Dermatopathology

To the Editor:

Kratom (Mitragyna speciosa) is an evergreen tree native to Southeast Asia.¹ Its leaves contain psychoactive compounds including mitragynine and 7-­hydroxymitragynine, which exert dose-dependent effects on the central nervous system through opioid and monoaminergic receptors.^2,3 At low doses (1–5 g), kratom elicits mild stimulant effects such as increased sociability, alertness, and talkativeness. At high doses (5–15 g), kratom has depressant effects that can provide relief from pain and opioid-withdrawal symptoms.³

Traditionally, kratom has been used in Southeast Asia for recreational and ceremonial purposes, to ease opioid-withdrawal symptoms, and to reduce fatigue from manual labor.⁴ In the 21st century, availability of kratom expanded to Europe, Australia, and the United States, largely facilitated by widespread dissemination of deceitful ­marketing and unregulated sales on the internet.¹ Although large-scale epidemiologic studies evaluating kratom’s prevalence are scarce, available evidence indicates rising worldwide usage, with a notable increase in kratom-related poison center calls between 2011 and 2017 in the United States.⁵ In July 2023, kratom made headlines due to the death of a woman in Florida following use of the substance.⁶

A cross-sectional study revealed that in the United States, kratom typically is used by White individuals for self-treatment of anxiety, depression, pain, and opioid withdrawal.⁷ However, the potential for severe adverse effects and dependence on kratom can outweigh the benefits.^6,8 Reported adverse effects of kratom include tachycardia, hypercholesteremia, liver injury, hallucinations, respiratory depression, seizure, coma, and death.^9,10 We present a case of kratom-induced photodistributed hyperpigmentation.

A 63-year-old man presented to the dermatology clinic with diffuse tender, pruritic, hyperpigmented skin lesions that developed over the course of 1 year. The lesions were distributed on sun-exposed areas, including the face, neck, and forearms (Figure 1). The patient reported no other major symptoms, and his health was otherwise unremarkable. He had a medical history of psoriasiform and spongiotic dermatitis consistent with eczema, psoriasis, hypercholesteremia, and hyperlipidemia. The patient was not taking any medications at the time of presentation. He had a family history of plaque psoriasis in his father. Five years prior to the current presentation, the patient was treated with adalimumab for steroid-resistant psoriasis; however, despite initial improvement, he experienced recurrence of scaly erythematous plaques and had discontinued adalimumab the year prior to presentation.

To the Editor:

Kratom (Mitragyna speciosa) is an evergreen tree native to Southeast Asia.¹ Its leaves contain psychoactive compounds including mitragynine and 7-­hydroxymitragynine, which exert dose-dependent effects on the central nervous system through opioid and monoaminergic receptors.^2,3 At low doses (1–5 g), kratom elicits mild stimulant effects such as increased sociability, alertness, and talkativeness. At high doses (5–15 g), kratom has depressant effects that can provide relief from pain and opioid-withdrawal symptoms.³

Traditionally, kratom has been used in Southeast Asia for recreational and ceremonial purposes, to ease opioid-withdrawal symptoms, and to reduce fatigue from manual labor.⁴ In the 21st century, availability of kratom expanded to Europe, Australia, and the United States, largely facilitated by widespread dissemination of deceitful ­marketing and unregulated sales on the internet.¹ Although large-scale epidemiologic studies evaluating kratom’s prevalence are scarce, available evidence indicates rising worldwide usage, with a notable increase in kratom-related poison center calls between 2011 and 2017 in the United States.⁵ In July 2023, kratom made headlines due to the death of a woman in Florida following use of the substance.⁶

A cross-sectional study revealed that in the United States, kratom typically is used by White individuals for self-treatment of anxiety, depression, pain, and opioid withdrawal.⁷ However, the potential for severe adverse effects and dependence on kratom can outweigh the benefits.^6,8 Reported adverse effects of kratom include tachycardia, hypercholesteremia, liver injury, hallucinations, respiratory depression, seizure, coma, and death.^9,10 We present a case of kratom-induced photodistributed hyperpigmentation.

A 63-year-old man presented to the dermatology clinic with diffuse tender, pruritic, hyperpigmented skin lesions that developed over the course of 1 year. The lesions were distributed on sun-exposed areas, including the face, neck, and forearms (Figure 1). The patient reported no other major symptoms, and his health was otherwise unremarkable. He had a medical history of psoriasiform and spongiotic dermatitis consistent with eczema, psoriasis, hypercholesteremia, and hyperlipidemia. The patient was not taking any medications at the time of presentation. He had a family history of plaque psoriasis in his father. Five years prior to the current presentation, the patient was treated with adalimumab for steroid-resistant psoriasis; however, despite initial improvement, he experienced recurrence of scaly erythematous plaques and had discontinued adalimumab the year prior to presentation.

To the Editor:

Kratom (Mitragyna speciosa) is an evergreen tree native to Southeast Asia.¹ Its leaves contain psychoactive compounds including mitragynine and 7-­hydroxymitragynine, which exert dose-dependent effects on the central nervous system through opioid and monoaminergic receptors.^2,3 At low doses (1–5 g), kratom elicits mild stimulant effects such as increased sociability, alertness, and talkativeness. At high doses (5–15 g), kratom has depressant effects that can provide relief from pain and opioid-withdrawal symptoms.³

Traditionally, kratom has been used in Southeast Asia for recreational and ceremonial purposes, to ease opioid-withdrawal symptoms, and to reduce fatigue from manual labor.⁴ In the 21st century, availability of kratom expanded to Europe, Australia, and the United States, largely facilitated by widespread dissemination of deceitful ­marketing and unregulated sales on the internet.¹ Although large-scale epidemiologic studies evaluating kratom’s prevalence are scarce, available evidence indicates rising worldwide usage, with a notable increase in kratom-related poison center calls between 2011 and 2017 in the United States.⁵ In July 2023, kratom made headlines due to the death of a woman in Florida following use of the substance.⁶

A cross-sectional study revealed that in the United States, kratom typically is used by White individuals for self-treatment of anxiety, depression, pain, and opioid withdrawal.⁷ However, the potential for severe adverse effects and dependence on kratom can outweigh the benefits.^6,8 Reported adverse effects of kratom include tachycardia, hypercholesteremia, liver injury, hallucinations, respiratory depression, seizure, coma, and death.^9,10 We present a case of kratom-induced photodistributed hyperpigmentation.

A 63-year-old man presented to the dermatology clinic with diffuse tender, pruritic, hyperpigmented skin lesions that developed over the course of 1 year. The lesions were distributed on sun-exposed areas, including the face, neck, and forearms (Figure 1). The patient reported no other major symptoms, and his health was otherwise unremarkable. He had a medical history of psoriasiform and spongiotic dermatitis consistent with eczema, psoriasis, hypercholesteremia, and hyperlipidemia. The patient was not taking any medications at the time of presentation. He had a family history of plaque psoriasis in his father. Five years prior to the current presentation, the patient was treated with adalimumab for steroid-resistant psoriasis; however, despite initial improvement, he experienced recurrence of scaly erythematous plaques and had discontinued adalimumab the year prior to presentation.

The Diagnosis: Erythema Nodosum Leprosum

Erythema nodosum leprosum (ENL) is a type 2 reaction sometimes seen in patients infected with Mycobacterium leprae—primarily those with lepromatous or borderline lepromatous subtypes. Clinically, ENL manifests with abrupt onset of tender erythematous papules with associated fevers and general malaise. Studies have demonstrated a complex immune system reaction in ENL, but the detailed pathophysiology is not fully understood.¹ Biopsies conducted within 24 hours of lesion formation are most elucidating. Foamy histiocytes admixed with neutrophils are seen in the subcutis, often causing a lobular panniculitis (quiz image).² Neutrophils rarely are seen in other types of leprosy and thus are a useful diagnostic clue for ENL. Vasculitis of small- to medium-sized vessels can be seen but is not a necessary diagnostic criterion. Fite staining will highlight many acid-fast bacilli within the histiocytes (Figure 1).

Erythema nodosum leprosum is treated with a combination of immunosuppressants such as prednisone and thalidomide. Our patient was taking triple-antibiotic therapy—dapsone, rifampin, and clofazimine—for lepromatous leprosy when the erythematous papules developed on the arms and legs. After a skin biopsy confirmed the diagnosis of ENL, he was started on prednisone 20 mg daily with plans for close follow-up. Unfortunately, the patient was subsequently lost to follow-up.

Acute febrile neutrophilic dermatosis (also known as Sweet syndrome) is an acute inflammatory disease characterized by abrupt onset of painful erythematous papules, plaques, or nodules on the skin. It often is seen in association with preceding infections (especially those in the upper respiratory or gastrointestinal tracts), hematologic malignancies, inflammatory bowel disease, or exposure to certain classes of medications (eg, granulocyte colony-stimulating factor, tyrosine kinase inhibitors, various antibiotics).³ Histologically, acute febrile neutrophilic dermatosis is characterized by dense neutrophilic infiltrates, often with notable dermal edema (Figure 2).⁴ Many cases also show leukocytoclastic vasculitis; however, foamy histiocytes are not a notable component of the inflammatory infiltrate, though a histiocytoid form of acute febrile neutrophilic dermatosis has been described.⁵ Infections must be rigorously ruled out prior to diagnosing a patient with acute febrile neutrophilic dermatosis, making it a diagnosis of exclusion.

Cutaneous coccidioidomycosis is an infection caused by the dimorphic fungi Coccidioides immitis or Coccidioides posadasii. Cutaneous disease is rare but can occur from direct inoculation or dissemination from pulmonary disease in immunocompetent or immunocompromised patients. Papules, pustules, or plaques are seen clinically. Histologically, cutaneous coccidioidomycosis shows spherules that vary from 10 to 100 μm and are filled with multiple smaller endospores (Figure 3).⁶ Pseudoepitheliomatous hyperplasia with dense suppurative and granulomatous infiltrates also is seen.

Erythema induratum is characterized by tender nodules on the lower extremities and has a substantial female predominance. Many cases are associated with Mycobacterium tuberculosis infection. The bacteria are not seen directly in the skin but are instead detectable through DNA polymerase chain reaction testing or investigation of other organ systems.^7,8 Histologically, lesions show a lobular panniculitis with a mixed infiltrate. Vasculitis is seen in approximately 90% of erythema induratum cases vs approximately 25% of classic ENL cases (Figure 4),^2,9 which has led some to use the term nodular vasculitis to describe this disease entity. Nodular vasculitis is considered by others to be a distinct disease entity in which there are clinical and histologic features similar to erythema induratum but no evidence of M tuberculosis infection.⁹

Polyarteritis nodosa is a vasculitis that affects medium- sized vessels of various organ systems. The presenting signs and symptoms vary based on the affected organ systems. Palpable to retiform purpura, livedo racemosa, subcutaneous nodules, or ulcers are seen when the skin is involved. The histologic hallmark is necrotizing vasculitis of medium-sized arterioles (Figure 5), although leukocytoclastic vasculitis of small-caliber vessels also can be seen in biopsies of affected skin.¹⁰ The vascular changes are said to be segmental, with uninvolved segments interspersed with involved segments. Antineutrophil cytoplasmic antibody (ANCA)– associated vasculitis also must be considered when one sees leukocytoclastic vasculitis of small-caliber vessels in the skin, as it can be distinguished most readily by detecting circulating antibodies specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA).

The Diagnosis: Erythema Nodosum Leprosum

Erythema nodosum leprosum (ENL) is a type 2 reaction sometimes seen in patients infected with Mycobacterium leprae—primarily those with lepromatous or borderline lepromatous subtypes. Clinically, ENL manifests with abrupt onset of tender erythematous papules with associated fevers and general malaise. Studies have demonstrated a complex immune system reaction in ENL, but the detailed pathophysiology is not fully understood.¹ Biopsies conducted within 24 hours of lesion formation are most elucidating. Foamy histiocytes admixed with neutrophils are seen in the subcutis, often causing a lobular panniculitis (quiz image).² Neutrophils rarely are seen in other types of leprosy and thus are a useful diagnostic clue for ENL. Vasculitis of small- to medium-sized vessels can be seen but is not a necessary diagnostic criterion. Fite staining will highlight many acid-fast bacilli within the histiocytes (Figure 1).

