an epidermal invagination that displays loss of the granular layer is found overlaying an eccrine duct with a dilated acrosyringium. Vacuolated and dyskeratotic keratinocytes are also typically present within the epidermal invagination.

The treatment for PEODDN remains elusive. Topical keratolytics, topical retinoids, topical steroids, topical calcipotriol, cryosurgery, phototherapy, and anthralin have been used to treat PEODDN unsuccessfully. Thus far, the most efficacious treatments include CO₂ laser and surgical excision for small lesions. Given the young age of this patient, emollient therapy was chosen as treatment until the patient reaches an age at which the lesion is cosmetically more disturbing and other therapies may be safely attempted.

In conclusion, this patient represents a classic case of the rare entity, PEODDN, and draws attention to recent discoveries that a genetic mutation in GJB2 is causative. Because PEODDN shares its pathogenic mutation with KID syndrome, clinicians should be aware that, if the same mutation also affects germline cells, offspring have the potential to express manifestations of KID syndrome.

This case and photo are courtesy of Molly B. Hirt, a medical student at Indiana University, Indianapolis; Carrie L. Davis, MD, of the Dermatology Center of Southern Indiana and Indiana University, Bloomington; and Anita N. Haggstrom, MD, of the departments of dermatology and pediatrics, Indiana University, Indianapolis.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

To the Editor:

Melanoma-associated hypopigmentation frequently has been reported during the disease course and can include different characteristics such as regression of the primary melanoma and/or its metastases as well as common vitiligolike hypopigmentation at sites distant from the melanoma.^1,2 Among patients who present with hypopigmentation, the most common clinical presentation is hypopigmented patches in a bilateral symmetric distribution that is similar to vitiligo.¹ We report a case of segmental vitiligo–like hypopigmentation associated with melanoma.

RELATED ARTICLE: Novel Melanoma Therapies and Their Side Effects

A 37-year-old man presented with achromic patches on the right side of the neck and lower face of 2 months’ duration. He had a history of melanoma (Breslow thickness, 1.37 mm; mitotic rate, 4/mm²) on the right retroauricular region that was treated by wide local excision 12 years prior; after 10 years, he began to have headaches. At that time, imaging studies including computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography revealed multiple nodules on the brain, lungs, pancreas, left scapula, and left suprarenal gland. A lung biopsy confirmed metastatic melanoma. Intravenous fotemustine (100 mg/m² weekly for 3 weeks) was initiated, followed by maintenance treatment (100 mg/m² once daily for 5 days) every 4 weeks.

On physical examination using a Wood lamp at the current presentation 2 months later, the achromic patches were linearly distributed on the inferior portion of the right cheek (Figure). A 2×3-cm atrophic scar was present on the right retroauricular region. No regional or distant lymph nodes were enlarged or hard on examination. Although vitiligo is diagnosed using clinical findings,³ a biopsy was performed and showed absence of melanocytes at the dermoepidermal junction (hematoxylin and eosin stain) and complete absence of melanin pigment (Fontana-Masson stain). The patient was treated with topical tacrolimus with poor improvement after 2 months.

The relationship between melanoma and vitiligolike hypopigmentation is a fascinating and controversial topic. Its association is considered to be a consequence of the immune-mediated response against antigens shared by normal melanocytes and melanoma cells.⁴ Vitiligolike hypopigmentation occurs in 2.8%² of melanoma patients and is reported in metastatic disease¹ as well as those undergoing immunotherapy with or without chemotherapy.⁵ Its development in patients with stage III or IV melanoma seems to represent an independent positive prognostic factor² and correlates with a better therapeutic outcome in patients undergoing treatment with biotherapy.⁵

In most cases, the onset of achromic lesions follows the diagnosis of melanoma. Hypopigmentation appears on average 4.8 years after the initial diagnosis and approximately 1 to 2 years after lymph node or distant metastasis.¹ In our case, it occurred 12 years after the initial diagnosis and 2 years after metastatic disease was diagnosed.

Despite having widespread metastatic melanoma, our patient only developed achromic patches on the area near the prior melanoma. However, most affected patients present with hypopigmented patches in a bilateral symmetric distribution pattern similar to common vitiligo. No correlation has been found between the hypopigmentation distribution and the location of the primary tumor.¹

Because fotemustine is not likely to induce hypopigmentation, we believe that the vitiligolike hypopigmentation in our patient was related to an immune-mediated response associated with melanoma. To help explain our findings, one hypothesis considered was that cutaneous mosaicism may be involved in segmental vitiligo.⁶ The tumor may have triggered an immune response that affected a close susceptible area of mosaic vitiligo, leading to these clinical findings.

To the Editor:

Melanoma-associated hypopigmentation frequently has been reported during the disease course and can include different characteristics such as regression of the primary melanoma and/or its metastases as well as common vitiligolike hypopigmentation at sites distant from the melanoma.^1,2 Among patients who present with hypopigmentation, the most common clinical presentation is hypopigmented patches in a bilateral symmetric distribution that is similar to vitiligo.¹ We report a case of segmental vitiligo–like hypopigmentation associated with melanoma.

RELATED ARTICLE: Novel Melanoma Therapies and Their Side Effects

A 37-year-old man presented with achromic patches on the right side of the neck and lower face of 2 months’ duration. He had a history of melanoma (Breslow thickness, 1.37 mm; mitotic rate, 4/mm²) on the right retroauricular region that was treated by wide local excision 12 years prior; after 10 years, he began to have headaches. At that time, imaging studies including computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography revealed multiple nodules on the brain, lungs, pancreas, left scapula, and left suprarenal gland. A lung biopsy confirmed metastatic melanoma. Intravenous fotemustine (100 mg/m² weekly for 3 weeks) was initiated, followed by maintenance treatment (100 mg/m² once daily for 5 days) every 4 weeks.

On physical examination using a Wood lamp at the current presentation 2 months later, the achromic patches were linearly distributed on the inferior portion of the right cheek (Figure). A 2×3-cm atrophic scar was present on the right retroauricular region. No regional or distant lymph nodes were enlarged or hard on examination. Although vitiligo is diagnosed using clinical findings,³ a biopsy was performed and showed absence of melanocytes at the dermoepidermal junction (hematoxylin and eosin stain) and complete absence of melanin pigment (Fontana-Masson stain). The patient was treated with topical tacrolimus with poor improvement after 2 months.

The relationship between melanoma and vitiligolike hypopigmentation is a fascinating and controversial topic. Its association is considered to be a consequence of the immune-mediated response against antigens shared by normal melanocytes and melanoma cells.⁴ Vitiligolike hypopigmentation occurs in 2.8%² of melanoma patients and is reported in metastatic disease¹ as well as those undergoing immunotherapy with or without chemotherapy.⁵ Its development in patients with stage III or IV melanoma seems to represent an independent positive prognostic factor² and correlates with a better therapeutic outcome in patients undergoing treatment with biotherapy.⁵

In most cases, the onset of achromic lesions follows the diagnosis of melanoma. Hypopigmentation appears on average 4.8 years after the initial diagnosis and approximately 1 to 2 years after lymph node or distant metastasis.¹ In our case, it occurred 12 years after the initial diagnosis and 2 years after metastatic disease was diagnosed.

Despite having widespread metastatic melanoma, our patient only developed achromic patches on the area near the prior melanoma. However, most affected patients present with hypopigmented patches in a bilateral symmetric distribution pattern similar to common vitiligo. No correlation has been found between the hypopigmentation distribution and the location of the primary tumor.¹

Because fotemustine is not likely to induce hypopigmentation, we believe that the vitiligolike hypopigmentation in our patient was related to an immune-mediated response associated with melanoma. To help explain our findings, one hypothesis considered was that cutaneous mosaicism may be involved in segmental vitiligo.⁶ The tumor may have triggered an immune response that affected a close susceptible area of mosaic vitiligo, leading to these clinical findings.

To the Editor:

Melanoma-associated hypopigmentation frequently has been reported during the disease course and can include different characteristics such as regression of the primary melanoma and/or its metastases as well as common vitiligolike hypopigmentation at sites distant from the melanoma.^1,2 Among patients who present with hypopigmentation, the most common clinical presentation is hypopigmented patches in a bilateral symmetric distribution that is similar to vitiligo.¹ We report a case of segmental vitiligo–like hypopigmentation associated with melanoma.

RELATED ARTICLE: Novel Melanoma Therapies and Their Side Effects

A 37-year-old man presented with achromic patches on the right side of the neck and lower face of 2 months’ duration. He had a history of melanoma (Breslow thickness, 1.37 mm; mitotic rate, 4/mm²) on the right retroauricular region that was treated by wide local excision 12 years prior; after 10 years, he began to have headaches. At that time, imaging studies including computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography revealed multiple nodules on the brain, lungs, pancreas, left scapula, and left suprarenal gland. A lung biopsy confirmed metastatic melanoma. Intravenous fotemustine (100 mg/m² weekly for 3 weeks) was initiated, followed by maintenance treatment (100 mg/m² once daily for 5 days) every 4 weeks.

On physical examination using a Wood lamp at the current presentation 2 months later, the achromic patches were linearly distributed on the inferior portion of the right cheek (Figure). A 2×3-cm atrophic scar was present on the right retroauricular region. No regional or distant lymph nodes were enlarged or hard on examination. Although vitiligo is diagnosed using clinical findings,³ a biopsy was performed and showed absence of melanocytes at the dermoepidermal junction (hematoxylin and eosin stain) and complete absence of melanin pigment (Fontana-Masson stain). The patient was treated with topical tacrolimus with poor improvement after 2 months.

The relationship between melanoma and vitiligolike hypopigmentation is a fascinating and controversial topic. Its association is considered to be a consequence of the immune-mediated response against antigens shared by normal melanocytes and melanoma cells.⁴ Vitiligolike hypopigmentation occurs in 2.8%² of melanoma patients and is reported in metastatic disease¹ as well as those undergoing immunotherapy with or without chemotherapy.⁵ Its development in patients with stage III or IV melanoma seems to represent an independent positive prognostic factor² and correlates with a better therapeutic outcome in patients undergoing treatment with biotherapy.⁵

In most cases, the onset of achromic lesions follows the diagnosis of melanoma. Hypopigmentation appears on average 4.8 years after the initial diagnosis and approximately 1 to 2 years after lymph node or distant metastasis.¹ In our case, it occurred 12 years after the initial diagnosis and 2 years after metastatic disease was diagnosed.

Despite having widespread metastatic melanoma, our patient only developed achromic patches on the area near the prior melanoma. However, most affected patients present with hypopigmented patches in a bilateral symmetric distribution pattern similar to common vitiligo. No correlation has been found between the hypopigmentation distribution and the location of the primary tumor.¹

Because fotemustine is not likely to induce hypopigmentation, we believe that the vitiligolike hypopigmentation in our patient was related to an immune-mediated response associated with melanoma. To help explain our findings, one hypothesis considered was that cutaneous mosaicism may be involved in segmental vitiligo.⁶ The tumor may have triggered an immune response that affected a close susceptible area of mosaic vitiligo, leading to these clinical findings.

MADRID – Thomsen-Friedenreich antigen activation is useful as a novel early predictor of empyema in pediatric community-acquired pneumonia, Chi-Jung Chang, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

In her retrospective study of 142 Taiwanese children and adolescents hospitalized for community-acquired pneumonia (CAP), Thomsen-Friedenreich antigen (TA) activation had 100% specificity, 100% positive predictive value, and 31% sensitivity for Streptococcus pneumoniae as the causative microorganism.

Moreover, the higher the TA activation titer, the more severe the pneumonia complications that followed, according to Dr. Chang of MacKay Children’s Hospital in Taipei, Taiwan.

The value of this lab test lies in its speed and accuracy for detection of S. pneumoniae CAP. Conventional culture methods are relatively slow and have poor sensitivity, because a child often already has been on empiric antimicrobial therapy and the culture specimen is unwittingly obtained from a sterile site, she explained.

Twenty-two of the 142 children and adolescents hospitalized for lobar CAP were TA activation positive at admission. They were considerably sicker than were the 120 patients who were TA activation negative. Their initial C-reactive protein level was 31.9 mg/dL, twice that of the negative group. Their peak CRP during the hospital stay was significantly higher as well, as was their peak WBC.

Hospital lengths of stay were longer in the TA activation–positive group. Eighteen of 22 TA activation–positive patients (82%) were admitted to the ICU for an average of 8 days, compared with 9% of the negative group.

All TA activation–positive patients had complicated pneumonia with parapneumonic effusions, empyema, necrotizing pneumonia, and/or lung abscesses, as did 36% of the negative group.

S. pneumoniae was the most common pathogen in this study of CAP. It was the responsible microbe in all 22 of the TA activation–positive patients and in 29% of the TA activation–negative ones. The most common serotype in the TA activation group was 19A, which accounted for 12 of the 22 cases. This also was the predominant serotype found in CAP across all Taiwan during the first half of this decade, when the study took place.

In a multivariate logistic regression analysis, TA activation was far and away the strongest independent predictor of empyema, with an associated 15.8-fold increased risk. The other two independent predictors – longer fever duration prior to hospitalization and a higher initial CRP level – were far less robust, according to Dr. Chang.
 

How TA activation works as a predictor

TA is present on the surface of erythrocytes, platelets, and glomeruli, but ordinarily it is covered by a layer of N-acetylneuraminic acid. Streptococcus pneumoniae produces circulating neuraminidases, which cleave the N-acetylneuraminic acid and expose the underlying TA. The TA then quickly becomes activated through interaction with the anti-TA antibodies, which are normally present in plasma. Once activated, the TA stays so for weeks to months.

Other neuraminidase-producing microorganisms include Clostridium perfringens, Escherichia coli, and Bacteroides.

Dr. Chang and her colleagues used the peanut lectin agglutination method in their TA activation testing.

She reported having no financial conflicts regarding her study.

[email protected]

MADRID – Thomsen-Friedenreich antigen activation is useful as a novel early predictor of empyema in pediatric community-acquired pneumonia, Chi-Jung Chang, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

In her retrospective study of 142 Taiwanese children and adolescents hospitalized for community-acquired pneumonia (CAP), Thomsen-Friedenreich antigen (TA) activation had 100% specificity, 100% positive predictive value, and 31% sensitivity for Streptococcus pneumoniae as the causative microorganism.

Moreover, the higher the TA activation titer, the more severe the pneumonia complications that followed, according to Dr. Chang of MacKay Children’s Hospital in Taipei, Taiwan.

The value of this lab test lies in its speed and accuracy for detection of S. pneumoniae CAP. Conventional culture methods are relatively slow and have poor sensitivity, because a child often already has been on empiric antimicrobial therapy and the culture specimen is unwittingly obtained from a sterile site, she explained.

Twenty-two of the 142 children and adolescents hospitalized for lobar CAP were TA activation positive at admission. They were considerably sicker than were the 120 patients who were TA activation negative. Their initial C-reactive protein level was 31.9 mg/dL, twice that of the negative group. Their peak CRP during the hospital stay was significantly higher as well, as was their peak WBC.

Hospital lengths of stay were longer in the TA activation–positive group. Eighteen of 22 TA activation–positive patients (82%) were admitted to the ICU for an average of 8 days, compared with 9% of the negative group.

All TA activation–positive patients had complicated pneumonia with parapneumonic effusions, empyema, necrotizing pneumonia, and/or lung abscesses, as did 36% of the negative group.

S. pneumoniae was the most common pathogen in this study of CAP. It was the responsible microbe in all 22 of the TA activation–positive patients and in 29% of the TA activation–negative ones. The most common serotype in the TA activation group was 19A, which accounted for 12 of the 22 cases. This also was the predominant serotype found in CAP across all Taiwan during the first half of this decade, when the study took place.

In a multivariate logistic regression analysis, TA activation was far and away the strongest independent predictor of empyema, with an associated 15.8-fold increased risk. The other two independent predictors – longer fever duration prior to hospitalization and a higher initial CRP level – were far less robust, according to Dr. Chang.
 

How TA activation works as a predictor

TA is present on the surface of erythrocytes, platelets, and glomeruli, but ordinarily it is covered by a layer of N-acetylneuraminic acid. Streptococcus pneumoniae produces circulating neuraminidases, which cleave the N-acetylneuraminic acid and expose the underlying TA. The TA then quickly becomes activated through interaction with the anti-TA antibodies, which are normally present in plasma. Once activated, the TA stays so for weeks to months.

Other neuraminidase-producing microorganisms include Clostridium perfringens, Escherichia coli, and Bacteroides.

Dr. Chang and her colleagues used the peanut lectin agglutination method in their TA activation testing.

She reported having no financial conflicts regarding her study.

[email protected]

MADRID – Thomsen-Friedenreich antigen activation is useful as a novel early predictor of empyema in pediatric community-acquired pneumonia, Chi-Jung Chang, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

In her retrospective study of 142 Taiwanese children and adolescents hospitalized for community-acquired pneumonia (CAP), Thomsen-Friedenreich antigen (TA) activation had 100% specificity, 100% positive predictive value, and 31% sensitivity for Streptococcus pneumoniae as the causative microorganism.

Moreover, the higher the TA activation titer, the more severe the pneumonia complications that followed, according to Dr. Chang of MacKay Children’s Hospital in Taipei, Taiwan.

The value of this lab test lies in its speed and accuracy for detection of S. pneumoniae CAP. Conventional culture methods are relatively slow and have poor sensitivity, because a child often already has been on empiric antimicrobial therapy and the culture specimen is unwittingly obtained from a sterile site, she explained.

Twenty-two of the 142 children and adolescents hospitalized for lobar CAP were TA activation positive at admission. They were considerably sicker than were the 120 patients who were TA activation negative. Their initial C-reactive protein level was 31.9 mg/dL, twice that of the negative group. Their peak CRP during the hospital stay was significantly higher as well, as was their peak WBC.

