The Journal of Family Practice

A skin scraping and potassium hydroxide (KOH) prep confirmed the presence of branching hyphae, consistent with tinea corporis. The large size of this plaque could have easily made this diagnosis more difficult. When tinea corporis is suspected, look at the edge of the plaque; there is often thin scale and sometimes small pustules corresponding to follicular involvement.

Commonly called by the misnomer “ringworm,” tinea corporis is a skin infection caused by a wide variety of dermatophytes and affects all ages, sexes, and skin types. Trichophyton, Microsporum, and Epidermophyton species are frequently isolated.¹ Patients with atopic dermatitis or weakened immunity may be more susceptible to more frequent or long-lasting episodes. Diabetes may have contributed to the extent of the disease in this case.

Patients with tinea corporis present with one or several annular patches to plaques that grow in size. When the source of contagion is an animal, inflammation can be dramatic. In the case above, there was minimal to no itching and the patient didn’t notice the rash; thus, it was able to enlarge for months.

Treatment options include systemic and topical antifungal therapy. Consideration should be given to the severity of the disease and causal organism. Azoles, terbinafine, and ciclopirox are common treatment options. Topical therapy with an appropriately selected antifungal for 1 to 6 weeks, based on clinical response, is safe and effective. It is important to consider other foci of infection, including the feet and hands. More extensive disease may be treated with oral therapy such as terbinafine, fluconazole, or itraconazole.

Because of the extent of the disease and the challenge of effective coverage with topical therapy, this patient was treated with oral terbinafine 250 mg daily for 3 weeks. The plaque cleared completely.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

A skin scraping and potassium hydroxide (KOH) prep confirmed the presence of branching hyphae, consistent with tinea corporis. The large size of this plaque could have easily made this diagnosis more difficult. When tinea corporis is suspected, look at the edge of the plaque; there is often thin scale and sometimes small pustules corresponding to follicular involvement.

Commonly called by the misnomer “ringworm,” tinea corporis is a skin infection caused by a wide variety of dermatophytes and affects all ages, sexes, and skin types. Trichophyton, Microsporum, and Epidermophyton species are frequently isolated.¹ Patients with atopic dermatitis or weakened immunity may be more susceptible to more frequent or long-lasting episodes. Diabetes may have contributed to the extent of the disease in this case.

Patients with tinea corporis present with one or several annular patches to plaques that grow in size. When the source of contagion is an animal, inflammation can be dramatic. In the case above, there was minimal to no itching and the patient didn’t notice the rash; thus, it was able to enlarge for months.

Treatment options include systemic and topical antifungal therapy. Consideration should be given to the severity of the disease and causal organism. Azoles, terbinafine, and ciclopirox are common treatment options. Topical therapy with an appropriately selected antifungal for 1 to 6 weeks, based on clinical response, is safe and effective. It is important to consider other foci of infection, including the feet and hands. More extensive disease may be treated with oral therapy such as terbinafine, fluconazole, or itraconazole.

Because of the extent of the disease and the challenge of effective coverage with topical therapy, this patient was treated with oral terbinafine 250 mg daily for 3 weeks. The plaque cleared completely.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

A skin scraping and potassium hydroxide (KOH) prep confirmed the presence of branching hyphae, consistent with tinea corporis. The large size of this plaque could have easily made this diagnosis more difficult. When tinea corporis is suspected, look at the edge of the plaque; there is often thin scale and sometimes small pustules corresponding to follicular involvement.

Commonly called by the misnomer “ringworm,” tinea corporis is a skin infection caused by a wide variety of dermatophytes and affects all ages, sexes, and skin types. Trichophyton, Microsporum, and Epidermophyton species are frequently isolated.¹ Patients with atopic dermatitis or weakened immunity may be more susceptible to more frequent or long-lasting episodes. Diabetes may have contributed to the extent of the disease in this case.

Patients with tinea corporis present with one or several annular patches to plaques that grow in size. When the source of contagion is an animal, inflammation can be dramatic. In the case above, there was minimal to no itching and the patient didn’t notice the rash; thus, it was able to enlarge for months.

Treatment options include systemic and topical antifungal therapy. Consideration should be given to the severity of the disease and causal organism. Azoles, terbinafine, and ciclopirox are common treatment options. Topical therapy with an appropriately selected antifungal for 1 to 6 weeks, based on clinical response, is safe and effective. It is important to consider other foci of infection, including the feet and hands. More extensive disease may be treated with oral therapy such as terbinafine, fluconazole, or itraconazole.

Because of the extent of the disease and the challenge of effective coverage with topical therapy, this patient was treated with oral terbinafine 250 mg daily for 3 weeks. The plaque cleared completely.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

THE COMPARISON

A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband ultraviolet B (UVB) treatment.

B Vitiligo on the hand in a young Hispanic male.

Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.¹

Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.²

Epidemiology

Vitiligo affects approximately 1% of the US population and up to 8% worldwide.² There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.¹

Key clinical features in people with darker skin tones

Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (FIGURES A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.² Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.²

An important distinction when making the diagnosis is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.³

Worth noting

Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.^4,5

Continue to: Treatment of vitiligo...

Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.¹ In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients ages 12 years and older.^6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase–signal transducers and activators of the transcription pathway.⁶ However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.⁸

Health disparity highlight

A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.⁷ In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.^9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.¹¹ Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).¹²

Final thoughts

FDA approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.¹³

THE COMPARISON

A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband ultraviolet B (UVB) treatment.

B Vitiligo on the hand in a young Hispanic male.

Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.¹

Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.²

Epidemiology

Vitiligo affects approximately 1% of the US population and up to 8% worldwide.² There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.¹

Key clinical features in people with darker skin tones

Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (FIGURES A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.² Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.²

An important distinction when making the diagnosis is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.³

Worth noting

Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.^4,5

Continue to: Treatment of vitiligo...

Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.¹ In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients ages 12 years and older.^6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase–signal transducers and activators of the transcription pathway.⁶ However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.⁸

Health disparity highlight

A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.⁷ In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.^9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.¹¹ Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).¹²

Final thoughts

FDA approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.¹³

THE COMPARISON

A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband ultraviolet B (UVB) treatment.

B Vitiligo on the hand in a young Hispanic male.

Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.¹

Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.²

Epidemiology

Vitiligo affects approximately 1% of the US population and up to 8% worldwide.² There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.¹

Key clinical features in people with darker skin tones

Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (FIGURES A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.² Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.²

An important distinction when making the diagnosis is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.³

Worth noting

Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.^4,5

Continue to: Treatment of vitiligo...

Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.¹ In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients ages 12 years and older.^6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase–signal transducers and activators of the transcription pathway.⁶ However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.⁸

Health disparity highlight

A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.⁷ In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.^9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.¹¹ Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).¹²

Final thoughts

FDA approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.¹³

This patient was experiencing a flare of his psoriasis. Three factors contributed to the flare: noncompliance with his treatment regimen, decreased sunlight in the winter, and his lithium therapy. Though carcinogenic, certain wavelengths of UV light are beneficial for psoriasis, and the shorter days of winter can cause flaring of psoriasis (or relative flaring). In addition, lithium—the most effective therapy for this patient’s bipolar disorder—can worsen psoriasis.

Psoriasis is a chronic multisystem inflammatory disorder with characteristic skin findings that include well-demarcated micaceous plaques, nail pitting, and sometimes tendon pain and inflammatory arthritis. Severity can range from small, thin plaques that are intermittently noticeable on the elbows or knees to widespread ash-like plaques covering most of the body.

Good topical choices for facial skin include hydrocortisone 2.5% cream or desonide 0.05%. Nonsteroidal topical therapies that are safe for facial skin include tacrolimus 0.1% ointment or pimecrolimus 1% cream.¹ These options may be used twice daily until the disease is controlled.

In many cases (as in this one), the patient’s previous psoriasis outbreaks could not be controlled with topical therapy alone. The patient had not responded to a previous methotrexate regimen, and more recently had been clear for several years on systemic ustekinumab, a monoclonal antibody. Dosed every 12 weeks, or sometimes every 8 weeks, ustekinumab is given by subcutaneous injection, usually in the abdomen, through normal skin. Ustekinumab was recently approved for home use with just 4 injections per year for maintenance therapy. However, the infrequency of the injections sometimes leads to noncompliance, as occurred with this patient. He had missed 2 doses since taking over his own dosing regimen.

