Garth Fraga, MD

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination demonstrated acanthosis and coarse hypergranulosis with enlarged keratinocytes exhibiting blue cytoplasmic discoloration (Figure), which was suggestive of acquired epidermodysplasia verruciformis (EV).  

Acquired EV is a rare dermatologic condition associated with specific human papillomavirus (HPV) types that presents with recalcitrant lesions most commonly in the setting of immunosuppression.¹ The most common HPV types associated with EV are HPV-5 and -8, but associations with HPV-3, -9, -10, -12, -14, -15, -17, -19 to -25, -36 to -38, -47, and -50 also have been reported.^1,2 Acquired EV has been identified in individuals with human immunodeficiency virus, as well as in immunosuppressed patients with organ transplantation, Hodgkin lymphoma, systemic lupus erythematosus, and IgM deficiency, and in patients taking immunosuppressive medications such as tumor necrosis factor α inhibitors.^1,3 The diagnosis is clinicopathological with potential polymerase chain reaction studies to identify underlying HPV types. 

Acquired EV presents as hypopigmented to red, tinea versicolor-like macules or as verrucous, flat-topped papules on the trunk, arms, and/or legs.⁴ Histopathology reveals viral epidermal cytopathic changes, blue cytoplasm, and coarse hypogranulosis.⁴ 

There is no standardized treatment regimen for acquired EV, and no single approach has proven to yield an efficacious clinical outcome. Topical treatment options include steroids, retinoids, immunomodulators, cryotherapy, and electrosurgery, whereas retinoids or interferon alfa have been used as oral systemic therapy. Photodynamic therapy also has been shown to improve symptoms.³ Combination therapy such as interferon alfa with zidovudine or imiquimod with oral isotretinoin has shown better results than any single treatment.⁴ Due to the underlying HPV infection and its role in promotion of skin cancer development, lesions can characteristically undergo malignant transformations into Bowen disease but most commonly invasive squamous cell carcinoma (SCC), with initial lesions preferentially affecting sun-exposed areas due to the synergistic effect of UV light with EV-HPV lesions. The EV-HPV strains ^{5, 8,} and 41 carry the highest oncogenic potential.5 Little is known of the true incidence of oncogenicity for acquired EV. Regardless, consistent sun protection and lifelong clinical examinations are critical for prognosis.⁵  

The differential diagnosis of EV presenting in a tattoo includes allergic contact dermatitis, cutaneous sarcoidosis, pityriasis versicolor, and SCC. The pathology is critical to differentiate between these entities. The most frequently reported skin reactions to tattoo ink include inflammatory diseases (eg, allergic contact dermatitis, granulomatous reaction) or infectious diseases (eg, bacterial, viral, fungal).⁶ Allergic contact dermatitis, typically red pigment, is a common tattoo reaction. The most common histologic feature, however, is spongiosis, which results from intercellular edema. It often is limited to the lower epidermis but may affect the upper layers if the reaction is severe.⁷ Cutaneous sarcoidosis is a great masquerader that can present in various ways; however, its salient features on pathology are noncaseating granuloma involving the basal cell layer and epithelioid granuloma consisting of Langerhans giant cells.⁸ Although pityriasis versicolor can present in young immunocompromised adults, histologically salient features are the presence of both spores and hyphae in the stratum corneum.⁹ Although immunosuppression is a known risk factor for SCC, it is characterized histologically by hyperkeratosis, parakeratosis, and acanthosis with thickened and elongated rete ridges. Scattered atypical cells and frequent mitoses are present.¹⁰ 

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination demonstrated acanthosis and coarse hypergranulosis with enlarged keratinocytes exhibiting blue cytoplasmic discoloration (Figure), which was suggestive of acquired epidermodysplasia verruciformis (EV).  

Acquired EV is a rare dermatologic condition associated with specific human papillomavirus (HPV) types that presents with recalcitrant lesions most commonly in the setting of immunosuppression.¹ The most common HPV types associated with EV are HPV-5 and -8, but associations with HPV-3, -9, -10, -12, -14, -15, -17, -19 to -25, -36 to -38, -47, and -50 also have been reported.^1,2 Acquired EV has been identified in individuals with human immunodeficiency virus, as well as in immunosuppressed patients with organ transplantation, Hodgkin lymphoma, systemic lupus erythematosus, and IgM deficiency, and in patients taking immunosuppressive medications such as tumor necrosis factor α inhibitors.^1,3 The diagnosis is clinicopathological with potential polymerase chain reaction studies to identify underlying HPV types. 

Acquired EV presents as hypopigmented to red, tinea versicolor-like macules or as verrucous, flat-topped papules on the trunk, arms, and/or legs.⁴ Histopathology reveals viral epidermal cytopathic changes, blue cytoplasm, and coarse hypogranulosis.⁴ 

There is no standardized treatment regimen for acquired EV, and no single approach has proven to yield an efficacious clinical outcome. Topical treatment options include steroids, retinoids, immunomodulators, cryotherapy, and electrosurgery, whereas retinoids or interferon alfa have been used as oral systemic therapy. Photodynamic therapy also has been shown to improve symptoms.³ Combination therapy such as interferon alfa with zidovudine or imiquimod with oral isotretinoin has shown better results than any single treatment.⁴ Due to the underlying HPV infection and its role in promotion of skin cancer development, lesions can characteristically undergo malignant transformations into Bowen disease but most commonly invasive squamous cell carcinoma (SCC), with initial lesions preferentially affecting sun-exposed areas due to the synergistic effect of UV light with EV-HPV lesions. The EV-HPV strains ^{5, 8,} and 41 carry the highest oncogenic potential.5 Little is known of the true incidence of oncogenicity for acquired EV. Regardless, consistent sun protection and lifelong clinical examinations are critical for prognosis.⁵  

