Pigmentation Disorders

To the Editor:

Chronic UV exposure has been linked to increased skin fragility and the development of purpuric lesions, a benign condition known as actinic purpura and commonly seen in elderly patients. Petechial skin changes acutely following intense sun exposure is a rare phenomenon referred to as sunburn purpura, photolocalized purpura, or solar purpura.

A 19-year-old woman presented with red and purple spots on the pretibial region of both legs extending to the thigh. One week prior to presentation she had a severe sunburn affecting most of the body, which resolved without blistering. Two days later, the spots appeared within the most severely sunburned areas of both legs. The patient reported that the lesions were mildly painful to palpation, but she was more concerned about the appearance. She denied any history of similar skin changes associated with sun exposure. The patient was otherwise healthy and denied any recent illnesses. She noted a history of mild bruising and bleeding with a resulting unremarkable workup by her primary care physician. The only medication taken was etonogestrel-ethinyl estradiol vaginal ring.

The scalp, face, arms, trunk, and legs were examined, and nonpalpable petechial changes were noted on the anterior aspect of the legs (Figure 1), with changes more prominent on the distal aspect of the legs. Mild superficial epidermal exfoliation was noted on both anterior thighs. The area of the lesions was not warm. The lesions were mildly tender to palpation. The remainder of the physical examination was unremarkable.

Given the timing of onset, preceding sun exposure, and the morphologic characteristics of the lesions, sunburn purpura was suspected. A punch biopsy of the anterior aspect of the left thigh was performed to rule out vasculitis. Microscopic examination revealed reactive epidermal changes with mild vascular ectasia and erythrocyte extravasation not associated with appreciable inflammation or evidence of vascular injury (Figure 2). Biopsy exposure to fluorescein-labeled antibodies directed against IgG, IgM, IgA, C3, and polyvalent immunoglobulins (IgG, IgM, and IgA) yielded no immunofluorescence. These biopsy results were consistent with sunburn purpura. Given the patient's normal platelet count, a diagnosis of idiopathic sunburn purpura was made. The patient was informed of the biopsy results and advised that the petechiae should resolve without treatment in 1 to 2 weeks, which occurred.

Sunburn purpura remains a rare phenomenon in which a petechial or purpuric rash develops acutely after intense sun exposure. We prefer the term sunburn purpura because it reflects the acuity of the phenomenon, as opposed to the previous labels solar purpura or photolocalized purpura, which also could suggest causality from chronic sun exposure. It has been proposed that sunburn purpura is a finding associated with a number of conditions rather than a unique entity.¹ The following characteristics can be helpful in describing the development of sunburn purpura: delay following UV exposure, gross morphology, histologic findings, and possible associated medical conditions.¹ Our case represents an important addition to the literature, as it differs from previously reported cases. Most importantly, the nonspecific biopsy findings and unremarkable laboratory findings associated with our case may represent primary or idiopathic sunburn purpura.

Previously reported cases of sunburn purpura have occurred in patients aged 10 to 66 years. It has been seen following UV exposure, vigorous exercise and high-dose aspirin, or concurrent fluoroquinolone therapy, or in the setting of erythropoietic protoporphyria, idiopathic thrombocytopenic purpura, or polymorphous light eruption.^2-8 When performed, histology has revealed capillaritis, solar elastosis, perivascular infiltrate, lymphocytic perivascular infiltrate with dermal edema, or leukocytoclastic vasculitis.^1,2,7-9 Our patient did not have a history of erythropoietic protoporphyria, polymorphous light eruption, or idiopathic thrombocytopenic purpura. She had not recently exercised, was not thrombocytopenic, and was not taking antiplatelet medications. She had no recent history of fluoroquinolone use. On histologic examination, our patient's biopsy demonstrated nonspecific petechial changes without signs of chronic UV exposure, dermal edema, vasculitis, lymphocytic infiltrate, or capillaritis.

Idiopathic sunburn purpura should only be diagnosed after other conditions are excluded. When evaluating a patient who presents with new-onset petechial rash following sun exposure, it is important to rule out vasculitis or thrombocytopenia as the cause, which is best achieved through skin biopsy and a platelet count, respectively. If there are no associated symptoms or thrombocytopenia and biopsy shows nonspecific vascular ectasia and erythrocyte extravasation, the physician should consider the diagnosis of idiopathic sunburn (solar or photolocalized) purpura. Along with regular UV protection, the physician should advise that the rash typically resolves without treatment in 1 to 2 weeks.

To the Editor:

Chronic UV exposure has been linked to increased skin fragility and the development of purpuric lesions, a benign condition known as actinic purpura and commonly seen in elderly patients. Petechial skin changes acutely following intense sun exposure is a rare phenomenon referred to as sunburn purpura, photolocalized purpura, or solar purpura.

A 19-year-old woman presented with red and purple spots on the pretibial region of both legs extending to the thigh. One week prior to presentation she had a severe sunburn affecting most of the body, which resolved without blistering. Two days later, the spots appeared within the most severely sunburned areas of both legs. The patient reported that the lesions were mildly painful to palpation, but she was more concerned about the appearance. She denied any history of similar skin changes associated with sun exposure. The patient was otherwise healthy and denied any recent illnesses. She noted a history of mild bruising and bleeding with a resulting unremarkable workup by her primary care physician. The only medication taken was etonogestrel-ethinyl estradiol vaginal ring.

The scalp, face, arms, trunk, and legs were examined, and nonpalpable petechial changes were noted on the anterior aspect of the legs (Figure 1), with changes more prominent on the distal aspect of the legs. Mild superficial epidermal exfoliation was noted on both anterior thighs. The area of the lesions was not warm. The lesions were mildly tender to palpation. The remainder of the physical examination was unremarkable.

Given the timing of onset, preceding sun exposure, and the morphologic characteristics of the lesions, sunburn purpura was suspected. A punch biopsy of the anterior aspect of the left thigh was performed to rule out vasculitis. Microscopic examination revealed reactive epidermal changes with mild vascular ectasia and erythrocyte extravasation not associated with appreciable inflammation or evidence of vascular injury (Figure 2). Biopsy exposure to fluorescein-labeled antibodies directed against IgG, IgM, IgA, C3, and polyvalent immunoglobulins (IgG, IgM, and IgA) yielded no immunofluorescence. These biopsy results were consistent with sunburn purpura. Given the patient's normal platelet count, a diagnosis of idiopathic sunburn purpura was made. The patient was informed of the biopsy results and advised that the petechiae should resolve without treatment in 1 to 2 weeks, which occurred.

Sunburn purpura remains a rare phenomenon in which a petechial or purpuric rash develops acutely after intense sun exposure. We prefer the term sunburn purpura because it reflects the acuity of the phenomenon, as opposed to the previous labels solar purpura or photolocalized purpura, which also could suggest causality from chronic sun exposure. It has been proposed that sunburn purpura is a finding associated with a number of conditions rather than a unique entity.¹ The following characteristics can be helpful in describing the development of sunburn purpura: delay following UV exposure, gross morphology, histologic findings, and possible associated medical conditions.¹ Our case represents an important addition to the literature, as it differs from previously reported cases. Most importantly, the nonspecific biopsy findings and unremarkable laboratory findings associated with our case may represent primary or idiopathic sunburn purpura.

Previously reported cases of sunburn purpura have occurred in patients aged 10 to 66 years. It has been seen following UV exposure, vigorous exercise and high-dose aspirin, or concurrent fluoroquinolone therapy, or in the setting of erythropoietic protoporphyria, idiopathic thrombocytopenic purpura, or polymorphous light eruption.^2-8 When performed, histology has revealed capillaritis, solar elastosis, perivascular infiltrate, lymphocytic perivascular infiltrate with dermal edema, or leukocytoclastic vasculitis.^1,2,7-9 Our patient did not have a history of erythropoietic protoporphyria, polymorphous light eruption, or idiopathic thrombocytopenic purpura. She had not recently exercised, was not thrombocytopenic, and was not taking antiplatelet medications. She had no recent history of fluoroquinolone use. On histologic examination, our patient's biopsy demonstrated nonspecific petechial changes without signs of chronic UV exposure, dermal edema, vasculitis, lymphocytic infiltrate, or capillaritis.

Idiopathic sunburn purpura should only be diagnosed after other conditions are excluded. When evaluating a patient who presents with new-onset petechial rash following sun exposure, it is important to rule out vasculitis or thrombocytopenia as the cause, which is best achieved through skin biopsy and a platelet count, respectively. If there are no associated symptoms or thrombocytopenia and biopsy shows nonspecific vascular ectasia and erythrocyte extravasation, the physician should consider the diagnosis of idiopathic sunburn (solar or photolocalized) purpura. Along with regular UV protection, the physician should advise that the rash typically resolves without treatment in 1 to 2 weeks.

To the Editor:

Chronic UV exposure has been linked to increased skin fragility and the development of purpuric lesions, a benign condition known as actinic purpura and commonly seen in elderly patients. Petechial skin changes acutely following intense sun exposure is a rare phenomenon referred to as sunburn purpura, photolocalized purpura, or solar purpura.

A 19-year-old woman presented with red and purple spots on the pretibial region of both legs extending to the thigh. One week prior to presentation she had a severe sunburn affecting most of the body, which resolved without blistering. Two days later, the spots appeared within the most severely sunburned areas of both legs. The patient reported that the lesions were mildly painful to palpation, but she was more concerned about the appearance. She denied any history of similar skin changes associated with sun exposure. The patient was otherwise healthy and denied any recent illnesses. She noted a history of mild bruising and bleeding with a resulting unremarkable workup by her primary care physician. The only medication taken was etonogestrel-ethinyl estradiol vaginal ring.

The scalp, face, arms, trunk, and legs were examined, and nonpalpable petechial changes were noted on the anterior aspect of the legs (Figure 1), with changes more prominent on the distal aspect of the legs. Mild superficial epidermal exfoliation was noted on both anterior thighs. The area of the lesions was not warm. The lesions were mildly tender to palpation. The remainder of the physical examination was unremarkable.

Given the timing of onset, preceding sun exposure, and the morphologic characteristics of the lesions, sunburn purpura was suspected. A punch biopsy of the anterior aspect of the left thigh was performed to rule out vasculitis. Microscopic examination revealed reactive epidermal changes with mild vascular ectasia and erythrocyte extravasation not associated with appreciable inflammation or evidence of vascular injury (Figure 2). Biopsy exposure to fluorescein-labeled antibodies directed against IgG, IgM, IgA, C3, and polyvalent immunoglobulins (IgG, IgM, and IgA) yielded no immunofluorescence. These biopsy results were consistent with sunburn purpura. Given the patient's normal platelet count, a diagnosis of idiopathic sunburn purpura was made. The patient was informed of the biopsy results and advised that the petechiae should resolve without treatment in 1 to 2 weeks, which occurred.