Erythema nodosum leprosum is treated with a combination of immunosuppressants such as prednisone and thalidomide. Our patient was taking triple-antibiotic therapy—dapsone, rifampin, and clofazimine—for lepromatous leprosy when the erythematous papules developed on the arms and legs. After a skin biopsy confirmed the diagnosis of ENL, he was started on prednisone 20 mg daily with plans for close follow-up. Unfortunately, the patient was subsequently lost to follow-up.

Acute febrile neutrophilic dermatosis (also known as Sweet syndrome) is an acute inflammatory disease characterized by abrupt onset of painful erythematous papules, plaques, or nodules on the skin. It often is seen in association with preceding infections (especially those in the upper respiratory or gastrointestinal tracts), hematologic malignancies, inflammatory bowel disease, or exposure to certain classes of medications (eg, granulocyte colony-stimulating factor, tyrosine kinase inhibitors, various antibiotics).³ Histologically, acute febrile neutrophilic dermatosis is characterized by dense neutrophilic infiltrates, often with notable dermal edema (Figure 2).⁴ Many cases also show leukocytoclastic vasculitis; however, foamy histiocytes are not a notable component of the inflammatory infiltrate, though a histiocytoid form of acute febrile neutrophilic dermatosis has been described.⁵ Infections must be rigorously ruled out prior to diagnosing a patient with acute febrile neutrophilic dermatosis, making it a diagnosis of exclusion.

Cutaneous coccidioidomycosis is an infection caused by the dimorphic fungi Coccidioides immitis or Coccidioides posadasii. Cutaneous disease is rare but can occur from direct inoculation or dissemination from pulmonary disease in immunocompetent or immunocompromised patients. Papules, pustules, or plaques are seen clinically. Histologically, cutaneous coccidioidomycosis shows spherules that vary from 10 to 100 μm and are filled with multiple smaller endospores (Figure 3).⁶ Pseudoepitheliomatous hyperplasia with dense suppurative and granulomatous infiltrates also is seen.

Erythema induratum is characterized by tender nodules on the lower extremities and has a substantial female predominance. Many cases are associated with Mycobacterium tuberculosis infection. The bacteria are not seen directly in the skin but are instead detectable through DNA polymerase chain reaction testing or investigation of other organ systems.^7,8 Histologically, lesions show a lobular panniculitis with a mixed infiltrate. Vasculitis is seen in approximately 90% of erythema induratum cases vs approximately 25% of classic ENL cases (Figure 4),^2,9 which has led some to use the term nodular vasculitis to describe this disease entity. Nodular vasculitis is considered by others to be a distinct disease entity in which there are clinical and histologic features similar to erythema induratum but no evidence of M tuberculosis infection.⁹

Polyarteritis nodosa is a vasculitis that affects medium- sized vessels of various organ systems. The presenting signs and symptoms vary based on the affected organ systems. Palpable to retiform purpura, livedo racemosa, subcutaneous nodules, or ulcers are seen when the skin is involved. The histologic hallmark is necrotizing vasculitis of medium-sized arterioles (Figure 5), although leukocytoclastic vasculitis of small-caliber vessels also can be seen in biopsies of affected skin.¹⁰ The vascular changes are said to be segmental, with uninvolved segments interspersed with involved segments. Antineutrophil cytoplasmic antibody (ANCA)– associated vasculitis also must be considered when one sees leukocytoclastic vasculitis of small-caliber vessels in the skin, as it can be distinguished most readily by detecting circulating antibodies specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA).

The Diagnosis: Erythema Nodosum Leprosum

Erythema nodosum leprosum (ENL) is a type 2 reaction sometimes seen in patients infected with Mycobacterium leprae—primarily those with lepromatous or borderline lepromatous subtypes. Clinically, ENL manifests with abrupt onset of tender erythematous papules with associated fevers and general malaise. Studies have demonstrated a complex immune system reaction in ENL, but the detailed pathophysiology is not fully understood.¹ Biopsies conducted within 24 hours of lesion formation are most elucidating. Foamy histiocytes admixed with neutrophils are seen in the subcutis, often causing a lobular panniculitis (quiz image).² Neutrophils rarely are seen in other types of leprosy and thus are a useful diagnostic clue for ENL. Vasculitis of small- to medium-sized vessels can be seen but is not a necessary diagnostic criterion. Fite staining will highlight many acid-fast bacilli within the histiocytes (Figure 1).

Erythema nodosum leprosum is treated with a combination of immunosuppressants such as prednisone and thalidomide. Our patient was taking triple-antibiotic therapy—dapsone, rifampin, and clofazimine—for lepromatous leprosy when the erythematous papules developed on the arms and legs. After a skin biopsy confirmed the diagnosis of ENL, he was started on prednisone 20 mg daily with plans for close follow-up. Unfortunately, the patient was subsequently lost to follow-up.

Acute febrile neutrophilic dermatosis (also known as Sweet syndrome) is an acute inflammatory disease characterized by abrupt onset of painful erythematous papules, plaques, or nodules on the skin. It often is seen in association with preceding infections (especially those in the upper respiratory or gastrointestinal tracts), hematologic malignancies, inflammatory bowel disease, or exposure to certain classes of medications (eg, granulocyte colony-stimulating factor, tyrosine kinase inhibitors, various antibiotics).³ Histologically, acute febrile neutrophilic dermatosis is characterized by dense neutrophilic infiltrates, often with notable dermal edema (Figure 2).⁴ Many cases also show leukocytoclastic vasculitis; however, foamy histiocytes are not a notable component of the inflammatory infiltrate, though a histiocytoid form of acute febrile neutrophilic dermatosis has been described.⁵ Infections must be rigorously ruled out prior to diagnosing a patient with acute febrile neutrophilic dermatosis, making it a diagnosis of exclusion.

Cutaneous coccidioidomycosis is an infection caused by the dimorphic fungi Coccidioides immitis or Coccidioides posadasii. Cutaneous disease is rare but can occur from direct inoculation or dissemination from pulmonary disease in immunocompetent or immunocompromised patients. Papules, pustules, or plaques are seen clinically. Histologically, cutaneous coccidioidomycosis shows spherules that vary from 10 to 100 μm and are filled with multiple smaller endospores (Figure 3).⁶ Pseudoepitheliomatous hyperplasia with dense suppurative and granulomatous infiltrates also is seen.

Erythema induratum is characterized by tender nodules on the lower extremities and has a substantial female predominance. Many cases are associated with Mycobacterium tuberculosis infection. The bacteria are not seen directly in the skin but are instead detectable through DNA polymerase chain reaction testing or investigation of other organ systems.^7,8 Histologically, lesions show a lobular panniculitis with a mixed infiltrate. Vasculitis is seen in approximately 90% of erythema induratum cases vs approximately 25% of classic ENL cases (Figure 4),^2,9 which has led some to use the term nodular vasculitis to describe this disease entity. Nodular vasculitis is considered by others to be a distinct disease entity in which there are clinical and histologic features similar to erythema induratum but no evidence of M tuberculosis infection.⁹

Polyarteritis nodosa is a vasculitis that affects medium- sized vessels of various organ systems. The presenting signs and symptoms vary based on the affected organ systems. Palpable to retiform purpura, livedo racemosa, subcutaneous nodules, or ulcers are seen when the skin is involved. The histologic hallmark is necrotizing vasculitis of medium-sized arterioles (Figure 5), although leukocytoclastic vasculitis of small-caliber vessels also can be seen in biopsies of affected skin.¹⁰ The vascular changes are said to be segmental, with uninvolved segments interspersed with involved segments. Antineutrophil cytoplasmic antibody (ANCA)– associated vasculitis also must be considered when one sees leukocytoclastic vasculitis of small-caliber vessels in the skin, as it can be distinguished most readily by detecting circulating antibodies specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA).

The Diagnosis: Pityriasis Lichenoides et Varioliformis Acuta

Sectioned punch biopsies were performed on the patient’s right arm. Histopathology showed acanthosis and parakeratosis in the epidermis, with vacuolar degeneration and dyskeratosis in the basal layer. Dermal changes included extravasated red blood cells in the papillary dermis as well as perivascular lymphocytic infiltrates in both the papillary and reticular dermis (Figure). Direct immunofluorescence of a perilesional biopsy using anti–human IgG, IgM, IgA, C3, and fibrin conjugates showed no findings of immune deposition. Biopsy results were consistent with pityriasis lichenoides et varioliformis acuta (PLEVA), and the patient was treated with a 5-day course of oral azithromycin, triamcinolone ointment 0.1% twice daily, and phototherapy with narrowband UVB ³ times weekly. Rapid improvement was noted at 2-month follow-up.

Pityriasis lichenoides et varioliformis acuta is a form of pityriasis lichenoides, a group of inflammatory dermatoses that are characterized clinically by successive crops of morphologically diverse lesions. Epidemiologic studies have shown a slight male predominance. It primarily affects children and young adults, with peak ages of 8 and 32 years in pediatric and adult populations, respectively.¹

The pathogenesis of PLEVA remains unclear. An abnormal immune response to Toxoplasma, Epstein-Barr virus, HIV, and other pathogens has been suggested based on serologic evidence of concurrent disease activity with the onset of lesions as well as cutaneous improvement in some patients after treatment of the infection.¹ A T-cell lymphoproliferative etiology also has been considered based on histopathologic similarities between PLEVA and lymphomatoid papulosis (LyP) as well as findings of clonality in T-cell receptor gene rearrangement in many patients.^1,2 Some clinicians consider LyP and PLEVA as separate entities on one disease spectrum.

Eruptions of PLEVA tend to favor the trunk and proximal extremities. Lesions may begin as macules measuring 2 to 3 mm in diameter that quickly evolve into papules with fine scale that remains attached centrally. Ulcerations with hemorrhagic crusts also may be noted as the lesions progress in stage. The rash may persist for weeks to years, and overlapping crops of macules and papules at varying stages of development may be seen in the same patient.¹

Histopathologic findings of PLEVA include spongiosis, dyskeratosis, parakeratosis, and focal keratinocyte necrosis within the epidermis, as well as vacuolar degeneration of the basal layer. Lymphocyte and erythrocyte extravasation may extend into the epidermis. Dermal findings may include edema and wedge-shaped perivascular lymphocytic infiltrates extending into the reticular dermis.¹

Important differential diagnoses to consider include LyP, mycosis fungoides (MF), pemphigus foliaceus, and varicella. Lymphomatoid papulosis is a benign CD30+ lymphoproliferative disorder that is characterized by an indolent course of recurrent, often self-resolving papules that occur most frequently on the trunk, arms, and legs of older patients. There are several histologic subtypes of LyP, but the most common (type A) may manifest with wedge-shaped perivascular lymphocytic infiltrates in the dermis, similar to PLEVA. T-cell receptor gene rearrangement studies characteristically reveal clonality in LyP, and clonality has been reported in PLEVA. However, LyP demonstrates a higher cytologic grade and lacks the characteristic parakeratotic scale and superficial dermal microhemorrhage of PLEVA.³

Mycosis fungoides is a malignant lymphoproliferative disorder that is characterized by an indolent clinical course of persistent patches, plaques, or tumors of various sizes that often manifest in non–sun-exposed areas of the skin. Early stages of MF are difficult to detect histologically, but biopsies may show atypical lymphocytes with hyperchromatic, irregularly contoured nuclei arranged along the basal layer of the epidermis. Epidermal aggregates of atypical lymphocytes (also known as Pautrier microabscesses) are considered highly specific for MF. T-cell receptor and immunopathologic studies also are important adjuncts in the diagnosis of MF.⁴