The differential diagnosis of EV presenting in a tattoo includes allergic contact dermatitis, cutaneous sarcoidosis, pityriasis versicolor, and SCC. The pathology is critical to differentiate between these entities. The most frequently reported skin reactions to tattoo ink include inflammatory diseases (eg, allergic contact dermatitis, granulomatous reaction) or infectious diseases (eg, bacterial, viral, fungal).⁶ Allergic contact dermatitis, typically red pigment, is a common tattoo reaction. The most common histologic feature, however, is spongiosis, which results from intercellular edema. It often is limited to the lower epidermis but may affect the upper layers if the reaction is severe.⁷ Cutaneous sarcoidosis is a great masquerader that can present in various ways; however, its salient features on pathology are noncaseating granuloma involving the basal cell layer and epithelioid granuloma consisting of Langerhans giant cells.⁸ Although pityriasis versicolor can present in young immunocompromised adults, histologically salient features are the presence of both spores and hyphae in the stratum corneum.⁹ Although immunosuppression is a known risk factor for SCC, it is characterized histologically by hyperkeratosis, parakeratosis, and acanthosis with thickened and elongated rete ridges. Scattered atypical cells and frequent mitoses are present.¹⁰ 

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination demonstrated acanthosis and coarse hypergranulosis with enlarged keratinocytes exhibiting blue cytoplasmic discoloration (Figure), which was suggestive of acquired epidermodysplasia verruciformis (EV).  

Acquired EV is a rare dermatologic condition associated with specific human papillomavirus (HPV) types that presents with recalcitrant lesions most commonly in the setting of immunosuppression.¹ The most common HPV types associated with EV are HPV-5 and -8, but associations with HPV-3, -9, -10, -12, -14, -15, -17, -19 to -25, -36 to -38, -47, and -50 also have been reported.^1,2 Acquired EV has been identified in individuals with human immunodeficiency virus, as well as in immunosuppressed patients with organ transplantation, Hodgkin lymphoma, systemic lupus erythematosus, and IgM deficiency, and in patients taking immunosuppressive medications such as tumor necrosis factor α inhibitors.^1,3 The diagnosis is clinicopathological with potential polymerase chain reaction studies to identify underlying HPV types. 

Acquired EV presents as hypopigmented to red, tinea versicolor-like macules or as verrucous, flat-topped papules on the trunk, arms, and/or legs.⁴ Histopathology reveals viral epidermal cytopathic changes, blue cytoplasm, and coarse hypogranulosis.⁴ 

There is no standardized treatment regimen for acquired EV, and no single approach has proven to yield an efficacious clinical outcome. Topical treatment options include steroids, retinoids, immunomodulators, cryotherapy, and electrosurgery, whereas retinoids or interferon alfa have been used as oral systemic therapy. Photodynamic therapy also has been shown to improve symptoms.³ Combination therapy such as interferon alfa with zidovudine or imiquimod with oral isotretinoin has shown better results than any single treatment.⁴ Due to the underlying HPV infection and its role in promotion of skin cancer development, lesions can characteristically undergo malignant transformations into Bowen disease but most commonly invasive squamous cell carcinoma (SCC), with initial lesions preferentially affecting sun-exposed areas due to the synergistic effect of UV light with EV-HPV lesions. The EV-HPV strains ^{5, 8,} and 41 carry the highest oncogenic potential.5 Little is known of the true incidence of oncogenicity for acquired EV. Regardless, consistent sun protection and lifelong clinical examinations are critical for prognosis.⁵  

The differential diagnosis of EV presenting in a tattoo includes allergic contact dermatitis, cutaneous sarcoidosis, pityriasis versicolor, and SCC. The pathology is critical to differentiate between these entities. The most frequently reported skin reactions to tattoo ink include inflammatory diseases (eg, allergic contact dermatitis, granulomatous reaction) or infectious diseases (eg, bacterial, viral, fungal).⁶ Allergic contact dermatitis, typically red pigment, is a common tattoo reaction. The most common histologic feature, however, is spongiosis, which results from intercellular edema. It often is limited to the lower epidermis but may affect the upper layers if the reaction is severe.⁷ Cutaneous sarcoidosis is a great masquerader that can present in various ways; however, its salient features on pathology are noncaseating granuloma involving the basal cell layer and epithelioid granuloma consisting of Langerhans giant cells.⁸ Although pityriasis versicolor can present in young immunocompromised adults, histologically salient features are the presence of both spores and hyphae in the stratum corneum.⁹ Although immunosuppression is a known risk factor for SCC, it is characterized histologically by hyperkeratosis, parakeratosis, and acanthosis with thickened and elongated rete ridges. Scattered atypical cells and frequent mitoses are present.¹⁰ 

To the Editor:

A 59-year-old man presented with a lesion on the right frontal scalp of 4 months’ duration and a lesion on the left frontal scalp of 1 month’s duration. Both lesions were tender, bleeding, nonhealing, and growing in size. The patient reported no improvement with the use of triple antibiotic ointment. He denied any associated symptoms or trauma to the affected areas. He had a history of stage IV esophageal adenocarcinoma that initially had been surgically removed 6 years prior but metastasized to the lungs and bone. The patient subsequently underwent treatment with FOLFOX (folinic acid, fluorouracil, oxaliplatin), trastuzumab, and radiation therapy.

Physical examination revealed a hyperkeratotic pink nodule with a central erosion and crust on the right frontal scalp measuring 1.5×2 cm in diameter (Figure 1A). The left frontal scalp lesion was a smooth pearly papule measuring 5×5 mm in diameter (Figure 1B). The differential diagnosis included basal cell carcinoma, squamous cell carcinoma, and cutaneous metastases from esophageal adenocarcinoma. Shave biopsies were taken of both scalp lesions.

