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The Diagnosis: Cutaneous Crohn Disease

A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.

Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.

Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.¹ This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.² The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.³

Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.¹ The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.^4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.⁶

Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.⁵

Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.³ Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.⁷ For disseminated disease, systemic corticosteroids have shown efficacy.³ Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.³

Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.

The Diagnosis: Cutaneous Crohn Disease

A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.

Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.

Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.¹ This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.² The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.³

Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.¹ The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.^4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.⁶

Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.⁵

Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.³ Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.⁷ For disseminated disease, systemic corticosteroids have shown efficacy.³ Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.³

Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.

The Diagnosis: Cutaneous Crohn Disease

A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.

Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.

Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.¹ This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.² The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.³

Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.¹ The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.^4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.⁶

Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.⁵

Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.³ Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.⁷ For disseminated disease, systemic corticosteroids have shown efficacy.³ Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.³

Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Wells Syndrome

A punch biopsy taken from the perimeter of the lesion demonstrated mild spongiosis overlying a dense nodular to diffuse infiltrate of lymphocytes, neutrophils, and numerous eosinophils, some involving underlying fat lobules (Figure, A and B). In some areas, eosinophilic degeneration of collagen bundles surrounded by a rim of histiocytes, "flame features," were observed (Figure C). The clinical and histological features were consistent with Wells syndrome (WS), also known as eosinophilic cellulitis. Given the localized mild nature of the disease, the patient was started on a midpotency topical corticosteroid.

Wells syndrome is a rare inflammatory condition characterized by clinical polymorphism, suggestive histologic findings, and a recurrent course.^1,2 This condition is especially rare in children.^3,4 Caputo et al1 described 7 variants in their case series of 19 patients: classic plaque-type variant (the most common clinical presentation in children); annular granuloma-like (the most common clinical presentation in adults); urticarialike; bullous; papulonodular; papulovesicular; and fixed drug eruption-like. Wells syndrome is thought to result from excess production of IL-5 in response to a hypersensitivity reaction to an exogenous or endogenous circulating antigen.^3,4 Increased levels of IL-5 enhance eosinophil accumulation in the skin, degranulation, and subsequent tissue destruction.^3,4 Reported triggers include insect bites, viral and bacterial infections, drug eruptions, recent vaccination, and paraphenylenediamine in henna tattoos.^3-7 Additionally, WS has been reported in the setting of gastrointestinal pathologies, such as celiac disease and ulcerative colitis, and with asthma exacerbations.^8,9 However, in half of pediatric cases, no trigger can be identified.⁷

Clinically, WS presents with pruritic, mildly tender plaques.⁷ Lesions may be localized or diffuse and range from mild annular or circinate plaques with infiltrated borders to cellulitic-appearing lesions that are occasionally associated with bullae.^5,6 Patients often report prodromal symptoms of burning and pruritus.^5,6 Lesions rapidly progress over 2 to 3 days, pass through a blue grayish discoloration phase, and gradually resolve over 2 to 8 weeks.^5,6,10 Although patients generally heal without scarring, WS lesions have been described to resolve with atrophy and hyperpigmentation resembling morphea.^5-7 Additionally, patients typically experience a relapsing remitting course over months to years with eventual spontaneous resolution.^1,5 Patients also may experience systemic symptoms including fever, lymphadenopathy, and arthralgia, though they do not develop more widespread systemic manifestations.^2,3,7

Diagnosis of WS is based on clinicopathologic correlation. Histopathology of WS lesions demonstrates 3 phases. The acute phase demonstrates edema of the superficial and mid dermis with a dense dermal eosinophilic infiltrate.^1,6,10 The subacute granulomatous phase demonstrates flame figures in the dermis.^1,2,6,7,10 Flame figures consist of palisading groups of eosinophils and histiocytes around a core of degenerating basophilic collagen bundles associated with major basic protein.^1,2,6,7,10 Finally, in the resolution phase, eosinophils gradually disappear while histiocytes and giant cells persist, forming microgranulomas.^1,2,10 Notably, no vasculitis is observed and direct immunofluorescence is negative.^3,7 Although flame figures are suggestive of WS, they are not pathognomonic and are observed in other conditions including Churg-Strauss syndrome, parasitic and fungal infections, herpes gestationis, bullous pemphigoid, and follicular mucinosis.^2,5

Wells syndrome is a self-resolving and benign condition.^1,10 Physicians are recommended to gather a complete history including review of medications and vaccinations; a history of insect bites, infections, and asthma; laboratory workup consisting of a complete blood cell count with differential and stool samples for ova and parasites; and a skin biopsy if the diagnosis is unclear.⁷ Identification and treatment of underlying causes often results in resolution.⁶ Systemic corticosteroids frequently are used in both adult and pediatric patients, though practitioners should consider alternative treatments when recurrences occur to avoid steroid side effects.^3,6 Midpotency topical corticosteroids present a safe alternative to systemic corticosteroids in the pediatric population, especially in cases of localized WS without systemic symptoms.³ Other medications reported in the literature include cyclosporine, dapsone, antimalarial medications, and azathioprine.⁶ Despite appropriate therapy, patients and physicians should anticipate recurrence over months to years.^1,6

The Diagnosis: Wells Syndrome

A punch biopsy taken from the perimeter of the lesion demonstrated mild spongiosis overlying a dense nodular to diffuse infiltrate of lymphocytes, neutrophils, and numerous eosinophils, some involving underlying fat lobules (Figure, A and B). In some areas, eosinophilic degeneration of collagen bundles surrounded by a rim of histiocytes, "flame features," were observed (Figure C). The clinical and histological features were consistent with Wells syndrome (WS), also known as eosinophilic cellulitis. Given the localized mild nature of the disease, the patient was started on a midpotency topical corticosteroid.

Wells syndrome is a rare inflammatory condition characterized by clinical polymorphism, suggestive histologic findings, and a recurrent course.^1,2 This condition is especially rare in children.^3,4 Caputo et al1 described 7 variants in their case series of 19 patients: classic plaque-type variant (the most common clinical presentation in children); annular granuloma-like (the most common clinical presentation in adults); urticarialike; bullous; papulonodular; papulovesicular; and fixed drug eruption-like. Wells syndrome is thought to result from excess production of IL-5 in response to a hypersensitivity reaction to an exogenous or endogenous circulating antigen.^3,4 Increased levels of IL-5 enhance eosinophil accumulation in the skin, degranulation, and subsequent tissue destruction.^3,4 Reported triggers include insect bites, viral and bacterial infections, drug eruptions, recent vaccination, and paraphenylenediamine in henna tattoos.^3-7 Additionally, WS has been reported in the setting of gastrointestinal pathologies, such as celiac disease and ulcerative colitis, and with asthma exacerbations.^8,9 However, in half of pediatric cases, no trigger can be identified.⁷

Clinically, WS presents with pruritic, mildly tender plaques.⁷ Lesions may be localized or diffuse and range from mild annular or circinate plaques with infiltrated borders to cellulitic-appearing lesions that are occasionally associated with bullae.^5,6 Patients often report prodromal symptoms of burning and pruritus.^5,6 Lesions rapidly progress over 2 to 3 days, pass through a blue grayish discoloration phase, and gradually resolve over 2 to 8 weeks.^5,6,10 Although patients generally heal without scarring, WS lesions have been described to resolve with atrophy and hyperpigmentation resembling morphea.^5-7 Additionally, patients typically experience a relapsing remitting course over months to years with eventual spontaneous resolution.^1,5 Patients also may experience systemic symptoms including fever, lymphadenopathy, and arthralgia, though they do not develop more widespread systemic manifestations.^2,3,7

Diagnosis of WS is based on clinicopathologic correlation. Histopathology of WS lesions demonstrates 3 phases. The acute phase demonstrates edema of the superficial and mid dermis with a dense dermal eosinophilic infiltrate.^1,6,10 The subacute granulomatous phase demonstrates flame figures in the dermis.^1,2,6,7,10 Flame figures consist of palisading groups of eosinophils and histiocytes around a core of degenerating basophilic collagen bundles associated with major basic protein.^1,2,6,7,10 Finally, in the resolution phase, eosinophils gradually disappear while histiocytes and giant cells persist, forming microgranulomas.^1,2,10 Notably, no vasculitis is observed and direct immunofluorescence is negative.^3,7 Although flame figures are suggestive of WS, they are not pathognomonic and are observed in other conditions including Churg-Strauss syndrome, parasitic and fungal infections, herpes gestationis, bullous pemphigoid, and follicular mucinosis.^2,5

Wells syndrome is a self-resolving and benign condition.^1,10 Physicians are recommended to gather a complete history including review of medications and vaccinations; a history of insect bites, infections, and asthma; laboratory workup consisting of a complete blood cell count with differential and stool samples for ova and parasites; and a skin biopsy if the diagnosis is unclear.⁷ Identification and treatment of underlying causes often results in resolution.⁶ Systemic corticosteroids frequently are used in both adult and pediatric patients, though practitioners should consider alternative treatments when recurrences occur to avoid steroid side effects.^3,6 Midpotency topical corticosteroids present a safe alternative to systemic corticosteroids in the pediatric population, especially in cases of localized WS without systemic symptoms.³ Other medications reported in the literature include cyclosporine, dapsone, antimalarial medications, and azathioprine.⁶ Despite appropriate therapy, patients and physicians should anticipate recurrence over months to years.^1,6

The Diagnosis: Wells Syndrome

A punch biopsy taken from the perimeter of the lesion demonstrated mild spongiosis overlying a dense nodular to diffuse infiltrate of lymphocytes, neutrophils, and numerous eosinophils, some involving underlying fat lobules (Figure, A and B). In some areas, eosinophilic degeneration of collagen bundles surrounded by a rim of histiocytes, "flame features," were observed (Figure C). The clinical and histological features were consistent with Wells syndrome (WS), also known as eosinophilic cellulitis. Given the localized mild nature of the disease, the patient was started on a midpotency topical corticosteroid.