Hospital lengths of stay were longer in the TA activation–positive group. Eighteen of 22 TA activation–positive patients (82%) were admitted to the ICU for an average of 8 days, compared with 9% of the negative group.

All TA activation–positive patients had complicated pneumonia with parapneumonic effusions, empyema, necrotizing pneumonia, and/or lung abscesses, as did 36% of the negative group.

S. pneumoniae was the most common pathogen in this study of CAP. It was the responsible microbe in all 22 of the TA activation–positive patients and in 29% of the TA activation–negative ones. The most common serotype in the TA activation group was 19A, which accounted for 12 of the 22 cases. This also was the predominant serotype found in CAP across all Taiwan during the first half of this decade, when the study took place.

In a multivariate logistic regression analysis, TA activation was far and away the strongest independent predictor of empyema, with an associated 15.8-fold increased risk. The other two independent predictors – longer fever duration prior to hospitalization and a higher initial CRP level – were far less robust, according to Dr. Chang.
 

How TA activation works as a predictor

TA is present on the surface of erythrocytes, platelets, and glomeruli, but ordinarily it is covered by a layer of N-acetylneuraminic acid. Streptococcus pneumoniae produces circulating neuraminidases, which cleave the N-acetylneuraminic acid and expose the underlying TA. The TA then quickly becomes activated through interaction with the anti-TA antibodies, which are normally present in plasma. Once activated, the TA stays so for weeks to months.

Other neuraminidase-producing microorganisms include Clostridium perfringens, Escherichia coli, and Bacteroides.

Dr. Chang and her colleagues used the peanut lectin agglutination method in their TA activation testing.

She reported having no financial conflicts regarding her study.

[email protected]

What does your patient need to know at the first visit?

Most important is what you need to know before the first visit. As the prescribing physician, you must be familiar with the iPLEDGE program. Because of the complexity of the program, consider identifying a physician in your area to refer patients if you are not going to be a regular prescriber of the medication. 

If you are enrolled in iPLEDGE, let your patients (and/or their parents/guardians) know that there is a great deal of misinformation on the Internet. Reiterate that you and your staff are available to discuss their concerns. Also, give them reliable sources of information, such as the American Academy of Dermatology's patient information sheet as well as the Mayo Clinic's acne information. Drugs.com is another resource.

All patients—males, females who cannot become pregnant, and females of childbearing potential (FCBPs)—must be aware that this medication can cause birth defects if taken during pregnancy. They must be informed that the medication is not to be shared with anyone and that they should not give blood while taking this medication.

What treatment course do you recommend?

My evidence-based approach is a course of isotretinoin totaling a minimum of 150 mg per kilogram body weight. Do not give a more abbreviated course unless the patient has cleared early; even then I tend to complete 150 mg when possible. There is published evidence that pushing the course to a total of 220 mg per kilogram body weight results in a longer remission. 

Generally, I do few laboratory tests other than pretreatment lipid panels as well as 1 or 2 follow-up lipid panels at monthly intervals. To comply with the iPLEDGE program, FCBP patients must have a monthly pregnancy test, which is reported on the iPLEDGE website before the patient can be prescribed the drug and receive the drug from a pharmacist who is participating in the iPLEDGE program.

One of the defects of the iPLEDGE system is that although only a 30-day supply of pills can be prescribed, it is difficult to always bring a patient back in exactly 30 days; for example, we work on a 4-week cycle and 30 days brings us into the next week or uncommonly the weekend when we do not see patients. Our male patients or females not of childbearing potential are not affected, but for our FCBP patients, it means usually scheduling visits at 35-day intervals because the pregnancy tests must be performed at minimum 28-day intervals and the prescription cannot be written and the pregnancy test recorded until after at least 30 days. 

What are the side effects?

The common side effects are what you would expect from a medicine that is supposed to dry up the oil on your skin: dryness of the lips, mouth, and skin, as well as rashes due to the dryness. There also can be minor swelling of the eyelids or lips, nosebleeds, upset stomach, and thinning of the hair; dryness of the scalp may occur. I recommend using a little petroleum jelly inside the nostrils at night to counteract the dryness that leads to nosebleeds, and saline drops or gel for the eyes, especially for contact lens wearers.

Joint aches and pains have been reported, though I rarely see those effects in patients who are physically active such as those participating in competitive sports. Mood changes have been reported, including suicidal ideation.

What do you do if patients refuse treatment?

There is so much false information on the Internet about the dangers of isotretinoin, leaving some patients (and parents/guardians) too afraid to use it. I sympathize with this anxiety, but I do endeavor to point out that the birth defects occur only in women taking the drug while pregnant and have not been reported to occur after the drug is out of the patient's system. 

Similarly, I point out that almost all of the evidence-based studies failed to confirm any association between the use of isotretinoin and depression, teenage suicide, and subsequent inflammatory bowel disease. Nonetheless, I mention these issues and recommend that the parents/guardians observe the teenager; in the case of adult patients, they themselves must be sensitive to symptoms.

Suggested Readings

American Academy of Dermatology Association. Position statement on isotretinoin. https://www.aad.org/Forms/Policies/Uploads/PS/PS-Isotretinoin.pdf. Published December 9, 2000. Updated November 13, 2010. Accessed May 18, 2017.

Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149:1392-1398.

What does your patient need to know at the first visit?

Most important is what you need to know before the first visit. As the prescribing physician, you must be familiar with the iPLEDGE program. Because of the complexity of the program, consider identifying a physician in your area to refer patients if you are not going to be a regular prescriber of the medication. 

If you are enrolled in iPLEDGE, let your patients (and/or their parents/guardians) know that there is a great deal of misinformation on the Internet. Reiterate that you and your staff are available to discuss their concerns. Also, give them reliable sources of information, such as the American Academy of Dermatology's patient information sheet as well as the Mayo Clinic's acne information. Drugs.com is another resource.

All patients—males, females who cannot become pregnant, and females of childbearing potential (FCBPs)—must be aware that this medication can cause birth defects if taken during pregnancy. They must be informed that the medication is not to be shared with anyone and that they should not give blood while taking this medication.

What treatment course do you recommend?

My evidence-based approach is a course of isotretinoin totaling a minimum of 150 mg per kilogram body weight. Do not give a more abbreviated course unless the patient has cleared early; even then I tend to complete 150 mg when possible. There is published evidence that pushing the course to a total of 220 mg per kilogram body weight results in a longer remission. 

Generally, I do few laboratory tests other than pretreatment lipid panels as well as 1 or 2 follow-up lipid panels at monthly intervals. To comply with the iPLEDGE program, FCBP patients must have a monthly pregnancy test, which is reported on the iPLEDGE website before the patient can be prescribed the drug and receive the drug from a pharmacist who is participating in the iPLEDGE program.

One of the defects of the iPLEDGE system is that although only a 30-day supply of pills can be prescribed, it is difficult to always bring a patient back in exactly 30 days; for example, we work on a 4-week cycle and 30 days brings us into the next week or uncommonly the weekend when we do not see patients. Our male patients or females not of childbearing potential are not affected, but for our FCBP patients, it means usually scheduling visits at 35-day intervals because the pregnancy tests must be performed at minimum 28-day intervals and the prescription cannot be written and the pregnancy test recorded until after at least 30 days. 

What are the side effects?

The common side effects are what you would expect from a medicine that is supposed to dry up the oil on your skin: dryness of the lips, mouth, and skin, as well as rashes due to the dryness. There also can be minor swelling of the eyelids or lips, nosebleeds, upset stomach, and thinning of the hair; dryness of the scalp may occur. I recommend using a little petroleum jelly inside the nostrils at night to counteract the dryness that leads to nosebleeds, and saline drops or gel for the eyes, especially for contact lens wearers.

Joint aches and pains have been reported, though I rarely see those effects in patients who are physically active such as those participating in competitive sports. Mood changes have been reported, including suicidal ideation.

What do you do if patients refuse treatment?

There is so much false information on the Internet about the dangers of isotretinoin, leaving some patients (and parents/guardians) too afraid to use it. I sympathize with this anxiety, but I do endeavor to point out that the birth defects occur only in women taking the drug while pregnant and have not been reported to occur after the drug is out of the patient's system. 

Similarly, I point out that almost all of the evidence-based studies failed to confirm any association between the use of isotretinoin and depression, teenage suicide, and subsequent inflammatory bowel disease. Nonetheless, I mention these issues and recommend that the parents/guardians observe the teenager; in the case of adult patients, they themselves must be sensitive to symptoms.

Suggested Readings

American Academy of Dermatology Association. Position statement on isotretinoin. https://www.aad.org/Forms/Policies/Uploads/PS/PS-Isotretinoin.pdf. Published December 9, 2000. Updated November 13, 2010. Accessed May 18, 2017.

Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149:1392-1398.

What does your patient need to know at the first visit?

Most important is what you need to know before the first visit. As the prescribing physician, you must be familiar with the iPLEDGE program. Because of the complexity of the program, consider identifying a physician in your area to refer patients if you are not going to be a regular prescriber of the medication. 

If you are enrolled in iPLEDGE, let your patients (and/or their parents/guardians) know that there is a great deal of misinformation on the Internet. Reiterate that you and your staff are available to discuss their concerns. Also, give them reliable sources of information, such as the American Academy of Dermatology's patient information sheet as well as the Mayo Clinic's acne information. Drugs.com is another resource.

All patients—males, females who cannot become pregnant, and females of childbearing potential (FCBPs)—must be aware that this medication can cause birth defects if taken during pregnancy. They must be informed that the medication is not to be shared with anyone and that they should not give blood while taking this medication.

What treatment course do you recommend?

My evidence-based approach is a course of isotretinoin totaling a minimum of 150 mg per kilogram body weight. Do not give a more abbreviated course unless the patient has cleared early; even then I tend to complete 150 mg when possible. There is published evidence that pushing the course to a total of 220 mg per kilogram body weight results in a longer remission. 

Generally, I do few laboratory tests other than pretreatment lipid panels as well as 1 or 2 follow-up lipid panels at monthly intervals. To comply with the iPLEDGE program, FCBP patients must have a monthly pregnancy test, which is reported on the iPLEDGE website before the patient can be prescribed the drug and receive the drug from a pharmacist who is participating in the iPLEDGE program.

One of the defects of the iPLEDGE system is that although only a 30-day supply of pills can be prescribed, it is difficult to always bring a patient back in exactly 30 days; for example, we work on a 4-week cycle and 30 days brings us into the next week or uncommonly the weekend when we do not see patients. Our male patients or females not of childbearing potential are not affected, but for our FCBP patients, it means usually scheduling visits at 35-day intervals because the pregnancy tests must be performed at minimum 28-day intervals and the prescription cannot be written and the pregnancy test recorded until after at least 30 days. 

What are the side effects?

The common side effects are what you would expect from a medicine that is supposed to dry up the oil on your skin: dryness of the lips, mouth, and skin, as well as rashes due to the dryness. There also can be minor swelling of the eyelids or lips, nosebleeds, upset stomach, and thinning of the hair; dryness of the scalp may occur. I recommend using a little petroleum jelly inside the nostrils at night to counteract the dryness that leads to nosebleeds, and saline drops or gel for the eyes, especially for contact lens wearers.

Joint aches and pains have been reported, though I rarely see those effects in patients who are physically active such as those participating in competitive sports. Mood changes have been reported, including suicidal ideation.

What do you do if patients refuse treatment?

There is so much false information on the Internet about the dangers of isotretinoin, leaving some patients (and parents/guardians) too afraid to use it. I sympathize with this anxiety, but I do endeavor to point out that the birth defects occur only in women taking the drug while pregnant and have not been reported to occur after the drug is out of the patient's system. 

Similarly, I point out that almost all of the evidence-based studies failed to confirm any association between the use of isotretinoin and depression, teenage suicide, and subsequent inflammatory bowel disease. Nonetheless, I mention these issues and recommend that the parents/guardians observe the teenager; in the case of adult patients, they themselves must be sensitive to symptoms.

Suggested Readings

American Academy of Dermatology Association. Position statement on isotretinoin. https://www.aad.org/Forms/Policies/Uploads/PS/PS-Isotretinoin.pdf. Published December 9, 2000. Updated November 13, 2010. Accessed May 18, 2017.

Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149:1392-1398.

Reflectance confocal microscopy (RCM) imaging received Category I Current Procedural Terminology (CPT) codes by the Centers for Medicare & Medicaid Services in January 2016 and can now be submitted to insurance companies with reimbursement comparable to a skin biopsy or a global skin pathology service.¹ This fairly new technology is a US Food and Drug Administration–cleared noninvasive imaging modality that provides high-resolution in vivo cellular images of the skin. It has been shown to be efficacious in differentiating benign and malignant skin lesions, increasing diagnostic accuracy, and reducing the number of unnecessary skin biopsies that are performed. In addition to skin cancer diagnosis, RCM imaging also can help guide management of malignant lesions by detecting lateral margins prior to surgery as well as monitoring the lesion over time for treatment efficacy or recurrence. The potential impact of RCM imaging is tremendous, and reimbursement may lead to increased use in clinical practice to the benefit of our patients. Herein, we present a brief review of RCM imaging and reimbursement as well as the benefits and limitations of this new technology for dermatologists.

Reflectance Confocal Microscopy

In vivo RCM allows us to visualize the epidermis in real time on a cellular level down to the papillary dermis at a high resolution (×30) comparable to histologic examination. With optical sections 3- to 5-µm thick and a lateral resolution of 0.5 to 1.0 µm, RCM produces a stack of 500×500-µm² images up to a depth of approximately 200 µm.^2,3 At any chosen depth, these smaller images are stitched together with sophisticated software into a block, or mosaic, increasing the field of view to up to 8×8 mm². Imaging is performed in en face planes oriented parallel to the skin surface, similar to dermoscopy.

Current CPT Guidelines and Reimbursement

The CPT codes for RCM imaging provide reimbursement on a per-lesion basis and are similar to those used for skin biopsy and pathology (Table).¹ Codes 96931 through 96933 are used for imaging of a single lesion on a patient. The first code—96931—is used when image acquisition, interpretation, and report creation are carried out by a single clinician. The next 2 codes are used when one clinician acquires the image—96932—comparable to the technical component of a pathology code, while another reads it and creates the report—96933—similar to a dermatopathologist billing for the professional component of a pathology report. For patients presenting with multiple lesions, the next 3 codes—96934, 96935, and 96936—are used in conjunction with the applicable first code for each additional lesion with similar global, technical, and professional components. Because these codes are not in the radiology or pathology sections of CPT, a single code cannot be used with modifier -TC (technical component) and modifier -26, as they are in those sections.

The wide-probe VivaScope 1500 (Caliber I.D., Inc) currently is the only confocal device that can be reported with a CPT code and routinely reimbursed. The handheld VivaScope 3000 (Caliber I.D., Inc) can only view a small stack and does not have the ability to acquire a full mosaic image; it is not covered by these codes.

Images can be viewed as a stack captured at the same horizontal position but at sequential depths or as a mosaic, which has a larger field of view but is limited to a single plane. To appropriately assess a lesion, clinicians must obtain a mosaic that needs to be assessed at multiple layers for a diagnosis to be made because it is a cross-section view.

Diagnosis

Studies have demonstrated the usefulness of RCM imaging in the diagnosis of a wide range of skin diseases, including melanoma and nonmelanoma skin cancers, infectious diseases, and inflammatory and autoimmune conditions, as well as wound healing and skin aging. Reflectance confocal microscopy imaging is not limited to the skin; it can be used to evaluate the hair, nails, oral mucosa, and other organs.

According to several studies, RCM imaging notably increases the diagnostic accuracy and detection rate of skin cancers over clinical and dermoscopic examination alone and therefore can act as an aid in differentiating lesions that are benign versus those that are suspicious and should be biopsied.

Reflectance confocal microscopy has been shown to have a mean sensitivity of 94% (range, 92%–96%) and specificity of 83% (range, 81%–84%) for all types of skin cancer when used with dermoscopy.⁴ In particular, for melanocytic lesions that are ambiguous on dermoscopy, RCM used in addition to dermoscopy increases the mean sensitivity and specificity for melanoma diagnosis to 93% (range, 89%–96%) and 76% (range, 68%–83%), respectively.⁵ Although these reported sensitivities are comparable to dermoscopy, the specificity is superior, especially for detecting hypomelanotic and amelanotic melanomas, which often lack specific features on dermoscopy.^6-8

The combination of RCM with dermoscopy has reduced the number of unnecessary excisions of benign nevi by more than 50% when compared to dermoscopy alone.⁹ One study showed that the number needed to treat (ie, excise) a melanoma decreased from 14.6 with dermoscopy alone to 6.8 when guided by dermoscopy and RCM imaging.⁹ In a similar study, the number needed to treat dropped from 19.41 with dermoscopy alone to 6.25 with dermoscopy and RCM.¹⁰

These studies were not looking to evaluate RCM as a replacement test but rather as an add-on test to dermoscopy. Reflectance confocal microscopy imaging takes longer than dermoscopy for each lesion; therefore, RCM should only be used as an adjunctive tool to dermoscopy and not as an initial screening test. Consequentially, a dermatologist skilled in dermoscopy is essential in deciding which lesions would be appropriate for subsequent RCM imaging.

In Vivo Margin Mapping as an Adjunct to Surgery

Oftentimes, tumor margins are poorly defined and can be difficult to map clinically and dermoscopically. Studies have demonstrated the use of RCM in delineation of surgical margins prior to surgery or excisional biopsies.^11,12 Alternatively, when complete removal at biopsy would be impractical (eg, for extremely large lesions or lesions located in cosmetically sensitive areas such as the face), RCM can be used to pick the best site for an appropriate biopsy, which decreases the chance of sampling error due to skip lesions and increases histologic accuracy.