Our case highlights multiple cutaneous metastases of the scalp from a primary esophageal adenocarcinoma. Although cutaneous scalp metastasis of esophageal adenocarcinoma is rare, it is essential to provide a full-body skin examination, including the scalp, in patients with a history of esophageal cancer and to biopsy any suspicious nodules or plaques. The 1-year survival rate after diagnosis of esophageal carcinoma is less than 50%, and the 5-year survival rate is less than 10%.¹³ Identifying cutaneous metastasis of an esophageal adenocarcinoma can either change the staging of the cancer (if it was the first distant metastasis noted) or indicate an insufficient response to treatment in a patient with known metastatic disease, prompting a potential change in treatment.⁷

This case illustrates a rare site of metastasis of a fairly common cancer and highlights the histopathology and accompanying immunohistochemical stains that can be useful in diagnosis as well as the spectrum of its clinical presentation.

To the Editor:

A 59-year-old man presented with a lesion on the right frontal scalp of 4 months’ duration and a lesion on the left frontal scalp of 1 month’s duration. Both lesions were tender, bleeding, nonhealing, and growing in size. The patient reported no improvement with the use of triple antibiotic ointment. He denied any associated symptoms or trauma to the affected areas. He had a history of stage IV esophageal adenocarcinoma that initially had been surgically removed 6 years prior but metastasized to the lungs and bone. The patient subsequently underwent treatment with FOLFOX (folinic acid, fluorouracil, oxaliplatin), trastuzumab, and radiation therapy.

Physical examination revealed a hyperkeratotic pink nodule with a central erosion and crust on the right frontal scalp measuring 1.5×2 cm in diameter (Figure 1A). The left frontal scalp lesion was a smooth pearly papule measuring 5×5 mm in diameter (Figure 1B). The differential diagnosis included basal cell carcinoma, squamous cell carcinoma, and cutaneous metastases from esophageal adenocarcinoma. Shave biopsies were taken of both scalp lesions.

Our case highlights multiple cutaneous metastases of the scalp from a primary esophageal adenocarcinoma. Although cutaneous scalp metastasis of esophageal adenocarcinoma is rare, it is essential to provide a full-body skin examination, including the scalp, in patients with a history of esophageal cancer and to biopsy any suspicious nodules or plaques. The 1-year survival rate after diagnosis of esophageal carcinoma is less than 50%, and the 5-year survival rate is less than 10%.¹³ Identifying cutaneous metastasis of an esophageal adenocarcinoma can either change the staging of the cancer (if it was the first distant metastasis noted) or indicate an insufficient response to treatment in a patient with known metastatic disease, prompting a potential change in treatment.⁷

This case illustrates a rare site of metastasis of a fairly common cancer and highlights the histopathology and accompanying immunohistochemical stains that can be useful in diagnosis as well as the spectrum of its clinical presentation.

To the Editor:

A 59-year-old man presented with a lesion on the right frontal scalp of 4 months’ duration and a lesion on the left frontal scalp of 1 month’s duration. Both lesions were tender, bleeding, nonhealing, and growing in size. The patient reported no improvement with the use of triple antibiotic ointment. He denied any associated symptoms or trauma to the affected areas. He had a history of stage IV esophageal adenocarcinoma that initially had been surgically removed 6 years prior but metastasized to the lungs and bone. The patient subsequently underwent treatment with FOLFOX (folinic acid, fluorouracil, oxaliplatin), trastuzumab, and radiation therapy.

Physical examination revealed a hyperkeratotic pink nodule with a central erosion and crust on the right frontal scalp measuring 1.5×2 cm in diameter (Figure 1A). The left frontal scalp lesion was a smooth pearly papule measuring 5×5 mm in diameter (Figure 1B). The differential diagnosis included basal cell carcinoma, squamous cell carcinoma, and cutaneous metastases from esophageal adenocarcinoma. Shave biopsies were taken of both scalp lesions.

Our case highlights multiple cutaneous metastases of the scalp from a primary esophageal adenocarcinoma. Although cutaneous scalp metastasis of esophageal adenocarcinoma is rare, it is essential to provide a full-body skin examination, including the scalp, in patients with a history of esophageal cancer and to biopsy any suspicious nodules or plaques. The 1-year survival rate after diagnosis of esophageal carcinoma is less than 50%, and the 5-year survival rate is less than 10%.¹³ Identifying cutaneous metastasis of an esophageal adenocarcinoma can either change the staging of the cancer (if it was the first distant metastasis noted) or indicate an insufficient response to treatment in a patient with known metastatic disease, prompting a potential change in treatment.⁷

This case illustrates a rare site of metastasis of a fairly common cancer and highlights the histopathology and accompanying immunohistochemical stains that can be useful in diagnosis as well as the spectrum of its clinical presentation.

The Diagnosis: Adult Colloid Milium 

A 4-mm punch biopsy was performed and histopathologic evaluation revealed collections of amorphic eosinophilic material and fissures in the papillary dermis with sparing of the dermoepidermal junction, indicating adult colloid milium (Figure 1).  

Adult colloid milium is an uncommon condition with grouped translucent to whitish papules that present on sun-exposed skin on the hands, face, neck, or ears in middle-aged adults.¹ It has been associated with petrochemical exposure, tanning bed use, and excessive sun exposure. Our patient had a history of sun exposure, specifically to the left hand while driving. This condition is widely thought to be a result of photoinduced damage to elastic fibers and may potentially be a popular variant of severe solar elastosis.² Due to vascular fragility, trauma to these locations often will result in hemorrhage into individual lesions, as observed in our patient (Figure 2).  

Adult colloid milium is diagnosed clinically and may mimic lichen or systemic amyloidosis, syringomas, lipoid proteinosis, molluscum contagiosum, steatocystoma multiplex, and sarcoidosis.²  

Biopsy often is helpful in determining the diagnosis. Histopathology reveals amorphous eosinophilic deposits with fissures in the papillary dermis. These deposits are thought to be remnants of degenerated elastic fibers. Stains often are helpful, as the deposits are weakly apple-green birefringent on Congo red stain and are periodic acid-Schiff and thioflavin T positive. Laminin and type IV collagen stains are negative with adult colloid milium but are positive with amyloidosis and lipoid proteinosis.³ Electron microscopy also may help distinguish between amyloidosis and adult colloid milium, as these conditions may have a similar histologic appearance.