Pemphigus foliaceus is an autoimmune blistering disease caused by antibodies directed against desmoglein 1, which is found in the granular layer of the epidermis. It manifests with a subtle onset of scattered crusted lesions in the seborrheic areas, such as the scalp, face, chest, and upper back. Histopathologic findings of early blisters may include acantholysis and dyskeratosis in the stratum granulosum as well as vacuolization of the granular layer. The blisters may coalesce into superficial bullae containing fibrin and neutrophils. Immunofluorescence studies that demonstrate intraepidermal C3 and IgG deposition are key to the diagnosis of pemphigus.⁵

Varicella (also known as chickenpox) manifests with crops of vesicles on an erythematous base in a centripetal distribution favoring the trunk and proximal extremities. It often is preceded by prodromal fever, malaise, and myalgia. Histopathologic evaluation of varicella is uncommon but may reveal acantholysis, multinucleation, and nuclear margination of keratinocytes. Viral culture or nucleic acid amplification testing of lesions can be used to verify the diagnosis.⁶

Most cases of PLEVA resolve without intervention.7 Treatment is directed at speeding recovery, providing symptomatic relief, and limiting permanent sequelae. Topical steroids often are used to alleviate inflammation and pruritus. Systemic antibiotics such as doxycycline, minocycline, and erythromycin have been used for their anti-inflammatory properties. Phototherapy of various wavelengths, including broadband and narrowband UVB as well as psoralen plus UVA, have led to improvements in affected patients. Refractory disease may warrant consideration of therapy with methotrexate, acitretin, dapsone, or cyclosporine.⁷

There have been rare reports of PLEVA evolving into its potentially lethal variant, febrile ulceronecrotic Mucha-Habermann disease, which is differentiated by the presence of systemic manifestations, including high fever, sore throat, diarrhea, central nervous system symptoms, abdominal pain, interstitial pneumonitis, splenomegaly, arthritis, sepsis, megaloblastic anemia, or conjunctival ulcers. The orogenital mucosa may be affected. Cutaneous lesions may rapidly progress to large, generalized, coalescent ulcers with necrotic crusts and vasculitic features on biopsy.8 Malignant transformation of PLEVA into LyP or MF rarely may occur and warrants continued follow-up of unresolved lesions.⁹

The Diagnosis: Pityriasis Lichenoides et Varioliformis Acuta

Sectioned punch biopsies were performed on the patient’s right arm. Histopathology showed acanthosis and parakeratosis in the epidermis, with vacuolar degeneration and dyskeratosis in the basal layer. Dermal changes included extravasated red blood cells in the papillary dermis as well as perivascular lymphocytic infiltrates in both the papillary and reticular dermis (Figure). Direct immunofluorescence of a perilesional biopsy using anti–human IgG, IgM, IgA, C3, and fibrin conjugates showed no findings of immune deposition. Biopsy results were consistent with pityriasis lichenoides et varioliformis acuta (PLEVA), and the patient was treated with a 5-day course of oral azithromycin, triamcinolone ointment 0.1% twice daily, and phototherapy with narrowband UVB ³ times weekly. Rapid improvement was noted at 2-month follow-up.

Pityriasis lichenoides et varioliformis acuta is a form of pityriasis lichenoides, a group of inflammatory dermatoses that are characterized clinically by successive crops of morphologically diverse lesions. Epidemiologic studies have shown a slight male predominance. It primarily affects children and young adults, with peak ages of 8 and 32 years in pediatric and adult populations, respectively.¹

The pathogenesis of PLEVA remains unclear. An abnormal immune response to Toxoplasma, Epstein-Barr virus, HIV, and other pathogens has been suggested based on serologic evidence of concurrent disease activity with the onset of lesions as well as cutaneous improvement in some patients after treatment of the infection.¹ A T-cell lymphoproliferative etiology also has been considered based on histopathologic similarities between PLEVA and lymphomatoid papulosis (LyP) as well as findings of clonality in T-cell receptor gene rearrangement in many patients.^1,2 Some clinicians consider LyP and PLEVA as separate entities on one disease spectrum.

Eruptions of PLEVA tend to favor the trunk and proximal extremities. Lesions may begin as macules measuring 2 to 3 mm in diameter that quickly evolve into papules with fine scale that remains attached centrally. Ulcerations with hemorrhagic crusts also may be noted as the lesions progress in stage. The rash may persist for weeks to years, and overlapping crops of macules and papules at varying stages of development may be seen in the same patient.¹

Histopathologic findings of PLEVA include spongiosis, dyskeratosis, parakeratosis, and focal keratinocyte necrosis within the epidermis, as well as vacuolar degeneration of the basal layer. Lymphocyte and erythrocyte extravasation may extend into the epidermis. Dermal findings may include edema and wedge-shaped perivascular lymphocytic infiltrates extending into the reticular dermis.¹

Important differential diagnoses to consider include LyP, mycosis fungoides (MF), pemphigus foliaceus, and varicella. Lymphomatoid papulosis is a benign CD30+ lymphoproliferative disorder that is characterized by an indolent course of recurrent, often self-resolving papules that occur most frequently on the trunk, arms, and legs of older patients. There are several histologic subtypes of LyP, but the most common (type A) may manifest with wedge-shaped perivascular lymphocytic infiltrates in the dermis, similar to PLEVA. T-cell receptor gene rearrangement studies characteristically reveal clonality in LyP, and clonality has been reported in PLEVA. However, LyP demonstrates a higher cytologic grade and lacks the characteristic parakeratotic scale and superficial dermal microhemorrhage of PLEVA.³

Mycosis fungoides is a malignant lymphoproliferative disorder that is characterized by an indolent clinical course of persistent patches, plaques, or tumors of various sizes that often manifest in non–sun-exposed areas of the skin. Early stages of MF are difficult to detect histologically, but biopsies may show atypical lymphocytes with hyperchromatic, irregularly contoured nuclei arranged along the basal layer of the epidermis. Epidermal aggregates of atypical lymphocytes (also known as Pautrier microabscesses) are considered highly specific for MF. T-cell receptor and immunopathologic studies also are important adjuncts in the diagnosis of MF.⁴

Pemphigus foliaceus is an autoimmune blistering disease caused by antibodies directed against desmoglein 1, which is found in the granular layer of the epidermis. It manifests with a subtle onset of scattered crusted lesions in the seborrheic areas, such as the scalp, face, chest, and upper back. Histopathologic findings of early blisters may include acantholysis and dyskeratosis in the stratum granulosum as well as vacuolization of the granular layer. The blisters may coalesce into superficial bullae containing fibrin and neutrophils. Immunofluorescence studies that demonstrate intraepidermal C3 and IgG deposition are key to the diagnosis of pemphigus.⁵

Varicella (also known as chickenpox) manifests with crops of vesicles on an erythematous base in a centripetal distribution favoring the trunk and proximal extremities. It often is preceded by prodromal fever, malaise, and myalgia. Histopathologic evaluation of varicella is uncommon but may reveal acantholysis, multinucleation, and nuclear margination of keratinocytes. Viral culture or nucleic acid amplification testing of lesions can be used to verify the diagnosis.⁶

Most cases of PLEVA resolve without intervention.7 Treatment is directed at speeding recovery, providing symptomatic relief, and limiting permanent sequelae. Topical steroids often are used to alleviate inflammation and pruritus. Systemic antibiotics such as doxycycline, minocycline, and erythromycin have been used for their anti-inflammatory properties. Phototherapy of various wavelengths, including broadband and narrowband UVB as well as psoralen plus UVA, have led to improvements in affected patients. Refractory disease may warrant consideration of therapy with methotrexate, acitretin, dapsone, or cyclosporine.⁷

There have been rare reports of PLEVA evolving into its potentially lethal variant, febrile ulceronecrotic Mucha-Habermann disease, which is differentiated by the presence of systemic manifestations, including high fever, sore throat, diarrhea, central nervous system symptoms, abdominal pain, interstitial pneumonitis, splenomegaly, arthritis, sepsis, megaloblastic anemia, or conjunctival ulcers. The orogenital mucosa may be affected. Cutaneous lesions may rapidly progress to large, generalized, coalescent ulcers with necrotic crusts and vasculitic features on biopsy.8 Malignant transformation of PLEVA into LyP or MF rarely may occur and warrants continued follow-up of unresolved lesions.⁹

The Diagnosis: Pityriasis Lichenoides et Varioliformis Acuta

Sectioned punch biopsies were performed on the patient’s right arm. Histopathology showed acanthosis and parakeratosis in the epidermis, with vacuolar degeneration and dyskeratosis in the basal layer. Dermal changes included extravasated red blood cells in the papillary dermis as well as perivascular lymphocytic infiltrates in both the papillary and reticular dermis (Figure). Direct immunofluorescence of a perilesional biopsy using anti–human IgG, IgM, IgA, C3, and fibrin conjugates showed no findings of immune deposition. Biopsy results were consistent with pityriasis lichenoides et varioliformis acuta (PLEVA), and the patient was treated with a 5-day course of oral azithromycin, triamcinolone ointment 0.1% twice daily, and phototherapy with narrowband UVB ³ times weekly. Rapid improvement was noted at 2-month follow-up.

Pityriasis lichenoides et varioliformis acuta is a form of pityriasis lichenoides, a group of inflammatory dermatoses that are characterized clinically by successive crops of morphologically diverse lesions. Epidemiologic studies have shown a slight male predominance. It primarily affects children and young adults, with peak ages of 8 and 32 years in pediatric and adult populations, respectively.¹

The pathogenesis of PLEVA remains unclear. An abnormal immune response to Toxoplasma, Epstein-Barr virus, HIV, and other pathogens has been suggested based on serologic evidence of concurrent disease activity with the onset of lesions as well as cutaneous improvement in some patients after treatment of the infection.¹ A T-cell lymphoproliferative etiology also has been considered based on histopathologic similarities between PLEVA and lymphomatoid papulosis (LyP) as well as findings of clonality in T-cell receptor gene rearrangement in many patients.^1,2 Some clinicians consider LyP and PLEVA as separate entities on one disease spectrum.