Ultimately, the patient’s flare resolved when he was transitioned back to in-office treatment with ustekinumab.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This patient was experiencing a flare of his psoriasis. Three factors contributed to the flare: noncompliance with his treatment regimen, decreased sunlight in the winter, and his lithium therapy. Though carcinogenic, certain wavelengths of UV light are beneficial for psoriasis, and the shorter days of winter can cause flaring of psoriasis (or relative flaring). In addition, lithium—the most effective therapy for this patient’s bipolar disorder—can worsen psoriasis.

Psoriasis is a chronic multisystem inflammatory disorder with characteristic skin findings that include well-demarcated micaceous plaques, nail pitting, and sometimes tendon pain and inflammatory arthritis. Severity can range from small, thin plaques that are intermittently noticeable on the elbows or knees to widespread ash-like plaques covering most of the body.

Good topical choices for facial skin include hydrocortisone 2.5% cream or desonide 0.05%. Nonsteroidal topical therapies that are safe for facial skin include tacrolimus 0.1% ointment or pimecrolimus 1% cream.¹ These options may be used twice daily until the disease is controlled.

In many cases (as in this one), the patient’s previous psoriasis outbreaks could not be controlled with topical therapy alone. The patient had not responded to a previous methotrexate regimen, and more recently had been clear for several years on systemic ustekinumab, a monoclonal antibody. Dosed every 12 weeks, or sometimes every 8 weeks, ustekinumab is given by subcutaneous injection, usually in the abdomen, through normal skin. Ustekinumab was recently approved for home use with just 4 injections per year for maintenance therapy. However, the infrequency of the injections sometimes leads to noncompliance, as occurred with this patient. He had missed 2 doses since taking over his own dosing regimen.

Ultimately, the patient’s flare resolved when he was transitioned back to in-office treatment with ustekinumab.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This patient was experiencing a flare of his psoriasis. Three factors contributed to the flare: noncompliance with his treatment regimen, decreased sunlight in the winter, and his lithium therapy. Though carcinogenic, certain wavelengths of UV light are beneficial for psoriasis, and the shorter days of winter can cause flaring of psoriasis (or relative flaring). In addition, lithium—the most effective therapy for this patient’s bipolar disorder—can worsen psoriasis.

Psoriasis is a chronic multisystem inflammatory disorder with characteristic skin findings that include well-demarcated micaceous plaques, nail pitting, and sometimes tendon pain and inflammatory arthritis. Severity can range from small, thin plaques that are intermittently noticeable on the elbows or knees to widespread ash-like plaques covering most of the body.

Good topical choices for facial skin include hydrocortisone 2.5% cream or desonide 0.05%. Nonsteroidal topical therapies that are safe for facial skin include tacrolimus 0.1% ointment or pimecrolimus 1% cream.¹ These options may be used twice daily until the disease is controlled.

In many cases (as in this one), the patient’s previous psoriasis outbreaks could not be controlled with topical therapy alone. The patient had not responded to a previous methotrexate regimen, and more recently had been clear for several years on systemic ustekinumab, a monoclonal antibody. Dosed every 12 weeks, or sometimes every 8 weeks, ustekinumab is given by subcutaneous injection, usually in the abdomen, through normal skin. Ustekinumab was recently approved for home use with just 4 injections per year for maintenance therapy. However, the infrequency of the injections sometimes leads to noncompliance, as occurred with this patient. He had missed 2 doses since taking over his own dosing regimen.

Ultimately, the patient’s flare resolved when he was transitioned back to in-office treatment with ustekinumab.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Using an 18-gauge needle, a simple incision and drainage was performed, and copious turbid and bloody material was expressed and cultured for aerobic and acid-fast bacteria, as well as fungus. The patient was started on trimethoprim sulfamethoxazole DS twice daily while cultures and sensitivities were pending. Cultures grew Staphylococcus lugdunensis, a coagulase-negative staph species known to cause a range of infections from simple skin infections to bacteremia and endocarditis.¹ If the drainage had been viscous and clear to blood-tinged, that would have been more consistent with a ganglion cyst. Lack of drainage would have prompted a small punch biopsy to exclude a tumor.

Fortunately, S lugdunensis is often broadly sensitive to antibiotics, although treatment choices should follow antibiotic sensitivity testing. Any signs of systemic illness should be worked up with blood cultures and consideration of endocarditis or involvement of an implant. Penicillin is recommended as a first line systemic agent if sensitivities support this, and for abscesses, incision and drainage is recommended. The length of treatment for skin infections is generally 1 to 2 weeks, guided by response to therapy.

This patient’s nodule resolved following the incision and drainage and 7 days of therapy with trimethoprim sulfamethoxazole DS.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Using an 18-gauge needle, a simple incision and drainage was performed, and copious turbid and bloody material was expressed and cultured for aerobic and acid-fast bacteria, as well as fungus. The patient was started on trimethoprim sulfamethoxazole DS twice daily while cultures and sensitivities were pending. Cultures grew Staphylococcus lugdunensis, a coagulase-negative staph species known to cause a range of infections from simple skin infections to bacteremia and endocarditis.¹ If the drainage had been viscous and clear to blood-tinged, that would have been more consistent with a ganglion cyst. Lack of drainage would have prompted a small punch biopsy to exclude a tumor.

Fortunately, S lugdunensis is often broadly sensitive to antibiotics, although treatment choices should follow antibiotic sensitivity testing. Any signs of systemic illness should be worked up with blood cultures and consideration of endocarditis or involvement of an implant. Penicillin is recommended as a first line systemic agent if sensitivities support this, and for abscesses, incision and drainage is recommended. The length of treatment for skin infections is generally 1 to 2 weeks, guided by response to therapy.

This patient’s nodule resolved following the incision and drainage and 7 days of therapy with trimethoprim sulfamethoxazole DS.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Using an 18-gauge needle, a simple incision and drainage was performed, and copious turbid and bloody material was expressed and cultured for aerobic and acid-fast bacteria, as well as fungus. The patient was started on trimethoprim sulfamethoxazole DS twice daily while cultures and sensitivities were pending. Cultures grew Staphylococcus lugdunensis, a coagulase-negative staph species known to cause a range of infections from simple skin infections to bacteremia and endocarditis.¹ If the drainage had been viscous and clear to blood-tinged, that would have been more consistent with a ganglion cyst. Lack of drainage would have prompted a small punch biopsy to exclude a tumor.

Fortunately, S lugdunensis is often broadly sensitive to antibiotics, although treatment choices should follow antibiotic sensitivity testing. Any signs of systemic illness should be worked up with blood cultures and consideration of endocarditis or involvement of an implant. Penicillin is recommended as a first line systemic agent if sensitivities support this, and for abscesses, incision and drainage is recommended. The length of treatment for skin infections is generally 1 to 2 weeks, guided by response to therapy.

This patient’s nodule resolved following the incision and drainage and 7 days of therapy with trimethoprim sulfamethoxazole DS.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermatopathology was consistent with a diagnosis of cutaneous myxoma (CM). There are very few dermoscopic descriptions of CM in the literature, so diagnostic features are not established. However, the absence of more diagnostic features of basal cell carcinoma or squamous cell carcinoma (SCC) increases the likelihood of a rare diagnosis, such as CM.

CMs are rare benign neoplasms that manifest most commonly in young adults as small (< 1 cm) flesh-colored to blue papules on the head, neck, and trunk. The size of this particular CM was an outlier. CMs may be associated with Carney Complex (CNC), a rare inherited syndrome that has been linked to multiple endocrine neoplasias—namely, pituitary adenomas, testicular Sertoli cell tumors, thyroid tumors, and cardiac atrial myxomas.¹ Additionally, in CNC, lentigines and multiple blue nevi develop on the skin and mucosal surfaces.