Wells syndrome is a rare inflammatory condition characterized by clinical polymorphism, suggestive histologic findings, and a recurrent course.^1,2 This condition is especially rare in children.^3,4 Caputo et al1 described 7 variants in their case series of 19 patients: classic plaque-type variant (the most common clinical presentation in children); annular granuloma-like (the most common clinical presentation in adults); urticarialike; bullous; papulonodular; papulovesicular; and fixed drug eruption-like. Wells syndrome is thought to result from excess production of IL-5 in response to a hypersensitivity reaction to an exogenous or endogenous circulating antigen.^3,4 Increased levels of IL-5 enhance eosinophil accumulation in the skin, degranulation, and subsequent tissue destruction.^3,4 Reported triggers include insect bites, viral and bacterial infections, drug eruptions, recent vaccination, and paraphenylenediamine in henna tattoos.^3-7 Additionally, WS has been reported in the setting of gastrointestinal pathologies, such as celiac disease and ulcerative colitis, and with asthma exacerbations.^8,9 However, in half of pediatric cases, no trigger can be identified.⁷

Clinically, WS presents with pruritic, mildly tender plaques.⁷ Lesions may be localized or diffuse and range from mild annular or circinate plaques with infiltrated borders to cellulitic-appearing lesions that are occasionally associated with bullae.^5,6 Patients often report prodromal symptoms of burning and pruritus.^5,6 Lesions rapidly progress over 2 to 3 days, pass through a blue grayish discoloration phase, and gradually resolve over 2 to 8 weeks.^5,6,10 Although patients generally heal without scarring, WS lesions have been described to resolve with atrophy and hyperpigmentation resembling morphea.^5-7 Additionally, patients typically experience a relapsing remitting course over months to years with eventual spontaneous resolution.^1,5 Patients also may experience systemic symptoms including fever, lymphadenopathy, and arthralgia, though they do not develop more widespread systemic manifestations.^2,3,7

Diagnosis of WS is based on clinicopathologic correlation. Histopathology of WS lesions demonstrates 3 phases. The acute phase demonstrates edema of the superficial and mid dermis with a dense dermal eosinophilic infiltrate.^1,6,10 The subacute granulomatous phase demonstrates flame figures in the dermis.^1,2,6,7,10 Flame figures consist of palisading groups of eosinophils and histiocytes around a core of degenerating basophilic collagen bundles associated with major basic protein.^1,2,6,7,10 Finally, in the resolution phase, eosinophils gradually disappear while histiocytes and giant cells persist, forming microgranulomas.^1,2,10 Notably, no vasculitis is observed and direct immunofluorescence is negative.^3,7 Although flame figures are suggestive of WS, they are not pathognomonic and are observed in other conditions including Churg-Strauss syndrome, parasitic and fungal infections, herpes gestationis, bullous pemphigoid, and follicular mucinosis.^2,5

Wells syndrome is a self-resolving and benign condition.^1,10 Physicians are recommended to gather a complete history including review of medications and vaccinations; a history of insect bites, infections, and asthma; laboratory workup consisting of a complete blood cell count with differential and stool samples for ova and parasites; and a skin biopsy if the diagnosis is unclear.⁷ Identification and treatment of underlying causes often results in resolution.⁶ Systemic corticosteroids frequently are used in both adult and pediatric patients, though practitioners should consider alternative treatments when recurrences occur to avoid steroid side effects.^3,6 Midpotency topical corticosteroids present a safe alternative to systemic corticosteroids in the pediatric population, especially in cases of localized WS without systemic symptoms.³ Other medications reported in the literature include cyclosporine, dapsone, antimalarial medications, and azathioprine.⁶ Despite appropriate therapy, patients and physicians should anticipate recurrence over months to years.^1,6

The Diagnosis: Cutaneous Collagenous Vasculopathy

Histopathologic examination revealed ectatic blood vessels lined with unremarkable endothelial cells and thickened, hyalinized vessel walls scattered within the papillary dermis (Figure 1). The epidermis was unremarkable. There was minimal associated inflammation and no extravasation of erythrocytes. The hyalinized material was weakly positive on periodic acid-Schiff staining (Figure 2) and negative on Congo red staining, which supported of a diagnosis of cutaneous collagenous vasculopathy (CCV).

The patient previously had been given a suspected diagnosis of generalized essential telangiectasia by an outside dermatologist several years prior to the current presentation, as CCV had yet to be recognized as its own entity and therefore few cases had been described in the literature. She had a known history of obesity, hypertension, hyperlipidemia, and type 2 diabetes mellitus, which are associated with the condition. Multiple specialists concluded that the disease was too extensive for laser treatment. A review of PubMed articles indexed for MEDLINE yielded no established treatment options.

Cutaneous collagenous vasculopathy is a rare acquired microangiopathy involving the small vessels of the skin. Its clinical presentation is indistinguishable from that of generalized essential telangiectasia (GET). Patients generally present with asymptomatic, widespread, blanching, symmetric telangiectasias that classically begin on the legs and steadily progress upward with classic sparing of the face (Figure 3). Whereas GET has been reported to involve the oral and conjunctival mucosa, mucosal involvement is not typically observed in CCV and is considered to be a distinguishing factor between the 2 conditions.^1,2 However, our patient reported oral symptoms, and oral erosions were seen on multiple physical examinations; therefore, ours is a rare case of mucosal involvement in conjunction with CCV. Given this finding, it is possible that more cases of CCV with mucosal involvement may exist but have been clinically misdiagnosed as GET.

First described by Salama and Rosenthal³ in 2000, CCV remains a rarely reported entity, with approximately 33 reported cases in the worldwide literature.^2,4-7 The condition typically arises in adults with an equal predilection for males and females.² The true incidence of CCV is unknown and likely is underreported given its close similarities to GET, which often is diagnosed clinically. The unique histopathologic finding of superficial ectatic vascular spaces with eosinophilic hyalinized vessel walls in CCV is key to distinguishing these similar entities, and even this finding can be subtle and is easily overlooked. Inflammation is sparse to absent. Deposited material is positive on periodic acid-Schiff and cytokeratin IV staining (representing reduplicated basement membrane-type collagen) and is diastase resistant. Smooth muscle actin staining is diminished or absent. Ultrastructural examination reveals reduplicated, laminated basement membrane; Luse bodies (abnormally long, widely spaced collagen fibers); and a decrease in or loss of pericytes. Of note, Luse bodies are nonspecific and their absence does not exclude a diagnosis of CCV.¹

The etiology of CCV is unclear, and multiple pathogenetic mechanisms have been proposed. Ultimately, this entity is thought to arise from repeated endothelial cell damage, although the trigger for the endothelial cell injury is not completely understood. Diabetes mellitus sometimes is associated with microangiopathy and may be a confounding but not causative factor in some cases.¹ Some investigators believe CCV is caused by a genetic defect that alters collagen production in the small vessels of the skin.⁵ Others have hypothesized that it is a secondary manifestation of an underlying disease or is associated with a medication; however, no disease or drug has been convincingly implicated in CCV.⁸

Cutaneous collagenous vasculopathy is limited to the skin, with no known reports of systemic involvement in the literature.⁷ There are no recommended laboratory studies to aid in diagnosis.¹ It is critical to exclude hereditary hemorrhagic telangiectasia (HHT), as these patients can have life-threatening systemic involvement. Patients with CCV generally have no history of a bleeding diathesis, patients with HHT classically report recurrent epistaxis and gastrointestinal bleeding.⁷ A family history of HHT also is helpful for diagnosis, as the condition is autosomal dominant.¹ Neither HHT or telangiectasia macularis eruptiva perstans, which also can be included in the differential diagnosis, demonstrate vessel wall hyalinization. 

Treatment options for CCV are limited. Basso et al⁶ reported notable improvement in a patient with CCV treated with a combined 595-nm pulsed dye laser and 1064-nm Nd:YAG laser and optimized pulsed light. In one patient, treatment with a 585-nm pulsed dye laser produced a blanching response, suggesting that this may be a potential treatment option.⁷ Treatment with sclerotherapy has been ineffective.²

It is critical for both dermatologists and dermatopathologists to recognize and report this newly described entity, as the unique finding of vessel wall hyalinization in CCV may be indicative of a certain pathogenetic mechanism and effective treatment avenue that has yet to be established due to the relatively few number of reports that currently exist in the literature.

The Diagnosis: Cutaneous Collagenous Vasculopathy

Histopathologic examination revealed ectatic blood vessels lined with unremarkable endothelial cells and thickened, hyalinized vessel walls scattered within the papillary dermis (Figure 1). The epidermis was unremarkable. There was minimal associated inflammation and no extravasation of erythrocytes. The hyalinized material was weakly positive on periodic acid-Schiff staining (Figure 2) and negative on Congo red staining, which supported of a diagnosis of cutaneous collagenous vasculopathy (CCV).

The patient previously had been given a suspected diagnosis of generalized essential telangiectasia by an outside dermatologist several years prior to the current presentation, as CCV had yet to be recognized as its own entity and therefore few cases had been described in the literature. She had a known history of obesity, hypertension, hyperlipidemia, and type 2 diabetes mellitus, which are associated with the condition. Multiple specialists concluded that the disease was too extensive for laser treatment. A review of PubMed articles indexed for MEDLINE yielded no established treatment options.

Cutaneous collagenous vasculopathy is a rare acquired microangiopathy involving the small vessels of the skin. Its clinical presentation is indistinguishable from that of generalized essential telangiectasia (GET). Patients generally present with asymptomatic, widespread, blanching, symmetric telangiectasias that classically begin on the legs and steadily progress upward with classic sparing of the face (Figure 3). Whereas GET has been reported to involve the oral and conjunctival mucosa, mucosal involvement is not typically observed in CCV and is considered to be a distinguishing factor between the 2 conditions.^1,2 However, our patient reported oral symptoms, and oral erosions were seen on multiple physical examinations; therefore, ours is a rare case of mucosal involvement in conjunction with CCV. Given this finding, it is possible that more cases of CCV with mucosal involvement may exist but have been clinically misdiagnosed as GET.

First described by Salama and Rosenthal³ in 2000, CCV remains a rarely reported entity, with approximately 33 reported cases in the worldwide literature.^2,4-7 The condition typically arises in adults with an equal predilection for males and females.² The true incidence of CCV is unknown and likely is underreported given its close similarities to GET, which often is diagnosed clinically. The unique histopathologic finding of superficial ectatic vascular spaces with eosinophilic hyalinized vessel walls in CCV is key to distinguishing these similar entities, and even this finding can be subtle and is easily overlooked. Inflammation is sparse to absent. Deposited material is positive on periodic acid-Schiff and cytokeratin IV staining (representing reduplicated basement membrane-type collagen) and is diastase resistant. Smooth muscle actin staining is diminished or absent. Ultrastructural examination reveals reduplicated, laminated basement membrane; Luse bodies (abnormally long, widely spaced collagen fibers); and a decrease in or loss of pericytes. Of note, Luse bodies are nonspecific and their absence does not exclude a diagnosis of CCV.¹

The etiology of CCV is unclear, and multiple pathogenetic mechanisms have been proposed. Ultimately, this entity is thought to arise from repeated endothelial cell damage, although the trigger for the endothelial cell injury is not completely understood. Diabetes mellitus sometimes is associated with microangiopathy and may be a confounding but not causative factor in some cases.¹ Some investigators believe CCV is caused by a genetic defect that alters collagen production in the small vessels of the skin.⁵ Others have hypothesized that it is a secondary manifestation of an underlying disease or is associated with a medication; however, no disease or drug has been convincingly implicated in CCV.⁸

Cutaneous collagenous vasculopathy is limited to the skin, with no known reports of systemic involvement in the literature.⁷ There are no recommended laboratory studies to aid in diagnosis.¹ It is critical to exclude hereditary hemorrhagic telangiectasia (HHT), as these patients can have life-threatening systemic involvement. Patients with CCV generally have no history of a bleeding diathesis, patients with HHT classically report recurrent epistaxis and gastrointestinal bleeding.⁷ A family history of HHT also is helpful for diagnosis, as the condition is autosomal dominant.¹ Neither HHT or telangiectasia macularis eruptiva perstans, which also can be included in the differential diagnosis, demonstrate vessel wall hyalinization. 