Sunburn purpura remains a rare phenomenon in which a petechial or purpuric rash develops acutely after intense sun exposure. We prefer the term sunburn purpura because it reflects the acuity of the phenomenon, as opposed to the previous labels solar purpura or photolocalized purpura, which also could suggest causality from chronic sun exposure. It has been proposed that sunburn purpura is a finding associated with a number of conditions rather than a unique entity.¹ The following characteristics can be helpful in describing the development of sunburn purpura: delay following UV exposure, gross morphology, histologic findings, and possible associated medical conditions.¹ Our case represents an important addition to the literature, as it differs from previously reported cases. Most importantly, the nonspecific biopsy findings and unremarkable laboratory findings associated with our case may represent primary or idiopathic sunburn purpura.

Previously reported cases of sunburn purpura have occurred in patients aged 10 to 66 years. It has been seen following UV exposure, vigorous exercise and high-dose aspirin, or concurrent fluoroquinolone therapy, or in the setting of erythropoietic protoporphyria, idiopathic thrombocytopenic purpura, or polymorphous light eruption.^2-8 When performed, histology has revealed capillaritis, solar elastosis, perivascular infiltrate, lymphocytic perivascular infiltrate with dermal edema, or leukocytoclastic vasculitis.^1,2,7-9 Our patient did not have a history of erythropoietic protoporphyria, polymorphous light eruption, or idiopathic thrombocytopenic purpura. She had not recently exercised, was not thrombocytopenic, and was not taking antiplatelet medications. She had no recent history of fluoroquinolone use. On histologic examination, our patient's biopsy demonstrated nonspecific petechial changes without signs of chronic UV exposure, dermal edema, vasculitis, lymphocytic infiltrate, or capillaritis.

Idiopathic sunburn purpura should only be diagnosed after other conditions are excluded. When evaluating a patient who presents with new-onset petechial rash following sun exposure, it is important to rule out vasculitis or thrombocytopenia as the cause, which is best achieved through skin biopsy and a platelet count, respectively. If there are no associated symptoms or thrombocytopenia and biopsy shows nonspecific vascular ectasia and erythrocyte extravasation, the physician should consider the diagnosis of idiopathic sunburn (solar or photolocalized) purpura. Along with regular UV protection, the physician should advise that the rash typically resolves without treatment in 1 to 2 weeks.

To the Editor:

Purpura annularis telangiectodes of Majocchi (PATM) is a type of pigmented purpuric dermatosis (PPD). Patients present with nonblanchable, annular, symmetric, purpuric, and telangiectatic patches, often on the legs, with histology revealing a perivascular lymphocytic infiltrate and extravasated erythrocytes.^1,2 A variety of medications have been linked to the development of PPD. We describe a case of levofloxacin-induced PATM.

RELATED ARTICLE: Granulomatous Changes Associated With Pigmented Purpuric Dermatosis

A 42-year-old man presented with a rash on the arms, trunk, abdomen, and legs of 1 month’s duration. He reported no associated itching, bleeding, or pain, and no history of a similar rash. He had a history of hypothyroidism and had been taking levothyroxine for years. He had no known allergies and no history of childhood eczema, asthma, or allergic rhinitis. Notably, the rash started shortly after the patient finished a 2-week course of levofloxacin, an antibiotic he had not taken in the past. The patient resided with his wife, 3 children, and a pet dog, and no family members had the rash. Prior to presentation, the patient had tried econazole cream and then triamcinolone acetonide cream 0.5% without any clinical improvement.

A complete review of systems was unremarkable. Physical examination revealed scattered, reddish brown, annular, nonscaly patches on the back, abdomen (Figure 1), arms, and legs with nonblanching petechiae within the patches.

A punch biopsy of the left inner thigh demonstrated patchy interface dermatitis, superficial perivascular inflammation, and numerous extravasated red blood cells in the papillary dermis (Figure 2). The histologic features were compatible with the clinical impression of PATM. The patient presented for a follow-up visit 2 weeks later with no new lesions and the old lesions were rapidly fading (Figure 3).

Pigmented purpuric dermatoses are a group of conditions that have different clinical morphologies but similar histopathologic examinations.² All PPDs are characterized by nonblanching, nonpalpable, purpuric lesions that often are bilaterally symmetrical and present on the legs.^2,3 Although the precise etiology of these conditions is not known, most cases include a perivascular lymphocytic infiltrate along with the presence of extravasated erythrocytes and hemosiderin deposition in the dermis.² Of note, PATM often is idiopathic and patients usually present with no associated comorbidities.³ The currently established PPDs include progressive pigmentary dermatosis (Schamberg disease), PATM, pigmented purpuric lichenoid dermatosis of Gougerot and Blum, lichen aureus, and eczematidlike purpura of Doucas and Kapetanakis.^2,4

RELATED ARTICLE: Granulomatous Pigmented Purpuric Dermatosis

The lesions of PATM are symmetrically distributed on the bilateral legs and may be symptomatic in most cases, with severe pruritus being reported in several drug-induced PATM cases.^3,5 Although the exact etiology of PPDs currently is unknown, some contributing factors that are thought to play a role include exercise, venous stasis, gravitational dependence, capillary fragility, hypertension, drugs, chemical exposure or ingestions, and contact allergy to dyes.³ Some of the drugs known to cause drug-induced PPDs fall into the class of sedatives, stimulants, antibiotics, cardiovascular drugs, vitamins, and nutritional supplements.^3,6 Some medications that have been reported to cause PPDs include acetaminophen, aspirin, carbamazepine, diltiazem, furosemide, glipizide, hydralazine, infliximab, isotretinoin, lorazepam, minocycline, nitroglycerine, and sildenafil.^3,7-15

Although the mechanism of drug-induced PPD is not completely understood, it is thought that the ingested substance leads to an immunologic response in the capillary endothelium, which results in a cell-mediated immune response causing vascular damage.³ The ingested substance may act as a hapten, stimulating antibody formation and immune-mediated injury, leading to the clinical presentation of nonblanching, symmetric, purpuric, telangiectatic, and atrophic patches at the site of injury.^1,3

Levofloxacin is a broad-spectrum antibiotic that has activity against both gram-positive and gram-negative bacteria. It inhibits the enzymes DNA gyrase and topoisomerase IV, preventing bacteria from undergoing proper DNA synthesis.¹⁶ Our patient’s rash began shortly after a 2-week course of levofloxacin and faded within a few weeks of discontinuing the drug; the clinical presentation, time course, and histologic appearance of the lesions were consistent with the diagnosis of drug-induced PPD. Of note, solar capillaritis has been reported following a phototoxic reaction induced by levofloxacin.¹⁷ Our case differs in that our patient had annular lesions on both photoprotected and photoexposed skin.

The first-line interventions for the treatment of PPDs are nonpharmacologic, such as discontinuation of an offending drug or allergen or wearing supportive stockings if there are signs of venous stasis. Other interventions include the use of a medium- or high-potency topical corticosteroid once to twice daily to affected areas for 4 to 6 weeks.¹⁸ Some case series also have shown improvement with narrowband UVB treatment after 24 to 28 treatment sessions or with psoralen plus UVA phototherapy within 7 to 20 treatments.^19,20 If the above measures are unsuccessful in resolving symptoms, other treatment alternatives may include pentoxifylline, griseofulvin, colchicine, cyclosporine, and methotrexate. The potential benefit of treatment must be weighed against the side-effect profile of these medications.^2,21-24 Of note, oral rutoside (50 mg twice daily) and ascorbic acid (500 mg twice daily) were administered to 3 patients with chronic progressive pigmented purpura. At the end of the 4-week treatment period, complete clearance of skin lesions was seen in all patients with no adverse reactions noted.²⁵

Despite these treatment options, PATM does not necessitate treatment given its benign course and often self-resolving nature.²⁶ In cases of drug-induced PPD such as in our patient, discontinuation of the offending drug often may lead to resolution.

In summary, PATM is a PPD that has been associated with different etiologic factors. If PATM is suspected to be caused by a drug, discontinuation of the offending agent usually results in resolution of symptoms, as it did in our case with fading of lesions within a few weeks after the patient was no longer taking levofloxacin.

To the Editor:

Purpura annularis telangiectodes of Majocchi (PATM) is a type of pigmented purpuric dermatosis (PPD). Patients present with nonblanchable, annular, symmetric, purpuric, and telangiectatic patches, often on the legs, with histology revealing a perivascular lymphocytic infiltrate and extravasated erythrocytes.^1,2 A variety of medications have been linked to the development of PPD. We describe a case of levofloxacin-induced PATM.

RELATED ARTICLE: Granulomatous Changes Associated With Pigmented Purpuric Dermatosis

A 42-year-old man presented with a rash on the arms, trunk, abdomen, and legs of 1 month’s duration. He reported no associated itching, bleeding, or pain, and no history of a similar rash. He had a history of hypothyroidism and had been taking levothyroxine for years. He had no known allergies and no history of childhood eczema, asthma, or allergic rhinitis. Notably, the rash started shortly after the patient finished a 2-week course of levofloxacin, an antibiotic he had not taken in the past. The patient resided with his wife, 3 children, and a pet dog, and no family members had the rash. Prior to presentation, the patient had tried econazole cream and then triamcinolone acetonide cream 0.5% without any clinical improvement.

A complete review of systems was unremarkable. Physical examination revealed scattered, reddish brown, annular, nonscaly patches on the back, abdomen (Figure 1), arms, and legs with nonblanching petechiae within the patches.

A punch biopsy of the left inner thigh demonstrated patchy interface dermatitis, superficial perivascular inflammation, and numerous extravasated red blood cells in the papillary dermis (Figure 2). The histologic features were compatible with the clinical impression of PATM. The patient presented for a follow-up visit 2 weeks later with no new lesions and the old lesions were rapidly fading (Figure 3).

Pigmented purpuric dermatoses are a group of conditions that have different clinical morphologies but similar histopathologic examinations.² All PPDs are characterized by nonblanching, nonpalpable, purpuric lesions that often are bilaterally symmetrical and present on the legs.^2,3 Although the precise etiology of these conditions is not known, most cases include a perivascular lymphocytic infiltrate along with the presence of extravasated erythrocytes and hemosiderin deposition in the dermis.² Of note, PATM often is idiopathic and patients usually present with no associated comorbidities.³ The currently established PPDs include progressive pigmentary dermatosis (Schamberg disease), PATM, pigmented purpuric lichenoid dermatosis of Gougerot and Blum, lichen aureus, and eczematidlike purpura of Doucas and Kapetanakis.^2,4

RELATED ARTICLE: Granulomatous Pigmented Purpuric Dermatosis

The lesions of PATM are symmetrically distributed on the bilateral legs and may be symptomatic in most cases, with severe pruritus being reported in several drug-induced PATM cases.^3,5 Although the exact etiology of PPDs currently is unknown, some contributing factors that are thought to play a role include exercise, venous stasis, gravitational dependence, capillary fragility, hypertension, drugs, chemical exposure or ingestions, and contact allergy to dyes.³ Some of the drugs known to cause drug-induced PPDs fall into the class of sedatives, stimulants, antibiotics, cardiovascular drugs, vitamins, and nutritional supplements.^3,6 Some medications that have been reported to cause PPDs include acetaminophen, aspirin, carbamazepine, diltiazem, furosemide, glipizide, hydralazine, infliximab, isotretinoin, lorazepam, minocycline, nitroglycerine, and sildenafil.^3,7-15

Although the mechanism of drug-induced PPD is not completely understood, it is thought that the ingested substance leads to an immunologic response in the capillary endothelium, which results in a cell-mediated immune response causing vascular damage.³ The ingested substance may act as a hapten, stimulating antibody formation and immune-mediated injury, leading to the clinical presentation of nonblanching, symmetric, purpuric, telangiectatic, and atrophic patches at the site of injury.^1,3

Levofloxacin is a broad-spectrum antibiotic that has activity against both gram-positive and gram-negative bacteria. It inhibits the enzymes DNA gyrase and topoisomerase IV, preventing bacteria from undergoing proper DNA synthesis.¹⁶ Our patient’s rash began shortly after a 2-week course of levofloxacin and faded within a few weeks of discontinuing the drug; the clinical presentation, time course, and histologic appearance of the lesions were consistent with the diagnosis of drug-induced PPD. Of note, solar capillaritis has been reported following a phototoxic reaction induced by levofloxacin.¹⁷ Our case differs in that our patient had annular lesions on both photoprotected and photoexposed skin.