The differential diagnosis for a large, pink to flesh-colored nodule of this size includes benign histiocytoma, SCC, CM, and dermatofibrosarcoma protuberans. Benign histiocytomas and SCCs are much more common than CM. Clinical features only hint at the correct diagnosis, which must be made histologically.

Patients with CMs benefit from ongoing dermatology surveillance to monitor for the development of atypical nevi or new CMs. In this case, a wide excision with generous margins was planned with plastic surgery. (CMs have been reported to recur after surgery, which is why wide margins are essential.)

Additionally, 2 factors prompted an echocardiogram: the association between CMs and possible cardiac tumors and the patient’s need to undergo future orthopedic surgery under general anesthesia. No cardiac tumors were visible on echocardiogram. Thyroid imaging and genetic evaluation were planned but not completed.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermatopathology was consistent with a diagnosis of cutaneous myxoma (CM). There are very few dermoscopic descriptions of CM in the literature, so diagnostic features are not established. However, the absence of more diagnostic features of basal cell carcinoma or squamous cell carcinoma (SCC) increases the likelihood of a rare diagnosis, such as CM.

CMs are rare benign neoplasms that manifest most commonly in young adults as small (< 1 cm) flesh-colored to blue papules on the head, neck, and trunk. The size of this particular CM was an outlier. CMs may be associated with Carney Complex (CNC), a rare inherited syndrome that has been linked to multiple endocrine neoplasias—namely, pituitary adenomas, testicular Sertoli cell tumors, thyroid tumors, and cardiac atrial myxomas.¹ Additionally, in CNC, lentigines and multiple blue nevi develop on the skin and mucosal surfaces.

The differential diagnosis for a large, pink to flesh-colored nodule of this size includes benign histiocytoma, SCC, CM, and dermatofibrosarcoma protuberans. Benign histiocytomas and SCCs are much more common than CM. Clinical features only hint at the correct diagnosis, which must be made histologically.

Patients with CMs benefit from ongoing dermatology surveillance to monitor for the development of atypical nevi or new CMs. In this case, a wide excision with generous margins was planned with plastic surgery. (CMs have been reported to recur after surgery, which is why wide margins are essential.)

Additionally, 2 factors prompted an echocardiogram: the association between CMs and possible cardiac tumors and the patient’s need to undergo future orthopedic surgery under general anesthesia. No cardiac tumors were visible on echocardiogram. Thyroid imaging and genetic evaluation were planned but not completed.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermatopathology was consistent with a diagnosis of cutaneous myxoma (CM). There are very few dermoscopic descriptions of CM in the literature, so diagnostic features are not established. However, the absence of more diagnostic features of basal cell carcinoma or squamous cell carcinoma (SCC) increases the likelihood of a rare diagnosis, such as CM.

CMs are rare benign neoplasms that manifest most commonly in young adults as small (< 1 cm) flesh-colored to blue papules on the head, neck, and trunk. The size of this particular CM was an outlier. CMs may be associated with Carney Complex (CNC), a rare inherited syndrome that has been linked to multiple endocrine neoplasias—namely, pituitary adenomas, testicular Sertoli cell tumors, thyroid tumors, and cardiac atrial myxomas.¹ Additionally, in CNC, lentigines and multiple blue nevi develop on the skin and mucosal surfaces.

The differential diagnosis for a large, pink to flesh-colored nodule of this size includes benign histiocytoma, SCC, CM, and dermatofibrosarcoma protuberans. Benign histiocytomas and SCCs are much more common than CM. Clinical features only hint at the correct diagnosis, which must be made histologically.

Patients with CMs benefit from ongoing dermatology surveillance to monitor for the development of atypical nevi or new CMs. In this case, a wide excision with generous margins was planned with plastic surgery. (CMs have been reported to recur after surgery, which is why wide margins are essential.)

Additionally, 2 factors prompted an echocardiogram: the association between CMs and possible cardiac tumors and the patient’s need to undergo future orthopedic surgery under general anesthesia. No cardiac tumors were visible on echocardiogram. Thyroid imaging and genetic evaluation were planned but not completed.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The US Preventive Services Task Force (USPSTF) recently released draft recommendations on screening for tuberculosis (TB).¹ The USPSTF continues to recommend screening for latent TB infection (LTBI) in those at high risk.

Why is this important? Up to one-quarter of the world’s population has been infected with TB, according to World Health Organization (WHO) estimates. In 2021, active TB was diagnosed in 10.6 million people, and it caused 1.6 million deaths.² Worldwide, TB is still a major cause of mortality: It is the 13th leading cause of death and is the leading cause of infectious disease mortality in non-COVID years.

Although the rate of active TB in the United States has been declining for decades (from 30.7/100,000 in 1960 to 2.4/100,000 in 2021), 7882 cases were reported in 2021, and an estimated 13 million people in the United States have LTBI.³ If not treated, 5% to 10% of LTBI cases will progress to active TB. This risk is higher in those with certain medical conditions.³ People born outside the United States currently account for 71.4% of reported TB cases in the United States.³

To reduce the morbidity and mortality of TB, the Centers for Disease Control and Prevention (CDC), WHO, and USPSTF all recommend screening for and treating LTBI. An effective approach to TB control also includes early detection and completion of treatment for active TB, as well as testing contacts of active TB cases.

Who should be screened? Those at high risk for LTBI include those who were born in, or who have resided in, countries with high rates of TB (eg, Latin America, the Caribbean, Africa, Asia, Eastern Europe, and Russia); those who have lived in a correctional facility or homeless shelter; household and other close contacts of active TB cases; and health care workers who provide care to patients with TB.

Some chronic medical conditions can increase risk for progression to active TB in those with LTBI. Patients who should be tested for LTBI as part of their routine care include those who are HIV positive; are receiving immunosuppressive therapy (chemotherapy, biological immune suppressants); have received an organ transplant; have silicosis; use illicit injected drugs; and/or have had a gastrectomy or jejunoileal bypass.

In addition, local communities may have populations or geographic regions in which TB rates are high. Family physicians can obtain this information from their state or local health departments.

There are 2 screening tests for LTBI: TB blood tests (interferon-gamma release assays [IGRAs]) and the Mantoux tuberculin skin test (TST). Two TB blood tests are available in the United States: QuantiFERON-TB Gold Plus (QFT-Plus) and T-SPOT.TB test (T-Spot).

There are advantages and disadvantages to both types of tests. A TST requires accurate administration and interpretation and 2 clinic visits, 48 to 72 hours apart. The cutoff on a positive test (5, 10, or 15 mm) depends on the patient’s age and risk.⁴ An IGRA should be processed within 8 to 32 hours and is more expensive. However, a major advantage is that it is more specific, because it is unaffected by previous vaccination with bacille Calmette-Guérin or by most nontuberculous mycobacteria infections.

To rule out active TB ... If a TB screening test is positive, the recommended work-up is to ask about TB symptoms and perform a chest x-ray to rule out active pulmonary TB. Sputum collection for acid-fast smear and culture should be ordered for anyone with a suspicious chest x-ray, respiratory symptoms consistent with TB, or HIV infection.

Treatment for LTBI markedly reduces the risk for active TB. There are 4 options:

• Isoniazid (INH) plus rifapentine (RPT) once per week for 3 months.
• Rifampin (RIF) daily for 4 months.
• INH plus RIF daily for 3 months.
• INH daily for 6 or 9 months.

Details about the variables to consider in choosing a regimen are described on the CDC website.^4,5

Know your resources. Local and state public health departments should have TB control programs and are sources of information on TB diagnosis and treatment; they also can assist with follow-up of TB contacts.⁶ Although LTBI is a reportable condition only in young children, any suspicion of community spread of active TB should be reported to the public health department.

The US Preventive Services Task Force (USPSTF) recently released draft recommendations on screening for tuberculosis (TB).¹ The USPSTF continues to recommend screening for latent TB infection (LTBI) in those at high risk.

Why is this important? Up to one-quarter of the world’s population has been infected with TB, according to World Health Organization (WHO) estimates. In 2021, active TB was diagnosed in 10.6 million people, and it caused 1.6 million deaths.² Worldwide, TB is still a major cause of mortality: It is the 13th leading cause of death and is the leading cause of infectious disease mortality in non-COVID years.

