Case Letter

To the Editor:

Syringoma is a relatively common benign adnexal neoplasm originating in the ducts of eccrine sweat glands. It can be divided into 4 variants based on clinical features: localized; familial; Down syndrome associated; and generalized, which includes multiple syringomas and eruptive syringoma (ES).¹ Eruptive syringoma is a rare variant of generalized syringoma that was first described by Jacquet and Darier² in 1887. Clinically, ES lesions manifest as multiple nonfused, flesh-colored to reddish-brown papules that are located most commonly on the anterior trunk during childhood or adolescence. Eruptive syringoma can be missed easily or misdiagnosed clinically. We present 3 rare cases of ES.

A 28-year-old man presented with multiple asymptomatic papules on the trunk and upper arms of 20 years’ duration (patient 1). He had been diagnosed with Darier disease 3 years prior to the current presentation and was treated with oral and topical retinoic acid without a response. After 3 months of oral treatment, the retinoic acid was stopped due to elevated liver enzymes. Physical examination at the current presentation revealed multiple smooth, firm, nonfused, 1- to 4-mm, reddish to dark red papules on the neck, chest, abdomen, and flexural surfaces of the upper arms (Figure 1A). Dermoscopy of the arm lesions showed light brown pigment networks and yellowish-white unstructured areas surrounded by linear vessels on a pink background under polarized light (Figure 1B). Histopathologic examination of a lesion on the left arm revealed epithelial cords, ducts, and cystic structures within the superficial and mid dermis. The ducts were lined by 2 rows of epithelial cells with a characteristic tadpolelike pattern and filled with eosinophilic amorphous substances (Figure 1C).

A 43-year-old man who was otherwise healthy presented with brownish flat-topped papules on the chest and abdomen of 19 years’ duration (Figure 3A)(patient 3). The lesions had remained stable and did not progress. He denied any treatment. Dermoscopy of the chest lesions showed a light brown pigment network as well as dotted and linear vessels on a pale yellow background (Figure 3B).

All 3 patients demonstrated classic histopathologic features of syringoma, and none had a family history of similar skin lesions. The clinical and dermoscopic findings along with the histopathology in all 3 patients were consistent with ES. In patient 1, three sessions of electrocautery treatments on both upper arms were performed with settings of short-fire mode (1–3 V) at 4- to 8-week intervals. After treatment, the lesions subsided but recurred 7 months later. Five months after recurrence, the rash gradually increased on the trunk and upper arms. In patient 2, two sessions of CO₂ laser treatments on the trunk were performed with settings of modulated pulse mode (1–2 W) at 4- to 8-week intervals. The lesions disappeared after treatment but recurred 6 months later. At 1-year follow-up after recurrence, the rash had increased slightly. Neither patient 1 nor patient 2 developed hyperpigmentation or scarring during the 1-year follow-up period after their respective treatments. Patient 3 opted not to undergo treatment after being informed that the lesions were benign, and his condition stabilized at 1-year follow-up.

The pathogenesis of ES is unclear, but it may be affected by hormones, autoimmune status, immunosuppression (eg, liver and kidney transplantation), and medications (eg, hypersensitivity, phototoxicity, and antiepileptic medications).^3-6 Guitart et al⁷ hypothesized that ES may be a hyperplastic response of the eccrine duct to an inflammatory reaction, such as trauma from waxing or chronic scratching. It also has been associated with systemic conditions such as Nicolau-Balus syndrome (syringomas, milia, and atrophoderma vermiculata) and Down syndrome.^8,9 The lesions manifest symmetrically and are characterized by flesh-colored to reddish-brown, shiny, or flat-topped papules; however, ES also can manifest as hyperpigmentation, erythema, positive Darier sign, or pseudokoebnerization.¹⁰ The lesions typically are located on the eyelids, neck, anterior chest, upper abdomen, upper arms, axillae, and genital region, and they rarely involve the palms, soles, and mucous membranes. Eruptive syringoma commonly is asymptomatic and in rare cases gradually subsides.¹¹

Sometimes the lesions of ES are atypical and clinically resemble Darier disease, Fox-Fordyce disease, lichen planus, mastocytosis, granuloma annulare, trichoepithelioma, and sarcoidosis. Additionally, Marfan syndrome and Ehlers-Danlos syndrome should be ruled out when lesions involve the eyelids.¹¹ The differential diagnosis in our patients included Darier disease and Fox-Fordyce disease, which can be differentiated from ES via noninvasive dermoscopy and pathologic biopsy. In most patients with ES, dermoscopic findings include reticular brown lines or fine pigment networks as well as dotted and linear or reticular vessels. Tiny whitish dots, multifocal hypopigmented areas, and glittering yellow-whitish round structures are dermoscopic hallmarks of the vulvar variant of ES.^12-14 Histopathology of ES has shown epithelial cords, ducts, and cystic structures within the dermis. The ducts are lined by 2 rows of epithelial cells with a characteristic comma-shaped/tadpolelike pattern and are filled with eosinophilic amorphous substances. The dermoscopic features of Darier disease differ from ES in that Darier disease usually manifests as a comedolike opening with a central polygonal yellowish-brownish structure surrounded by a whitish halo on a pink background.¹⁵Histopathology of Darier disease has shown acantholysis above the basal layer of the epidermis and dyskeratotic keratinocytes. Dermoscopic findings in Fox-Fordyce disease include typical light brown to dark brown, folliculocentric, structureless areas with loss of dermatoglyphics. Some of the lesions also show hyperkeratotic follicular plugging.¹⁶ Histopathology of Fox-Fordyce disease includes infundibulum dilation, hyperkeratosis, plugging, acanthosis, a lymphohistiocytic infiltrate, and a perifollicular foam cell infiltrate.¹⁷Eruptive syringoma is a benign condition that generally requires no treatment. The goal of treatment is to improve cosmesis and primarily includes physical and chemical therapies such as surgical resection, cryosurgery, electrodesiccation, CO₂ laser (alone and in combination with trichloroacetic acid¹⁰), argon laser, fractional photothermolysis, dermabrasion, and chemical peeling. However, because ES involves deeper areas of the dermis, some treatments may cause hyperpigmentation, scar formation, or recurrence of the lesions and may be less effective for lesions on the eyelids, which may remain untreated. Systemic therapy consists of oral retinoic acid or tranilast.¹⁸The use of topical retinoic acid and atropine also have been reported,¹⁹ but their efficacy remains uncertain. The lesions in patient 1 did not resolve after receiving oral and topical retinoic acid. Although ES lesions may decrease in size or subside without inter­vention in rare cases, the disease was not self-limiting in our patients.

To the Editor:

Syringoma is a relatively common benign adnexal neoplasm originating in the ducts of eccrine sweat glands. It can be divided into 4 variants based on clinical features: localized; familial; Down syndrome associated; and generalized, which includes multiple syringomas and eruptive syringoma (ES).¹ Eruptive syringoma is a rare variant of generalized syringoma that was first described by Jacquet and Darier² in 1887. Clinically, ES lesions manifest as multiple nonfused, flesh-colored to reddish-brown papules that are located most commonly on the anterior trunk during childhood or adolescence. Eruptive syringoma can be missed easily or misdiagnosed clinically. We present 3 rare cases of ES.

A 28-year-old man presented with multiple asymptomatic papules on the trunk and upper arms of 20 years’ duration (patient 1). He had been diagnosed with Darier disease 3 years prior to the current presentation and was treated with oral and topical retinoic acid without a response. After 3 months of oral treatment, the retinoic acid was stopped due to elevated liver enzymes. Physical examination at the current presentation revealed multiple smooth, firm, nonfused, 1- to 4-mm, reddish to dark red papules on the neck, chest, abdomen, and flexural surfaces of the upper arms (Figure 1A). Dermoscopy of the arm lesions showed light brown pigment networks and yellowish-white unstructured areas surrounded by linear vessels on a pink background under polarized light (Figure 1B). Histopathologic examination of a lesion on the left arm revealed epithelial cords, ducts, and cystic structures within the superficial and mid dermis. The ducts were lined by 2 rows of epithelial cells with a characteristic tadpolelike pattern and filled with eosinophilic amorphous substances (Figure 1C).

A 43-year-old man who was otherwise healthy presented with brownish flat-topped papules on the chest and abdomen of 19 years’ duration (Figure 3A)(patient 3). The lesions had remained stable and did not progress. He denied any treatment. Dermoscopy of the chest lesions showed a light brown pigment network as well as dotted and linear vessels on a pale yellow background (Figure 3B).

All 3 patients demonstrated classic histopathologic features of syringoma, and none had a family history of similar skin lesions. The clinical and dermoscopic findings along with the histopathology in all 3 patients were consistent with ES. In patient 1, three sessions of electrocautery treatments on both upper arms were performed with settings of short-fire mode (1–3 V) at 4- to 8-week intervals. After treatment, the lesions subsided but recurred 7 months later. Five months after recurrence, the rash gradually increased on the trunk and upper arms. In patient 2, two sessions of CO₂ laser treatments on the trunk were performed with settings of modulated pulse mode (1–2 W) at 4- to 8-week intervals. The lesions disappeared after treatment but recurred 6 months later. At 1-year follow-up after recurrence, the rash had increased slightly. Neither patient 1 nor patient 2 developed hyperpigmentation or scarring during the 1-year follow-up period after their respective treatments. Patient 3 opted not to undergo treatment after being informed that the lesions were benign, and his condition stabilized at 1-year follow-up.

The pathogenesis of ES is unclear, but it may be affected by hormones, autoimmune status, immunosuppression (eg, liver and kidney transplantation), and medications (eg, hypersensitivity, phototoxicity, and antiepileptic medications).^3-6 Guitart et al⁷ hypothesized that ES may be a hyperplastic response of the eccrine duct to an inflammatory reaction, such as trauma from waxing or chronic scratching. It also has been associated with systemic conditions such as Nicolau-Balus syndrome (syringomas, milia, and atrophoderma vermiculata) and Down syndrome.^8,9 The lesions manifest symmetrically and are characterized by flesh-colored to reddish-brown, shiny, or flat-topped papules; however, ES also can manifest as hyperpigmentation, erythema, positive Darier sign, or pseudokoebnerization.¹⁰ The lesions typically are located on the eyelids, neck, anterior chest, upper abdomen, upper arms, axillae, and genital region, and they rarely involve the palms, soles, and mucous membranes. Eruptive syringoma commonly is asymptomatic and in rare cases gradually subsides.¹¹

Sometimes the lesions of ES are atypical and clinically resemble Darier disease, Fox-Fordyce disease, lichen planus, mastocytosis, granuloma annulare, trichoepithelioma, and sarcoidosis. Additionally, Marfan syndrome and Ehlers-Danlos syndrome should be ruled out when lesions involve the eyelids.¹¹ The differential diagnosis in our patients included Darier disease and Fox-Fordyce disease, which can be differentiated from ES via noninvasive dermoscopy and pathologic biopsy. In most patients with ES, dermoscopic findings include reticular brown lines or fine pigment networks as well as dotted and linear or reticular vessels. Tiny whitish dots, multifocal hypopigmented areas, and glittering yellow-whitish round structures are dermoscopic hallmarks of the vulvar variant of ES.^12-14 Histopathology of ES has shown epithelial cords, ducts, and cystic structures within the dermis. The ducts are lined by 2 rows of epithelial cells with a characteristic comma-shaped/tadpolelike pattern and are filled with eosinophilic amorphous substances. The dermoscopic features of Darier disease differ from ES in that Darier disease usually manifests as a comedolike opening with a central polygonal yellowish-brownish structure surrounded by a whitish halo on a pink background.¹⁵Histopathology of Darier disease has shown acantholysis above the basal layer of the epidermis and dyskeratotic keratinocytes. Dermoscopic findings in Fox-Fordyce disease include typical light brown to dark brown, folliculocentric, structureless areas with loss of dermatoglyphics. Some of the lesions also show hyperkeratotic follicular plugging.¹⁶ Histopathology of Fox-Fordyce disease includes infundibulum dilation, hyperkeratosis, plugging, acanthosis, a lymphohistiocytic infiltrate, and a perifollicular foam cell infiltrate.¹⁷Eruptive syringoma is a benign condition that generally requires no treatment. The goal of treatment is to improve cosmesis and primarily includes physical and chemical therapies such as surgical resection, cryosurgery, electrodesiccation, CO₂ laser (alone and in combination with trichloroacetic acid¹⁰), argon laser, fractional photothermolysis, dermabrasion, and chemical peeling. However, because ES involves deeper areas of the dermis, some treatments may cause hyperpigmentation, scar formation, or recurrence of the lesions and may be less effective for lesions on the eyelids, which may remain untreated. Systemic therapy consists of oral retinoic acid or tranilast.¹⁸The use of topical retinoic acid and atropine also have been reported,¹⁹ but their efficacy remains uncertain. The lesions in patient 1 did not resolve after receiving oral and topical retinoic acid. Although ES lesions may decrease in size or subside without inter­vention in rare cases, the disease was not self-limiting in our patients.

To the Editor:

Syringoma is a relatively common benign adnexal neoplasm originating in the ducts of eccrine sweat glands. It can be divided into 4 variants based on clinical features: localized; familial; Down syndrome associated; and generalized, which includes multiple syringomas and eruptive syringoma (ES).¹ Eruptive syringoma is a rare variant of generalized syringoma that was first described by Jacquet and Darier² in 1887. Clinically, ES lesions manifest as multiple nonfused, flesh-colored to reddish-brown papules that are located most commonly on the anterior trunk during childhood or adolescence. Eruptive syringoma can be missed easily or misdiagnosed clinically. We present 3 rare cases of ES.

A 28-year-old man presented with multiple asymptomatic papules on the trunk and upper arms of 20 years’ duration (patient 1). He had been diagnosed with Darier disease 3 years prior to the current presentation and was treated with oral and topical retinoic acid without a response. After 3 months of oral treatment, the retinoic acid was stopped due to elevated liver enzymes. Physical examination at the current presentation revealed multiple smooth, firm, nonfused, 1- to 4-mm, reddish to dark red papules on the neck, chest, abdomen, and flexural surfaces of the upper arms (Figure 1A). Dermoscopy of the arm lesions showed light brown pigment networks and yellowish-white unstructured areas surrounded by linear vessels on a pink background under polarized light (Figure 1B). Histopathologic examination of a lesion on the left arm revealed epithelial cords, ducts, and cystic structures within the superficial and mid dermis. The ducts were lined by 2 rows of epithelial cells with a characteristic tadpolelike pattern and filled with eosinophilic amorphous substances (Figure 1C).