Treatment has not proven to be consistently helpful, as cryotherapy and dermabrasion have been the mainstay of treatment, often with disappointing results.⁴ Laser treatment has been shown to be of some benefit in treating these lesions.² 

The Diagnosis: Adult Colloid Milium 

A 4-mm punch biopsy was performed and histopathologic evaluation revealed collections of amorphic eosinophilic material and fissures in the papillary dermis with sparing of the dermoepidermal junction, indicating adult colloid milium (Figure 1).  

Adult colloid milium is an uncommon condition with grouped translucent to whitish papules that present on sun-exposed skin on the hands, face, neck, or ears in middle-aged adults.¹ It has been associated with petrochemical exposure, tanning bed use, and excessive sun exposure. Our patient had a history of sun exposure, specifically to the left hand while driving. This condition is widely thought to be a result of photoinduced damage to elastic fibers and may potentially be a popular variant of severe solar elastosis.² Due to vascular fragility, trauma to these locations often will result in hemorrhage into individual lesions, as observed in our patient (Figure 2).  

Adult colloid milium is diagnosed clinically and may mimic lichen or systemic amyloidosis, syringomas, lipoid proteinosis, molluscum contagiosum, steatocystoma multiplex, and sarcoidosis.²  

Biopsy often is helpful in determining the diagnosis. Histopathology reveals amorphous eosinophilic deposits with fissures in the papillary dermis. These deposits are thought to be remnants of degenerated elastic fibers. Stains often are helpful, as the deposits are weakly apple-green birefringent on Congo red stain and are periodic acid-Schiff and thioflavin T positive. Laminin and type IV collagen stains are negative with adult colloid milium but are positive with amyloidosis and lipoid proteinosis.³ Electron microscopy also may help distinguish between amyloidosis and adult colloid milium, as these conditions may have a similar histologic appearance.

Treatment has not proven to be consistently helpful, as cryotherapy and dermabrasion have been the mainstay of treatment, often with disappointing results.⁴ Laser treatment has been shown to be of some benefit in treating these lesions.² 

The Diagnosis: Adult Colloid Milium 

A 4-mm punch biopsy was performed and histopathologic evaluation revealed collections of amorphic eosinophilic material and fissures in the papillary dermis with sparing of the dermoepidermal junction, indicating adult colloid milium (Figure 1).  

Adult colloid milium is an uncommon condition with grouped translucent to whitish papules that present on sun-exposed skin on the hands, face, neck, or ears in middle-aged adults.¹ It has been associated with petrochemical exposure, tanning bed use, and excessive sun exposure. Our patient had a history of sun exposure, specifically to the left hand while driving. This condition is widely thought to be a result of photoinduced damage to elastic fibers and may potentially be a popular variant of severe solar elastosis.² Due to vascular fragility, trauma to these locations often will result in hemorrhage into individual lesions, as observed in our patient (Figure 2).  

Adult colloid milium is diagnosed clinically and may mimic lichen or systemic amyloidosis, syringomas, lipoid proteinosis, molluscum contagiosum, steatocystoma multiplex, and sarcoidosis.²  

Biopsy often is helpful in determining the diagnosis. Histopathology reveals amorphous eosinophilic deposits with fissures in the papillary dermis. These deposits are thought to be remnants of degenerated elastic fibers. Stains often are helpful, as the deposits are weakly apple-green birefringent on Congo red stain and are periodic acid-Schiff and thioflavin T positive. Laminin and type IV collagen stains are negative with adult colloid milium but are positive with amyloidosis and lipoid proteinosis.³ Electron microscopy also may help distinguish between amyloidosis and adult colloid milium, as these conditions may have a similar histologic appearance.

Treatment has not proven to be consistently helpful, as cryotherapy and dermabrasion have been the mainstay of treatment, often with disappointing results.⁴ Laser treatment has been shown to be of some benefit in treating these lesions.² 

The Diagnosis: Bullous Systemic Lupus Erythematosus  

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease that affects patients with systemic lupus erythematosus (SLE). Our patient had a several-year history of SLE and was being managed by a rheumatologist. She was taking hydroxychloroquine at the time of the flare. Although BSLE tends to present in those with SLE that has already been diagnosed, BSLE has been reported as a possible initial manifestation of SLE.¹  

Bullous systemic lupus erythematosus is estimated to occur in less than 5% of patients with SLE and is more common in black women between the second and third decades of life,² though it also can be seen in the pediatric population.³ The lesions of BSLE usually present as subepidermal blisters often located on the face, neck, and arms on an erythematous or possibly urticarial base. Although non-BSLE vesiculobullous eruptions may be seen in patients with SLE, BSLE is differentiated from these other eruptions by its appearance on sun-exposed and non-sun-exposed areas of the body, while other vesiculobullous eruptions associated with SLE typically are limited to sun-exposed sites.⁴  

Due to its clinical presentation overlapping with several vesiculobullous conditions, a set of diagnostic criteria have been suggested for BSLE, including the following: (1) fulfillment of the American Rheumatism Association's criteria for SLE⁵; (2) a new-onset vesiculobullous eruption, primarily on sun-exposed skin; (3) histology showing a subepidermal blister with a predominantly neutrophilic infiltrate; (4) presence of IgG, IgA, IgM, and C3 at the basement membrane zone; (5) evidence of antibodies to type VII collagen; and (6) immunoelectron microscopy showing codistribution of immunoglobulin deposits with anchoring fibrils/type VII collagen. To meet the diagnosis of type I BSLE, all 6 criteria must be satisfied. To meet the diagnosis of type II BSLE, only criteria 1 to 4 need to be satisfied.⁶  