Although the rate of active TB in the United States has been declining for decades (from 30.7/100,000 in 1960 to 2.4/100,000 in 2021), 7882 cases were reported in 2021, and an estimated 13 million people in the United States have LTBI.³ If not treated, 5% to 10% of LTBI cases will progress to active TB. This risk is higher in those with certain medical conditions.³ People born outside the United States currently account for 71.4% of reported TB cases in the United States.³

To reduce the morbidity and mortality of TB, the Centers for Disease Control and Prevention (CDC), WHO, and USPSTF all recommend screening for and treating LTBI. An effective approach to TB control also includes early detection and completion of treatment for active TB, as well as testing contacts of active TB cases.

Who should be screened? Those at high risk for LTBI include those who were born in, or who have resided in, countries with high rates of TB (eg, Latin America, the Caribbean, Africa, Asia, Eastern Europe, and Russia); those who have lived in a correctional facility or homeless shelter; household and other close contacts of active TB cases; and health care workers who provide care to patients with TB.

Some chronic medical conditions can increase risk for progression to active TB in those with LTBI. Patients who should be tested for LTBI as part of their routine care include those who are HIV positive; are receiving immunosuppressive therapy (chemotherapy, biological immune suppressants); have received an organ transplant; have silicosis; use illicit injected drugs; and/or have had a gastrectomy or jejunoileal bypass.

In addition, local communities may have populations or geographic regions in which TB rates are high. Family physicians can obtain this information from their state or local health departments.

There are 2 screening tests for LTBI: TB blood tests (interferon-gamma release assays [IGRAs]) and the Mantoux tuberculin skin test (TST). Two TB blood tests are available in the United States: QuantiFERON-TB Gold Plus (QFT-Plus) and T-SPOT.TB test (T-Spot).

There are advantages and disadvantages to both types of tests. A TST requires accurate administration and interpretation and 2 clinic visits, 48 to 72 hours apart. The cutoff on a positive test (5, 10, or 15 mm) depends on the patient’s age and risk.⁴ An IGRA should be processed within 8 to 32 hours and is more expensive. However, a major advantage is that it is more specific, because it is unaffected by previous vaccination with bacille Calmette-Guérin or by most nontuberculous mycobacteria infections.

To rule out active TB ... If a TB screening test is positive, the recommended work-up is to ask about TB symptoms and perform a chest x-ray to rule out active pulmonary TB. Sputum collection for acid-fast smear and culture should be ordered for anyone with a suspicious chest x-ray, respiratory symptoms consistent with TB, or HIV infection.

Treatment for LTBI markedly reduces the risk for active TB. There are 4 options:

• Isoniazid (INH) plus rifapentine (RPT) once per week for 3 months.
• Rifampin (RIF) daily for 4 months.
• INH plus RIF daily for 3 months.
• INH daily for 6 or 9 months.

Details about the variables to consider in choosing a regimen are described on the CDC website.^4,5

Know your resources. Local and state public health departments should have TB control programs and are sources of information on TB diagnosis and treatment; they also can assist with follow-up of TB contacts.⁶ Although LTBI is a reportable condition only in young children, any suspicion of community spread of active TB should be reported to the public health department.

The US Preventive Services Task Force (USPSTF) recently released draft recommendations on screening for tuberculosis (TB).¹ The USPSTF continues to recommend screening for latent TB infection (LTBI) in those at high risk.

Why is this important? Up to one-quarter of the world’s population has been infected with TB, according to World Health Organization (WHO) estimates. In 2021, active TB was diagnosed in 10.6 million people, and it caused 1.6 million deaths.² Worldwide, TB is still a major cause of mortality: It is the 13th leading cause of death and is the leading cause of infectious disease mortality in non-COVID years.

Although the rate of active TB in the United States has been declining for decades (from 30.7/100,000 in 1960 to 2.4/100,000 in 2021), 7882 cases were reported in 2021, and an estimated 13 million people in the United States have LTBI.³ If not treated, 5% to 10% of LTBI cases will progress to active TB. This risk is higher in those with certain medical conditions.³ People born outside the United States currently account for 71.4% of reported TB cases in the United States.³

To reduce the morbidity and mortality of TB, the Centers for Disease Control and Prevention (CDC), WHO, and USPSTF all recommend screening for and treating LTBI. An effective approach to TB control also includes early detection and completion of treatment for active TB, as well as testing contacts of active TB cases.

Who should be screened? Those at high risk for LTBI include those who were born in, or who have resided in, countries with high rates of TB (eg, Latin America, the Caribbean, Africa, Asia, Eastern Europe, and Russia); those who have lived in a correctional facility or homeless shelter; household and other close contacts of active TB cases; and health care workers who provide care to patients with TB.

Some chronic medical conditions can increase risk for progression to active TB in those with LTBI. Patients who should be tested for LTBI as part of their routine care include those who are HIV positive; are receiving immunosuppressive therapy (chemotherapy, biological immune suppressants); have received an organ transplant; have silicosis; use illicit injected drugs; and/or have had a gastrectomy or jejunoileal bypass.

In addition, local communities may have populations or geographic regions in which TB rates are high. Family physicians can obtain this information from their state or local health departments.

There are 2 screening tests for LTBI: TB blood tests (interferon-gamma release assays [IGRAs]) and the Mantoux tuberculin skin test (TST). Two TB blood tests are available in the United States: QuantiFERON-TB Gold Plus (QFT-Plus) and T-SPOT.TB test (T-Spot).

There are advantages and disadvantages to both types of tests. A TST requires accurate administration and interpretation and 2 clinic visits, 48 to 72 hours apart. The cutoff on a positive test (5, 10, or 15 mm) depends on the patient’s age and risk.⁴ An IGRA should be processed within 8 to 32 hours and is more expensive. However, a major advantage is that it is more specific, because it is unaffected by previous vaccination with bacille Calmette-Guérin or by most nontuberculous mycobacteria infections.

To rule out active TB ... If a TB screening test is positive, the recommended work-up is to ask about TB symptoms and perform a chest x-ray to rule out active pulmonary TB. Sputum collection for acid-fast smear and culture should be ordered for anyone with a suspicious chest x-ray, respiratory symptoms consistent with TB, or HIV infection.

Treatment for LTBI markedly reduces the risk for active TB. There are 4 options:

• Isoniazid (INH) plus rifapentine (RPT) once per week for 3 months.
• Rifampin (RIF) daily for 4 months.
• INH plus RIF daily for 3 months.
• INH daily for 6 or 9 months.

Details about the variables to consider in choosing a regimen are described on the CDC website.^4,5

Know your resources. Local and state public health departments should have TB control programs and are sources of information on TB diagnosis and treatment; they also can assist with follow-up of TB contacts.⁶ Although LTBI is a reportable condition only in young children, any suspicion of community spread of active TB should be reported to the public health department.

In this issue, Mayo and colleagues¹ summarize what we know about patients with long COVID. The report made me pause and realize that it has been 3 years since we heard the very first reports of patients infected with SARS-CoV-2, which would eventually cause the COVID-19 pandemic. I suspect that I am not alone in having been fascinated by the rapid communication of information (of variable quality and veracity) via peer-reviewed papers, pre-print servers, the media, and social media.

The early studies were largely descriptive, focusing on symptom constellations and outbreak data. Much of what we had by way of treatment was supportive and “let’s try anything”—whether reasonable or, in some cases, not. In relatively short order, though, we developed effective vaccines to help protect people from getting seriously ill, being hospitalized, and dying; we also identified targeted therapies for those who became ill.² But variants continued—or rather, continue—to emerge, and we remain committed to meeting the demands of the day.

The Centers for Disease Control and Prevention reports that more than 98 million Americans have contracted COVID, and more than 1 million have died.³ Besides the astonishingly high total mortality, the ravages of COVID-19 include new-onset respiratory, cardiovascular, neurologic, and psychiatric illnesses.^4,5 As many as half of adults hospitalized for COVID report having persistent symptoms.⁶

As described in this issue, what we know about long COVID appears to be following the early course of its parent illness. As was true then, we are learning about the symptoms, etiology, and best ways to manage our patients. As in the early days of the pandemic, treatment is supportive, and we await definitive therapies.