A 43-year-old man who was otherwise healthy presented with brownish flat-topped papules on the chest and abdomen of 19 years’ duration (Figure 3A)(patient 3). The lesions had remained stable and did not progress. He denied any treatment. Dermoscopy of the chest lesions showed a light brown pigment network as well as dotted and linear vessels on a pale yellow background (Figure 3B).

All 3 patients demonstrated classic histopathologic features of syringoma, and none had a family history of similar skin lesions. The clinical and dermoscopic findings along with the histopathology in all 3 patients were consistent with ES. In patient 1, three sessions of electrocautery treatments on both upper arms were performed with settings of short-fire mode (1–3 V) at 4- to 8-week intervals. After treatment, the lesions subsided but recurred 7 months later. Five months after recurrence, the rash gradually increased on the trunk and upper arms. In patient 2, two sessions of CO₂ laser treatments on the trunk were performed with settings of modulated pulse mode (1–2 W) at 4- to 8-week intervals. The lesions disappeared after treatment but recurred 6 months later. At 1-year follow-up after recurrence, the rash had increased slightly. Neither patient 1 nor patient 2 developed hyperpigmentation or scarring during the 1-year follow-up period after their respective treatments. Patient 3 opted not to undergo treatment after being informed that the lesions were benign, and his condition stabilized at 1-year follow-up.

The pathogenesis of ES is unclear, but it may be affected by hormones, autoimmune status, immunosuppression (eg, liver and kidney transplantation), and medications (eg, hypersensitivity, phototoxicity, and antiepileptic medications).^3-6 Guitart et al⁷ hypothesized that ES may be a hyperplastic response of the eccrine duct to an inflammatory reaction, such as trauma from waxing or chronic scratching. It also has been associated with systemic conditions such as Nicolau-Balus syndrome (syringomas, milia, and atrophoderma vermiculata) and Down syndrome.^8,9 The lesions manifest symmetrically and are characterized by flesh-colored to reddish-brown, shiny, or flat-topped papules; however, ES also can manifest as hyperpigmentation, erythema, positive Darier sign, or pseudokoebnerization.¹⁰ The lesions typically are located on the eyelids, neck, anterior chest, upper abdomen, upper arms, axillae, and genital region, and they rarely involve the palms, soles, and mucous membranes. Eruptive syringoma commonly is asymptomatic and in rare cases gradually subsides.¹¹

Sometimes the lesions of ES are atypical and clinically resemble Darier disease, Fox-Fordyce disease, lichen planus, mastocytosis, granuloma annulare, trichoepithelioma, and sarcoidosis. Additionally, Marfan syndrome and Ehlers-Danlos syndrome should be ruled out when lesions involve the eyelids.¹¹ The differential diagnosis in our patients included Darier disease and Fox-Fordyce disease, which can be differentiated from ES via noninvasive dermoscopy and pathologic biopsy. In most patients with ES, dermoscopic findings include reticular brown lines or fine pigment networks as well as dotted and linear or reticular vessels. Tiny whitish dots, multifocal hypopigmented areas, and glittering yellow-whitish round structures are dermoscopic hallmarks of the vulvar variant of ES.^12-14 Histopathology of ES has shown epithelial cords, ducts, and cystic structures within the dermis. The ducts are lined by 2 rows of epithelial cells with a characteristic comma-shaped/tadpolelike pattern and are filled with eosinophilic amorphous substances. The dermoscopic features of Darier disease differ from ES in that Darier disease usually manifests as a comedolike opening with a central polygonal yellowish-brownish structure surrounded by a whitish halo on a pink background.¹⁵Histopathology of Darier disease has shown acantholysis above the basal layer of the epidermis and dyskeratotic keratinocytes. Dermoscopic findings in Fox-Fordyce disease include typical light brown to dark brown, folliculocentric, structureless areas with loss of dermatoglyphics. Some of the lesions also show hyperkeratotic follicular plugging.¹⁶ Histopathology of Fox-Fordyce disease includes infundibulum dilation, hyperkeratosis, plugging, acanthosis, a lymphohistiocytic infiltrate, and a perifollicular foam cell infiltrate.¹⁷Eruptive syringoma is a benign condition that generally requires no treatment. The goal of treatment is to improve cosmesis and primarily includes physical and chemical therapies such as surgical resection, cryosurgery, electrodesiccation, CO₂ laser (alone and in combination with trichloroacetic acid¹⁰), argon laser, fractional photothermolysis, dermabrasion, and chemical peeling. However, because ES involves deeper areas of the dermis, some treatments may cause hyperpigmentation, scar formation, or recurrence of the lesions and may be less effective for lesions on the eyelids, which may remain untreated. Systemic therapy consists of oral retinoic acid or tranilast.¹⁸The use of topical retinoic acid and atropine also have been reported,¹⁹ but their efficacy remains uncertain. The lesions in patient 1 did not resolve after receiving oral and topical retinoic acid. Although ES lesions may decrease in size or subside without inter­vention in rare cases, the disease was not self-limiting in our patients.

To the Editor:

Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory skin disease affecting 1% to 4% of Europeans. It is characterized by recurrent inflamed nodules, abscesses, and sinus tracts in intertriginous regions.¹ The genital area is affected in 11% of cases² and usually is connected to severe forms of HS in both men and women.³ The prevalence of HS-associated genital lymphedema remains unknown.

Saxophone penis is a specific penile malformation characterized by a saxophone shape due to inflammation of the major penile lymphatic vessels that cause fibrosis of the surrounding connective tissue. Poor blood flow further causes contracture and distortion of the penile axis.⁴ Saxophone penis also has been associated with primary lymphedema, lymphogranuloma venereum, filariasis,⁵ and administration of paraffin injections.⁶ We describe 3 men with HS who presented with saxophone penis.

A 33-year-old man with Hurley stage III HS presented with a medical history of groin lesions and progressive penoscrotal edema of 13 years’ duration. He had a body mass index (BMI) of 37, no family history of HS or comorbidities, and a 15-year history of smoking 20 cigarettes per day. After repeated surgical drainage of the HS lesions as well as antibiotic treatment with clindamycin 600 mg/d and rifampicin 600 mg/d, the patient was kept on a maintenance therapy with adalimumab 40 mg/wk. Due to lack of response, treatment was discontinued at week 16. Clindamycin and ­rifampicin 300 mg were immediately reintroduced with no benefit on the genital lesions. The patient underwent genital reconstruction, including penile degloving, scrotoplasty, infrapubic fat pad removal, and perineoplasty (Figure 1). The patient currently is not undergoing any therapies.

A 55-year-old man presented with Hurley stage II HS of 33 years’ duration. He had a BMI of 52; a history of hypertension, hyperuricemia, severe hip and knee osteoarthritis, and orchiopexy in childhood; a smoking history of 40 cigarettes per day; and an alcohol consumption history of 200 mL per day since 18 years of age. He had radical excision of axillary lesions 8 years prior. One year later, he was treated with concomitant clindamycin and rifampicin 300 mg twice daily for 3 months with no desirable effects. Adalimumab 40 mg/wk was initiated. After 12 weeks of treatment, he experienced 80% improvement in all areas except the genital region. He continued adalimumab for 3 years with good clinical response in all HS-affected sites except the genital region.

A 66-year-old man presented with Hurley stage III HS of 37 years’ duration. He had a smoking history of 10 cigarettes per day for 30 years, a BMI of 24.6, and a medical history of long-standing hypertension and hypothyroidism. A 3-month course of clindamycin and rifampicin 600 mg/d was ineffective; adalimumab 40 mg/wk was initiated. All affected areas improved, except for the saxophone penis. He continues his fifth year of therapy with adalimumab (Figure 2).

Hidradenitis suppurativa is associated with chronic pain, purulent malodor, and scarring with structural deformity. Repetitive inflammation causes fibrosis, scar formation, and soft-tissue destruction of lymphatic vessels, leading to lymphedema; primary lymphedema of the genitals in men has been reported to result in a saxophone penis.⁴

The only approved biologic treatments for moderate to severe HS are the tumor necrosis factor α inhibitor adalimumab and anti-IL-17 secukinumab.¹ All 3 of our patients with HS were treated with adalimumab with reasonable success; however, the penile condition remained refractory, which we speculate may be due to adalimumab’s ability to control only active inflammatory lesions but not scars or fibrotic tissue.⁷ Higher adalimumab dosages were unlikely to be beneficial for their penile condition; some improvements have been reported following fluoroquinolone therapy. To our knowledge, there is no effective medical treatment for saxophone penis. However, surgery showed good results in one of our patients. Among our 3 adalimumab-treated patients, only 1 patient had corrective surgery that resulted in improvement in the penile deformity, further confirming adalimumab’s limited role in genital lymphedema.⁷ Extensive resection of the lymphedematous tissue, scrotoplasty, and Charles procedure are treatment options.⁸

Genital lymphedema has been associated with lymphangiectasia, lymphangioma circumscriptum, infections, and neoplasms such as lymphangiosarcoma and squamous cell carcinoma.⁹ Our patients reported discomfort, hygiene issues, and swelling. One patient reported micturition, and 2 patients reported sexual dysfunction.

Saxophone penis remains a disabling sequela of HS. Early diagnosis and treatment of HS may help prevent development of this condition.

To the Editor:

Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory skin disease affecting 1% to 4% of Europeans. It is characterized by recurrent inflamed nodules, abscesses, and sinus tracts in intertriginous regions.¹ The genital area is affected in 11% of cases² and usually is connected to severe forms of HS in both men and women.³ The prevalence of HS-associated genital lymphedema remains unknown.

Saxophone penis is a specific penile malformation characterized by a saxophone shape due to inflammation of the major penile lymphatic vessels that cause fibrosis of the surrounding connective tissue. Poor blood flow further causes contracture and distortion of the penile axis.⁴ Saxophone penis also has been associated with primary lymphedema, lymphogranuloma venereum, filariasis,⁵ and administration of paraffin injections.⁶ We describe 3 men with HS who presented with saxophone penis.

A 33-year-old man with Hurley stage III HS presented with a medical history of groin lesions and progressive penoscrotal edema of 13 years’ duration. He had a body mass index (BMI) of 37, no family history of HS or comorbidities, and a 15-year history of smoking 20 cigarettes per day. After repeated surgical drainage of the HS lesions as well as antibiotic treatment with clindamycin 600 mg/d and rifampicin 600 mg/d, the patient was kept on a maintenance therapy with adalimumab 40 mg/wk. Due to lack of response, treatment was discontinued at week 16. Clindamycin and ­rifampicin 300 mg were immediately reintroduced with no benefit on the genital lesions. The patient underwent genital reconstruction, including penile degloving, scrotoplasty, infrapubic fat pad removal, and perineoplasty (Figure 1). The patient currently is not undergoing any therapies.

A 55-year-old man presented with Hurley stage II HS of 33 years’ duration. He had a BMI of 52; a history of hypertension, hyperuricemia, severe hip and knee osteoarthritis, and orchiopexy in childhood; a smoking history of 40 cigarettes per day; and an alcohol consumption history of 200 mL per day since 18 years of age. He had radical excision of axillary lesions 8 years prior. One year later, he was treated with concomitant clindamycin and rifampicin 300 mg twice daily for 3 months with no desirable effects. Adalimumab 40 mg/wk was initiated. After 12 weeks of treatment, he experienced 80% improvement in all areas except the genital region. He continued adalimumab for 3 years with good clinical response in all HS-affected sites except the genital region.

A 66-year-old man presented with Hurley stage III HS of 37 years’ duration. He had a smoking history of 10 cigarettes per day for 30 years, a BMI of 24.6, and a medical history of long-standing hypertension and hypothyroidism. A 3-month course of clindamycin and rifampicin 600 mg/d was ineffective; adalimumab 40 mg/wk was initiated. All affected areas improved, except for the saxophone penis. He continues his fifth year of therapy with adalimumab (Figure 2).

Hidradenitis suppurativa is associated with chronic pain, purulent malodor, and scarring with structural deformity. Repetitive inflammation causes fibrosis, scar formation, and soft-tissue destruction of lymphatic vessels, leading to lymphedema; primary lymphedema of the genitals in men has been reported to result in a saxophone penis.⁴

The only approved biologic treatments for moderate to severe HS are the tumor necrosis factor α inhibitor adalimumab and anti-IL-17 secukinumab.¹ All 3 of our patients with HS were treated with adalimumab with reasonable success; however, the penile condition remained refractory, which we speculate may be due to adalimumab’s ability to control only active inflammatory lesions but not scars or fibrotic tissue.⁷ Higher adalimumab dosages were unlikely to be beneficial for their penile condition; some improvements have been reported following fluoroquinolone therapy. To our knowledge, there is no effective medical treatment for saxophone penis. However, surgery showed good results in one of our patients. Among our 3 adalimumab-treated patients, only 1 patient had corrective surgery that resulted in improvement in the penile deformity, further confirming adalimumab’s limited role in genital lymphedema.⁷ Extensive resection of the lymphedematous tissue, scrotoplasty, and Charles procedure are treatment options.⁸

Genital lymphedema has been associated with lymphangiectasia, lymphangioma circumscriptum, infections, and neoplasms such as lymphangiosarcoma and squamous cell carcinoma.⁹ Our patients reported discomfort, hygiene issues, and swelling. One patient reported micturition, and 2 patients reported sexual dysfunction.

Saxophone penis remains a disabling sequela of HS. Early diagnosis and treatment of HS may help prevent development of this condition.

To the Editor:

Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory skin disease affecting 1% to 4% of Europeans. It is characterized by recurrent inflamed nodules, abscesses, and sinus tracts in intertriginous regions.¹ The genital area is affected in 11% of cases² and usually is connected to severe forms of HS in both men and women.³ The prevalence of HS-associated genital lymphedema remains unknown.