The first-line interventions for the treatment of PPDs are nonpharmacologic, such as discontinuation of an offending drug or allergen or wearing supportive stockings if there are signs of venous stasis. Other interventions include the use of a medium- or high-potency topical corticosteroid once to twice daily to affected areas for 4 to 6 weeks.¹⁸ Some case series also have shown improvement with narrowband UVB treatment after 24 to 28 treatment sessions or with psoralen plus UVA phototherapy within 7 to 20 treatments.^19,20 If the above measures are unsuccessful in resolving symptoms, other treatment alternatives may include pentoxifylline, griseofulvin, colchicine, cyclosporine, and methotrexate. The potential benefit of treatment must be weighed against the side-effect profile of these medications.^2,21-24 Of note, oral rutoside (50 mg twice daily) and ascorbic acid (500 mg twice daily) were administered to 3 patients with chronic progressive pigmented purpura. At the end of the 4-week treatment period, complete clearance of skin lesions was seen in all patients with no adverse reactions noted.²⁵

Despite these treatment options, PATM does not necessitate treatment given its benign course and often self-resolving nature.²⁶ In cases of drug-induced PPD such as in our patient, discontinuation of the offending drug often may lead to resolution.

In summary, PATM is a PPD that has been associated with different etiologic factors. If PATM is suspected to be caused by a drug, discontinuation of the offending agent usually results in resolution of symptoms, as it did in our case with fading of lesions within a few weeks after the patient was no longer taking levofloxacin.

To the Editor:

Purpura annularis telangiectodes of Majocchi (PATM) is a type of pigmented purpuric dermatosis (PPD). Patients present with nonblanchable, annular, symmetric, purpuric, and telangiectatic patches, often on the legs, with histology revealing a perivascular lymphocytic infiltrate and extravasated erythrocytes.^1,2 A variety of medications have been linked to the development of PPD. We describe a case of levofloxacin-induced PATM.

RELATED ARTICLE: Granulomatous Changes Associated With Pigmented Purpuric Dermatosis

A 42-year-old man presented with a rash on the arms, trunk, abdomen, and legs of 1 month’s duration. He reported no associated itching, bleeding, or pain, and no history of a similar rash. He had a history of hypothyroidism and had been taking levothyroxine for years. He had no known allergies and no history of childhood eczema, asthma, or allergic rhinitis. Notably, the rash started shortly after the patient finished a 2-week course of levofloxacin, an antibiotic he had not taken in the past. The patient resided with his wife, 3 children, and a pet dog, and no family members had the rash. Prior to presentation, the patient had tried econazole cream and then triamcinolone acetonide cream 0.5% without any clinical improvement.

A complete review of systems was unremarkable. Physical examination revealed scattered, reddish brown, annular, nonscaly patches on the back, abdomen (Figure 1), arms, and legs with nonblanching petechiae within the patches.

A punch biopsy of the left inner thigh demonstrated patchy interface dermatitis, superficial perivascular inflammation, and numerous extravasated red blood cells in the papillary dermis (Figure 2). The histologic features were compatible with the clinical impression of PATM. The patient presented for a follow-up visit 2 weeks later with no new lesions and the old lesions were rapidly fading (Figure 3).

Pigmented purpuric dermatoses are a group of conditions that have different clinical morphologies but similar histopathologic examinations.² All PPDs are characterized by nonblanching, nonpalpable, purpuric lesions that often are bilaterally symmetrical and present on the legs.^2,3 Although the precise etiology of these conditions is not known, most cases include a perivascular lymphocytic infiltrate along with the presence of extravasated erythrocytes and hemosiderin deposition in the dermis.² Of note, PATM often is idiopathic and patients usually present with no associated comorbidities.³ The currently established PPDs include progressive pigmentary dermatosis (Schamberg disease), PATM, pigmented purpuric lichenoid dermatosis of Gougerot and Blum, lichen aureus, and eczematidlike purpura of Doucas and Kapetanakis.^2,4

RELATED ARTICLE: Granulomatous Pigmented Purpuric Dermatosis

The lesions of PATM are symmetrically distributed on the bilateral legs and may be symptomatic in most cases, with severe pruritus being reported in several drug-induced PATM cases.^3,5 Although the exact etiology of PPDs currently is unknown, some contributing factors that are thought to play a role include exercise, venous stasis, gravitational dependence, capillary fragility, hypertension, drugs, chemical exposure or ingestions, and contact allergy to dyes.³ Some of the drugs known to cause drug-induced PPDs fall into the class of sedatives, stimulants, antibiotics, cardiovascular drugs, vitamins, and nutritional supplements.^3,6 Some medications that have been reported to cause PPDs include acetaminophen, aspirin, carbamazepine, diltiazem, furosemide, glipizide, hydralazine, infliximab, isotretinoin, lorazepam, minocycline, nitroglycerine, and sildenafil.^3,7-15

Although the mechanism of drug-induced PPD is not completely understood, it is thought that the ingested substance leads to an immunologic response in the capillary endothelium, which results in a cell-mediated immune response causing vascular damage.³ The ingested substance may act as a hapten, stimulating antibody formation and immune-mediated injury, leading to the clinical presentation of nonblanching, symmetric, purpuric, telangiectatic, and atrophic patches at the site of injury.^1,3

Levofloxacin is a broad-spectrum antibiotic that has activity against both gram-positive and gram-negative bacteria. It inhibits the enzymes DNA gyrase and topoisomerase IV, preventing bacteria from undergoing proper DNA synthesis.¹⁶ Our patient’s rash began shortly after a 2-week course of levofloxacin and faded within a few weeks of discontinuing the drug; the clinical presentation, time course, and histologic appearance of the lesions were consistent with the diagnosis of drug-induced PPD. Of note, solar capillaritis has been reported following a phototoxic reaction induced by levofloxacin.¹⁷ Our case differs in that our patient had annular lesions on both photoprotected and photoexposed skin.

The first-line interventions for the treatment of PPDs are nonpharmacologic, such as discontinuation of an offending drug or allergen or wearing supportive stockings if there are signs of venous stasis. Other interventions include the use of a medium- or high-potency topical corticosteroid once to twice daily to affected areas for 4 to 6 weeks.¹⁸ Some case series also have shown improvement with narrowband UVB treatment after 24 to 28 treatment sessions or with psoralen plus UVA phototherapy within 7 to 20 treatments.^19,20 If the above measures are unsuccessful in resolving symptoms, other treatment alternatives may include pentoxifylline, griseofulvin, colchicine, cyclosporine, and methotrexate. The potential benefit of treatment must be weighed against the side-effect profile of these medications.^2,21-24 Of note, oral rutoside (50 mg twice daily) and ascorbic acid (500 mg twice daily) were administered to 3 patients with chronic progressive pigmented purpura. At the end of the 4-week treatment period, complete clearance of skin lesions was seen in all patients with no adverse reactions noted.²⁵

Despite these treatment options, PATM does not necessitate treatment given its benign course and often self-resolving nature.²⁶ In cases of drug-induced PPD such as in our patient, discontinuation of the offending drug often may lead to resolution.

In summary, PATM is a PPD that has been associated with different etiologic factors. If PATM is suspected to be caused by a drug, discontinuation of the offending agent usually results in resolution of symptoms, as it did in our case with fading of lesions within a few weeks after the patient was no longer taking levofloxacin.

The Diagnosis: Phakomatosis Pigmentovascularis With Sturge-Weber Syndrome

The erythematous patches were identified as capillary malformations (port-wine stains) and the slate gray pigmentary changes as dermal melanocytosis (Mongolian spots)(Figure). In fact, the diagnosis of phakomatosis pigmentovascularis (PPV) type II requires dermal melanocytosis and capillary malformation with and without nevus anemicus.1 In one case series, 46% (7/15) of patients with PPV had nevus anemicus² but our patient did not.

Phakomatosis pigmentovascularis was divided into 4 types in 1985,³ then later 5 types.⁴ Subcategories of the 5 types include type A, which denotes a lack of extracutaneous involvement, and type B, which is used when internal manifestations have been exhibited. Since 1947, approximately 222 cases of PPV have been described in the literature.²

A case of PPV associated with Sturge-Weber syndrome (SWS) was reported in 1997.⁵ Since then, PPV occasionally has been linked with SWS,^5-9 though there have been other syndromic associations including Klippel-Trenaunay-Weber syndrome and melanosis oculi.² The incidence and prevalence of overlap of PPV and SWS is unknown but is likely to be rare. In our case, magnetic resonance imaging of the patient's brain did not reveal the characteristic tram-track appearance of SWS; however, the diagnosis of SWS type II only requires facial angioma with or without glaucoma.^9,10 Most cases of PPV originate from Japan, Argentina, and Mexico.² Interestingly, our patient's parents were both of Mexican ancestry. Phakomatosis pigmentovascularis type IIb is the most common, followed by type IIa.² Most cases have been described as sporadic, though our patient's mother also exhibited a port-wine stain on the right neck, suggesting a possible genetic association.

The etiology of PPV has been postulated as twin spotting or didymosis (Greek for twin), most commonly seen in plants and animals. A previous review defined twin spotting as 2 mutant tissues situated adjacent to one another and unique from the normal tissue surrounding both of them.² When the cell loses its heterozygosity, this phenomenon appears. An alternative etiology supplants that a drug or virus toxic to the nervous system causes aberrant angioblasts and melanoblasts.^11,12 The etiology of SWS also is unknown, though vasomotor instability has been postulated as a cause.^6,13

It is important to exclude associated internal organ involvement with both of these syndromes because approximately 50% of PPV cases have extracutaneous organ involvement.^2,14 In fact, PPV is known to involve the brain, skeletal system, and eye, potentially manifesting as deafness, hydrocephalus, extremity overgrowth, scoliosis, cataracts, and more.² Patients with SWS often exhibit brain and eye symptoms including seizures.¹ To screen for extracutaneous involvement, multiple imaging studies should be performed. In our patient, an echocardiogram revealed a patent foramen ovale and normal cardiac anatomy for his age. Brain imaging revealed a hypoplastic left sigmoid and transverse sinus without venous thrombosis and unremarkable appearance of the brain. An ultrasound of the liver, spleen, kidneys, and pancreas revealed no evidence of solid, cystic, or vascular lesions, though the gallbladder exhibited hyperechoic areas.