I am optimistic, though. Why? Because shortly after the first reports of ­COVID-19, the virus’ DNA sequence was shared online. Based on that information, diagnostic assays were developed. Within 2 years of the outbreak, we had effective vaccines and specific therapies.

Another call to action. If 5% of patients contracting COVID (a very low estimate) develop long COVID, that would translate to 4.9 million people with long ­COVID in the United States. That is an astounding burden of suffering that I have no doubt will motivate innovation.

Innovation is a strength of the US health care system. I believe we will rise to the next challenge that COVID-19 has put before us. We have reason to be hopeful.

In this issue, Mayo and colleagues¹ summarize what we know about patients with long COVID. The report made me pause and realize that it has been 3 years since we heard the very first reports of patients infected with SARS-CoV-2, which would eventually cause the COVID-19 pandemic. I suspect that I am not alone in having been fascinated by the rapid communication of information (of variable quality and veracity) via peer-reviewed papers, pre-print servers, the media, and social media.

The early studies were largely descriptive, focusing on symptom constellations and outbreak data. Much of what we had by way of treatment was supportive and “let’s try anything”—whether reasonable or, in some cases, not. In relatively short order, though, we developed effective vaccines to help protect people from getting seriously ill, being hospitalized, and dying; we also identified targeted therapies for those who became ill.² But variants continued—or rather, continue—to emerge, and we remain committed to meeting the demands of the day.

The Centers for Disease Control and Prevention reports that more than 98 million Americans have contracted COVID, and more than 1 million have died.³ Besides the astonishingly high total mortality, the ravages of COVID-19 include new-onset respiratory, cardiovascular, neurologic, and psychiatric illnesses.^4,5 As many as half of adults hospitalized for COVID report having persistent symptoms.⁶

As described in this issue, what we know about long COVID appears to be following the early course of its parent illness. As was true then, we are learning about the symptoms, etiology, and best ways to manage our patients. As in the early days of the pandemic, treatment is supportive, and we await definitive therapies.

I am optimistic, though. Why? Because shortly after the first reports of ­COVID-19, the virus’ DNA sequence was shared online. Based on that information, diagnostic assays were developed. Within 2 years of the outbreak, we had effective vaccines and specific therapies.

Another call to action. If 5% of patients contracting COVID (a very low estimate) develop long COVID, that would translate to 4.9 million people with long ­COVID in the United States. That is an astounding burden of suffering that I have no doubt will motivate innovation.

Innovation is a strength of the US health care system. I believe we will rise to the next challenge that COVID-19 has put before us. We have reason to be hopeful.

In this issue, Mayo and colleagues¹ summarize what we know about patients with long COVID. The report made me pause and realize that it has been 3 years since we heard the very first reports of patients infected with SARS-CoV-2, which would eventually cause the COVID-19 pandemic. I suspect that I am not alone in having been fascinated by the rapid communication of information (of variable quality and veracity) via peer-reviewed papers, pre-print servers, the media, and social media.

The early studies were largely descriptive, focusing on symptom constellations and outbreak data. Much of what we had by way of treatment was supportive and “let’s try anything”—whether reasonable or, in some cases, not. In relatively short order, though, we developed effective vaccines to help protect people from getting seriously ill, being hospitalized, and dying; we also identified targeted therapies for those who became ill.² But variants continued—or rather, continue—to emerge, and we remain committed to meeting the demands of the day.

The Centers for Disease Control and Prevention reports that more than 98 million Americans have contracted COVID, and more than 1 million have died.³ Besides the astonishingly high total mortality, the ravages of COVID-19 include new-onset respiratory, cardiovascular, neurologic, and psychiatric illnesses.^4,5 As many as half of adults hospitalized for COVID report having persistent symptoms.⁶

As described in this issue, what we know about long COVID appears to be following the early course of its parent illness. As was true then, we are learning about the symptoms, etiology, and best ways to manage our patients. As in the early days of the pandemic, treatment is supportive, and we await definitive therapies.

I am optimistic, though. Why? Because shortly after the first reports of ­COVID-19, the virus’ DNA sequence was shared online. Based on that information, diagnostic assays were developed. Within 2 years of the outbreak, we had effective vaccines and specific therapies.

Another call to action. If 5% of patients contracting COVID (a very low estimate) develop long COVID, that would translate to 4.9 million people with long ­COVID in the United States. That is an astounding burden of suffering that I have no doubt will motivate innovation.

Innovation is a strength of the US health care system. I believe we will rise to the next challenge that COVID-19 has put before us. We have reason to be hopeful.

A 68-year-old man with type 2 diabetes ­presented with progressive hyperpigmentation of the lower extremities and face over the past 3 years. Clinical examination revealed confluent, blue-black hyperpigmentation of the lower extremities (Figure), upper extremities, neck, and face. Laboratory tests and arterial studies were within normal ranges. The patient’s medication list included lisinopril 10 mg/d, metformin 1000 mg twice daily, minocycline 100 mg twice daily, and omeprazole 20 mg/d.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Hyperpigmentation is a rare but not uncommon adverse effect of long-term minocycline use. In this case, our patient had been taking minocycline for more than 5 years. When seen in our clinic, he said he could not remember why he was taking minocycline and incorrectly assumed it was for his diabetes. Chart review of outside records revealed that it had been prescribed, and refilled annually, by his primary physician for rosacea.

Minocycline hyperpigmentation is subdivided into 3 types:

• Type I manifests with blue-black discoloration in previously inflamed areas of skin.
• Type II manifests with blue-gray pigmentation in previously normal skin areas.
• Type III manifests diffusely with muddy-brown hyperpigmentation on photoexposed skin.

Furthermore, noncutaneous manifestations may occur on the sclera, nails, ear cartilage, bone, oral mucosa, teeth, and thyroid gland.¹

Diagnosis focuses on identifying the source

Minocycline is one of many drugs that can induce hyperpigmentation of the skin. In addition to history, examination, and review of the patient’s medication list, there are some clues on exam that may suggest a certain type of medication at play.

Continue to: Antimalarials

Antimalarials. Chloroquine, hydroxychloroquine, and quinacrine can cause blue-black skin hyperpigmentation in as many as 25% of patients. Common locations include the shins, face, oral mucosa, and subungual skin. This hyperpigmentation rarely fully resolves.²

Amiodarone. Hyperpigmentation secondary to amiodarone use typically is slate-gray in color and involves photoexposed skin. Patients should be counseled that pigmentation may—but does not always—fade with time after discontinuation of the drug.²

Heavy metals. Argyria results from exposure to silver, either ingested orally or applied externally. A common cause of argyria is ingestion of excessive amounts of silver-­containing supplements.³ Affected patients present with diffuse slate-gray discoloration of the skin.

This case underscores the importance of routinely reassessing patients’ understanding of their medications and treatment plans.

Other metals implicated in skin hyperpigmentation include arsenic, gold, mercury, and iron. Review of all supplements and herbal remedies in patients presenting with skin hyperpigmentation is crucial.

Bleomycin is a chemotherapeutic agent with a rare but unique adverse effect of inducing flagellate hyperpigmentation that favors the chest, abdomen, or back. This may be induced by trauma or scratching and is often transient. Hyperpigmentation can occur secondary to either intravenous or intralesional injection of the medication.²

Continue to: In addition to medication...

In addition to medication- or supple­ment-­induced hyperpigmentation, there is a physiologic source that should be considered when a patient presents with ­lower-extremity hyperpigmentation:

Stasis hyperpigmentation. Patients with chronic venous insufficiency may present with hyperpigmentation of the lower extremities. Commonly due to dysfunctional venous valves or obstruction, stasis hyperpigmentation manifests with red-brown discoloration from dermal hemosiderin deposition.⁴

Unlike our patient, those with stasis hyperpigmentation may present symptomatically, with associated dry skin, pruritus, induration, and inflammation. Treatment involves management of the underlying venous insufficiency.⁴

When there’s no obvious cause, be prepared to dig deeper

At the time of initial assessment, a thorough review of systems and detailed medication history, including over-the-counter supplements, should be obtained. Physical examination revealing diffuse, generalized hyperpigmentation with no reliable culprit medication in the patient’s history warrants further laboratory evaluation. This includes ordering renal and liver studies and tests for thyroid-stimulating hormone and ferritin and cortisol levels to rule out metabolic or endocrine hyperpigmentation disorders.