Eruptions of PLEVA tend to favor the trunk and proximal extremities. Lesions may begin as macules measuring 2 to 3 mm in diameter that quickly evolve into papules with fine scale that remains attached centrally. Ulcerations with hemorrhagic crusts also may be noted as the lesions progress in stage. The rash may persist for weeks to years, and overlapping crops of macules and papules at varying stages of development may be seen in the same patient.¹

Histopathologic findings of PLEVA include spongiosis, dyskeratosis, parakeratosis, and focal keratinocyte necrosis within the epidermis, as well as vacuolar degeneration of the basal layer. Lymphocyte and erythrocyte extravasation may extend into the epidermis. Dermal findings may include edema and wedge-shaped perivascular lymphocytic infiltrates extending into the reticular dermis.¹

Important differential diagnoses to consider include LyP, mycosis fungoides (MF), pemphigus foliaceus, and varicella. Lymphomatoid papulosis is a benign CD30+ lymphoproliferative disorder that is characterized by an indolent course of recurrent, often self-resolving papules that occur most frequently on the trunk, arms, and legs of older patients. There are several histologic subtypes of LyP, but the most common (type A) may manifest with wedge-shaped perivascular lymphocytic infiltrates in the dermis, similar to PLEVA. T-cell receptor gene rearrangement studies characteristically reveal clonality in LyP, and clonality has been reported in PLEVA. However, LyP demonstrates a higher cytologic grade and lacks the characteristic parakeratotic scale and superficial dermal microhemorrhage of PLEVA.³

Mycosis fungoides is a malignant lymphoproliferative disorder that is characterized by an indolent clinical course of persistent patches, plaques, or tumors of various sizes that often manifest in non–sun-exposed areas of the skin. Early stages of MF are difficult to detect histologically, but biopsies may show atypical lymphocytes with hyperchromatic, irregularly contoured nuclei arranged along the basal layer of the epidermis. Epidermal aggregates of atypical lymphocytes (also known as Pautrier microabscesses) are considered highly specific for MF. T-cell receptor and immunopathologic studies also are important adjuncts in the diagnosis of MF.⁴

Pemphigus foliaceus is an autoimmune blistering disease caused by antibodies directed against desmoglein 1, which is found in the granular layer of the epidermis. It manifests with a subtle onset of scattered crusted lesions in the seborrheic areas, such as the scalp, face, chest, and upper back. Histopathologic findings of early blisters may include acantholysis and dyskeratosis in the stratum granulosum as well as vacuolization of the granular layer. The blisters may coalesce into superficial bullae containing fibrin and neutrophils. Immunofluorescence studies that demonstrate intraepidermal C3 and IgG deposition are key to the diagnosis of pemphigus.⁵

Varicella (also known as chickenpox) manifests with crops of vesicles on an erythematous base in a centripetal distribution favoring the trunk and proximal extremities. It often is preceded by prodromal fever, malaise, and myalgia. Histopathologic evaluation of varicella is uncommon but may reveal acantholysis, multinucleation, and nuclear margination of keratinocytes. Viral culture or nucleic acid amplification testing of lesions can be used to verify the diagnosis.⁶

Most cases of PLEVA resolve without intervention.7 Treatment is directed at speeding recovery, providing symptomatic relief, and limiting permanent sequelae. Topical steroids often are used to alleviate inflammation and pruritus. Systemic antibiotics such as doxycycline, minocycline, and erythromycin have been used for their anti-inflammatory properties. Phototherapy of various wavelengths, including broadband and narrowband UVB as well as psoralen plus UVA, have led to improvements in affected patients. Refractory disease may warrant consideration of therapy with methotrexate, acitretin, dapsone, or cyclosporine.⁷

There have been rare reports of PLEVA evolving into its potentially lethal variant, febrile ulceronecrotic Mucha-Habermann disease, which is differentiated by the presence of systemic manifestations, including high fever, sore throat, diarrhea, central nervous system symptoms, abdominal pain, interstitial pneumonitis, splenomegaly, arthritis, sepsis, megaloblastic anemia, or conjunctival ulcers. The orogenital mucosa may be affected. Cutaneous lesions may rapidly progress to large, generalized, coalescent ulcers with necrotic crusts and vasculitic features on biopsy.8 Malignant transformation of PLEVA into LyP or MF rarely may occur and warrants continued follow-up of unresolved lesions.⁹

The Diagnosis: Brunsting-Perry Cicatricial Pemphigoid

Physical examination and histopathology are paramount in diagnosing Brunsting-Perry cicatricial pemphigoid (BPCP). In our patient, histopathology showed subepidermal blistering with a mixed superficial dermal inflammatory cell infiltrate. Direct immunofluorescence was positive for linear IgG and C3 antibodies along the basement membrane. The scarring erosions on the scalp combined with the autoantibody findings on direct immunofluorescence were consistent with BPCP. He was started on dapsone 100 mg daily and demonstrated complete resolution of symptoms after 10 months, with the exception of persistent scarring hair loss (Figure).

Brunsting-Perry cicatricial pemphigoid is a rare dermatologic condition. It was first defined in 1957 when Brunsting and Perry¹ examined 7 patients with cicatricial pemphigoid that predominantly affected the head and neck region, with occasional mucous membrane involvement but no mucosal scarring. Characteristically, BPCP manifests as scarring herpetiform plaques with varied blisters, erosions, crusts, and scarring.¹ It primarily affects middle-aged men.²

Historically, BPCP has been considered a variant of cicatricial pemphigoid (now known as mucous membrane pemphigoid), bullous pemphigoid, or epidermolysis bullosa acquisita.³ The antigen target has not been established clearly; however, autoantibodies against laminin 332, collagen VII, and BP180 and BP230 have been proposed.^2,4,5 Jacoby et al6 described BPCP on a spectrum with bullous pemphigoid and cicatricial pemphigoid, with primarily circulating autoantibodies on one end and tissue-fixed autoantibodies on the other.

The differential for BPCP also includes anti-p200 pemphigoid and anti–laminin 332 pemphigoid. Anti-p200 pemphigoid also is known as bullous pemphigoid with antibodies against the 200-kDa protein.⁷ It may clinically manifest similar to bullous pemphigoid and other subepidermal autoimmune blistering diseases; thus, immunopathologic differentiation can be helpful. Anti–laminin 332 pemphigoid (also known as anti–laminin gamma-1 pemphigoid) is characterized by autoantibodies targeting the laminin 332 protein in the basement membrane zone, resulting in blistering and erosions.⁸ Similar to BPCP and epidermolysis bullosa aquisita, anti–laminin 332 pemphigoid may affect cephalic regions and mucous membrane surfaces, resulting in scarring and cicatricial changes. Anti–laminin 332 pemphigoid also has been associated with internal malignancy.⁸ The use of the salt-split skin technique can be utilized to differentiate these entities based on their autoantibody-binding patterns in relation to the lamina densa.

Treatment options for mild BPCP include potent topical or intralesional steroids and dapsone, while more severe cases may require systemic therapy with rituximab, azathioprine, mycophenolate mofetil, or cyclophosphamide.⁴

This case highlights the importance of histopathologic examination of skin lesions with an unusual history or clinical presentation. Dermatologists should consider BPCP when presented with erosions, ulcerations, or blisters of the head and neck in middle-aged male patients.

The Diagnosis: Brunsting-Perry Cicatricial Pemphigoid

Physical examination and histopathology are paramount in diagnosing Brunsting-Perry cicatricial pemphigoid (BPCP). In our patient, histopathology showed subepidermal blistering with a mixed superficial dermal inflammatory cell infiltrate. Direct immunofluorescence was positive for linear IgG and C3 antibodies along the basement membrane. The scarring erosions on the scalp combined with the autoantibody findings on direct immunofluorescence were consistent with BPCP. He was started on dapsone 100 mg daily and demonstrated complete resolution of symptoms after 10 months, with the exception of persistent scarring hair loss (Figure).

Brunsting-Perry cicatricial pemphigoid is a rare dermatologic condition. It was first defined in 1957 when Brunsting and Perry¹ examined 7 patients with cicatricial pemphigoid that predominantly affected the head and neck region, with occasional mucous membrane involvement but no mucosal scarring. Characteristically, BPCP manifests as scarring herpetiform plaques with varied blisters, erosions, crusts, and scarring.¹ It primarily affects middle-aged men.²

Historically, BPCP has been considered a variant of cicatricial pemphigoid (now known as mucous membrane pemphigoid), bullous pemphigoid, or epidermolysis bullosa acquisita.³ The antigen target has not been established clearly; however, autoantibodies against laminin 332, collagen VII, and BP180 and BP230 have been proposed.^2,4,5 Jacoby et al6 described BPCP on a spectrum with bullous pemphigoid and cicatricial pemphigoid, with primarily circulating autoantibodies on one end and tissue-fixed autoantibodies on the other.

The differential for BPCP also includes anti-p200 pemphigoid and anti–laminin 332 pemphigoid. Anti-p200 pemphigoid also is known as bullous pemphigoid with antibodies against the 200-kDa protein.⁷ It may clinically manifest similar to bullous pemphigoid and other subepidermal autoimmune blistering diseases; thus, immunopathologic differentiation can be helpful. Anti–laminin 332 pemphigoid (also known as anti–laminin gamma-1 pemphigoid) is characterized by autoantibodies targeting the laminin 332 protein in the basement membrane zone, resulting in blistering and erosions.⁸ Similar to BPCP and epidermolysis bullosa aquisita, anti–laminin 332 pemphigoid may affect cephalic regions and mucous membrane surfaces, resulting in scarring and cicatricial changes. Anti–laminin 332 pemphigoid also has been associated with internal malignancy.⁸ The use of the salt-split skin technique can be utilized to differentiate these entities based on their autoantibody-binding patterns in relation to the lamina densa.

Treatment options for mild BPCP include potent topical or intralesional steroids and dapsone, while more severe cases may require systemic therapy with rituximab, azathioprine, mycophenolate mofetil, or cyclophosphamide.⁴

This case highlights the importance of histopathologic examination of skin lesions with an unusual history or clinical presentation. Dermatologists should consider BPCP when presented with erosions, ulcerations, or blisters of the head and neck in middle-aged male patients.

The Diagnosis: Brunsting-Perry Cicatricial Pemphigoid

Physical examination and histopathology are paramount in diagnosing Brunsting-Perry cicatricial pemphigoid (BPCP). In our patient, histopathology showed subepidermal blistering with a mixed superficial dermal inflammatory cell infiltrate. Direct immunofluorescence was positive for linear IgG and C3 antibodies along the basement membrane. The scarring erosions on the scalp combined with the autoantibody findings on direct immunofluorescence were consistent with BPCP. He was started on dapsone 100 mg daily and demonstrated complete resolution of symptoms after 10 months, with the exception of persistent scarring hair loss (Figure).

Brunsting-Perry cicatricial pemphigoid is a rare dermatologic condition. It was first defined in 1957 when Brunsting and Perry¹ examined 7 patients with cicatricial pemphigoid that predominantly affected the head and neck region, with occasional mucous membrane involvement but no mucosal scarring. Characteristically, BPCP manifests as scarring herpetiform plaques with varied blisters, erosions, crusts, and scarring.¹ It primarily affects middle-aged men.²

Historically, BPCP has been considered a variant of cicatricial pemphigoid (now known as mucous membrane pemphigoid), bullous pemphigoid, or epidermolysis bullosa acquisita.³ The antigen target has not been established clearly; however, autoantibodies against laminin 332, collagen VII, and BP180 and BP230 have been proposed.^2,4,5 Jacoby et al6 described BPCP on a spectrum with bullous pemphigoid and cicatricial pemphigoid, with primarily circulating autoantibodies on one end and tissue-fixed autoantibodies on the other.

The differential for BPCP also includes anti-p200 pemphigoid and anti–laminin 332 pemphigoid. Anti-p200 pemphigoid also is known as bullous pemphigoid with antibodies against the 200-kDa protein.⁷ It may clinically manifest similar to bullous pemphigoid and other subepidermal autoimmune blistering diseases; thus, immunopathologic differentiation can be helpful. Anti–laminin 332 pemphigoid (also known as anti–laminin gamma-1 pemphigoid) is characterized by autoantibodies targeting the laminin 332 protein in the basement membrane zone, resulting in blistering and erosions.⁸ Similar to BPCP and epidermolysis bullosa aquisita, anti–laminin 332 pemphigoid may affect cephalic regions and mucous membrane surfaces, resulting in scarring and cicatricial changes. Anti–laminin 332 pemphigoid also has been associated with internal malignancy.⁸ The use of the salt-split skin technique can be utilized to differentiate these entities based on their autoantibody-binding patterns in relation to the lamina densa.

Treatment options for mild BPCP include potent topical or intralesional steroids and dapsone, while more severe cases may require systemic therapy with rituximab, azathioprine, mycophenolate mofetil, or cyclophosphamide.⁴

This case highlights the importance of histopathologic examination of skin lesions with an unusual history or clinical presentation. Dermatologists should consider BPCP when presented with erosions, ulcerations, or blisters of the head and neck in middle-aged male patients.