To manage the skin lesions, some authors recommend Q-switched lasers for pigmented lesions and pulsed dye lasers for capillary malformations.¹⁵ Paller and Mancini¹ cited evidence that pulsed dye laser treatment before the age of 1 year may offer a psychological advantage, while other views have been offered.¹⁶ Some physicians believe that no urgent treatment of capillary malformations is needed unless internal organs are involved.^2,15

The Diagnosis: Phakomatosis Pigmentovascularis With Sturge-Weber Syndrome

The erythematous patches were identified as capillary malformations (port-wine stains) and the slate gray pigmentary changes as dermal melanocytosis (Mongolian spots)(Figure). In fact, the diagnosis of phakomatosis pigmentovascularis (PPV) type II requires dermal melanocytosis and capillary malformation with and without nevus anemicus.1 In one case series, 46% (7/15) of patients with PPV had nevus anemicus² but our patient did not.

Phakomatosis pigmentovascularis was divided into 4 types in 1985,³ then later 5 types.⁴ Subcategories of the 5 types include type A, which denotes a lack of extracutaneous involvement, and type B, which is used when internal manifestations have been exhibited. Since 1947, approximately 222 cases of PPV have been described in the literature.²

A case of PPV associated with Sturge-Weber syndrome (SWS) was reported in 1997.⁵ Since then, PPV occasionally has been linked with SWS,^5-9 though there have been other syndromic associations including Klippel-Trenaunay-Weber syndrome and melanosis oculi.² The incidence and prevalence of overlap of PPV and SWS is unknown but is likely to be rare. In our case, magnetic resonance imaging of the patient's brain did not reveal the characteristic tram-track appearance of SWS; however, the diagnosis of SWS type II only requires facial angioma with or without glaucoma.^9,10 Most cases of PPV originate from Japan, Argentina, and Mexico.² Interestingly, our patient's parents were both of Mexican ancestry. Phakomatosis pigmentovascularis type IIb is the most common, followed by type IIa.² Most cases have been described as sporadic, though our patient's mother also exhibited a port-wine stain on the right neck, suggesting a possible genetic association.

The etiology of PPV has been postulated as twin spotting or didymosis (Greek for twin), most commonly seen in plants and animals. A previous review defined twin spotting as 2 mutant tissues situated adjacent to one another and unique from the normal tissue surrounding both of them.² When the cell loses its heterozygosity, this phenomenon appears. An alternative etiology supplants that a drug or virus toxic to the nervous system causes aberrant angioblasts and melanoblasts.^11,12 The etiology of SWS also is unknown, though vasomotor instability has been postulated as a cause.^6,13

It is important to exclude associated internal organ involvement with both of these syndromes because approximately 50% of PPV cases have extracutaneous organ involvement.^2,14 In fact, PPV is known to involve the brain, skeletal system, and eye, potentially manifesting as deafness, hydrocephalus, extremity overgrowth, scoliosis, cataracts, and more.² Patients with SWS often exhibit brain and eye symptoms including seizures.¹ To screen for extracutaneous involvement, multiple imaging studies should be performed. In our patient, an echocardiogram revealed a patent foramen ovale and normal cardiac anatomy for his age. Brain imaging revealed a hypoplastic left sigmoid and transverse sinus without venous thrombosis and unremarkable appearance of the brain. An ultrasound of the liver, spleen, kidneys, and pancreas revealed no evidence of solid, cystic, or vascular lesions, though the gallbladder exhibited hyperechoic areas.

To manage the skin lesions, some authors recommend Q-switched lasers for pigmented lesions and pulsed dye lasers for capillary malformations.¹⁵ Paller and Mancini¹ cited evidence that pulsed dye laser treatment before the age of 1 year may offer a psychological advantage, while other views have been offered.¹⁶ Some physicians believe that no urgent treatment of capillary malformations is needed unless internal organs are involved.^2,15

The Diagnosis: Phakomatosis Pigmentovascularis With Sturge-Weber Syndrome

The erythematous patches were identified as capillary malformations (port-wine stains) and the slate gray pigmentary changes as dermal melanocytosis (Mongolian spots)(Figure). In fact, the diagnosis of phakomatosis pigmentovascularis (PPV) type II requires dermal melanocytosis and capillary malformation with and without nevus anemicus.1 In one case series, 46% (7/15) of patients with PPV had nevus anemicus² but our patient did not.

Phakomatosis pigmentovascularis was divided into 4 types in 1985,³ then later 5 types.⁴ Subcategories of the 5 types include type A, which denotes a lack of extracutaneous involvement, and type B, which is used when internal manifestations have been exhibited. Since 1947, approximately 222 cases of PPV have been described in the literature.²

A case of PPV associated with Sturge-Weber syndrome (SWS) was reported in 1997.⁵ Since then, PPV occasionally has been linked with SWS,^5-9 though there have been other syndromic associations including Klippel-Trenaunay-Weber syndrome and melanosis oculi.² The incidence and prevalence of overlap of PPV and SWS is unknown but is likely to be rare. In our case, magnetic resonance imaging of the patient's brain did not reveal the characteristic tram-track appearance of SWS; however, the diagnosis of SWS type II only requires facial angioma with or without glaucoma.^9,10 Most cases of PPV originate from Japan, Argentina, and Mexico.² Interestingly, our patient's parents were both of Mexican ancestry. Phakomatosis pigmentovascularis type IIb is the most common, followed by type IIa.² Most cases have been described as sporadic, though our patient's mother also exhibited a port-wine stain on the right neck, suggesting a possible genetic association.

The etiology of PPV has been postulated as twin spotting or didymosis (Greek for twin), most commonly seen in plants and animals. A previous review defined twin spotting as 2 mutant tissues situated adjacent to one another and unique from the normal tissue surrounding both of them.² When the cell loses its heterozygosity, this phenomenon appears. An alternative etiology supplants that a drug or virus toxic to the nervous system causes aberrant angioblasts and melanoblasts.^11,12 The etiology of SWS also is unknown, though vasomotor instability has been postulated as a cause.^6,13

It is important to exclude associated internal organ involvement with both of these syndromes because approximately 50% of PPV cases have extracutaneous organ involvement.^2,14 In fact, PPV is known to involve the brain, skeletal system, and eye, potentially manifesting as deafness, hydrocephalus, extremity overgrowth, scoliosis, cataracts, and more.² Patients with SWS often exhibit brain and eye symptoms including seizures.¹ To screen for extracutaneous involvement, multiple imaging studies should be performed. In our patient, an echocardiogram revealed a patent foramen ovale and normal cardiac anatomy for his age. Brain imaging revealed a hypoplastic left sigmoid and transverse sinus without venous thrombosis and unremarkable appearance of the brain. An ultrasound of the liver, spleen, kidneys, and pancreas revealed no evidence of solid, cystic, or vascular lesions, though the gallbladder exhibited hyperechoic areas.

To manage the skin lesions, some authors recommend Q-switched lasers for pigmented lesions and pulsed dye lasers for capillary malformations.¹⁵ Paller and Mancini¹ cited evidence that pulsed dye laser treatment before the age of 1 year may offer a psychological advantage, while other views have been offered.¹⁶ Some physicians believe that no urgent treatment of capillary malformations is needed unless internal organs are involved.^2,15

Sturge-Weber syndrome (SWS) is a disease of dermatologic, neurologic, and ocular significance.¹ The most distinctive manifestation is facial capillary malformation, commonly referred to as a port-wine stain or nevus flammeus. The dysregulated angiogenesis, caused by somatic mutations of the G protein subunit alpha Q gene, GNAQ, also affects the central nervous system.² Seizures, intellectual disability, and glaucoma are common consequences.¹ Not all port-wine stains are associated with SWS.³ Distribution in the ophthalmic dermatome is associated with increased risk for SWS, with 8% of patients with port-wine stains also having SWS.⁴ The disease is more serious when bilateral lesions are present.⁵ Diagnosis is clinical based on dermatologic, nervous system, and ophthalmologic findings.⁶ The disease is nonheritable because the mutation is found only in the somatic cell lines.² The possibility of epigenetic influence on disease development has to be investigated. The treatment is aimed at managing complications, as there is no cure.⁷

Infantile hemangioma (IH) likewise represents a disruption in the process of vascular development but without the widespread consequences of SWS. The pathogenesis of hemangioma development has not been fully elucidated, with presence of GLUT1 (glucose transporter 1) protein implicated in lesions.⁴ Facial infantile hemangiomas have an incidence of approximately 5 in every 100 births, and the prevalence decreases with age. Most hemangiomas undergo growth followed by an involution process, with most lesions vanishing by 5 years of age.⁴ They typically are seen at 2 to 3 weeks of age, growing rapidly for the first 6 months, which is a contrast to the static nature of nevus flammeus. Infantile hemangiomas are regarded as sporadic, though autosomal-dominant inheritance patterns have been observed.⁴ Our patient demonstrated facial IH at birth, which is a rare and interesting finding suggesting that some epigenetic factors influenced this modification of the disease course in this patient.

Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular condition found in newborns. Its extraordinary infrequency is reflected in the fact that only 300 cases have been reported worldwide.⁸ At birth, CMTC manifests as a pinkish reticulated pattern all over the body mimicking cutis marmorata; however, unlike cutis marmorata, the lesions do not improve with warming.⁹ The lesions of CMTC gradually lighten as the patient ages.⁸ Limb asymmetry is the most common extravascular complication of CMTC and, similar to SWS, glaucoma also can occur.¹⁰ Cutis marmorata telangiectatica congenita has been known to occur simultaneously with SWS or IH, but the combination of all 3 conditions in our patient is unique. Due to the scarcity of cases, the pathophysiology and treatment is poorly understood, with appropriate monitoring for sequelae recommended.⁹

Case Report

The patient was born at 39 weeks’ gestation following an uncomplicated pregnancy and delivery. She weighed 2950 g, her length was 19 in, and her head circumference was 13.25 in, correlating to the 10th, 50th, and 25th percentiles, respectively. Her Apgar score was 8/9 at 1 and 5 minutes. Her parents were nonconsanguineous and in good health. The patient’s family lived in poverty, which led us to conjecture about the role that toxins played in the epigenetics of the patient and her family. It was the mother’s third pregnancy; both prior pregnancies resulted in healthy children. The patient was breastfed. No family history of heritable vascular disorders was reported.

