Photo Challenge

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Dermatitis Herpetiformis 

Dermatitis herpetiformis (DH), also known as Duhring disease, is a rare autoimmune disease. It is the cutaneous manifestation of gluten sensitivity with antibodies targeting epidermal transglutaminase.¹ Symptoms of DH generally arise in the fourth decade of life, and children are less commonly affected,² though the diagnosis should be considered at any age, as our patient was aged 19 years at the time of presentation. Dermatitis herpetiformis predominantly affects white individuals of Northern European heritage, and males more often are affected than females.² There is a strong association with HLA-B8, HLA-DR3, and HLA-DQw2.³ It also is associated with other autoimmune disorders, including autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia.² 

Clinically, DH is characterized by groups of intensely pruritic papulovesicles that are symmetrically located on the extensor surfaces of the upper and lower extremities, scalp, nuchal area, back, and buttocks (quiz image). Less often, the groin also may be involved, as it was in our patient (Figure 1).⁴ Lesions can be papulovesicular or bullous, though they often are excoriated, and primary lesions may be difficult to identify.² The disease may have spontaneous remissions with frequent relapses. Most patients with DH have an asymptomatic gluten-sensitive enteropathy.³ 

A punch biopsy of a representative nonexcoriated lesion from our patient showed the characteristic collections of neutrophils and fibrin at the tips of dermal papillae on hematoxylin and eosin staining (Figure 2). These findings are suggestive of DH.¹ However, other bullous diseases, such as linear IgA dermatosis and epidermolysis bullosa acquisita, may have similar appearance on histology.¹ Direct immunofluorescence (DIF) of perilesional skin is the gold standard for diagnosing DH, with a sensitivity and specificity close to 100%.¹ Deposits of IgA generally are concentrated in previously involved skin or noninflamed perilesional skin; DIF of erythematous or lesional skin may be false negative.⁵ In our patient, DIF of perilesional uninvolved skin showed granular deposits of IgA at the dermoepidermal junction with accentuation in the dermal papillae (Figure 3), further suggestive of the diagnosis of DH.⁶ 

Patients with DH frequently will have specific IgA antibodies including anti-tissue transglutaminase (tTG), anti-epidermal transglutaminase, antiendomysial antibodies, and anti-synthetic deamidated gliadin peptides.¹ Only some of these tests are widely available, and the anti-tTG enzyme-linked immunosorbent assay is the least expensive and easiest to perform. A positive anti-tTG antibody test has a sensitivity ranging from 47% to 95% and a specificity greater than 90%.¹ Our patient tested positive for anti-tTG and anti-deamidated synthetic gliadin-derived peptides. A diagnostic algorithm based on current evidence suggests that in patients with clinical evidence of DH, typical DIF findings combined with positive anti-tTG antibodies confirms the diagnosis of DH, as was seen in our patient.^1,7 In situations where histopathology and/or antibody testing are inconclusive, additional testing to include HLA antigen typing, duodenal biopsy, and supplemental skin biopsies may be performed to help confirm or exclude a diagnosis of DH. It is unnecessary to perform a duodenal biopsy in patients with a confirmed diagnosis of DH, as DH is considered the specific cutaneous manifestation of celiac disease, and the diagnosis of DH is a diagnosis of celiac disease.¹  

Although pruritic papules may be found in several conditions, clinical, histopathologic, and DIF findings can help to confirm the diagnosis. Allergic contact dermatitis is a type IV hypersensitivity reaction causing eruptions of varying morphology, generally manifesting as pruritic scaly plaques that can occur anywhere on the body exposed to the offending allergen. Key histopathologic features of allergic contact dermatitis are eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes.⁸ Papular urticaria is a hypersensitivity disorder to insect bites that consists of pruritic papules on exposed areas of skin, typically in children younger than 10 years. Genital and axillary areas usually are spared. The diagnosis is clinical.⁹ Recurrent herpes simplex virus infection is a short-lived outbreak that generally improves within 10 days. Herpes simplex virus infections usually are comprised of small vesicular or ulcerative lesions. Tzanck smear, skin biopsy, direct fluorescent antibody, viral culture, and polymerase chain reaction are diagnostic methods for herpes simplex virus.¹⁰ Scabies lesions typically are pruritic, erythematous, often excoriated papules and burrows located most commonly in the webs of fingers, wrists, axillae, areolae, waist, and genitalia. Diagnosis can be confirmed with scabies preparation (skin scraping showing mites, eggs, or feces), dermoscopy showing mites and burrows in vivo, or biopsy.¹¹  

First-line treatment in patients with DH and celiac disease is a strict gluten-free diet (GFD).¹ A GFD will resolve the cutaneous and gastrointestinal manifestations and is the only thing that will reduce the risk for lymphoma and other diseases associated with gluten-induced enteropathy.^1,2 A GFD alone will provide symptomatic relief over several months; dapsone and sulfapyridine can provide rapid relief of the pruritus and skin manifestations and usually can be weaned or discontinued after several months of following a strict GFD.¹² Patients on sulfone therapy require regular follow-up and monitoring due to the risk for hemolytic anemia and other adverse effects as well as to determine the appropriate time to discontinue the medication.¹² Although some patients are able to tolerate reintroduction of gluten into their diets after a period of remission, most will experience recurrent dermatologic manifestations if they continue to consume gluten.³ 

Because of our patient's impending move out of the area, no oral medications were started, and he was instructed to follow a GFD and seek medical care at his new location. The patient was contacted 6 months later and reported resolution of all skin lesions with just a GFD. The patient continued to follow-up with a dermatologist and gastroenterologist at his new location.

The Diagnosis: Dermatitis Herpetiformis 

Dermatitis herpetiformis (DH), also known as Duhring disease, is a rare autoimmune disease. It is the cutaneous manifestation of gluten sensitivity with antibodies targeting epidermal transglutaminase.¹ Symptoms of DH generally arise in the fourth decade of life, and children are less commonly affected,² though the diagnosis should be considered at any age, as our patient was aged 19 years at the time of presentation. Dermatitis herpetiformis predominantly affects white individuals of Northern European heritage, and males more often are affected than females.² There is a strong association with HLA-B8, HLA-DR3, and HLA-DQw2.³ It also is associated with other autoimmune disorders, including autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia.² 

Clinically, DH is characterized by groups of intensely pruritic papulovesicles that are symmetrically located on the extensor surfaces of the upper and lower extremities, scalp, nuchal area, back, and buttocks (quiz image). Less often, the groin also may be involved, as it was in our patient (Figure 1).⁴ Lesions can be papulovesicular or bullous, though they often are excoriated, and primary lesions may be difficult to identify.² The disease may have spontaneous remissions with frequent relapses. Most patients with DH have an asymptomatic gluten-sensitive enteropathy.³ 

A punch biopsy of a representative nonexcoriated lesion from our patient showed the characteristic collections of neutrophils and fibrin at the tips of dermal papillae on hematoxylin and eosin staining (Figure 2). These findings are suggestive of DH.¹ However, other bullous diseases, such as linear IgA dermatosis and epidermolysis bullosa acquisita, may have similar appearance on histology.¹ Direct immunofluorescence (DIF) of perilesional skin is the gold standard for diagnosing DH, with a sensitivity and specificity close to 100%.¹ Deposits of IgA generally are concentrated in previously involved skin or noninflamed perilesional skin; DIF of erythematous or lesional skin may be false negative.⁵ In our patient, DIF of perilesional uninvolved skin showed granular deposits of IgA at the dermoepidermal junction with accentuation in the dermal papillae (Figure 3), further suggestive of the diagnosis of DH.⁶ 

Patients with DH frequently will have specific IgA antibodies including anti-tissue transglutaminase (tTG), anti-epidermal transglutaminase, antiendomysial antibodies, and anti-synthetic deamidated gliadin peptides.¹ Only some of these tests are widely available, and the anti-tTG enzyme-linked immunosorbent assay is the least expensive and easiest to perform. A positive anti-tTG antibody test has a sensitivity ranging from 47% to 95% and a specificity greater than 90%.¹ Our patient tested positive for anti-tTG and anti-deamidated synthetic gliadin-derived peptides. A diagnostic algorithm based on current evidence suggests that in patients with clinical evidence of DH, typical DIF findings combined with positive anti-tTG antibodies confirms the diagnosis of DH, as was seen in our patient.^1,7 In situations where histopathology and/or antibody testing are inconclusive, additional testing to include HLA antigen typing, duodenal biopsy, and supplemental skin biopsies may be performed to help confirm or exclude a diagnosis of DH. It is unnecessary to perform a duodenal biopsy in patients with a confirmed diagnosis of DH, as DH is considered the specific cutaneous manifestation of celiac disease, and the diagnosis of DH is a diagnosis of celiac disease.¹  

Although pruritic papules may be found in several conditions, clinical, histopathologic, and DIF findings can help to confirm the diagnosis. Allergic contact dermatitis is a type IV hypersensitivity reaction causing eruptions of varying morphology, generally manifesting as pruritic scaly plaques that can occur anywhere on the body exposed to the offending allergen. Key histopathologic features of allergic contact dermatitis are eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes.⁸ Papular urticaria is a hypersensitivity disorder to insect bites that consists of pruritic papules on exposed areas of skin, typically in children younger than 10 years. Genital and axillary areas usually are spared. The diagnosis is clinical.⁹ Recurrent herpes simplex virus infection is a short-lived outbreak that generally improves within 10 days. Herpes simplex virus infections usually are comprised of small vesicular or ulcerative lesions. Tzanck smear, skin biopsy, direct fluorescent antibody, viral culture, and polymerase chain reaction are diagnostic methods for herpes simplex virus.¹⁰ Scabies lesions typically are pruritic, erythematous, often excoriated papules and burrows located most commonly in the webs of fingers, wrists, axillae, areolae, waist, and genitalia. Diagnosis can be confirmed with scabies preparation (skin scraping showing mites, eggs, or feces), dermoscopy showing mites and burrows in vivo, or biopsy.¹¹  

First-line treatment in patients with DH and celiac disease is a strict gluten-free diet (GFD).¹ A GFD will resolve the cutaneous and gastrointestinal manifestations and is the only thing that will reduce the risk for lymphoma and other diseases associated with gluten-induced enteropathy.^1,2 A GFD alone will provide symptomatic relief over several months; dapsone and sulfapyridine can provide rapid relief of the pruritus and skin manifestations and usually can be weaned or discontinued after several months of following a strict GFD.¹² Patients on sulfone therapy require regular follow-up and monitoring due to the risk for hemolytic anemia and other adverse effects as well as to determine the appropriate time to discontinue the medication.¹² Although some patients are able to tolerate reintroduction of gluten into their diets after a period of remission, most will experience recurrent dermatologic manifestations if they continue to consume gluten.³ 

Because of our patient's impending move out of the area, no oral medications were started, and he was instructed to follow a GFD and seek medical care at his new location. The patient was contacted 6 months later and reported resolution of all skin lesions with just a GFD. The patient continued to follow-up with a dermatologist and gastroenterologist at his new location.