The Diagnosis: Mycobacterium marinum Infection

A repeat excisional biopsy showed suppurative granulomatous dermatitis with negative stains for infectious organisms; however, tissue culture grew Mycobacterium marinum. The patient had a history of exposure to fish tanks, which are a potential habitat for nontuberculous mycobacteria. These bacteria can enter the body through a minor laceration or cut in the skin, which was likely due to her occupation and pet care activities.¹ Her fish tank exposure combined with the cutaneous findings of a long-standing indurated plaque with proximal nodular lymphangitis made M marinum infection the most likely diagnosis.²

Due to the limited specificity and sensitivity of patient symptoms, histologic staining, and direct microscopy, the gold standard for diagnosing acid-fast bacilli is tissue culture. ³ Tissue polymerase chain reaction testing is most useful in identifying the species of mycobacteria when histologic stains identify acid-fast bacilli but repeated tissue cultures are negative.⁴ With M marinum, a high clinical suspicion is needed to acquire a positive tissue culture because it needs to be grown for several weeks and at a temperature of 30 °C.⁵ Therefore, the physician should inform the laboratory if there is any suspicion for M marinum to increase the likelihood of obtaining a positive culture.

The differential diagnosis for M marinum infection includes other skin diseases that can cause nodular lymphangitis (also known as sporotrichoid spread) such as sporotrichosis, leishmaniasis, and certain bacterial and fungal infections. Although cat scratch disease, which is caused by Bartonella henselae, can appear similar to M marinum on histopathology, it clinically manifests with a single papulovesicular lesion at the site of inoculation that then forms a central eschar and resolves within a few weeks. Cat scratch disease typically causes painful lymphadenopathy, but it does not cause nodular lymphangitis or sporotrichoid spread.⁶ Sporotrichosis can have a similar clinical and histologic manifestation to M marinum infection, but the patient history typically includes exposure to Sporothrix schenckii through gardening or other contact with thorns, plants, or soil.² Cutaneous sarcoidosis can have a similar clinical appearance to M marinum infection, but nodular lymphangitis does not occur and histopathology would demonstrate noncaseating epithelioid cell granulomas.⁷ Lastly, although vegetative pyoderma gangrenosum can have some of the same histologic findings as M marinum, it typically also demonstrates sinus tract formation, which was not present in our case. Additionally, vegetative pyoderma gangrenosum manifests with a verrucous and pustular plaque that would not have lymphocutaneous spread.⁸

Treatment of cutaneous M marinum infection is guided by antibiotic susceptibility testing. One regimen is clarithromycin (500 mg twice daily⁹) plus ethambutol. ¹⁰ Treatment often entails a multidrug combination due to the high rates of antibiotic resistance. Other antibiotics that potentially can be used include rifampin, trimethoprim-sulfamethoxazole, minocycline, and quinolones. The treatment duration typically is more than 3 months, and therapy is continued for 4 to 6 weeks after the skin lesions resolve.¹¹ Excision of the lesion is reserved for patients with M marinum infection that fails to respond to antibiotic therapy.⁵

The Diagnosis: Mycobacterium marinum Infection

A repeat excisional biopsy showed suppurative granulomatous dermatitis with negative stains for infectious organisms; however, tissue culture grew Mycobacterium marinum. The patient had a history of exposure to fish tanks, which are a potential habitat for nontuberculous mycobacteria. These bacteria can enter the body through a minor laceration or cut in the skin, which was likely due to her occupation and pet care activities.¹ Her fish tank exposure combined with the cutaneous findings of a long-standing indurated plaque with proximal nodular lymphangitis made M marinum infection the most likely diagnosis.²

Due to the limited specificity and sensitivity of patient symptoms, histologic staining, and direct microscopy, the gold standard for diagnosing acid-fast bacilli is tissue culture. ³ Tissue polymerase chain reaction testing is most useful in identifying the species of mycobacteria when histologic stains identify acid-fast bacilli but repeated tissue cultures are negative.⁴ With M marinum, a high clinical suspicion is needed to acquire a positive tissue culture because it needs to be grown for several weeks and at a temperature of 30 °C.⁵ Therefore, the physician should inform the laboratory if there is any suspicion for M marinum to increase the likelihood of obtaining a positive culture.

The differential diagnosis for M marinum infection includes other skin diseases that can cause nodular lymphangitis (also known as sporotrichoid spread) such as sporotrichosis, leishmaniasis, and certain bacterial and fungal infections. Although cat scratch disease, which is caused by Bartonella henselae, can appear similar to M marinum on histopathology, it clinically manifests with a single papulovesicular lesion at the site of inoculation that then forms a central eschar and resolves within a few weeks. Cat scratch disease typically causes painful lymphadenopathy, but it does not cause nodular lymphangitis or sporotrichoid spread.⁶ Sporotrichosis can have a similar clinical and histologic manifestation to M marinum infection, but the patient history typically includes exposure to Sporothrix schenckii through gardening or other contact with thorns, plants, or soil.² Cutaneous sarcoidosis can have a similar clinical appearance to M marinum infection, but nodular lymphangitis does not occur and histopathology would demonstrate noncaseating epithelioid cell granulomas.⁷ Lastly, although vegetative pyoderma gangrenosum can have some of the same histologic findings as M marinum, it typically also demonstrates sinus tract formation, which was not present in our case. Additionally, vegetative pyoderma gangrenosum manifests with a verrucous and pustular plaque that would not have lymphocutaneous spread.⁸

Treatment of cutaneous M marinum infection is guided by antibiotic susceptibility testing. One regimen is clarithromycin (500 mg twice daily⁹) plus ethambutol. ¹⁰ Treatment often entails a multidrug combination due to the high rates of antibiotic resistance. Other antibiotics that potentially can be used include rifampin, trimethoprim-sulfamethoxazole, minocycline, and quinolones. The treatment duration typically is more than 3 months, and therapy is continued for 4 to 6 weeks after the skin lesions resolve.¹¹ Excision of the lesion is reserved for patients with M marinum infection that fails to respond to antibiotic therapy.⁵

The Diagnosis: Mycobacterium marinum Infection

A repeat excisional biopsy showed suppurative granulomatous dermatitis with negative stains for infectious organisms; however, tissue culture grew Mycobacterium marinum. The patient had a history of exposure to fish tanks, which are a potential habitat for nontuberculous mycobacteria. These bacteria can enter the body through a minor laceration or cut in the skin, which was likely due to her occupation and pet care activities.¹ Her fish tank exposure combined with the cutaneous findings of a long-standing indurated plaque with proximal nodular lymphangitis made M marinum infection the most likely diagnosis.²

Due to the limited specificity and sensitivity of patient symptoms, histologic staining, and direct microscopy, the gold standard for diagnosing acid-fast bacilli is tissue culture. ³ Tissue polymerase chain reaction testing is most useful in identifying the species of mycobacteria when histologic stains identify acid-fast bacilli but repeated tissue cultures are negative.⁴ With M marinum, a high clinical suspicion is needed to acquire a positive tissue culture because it needs to be grown for several weeks and at a temperature of 30 °C.⁵ Therefore, the physician should inform the laboratory if there is any suspicion for M marinum to increase the likelihood of obtaining a positive culture.

The differential diagnosis for M marinum infection includes other skin diseases that can cause nodular lymphangitis (also known as sporotrichoid spread) such as sporotrichosis, leishmaniasis, and certain bacterial and fungal infections. Although cat scratch disease, which is caused by Bartonella henselae, can appear similar to M marinum on histopathology, it clinically manifests with a single papulovesicular lesion at the site of inoculation that then forms a central eschar and resolves within a few weeks. Cat scratch disease typically causes painful lymphadenopathy, but it does not cause nodular lymphangitis or sporotrichoid spread.⁶ Sporotrichosis can have a similar clinical and histologic manifestation to M marinum infection, but the patient history typically includes exposure to Sporothrix schenckii through gardening or other contact with thorns, plants, or soil.² Cutaneous sarcoidosis can have a similar clinical appearance to M marinum infection, but nodular lymphangitis does not occur and histopathology would demonstrate noncaseating epithelioid cell granulomas.⁷ Lastly, although vegetative pyoderma gangrenosum can have some of the same histologic findings as M marinum, it typically also demonstrates sinus tract formation, which was not present in our case. Additionally, vegetative pyoderma gangrenosum manifests with a verrucous and pustular plaque that would not have lymphocutaneous spread.⁸

Treatment of cutaneous M marinum infection is guided by antibiotic susceptibility testing. One regimen is clarithromycin (500 mg twice daily⁹) plus ethambutol. ¹⁰ Treatment often entails a multidrug combination due to the high rates of antibiotic resistance. Other antibiotics that potentially can be used include rifampin, trimethoprim-sulfamethoxazole, minocycline, and quinolones. The treatment duration typically is more than 3 months, and therapy is continued for 4 to 6 weeks after the skin lesions resolve.¹¹ Excision of the lesion is reserved for patients with M marinum infection that fails to respond to antibiotic therapy.⁵

The Diagnosis: Microsecretory Adenocarcinoma

Microscopically, the tumor was relatively well circumscribed but had irregular borders. It consisted of microcysts and tubules lined by flattened to plump eosinophilic cells with mildly enlarged nuclei and intraluminal basophilic secretions. Peripheral lymphocytic aggregates also were seen in the mid and deep reticular dermis. Tumor necrosis, lymphovascular invasion, and notable mitotic activity were absent. Immunohistochemistry was diffusely positive for cytokeratin (CK) 7 and CK5/6. Occasional tumor cells showed variable expression of alpha smooth muscle actin, S-100 protein, and p40 and p63 antibodies. Immunohistochemistry was negative for CK20; GATA binding protein 3; MYB proto-oncogene, transcription factor; and insulinoma-associated protein ¹. A dual-color, break-apart fluorescence in situ hybridization probe identified a rearrangement of the SS18 (SYT) gene locus on chromosome 18. The nodule was excised with clear surgical margins, and the patient had no evidence of recurrent disease or metastasis at 2-year follow-up.

In recent years, there has been a growing recognition of the pivotal role played by gene fusions in driving oncogenesis, encompassing a diverse range of benign and malignant cutaneous neoplasms. These investigations have shed light on previously unknown mechanisms and pathways contributing to the pathogenesis of these neoplastic conditions, offering invaluable insights into their underlying biology. As a result, our ability to classify and diagnose these cutaneous tumors has improved. A notable example of how our current understanding has evolved is the discovery of the new cutaneous adnexal tumor microsecretory adenocarcinoma (MSA). Initially described by Bishop et al¹ in 2019 as predominantly occurring in the intraoral minor salivary glands, rare instances of primary cutaneous MSA involving the head and neck regions also have been reported.² Microsecretory adenocarcinoma represents an important addition to the group of fusion-driven tumors with both salivary gland and cutaneous adnexal analogues, characterized by a MEF2C::SS18 gene fusion. This entity is now recognized as a group of cutaneous adnexal tumors with distinct gene fusions, including both relatively recently discovered entities (eg, secretory carcinoma with NTRK fusions) and previously known entities with newly identified gene fusions (eg, poroid neoplasms with NUTM1, YAP1, or WWTR1 fusions; hidradenomatous neoplasms with CRTC1::MAML2 fusions; and adenoid cystic carcinoma with MYB, MYBL1, and/or NFIB rearrangements).³

Microsecretory adenocarcinoma exhibits a high degree of morphologic consistency, characterized by a microcystic-predominant growth pattern, uniform intercalated ductlike tumor cells with attenuated eosinophilic to clear cytoplasm, monotonous oval hyperchromatic nuclei with indistinct nucleoli, abundant basophilic luminal secretions, and a variably cellular fibromyxoid stroma. It also shows rounded borders with subtle infiltrative growth. Occasionally, pseudoepitheliomatous hyperplasia, tumor-associated lymphoid proliferation, or metaplastic bone formation may accompany MSA. Perineural invasion is rare, necrosis is absent, and mitotic rates generally are low, contributing to its distinctive histopathologic features that aid in accurate diagnosis and differentiation from other entities. Immunohistochemistry reveals diffuse positivity for CK7 and patchy to diffuse expression of S-100 in tumor cells as well as variable expression of p40 and p63. Highly specific SS18 gene translocations at chromosome 18q are useful for diagnosing MSA when found alongside its characteristic appearance, and SS18 break-apart fluorescence in situ hybridization can serve reliably as an accurate diagnostic method (Figure 1).⁴ Our case illustrates how molecular analysis assists in distinguishing MSA from other cutaneous adnexal tumors, exemplifying the power of our evolving understanding in refining diagnostic accuracy and guiding targeted therapies in clinical practice.

