Anand Rajpara, MD

The Diagnosis: Eosinophilic Folliculitis 

A  shave biopsy specimen of an intact pustule on the left side of the chest was obtained. Histopathologic examination revealed follicular inflammation with copious eosinophils (Figure, A and B). Based on the histopathology and clinical presentation, a diagnosis of human immunodeficiency virus (HIV)-associated eosinophilic folliculitis (EF) was made. 

The patient was started on triamcinolone ointment 0.1% twice daily to active lesions, oral cetirizine 10 mg in the morning, and oral hydroxyzine 25 mg at bedtime. Laboratory evaluation at the time of diagnosis showed eosinophilia with a peripheral blood eosinophil count of 0.5 K/μL (reference range, 0.03–0.48 K/μL).

Human immunodeficiency virus-associated EF is a pruritic follicular eruption that occurs in HIV-positive individuals with advanced disease. Clinically, it is characterized by intermittent, urticarial, red or flesh-colored, 2- to 5-mm papules with sparse pustules involving the head, neck, arms, and upper trunk.^1,2 The cardinal clinical feature of the disorder is intense pruritus, with overlying crusts and excoriations present on physical examination.³  

Patients usually have a CD4 count of less than 250 cells/mm³.^2,3 Patients with HIV can develop an exacerbation of EF in the first 3 to 6 months after initiating antiretroviral therapy. This clinical pattern is believed to be due to the reconstituted immune system and increased circulation of inflammatory cells.⁴ Peripheral eosinophilia and elevated serum IgE levels are found in 25% to 50% of patients with HIV-associated EF.^2,3  

Clinically, the differential diagnosis of intensely pruritic papules with excoriations should include scabies.³ Other diagnoses to consider include opportunistic infections and papular urticaria.⁵ Acne vulgaris and Demodex folliculitis also may present with lesions similar to HIV-associated EF; however, these lesions tend not to be as intensely pruritic.^1,5 

The etiology of HIV-associated EF is unknown.³ One proposed mechanism involves a hypersensitivity reaction to Pityrosporum or Demodex mite fragments, as evidenced by studies that found fragments of these microorganisms in biopsied lesions of HIV-associated EF.^3,6 In our patient's histopathology, it was noted that the afflicted hair follicle held a single Demodex mite (Figure, C). 

The histopathology is characterized by a perifollicular inflammatory infiltrate of eosinophils and CD8+ lymphocytes with areas of sebaceous lysis.^3,6 Spongiosis of the follicular epithelium is seen in early lesions of HIV-associated EF.⁶ 

The first-line treatment of HIV-associated EF includes antiretroviral therapy with topical steroids and antihistamines. Human immunodeficiency virus-associated EF improves as CD4 helper T-cell counts rise above 250 cells/mm³ with continued antiretroviral therapy, though it initially can cause a flare of the condition.⁴ High-potency steroids and antihistamines are added during this period to treat the severe pruritus.^1,7 In particular, daily cetirizine has been shown to be effective, which may be due to its ability to block eosinophil migration in addition to H1-receptor antagonist properties.^3,7 

Various alternative therapies have been described in case reports and case series; however, there have been no controlled studies comparing therapies. Phototherapy with UVB light 3 times weekly for 3 to 6 weeks has been effective and curative in recalcitrant cases.⁷ Other frequently used treatments include oral metronidazole, oral itraconazole, and permethrin cream 5%. The effectiveness of the latter 2 treatments is believed to be related to the proposed role of Pityrosporum and Demodex in the pathogenesis.³  

Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his help compiling the histopathological images and their diagnostic descriptions.  
 

The Diagnosis: Eosinophilic Folliculitis 

A  shave biopsy specimen of an intact pustule on the left side of the chest was obtained. Histopathologic examination revealed follicular inflammation with copious eosinophils (Figure, A and B). Based on the histopathology and clinical presentation, a diagnosis of human immunodeficiency virus (HIV)-associated eosinophilic folliculitis (EF) was made. 

The patient was started on triamcinolone ointment 0.1% twice daily to active lesions, oral cetirizine 10 mg in the morning, and oral hydroxyzine 25 mg at bedtime. Laboratory evaluation at the time of diagnosis showed eosinophilia with a peripheral blood eosinophil count of 0.5 K/μL (reference range, 0.03–0.48 K/μL).