Nonsurgical Treatment Monitoring

One advantage of RCM over conventional histology is that RCM imaging leaves the tissue intact, allowing dynamic changes to be studied over time, which is useful for monitoring nonmelanoma skin cancers and lentigo maligna being treated with noninvasive therapeutic modalities.¹³ If not as a definitive treatment, RCM can act as an adjunct for surgery by monitoring reduction in lesion size prior to Mohs micrographic surgery, thereby decreasing the resulting surgical defect.¹⁴

Limitations

Imaging Depth
Although RCM is a revolutionary device in the field of dermatology, it has several limitations. With a maximal imaging depth of 350 µm, the imaging resolution decreases substantially with depth, limiting accurate interpretation to 200 µm. Reflectance confocal microscopy can only image the superficial portion of a lesion; therefore, deep tumor margins cannot be assessed. Hypertrophic or hyperkeratotic lesions, including lesions on the palms and soles, also are unable to be imaged with RCM. This limitation in depth penetration makes treatment monitoring impossible for invasive lesions that extend into the dermal layer.

Difficult-to-Reach Areas
Another limitation is the difficulty imaging areas such as the ocular canthi, nasal alae, or helices of the ear due to the wide probe size on the VivaScope 1500. The advent of the smaller handheld VivaScope 3000 device allows for improved imaging of concave services and difficult lesions at the risk of less accurate imaging, low field of view, and no reimbursement at present.

False-Positive Results
Although RCM has been shown to be helpful in reducing unnecessary biopsies, there still is the issue of false-positives on imaging. False-positives most commonly occur in nevi with severe atypia or when Langerhans cells are present that cannot always be differentiated from melanocytic cells.^3,15,16 One prospective study found 7 false-positive results from 63 sites using RCM for the diagnosis of lentigo malignas.¹⁶ False-negatives can occur in the presence of inflammatory infiltrates and scar tissue that can hide cellular morphology or in sampling errors due to skip lesions.^3,16

Time Efficiency
The time required for acquisition of RCM mosaics and stacks followed by reading and interpretation can be substantial depending on the size and complexity of the lesion, which is a major limitation for use of RCM in busy dermatology practices; therefore, RCM should be reserved for lesions selected to undergo biopsy that are clinically equivocal for malignancy prior to RCM examination.¹⁷ It would not be cost-effective or time effective to evaluate lesions that either clinically or dermoscopically have a high probability of malignancy; however, patients and physicians may opt for increased specificity at the expense of time, particularly when a lesion is located on a cosmetically sensitive area, as patients can avoid initial histologic biopsy and gain the cosmetic benefit of going straight to surgery versus obtaining an initial diagnostic biopsy.

Cost
Lastly, the high cost involved in purchasing an RCM device and the training involved to use and interpret RCM images currently limits RCM to large academic centers. Reimbursement may make more widespread use feasible. In any event, RCM imaging should be part of the curriculum for both dermatology and pathology trainees.

Future Directions

In vivo RCM is a noninvasive imaging modality that allows for real-time evaluation of the skin. Used in conjunction with dermoscopy, RCM can substantially improve diagnostic accuracy and reduce the number of unnecessary biopsies. Now that RCM has finally gained foundational CPT codes and insurance reimbursement, there may be a growing demand for clinicians to incorporate this technology into their clinical practice.

Reflectance confocal microscopy (RCM) imaging received Category I Current Procedural Terminology (CPT) codes by the Centers for Medicare & Medicaid Services in January 2016 and can now be submitted to insurance companies with reimbursement comparable to a skin biopsy or a global skin pathology service.¹ This fairly new technology is a US Food and Drug Administration–cleared noninvasive imaging modality that provides high-resolution in vivo cellular images of the skin. It has been shown to be efficacious in differentiating benign and malignant skin lesions, increasing diagnostic accuracy, and reducing the number of unnecessary skin biopsies that are performed. In addition to skin cancer diagnosis, RCM imaging also can help guide management of malignant lesions by detecting lateral margins prior to surgery as well as monitoring the lesion over time for treatment efficacy or recurrence. The potential impact of RCM imaging is tremendous, and reimbursement may lead to increased use in clinical practice to the benefit of our patients. Herein, we present a brief review of RCM imaging and reimbursement as well as the benefits and limitations of this new technology for dermatologists.

Reflectance Confocal Microscopy

In vivo RCM allows us to visualize the epidermis in real time on a cellular level down to the papillary dermis at a high resolution (×30) comparable to histologic examination. With optical sections 3- to 5-µm thick and a lateral resolution of 0.5 to 1.0 µm, RCM produces a stack of 500×500-µm² images up to a depth of approximately 200 µm.^2,3 At any chosen depth, these smaller images are stitched together with sophisticated software into a block, or mosaic, increasing the field of view to up to 8×8 mm². Imaging is performed in en face planes oriented parallel to the skin surface, similar to dermoscopy.

Current CPT Guidelines and Reimbursement

The CPT codes for RCM imaging provide reimbursement on a per-lesion basis and are similar to those used for skin biopsy and pathology (Table).¹ Codes 96931 through 96933 are used for imaging of a single lesion on a patient. The first code—96931—is used when image acquisition, interpretation, and report creation are carried out by a single clinician. The next 2 codes are used when one clinician acquires the image—96932—comparable to the technical component of a pathology code, while another reads it and creates the report—96933—similar to a dermatopathologist billing for the professional component of a pathology report. For patients presenting with multiple lesions, the next 3 codes—96934, 96935, and 96936—are used in conjunction with the applicable first code for each additional lesion with similar global, technical, and professional components. Because these codes are not in the radiology or pathology sections of CPT, a single code cannot be used with modifier -TC (technical component) and modifier -26, as they are in those sections.

The wide-probe VivaScope 1500 (Caliber I.D., Inc) currently is the only confocal device that can be reported with a CPT code and routinely reimbursed. The handheld VivaScope 3000 (Caliber I.D., Inc) can only view a small stack and does not have the ability to acquire a full mosaic image; it is not covered by these codes.

Images can be viewed as a stack captured at the same horizontal position but at sequential depths or as a mosaic, which has a larger field of view but is limited to a single plane. To appropriately assess a lesion, clinicians must obtain a mosaic that needs to be assessed at multiple layers for a diagnosis to be made because it is a cross-section view.

Diagnosis

Studies have demonstrated the usefulness of RCM imaging in the diagnosis of a wide range of skin diseases, including melanoma and nonmelanoma skin cancers, infectious diseases, and inflammatory and autoimmune conditions, as well as wound healing and skin aging. Reflectance confocal microscopy imaging is not limited to the skin; it can be used to evaluate the hair, nails, oral mucosa, and other organs.

According to several studies, RCM imaging notably increases the diagnostic accuracy and detection rate of skin cancers over clinical and dermoscopic examination alone and therefore can act as an aid in differentiating lesions that are benign versus those that are suspicious and should be biopsied.

Reflectance confocal microscopy has been shown to have a mean sensitivity of 94% (range, 92%–96%) and specificity of 83% (range, 81%–84%) for all types of skin cancer when used with dermoscopy.⁴ In particular, for melanocytic lesions that are ambiguous on dermoscopy, RCM used in addition to dermoscopy increases the mean sensitivity and specificity for melanoma diagnosis to 93% (range, 89%–96%) and 76% (range, 68%–83%), respectively.⁵ Although these reported sensitivities are comparable to dermoscopy, the specificity is superior, especially for detecting hypomelanotic and amelanotic melanomas, which often lack specific features on dermoscopy.^6-8

The combination of RCM with dermoscopy has reduced the number of unnecessary excisions of benign nevi by more than 50% when compared to dermoscopy alone.⁹ One study showed that the number needed to treat (ie, excise) a melanoma decreased from 14.6 with dermoscopy alone to 6.8 when guided by dermoscopy and RCM imaging.⁹ In a similar study, the number needed to treat dropped from 19.41 with dermoscopy alone to 6.25 with dermoscopy and RCM.¹⁰

These studies were not looking to evaluate RCM as a replacement test but rather as an add-on test to dermoscopy. Reflectance confocal microscopy imaging takes longer than dermoscopy for each lesion; therefore, RCM should only be used as an adjunctive tool to dermoscopy and not as an initial screening test. Consequentially, a dermatologist skilled in dermoscopy is essential in deciding which lesions would be appropriate for subsequent RCM imaging.

In Vivo Margin Mapping as an Adjunct to Surgery

Oftentimes, tumor margins are poorly defined and can be difficult to map clinically and dermoscopically. Studies have demonstrated the use of RCM in delineation of surgical margins prior to surgery or excisional biopsies.^11,12 Alternatively, when complete removal at biopsy would be impractical (eg, for extremely large lesions or lesions located in cosmetically sensitive areas such as the face), RCM can be used to pick the best site for an appropriate biopsy, which decreases the chance of sampling error due to skip lesions and increases histologic accuracy.

Nonsurgical Treatment Monitoring

One advantage of RCM over conventional histology is that RCM imaging leaves the tissue intact, allowing dynamic changes to be studied over time, which is useful for monitoring nonmelanoma skin cancers and lentigo maligna being treated with noninvasive therapeutic modalities.¹³ If not as a definitive treatment, RCM can act as an adjunct for surgery by monitoring reduction in lesion size prior to Mohs micrographic surgery, thereby decreasing the resulting surgical defect.¹⁴

Limitations

Imaging Depth
Although RCM is a revolutionary device in the field of dermatology, it has several limitations. With a maximal imaging depth of 350 µm, the imaging resolution decreases substantially with depth, limiting accurate interpretation to 200 µm. Reflectance confocal microscopy can only image the superficial portion of a lesion; therefore, deep tumor margins cannot be assessed. Hypertrophic or hyperkeratotic lesions, including lesions on the palms and soles, also are unable to be imaged with RCM. This limitation in depth penetration makes treatment monitoring impossible for invasive lesions that extend into the dermal layer.

Difficult-to-Reach Areas
Another limitation is the difficulty imaging areas such as the ocular canthi, nasal alae, or helices of the ear due to the wide probe size on the VivaScope 1500. The advent of the smaller handheld VivaScope 3000 device allows for improved imaging of concave services and difficult lesions at the risk of less accurate imaging, low field of view, and no reimbursement at present.

False-Positive Results
Although RCM has been shown to be helpful in reducing unnecessary biopsies, there still is the issue of false-positives on imaging. False-positives most commonly occur in nevi with severe atypia or when Langerhans cells are present that cannot always be differentiated from melanocytic cells.^3,15,16 One prospective study found 7 false-positive results from 63 sites using RCM for the diagnosis of lentigo malignas.¹⁶ False-negatives can occur in the presence of inflammatory infiltrates and scar tissue that can hide cellular morphology or in sampling errors due to skip lesions.^3,16

Time Efficiency
The time required for acquisition of RCM mosaics and stacks followed by reading and interpretation can be substantial depending on the size and complexity of the lesion, which is a major limitation for use of RCM in busy dermatology practices; therefore, RCM should be reserved for lesions selected to undergo biopsy that are clinically equivocal for malignancy prior to RCM examination.¹⁷ It would not be cost-effective or time effective to evaluate lesions that either clinically or dermoscopically have a high probability of malignancy; however, patients and physicians may opt for increased specificity at the expense of time, particularly when a lesion is located on a cosmetically sensitive area, as patients can avoid initial histologic biopsy and gain the cosmetic benefit of going straight to surgery versus obtaining an initial diagnostic biopsy.

Cost
Lastly, the high cost involved in purchasing an RCM device and the training involved to use and interpret RCM images currently limits RCM to large academic centers. Reimbursement may make more widespread use feasible. In any event, RCM imaging should be part of the curriculum for both dermatology and pathology trainees.

Future Directions

In vivo RCM is a noninvasive imaging modality that allows for real-time evaluation of the skin. Used in conjunction with dermoscopy, RCM can substantially improve diagnostic accuracy and reduce the number of unnecessary biopsies. Now that RCM has finally gained foundational CPT codes and insurance reimbursement, there may be a growing demand for clinicians to incorporate this technology into their clinical practice.

Reflectance confocal microscopy (RCM) imaging received Category I Current Procedural Terminology (CPT) codes by the Centers for Medicare & Medicaid Services in January 2016 and can now be submitted to insurance companies with reimbursement comparable to a skin biopsy or a global skin pathology service.¹ This fairly new technology is a US Food and Drug Administration–cleared noninvasive imaging modality that provides high-resolution in vivo cellular images of the skin. It has been shown to be efficacious in differentiating benign and malignant skin lesions, increasing diagnostic accuracy, and reducing the number of unnecessary skin biopsies that are performed. In addition to skin cancer diagnosis, RCM imaging also can help guide management of malignant lesions by detecting lateral margins prior to surgery as well as monitoring the lesion over time for treatment efficacy or recurrence. The potential impact of RCM imaging is tremendous, and reimbursement may lead to increased use in clinical practice to the benefit of our patients. Herein, we present a brief review of RCM imaging and reimbursement as well as the benefits and limitations of this new technology for dermatologists.

Reflectance Confocal Microscopy

In vivo RCM allows us to visualize the epidermis in real time on a cellular level down to the papillary dermis at a high resolution (×30) comparable to histologic examination. With optical sections 3- to 5-µm thick and a lateral resolution of 0.5 to 1.0 µm, RCM produces a stack of 500×500-µm² images up to a depth of approximately 200 µm.^2,3 At any chosen depth, these smaller images are stitched together with sophisticated software into a block, or mosaic, increasing the field of view to up to 8×8 mm². Imaging is performed in en face planes oriented parallel to the skin surface, similar to dermoscopy.

Current CPT Guidelines and Reimbursement

The CPT codes for RCM imaging provide reimbursement on a per-lesion basis and are similar to those used for skin biopsy and pathology (Table).¹ Codes 96931 through 96933 are used for imaging of a single lesion on a patient. The first code—96931—is used when image acquisition, interpretation, and report creation are carried out by a single clinician. The next 2 codes are used when one clinician acquires the image—96932—comparable to the technical component of a pathology code, while another reads it and creates the report—96933—similar to a dermatopathologist billing for the professional component of a pathology report. For patients presenting with multiple lesions, the next 3 codes—96934, 96935, and 96936—are used in conjunction with the applicable first code for each additional lesion with similar global, technical, and professional components. Because these codes are not in the radiology or pathology sections of CPT, a single code cannot be used with modifier -TC (technical component) and modifier -26, as they are in those sections.

The wide-probe VivaScope 1500 (Caliber I.D., Inc) currently is the only confocal device that can be reported with a CPT code and routinely reimbursed. The handheld VivaScope 3000 (Caliber I.D., Inc) can only view a small stack and does not have the ability to acquire a full mosaic image; it is not covered by these codes.

Images can be viewed as a stack captured at the same horizontal position but at sequential depths or as a mosaic, which has a larger field of view but is limited to a single plane. To appropriately assess a lesion, clinicians must obtain a mosaic that needs to be assessed at multiple layers for a diagnosis to be made because it is a cross-section view.

Diagnosis

Studies have demonstrated the usefulness of RCM imaging in the diagnosis of a wide range of skin diseases, including melanoma and nonmelanoma skin cancers, infectious diseases, and inflammatory and autoimmune conditions, as well as wound healing and skin aging. Reflectance confocal microscopy imaging is not limited to the skin; it can be used to evaluate the hair, nails, oral mucosa, and other organs.

According to several studies, RCM imaging notably increases the diagnostic accuracy and detection rate of skin cancers over clinical and dermoscopic examination alone and therefore can act as an aid in differentiating lesions that are benign versus those that are suspicious and should be biopsied.

Reflectance confocal microscopy has been shown to have a mean sensitivity of 94% (range, 92%–96%) and specificity of 83% (range, 81%–84%) for all types of skin cancer when used with dermoscopy.⁴ In particular, for melanocytic lesions that are ambiguous on dermoscopy, RCM used in addition to dermoscopy increases the mean sensitivity and specificity for melanoma diagnosis to 93% (range, 89%–96%) and 76% (range, 68%–83%), respectively.⁵ Although these reported sensitivities are comparable to dermoscopy, the specificity is superior, especially for detecting hypomelanotic and amelanotic melanomas, which often lack specific features on dermoscopy.^6-8

The combination of RCM with dermoscopy has reduced the number of unnecessary excisions of benign nevi by more than 50% when compared to dermoscopy alone.⁹ One study showed that the number needed to treat (ie, excise) a melanoma decreased from 14.6 with dermoscopy alone to 6.8 when guided by dermoscopy and RCM imaging.⁹ In a similar study, the number needed to treat dropped from 19.41 with dermoscopy alone to 6.25 with dermoscopy and RCM.¹⁰

These studies were not looking to evaluate RCM as a replacement test but rather as an add-on test to dermoscopy. Reflectance confocal microscopy imaging takes longer than dermoscopy for each lesion; therefore, RCM should only be used as an adjunctive tool to dermoscopy and not as an initial screening test. Consequentially, a dermatologist skilled in dermoscopy is essential in deciding which lesions would be appropriate for subsequent RCM imaging.

In Vivo Margin Mapping as an Adjunct to Surgery

Oftentimes, tumor margins are poorly defined and can be difficult to map clinically and dermoscopically. Studies have demonstrated the use of RCM in delineation of surgical margins prior to surgery or excisional biopsies.^11,12 Alternatively, when complete removal at biopsy would be impractical (eg, for extremely large lesions or lesions located in cosmetically sensitive areas such as the face), RCM can be used to pick the best site for an appropriate biopsy, which decreases the chance of sampling error due to skip lesions and increases histologic accuracy.