On the first day of life during the newborn examination, dark red pigment changes were noticed under the nose and erythematous pigmentation over the whole body was observed (Figure). On examination, 2-toned reticular lesions identified as extensive nevus flammeus were found bilaterally over the distribution of the ophthalmic division of the trigeminal nerve. A separate erythematous plaque over the maxilla also was recognized. The pediatrician suspected SWS and facial IH. The patient was discharged after 3 days with a referral to pediatric dermatology, and appropriate follow-up with a pediatrician was scheduled. The patient returned for these appointments and the significance of SWS was explained to her parents. Consultation with pediatric dermatology at 2 weeks of age confirmed the diagnosis of SWS as well as facial IH.

Upon further follow-up with pediatric dermatology at 2 months of age, the patient received an additional diagnosis of CMTC. These exceedingly rare lesions were located over the back, trunk, arms, and legs. The patient’s parents were counseled about the management of these conditions and appropriate follow-up.

Comment

This case describes 3 different vascular malformations in the same patient. Cutis marmorata telangiectatica congenita is rare and yet is described in this patient along with 2 other notable endothelial abnormalities. The clinical interest of this case is heightened by the presence of CMTC.

The causative factor of SWS is a well-documented mutation of the GNAQ gene, but there is considerable variability in how it affects the patient. Unlike in SWS, no single factor can be attributed to the development of IH. This case shows that these 3 diseases are not mutually exclusive and can present with unusually severe features when they occur concomitantly. The embryologic basis of SWS traces its roots back to the first trimester during vascular development, where lack of regression and development of the primitive cephalic venous plexus occur.¹⁰The presence of a large IH on the patient’s philtrum that demonstrated markers of pericyte and neural crest cells illustrates that the developmental origins of one neurocutaneous disorder do not necessarily interfere with the development of other cutaneous conditions.¹¹

The severity of the SWS in our patient was highlighted by the extensive nevus flammeus. These lesions occurred over the face, trunk, arms, and legs. The port-wine stain with dermatomal distribution of the ophthalmic nerve was the most concerning feature regarding the development of neurologic complications in this patient. Although the developmental delays associated with SWS can be serious, early intervention is important and can improve long-term outcomes. The facial IH arising at birth was contrary to the typical presentation. All of these factors will be kept in mind as the patient progresses and patient-centered care is provided. Because this patient’s presentation differed from other patients with IH, we will be more vigilant in providing close follow-up and monitoring for other medical problems involving other organs (eg, the brain); for instance, we will monitor for seizures and developmental delay.

Conclusion

In our patient, a unique pattern of SWS, facial IH, and CMTC are described in a pediatric patient. Many disciplines are involved in the treatment. In the patient’s first days of life, extensive collaboration between pediatrics and dermatologists was pivotal, with ophthalmology, pathology, and radiology consultations at hand. This case highlights that several vascular malformations of different origins can occur in the same patient. Epigenetic along with genetic factors likely contributed to this fascinating presentation. The importance of parental education and maintaining appropriate follow-up for this patient is crucial for a favorable outcome.

Sturge-Weber syndrome (SWS) is a disease of dermatologic, neurologic, and ocular significance.¹ The most distinctive manifestation is facial capillary malformation, commonly referred to as a port-wine stain or nevus flammeus. The dysregulated angiogenesis, caused by somatic mutations of the G protein subunit alpha Q gene, GNAQ, also affects the central nervous system.² Seizures, intellectual disability, and glaucoma are common consequences.¹ Not all port-wine stains are associated with SWS.³ Distribution in the ophthalmic dermatome is associated with increased risk for SWS, with 8% of patients with port-wine stains also having SWS.⁴ The disease is more serious when bilateral lesions are present.⁵ Diagnosis is clinical based on dermatologic, nervous system, and ophthalmologic findings.⁶ The disease is nonheritable because the mutation is found only in the somatic cell lines.² The possibility of epigenetic influence on disease development has to be investigated. The treatment is aimed at managing complications, as there is no cure.⁷

Infantile hemangioma (IH) likewise represents a disruption in the process of vascular development but without the widespread consequences of SWS. The pathogenesis of hemangioma development has not been fully elucidated, with presence of GLUT1 (glucose transporter 1) protein implicated in lesions.⁴ Facial infantile hemangiomas have an incidence of approximately 5 in every 100 births, and the prevalence decreases with age. Most hemangiomas undergo growth followed by an involution process, with most lesions vanishing by 5 years of age.⁴ They typically are seen at 2 to 3 weeks of age, growing rapidly for the first 6 months, which is a contrast to the static nature of nevus flammeus. Infantile hemangiomas are regarded as sporadic, though autosomal-dominant inheritance patterns have been observed.⁴ Our patient demonstrated facial IH at birth, which is a rare and interesting finding suggesting that some epigenetic factors influenced this modification of the disease course in this patient.

Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular condition found in newborns. Its extraordinary infrequency is reflected in the fact that only 300 cases have been reported worldwide.⁸ At birth, CMTC manifests as a pinkish reticulated pattern all over the body mimicking cutis marmorata; however, unlike cutis marmorata, the lesions do not improve with warming.⁹ The lesions of CMTC gradually lighten as the patient ages.⁸ Limb asymmetry is the most common extravascular complication of CMTC and, similar to SWS, glaucoma also can occur.¹⁰ Cutis marmorata telangiectatica congenita has been known to occur simultaneously with SWS or IH, but the combination of all 3 conditions in our patient is unique. Due to the scarcity of cases, the pathophysiology and treatment is poorly understood, with appropriate monitoring for sequelae recommended.⁹

Case Report

The patient was born at 39 weeks’ gestation following an uncomplicated pregnancy and delivery. She weighed 2950 g, her length was 19 in, and her head circumference was 13.25 in, correlating to the 10th, 50th, and 25th percentiles, respectively. Her Apgar score was 8/9 at 1 and 5 minutes. Her parents were nonconsanguineous and in good health. The patient’s family lived in poverty, which led us to conjecture about the role that toxins played in the epigenetics of the patient and her family. It was the mother’s third pregnancy; both prior pregnancies resulted in healthy children. The patient was breastfed. No family history of heritable vascular disorders was reported.

On the first day of life during the newborn examination, dark red pigment changes were noticed under the nose and erythematous pigmentation over the whole body was observed (Figure). On examination, 2-toned reticular lesions identified as extensive nevus flammeus were found bilaterally over the distribution of the ophthalmic division of the trigeminal nerve. A separate erythematous plaque over the maxilla also was recognized. The pediatrician suspected SWS and facial IH. The patient was discharged after 3 days with a referral to pediatric dermatology, and appropriate follow-up with a pediatrician was scheduled. The patient returned for these appointments and the significance of SWS was explained to her parents. Consultation with pediatric dermatology at 2 weeks of age confirmed the diagnosis of SWS as well as facial IH.

Upon further follow-up with pediatric dermatology at 2 months of age, the patient received an additional diagnosis of CMTC. These exceedingly rare lesions were located over the back, trunk, arms, and legs. The patient’s parents were counseled about the management of these conditions and appropriate follow-up.

Comment

This case describes 3 different vascular malformations in the same patient. Cutis marmorata telangiectatica congenita is rare and yet is described in this patient along with 2 other notable endothelial abnormalities. The clinical interest of this case is heightened by the presence of CMTC.

The causative factor of SWS is a well-documented mutation of the GNAQ gene, but there is considerable variability in how it affects the patient. Unlike in SWS, no single factor can be attributed to the development of IH. This case shows that these 3 diseases are not mutually exclusive and can present with unusually severe features when they occur concomitantly. The embryologic basis of SWS traces its roots back to the first trimester during vascular development, where lack of regression and development of the primitive cephalic venous plexus occur.¹⁰The presence of a large IH on the patient’s philtrum that demonstrated markers of pericyte and neural crest cells illustrates that the developmental origins of one neurocutaneous disorder do not necessarily interfere with the development of other cutaneous conditions.¹¹

The severity of the SWS in our patient was highlighted by the extensive nevus flammeus. These lesions occurred over the face, trunk, arms, and legs. The port-wine stain with dermatomal distribution of the ophthalmic nerve was the most concerning feature regarding the development of neurologic complications in this patient. Although the developmental delays associated with SWS can be serious, early intervention is important and can improve long-term outcomes. The facial IH arising at birth was contrary to the typical presentation. All of these factors will be kept in mind as the patient progresses and patient-centered care is provided. Because this patient’s presentation differed from other patients with IH, we will be more vigilant in providing close follow-up and monitoring for other medical problems involving other organs (eg, the brain); for instance, we will monitor for seizures and developmental delay.

Conclusion

In our patient, a unique pattern of SWS, facial IH, and CMTC are described in a pediatric patient. Many disciplines are involved in the treatment. In the patient’s first days of life, extensive collaboration between pediatrics and dermatologists was pivotal, with ophthalmology, pathology, and radiology consultations at hand. This case highlights that several vascular malformations of different origins can occur in the same patient. Epigenetic along with genetic factors likely contributed to this fascinating presentation. The importance of parental education and maintaining appropriate follow-up for this patient is crucial for a favorable outcome.

Sturge-Weber syndrome (SWS) is a disease of dermatologic, neurologic, and ocular significance.¹ The most distinctive manifestation is facial capillary malformation, commonly referred to as a port-wine stain or nevus flammeus. The dysregulated angiogenesis, caused by somatic mutations of the G protein subunit alpha Q gene, GNAQ, also affects the central nervous system.² Seizures, intellectual disability, and glaucoma are common consequences.¹ Not all port-wine stains are associated with SWS.³ Distribution in the ophthalmic dermatome is associated with increased risk for SWS, with 8% of patients with port-wine stains also having SWS.⁴ The disease is more serious when bilateral lesions are present.⁵ Diagnosis is clinical based on dermatologic, nervous system, and ophthalmologic findings.⁶ The disease is nonheritable because the mutation is found only in the somatic cell lines.² The possibility of epigenetic influence on disease development has to be investigated. The treatment is aimed at managing complications, as there is no cure.⁷

Infantile hemangioma (IH) likewise represents a disruption in the process of vascular development but without the widespread consequences of SWS. The pathogenesis of hemangioma development has not been fully elucidated, with presence of GLUT1 (glucose transporter 1) protein implicated in lesions.⁴ Facial infantile hemangiomas have an incidence of approximately 5 in every 100 births, and the prevalence decreases with age. Most hemangiomas undergo growth followed by an involution process, with most lesions vanishing by 5 years of age.⁴ They typically are seen at 2 to 3 weeks of age, growing rapidly for the first 6 months, which is a contrast to the static nature of nevus flammeus. Infantile hemangiomas are regarded as sporadic, though autosomal-dominant inheritance patterns have been observed.⁴ Our patient demonstrated facial IH at birth, which is a rare and interesting finding suggesting that some epigenetic factors influenced this modification of the disease course in this patient.

Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular condition found in newborns. Its extraordinary infrequency is reflected in the fact that only 300 cases have been reported worldwide.⁸ At birth, CMTC manifests as a pinkish reticulated pattern all over the body mimicking cutis marmorata; however, unlike cutis marmorata, the lesions do not improve with warming.⁹ The lesions of CMTC gradually lighten as the patient ages.⁸ Limb asymmetry is the most common extravascular complication of CMTC and, similar to SWS, glaucoma also can occur.¹⁰ Cutis marmorata telangiectatica congenita has been known to occur simultaneously with SWS or IH, but the combination of all 3 conditions in our patient is unique. Due to the scarcity of cases, the pathophysiology and treatment is poorly understood, with appropriate monitoring for sequelae recommended.⁹

Case Report

The patient was born at 39 weeks’ gestation following an uncomplicated pregnancy and delivery. She weighed 2950 g, her length was 19 in, and her head circumference was 13.25 in, correlating to the 10th, 50th, and 25th percentiles, respectively. Her Apgar score was 8/9 at 1 and 5 minutes. Her parents were nonconsanguineous and in good health. The patient’s family lived in poverty, which led us to conjecture about the role that toxins played in the epigenetics of the patient and her family. It was the mother’s third pregnancy; both prior pregnancies resulted in healthy children. The patient was breastfed. No family history of heritable vascular disorders was reported.

On the first day of life during the newborn examination, dark red pigment changes were noticed under the nose and erythematous pigmentation over the whole body was observed (Figure). On examination, 2-toned reticular lesions identified as extensive nevus flammeus were found bilaterally over the distribution of the ophthalmic division of the trigeminal nerve. A separate erythematous plaque over the maxilla also was recognized. The pediatrician suspected SWS and facial IH. The patient was discharged after 3 days with a referral to pediatric dermatology, and appropriate follow-up with a pediatrician was scheduled. The patient returned for these appointments and the significance of SWS was explained to her parents. Consultation with pediatric dermatology at 2 weeks of age confirmed the diagnosis of SWS as well as facial IH.

Upon further follow-up with pediatric dermatology at 2 months of age, the patient received an additional diagnosis of CMTC. These exceedingly rare lesions were located over the back, trunk, arms, and legs. The patient’s parents were counseled about the management of these conditions and appropriate follow-up.

Comment

This case describes 3 different vascular malformations in the same patient. Cutis marmorata telangiectatica congenita is rare and yet is described in this patient along with 2 other notable endothelial abnormalities. The clinical interest of this case is heightened by the presence of CMTC.

The causative factor of SWS is a well-documented mutation of the GNAQ gene, but there is considerable variability in how it affects the patient. Unlike in SWS, no single factor can be attributed to the development of IH. This case shows that these 3 diseases are not mutually exclusive and can present with unusually severe features when they occur concomitantly. The embryologic basis of SWS traces its roots back to the first trimester during vascular development, where lack of regression and development of the primitive cephalic venous plexus occur.¹⁰The presence of a large IH on the patient’s philtrum that demonstrated markers of pericyte and neural crest cells illustrates that the developmental origins of one neurocutaneous disorder do not necessarily interfere with the development of other cutaneous conditions.¹¹

The severity of the SWS in our patient was highlighted by the extensive nevus flammeus. These lesions occurred over the face, trunk, arms, and legs. The port-wine stain with dermatomal distribution of the ophthalmic nerve was the most concerning feature regarding the development of neurologic complications in this patient. Although the developmental delays associated with SWS can be serious, early intervention is important and can improve long-term outcomes. The facial IH arising at birth was contrary to the typical presentation. All of these factors will be kept in mind as the patient progresses and patient-centered care is provided. Because this patient’s presentation differed from other patients with IH, we will be more vigilant in providing close follow-up and monitoring for other medical problems involving other organs (eg, the brain); for instance, we will monitor for seizures and developmental delay.

Conclusion

In our patient, a unique pattern of SWS, facial IH, and CMTC are described in a pediatric patient. Many disciplines are involved in the treatment. In the patient’s first days of life, extensive collaboration between pediatrics and dermatologists was pivotal, with ophthalmology, pathology, and radiology consultations at hand. This case highlights that several vascular malformations of different origins can occur in the same patient. Epigenetic along with genetic factors likely contributed to this fascinating presentation. The importance of parental education and maintaining appropriate follow-up for this patient is crucial for a favorable outcome.

To the Editor:

A 55-year-old man presented with hyperpigmented brown macules on the lips, hands, and fingertips of 6 years’ duration. The spots were persistent, asymptomatic, and had not changed in size. The patient denied a history of alopecia or dystrophic nails. He also denied a family history of similar skin findings. He had no personal history of cancer and a colonoscopy performed 5 years prior revealed no notable abnormalities. His medications included amlodipine and hydrocodone-acetaminophen. His mother died of “abdominal bleeding” at 74 years of age and his father died of a brain tumor at 64 years of age. Physical examination demonstrated numerous well-defined, dark brown macules of variable size distributed on the lower and upper mucosal lips (Figure 1A), buccal mucosa, hard palate, and gingiva, as well as the dorsal aspect of the fingers (Figure 1B) and volar aspect of the fingertips (Figure 1C).

A shave biopsy of a dark brown macule from the lower lip (Figure 2) was performed. Histopathologic examination revealed pigmentation of the basal layer of the epidermis with pigment-laden cells in the dermis immediately deep to the surface epithelium. Immunoperoxidase stains showed a normal number and distribution of melanocytes.

A diagnosis of Laugier-Hunziker syndrome (LHS) was made given the age of onset; distribution of pigmentation; and lack of pathologic colonoscopic findings, personal history of cancer, or gastrointestinal tract symptoms.

Benign hyperpigmentation of the lips and fingers has been reported.¹ The average age of onset of LHS is 52 years, and it typically is diagnosed in white adults.^1,2 In LHS, pigmentation is most commonly distributed on the lips, especially the lower lips and oral mucosa.² Pigmentation of the nails in the form of longitudinal melanonychia is present in approximately half of cases.^2,3 There also may be pigmentation of the neck; thorax; abdomen; and acral surfaces, especially the fingertips.^1-3 Rarely, pigmented macules can occur on the genitalia or sclera.^1,2 Unlike Peutz-Jeghers syndrome, the diagnosis of LHS does not result from a germline mutation and carries no risk of gastrointestinal polyposis or internal malignancy.^3,4 The histopathology of a pigmented macule of LHS shows a normal number and morphology of melanocytes. Epidermal basement membrane pigmentation is common, with pigment-laden macrophages evident in the papillary dermis.³

RELATED ARTICLE: Asymptomatic Lower Lip Hyperpigmentation From Laugier-Hunziker Syndrome

The differential diagnosis of multiple lentigines is broad and includes Peutz-Jeghers syndrome; LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome; Carney complexes, including LAMB (lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) syndromes⁵; primary adrenocortical insufficiency (Addison disease); and idiopathic melanoplakia^.2 Peutz-Jeghers syndrome, an autosomal-dominant syndrome with mucocutaneous lentigines, has a similar clinical appearance to LHS; therefore, it is necessary to exclude this diagnosis due to its association with intestinal hamartomatous polyps and internal malignancies (Table).^3,6,7

Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and intestinal hamartomatous polyposis and is associated with internal malignancies of the colon, breast, pancreas, stomach, small intestines, ovaries, lung, and Sertoli cells in men.^6,7 Associated gastrointestinal tract malignancies in descending order of frequency are colon (39%), pancreatic (36%), gastric (29%), and small intestine (13%).¹ It is caused by a germ line mutation of the serine/threonine kinase 11 gene, STK11. Although the appearance and distribution of the mucocutaneous lentigines is similar to individuals with LHS, by contrast the lentiginosis in individuals with Peutz-Jeghers syndrome is present from birth or develops during infancy.⁶ Aggressive cancer screening guidelines aid in early detection and begin at 8 years of age with a baseline colonoscopy and esophagogastroduodenoscopy; future screening is dictated by the presence or absence of polyps. If no polyps are detected at 8 years of age, a colonoscopy and esophagogastroduodenoscopy are repeated at 18 years of age and then every 3 years until 50 years of age.⁸

In an adult patient, the diagnosis of LHS can be made clinically and a correct diagnosis prevents frequent and unpleasant gastrointestinal tract cancer screening examinations. Lampe et al² described a man with LHS who was incorrectly diagnosed with Peutz-Jeghers syndrome and experienced a colonic perforation as a complication of a screening colonoscopy. Their case report underscores the importance of making the correct diagnosis of LHS to avoid undertaking unnecessary aggressive cancer screening regimens.²

Although LHS is a benign condition that does not require treatment, Q-switched alexandrite or erbium:YAG laser therapy has been shown to improve the pigmentary findings associated with LHS.^9,10 It has been suggested that LHS should be renamed Laugier-Hunziker pigmentation² or mucocutaneous lentiginosis of Laugier and Hunziker¹ to differentiate LHS as simply a disorder of pigmentation rather than a potentially morbid genetic defect, as in Peutz-Jeghers syndrome.

To the Editor:

A 55-year-old man presented with hyperpigmented brown macules on the lips, hands, and fingertips of 6 years’ duration. The spots were persistent, asymptomatic, and had not changed in size. The patient denied a history of alopecia or dystrophic nails. He also denied a family history of similar skin findings. He had no personal history of cancer and a colonoscopy performed 5 years prior revealed no notable abnormalities. His medications included amlodipine and hydrocodone-acetaminophen. His mother died of “abdominal bleeding” at 74 years of age and his father died of a brain tumor at 64 years of age. Physical examination demonstrated numerous well-defined, dark brown macules of variable size distributed on the lower and upper mucosal lips (Figure 1A), buccal mucosa, hard palate, and gingiva, as well as the dorsal aspect of the fingers (Figure 1B) and volar aspect of the fingertips (Figure 1C).

A shave biopsy of a dark brown macule from the lower lip (Figure 2) was performed. Histopathologic examination revealed pigmentation of the basal layer of the epidermis with pigment-laden cells in the dermis immediately deep to the surface epithelium. Immunoperoxidase stains showed a normal number and distribution of melanocytes.

A diagnosis of Laugier-Hunziker syndrome (LHS) was made given the age of onset; distribution of pigmentation; and lack of pathologic colonoscopic findings, personal history of cancer, or gastrointestinal tract symptoms.