Human immunodeficiency virus-associated EF is a pruritic follicular eruption that occurs in HIV-positive individuals with advanced disease. Clinically, it is characterized by intermittent, urticarial, red or flesh-colored, 2- to 5-mm papules with sparse pustules involving the head, neck, arms, and upper trunk.^1,2 The cardinal clinical feature of the disorder is intense pruritus, with overlying crusts and excoriations present on physical examination.³  

Patients usually have a CD4 count of less than 250 cells/mm³.^2,3 Patients with HIV can develop an exacerbation of EF in the first 3 to 6 months after initiating antiretroviral therapy. This clinical pattern is believed to be due to the reconstituted immune system and increased circulation of inflammatory cells.⁴ Peripheral eosinophilia and elevated serum IgE levels are found in 25% to 50% of patients with HIV-associated EF.^2,3  

Clinically, the differential diagnosis of intensely pruritic papules with excoriations should include scabies.³ Other diagnoses to consider include opportunistic infections and papular urticaria.⁵ Acne vulgaris and Demodex folliculitis also may present with lesions similar to HIV-associated EF; however, these lesions tend not to be as intensely pruritic.^1,5 

The etiology of HIV-associated EF is unknown.³ One proposed mechanism involves a hypersensitivity reaction to Pityrosporum or Demodex mite fragments, as evidenced by studies that found fragments of these microorganisms in biopsied lesions of HIV-associated EF.^3,6 In our patient's histopathology, it was noted that the afflicted hair follicle held a single Demodex mite (Figure, C). 

The histopathology is characterized by a perifollicular inflammatory infiltrate of eosinophils and CD8+ lymphocytes with areas of sebaceous lysis.^3,6 Spongiosis of the follicular epithelium is seen in early lesions of HIV-associated EF.⁶ 

The first-line treatment of HIV-associated EF includes antiretroviral therapy with topical steroids and antihistamines. Human immunodeficiency virus-associated EF improves as CD4 helper T-cell counts rise above 250 cells/mm³ with continued antiretroviral therapy, though it initially can cause a flare of the condition.⁴ High-potency steroids and antihistamines are added during this period to treat the severe pruritus.^1,7 In particular, daily cetirizine has been shown to be effective, which may be due to its ability to block eosinophil migration in addition to H1-receptor antagonist properties.^3,7 

Various alternative therapies have been described in case reports and case series; however, there have been no controlled studies comparing therapies. Phototherapy with UVB light 3 times weekly for 3 to 6 weeks has been effective and curative in recalcitrant cases.⁷ Other frequently used treatments include oral metronidazole, oral itraconazole, and permethrin cream 5%. The effectiveness of the latter 2 treatments is believed to be related to the proposed role of Pityrosporum and Demodex in the pathogenesis.³  

Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his help compiling the histopathological images and their diagnostic descriptions.  
 

The Diagnosis: Eosinophilic Folliculitis 

A  shave biopsy specimen of an intact pustule on the left side of the chest was obtained. Histopathologic examination revealed follicular inflammation with copious eosinophils (Figure, A and B). Based on the histopathology and clinical presentation, a diagnosis of human immunodeficiency virus (HIV)-associated eosinophilic folliculitis (EF) was made. 

The patient was started on triamcinolone ointment 0.1% twice daily to active lesions, oral cetirizine 10 mg in the morning, and oral hydroxyzine 25 mg at bedtime. Laboratory evaluation at the time of diagnosis showed eosinophilia with a peripheral blood eosinophil count of 0.5 K/μL (reference range, 0.03–0.48 K/μL).

Human immunodeficiency virus-associated EF is a pruritic follicular eruption that occurs in HIV-positive individuals with advanced disease. Clinically, it is characterized by intermittent, urticarial, red or flesh-colored, 2- to 5-mm papules with sparse pustules involving the head, neck, arms, and upper trunk.^1,2 The cardinal clinical feature of the disorder is intense pruritus, with overlying crusts and excoriations present on physical examination.³  

Patients usually have a CD4 count of less than 250 cells/mm³.^2,3 Patients with HIV can develop an exacerbation of EF in the first 3 to 6 months after initiating antiretroviral therapy. This clinical pattern is believed to be due to the reconstituted immune system and increased circulation of inflammatory cells.⁴ Peripheral eosinophilia and elevated serum IgE levels are found in 25% to 50% of patients with HIV-associated EF.^2,3  

Clinically, the differential diagnosis of intensely pruritic papules with excoriations should include scabies.³ Other diagnoses to consider include opportunistic infections and papular urticaria.⁵ Acne vulgaris and Demodex folliculitis also may present with lesions similar to HIV-associated EF; however, these lesions tend not to be as intensely pruritic.^1,5 

The etiology of HIV-associated EF is unknown.³ One proposed mechanism involves a hypersensitivity reaction to Pityrosporum or Demodex mite fragments, as evidenced by studies that found fragments of these microorganisms in biopsied lesions of HIV-associated EF.^3,6 In our patient's histopathology, it was noted that the afflicted hair follicle held a single Demodex mite (Figure, C). 