Nonsurgical Treatment Monitoring

One advantage of RCM over conventional histology is that RCM imaging leaves the tissue intact, allowing dynamic changes to be studied over time, which is useful for monitoring nonmelanoma skin cancers and lentigo maligna being treated with noninvasive therapeutic modalities.¹³ If not as a definitive treatment, RCM can act as an adjunct for surgery by monitoring reduction in lesion size prior to Mohs micrographic surgery, thereby decreasing the resulting surgical defect.¹⁴

Limitations

Imaging Depth
Although RCM is a revolutionary device in the field of dermatology, it has several limitations. With a maximal imaging depth of 350 µm, the imaging resolution decreases substantially with depth, limiting accurate interpretation to 200 µm. Reflectance confocal microscopy can only image the superficial portion of a lesion; therefore, deep tumor margins cannot be assessed. Hypertrophic or hyperkeratotic lesions, including lesions on the palms and soles, also are unable to be imaged with RCM. This limitation in depth penetration makes treatment monitoring impossible for invasive lesions that extend into the dermal layer.

Difficult-to-Reach Areas
Another limitation is the difficulty imaging areas such as the ocular canthi, nasal alae, or helices of the ear due to the wide probe size on the VivaScope 1500. The advent of the smaller handheld VivaScope 3000 device allows for improved imaging of concave services and difficult lesions at the risk of less accurate imaging, low field of view, and no reimbursement at present.

False-Positive Results
Although RCM has been shown to be helpful in reducing unnecessary biopsies, there still is the issue of false-positives on imaging. False-positives most commonly occur in nevi with severe atypia or when Langerhans cells are present that cannot always be differentiated from melanocytic cells.^3,15,16 One prospective study found 7 false-positive results from 63 sites using RCM for the diagnosis of lentigo malignas.¹⁶ False-negatives can occur in the presence of inflammatory infiltrates and scar tissue that can hide cellular morphology or in sampling errors due to skip lesions.^3,16

Time Efficiency
The time required for acquisition of RCM mosaics and stacks followed by reading and interpretation can be substantial depending on the size and complexity of the lesion, which is a major limitation for use of RCM in busy dermatology practices; therefore, RCM should be reserved for lesions selected to undergo biopsy that are clinically equivocal for malignancy prior to RCM examination.¹⁷ It would not be cost-effective or time effective to evaluate lesions that either clinically or dermoscopically have a high probability of malignancy; however, patients and physicians may opt for increased specificity at the expense of time, particularly when a lesion is located on a cosmetically sensitive area, as patients can avoid initial histologic biopsy and gain the cosmetic benefit of going straight to surgery versus obtaining an initial diagnostic biopsy.

Cost
Lastly, the high cost involved in purchasing an RCM device and the training involved to use and interpret RCM images currently limits RCM to large academic centers. Reimbursement may make more widespread use feasible. In any event, RCM imaging should be part of the curriculum for both dermatology and pathology trainees.

Future Directions

In vivo RCM is a noninvasive imaging modality that allows for real-time evaluation of the skin. Used in conjunction with dermoscopy, RCM can substantially improve diagnostic accuracy and reduce the number of unnecessary biopsies. Now that RCM has finally gained foundational CPT codes and insurance reimbursement, there may be a growing demand for clinicians to incorporate this technology into their clinical practice.

It is easy to look at the changes required to mitigate burnout and improve compassionate care and see the burden being placed mainly on the physician. Many of the proposed modifications seem to require the one commodity surgeons lack most, time. Any widespread effort to mitigate the burnout crisis must involve decreasing the barriers to patient care and reducing the physicians’ time constraints.

This may seem daunting, but broad changes in our healthcare system have been implemented in the name of quality, reducing errors, and alleviating trainee fatigue. Burnout can be a similar force for change. Much like the resident’s 80-hour workweek, however, in what manner this change is applied will be the ultimate determinant of the movement’s success.

The characteristics of compassionate care have been well described by patients, and, not surprisingly, only 53% reported that their last encounter with the health care system was compassionate. In 2014, a multidisciplinary consortium published recommendations for advancing compassionate person- and family-centered care. They detailed the attributes, values, and behaviors of such care, including focusing one’s attention, recognizing nonverbal clues, active listening, demonstrating nonjudgmental interest in the whole person, understanding the context of a person’s disease, and asking about the patient’s chief concerns in addition to their chief complaints. Most significantly, the authors outlined how these attributes could be integrated into existing competency documents such as those provided by the Association of American Medical Colleges (AAMC) Entrustable Professional Activities, or the milestones programs of the Accreditation Council of Graduate Medical Education (ACGME) and the American Board of Internal Medicine (ABIM). 

It is but a small step to enhance current criteria for certification, clinical appointment, and privileging by including these professional attributes. Bear in mind that these skills are teachable and easily incorporated into health professional education and clinical care. As for metrics, the Schwartz Compassionate Care Scale is a validated patient-rated questionnaire that reliably measures physicians’ compassion and overall patient satisfaction and is available in the public domain. It also provides a metric that is important to clinicians and, when placed on the hospital dashboard, highlights that compassion is an organizational priority. Such priorities become the fabric of the workforce when organizational leadership installs programs such as values-based recruitment, retention, and promotion as Vivian Lee describes at the University of Utah Health System. Mitigating burnout requires changing the culture in which clinicians work and with whom they work.  

Vascular surgeons and their professional surgical societies have a leadership opportunity to design high performing teams. Most patient care models have been structured around traditional medical and surgical departments. This paradigm overlooks the fact that patients do not “get sick” within traditional teaching disciplines but do so across varied medical and surgical specialties. Changes in organizational hierarchy are needed so that team-based care is supported. In addition to physician and nurse clinicians, the new teams would do well to expand to all “caregivers,” i.e. everyone who touches the patient (technologists, interpreters, pharmacists, transport workers, support staff, and administrators).

On the front line
On April 15, 2013, at 2:49 pm, two homemade bombs detonated near the finish line of the Boston Marathon killing three people at the scene and injuring 264 others; the most severe sustaining mutilating lower extremity injuries. Much has been written about the preparedness, the emergency response, and the fact that all those who made it to the hospital survived. Jeffrey Kalish, MD, a vascular surgeon at Boston Medical Center and SVS member, was on the front line that day. We asked him to share his personal experience of caring for the victims through the lens of compassionate collaborative care.   

“It has been over four years since I went from being a spectator near the Boston Marathon finish line to rushing directly to the operating rooms at Boston Medical Center to help our teams perform lifesaving procedures on critically ill patients, including amputations and complex vascular repairs. While I have learned a tremendous amount since that experience with regard to limb salvage and amputation, reconstructive techniques, and prosthetics, I will focus here on the care the patients and their families received, the lessons our hospital learned from the weeks and months that followed, and how we modeled this care going forward for all amputation patients at Boston Medical Center.  

"Based on lessons from the Boston Marathon bombings, I aligned a multidisciplinary team of health care providers in order to formalize and standardize best practices to benefit our amputation patients. STRONG (Surgery To Rehab Ongoing Needs Group) continues to strive toward the ultimate goal of improving and coordinating care for amputation patients and their families as they transition from the hospital setting to rehabilitation. Some of our guiding principles, along with their positive impacts on patient care and physician well-being, are highlighted below:
1. Sustaining hope with a new mindset: Although surgeons have historically considered amputation as a treatment failure, a more appropriate mindset is that amputation can often be a reconstructive procedure in the surgical armamentarium designed to restore a patient back to full function.
2. Seeing the patient in context: Shared decision making can occur more readily once a surgeon and the care team seek to understand the whole person and their family, including what that person does for work and leisure.
3. Communication with colleagues, patients, and families: Patient and family fear and confusion can often be reduced after establishment of a multi-disciplinary team with daily care coordination and consistent messaging. Breaking down traditional hospital silos to allow for improved coordination of care benefits both the patients and the practitioners.
4. Managing emotional and physical suffering:  Introducing social workers, mental health professionals, or pastoral care advocates into the care team as soon as a patient is ready can help manage the emotional and psychosocial needs of patients and their families.
5. Sustaining long term surgeon/patient relationships:  As clinicians, we can feel rewarded after restoring functional performance in our patients and by meeting the needs of our patients and families. This can occur both in the short-term during the acute hospital stay and in the long-term as we follow our patients’ progress towards achievement of their ultimate goals.  
6. Attend to one’s own well-being and foster resilience. There will never be a substitute in our profession for the human connection between our patients and ourselves as their caregivers, and this connection should be one of the most treasured aspects of our work life.  We should seek daily reminders of these positive interactions to nurture our ability to cope with a grueling and challenging field, where the outcomes are not always as ideal as we hope.  

For me, STRONG is now a consistent and powerful reminder of why I originally became a doctor in the first place, and I strive to propagate this model of compassionate care to benefit future patients as we move forward together.”

We are at an inflexion point in health care. No amount of individual resilience can withstand a toxic or nonsupportive environment. It is unreasonable to think that simply by taking better care of ourselves we are going to resolve the issue of burnout. We need to rethink our current systems of care and focus our energy on developing those that support our ability to deliver the kind of care we know our patients need and deserve. We have an opportunity to alleviate the suffering many providers are experiencing as they strive to heal their patients. We have an opportunity to improve both physician and patient engagement, develop care delivery systems we know our patients deserve, and restore the deep sense of satisfaction that comes from practicing medicine and surgery. There is abundant expertise within our professional medical and surgical societies. The SVS has the courage and the duty to lead.

Drs. Colman, Kalish, and Sheahan extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, M.D., Scholar in Residence, Schwartz Center for Compassionate Care, Boston, Mass., and Clinical Professor of Orthopedics at Seattle Children’s Hospital. 

Bibliography
1. Acad Med (2016) 91:338-344
2. Health Aff (2011) 30:1772-1778
3. Patient Educ Couns (2015) 98:1005-10
4. Acad Med (2016) 91:310-316 
5. http://www.theschwartzcenter.org/media/Triple-C-Conference-Framework-Tables_FINAL.pdf  
6. http://www.theschwartzcenter.org/media/Triple-C-Conference-Recommendations-Report_FINAL1.pdf
7. JAMA (2017) 317: 901-2
8. Clin Orthop Relat Res. (2017) 475:1309-14. 

It is easy to look at the changes required to mitigate burnout and improve compassionate care and see the burden being placed mainly on the physician. Many of the proposed modifications seem to require the one commodity surgeons lack most, time. Any widespread effort to mitigate the burnout crisis must involve decreasing the barriers to patient care and reducing the physicians’ time constraints.

This may seem daunting, but broad changes in our healthcare system have been implemented in the name of quality, reducing errors, and alleviating trainee fatigue. Burnout can be a similar force for change. Much like the resident’s 80-hour workweek, however, in what manner this change is applied will be the ultimate determinant of the movement’s success.

The characteristics of compassionate care have been well described by patients, and, not surprisingly, only 53% reported that their last encounter with the health care system was compassionate. In 2014, a multidisciplinary consortium published recommendations for advancing compassionate person- and family-centered care. They detailed the attributes, values, and behaviors of such care, including focusing one’s attention, recognizing nonverbal clues, active listening, demonstrating nonjudgmental interest in the whole person, understanding the context of a person’s disease, and asking about the patient’s chief concerns in addition to their chief complaints. Most significantly, the authors outlined how these attributes could be integrated into existing competency documents such as those provided by the Association of American Medical Colleges (AAMC) Entrustable Professional Activities, or the milestones programs of the Accreditation Council of Graduate Medical Education (ACGME) and the American Board of Internal Medicine (ABIM). 

It is but a small step to enhance current criteria for certification, clinical appointment, and privileging by including these professional attributes. Bear in mind that these skills are teachable and easily incorporated into health professional education and clinical care. As for metrics, the Schwartz Compassionate Care Scale is a validated patient-rated questionnaire that reliably measures physicians’ compassion and overall patient satisfaction and is available in the public domain. It also provides a metric that is important to clinicians and, when placed on the hospital dashboard, highlights that compassion is an organizational priority. Such priorities become the fabric of the workforce when organizational leadership installs programs such as values-based recruitment, retention, and promotion as Vivian Lee describes at the University of Utah Health System. Mitigating burnout requires changing the culture in which clinicians work and with whom they work.  

Vascular surgeons and their professional surgical societies have a leadership opportunity to design high performing teams. Most patient care models have been structured around traditional medical and surgical departments. This paradigm overlooks the fact that patients do not “get sick” within traditional teaching disciplines but do so across varied medical and surgical specialties. Changes in organizational hierarchy are needed so that team-based care is supported. In addition to physician and nurse clinicians, the new teams would do well to expand to all “caregivers,” i.e. everyone who touches the patient (technologists, interpreters, pharmacists, transport workers, support staff, and administrators).

On the front line
On April 15, 2013, at 2:49 pm, two homemade bombs detonated near the finish line of the Boston Marathon killing three people at the scene and injuring 264 others; the most severe sustaining mutilating lower extremity injuries. Much has been written about the preparedness, the emergency response, and the fact that all those who made it to the hospital survived. Jeffrey Kalish, MD, a vascular surgeon at Boston Medical Center and SVS member, was on the front line that day. We asked him to share his personal experience of caring for the victims through the lens of compassionate collaborative care.   

“It has been over four years since I went from being a spectator near the Boston Marathon finish line to rushing directly to the operating rooms at Boston Medical Center to help our teams perform lifesaving procedures on critically ill patients, including amputations and complex vascular repairs. While I have learned a tremendous amount since that experience with regard to limb salvage and amputation, reconstructive techniques, and prosthetics, I will focus here on the care the patients and their families received, the lessons our hospital learned from the weeks and months that followed, and how we modeled this care going forward for all amputation patients at Boston Medical Center.  

"Based on lessons from the Boston Marathon bombings, I aligned a multidisciplinary team of health care providers in order to formalize and standardize best practices to benefit our amputation patients. STRONG (Surgery To Rehab Ongoing Needs Group) continues to strive toward the ultimate goal of improving and coordinating care for amputation patients and their families as they transition from the hospital setting to rehabilitation. Some of our guiding principles, along with their positive impacts on patient care and physician well-being, are highlighted below:
1. Sustaining hope with a new mindset: Although surgeons have historically considered amputation as a treatment failure, a more appropriate mindset is that amputation can often be a reconstructive procedure in the surgical armamentarium designed to restore a patient back to full function.
2. Seeing the patient in context: Shared decision making can occur more readily once a surgeon and the care team seek to understand the whole person and their family, including what that person does for work and leisure.
3. Communication with colleagues, patients, and families: Patient and family fear and confusion can often be reduced after establishment of a multi-disciplinary team with daily care coordination and consistent messaging. Breaking down traditional hospital silos to allow for improved coordination of care benefits both the patients and the practitioners.
4. Managing emotional and physical suffering:  Introducing social workers, mental health professionals, or pastoral care advocates into the care team as soon as a patient is ready can help manage the emotional and psychosocial needs of patients and their families.
5. Sustaining long term surgeon/patient relationships:  As clinicians, we can feel rewarded after restoring functional performance in our patients and by meeting the needs of our patients and families. This can occur both in the short-term during the acute hospital stay and in the long-term as we follow our patients’ progress towards achievement of their ultimate goals.  
6. Attend to one’s own well-being and foster resilience. There will never be a substitute in our profession for the human connection between our patients and ourselves as their caregivers, and this connection should be one of the most treasured aspects of our work life.  We should seek daily reminders of these positive interactions to nurture our ability to cope with a grueling and challenging field, where the outcomes are not always as ideal as we hope.  

For me, STRONG is now a consistent and powerful reminder of why I originally became a doctor in the first place, and I strive to propagate this model of compassionate care to benefit future patients as we move forward together.”

We are at an inflexion point in health care. No amount of individual resilience can withstand a toxic or nonsupportive environment. It is unreasonable to think that simply by taking better care of ourselves we are going to resolve the issue of burnout. We need to rethink our current systems of care and focus our energy on developing those that support our ability to deliver the kind of care we know our patients need and deserve. We have an opportunity to alleviate the suffering many providers are experiencing as they strive to heal their patients. We have an opportunity to improve both physician and patient engagement, develop care delivery systems we know our patients deserve, and restore the deep sense of satisfaction that comes from practicing medicine and surgery. There is abundant expertise within our professional medical and surgical societies. The SVS has the courage and the duty to lead.

Drs. Colman, Kalish, and Sheahan extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, M.D., Scholar in Residence, Schwartz Center for Compassionate Care, Boston, Mass., and Clinical Professor of Orthopedics at Seattle Children’s Hospital. 

Bibliography
1. Acad Med (2016) 91:338-344
2. Health Aff (2011) 30:1772-1778
3. Patient Educ Couns (2015) 98:1005-10
4. Acad Med (2016) 91:310-316 
5. http://www.theschwartzcenter.org/media/Triple-C-Conference-Framework-Tables_FINAL.pdf  
6. http://www.theschwartzcenter.org/media/Triple-C-Conference-Recommendations-Report_FINAL1.pdf
7. JAMA (2017) 317: 901-2
8. Clin Orthop Relat Res. (2017) 475:1309-14. 

It is easy to look at the changes required to mitigate burnout and improve compassionate care and see the burden being placed mainly on the physician. Many of the proposed modifications seem to require the one commodity surgeons lack most, time. Any widespread effort to mitigate the burnout crisis must involve decreasing the barriers to patient care and reducing the physicians’ time constraints.

This may seem daunting, but broad changes in our healthcare system have been implemented in the name of quality, reducing errors, and alleviating trainee fatigue. Burnout can be a similar force for change. Much like the resident’s 80-hour workweek, however, in what manner this change is applied will be the ultimate determinant of the movement’s success.

The characteristics of compassionate care have been well described by patients, and, not surprisingly, only 53% reported that their last encounter with the health care system was compassionate. In 2014, a multidisciplinary consortium published recommendations for advancing compassionate person- and family-centered care. They detailed the attributes, values, and behaviors of such care, including focusing one’s attention, recognizing nonverbal clues, active listening, demonstrating nonjudgmental interest in the whole person, understanding the context of a person’s disease, and asking about the patient’s chief concerns in addition to their chief complaints. Most significantly, the authors outlined how these attributes could be integrated into existing competency documents such as those provided by the Association of American Medical Colleges (AAMC) Entrustable Professional Activities, or the milestones programs of the Accreditation Council of Graduate Medical Education (ACGME) and the American Board of Internal Medicine (ABIM). 