The Diagnosis: Dermatitis Herpetiformis 

Dermatitis herpetiformis (DH), also known as Duhring disease, is a rare autoimmune disease. It is the cutaneous manifestation of gluten sensitivity with antibodies targeting epidermal transglutaminase.¹ Symptoms of DH generally arise in the fourth decade of life, and children are less commonly affected,² though the diagnosis should be considered at any age, as our patient was aged 19 years at the time of presentation. Dermatitis herpetiformis predominantly affects white individuals of Northern European heritage, and males more often are affected than females.² There is a strong association with HLA-B8, HLA-DR3, and HLA-DQw2.³ It also is associated with other autoimmune disorders, including autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia.² 

Clinically, DH is characterized by groups of intensely pruritic papulovesicles that are symmetrically located on the extensor surfaces of the upper and lower extremities, scalp, nuchal area, back, and buttocks (quiz image). Less often, the groin also may be involved, as it was in our patient (Figure 1).⁴ Lesions can be papulovesicular or bullous, though they often are excoriated, and primary lesions may be difficult to identify.² The disease may have spontaneous remissions with frequent relapses. Most patients with DH have an asymptomatic gluten-sensitive enteropathy.³ 

A punch biopsy of a representative nonexcoriated lesion from our patient showed the characteristic collections of neutrophils and fibrin at the tips of dermal papillae on hematoxylin and eosin staining (Figure 2). These findings are suggestive of DH.¹ However, other bullous diseases, such as linear IgA dermatosis and epidermolysis bullosa acquisita, may have similar appearance on histology.¹ Direct immunofluorescence (DIF) of perilesional skin is the gold standard for diagnosing DH, with a sensitivity and specificity close to 100%.¹ Deposits of IgA generally are concentrated in previously involved skin or noninflamed perilesional skin; DIF of erythematous or lesional skin may be false negative.⁵ In our patient, DIF of perilesional uninvolved skin showed granular deposits of IgA at the dermoepidermal junction with accentuation in the dermal papillae (Figure 3), further suggestive of the diagnosis of DH.⁶ 

Patients with DH frequently will have specific IgA antibodies including anti-tissue transglutaminase (tTG), anti-epidermal transglutaminase, antiendomysial antibodies, and anti-synthetic deamidated gliadin peptides.¹ Only some of these tests are widely available, and the anti-tTG enzyme-linked immunosorbent assay is the least expensive and easiest to perform. A positive anti-tTG antibody test has a sensitivity ranging from 47% to 95% and a specificity greater than 90%.¹ Our patient tested positive for anti-tTG and anti-deamidated synthetic gliadin-derived peptides. A diagnostic algorithm based on current evidence suggests that in patients with clinical evidence of DH, typical DIF findings combined with positive anti-tTG antibodies confirms the diagnosis of DH, as was seen in our patient.^1,7 In situations where histopathology and/or antibody testing are inconclusive, additional testing to include HLA antigen typing, duodenal biopsy, and supplemental skin biopsies may be performed to help confirm or exclude a diagnosis of DH. It is unnecessary to perform a duodenal biopsy in patients with a confirmed diagnosis of DH, as DH is considered the specific cutaneous manifestation of celiac disease, and the diagnosis of DH is a diagnosis of celiac disease.¹  

Although pruritic papules may be found in several conditions, clinical, histopathologic, and DIF findings can help to confirm the diagnosis. Allergic contact dermatitis is a type IV hypersensitivity reaction causing eruptions of varying morphology, generally manifesting as pruritic scaly plaques that can occur anywhere on the body exposed to the offending allergen. Key histopathologic features of allergic contact dermatitis are eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes.⁸ Papular urticaria is a hypersensitivity disorder to insect bites that consists of pruritic papules on exposed areas of skin, typically in children younger than 10 years. Genital and axillary areas usually are spared. The diagnosis is clinical.⁹ Recurrent herpes simplex virus infection is a short-lived outbreak that generally improves within 10 days. Herpes simplex virus infections usually are comprised of small vesicular or ulcerative lesions. Tzanck smear, skin biopsy, direct fluorescent antibody, viral culture, and polymerase chain reaction are diagnostic methods for herpes simplex virus.¹⁰ Scabies lesions typically are pruritic, erythematous, often excoriated papules and burrows located most commonly in the webs of fingers, wrists, axillae, areolae, waist, and genitalia. Diagnosis can be confirmed with scabies preparation (skin scraping showing mites, eggs, or feces), dermoscopy showing mites and burrows in vivo, or biopsy.¹¹  

First-line treatment in patients with DH and celiac disease is a strict gluten-free diet (GFD).¹ A GFD will resolve the cutaneous and gastrointestinal manifestations and is the only thing that will reduce the risk for lymphoma and other diseases associated with gluten-induced enteropathy.^1,2 A GFD alone will provide symptomatic relief over several months; dapsone and sulfapyridine can provide rapid relief of the pruritus and skin manifestations and usually can be weaned or discontinued after several months of following a strict GFD.¹² Patients on sulfone therapy require regular follow-up and monitoring due to the risk for hemolytic anemia and other adverse effects as well as to determine the appropriate time to discontinue the medication.¹² Although some patients are able to tolerate reintroduction of gluten into their diets after a period of remission, most will experience recurrent dermatologic manifestations if they continue to consume gluten.³ 

Because of our patient's impending move out of the area, no oral medications were started, and he was instructed to follow a GFD and seek medical care at his new location. The patient was contacted 6 months later and reported resolution of all skin lesions with just a GFD. The patient continued to follow-up with a dermatologist and gastroenterologist at his new location.

Shiitake Mushroom Dermatitis 

Given the scattered and erythematous 1- to 2-mm macules and patches in a flagellate pattern on the shoulders, back, and neck, the differential diagnosis included shiitake mushroom dermatitis, bleomycin-induced flagellate dermatitis, dermatomyositis flagellate erythema, excoriation disorder, dermatographism, and keratosis lichenoides chronica. On further questioning, the patient indicated that he had consumed raw shiitake mushrooms 3 days before the onset of the rash. Although the clinical variability for all the conditions on the differential is notable, our patient had a history of consuming raw shiitake mushrooms, denied taking any medications, reported no repeated trauma, and had no muscular involvement or systemic symptoms, making shiitake mushroom dermatitis the most likely diagnosis.¹ Skin biopsy and blood tests were deemed unnecessary. Instead, the patient was prescribed triamcinolone cream 0.1%, counseled to avoid raw or undercooked shiitake mushrooms in the future, and told to follow-up if symptoms did not resolve. The patient's symptoms resolved, as expected. 

Nakamura² first described shiitake mushroom dermatitis in 1977. The condition also is known as flagellate mushroom dermatitis or shiitake toxicoderma. It classically manifests in susceptible patients as a pruritic, linear, flagellated dermatitis within 24 to 48 hours after the consumption of raw or undercooked shiitake mushrooms (Lentinula edodes).³ Although the complete pathogenesis remains unclear, research suggests that either a toxic reaction or a type IV hypersensitivity reaction to lentinan causes the eruption. Lentinan is a thermolabile polysaccharide within the mushroom that is believed to increase the production of IL-1 and cause vasodilatation.⁴  

Shiitake mushroom dermatitis is a clinical diagnosis based on the most common findings of a flagellate-pattern dermatitis consisting of pruritic and erythematous papular or urticarial lesions, usually found on the trunk. Laboratory tests, skin biopsies, and allergy tests have been shown to be nonspecific and inconsistent.⁵ 

Shiitake mushroom dermatitis is a self-limiting condition, with the majority of symptoms resolving after one to several weeks.⁵ The mainstay of treatment is aimed at symptomatic management and usually consists of topical corticosteroids and antihistamines.³ More rapid resolution of symptoms has been reported with the use of short-term balneo-psoralen plus UVA therapy.⁶ 

Although a 2017 review of the literature described only 9 published cases of shiitake mushroom dermatitis within the United States as of July 2015, this number may be misleading given the possibility of more variable and subtle presentations misdiagnosed as a nonspecific dermatitis.⁵ Given this information and the fact that shiitake mushrooms continue to be a popular choice in American cuisine, this case reminds health care providers of the clinical manifestations, differential diagnosis, and management of flagellate dermatitis caused by consuming shiitake mushrooms.

Shiitake Mushroom Dermatitis 

Given the scattered and erythematous 1- to 2-mm macules and patches in a flagellate pattern on the shoulders, back, and neck, the differential diagnosis included shiitake mushroom dermatitis, bleomycin-induced flagellate dermatitis, dermatomyositis flagellate erythema, excoriation disorder, dermatographism, and keratosis lichenoides chronica. On further questioning, the patient indicated that he had consumed raw shiitake mushrooms 3 days before the onset of the rash. Although the clinical variability for all the conditions on the differential is notable, our patient had a history of consuming raw shiitake mushrooms, denied taking any medications, reported no repeated trauma, and had no muscular involvement or systemic symptoms, making shiitake mushroom dermatitis the most likely diagnosis.¹ Skin biopsy and blood tests were deemed unnecessary. Instead, the patient was prescribed triamcinolone cream 0.1%, counseled to avoid raw or undercooked shiitake mushrooms in the future, and told to follow-up if symptoms did not resolve. The patient's symptoms resolved, as expected. 

Nakamura² first described shiitake mushroom dermatitis in 1977. The condition also is known as flagellate mushroom dermatitis or shiitake toxicoderma. It classically manifests in susceptible patients as a pruritic, linear, flagellated dermatitis within 24 to 48 hours after the consumption of raw or undercooked shiitake mushrooms (Lentinula edodes).³ Although the complete pathogenesis remains unclear, research suggests that either a toxic reaction or a type IV hypersensitivity reaction to lentinan causes the eruption. Lentinan is a thermolabile polysaccharide within the mushroom that is believed to increase the production of IL-1 and cause vasodilatation.⁴  

Shiitake mushroom dermatitis is a clinical diagnosis based on the most common findings of a flagellate-pattern dermatitis consisting of pruritic and erythematous papular or urticarial lesions, usually found on the trunk. Laboratory tests, skin biopsies, and allergy tests have been shown to be nonspecific and inconsistent.⁵ 

Shiitake mushroom dermatitis is a self-limiting condition, with the majority of symptoms resolving after one to several weeks.⁵ The mainstay of treatment is aimed at symptomatic management and usually consists of topical corticosteroids and antihistamines.³ More rapid resolution of symptoms has been reported with the use of short-term balneo-psoralen plus UVA therapy.⁶ 

Although a 2017 review of the literature described only 9 published cases of shiitake mushroom dermatitis within the United States as of July 2015, this number may be misleading given the possibility of more variable and subtle presentations misdiagnosed as a nonspecific dermatitis.⁵ Given this information and the fact that shiitake mushrooms continue to be a popular choice in American cuisine, this case reminds health care providers of the clinical manifestations, differential diagnosis, and management of flagellate dermatitis caused by consuming shiitake mushrooms.

Shiitake Mushroom Dermatitis 

Given the scattered and erythematous 1- to 2-mm macules and patches in a flagellate pattern on the shoulders, back, and neck, the differential diagnosis included shiitake mushroom dermatitis, bleomycin-induced flagellate dermatitis, dermatomyositis flagellate erythema, excoriation disorder, dermatographism, and keratosis lichenoides chronica. On further questioning, the patient indicated that he had consumed raw shiitake mushrooms 3 days before the onset of the rash. Although the clinical variability for all the conditions on the differential is notable, our patient had a history of consuming raw shiitake mushrooms, denied taking any medications, reported no repeated trauma, and had no muscular involvement or systemic symptoms, making shiitake mushroom dermatitis the most likely diagnosis.¹ Skin biopsy and blood tests were deemed unnecessary. Instead, the patient was prescribed triamcinolone cream 0.1%, counseled to avoid raw or undercooked shiitake mushrooms in the future, and told to follow-up if symptoms did not resolve. The patient's symptoms resolved, as expected. 