The differential diagnosis of MSA includes tubular adenoma, secretory carcinoma, cribriform tumor (previously carcinoma), and metastatic adenocarcinoma. Tubular adenoma is a rare benign neoplasm that predominantly affects females and can manifest at any age in adulthood. It typically manifests as a slow-growing, occasionally pedunculated nodule, often measuring less than 2 cm. Although it most commonly manifests on the scalp, tubular adenoma also may arise in diverse sites such as the face, axillae, lower extremities, or genitalia.

Notably, scalp lesions often are associated with nevus sebaceus of Jadassohn or syringocystadenoma papilliferum. Microscopically, tubular adenoma is well circumscribed within the dermis and may extend into the subcutis in some cases. Its distinctive appearance consists of variably sized tubules lined by a double or multilayered cuboidal to columnar epithelium, frequently displaying apocrine decapitation secretion (Figure 2). Cystic changes and intraluminal papillae devoid of true fibrovascular cores frequently are observed. Immunohistochemically, luminal epithelial cells express epithelial membrane antigen and carcinoembryonic antigen, while the myoepithelial layer expresses smooth muscle markers, p40, and S-100 protein. BRAF V600E mutation can be detected using immunohistochemistry, with excellent sensitivity and specificity using the anti-BRAF V600E antibody (clone VE1).⁵ Distinguishing tubular adenoma from MSA is achievable by observing its larger, more variable tubules, along with the consistent presence of a peripheral myoepithelial layer.

Secretory carcinoma is recognized as a low-grade gene fusion–driven carcinoma that primarily arises in salivary glands (both major and minor), with occasional occurrences in the breast and extremely rare instances in other locations such as the skin, thyroid gland, and lung.⁶ Although the axilla is the most common cutaneous site, diverse locations such as the neck, eyelids, extremities, and nipples also have been documented. Secretory carcinoma affects individuals across a wide age range (13–71 years).⁶ The hallmark tumors exhibit densely packed, sievelike microcystic glands and tubular spaces filled with abundant eosinophilic intraluminal secretions (Figure 3). Additionally, morphologic variants, such as predominantly papillary, papillary-cystic, macrocystic, solid, partially mucinous, and mixed-pattern neoplasms, have been described. Secretory carcinoma shares certain features with MSA; however, it is distinguished by the presence of pronounced eosinophilic secretions, plump and vacuolated cytoplasm, and a less conspicuous fibromyxoid stroma. Immunohistochemistry reveals tumor cells that are positive for CK7, SOX-10, S-100, mammaglobin, MUC4, and variably GATA-3. Genetically, secretory carcinoma exhibits distinct characteristics, commonly showing the ETV6::NTRK3 fusion, detectable through molecular techniques or pan-TRK immunohistochemistry, while RET fusions and other rare variants are less frequent.⁷

In 1998, Requena et al⁸ introduced the concept of primary cutaneous cribriform carcinoma. Despite initially being classified as a carcinoma, the malignant potential of this tumor remains uncertain. Consequently, the term cribriform tumor now has become the preferred terminology for denoting this rare entity.⁹ Primary cutaneous cribriform tumors are observed more commonly in women and typically affect individuals aged 20 to 55 years (mean, 44 years). Predominant locations include the upper and lower extremities, especially the thighs, knees, and legs, with additional cases occurring on the head and trunk. Microscopically, cribriform tumor is characterized by a partially circumscribed, unencapsulated dermal nodule composed of round or oval nuclei displaying hyperchromatism and mild pleomorphism. The defining aspect of its morphology revolves around interspersed small round cavities that give rise to the hallmark cribriform pattern (Figure 4). Although MSA occasionally may exhibit a cribriform architectural pattern, it typically lacks the distinctive feature of thin, threadlike, intraluminal bridging strands observed in cribriform tumors. Similarly, luminal cells within the cribriform tumor express CK7 and exhibit variable S-100 expression. It is recognized as an indolent neoplasm with uncertain malignant potential.

The histopathologic features of metastatic carcinomas can overlap with those of primary cutaneous tumors, particularly adnexal neoplasms.¹⁰ However, several key features can aid in the differentiation of cutaneous metastases, including a dermal-based growth pattern with or without subcutaneous involvement, the presence of multiple lesions, and the occurrence of lymphovascular invasion (Figure 5). Conversely, features that suggest a primary cutaneous adnexal neoplasm include the presence of superimposed in situ disease, carcinoma developing within a benign adnexal neoplasm, and notable stromal and/or vascular hyalinization within benign-appearing areas. In some cases, it can be difficult to determine the primary site of origin of a metastatic carcinoma to the skin based on morphologic features alone. In these cases, immunohistochemistry can be helpful. The most cost-effective and time-efficient approach to accurate diagnosis is to obtain a comprehensive clinical history. If there is a known history of cancer, a small panel of organ-specific immunohistochemical studies can be performed to confirm the diagnosis. If there is no known history, an algorithmic approach can be used to identify the primary site of origin. In all circumstances, it cannot be stressed enough that acquiring a thorough clinical history before conducting any diagnostic examinations is paramount.

The Diagnosis: Microsecretory Adenocarcinoma

Microscopically, the tumor was relatively well circumscribed but had irregular borders. It consisted of microcysts and tubules lined by flattened to plump eosinophilic cells with mildly enlarged nuclei and intraluminal basophilic secretions. Peripheral lymphocytic aggregates also were seen in the mid and deep reticular dermis. Tumor necrosis, lymphovascular invasion, and notable mitotic activity were absent. Immunohistochemistry was diffusely positive for cytokeratin (CK) 7 and CK5/6. Occasional tumor cells showed variable expression of alpha smooth muscle actin, S-100 protein, and p40 and p63 antibodies. Immunohistochemistry was negative for CK20; GATA binding protein 3; MYB proto-oncogene, transcription factor; and insulinoma-associated protein ¹. A dual-color, break-apart fluorescence in situ hybridization probe identified a rearrangement of the SS18 (SYT) gene locus on chromosome 18. The nodule was excised with clear surgical margins, and the patient had no evidence of recurrent disease or metastasis at 2-year follow-up.

In recent years, there has been a growing recognition of the pivotal role played by gene fusions in driving oncogenesis, encompassing a diverse range of benign and malignant cutaneous neoplasms. These investigations have shed light on previously unknown mechanisms and pathways contributing to the pathogenesis of these neoplastic conditions, offering invaluable insights into their underlying biology. As a result, our ability to classify and diagnose these cutaneous tumors has improved. A notable example of how our current understanding has evolved is the discovery of the new cutaneous adnexal tumor microsecretory adenocarcinoma (MSA). Initially described by Bishop et al¹ in 2019 as predominantly occurring in the intraoral minor salivary glands, rare instances of primary cutaneous MSA involving the head and neck regions also have been reported.² Microsecretory adenocarcinoma represents an important addition to the group of fusion-driven tumors with both salivary gland and cutaneous adnexal analogues, characterized by a MEF2C::SS18 gene fusion. This entity is now recognized as a group of cutaneous adnexal tumors with distinct gene fusions, including both relatively recently discovered entities (eg, secretory carcinoma with NTRK fusions) and previously known entities with newly identified gene fusions (eg, poroid neoplasms with NUTM1, YAP1, or WWTR1 fusions; hidradenomatous neoplasms with CRTC1::MAML2 fusions; and adenoid cystic carcinoma with MYB, MYBL1, and/or NFIB rearrangements).³

Microsecretory adenocarcinoma exhibits a high degree of morphologic consistency, characterized by a microcystic-predominant growth pattern, uniform intercalated ductlike tumor cells with attenuated eosinophilic to clear cytoplasm, monotonous oval hyperchromatic nuclei with indistinct nucleoli, abundant basophilic luminal secretions, and a variably cellular fibromyxoid stroma. It also shows rounded borders with subtle infiltrative growth. Occasionally, pseudoepitheliomatous hyperplasia, tumor-associated lymphoid proliferation, or metaplastic bone formation may accompany MSA. Perineural invasion is rare, necrosis is absent, and mitotic rates generally are low, contributing to its distinctive histopathologic features that aid in accurate diagnosis and differentiation from other entities. Immunohistochemistry reveals diffuse positivity for CK7 and patchy to diffuse expression of S-100 in tumor cells as well as variable expression of p40 and p63. Highly specific SS18 gene translocations at chromosome 18q are useful for diagnosing MSA when found alongside its characteristic appearance, and SS18 break-apart fluorescence in situ hybridization can serve reliably as an accurate diagnostic method (Figure 1).⁴ Our case illustrates how molecular analysis assists in distinguishing MSA from other cutaneous adnexal tumors, exemplifying the power of our evolving understanding in refining diagnostic accuracy and guiding targeted therapies in clinical practice.

The differential diagnosis of MSA includes tubular adenoma, secretory carcinoma, cribriform tumor (previously carcinoma), and metastatic adenocarcinoma. Tubular adenoma is a rare benign neoplasm that predominantly affects females and can manifest at any age in adulthood. It typically manifests as a slow-growing, occasionally pedunculated nodule, often measuring less than 2 cm. Although it most commonly manifests on the scalp, tubular adenoma also may arise in diverse sites such as the face, axillae, lower extremities, or genitalia.

Notably, scalp lesions often are associated with nevus sebaceus of Jadassohn or syringocystadenoma papilliferum. Microscopically, tubular adenoma is well circumscribed within the dermis and may extend into the subcutis in some cases. Its distinctive appearance consists of variably sized tubules lined by a double or multilayered cuboidal to columnar epithelium, frequently displaying apocrine decapitation secretion (Figure 2). Cystic changes and intraluminal papillae devoid of true fibrovascular cores frequently are observed. Immunohistochemically, luminal epithelial cells express epithelial membrane antigen and carcinoembryonic antigen, while the myoepithelial layer expresses smooth muscle markers, p40, and S-100 protein. BRAF V600E mutation can be detected using immunohistochemistry, with excellent sensitivity and specificity using the anti-BRAF V600E antibody (clone VE1).⁵ Distinguishing tubular adenoma from MSA is achievable by observing its larger, more variable tubules, along with the consistent presence of a peripheral myoepithelial layer.