Stopping the offending medication is the first step

Discontinuation of the offending medication may result in mild improvement in skin hyperpigmentation over time. Some patients may not experience any improvement. If improvement occurs, it is important to educate patients that it can take several months to years. Dermatology guidelines favor discontinuation of antibiotics for acne or rosacea after 3 to 6 months to avoid bacterial resistance.⁵ Worsening hyperpigmentation despite medication discontinuation warrants further work-up.

Patients who are distressed by persistent hyperpigmentation can be treated using picosecond or Q-switched lasers.⁶

Our patient was advised to discontinue the minocycline. Three test spots on his face were treated with pulsed-dye laser, carbon dioxide laser, and dermabrasion. The patient noted that the spots responded better to the carbon dioxide laser and dermabrasion compared to the pulsed-dye laser. He did not ­follow up for further treatment.

A 68-year-old man with type 2 diabetes ­presented with progressive hyperpigmentation of the lower extremities and face over the past 3 years. Clinical examination revealed confluent, blue-black hyperpigmentation of the lower extremities (Figure), upper extremities, neck, and face. Laboratory tests and arterial studies were within normal ranges. The patient’s medication list included lisinopril 10 mg/d, metformin 1000 mg twice daily, minocycline 100 mg twice daily, and omeprazole 20 mg/d.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Hyperpigmentation is a rare but not uncommon adverse effect of long-term minocycline use. In this case, our patient had been taking minocycline for more than 5 years. When seen in our clinic, he said he could not remember why he was taking minocycline and incorrectly assumed it was for his diabetes. Chart review of outside records revealed that it had been prescribed, and refilled annually, by his primary physician for rosacea.

Minocycline hyperpigmentation is subdivided into 3 types:

• Type I manifests with blue-black discoloration in previously inflamed areas of skin.
• Type II manifests with blue-gray pigmentation in previously normal skin areas.
• Type III manifests diffusely with muddy-brown hyperpigmentation on photoexposed skin.

Furthermore, noncutaneous manifestations may occur on the sclera, nails, ear cartilage, bone, oral mucosa, teeth, and thyroid gland.¹

Diagnosis focuses on identifying the source

Minocycline is one of many drugs that can induce hyperpigmentation of the skin. In addition to history, examination, and review of the patient’s medication list, there are some clues on exam that may suggest a certain type of medication at play.

Continue to: Antimalarials

Antimalarials. Chloroquine, hydroxychloroquine, and quinacrine can cause blue-black skin hyperpigmentation in as many as 25% of patients. Common locations include the shins, face, oral mucosa, and subungual skin. This hyperpigmentation rarely fully resolves.²

Amiodarone. Hyperpigmentation secondary to amiodarone use typically is slate-gray in color and involves photoexposed skin. Patients should be counseled that pigmentation may—but does not always—fade with time after discontinuation of the drug.²

Heavy metals. Argyria results from exposure to silver, either ingested orally or applied externally. A common cause of argyria is ingestion of excessive amounts of silver-­containing supplements.³ Affected patients present with diffuse slate-gray discoloration of the skin.

This case underscores the importance of routinely reassessing patients’ understanding of their medications and treatment plans.

Other metals implicated in skin hyperpigmentation include arsenic, gold, mercury, and iron. Review of all supplements and herbal remedies in patients presenting with skin hyperpigmentation is crucial.

Bleomycin is a chemotherapeutic agent with a rare but unique adverse effect of inducing flagellate hyperpigmentation that favors the chest, abdomen, or back. This may be induced by trauma or scratching and is often transient. Hyperpigmentation can occur secondary to either intravenous or intralesional injection of the medication.²

Continue to: In addition to medication...

In addition to medication- or supple­ment-­induced hyperpigmentation, there is a physiologic source that should be considered when a patient presents with ­lower-extremity hyperpigmentation:

Stasis hyperpigmentation. Patients with chronic venous insufficiency may present with hyperpigmentation of the lower extremities. Commonly due to dysfunctional venous valves or obstruction, stasis hyperpigmentation manifests with red-brown discoloration from dermal hemosiderin deposition.⁴

Unlike our patient, those with stasis hyperpigmentation may present symptomatically, with associated dry skin, pruritus, induration, and inflammation. Treatment involves management of the underlying venous insufficiency.⁴

When there’s no obvious cause, be prepared to dig deeper

At the time of initial assessment, a thorough review of systems and detailed medication history, including over-the-counter supplements, should be obtained. Physical examination revealing diffuse, generalized hyperpigmentation with no reliable culprit medication in the patient’s history warrants further laboratory evaluation. This includes ordering renal and liver studies and tests for thyroid-stimulating hormone and ferritin and cortisol levels to rule out metabolic or endocrine hyperpigmentation disorders.

Stopping the offending medication is the first step

Discontinuation of the offending medication may result in mild improvement in skin hyperpigmentation over time. Some patients may not experience any improvement. If improvement occurs, it is important to educate patients that it can take several months to years. Dermatology guidelines favor discontinuation of antibiotics for acne or rosacea after 3 to 6 months to avoid bacterial resistance.⁵ Worsening hyperpigmentation despite medication discontinuation warrants further work-up.

Patients who are distressed by persistent hyperpigmentation can be treated using picosecond or Q-switched lasers.⁶

Our patient was advised to discontinue the minocycline. Three test spots on his face were treated with pulsed-dye laser, carbon dioxide laser, and dermabrasion. The patient noted that the spots responded better to the carbon dioxide laser and dermabrasion compared to the pulsed-dye laser. He did not ­follow up for further treatment.

A 68-year-old man with type 2 diabetes ­presented with progressive hyperpigmentation of the lower extremities and face over the past 3 years. Clinical examination revealed confluent, blue-black hyperpigmentation of the lower extremities (Figure), upper extremities, neck, and face. Laboratory tests and arterial studies were within normal ranges. The patient’s medication list included lisinopril 10 mg/d, metformin 1000 mg twice daily, minocycline 100 mg twice daily, and omeprazole 20 mg/d.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Hyperpigmentation is a rare but not uncommon adverse effect of long-term minocycline use. In this case, our patient had been taking minocycline for more than 5 years. When seen in our clinic, he said he could not remember why he was taking minocycline and incorrectly assumed it was for his diabetes. Chart review of outside records revealed that it had been prescribed, and refilled annually, by his primary physician for rosacea.

Minocycline hyperpigmentation is subdivided into 3 types:

• Type I manifests with blue-black discoloration in previously inflamed areas of skin.
• Type II manifests with blue-gray pigmentation in previously normal skin areas.
• Type III manifests diffusely with muddy-brown hyperpigmentation on photoexposed skin.

Furthermore, noncutaneous manifestations may occur on the sclera, nails, ear cartilage, bone, oral mucosa, teeth, and thyroid gland.¹

Diagnosis focuses on identifying the source

Minocycline is one of many drugs that can induce hyperpigmentation of the skin. In addition to history, examination, and review of the patient’s medication list, there are some clues on exam that may suggest a certain type of medication at play.

Continue to: Antimalarials

Antimalarials. Chloroquine, hydroxychloroquine, and quinacrine can cause blue-black skin hyperpigmentation in as many as 25% of patients. Common locations include the shins, face, oral mucosa, and subungual skin. This hyperpigmentation rarely fully resolves.²

Amiodarone. Hyperpigmentation secondary to amiodarone use typically is slate-gray in color and involves photoexposed skin. Patients should be counseled that pigmentation may—but does not always—fade with time after discontinuation of the drug.²

Heavy metals. Argyria results from exposure to silver, either ingested orally or applied externally. A common cause of argyria is ingestion of excessive amounts of silver-­containing supplements.³ Affected patients present with diffuse slate-gray discoloration of the skin.