Nakamura² first described shiitake mushroom dermatitis in 1977. The condition also is known as flagellate mushroom dermatitis or shiitake toxicoderma. It classically manifests in susceptible patients as a pruritic, linear, flagellated dermatitis within 24 to 48 hours after the consumption of raw or undercooked shiitake mushrooms (Lentinula edodes).³ Although the complete pathogenesis remains unclear, research suggests that either a toxic reaction or a type IV hypersensitivity reaction to lentinan causes the eruption. Lentinan is a thermolabile polysaccharide within the mushroom that is believed to increase the production of IL-1 and cause vasodilatation.⁴  

Shiitake mushroom dermatitis is a clinical diagnosis based on the most common findings of a flagellate-pattern dermatitis consisting of pruritic and erythematous papular or urticarial lesions, usually found on the trunk. Laboratory tests, skin biopsies, and allergy tests have been shown to be nonspecific and inconsistent.⁵ 

Shiitake mushroom dermatitis is a self-limiting condition, with the majority of symptoms resolving after one to several weeks.⁵ The mainstay of treatment is aimed at symptomatic management and usually consists of topical corticosteroids and antihistamines.³ More rapid resolution of symptoms has been reported with the use of short-term balneo-psoralen plus UVA therapy.⁶ 

Although a 2017 review of the literature described only 9 published cases of shiitake mushroom dermatitis within the United States as of July 2015, this number may be misleading given the possibility of more variable and subtle presentations misdiagnosed as a nonspecific dermatitis.⁵ Given this information and the fact that shiitake mushrooms continue to be a popular choice in American cuisine, this case reminds health care providers of the clinical manifestations, differential diagnosis, and management of flagellate dermatitis caused by consuming shiitake mushrooms.

The Diagnosis: Birt-Hogg-Dubé Syndrome 

Histopathologic examination revealed a collection of bland spindle cells with perifollicular fibrosis consistent with a fibrofolliculoma, confirming the diagnosis of Birt-Hogg-Dubé syndrome (Figure). Cosmetic treatment with ablative therapy was offered, but the patient declined.  

Birt-Hogg-Dubé syndrome is an autosomal-dominant genodermatosis caused by a loss-of-function mutation in the folliculin gene, FLCN, on chromosome arm 17p11.2.¹ Cutaneous findings include benign follicular hamartomas, such as fibrofolliculomas and trichodiscomas. Angiofibromas, perifollicular fibromas, oral papillomas, and acrochordons also can be present.¹ Cutaneous lesions usually appear on the head and neck in the third decade of life.  

Patients with Birt-Hogg-Dubé syndrome are at an increased risk for pneumothorax and renal cancer, specifically hybrid oncocytic-chromophobe renal cell carcinomas.² In a study of 89 patients with a FLCN mutation, 90% (80/89) of patients had cutaneous lesions, 84% (34/89) had pulmonary cysts, and 34% (30/89) had kidney tumors. Affected individuals were at a higher risk for pneumothorax and kidney tumors if there was a family history of these tumors.²  

Proposed diagnostic criteria include any 1 of the following: 2 or more skin lesions clinically consistent with fibrofolliculomas and 1 histologically confirmed fibrofolliculoma; multiple bilateral pulmonary cysts in the basilar lung with or without pneumothorax before 40 years of age; bilateral multifocal chromophobe renal carcinomas or hybrid oncocytic tumors; combination of cutaneous, pulmonary, or renal manifestation in the patient and family; or a FLCN mutation.³  

Current recommendations for the workup of a patient with Birt-Hogg-Dubé syndrome include referral to genetic counseling for the patient and family, a baseline computed tomography of the chest to evaluate for pulmonary cysts, and gadolinium-enhanced abdominal magnetic resonance imaging starting at 20 years of age and repeated every 3 to 4 years to screen for renal tumors.¹ Pulmonary function tests can be considered if the patient is symptomatic or has a high cyst burden. Patients should be advised against smoking and scuba diving. 

The differential diagnosis of multiple facial papules includes Cowden syndrome, tuberous sclerosis, Brooke-Spiegler syndrome, and Muir-Torre syndrome. Cowden syndrome is caused by a mutation in the protein tyrosine phosphatase gene, PTEN.⁴ The characteristic cutaneous findings on the face are trichilemmomas, which appear as flesh-colored papules that may have a verrucous surface.  

Tuberous sclerosis is caused by mutations in hamartin (TSC1) or tuberin (TSC2). Angiofibromas are most commonly found on the face and appear as flesh-colored to red-brown papules. Fibrous plaques, periungual fibromas, gingival fibromas, hypopigmented macules, and connective tissue nevi also are found in tuberous sclerosis.⁵  

Brooke-Spiegler syndrome is caused by a mutation in the CYLD lysine 63 deubiquitinase gene, CYLD. Trichoepitheliomas, cylindromas, and spiradenomas are caused by the CYLD mutation and appear on the head and neck. Trichoepitheliomas are flesh-colored to pink papules found on the face, often concentrated in the nasolabial folds.⁶ Cylindromas and spiradenomas are flesh-colored to pink papules or nodules most commonly found on the scalp.⁶  

Muir-Torre syndrome is caused by a mutation in DNA mismatch repair genes MSH2 and/or MLH1.⁷ Sebaceous neoplasms, including sebaceous adenomas, sebaceomas, and less frequently sebaceous carcinomas, are characteristic cutaneous findings and appear as pink to yellow papules commonly found on the head and neck.  

Careful history taking, physical examination, and histopathologic analysis are important in recognizing the features of Birt-Hogg-Dubé syndrome. Accurate and timely diagnosis is essential for the appropriate care of patients and their families, given the syndrome's systemic implications.  

The Diagnosis: Birt-Hogg-Dubé Syndrome 

Histopathologic examination revealed a collection of bland spindle cells with perifollicular fibrosis consistent with a fibrofolliculoma, confirming the diagnosis of Birt-Hogg-Dubé syndrome (Figure). Cosmetic treatment with ablative therapy was offered, but the patient declined.  

Birt-Hogg-Dubé syndrome is an autosomal-dominant genodermatosis caused by a loss-of-function mutation in the folliculin gene, FLCN, on chromosome arm 17p11.2.¹ Cutaneous findings include benign follicular hamartomas, such as fibrofolliculomas and trichodiscomas. Angiofibromas, perifollicular fibromas, oral papillomas, and acrochordons also can be present.¹ Cutaneous lesions usually appear on the head and neck in the third decade of life.  

Patients with Birt-Hogg-Dubé syndrome are at an increased risk for pneumothorax and renal cancer, specifically hybrid oncocytic-chromophobe renal cell carcinomas.² In a study of 89 patients with a FLCN mutation, 90% (80/89) of patients had cutaneous lesions, 84% (34/89) had pulmonary cysts, and 34% (30/89) had kidney tumors. Affected individuals were at a higher risk for pneumothorax and kidney tumors if there was a family history of these tumors.²  

Proposed diagnostic criteria include any 1 of the following: 2 or more skin lesions clinically consistent with fibrofolliculomas and 1 histologically confirmed fibrofolliculoma; multiple bilateral pulmonary cysts in the basilar lung with or without pneumothorax before 40 years of age; bilateral multifocal chromophobe renal carcinomas or hybrid oncocytic tumors; combination of cutaneous, pulmonary, or renal manifestation in the patient and family; or a FLCN mutation.³  

Current recommendations for the workup of a patient with Birt-Hogg-Dubé syndrome include referral to genetic counseling for the patient and family, a baseline computed tomography of the chest to evaluate for pulmonary cysts, and gadolinium-enhanced abdominal magnetic resonance imaging starting at 20 years of age and repeated every 3 to 4 years to screen for renal tumors.¹ Pulmonary function tests can be considered if the patient is symptomatic or has a high cyst burden. Patients should be advised against smoking and scuba diving. 

The differential diagnosis of multiple facial papules includes Cowden syndrome, tuberous sclerosis, Brooke-Spiegler syndrome, and Muir-Torre syndrome. Cowden syndrome is caused by a mutation in the protein tyrosine phosphatase gene, PTEN.⁴ The characteristic cutaneous findings on the face are trichilemmomas, which appear as flesh-colored papules that may have a verrucous surface.  

Tuberous sclerosis is caused by mutations in hamartin (TSC1) or tuberin (TSC2). Angiofibromas are most commonly found on the face and appear as flesh-colored to red-brown papules. Fibrous plaques, periungual fibromas, gingival fibromas, hypopigmented macules, and connective tissue nevi also are found in tuberous sclerosis.⁵  

Brooke-Spiegler syndrome is caused by a mutation in the CYLD lysine 63 deubiquitinase gene, CYLD. Trichoepitheliomas, cylindromas, and spiradenomas are caused by the CYLD mutation and appear on the head and neck. Trichoepitheliomas are flesh-colored to pink papules found on the face, often concentrated in the nasolabial folds.⁶ Cylindromas and spiradenomas are flesh-colored to pink papules or nodules most commonly found on the scalp.⁶  

Muir-Torre syndrome is caused by a mutation in DNA mismatch repair genes MSH2 and/or MLH1.⁷ Sebaceous neoplasms, including sebaceous adenomas, sebaceomas, and less frequently sebaceous carcinomas, are characteristic cutaneous findings and appear as pink to yellow papules commonly found on the head and neck.  

Careful history taking, physical examination, and histopathologic analysis are important in recognizing the features of Birt-Hogg-Dubé syndrome. Accurate and timely diagnosis is essential for the appropriate care of patients and their families, given the syndrome's systemic implications.  

The Diagnosis: Birt-Hogg-Dubé Syndrome 

Histopathologic examination revealed a collection of bland spindle cells with perifollicular fibrosis consistent with a fibrofolliculoma, confirming the diagnosis of Birt-Hogg-Dubé syndrome (Figure). Cosmetic treatment with ablative therapy was offered, but the patient declined.  

Birt-Hogg-Dubé syndrome is an autosomal-dominant genodermatosis caused by a loss-of-function mutation in the folliculin gene, FLCN, on chromosome arm 17p11.2.¹ Cutaneous findings include benign follicular hamartomas, such as fibrofolliculomas and trichodiscomas. Angiofibromas, perifollicular fibromas, oral papillomas, and acrochordons also can be present.¹ Cutaneous lesions usually appear on the head and neck in the third decade of life.  

Patients with Birt-Hogg-Dubé syndrome are at an increased risk for pneumothorax and renal cancer, specifically hybrid oncocytic-chromophobe renal cell carcinomas.² In a study of 89 patients with a FLCN mutation, 90% (80/89) of patients had cutaneous lesions, 84% (34/89) had pulmonary cysts, and 34% (30/89) had kidney tumors. Affected individuals were at a higher risk for pneumothorax and kidney tumors if there was a family history of these tumors.²  

Proposed diagnostic criteria include any 1 of the following: 2 or more skin lesions clinically consistent with fibrofolliculomas and 1 histologically confirmed fibrofolliculoma; multiple bilateral pulmonary cysts in the basilar lung with or without pneumothorax before 40 years of age; bilateral multifocal chromophobe renal carcinomas or hybrid oncocytic tumors; combination of cutaneous, pulmonary, or renal manifestation in the patient and family; or a FLCN mutation.³  

Current recommendations for the workup of a patient with Birt-Hogg-Dubé syndrome include referral to genetic counseling for the patient and family, a baseline computed tomography of the chest to evaluate for pulmonary cysts, and gadolinium-enhanced abdominal magnetic resonance imaging starting at 20 years of age and repeated every 3 to 4 years to screen for renal tumors.¹ Pulmonary function tests can be considered if the patient is symptomatic or has a high cyst burden. Patients should be advised against smoking and scuba diving. 

The differential diagnosis of multiple facial papules includes Cowden syndrome, tuberous sclerosis, Brooke-Spiegler syndrome, and Muir-Torre syndrome. Cowden syndrome is caused by a mutation in the protein tyrosine phosphatase gene, PTEN.⁴ The characteristic cutaneous findings on the face are trichilemmomas, which appear as flesh-colored papules that may have a verrucous surface.  