Treatment options for CCV are limited. Basso et al⁶ reported notable improvement in a patient with CCV treated with a combined 595-nm pulsed dye laser and 1064-nm Nd:YAG laser and optimized pulsed light. In one patient, treatment with a 585-nm pulsed dye laser produced a blanching response, suggesting that this may be a potential treatment option.⁷ Treatment with sclerotherapy has been ineffective.²

It is critical for both dermatologists and dermatopathologists to recognize and report this newly described entity, as the unique finding of vessel wall hyalinization in CCV may be indicative of a certain pathogenetic mechanism and effective treatment avenue that has yet to be established due to the relatively few number of reports that currently exist in the literature.

The Diagnosis: Cutaneous Collagenous Vasculopathy

Histopathologic examination revealed ectatic blood vessels lined with unremarkable endothelial cells and thickened, hyalinized vessel walls scattered within the papillary dermis (Figure 1). The epidermis was unremarkable. There was minimal associated inflammation and no extravasation of erythrocytes. The hyalinized material was weakly positive on periodic acid-Schiff staining (Figure 2) and negative on Congo red staining, which supported of a diagnosis of cutaneous collagenous vasculopathy (CCV).

The patient previously had been given a suspected diagnosis of generalized essential telangiectasia by an outside dermatologist several years prior to the current presentation, as CCV had yet to be recognized as its own entity and therefore few cases had been described in the literature. She had a known history of obesity, hypertension, hyperlipidemia, and type 2 diabetes mellitus, which are associated with the condition. Multiple specialists concluded that the disease was too extensive for laser treatment. A review of PubMed articles indexed for MEDLINE yielded no established treatment options.

Cutaneous collagenous vasculopathy is a rare acquired microangiopathy involving the small vessels of the skin. Its clinical presentation is indistinguishable from that of generalized essential telangiectasia (GET). Patients generally present with asymptomatic, widespread, blanching, symmetric telangiectasias that classically begin on the legs and steadily progress upward with classic sparing of the face (Figure 3). Whereas GET has been reported to involve the oral and conjunctival mucosa, mucosal involvement is not typically observed in CCV and is considered to be a distinguishing factor between the 2 conditions.^1,2 However, our patient reported oral symptoms, and oral erosions were seen on multiple physical examinations; therefore, ours is a rare case of mucosal involvement in conjunction with CCV. Given this finding, it is possible that more cases of CCV with mucosal involvement may exist but have been clinically misdiagnosed as GET.

First described by Salama and Rosenthal³ in 2000, CCV remains a rarely reported entity, with approximately 33 reported cases in the worldwide literature.^2,4-7 The condition typically arises in adults with an equal predilection for males and females.² The true incidence of CCV is unknown and likely is underreported given its close similarities to GET, which often is diagnosed clinically. The unique histopathologic finding of superficial ectatic vascular spaces with eosinophilic hyalinized vessel walls in CCV is key to distinguishing these similar entities, and even this finding can be subtle and is easily overlooked. Inflammation is sparse to absent. Deposited material is positive on periodic acid-Schiff and cytokeratin IV staining (representing reduplicated basement membrane-type collagen) and is diastase resistant. Smooth muscle actin staining is diminished or absent. Ultrastructural examination reveals reduplicated, laminated basement membrane; Luse bodies (abnormally long, widely spaced collagen fibers); and a decrease in or loss of pericytes. Of note, Luse bodies are nonspecific and their absence does not exclude a diagnosis of CCV.¹

The etiology of CCV is unclear, and multiple pathogenetic mechanisms have been proposed. Ultimately, this entity is thought to arise from repeated endothelial cell damage, although the trigger for the endothelial cell injury is not completely understood. Diabetes mellitus sometimes is associated with microangiopathy and may be a confounding but not causative factor in some cases.¹ Some investigators believe CCV is caused by a genetic defect that alters collagen production in the small vessels of the skin.⁵ Others have hypothesized that it is a secondary manifestation of an underlying disease or is associated with a medication; however, no disease or drug has been convincingly implicated in CCV.⁸

Cutaneous collagenous vasculopathy is limited to the skin, with no known reports of systemic involvement in the literature.⁷ There are no recommended laboratory studies to aid in diagnosis.¹ It is critical to exclude hereditary hemorrhagic telangiectasia (HHT), as these patients can have life-threatening systemic involvement. Patients with CCV generally have no history of a bleeding diathesis, patients with HHT classically report recurrent epistaxis and gastrointestinal bleeding.⁷ A family history of HHT also is helpful for diagnosis, as the condition is autosomal dominant.¹ Neither HHT or telangiectasia macularis eruptiva perstans, which also can be included in the differential diagnosis, demonstrate vessel wall hyalinization. 

Treatment options for CCV are limited. Basso et al⁶ reported notable improvement in a patient with CCV treated with a combined 595-nm pulsed dye laser and 1064-nm Nd:YAG laser and optimized pulsed light. In one patient, treatment with a 585-nm pulsed dye laser produced a blanching response, suggesting that this may be a potential treatment option.⁷ Treatment with sclerotherapy has been ineffective.²

It is critical for both dermatologists and dermatopathologists to recognize and report this newly described entity, as the unique finding of vessel wall hyalinization in CCV may be indicative of a certain pathogenetic mechanism and effective treatment avenue that has yet to be established due to the relatively few number of reports that currently exist in the literature.

The Diagnosis: Superficial Migratory Thrombophlebitis

On initial presentation, the differential diagnosis included livedoid vasculopathy, cutaneous polyarteritis nodosa, erythema ab igne, cholesterol embolism, and livedo reticularis. Laboratory investigation included antiphospholipid antibody syndrome (APS), antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, serum protein electrophoresis, and coagulation tests. Pertinent findings included transient low total complement activity but normal complement protein C2, C3, and C5 levels and negative cryoglobulins. Additional laboratory testing revealed elevated antiphosphatidylserine IgG, which remained elevated 12 weeks later.

New lesions continued to appear over the next several months as painful, erythematous, linear, pruritic nodules that resolved as hyperpigmented linear patches, which intersected to form a livedo reticularis-like pattern that covered the lower legs. Biopsy of an erythematous nodule on the right leg revealed fibrin occlusion of a medium-sized vein in the subcutaneous fat. Direct immunofluorescence was not specific. Venous duplex ultrasonography demonstrated chronic superficial thrombophlebitis and was crucial to the diagnosis. Ultimately, the patient's history, clinical presentation, laboratory results, venous studies, and histopathologic analysis were consistent with a diagnosis of superficial migratory thrombophlebitis (SMT) with resultant postinflammatory hyperpigmentation presenting in a reticular pattern that mimicked livedoid vasculopathy, livedo reticularis, or erythema ab igne.

Superficial migratory thrombophlebitis, also known as thrombophlebitis migrans, is defined as the recurrent formation of thrombi within superficial veins.¹ The presence of a thrombus in a superficial vein evokes an inflammatory response, resulting in swelling, tenderness, erythema, and warmth in the affected area. Superficial migratory thrombophlebitis has been associated with several etiologies, including pregnancy, oral contraceptive use, APS, vasculitic disorders, and malignancies (eg, pancreas, lung, breast), as well as infections such as secondary syphilis.¹

When SMT is associated with an occult malignancy, it is known as Trousseau syndrome. Common malignancies found in association with Trousseau syndrome include pancreatic, lung, and breast cancers.² A systematic review from 2008 evaluated the utility of extensive cancer screening strategies in patients with newly diagnosed, unprovoked venous thromboembolic events.³ Using a wide screening strategy that included computed tomography of the abdomen and pelvis, the investigators detected a considerable number of formerly undiagnosed cancers, increasing detection rates from 49.4% to 69.7%. After the diagnosis of SMT was made in our patient, computed tomography of the chest, abdomen, and pelvis was performed, but the findings were unremarkable.

Because occult malignancy was excluded in our patient, the likely etiology of SMT was APS, an acquired autoimmune condition diagnosed based on the presence of a vascular thrombosis and/or pregnancy failure in women as well as elevation of at least one antiphospholipid antibody laboratory marker (eg, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I antibody) on 2 or more occasions at least 12 weeks apart.⁴ Other antibodies such as those directed against negatively charged phospholipids (eg, antiphosphatidylserine [which was elevated in our patient], phosphatidylinositol, phosphatidic acid) have been reported in patients with APS, although their diagnostic use is controversial.⁵ For example, the presence of antiphosphatidylserine antibodies has been considered common but not specific in patients with APS.⁴ However, a recent observational study demonstrated that antiphosphatidylserine antibodies are highly specific (87%) and useful in diagnosing clinical APS cases in the presence of other negative markers.⁶

In our patient, diagnosis of SMT with resultant postinflammatory hyperpigmentation in a reticular pattern was based on the patient's medical history, clinical examination, and histopathologic findings, as well as laboratory results and venous studies. However, it is important to note that a livedo reticularis-like pattern also is a very common finding in APS and must be included in the differential diagnosis of a reticular network on the skin.⁷ Moreover, differentiating livedo reticularis from SMT has prognostic importance since SMT may be associated with underlying malignancies while livedo reticularis may be associated with Sneddon syndrome, a disorder in which neurologic vascular events (eg, cerebrovascular accidents) are present.⁸ While this distinction is important, there are no pathognomonic histologic findings seen in livedo reticularis, and consideration of the clinical picture and additional testing is critical.^4,8

Livedo vasculopathy was excluded in our patient due to the lack of diagnostic histopathologic findings, such as fibrin deposition and thrombus formation involving the upper- and mid-dermal capillaries.⁹ Furthermore, characteristic direct immunofluorescence findings of a homogenous or granular deposition in the vessel wall consisting of immune complexes, complement, and fibrin were absent in our patient.⁹ Our patient also lacked common clinical findings found in livedo vasculopathy such as small ulcerations or atrophic, porcelain-white scars on the lower legs. Erythema ab igne also was excluded in our patient due to the absence of heat exposure and presence of fibrin occlusion in the superficial leg veins. Physiologic livedo reticularis, defined as a livedoid pattern due to physiologic changes in the skin in response to cold exposure,¹⁰ also was excluded, as our patient's cutaneous changes included an alteration in pigmentation with a brown reticular pattern and no blanching, erythematous or violaceous hue, warmth, or tenderness.