Saxophone penis is a specific penile malformation characterized by a saxophone shape due to inflammation of the major penile lymphatic vessels that cause fibrosis of the surrounding connective tissue. Poor blood flow further causes contracture and distortion of the penile axis.⁴ Saxophone penis also has been associated with primary lymphedema, lymphogranuloma venereum, filariasis,⁵ and administration of paraffin injections.⁶ We describe 3 men with HS who presented with saxophone penis.

A 33-year-old man with Hurley stage III HS presented with a medical history of groin lesions and progressive penoscrotal edema of 13 years’ duration. He had a body mass index (BMI) of 37, no family history of HS or comorbidities, and a 15-year history of smoking 20 cigarettes per day. After repeated surgical drainage of the HS lesions as well as antibiotic treatment with clindamycin 600 mg/d and rifampicin 600 mg/d, the patient was kept on a maintenance therapy with adalimumab 40 mg/wk. Due to lack of response, treatment was discontinued at week 16. Clindamycin and ­rifampicin 300 mg were immediately reintroduced with no benefit on the genital lesions. The patient underwent genital reconstruction, including penile degloving, scrotoplasty, infrapubic fat pad removal, and perineoplasty (Figure 1). The patient currently is not undergoing any therapies.

A 55-year-old man presented with Hurley stage II HS of 33 years’ duration. He had a BMI of 52; a history of hypertension, hyperuricemia, severe hip and knee osteoarthritis, and orchiopexy in childhood; a smoking history of 40 cigarettes per day; and an alcohol consumption history of 200 mL per day since 18 years of age. He had radical excision of axillary lesions 8 years prior. One year later, he was treated with concomitant clindamycin and rifampicin 300 mg twice daily for 3 months with no desirable effects. Adalimumab 40 mg/wk was initiated. After 12 weeks of treatment, he experienced 80% improvement in all areas except the genital region. He continued adalimumab for 3 years with good clinical response in all HS-affected sites except the genital region.

A 66-year-old man presented with Hurley stage III HS of 37 years’ duration. He had a smoking history of 10 cigarettes per day for 30 years, a BMI of 24.6, and a medical history of long-standing hypertension and hypothyroidism. A 3-month course of clindamycin and rifampicin 600 mg/d was ineffective; adalimumab 40 mg/wk was initiated. All affected areas improved, except for the saxophone penis. He continues his fifth year of therapy with adalimumab (Figure 2).

Hidradenitis suppurativa is associated with chronic pain, purulent malodor, and scarring with structural deformity. Repetitive inflammation causes fibrosis, scar formation, and soft-tissue destruction of lymphatic vessels, leading to lymphedema; primary lymphedema of the genitals in men has been reported to result in a saxophone penis.⁴

The only approved biologic treatments for moderate to severe HS are the tumor necrosis factor α inhibitor adalimumab and anti-IL-17 secukinumab.¹ All 3 of our patients with HS were treated with adalimumab with reasonable success; however, the penile condition remained refractory, which we speculate may be due to adalimumab’s ability to control only active inflammatory lesions but not scars or fibrotic tissue.⁷ Higher adalimumab dosages were unlikely to be beneficial for their penile condition; some improvements have been reported following fluoroquinolone therapy. To our knowledge, there is no effective medical treatment for saxophone penis. However, surgery showed good results in one of our patients. Among our 3 adalimumab-treated patients, only 1 patient had corrective surgery that resulted in improvement in the penile deformity, further confirming adalimumab’s limited role in genital lymphedema.⁷ Extensive resection of the lymphedematous tissue, scrotoplasty, and Charles procedure are treatment options.⁸

Genital lymphedema has been associated with lymphangiectasia, lymphangioma circumscriptum, infections, and neoplasms such as lymphangiosarcoma and squamous cell carcinoma.⁹ Our patients reported discomfort, hygiene issues, and swelling. One patient reported micturition, and 2 patients reported sexual dysfunction.

Saxophone penis remains a disabling sequela of HS. Early diagnosis and treatment of HS may help prevent development of this condition.

To the Editor:

Henoch-Schönlein purpura (HSP)(also known as IgA vasculitis) is a small vessel vasculitis characterized by deposition of IgA in small vessels, resulting in the development of purpura on the legs. Based on the European Alliance of Associations for Rheumatology criteria,¹ the patient also must have at least 1 of the following: arthritis, arthralgia, abdominal pain, leukocytoclastic vasculitis with IgA deposition, or kidney involvement. The disease can be triggered by infection—with more than 75% of patients reporting an antecedent upper respiratory tract infection²—as well as medications, circulating immune complexes, certain foods, vaccines, and rarely cancer.^3,4 The disease more commonly occurs in children but also can affect adults.

Several cases of HSP have been reported following COVID-19 vaccination.⁵ We report a case of HSP developing days after the messenger RNA Pfizer-BioNTech COVID-19 vaccine booster that was associated with anti-Smith and anti–double-stranded DNA (dsDNA) antibodies as well as antineutrophil cytoplasmic antibodies (ANCAs).

A 24-year-old man presented to dermatology with a rash of 3 weeks’ duration that first appeared 1 week after receiving his second booster of the messenger RNA Pfizer-BioNTech COVID-19 vaccine. Physical examination revealed petechiae with nonblanching erythematous macules and papules covering the legs below the knees (Figure 1) as well as the back of the right arm. A few days later, he developed arthralgia in the knees, hands, and feet. The patient denied any recent infections as well as respiratory and urinary tract symptoms. Approximately 10 days after the rash appeared, he developed epigastric abdominal pain that gradually worsened and sought care from his primary care physician, who ordered computed tomography and referred him for endoscopy. Computed tomography with and without contrast was suspicious for colitis. Colonoscopy and endoscopy were unremarkable. Laboratory tests were notable for elevated white blood cell count (17.08×10³/µL [reference range, 3.66–10.60×10³/µL]), serum IgA (437 mg/dL [reference range, 70–400 mg/dL]), C-reactive protein (1.5 mg/dL [reference range, <0.5 mg/dL]), anti-Smith antibody (28.1 CU [reference range, <20 CU), positive antinuclear antibody with titer (1:160 [reference range, <1:80]), anti-dsDNA (40.4 IU/mL [reference range, <27 IU/mL]), and cytoplasmic ANCA (c-ANCA) titer (1:320 [reference range, <1:20]). Blood urea nitrogen, creatinine, and estimated glomerular filtration rate were all within reference range. Urinalysis with microscopic examination was notable for 2 to 5 red blood cells per high-power field (reference range, 0) and proteinuria of 1+ (reference range, negative for protein).

The patient’s rash progressively worsened over the next few weeks, spreading proximally on the legs to the buttocks and the back of both elbows. A repeat complete blood cell count showed resolution of the leukocytosis. Two biopsies were taken from a lesion on the left proximal thigh: 1 for hematoxylin and eosin stain for histopathologic examination and 1 for direct immunofluorescence examination.

The patient was preliminarily diagnosed with HSP, and dermatology prescribed oral tofacitinib 5 mg twice daily for 5 days, which was supposed to be increased to 10 mg twice daily on the sixth day of treatment; however, the patient discontinued the medication after 4 days based on his primary care physician’s recommendation due to clotting concerns. The rash and arthralgia temporarily improved for 1 week, then relapsed.

Histopathology revealed neutrophils surrounding and infiltrating small dermal blood vessel walls as well as associated neutrophilic debris and erythrocytes, consistent with leukocytoclastic vasculitis (Figure 2). Direct immunofluorescence was negative for IgA antibodies. His primary care physician, in consultation with his dermatologist, then started the patient on oral prednisone 70 mg once daily for 7 days with a plan to taper. Three days after prednisone was started, the arthralgia and abdominal pain resolved, and the rash became lighter in color. After 1 week, the rash resolved completely.

Due to the unusual antibodies, the patient was referred to a rheumatologist, who repeated the blood tests approximately 1 week after the patient started prednisone. The tests were negative for anti-Smith, anti-dsDNA, and c-ANCA but showed an elevated atypical perinuclear ANCA (p-ANCA) titer of 1:80 (reference range [negative], <1:20). A repeat urinalysis was unremarkable. The patient slowly tapered the prednisone over the course of 3 months and was subsequently lost to follow-up. The rash and other symptoms had not recurred as of the patient’s last physician contact. The most recent laboratory results showed a white blood cell count of 14.0×10³/µL (reference range, 3.4–10.8×10³/µL), likely due to the prednisone; blood urea nitrogen, creatinine, and estimated glomerular filtration rate were within reference range. The urinalysis was notable for occult blood and was negative for protein. C-reactive protein was 1 mg/dL (reference range, 0–10 mg/dL); p-ANCA, c-ANCA, and atypical p-ANCA, as well as antinuclear antibody, were negative. As of his last follow-up, the patient felt well.

The major differential diagnoses for our patient included HSP, ANCA vasculitis, and systemic lupus erythematosus. Although ANCA vasculitis has been reported after SARS-CoV-2 infection,⁶ the lack of pulmonary symptoms made this diagnosis unlikely.⁷ Although our patient initially had elevated anti-Smith and anti-dsDNA antibodies as well as mild renal involvement, he fulfilled at most only 2 of the 11 criteria necessary for diagnosing lupus: malar rash, discoid rash (includes alopecia), photosensitivity, ocular ulcers, nonerosive arthritis, serositis, renal disorder (protein >500 mg/24 h, red blood cells, casts), neurologic disorder (seizures, psychosis), hematologic disorders (hemolytic anemia, leukopenia), ANA, and immunologic disorder (anti-Smith). Four of the 11 criteria are necessary for the diagnosis of lupus.⁸

Torraca et al⁷ reported a case of HSP with positive c-ANCA (1:640) in a patient lacking pulmonary symptoms who was diagnosed with HSP. Cytoplasmic ANCA is not a typical finding in HSP. However, the additional findings of anti-Smith, anti-dsDNA, and mildly elevated atypical p-ANCA antibodies in our patient were unexpected and could be explained by the proposed pathogenesis of HSP—an overzealous immune response resulting in aberrant antibody complex deposition with ensuing complement activation.^5,9 Production of these additional antibodies could be part of the overzealous response to COVID-19 vaccination.

Acknowledgment—We thank our patient for granting permission to publish this information.

To the Editor:

Henoch-Schönlein purpura (HSP)(also known as IgA vasculitis) is a small vessel vasculitis characterized by deposition of IgA in small vessels, resulting in the development of purpura on the legs. Based on the European Alliance of Associations for Rheumatology criteria,¹ the patient also must have at least 1 of the following: arthritis, arthralgia, abdominal pain, leukocytoclastic vasculitis with IgA deposition, or kidney involvement. The disease can be triggered by infection—with more than 75% of patients reporting an antecedent upper respiratory tract infection²—as well as medications, circulating immune complexes, certain foods, vaccines, and rarely cancer.^3,4 The disease more commonly occurs in children but also can affect adults.

Several cases of HSP have been reported following COVID-19 vaccination.⁵ We report a case of HSP developing days after the messenger RNA Pfizer-BioNTech COVID-19 vaccine booster that was associated with anti-Smith and anti–double-stranded DNA (dsDNA) antibodies as well as antineutrophil cytoplasmic antibodies (ANCAs).

A 24-year-old man presented to dermatology with a rash of 3 weeks’ duration that first appeared 1 week after receiving his second booster of the messenger RNA Pfizer-BioNTech COVID-19 vaccine. Physical examination revealed petechiae with nonblanching erythematous macules and papules covering the legs below the knees (Figure 1) as well as the back of the right arm. A few days later, he developed arthralgia in the knees, hands, and feet. The patient denied any recent infections as well as respiratory and urinary tract symptoms. Approximately 10 days after the rash appeared, he developed epigastric abdominal pain that gradually worsened and sought care from his primary care physician, who ordered computed tomography and referred him for endoscopy. Computed tomography with and without contrast was suspicious for colitis. Colonoscopy and endoscopy were unremarkable. Laboratory tests were notable for elevated white blood cell count (17.08×10³/µL [reference range, 3.66–10.60×10³/µL]), serum IgA (437 mg/dL [reference range, 70–400 mg/dL]), C-reactive protein (1.5 mg/dL [reference range, <0.5 mg/dL]), anti-Smith antibody (28.1 CU [reference range, <20 CU), positive antinuclear antibody with titer (1:160 [reference range, <1:80]), anti-dsDNA (40.4 IU/mL [reference range, <27 IU/mL]), and cytoplasmic ANCA (c-ANCA) titer (1:320 [reference range, <1:20]). Blood urea nitrogen, creatinine, and estimated glomerular filtration rate were all within reference range. Urinalysis with microscopic examination was notable for 2 to 5 red blood cells per high-power field (reference range, 0) and proteinuria of 1+ (reference range, negative for protein).

The patient’s rash progressively worsened over the next few weeks, spreading proximally on the legs to the buttocks and the back of both elbows. A repeat complete blood cell count showed resolution of the leukocytosis. Two biopsies were taken from a lesion on the left proximal thigh: 1 for hematoxylin and eosin stain for histopathologic examination and 1 for direct immunofluorescence examination.

The patient was preliminarily diagnosed with HSP, and dermatology prescribed oral tofacitinib 5 mg twice daily for 5 days, which was supposed to be increased to 10 mg twice daily on the sixth day of treatment; however, the patient discontinued the medication after 4 days based on his primary care physician’s recommendation due to clotting concerns. The rash and arthralgia temporarily improved for 1 week, then relapsed.

Histopathology revealed neutrophils surrounding and infiltrating small dermal blood vessel walls as well as associated neutrophilic debris and erythrocytes, consistent with leukocytoclastic vasculitis (Figure 2). Direct immunofluorescence was negative for IgA antibodies. His primary care physician, in consultation with his dermatologist, then started the patient on oral prednisone 70 mg once daily for 7 days with a plan to taper. Three days after prednisone was started, the arthralgia and abdominal pain resolved, and the rash became lighter in color. After 1 week, the rash resolved completely.

Due to the unusual antibodies, the patient was referred to a rheumatologist, who repeated the blood tests approximately 1 week after the patient started prednisone. The tests were negative for anti-Smith, anti-dsDNA, and c-ANCA but showed an elevated atypical perinuclear ANCA (p-ANCA) titer of 1:80 (reference range [negative], <1:20). A repeat urinalysis was unremarkable. The patient slowly tapered the prednisone over the course of 3 months and was subsequently lost to follow-up. The rash and other symptoms had not recurred as of the patient’s last physician contact. The most recent laboratory results showed a white blood cell count of 14.0×10³/µL (reference range, 3.4–10.8×10³/µL), likely due to the prednisone; blood urea nitrogen, creatinine, and estimated glomerular filtration rate were within reference range. The urinalysis was notable for occult blood and was negative for protein. C-reactive protein was 1 mg/dL (reference range, 0–10 mg/dL); p-ANCA, c-ANCA, and atypical p-ANCA, as well as antinuclear antibody, were negative. As of his last follow-up, the patient felt well.