Tuberous sclerosis is caused by mutations in hamartin (TSC1) or tuberin (TSC2). Angiofibromas are most commonly found on the face and appear as flesh-colored to red-brown papules. Fibrous plaques, periungual fibromas, gingival fibromas, hypopigmented macules, and connective tissue nevi also are found in tuberous sclerosis.⁵  

Brooke-Spiegler syndrome is caused by a mutation in the CYLD lysine 63 deubiquitinase gene, CYLD. Trichoepitheliomas, cylindromas, and spiradenomas are caused by the CYLD mutation and appear on the head and neck. Trichoepitheliomas are flesh-colored to pink papules found on the face, often concentrated in the nasolabial folds.⁶ Cylindromas and spiradenomas are flesh-colored to pink papules or nodules most commonly found on the scalp.⁶  

Muir-Torre syndrome is caused by a mutation in DNA mismatch repair genes MSH2 and/or MLH1.⁷ Sebaceous neoplasms, including sebaceous adenomas, sebaceomas, and less frequently sebaceous carcinomas, are characteristic cutaneous findings and appear as pink to yellow papules commonly found on the head and neck.  

Careful history taking, physical examination, and histopathologic analysis are important in recognizing the features of Birt-Hogg-Dubé syndrome. Accurate and timely diagnosis is essential for the appropriate care of patients and their families, given the syndrome's systemic implications.  

The Diagnosis: Actinic Comedonal Plaque  

Histopathologic examination showed multiple small, keratin-filled cystic spaces in the superficial dermis lined by stratified squamous epithelium that keratinized with a granular layer with surrounding solar elastosis (Figure 1). These findings were consistent with an actinic comedonal plaque (ACP), a rare variant of Favre-Racouchot syndrome (FRS). Due to other cases of invasive squamous cell carcinomas developing within these lesions¹ and the patient's history of basal cell carcinoma in the area, it was important to rule out malignancy and further confirm the diagnosis. Thus, an additional biopsy was obtained, which revealed no sign of cellular atypia. The patient was bothered by the appearance and texture of the lesion, so he elected to pursue treatment. Because of the lesion's moderate size and location, surgical excision was not recommended. He was treated with cryosurgery followed by tretinoin gel 0.025% for 3 months (Figure 2). At 1-year follow-up, there was no recurrence and an acceptable cosmetic outcome.  

Actinic comedonal plaques are characterized by cysts, comedones, and papules that form well-defined yellow plaques on the skin after chronic sun exposure.² First described in 1980 by Eastern and Martin,³ these lesions are most often found on the neck, thorax, nasal dorsum, helix, and forearms; they often are mistaken for basal cell carcinomas, chondrodermatitis nodularis chronica helicis, and amyloidosis.^2,4 

Similar to the cases described by Eastern and Martin,³ our patient presented with a solitary 2.8×1.6-cm yellowish and bumpy plaque that was growing on chronically sun-exposed skin of the medial right cheek. The patient's history of smoking and basal cell carcinoma removal led to the following differential diagnoses: recurrent malignancy, tumors of dermal appendages, and xanthelasmalike deposition within a scar, among others.  

Histologic examination demonstrated keratin-filled cystic spaces in the superficial dermis, along with hyperkeratosis and solar elastosis. These findings were consistent with the original histologic descriptions of ACP that were cited as a rare ectopic form of FRS.⁵ Leeuwis-Fedorovich et al¹ described multifocal squamous cell carcinomas arising in a FRS lesion in 2 cases. Additional biopsy was performed in our patient to rule out this possibility. 

Aside from its role in dermatologic malignancy, exposure to UV light can lead to dilation of the sebaceous gland infundibulum and formation of comedones in various locations.² Histologically, lesions of ACP feature dilated, keratin-filled follicles within a matrix of amorphous damaged collagen in the middle and lower dermis, along with elastosis and basophilic degeneration with fragmentation of collagen bundles in the upper dermis coated with flattened epidermis.^2,3  

Several clinical diagnoses were considered in the differential for our patient. In contrast to our patient's solitary lesion, classic FRS--nodular elastosis with cysts and comedones--is characterized by a diffuse yellowish hue of large open black comedones that are symmetrically distributed on the temporal and periorbital areas.⁶  

Xanthoma has several clinical presentations. Plane xanthomas typically develop in skin folds, especially in palmar creases, while xanthelasma typically consists of yellow soft plaques on the eyelids and periorbital skin. Histologically, xanthomas contain lipid-laden macrophages, which were absent in our patient.⁷ 

Cutaneous amyloidosis can be characterized as macular, papular, and nodular. Nodular, the rarest subtype, commonly manifests on the face.⁸ However, its characteristic histologic features include atrophic epidermal changes with an amorphous, eosinophilic-appearing dermis due to amyloid deposition. These findings were absent in our case.  

Recurrent neoplasm would be in the differential diagnosis of any solitary nodule arising within a previously treated site of malignancy, which was excluded by histologic examination of our patient.⁷ 

Topical tretinoin has been demonstrated as effective treatment of both FRS and ACP.^2,9 Other effective treatment modalities include cryotherapy and photoprotection.⁹ For our patient, a combination of cryosurgery and topical tretinoin resulted in depression of the plaque and a good cosmetic outcome. 
 
Acknowledgments
We thank the patient for granting permission to publish this article. We also are indebted to Morgan L. Wilson, MD (Springfield, Illinois), for his expert dermatopathologic evaluation in this case. He has received no compensation for his contribution.  
 

The Diagnosis: Actinic Comedonal Plaque  

Histopathologic examination showed multiple small, keratin-filled cystic spaces in the superficial dermis lined by stratified squamous epithelium that keratinized with a granular layer with surrounding solar elastosis (Figure 1). These findings were consistent with an actinic comedonal plaque (ACP), a rare variant of Favre-Racouchot syndrome (FRS). Due to other cases of invasive squamous cell carcinomas developing within these lesions¹ and the patient's history of basal cell carcinoma in the area, it was important to rule out malignancy and further confirm the diagnosis. Thus, an additional biopsy was obtained, which revealed no sign of cellular atypia. The patient was bothered by the appearance and texture of the lesion, so he elected to pursue treatment. Because of the lesion's moderate size and location, surgical excision was not recommended. He was treated with cryosurgery followed by tretinoin gel 0.025% for 3 months (Figure 2). At 1-year follow-up, there was no recurrence and an acceptable cosmetic outcome.  

Actinic comedonal plaques are characterized by cysts, comedones, and papules that form well-defined yellow plaques on the skin after chronic sun exposure.² First described in 1980 by Eastern and Martin,³ these lesions are most often found on the neck, thorax, nasal dorsum, helix, and forearms; they often are mistaken for basal cell carcinomas, chondrodermatitis nodularis chronica helicis, and amyloidosis.^2,4 

Similar to the cases described by Eastern and Martin,³ our patient presented with a solitary 2.8×1.6-cm yellowish and bumpy plaque that was growing on chronically sun-exposed skin of the medial right cheek. The patient's history of smoking and basal cell carcinoma removal led to the following differential diagnoses: recurrent malignancy, tumors of dermal appendages, and xanthelasmalike deposition within a scar, among others.  

Histologic examination demonstrated keratin-filled cystic spaces in the superficial dermis, along with hyperkeratosis and solar elastosis. These findings were consistent with the original histologic descriptions of ACP that were cited as a rare ectopic form of FRS.⁵ Leeuwis-Fedorovich et al¹ described multifocal squamous cell carcinomas arising in a FRS lesion in 2 cases. Additional biopsy was performed in our patient to rule out this possibility. 

Aside from its role in dermatologic malignancy, exposure to UV light can lead to dilation of the sebaceous gland infundibulum and formation of comedones in various locations.² Histologically, lesions of ACP feature dilated, keratin-filled follicles within a matrix of amorphous damaged collagen in the middle and lower dermis, along with elastosis and basophilic degeneration with fragmentation of collagen bundles in the upper dermis coated with flattened epidermis.^2,3  

Several clinical diagnoses were considered in the differential for our patient. In contrast to our patient's solitary lesion, classic FRS--nodular elastosis with cysts and comedones--is characterized by a diffuse yellowish hue of large open black comedones that are symmetrically distributed on the temporal and periorbital areas.⁶  

Xanthoma has several clinical presentations. Plane xanthomas typically develop in skin folds, especially in palmar creases, while xanthelasma typically consists of yellow soft plaques on the eyelids and periorbital skin. Histologically, xanthomas contain lipid-laden macrophages, which were absent in our patient.⁷ 

Cutaneous amyloidosis can be characterized as macular, papular, and nodular. Nodular, the rarest subtype, commonly manifests on the face.⁸ However, its characteristic histologic features include atrophic epidermal changes with an amorphous, eosinophilic-appearing dermis due to amyloid deposition. These findings were absent in our case.  

Recurrent neoplasm would be in the differential diagnosis of any solitary nodule arising within a previously treated site of malignancy, which was excluded by histologic examination of our patient.⁷ 

Topical tretinoin has been demonstrated as effective treatment of both FRS and ACP.^2,9 Other effective treatment modalities include cryotherapy and photoprotection.⁹ For our patient, a combination of cryosurgery and topical tretinoin resulted in depression of the plaque and a good cosmetic outcome. 
 
Acknowledgments
We thank the patient for granting permission to publish this article. We also are indebted to Morgan L. Wilson, MD (Springfield, Illinois), for his expert dermatopathologic evaluation in this case. He has received no compensation for his contribution.  
 

The Diagnosis: Actinic Comedonal Plaque  

Histopathologic examination showed multiple small, keratin-filled cystic spaces in the superficial dermis lined by stratified squamous epithelium that keratinized with a granular layer with surrounding solar elastosis (Figure 1). These findings were consistent with an actinic comedonal plaque (ACP), a rare variant of Favre-Racouchot syndrome (FRS). Due to other cases of invasive squamous cell carcinomas developing within these lesions¹ and the patient's history of basal cell carcinoma in the area, it was important to rule out malignancy and further confirm the diagnosis. Thus, an additional biopsy was obtained, which revealed no sign of cellular atypia. The patient was bothered by the appearance and texture of the lesion, so he elected to pursue treatment. Because of the lesion's moderate size and location, surgical excision was not recommended. He was treated with cryosurgery followed by tretinoin gel 0.025% for 3 months (Figure 2). At 1-year follow-up, there was no recurrence and an acceptable cosmetic outcome.  

Actinic comedonal plaques are characterized by cysts, comedones, and papules that form well-defined yellow plaques on the skin after chronic sun exposure.² First described in 1980 by Eastern and Martin,³ these lesions are most often found on the neck, thorax, nasal dorsum, helix, and forearms; they often are mistaken for basal cell carcinomas, chondrodermatitis nodularis chronica helicis, and amyloidosis.^2,4 

Similar to the cases described by Eastern and Martin,³ our patient presented with a solitary 2.8×1.6-cm yellowish and bumpy plaque that was growing on chronically sun-exposed skin of the medial right cheek. The patient's history of smoking and basal cell carcinoma removal led to the following differential diagnoses: recurrent malignancy, tumors of dermal appendages, and xanthelasmalike deposition within a scar, among others.  

Histologic examination demonstrated keratin-filled cystic spaces in the superficial dermis, along with hyperkeratosis and solar elastosis. These findings were consistent with the original histologic descriptions of ACP that were cited as a rare ectopic form of FRS.⁵ Leeuwis-Fedorovich et al¹ described multifocal squamous cell carcinomas arising in a FRS lesion in 2 cases. Additional biopsy was performed in our patient to rule out this possibility. 