In conclusion, SMT is a disorder with multiple associations that may clinically mimic livedo reticularis and livedoid vasculopathy when postinflammatory hyperpigmentation has a lacelike or livedoid pattern. While nontraditional antibodies may be useful in diagnosis in patients suspected of having APS with otherwise negative markers, standardized assays and further studies are needed to determine the specificity and value of these antibodies, particularly when used in isolation. Our patient's elevated antiphosphatidylserine IgG may have been the cause of her hypercoagulable state causing the SMT. A livedoid pattern is a common finding in APS and also was seen in our patient with SMT, but the differentiation of the brown pigmentary change and more active erythema was critical to the appropriate clinical workup of our patient.

The Diagnosis: Superficial Migratory Thrombophlebitis

On initial presentation, the differential diagnosis included livedoid vasculopathy, cutaneous polyarteritis nodosa, erythema ab igne, cholesterol embolism, and livedo reticularis. Laboratory investigation included antiphospholipid antibody syndrome (APS), antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, serum protein electrophoresis, and coagulation tests. Pertinent findings included transient low total complement activity but normal complement protein C2, C3, and C5 levels and negative cryoglobulins. Additional laboratory testing revealed elevated antiphosphatidylserine IgG, which remained elevated 12 weeks later.

New lesions continued to appear over the next several months as painful, erythematous, linear, pruritic nodules that resolved as hyperpigmented linear patches, which intersected to form a livedo reticularis-like pattern that covered the lower legs. Biopsy of an erythematous nodule on the right leg revealed fibrin occlusion of a medium-sized vein in the subcutaneous fat. Direct immunofluorescence was not specific. Venous duplex ultrasonography demonstrated chronic superficial thrombophlebitis and was crucial to the diagnosis. Ultimately, the patient's history, clinical presentation, laboratory results, venous studies, and histopathologic analysis were consistent with a diagnosis of superficial migratory thrombophlebitis (SMT) with resultant postinflammatory hyperpigmentation presenting in a reticular pattern that mimicked livedoid vasculopathy, livedo reticularis, or erythema ab igne.

Superficial migratory thrombophlebitis, also known as thrombophlebitis migrans, is defined as the recurrent formation of thrombi within superficial veins.¹ The presence of a thrombus in a superficial vein evokes an inflammatory response, resulting in swelling, tenderness, erythema, and warmth in the affected area. Superficial migratory thrombophlebitis has been associated with several etiologies, including pregnancy, oral contraceptive use, APS, vasculitic disorders, and malignancies (eg, pancreas, lung, breast), as well as infections such as secondary syphilis.¹

When SMT is associated with an occult malignancy, it is known as Trousseau syndrome. Common malignancies found in association with Trousseau syndrome include pancreatic, lung, and breast cancers.² A systematic review from 2008 evaluated the utility of extensive cancer screening strategies in patients with newly diagnosed, unprovoked venous thromboembolic events.³ Using a wide screening strategy that included computed tomography of the abdomen and pelvis, the investigators detected a considerable number of formerly undiagnosed cancers, increasing detection rates from 49.4% to 69.7%. After the diagnosis of SMT was made in our patient, computed tomography of the chest, abdomen, and pelvis was performed, but the findings were unremarkable.

Because occult malignancy was excluded in our patient, the likely etiology of SMT was APS, an acquired autoimmune condition diagnosed based on the presence of a vascular thrombosis and/or pregnancy failure in women as well as elevation of at least one antiphospholipid antibody laboratory marker (eg, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I antibody) on 2 or more occasions at least 12 weeks apart.⁴ Other antibodies such as those directed against negatively charged phospholipids (eg, antiphosphatidylserine [which was elevated in our patient], phosphatidylinositol, phosphatidic acid) have been reported in patients with APS, although their diagnostic use is controversial.⁵ For example, the presence of antiphosphatidylserine antibodies has been considered common but not specific in patients with APS.⁴ However, a recent observational study demonstrated that antiphosphatidylserine antibodies are highly specific (87%) and useful in diagnosing clinical APS cases in the presence of other negative markers.⁶

In our patient, diagnosis of SMT with resultant postinflammatory hyperpigmentation in a reticular pattern was based on the patient's medical history, clinical examination, and histopathologic findings, as well as laboratory results and venous studies. However, it is important to note that a livedo reticularis-like pattern also is a very common finding in APS and must be included in the differential diagnosis of a reticular network on the skin.⁷ Moreover, differentiating livedo reticularis from SMT has prognostic importance since SMT may be associated with underlying malignancies while livedo reticularis may be associated with Sneddon syndrome, a disorder in which neurologic vascular events (eg, cerebrovascular accidents) are present.⁸ While this distinction is important, there are no pathognomonic histologic findings seen in livedo reticularis, and consideration of the clinical picture and additional testing is critical.^4,8

Livedo vasculopathy was excluded in our patient due to the lack of diagnostic histopathologic findings, such as fibrin deposition and thrombus formation involving the upper- and mid-dermal capillaries.⁹ Furthermore, characteristic direct immunofluorescence findings of a homogenous or granular deposition in the vessel wall consisting of immune complexes, complement, and fibrin were absent in our patient.⁹ Our patient also lacked common clinical findings found in livedo vasculopathy such as small ulcerations or atrophic, porcelain-white scars on the lower legs. Erythema ab igne also was excluded in our patient due to the absence of heat exposure and presence of fibrin occlusion in the superficial leg veins. Physiologic livedo reticularis, defined as a livedoid pattern due to physiologic changes in the skin in response to cold exposure,¹⁰ also was excluded, as our patient's cutaneous changes included an alteration in pigmentation with a brown reticular pattern and no blanching, erythematous or violaceous hue, warmth, or tenderness.

In conclusion, SMT is a disorder with multiple associations that may clinically mimic livedo reticularis and livedoid vasculopathy when postinflammatory hyperpigmentation has a lacelike or livedoid pattern. While nontraditional antibodies may be useful in diagnosis in patients suspected of having APS with otherwise negative markers, standardized assays and further studies are needed to determine the specificity and value of these antibodies, particularly when used in isolation. Our patient's elevated antiphosphatidylserine IgG may have been the cause of her hypercoagulable state causing the SMT. A livedoid pattern is a common finding in APS and also was seen in our patient with SMT, but the differentiation of the brown pigmentary change and more active erythema was critical to the appropriate clinical workup of our patient.

The Diagnosis: Superficial Migratory Thrombophlebitis

On initial presentation, the differential diagnosis included livedoid vasculopathy, cutaneous polyarteritis nodosa, erythema ab igne, cholesterol embolism, and livedo reticularis. Laboratory investigation included antiphospholipid antibody syndrome (APS), antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, serum protein electrophoresis, and coagulation tests. Pertinent findings included transient low total complement activity but normal complement protein C2, C3, and C5 levels and negative cryoglobulins. Additional laboratory testing revealed elevated antiphosphatidylserine IgG, which remained elevated 12 weeks later.

New lesions continued to appear over the next several months as painful, erythematous, linear, pruritic nodules that resolved as hyperpigmented linear patches, which intersected to form a livedo reticularis-like pattern that covered the lower legs. Biopsy of an erythematous nodule on the right leg revealed fibrin occlusion of a medium-sized vein in the subcutaneous fat. Direct immunofluorescence was not specific. Venous duplex ultrasonography demonstrated chronic superficial thrombophlebitis and was crucial to the diagnosis. Ultimately, the patient's history, clinical presentation, laboratory results, venous studies, and histopathologic analysis were consistent with a diagnosis of superficial migratory thrombophlebitis (SMT) with resultant postinflammatory hyperpigmentation presenting in a reticular pattern that mimicked livedoid vasculopathy, livedo reticularis, or erythema ab igne.

Superficial migratory thrombophlebitis, also known as thrombophlebitis migrans, is defined as the recurrent formation of thrombi within superficial veins.¹ The presence of a thrombus in a superficial vein evokes an inflammatory response, resulting in swelling, tenderness, erythema, and warmth in the affected area. Superficial migratory thrombophlebitis has been associated with several etiologies, including pregnancy, oral contraceptive use, APS, vasculitic disorders, and malignancies (eg, pancreas, lung, breast), as well as infections such as secondary syphilis.¹

When SMT is associated with an occult malignancy, it is known as Trousseau syndrome. Common malignancies found in association with Trousseau syndrome include pancreatic, lung, and breast cancers.² A systematic review from 2008 evaluated the utility of extensive cancer screening strategies in patients with newly diagnosed, unprovoked venous thromboembolic events.³ Using a wide screening strategy that included computed tomography of the abdomen and pelvis, the investigators detected a considerable number of formerly undiagnosed cancers, increasing detection rates from 49.4% to 69.7%. After the diagnosis of SMT was made in our patient, computed tomography of the chest, abdomen, and pelvis was performed, but the findings were unremarkable.