Secretory carcinoma is recognized as a low-grade gene fusion–driven carcinoma that primarily arises in salivary glands (both major and minor), with occasional occurrences in the breast and extremely rare instances in other locations such as the skin, thyroid gland, and lung.⁶ Although the axilla is the most common cutaneous site, diverse locations such as the neck, eyelids, extremities, and nipples also have been documented. Secretory carcinoma affects individuals across a wide age range (13–71 years).⁶ The hallmark tumors exhibit densely packed, sievelike microcystic glands and tubular spaces filled with abundant eosinophilic intraluminal secretions (Figure 3). Additionally, morphologic variants, such as predominantly papillary, papillary-cystic, macrocystic, solid, partially mucinous, and mixed-pattern neoplasms, have been described. Secretory carcinoma shares certain features with MSA; however, it is distinguished by the presence of pronounced eosinophilic secretions, plump and vacuolated cytoplasm, and a less conspicuous fibromyxoid stroma. Immunohistochemistry reveals tumor cells that are positive for CK7, SOX-10, S-100, mammaglobin, MUC4, and variably GATA-3. Genetically, secretory carcinoma exhibits distinct characteristics, commonly showing the ETV6::NTRK3 fusion, detectable through molecular techniques or pan-TRK immunohistochemistry, while RET fusions and other rare variants are less frequent.⁷

In 1998, Requena et al⁸ introduced the concept of primary cutaneous cribriform carcinoma. Despite initially being classified as a carcinoma, the malignant potential of this tumor remains uncertain. Consequently, the term cribriform tumor now has become the preferred terminology for denoting this rare entity.⁹ Primary cutaneous cribriform tumors are observed more commonly in women and typically affect individuals aged 20 to 55 years (mean, 44 years). Predominant locations include the upper and lower extremities, especially the thighs, knees, and legs, with additional cases occurring on the head and trunk. Microscopically, cribriform tumor is characterized by a partially circumscribed, unencapsulated dermal nodule composed of round or oval nuclei displaying hyperchromatism and mild pleomorphism. The defining aspect of its morphology revolves around interspersed small round cavities that give rise to the hallmark cribriform pattern (Figure 4). Although MSA occasionally may exhibit a cribriform architectural pattern, it typically lacks the distinctive feature of thin, threadlike, intraluminal bridging strands observed in cribriform tumors. Similarly, luminal cells within the cribriform tumor express CK7 and exhibit variable S-100 expression. It is recognized as an indolent neoplasm with uncertain malignant potential.

The histopathologic features of metastatic carcinomas can overlap with those of primary cutaneous tumors, particularly adnexal neoplasms.¹⁰ However, several key features can aid in the differentiation of cutaneous metastases, including a dermal-based growth pattern with or without subcutaneous involvement, the presence of multiple lesions, and the occurrence of lymphovascular invasion (Figure 5). Conversely, features that suggest a primary cutaneous adnexal neoplasm include the presence of superimposed in situ disease, carcinoma developing within a benign adnexal neoplasm, and notable stromal and/or vascular hyalinization within benign-appearing areas. In some cases, it can be difficult to determine the primary site of origin of a metastatic carcinoma to the skin based on morphologic features alone. In these cases, immunohistochemistry can be helpful. The most cost-effective and time-efficient approach to accurate diagnosis is to obtain a comprehensive clinical history. If there is a known history of cancer, a small panel of organ-specific immunohistochemical studies can be performed to confirm the diagnosis. If there is no known history, an algorithmic approach can be used to identify the primary site of origin. In all circumstances, it cannot be stressed enough that acquiring a thorough clinical history before conducting any diagnostic examinations is paramount.

The Diagnosis: Microsecretory Adenocarcinoma

Microscopically, the tumor was relatively well circumscribed but had irregular borders. It consisted of microcysts and tubules lined by flattened to plump eosinophilic cells with mildly enlarged nuclei and intraluminal basophilic secretions. Peripheral lymphocytic aggregates also were seen in the mid and deep reticular dermis. Tumor necrosis, lymphovascular invasion, and notable mitotic activity were absent. Immunohistochemistry was diffusely positive for cytokeratin (CK) 7 and CK5/6. Occasional tumor cells showed variable expression of alpha smooth muscle actin, S-100 protein, and p40 and p63 antibodies. Immunohistochemistry was negative for CK20; GATA binding protein 3; MYB proto-oncogene, transcription factor; and insulinoma-associated protein ¹. A dual-color, break-apart fluorescence in situ hybridization probe identified a rearrangement of the SS18 (SYT) gene locus on chromosome 18. The nodule was excised with clear surgical margins, and the patient had no evidence of recurrent disease or metastasis at 2-year follow-up.

In recent years, there has been a growing recognition of the pivotal role played by gene fusions in driving oncogenesis, encompassing a diverse range of benign and malignant cutaneous neoplasms. These investigations have shed light on previously unknown mechanisms and pathways contributing to the pathogenesis of these neoplastic conditions, offering invaluable insights into their underlying biology. As a result, our ability to classify and diagnose these cutaneous tumors has improved. A notable example of how our current understanding has evolved is the discovery of the new cutaneous adnexal tumor microsecretory adenocarcinoma (MSA). Initially described by Bishop et al¹ in 2019 as predominantly occurring in the intraoral minor salivary glands, rare instances of primary cutaneous MSA involving the head and neck regions also have been reported.² Microsecretory adenocarcinoma represents an important addition to the group of fusion-driven tumors with both salivary gland and cutaneous adnexal analogues, characterized by a MEF2C::SS18 gene fusion. This entity is now recognized as a group of cutaneous adnexal tumors with distinct gene fusions, including both relatively recently discovered entities (eg, secretory carcinoma with NTRK fusions) and previously known entities with newly identified gene fusions (eg, poroid neoplasms with NUTM1, YAP1, or WWTR1 fusions; hidradenomatous neoplasms with CRTC1::MAML2 fusions; and adenoid cystic carcinoma with MYB, MYBL1, and/or NFIB rearrangements).³

Microsecretory adenocarcinoma exhibits a high degree of morphologic consistency, characterized by a microcystic-predominant growth pattern, uniform intercalated ductlike tumor cells with attenuated eosinophilic to clear cytoplasm, monotonous oval hyperchromatic nuclei with indistinct nucleoli, abundant basophilic luminal secretions, and a variably cellular fibromyxoid stroma. It also shows rounded borders with subtle infiltrative growth. Occasionally, pseudoepitheliomatous hyperplasia, tumor-associated lymphoid proliferation, or metaplastic bone formation may accompany MSA. Perineural invasion is rare, necrosis is absent, and mitotic rates generally are low, contributing to its distinctive histopathologic features that aid in accurate diagnosis and differentiation from other entities. Immunohistochemistry reveals diffuse positivity for CK7 and patchy to diffuse expression of S-100 in tumor cells as well as variable expression of p40 and p63. Highly specific SS18 gene translocations at chromosome 18q are useful for diagnosing MSA when found alongside its characteristic appearance, and SS18 break-apart fluorescence in situ hybridization can serve reliably as an accurate diagnostic method (Figure 1).⁴ Our case illustrates how molecular analysis assists in distinguishing MSA from other cutaneous adnexal tumors, exemplifying the power of our evolving understanding in refining diagnostic accuracy and guiding targeted therapies in clinical practice.

The differential diagnosis of MSA includes tubular adenoma, secretory carcinoma, cribriform tumor (previously carcinoma), and metastatic adenocarcinoma. Tubular adenoma is a rare benign neoplasm that predominantly affects females and can manifest at any age in adulthood. It typically manifests as a slow-growing, occasionally pedunculated nodule, often measuring less than 2 cm. Although it most commonly manifests on the scalp, tubular adenoma also may arise in diverse sites such as the face, axillae, lower extremities, or genitalia.

Notably, scalp lesions often are associated with nevus sebaceus of Jadassohn or syringocystadenoma papilliferum. Microscopically, tubular adenoma is well circumscribed within the dermis and may extend into the subcutis in some cases. Its distinctive appearance consists of variably sized tubules lined by a double or multilayered cuboidal to columnar epithelium, frequently displaying apocrine decapitation secretion (Figure 2). Cystic changes and intraluminal papillae devoid of true fibrovascular cores frequently are observed. Immunohistochemically, luminal epithelial cells express epithelial membrane antigen and carcinoembryonic antigen, while the myoepithelial layer expresses smooth muscle markers, p40, and S-100 protein. BRAF V600E mutation can be detected using immunohistochemistry, with excellent sensitivity and specificity using the anti-BRAF V600E antibody (clone VE1).⁵ Distinguishing tubular adenoma from MSA is achievable by observing its larger, more variable tubules, along with the consistent presence of a peripheral myoepithelial layer.

Secretory carcinoma is recognized as a low-grade gene fusion–driven carcinoma that primarily arises in salivary glands (both major and minor), with occasional occurrences in the breast and extremely rare instances in other locations such as the skin, thyroid gland, and lung.⁶ Although the axilla is the most common cutaneous site, diverse locations such as the neck, eyelids, extremities, and nipples also have been documented. Secretory carcinoma affects individuals across a wide age range (13–71 years).⁶ The hallmark tumors exhibit densely packed, sievelike microcystic glands and tubular spaces filled with abundant eosinophilic intraluminal secretions (Figure 3). Additionally, morphologic variants, such as predominantly papillary, papillary-cystic, macrocystic, solid, partially mucinous, and mixed-pattern neoplasms, have been described. Secretory carcinoma shares certain features with MSA; however, it is distinguished by the presence of pronounced eosinophilic secretions, plump and vacuolated cytoplasm, and a less conspicuous fibromyxoid stroma. Immunohistochemistry reveals tumor cells that are positive for CK7, SOX-10, S-100, mammaglobin, MUC4, and variably GATA-3. Genetically, secretory carcinoma exhibits distinct characteristics, commonly showing the ETV6::NTRK3 fusion, detectable through molecular techniques or pan-TRK immunohistochemistry, while RET fusions and other rare variants are less frequent.⁷

In 1998, Requena et al⁸ introduced the concept of primary cutaneous cribriform carcinoma. Despite initially being classified as a carcinoma, the malignant potential of this tumor remains uncertain. Consequently, the term cribriform tumor now has become the preferred terminology for denoting this rare entity.⁹ Primary cutaneous cribriform tumors are observed more commonly in women and typically affect individuals aged 20 to 55 years (mean, 44 years). Predominant locations include the upper and lower extremities, especially the thighs, knees, and legs, with additional cases occurring on the head and trunk. Microscopically, cribriform tumor is characterized by a partially circumscribed, unencapsulated dermal nodule composed of round or oval nuclei displaying hyperchromatism and mild pleomorphism. The defining aspect of its morphology revolves around interspersed small round cavities that give rise to the hallmark cribriform pattern (Figure 4). Although MSA occasionally may exhibit a cribriform architectural pattern, it typically lacks the distinctive feature of thin, threadlike, intraluminal bridging strands observed in cribriform tumors. Similarly, luminal cells within the cribriform tumor express CK7 and exhibit variable S-100 expression. It is recognized as an indolent neoplasm with uncertain malignant potential.

The histopathologic features of metastatic carcinomas can overlap with those of primary cutaneous tumors, particularly adnexal neoplasms.¹⁰ However, several key features can aid in the differentiation of cutaneous metastases, including a dermal-based growth pattern with or without subcutaneous involvement, the presence of multiple lesions, and the occurrence of lymphovascular invasion (Figure 5). Conversely, features that suggest a primary cutaneous adnexal neoplasm include the presence of superimposed in situ disease, carcinoma developing within a benign adnexal neoplasm, and notable stromal and/or vascular hyalinization within benign-appearing areas. In some cases, it can be difficult to determine the primary site of origin of a metastatic carcinoma to the skin based on morphologic features alone. In these cases, immunohistochemistry can be helpful. The most cost-effective and time-efficient approach to accurate diagnosis is to obtain a comprehensive clinical history. If there is a known history of cancer, a small panel of organ-specific immunohistochemical studies can be performed to confirm the diagnosis. If there is no known history, an algorithmic approach can be used to identify the primary site of origin. In all circumstances, it cannot be stressed enough that acquiring a thorough clinical history before conducting any diagnostic examinations is paramount.