Patients with BSLE may be presumed to have a different but clinically similar vesiculobullous condition (eg, bullous pemphigoid, cutaneous manifestations of SLE) and may be started on systemic corticosteroids. However, BSLE patients often do not show great improvement while on corticosteroids and may even flare shortly after beginning systemic corticosteroid treatment. The current treatment of choice for BSLE is dapsone, a sulfa drug that is thought to exhibit its anti-inflammatory properties via the inhibition of the alternative pathway of the complement system and through the inhibition of polymorphonuclear leukocyte functions.⁷ A response to dapsone helps differentiate BSLE from histopathologically and immunopathologically identical conditions such as epidermolysis bullosa acquisita.⁴ Bullous systemic lupus erythematosus can be differentiated from dermatitis herpetiformis with the presence of antigliadin and antitissue transglutaminase antibodies, which are found in the latter.  Additionally, BSLE may show the presence of IgG and IgM deposition in addition to IgA deposition, as opposed to dermatitis herpetiformis where only IgA is found.⁸ The presence of these additional antibody depositions also help differentiate BSLE from linear IgA bullous dermatosis (LABD), as LABD will only have IgA depositions and often presents with an annular, crown of jewels-like appearance.  Finally, there is a well-described phenomenon of LABD being drug induced, particularly after a course of vancomycin,⁹ and such an association with vancomycin has not been documented for BSLE. 

Our patient was diagnosed with BSLE following the flare approximately 1.5 years prior to the current presentation. She had been started on dapsone 75 mg daily at that time and was taking 75 mg at the time of presentation. She was admitted and treated as an inpatient with high-dose (1 mg/kg) intravenous prednisone due to the extensive current flare. 

The Diagnosis: Bullous Systemic Lupus Erythematosus  

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease that affects patients with systemic lupus erythematosus (SLE). Our patient had a several-year history of SLE and was being managed by a rheumatologist. She was taking hydroxychloroquine at the time of the flare. Although BSLE tends to present in those with SLE that has already been diagnosed, BSLE has been reported as a possible initial manifestation of SLE.¹  

Bullous systemic lupus erythematosus is estimated to occur in less than 5% of patients with SLE and is more common in black women between the second and third decades of life,² though it also can be seen in the pediatric population.³ The lesions of BSLE usually present as subepidermal blisters often located on the face, neck, and arms on an erythematous or possibly urticarial base. Although non-BSLE vesiculobullous eruptions may be seen in patients with SLE, BSLE is differentiated from these other eruptions by its appearance on sun-exposed and non-sun-exposed areas of the body, while other vesiculobullous eruptions associated with SLE typically are limited to sun-exposed sites.⁴  

Due to its clinical presentation overlapping with several vesiculobullous conditions, a set of diagnostic criteria have been suggested for BSLE, including the following: (1) fulfillment of the American Rheumatism Association's criteria for SLE⁵; (2) a new-onset vesiculobullous eruption, primarily on sun-exposed skin; (3) histology showing a subepidermal blister with a predominantly neutrophilic infiltrate; (4) presence of IgG, IgA, IgM, and C3 at the basement membrane zone; (5) evidence of antibodies to type VII collagen; and (6) immunoelectron microscopy showing codistribution of immunoglobulin deposits with anchoring fibrils/type VII collagen. To meet the diagnosis of type I BSLE, all 6 criteria must be satisfied. To meet the diagnosis of type II BSLE, only criteria 1 to 4 need to be satisfied.⁶  

Patients with BSLE may be presumed to have a different but clinically similar vesiculobullous condition (eg, bullous pemphigoid, cutaneous manifestations of SLE) and may be started on systemic corticosteroids. However, BSLE patients often do not show great improvement while on corticosteroids and may even flare shortly after beginning systemic corticosteroid treatment. The current treatment of choice for BSLE is dapsone, a sulfa drug that is thought to exhibit its anti-inflammatory properties via the inhibition of the alternative pathway of the complement system and through the inhibition of polymorphonuclear leukocyte functions.⁷ A response to dapsone helps differentiate BSLE from histopathologically and immunopathologically identical conditions such as epidermolysis bullosa acquisita.⁴ Bullous systemic lupus erythematosus can be differentiated from dermatitis herpetiformis with the presence of antigliadin and antitissue transglutaminase antibodies, which are found in the latter.  Additionally, BSLE may show the presence of IgG and IgM deposition in addition to IgA deposition, as opposed to dermatitis herpetiformis where only IgA is found.⁸ The presence of these additional antibody depositions also help differentiate BSLE from linear IgA bullous dermatosis (LABD), as LABD will only have IgA depositions and often presents with an annular, crown of jewels-like appearance.  Finally, there is a well-described phenomenon of LABD being drug induced, particularly after a course of vancomycin,⁹ and such an association with vancomycin has not been documented for BSLE. 

Our patient was diagnosed with BSLE following the flare approximately 1.5 years prior to the current presentation. She had been started on dapsone 75 mg daily at that time and was taking 75 mg at the time of presentation. She was admitted and treated as an inpatient with high-dose (1 mg/kg) intravenous prednisone due to the extensive current flare. 

The Diagnosis: Bullous Systemic Lupus Erythematosus  

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease that affects patients with systemic lupus erythematosus (SLE). Our patient had a several-year history of SLE and was being managed by a rheumatologist. She was taking hydroxychloroquine at the time of the flare. Although BSLE tends to present in those with SLE that has already been diagnosed, BSLE has been reported as a possible initial manifestation of SLE.¹  

Bullous systemic lupus erythematosus is estimated to occur in less than 5% of patients with SLE and is more common in black women between the second and third decades of life,² though it also can be seen in the pediatric population.³ The lesions of BSLE usually present as subepidermal blisters often located on the face, neck, and arms on an erythematous or possibly urticarial base. Although non-BSLE vesiculobullous eruptions may be seen in patients with SLE, BSLE is differentiated from these other eruptions by its appearance on sun-exposed and non-sun-exposed areas of the body, while other vesiculobullous eruptions associated with SLE typically are limited to sun-exposed sites.⁴  