Aside from its role in dermatologic malignancy, exposure to UV light can lead to dilation of the sebaceous gland infundibulum and formation of comedones in various locations.² Histologically, lesions of ACP feature dilated, keratin-filled follicles within a matrix of amorphous damaged collagen in the middle and lower dermis, along with elastosis and basophilic degeneration with fragmentation of collagen bundles in the upper dermis coated with flattened epidermis.^2,3  

Several clinical diagnoses were considered in the differential for our patient. In contrast to our patient's solitary lesion, classic FRS--nodular elastosis with cysts and comedones--is characterized by a diffuse yellowish hue of large open black comedones that are symmetrically distributed on the temporal and periorbital areas.⁶  

Xanthoma has several clinical presentations. Plane xanthomas typically develop in skin folds, especially in palmar creases, while xanthelasma typically consists of yellow soft plaques on the eyelids and periorbital skin. Histologically, xanthomas contain lipid-laden macrophages, which were absent in our patient.⁷ 

Cutaneous amyloidosis can be characterized as macular, papular, and nodular. Nodular, the rarest subtype, commonly manifests on the face.⁸ However, its characteristic histologic features include atrophic epidermal changes with an amorphous, eosinophilic-appearing dermis due to amyloid deposition. These findings were absent in our case.  

Recurrent neoplasm would be in the differential diagnosis of any solitary nodule arising within a previously treated site of malignancy, which was excluded by histologic examination of our patient.⁷ 

Topical tretinoin has been demonstrated as effective treatment of both FRS and ACP.^2,9 Other effective treatment modalities include cryotherapy and photoprotection.⁹ For our patient, a combination of cryosurgery and topical tretinoin resulted in depression of the plaque and a good cosmetic outcome. 
 
Acknowledgments
We thank the patient for granting permission to publish this article. We also are indebted to Morgan L. Wilson, MD (Springfield, Illinois), for his expert dermatopathologic evaluation in this case. He has received no compensation for his contribution.  
 

The Diagnosis: Mosaic Tuberous Sclerosis 

A punch biopsy of the facial lesion was stained with hematoxylin and eosin, which demonstrated spindled and stellate fibroblasts with dilated blood vessels (Figure), consistent with an angiofibroma. Given the clinical presentation and histologic findings, there was concern for a diagnosis of tuberous sclerosis (TSC). The patient was referred for genetic workup but tested negative for mutations of the TSC genes in the blood. Because the patient had only unilateral facial lesions, a possible cortical tuber, no other symptoms, and tested negative for TSC gene mutations, mosaic TSC was considered a likely diagnosis. Her facial lesions were treated with pulsed dye vascular laser therapy. 

Tuberous sclerosis is an autosomal-dominant neurocutaneous disorder caused by inactivation of the genes TSC1 (encoding hamartin) and TSC2 (encoding tuberin). Mutation results in overactivation of the downstream mTOR (mammalian target of rapamycin) pathway, resulting in abnormal cellular proliferation and hamartomas. These benign tumors can be found in nearly every organ, most often in the central nervous system and skin, and they provide for a highly variable presentation of the disease.¹ 

Tuberous sclerosis affects 1 in 6000 to 10,000 live births and has a prevalence of 1 in 20,000 individuals. Of these individuals, 75% carry sporadic mutations, and 75% to 90% eventually test positive for a TSC gene mutation.² Genetic mosaicism has been reported in 28% of cases affected by large deletions¹ and as few as 1% of cases involving small mutations.³ 

The dermatologic manifestation of mosaic TSC most often includes unilateral angiofibromas, whereas in nonmosaic cases, angiofibromas cover both cheeks, the forehead, and the eyelids. The other skin lesions of TSC--shagreen patches, forehead plaques, hypomelanotic macules, and ungual fibromas--are seen less frequently.^4-6 Additionally, neurologic disease in mosaic patients is notably milder, with 57% of mosaic patients found to have epilepsy compared to 91% of nonmosaic patients.⁷ Our patient had both unilateral facial angiofibromas and a cortical lesion suspicious for a tuber, prompting a suspected diagnosis of mosaic TSC. 

The methods of diagnosis outlined by the International Tuberous Sclerosis Complex Consensus Group pose a challenge in diagnosing mosaic TSC. The clinical criteria require 2 major (eg, multiple angiofibromas, angiomyolipomas, a shagreen patch) and 1 minor feature (eg, dental enamel pit, renal cyst).² However, case reports detailing unilateral facial angiofibromas have described patients with isolated dermatologic findings.^5,6 Further, it has been demonstrated that genetic studies in mosaic TSC can be unreliable depending on the tissue sampled.⁸ Thus, for patients who have mosaic TSC, establishing a definitive diagnosis is not always possible and may rely solely on the clinical picture. 

Considering the differential diagnosis, benign cephalic histiocytosis usually would present with small red-brown macules and papules symmetrically located on the head and neck. The lesions occur at a younger age, usually in the first year or two of life. Fibrofolliculomas present as multiple whitish, slightly larger papules found on the central face. They are a marker for Birt-Hogg-Dubé syndrome, which also is associated with spontaneous pneumothorax.  

Agminated means clustering or grouping of lesions. Agminated melanocytic nevi and agminated Spitz nevi are clusters of nevi. These lesions can vary in size and color. They may be elevated or flat. Melanocytic nevi usually are tan-brown or black. Spitz nevi may be pink or pigmented brown or black. To definitively differentiate between these 2 diagnoses and this patient's diagnosis of angiofibroma, a biopsy is needed.

The Diagnosis: Mosaic Tuberous Sclerosis 

A punch biopsy of the facial lesion was stained with hematoxylin and eosin, which demonstrated spindled and stellate fibroblasts with dilated blood vessels (Figure), consistent with an angiofibroma. Given the clinical presentation and histologic findings, there was concern for a diagnosis of tuberous sclerosis (TSC). The patient was referred for genetic workup but tested negative for mutations of the TSC genes in the blood. Because the patient had only unilateral facial lesions, a possible cortical tuber, no other symptoms, and tested negative for TSC gene mutations, mosaic TSC was considered a likely diagnosis. Her facial lesions were treated with pulsed dye vascular laser therapy. 

Tuberous sclerosis is an autosomal-dominant neurocutaneous disorder caused by inactivation of the genes TSC1 (encoding hamartin) and TSC2 (encoding tuberin). Mutation results in overactivation of the downstream mTOR (mammalian target of rapamycin) pathway, resulting in abnormal cellular proliferation and hamartomas. These benign tumors can be found in nearly every organ, most often in the central nervous system and skin, and they provide for a highly variable presentation of the disease.¹ 

Tuberous sclerosis affects 1 in 6000 to 10,000 live births and has a prevalence of 1 in 20,000 individuals. Of these individuals, 75% carry sporadic mutations, and 75% to 90% eventually test positive for a TSC gene mutation.² Genetic mosaicism has been reported in 28% of cases affected by large deletions¹ and as few as 1% of cases involving small mutations.³ 

The dermatologic manifestation of mosaic TSC most often includes unilateral angiofibromas, whereas in nonmosaic cases, angiofibromas cover both cheeks, the forehead, and the eyelids. The other skin lesions of TSC--shagreen patches, forehead plaques, hypomelanotic macules, and ungual fibromas--are seen less frequently.^4-6 Additionally, neurologic disease in mosaic patients is notably milder, with 57% of mosaic patients found to have epilepsy compared to 91% of nonmosaic patients.⁷ Our patient had both unilateral facial angiofibromas and a cortical lesion suspicious for a tuber, prompting a suspected diagnosis of mosaic TSC. 

The methods of diagnosis outlined by the International Tuberous Sclerosis Complex Consensus Group pose a challenge in diagnosing mosaic TSC. The clinical criteria require 2 major (eg, multiple angiofibromas, angiomyolipomas, a shagreen patch) and 1 minor feature (eg, dental enamel pit, renal cyst).² However, case reports detailing unilateral facial angiofibromas have described patients with isolated dermatologic findings.^5,6 Further, it has been demonstrated that genetic studies in mosaic TSC can be unreliable depending on the tissue sampled.⁸ Thus, for patients who have mosaic TSC, establishing a definitive diagnosis is not always possible and may rely solely on the clinical picture. 

Considering the differential diagnosis, benign cephalic histiocytosis usually would present with small red-brown macules and papules symmetrically located on the head and neck. The lesions occur at a younger age, usually in the first year or two of life. Fibrofolliculomas present as multiple whitish, slightly larger papules found on the central face. They are a marker for Birt-Hogg-Dubé syndrome, which also is associated with spontaneous pneumothorax.  

Agminated means clustering or grouping of lesions. Agminated melanocytic nevi and agminated Spitz nevi are clusters of nevi. These lesions can vary in size and color. They may be elevated or flat. Melanocytic nevi usually are tan-brown or black. Spitz nevi may be pink or pigmented brown or black. To definitively differentiate between these 2 diagnoses and this patient's diagnosis of angiofibroma, a biopsy is needed.

The Diagnosis: Mosaic Tuberous Sclerosis 

A punch biopsy of the facial lesion was stained with hematoxylin and eosin, which demonstrated spindled and stellate fibroblasts with dilated blood vessels (Figure), consistent with an angiofibroma. Given the clinical presentation and histologic findings, there was concern for a diagnosis of tuberous sclerosis (TSC). The patient was referred for genetic workup but tested negative for mutations of the TSC genes in the blood. Because the patient had only unilateral facial lesions, a possible cortical tuber, no other symptoms, and tested negative for TSC gene mutations, mosaic TSC was considered a likely diagnosis. Her facial lesions were treated with pulsed dye vascular laser therapy. 

Tuberous sclerosis is an autosomal-dominant neurocutaneous disorder caused by inactivation of the genes TSC1 (encoding hamartin) and TSC2 (encoding tuberin). Mutation results in overactivation of the downstream mTOR (mammalian target of rapamycin) pathway, resulting in abnormal cellular proliferation and hamartomas. These benign tumors can be found in nearly every organ, most often in the central nervous system and skin, and they provide for a highly variable presentation of the disease.¹ 

Tuberous sclerosis affects 1 in 6000 to 10,000 live births and has a prevalence of 1 in 20,000 individuals. Of these individuals, 75% carry sporadic mutations, and 75% to 90% eventually test positive for a TSC gene mutation.² Genetic mosaicism has been reported in 28% of cases affected by large deletions¹ and as few as 1% of cases involving small mutations.³ 

The dermatologic manifestation of mosaic TSC most often includes unilateral angiofibromas, whereas in nonmosaic cases, angiofibromas cover both cheeks, the forehead, and the eyelids. The other skin lesions of TSC--shagreen patches, forehead plaques, hypomelanotic macules, and ungual fibromas--are seen less frequently.^4-6 Additionally, neurologic disease in mosaic patients is notably milder, with 57% of mosaic patients found to have epilepsy compared to 91% of nonmosaic patients.⁷ Our patient had both unilateral facial angiofibromas and a cortical lesion suspicious for a tuber, prompting a suspected diagnosis of mosaic TSC. 

The methods of diagnosis outlined by the International Tuberous Sclerosis Complex Consensus Group pose a challenge in diagnosing mosaic TSC. The clinical criteria require 2 major (eg, multiple angiofibromas, angiomyolipomas, a shagreen patch) and 1 minor feature (eg, dental enamel pit, renal cyst).² However, case reports detailing unilateral facial angiofibromas have described patients with isolated dermatologic findings.^5,6 Further, it has been demonstrated that genetic studies in mosaic TSC can be unreliable depending on the tissue sampled.⁸ Thus, for patients who have mosaic TSC, establishing a definitive diagnosis is not always possible and may rely solely on the clinical picture. 