The major differential diagnoses for our patient included HSP, ANCA vasculitis, and systemic lupus erythematosus. Although ANCA vasculitis has been reported after SARS-CoV-2 infection,⁶ the lack of pulmonary symptoms made this diagnosis unlikely.⁷ Although our patient initially had elevated anti-Smith and anti-dsDNA antibodies as well as mild renal involvement, he fulfilled at most only 2 of the 11 criteria necessary for diagnosing lupus: malar rash, discoid rash (includes alopecia), photosensitivity, ocular ulcers, nonerosive arthritis, serositis, renal disorder (protein >500 mg/24 h, red blood cells, casts), neurologic disorder (seizures, psychosis), hematologic disorders (hemolytic anemia, leukopenia), ANA, and immunologic disorder (anti-Smith). Four of the 11 criteria are necessary for the diagnosis of lupus.⁸

Torraca et al⁷ reported a case of HSP with positive c-ANCA (1:640) in a patient lacking pulmonary symptoms who was diagnosed with HSP. Cytoplasmic ANCA is not a typical finding in HSP. However, the additional findings of anti-Smith, anti-dsDNA, and mildly elevated atypical p-ANCA antibodies in our patient were unexpected and could be explained by the proposed pathogenesis of HSP—an overzealous immune response resulting in aberrant antibody complex deposition with ensuing complement activation.^5,9 Production of these additional antibodies could be part of the overzealous response to COVID-19 vaccination.

Acknowledgment—We thank our patient for granting permission to publish this information.

To the Editor:

Henoch-Schönlein purpura (HSP)(also known as IgA vasculitis) is a small vessel vasculitis characterized by deposition of IgA in small vessels, resulting in the development of purpura on the legs. Based on the European Alliance of Associations for Rheumatology criteria,¹ the patient also must have at least 1 of the following: arthritis, arthralgia, abdominal pain, leukocytoclastic vasculitis with IgA deposition, or kidney involvement. The disease can be triggered by infection—with more than 75% of patients reporting an antecedent upper respiratory tract infection²—as well as medications, circulating immune complexes, certain foods, vaccines, and rarely cancer.^3,4 The disease more commonly occurs in children but also can affect adults.

Several cases of HSP have been reported following COVID-19 vaccination.⁵ We report a case of HSP developing days after the messenger RNA Pfizer-BioNTech COVID-19 vaccine booster that was associated with anti-Smith and anti–double-stranded DNA (dsDNA) antibodies as well as antineutrophil cytoplasmic antibodies (ANCAs).

A 24-year-old man presented to dermatology with a rash of 3 weeks’ duration that first appeared 1 week after receiving his second booster of the messenger RNA Pfizer-BioNTech COVID-19 vaccine. Physical examination revealed petechiae with nonblanching erythematous macules and papules covering the legs below the knees (Figure 1) as well as the back of the right arm. A few days later, he developed arthralgia in the knees, hands, and feet. The patient denied any recent infections as well as respiratory and urinary tract symptoms. Approximately 10 days after the rash appeared, he developed epigastric abdominal pain that gradually worsened and sought care from his primary care physician, who ordered computed tomography and referred him for endoscopy. Computed tomography with and without contrast was suspicious for colitis. Colonoscopy and endoscopy were unremarkable. Laboratory tests were notable for elevated white blood cell count (17.08×10³/µL [reference range, 3.66–10.60×10³/µL]), serum IgA (437 mg/dL [reference range, 70–400 mg/dL]), C-reactive protein (1.5 mg/dL [reference range, <0.5 mg/dL]), anti-Smith antibody (28.1 CU [reference range, <20 CU), positive antinuclear antibody with titer (1:160 [reference range, <1:80]), anti-dsDNA (40.4 IU/mL [reference range, <27 IU/mL]), and cytoplasmic ANCA (c-ANCA) titer (1:320 [reference range, <1:20]). Blood urea nitrogen, creatinine, and estimated glomerular filtration rate were all within reference range. Urinalysis with microscopic examination was notable for 2 to 5 red blood cells per high-power field (reference range, 0) and proteinuria of 1+ (reference range, negative for protein).

The patient’s rash progressively worsened over the next few weeks, spreading proximally on the legs to the buttocks and the back of both elbows. A repeat complete blood cell count showed resolution of the leukocytosis. Two biopsies were taken from a lesion on the left proximal thigh: 1 for hematoxylin and eosin stain for histopathologic examination and 1 for direct immunofluorescence examination.

The patient was preliminarily diagnosed with HSP, and dermatology prescribed oral tofacitinib 5 mg twice daily for 5 days, which was supposed to be increased to 10 mg twice daily on the sixth day of treatment; however, the patient discontinued the medication after 4 days based on his primary care physician’s recommendation due to clotting concerns. The rash and arthralgia temporarily improved for 1 week, then relapsed.

Histopathology revealed neutrophils surrounding and infiltrating small dermal blood vessel walls as well as associated neutrophilic debris and erythrocytes, consistent with leukocytoclastic vasculitis (Figure 2). Direct immunofluorescence was negative for IgA antibodies. His primary care physician, in consultation with his dermatologist, then started the patient on oral prednisone 70 mg once daily for 7 days with a plan to taper. Three days after prednisone was started, the arthralgia and abdominal pain resolved, and the rash became lighter in color. After 1 week, the rash resolved completely.

Due to the unusual antibodies, the patient was referred to a rheumatologist, who repeated the blood tests approximately 1 week after the patient started prednisone. The tests were negative for anti-Smith, anti-dsDNA, and c-ANCA but showed an elevated atypical perinuclear ANCA (p-ANCA) titer of 1:80 (reference range [negative], <1:20). A repeat urinalysis was unremarkable. The patient slowly tapered the prednisone over the course of 3 months and was subsequently lost to follow-up. The rash and other symptoms had not recurred as of the patient’s last physician contact. The most recent laboratory results showed a white blood cell count of 14.0×10³/µL (reference range, 3.4–10.8×10³/µL), likely due to the prednisone; blood urea nitrogen, creatinine, and estimated glomerular filtration rate were within reference range. The urinalysis was notable for occult blood and was negative for protein. C-reactive protein was 1 mg/dL (reference range, 0–10 mg/dL); p-ANCA, c-ANCA, and atypical p-ANCA, as well as antinuclear antibody, were negative. As of his last follow-up, the patient felt well.

The major differential diagnoses for our patient included HSP, ANCA vasculitis, and systemic lupus erythematosus. Although ANCA vasculitis has been reported after SARS-CoV-2 infection,⁶ the lack of pulmonary symptoms made this diagnosis unlikely.⁷ Although our patient initially had elevated anti-Smith and anti-dsDNA antibodies as well as mild renal involvement, he fulfilled at most only 2 of the 11 criteria necessary for diagnosing lupus: malar rash, discoid rash (includes alopecia), photosensitivity, ocular ulcers, nonerosive arthritis, serositis, renal disorder (protein >500 mg/24 h, red blood cells, casts), neurologic disorder (seizures, psychosis), hematologic disorders (hemolytic anemia, leukopenia), ANA, and immunologic disorder (anti-Smith). Four of the 11 criteria are necessary for the diagnosis of lupus.⁸

Torraca et al⁷ reported a case of HSP with positive c-ANCA (1:640) in a patient lacking pulmonary symptoms who was diagnosed with HSP. Cytoplasmic ANCA is not a typical finding in HSP. However, the additional findings of anti-Smith, anti-dsDNA, and mildly elevated atypical p-ANCA antibodies in our patient were unexpected and could be explained by the proposed pathogenesis of HSP—an overzealous immune response resulting in aberrant antibody complex deposition with ensuing complement activation.^5,9 Production of these additional antibodies could be part of the overzealous response to COVID-19 vaccination.

Acknowledgment—We thank our patient for granting permission to publish this information.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

A 48-year-old man presented with nodular lesions in a sporotrichoid pattern on the right hand and forearm of 3 months’ duration (Figure). There were no lymphadeno-pathies, and he had no notable medical history. He denied fever and other systemic symptoms. The patient recently had manipulated a warm water fish aquarium. Although he did not recall a clear injury, inadvertent mild trauma was a possibility. He denied other contact or trauma in relation to animals or vegetables.

Histopathology from a punch biopsy of the forearm revealed a granulomatous infiltrate with necrosis at the deep dermis level at the interface with the subcutaneous cellular tissue that was composed of mainly epithelioid cells with a few multinucleated giant cells. No acid-fast bacilli or fungi were observed with special stains.

A polymerase chain reaction assay for atypical mycobacteria was positive for Mycobacterium interjectum. The culture of the skin biopsy was negative for fungi and mycobacteria after long incubation (6 weeks) on 2 occasions, and an antibiogram was not available. Complementary tests including hemogram, HIV serology, and chest and upper extremity radiographs did not reveal any abnormalities.

To the Editor:

A 48-year-old man presented with nodular lesions in a sporotrichoid pattern on the right hand and forearm of 3 months’ duration (Figure). There were no lymphadeno-pathies, and he had no notable medical history. He denied fever and other systemic symptoms. The patient recently had manipulated a warm water fish aquarium. Although he did not recall a clear injury, inadvertent mild trauma was a possibility. He denied other contact or trauma in relation to animals or vegetables.

Histopathology from a punch biopsy of the forearm revealed a granulomatous infiltrate with necrosis at the deep dermis level at the interface with the subcutaneous cellular tissue that was composed of mainly epithelioid cells with a few multinucleated giant cells. No acid-fast bacilli or fungi were observed with special stains.

A polymerase chain reaction assay for atypical mycobacteria was positive for Mycobacterium interjectum. The culture of the skin biopsy was negative for fungi and mycobacteria after long incubation (6 weeks) on 2 occasions, and an antibiogram was not available. Complementary tests including hemogram, HIV serology, and chest and upper extremity radiographs did not reveal any abnormalities.

To the Editor:

A 48-year-old man presented with nodular lesions in a sporotrichoid pattern on the right hand and forearm of 3 months’ duration (Figure). There were no lymphadeno-pathies, and he had no notable medical history. He denied fever and other systemic symptoms. The patient recently had manipulated a warm water fish aquarium. Although he did not recall a clear injury, inadvertent mild trauma was a possibility. He denied other contact or trauma in relation to animals or vegetables.

Histopathology from a punch biopsy of the forearm revealed a granulomatous infiltrate with necrosis at the deep dermis level at the interface with the subcutaneous cellular tissue that was composed of mainly epithelioid cells with a few multinucleated giant cells. No acid-fast bacilli or fungi were observed with special stains.

A polymerase chain reaction assay for atypical mycobacteria was positive for Mycobacterium interjectum. The culture of the skin biopsy was negative for fungi and mycobacteria after long incubation (6 weeks) on 2 occasions, and an antibiogram was not available. Complementary tests including hemogram, HIV serology, and chest and upper extremity radiographs did not reveal any abnormalities.

To the Editor:

Neutrophilic dermatoses—a group of inflammatory cutaneous conditions—include acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and neutrophilic dermatosis of the dorsal hands. Histopathology shows a dense dermal infiltrate of mature neutrophils. In 2005, the histiocytoid subtype of Sweet syndrome was introduced with histopathologic findings of a dermal infiltrate composed of immature myeloid cells that resemble histiocytes in appearance but stain strongly with neutrophil markers on immunohistochemistry.¹ We present a case of histiocytoid pyoderma gangrenosum with histopathology that showed a dense dermal histiocytoid infiltrate with strong positivity for neutrophil markers on immunohistochemistry.

An 85-year-old man was seen by dermatology in the inpatient setting for a new-onset painful abdominal wound. He had a medical history of myelodysplastic syndrome (MDS), high-grade invasive papillary urothelial carcinoma of the bladder, and a recent diagnosis of low-grade invasive ascending colon adenocarcinoma. Ten days prior he underwent a right colectomy without intraoperative complications that was followed by septic shock. Workup with urinalysis and urine culture showed minimal pyuria with Pseudomonas aeruginosa. Additional studies, including blood cultures, abdominal wound cultures, computed tomography of the abdomen and pelvis, renal ultrasound, and chest radiographs, were unremarkable and showed no signs of surgical site infection, intra-abdominal or pelvic abscess formation, or pulmonary embolism. Broad-spectrum antibiotics—vancomycin and piperacillin-tazobactam—were started. Persistent fever (T_max of 102.3 °F [39.1 °C]) and leukocytosis (45.3×10⁹/L [4.2–10×10⁹/L]) despite antibiotic therapy, increasing pressor requirements, and progressive painful erythema and purulence at the abdominal surgical site led to debridement of the wound by the general surgery team on day 9 following the initial surgery due to suspected necrotizing infection. Within 24 hours, dermatology was consulted for continued rapid expansion of the wound. Physical examination of the abdomen revealed a large, well-demarcated, pink-red, indurated, ulcerated plaque with clear to purulent exudate and superficial erosions with violaceous undermined borders extending centrifugally from the abdominal surgical incision line (Figure 1A). Two punch biopsies sent for histopathologic evaluation and tissue culture showed dermal edema with a dense histiocytic infiltrate with nodular foci and admixed mature neutrophils to a lesser degree (Figure 2). Special staining was negative for bacteria, fungi, and mycobacteria. Immunohistochemistry revealed positive staining of the dermal inflammatory infiltrate with CD68, myeloperoxidase, and lysozyme, as well as negative staining with CD34 (Figure 3). These findings were suggestive of a histiocytoid neutrophilic dermatosis such as Sweet syndrome or pyoderma gangrenosum. Due to the morphology of the solitary lesion and the abrupt exacerbation shortly after surgical intervention, the patient was diagnosed with histiocytoid pyoderma gangrenosum. At the same time, the patient’s septic shock was treated with intravenous hydrocortisone (100 mg 3 times daily) for 2 days and also achieved a prompt response in the cutaneous symptoms (Figure 1B).