To the Editor:

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

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

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

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

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

To the Editor:

We read with interest the Case Letter from Wang et al¹ (Cutis. 2023;112:E13-E15) of a 60-year-old man whose metastatic salivary duct adenocarcinoma manifested with the shield sign as well as carcinoma hemorrhagiectoides. Cutaneous metastases have seldom been described in association with salivary duct carcinoma.^2-7 In addition, carcinoma hemorrhagiectoides–associated shield sign has not been commonly reported.^5,8-12

Salivary duct carcinoma—an uncommon head and neck malignancy characterized by androgen receptor expression—rarely is associated with cutaneous metastases. Based on a PubMed search of articles indexed for MEDLINE using the terms cutaneous, metastatic, salivary duct carcinoma, and/or skin, including the patient described by Wang et al,¹ there have been 8 individuals with cutaneous metastases from this cancer. The morphology of the cutaneous metastases has varied from angiomatous to angiokeratomalike (black and keratotic) papules, bullae, macules (red), papules and nodules (erythematous and scaly), plaques (cellulitislike and confluent that were purpuric, hemorrhagic, and violaceous), pseudovesicles, purpuric papules, subcutaneous nodules, and an ulcer (superficial and mimicked a basal cell carcinoma).^1-7 Remarkably, 4 of 8 patients (50%) with salivary duct carcinoma cutaneous metastases presented with a shield sign,^5,7 including the case reported by Wang et al.¹

The shield sign is a distinctive clinical manifestation of cutaneous metastasis.¹⁰ It was named to describe the skin metastases located predominantly on the chest area that would be covered by a medieval knight’s shield^5,10,12; metastatic lesions also have been noted on the proximal arm and/or the upper back in a similar distribution.^8,9 To date, based on a PubMed search of articles indexed for MEDLINE using the search terms breast cancer, carcinoma, hemorrhagiectoides, metastases, salivary duct carcinoma, shield, and/or sign, the shield sign has been described in 6 patients with cutaneous metastases either from salivary duct carcinoma (4 patients)^1,5,7 or breast cancer (2 patients).^8,9 The shield sign pathologically corresponds to carcinoma hemorrhagiectoides, an inflammatory pattern of cutaneous metastases.^5,11

Inflammatory cutaneous metastatic carcinoma has 3 distinctive clinical and pathologic manifestations.¹¹ Carcinoma erysipelatoides and carcinoma telangiectoides were the earlier described variants.¹¹ In 2012, carcinoma hemorrhagiectoides was described as the third pattern of inflammatory cutaneous metastasis.⁵

Carcinoma erysipelatoides, which clinically mimics cutaneous streptococcal cellulitis, appears as a well-defined erythematous patch or plaque; the tumor cells can be found in the lymphatic vessels and either are absent or minimally present in the dermis. Carcinoma telangiectoides, which clinically mimics idiopathic telangiectases, appears as an erythematous patch with prominent telangiectases; the tumor cells can be found in the blood vessels and are either absent or minimally present in the dermis. Carcinoma hemorrhagiectoides appears as purpuric or violaceous indurated plaques; the tumor cells are not only found in the blood vessels, in the lymphatic vessels, or both, but also can be mildly to extensively present in the dermis.^5,10,11

In conclusion, the shield sign is a unique presentation of inflammatory cutaneous metastatic carcinoma, which is associated with carcinoma hemorrhagiectoides. The clinical features of the infiltrated plaques correspond to the presence of tumor cells in the blood vessels, lymphatic vessels, and the dermis; in addition, the purpuric and violaceous appearance correlates with the presence of extravasated erythrocytes or hemorrhage in the dermis. To date, half of the patients with skin metastases from salivary duct carcinoma have presented with carcinoma hemorrhagiectoides–associated shield sign.

Authors’ Response

We appreciate and welcome the comments provided by the authors. Drawing attention to unusual pathologic manifestations of cutaneous metastatic salivary duct carcinoma manifesting with the shield sign, the authors present a comprehensive review of 3 distinctive presentations: carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma hemorrhagiectoides. The inclusion of these variants enriches the discussion and makes this letter a valuable addition to the literature on cutaneous metastatic carcinoma, particularly metastatic salivary duct carcinoma.

Xintong Wang, MD; William H. Westra, MD

From the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

The authors report no conflict of interest.

To the Editor:

We read with interest the Case Letter from Wang et al¹ (Cutis. 2023;112:E13-E15) of a 60-year-old man whose metastatic salivary duct adenocarcinoma manifested with the shield sign as well as carcinoma hemorrhagiectoides. Cutaneous metastases have seldom been described in association with salivary duct carcinoma.^2-7 In addition, carcinoma hemorrhagiectoides–associated shield sign has not been commonly reported.^5,8-12

Salivary duct carcinoma—an uncommon head and neck malignancy characterized by androgen receptor expression—rarely is associated with cutaneous metastases. Based on a PubMed search of articles indexed for MEDLINE using the terms cutaneous, metastatic, salivary duct carcinoma, and/or skin, including the patient described by Wang et al,¹ there have been 8 individuals with cutaneous metastases from this cancer. The morphology of the cutaneous metastases has varied from angiomatous to angiokeratomalike (black and keratotic) papules, bullae, macules (red), papules and nodules (erythematous and scaly), plaques (cellulitislike and confluent that were purpuric, hemorrhagic, and violaceous), pseudovesicles, purpuric papules, subcutaneous nodules, and an ulcer (superficial and mimicked a basal cell carcinoma).^1-7 Remarkably, 4 of 8 patients (50%) with salivary duct carcinoma cutaneous metastases presented with a shield sign,^5,7 including the case reported by Wang et al.¹

The shield sign is a distinctive clinical manifestation of cutaneous metastasis.¹⁰ It was named to describe the skin metastases located predominantly on the chest area that would be covered by a medieval knight’s shield^5,10,12; metastatic lesions also have been noted on the proximal arm and/or the upper back in a similar distribution.^8,9 To date, based on a PubMed search of articles indexed for MEDLINE using the search terms breast cancer, carcinoma, hemorrhagiectoides, metastases, salivary duct carcinoma, shield, and/or sign, the shield sign has been described in 6 patients with cutaneous metastases either from salivary duct carcinoma (4 patients)^1,5,7 or breast cancer (2 patients).^8,9 The shield sign pathologically corresponds to carcinoma hemorrhagiectoides, an inflammatory pattern of cutaneous metastases.^5,11

Inflammatory cutaneous metastatic carcinoma has 3 distinctive clinical and pathologic manifestations.¹¹ Carcinoma erysipelatoides and carcinoma telangiectoides were the earlier described variants.¹¹ In 2012, carcinoma hemorrhagiectoides was described as the third pattern of inflammatory cutaneous metastasis.⁵

Carcinoma erysipelatoides, which clinically mimics cutaneous streptococcal cellulitis, appears as a well-defined erythematous patch or plaque; the tumor cells can be found in the lymphatic vessels and either are absent or minimally present in the dermis. Carcinoma telangiectoides, which clinically mimics idiopathic telangiectases, appears as an erythematous patch with prominent telangiectases; the tumor cells can be found in the blood vessels and are either absent or minimally present in the dermis. Carcinoma hemorrhagiectoides appears as purpuric or violaceous indurated plaques; the tumor cells are not only found in the blood vessels, in the lymphatic vessels, or both, but also can be mildly to extensively present in the dermis.^5,10,11

In conclusion, the shield sign is a unique presentation of inflammatory cutaneous metastatic carcinoma, which is associated with carcinoma hemorrhagiectoides. The clinical features of the infiltrated plaques correspond to the presence of tumor cells in the blood vessels, lymphatic vessels, and the dermis; in addition, the purpuric and violaceous appearance correlates with the presence of extravasated erythrocytes or hemorrhage in the dermis. To date, half of the patients with skin metastases from salivary duct carcinoma have presented with carcinoma hemorrhagiectoides–associated shield sign.

Authors’ Response

We appreciate and welcome the comments provided by the authors. Drawing attention to unusual pathologic manifestations of cutaneous metastatic salivary duct carcinoma manifesting with the shield sign, the authors present a comprehensive review of 3 distinctive presentations: carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma hemorrhagiectoides. The inclusion of these variants enriches the discussion and makes this letter a valuable addition to the literature on cutaneous metastatic carcinoma, particularly metastatic salivary duct carcinoma.

Xintong Wang, MD; William H. Westra, MD

From the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

The authors report no conflict of interest.

To the Editor:

We read with interest the Case Letter from Wang et al¹ (Cutis. 2023;112:E13-E15) of a 60-year-old man whose metastatic salivary duct adenocarcinoma manifested with the shield sign as well as carcinoma hemorrhagiectoides. Cutaneous metastases have seldom been described in association with salivary duct carcinoma.^2-7 In addition, carcinoma hemorrhagiectoides–associated shield sign has not been commonly reported.^5,8-12

Salivary duct carcinoma—an uncommon head and neck malignancy characterized by androgen receptor expression—rarely is associated with cutaneous metastases. Based on a PubMed search of articles indexed for MEDLINE using the terms cutaneous, metastatic, salivary duct carcinoma, and/or skin, including the patient described by Wang et al,¹ there have been 8 individuals with cutaneous metastases from this cancer. The morphology of the cutaneous metastases has varied from angiomatous to angiokeratomalike (black and keratotic) papules, bullae, macules (red), papules and nodules (erythematous and scaly), plaques (cellulitislike and confluent that were purpuric, hemorrhagic, and violaceous), pseudovesicles, purpuric papules, subcutaneous nodules, and an ulcer (superficial and mimicked a basal cell carcinoma).^1-7 Remarkably, 4 of 8 patients (50%) with salivary duct carcinoma cutaneous metastases presented with a shield sign,^5,7 including the case reported by Wang et al.¹

The shield sign is a distinctive clinical manifestation of cutaneous metastasis.¹⁰ It was named to describe the skin metastases located predominantly on the chest area that would be covered by a medieval knight’s shield^5,10,12; metastatic lesions also have been noted on the proximal arm and/or the upper back in a similar distribution.^8,9 To date, based on a PubMed search of articles indexed for MEDLINE using the search terms breast cancer, carcinoma, hemorrhagiectoides, metastases, salivary duct carcinoma, shield, and/or sign, the shield sign has been described in 6 patients with cutaneous metastases either from salivary duct carcinoma (4 patients)^1,5,7 or breast cancer (2 patients).^8,9 The shield sign pathologically corresponds to carcinoma hemorrhagiectoides, an inflammatory pattern of cutaneous metastases.^5,11

Inflammatory cutaneous metastatic carcinoma has 3 distinctive clinical and pathologic manifestations.¹¹ Carcinoma erysipelatoides and carcinoma telangiectoides were the earlier described variants.¹¹ In 2012, carcinoma hemorrhagiectoides was described as the third pattern of inflammatory cutaneous metastasis.⁵

Carcinoma erysipelatoides, which clinically mimics cutaneous streptococcal cellulitis, appears as a well-defined erythematous patch or plaque; the tumor cells can be found in the lymphatic vessels and either are absent or minimally present in the dermis. Carcinoma telangiectoides, which clinically mimics idiopathic telangiectases, appears as an erythematous patch with prominent telangiectases; the tumor cells can be found in the blood vessels and are either absent or minimally present in the dermis. Carcinoma hemorrhagiectoides appears as purpuric or violaceous indurated plaques; the tumor cells are not only found in the blood vessels, in the lymphatic vessels, or both, but also can be mildly to extensively present in the dermis.^5,10,11

In conclusion, the shield sign is a unique presentation of inflammatory cutaneous metastatic carcinoma, which is associated with carcinoma hemorrhagiectoides. The clinical features of the infiltrated plaques correspond to the presence of tumor cells in the blood vessels, lymphatic vessels, and the dermis; in addition, the purpuric and violaceous appearance correlates with the presence of extravasated erythrocytes or hemorrhage in the dermis. To date, half of the patients with skin metastases from salivary duct carcinoma have presented with carcinoma hemorrhagiectoides–associated shield sign.

Authors’ Response

We appreciate and welcome the comments provided by the authors. Drawing attention to unusual pathologic manifestations of cutaneous metastatic salivary duct carcinoma manifesting with the shield sign, the authors present a comprehensive review of 3 distinctive presentations: carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma hemorrhagiectoides. The inclusion of these variants enriches the discussion and makes this letter a valuable addition to the literature on cutaneous metastatic carcinoma, particularly metastatic salivary duct carcinoma.

Xintong Wang, MD; William H. Westra, MD

From the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

The authors report no conflict of interest.

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

A version of this article first appeared on Medscape.com.