Because occult malignancy was excluded in our patient, the likely etiology of SMT was APS, an acquired autoimmune condition diagnosed based on the presence of a vascular thrombosis and/or pregnancy failure in women as well as elevation of at least one antiphospholipid antibody laboratory marker (eg, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I antibody) on 2 or more occasions at least 12 weeks apart.⁴ Other antibodies such as those directed against negatively charged phospholipids (eg, antiphosphatidylserine [which was elevated in our patient], phosphatidylinositol, phosphatidic acid) have been reported in patients with APS, although their diagnostic use is controversial.⁵ For example, the presence of antiphosphatidylserine antibodies has been considered common but not specific in patients with APS.⁴ However, a recent observational study demonstrated that antiphosphatidylserine antibodies are highly specific (87%) and useful in diagnosing clinical APS cases in the presence of other negative markers.⁶

In our patient, diagnosis of SMT with resultant postinflammatory hyperpigmentation in a reticular pattern was based on the patient's medical history, clinical examination, and histopathologic findings, as well as laboratory results and venous studies. However, it is important to note that a livedo reticularis-like pattern also is a very common finding in APS and must be included in the differential diagnosis of a reticular network on the skin.⁷ Moreover, differentiating livedo reticularis from SMT has prognostic importance since SMT may be associated with underlying malignancies while livedo reticularis may be associated with Sneddon syndrome, a disorder in which neurologic vascular events (eg, cerebrovascular accidents) are present.⁸ While this distinction is important, there are no pathognomonic histologic findings seen in livedo reticularis, and consideration of the clinical picture and additional testing is critical.^4,8

Livedo vasculopathy was excluded in our patient due to the lack of diagnostic histopathologic findings, such as fibrin deposition and thrombus formation involving the upper- and mid-dermal capillaries.⁹ Furthermore, characteristic direct immunofluorescence findings of a homogenous or granular deposition in the vessel wall consisting of immune complexes, complement, and fibrin were absent in our patient.⁹ Our patient also lacked common clinical findings found in livedo vasculopathy such as small ulcerations or atrophic, porcelain-white scars on the lower legs. Erythema ab igne also was excluded in our patient due to the absence of heat exposure and presence of fibrin occlusion in the superficial leg veins. Physiologic livedo reticularis, defined as a livedoid pattern due to physiologic changes in the skin in response to cold exposure,¹⁰ also was excluded, as our patient's cutaneous changes included an alteration in pigmentation with a brown reticular pattern and no blanching, erythematous or violaceous hue, warmth, or tenderness.

In conclusion, SMT is a disorder with multiple associations that may clinically mimic livedo reticularis and livedoid vasculopathy when postinflammatory hyperpigmentation has a lacelike or livedoid pattern. While nontraditional antibodies may be useful in diagnosis in patients suspected of having APS with otherwise negative markers, standardized assays and further studies are needed to determine the specificity and value of these antibodies, particularly when used in isolation. Our patient's elevated antiphosphatidylserine IgG may have been the cause of her hypercoagulable state causing the SMT. A livedoid pattern is a common finding in APS and also was seen in our patient with SMT, but the differentiation of the brown pigmentary change and more active erythema was critical to the appropriate clinical workup of our patient.

The Diagnosis: Polypoid Dermatofibroma

Histologic examination revealed a poorly demarcated lesion localized in the dermis that was composed of an admixture of fibroblastlike cells, histiocytes, siderophages, multinucleated giant cells, and hemorrhage (Figure). Based on these findings, a diagnosis of polypoid dermatofibroma (DF) was made. No further treatment was necessary because the lesion was completely excised.

Dermatofibromas, also known as benign fibrous histiocytomas, are common, benign, mesenchymal, fibrosing tumors of the skin that appear predominantly on the legs in in women, but any part of the body in either sex can be affected. Clinically, DFs show the dimple sign when laterally squeezed and can be painful spontaneously or when rubbed. Histologically, DFs are poorly demarcated lesions composed of a variable admixture of fibroblastlike cells, histiocytes (some of which may be xanthomatous or multinucleated), and blood vessels. The etiology still remains unclear. Most investigators consider DF to be a reactive process, but some think that it is a benign mesenchymal tumor.^1,2

Many subtypes of DF have been described based on their unique architectural, cellular, stromal, and clinical features.^2,3 Polypoid DF is a rare variant that comprises only 3% of reported cases4 and tends to be larger than other DF subtypes. Requena et al⁵ reported 12 cases of giant DF, another clinical subtype, that were larger than 5 cm in diameter, most of which had a polypoid appearance.

Moreover, 3 distinct variants of DF with unique histologic features tend to show polypoid morphology.^3,4 In epithelioid fibrous histiocytoma, also known as epithelioid cell histiocytoma, at least 50% of the lesion is composed of rounded or polygonal epithelioid cells with abundant eosinophilic cytoplasm and round to oval nuclei containing small eosinophilic nucleoli.⁴ A grenz zone generally is lacking and numerous small blood vessels are a constant feature of epithelioid fibrous histiocytoma. The other variant of DF that also tends to have a polypoid appearance is lipidized fibrous histiocytoma, or ankle-type fibrous histiocytoma, which usually arises below the knee, especially around the ankle, and often becomes larger than common DF.⁴ Lastly, atypical polypoid DF is a benign, polyp-shaped lesion that shows hypercellularity with striking nuclear atypism and scattered mitotic figures in addition to the ordinary histologic features of DF.³

Acquired fibrokeratomas manifest as solitary dome-shaped, flesh-colored protrusions usually located on the feet and hands. Sclerotic fibroma is a rare cutaneous neoplasm that presents as a solitary, translucent or waxy nodule or as multiple nodules when it is part of Cowden disease. Fibromas, also known as skin tags, are common cutaneous tumors that appear in intertriginous areas and frequently adopt a pedunculated morphology. Although clinically some of these lesions may resemble polypoid DF, the differential diagnosis is made by histologic examination.

Dermatofibroma is a common cutaneous tumor that follows a benign course. It can adopt multiple morphologies. Awareness of this rare variant may aid in its appropriate diagnosis and management. Dermatofibromas are benign neoplasms, and therefore they usually do not require treatment. If they become symptomatic or are bothersome to the patient, the treatment of choice is surgical removal.
 

The Diagnosis: Polypoid Dermatofibroma

Histologic examination revealed a poorly demarcated lesion localized in the dermis that was composed of an admixture of fibroblastlike cells, histiocytes, siderophages, multinucleated giant cells, and hemorrhage (Figure). Based on these findings, a diagnosis of polypoid dermatofibroma (DF) was made. No further treatment was necessary because the lesion was completely excised.

Dermatofibromas, also known as benign fibrous histiocytomas, are common, benign, mesenchymal, fibrosing tumors of the skin that appear predominantly on the legs in in women, but any part of the body in either sex can be affected. Clinically, DFs show the dimple sign when laterally squeezed and can be painful spontaneously or when rubbed. Histologically, DFs are poorly demarcated lesions composed of a variable admixture of fibroblastlike cells, histiocytes (some of which may be xanthomatous or multinucleated), and blood vessels. The etiology still remains unclear. Most investigators consider DF to be a reactive process, but some think that it is a benign mesenchymal tumor.^1,2

Many subtypes of DF have been described based on their unique architectural, cellular, stromal, and clinical features.^2,3 Polypoid DF is a rare variant that comprises only 3% of reported cases4 and tends to be larger than other DF subtypes. Requena et al⁵ reported 12 cases of giant DF, another clinical subtype, that were larger than 5 cm in diameter, most of which had a polypoid appearance.

Moreover, 3 distinct variants of DF with unique histologic features tend to show polypoid morphology.^3,4 In epithelioid fibrous histiocytoma, also known as epithelioid cell histiocytoma, at least 50% of the lesion is composed of rounded or polygonal epithelioid cells with abundant eosinophilic cytoplasm and round to oval nuclei containing small eosinophilic nucleoli.⁴ A grenz zone generally is lacking and numerous small blood vessels are a constant feature of epithelioid fibrous histiocytoma. The other variant of DF that also tends to have a polypoid appearance is lipidized fibrous histiocytoma, or ankle-type fibrous histiocytoma, which usually arises below the knee, especially around the ankle, and often becomes larger than common DF.⁴ Lastly, atypical polypoid DF is a benign, polyp-shaped lesion that shows hypercellularity with striking nuclear atypism and scattered mitotic figures in addition to the ordinary histologic features of DF.³

Acquired fibrokeratomas manifest as solitary dome-shaped, flesh-colored protrusions usually located on the feet and hands. Sclerotic fibroma is a rare cutaneous neoplasm that presents as a solitary, translucent or waxy nodule or as multiple nodules when it is part of Cowden disease. Fibromas, also known as skin tags, are common cutaneous tumors that appear in intertriginous areas and frequently adopt a pedunculated morphology. Although clinically some of these lesions may resemble polypoid DF, the differential diagnosis is made by histologic examination.

Dermatofibroma is a common cutaneous tumor that follows a benign course. It can adopt multiple morphologies. Awareness of this rare variant may aid in its appropriate diagnosis and management. Dermatofibromas are benign neoplasms, and therefore they usually do not require treatment. If they become symptomatic or are bothersome to the patient, the treatment of choice is surgical removal.
 

The Diagnosis: Polypoid Dermatofibroma

Histologic examination revealed a poorly demarcated lesion localized in the dermis that was composed of an admixture of fibroblastlike cells, histiocytes, siderophages, multinucleated giant cells, and hemorrhage (Figure). Based on these findings, a diagnosis of polypoid dermatofibroma (DF) was made. No further treatment was necessary because the lesion was completely excised.

Dermatofibromas, also known as benign fibrous histiocytomas, are common, benign, mesenchymal, fibrosing tumors of the skin that appear predominantly on the legs in in women, but any part of the body in either sex can be affected. Clinically, DFs show the dimple sign when laterally squeezed and can be painful spontaneously or when rubbed. Histologically, DFs are poorly demarcated lesions composed of a variable admixture of fibroblastlike cells, histiocytes (some of which may be xanthomatous or multinucleated), and blood vessels. The etiology still remains unclear. Most investigators consider DF to be a reactive process, but some think that it is a benign mesenchymal tumor.^1,2

Many subtypes of DF have been described based on their unique architectural, cellular, stromal, and clinical features.^2,3 Polypoid DF is a rare variant that comprises only 3% of reported cases4 and tends to be larger than other DF subtypes. Requena et al⁵ reported 12 cases of giant DF, another clinical subtype, that were larger than 5 cm in diameter, most of which had a polypoid appearance.

Moreover, 3 distinct variants of DF with unique histologic features tend to show polypoid morphology.^3,4 In epithelioid fibrous histiocytoma, also known as epithelioid cell histiocytoma, at least 50% of the lesion is composed of rounded or polygonal epithelioid cells with abundant eosinophilic cytoplasm and round to oval nuclei containing small eosinophilic nucleoli.⁴ A grenz zone generally is lacking and numerous small blood vessels are a constant feature of epithelioid fibrous histiocytoma. The other variant of DF that also tends to have a polypoid appearance is lipidized fibrous histiocytoma, or ankle-type fibrous histiocytoma, which usually arises below the knee, especially around the ankle, and often becomes larger than common DF.⁴ Lastly, atypical polypoid DF is a benign, polyp-shaped lesion that shows hypercellularity with striking nuclear atypism and scattered mitotic figures in addition to the ordinary histologic features of DF.³

Acquired fibrokeratomas manifest as solitary dome-shaped, flesh-colored protrusions usually located on the feet and hands. Sclerotic fibroma is a rare cutaneous neoplasm that presents as a solitary, translucent or waxy nodule or as multiple nodules when it is part of Cowden disease. Fibromas, also known as skin tags, are common cutaneous tumors that appear in intertriginous areas and frequently adopt a pedunculated morphology. Although clinically some of these lesions may resemble polypoid DF, the differential diagnosis is made by histologic examination.