Sweet syndrome and pyoderma gangrenosum are considered distinct neutrophilic dermatoses that rarely coexist but share several clinical and histopathologic features, which can become a diagnostic challenge.² Both conditions can manifest clinically as abrupt-onset, tender, erythematous papules; vesiculopustular lesions; or bullae with ulcerative changes. They also exhibit pathergy; present with systemic symptoms such as pyrexia, malaise, and joint pain; are associated with underlying systemic conditions such as infections and/or malignancy; demonstrate a dense neutrophilic infiltrate in the dermis on histopathology; and respond promptly to systemic corticosteroids.^2-6 Bullous Sweet syndrome, which can present as vesicles, pustules, or bullae that progress to superficial ulcerations, may represent a variant of neutrophilic dermatosis characterized by features seen in both Sweet syndrome and pyoderma gangrenosum, suggesting that these 2 conditions may be on a spectrum.⁵Clinical features such as erythema with a blue, gray, or purple hue; undermined and ragged borders; and healing of skin lesions with atrophic or cribriform scarring may favor pyoderma gangrenosum, whereas a dull red or plum color and resolution of lesions without scarring may support the diagnosis of Sweet syndrome.⁷ Although both conditions can exhibit pathergy secondary to minor skin trauma such as venipuncture and biopsies,^2,3,5,8 Sweet syndrome rarely has been described to develop after surgery in a patient without a known history of the condition.⁹ In contrast, postsurgical pyoderma gangrenosum has been well described as secondary to the pathergy phenomenon.⁵

Our patient was favored to have pyoderma gangrenosum given the solitary lesion, its abrupt development after surgery, and the morphology of the lesion that exhibited a large violaceous to red ulcerative and exudative plaque with undermined borders with atrophic scarring. In patients with skin disease that cannot be distinguished with certainty as either Sweet syndrome or pyoderma gangrenosum, it is essential to recognize that, as neutrophilic dermatoses, both conditions can be managed with either the first-line treatment option of high-dose systemic steroids or one of the shared alternative first-line or second-line steroid-sparing treatments, such as dapsone and cyclosporine.²

Although the exact pathogenesis of pyoderma gangrenosum remains to be fully understood, paraneoplastic pyoderma gangrenosum is a frequently described phenomenon.^10,11 Our patient’s history of multiple malignancies, both solid and hematologic, supports the likelihood of malignancy-induced pyoderma gangrenosum; however, given his history of MDS, several other conditions were ruled out prior to making the diagnosis of pyoderma gangrenosum.

Classically, neutrophilic dermatoses such as pyoderma gangrenosum have a dense dermal neutrophilic infiltrate. Concurrent myeloproliferative disorders can alter the maturation of leukocytes, subsequently leading to an atypical appearance of the inflammatory cells on histopathology. Further, in the setting of myeloproliferative disorders, conditions such as leukemia cutis, in which there can be a cutaneous infiltrate of immature or mature myeloid or lymphocytic cells, must be considered. To ensure our patient’s abdominal skin changes were not a cutaneous manifestation of hematologic malignancy, immunohistochemical staining with CD20 and CD3 was performed and showed only the rare presence of B and T lymphocytes, respectively. Staining with CD34 for lymphocytic and myeloid progenitor cells was negative in the dermal infiltrate and further reduced the likelihood of leukemia cutis. Alternatively, patients can have aleukemic cutaneous myeloid sarcoma or leukemia cutis without an underlying hematologic condition or with latent peripheral blood or bone marrow myeloproliferative disorder, but our patient’s history of MDS eliminated this possibility.¹² After exclusion of cutaneous infiltration by malignant leukocytes, our patient was diagnosed with histiocytoid neutrophilic dermatosis.

To the Editor:

Neutrophilic dermatoses—a group of inflammatory cutaneous conditions—include acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and neutrophilic dermatosis of the dorsal hands. Histopathology shows a dense dermal infiltrate of mature neutrophils. In 2005, the histiocytoid subtype of Sweet syndrome was introduced with histopathologic findings of a dermal infiltrate composed of immature myeloid cells that resemble histiocytes in appearance but stain strongly with neutrophil markers on immunohistochemistry.¹ We present a case of histiocytoid pyoderma gangrenosum with histopathology that showed a dense dermal histiocytoid infiltrate with strong positivity for neutrophil markers on immunohistochemistry.

An 85-year-old man was seen by dermatology in the inpatient setting for a new-onset painful abdominal wound. He had a medical history of myelodysplastic syndrome (MDS), high-grade invasive papillary urothelial carcinoma of the bladder, and a recent diagnosis of low-grade invasive ascending colon adenocarcinoma. Ten days prior he underwent a right colectomy without intraoperative complications that was followed by septic shock. Workup with urinalysis and urine culture showed minimal pyuria with Pseudomonas aeruginosa. Additional studies, including blood cultures, abdominal wound cultures, computed tomography of the abdomen and pelvis, renal ultrasound, and chest radiographs, were unremarkable and showed no signs of surgical site infection, intra-abdominal or pelvic abscess formation, or pulmonary embolism. Broad-spectrum antibiotics—vancomycin and piperacillin-tazobactam—were started. Persistent fever (T_max of 102.3 °F [39.1 °C]) and leukocytosis (45.3×10⁹/L [4.2–10×10⁹/L]) despite antibiotic therapy, increasing pressor requirements, and progressive painful erythema and purulence at the abdominal surgical site led to debridement of the wound by the general surgery team on day 9 following the initial surgery due to suspected necrotizing infection. Within 24 hours, dermatology was consulted for continued rapid expansion of the wound. Physical examination of the abdomen revealed a large, well-demarcated, pink-red, indurated, ulcerated plaque with clear to purulent exudate and superficial erosions with violaceous undermined borders extending centrifugally from the abdominal surgical incision line (Figure 1A). Two punch biopsies sent for histopathologic evaluation and tissue culture showed dermal edema with a dense histiocytic infiltrate with nodular foci and admixed mature neutrophils to a lesser degree (Figure 2). Special staining was negative for bacteria, fungi, and mycobacteria. Immunohistochemistry revealed positive staining of the dermal inflammatory infiltrate with CD68, myeloperoxidase, and lysozyme, as well as negative staining with CD34 (Figure 3). These findings were suggestive of a histiocytoid neutrophilic dermatosis such as Sweet syndrome or pyoderma gangrenosum. Due to the morphology of the solitary lesion and the abrupt exacerbation shortly after surgical intervention, the patient was diagnosed with histiocytoid pyoderma gangrenosum. At the same time, the patient’s septic shock was treated with intravenous hydrocortisone (100 mg 3 times daily) for 2 days and also achieved a prompt response in the cutaneous symptoms (Figure 1B).

Sweet syndrome and pyoderma gangrenosum are considered distinct neutrophilic dermatoses that rarely coexist but share several clinical and histopathologic features, which can become a diagnostic challenge.² Both conditions can manifest clinically as abrupt-onset, tender, erythematous papules; vesiculopustular lesions; or bullae with ulcerative changes. They also exhibit pathergy; present with systemic symptoms such as pyrexia, malaise, and joint pain; are associated with underlying systemic conditions such as infections and/or malignancy; demonstrate a dense neutrophilic infiltrate in the dermis on histopathology; and respond promptly to systemic corticosteroids.^2-6 Bullous Sweet syndrome, which can present as vesicles, pustules, or bullae that progress to superficial ulcerations, may represent a variant of neutrophilic dermatosis characterized by features seen in both Sweet syndrome and pyoderma gangrenosum, suggesting that these 2 conditions may be on a spectrum.⁵Clinical features such as erythema with a blue, gray, or purple hue; undermined and ragged borders; and healing of skin lesions with atrophic or cribriform scarring may favor pyoderma gangrenosum, whereas a dull red or plum color and resolution of lesions without scarring may support the diagnosis of Sweet syndrome.⁷ Although both conditions can exhibit pathergy secondary to minor skin trauma such as venipuncture and biopsies,^2,3,5,8 Sweet syndrome rarely has been described to develop after surgery in a patient without a known history of the condition.⁹ In contrast, postsurgical pyoderma gangrenosum has been well described as secondary to the pathergy phenomenon.⁵

Our patient was favored to have pyoderma gangrenosum given the solitary lesion, its abrupt development after surgery, and the morphology of the lesion that exhibited a large violaceous to red ulcerative and exudative plaque with undermined borders with atrophic scarring. In patients with skin disease that cannot be distinguished with certainty as either Sweet syndrome or pyoderma gangrenosum, it is essential to recognize that, as neutrophilic dermatoses, both conditions can be managed with either the first-line treatment option of high-dose systemic steroids or one of the shared alternative first-line or second-line steroid-sparing treatments, such as dapsone and cyclosporine.²

Although the exact pathogenesis of pyoderma gangrenosum remains to be fully understood, paraneoplastic pyoderma gangrenosum is a frequently described phenomenon.^10,11 Our patient’s history of multiple malignancies, both solid and hematologic, supports the likelihood of malignancy-induced pyoderma gangrenosum; however, given his history of MDS, several other conditions were ruled out prior to making the diagnosis of pyoderma gangrenosum.

Classically, neutrophilic dermatoses such as pyoderma gangrenosum have a dense dermal neutrophilic infiltrate. Concurrent myeloproliferative disorders can alter the maturation of leukocytes, subsequently leading to an atypical appearance of the inflammatory cells on histopathology. Further, in the setting of myeloproliferative disorders, conditions such as leukemia cutis, in which there can be a cutaneous infiltrate of immature or mature myeloid or lymphocytic cells, must be considered. To ensure our patient’s abdominal skin changes were not a cutaneous manifestation of hematologic malignancy, immunohistochemical staining with CD20 and CD3 was performed and showed only the rare presence of B and T lymphocytes, respectively. Staining with CD34 for lymphocytic and myeloid progenitor cells was negative in the dermal infiltrate and further reduced the likelihood of leukemia cutis. Alternatively, patients can have aleukemic cutaneous myeloid sarcoma or leukemia cutis without an underlying hematologic condition or with latent peripheral blood or bone marrow myeloproliferative disorder, but our patient’s history of MDS eliminated this possibility.¹² After exclusion of cutaneous infiltration by malignant leukocytes, our patient was diagnosed with histiocytoid neutrophilic dermatosis.

To the Editor:

Neutrophilic dermatoses—a group of inflammatory cutaneous conditions—include acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and neutrophilic dermatosis of the dorsal hands. Histopathology shows a dense dermal infiltrate of mature neutrophils. In 2005, the histiocytoid subtype of Sweet syndrome was introduced with histopathologic findings of a dermal infiltrate composed of immature myeloid cells that resemble histiocytes in appearance but stain strongly with neutrophil markers on immunohistochemistry.¹ We present a case of histiocytoid pyoderma gangrenosum with histopathology that showed a dense dermal histiocytoid infiltrate with strong positivity for neutrophil markers on immunohistochemistry.

An 85-year-old man was seen by dermatology in the inpatient setting for a new-onset painful abdominal wound. He had a medical history of myelodysplastic syndrome (MDS), high-grade invasive papillary urothelial carcinoma of the bladder, and a recent diagnosis of low-grade invasive ascending colon adenocarcinoma. Ten days prior he underwent a right colectomy without intraoperative complications that was followed by septic shock. Workup with urinalysis and urine culture showed minimal pyuria with Pseudomonas aeruginosa. Additional studies, including blood cultures, abdominal wound cultures, computed tomography of the abdomen and pelvis, renal ultrasound, and chest radiographs, were unremarkable and showed no signs of surgical site infection, intra-abdominal or pelvic abscess formation, or pulmonary embolism. Broad-spectrum antibiotics—vancomycin and piperacillin-tazobactam—were started. Persistent fever (T_max of 102.3 °F [39.1 °C]) and leukocytosis (45.3×10⁹/L [4.2–10×10⁹/L]) despite antibiotic therapy, increasing pressor requirements, and progressive painful erythema and purulence at the abdominal surgical site led to debridement of the wound by the general surgery team on day 9 following the initial surgery due to suspected necrotizing infection. Within 24 hours, dermatology was consulted for continued rapid expansion of the wound. Physical examination of the abdomen revealed a large, well-demarcated, pink-red, indurated, ulcerated plaque with clear to purulent exudate and superficial erosions with violaceous undermined borders extending centrifugally from the abdominal surgical incision line (Figure 1A). Two punch biopsies sent for histopathologic evaluation and tissue culture showed dermal edema with a dense histiocytic infiltrate with nodular foci and admixed mature neutrophils to a lesser degree (Figure 2). Special staining was negative for bacteria, fungi, and mycobacteria. Immunohistochemistry revealed positive staining of the dermal inflammatory infiltrate with CD68, myeloperoxidase, and lysozyme, as well as negative staining with CD34 (Figure 3). These findings were suggestive of a histiocytoid neutrophilic dermatosis such as Sweet syndrome or pyoderma gangrenosum. Due to the morphology of the solitary lesion and the abrupt exacerbation shortly after surgical intervention, the patient was diagnosed with histiocytoid pyoderma gangrenosum. At the same time, the patient’s septic shock was treated with intravenous hydrocortisone (100 mg 3 times daily) for 2 days and also achieved a prompt response in the cutaneous symptoms (Figure 1B).