Considering the differential diagnosis, benign cephalic histiocytosis usually would present with small red-brown macules and papules symmetrically located on the head and neck. The lesions occur at a younger age, usually in the first year or two of life. Fibrofolliculomas present as multiple whitish, slightly larger papules found on the central face. They are a marker for Birt-Hogg-Dubé syndrome, which also is associated with spontaneous pneumothorax.  

Agminated means clustering or grouping of lesions. Agminated melanocytic nevi and agminated Spitz nevi are clusters of nevi. These lesions can vary in size and color. They may be elevated or flat. Melanocytic nevi usually are tan-brown or black. Spitz nevi may be pink or pigmented brown or black. To definitively differentiate between these 2 diagnoses and this patient's diagnosis of angiofibroma, a biopsy is needed.

The Diagnosis: Congenital Self-healing Reticulohistiocytosis 

Biopsy of a representative lesion from this patient was consistent with congenital self-healing reticulohistiocytosis, as shown in the Figure. Characteristic Langerhans cells were present in the dermis that stained CD1a positive, S-100 positive, and CD68 negative to confirm the diagnosis.

Congenital self-healing reticulohistiocytosis, or Hashimoto-Pritzker syndrome, is a rare benign form of Langerhans cell histiocytosis. It is twice as common in males than females and typically noted at birth or early during the neonatal period. Lesions may present as pink, firm, asymptomatic papulonodular lesions that often ulcerate with possible residual hypopigmentation or hyperpigmentation.¹ The differential diagnosis includes congenital infectious and hematologic diseases typically associated with blueberry muffin baby. Thus, varicella, cytomegalovirus, syphilis, toxoplasmosis, rubella, neuroblastoma, leukemia cutis, and extramedullary hematopoiesis, among others, may be considered. Juvenile xanthogranuloma or urticaria pigmentosa also enter the differential diagnosis given the yellow-brown appearance. As a clonal proliferation of Langerhans cells, pathology reveals lesions that stain positive for CD1a and S-100.²  

Although typically absent, evaluation for systemic involvement is warranted, which may be an early presentation of multisystem Langerhans cell histiocytosis. Continued monitoring is recommended given the risk of relapse and associated mortality. Our patient continues to do well. He will continue to be followed by our team and hematology/oncology during early childhood.  

The treatment of congenital self-healing reticulohistiocytosis may include conservative monitoring, topical steroids, topical nitrogen mustard, tacrolimus, or psoralen plus UVA.³ Surgical excision may be considered for large lesions.  

The Diagnosis: Congenital Self-healing Reticulohistiocytosis 

Biopsy of a representative lesion from this patient was consistent with congenital self-healing reticulohistiocytosis, as shown in the Figure. Characteristic Langerhans cells were present in the dermis that stained CD1a positive, S-100 positive, and CD68 negative to confirm the diagnosis.

Congenital self-healing reticulohistiocytosis, or Hashimoto-Pritzker syndrome, is a rare benign form of Langerhans cell histiocytosis. It is twice as common in males than females and typically noted at birth or early during the neonatal period. Lesions may present as pink, firm, asymptomatic papulonodular lesions that often ulcerate with possible residual hypopigmentation or hyperpigmentation.¹ The differential diagnosis includes congenital infectious and hematologic diseases typically associated with blueberry muffin baby. Thus, varicella, cytomegalovirus, syphilis, toxoplasmosis, rubella, neuroblastoma, leukemia cutis, and extramedullary hematopoiesis, among others, may be considered. Juvenile xanthogranuloma or urticaria pigmentosa also enter the differential diagnosis given the yellow-brown appearance. As a clonal proliferation of Langerhans cells, pathology reveals lesions that stain positive for CD1a and S-100.²  

Although typically absent, evaluation for systemic involvement is warranted, which may be an early presentation of multisystem Langerhans cell histiocytosis. Continued monitoring is recommended given the risk of relapse and associated mortality. Our patient continues to do well. He will continue to be followed by our team and hematology/oncology during early childhood.  

The treatment of congenital self-healing reticulohistiocytosis may include conservative monitoring, topical steroids, topical nitrogen mustard, tacrolimus, or psoralen plus UVA.³ Surgical excision may be considered for large lesions.  

The Diagnosis: Congenital Self-healing Reticulohistiocytosis 

Biopsy of a representative lesion from this patient was consistent with congenital self-healing reticulohistiocytosis, as shown in the Figure. Characteristic Langerhans cells were present in the dermis that stained CD1a positive, S-100 positive, and CD68 negative to confirm the diagnosis.

Congenital self-healing reticulohistiocytosis, or Hashimoto-Pritzker syndrome, is a rare benign form of Langerhans cell histiocytosis. It is twice as common in males than females and typically noted at birth or early during the neonatal period. Lesions may present as pink, firm, asymptomatic papulonodular lesions that often ulcerate with possible residual hypopigmentation or hyperpigmentation.¹ The differential diagnosis includes congenital infectious and hematologic diseases typically associated with blueberry muffin baby. Thus, varicella, cytomegalovirus, syphilis, toxoplasmosis, rubella, neuroblastoma, leukemia cutis, and extramedullary hematopoiesis, among others, may be considered. Juvenile xanthogranuloma or urticaria pigmentosa also enter the differential diagnosis given the yellow-brown appearance. As a clonal proliferation of Langerhans cells, pathology reveals lesions that stain positive for CD1a and S-100.²  

Although typically absent, evaluation for systemic involvement is warranted, which may be an early presentation of multisystem Langerhans cell histiocytosis. Continued monitoring is recommended given the risk of relapse and associated mortality. Our patient continues to do well. He will continue to be followed by our team and hematology/oncology during early childhood.  

The treatment of congenital self-healing reticulohistiocytosis may include conservative monitoring, topical steroids, topical nitrogen mustard, tacrolimus, or psoralen plus UVA.³ Surgical excision may be considered for large lesions.  

The Diagnosis: Herpes Simplex Virus 

A skin biopsy was sent for tissue culture and was negative for mycobacterial, bacterial, and fungal growth. Histopathologic examination showed ballooning degeneration of keratinocytes with herpetic cytopathic effect consistent with herpetic ulceration (Figure). A swab of the lesion on the buttock was sent for human herpesvirus (HHV) and varicella-zoster virus nucleic acid testing, which was positive for HHV-2. She was started on oral valacyclovir 1000 mg twice daily for 10 days and then was continued on chronic suppression with 500 mg once daily. The patient's ulcerations healed slowly over the following few weeks.  

Human herpesvirus 2 is the most common cause of genital ulcer disease and may present as chronic and recurrent ulcers in immunocompromised patients.¹ It usually is spread by sexual contact. Primary infection typically occurs in the cells of the dermis and epidermis. Two weeks after the primary infection, extragenital lesions can occur in the lumbosacral area on the buttocks, fingers, groin, or thighs, as seen in our patient,² which is a direct result of viral shedding and spread. Reactivation of HHV from the ganglia can occur with or without symptoms. Common locations for viral shedding in women are the cervix, vulva, and perianal areas.³ Patients should be counseled to avoid sexual contact during recurrences. 

Cancer patients have a particularly increased risk for developing HHV-2 due to their limited cell-mediated immunity and exposure to immunosuppressive drugs.⁴ Moreover, approximately 5% of immunocompromised patients develop resistance to antiviral therapy.⁵ Although this phenomenon was not observed in our patient, identification of novel strategies to treat these new groups of patients will be essential.  

The differential diagnosis includes perianal candidiasis, which is classified by erythematous plaques with satellite vesicles and pustules. Contact dermatitis is common in the buttock area and usually secondary to ingredients in cleansing wipes and topical treatments. It is defined by a well-demarcated, symmetric rash, which is more eczematous in nature. Cutaneous T-cell lymphoma was high in our differential given the patient's history of the disease. There are many variants, and tumor-stage disease may result in ulceration of the skin. Cutaneous T-cell lymphoma is differentiated by histology with immunophenotyping in conjunction with the clinical picture. Epstein-Barr virus (EBV) may cause genital ulcerations, which can be diagnosed with a positive EBV serology and detection of EBV by a polymerase chain reaction swab of the ulceration. 

The Diagnosis: Herpes Simplex Virus 

A skin biopsy was sent for tissue culture and was negative for mycobacterial, bacterial, and fungal growth. Histopathologic examination showed ballooning degeneration of keratinocytes with herpetic cytopathic effect consistent with herpetic ulceration (Figure). A swab of the lesion on the buttock was sent for human herpesvirus (HHV) and varicella-zoster virus nucleic acid testing, which was positive for HHV-2. She was started on oral valacyclovir 1000 mg twice daily for 10 days and then was continued on chronic suppression with 500 mg once daily. The patient's ulcerations healed slowly over the following few weeks.  

Human herpesvirus 2 is the most common cause of genital ulcer disease and may present as chronic and recurrent ulcers in immunocompromised patients.¹ It usually is spread by sexual contact. Primary infection typically occurs in the cells of the dermis and epidermis. Two weeks after the primary infection, extragenital lesions can occur in the lumbosacral area on the buttocks, fingers, groin, or thighs, as seen in our patient,² which is a direct result of viral shedding and spread. Reactivation of HHV from the ganglia can occur with or without symptoms. Common locations for viral shedding in women are the cervix, vulva, and perianal areas.³ Patients should be counseled to avoid sexual contact during recurrences. 

Cancer patients have a particularly increased risk for developing HHV-2 due to their limited cell-mediated immunity and exposure to immunosuppressive drugs.⁴ Moreover, approximately 5% of immunocompromised patients develop resistance to antiviral therapy.⁵ Although this phenomenon was not observed in our patient, identification of novel strategies to treat these new groups of patients will be essential.  

The differential diagnosis includes perianal candidiasis, which is classified by erythematous plaques with satellite vesicles and pustules. Contact dermatitis is common in the buttock area and usually secondary to ingredients in cleansing wipes and topical treatments. It is defined by a well-demarcated, symmetric rash, which is more eczematous in nature. Cutaneous T-cell lymphoma was high in our differential given the patient's history of the disease. There are many variants, and tumor-stage disease may result in ulceration of the skin. Cutaneous T-cell lymphoma is differentiated by histology with immunophenotyping in conjunction with the clinical picture. Epstein-Barr virus (EBV) may cause genital ulcerations, which can be diagnosed with a positive EBV serology and detection of EBV by a polymerase chain reaction swab of the ulceration. 

The Diagnosis: Herpes Simplex Virus 

A skin biopsy was sent for tissue culture and was negative for mycobacterial, bacterial, and fungal growth. Histopathologic examination showed ballooning degeneration of keratinocytes with herpetic cytopathic effect consistent with herpetic ulceration (Figure). A swab of the lesion on the buttock was sent for human herpesvirus (HHV) and varicella-zoster virus nucleic acid testing, which was positive for HHV-2. She was started on oral valacyclovir 1000 mg twice daily for 10 days and then was continued on chronic suppression with 500 mg once daily. The patient's ulcerations healed slowly over the following few weeks.  

Human herpesvirus 2 is the most common cause of genital ulcer disease and may present as chronic and recurrent ulcers in immunocompromised patients.¹ It usually is spread by sexual contact. Primary infection typically occurs in the cells of the dermis and epidermis. Two weeks after the primary infection, extragenital lesions can occur in the lumbosacral area on the buttocks, fingers, groin, or thighs, as seen in our patient,² which is a direct result of viral shedding and spread. Reactivation of HHV from the ganglia can occur with or without symptoms. Common locations for viral shedding in women are the cervix, vulva, and perianal areas.³ Patients should be counseled to avoid sexual contact during recurrences. 