Benign hyperpigmentation of the lips and fingers has been reported.¹ The average age of onset of LHS is 52 years, and it typically is diagnosed in white adults.^1,2 In LHS, pigmentation is most commonly distributed on the lips, especially the lower lips and oral mucosa.² Pigmentation of the nails in the form of longitudinal melanonychia is present in approximately half of cases.^2,3 There also may be pigmentation of the neck; thorax; abdomen; and acral surfaces, especially the fingertips.^1-3 Rarely, pigmented macules can occur on the genitalia or sclera.^1,2 Unlike Peutz-Jeghers syndrome, the diagnosis of LHS does not result from a germline mutation and carries no risk of gastrointestinal polyposis or internal malignancy.^3,4 The histopathology of a pigmented macule of LHS shows a normal number and morphology of melanocytes. Epidermal basement membrane pigmentation is common, with pigment-laden macrophages evident in the papillary dermis.³

RELATED ARTICLE: Asymptomatic Lower Lip Hyperpigmentation From Laugier-Hunziker Syndrome

The differential diagnosis of multiple lentigines is broad and includes Peutz-Jeghers syndrome; LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome; Carney complexes, including LAMB (lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) syndromes⁵; primary adrenocortical insufficiency (Addison disease); and idiopathic melanoplakia^.2 Peutz-Jeghers syndrome, an autosomal-dominant syndrome with mucocutaneous lentigines, has a similar clinical appearance to LHS; therefore, it is necessary to exclude this diagnosis due to its association with intestinal hamartomatous polyps and internal malignancies (Table).^3,6,7

Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and intestinal hamartomatous polyposis and is associated with internal malignancies of the colon, breast, pancreas, stomach, small intestines, ovaries, lung, and Sertoli cells in men.^6,7 Associated gastrointestinal tract malignancies in descending order of frequency are colon (39%), pancreatic (36%), gastric (29%), and small intestine (13%).¹ It is caused by a germ line mutation of the serine/threonine kinase 11 gene, STK11. Although the appearance and distribution of the mucocutaneous lentigines is similar to individuals with LHS, by contrast the lentiginosis in individuals with Peutz-Jeghers syndrome is present from birth or develops during infancy.⁶ Aggressive cancer screening guidelines aid in early detection and begin at 8 years of age with a baseline colonoscopy and esophagogastroduodenoscopy; future screening is dictated by the presence or absence of polyps. If no polyps are detected at 8 years of age, a colonoscopy and esophagogastroduodenoscopy are repeated at 18 years of age and then every 3 years until 50 years of age.⁸

In an adult patient, the diagnosis of LHS can be made clinically and a correct diagnosis prevents frequent and unpleasant gastrointestinal tract cancer screening examinations. Lampe et al² described a man with LHS who was incorrectly diagnosed with Peutz-Jeghers syndrome and experienced a colonic perforation as a complication of a screening colonoscopy. Their case report underscores the importance of making the correct diagnosis of LHS to avoid undertaking unnecessary aggressive cancer screening regimens.²

Although LHS is a benign condition that does not require treatment, Q-switched alexandrite or erbium:YAG laser therapy has been shown to improve the pigmentary findings associated with LHS.^9,10 It has been suggested that LHS should be renamed Laugier-Hunziker pigmentation² or mucocutaneous lentiginosis of Laugier and Hunziker¹ to differentiate LHS as simply a disorder of pigmentation rather than a potentially morbid genetic defect, as in Peutz-Jeghers syndrome.

To the Editor:

A 55-year-old man presented with hyperpigmented brown macules on the lips, hands, and fingertips of 6 years’ duration. The spots were persistent, asymptomatic, and had not changed in size. The patient denied a history of alopecia or dystrophic nails. He also denied a family history of similar skin findings. He had no personal history of cancer and a colonoscopy performed 5 years prior revealed no notable abnormalities. His medications included amlodipine and hydrocodone-acetaminophen. His mother died of “abdominal bleeding” at 74 years of age and his father died of a brain tumor at 64 years of age. Physical examination demonstrated numerous well-defined, dark brown macules of variable size distributed on the lower and upper mucosal lips (Figure 1A), buccal mucosa, hard palate, and gingiva, as well as the dorsal aspect of the fingers (Figure 1B) and volar aspect of the fingertips (Figure 1C).

A shave biopsy of a dark brown macule from the lower lip (Figure 2) was performed. Histopathologic examination revealed pigmentation of the basal layer of the epidermis with pigment-laden cells in the dermis immediately deep to the surface epithelium. Immunoperoxidase stains showed a normal number and distribution of melanocytes.

A diagnosis of Laugier-Hunziker syndrome (LHS) was made given the age of onset; distribution of pigmentation; and lack of pathologic colonoscopic findings, personal history of cancer, or gastrointestinal tract symptoms.

Benign hyperpigmentation of the lips and fingers has been reported.¹ The average age of onset of LHS is 52 years, and it typically is diagnosed in white adults.^1,2 In LHS, pigmentation is most commonly distributed on the lips, especially the lower lips and oral mucosa.² Pigmentation of the nails in the form of longitudinal melanonychia is present in approximately half of cases.^2,3 There also may be pigmentation of the neck; thorax; abdomen; and acral surfaces, especially the fingertips.^1-3 Rarely, pigmented macules can occur on the genitalia or sclera.^1,2 Unlike Peutz-Jeghers syndrome, the diagnosis of LHS does not result from a germline mutation and carries no risk of gastrointestinal polyposis or internal malignancy.^3,4 The histopathology of a pigmented macule of LHS shows a normal number and morphology of melanocytes. Epidermal basement membrane pigmentation is common, with pigment-laden macrophages evident in the papillary dermis.³

RELATED ARTICLE: Asymptomatic Lower Lip Hyperpigmentation From Laugier-Hunziker Syndrome

The differential diagnosis of multiple lentigines is broad and includes Peutz-Jeghers syndrome; LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome; Carney complexes, including LAMB (lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) syndromes⁵; primary adrenocortical insufficiency (Addison disease); and idiopathic melanoplakia^.2 Peutz-Jeghers syndrome, an autosomal-dominant syndrome with mucocutaneous lentigines, has a similar clinical appearance to LHS; therefore, it is necessary to exclude this diagnosis due to its association with intestinal hamartomatous polyps and internal malignancies (Table).^3,6,7

Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and intestinal hamartomatous polyposis and is associated with internal malignancies of the colon, breast, pancreas, stomach, small intestines, ovaries, lung, and Sertoli cells in men.^6,7 Associated gastrointestinal tract malignancies in descending order of frequency are colon (39%), pancreatic (36%), gastric (29%), and small intestine (13%).¹ It is caused by a germ line mutation of the serine/threonine kinase 11 gene, STK11. Although the appearance and distribution of the mucocutaneous lentigines is similar to individuals with LHS, by contrast the lentiginosis in individuals with Peutz-Jeghers syndrome is present from birth or develops during infancy.⁶ Aggressive cancer screening guidelines aid in early detection and begin at 8 years of age with a baseline colonoscopy and esophagogastroduodenoscopy; future screening is dictated by the presence or absence of polyps. If no polyps are detected at 8 years of age, a colonoscopy and esophagogastroduodenoscopy are repeated at 18 years of age and then every 3 years until 50 years of age.⁸

In an adult patient, the diagnosis of LHS can be made clinically and a correct diagnosis prevents frequent and unpleasant gastrointestinal tract cancer screening examinations. Lampe et al² described a man with LHS who was incorrectly diagnosed with Peutz-Jeghers syndrome and experienced a colonic perforation as a complication of a screening colonoscopy. Their case report underscores the importance of making the correct diagnosis of LHS to avoid undertaking unnecessary aggressive cancer screening regimens.²

Although LHS is a benign condition that does not require treatment, Q-switched alexandrite or erbium:YAG laser therapy has been shown to improve the pigmentary findings associated with LHS.^9,10 It has been suggested that LHS should be renamed Laugier-Hunziker pigmentation² or mucocutaneous lentiginosis of Laugier and Hunziker¹ to differentiate LHS as simply a disorder of pigmentation rather than a potentially morbid genetic defect, as in Peutz-Jeghers syndrome.

Imipramine is a tricyclic medication uncommonly used to treat depression, anxiety, and other psychiatric illnesses. Although relatively rare, it has been associated with hyperpigmentation of the skin including slate gray discoloration of sun-exposed areas.

We present the case of a 63-year-old woman who had been taking imipramine for more than 20 years when she developed bluish gray discoloration on the face and neck. Histopathology of biopsy specimens showed numerous perivascular and interstitial brown globules in the dermis that were composed of melanin only, as evidenced by positive Fontana-Masson staining and negative Perls Prussian blue staining. A diagnosis of imipramine-induced hyperpigmentation was made based on histopathology and clinical history.

In addition to the case presentation, we provide a review of drugs that commonly cause hyperpigmentation as well as their associated histopathologic staining characteristics.

Case Report

A 63-year-old woman presented with blue-gray discoloration on the face and neck. She first noted the discoloration on the left side of the forehead 3 years prior; it then spread to the right side of the forehead, cheeks, and neck. She denied pruritus, pain, redness, and scaling of the involved areas; any recent changes in medications; or the use of any topical products on the affected areas. Her medical history was remarkable for hypertension, which was inconsistently controlled with lisinopril and hydrochlorothiazide, and depression, which had been managed with oral imipramine.

Physical examination disclosed blue-gray hyperpigmented patches with irregular borders on the bilateral forehead, temples, and periorbital skin (Figure 1). Reticulated brown patches were noted on the bilateral cheeks, and the neck displayed diffuse muddy brown patches with sparing of the submental areas.

Punch biopsies obtained from the lateral forehead showed an unremarkable epidermis with deposition of numerous golden brown granules in the upper and mid dermis and in perivascular macrophages (Figure 2). The pigmented granules showed positive staining with Fontana-Masson (Figure 3), and a Perls Prussian blue stain for hemosiderin was negative. Based on the clinical history, a diagnosis of imipramine-induced hyperpigmentation was made.

The patient revealed that she had taken imipramine for more than 20 years for depression as prescribed by her mental health professional. She had tried several other antidepressants but none were as effective as imipramine. Therefore, she was not willing to discontinue it despite the likelihood that the hyperpigmentation would persist and could worsen with continued use of the medication. Diligent photoprotection was advised. Additionally, she started taking lisinopril some time after the appearance of the hyperpigmentation presented and had not taken hydrochlorothiazide consistently for several years. Although these drugs are known to cause various cutaneous reactions, it was not considered likely in this case.

Comment

Drug-induced hyperpigmentation accounts for 10% to 20% of all cases of acquired hyperpigmentation.¹ Common causative drugs include amiodarone, antimalarials, minocycline, and rarely psychotropics including phenothiazines and tricyclic antidepressants such as imipramine.^1-4 Although amiodarone-induced hyperpigmentation is associated with lipofuscin in addition to melanin, most other medications, including imipramine, induce cutaneous effects through deposition of melanin and/or hemosiderin. A review of the histopathologic staining characteristics in pigment anomalies caused by these drugs is summarized in the Table.