Sweet syndrome and pyoderma gangrenosum are considered distinct neutrophilic dermatoses that rarely coexist but share several clinical and histopathologic features, which can become a diagnostic challenge.² Both conditions can manifest clinically as abrupt-onset, tender, erythematous papules; vesiculopustular lesions; or bullae with ulcerative changes. They also exhibit pathergy; present with systemic symptoms such as pyrexia, malaise, and joint pain; are associated with underlying systemic conditions such as infections and/or malignancy; demonstrate a dense neutrophilic infiltrate in the dermis on histopathology; and respond promptly to systemic corticosteroids.^2-6 Bullous Sweet syndrome, which can present as vesicles, pustules, or bullae that progress to superficial ulcerations, may represent a variant of neutrophilic dermatosis characterized by features seen in both Sweet syndrome and pyoderma gangrenosum, suggesting that these 2 conditions may be on a spectrum.⁵Clinical features such as erythema with a blue, gray, or purple hue; undermined and ragged borders; and healing of skin lesions with atrophic or cribriform scarring may favor pyoderma gangrenosum, whereas a dull red or plum color and resolution of lesions without scarring may support the diagnosis of Sweet syndrome.⁷ Although both conditions can exhibit pathergy secondary to minor skin trauma such as venipuncture and biopsies,^2,3,5,8 Sweet syndrome rarely has been described to develop after surgery in a patient without a known history of the condition.⁹ In contrast, postsurgical pyoderma gangrenosum has been well described as secondary to the pathergy phenomenon.⁵

Our patient was favored to have pyoderma gangrenosum given the solitary lesion, its abrupt development after surgery, and the morphology of the lesion that exhibited a large violaceous to red ulcerative and exudative plaque with undermined borders with atrophic scarring. In patients with skin disease that cannot be distinguished with certainty as either Sweet syndrome or pyoderma gangrenosum, it is essential to recognize that, as neutrophilic dermatoses, both conditions can be managed with either the first-line treatment option of high-dose systemic steroids or one of the shared alternative first-line or second-line steroid-sparing treatments, such as dapsone and cyclosporine.²

Although the exact pathogenesis of pyoderma gangrenosum remains to be fully understood, paraneoplastic pyoderma gangrenosum is a frequently described phenomenon.^10,11 Our patient’s history of multiple malignancies, both solid and hematologic, supports the likelihood of malignancy-induced pyoderma gangrenosum; however, given his history of MDS, several other conditions were ruled out prior to making the diagnosis of pyoderma gangrenosum.

Classically, neutrophilic dermatoses such as pyoderma gangrenosum have a dense dermal neutrophilic infiltrate. Concurrent myeloproliferative disorders can alter the maturation of leukocytes, subsequently leading to an atypical appearance of the inflammatory cells on histopathology. Further, in the setting of myeloproliferative disorders, conditions such as leukemia cutis, in which there can be a cutaneous infiltrate of immature or mature myeloid or lymphocytic cells, must be considered. To ensure our patient’s abdominal skin changes were not a cutaneous manifestation of hematologic malignancy, immunohistochemical staining with CD20 and CD3 was performed and showed only the rare presence of B and T lymphocytes, respectively. Staining with CD34 for lymphocytic and myeloid progenitor cells was negative in the dermal infiltrate and further reduced the likelihood of leukemia cutis. Alternatively, patients can have aleukemic cutaneous myeloid sarcoma or leukemia cutis without an underlying hematologic condition or with latent peripheral blood or bone marrow myeloproliferative disorder, but our patient’s history of MDS eliminated this possibility.¹² After exclusion of cutaneous infiltration by malignant leukocytes, our patient was diagnosed with histiocytoid neutrophilic dermatosis.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Cardiac rhabdomyomas are benign hamartomas that are common in patients with tuberous sclerosis complex (TSC).¹ We describe a patient who presented with large infantile hemangiomas (IHs) and hypopigmented macules, which prompted further testing that eventually showed concomitant multiple cardiac rhabdomyomas in the context of TSC.

A 5-week-old girl—who was born at 38 weeks and 3 days’ gestation via uncomplicated vaginal delivery—was referred to our pediatric dermatology clinic for evaluation of multiple erythematous lesions on the scalp and left buttock that were first noticed 2 weeks prior to presentation. There was a family history of seizures in the patient’s mother. The patient’s older brother did not have similar symptoms.

Physical examination revealed 2 nonulcerating erythematous nodules on the middle and posterior left vertex scalp that measured 2.5×2 cm (Figure 1A) as well as 1 bright red plaque on the left buttock (Figure 1B). Five hypopigmented macules, ranging from 5 mm to 1.5 cm in diameter, also were detected on the left thorax (Figure 2A) as well as the middle and lower back (Figure 2B). These findings, along with the history of seizures in the patient’s mother, prompted further evaluation of the family history, which uncovered TSC in the patient’s mother, maternal aunt, and maternal grandmother.

The large IHs on the scalp did not pose concerns for potential functional impairment but were still considered high risk for permanent alopecia based on clinical practice guidelines for the management of IH.² Treatment with oral propranolol was recommended; however, because of a strong suspicion of TSC due to the presence of 5 hypopigmented macules measuring more than 5 mm in diameter (≥3 hypopigmented macules of ≥5 mm is one of the major criterion for TSC), the patient was referred to cardiology prior to initiation of propranolol.

Echocardiography revealed 3 intracardiac masses measuring 4 to 5 mm in diameter in the left ventricle (LV), along the interventricular septum and the LV posterior wall. These masses were consistent with rhabdomyomas (Figure 3)—a major criterion for TSC—which had not been detected by prenatal ultrasonography. No obstruction to LV inflow or outflow was observed. Additionally, no arrhythmias were detected on electrocardiography.

The patient was cleared for propranolol, which was slowly uptitrated to 2 mg/kg/d. She completed the course without adverse effects. The treatment of IH was successful with substantial reduction in size over the following months until clearance. She also was referred to neurology for magnetic resonance imaging of the brain, which showed a 3-mm subependymal nodule in the lateral right ventricle, another major feature of TSC.

Cardiac rhabdomyomas are benign hamartomas that affect as many as 80% of patients with TSC¹ and are primarily localized in the ventricles. Although cardiac rhabdomyomas usually regress over time, they can compromise ventricular function or valvular function, or both, and result in outflow obstruction, arrhythmias, and Wolff- Parkinson-White syndrome.³ Surgical resection may be needed in patients whose condition is refractory to medical management for heart failure.

The pathophysiologic mechanism behind the natural involution of cardiac rhabdomyomas has not been fully elucidated. It has been hypothesized that these masses stem from the inability of rhabdomyoma cells to divide after birth due to their embryonic myocyte derivation.⁴

According to the TSC diagnostic criteria from the Tuberous Sclerosis Complex International Consensus Group, at least 2 major features or 1 major and 2 minor features are required to make a definitive diagnosis of TSC. Cutaneous signs represent more than one-third of major features of TSC; almost all patients with TSC have skin findings.⁵

Identification of pathogenic mutations in either TSC¹ (on chromosome 9q34.3, encoding for hamartin) or TSC² (on chromosome 16p13.3, encoding for tuberin), resulting in constitutive activation of mammalian target of rapamycin and subsequent increased cell growth, is sufficient for a definitive diagnosis of TSC. However, mutations cannot be identified by conventional genetic testing in as many as one-quarter of patients with TSC; therefore, a negative result does not exclude TSC if the patient meets clinical diagnostic criteria.

Although a cardiology workup is indicated prior to initiating propranolol in the presence of possible cardiac rhabdomyomas, most of those lesions are hemodynamically stable and do not require treatment. There also is no contraindication for β-blocker therapy. In fact, propranolol has been reported as a successful treatment in rhabdomyoma-associated arrhythmias in children.⁶ Notably, obstructive cardiac rhabdomyomas have been successfully treated with mammalian target of rapamycin inhibitors, such as sirolimus⁷ and everolimus.⁸

Baseline cardiology screening with echocardiography prior to initiating propranolol for treatment of IH is not routinely indicated in babies with uncomplicated IH. However, in a patient with TSC, cardiology screening is necessary to rule out rhabdomyomas with associated arrhythmias or obstructed blood flow, or both, prior to initiating treatment.

We presented a case of concomitant IH and TSC in a patient with cardiac rhabdomyomas. The manifestation of large IHs in our patient prompted further testing that revealed multiple cardiac rhabdomyomas in the context of TSC. It is imperative for cardiologists, cardiac surgeons, and dermatologists to be familiar with the TSC diagnostic criteria so that they can reach a prompt diagnosis and make appropriate referrals for further evaluation of cardiac, neurologic, and ophthalmologic signs.

To the Editor:

Cardiac rhabdomyomas are benign hamartomas that are common in patients with tuberous sclerosis complex (TSC).¹ We describe a patient who presented with large infantile hemangiomas (IHs) and hypopigmented macules, which prompted further testing that eventually showed concomitant multiple cardiac rhabdomyomas in the context of TSC.

A 5-week-old girl—who was born at 38 weeks and 3 days’ gestation via uncomplicated vaginal delivery—was referred to our pediatric dermatology clinic for evaluation of multiple erythematous lesions on the scalp and left buttock that were first noticed 2 weeks prior to presentation. There was a family history of seizures in the patient’s mother. The patient’s older brother did not have similar symptoms.

Physical examination revealed 2 nonulcerating erythematous nodules on the middle and posterior left vertex scalp that measured 2.5×2 cm (Figure 1A) as well as 1 bright red plaque on the left buttock (Figure 1B). Five hypopigmented macules, ranging from 5 mm to 1.5 cm in diameter, also were detected on the left thorax (Figure 2A) as well as the middle and lower back (Figure 2B). These findings, along with the history of seizures in the patient’s mother, prompted further evaluation of the family history, which uncovered TSC in the patient’s mother, maternal aunt, and maternal grandmother.

The large IHs on the scalp did not pose concerns for potential functional impairment but were still considered high risk for permanent alopecia based on clinical practice guidelines for the management of IH.² Treatment with oral propranolol was recommended; however, because of a strong suspicion of TSC due to the presence of 5 hypopigmented macules measuring more than 5 mm in diameter (≥3 hypopigmented macules of ≥5 mm is one of the major criterion for TSC), the patient was referred to cardiology prior to initiation of propranolol.

Echocardiography revealed 3 intracardiac masses measuring 4 to 5 mm in diameter in the left ventricle (LV), along the interventricular septum and the LV posterior wall. These masses were consistent with rhabdomyomas (Figure 3)—a major criterion for TSC—which had not been detected by prenatal ultrasonography. No obstruction to LV inflow or outflow was observed. Additionally, no arrhythmias were detected on electrocardiography.

The patient was cleared for propranolol, which was slowly uptitrated to 2 mg/kg/d. She completed the course without adverse effects. The treatment of IH was successful with substantial reduction in size over the following months until clearance. She also was referred to neurology for magnetic resonance imaging of the brain, which showed a 3-mm subependymal nodule in the lateral right ventricle, another major feature of TSC.

Cardiac rhabdomyomas are benign hamartomas that affect as many as 80% of patients with TSC¹ and are primarily localized in the ventricles. Although cardiac rhabdomyomas usually regress over time, they can compromise ventricular function or valvular function, or both, and result in outflow obstruction, arrhythmias, and Wolff- Parkinson-White syndrome.³ Surgical resection may be needed in patients whose condition is refractory to medical management for heart failure.

The pathophysiologic mechanism behind the natural involution of cardiac rhabdomyomas has not been fully elucidated. It has been hypothesized that these masses stem from the inability of rhabdomyoma cells to divide after birth due to their embryonic myocyte derivation.⁴

According to the TSC diagnostic criteria from the Tuberous Sclerosis Complex International Consensus Group, at least 2 major features or 1 major and 2 minor features are required to make a definitive diagnosis of TSC. Cutaneous signs represent more than one-third of major features of TSC; almost all patients with TSC have skin findings.⁵

Identification of pathogenic mutations in either TSC¹ (on chromosome 9q34.3, encoding for hamartin) or TSC² (on chromosome 16p13.3, encoding for tuberin), resulting in constitutive activation of mammalian target of rapamycin and subsequent increased cell growth, is sufficient for a definitive diagnosis of TSC. However, mutations cannot be identified by conventional genetic testing in as many as one-quarter of patients with TSC; therefore, a negative result does not exclude TSC if the patient meets clinical diagnostic criteria.

Although a cardiology workup is indicated prior to initiating propranolol in the presence of possible cardiac rhabdomyomas, most of those lesions are hemodynamically stable and do not require treatment. There also is no contraindication for β-blocker therapy. In fact, propranolol has been reported as a successful treatment in rhabdomyoma-associated arrhythmias in children.⁶ Notably, obstructive cardiac rhabdomyomas have been successfully treated with mammalian target of rapamycin inhibitors, such as sirolimus⁷ and everolimus.⁸

Baseline cardiology screening with echocardiography prior to initiating propranolol for treatment of IH is not routinely indicated in babies with uncomplicated IH. However, in a patient with TSC, cardiology screening is necessary to rule out rhabdomyomas with associated arrhythmias or obstructed blood flow, or both, prior to initiating treatment.

We presented a case of concomitant IH and TSC in a patient with cardiac rhabdomyomas. The manifestation of large IHs in our patient prompted further testing that revealed multiple cardiac rhabdomyomas in the context of TSC. It is imperative for cardiologists, cardiac surgeons, and dermatologists to be familiar with the TSC diagnostic criteria so that they can reach a prompt diagnosis and make appropriate referrals for further evaluation of cardiac, neurologic, and ophthalmologic signs.

To the Editor:

Cardiac rhabdomyomas are benign hamartomas that are common in patients with tuberous sclerosis complex (TSC).¹ We describe a patient who presented with large infantile hemangiomas (IHs) and hypopigmented macules, which prompted further testing that eventually showed concomitant multiple cardiac rhabdomyomas in the context of TSC.

A 5-week-old girl—who was born at 38 weeks and 3 days’ gestation via uncomplicated vaginal delivery—was referred to our pediatric dermatology clinic for evaluation of multiple erythematous lesions on the scalp and left buttock that were first noticed 2 weeks prior to presentation. There was a family history of seizures in the patient’s mother. The patient’s older brother did not have similar symptoms.

Physical examination revealed 2 nonulcerating erythematous nodules on the middle and posterior left vertex scalp that measured 2.5×2 cm (Figure 1A) as well as 1 bright red plaque on the left buttock (Figure 1B). Five hypopigmented macules, ranging from 5 mm to 1.5 cm in diameter, also were detected on the left thorax (Figure 2A) as well as the middle and lower back (Figure 2B). These findings, along with the history of seizures in the patient’s mother, prompted further evaluation of the family history, which uncovered TSC in the patient’s mother, maternal aunt, and maternal grandmother.

The large IHs on the scalp did not pose concerns for potential functional impairment but were still considered high risk for permanent alopecia based on clinical practice guidelines for the management of IH.² Treatment with oral propranolol was recommended; however, because of a strong suspicion of TSC due to the presence of 5 hypopigmented macules measuring more than 5 mm in diameter (≥3 hypopigmented macules of ≥5 mm is one of the major criterion for TSC), the patient was referred to cardiology prior to initiation of propranolol.