The histopathology is characterized by a perifollicular inflammatory infiltrate of eosinophils and CD8+ lymphocytes with areas of sebaceous lysis.^3,6 Spongiosis of the follicular epithelium is seen in early lesions of HIV-associated EF.⁶ 

The first-line treatment of HIV-associated EF includes antiretroviral therapy with topical steroids and antihistamines. Human immunodeficiency virus-associated EF improves as CD4 helper T-cell counts rise above 250 cells/mm³ with continued antiretroviral therapy, though it initially can cause a flare of the condition.⁴ High-potency steroids and antihistamines are added during this period to treat the severe pruritus.^1,7 In particular, daily cetirizine has been shown to be effective, which may be due to its ability to block eosinophil migration in addition to H1-receptor antagonist properties.^3,7 

Various alternative therapies have been described in case reports and case series; however, there have been no controlled studies comparing therapies. Phototherapy with UVB light 3 times weekly for 3 to 6 weeks has been effective and curative in recalcitrant cases.⁷ Other frequently used treatments include oral metronidazole, oral itraconazole, and permethrin cream 5%. The effectiveness of the latter 2 treatments is believed to be related to the proposed role of Pityrosporum and Demodex in the pathogenesis.³  

Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his help compiling the histopathological images and their diagnostic descriptions.  
 

The Diagnosis: Epidermolysis Bullosa Acquisita 

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder characterized by tense bullae, skin fragility, atrophic scarring, and milia formation.¹ Blisters occur on a noninflammatory base in the classic variant and are trauma induced, hence the predilection for the extensor surfaces.² Mucosal involvement also has been described.¹ The characteristic findings in EBA are IgG autoantibodies directed at the N-terminal collagenous domain of type VII collagen, which composes the anchoring fibrils in the basement membrane zone.¹ Differentiating EBA from other subepidermal bullous diseases, especially bullous pemphigoid (BP), can be difficult, necessitating specialized tests.  

Biopsy of the perilesional skin can help identify the location of the blister formation. Our patient's biopsy showed a subepidermal blister with granulocytes. The differential diagnosis of a subepidermal blister includes BP, herpes gestationis, cicatricial pemphigoid, EBA, bullous systemic lupus erythematosus, dermatitis herpetiformis, linear IgA disease, and porphyria cutanea tarda. 

Direct immunofluorescence (DIF) was performed on the biopsy from our patient, which showed linear/particulate IgG, C3, and IgA deposits in the basement membrane zone, narrowing the differential diagnosis to BP or EBA. To differentiate EBA from BP, DIF of perilesional skin using a salt-split preparation was performed. This test distinguishes the location of the immunoreactants at the basement membrane zone. The antibody complexes in BP are found on the epidermal side of the split, while the antibody complexes in EBA are found on the dermal side of the split. Indirect immunofluorescence on salt-split skin also has been used to distinguish EBA from BP but is only conclusive if there are circulating autoantibodies to the basement membrane zone in the serum, which occurs in approximately 50% of patients with EBA and 15% of patients with BP.³ The immune complexes in our patient were found to be on the dermal side of the split after DIF on salt-split skin, confirming the diagnosis of EBA (Figure).  

Differentiating EBA from BP has great value, as the diagnosis affects treatment options. Bullous pemphigoid is fairly easy to treat, with most patients responding to prednisone.³ Epidermolysis bullosa acquisita usually is resistant to therapy. The disease course is chronic with  exacerbations and remissions. Dapsone often is used to control the disease, though this therapy for EBA is not currently approved by the US Food and Drug Administration. The recommended initial dose of dapsone is 50 mg daily and should be increased by 50 mg each week until remission, usually 100 to 250 mg.⁴ We prescribed dapsone for our patient upon clinical suspicion of EBA before the DIF on salt-split skin was completed. A trial of prednisone may be warranted for EBA if there is no response to dapsone or colchicine, but the response is unpredictable. Cyclosporine usually results in a quick response and may be considered if there is clinically severe disease and other treatment alternatives have failed.⁴ 

The Diagnosis: Epidermolysis Bullosa Acquisita 

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder characterized by tense bullae, skin fragility, atrophic scarring, and milia formation.¹ Blisters occur on a noninflammatory base in the classic variant and are trauma induced, hence the predilection for the extensor surfaces.² Mucosal involvement also has been described.¹ The characteristic findings in EBA are IgG autoantibodies directed at the N-terminal collagenous domain of type VII collagen, which composes the anchoring fibrils in the basement membrane zone.¹ Differentiating EBA from other subepidermal bullous diseases, especially bullous pemphigoid (BP), can be difficult, necessitating specialized tests.  

Biopsy of the perilesional skin can help identify the location of the blister formation. Our patient's biopsy showed a subepidermal blister with granulocytes. The differential diagnosis of a subepidermal blister includes BP, herpes gestationis, cicatricial pemphigoid, EBA, bullous systemic lupus erythematosus, dermatitis herpetiformis, linear IgA disease, and porphyria cutanea tarda. 

Direct immunofluorescence (DIF) was performed on the biopsy from our patient, which showed linear/particulate IgG, C3, and IgA deposits in the basement membrane zone, narrowing the differential diagnosis to BP or EBA. To differentiate EBA from BP, DIF of perilesional skin using a salt-split preparation was performed. This test distinguishes the location of the immunoreactants at the basement membrane zone. The antibody complexes in BP are found on the epidermal side of the split, while the antibody complexes in EBA are found on the dermal side of the split. Indirect immunofluorescence on salt-split skin also has been used to distinguish EBA from BP but is only conclusive if there are circulating autoantibodies to the basement membrane zone in the serum, which occurs in approximately 50% of patients with EBA and 15% of patients with BP.³ The immune complexes in our patient were found to be on the dermal side of the split after DIF on salt-split skin, confirming the diagnosis of EBA (Figure).  