Dermatofibroma is a common cutaneous tumor that follows a benign course. It can adopt multiple morphologies. Awareness of this rare variant may aid in its appropriate diagnosis and management. Dermatofibromas are benign neoplasms, and therefore they usually do not require treatment. If they become symptomatic or are bothersome to the patient, the treatment of choice is surgical removal.
 

The Diagnosis: Aneurysmal Dermatofibroma

Biopsy of the lesion revealed a circumscribed dermal nodule comprised of storiform arrangements of enlarged, plump, fibrohistiocytic cells punctuated by variably sized clefts and large cystic spaces filled with blood that lacked an endothelial lining. No bizarre nuclear pleomorphism, atypical mitoses, or tumor necrosis were identified. The overlying epidermis exhibited mild acanthosis with broadening of the rete ridges. Proliferative spindled cells entrapped dermal collagen bundles at the periphery. Hemosiderin-laden macrophages were present throughout the proliferation and in the adjacent dermis (Figure). These findings supported the diagnosis of aneurysmal dermatofibroma (ADF).

Aneurysmal dermatofibroma, also known as aneurysmal fibrous histiocytoma, is a rare variant of dermatofibroma that was described by Santa Cruz et al¹ in 1981 and represents 2% to 6% of dermatofibromas.^1,2 Aneurysmal dermatofibromas often lack the characteristic clinical and dermoscopic findings of conventional dermatofibromas, creating a diagnostic challenge for the clinician.³ Incomplete excision of this benign tumor was associated with a local recurrence rate of 19% (5/26) in one study,⁴ in contrast with the exceedingly low rate of local recurrence (<2%) attributed to conventional dermatofibromas.^2,4

Clinically, ADFs commonly appear as blue-brown nodules on the arms and legs, often with a history of rapid and sometimes painful growth.¹ Clinically, an ADF can have vascular, cystic, or melanocytic features that, in the context of lacking typical clinical findings of a dermatofibroma, can complicate clinical diagnosis; for example, ADFs can demonstrate several melanomalike features including atypical vessels, chrysalis structures, blue-white structures, a pinkish-white veil, irregular brown globulelike structures, an atypical pigment network, color variegation, a multicomponent pattern, and ulceration.³ Alternatively, ADFs can present with a vascular tumor-like pattern consisting of white areas and globular blue-red areas or a polymorphous vascular pattern with a peripheral collarette.

Our case illustrates the classic histologic appearance of an ADF. Large cavities and slitlike spaces filled with blood distinguish this entity from conventional dermatofibroma and other dermatofibroma variants; for example, cellular dermatofibroma is a benign variant of dermatofibroma that exhibits crowded fascicular architecture without an increase in vascular spaces. Aneurysmal dermatofibromas also should be distinguished from angiomatoid fibrous histiocytoma, which has intermediate malignant potential despite a similar-sounding name and a similar nodular appearance with large blood-filled spaces; however, many cases are located predominantly in the subcutis with epithelioid morphology, desmin immunohistochemical reactivity, and prominent tumor-associated lymphoid proliferation that can be mistaken for a lymph node.⁵ Furthermore, in contrast with vascular tumors, the blood-filled spaces of ADFs do not have an endothelial lining.

In summary, ADF is a rare dermatofibroma variant that has a variety of clinical presentations, often masquerading as a cyst, vascular tumor, or melanocytic neoplasm. The classic histopathologic features confirm the diagnosis. Although ADFs can be painful and have a tendency to recur, these lesions have a benign clinical course.

The Diagnosis: Aneurysmal Dermatofibroma

Biopsy of the lesion revealed a circumscribed dermal nodule comprised of storiform arrangements of enlarged, plump, fibrohistiocytic cells punctuated by variably sized clefts and large cystic spaces filled with blood that lacked an endothelial lining. No bizarre nuclear pleomorphism, atypical mitoses, or tumor necrosis were identified. The overlying epidermis exhibited mild acanthosis with broadening of the rete ridges. Proliferative spindled cells entrapped dermal collagen bundles at the periphery. Hemosiderin-laden macrophages were present throughout the proliferation and in the adjacent dermis (Figure). These findings supported the diagnosis of aneurysmal dermatofibroma (ADF).

Aneurysmal dermatofibroma, also known as aneurysmal fibrous histiocytoma, is a rare variant of dermatofibroma that was described by Santa Cruz et al¹ in 1981 and represents 2% to 6% of dermatofibromas.^1,2 Aneurysmal dermatofibromas often lack the characteristic clinical and dermoscopic findings of conventional dermatofibromas, creating a diagnostic challenge for the clinician.³ Incomplete excision of this benign tumor was associated with a local recurrence rate of 19% (5/26) in one study,⁴ in contrast with the exceedingly low rate of local recurrence (<2%) attributed to conventional dermatofibromas.^2,4

Clinically, ADFs commonly appear as blue-brown nodules on the arms and legs, often with a history of rapid and sometimes painful growth.¹ Clinically, an ADF can have vascular, cystic, or melanocytic features that, in the context of lacking typical clinical findings of a dermatofibroma, can complicate clinical diagnosis; for example, ADFs can demonstrate several melanomalike features including atypical vessels, chrysalis structures, blue-white structures, a pinkish-white veil, irregular brown globulelike structures, an atypical pigment network, color variegation, a multicomponent pattern, and ulceration.³ Alternatively, ADFs can present with a vascular tumor-like pattern consisting of white areas and globular blue-red areas or a polymorphous vascular pattern with a peripheral collarette.

Our case illustrates the classic histologic appearance of an ADF. Large cavities and slitlike spaces filled with blood distinguish this entity from conventional dermatofibroma and other dermatofibroma variants; for example, cellular dermatofibroma is a benign variant of dermatofibroma that exhibits crowded fascicular architecture without an increase in vascular spaces. Aneurysmal dermatofibromas also should be distinguished from angiomatoid fibrous histiocytoma, which has intermediate malignant potential despite a similar-sounding name and a similar nodular appearance with large blood-filled spaces; however, many cases are located predominantly in the subcutis with epithelioid morphology, desmin immunohistochemical reactivity, and prominent tumor-associated lymphoid proliferation that can be mistaken for a lymph node.⁵ Furthermore, in contrast with vascular tumors, the blood-filled spaces of ADFs do not have an endothelial lining.

In summary, ADF is a rare dermatofibroma variant that has a variety of clinical presentations, often masquerading as a cyst, vascular tumor, or melanocytic neoplasm. The classic histopathologic features confirm the diagnosis. Although ADFs can be painful and have a tendency to recur, these lesions have a benign clinical course.

The Diagnosis: Aneurysmal Dermatofibroma

Biopsy of the lesion revealed a circumscribed dermal nodule comprised of storiform arrangements of enlarged, plump, fibrohistiocytic cells punctuated by variably sized clefts and large cystic spaces filled with blood that lacked an endothelial lining. No bizarre nuclear pleomorphism, atypical mitoses, or tumor necrosis were identified. The overlying epidermis exhibited mild acanthosis with broadening of the rete ridges. Proliferative spindled cells entrapped dermal collagen bundles at the periphery. Hemosiderin-laden macrophages were present throughout the proliferation and in the adjacent dermis (Figure). These findings supported the diagnosis of aneurysmal dermatofibroma (ADF).

Aneurysmal dermatofibroma, also known as aneurysmal fibrous histiocytoma, is a rare variant of dermatofibroma that was described by Santa Cruz et al¹ in 1981 and represents 2% to 6% of dermatofibromas.^1,2 Aneurysmal dermatofibromas often lack the characteristic clinical and dermoscopic findings of conventional dermatofibromas, creating a diagnostic challenge for the clinician.³ Incomplete excision of this benign tumor was associated with a local recurrence rate of 19% (5/26) in one study,⁴ in contrast with the exceedingly low rate of local recurrence (<2%) attributed to conventional dermatofibromas.^2,4

Clinically, ADFs commonly appear as blue-brown nodules on the arms and legs, often with a history of rapid and sometimes painful growth.¹ Clinically, an ADF can have vascular, cystic, or melanocytic features that, in the context of lacking typical clinical findings of a dermatofibroma, can complicate clinical diagnosis; for example, ADFs can demonstrate several melanomalike features including atypical vessels, chrysalis structures, blue-white structures, a pinkish-white veil, irregular brown globulelike structures, an atypical pigment network, color variegation, a multicomponent pattern, and ulceration.³ Alternatively, ADFs can present with a vascular tumor-like pattern consisting of white areas and globular blue-red areas or a polymorphous vascular pattern with a peripheral collarette.

Our case illustrates the classic histologic appearance of an ADF. Large cavities and slitlike spaces filled with blood distinguish this entity from conventional dermatofibroma and other dermatofibroma variants; for example, cellular dermatofibroma is a benign variant of dermatofibroma that exhibits crowded fascicular architecture without an increase in vascular spaces. Aneurysmal dermatofibromas also should be distinguished from angiomatoid fibrous histiocytoma, which has intermediate malignant potential despite a similar-sounding name and a similar nodular appearance with large blood-filled spaces; however, many cases are located predominantly in the subcutis with epithelioid morphology, desmin immunohistochemical reactivity, and prominent tumor-associated lymphoid proliferation that can be mistaken for a lymph node.⁵ Furthermore, in contrast with vascular tumors, the blood-filled spaces of ADFs do not have an endothelial lining.

In summary, ADF is a rare dermatofibroma variant that has a variety of clinical presentations, often masquerading as a cyst, vascular tumor, or melanocytic neoplasm. The classic histopathologic features confirm the diagnosis. Although ADFs can be painful and have a tendency to recur, these lesions have a benign clinical course.

The Diagnosis: Lues Maligna

Laboratory evaluation demonstrated a total CD4 count of 26 cells/μL (reference range, 443-1471 cells/μL) with a viral load of 1,770,111 copies/mL (reference range, 0 copies/mL), as well as a positive rapid plasma reagin (RPR) test with a titer of 1:8 (reference range, nonreactive). A reactive treponemal antibody test confirmed a true positive RPR test result. Viral culture as well as direct fluorescence antibodies for varicella-zoster virus and an active vesicle of herpes simplex virus (HSV) were negative. Serum immunoglobulin titers for varicella-zoster virus demonstrated low IgM with a positive IgG demonstrating immunity without recent infection. Blood and lesional skin tissue cultures were negative for additional infectious etiologies including bacterial and fungal elements. A lumbar puncture was not performed.