Cancer patients have a particularly increased risk for developing HHV-2 due to their limited cell-mediated immunity and exposure to immunosuppressive drugs.⁴ Moreover, approximately 5% of immunocompromised patients develop resistance to antiviral therapy.⁵ Although this phenomenon was not observed in our patient, identification of novel strategies to treat these new groups of patients will be essential.  

The differential diagnosis includes perianal candidiasis, which is classified by erythematous plaques with satellite vesicles and pustules. Contact dermatitis is common in the buttock area and usually secondary to ingredients in cleansing wipes and topical treatments. It is defined by a well-demarcated, symmetric rash, which is more eczematous in nature. Cutaneous T-cell lymphoma was high in our differential given the patient's history of the disease. There are many variants, and tumor-stage disease may result in ulceration of the skin. Cutaneous T-cell lymphoma is differentiated by histology with immunophenotyping in conjunction with the clinical picture. Epstein-Barr virus (EBV) may cause genital ulcerations, which can be diagnosed with a positive EBV serology and detection of EBV by a polymerase chain reaction swab of the ulceration. 

The Diagnosis: Inflammatory Urothelial Carcinoma 

Microscopic examination revealed metastatic carcinoma with extensive dermal lymphatic invasion (Figure). Immunohistochemical stains were positive for p63 and GATA3, markers for urothelial carcinomas, and negative for S-100 and Melan-A, markers for melanoma. Thus, the biopsy was compatible with a diagnosis of urothelial carcinoma. Gram and Grocott-Gomori methenamine-silver stains were negative for bacterial or fungal organisms. An additional 4-mm punch biopsy was performed of the left thigh at the distal-most aspect of the eruption to determine the extent of cutaneous metastasis. Pathology again showed metastatic urothelial carcinoma with extensive dermal lymphatic involvement and overlying epidermal spongiosis.

The patient had a history of bladder cancer diagnosed 1.5 years prior to presentation. It was a high-grade (World Health Organization) urothelial carcinoma that penetrated the bladder muscular wall, focally infiltrating into pericystic fat with multifocal seeding of pericystic lymphatics. It was unresponsive to bacillus Calmette-Guérin therapy. He underwent a cystoprostatectomy and bilateral staging lymph node dissection with clear surgical margins without adjuvant chemotherapy or radiation. He also reported a history of 2 prior cutaneous melanomas that were excised without sentinel lymph node biopsy. 

Four months prior to presentation, he developed a mildly pruritic cutaneous eruption on the abdomen that was treated with topical miconazole for presumed tinea cruris without improvement. He also was previously diagnosed with candidiasis of his urostomy and was taking oral fluconazole. The patient was admitted for the abdominal pain and distension, and computed tomography of the abdomen and pelvis revealed peritoneal carcinomatosis resulting in mechanical small bowel obstruction as well as enlarged pelvic and retroperitoneal lymph nodes. Confirmation of metastatic disease via skin biopsy avoided an invasive peritoneal biopsy. He was treated with triamcinolone acetonide ointment 0.1% with moderate relief of pruritus, and a palliative percutaneous endoscopic gastrostomy tube was placed for bowel decompression. The patient's hospital course was complicated by Proteus mirabilis bacteremia requiring cefepime. He was transitioned to home hospice and died 1 month after presentation. 

Inflammatory carcinoma, also called carcinoma erysipeloides, is a type of cutaneous metastasis most commonly seen in breast adenocarcinoma. Reported cases secondary to urothelial carcinoma are rare and most often involve the abdomen, groin, and lower extremities.^1-5 Clinically, inflammatory carcinoma presents as erythematous indurated patches or plaques with well-defined borders, often with edema, warmth, and tenderness. Its morphologic appearance is due to the obstruction of lymphatic vessels by tumor cells and the release of inflammatory cytokines. Its presentation can mimic other dermatoses such as cellulitis, erysipelas, fungal infection, radiation dermatitis, Majocchi granuloma, or contact dermatitis.⁶ Cutaneous metastases may be the first clinical manifestations of metastatic disease, and they may occur due to hematogenous and lymphatic spread, direct contiguous tissue invasion, or iatrogenic implantation following surgical excision of the primary tumor. Histologically, nuclear markers GATA3 and p63 stain positively in urothelial carcinomas and are negative in prostatic adenocarcinomas.^7,8 Other markers may be used such as cytokeratins 7 and 20, which are cytoplasmic epithelial markers that both stain positive in urothelial neoplasms.⁹  

Inflammatory carcinoma may be treated with radiation or systemic chemotherapy depending on the extent of systemic involvement in the patient; however, its presence portends a poor prognosis. Less than 1% of genitourinary malignancies have cutaneous involvement, and median disease-specific survival is less than 6 months from presentation of the cutaneous metastasis.¹⁰ Clinicians faced with a recalcitrant inflammatory cutaneous eruption should maintain a high index of suspicion for cutaneous metastases, particularly in patients with a history of cancer. Early dermatology referral may help establish the diagnosis and guide disease-targeted therapy or goals of care discussions. 

The Diagnosis: Inflammatory Urothelial Carcinoma 

Microscopic examination revealed metastatic carcinoma with extensive dermal lymphatic invasion (Figure). Immunohistochemical stains were positive for p63 and GATA3, markers for urothelial carcinomas, and negative for S-100 and Melan-A, markers for melanoma. Thus, the biopsy was compatible with a diagnosis of urothelial carcinoma. Gram and Grocott-Gomori methenamine-silver stains were negative for bacterial or fungal organisms. An additional 4-mm punch biopsy was performed of the left thigh at the distal-most aspect of the eruption to determine the extent of cutaneous metastasis. Pathology again showed metastatic urothelial carcinoma with extensive dermal lymphatic involvement and overlying epidermal spongiosis.

The patient had a history of bladder cancer diagnosed 1.5 years prior to presentation. It was a high-grade (World Health Organization) urothelial carcinoma that penetrated the bladder muscular wall, focally infiltrating into pericystic fat with multifocal seeding of pericystic lymphatics. It was unresponsive to bacillus Calmette-Guérin therapy. He underwent a cystoprostatectomy and bilateral staging lymph node dissection with clear surgical margins without adjuvant chemotherapy or radiation. He also reported a history of 2 prior cutaneous melanomas that were excised without sentinel lymph node biopsy. 

Four months prior to presentation, he developed a mildly pruritic cutaneous eruption on the abdomen that was treated with topical miconazole for presumed tinea cruris without improvement. He also was previously diagnosed with candidiasis of his urostomy and was taking oral fluconazole. The patient was admitted for the abdominal pain and distension, and computed tomography of the abdomen and pelvis revealed peritoneal carcinomatosis resulting in mechanical small bowel obstruction as well as enlarged pelvic and retroperitoneal lymph nodes. Confirmation of metastatic disease via skin biopsy avoided an invasive peritoneal biopsy. He was treated with triamcinolone acetonide ointment 0.1% with moderate relief of pruritus, and a palliative percutaneous endoscopic gastrostomy tube was placed for bowel decompression. The patient's hospital course was complicated by Proteus mirabilis bacteremia requiring cefepime. He was transitioned to home hospice and died 1 month after presentation. 

Inflammatory carcinoma, also called carcinoma erysipeloides, is a type of cutaneous metastasis most commonly seen in breast adenocarcinoma. Reported cases secondary to urothelial carcinoma are rare and most often involve the abdomen, groin, and lower extremities.^1-5 Clinically, inflammatory carcinoma presents as erythematous indurated patches or plaques with well-defined borders, often with edema, warmth, and tenderness. Its morphologic appearance is due to the obstruction of lymphatic vessels by tumor cells and the release of inflammatory cytokines. Its presentation can mimic other dermatoses such as cellulitis, erysipelas, fungal infection, radiation dermatitis, Majocchi granuloma, or contact dermatitis.⁶ Cutaneous metastases may be the first clinical manifestations of metastatic disease, and they may occur due to hematogenous and lymphatic spread, direct contiguous tissue invasion, or iatrogenic implantation following surgical excision of the primary tumor. Histologically, nuclear markers GATA3 and p63 stain positively in urothelial carcinomas and are negative in prostatic adenocarcinomas.^7,8 Other markers may be used such as cytokeratins 7 and 20, which are cytoplasmic epithelial markers that both stain positive in urothelial neoplasms.⁹  

Inflammatory carcinoma may be treated with radiation or systemic chemotherapy depending on the extent of systemic involvement in the patient; however, its presence portends a poor prognosis. Less than 1% of genitourinary malignancies have cutaneous involvement, and median disease-specific survival is less than 6 months from presentation of the cutaneous metastasis.¹⁰ Clinicians faced with a recalcitrant inflammatory cutaneous eruption should maintain a high index of suspicion for cutaneous metastases, particularly in patients with a history of cancer. Early dermatology referral may help establish the diagnosis and guide disease-targeted therapy or goals of care discussions. 

The Diagnosis: Inflammatory Urothelial Carcinoma 

Microscopic examination revealed metastatic carcinoma with extensive dermal lymphatic invasion (Figure). Immunohistochemical stains were positive for p63 and GATA3, markers for urothelial carcinomas, and negative for S-100 and Melan-A, markers for melanoma. Thus, the biopsy was compatible with a diagnosis of urothelial carcinoma. Gram and Grocott-Gomori methenamine-silver stains were negative for bacterial or fungal organisms. An additional 4-mm punch biopsy was performed of the left thigh at the distal-most aspect of the eruption to determine the extent of cutaneous metastasis. Pathology again showed metastatic urothelial carcinoma with extensive dermal lymphatic involvement and overlying epidermal spongiosis.

The patient had a history of bladder cancer diagnosed 1.5 years prior to presentation. It was a high-grade (World Health Organization) urothelial carcinoma that penetrated the bladder muscular wall, focally infiltrating into pericystic fat with multifocal seeding of pericystic lymphatics. It was unresponsive to bacillus Calmette-Guérin therapy. He underwent a cystoprostatectomy and bilateral staging lymph node dissection with clear surgical margins without adjuvant chemotherapy or radiation. He also reported a history of 2 prior cutaneous melanomas that were excised without sentinel lymph node biopsy. 

Four months prior to presentation, he developed a mildly pruritic cutaneous eruption on the abdomen that was treated with topical miconazole for presumed tinea cruris without improvement. He also was previously diagnosed with candidiasis of his urostomy and was taking oral fluconazole. The patient was admitted for the abdominal pain and distension, and computed tomography of the abdomen and pelvis revealed peritoneal carcinomatosis resulting in mechanical small bowel obstruction as well as enlarged pelvic and retroperitoneal lymph nodes. Confirmation of metastatic disease via skin biopsy avoided an invasive peritoneal biopsy. He was treated with triamcinolone acetonide ointment 0.1% with moderate relief of pruritus, and a palliative percutaneous endoscopic gastrostomy tube was placed for bowel decompression. The patient's hospital course was complicated by Proteus mirabilis bacteremia requiring cefepime. He was transitioned to home hospice and died 1 month after presentation. 