Due to its clinical presentation overlapping with several vesiculobullous conditions, a set of diagnostic criteria have been suggested for BSLE, including the following: (1) fulfillment of the American Rheumatism Association's criteria for SLE⁵; (2) a new-onset vesiculobullous eruption, primarily on sun-exposed skin; (3) histology showing a subepidermal blister with a predominantly neutrophilic infiltrate; (4) presence of IgG, IgA, IgM, and C3 at the basement membrane zone; (5) evidence of antibodies to type VII collagen; and (6) immunoelectron microscopy showing codistribution of immunoglobulin deposits with anchoring fibrils/type VII collagen. To meet the diagnosis of type I BSLE, all 6 criteria must be satisfied. To meet the diagnosis of type II BSLE, only criteria 1 to 4 need to be satisfied.⁶  

Patients with BSLE may be presumed to have a different but clinically similar vesiculobullous condition (eg, bullous pemphigoid, cutaneous manifestations of SLE) and may be started on systemic corticosteroids. However, BSLE patients often do not show great improvement while on corticosteroids and may even flare shortly after beginning systemic corticosteroid treatment. The current treatment of choice for BSLE is dapsone, a sulfa drug that is thought to exhibit its anti-inflammatory properties via the inhibition of the alternative pathway of the complement system and through the inhibition of polymorphonuclear leukocyte functions.⁷ A response to dapsone helps differentiate BSLE from histopathologically and immunopathologically identical conditions such as epidermolysis bullosa acquisita.⁴ Bullous systemic lupus erythematosus can be differentiated from dermatitis herpetiformis with the presence of antigliadin and antitissue transglutaminase antibodies, which are found in the latter.  Additionally, BSLE may show the presence of IgG and IgM deposition in addition to IgA deposition, as opposed to dermatitis herpetiformis where only IgA is found.⁸ The presence of these additional antibody depositions also help differentiate BSLE from linear IgA bullous dermatosis (LABD), as LABD will only have IgA depositions and often presents with an annular, crown of jewels-like appearance.  Finally, there is a well-described phenomenon of LABD being drug induced, particularly after a course of vancomycin,⁹ and such an association with vancomycin has not been documented for BSLE. 

Our patient was diagnosed with BSLE following the flare approximately 1.5 years prior to the current presentation. She had been started on dapsone 75 mg daily at that time and was taking 75 mg at the time of presentation. She was admitted and treated as an inpatient with high-dose (1 mg/kg) intravenous prednisone due to the extensive current flare. 

To the Editor:

A 42-year-old woman with Crohn disease of 10 years’ duration presented to the clinic with a chief concern of nonpruritic pustular lesions on the bilateral arms. Physical examination revealed several pustules on the arms with secondary excoriation. She also had a warm tender nodule on the left upper shin and subungual hemorrhages under the fingernails (Figure 1). The patient had previously undergone infliximab therapy, which was discontinued 10 months prior to presentation in anticipation of a partial colectomy and temporary ileostomy that was performed 8 months prior to presentation. She recently had developed bilateral, radiating, sharp lower extremity pain extending from the feet to the hips over the last 2 weeks and swelling of the bilateral legs that impaired her ability to ambulate. Additionally, she had recently traveled to Colorado and a Lyme disease workup was initiated at an outside hospital in Colorado; however, the results were pending. The outside hospital also performed a spinal tap that was negative. At our clinic, biopsies were performed on the shin nodule and a right palmar pustule (Figure 2). There was clinical suspicion of erythema nodosum and subcorneal pustular dermatosis or a vesiculopustular skin manifestation of the patient’s Crohn disease. The patient was switched from generic doxycycline to a brand name variant 150 mg every night at bedtime for 2 weeks. She subsequently was admitted to the inpatient rheumatology service for a complete systemic workup.

The punch biopsy of the left upper shin demonstrated operative hemorrhage and periadnexal lymphocytic inflammation without evidence of fungal or bacterial elements by Gram or Gomori methenamine-silver stain. Clinically, the diagnosis was most likely erythema nodosum, though insufficient hypodermis was present to make the diagnosis with pathology. The shave biopsy of the right medial palm was nondiagnostic but showed a transected pustule with no bacterial or fungal elements by Gram or Gomori methenamine-silver stain (Figure 3). Given the clinical context, the likely pathologic diagnosis was vesiculopustular Crohn disease.

Our patient was started on an empiric steroid trial with rapid improvement of the arthralgia and rash. The presumed diagnosis was a Crohn disease flare and the patient was discharged on an 8-week steroid taper. Three weeks later at a follow-up appointment, the patient’s skin lesions had nearly resolved. The swelling of the legs and feet had substantially decreased, but the joint pain, primarily in the ankles, persisted.

Routine laboratory studies showed a hemoglobin level of 11.6 g/dL (reference range, 12–15 g/dL), white blood cell count of 9.1 K/μL (reference range, 4.5–11.0 K/μL), C-reactive protein level of 20.15 mg/dL (reference range, <1.0 mg/dL), and an antinuclear antibody titer of 160 (<80). Serology for Lyme disease was negative. Serum chemistries were all within reference range and an echocardiogram was normal.

Up to one-third of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations of their condition. Of these patients, nearly one-third will develop cutaneous manifestations.¹ The most common skin diseases associated with IBD are pyoderma gangrenosum and erythema nodosum.² The differential diagnoses considered in this unique case included early pyoderma gangrenosum, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), and vesiculopustular Crohn disease. Vesiculopustular Crohn disease is a rare component of IBD and also can be present in bowel-associated dermatosis-arthritis syndrome (BADAS). In BADAS, symptoms often include arthritis and systemic symptoms such as fever and malaise. The skin manifestations typically involve the arms and trunk. It often is seen after intestinal bypass surgery but also can be present in patients with gastrointestinal diseases such as IBD.³ Due to its early association with bypass surgery, BADAS previously was referred to as bowel bypass syndrome but has since been seen in relation to other intestinal surgeries and IBD.⁴ Patients with BADAS often present with episodes of fever, fatigue, and malaise, in addition to arthralgia and cutaneous eruptions. Cases of BADAS related to IBD instead of bypass surgery often can be less severe in nature. Unlike many of these previously reported cases, our patient’s joint pain primarily was in the knees and ankles, whereas typical cases of BADAS cause upper extremity (ie, shoulder, elbow) arthralgia. Our patient occasionally experienced upper extremity pain, but it was less frequent and less severe than the knee and ankle pain. The vesiculopustular lesions in BADAS usually begin as 3- to 10-mm painful macules that then develop into aseptic pustular lesions. These manifestations arise on the upper arms and chest or trunk and can be accompanied by erythema nodosum on the legs.⁴