Echocardiography revealed 3 intracardiac masses measuring 4 to 5 mm in diameter in the left ventricle (LV), along the interventricular septum and the LV posterior wall. These masses were consistent with rhabdomyomas (Figure 3)—a major criterion for TSC—which had not been detected by prenatal ultrasonography. No obstruction to LV inflow or outflow was observed. Additionally, no arrhythmias were detected on electrocardiography.

The patient was cleared for propranolol, which was slowly uptitrated to 2 mg/kg/d. She completed the course without adverse effects. The treatment of IH was successful with substantial reduction in size over the following months until clearance. She also was referred to neurology for magnetic resonance imaging of the brain, which showed a 3-mm subependymal nodule in the lateral right ventricle, another major feature of TSC.

Cardiac rhabdomyomas are benign hamartomas that affect as many as 80% of patients with TSC¹ and are primarily localized in the ventricles. Although cardiac rhabdomyomas usually regress over time, they can compromise ventricular function or valvular function, or both, and result in outflow obstruction, arrhythmias, and Wolff- Parkinson-White syndrome.³ Surgical resection may be needed in patients whose condition is refractory to medical management for heart failure.

The pathophysiologic mechanism behind the natural involution of cardiac rhabdomyomas has not been fully elucidated. It has been hypothesized that these masses stem from the inability of rhabdomyoma cells to divide after birth due to their embryonic myocyte derivation.⁴

According to the TSC diagnostic criteria from the Tuberous Sclerosis Complex International Consensus Group, at least 2 major features or 1 major and 2 minor features are required to make a definitive diagnosis of TSC. Cutaneous signs represent more than one-third of major features of TSC; almost all patients with TSC have skin findings.⁵

Identification of pathogenic mutations in either TSC¹ (on chromosome 9q34.3, encoding for hamartin) or TSC² (on chromosome 16p13.3, encoding for tuberin), resulting in constitutive activation of mammalian target of rapamycin and subsequent increased cell growth, is sufficient for a definitive diagnosis of TSC. However, mutations cannot be identified by conventional genetic testing in as many as one-quarter of patients with TSC; therefore, a negative result does not exclude TSC if the patient meets clinical diagnostic criteria.

Although a cardiology workup is indicated prior to initiating propranolol in the presence of possible cardiac rhabdomyomas, most of those lesions are hemodynamically stable and do not require treatment. There also is no contraindication for β-blocker therapy. In fact, propranolol has been reported as a successful treatment in rhabdomyoma-associated arrhythmias in children.⁶ Notably, obstructive cardiac rhabdomyomas have been successfully treated with mammalian target of rapamycin inhibitors, such as sirolimus⁷ and everolimus.⁸

Baseline cardiology screening with echocardiography prior to initiating propranolol for treatment of IH is not routinely indicated in babies with uncomplicated IH. However, in a patient with TSC, cardiology screening is necessary to rule out rhabdomyomas with associated arrhythmias or obstructed blood flow, or both, prior to initiating treatment.

We presented a case of concomitant IH and TSC in a patient with cardiac rhabdomyomas. The manifestation of large IHs in our patient prompted further testing that revealed multiple cardiac rhabdomyomas in the context of TSC. It is imperative for cardiologists, cardiac surgeons, and dermatologists to be familiar with the TSC diagnostic criteria so that they can reach a prompt diagnosis and make appropriate referrals for further evaluation of cardiac, neurologic, and ophthalmologic signs.

To the Editor:

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia caused by accumulation of clonal Langerhans cells in 1 or more organs. The clinical spectrum is diverse, ranging from mild, single-organ involvement that may resolve spontaneously to severe progressive multisystem disease that can be fatal. It is most prevalent in children, affecting an estimated 4 to 5 children for every 1 million annually, with male predominance.¹ The pathogenesis is driven by activating mutations in the mitogen-activated protein kinase pathway, with the BRAF V600E mutation detected in most LCH patients, resulting in proliferation of pathologic Langerhans cells and dysregulated expression of inflammatory cytokines in LCH lesions.² A biopsy of lesional tissue is required for definitive diagnosis. Histopathology reveals a mixed inflammatory infiltrate and characteristic mononuclear cells with reniform nuclei that are positive for CD1a and CD207 proteins on immunohistochemical staining.³

Langerhans cell histiocytosis is categorized by the extent of organ involvement. It commonly affects the bones, skin, pituitary gland, liver, lungs, bone marrow, and lymph nodes.⁴ Single-system LCH involves a single organ with unifocal or multifocal lesions; multisystem LCH involves 2 or more organs and has a worse prognosis if risk organs (eg, liver, spleen, bone marrow) are involved.⁴

Skin lesions are reported in more than half of LCH cases and are the most common initial manifestation in patients younger than 2 years.⁴ Cutaneous findings are highly variable, which poses a diagnostic challenge. Common morphologies include erythematous papules, pustules, papulovesicles, scaly plaques, erosions, and petechiae. Lesions can be solitary or widespread and favor the trunk, head, and face.⁴ We describe an atypical case of hypopigmented cutaneous LCH and review the literature on this morphology in patients with skin of color.

A 7-month-old Hispanic male infant who was otherwise healthy presented with numerous hypopigmented macules and pink papules on the trunk and groin that had progressed since birth. A review of systems was unremarkable. Physical examination revealed 1- to 3-mm, discrete, hypopigmented macules intermixed with 1- to 2-mm pearly pink papules scattered on the back, chest, abdomen, and inguinal folds (Figure 1). Some lesions appeared koebnerized; however, the parents denied a history of scratching or trauma.

Histopathology of a lesion in the inguinal fold showed aggregates of mononuclear cells with reniform nuclei and abundant amphophilic cytoplasm in the papillary dermis, with focal extension into the epidermis. Scattered eosinophils and multinucleated giant cells were present in the dermal inflammatory infiltrate (Figure 2). Immunohistochemical staining was positive for CD1a (Figure 3) and S-100 protein (Figure 4). Although epidermal Langerhans cell collections also can be seen in allergic contact dermatitis,⁵ predominant involvement of the papillary dermis and the presence of multinucleated giant cells are characteristic of LCH.⁴ Given these findings, which were consistent with LCH, the dermatopathology deemed BRAF V600E immunostaining unnecessary for diagnostic purposes.

The patient was referred to the hematology and oncology department to undergo thorough evaluation for extracutaneous involvement. The workup included a complete blood cell count, liver function testing, electrolyte assessment, skeletal survey, chest radiography, and ultrasonography of the liver and spleen. All results were negative, suggesting a diagnosis of single-system cutaneous LCH.

Three months later, the patient presented to dermatology with spontaneous regression of all skin lesions. Continued follow-up—every 6 months for 5 years—was recommended to monitor for disease recurrence or progression to multisystem disease.

Cutaneous LCH is a clinically heterogeneous disease with the potential for multisystem involvement and long-term sequelae; therefore, timely diagnosis is paramount to optimize outcomes. However, delayed diagnosis is common because of the spectrum of skin findings that can mimic common pediatric dermatoses, such as seborrheic dermatitis, atopic dermatitis, and diaper dermatitis.⁴ In one study, the median time from onset of skin lesions to diagnostic biopsy was longer than 3 months (maximum, 5 years).⁶ Our patient was referred to dermatology 7 months after onset of hypopigmented macules, a rarely reported cutaneous manifestation of LCH.

A PubMed search of articles indexed for MEDLINE from 1994 to 2019 using the terms Langerhans cell histiocytotis and hypopigmented yielded 17 cases of LCH presenting as hypopigmented skin lesions (Table).^7-22 All cases occurred in patients with skin of color (ie, patients of Asian, Hispanic, or African descent). Hypopigmented macules were the only cutaneous manifestation in 10 (59%) cases. Lesions most commonly were distributed on the trunk (16/17 [94%]) and extremities (8/17 [47%]). The median age of onset was 1 month; 76% (13/17) of patients developed skin lesions before 1 year of age, indicating that this morphology may be more common in newborns. In most patients, the diagnosis was single-system cutaneous LCH; they exhibited spontaneous regression by 8 months of age on average, suggesting that this variant may be associated with a better prognosis. Mori and colleagues²¹ hypothesized that hypopigmented lesions may represent the resolving stage of active LCH based on histopathologic findings of dermal pallor and fibrosis in a hypopigmented LCH lesion. However, systemic involvement was reported in 7 cases of hypopigmented LCH, highlighting the importance of assessing for multisystem disease regardless of cutaneous morphology.²¹Langerhans cell histiocytosis should be considered in the differential diagnosis when evaluating hypopigmented skin eruptions in infants with darker skin types. Prompt diagnosis of this atypical variant requires a higher index of suspicion because of its rarity and the polymorphic nature of cutaneous LCH. This morphology may go undiagnosed in the setting of mild or spontaneously resolving disease; notwithstanding, accurate diagnosis and longitudinal surveillance are necessary given the potential for progressive systemic involvement.

To the Editor:

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia caused by accumulation of clonal Langerhans cells in 1 or more organs. The clinical spectrum is diverse, ranging from mild, single-organ involvement that may resolve spontaneously to severe progressive multisystem disease that can be fatal. It is most prevalent in children, affecting an estimated 4 to 5 children for every 1 million annually, with male predominance.¹ The pathogenesis is driven by activating mutations in the mitogen-activated protein kinase pathway, with the BRAF V600E mutation detected in most LCH patients, resulting in proliferation of pathologic Langerhans cells and dysregulated expression of inflammatory cytokines in LCH lesions.² A biopsy of lesional tissue is required for definitive diagnosis. Histopathology reveals a mixed inflammatory infiltrate and characteristic mononuclear cells with reniform nuclei that are positive for CD1a and CD207 proteins on immunohistochemical staining.³

Langerhans cell histiocytosis is categorized by the extent of organ involvement. It commonly affects the bones, skin, pituitary gland, liver, lungs, bone marrow, and lymph nodes.⁴ Single-system LCH involves a single organ with unifocal or multifocal lesions; multisystem LCH involves 2 or more organs and has a worse prognosis if risk organs (eg, liver, spleen, bone marrow) are involved.⁴

Skin lesions are reported in more than half of LCH cases and are the most common initial manifestation in patients younger than 2 years.⁴ Cutaneous findings are highly variable, which poses a diagnostic challenge. Common morphologies include erythematous papules, pustules, papulovesicles, scaly plaques, erosions, and petechiae. Lesions can be solitary or widespread and favor the trunk, head, and face.⁴ We describe an atypical case of hypopigmented cutaneous LCH and review the literature on this morphology in patients with skin of color.

A 7-month-old Hispanic male infant who was otherwise healthy presented with numerous hypopigmented macules and pink papules on the trunk and groin that had progressed since birth. A review of systems was unremarkable. Physical examination revealed 1- to 3-mm, discrete, hypopigmented macules intermixed with 1- to 2-mm pearly pink papules scattered on the back, chest, abdomen, and inguinal folds (Figure 1). Some lesions appeared koebnerized; however, the parents denied a history of scratching or trauma.

Histopathology of a lesion in the inguinal fold showed aggregates of mononuclear cells with reniform nuclei and abundant amphophilic cytoplasm in the papillary dermis, with focal extension into the epidermis. Scattered eosinophils and multinucleated giant cells were present in the dermal inflammatory infiltrate (Figure 2). Immunohistochemical staining was positive for CD1a (Figure 3) and S-100 protein (Figure 4). Although epidermal Langerhans cell collections also can be seen in allergic contact dermatitis,⁵ predominant involvement of the papillary dermis and the presence of multinucleated giant cells are characteristic of LCH.⁴ Given these findings, which were consistent with LCH, the dermatopathology deemed BRAF V600E immunostaining unnecessary for diagnostic purposes.

The patient was referred to the hematology and oncology department to undergo thorough evaluation for extracutaneous involvement. The workup included a complete blood cell count, liver function testing, electrolyte assessment, skeletal survey, chest radiography, and ultrasonography of the liver and spleen. All results were negative, suggesting a diagnosis of single-system cutaneous LCH.

Three months later, the patient presented to dermatology with spontaneous regression of all skin lesions. Continued follow-up—every 6 months for 5 years—was recommended to monitor for disease recurrence or progression to multisystem disease.

Cutaneous LCH is a clinically heterogeneous disease with the potential for multisystem involvement and long-term sequelae; therefore, timely diagnosis is paramount to optimize outcomes. However, delayed diagnosis is common because of the spectrum of skin findings that can mimic common pediatric dermatoses, such as seborrheic dermatitis, atopic dermatitis, and diaper dermatitis.⁴ In one study, the median time from onset of skin lesions to diagnostic biopsy was longer than 3 months (maximum, 5 years).⁶ Our patient was referred to dermatology 7 months after onset of hypopigmented macules, a rarely reported cutaneous manifestation of LCH.

A PubMed search of articles indexed for MEDLINE from 1994 to 2019 using the terms Langerhans cell histiocytotis and hypopigmented yielded 17 cases of LCH presenting as hypopigmented skin lesions (Table).^7-22 All cases occurred in patients with skin of color (ie, patients of Asian, Hispanic, or African descent). Hypopigmented macules were the only cutaneous manifestation in 10 (59%) cases. Lesions most commonly were distributed on the trunk (16/17 [94%]) and extremities (8/17 [47%]). The median age of onset was 1 month; 76% (13/17) of patients developed skin lesions before 1 year of age, indicating that this morphology may be more common in newborns. In most patients, the diagnosis was single-system cutaneous LCH; they exhibited spontaneous regression by 8 months of age on average, suggesting that this variant may be associated with a better prognosis. Mori and colleagues²¹ hypothesized that hypopigmented lesions may represent the resolving stage of active LCH based on histopathologic findings of dermal pallor and fibrosis in a hypopigmented LCH lesion. However, systemic involvement was reported in 7 cases of hypopigmented LCH, highlighting the importance of assessing for multisystem disease regardless of cutaneous morphology.²¹Langerhans cell histiocytosis should be considered in the differential diagnosis when evaluating hypopigmented skin eruptions in infants with darker skin types. Prompt diagnosis of this atypical variant requires a higher index of suspicion because of its rarity and the polymorphic nature of cutaneous LCH. This morphology may go undiagnosed in the setting of mild or spontaneously resolving disease; notwithstanding, accurate diagnosis and longitudinal surveillance are necessary given the potential for progressive systemic involvement.