Differentiating EBA from BP has great value, as the diagnosis affects treatment options. Bullous pemphigoid is fairly easy to treat, with most patients responding to prednisone.³ Epidermolysis bullosa acquisita usually is resistant to therapy. The disease course is chronic with  exacerbations and remissions. Dapsone often is used to control the disease, though this therapy for EBA is not currently approved by the US Food and Drug Administration. The recommended initial dose of dapsone is 50 mg daily and should be increased by 50 mg each week until remission, usually 100 to 250 mg.⁴ We prescribed dapsone for our patient upon clinical suspicion of EBA before the DIF on salt-split skin was completed. A trial of prednisone may be warranted for EBA if there is no response to dapsone or colchicine, but the response is unpredictable. Cyclosporine usually results in a quick response and may be considered if there is clinically severe disease and other treatment alternatives have failed.⁴ 

The Diagnosis: Epidermolysis Bullosa Acquisita 

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder characterized by tense bullae, skin fragility, atrophic scarring, and milia formation.¹ Blisters occur on a noninflammatory base in the classic variant and are trauma induced, hence the predilection for the extensor surfaces.² Mucosal involvement also has been described.¹ The characteristic findings in EBA are IgG autoantibodies directed at the N-terminal collagenous domain of type VII collagen, which composes the anchoring fibrils in the basement membrane zone.¹ Differentiating EBA from other subepidermal bullous diseases, especially bullous pemphigoid (BP), can be difficult, necessitating specialized tests.  

Biopsy of the perilesional skin can help identify the location of the blister formation. Our patient's biopsy showed a subepidermal blister with granulocytes. The differential diagnosis of a subepidermal blister includes BP, herpes gestationis, cicatricial pemphigoid, EBA, bullous systemic lupus erythematosus, dermatitis herpetiformis, linear IgA disease, and porphyria cutanea tarda. 

Direct immunofluorescence (DIF) was performed on the biopsy from our patient, which showed linear/particulate IgG, C3, and IgA deposits in the basement membrane zone, narrowing the differential diagnosis to BP or EBA. To differentiate EBA from BP, DIF of perilesional skin using a salt-split preparation was performed. This test distinguishes the location of the immunoreactants at the basement membrane zone. The antibody complexes in BP are found on the epidermal side of the split, while the antibody complexes in EBA are found on the dermal side of the split. Indirect immunofluorescence on salt-split skin also has been used to distinguish EBA from BP but is only conclusive if there are circulating autoantibodies to the basement membrane zone in the serum, which occurs in approximately 50% of patients with EBA and 15% of patients with BP.³ The immune complexes in our patient were found to be on the dermal side of the split after DIF on salt-split skin, confirming the diagnosis of EBA (Figure).  

Differentiating EBA from BP has great value, as the diagnosis affects treatment options. Bullous pemphigoid is fairly easy to treat, with most patients responding to prednisone.³ Epidermolysis bullosa acquisita usually is resistant to therapy. The disease course is chronic with  exacerbations and remissions. Dapsone often is used to control the disease, though this therapy for EBA is not currently approved by the US Food and Drug Administration. The recommended initial dose of dapsone is 50 mg daily and should be increased by 50 mg each week until remission, usually 100 to 250 mg.⁴ We prescribed dapsone for our patient upon clinical suspicion of EBA before the DIF on salt-split skin was completed. A trial of prednisone may be warranted for EBA if there is no response to dapsone or colchicine, but the response is unpredictable. Cyclosporine usually results in a quick response and may be considered if there is clinically severe disease and other treatment alternatives have failed.⁴ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

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: Steatocystoma Multiplex 

The punch biopsy of an abdominal lesion demonstrated a folded cyst wall with a wavy eosinophilic cuticle (Figure), characteristics consistent with steatocystoma multiplex (SM).  

Also known as eruptive steatocystoma, SM consists of numerous flesh-colored, dome-shaped papules and nodules that most commonly arise during adolescence, with a median age of onset of 26 years.¹ These hamartomatous nevoid malformations arise in areas with well-developed pilosebaceous units, such as the upper extremities, neck, axillae, and trunk.^1,2 They occur less commonly on the scalp, face, and acral surfaces.^2-5 The lesions range in size from 2 to 30 mm⁶ and usually are asymptomatic.¹ Occasionally, steatocystomas become tender or can rupture.⁷ 