It has been hypothesized that BADAS occurs as an immune reaction to bacterial overgrowth in the bowel from IBD, infection, or surgery. The reaction is in response to a bacterial antigen and manifests cutaneously.⁵ This same pathogenesis is thought to cause various other manifestations of Crohn disease such as erythema nodosum. Bacteria that incite this immune response include Bacteroides fragilis, Escherichia coli, and Streptococcus.

Resolution of both vesiculopustular Crohn disease and of BADAS often occurs with treatment of the underlying IBD but also can be improved with steroids and antibiotics. However, response to antibiotics often is variable.^5,6 The mainstay for treatment remains steroids and management of underlying bowel disease.

Bowel-associated dermatosis-arthritis syndrome often is overlooked when compiling differential diagnoses for neutrophilic dermatoses but should be considered in patients with bowel disease or recent surgery. Because the syndrome can be recurrent, early diagnosis can help to prevent and treat relapsing courses of BADAS.

To the Editor:

A 42-year-old woman with Crohn disease of 10 years’ duration presented to the clinic with a chief concern of nonpruritic pustular lesions on the bilateral arms. Physical examination revealed several pustules on the arms with secondary excoriation. She also had a warm tender nodule on the left upper shin and subungual hemorrhages under the fingernails (Figure 1). The patient had previously undergone infliximab therapy, which was discontinued 10 months prior to presentation in anticipation of a partial colectomy and temporary ileostomy that was performed 8 months prior to presentation. She recently had developed bilateral, radiating, sharp lower extremity pain extending from the feet to the hips over the last 2 weeks and swelling of the bilateral legs that impaired her ability to ambulate. Additionally, she had recently traveled to Colorado and a Lyme disease workup was initiated at an outside hospital in Colorado; however, the results were pending. The outside hospital also performed a spinal tap that was negative. At our clinic, biopsies were performed on the shin nodule and a right palmar pustule (Figure 2). There was clinical suspicion of erythema nodosum and subcorneal pustular dermatosis or a vesiculopustular skin manifestation of the patient’s Crohn disease. The patient was switched from generic doxycycline to a brand name variant 150 mg every night at bedtime for 2 weeks. She subsequently was admitted to the inpatient rheumatology service for a complete systemic workup.

The punch biopsy of the left upper shin demonstrated operative hemorrhage and periadnexal lymphocytic inflammation without evidence of fungal or bacterial elements by Gram or Gomori methenamine-silver stain. Clinically, the diagnosis was most likely erythema nodosum, though insufficient hypodermis was present to make the diagnosis with pathology. The shave biopsy of the right medial palm was nondiagnostic but showed a transected pustule with no bacterial or fungal elements by Gram or Gomori methenamine-silver stain (Figure 3). Given the clinical context, the likely pathologic diagnosis was vesiculopustular Crohn disease.

Our patient was started on an empiric steroid trial with rapid improvement of the arthralgia and rash. The presumed diagnosis was a Crohn disease flare and the patient was discharged on an 8-week steroid taper. Three weeks later at a follow-up appointment, the patient’s skin lesions had nearly resolved. The swelling of the legs and feet had substantially decreased, but the joint pain, primarily in the ankles, persisted.

Routine laboratory studies showed a hemoglobin level of 11.6 g/dL (reference range, 12–15 g/dL), white blood cell count of 9.1 K/μL (reference range, 4.5–11.0 K/μL), C-reactive protein level of 20.15 mg/dL (reference range, <1.0 mg/dL), and an antinuclear antibody titer of 160 (<80). Serology for Lyme disease was negative. Serum chemistries were all within reference range and an echocardiogram was normal.

Up to one-third of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations of their condition. Of these patients, nearly one-third will develop cutaneous manifestations.¹ The most common skin diseases associated with IBD are pyoderma gangrenosum and erythema nodosum.² The differential diagnoses considered in this unique case included early pyoderma gangrenosum, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), and vesiculopustular Crohn disease. Vesiculopustular Crohn disease is a rare component of IBD and also can be present in bowel-associated dermatosis-arthritis syndrome (BADAS). In BADAS, symptoms often include arthritis and systemic symptoms such as fever and malaise. The skin manifestations typically involve the arms and trunk. It often is seen after intestinal bypass surgery but also can be present in patients with gastrointestinal diseases such as IBD.³ Due to its early association with bypass surgery, BADAS previously was referred to as bowel bypass syndrome but has since been seen in relation to other intestinal surgeries and IBD.⁴ Patients with BADAS often present with episodes of fever, fatigue, and malaise, in addition to arthralgia and cutaneous eruptions. Cases of BADAS related to IBD instead of bypass surgery often can be less severe in nature. Unlike many of these previously reported cases, our patient’s joint pain primarily was in the knees and ankles, whereas typical cases of BADAS cause upper extremity (ie, shoulder, elbow) arthralgia. Our patient occasionally experienced upper extremity pain, but it was less frequent and less severe than the knee and ankle pain. The vesiculopustular lesions in BADAS usually begin as 3- to 10-mm painful macules that then develop into aseptic pustular lesions. These manifestations arise on the upper arms and chest or trunk and can be accompanied by erythema nodosum on the legs.⁴

It has been hypothesized that BADAS occurs as an immune reaction to bacterial overgrowth in the bowel from IBD, infection, or surgery. The reaction is in response to a bacterial antigen and manifests cutaneously.⁵ This same pathogenesis is thought to cause various other manifestations of Crohn disease such as erythema nodosum. Bacteria that incite this immune response include Bacteroides fragilis, Escherichia coli, and Streptococcus.