This case underscores the importance of routinely reassessing patients’ understanding of their medications and treatment plans.

Other metals implicated in skin hyperpigmentation include arsenic, gold, mercury, and iron. Review of all supplements and herbal remedies in patients presenting with skin hyperpigmentation is crucial.

Bleomycin is a chemotherapeutic agent with a rare but unique adverse effect of inducing flagellate hyperpigmentation that favors the chest, abdomen, or back. This may be induced by trauma or scratching and is often transient. Hyperpigmentation can occur secondary to either intravenous or intralesional injection of the medication.²

Continue to: In addition to medication...

In addition to medication- or supple­ment-­induced hyperpigmentation, there is a physiologic source that should be considered when a patient presents with ­lower-extremity hyperpigmentation:

Stasis hyperpigmentation. Patients with chronic venous insufficiency may present with hyperpigmentation of the lower extremities. Commonly due to dysfunctional venous valves or obstruction, stasis hyperpigmentation manifests with red-brown discoloration from dermal hemosiderin deposition.⁴

Unlike our patient, those with stasis hyperpigmentation may present symptomatically, with associated dry skin, pruritus, induration, and inflammation. Treatment involves management of the underlying venous insufficiency.⁴

When there’s no obvious cause, be prepared to dig deeper

At the time of initial assessment, a thorough review of systems and detailed medication history, including over-the-counter supplements, should be obtained. Physical examination revealing diffuse, generalized hyperpigmentation with no reliable culprit medication in the patient’s history warrants further laboratory evaluation. This includes ordering renal and liver studies and tests for thyroid-stimulating hormone and ferritin and cortisol levels to rule out metabolic or endocrine hyperpigmentation disorders.

Stopping the offending medication is the first step

Discontinuation of the offending medication may result in mild improvement in skin hyperpigmentation over time. Some patients may not experience any improvement. If improvement occurs, it is important to educate patients that it can take several months to years. Dermatology guidelines favor discontinuation of antibiotics for acne or rosacea after 3 to 6 months to avoid bacterial resistance.⁵ Worsening hyperpigmentation despite medication discontinuation warrants further work-up.

Patients who are distressed by persistent hyperpigmentation can be treated using picosecond or Q-switched lasers.⁶

Our patient was advised to discontinue the minocycline. Three test spots on his face were treated with pulsed-dye laser, carbon dioxide laser, and dermabrasion. The patient noted that the spots responded better to the carbon dioxide laser and dermabrasion compared to the pulsed-dye laser. He did not ­follow up for further treatment.

ILLUSTRATIVE CASE

A 72-year-old man with a history of hypertension, permanent atrial fibrillation, and heart failure (HF) comes into your clinic for follow-up. He was hospitalized a few months ago for HF requiring diuresis. His echocardiogram at that time showed an EF of 50% and no significant valvular disease. He does not have a history of diabetes or tobacco use. His medication regimen includes metoprolol, lisinopril-hydrochlorothiazide, apixaban, and atorvastatin. The patient is still symptomatic from his HF and asks you if there is anything else he can do to prevent another hospitalization for HF.

HFpEF was first defined as HF in patients with a left ventricular ejection fraction (LVEF) > 40%. However, HF with an LVEF between 41% and 49% has been reclassified as its own category: heart failure with mildly reduced ejection fraction (HFmrEF).² HFpEF is now diagnosed when the patient has HF symptoms and an LVEF ≥ 50%, mimickers (lung disease, pulmonary embolism, pulmonary hypertension, and renal disease) have been excluded, and there is evidence of elevated left ventricular filling pressure or noninvasive correlates such as elevated natriuretic peptides. It is estimated that HFpEF comprises half of all patients with HF.³

In comparison with HF with reduced ejection fraction (HFrEF), there are limited proven treatment options with cardiovascular (CV) benefit in HFpEF.⁴ Spironolactone is associated with a slight decrease in HF-­related hospitalizations but not with a reduction in CV or all-cause mortality for patients with HFpEF.^4,5 Angiotensin-­converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers have not been shown to reduce morbidity or mortality in HFpEF when not indicated for another reason.^6,7 Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to decrease the development and progression of HFrEF⁸; however, the effect of SGLT2 inhibition in patients with HFpEF remains unclear. Post hoc analyses of a multicenter trial of dapagliflozin in type 2 diabetes indicated no reduction in CV death, hospitalization, or all-cause mortality in HFpEF.⁹ Another study found improved CV mortality and decreased HF-related urgent visits and hospitalizations with sotagliflozin, but the number of events was too small to estimate a treatment effect.¹⁰ Given this uncertainty, the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-­Preserved) was conducted to evaluate the effects of SGLT2 inhibition with empagliflozin in patients with HFpEF.¹

STUDY SUMMARY

Confirmation of benefit of empagliflozin for patients with HFpEF

The EMPEROR-Preserved study was a ­double-blind, placebo-controlled trial that randomized adult patients with HFpEF (defined by an LVEF > 40%) to either placebo or empagliflozin 10 mg/d, in addition to usual therapy. Patients were randomized in a 1:1 ratio stratified by geographic region, diabetes status, renal function (estimated glomerular filtration rate [eGFR] either < 60 or ≥ 60 mL/min/1.73 m²), and LVEF > 40% to < 50% or LVEF ≥ 50%.

For patients with HFpEF, empagliflozin added to usual care significantly reduced the risk of hospitalization for heart failure, regardless of whether patients had diabetes.

Included patients were 18 years or older and had an NT-proBNP level > 300 pg/mL (or > 900 pg/mL if the patient had atrial fibrillation at baseline), an LVEF > 40%, and New York Heart Association (NYHA) class II-IV symptoms at baseline. Patients with a CV event in the preceding 90 days, systolic blood pressure ≥ 180 mm Hg, or significant valvular disease were excluded from the study.

The primary outcome was a composite of CV death or first hospitalization for HF. The secondary outcomes were all hospitalizations for HF and the rate of decline in eGFR.

Of the 5988 patients in the trial, 2997 were randomized to receive empagliflozin and 2991 were randomized to placebo. The average age was 72 years in each group, 45% of patients were women, about 76% were White, and 12% were from North America. About 81% of patients were classified as NYHA class II, nearly half had diabetes, and half had an eGFR < 60 mL/min/1.73 m². The median body mass index (BMI) was 30, and the median LVEF was 54%. At baseline, the groups were similar in BMI, history of HF hospitalization in the past 12 months, history of common risk factors for HFpEF (atrial fibrillation, diabetes, and hypertension), and prescribed CV medications (ACE inhibitor or ARB with or without a neprilysin inhibitor, spironolactone, beta-blocker, digitalis glycosides, aspirin, and statins). Patients were followed for a median of 26.2 months.

Continue to: The primary composite...

The primary composite outcome of death from CV causes or HF-related hospitalization occurred in 415 patients (13.8%) in the empagliflozin group and in 511 patients (17.1%) in the placebo group (hazard ratio [HR] = 0.79; 95% CI, 0.69-0.90; P < .001). The number needed to treat to prevent 1 primary outcome event was 31 (95% CI, 20-69). Hospitalization for HF occurred in 259 patients (8.6%) with empagliflozin vs 352 patients (11.8%) with placebo (HR = 0.71; 95% CI, 0.60-0.83), and CV death occurred in 219 patients (7.3%) with empagliflozin vs 244 patients (8.2%) with placebo (HR = 0.91; 95% CI, 0.76-1.09). The effect was consistent in patients with or without diabetes at baseline; however, the largest reduction in the primary composite outcome was seen in those with an LVEF < 50%, age ≥ 70 years old, BMI < 30, and NYHA class II status.

The secondary outcome of total number of hospitalizations for HF was 407 with empagliflozin vs 541 with placebo (HR = 0.73; 95% CI, 0.61-0.88; P < .001). The rate of decline in the eGFR per year was –1.25 in the empagliflozin group vs –2.62 in the placebo group (P < .001), indicating that those taking empagliflozin had preserved renal function compared with those taking placebo.