Steatocystoma multiplex may arise sporadically or may be inherited in an autosomal-dominant fashion. Mutations in exon 1 of the keratin 17 gene, KRT17, have been identified in autosomal-dominant SM.^6,8KRT17 mutations also are responsible for pachyonychia congenita type 2, which is associated with SM.⁹ Some patients with pachyonychia congenita type 2 who have prominent SM and mild nail findings may be misdiagnosed as having pure SM.² 

The histopathologic features of SM were described in a study by Cho and colleagues¹ of 64 patients. Steatocystomas have cyst walls that may be either intricately folded or round/oval, comprised of an average of 4.9 epithelial cell layers. In most cases, the cyst wall contains sebaceous lobules. In all cases, an acellular eosinophilic cuticle was present, and no granular layer was seen. Few vellus hairs may be observed in the cystic cavity.¹ 

The differential diagnosis of SM includes eruptive vellus hair cysts, lipomas, Muir-Torre syndrome, and Gardner syndrome. Some have suggested that eruptive vellus hair cysts and SM exist on a disease spectrum because of their similar clinical presentation.¹⁰ In contrast to SM, however, eruptive vellus hair cysts originate in the infundibulum of the hair shaft rather than the sebaceous duct, and more numerous vellus hair shafts are seen on histopathology.¹ 

Various treatment modalities have been described, including isotretinoin for inflamed lesions,¹¹ cryotherapy for noninflamed lesions,¹¹ aspiration of lesions smallerthan 1 cm,¹² and electrocautery combined with topical retinoids.¹³ Laser treatment has been described, with a 1450-nm diode laser used to target the abnormal sebaceous glands and a 1550-nm fractionated erbium-doped fiber laser used to target the dermal cysts.¹⁴ Carbon dioxide lasers also may be used to open the cyst for drainage.¹⁵ Surgical excision or mini-incision also may be performed.^16,17  
 
Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his assistance with interpretation of the dermatopathology in this case.  

The Diagnosis: Steatocystoma Multiplex 

The punch biopsy of an abdominal lesion demonstrated a folded cyst wall with a wavy eosinophilic cuticle (Figure), characteristics consistent with steatocystoma multiplex (SM).  

Also known as eruptive steatocystoma, SM consists of numerous flesh-colored, dome-shaped papules and nodules that most commonly arise during adolescence, with a median age of onset of 26 years.¹ These hamartomatous nevoid malformations arise in areas with well-developed pilosebaceous units, such as the upper extremities, neck, axillae, and trunk.^1,2 They occur less commonly on the scalp, face, and acral surfaces.^2-5 The lesions range in size from 2 to 30 mm⁶ and usually are asymptomatic.¹ Occasionally, steatocystomas become tender or can rupture.⁷ 

Steatocystoma multiplex may arise sporadically or may be inherited in an autosomal-dominant fashion. Mutations in exon 1 of the keratin 17 gene, KRT17, have been identified in autosomal-dominant SM.^6,8KRT17 mutations also are responsible for pachyonychia congenita type 2, which is associated with SM.⁹ Some patients with pachyonychia congenita type 2 who have prominent SM and mild nail findings may be misdiagnosed as having pure SM.² 

The histopathologic features of SM were described in a study by Cho and colleagues¹ of 64 patients. Steatocystomas have cyst walls that may be either intricately folded or round/oval, comprised of an average of 4.9 epithelial cell layers. In most cases, the cyst wall contains sebaceous lobules. In all cases, an acellular eosinophilic cuticle was present, and no granular layer was seen. Few vellus hairs may be observed in the cystic cavity.¹ 

The differential diagnosis of SM includes eruptive vellus hair cysts, lipomas, Muir-Torre syndrome, and Gardner syndrome. Some have suggested that eruptive vellus hair cysts and SM exist on a disease spectrum because of their similar clinical presentation.¹⁰ In contrast to SM, however, eruptive vellus hair cysts originate in the infundibulum of the hair shaft rather than the sebaceous duct, and more numerous vellus hair shafts are seen on histopathology.¹ 

Various treatment modalities have been described, including isotretinoin for inflamed lesions,¹¹ cryotherapy for noninflamed lesions,¹¹ aspiration of lesions smallerthan 1 cm,¹² and electrocautery combined with topical retinoids.¹³ Laser treatment has been described, with a 1450-nm diode laser used to target the abnormal sebaceous glands and a 1550-nm fractionated erbium-doped fiber laser used to target the dermal cysts.¹⁴ Carbon dioxide lasers also may be used to open the cyst for drainage.¹⁵ Surgical excision or mini-incision also may be performed.^16,17  
 
Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his assistance with interpretation of the dermatopathology in this case.  

The Diagnosis: Steatocystoma Multiplex 

The punch biopsy of an abdominal lesion demonstrated a folded cyst wall with a wavy eosinophilic cuticle (Figure), characteristics consistent with steatocystoma multiplex (SM).  