It is but a small step to enhance current criteria for certification, clinical appointment, and privileging by including these professional attributes. Bear in mind that these skills are teachable and easily incorporated into health professional education and clinical care. As for metrics, the Schwartz Compassionate Care Scale is a validated patient-rated questionnaire that reliably measures physicians’ compassion and overall patient satisfaction and is available in the public domain. It also provides a metric that is important to clinicians and, when placed on the hospital dashboard, highlights that compassion is an organizational priority. Such priorities become the fabric of the workforce when organizational leadership installs programs such as values-based recruitment, retention, and promotion as Vivian Lee describes at the University of Utah Health System. Mitigating burnout requires changing the culture in which clinicians work and with whom they work.  

Vascular surgeons and their professional surgical societies have a leadership opportunity to design high performing teams. Most patient care models have been structured around traditional medical and surgical departments. This paradigm overlooks the fact that patients do not “get sick” within traditional teaching disciplines but do so across varied medical and surgical specialties. Changes in organizational hierarchy are needed so that team-based care is supported. In addition to physician and nurse clinicians, the new teams would do well to expand to all “caregivers,” i.e. everyone who touches the patient (technologists, interpreters, pharmacists, transport workers, support staff, and administrators).

On the front line
On April 15, 2013, at 2:49 pm, two homemade bombs detonated near the finish line of the Boston Marathon killing three people at the scene and injuring 264 others; the most severe sustaining mutilating lower extremity injuries. Much has been written about the preparedness, the emergency response, and the fact that all those who made it to the hospital survived. Jeffrey Kalish, MD, a vascular surgeon at Boston Medical Center and SVS member, was on the front line that day. We asked him to share his personal experience of caring for the victims through the lens of compassionate collaborative care.   

“It has been over four years since I went from being a spectator near the Boston Marathon finish line to rushing directly to the operating rooms at Boston Medical Center to help our teams perform lifesaving procedures on critically ill patients, including amputations and complex vascular repairs. While I have learned a tremendous amount since that experience with regard to limb salvage and amputation, reconstructive techniques, and prosthetics, I will focus here on the care the patients and their families received, the lessons our hospital learned from the weeks and months that followed, and how we modeled this care going forward for all amputation patients at Boston Medical Center.  

"Based on lessons from the Boston Marathon bombings, I aligned a multidisciplinary team of health care providers in order to formalize and standardize best practices to benefit our amputation patients. STRONG (Surgery To Rehab Ongoing Needs Group) continues to strive toward the ultimate goal of improving and coordinating care for amputation patients and their families as they transition from the hospital setting to rehabilitation. Some of our guiding principles, along with their positive impacts on patient care and physician well-being, are highlighted below:
1. Sustaining hope with a new mindset: Although surgeons have historically considered amputation as a treatment failure, a more appropriate mindset is that amputation can often be a reconstructive procedure in the surgical armamentarium designed to restore a patient back to full function.
2. Seeing the patient in context: Shared decision making can occur more readily once a surgeon and the care team seek to understand the whole person and their family, including what that person does for work and leisure.
3. Communication with colleagues, patients, and families: Patient and family fear and confusion can often be reduced after establishment of a multi-disciplinary team with daily care coordination and consistent messaging. Breaking down traditional hospital silos to allow for improved coordination of care benefits both the patients and the practitioners.
4. Managing emotional and physical suffering:  Introducing social workers, mental health professionals, or pastoral care advocates into the care team as soon as a patient is ready can help manage the emotional and psychosocial needs of patients and their families.
5. Sustaining long term surgeon/patient relationships:  As clinicians, we can feel rewarded after restoring functional performance in our patients and by meeting the needs of our patients and families. This can occur both in the short-term during the acute hospital stay and in the long-term as we follow our patients’ progress towards achievement of their ultimate goals.  
6. Attend to one’s own well-being and foster resilience. There will never be a substitute in our profession for the human connection between our patients and ourselves as their caregivers, and this connection should be one of the most treasured aspects of our work life.  We should seek daily reminders of these positive interactions to nurture our ability to cope with a grueling and challenging field, where the outcomes are not always as ideal as we hope.  

For me, STRONG is now a consistent and powerful reminder of why I originally became a doctor in the first place, and I strive to propagate this model of compassionate care to benefit future patients as we move forward together.”

We are at an inflexion point in health care. No amount of individual resilience can withstand a toxic or nonsupportive environment. It is unreasonable to think that simply by taking better care of ourselves we are going to resolve the issue of burnout. We need to rethink our current systems of care and focus our energy on developing those that support our ability to deliver the kind of care we know our patients need and deserve. We have an opportunity to alleviate the suffering many providers are experiencing as they strive to heal their patients. We have an opportunity to improve both physician and patient engagement, develop care delivery systems we know our patients deserve, and restore the deep sense of satisfaction that comes from practicing medicine and surgery. There is abundant expertise within our professional medical and surgical societies. The SVS has the courage and the duty to lead.

Drs. Colman, Kalish, and Sheahan extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, M.D., Scholar in Residence, Schwartz Center for Compassionate Care, Boston, Mass., and Clinical Professor of Orthopedics at Seattle Children’s Hospital. 

Bibliography
1. Acad Med (2016) 91:338-344
2. Health Aff (2011) 30:1772-1778
3. Patient Educ Couns (2015) 98:1005-10
4. Acad Med (2016) 91:310-316 
5. http://www.theschwartzcenter.org/media/Triple-C-Conference-Framework-Tables_FINAL.pdf  
6. http://www.theschwartzcenter.org/media/Triple-C-Conference-Recommendations-Report_FINAL1.pdf
7. JAMA (2017) 317: 901-2
8. Clin Orthop Relat Res. (2017) 475:1309-14. 

SAN DIEGO – Injuries and lawsuits related to laser cosmetic surgery are increasing and potential legal threats are not always easy to predict, according to two dermatologists who spoke at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).

A laser procedure could go smoothly, for example, but the patient might be able to successfully sue if he or she is allowed to drive home after receiving a sedative. Or a physician might get sued because his or her nurse set a laser at the wrong setting and singed a patient.

The risk of a lawsuit is high, H. Ray Jalian, MD, a dermatologist in Los Angeles, said at the meeting. “The reality is that we’re all at some point going to face this.”

• You may have a duty to protect your patient from bad choices.

Physicians aren’t expected to keep patients from making certain bad decisions such as sunbathing after a traditional resurfacing procedure, said Dr. Avram, of the department of dermatology, Harvard Medical School, Boston, and the ASLMS president. But in some cases, he said, the law may expect the physician to step in to prevent harm. For example, he said, a patient who has undergone a fractional ablative laser procedure and has received a sedative should not be allowed to drive home.

• You may get sued even if your employee is at fault.

The 2013 study found physicians were often sued even when they did not perform the laser procedure in question. Nonphysicians such as physician assistants and nurses often perform laser operations, and many states allow them to do so. “Nonphysicians were less likely to be sued even if they were the operators,” Dr. Jalian said. In the study, almost 38% of the 174 analyzed cases involved nonphysician operators, but they were sued in just 26% of the cases. In 33 of the 174 cases in the study, plaintiffs alleged failure to properly hire, train, or supervise staff.

He recommended looking at state laws, which differ greatly in their regulations – or lack of them – regarding the operation of medical lasers. In some cases, physicians must supervise laser use, he said. “But what are the requirements? Can you be available by phone down the street or in the Caribbean?”

Dr. Jalian, Dr. Avram, and a colleague followed up the 2013 study with another study that tracked 175 legal cases from 1999 to 2012 involving alleged injuries from cutaneous laser surgery. During this time period, 75 (43%) involved a nonphysician operating a laser, increasing from 36% in 2008 to 78% in 2012.

In almost two-thirds of cases, the procedures in question were done by nonphysicians outside a “traditional medical setting” such as a salon or spa (JAMA Dermatol. 2014 Apr;150[4]:407-11).

• Delayed side effects could mean delayed lawsuits.

According to Dr. Avram, statutes of limitations – the length of time in which a patient can file a lawsuit – typically last for 2-3 years in malpractice cases. But he said that the period begins when the physician is alleged to have made a mistake or when the patient becomes aware of – or should reasonably be aware of – an injury. Therefore, physicians could face legal trouble over delayed hypopigmentation that appears 6 months after a laser resurfacing treatment, or granulomas that appear years after a filler treatment, he said.

• A signed form is not a cure-all.

It is wise to make patients sign an extensive informed consent form, but this will not protect a physician against a claim of negligence, Dr. Avram said. And the reverse is also true: If a patient did not sign a proper consent form, he or she could still sue even if the procedure went perfectly, he noted.

• Your instincts are worth trusting.

When it comes to lawsuit prevention, Dr. Avram said, “by far the most important thing you can do happens within a minute of when you see the patient. Assess and trust your own intuition and your staff’s intuition. For elective, cosmetic treatments, don’t be afraid to say no. There’s no legal obligation to perform a cosmetic treatment on a patient.”

If you do choose to treat a patient, he advised, be open about the procedure and “maybe even tell them some of the tougher, worse-case scenarios.” If a procedure goes poorly, he said, consider how to fix it. “Many complications can be significantly improved or cleared with timely and appropriate intervention,” he said.

In some cases, refunding the patient’s money can be considered, with the patient signing a release, he said. “Document that you are refunding the money in order to preserve the doctor-patient relationship, not to avoid negligence.”

Dr. Jalian and Dr. Avram reported no relevant disclosures.

SAN DIEGO – Injuries and lawsuits related to laser cosmetic surgery are increasing and potential legal threats are not always easy to predict, according to two dermatologists who spoke at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).

A laser procedure could go smoothly, for example, but the patient might be able to successfully sue if he or she is allowed to drive home after receiving a sedative. Or a physician might get sued because his or her nurse set a laser at the wrong setting and singed a patient.

The risk of a lawsuit is high, H. Ray Jalian, MD, a dermatologist in Los Angeles, said at the meeting. “The reality is that we’re all at some point going to face this.”

• You may have a duty to protect your patient from bad choices.

Physicians aren’t expected to keep patients from making certain bad decisions such as sunbathing after a traditional resurfacing procedure, said Dr. Avram, of the department of dermatology, Harvard Medical School, Boston, and the ASLMS president. But in some cases, he said, the law may expect the physician to step in to prevent harm. For example, he said, a patient who has undergone a fractional ablative laser procedure and has received a sedative should not be allowed to drive home.

• You may get sued even if your employee is at fault.

The 2013 study found physicians were often sued even when they did not perform the laser procedure in question. Nonphysicians such as physician assistants and nurses often perform laser operations, and many states allow them to do so. “Nonphysicians were less likely to be sued even if they were the operators,” Dr. Jalian said. In the study, almost 38% of the 174 analyzed cases involved nonphysician operators, but they were sued in just 26% of the cases. In 33 of the 174 cases in the study, plaintiffs alleged failure to properly hire, train, or supervise staff.

He recommended looking at state laws, which differ greatly in their regulations – or lack of them – regarding the operation of medical lasers. In some cases, physicians must supervise laser use, he said. “But what are the requirements? Can you be available by phone down the street or in the Caribbean?”

Dr. Jalian, Dr. Avram, and a colleague followed up the 2013 study with another study that tracked 175 legal cases from 1999 to 2012 involving alleged injuries from cutaneous laser surgery. During this time period, 75 (43%) involved a nonphysician operating a laser, increasing from 36% in 2008 to 78% in 2012.

In almost two-thirds of cases, the procedures in question were done by nonphysicians outside a “traditional medical setting” such as a salon or spa (JAMA Dermatol. 2014 Apr;150[4]:407-11).

• Delayed side effects could mean delayed lawsuits.

According to Dr. Avram, statutes of limitations – the length of time in which a patient can file a lawsuit – typically last for 2-3 years in malpractice cases. But he said that the period begins when the physician is alleged to have made a mistake or when the patient becomes aware of – or should reasonably be aware of – an injury. Therefore, physicians could face legal trouble over delayed hypopigmentation that appears 6 months after a laser resurfacing treatment, or granulomas that appear years after a filler treatment, he said.

• A signed form is not a cure-all.

It is wise to make patients sign an extensive informed consent form, but this will not protect a physician against a claim of negligence, Dr. Avram said. And the reverse is also true: If a patient did not sign a proper consent form, he or she could still sue even if the procedure went perfectly, he noted.

• Your instincts are worth trusting.

When it comes to lawsuit prevention, Dr. Avram said, “by far the most important thing you can do happens within a minute of when you see the patient. Assess and trust your own intuition and your staff’s intuition. For elective, cosmetic treatments, don’t be afraid to say no. There’s no legal obligation to perform a cosmetic treatment on a patient.”

If you do choose to treat a patient, he advised, be open about the procedure and “maybe even tell them some of the tougher, worse-case scenarios.” If a procedure goes poorly, he said, consider how to fix it. “Many complications can be significantly improved or cleared with timely and appropriate intervention,” he said.

In some cases, refunding the patient’s money can be considered, with the patient signing a release, he said. “Document that you are refunding the money in order to preserve the doctor-patient relationship, not to avoid negligence.”

Dr. Jalian and Dr. Avram reported no relevant disclosures.

SAN DIEGO – Injuries and lawsuits related to laser cosmetic surgery are increasing and potential legal threats are not always easy to predict, according to two dermatologists who spoke at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).

A laser procedure could go smoothly, for example, but the patient might be able to successfully sue if he or she is allowed to drive home after receiving a sedative. Or a physician might get sued because his or her nurse set a laser at the wrong setting and singed a patient.

The risk of a lawsuit is high, H. Ray Jalian, MD, a dermatologist in Los Angeles, said at the meeting. “The reality is that we’re all at some point going to face this.”

• You may have a duty to protect your patient from bad choices.

Physicians aren’t expected to keep patients from making certain bad decisions such as sunbathing after a traditional resurfacing procedure, said Dr. Avram, of the department of dermatology, Harvard Medical School, Boston, and the ASLMS president. But in some cases, he said, the law may expect the physician to step in to prevent harm. For example, he said, a patient who has undergone a fractional ablative laser procedure and has received a sedative should not be allowed to drive home.

• You may get sued even if your employee is at fault.

The 2013 study found physicians were often sued even when they did not perform the laser procedure in question. Nonphysicians such as physician assistants and nurses often perform laser operations, and many states allow them to do so. “Nonphysicians were less likely to be sued even if they were the operators,” Dr. Jalian said. In the study, almost 38% of the 174 analyzed cases involved nonphysician operators, but they were sued in just 26% of the cases. In 33 of the 174 cases in the study, plaintiffs alleged failure to properly hire, train, or supervise staff.

He recommended looking at state laws, which differ greatly in their regulations – or lack of them – regarding the operation of medical lasers. In some cases, physicians must supervise laser use, he said. “But what are the requirements? Can you be available by phone down the street or in the Caribbean?”

Dr. Jalian, Dr. Avram, and a colleague followed up the 2013 study with another study that tracked 175 legal cases from 1999 to 2012 involving alleged injuries from cutaneous laser surgery. During this time period, 75 (43%) involved a nonphysician operating a laser, increasing from 36% in 2008 to 78% in 2012.

In almost two-thirds of cases, the procedures in question were done by nonphysicians outside a “traditional medical setting” such as a salon or spa (JAMA Dermatol. 2014 Apr;150[4]:407-11).

• Delayed side effects could mean delayed lawsuits.

According to Dr. Avram, statutes of limitations – the length of time in which a patient can file a lawsuit – typically last for 2-3 years in malpractice cases. But he said that the period begins when the physician is alleged to have made a mistake or when the patient becomes aware of – or should reasonably be aware of – an injury. Therefore, physicians could face legal trouble over delayed hypopigmentation that appears 6 months after a laser resurfacing treatment, or granulomas that appear years after a filler treatment, he said.

• A signed form is not a cure-all.

It is wise to make patients sign an extensive informed consent form, but this will not protect a physician against a claim of negligence, Dr. Avram said. And the reverse is also true: If a patient did not sign a proper consent form, he or she could still sue even if the procedure went perfectly, he noted.

• Your instincts are worth trusting.

When it comes to lawsuit prevention, Dr. Avram said, “by far the most important thing you can do happens within a minute of when you see the patient. Assess and trust your own intuition and your staff’s intuition. For elective, cosmetic treatments, don’t be afraid to say no. There’s no legal obligation to perform a cosmetic treatment on a patient.”

If you do choose to treat a patient, he advised, be open about the procedure and “maybe even tell them some of the tougher, worse-case scenarios.” If a procedure goes poorly, he said, consider how to fix it. “Many complications can be significantly improved or cleared with timely and appropriate intervention,” he said.

In some cases, refunding the patient’s money can be considered, with the patient signing a release, he said. “Document that you are refunding the money in order to preserve the doctor-patient relationship, not to avoid negligence.”

Dr. Jalian and Dr. Avram reported no relevant disclosures.

SAN FRANCISCO – Nearly 40% of breast cancer patients experience prolonged depression lasting for at least 16 months after diagnosis of their malignancy; those at increased risk may be identifiable in a timely way by their exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy, according to Kate R. Kuhlman, PhD.

“There are several psychological interventions that mitigate depressive symptoms and psychologic distress in women with breast cancer. This time period immediately following cancer diagnosis and surgery may be the optimal time to intervene,” said Dr. Kuhlman, a psychologist at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Nearly 40% of breast cancer patients experience prolonged depression lasting for at least 16 months after diagnosis of their malignancy; those at increased risk may be identifiable in a timely way by their exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy, according to Kate R. Kuhlman, PhD.