Death from any cause occurred in 422 patients (14.1%) in the empagliflozin group and 427 patients (14.3%) in the placebo group (HR = 1.00; 95% CI, 0.87-1.15). Empagliflozin treatment was associated with higher rates of genital infections (2.2% vs 0.7%; P value not provided), urinary tract infections (9.9% vs 8.1%; P value not provided), and hypotension (10.4% vs 8.6%; P value not provided), compared to placebo.

WHAT’S NEW

Risk of hospitalization significantly reduced for patients with HFpEF

In the EMPEROR-Preserved study, empagliflozin led to a lower incidence of hospitalization for HF in patients with HFpEF but did not significantly reduce the number of deaths from CV disease or other causes. In comparison, in the similarly designed EMPEROR-Reduced trial, treatment with empagliflozin reduced CV and all-cause mortality in individuals with HFrEF.⁸

CAVEATS

HF criteria, study population may limit generalizability

The reduction in the primary outcome of CV death or first hospitalization was most pronounced in patients with an LVEF > 40% to < 50%, typically defined as HFmrEF, who often have clinical features similar to those with HFrEF. This raises the question of how generalizable these results are for all patients with HFpEF.

Continue to: The study's generalizability...

Empagliflozin treatment, however, was associated with higher rates of genital infections, urinary tract infections, and hypotension, compared to placebo.

The study’s generalizability was further limited by its significant exclusion criteria, which included elevated blood pressure, chronic obstructive pulmonary disease on home oxygen, liver disease, renal disease with an eGFR < 20 mL/min/1.73 m² or requiring dialysis, and BMI ≥ 45.

Finally, only 12% of patients were from North America, and results were not significant for this subgroup (HR = 0.72; 95% CI, 0.52-1.00), which may challenge its external validity. The authors noted that 23% of patients discontinued treatment for reasons other than death, which may have driven the null effect.

CHALLENGES TO IMPLEMENTATION

Empagliflozin is expensive,but coverage may improve

Cost could be a major barrier to implementation. Retail pricing for empagliflozin is estimated to be more than $550 per month, which may be prohibitive for patients with no insurance or with higher-deductible plans.¹¹ However, the US Food and Drug Administration has approved empagliflozin to reduce the risk of CV death and hospitalization for HF in adults,¹² which may help to improve insurance coverage.

ILLUSTRATIVE CASE

A 72-year-old man with a history of hypertension, permanent atrial fibrillation, and heart failure (HF) comes into your clinic for follow-up. He was hospitalized a few months ago for HF requiring diuresis. His echocardiogram at that time showed an EF of 50% and no significant valvular disease. He does not have a history of diabetes or tobacco use. His medication regimen includes metoprolol, lisinopril-hydrochlorothiazide, apixaban, and atorvastatin. The patient is still symptomatic from his HF and asks you if there is anything else he can do to prevent another hospitalization for HF.

HFpEF was first defined as HF in patients with a left ventricular ejection fraction (LVEF) > 40%. However, HF with an LVEF between 41% and 49% has been reclassified as its own category: heart failure with mildly reduced ejection fraction (HFmrEF).² HFpEF is now diagnosed when the patient has HF symptoms and an LVEF ≥ 50%, mimickers (lung disease, pulmonary embolism, pulmonary hypertension, and renal disease) have been excluded, and there is evidence of elevated left ventricular filling pressure or noninvasive correlates such as elevated natriuretic peptides. It is estimated that HFpEF comprises half of all patients with HF.³

In comparison with HF with reduced ejection fraction (HFrEF), there are limited proven treatment options with cardiovascular (CV) benefit in HFpEF.⁴ Spironolactone is associated with a slight decrease in HF-­related hospitalizations but not with a reduction in CV or all-cause mortality for patients with HFpEF.^4,5 Angiotensin-­converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers have not been shown to reduce morbidity or mortality in HFpEF when not indicated for another reason.^6,7 Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to decrease the development and progression of HFrEF⁸; however, the effect of SGLT2 inhibition in patients with HFpEF remains unclear. Post hoc analyses of a multicenter trial of dapagliflozin in type 2 diabetes indicated no reduction in CV death, hospitalization, or all-cause mortality in HFpEF.⁹ Another study found improved CV mortality and decreased HF-related urgent visits and hospitalizations with sotagliflozin, but the number of events was too small to estimate a treatment effect.¹⁰ Given this uncertainty, the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-­Preserved) was conducted to evaluate the effects of SGLT2 inhibition with empagliflozin in patients with HFpEF.¹

STUDY SUMMARY

Confirmation of benefit of empagliflozin for patients with HFpEF

The EMPEROR-Preserved study was a ­double-blind, placebo-controlled trial that randomized adult patients with HFpEF (defined by an LVEF > 40%) to either placebo or empagliflozin 10 mg/d, in addition to usual therapy. Patients were randomized in a 1:1 ratio stratified by geographic region, diabetes status, renal function (estimated glomerular filtration rate [eGFR] either < 60 or ≥ 60 mL/min/1.73 m²), and LVEF > 40% to < 50% or LVEF ≥ 50%.

For patients with HFpEF, empagliflozin added to usual care significantly reduced the risk of hospitalization for heart failure, regardless of whether patients had diabetes.

Included patients were 18 years or older and had an NT-proBNP level > 300 pg/mL (or > 900 pg/mL if the patient had atrial fibrillation at baseline), an LVEF > 40%, and New York Heart Association (NYHA) class II-IV symptoms at baseline. Patients with a CV event in the preceding 90 days, systolic blood pressure ≥ 180 mm Hg, or significant valvular disease were excluded from the study.

The primary outcome was a composite of CV death or first hospitalization for HF. The secondary outcomes were all hospitalizations for HF and the rate of decline in eGFR.

Of the 5988 patients in the trial, 2997 were randomized to receive empagliflozin and 2991 were randomized to placebo. The average age was 72 years in each group, 45% of patients were women, about 76% were White, and 12% were from North America. About 81% of patients were classified as NYHA class II, nearly half had diabetes, and half had an eGFR < 60 mL/min/1.73 m². The median body mass index (BMI) was 30, and the median LVEF was 54%. At baseline, the groups were similar in BMI, history of HF hospitalization in the past 12 months, history of common risk factors for HFpEF (atrial fibrillation, diabetes, and hypertension), and prescribed CV medications (ACE inhibitor or ARB with or without a neprilysin inhibitor, spironolactone, beta-blocker, digitalis glycosides, aspirin, and statins). Patients were followed for a median of 26.2 months.

Continue to: The primary composite...

The primary composite outcome of death from CV causes or HF-related hospitalization occurred in 415 patients (13.8%) in the empagliflozin group and in 511 patients (17.1%) in the placebo group (hazard ratio [HR] = 0.79; 95% CI, 0.69-0.90; P < .001). The number needed to treat to prevent 1 primary outcome event was 31 (95% CI, 20-69). Hospitalization for HF occurred in 259 patients (8.6%) with empagliflozin vs 352 patients (11.8%) with placebo (HR = 0.71; 95% CI, 0.60-0.83), and CV death occurred in 219 patients (7.3%) with empagliflozin vs 244 patients (8.2%) with placebo (HR = 0.91; 95% CI, 0.76-1.09). The effect was consistent in patients with or without diabetes at baseline; however, the largest reduction in the primary composite outcome was seen in those with an LVEF < 50%, age ≥ 70 years old, BMI < 30, and NYHA class II status.

The secondary outcome of total number of hospitalizations for HF was 407 with empagliflozin vs 541 with placebo (HR = 0.73; 95% CI, 0.61-0.88; P < .001). The rate of decline in the eGFR per year was –1.25 in the empagliflozin group vs –2.62 in the placebo group (P < .001), indicating that those taking empagliflozin had preserved renal function compared with those taking placebo.

Death from any cause occurred in 422 patients (14.1%) in the empagliflozin group and 427 patients (14.3%) in the placebo group (HR = 1.00; 95% CI, 0.87-1.15). Empagliflozin treatment was associated with higher rates of genital infections (2.2% vs 0.7%; P value not provided), urinary tract infections (9.9% vs 8.1%; P value not provided), and hypotension (10.4% vs 8.6%; P value not provided), compared to placebo.

WHAT’S NEW