Also known as eruptive steatocystoma, SM consists of numerous flesh-colored, dome-shaped papules and nodules that most commonly arise during adolescence, with a median age of onset of 26 years.¹ These hamartomatous nevoid malformations arise in areas with well-developed pilosebaceous units, such as the upper extremities, neck, axillae, and trunk.^1,2 They occur less commonly on the scalp, face, and acral surfaces.^2-5 The lesions range in size from 2 to 30 mm⁶ and usually are asymptomatic.¹ Occasionally, steatocystomas become tender or can rupture.⁷ 

Steatocystoma multiplex may arise sporadically or may be inherited in an autosomal-dominant fashion. Mutations in exon 1 of the keratin 17 gene, KRT17, have been identified in autosomal-dominant SM.^6,8KRT17 mutations also are responsible for pachyonychia congenita type 2, which is associated with SM.⁹ Some patients with pachyonychia congenita type 2 who have prominent SM and mild nail findings may be misdiagnosed as having pure SM.² 

The histopathologic features of SM were described in a study by Cho and colleagues¹ of 64 patients. Steatocystomas have cyst walls that may be either intricately folded or round/oval, comprised of an average of 4.9 epithelial cell layers. In most cases, the cyst wall contains sebaceous lobules. In all cases, an acellular eosinophilic cuticle was present, and no granular layer was seen. Few vellus hairs may be observed in the cystic cavity.¹ 

The differential diagnosis of SM includes eruptive vellus hair cysts, lipomas, Muir-Torre syndrome, and Gardner syndrome. Some have suggested that eruptive vellus hair cysts and SM exist on a disease spectrum because of their similar clinical presentation.¹⁰ In contrast to SM, however, eruptive vellus hair cysts originate in the infundibulum of the hair shaft rather than the sebaceous duct, and more numerous vellus hair shafts are seen on histopathology.¹ 

Various treatment modalities have been described, including isotretinoin for inflamed lesions,¹¹ cryotherapy for noninflamed lesions,¹¹ aspiration of lesions smallerthan 1 cm,¹² and electrocautery combined with topical retinoids.¹³ Laser treatment has been described, with a 1450-nm diode laser used to target the abnormal sebaceous glands and a 1550-nm fractionated erbium-doped fiber laser used to target the dermal cysts.¹⁴ Carbon dioxide lasers also may be used to open the cyst for drainage.¹⁵ Surgical excision or mini-incision also may be performed.^16,17  
 
Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his assistance with interpretation of the dermatopathology in this case.  

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. 

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

The Diagnosis: Unilateral Nevoid Telangiectasia

Unilateral nevoid telangiectasia (UNT) is an uncommon, or perhaps underreported, cutaneous condition involving telangiectatic patches in a unilateral dermatomal or blaschkoid pattern.¹ The condition has been described as either congenital or acquired. Congenital UNT is thought to be a result of somatic mosaicism, whereby a mutation during embryogenesis leads to a distinct population of cells expressing the vascular malformation.¹ Congenital UNT has been associated with Becker nevus, which also is thought to be a result of somatic mosaicism, further providing evidence for this theory, though it is unclear whether this finding is incidental.² The acquired form often is associated with fluctuation of hormones, such as in pregnancy or with oral contraceptive initiation, as well as with hepatic disease as seen in our patient. However, there are many cases of acquired UNT with no implicated underlying disease, alcohol abuse, or hormonal changes, which calls into question if UNT is definitively an estrogen-related condition.³ One study demonstrated an increased level of estrogen and progesterone receptors in affected skin, which may have led to expression of the cutaneous changes at that site.⁴ More research is needed to elucidate this point, as other studies have not reproduced similar findings.

Congenital UNT occurs more commonly in males, whereas the acquired variant is seen more frequently in females. The third and fourth cervical dermatomes most often are involved.⁵ Most lesions persist without spontaneous resolution. Treatment options are limited and include pulsed dye laser treatment and makeup application to cover the telangiectatic patches. The main side effect seen with pulsed dye laser treatment is reversible pigmentary changes, with 1 report of textural skin change.⁶

A biopsy was deemed unnecessary for the clinical diagnosis in our patient because there was a clear explanation for the physical examination findings due to long-standing underlying liver disease. When biopsied, UNT characteristically demonstrates dilated dermal capillaries.⁵ Our patient elected not to pursue laser therapy but expressed interest in using makeup to camouflage the lesion.

The differential diagnosis includes acquired nevus flammeus, which typically is present on the face and often appears following mechanical or thermal trauma. Angioma serpiginosum most often occurs on the buttocks and legs as small red papules or puncta coalescing into a serpiginous linear arrangement. It often appears in childhood. Angiosarcoma is an aggressive malignancy that often occurs on the head and neck in elderly patients. It is associated with areas of long-standing lymphedema and often appears as a bruiselike lesion. Rosacea typically is not fixed in its clinical appearance and presents as transitory flushing of the head and neck with or without a history of acneform eruptions on the face. It typically is not unilateral.