“There are several psychological interventions that mitigate depressive symptoms and psychologic distress in women with breast cancer. This time period immediately following cancer diagnosis and surgery may be the optimal time to intervene,” said Dr. Kuhlman, a psychologist at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Nearly 40% of breast cancer patients experience prolonged depression lasting for at least 16 months after diagnosis of their malignancy; those at increased risk may be identifiable in a timely way by their exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy, according to Kate R. Kuhlman, PhD.

“There are several psychological interventions that mitigate depressive symptoms and psychologic distress in women with breast cancer. This time period immediately following cancer diagnosis and surgery may be the optimal time to intervene,” said Dr. Kuhlman, a psychologist at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

[email protected]

Muckle-Wells syndrome (MWS) was first described in 1962 and is part of a broad category of hereditary periodic fever syndromes that include the autoinflammatory syndromes and the cryopyrin-associated periodic syndromes (CAPSs). Unlike autoimmune diseases, autoinflammatory syndromes are not associated with antigen-specific T-cell responses or high titers of autoantibodies but are related to disorders of the innate immune system. Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare genodermatosis inherited in an autosomal-dominant fashion that is characterized by a broad range of anomalies. Most notable is the early and strong predisposition to develop several to hundreds of basal cell carcinomas (BCCs). Classic clinical features of MWS and a thorough history and physical examination can assist in the diagnosis of this rare entity.

Case Report

A 35-year-old woman with a history of BCNS, which had been diagnosed at 24 years of age based on the presence of more than 2 BCCs and a family history of BCNS in her mother, presented with intermittent pruritic urticaria on the chest and back, episodic fevers, associated joint pain and swelling that worsened several hours after exercise, headache, conjunctivitis, blurred vision, and severe debilitating fatigue that had been present since childhood. The symptoms had progressively worsened with age and symptom-free intervals became shorter. She was diagnosed by her rheumatologist with biopsy-proven MWS and a positive NLRP3 (NLR family pyrin domain containing 3) gene mutation at 29 years of age. She was treated unsuccessfully with prednisone and antihistamines and entered a trial with anakinra. She showed improvement for 2 weeks but developed severe swelling and erythema at the injection sites at week 3, along with large leathery patches on the legs and difficulty ambulating.

The patient subsequently underwent excision of her BCCs and reported each site became erythematous, edematous, warm, and painful 6 hours after excision, which lasted for hours to days (Figures 1–3). After the first excision on the right forearm, she was seen in the emergency department, started on intravenous antibiotics and prednisone, and kept overnight in the hospital. She was discharged the following day and the edema in the right forearm subsided over several days. Bacterial culture and laboratory evaluation for infection were negative after the first excision on the right forearm. Because of the symptoms she experienced following this excision, she was referred to the plastic surgery department for excision followed by postoperative monitoring in the hospital. The patient continued to undergo excisions for BCCs and developed more severe symptoms including erythema, edema, warmth, and tenderness at the surrounding sites. Once again, the excision sites were cultured and laboratory work to rule out infection was ordered with a negative result. After several excisions and subsequent clinical findings, the patients’ symptoms were deemed consistent with MWS and not a result of infectious etiology. A diagnosis of MWS and BCNS with exacerbation of MWS with surgical procedures was made.

The patient has continued therapy with rilonacept for MWS, which is managed by her rheumatologist. She has tolerated rilonacept without adverse effects and has experienced a reduction in symptoms that has enhanced her quality of life and allows for further treatment of her BCNS. Her dermatologist (J.W.L.) has been treating her BCCs with vismodegib, but treatment has been sporadic due to muscle cramping after 7 days of therapy. She reported subjective improvement to her dermatologist and has tried alternating 7 days on and 7 days off vismodegib. The muscle cramping still has limited her treatment with this regimen, and she is currently on a trial of 3 days on, 4 days off per week.

Comment

Classification and Clinical Presentation
The hereditary periodic fever syndromes include the autoinflammatory syndromes and the CAPSs. The autoinflammatory syndromes include familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fever syndrome, and tumor necrosis factor receptor–associated periodic syndrome. The CAPSs are similar but distinct and include familial cold autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic cutaneous and articular syndrome, or cutaneous articular syndrome) and MWS.^1,2

Cryopyrin-associated periodic syndromes are rare inherited diseases that result from mutations in the NLRP3 gene. There is a gain-of-function mutation on the NLRP3 gene located on the long arm of chromosome 1 at position 44, which codes for cryopyrin. An NLRP3 gene mutation causes cryopyrin to become hyperactive, leading to the formation of an inflammasome, which is a group of cryopyrin molecules. Inflammasomes, along with other proteins, activate caspase 1 to produce excess IL-1β, leading to persistent inflammatory symptoms.³ IL-1β is one of the key mediators of the body’s response to microbial invasion, inflammation, immunologic reactions, and tissue injury. It affects a large range of cells and organs. Although IL-1β production is critical for the control of pathogenic infections, excessive cytokine production is harmful to the host and can even be fatal.^3,4

Cryopyrin-associated periodic syndromes encompass a disease continuum. The 3 distinct entities share many overlapping features as well as unique and distinguishing characteristics. Familial cold autoinflammatory syndrome is the mildest phenotype and is inherited in an autosomal-dominant fashion. It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk. A low-grade fever often is seen along with musculoskeletal concerns of arthralgia and pain. Other commonly reported symptoms include conjunctivitis, myalgia, fatigue, and headache. Neurologic symptoms can include headaches. Symptoms usually begin 1 to 2 hours after cold exposure and last less than 24 hours.^5-8

Neonatal-onset multisystem inflammatory disease is the most severe phenotype and occurs sporadically. Continuous symptoms and flares are characteristic and the length of the flare can vary from minutes to days. The cutaneous eruption favors the face, trunk, arms, and legs, and varies in intensity, beginning in infancy or childhood. Fever may be intermittent, mild, or absent. Rheumatologic manifestations include arthralgia and swelling, with approximately one-third of patients experiencing severe disabling arthropathy that causes gross joint deformity. Ocular findings include conjunctivitis, uveitis, papilledema, and even blindness. Neurologic sequelae include headaches, sensorineural hearing loss, and aseptic meningitis. Amyloidosis has been seen as a late complication.^5,8

Muckle-Wells syndrome is a rare hereditary inflammatory disorder. It has no ethnic predisposition and is mostly inherited in an autosomal-dominant fashion. Classically, the condition is characterized by recurrent urticaria beginning at birth with intermittent episodic fever and malaise. The eruption has a predilection for the face, trunk, arms, and legs, which is similar to neonatal-onset multisystem inflammatory disease. Associated myalgia and arthralgia are common as well as ocular findings of conjunctivitis and episcleritis. Neurologic manifestations include headache and progressive sensorineural hearing loss in 60% to 70% of patients.⁶ Abdominal pain may be seen along with rare serositis in MWS but is rare in the other CAPSs. Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment. Symptoms of MWS may occur daily but vary individually, are broad in intensity and duration, and can last 1 to 2 days before resolving spontaneously. The symptoms can result from metabolic stressors including cold, stress, and exercise, as well as microbial pathogens. Leukocytosis and increased acute-phase reactants are observed during episodes of inflammation.^4,6,8

Histopathology
Mild phenotypic variability exists between individuals, and many of the symptoms overlap in CAPSs. Although CAPSs display several distinguishing clinical characteristics, interestingly they share the same histopathological features regardless of the syndrome. The typical histopathological finding is a dermal neutrophilic infiltrate that tends to be perivascular and also may be perieccrine. Vasodilation and dermal edema also may be seen. These histopathological findings contrast with the typical lymphocytic and eosinophilic infiltrate seen in classic urticaria. Similar histopathologic findings have been seen in other neutrophilic urticarial dermatoses such as Schnitzler syndrome.^4,6

Differential
The differential diagnoses for CAPSs include Schnitzler syndrome, cold urticaria, systemic-onset juvenile idiopathic arthritis/adult-onset Still disease, and deficiency in IL-1ra. It is important to consider these differential diagnoses for management and treatment options.

Management
The discovery of the NLRP3 gene mutation as well as an understanding of IL-1 biology has led to targeted therapy for these syndromes. Cryopyrin-associated periodic syndromes are mediated by IL-1β with an in vivo rate 5 times higher than in healthy patients.⁴ The blockade of IL-1β results in complete resolution of symptoms.

In the last several years, anakinra, rilonacept, and canakinumab have shown efficacy in targeting IL-1β as receptor antagonists. Anakinra is a short-acting recombinant IL-1ra with a half-life of 4 to 6 hours. This short half-life requires daily injections and the most common adverse events included injection-site reaction and upper respiratory tract infection.^2,4 Rilonacept is a dimeric fusion protein that contains binding regions for the type 1 receptor and the IL-1 receptor accessory protein and is fused to the fragment, crystallizable (Fc) portion of human IgG1. Rilonacept is long acting with a circulating half-life of 8.6 days and offers patients ease of dosing with weekly subcutaneous injections. Rilonacept generally is well tolerated, with the most frequent adverse effects being injection-site reaction, upper respiratory tract infection, headache, arthralgia, and diarrhea.^2,7

The newest of the treatments for patients with CAPS is canakinumab. It is a fully human IL-1β monoclonal antibody that is specific for IL-1β and not other members of the IL-1 family. It has a mean half-life of 26 days and is dosed subcutaneously once every 8 weeks. The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo.⁴ In one study, most patients did not report injection-site reactions.⁷ Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream in the IL-1β pathway. Treatment with anakinra, rilonacept, and canakinumab generally offers rapid and sustained remission in the majority of MWS patients and helps prevent the development of systemic amyloidosis and lessens the potential for end organ damage.^2,7

MWS and BCNS
Our patient had an unusual presentation of MWS complicated by BCNS, another rare autosomal-dominant inherited genodermatosis. In an extensive review of PubMed articles indexed for MEDLINE using the search terms Muckle-Wells syndrome and basal cell nevus syndrome, no association was identified between MWS and BCNS. Basal cell nevus syndrome is linked to PTCH1 (patched 1) gene mutation with an incidence of 1:150,000 in the United States and Europe and is characterized by a broad range of anomalies including skeletal abnormalities, ectopic calcification, odontogenic keratocysts, facial dysmorphism with macrocephaly, palmoplantar pits, and numerous tumors. Most notable is the early and strong predisposition to develop several to hundreds of BCCs.⁹

Conclusion

Muckle-Wells syndrome may go undiagnosed for many years or may be misdiagnosed as refractory urticaria, as in our patient. It is important to include periodic fever syndromes in the differential diagnosis of refractory urticaria with episodic fever to diagnose these cases of MWS earlier.

Muckle-Wells syndrome (MWS) was first described in 1962 and is part of a broad category of hereditary periodic fever syndromes that include the autoinflammatory syndromes and the cryopyrin-associated periodic syndromes (CAPSs). Unlike autoimmune diseases, autoinflammatory syndromes are not associated with antigen-specific T-cell responses or high titers of autoantibodies but are related to disorders of the innate immune system. Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare genodermatosis inherited in an autosomal-dominant fashion that is characterized by a broad range of anomalies. Most notable is the early and strong predisposition to develop several to hundreds of basal cell carcinomas (BCCs). Classic clinical features of MWS and a thorough history and physical examination can assist in the diagnosis of this rare entity.

Case Report

A 35-year-old woman with a history of BCNS, which had been diagnosed at 24 years of age based on the presence of more than 2 BCCs and a family history of BCNS in her mother, presented with intermittent pruritic urticaria on the chest and back, episodic fevers, associated joint pain and swelling that worsened several hours after exercise, headache, conjunctivitis, blurred vision, and severe debilitating fatigue that had been present since childhood. The symptoms had progressively worsened with age and symptom-free intervals became shorter. She was diagnosed by her rheumatologist with biopsy-proven MWS and a positive NLRP3 (NLR family pyrin domain containing 3) gene mutation at 29 years of age. She was treated unsuccessfully with prednisone and antihistamines and entered a trial with anakinra. She showed improvement for 2 weeks but developed severe swelling and erythema at the injection sites at week 3, along with large leathery patches on the legs and difficulty ambulating.

The patient subsequently underwent excision of her BCCs and reported each site became erythematous, edematous, warm, and painful 6 hours after excision, which lasted for hours to days (Figures 1–3). After the first excision on the right forearm, she was seen in the emergency department, started on intravenous antibiotics and prednisone, and kept overnight in the hospital. She was discharged the following day and the edema in the right forearm subsided over several days. Bacterial culture and laboratory evaluation for infection were negative after the first excision on the right forearm. Because of the symptoms she experienced following this excision, she was referred to the plastic surgery department for excision followed by postoperative monitoring in the hospital. The patient continued to undergo excisions for BCCs and developed more severe symptoms including erythema, edema, warmth, and tenderness at the surrounding sites. Once again, the excision sites were cultured and laboratory work to rule out infection was ordered with a negative result. After several excisions and subsequent clinical findings, the patients’ symptoms were deemed consistent with MWS and not a result of infectious etiology. A diagnosis of MWS and BCNS with exacerbation of MWS with surgical procedures was made.

The patient has continued therapy with rilonacept for MWS, which is managed by her rheumatologist. She has tolerated rilonacept without adverse effects and has experienced a reduction in symptoms that has enhanced her quality of life and allows for further treatment of her BCNS. Her dermatologist (J.W.L.) has been treating her BCCs with vismodegib, but treatment has been sporadic due to muscle cramping after 7 days of therapy. She reported subjective improvement to her dermatologist and has tried alternating 7 days on and 7 days off vismodegib. The muscle cramping still has limited her treatment with this regimen, and she is currently on a trial of 3 days on, 4 days off per week.

Comment

Classification and Clinical Presentation
The hereditary periodic fever syndromes include the autoinflammatory syndromes and the CAPSs. The autoinflammatory syndromes include familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fever syndrome, and tumor necrosis factor receptor–associated periodic syndrome. The CAPSs are similar but distinct and include familial cold autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic cutaneous and articular syndrome, or cutaneous articular syndrome) and MWS.^1,2

Cryopyrin-associated periodic syndromes are rare inherited diseases that result from mutations in the NLRP3 gene. There is a gain-of-function mutation on the NLRP3 gene located on the long arm of chromosome 1 at position 44, which codes for cryopyrin. An NLRP3 gene mutation causes cryopyrin to become hyperactive, leading to the formation of an inflammasome, which is a group of cryopyrin molecules. Inflammasomes, along with other proteins, activate caspase 1 to produce excess IL-1β, leading to persistent inflammatory symptoms.³ IL-1β is one of the key mediators of the body’s response to microbial invasion, inflammation, immunologic reactions, and tissue injury. It affects a large range of cells and organs. Although IL-1β production is critical for the control of pathogenic infections, excessive cytokine production is harmful to the host and can even be fatal.^3,4

Cryopyrin-associated periodic syndromes encompass a disease continuum. The 3 distinct entities share many overlapping features as well as unique and distinguishing characteristics. Familial cold autoinflammatory syndrome is the mildest phenotype and is inherited in an autosomal-dominant fashion. It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk. A low-grade fever often is seen along with musculoskeletal concerns of arthralgia and pain. Other commonly reported symptoms include conjunctivitis, myalgia, fatigue, and headache. Neurologic symptoms can include headaches. Symptoms usually begin 1 to 2 hours after cold exposure and last less than 24 hours.^5-8

Neonatal-onset multisystem inflammatory disease is the most severe phenotype and occurs sporadically. Continuous symptoms and flares are characteristic and the length of the flare can vary from minutes to days. The cutaneous eruption favors the face, trunk, arms, and legs, and varies in intensity, beginning in infancy or childhood. Fever may be intermittent, mild, or absent. Rheumatologic manifestations include arthralgia and swelling, with approximately one-third of patients experiencing severe disabling arthropathy that causes gross joint deformity. Ocular findings include conjunctivitis, uveitis, papilledema, and even blindness. Neurologic sequelae include headaches, sensorineural hearing loss, and aseptic meningitis. Amyloidosis has been seen as a late complication.^5,8

Muckle-Wells syndrome is a rare hereditary inflammatory disorder. It has no ethnic predisposition and is mostly inherited in an autosomal-dominant fashion. Classically, the condition is characterized by recurrent urticaria beginning at birth with intermittent episodic fever and malaise. The eruption has a predilection for the face, trunk, arms, and legs, which is similar to neonatal-onset multisystem inflammatory disease. Associated myalgia and arthralgia are common as well as ocular findings of conjunctivitis and episcleritis. Neurologic manifestations include headache and progressive sensorineural hearing loss in 60% to 70% of patients.⁶ Abdominal pain may be seen along with rare serositis in MWS but is rare in the other CAPSs. Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment. Symptoms of MWS may occur daily but vary individually, are broad in intensity and duration, and can last 1 to 2 days before resolving spontaneously. The symptoms can result from metabolic stressors including cold, stress, and exercise, as well as microbial pathogens. Leukocytosis and increased acute-phase reactants are observed during episodes of inflammation.^4,6,8

Histopathology
Mild phenotypic variability exists between individuals, and many of the symptoms overlap in CAPSs. Although CAPSs display several distinguishing clinical characteristics, interestingly they share the same histopathological features regardless of the syndrome. The typical histopathological finding is a dermal neutrophilic infiltrate that tends to be perivascular and also may be perieccrine. Vasodilation and dermal edema also may be seen. These histopathological findings contrast with the typical lymphocytic and eosinophilic infiltrate seen in classic urticaria. Similar histopathologic findings have been seen in other neutrophilic urticarial dermatoses such as Schnitzler syndrome.^4,6

Differential
The differential diagnoses for CAPSs include Schnitzler syndrome, cold urticaria, systemic-onset juvenile idiopathic arthritis/adult-onset Still disease, and deficiency in IL-1ra. It is important to consider these differential diagnoses for management and treatment options.