To the Editor:

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia caused by accumulation of clonal Langerhans cells in 1 or more organs. The clinical spectrum is diverse, ranging from mild, single-organ involvement that may resolve spontaneously to severe progressive multisystem disease that can be fatal. It is most prevalent in children, affecting an estimated 4 to 5 children for every 1 million annually, with male predominance.¹ The pathogenesis is driven by activating mutations in the mitogen-activated protein kinase pathway, with the BRAF V600E mutation detected in most LCH patients, resulting in proliferation of pathologic Langerhans cells and dysregulated expression of inflammatory cytokines in LCH lesions.² A biopsy of lesional tissue is required for definitive diagnosis. Histopathology reveals a mixed inflammatory infiltrate and characteristic mononuclear cells with reniform nuclei that are positive for CD1a and CD207 proteins on immunohistochemical staining.³

Langerhans cell histiocytosis is categorized by the extent of organ involvement. It commonly affects the bones, skin, pituitary gland, liver, lungs, bone marrow, and lymph nodes.⁴ Single-system LCH involves a single organ with unifocal or multifocal lesions; multisystem LCH involves 2 or more organs and has a worse prognosis if risk organs (eg, liver, spleen, bone marrow) are involved.⁴

Skin lesions are reported in more than half of LCH cases and are the most common initial manifestation in patients younger than 2 years.⁴ Cutaneous findings are highly variable, which poses a diagnostic challenge. Common morphologies include erythematous papules, pustules, papulovesicles, scaly plaques, erosions, and petechiae. Lesions can be solitary or widespread and favor the trunk, head, and face.⁴ We describe an atypical case of hypopigmented cutaneous LCH and review the literature on this morphology in patients with skin of color.

A 7-month-old Hispanic male infant who was otherwise healthy presented with numerous hypopigmented macules and pink papules on the trunk and groin that had progressed since birth. A review of systems was unremarkable. Physical examination revealed 1- to 3-mm, discrete, hypopigmented macules intermixed with 1- to 2-mm pearly pink papules scattered on the back, chest, abdomen, and inguinal folds (Figure 1). Some lesions appeared koebnerized; however, the parents denied a history of scratching or trauma.

Histopathology of a lesion in the inguinal fold showed aggregates of mononuclear cells with reniform nuclei and abundant amphophilic cytoplasm in the papillary dermis, with focal extension into the epidermis. Scattered eosinophils and multinucleated giant cells were present in the dermal inflammatory infiltrate (Figure 2). Immunohistochemical staining was positive for CD1a (Figure 3) and S-100 protein (Figure 4). Although epidermal Langerhans cell collections also can be seen in allergic contact dermatitis,⁵ predominant involvement of the papillary dermis and the presence of multinucleated giant cells are characteristic of LCH.⁴ Given these findings, which were consistent with LCH, the dermatopathology deemed BRAF V600E immunostaining unnecessary for diagnostic purposes.

The patient was referred to the hematology and oncology department to undergo thorough evaluation for extracutaneous involvement. The workup included a complete blood cell count, liver function testing, electrolyte assessment, skeletal survey, chest radiography, and ultrasonography of the liver and spleen. All results were negative, suggesting a diagnosis of single-system cutaneous LCH.

Three months later, the patient presented to dermatology with spontaneous regression of all skin lesions. Continued follow-up—every 6 months for 5 years—was recommended to monitor for disease recurrence or progression to multisystem disease.

Cutaneous LCH is a clinically heterogeneous disease with the potential for multisystem involvement and long-term sequelae; therefore, timely diagnosis is paramount to optimize outcomes. However, delayed diagnosis is common because of the spectrum of skin findings that can mimic common pediatric dermatoses, such as seborrheic dermatitis, atopic dermatitis, and diaper dermatitis.⁴ In one study, the median time from onset of skin lesions to diagnostic biopsy was longer than 3 months (maximum, 5 years).⁶ Our patient was referred to dermatology 7 months after onset of hypopigmented macules, a rarely reported cutaneous manifestation of LCH.

A PubMed search of articles indexed for MEDLINE from 1994 to 2019 using the terms Langerhans cell histiocytotis and hypopigmented yielded 17 cases of LCH presenting as hypopigmented skin lesions (Table).^7-22 All cases occurred in patients with skin of color (ie, patients of Asian, Hispanic, or African descent). Hypopigmented macules were the only cutaneous manifestation in 10 (59%) cases. Lesions most commonly were distributed on the trunk (16/17 [94%]) and extremities (8/17 [47%]). The median age of onset was 1 month; 76% (13/17) of patients developed skin lesions before 1 year of age, indicating that this morphology may be more common in newborns. In most patients, the diagnosis was single-system cutaneous LCH; they exhibited spontaneous regression by 8 months of age on average, suggesting that this variant may be associated with a better prognosis. Mori and colleagues²¹ hypothesized that hypopigmented lesions may represent the resolving stage of active LCH based on histopathologic findings of dermal pallor and fibrosis in a hypopigmented LCH lesion. However, systemic involvement was reported in 7 cases of hypopigmented LCH, highlighting the importance of assessing for multisystem disease regardless of cutaneous morphology.²¹Langerhans cell histiocytosis should be considered in the differential diagnosis when evaluating hypopigmented skin eruptions in infants with darker skin types. Prompt diagnosis of this atypical variant requires a higher index of suspicion because of its rarity and the polymorphic nature of cutaneous LCH. This morphology may go undiagnosed in the setting of mild or spontaneously resolving disease; notwithstanding, accurate diagnosis and longitudinal surveillance are necessary given the potential for progressive systemic involvement.

To the Editor:

The term palisaded neutrophilic and granulomatous dermatitis (PNGD) has been proposed to encompass various conditions, including Winkelmann granuloma and superficial ulcerating rheumatoid necrobiosis. More recently, PNGD has been classified along with interstitial granulomatous dermatitis and interstitial granulomatous drug reaction under a unifying rubric of reactive granulomatous dermatitis (RGD).^1-4 The diagnosis of RGD can be challenging because of a range of clinical and histopathologic features as well as variable nomenclature.^1-3,5

Palisaded neutrophilic and granulomatous dermatitis classically manifests with papules and small plaques on the extensor extremities, with histopathology showing characteristic necrobiosis with both neutrophils and histiocytes.^1,2,6 We report 6 cases of RGD, including an index case in which a predominance of neutrophils in the infiltrate impeded the diagnosis.

An 85-year-old woman (the index patient) presented with a several-week history of asymmetric crusted papules on the right upper extremity—3 lesions on the elbow and forearm and 1 lesion on a finger. She was an avid gardener with severe rheumatoid arthritis treated with Janus kinase (JAK) inhibitor therapy. An initial biopsy of the elbow revealed a dense infiltrate of neutrophils and sparse eosinophils within the dermis. Special stains for bacterial, fungal, and acid-fast organisms were negative.

Because infection with sporotrichoid spread remained high in the differential diagnosis, the JAK inhibitor was discontinued and an antifungal agent was initiated. Given the persistence of the lesions, a subsequent biopsy of the right finger revealed scarce neutrophils and predominant histiocytes with rare foci of degenerated collagen. Sporotrichosis remained the leading diagnosis for these unilateral lesions. The patient subsequently developed additional crusted papules on the left arm (Figure 1). A biopsy of a left elbow lesion revealed palisades of histiocytes around degenerated collagen and collections of neutrophils compatible with RGD (Figures 2 and 3). Incidentally, the patient also presented with bilateral lower extremity palpable purpura, with a biopsy showing leukocytoclastic vasculitis. Antifungal therapy was discontinued and JAK inhibitor therapy resumed, with partial resolution of both the arm and right finger lesions and complete resolution of the lower extremity palpable purpura over several months.

The dense neutrophilic infiltrate and asymmetric presentation seen in our index patient’s initial biopsy hindered categorization of the cutaneous findings as RGD in association with her rheumatoid arthritis rather than as an infectious process. To ascertain whether diagnosis also was difficult in other cases of RGD, we conducted a search of the Yale Dermatopathology database for the diagnosis palisaded neutrophilic and granulomatous dermatitis, a term consistently used at our institution over the past decade. This study was approved by the institutional review board of Yale University (New Haven, Connecticut), and informed consent was waived. The search covered a 10-year period; 13 patients were found. Eight patients were eliminated because further clinical information or follow-up could not be obtained, leaving 5 additional cases (Table). The 8 eliminated cases were consultations submitted to the laboratory by outside pathologists from other institutions.

To the Editor:

The term palisaded neutrophilic and granulomatous dermatitis (PNGD) has been proposed to encompass various conditions, including Winkelmann granuloma and superficial ulcerating rheumatoid necrobiosis. More recently, PNGD has been classified along with interstitial granulomatous dermatitis and interstitial granulomatous drug reaction under a unifying rubric of reactive granulomatous dermatitis (RGD).^1-4 The diagnosis of RGD can be challenging because of a range of clinical and histopathologic features as well as variable nomenclature.^1-3,5

Palisaded neutrophilic and granulomatous dermatitis classically manifests with papules and small plaques on the extensor extremities, with histopathology showing characteristic necrobiosis with both neutrophils and histiocytes.^1,2,6 We report 6 cases of RGD, including an index case in which a predominance of neutrophils in the infiltrate impeded the diagnosis.

An 85-year-old woman (the index patient) presented with a several-week history of asymmetric crusted papules on the right upper extremity—3 lesions on the elbow and forearm and 1 lesion on a finger. She was an avid gardener with severe rheumatoid arthritis treated with Janus kinase (JAK) inhibitor therapy. An initial biopsy of the elbow revealed a dense infiltrate of neutrophils and sparse eosinophils within the dermis. Special stains for bacterial, fungal, and acid-fast organisms were negative.

Because infection with sporotrichoid spread remained high in the differential diagnosis, the JAK inhibitor was discontinued and an antifungal agent was initiated. Given the persistence of the lesions, a subsequent biopsy of the right finger revealed scarce neutrophils and predominant histiocytes with rare foci of degenerated collagen. Sporotrichosis remained the leading diagnosis for these unilateral lesions. The patient subsequently developed additional crusted papules on the left arm (Figure 1). A biopsy of a left elbow lesion revealed palisades of histiocytes around degenerated collagen and collections of neutrophils compatible with RGD (Figures 2 and 3). Incidentally, the patient also presented with bilateral lower extremity palpable purpura, with a biopsy showing leukocytoclastic vasculitis. Antifungal therapy was discontinued and JAK inhibitor therapy resumed, with partial resolution of both the arm and right finger lesions and complete resolution of the lower extremity palpable purpura over several months.

The dense neutrophilic infiltrate and asymmetric presentation seen in our index patient’s initial biopsy hindered categorization of the cutaneous findings as RGD in association with her rheumatoid arthritis rather than as an infectious process. To ascertain whether diagnosis also was difficult in other cases of RGD, we conducted a search of the Yale Dermatopathology database for the diagnosis palisaded neutrophilic and granulomatous dermatitis, a term consistently used at our institution over the past decade. This study was approved by the institutional review board of Yale University (New Haven, Connecticut), and informed consent was waived. The search covered a 10-year period; 13 patients were found. Eight patients were eliminated because further clinical information or follow-up could not be obtained, leaving 5 additional cases (Table). The 8 eliminated cases were consultations submitted to the laboratory by outside pathologists from other institutions.

To the Editor:

The term palisaded neutrophilic and granulomatous dermatitis (PNGD) has been proposed to encompass various conditions, including Winkelmann granuloma and superficial ulcerating rheumatoid necrobiosis. More recently, PNGD has been classified along with interstitial granulomatous dermatitis and interstitial granulomatous drug reaction under a unifying rubric of reactive granulomatous dermatitis (RGD).^1-4 The diagnosis of RGD can be challenging because of a range of clinical and histopathologic features as well as variable nomenclature.^1-3,5

Palisaded neutrophilic and granulomatous dermatitis classically manifests with papules and small plaques on the extensor extremities, with histopathology showing characteristic necrobiosis with both neutrophils and histiocytes.^1,2,6 We report 6 cases of RGD, including an index case in which a predominance of neutrophils in the infiltrate impeded the diagnosis.

An 85-year-old woman (the index patient) presented with a several-week history of asymmetric crusted papules on the right upper extremity—3 lesions on the elbow and forearm and 1 lesion on a finger. She was an avid gardener with severe rheumatoid arthritis treated with Janus kinase (JAK) inhibitor therapy. An initial biopsy of the elbow revealed a dense infiltrate of neutrophils and sparse eosinophils within the dermis. Special stains for bacterial, fungal, and acid-fast organisms were negative.

Because infection with sporotrichoid spread remained high in the differential diagnosis, the JAK inhibitor was discontinued and an antifungal agent was initiated. Given the persistence of the lesions, a subsequent biopsy of the right finger revealed scarce neutrophils and predominant histiocytes with rare foci of degenerated collagen. Sporotrichosis remained the leading diagnosis for these unilateral lesions. The patient subsequently developed additional crusted papules on the left arm (Figure 1). A biopsy of a left elbow lesion revealed palisades of histiocytes around degenerated collagen and collections of neutrophils compatible with RGD (Figures 2 and 3). Incidentally, the patient also presented with bilateral lower extremity palpable purpura, with a biopsy showing leukocytoclastic vasculitis. Antifungal therapy was discontinued and JAK inhibitor therapy resumed, with partial resolution of both the arm and right finger lesions and complete resolution of the lower extremity palpable purpura over several months.

The dense neutrophilic infiltrate and asymmetric presentation seen in our index patient’s initial biopsy hindered categorization of the cutaneous findings as RGD in association with her rheumatoid arthritis rather than as an infectious process. To ascertain whether diagnosis also was difficult in other cases of RGD, we conducted a search of the Yale Dermatopathology database for the diagnosis palisaded neutrophilic and granulomatous dermatitis, a term consistently used at our institution over the past decade. This study was approved by the institutional review board of Yale University (New Haven, Connecticut), and informed consent was waived. The search covered a 10-year period; 13 patients were found. Eight patients were eliminated because further clinical information or follow-up could not be obtained, leaving 5 additional cases (Table). The 8 eliminated cases were consultations submitted to the laboratory by outside pathologists from other institutions.