Biopsy of a papulonodule on the left arm demonstrated a lichenoid lymphohistiocytic infiltrate with superficial and deep inflammation (Figure 1). Neutrophils also were noted within a follicle with ballooning and acantholysis within the follicular epithelium. Additional staining for Mycobacterium, HSV-1, HSV-2, and Treponema were negative. In the clinical setting, this histologic pattern was most consistent with secondary syphilis. Pityriasis lichenoides et varioliformis acuta also was included in the histopathologic differential diagnosis by a dermatopathologist (M.C.).

Based on the clinical, microbiologic, and histopathologic findings, a diagnosis of lues maligna (cutaneous secondary syphilis) with a vesiculonecrotic presentation was made. The patient's low RPR titer was attributed to profound immunosuppression, while a confirmation of syphilis infection was made with treponemal antibody testing. Histopathologic examination was consistent with lues maligna and did not demonstrate evidence of any other infectious etiologies.

Following 7 days of intravenous penicillin, the patient demonstrated dramatic improvement of all skin lesions and was discharged receiving once-weekly intramuscular penicillin for 4 weeks. In accordance with the diagnosis, the patient demonstrated rapid improvement of the lesions following appropriate antibiotic therapy.

After the diagnosis of lues maligna was made, the patient disclosed a sexual encounter with a male partner 6 weeks prior to the current presentation, after which he developed a self-resolving genital ulcer suspicious for a primary chancre.

Increasing rates of syphilis transmission have been attributed to males aged 15 to 44 years who have sexual encounters with other males.¹ Although syphilis commonly is known as the great mimicker, syphilology texts state that lesions are not associated with syphilis if vesicles are part of the cutaneous eruption in an adult.² However, rare reports of secondary syphilis presenting as vesicles, pustules, bullae, and pityriasis lichenoides et varioliformis acuta-like eruptions also have been documented.^2-4

Initial screening for suspected syphilis involves sensitive, but not specific, nontreponemal RPR testing reported in the form of a titer. Nontreponemal titers in human immunodeficiency virus-positive individuals can be unusually high or low, fluctuate rapidly, and/or be unresponsive to antibiotic therapy.¹

Lues maligna is a rare form of malignant secondary syphilis that most commonly presents in human immunodeficiency virus-positive hosts.⁵ Although lues maligna often presents with ulceronodular lesions, 2 cases presenting with vesiculonecrotic lesions also have been reported.⁶ Patients often experience systemic symptoms including fever, fatigue, and joint pain. Rapid plasma reagin titers can range from 1:8 to 1:128 in affected individuals.⁶ Diagnosis is dependent on serologic and histologic confirmation while ruling out viral, fungal, and bacterial etiologies. Characteristic red-brown lesions of secondary syphilis involving the palms and soles (Figure 2) alsoaid in diagnosis.¹ Additionally, identification of the Jarisch-Herxheimer reaction following treatment and rapid response to antibiotic therapy are helpful diagnostic findings.^6,7 While histopathologic examination of lues maligna typically does not reveal evidence of spirochetes, it also is important to rule out other infectious etiologies.⁷

Our case emphasizes the importance of early recognition and treatment of the variable clinical, laboratory, and histologic presentations of lues maligna.

The Diagnosis: Lues Maligna

Laboratory evaluation demonstrated a total CD4 count of 26 cells/μL (reference range, 443-1471 cells/μL) with a viral load of 1,770,111 copies/mL (reference range, 0 copies/mL), as well as a positive rapid plasma reagin (RPR) test with a titer of 1:8 (reference range, nonreactive). A reactive treponemal antibody test confirmed a true positive RPR test result. Viral culture as well as direct fluorescence antibodies for varicella-zoster virus and an active vesicle of herpes simplex virus (HSV) were negative. Serum immunoglobulin titers for varicella-zoster virus demonstrated low IgM with a positive IgG demonstrating immunity without recent infection. Blood and lesional skin tissue cultures were negative for additional infectious etiologies including bacterial and fungal elements. A lumbar puncture was not performed.

Biopsy of a papulonodule on the left arm demonstrated a lichenoid lymphohistiocytic infiltrate with superficial and deep inflammation (Figure 1). Neutrophils also were noted within a follicle with ballooning and acantholysis within the follicular epithelium. Additional staining for Mycobacterium, HSV-1, HSV-2, and Treponema were negative. In the clinical setting, this histologic pattern was most consistent with secondary syphilis. Pityriasis lichenoides et varioliformis acuta also was included in the histopathologic differential diagnosis by a dermatopathologist (M.C.).

Based on the clinical, microbiologic, and histopathologic findings, a diagnosis of lues maligna (cutaneous secondary syphilis) with a vesiculonecrotic presentation was made. The patient's low RPR titer was attributed to profound immunosuppression, while a confirmation of syphilis infection was made with treponemal antibody testing. Histopathologic examination was consistent with lues maligna and did not demonstrate evidence of any other infectious etiologies.

Following 7 days of intravenous penicillin, the patient demonstrated dramatic improvement of all skin lesions and was discharged receiving once-weekly intramuscular penicillin for 4 weeks. In accordance with the diagnosis, the patient demonstrated rapid improvement of the lesions following appropriate antibiotic therapy.

After the diagnosis of lues maligna was made, the patient disclosed a sexual encounter with a male partner 6 weeks prior to the current presentation, after which he developed a self-resolving genital ulcer suspicious for a primary chancre.

Increasing rates of syphilis transmission have been attributed to males aged 15 to 44 years who have sexual encounters with other males.¹ Although syphilis commonly is known as the great mimicker, syphilology texts state that lesions are not associated with syphilis if vesicles are part of the cutaneous eruption in an adult.² However, rare reports of secondary syphilis presenting as vesicles, pustules, bullae, and pityriasis lichenoides et varioliformis acuta-like eruptions also have been documented.^2-4

Initial screening for suspected syphilis involves sensitive, but not specific, nontreponemal RPR testing reported in the form of a titer. Nontreponemal titers in human immunodeficiency virus-positive individuals can be unusually high or low, fluctuate rapidly, and/or be unresponsive to antibiotic therapy.¹

Lues maligna is a rare form of malignant secondary syphilis that most commonly presents in human immunodeficiency virus-positive hosts.⁵ Although lues maligna often presents with ulceronodular lesions, 2 cases presenting with vesiculonecrotic lesions also have been reported.⁶ Patients often experience systemic symptoms including fever, fatigue, and joint pain. Rapid plasma reagin titers can range from 1:8 to 1:128 in affected individuals.⁶ Diagnosis is dependent on serologic and histologic confirmation while ruling out viral, fungal, and bacterial etiologies. Characteristic red-brown lesions of secondary syphilis involving the palms and soles (Figure 2) alsoaid in diagnosis.¹ Additionally, identification of the Jarisch-Herxheimer reaction following treatment and rapid response to antibiotic therapy are helpful diagnostic findings.^6,7 While histopathologic examination of lues maligna typically does not reveal evidence of spirochetes, it also is important to rule out other infectious etiologies.⁷

Our case emphasizes the importance of early recognition and treatment of the variable clinical, laboratory, and histologic presentations of lues maligna.

The Diagnosis: Lues Maligna

Laboratory evaluation demonstrated a total CD4 count of 26 cells/μL (reference range, 443-1471 cells/μL) with a viral load of 1,770,111 copies/mL (reference range, 0 copies/mL), as well as a positive rapid plasma reagin (RPR) test with a titer of 1:8 (reference range, nonreactive). A reactive treponemal antibody test confirmed a true positive RPR test result. Viral culture as well as direct fluorescence antibodies for varicella-zoster virus and an active vesicle of herpes simplex virus (HSV) were negative. Serum immunoglobulin titers for varicella-zoster virus demonstrated low IgM with a positive IgG demonstrating immunity without recent infection. Blood and lesional skin tissue cultures were negative for additional infectious etiologies including bacterial and fungal elements. A lumbar puncture was not performed.

Biopsy of a papulonodule on the left arm demonstrated a lichenoid lymphohistiocytic infiltrate with superficial and deep inflammation (Figure 1). Neutrophils also were noted within a follicle with ballooning and acantholysis within the follicular epithelium. Additional staining for Mycobacterium, HSV-1, HSV-2, and Treponema were negative. In the clinical setting, this histologic pattern was most consistent with secondary syphilis. Pityriasis lichenoides et varioliformis acuta also was included in the histopathologic differential diagnosis by a dermatopathologist (M.C.).

Based on the clinical, microbiologic, and histopathologic findings, a diagnosis of lues maligna (cutaneous secondary syphilis) with a vesiculonecrotic presentation was made. The patient's low RPR titer was attributed to profound immunosuppression, while a confirmation of syphilis infection was made with treponemal antibody testing. Histopathologic examination was consistent with lues maligna and did not demonstrate evidence of any other infectious etiologies.

Following 7 days of intravenous penicillin, the patient demonstrated dramatic improvement of all skin lesions and was discharged receiving once-weekly intramuscular penicillin for 4 weeks. In accordance with the diagnosis, the patient demonstrated rapid improvement of the lesions following appropriate antibiotic therapy.

After the diagnosis of lues maligna was made, the patient disclosed a sexual encounter with a male partner 6 weeks prior to the current presentation, after which he developed a self-resolving genital ulcer suspicious for a primary chancre.

Increasing rates of syphilis transmission have been attributed to males aged 15 to 44 years who have sexual encounters with other males.¹ Although syphilis commonly is known as the great mimicker, syphilology texts state that lesions are not associated with syphilis if vesicles are part of the cutaneous eruption in an adult.² However, rare reports of secondary syphilis presenting as vesicles, pustules, bullae, and pityriasis lichenoides et varioliformis acuta-like eruptions also have been documented.^2-4

Initial screening for suspected syphilis involves sensitive, but not specific, nontreponemal RPR testing reported in the form of a titer. Nontreponemal titers in human immunodeficiency virus-positive individuals can be unusually high or low, fluctuate rapidly, and/or be unresponsive to antibiotic therapy.¹

Lues maligna is a rare form of malignant secondary syphilis that most commonly presents in human immunodeficiency virus-positive hosts.⁵ Although lues maligna often presents with ulceronodular lesions, 2 cases presenting with vesiculonecrotic lesions also have been reported.⁶ Patients often experience systemic symptoms including fever, fatigue, and joint pain. Rapid plasma reagin titers can range from 1:8 to 1:128 in affected individuals.⁶ Diagnosis is dependent on serologic and histologic confirmation while ruling out viral, fungal, and bacterial etiologies. Characteristic red-brown lesions of secondary syphilis involving the palms and soles (Figure 2) alsoaid in diagnosis.¹ Additionally, identification of the Jarisch-Herxheimer reaction following treatment and rapid response to antibiotic therapy are helpful diagnostic findings.^6,7 While histopathologic examination of lues maligna typically does not reveal evidence of spirochetes, it also is important to rule out other infectious etiologies.⁷

Our case emphasizes the importance of early recognition and treatment of the variable clinical, laboratory, and histologic presentations of lues maligna.