Management
The discovery of the NLRP3 gene mutation as well as an understanding of IL-1 biology has led to targeted therapy for these syndromes. Cryopyrin-associated periodic syndromes are mediated by IL-1β with an in vivo rate 5 times higher than in healthy patients.⁴ The blockade of IL-1β results in complete resolution of symptoms.

In the last several years, anakinra, rilonacept, and canakinumab have shown efficacy in targeting IL-1β as receptor antagonists. Anakinra is a short-acting recombinant IL-1ra with a half-life of 4 to 6 hours. This short half-life requires daily injections and the most common adverse events included injection-site reaction and upper respiratory tract infection.^2,4 Rilonacept is a dimeric fusion protein that contains binding regions for the type 1 receptor and the IL-1 receptor accessory protein and is fused to the fragment, crystallizable (Fc) portion of human IgG1. Rilonacept is long acting with a circulating half-life of 8.6 days and offers patients ease of dosing with weekly subcutaneous injections. Rilonacept generally is well tolerated, with the most frequent adverse effects being injection-site reaction, upper respiratory tract infection, headache, arthralgia, and diarrhea.^2,7

The newest of the treatments for patients with CAPS is canakinumab. It is a fully human IL-1β monoclonal antibody that is specific for IL-1β and not other members of the IL-1 family. It has a mean half-life of 26 days and is dosed subcutaneously once every 8 weeks. The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo.⁴ In one study, most patients did not report injection-site reactions.⁷ Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream in the IL-1β pathway. Treatment with anakinra, rilonacept, and canakinumab generally offers rapid and sustained remission in the majority of MWS patients and helps prevent the development of systemic amyloidosis and lessens the potential for end organ damage.^2,7

MWS and BCNS
Our patient had an unusual presentation of MWS complicated by BCNS, another rare autosomal-dominant inherited genodermatosis. In an extensive review of PubMed articles indexed for MEDLINE using the search terms Muckle-Wells syndrome and basal cell nevus syndrome, no association was identified between MWS and BCNS. Basal cell nevus syndrome is linked to PTCH1 (patched 1) gene mutation with an incidence of 1:150,000 in the United States and Europe and is characterized by a broad range of anomalies including skeletal abnormalities, ectopic calcification, odontogenic keratocysts, facial dysmorphism with macrocephaly, palmoplantar pits, and numerous tumors. Most notable is the early and strong predisposition to develop several to hundreds of BCCs.⁹

Conclusion

Muckle-Wells syndrome may go undiagnosed for many years or may be misdiagnosed as refractory urticaria, as in our patient. It is important to include periodic fever syndromes in the differential diagnosis of refractory urticaria with episodic fever to diagnose these cases of MWS earlier.

Muckle-Wells syndrome (MWS) was first described in 1962 and is part of a broad category of hereditary periodic fever syndromes that include the autoinflammatory syndromes and the cryopyrin-associated periodic syndromes (CAPSs). Unlike autoimmune diseases, autoinflammatory syndromes are not associated with antigen-specific T-cell responses or high titers of autoantibodies but are related to disorders of the innate immune system. Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare genodermatosis inherited in an autosomal-dominant fashion that is characterized by a broad range of anomalies. Most notable is the early and strong predisposition to develop several to hundreds of basal cell carcinomas (BCCs). Classic clinical features of MWS and a thorough history and physical examination can assist in the diagnosis of this rare entity.

Case Report

A 35-year-old woman with a history of BCNS, which had been diagnosed at 24 years of age based on the presence of more than 2 BCCs and a family history of BCNS in her mother, presented with intermittent pruritic urticaria on the chest and back, episodic fevers, associated joint pain and swelling that worsened several hours after exercise, headache, conjunctivitis, blurred vision, and severe debilitating fatigue that had been present since childhood. The symptoms had progressively worsened with age and symptom-free intervals became shorter. She was diagnosed by her rheumatologist with biopsy-proven MWS and a positive NLRP3 (NLR family pyrin domain containing 3) gene mutation at 29 years of age. She was treated unsuccessfully with prednisone and antihistamines and entered a trial with anakinra. She showed improvement for 2 weeks but developed severe swelling and erythema at the injection sites at week 3, along with large leathery patches on the legs and difficulty ambulating.

The patient subsequently underwent excision of her BCCs and reported each site became erythematous, edematous, warm, and painful 6 hours after excision, which lasted for hours to days (Figures 1–3). After the first excision on the right forearm, she was seen in the emergency department, started on intravenous antibiotics and prednisone, and kept overnight in the hospital. She was discharged the following day and the edema in the right forearm subsided over several days. Bacterial culture and laboratory evaluation for infection were negative after the first excision on the right forearm. Because of the symptoms she experienced following this excision, she was referred to the plastic surgery department for excision followed by postoperative monitoring in the hospital. The patient continued to undergo excisions for BCCs and developed more severe symptoms including erythema, edema, warmth, and tenderness at the surrounding sites. Once again, the excision sites were cultured and laboratory work to rule out infection was ordered with a negative result. After several excisions and subsequent clinical findings, the patients’ symptoms were deemed consistent with MWS and not a result of infectious etiology. A diagnosis of MWS and BCNS with exacerbation of MWS with surgical procedures was made.

The patient has continued therapy with rilonacept for MWS, which is managed by her rheumatologist. She has tolerated rilonacept without adverse effects and has experienced a reduction in symptoms that has enhanced her quality of life and allows for further treatment of her BCNS. Her dermatologist (J.W.L.) has been treating her BCCs with vismodegib, but treatment has been sporadic due to muscle cramping after 7 days of therapy. She reported subjective improvement to her dermatologist and has tried alternating 7 days on and 7 days off vismodegib. The muscle cramping still has limited her treatment with this regimen, and she is currently on a trial of 3 days on, 4 days off per week.

Comment

Classification and Clinical Presentation
The hereditary periodic fever syndromes include the autoinflammatory syndromes and the CAPSs. The autoinflammatory syndromes include familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fever syndrome, and tumor necrosis factor receptor–associated periodic syndrome. The CAPSs are similar but distinct and include familial cold autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic cutaneous and articular syndrome, or cutaneous articular syndrome) and MWS.^1,2

Cryopyrin-associated periodic syndromes are rare inherited diseases that result from mutations in the NLRP3 gene. There is a gain-of-function mutation on the NLRP3 gene located on the long arm of chromosome 1 at position 44, which codes for cryopyrin. An NLRP3 gene mutation causes cryopyrin to become hyperactive, leading to the formation of an inflammasome, which is a group of cryopyrin molecules. Inflammasomes, along with other proteins, activate caspase 1 to produce excess IL-1β, leading to persistent inflammatory symptoms.³ IL-1β is one of the key mediators of the body’s response to microbial invasion, inflammation, immunologic reactions, and tissue injury. It affects a large range of cells and organs. Although IL-1β production is critical for the control of pathogenic infections, excessive cytokine production is harmful to the host and can even be fatal.^3,4

Cryopyrin-associated periodic syndromes encompass a disease continuum. The 3 distinct entities share many overlapping features as well as unique and distinguishing characteristics. Familial cold autoinflammatory syndrome is the mildest phenotype and is inherited in an autosomal-dominant fashion. It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk. A low-grade fever often is seen along with musculoskeletal concerns of arthralgia and pain. Other commonly reported symptoms include conjunctivitis, myalgia, fatigue, and headache. Neurologic symptoms can include headaches. Symptoms usually begin 1 to 2 hours after cold exposure and last less than 24 hours.^5-8

Neonatal-onset multisystem inflammatory disease is the most severe phenotype and occurs sporadically. Continuous symptoms and flares are characteristic and the length of the flare can vary from minutes to days. The cutaneous eruption favors the face, trunk, arms, and legs, and varies in intensity, beginning in infancy or childhood. Fever may be intermittent, mild, or absent. Rheumatologic manifestations include arthralgia and swelling, with approximately one-third of patients experiencing severe disabling arthropathy that causes gross joint deformity. Ocular findings include conjunctivitis, uveitis, papilledema, and even blindness. Neurologic sequelae include headaches, sensorineural hearing loss, and aseptic meningitis. Amyloidosis has been seen as a late complication.^5,8

Muckle-Wells syndrome is a rare hereditary inflammatory disorder. It has no ethnic predisposition and is mostly inherited in an autosomal-dominant fashion. Classically, the condition is characterized by recurrent urticaria beginning at birth with intermittent episodic fever and malaise. The eruption has a predilection for the face, trunk, arms, and legs, which is similar to neonatal-onset multisystem inflammatory disease. Associated myalgia and arthralgia are common as well as ocular findings of conjunctivitis and episcleritis. Neurologic manifestations include headache and progressive sensorineural hearing loss in 60% to 70% of patients.⁶ Abdominal pain may be seen along with rare serositis in MWS but is rare in the other CAPSs. Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment. Symptoms of MWS may occur daily but vary individually, are broad in intensity and duration, and can last 1 to 2 days before resolving spontaneously. The symptoms can result from metabolic stressors including cold, stress, and exercise, as well as microbial pathogens. Leukocytosis and increased acute-phase reactants are observed during episodes of inflammation.^4,6,8

Histopathology
Mild phenotypic variability exists between individuals, and many of the symptoms overlap in CAPSs. Although CAPSs display several distinguishing clinical characteristics, interestingly they share the same histopathological features regardless of the syndrome. The typical histopathological finding is a dermal neutrophilic infiltrate that tends to be perivascular and also may be perieccrine. Vasodilation and dermal edema also may be seen. These histopathological findings contrast with the typical lymphocytic and eosinophilic infiltrate seen in classic urticaria. Similar histopathologic findings have been seen in other neutrophilic urticarial dermatoses such as Schnitzler syndrome.^4,6

Differential
The differential diagnoses for CAPSs include Schnitzler syndrome, cold urticaria, systemic-onset juvenile idiopathic arthritis/adult-onset Still disease, and deficiency in IL-1ra. It is important to consider these differential diagnoses for management and treatment options.

Management
The discovery of the NLRP3 gene mutation as well as an understanding of IL-1 biology has led to targeted therapy for these syndromes. Cryopyrin-associated periodic syndromes are mediated by IL-1β with an in vivo rate 5 times higher than in healthy patients.⁴ The blockade of IL-1β results in complete resolution of symptoms.

In the last several years, anakinra, rilonacept, and canakinumab have shown efficacy in targeting IL-1β as receptor antagonists. Anakinra is a short-acting recombinant IL-1ra with a half-life of 4 to 6 hours. This short half-life requires daily injections and the most common adverse events included injection-site reaction and upper respiratory tract infection.^2,4 Rilonacept is a dimeric fusion protein that contains binding regions for the type 1 receptor and the IL-1 receptor accessory protein and is fused to the fragment, crystallizable (Fc) portion of human IgG1. Rilonacept is long acting with a circulating half-life of 8.6 days and offers patients ease of dosing with weekly subcutaneous injections. Rilonacept generally is well tolerated, with the most frequent adverse effects being injection-site reaction, upper respiratory tract infection, headache, arthralgia, and diarrhea.^2,7

The newest of the treatments for patients with CAPS is canakinumab. It is a fully human IL-1β monoclonal antibody that is specific for IL-1β and not other members of the IL-1 family. It has a mean half-life of 26 days and is dosed subcutaneously once every 8 weeks. The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo.⁴ In one study, most patients did not report injection-site reactions.⁷ Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream in the IL-1β pathway. Treatment with anakinra, rilonacept, and canakinumab generally offers rapid and sustained remission in the majority of MWS patients and helps prevent the development of systemic amyloidosis and lessens the potential for end organ damage.^2,7

MWS and BCNS
Our patient had an unusual presentation of MWS complicated by BCNS, another rare autosomal-dominant inherited genodermatosis. In an extensive review of PubMed articles indexed for MEDLINE using the search terms Muckle-Wells syndrome and basal cell nevus syndrome, no association was identified between MWS and BCNS. Basal cell nevus syndrome is linked to PTCH1 (patched 1) gene mutation with an incidence of 1:150,000 in the United States and Europe and is characterized by a broad range of anomalies including skeletal abnormalities, ectopic calcification, odontogenic keratocysts, facial dysmorphism with macrocephaly, palmoplantar pits, and numerous tumors. Most notable is the early and strong predisposition to develop several to hundreds of BCCs.⁹

Conclusion

Muckle-Wells syndrome may go undiagnosed for many years or may be misdiagnosed as refractory urticaria, as in our patient. It is important to include periodic fever syndromes in the differential diagnosis of refractory urticaria with episodic fever to diagnose these cases of MWS earlier.

Dermatologic surgeons are susceptible to work-related ailments given the nature of their working posture, the most common of which are pain and stiffness in the neck, shoulders, and lower back, as well as headaches.^1,2 Awkward posture and positioning, for the sake of getting a better view of the task at hand, puts the surgeon in ergonomically disagreeable positions. Because the prime working years for a dermatologic surgeon tend to coincide with the age of presbyopia onset, magnification may help reduce and thwart musculoskeletal problems and eye strain. Indeed, a multitude of surgical specialties and dentists use intraoperative magnification.³ Knowledge and use of available magnification options can be a key addition to the dermatologic surgeon’s armamentarium. We discuss the need for magnification and review magnification devices that are readily available to the dermatologic surgeon. Table 1 presents a summary of all magnification options discussed.

Need for Magnification

Presbyopia is a condition of aging in which one loses the ability to accommodate and focus at near distances. The estimated prevalence of presbyopia in North America is 83%, typically with onset by 45 years of age.⁴ Individuals with presbyopia often hold objects farther away from their eyes to bring them into focus, causing eye strain, headaches, and musculoskeletal injury.

Use of intraoperative magnification allows for enhanced visualization of fine anatomic details and precise suture placement for the surgeon with or without presbyopia. Higher magnification produces a larger image; however, it also reduces field of view and depth of field (ie, the amount of depth that stays in focus without repositioning). The resolution and quality of the image are dependent on the optical properties of the lens system. The ideal optic system is surgeon dependent and involves a combination of magnification level that will not result in dramatic loss of view and depth of field, while maintaining crispness and quality of image.

Intraoperative magnification yields ergonomic benefits by promoting a safer neck flexion angle by increasing the working distance to a more ideal position (Figure). In doing so, it improves posture and minimizes eye and musculoskeletal strain secondary to awkward positioning and presbyopia.^1,5 Stationary working position and neck flexion and rotation with precise and repetitive tasks are risk factors for strain and injuries that dermatologic surgeons often encounter.¹ Magnification devices are tools that the dermatologic surgeon can utilize for a more ergonomically sound practice. Indeed, magnification has been shown to improve posture in the dental literature, a specialty with similar occupational risk factors to dermatologic surgery.^6-8 Ergonomic practice reduces occupational injuries and improves work quality and productivity, thereby having a favorable effect on both the patient and the physician.

Improved Outcomes With Magnification

There are many examples of improved surgical quality and outcomes with magnification in other specialties. Hart and Hall⁵ illustrated the advantage of magnification in laceration repairs in the emergency department. In one study, increased magnification resulted in a substantial decrease in positive surgical margin rates in open radical retropubic prostatectomy.⁹ Schoeffl et al¹⁰ demonstrated that the microsurgical success of fine surgical procedures was directly related to optical magnification strength when comparing the unaided eye, surgical loupes, and the operating microscope. The dental literature also has numerous examples of magnification producing improved quality dentistry.^11-13 Although magnification is not a novel concept to dermatologic surgery, little has been written about its use in the dermatologic surgery literature.

Magnification Options

One-Piece Bifocal Magnifying Safety Glasses
Bifocal magnifying safety glasses are polycarbonate safety glasses made with lenses in which the lower half is a magnifying lens. They are available in +1.5, +2.0, +2.5, and +3.0 diopter strengths. The total magnification power is calculated as follows: (diopter/4) + 1. The glasses are lightweight, easy to wear, inexpensive, and protect the eyes; however, they provide minimal magnification and do not compensate for differences in vision between both eyes.

Magnification Visor
The magnification visor is a headband visor with magnification lenses. It comes in various levels of magnification ranging from ×1.5 to ×3.5. It can be worn over prescription or safety glasses, may be pivoted out of the way when not in use, and is inexpensive. Conversely, it may be bulky to wear, cannot be customized, and does not offer the best resolution.

Magnification Clips
Magnification clips are hard-coated magnifying lens plates that fasten to eyeglass frames and range in level of magnification from ×1.5 to ×3.5. They can be pivoted out of the viewing angle, are lightweight, and are inexpensive; however, positioning may be difficult for ideal working distance and viewing angle.

Magnifier With Frame/Headband
The magnifier with frame is similar to magnification clips, but the magnification lens plate comes with a frame. It can be used with or without glasses and comes in magnification levels of ×1.5 to ×3.5. It is light, inexpensive, and may be pivoted out of sight, but similar to magnification clips, positioning for the right viewing angle and working distance may be difficult.

The magnifier with headband is essentially the same as the magnifier with frame. The only difference is the magnification plate is attached to a headband as opposed to a frame. It has similar benefits and limitations as the magnifier with frame.

Magnification Stand
The magnification stand comes as a large magnification lens with a flexible arm attached to a stand. It is a basic magnification tool and does not need to be worn; however, the stand is not easily portable and may be cumbersome to use.

Surgical Loupes
Surgical loupes are a robust magnification choice and the mainstay in magnification for the dermatologic surgeon. Loupes have proven to have comparable results in some procedures to the powerful operating surgical microscope.^14-17 Factors to consider with loupes include brand, design, lens, magnification, resolution, optimal working distance, field depth, and declination angle.¹⁸

The 2 surgical loupe designs—flip-up loupes and through-the-lens loupes—differ in the mounting of the optic lenses on safety glasses. Flip-up loupes have the optics mounted to the bridge of the frame, whereas through-the-lens loupes are fixed in the lenses.