Inflammatory carcinoma, also called carcinoma erysipeloides, is a type of cutaneous metastasis most commonly seen in breast adenocarcinoma. Reported cases secondary to urothelial carcinoma are rare and most often involve the abdomen, groin, and lower extremities.^1-5 Clinically, inflammatory carcinoma presents as erythematous indurated patches or plaques with well-defined borders, often with edema, warmth, and tenderness. Its morphologic appearance is due to the obstruction of lymphatic vessels by tumor cells and the release of inflammatory cytokines. Its presentation can mimic other dermatoses such as cellulitis, erysipelas, fungal infection, radiation dermatitis, Majocchi granuloma, or contact dermatitis.⁶ Cutaneous metastases may be the first clinical manifestations of metastatic disease, and they may occur due to hematogenous and lymphatic spread, direct contiguous tissue invasion, or iatrogenic implantation following surgical excision of the primary tumor. Histologically, nuclear markers GATA3 and p63 stain positively in urothelial carcinomas and are negative in prostatic adenocarcinomas.^7,8 Other markers may be used such as cytokeratins 7 and 20, which are cytoplasmic epithelial markers that both stain positive in urothelial neoplasms.⁹  

Inflammatory carcinoma may be treated with radiation or systemic chemotherapy depending on the extent of systemic involvement in the patient; however, its presence portends a poor prognosis. Less than 1% of genitourinary malignancies have cutaneous involvement, and median disease-specific survival is less than 6 months from presentation of the cutaneous metastasis.¹⁰ Clinicians faced with a recalcitrant inflammatory cutaneous eruption should maintain a high index of suspicion for cutaneous metastases, particularly in patients with a history of cancer. Early dermatology referral may help establish the diagnosis and guide disease-targeted therapy or goals of care discussions. 

The Diagnosis: Irritant Contact Dermatitis and Hyperpigmentation Due to Juglone  

Clinical suspicion, resemblance to similar cases, and questioning the patient about his behavior prior to the onset of symptoms led to the diagnosis of irritant contact dermatitis and hyperpigmentation due to juglone in this case. Walnuts belong to the botanical family of Juglandaceae and are the seed of the trees of the genus Juglans, which encompass 24 different species. The nuts from all species included in this genus are edible.¹ The most well-known species of walnut is the common walnut (Juglans regia), which is native to the Balkans region in southeast Europe, southwest and central Asia extending to the Himalayas, and southwest China.¹  

Walnut fruits are rich in phenolic compounds. Thirteen phenolic compounds have been identified in walnut husks including chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, gallic acid, ellagic acid, protocatechuic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin, and juglone.² Juglone, also called 5-hydroxy-1,4-napthoquinone, is a yellow naphthoquinone pigment that occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut (Juglans nigra).^3,4 

Juglans regia, also known as English or Persian walnut, contains potent chemical constituents and has been used to treat diverse ailments such as diarrhea, hyperglycemia, cancer, infectious diseases, anorexia, asthma, helminthiasis, arthritis, sinusitis, stomachache, and skin disorders (eg, eczema; acne; alopecia; scalp itching, peeling, and dandruff), and as an adjunctive emollient and itch-relieving treatment.^5,6 

The juice of walnut shells from the J regia tree have been used for centuries to color the skin and hair.⁷ Irritation and skin hyperpigmentation have been associated with topical walnut use.⁵ As a naphthoquinone, juglone also is reported to exert some toxic effects on normal tissues including acute irritant contact dermatitis.⁴ As the active ingredient from the green husk of walnuts, it has been considered a strong sensitizer in guinea pigs,¹ but contact sensitivity in humans rarely has been reported.⁷  

Juglone is known to react with the keratin proteins present in the skin to form sclerojuglonic compounds, which have UV protection properties and a red-brown color.⁸ The resulting reaction gives rise to chromophore groups with a strong pigmenting action that absorbs visible colors (especially violet) and reflects yellow and red, resulting in the coloration ranging from red to deep brown.⁷ The mechanism of skin pigmentation does not involve the melanocytes. Hyperchromia involving the hands--particularly the palms, fingers, and nails--lasts 1 to 4 weeks depending on the intensity of the pigmentation. Housewives and agricultural workers are the at-risk population.⁷ Acute irritant contact dermatitis and hyperpigmentation due to juglone mainly has been observed during the early autumn in agricultural workers and housewives who remove the green husk of walnuts.⁹  

Addison disease can present with pigmentary changes in the skin and mucous membranes; it also is accompanied by fatigue, anorexia, weakness, and weight loss, none of which were noted in our patient. A fixed drug eruption tends to have an annular or oval form and is related to the intake of medication (mostly antibiotics) up to 2 weeks prior to the onset of the dermatosis. Our patient did not have any chronic disease or take any medication prior to the dermatosis and lacked the classic clinical morphology of this entity. Hemochromatosis affects not only the skin but also the liver, myocardial fibers, and other internal organs. Our patient did not have any clinical manifestations of liver or heart failure or diabetes mellitus.  

Our patient was treated with drainage of the blisters. Due to the extent of the dermatosis, prednisone 25 mg/d also was initiated. The patient was instructed to avoid direct contact with the husk of walnuts. At 1-month follow-up, the hyperpigmentation had resolved with no relapse (Figure). 

The Diagnosis: Irritant Contact Dermatitis and Hyperpigmentation Due to Juglone  

Clinical suspicion, resemblance to similar cases, and questioning the patient about his behavior prior to the onset of symptoms led to the diagnosis of irritant contact dermatitis and hyperpigmentation due to juglone in this case. Walnuts belong to the botanical family of Juglandaceae and are the seed of the trees of the genus Juglans, which encompass 24 different species. The nuts from all species included in this genus are edible.¹ The most well-known species of walnut is the common walnut (Juglans regia), which is native to the Balkans region in southeast Europe, southwest and central Asia extending to the Himalayas, and southwest China.¹  

Walnut fruits are rich in phenolic compounds. Thirteen phenolic compounds have been identified in walnut husks including chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, gallic acid, ellagic acid, protocatechuic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin, and juglone.² Juglone, also called 5-hydroxy-1,4-napthoquinone, is a yellow naphthoquinone pigment that occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut (Juglans nigra).^3,4 

Juglans regia, also known as English or Persian walnut, contains potent chemical constituents and has been used to treat diverse ailments such as diarrhea, hyperglycemia, cancer, infectious diseases, anorexia, asthma, helminthiasis, arthritis, sinusitis, stomachache, and skin disorders (eg, eczema; acne; alopecia; scalp itching, peeling, and dandruff), and as an adjunctive emollient and itch-relieving treatment.^5,6 

The juice of walnut shells from the J regia tree have been used for centuries to color the skin and hair.⁷ Irritation and skin hyperpigmentation have been associated with topical walnut use.⁵ As a naphthoquinone, juglone also is reported to exert some toxic effects on normal tissues including acute irritant contact dermatitis.⁴ As the active ingredient from the green husk of walnuts, it has been considered a strong sensitizer in guinea pigs,¹ but contact sensitivity in humans rarely has been reported.⁷  

Juglone is known to react with the keratin proteins present in the skin to form sclerojuglonic compounds, which have UV protection properties and a red-brown color.⁸ The resulting reaction gives rise to chromophore groups with a strong pigmenting action that absorbs visible colors (especially violet) and reflects yellow and red, resulting in the coloration ranging from red to deep brown.⁷ The mechanism of skin pigmentation does not involve the melanocytes. Hyperchromia involving the hands--particularly the palms, fingers, and nails--lasts 1 to 4 weeks depending on the intensity of the pigmentation. Housewives and agricultural workers are the at-risk population.⁷ Acute irritant contact dermatitis and hyperpigmentation due to juglone mainly has been observed during the early autumn in agricultural workers and housewives who remove the green husk of walnuts.⁹  

Addison disease can present with pigmentary changes in the skin and mucous membranes; it also is accompanied by fatigue, anorexia, weakness, and weight loss, none of which were noted in our patient. A fixed drug eruption tends to have an annular or oval form and is related to the intake of medication (mostly antibiotics) up to 2 weeks prior to the onset of the dermatosis. Our patient did not have any chronic disease or take any medication prior to the dermatosis and lacked the classic clinical morphology of this entity. Hemochromatosis affects not only the skin but also the liver, myocardial fibers, and other internal organs. Our patient did not have any clinical manifestations of liver or heart failure or diabetes mellitus.  

Our patient was treated with drainage of the blisters. Due to the extent of the dermatosis, prednisone 25 mg/d also was initiated. The patient was instructed to avoid direct contact with the husk of walnuts. At 1-month follow-up, the hyperpigmentation had resolved with no relapse (Figure). 

The Diagnosis: Irritant Contact Dermatitis and Hyperpigmentation Due to Juglone  

Clinical suspicion, resemblance to similar cases, and questioning the patient about his behavior prior to the onset of symptoms led to the diagnosis of irritant contact dermatitis and hyperpigmentation due to juglone in this case. Walnuts belong to the botanical family of Juglandaceae and are the seed of the trees of the genus Juglans, which encompass 24 different species. The nuts from all species included in this genus are edible.¹ The most well-known species of walnut is the common walnut (Juglans regia), which is native to the Balkans region in southeast Europe, southwest and central Asia extending to the Himalayas, and southwest China.¹  

Walnut fruits are rich in phenolic compounds. Thirteen phenolic compounds have been identified in walnut husks including chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, gallic acid, ellagic acid, protocatechuic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin, and juglone.² Juglone, also called 5-hydroxy-1,4-napthoquinone, is a yellow naphthoquinone pigment that occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut (Juglans nigra).^3,4 

Juglans regia, also known as English or Persian walnut, contains potent chemical constituents and has been used to treat diverse ailments such as diarrhea, hyperglycemia, cancer, infectious diseases, anorexia, asthma, helminthiasis, arthritis, sinusitis, stomachache, and skin disorders (eg, eczema; acne; alopecia; scalp itching, peeling, and dandruff), and as an adjunctive emollient and itch-relieving treatment.^5,6 

The juice of walnut shells from the J regia tree have been used for centuries to color the skin and hair.⁷ Irritation and skin hyperpigmentation have been associated with topical walnut use.⁵ As a naphthoquinone, juglone also is reported to exert some toxic effects on normal tissues including acute irritant contact dermatitis.⁴ As the active ingredient from the green husk of walnuts, it has been considered a strong sensitizer in guinea pigs,¹ but contact sensitivity in humans rarely has been reported.⁷  

Juglone is known to react with the keratin proteins present in the skin to form sclerojuglonic compounds, which have UV protection properties and a red-brown color.⁸ The resulting reaction gives rise to chromophore groups with a strong pigmenting action that absorbs visible colors (especially violet) and reflects yellow and red, resulting in the coloration ranging from red to deep brown.⁷ The mechanism of skin pigmentation does not involve the melanocytes. Hyperchromia involving the hands--particularly the palms, fingers, and nails--lasts 1 to 4 weeks depending on the intensity of the pigmentation. Housewives and agricultural workers are the at-risk population.⁷ Acute irritant contact dermatitis and hyperpigmentation due to juglone mainly has been observed during the early autumn in agricultural workers and housewives who remove the green husk of walnuts.⁹  

Addison disease can present with pigmentary changes in the skin and mucous membranes; it also is accompanied by fatigue, anorexia, weakness, and weight loss, none of which were noted in our patient. A fixed drug eruption tends to have an annular or oval form and is related to the intake of medication (mostly antibiotics) up to 2 weeks prior to the onset of the dermatosis. Our patient did not have any chronic disease or take any medication prior to the dermatosis and lacked the classic clinical morphology of this entity. Hemochromatosis affects not only the skin but also the liver, myocardial fibers, and other internal organs. Our patient did not have any clinical manifestations of liver or heart failure or diabetes mellitus.  

Our patient was treated with drainage of the blisters. Due to the extent of the dermatosis, prednisone 25 mg/d also was initiated. The patient was instructed to avoid direct contact with the husk of walnuts. At 1-month follow-up, the hyperpigmentation had resolved with no relapse (Figure).