The Diagnosis: Unilateral Nevoid Telangiectasia

Unilateral nevoid telangiectasia (UNT) is an uncommon, or perhaps underreported, cutaneous condition involving telangiectatic patches in a unilateral dermatomal or blaschkoid pattern.¹ The condition has been described as either congenital or acquired. Congenital UNT is thought to be a result of somatic mosaicism, whereby a mutation during embryogenesis leads to a distinct population of cells expressing the vascular malformation.¹ Congenital UNT has been associated with Becker nevus, which also is thought to be a result of somatic mosaicism, further providing evidence for this theory, though it is unclear whether this finding is incidental.² The acquired form often is associated with fluctuation of hormones, such as in pregnancy or with oral contraceptive initiation, as well as with hepatic disease as seen in our patient. However, there are many cases of acquired UNT with no implicated underlying disease, alcohol abuse, or hormonal changes, which calls into question if UNT is definitively an estrogen-related condition.³ One study demonstrated an increased level of estrogen and progesterone receptors in affected skin, which may have led to expression of the cutaneous changes at that site.⁴ More research is needed to elucidate this point, as other studies have not reproduced similar findings.

Congenital UNT occurs more commonly in males, whereas the acquired variant is seen more frequently in females. The third and fourth cervical dermatomes most often are involved.⁵ Most lesions persist without spontaneous resolution. Treatment options are limited and include pulsed dye laser treatment and makeup application to cover the telangiectatic patches. The main side effect seen with pulsed dye laser treatment is reversible pigmentary changes, with 1 report of textural skin change.⁶

A biopsy was deemed unnecessary for the clinical diagnosis in our patient because there was a clear explanation for the physical examination findings due to long-standing underlying liver disease. When biopsied, UNT characteristically demonstrates dilated dermal capillaries.⁵ Our patient elected not to pursue laser therapy but expressed interest in using makeup to camouflage the lesion.

The differential diagnosis includes acquired nevus flammeus, which typically is present on the face and often appears following mechanical or thermal trauma. Angioma serpiginosum most often occurs on the buttocks and legs as small red papules or puncta coalescing into a serpiginous linear arrangement. It often appears in childhood. Angiosarcoma is an aggressive malignancy that often occurs on the head and neck in elderly patients. It is associated with areas of long-standing lymphedema and often appears as a bruiselike lesion. Rosacea typically is not fixed in its clinical appearance and presents as transitory flushing of the head and neck with or without a history of acneform eruptions on the face. It typically is not unilateral.

The Diagnosis: Unilateral Nevoid Telangiectasia

Unilateral nevoid telangiectasia (UNT) is an uncommon, or perhaps underreported, cutaneous condition involving telangiectatic patches in a unilateral dermatomal or blaschkoid pattern.¹ The condition has been described as either congenital or acquired. Congenital UNT is thought to be a result of somatic mosaicism, whereby a mutation during embryogenesis leads to a distinct population of cells expressing the vascular malformation.¹ Congenital UNT has been associated with Becker nevus, which also is thought to be a result of somatic mosaicism, further providing evidence for this theory, though it is unclear whether this finding is incidental.² The acquired form often is associated with fluctuation of hormones, such as in pregnancy or with oral contraceptive initiation, as well as with hepatic disease as seen in our patient. However, there are many cases of acquired UNT with no implicated underlying disease, alcohol abuse, or hormonal changes, which calls into question if UNT is definitively an estrogen-related condition.³ One study demonstrated an increased level of estrogen and progesterone receptors in affected skin, which may have led to expression of the cutaneous changes at that site.⁴ More research is needed to elucidate this point, as other studies have not reproduced similar findings.

Congenital UNT occurs more commonly in males, whereas the acquired variant is seen more frequently in females. The third and fourth cervical dermatomes most often are involved.⁵ Most lesions persist without spontaneous resolution. Treatment options are limited and include pulsed dye laser treatment and makeup application to cover the telangiectatic patches. The main side effect seen with pulsed dye laser treatment is reversible pigmentary changes, with 1 report of textural skin change.⁶

A biopsy was deemed unnecessary for the clinical diagnosis in our patient because there was a clear explanation for the physical examination findings due to long-standing underlying liver disease. When biopsied, UNT characteristically demonstrates dilated dermal capillaries.⁵ Our patient elected not to pursue laser therapy but expressed interest in using makeup to camouflage the lesion.

The differential diagnosis includes acquired nevus flammeus, which typically is present on the face and often appears following mechanical or thermal trauma. Angioma serpiginosum most often occurs on the buttocks and legs as small red papules or puncta coalescing into a serpiginous linear arrangement. It often appears in childhood. Angiosarcoma is an aggressive malignancy that often occurs on the head and neck in elderly patients. It is associated with areas of long-standing lymphedema and often appears as a bruiselike lesion. Rosacea typically is not fixed in its clinical appearance and presents as transitory flushing of the head and neck with or without a history of acneform eruptions on the face. It typically is not unilateral.