There are 3 different optical systems for surgical loupe magnification: simple, compound, and prismatic. Simple lenses consist of one pair of positive meniscus lenses similar to reading glasses. Compound lenses are made of 2 magnification lenses. Prismatic lenses magnify using a prism that folds and lengthens the light path.^19,20

Loupes range in magnification level from ×2.5 to ×4.5. Compared to other magnification modalities, they can be customized and offer better resolution with quality magnification. Additionally, loupes can be fitted with a light source; however, they are expensive and surgeons need time to get used to the increased magnification as well as wearing the loupes.

There are advantages and disadvantages to the different loupe designs (Table 2). Flip-up loupes are more versatile, allowing for use on various safety glasses. They can be flipped out of view, and the declination angle may be altered; however, flip-up loupes have a narrower field of view and are heavier and bulkier than through-the-lens loupes. Through-the-lens loupes are lighter and have a larger field of view, as the optics are closer to the eye. They are customized to the declination angle and working distance of the surgeon. Conversely, through-the-lens loupes are more expensive and cannot be adjusted or moved from the line of vision.

Operating Surgical Microscope
The operating surgical microscope is not practical in the dermatologic surgeon’s practice. It is expensive and provides unnecessarily powerful magnification for dermatologic surgery. This tool usually is used in the operating room for suturing nerves and vessels with sutures sized 8-0 and smaller. Most skin procedures require size 6-0 and larger sutures.

Dermoscope
Dermoscopy, also known as epiluminescence microscopy, is a technique utilizing a handheld device made up of polarized light and a ×10 magnifying lens to evaluate skin lesions. In skilled hands, dermoscopy allows for the examination of characteristic patterns and morphologic features of skin lesions to enhance the clinician’s diagnostic accuracy.²¹ It may aid the dermatologic surgeon in identifying the surgical margins of difficult-to-define skin cancers. It is small and mobile; however, it has minimal benefit to the dermatologic surgeon during surgery because it is handheld and has a small field of view.

Conclusion

Good ergonomic practices facilitate a healthier and prolonged career for the dermatologic surgeon. When used properly, magnification devices can be a beneficial adjunct to the dermatologic surgeon by promoting better posture, preventing eyestrain, and providing enhanced visualization of the operating field and instruments. Use of magnification devices has been demonstrated to improve patient outcomes in other specialties. There are opportunities for further research specific to magnification improving dermatologic surgery outcomes given the high level of precision and accuracy needed for Mohs micrographic surgery, wound reconstruction, nail surgery, and hair transplantation.

Dermatologic surgeons are susceptible to work-related ailments given the nature of their working posture, the most common of which are pain and stiffness in the neck, shoulders, and lower back, as well as headaches.^1,2 Awkward posture and positioning, for the sake of getting a better view of the task at hand, puts the surgeon in ergonomically disagreeable positions. Because the prime working years for a dermatologic surgeon tend to coincide with the age of presbyopia onset, magnification may help reduce and thwart musculoskeletal problems and eye strain. Indeed, a multitude of surgical specialties and dentists use intraoperative magnification.³ Knowledge and use of available magnification options can be a key addition to the dermatologic surgeon’s armamentarium. We discuss the need for magnification and review magnification devices that are readily available to the dermatologic surgeon. Table 1 presents a summary of all magnification options discussed.

Need for Magnification

Presbyopia is a condition of aging in which one loses the ability to accommodate and focus at near distances. The estimated prevalence of presbyopia in North America is 83%, typically with onset by 45 years of age.⁴ Individuals with presbyopia often hold objects farther away from their eyes to bring them into focus, causing eye strain, headaches, and musculoskeletal injury.

Use of intraoperative magnification allows for enhanced visualization of fine anatomic details and precise suture placement for the surgeon with or without presbyopia. Higher magnification produces a larger image; however, it also reduces field of view and depth of field (ie, the amount of depth that stays in focus without repositioning). The resolution and quality of the image are dependent on the optical properties of the lens system. The ideal optic system is surgeon dependent and involves a combination of magnification level that will not result in dramatic loss of view and depth of field, while maintaining crispness and quality of image.

Intraoperative magnification yields ergonomic benefits by promoting a safer neck flexion angle by increasing the working distance to a more ideal position (Figure). In doing so, it improves posture and minimizes eye and musculoskeletal strain secondary to awkward positioning and presbyopia.^1,5 Stationary working position and neck flexion and rotation with precise and repetitive tasks are risk factors for strain and injuries that dermatologic surgeons often encounter.¹ Magnification devices are tools that the dermatologic surgeon can utilize for a more ergonomically sound practice. Indeed, magnification has been shown to improve posture in the dental literature, a specialty with similar occupational risk factors to dermatologic surgery.^6-8 Ergonomic practice reduces occupational injuries and improves work quality and productivity, thereby having a favorable effect on both the patient and the physician.

Improved Outcomes With Magnification

There are many examples of improved surgical quality and outcomes with magnification in other specialties. Hart and Hall⁵ illustrated the advantage of magnification in laceration repairs in the emergency department. In one study, increased magnification resulted in a substantial decrease in positive surgical margin rates in open radical retropubic prostatectomy.⁹ Schoeffl et al¹⁰ demonstrated that the microsurgical success of fine surgical procedures was directly related to optical magnification strength when comparing the unaided eye, surgical loupes, and the operating microscope. The dental literature also has numerous examples of magnification producing improved quality dentistry.^11-13 Although magnification is not a novel concept to dermatologic surgery, little has been written about its use in the dermatologic surgery literature.

Magnification Options

One-Piece Bifocal Magnifying Safety Glasses
Bifocal magnifying safety glasses are polycarbonate safety glasses made with lenses in which the lower half is a magnifying lens. They are available in +1.5, +2.0, +2.5, and +3.0 diopter strengths. The total magnification power is calculated as follows: (diopter/4) + 1. The glasses are lightweight, easy to wear, inexpensive, and protect the eyes; however, they provide minimal magnification and do not compensate for differences in vision between both eyes.

Magnification Visor
The magnification visor is a headband visor with magnification lenses. It comes in various levels of magnification ranging from ×1.5 to ×3.5. It can be worn over prescription or safety glasses, may be pivoted out of the way when not in use, and is inexpensive. Conversely, it may be bulky to wear, cannot be customized, and does not offer the best resolution.

Magnification Clips
Magnification clips are hard-coated magnifying lens plates that fasten to eyeglass frames and range in level of magnification from ×1.5 to ×3.5. They can be pivoted out of the viewing angle, are lightweight, and are inexpensive; however, positioning may be difficult for ideal working distance and viewing angle.

Magnifier With Frame/Headband
The magnifier with frame is similar to magnification clips, but the magnification lens plate comes with a frame. It can be used with or without glasses and comes in magnification levels of ×1.5 to ×3.5. It is light, inexpensive, and may be pivoted out of sight, but similar to magnification clips, positioning for the right viewing angle and working distance may be difficult.

The magnifier with headband is essentially the same as the magnifier with frame. The only difference is the magnification plate is attached to a headband as opposed to a frame. It has similar benefits and limitations as the magnifier with frame.

Magnification Stand
The magnification stand comes as a large magnification lens with a flexible arm attached to a stand. It is a basic magnification tool and does not need to be worn; however, the stand is not easily portable and may be cumbersome to use.

Surgical Loupes
Surgical loupes are a robust magnification choice and the mainstay in magnification for the dermatologic surgeon. Loupes have proven to have comparable results in some procedures to the powerful operating surgical microscope.^14-17 Factors to consider with loupes include brand, design, lens, magnification, resolution, optimal working distance, field depth, and declination angle.¹⁸

The 2 surgical loupe designs—flip-up loupes and through-the-lens loupes—differ in the mounting of the optic lenses on safety glasses. Flip-up loupes have the optics mounted to the bridge of the frame, whereas through-the-lens loupes are fixed in the lenses.

There are 3 different optical systems for surgical loupe magnification: simple, compound, and prismatic. Simple lenses consist of one pair of positive meniscus lenses similar to reading glasses. Compound lenses are made of 2 magnification lenses. Prismatic lenses magnify using a prism that folds and lengthens the light path.^19,20

Loupes range in magnification level from ×2.5 to ×4.5. Compared to other magnification modalities, they can be customized and offer better resolution with quality magnification. Additionally, loupes can be fitted with a light source; however, they are expensive and surgeons need time to get used to the increased magnification as well as wearing the loupes.

There are advantages and disadvantages to the different loupe designs (Table 2). Flip-up loupes are more versatile, allowing for use on various safety glasses. They can be flipped out of view, and the declination angle may be altered; however, flip-up loupes have a narrower field of view and are heavier and bulkier than through-the-lens loupes. Through-the-lens loupes are lighter and have a larger field of view, as the optics are closer to the eye. They are customized to the declination angle and working distance of the surgeon. Conversely, through-the-lens loupes are more expensive and cannot be adjusted or moved from the line of vision.

Operating Surgical Microscope
The operating surgical microscope is not practical in the dermatologic surgeon’s practice. It is expensive and provides unnecessarily powerful magnification for dermatologic surgery. This tool usually is used in the operating room for suturing nerves and vessels with sutures sized 8-0 and smaller. Most skin procedures require size 6-0 and larger sutures.

Dermoscope
Dermoscopy, also known as epiluminescence microscopy, is a technique utilizing a handheld device made up of polarized light and a ×10 magnifying lens to evaluate skin lesions. In skilled hands, dermoscopy allows for the examination of characteristic patterns and morphologic features of skin lesions to enhance the clinician’s diagnostic accuracy.²¹ It may aid the dermatologic surgeon in identifying the surgical margins of difficult-to-define skin cancers. It is small and mobile; however, it has minimal benefit to the dermatologic surgeon during surgery because it is handheld and has a small field of view.

Conclusion

Good ergonomic practices facilitate a healthier and prolonged career for the dermatologic surgeon. When used properly, magnification devices can be a beneficial adjunct to the dermatologic surgeon by promoting better posture, preventing eyestrain, and providing enhanced visualization of the operating field and instruments. Use of magnification devices has been demonstrated to improve patient outcomes in other specialties. There are opportunities for further research specific to magnification improving dermatologic surgery outcomes given the high level of precision and accuracy needed for Mohs micrographic surgery, wound reconstruction, nail surgery, and hair transplantation.

Dermatologic surgeons are susceptible to work-related ailments given the nature of their working posture, the most common of which are pain and stiffness in the neck, shoulders, and lower back, as well as headaches.^1,2 Awkward posture and positioning, for the sake of getting a better view of the task at hand, puts the surgeon in ergonomically disagreeable positions. Because the prime working years for a dermatologic surgeon tend to coincide with the age of presbyopia onset, magnification may help reduce and thwart musculoskeletal problems and eye strain. Indeed, a multitude of surgical specialties and dentists use intraoperative magnification.³ Knowledge and use of available magnification options can be a key addition to the dermatologic surgeon’s armamentarium. We discuss the need for magnification and review magnification devices that are readily available to the dermatologic surgeon. Table 1 presents a summary of all magnification options discussed.

Need for Magnification

Presbyopia is a condition of aging in which one loses the ability to accommodate and focus at near distances. The estimated prevalence of presbyopia in North America is 83%, typically with onset by 45 years of age.⁴ Individuals with presbyopia often hold objects farther away from their eyes to bring them into focus, causing eye strain, headaches, and musculoskeletal injury.

Use of intraoperative magnification allows for enhanced visualization of fine anatomic details and precise suture placement for the surgeon with or without presbyopia. Higher magnification produces a larger image; however, it also reduces field of view and depth of field (ie, the amount of depth that stays in focus without repositioning). The resolution and quality of the image are dependent on the optical properties of the lens system. The ideal optic system is surgeon dependent and involves a combination of magnification level that will not result in dramatic loss of view and depth of field, while maintaining crispness and quality of image.

Intraoperative magnification yields ergonomic benefits by promoting a safer neck flexion angle by increasing the working distance to a more ideal position (Figure). In doing so, it improves posture and minimizes eye and musculoskeletal strain secondary to awkward positioning and presbyopia.^1,5 Stationary working position and neck flexion and rotation with precise and repetitive tasks are risk factors for strain and injuries that dermatologic surgeons often encounter.¹ Magnification devices are tools that the dermatologic surgeon can utilize for a more ergonomically sound practice. Indeed, magnification has been shown to improve posture in the dental literature, a specialty with similar occupational risk factors to dermatologic surgery.^6-8 Ergonomic practice reduces occupational injuries and improves work quality and productivity, thereby having a favorable effect on both the patient and the physician.

Improved Outcomes With Magnification

There are many examples of improved surgical quality and outcomes with magnification in other specialties. Hart and Hall⁵ illustrated the advantage of magnification in laceration repairs in the emergency department. In one study, increased magnification resulted in a substantial decrease in positive surgical margin rates in open radical retropubic prostatectomy.⁹ Schoeffl et al¹⁰ demonstrated that the microsurgical success of fine surgical procedures was directly related to optical magnification strength when comparing the unaided eye, surgical loupes, and the operating microscope. The dental literature also has numerous examples of magnification producing improved quality dentistry.^11-13 Although magnification is not a novel concept to dermatologic surgery, little has been written about its use in the dermatologic surgery literature.

Magnification Options

One-Piece Bifocal Magnifying Safety Glasses
Bifocal magnifying safety glasses are polycarbonate safety glasses made with lenses in which the lower half is a magnifying lens. They are available in +1.5, +2.0, +2.5, and +3.0 diopter strengths. The total magnification power is calculated as follows: (diopter/4) + 1. The glasses are lightweight, easy to wear, inexpensive, and protect the eyes; however, they provide minimal magnification and do not compensate for differences in vision between both eyes.

Magnification Visor
The magnification visor is a headband visor with magnification lenses. It comes in various levels of magnification ranging from ×1.5 to ×3.5. It can be worn over prescription or safety glasses, may be pivoted out of the way when not in use, and is inexpensive. Conversely, it may be bulky to wear, cannot be customized, and does not offer the best resolution.

Magnification Clips
Magnification clips are hard-coated magnifying lens plates that fasten to eyeglass frames and range in level of magnification from ×1.5 to ×3.5. They can be pivoted out of the viewing angle, are lightweight, and are inexpensive; however, positioning may be difficult for ideal working distance and viewing angle.

Magnifier With Frame/Headband
The magnifier with frame is similar to magnification clips, but the magnification lens plate comes with a frame. It can be used with or without glasses and comes in magnification levels of ×1.5 to ×3.5. It is light, inexpensive, and may be pivoted out of sight, but similar to magnification clips, positioning for the right viewing angle and working distance may be difficult.

The magnifier with headband is essentially the same as the magnifier with frame. The only difference is the magnification plate is attached to a headband as opposed to a frame. It has similar benefits and limitations as the magnifier with frame.

Magnification Stand
The magnification stand comes as a large magnification lens with a flexible arm attached to a stand. It is a basic magnification tool and does not need to be worn; however, the stand is not easily portable and may be cumbersome to use.

Surgical Loupes
Surgical loupes are a robust magnification choice and the mainstay in magnification for the dermatologic surgeon. Loupes have proven to have comparable results in some procedures to the powerful operating surgical microscope.^14-17 Factors to consider with loupes include brand, design, lens, magnification, resolution, optimal working distance, field depth, and declination angle.¹⁸

The 2 surgical loupe designs—flip-up loupes and through-the-lens loupes—differ in the mounting of the optic lenses on safety glasses. Flip-up loupes have the optics mounted to the bridge of the frame, whereas through-the-lens loupes are fixed in the lenses.

There are 3 different optical systems for surgical loupe magnification: simple, compound, and prismatic. Simple lenses consist of one pair of positive meniscus lenses similar to reading glasses. Compound lenses are made of 2 magnification lenses. Prismatic lenses magnify using a prism that folds and lengthens the light path.^19,20

Loupes range in magnification level from ×2.5 to ×4.5. Compared to other magnification modalities, they can be customized and offer better resolution with quality magnification. Additionally, loupes can be fitted with a light source; however, they are expensive and surgeons need time to get used to the increased magnification as well as wearing the loupes.

There are advantages and disadvantages to the different loupe designs (Table 2). Flip-up loupes are more versatile, allowing for use on various safety glasses. They can be flipped out of view, and the declination angle may be altered; however, flip-up loupes have a narrower field of view and are heavier and bulkier than through-the-lens loupes. Through-the-lens loupes are lighter and have a larger field of view, as the optics are closer to the eye. They are customized to the declination angle and working distance of the surgeon. Conversely, through-the-lens loupes are more expensive and cannot be adjusted or moved from the line of vision.

Operating Surgical Microscope
The operating surgical microscope is not practical in the dermatologic surgeon’s practice. It is expensive and provides unnecessarily powerful magnification for dermatologic surgery. This tool usually is used in the operating room for suturing nerves and vessels with sutures sized 8-0 and smaller. Most skin procedures require size 6-0 and larger sutures.

Dermoscope
Dermoscopy, also known as epiluminescence microscopy, is a technique utilizing a handheld device made up of polarized light and a ×10 magnifying lens to evaluate skin lesions. In skilled hands, dermoscopy allows for the examination of characteristic patterns and morphologic features of skin lesions to enhance the clinician’s diagnostic accuracy.²¹ It may aid the dermatologic surgeon in identifying the surgical margins of difficult-to-define skin cancers. It is small and mobile; however, it has minimal benefit to the dermatologic surgeon during surgery because it is handheld and has a small field of view.

Conclusion

Good ergonomic practices facilitate a healthier and prolonged career for the dermatologic surgeon. When used properly, magnification devices can be a beneficial adjunct to the dermatologic surgeon by promoting better posture, preventing eyestrain, and providing enhanced visualization of the operating field and instruments. Use of magnification devices has been demonstrated to improve patient outcomes in other specialties. There are opportunities for further research specific to magnification improving dermatologic surgery outcomes given the high level of precision and accuracy needed for Mohs micrographic surgery, wound reconstruction, nail surgery, and hair transplantation.