Resolution of both vesiculopustular Crohn disease and of BADAS often occurs with treatment of the underlying IBD but also can be improved with steroids and antibiotics. However, response to antibiotics often is variable.^5,6 The mainstay for treatment remains steroids and management of underlying bowel disease.

Bowel-associated dermatosis-arthritis syndrome often is overlooked when compiling differential diagnoses for neutrophilic dermatoses but should be considered in patients with bowel disease or recent surgery. Because the syndrome can be recurrent, early diagnosis can help to prevent and treat relapsing courses of BADAS.

To the Editor:

A 42-year-old woman with Crohn disease of 10 years’ duration presented to the clinic with a chief concern of nonpruritic pustular lesions on the bilateral arms. Physical examination revealed several pustules on the arms with secondary excoriation. She also had a warm tender nodule on the left upper shin and subungual hemorrhages under the fingernails (Figure 1). The patient had previously undergone infliximab therapy, which was discontinued 10 months prior to presentation in anticipation of a partial colectomy and temporary ileostomy that was performed 8 months prior to presentation. She recently had developed bilateral, radiating, sharp lower extremity pain extending from the feet to the hips over the last 2 weeks and swelling of the bilateral legs that impaired her ability to ambulate. Additionally, she had recently traveled to Colorado and a Lyme disease workup was initiated at an outside hospital in Colorado; however, the results were pending. The outside hospital also performed a spinal tap that was negative. At our clinic, biopsies were performed on the shin nodule and a right palmar pustule (Figure 2). There was clinical suspicion of erythema nodosum and subcorneal pustular dermatosis or a vesiculopustular skin manifestation of the patient’s Crohn disease. The patient was switched from generic doxycycline to a brand name variant 150 mg every night at bedtime for 2 weeks. She subsequently was admitted to the inpatient rheumatology service for a complete systemic workup.

The punch biopsy of the left upper shin demonstrated operative hemorrhage and periadnexal lymphocytic inflammation without evidence of fungal or bacterial elements by Gram or Gomori methenamine-silver stain. Clinically, the diagnosis was most likely erythema nodosum, though insufficient hypodermis was present to make the diagnosis with pathology. The shave biopsy of the right medial palm was nondiagnostic but showed a transected pustule with no bacterial or fungal elements by Gram or Gomori methenamine-silver stain (Figure 3). Given the clinical context, the likely pathologic diagnosis was vesiculopustular Crohn disease.

Our patient was started on an empiric steroid trial with rapid improvement of the arthralgia and rash. The presumed diagnosis was a Crohn disease flare and the patient was discharged on an 8-week steroid taper. Three weeks later at a follow-up appointment, the patient’s skin lesions had nearly resolved. The swelling of the legs and feet had substantially decreased, but the joint pain, primarily in the ankles, persisted.

Routine laboratory studies showed a hemoglobin level of 11.6 g/dL (reference range, 12–15 g/dL), white blood cell count of 9.1 K/μL (reference range, 4.5–11.0 K/μL), C-reactive protein level of 20.15 mg/dL (reference range, <1.0 mg/dL), and an antinuclear antibody titer of 160 (<80). Serology for Lyme disease was negative. Serum chemistries were all within reference range and an echocardiogram was normal.

Up to one-third of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations of their condition. Of these patients, nearly one-third will develop cutaneous manifestations.¹ The most common skin diseases associated with IBD are pyoderma gangrenosum and erythema nodosum.² The differential diagnoses considered in this unique case included early pyoderma gangrenosum, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), and vesiculopustular Crohn disease. Vesiculopustular Crohn disease is a rare component of IBD and also can be present in bowel-associated dermatosis-arthritis syndrome (BADAS). In BADAS, symptoms often include arthritis and systemic symptoms such as fever and malaise. The skin manifestations typically involve the arms and trunk. It often is seen after intestinal bypass surgery but also can be present in patients with gastrointestinal diseases such as IBD.³ Due to its early association with bypass surgery, BADAS previously was referred to as bowel bypass syndrome but has since been seen in relation to other intestinal surgeries and IBD.⁴ Patients with BADAS often present with episodes of fever, fatigue, and malaise, in addition to arthralgia and cutaneous eruptions. Cases of BADAS related to IBD instead of bypass surgery often can be less severe in nature. Unlike many of these previously reported cases, our patient’s joint pain primarily was in the knees and ankles, whereas typical cases of BADAS cause upper extremity (ie, shoulder, elbow) arthralgia. Our patient occasionally experienced upper extremity pain, but it was less frequent and less severe than the knee and ankle pain. The vesiculopustular lesions in BADAS usually begin as 3- to 10-mm painful macules that then develop into aseptic pustular lesions. These manifestations arise on the upper arms and chest or trunk and can be accompanied by erythema nodosum on the legs.⁴

It has been hypothesized that BADAS occurs as an immune reaction to bacterial overgrowth in the bowel from IBD, infection, or surgery. The reaction is in response to a bacterial antigen and manifests cutaneously.⁵ This same pathogenesis is thought to cause various other manifestations of Crohn disease such as erythema nodosum. Bacteria that incite this immune response include Bacteroides fragilis, Escherichia coli, and Streptococcus.

Resolution of both vesiculopustular Crohn disease and of BADAS often occurs with treatment of the underlying IBD but also can be improved with steroids and antibiotics. However, response to antibiotics often is variable.^5,6 The mainstay for treatment remains steroids and management of underlying bowel disease.

Bowel-associated dermatosis-arthritis syndrome often is overlooked when compiling differential diagnoses for neutrophilic dermatoses but should be considered in patients with bowel disease or recent surgery. Because the syndrome can be recurrent, early diagnosis can help to prevent and treat relapsing courses of BADAS.