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Acrodermatitis Continua of Hallopeau

Acrodermatitis continua of Hallopeau (ACH) is considered to be a form of acropustular psoriasis that presents as a sterile, pustular eruption initially affecting the fingertips and/or toes.¹ The slow-growing pustules typically progress locally and can lead to onychodystrophy and/or osteolysis of the underlying bone.^2,3 Most commonly affecting adult women, ACH often begins following local trauma to or infection of a single digit.⁴ As the disease progresses proximally, the small pustules burst, leaving a shiny, erythematous surface on which new pustules can develop. These pustules have a tendency to amalgamate, leading to the characteristic clinical finding of lakes of pus. Pustules frequently appear on the nail matrix and nail bed presenting as severe onychodystrophy and ultimately anonychia.^5,6 Rarely, ACH can be associated with generalized pustular psoriasis as well as conjunctivitis, balanitis, and fissuring or annulus migrans of the tongue.^2,7

Diagnosis can be established based on clinical findings, biopsy, and bacterial and fungal cultures revealing sterile pustules.^8,9 Histologic findings are similar to those seen in pustular psoriasis, demonstrating subcorneal neutrophilic pustules, Munro microabscesses, and dilated blood vessels with lymphocytic infiltrate in the papillary dermis.¹⁰

Due to the refractory nature of the disease, there are no recommended guidelines for treatment of ACH. Most successful treatment regimens consist of topical psoriasis medications combined with systemic psoriatic therapies such as cyclosporine, methotrexate, acitretin, or biologic therapy.^8,11-16 Our patient achieved satisfactory clinical improvement with clobetasol propionate ointment 0.05% twice daily alternating with calcipotriene cream 0.005% twice daily.

The Diagnosis: Acrodermatitis Continua of Hallopeau

Acrodermatitis continua of Hallopeau (ACH) is considered to be a form of acropustular psoriasis that presents as a sterile, pustular eruption initially affecting the fingertips and/or toes.¹ The slow-growing pustules typically progress locally and can lead to onychodystrophy and/or osteolysis of the underlying bone.^2,3 Most commonly affecting adult women, ACH often begins following local trauma to or infection of a single digit.⁴ As the disease progresses proximally, the small pustules burst, leaving a shiny, erythematous surface on which new pustules can develop. These pustules have a tendency to amalgamate, leading to the characteristic clinical finding of lakes of pus. Pustules frequently appear on the nail matrix and nail bed presenting as severe onychodystrophy and ultimately anonychia.^5,6 Rarely, ACH can be associated with generalized pustular psoriasis as well as conjunctivitis, balanitis, and fissuring or annulus migrans of the tongue.^2,7

Diagnosis can be established based on clinical findings, biopsy, and bacterial and fungal cultures revealing sterile pustules.^8,9 Histologic findings are similar to those seen in pustular psoriasis, demonstrating subcorneal neutrophilic pustules, Munro microabscesses, and dilated blood vessels with lymphocytic infiltrate in the papillary dermis.¹⁰

Due to the refractory nature of the disease, there are no recommended guidelines for treatment of ACH. Most successful treatment regimens consist of topical psoriasis medications combined with systemic psoriatic therapies such as cyclosporine, methotrexate, acitretin, or biologic therapy.^8,11-16 Our patient achieved satisfactory clinical improvement with clobetasol propionate ointment 0.05% twice daily alternating with calcipotriene cream 0.005% twice daily.

The Diagnosis: Acrodermatitis Continua of Hallopeau

Acrodermatitis continua of Hallopeau (ACH) is considered to be a form of acropustular psoriasis that presents as a sterile, pustular eruption initially affecting the fingertips and/or toes.¹ The slow-growing pustules typically progress locally and can lead to onychodystrophy and/or osteolysis of the underlying bone.^2,3 Most commonly affecting adult women, ACH often begins following local trauma to or infection of a single digit.⁴ As the disease progresses proximally, the small pustules burst, leaving a shiny, erythematous surface on which new pustules can develop. These pustules have a tendency to amalgamate, leading to the characteristic clinical finding of lakes of pus. Pustules frequently appear on the nail matrix and nail bed presenting as severe onychodystrophy and ultimately anonychia.^5,6 Rarely, ACH can be associated with generalized pustular psoriasis as well as conjunctivitis, balanitis, and fissuring or annulus migrans of the tongue.^2,7

Diagnosis can be established based on clinical findings, biopsy, and bacterial and fungal cultures revealing sterile pustules.^8,9 Histologic findings are similar to those seen in pustular psoriasis, demonstrating subcorneal neutrophilic pustules, Munro microabscesses, and dilated blood vessels with lymphocytic infiltrate in the papillary dermis.¹⁰

Due to the refractory nature of the disease, there are no recommended guidelines for treatment of ACH. Most successful treatment regimens consist of topical psoriasis medications combined with systemic psoriatic therapies such as cyclosporine, methotrexate, acitretin, or biologic therapy.^8,11-16 Our patient achieved satisfactory clinical improvement with clobetasol propionate ointment 0.05% twice daily alternating with calcipotriene cream 0.005% twice daily.