The Diagnosis: Cutaneous Deposits Of Myeloma

Cutaneous deposits of myeloma are a rare skin manifestation of multiple myeloma that typically occur in less than 5% of patients.^1,2 The lesions represent monoclonal proliferations of plasma cells and arise from direct extension of a neoplastic mass or less commonly from hematogenous or lymphatic spread. This secondary cutaneous involvement by plasma cell myeloma has been referred to in the literature as metastatic or extramedullary cutaneous plasmacytoma.^1,2 This condition must be distinguished from cutaneous plasma cell infiltrates without underlying bone marrow involvement, classified by the World Health Organization as primary cutaneous marginal zone B-cell lymphoma and previously referred to as primary cutaneous plasmacytoma.³

Clinically, cutaneous deposits of myeloma manifest as erythematous to violaceous papules, plaques, or nodules with a smooth surface and firm consistency.^1,2 The lesions typically occur on the trunk and less commonly on the head, neck, arms, and legs. In a review of  83 cases of metastatic cutaneous plasmacytoma and primary cutaneous plasmacytoma in multiple myeloma, Kato et al⁴ found that 52% (43/83) of cases occurred in IgG myelomas and 23% (19/83) in IgA myelomas.

In our patient, a 4-mm punch biopsy of an umbilical plaque demonstrated a dense infiltrate of atypical plasmacytoid cells through the full thickness of the dermis with nuclear pleomorphism, prominent nucleoli, and frequent mitoses (Figure 1). Immunohistochemical staining was positive for IgA λ light chain (Figure 2A) and CD138 (Figure 2B) and was negative for CD20, which was consistent with the patient's known plasma cell myeloma. Positron emission tomography revealed progression of underlying disease compared to prior studies with hypermetabolic mediastinal, retroperitoneal, and pelvic side wall lymphadenopathy, as well as extensive hypermetabolic soft tissue masses with involvement of the periumbilical region.

The differential diagnosis for violaceous periumbilical plaques includes cutaneous marginal zone B-cell lymphoma (primary or secondary) or T-cell lymphoma (primary or secondary), cutaneous metastases from solid organ or hematologic malignancies (eg, Sister Mary Joseph nodule), AIDS-associated Kaposi sarcoma (plum-colored plaques that may be extensive), and cutaneous endometriosis (umbilical nodules that may develop in women after surgical excision of endometrial tissue).

The mainstay of therapy for secondary cutaneous involvement of plasma cell myeloma includes treatment with chemotherapy and local radiotherapy.^1,2,5 After the diagnosis of cutaneous deposits of myeloma was made in our patient, he was treated with bortezomib, cyclophosphamide with dexamethasone, and local radiotherapy to symptomatic bony lesions; however, he was unresponsive to therapy and the disease progressed with numerous extramedullary lesions of the mediastinum, gastrointestinal tract, and retroperitoneum 2 months later. The patient developed hydronephrosis from external renal compression necessitating nephrostomy tube and malignant pleural effusions requiring intubation. He experienced rapid clinical decline and died 3 months after the initial presentation due to multiorgan failure.

Cutaneous deposits of myeloma are a sign of underlying disease progression in plasma cell myeloma and often herald a fulminant course (eg, death within 12 months of presentation), as seen in our patient.⁵ Clinicians should be aware of this rare manifestation of plasma cell myeloma and pursue aggressive therapy given the poor prognostic nature of these cutaneous findings.

The Diagnosis: Cutaneous Deposits Of Myeloma

Cutaneous deposits of myeloma are a rare skin manifestation of multiple myeloma that typically occur in less than 5% of patients.^1,2 The lesions represent monoclonal proliferations of plasma cells and arise from direct extension of a neoplastic mass or less commonly from hematogenous or lymphatic spread. This secondary cutaneous involvement by plasma cell myeloma has been referred to in the literature as metastatic or extramedullary cutaneous plasmacytoma.^1,2 This condition must be distinguished from cutaneous plasma cell infiltrates without underlying bone marrow involvement, classified by the World Health Organization as primary cutaneous marginal zone B-cell lymphoma and previously referred to as primary cutaneous plasmacytoma.³

Clinically, cutaneous deposits of myeloma manifest as erythematous to violaceous papules, plaques, or nodules with a smooth surface and firm consistency.^1,2 The lesions typically occur on the trunk and less commonly on the head, neck, arms, and legs. In a review of  83 cases of metastatic cutaneous plasmacytoma and primary cutaneous plasmacytoma in multiple myeloma, Kato et al⁴ found that 52% (43/83) of cases occurred in IgG myelomas and 23% (19/83) in IgA myelomas.

In our patient, a 4-mm punch biopsy of an umbilical plaque demonstrated a dense infiltrate of atypical plasmacytoid cells through the full thickness of the dermis with nuclear pleomorphism, prominent nucleoli, and frequent mitoses (Figure 1). Immunohistochemical staining was positive for IgA λ light chain (Figure 2A) and CD138 (Figure 2B) and was negative for CD20, which was consistent with the patient's known plasma cell myeloma. Positron emission tomography revealed progression of underlying disease compared to prior studies with hypermetabolic mediastinal, retroperitoneal, and pelvic side wall lymphadenopathy, as well as extensive hypermetabolic soft tissue masses with involvement of the periumbilical region.

The differential diagnosis for violaceous periumbilical plaques includes cutaneous marginal zone B-cell lymphoma (primary or secondary) or T-cell lymphoma (primary or secondary), cutaneous metastases from solid organ or hematologic malignancies (eg, Sister Mary Joseph nodule), AIDS-associated Kaposi sarcoma (plum-colored plaques that may be extensive), and cutaneous endometriosis (umbilical nodules that may develop in women after surgical excision of endometrial tissue).

The mainstay of therapy for secondary cutaneous involvement of plasma cell myeloma includes treatment with chemotherapy and local radiotherapy.^1,2,5 After the diagnosis of cutaneous deposits of myeloma was made in our patient, he was treated with bortezomib, cyclophosphamide with dexamethasone, and local radiotherapy to symptomatic bony lesions; however, he was unresponsive to therapy and the disease progressed with numerous extramedullary lesions of the mediastinum, gastrointestinal tract, and retroperitoneum 2 months later. The patient developed hydronephrosis from external renal compression necessitating nephrostomy tube and malignant pleural effusions requiring intubation. He experienced rapid clinical decline and died 3 months after the initial presentation due to multiorgan failure.

Cutaneous deposits of myeloma are a sign of underlying disease progression in plasma cell myeloma and often herald a fulminant course (eg, death within 12 months of presentation), as seen in our patient.⁵ Clinicians should be aware of this rare manifestation of plasma cell myeloma and pursue aggressive therapy given the poor prognostic nature of these cutaneous findings.

The Diagnosis: Cutaneous Deposits Of Myeloma

Cutaneous deposits of myeloma are a rare skin manifestation of multiple myeloma that typically occur in less than 5% of patients.^1,2 The lesions represent monoclonal proliferations of plasma cells and arise from direct extension of a neoplastic mass or less commonly from hematogenous or lymphatic spread. This secondary cutaneous involvement by plasma cell myeloma has been referred to in the literature as metastatic or extramedullary cutaneous plasmacytoma.^1,2 This condition must be distinguished from cutaneous plasma cell infiltrates without underlying bone marrow involvement, classified by the World Health Organization as primary cutaneous marginal zone B-cell lymphoma and previously referred to as primary cutaneous plasmacytoma.³

Clinically, cutaneous deposits of myeloma manifest as erythematous to violaceous papules, plaques, or nodules with a smooth surface and firm consistency.^1,2 The lesions typically occur on the trunk and less commonly on the head, neck, arms, and legs. In a review of  83 cases of metastatic cutaneous plasmacytoma and primary cutaneous plasmacytoma in multiple myeloma, Kato et al⁴ found that 52% (43/83) of cases occurred in IgG myelomas and 23% (19/83) in IgA myelomas.

In our patient, a 4-mm punch biopsy of an umbilical plaque demonstrated a dense infiltrate of atypical plasmacytoid cells through the full thickness of the dermis with nuclear pleomorphism, prominent nucleoli, and frequent mitoses (Figure 1). Immunohistochemical staining was positive for IgA λ light chain (Figure 2A) and CD138 (Figure 2B) and was negative for CD20, which was consistent with the patient's known plasma cell myeloma. Positron emission tomography revealed progression of underlying disease compared to prior studies with hypermetabolic mediastinal, retroperitoneal, and pelvic side wall lymphadenopathy, as well as extensive hypermetabolic soft tissue masses with involvement of the periumbilical region.

The differential diagnosis for violaceous periumbilical plaques includes cutaneous marginal zone B-cell lymphoma (primary or secondary) or T-cell lymphoma (primary or secondary), cutaneous metastases from solid organ or hematologic malignancies (eg, Sister Mary Joseph nodule), AIDS-associated Kaposi sarcoma (plum-colored plaques that may be extensive), and cutaneous endometriosis (umbilical nodules that may develop in women after surgical excision of endometrial tissue).

The mainstay of therapy for secondary cutaneous involvement of plasma cell myeloma includes treatment with chemotherapy and local radiotherapy.^1,2,5 After the diagnosis of cutaneous deposits of myeloma was made in our patient, he was treated with bortezomib, cyclophosphamide with dexamethasone, and local radiotherapy to symptomatic bony lesions; however, he was unresponsive to therapy and the disease progressed with numerous extramedullary lesions of the mediastinum, gastrointestinal tract, and retroperitoneum 2 months later. The patient developed hydronephrosis from external renal compression necessitating nephrostomy tube and malignant pleural effusions requiring intubation. He experienced rapid clinical decline and died 3 months after the initial presentation due to multiorgan failure.

Cutaneous deposits of myeloma are a sign of underlying disease progression in plasma cell myeloma and often herald a fulminant course (eg, death within 12 months of presentation), as seen in our patient.⁵ Clinicians should be aware of this rare manifestation of plasma cell myeloma and pursue aggressive therapy given the poor prognostic nature of these cutaneous findings.

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