Imipramine-induced hyperpigmentation presents as slate gray discrete macules and patches on sun-exposed skin that may appear anywhere from 2 to 22 years after initiating the medication.^1-4 Affected areas include the malar cheeks, temples, periorbital areas, hands, forearms, and seldom the iris and sclera.^2-4 Although the blue to slate gray coloring is classic, other colors have been described including brown, golden brown, and purple.²

Histopathology of imipramine-induced hyperpigmentation shows golden brown, round to oval granules in the superficial dermis and within dermal macrophages.^1,3 Generally, Fontana-Masson staining is positive for melanin and Perls Prussian blue staining is negative for iron.^1,2,4

Imipramine-induced hyperpigmentation likely results from photoexcitation of imipramine or one of its metabolites. These compounds activate tyrosinase, increasing melanogenesis and leading to formation of melanin-imipramine or melanin-metabolite complexes.^1-3 Complexes are deposited in the dermis and basal layer or are engulfed by dermal macrophages and darkened on sun exposure due to their high melanin content.¹ Other possible mechanisms of hyperpigmentation include nonspecific inflammation caused by the drug in the skin, hemosiderin deposition from vessel damage and subsequent erythrocyte extravasation, or deposition of newly formed pigments related to the drug.¹

Most patients report satisfactory resolution of imipramine-induced discoloration within 1 year of stopping imipramine or switching to a different antidepressant.^1,4 Patients who are unwilling to discontinue imipramine may achieve resolution with alexandrite or Q-switched ruby laser therapy.^1,4 Strict sun protective measures are necessary, both to prevent new deposition of melanin and to prevent darkening of existing pigment.

Despite the advent of new psychotropic medications, imipramine remains the antidepressant of choice for many patients. Although rare, it is important to be able to recognize imipramine-induced hyperpigmentation and to encourage patient-psychiatrist communication to determine an antidepressant regimen that avoids unnecessary cutaneous side effects.

Imipramine is a tricyclic medication uncommonly used to treat depression, anxiety, and other psychiatric illnesses. Although relatively rare, it has been associated with hyperpigmentation of the skin including slate gray discoloration of sun-exposed areas.

We present the case of a 63-year-old woman who had been taking imipramine for more than 20 years when she developed bluish gray discoloration on the face and neck. Histopathology of biopsy specimens showed numerous perivascular and interstitial brown globules in the dermis that were composed of melanin only, as evidenced by positive Fontana-Masson staining and negative Perls Prussian blue staining. A diagnosis of imipramine-induced hyperpigmentation was made based on histopathology and clinical history.

In addition to the case presentation, we provide a review of drugs that commonly cause hyperpigmentation as well as their associated histopathologic staining characteristics.

Case Report

A 63-year-old woman presented with blue-gray discoloration on the face and neck. She first noted the discoloration on the left side of the forehead 3 years prior; it then spread to the right side of the forehead, cheeks, and neck. She denied pruritus, pain, redness, and scaling of the involved areas; any recent changes in medications; or the use of any topical products on the affected areas. Her medical history was remarkable for hypertension, which was inconsistently controlled with lisinopril and hydrochlorothiazide, and depression, which had been managed with oral imipramine.

Physical examination disclosed blue-gray hyperpigmented patches with irregular borders on the bilateral forehead, temples, and periorbital skin (Figure 1). Reticulated brown patches were noted on the bilateral cheeks, and the neck displayed diffuse muddy brown patches with sparing of the submental areas.

Punch biopsies obtained from the lateral forehead showed an unremarkable epidermis with deposition of numerous golden brown granules in the upper and mid dermis and in perivascular macrophages (Figure 2). The pigmented granules showed positive staining with Fontana-Masson (Figure 3), and a Perls Prussian blue stain for hemosiderin was negative. Based on the clinical history, a diagnosis of imipramine-induced hyperpigmentation was made.

The patient revealed that she had taken imipramine for more than 20 years for depression as prescribed by her mental health professional. She had tried several other antidepressants but none were as effective as imipramine. Therefore, she was not willing to discontinue it despite the likelihood that the hyperpigmentation would persist and could worsen with continued use of the medication. Diligent photoprotection was advised. Additionally, she started taking lisinopril some time after the appearance of the hyperpigmentation presented and had not taken hydrochlorothiazide consistently for several years. Although these drugs are known to cause various cutaneous reactions, it was not considered likely in this case.

Comment

Drug-induced hyperpigmentation accounts for 10% to 20% of all cases of acquired hyperpigmentation.¹ Common causative drugs include amiodarone, antimalarials, minocycline, and rarely psychotropics including phenothiazines and tricyclic antidepressants such as imipramine.^1-4 Although amiodarone-induced hyperpigmentation is associated with lipofuscin in addition to melanin, most other medications, including imipramine, induce cutaneous effects through deposition of melanin and/or hemosiderin. A review of the histopathologic staining characteristics in pigment anomalies caused by these drugs is summarized in the Table.

Imipramine-induced hyperpigmentation presents as slate gray discrete macules and patches on sun-exposed skin that may appear anywhere from 2 to 22 years after initiating the medication.^1-4 Affected areas include the malar cheeks, temples, periorbital areas, hands, forearms, and seldom the iris and sclera.^2-4 Although the blue to slate gray coloring is classic, other colors have been described including brown, golden brown, and purple.²

Histopathology of imipramine-induced hyperpigmentation shows golden brown, round to oval granules in the superficial dermis and within dermal macrophages.^1,3 Generally, Fontana-Masson staining is positive for melanin and Perls Prussian blue staining is negative for iron.^1,2,4

Imipramine-induced hyperpigmentation likely results from photoexcitation of imipramine or one of its metabolites. These compounds activate tyrosinase, increasing melanogenesis and leading to formation of melanin-imipramine or melanin-metabolite complexes.^1-3 Complexes are deposited in the dermis and basal layer or are engulfed by dermal macrophages and darkened on sun exposure due to their high melanin content.¹ Other possible mechanisms of hyperpigmentation include nonspecific inflammation caused by the drug in the skin, hemosiderin deposition from vessel damage and subsequent erythrocyte extravasation, or deposition of newly formed pigments related to the drug.¹

Most patients report satisfactory resolution of imipramine-induced discoloration within 1 year of stopping imipramine or switching to a different antidepressant.^1,4 Patients who are unwilling to discontinue imipramine may achieve resolution with alexandrite or Q-switched ruby laser therapy.^1,4 Strict sun protective measures are necessary, both to prevent new deposition of melanin and to prevent darkening of existing pigment.

Despite the advent of new psychotropic medications, imipramine remains the antidepressant of choice for many patients. Although rare, it is important to be able to recognize imipramine-induced hyperpigmentation and to encourage patient-psychiatrist communication to determine an antidepressant regimen that avoids unnecessary cutaneous side effects.

Imipramine is a tricyclic medication uncommonly used to treat depression, anxiety, and other psychiatric illnesses. Although relatively rare, it has been associated with hyperpigmentation of the skin including slate gray discoloration of sun-exposed areas.

We present the case of a 63-year-old woman who had been taking imipramine for more than 20 years when she developed bluish gray discoloration on the face and neck. Histopathology of biopsy specimens showed numerous perivascular and interstitial brown globules in the dermis that were composed of melanin only, as evidenced by positive Fontana-Masson staining and negative Perls Prussian blue staining. A diagnosis of imipramine-induced hyperpigmentation was made based on histopathology and clinical history.

In addition to the case presentation, we provide a review of drugs that commonly cause hyperpigmentation as well as their associated histopathologic staining characteristics.

Case Report

A 63-year-old woman presented with blue-gray discoloration on the face and neck. She first noted the discoloration on the left side of the forehead 3 years prior; it then spread to the right side of the forehead, cheeks, and neck. She denied pruritus, pain, redness, and scaling of the involved areas; any recent changes in medications; or the use of any topical products on the affected areas. Her medical history was remarkable for hypertension, which was inconsistently controlled with lisinopril and hydrochlorothiazide, and depression, which had been managed with oral imipramine.

Physical examination disclosed blue-gray hyperpigmented patches with irregular borders on the bilateral forehead, temples, and periorbital skin (Figure 1). Reticulated brown patches were noted on the bilateral cheeks, and the neck displayed diffuse muddy brown patches with sparing of the submental areas.

Punch biopsies obtained from the lateral forehead showed an unremarkable epidermis with deposition of numerous golden brown granules in the upper and mid dermis and in perivascular macrophages (Figure 2). The pigmented granules showed positive staining with Fontana-Masson (Figure 3), and a Perls Prussian blue stain for hemosiderin was negative. Based on the clinical history, a diagnosis of imipramine-induced hyperpigmentation was made.

The patient revealed that she had taken imipramine for more than 20 years for depression as prescribed by her mental health professional. She had tried several other antidepressants but none were as effective as imipramine. Therefore, she was not willing to discontinue it despite the likelihood that the hyperpigmentation would persist and could worsen with continued use of the medication. Diligent photoprotection was advised. Additionally, she started taking lisinopril some time after the appearance of the hyperpigmentation presented and had not taken hydrochlorothiazide consistently for several years. Although these drugs are known to cause various cutaneous reactions, it was not considered likely in this case.

Comment

Drug-induced hyperpigmentation accounts for 10% to 20% of all cases of acquired hyperpigmentation.¹ Common causative drugs include amiodarone, antimalarials, minocycline, and rarely psychotropics including phenothiazines and tricyclic antidepressants such as imipramine.^1-4 Although amiodarone-induced hyperpigmentation is associated with lipofuscin in addition to melanin, most other medications, including imipramine, induce cutaneous effects through deposition of melanin and/or hemosiderin. A review of the histopathologic staining characteristics in pigment anomalies caused by these drugs is summarized in the Table.

Imipramine-induced hyperpigmentation presents as slate gray discrete macules and patches on sun-exposed skin that may appear anywhere from 2 to 22 years after initiating the medication.^1-4 Affected areas include the malar cheeks, temples, periorbital areas, hands, forearms, and seldom the iris and sclera.^2-4 Although the blue to slate gray coloring is classic, other colors have been described including brown, golden brown, and purple.²

Histopathology of imipramine-induced hyperpigmentation shows golden brown, round to oval granules in the superficial dermis and within dermal macrophages.^1,3 Generally, Fontana-Masson staining is positive for melanin and Perls Prussian blue staining is negative for iron.^1,2,4

Imipramine-induced hyperpigmentation likely results from photoexcitation of imipramine or one of its metabolites. These compounds activate tyrosinase, increasing melanogenesis and leading to formation of melanin-imipramine or melanin-metabolite complexes.^1-3 Complexes are deposited in the dermis and basal layer or are engulfed by dermal macrophages and darkened on sun exposure due to their high melanin content.¹ Other possible mechanisms of hyperpigmentation include nonspecific inflammation caused by the drug in the skin, hemosiderin deposition from vessel damage and subsequent erythrocyte extravasation, or deposition of newly formed pigments related to the drug.¹

Most patients report satisfactory resolution of imipramine-induced discoloration within 1 year of stopping imipramine or switching to a different antidepressant.^1,4 Patients who are unwilling to discontinue imipramine may achieve resolution with alexandrite or Q-switched ruby laser therapy.^1,4 Strict sun protective measures are necessary, both to prevent new deposition of melanin and to prevent darkening of existing pigment.

Despite the advent of new psychotropic medications, imipramine remains the antidepressant of choice for many patients. Although rare, it is important to be able to recognize imipramine-induced hyperpigmentation and to encourage patient-psychiatrist communication to determine an antidepressant regimen that avoids unnecessary cutaneous side effects.

SAN FRANCISCO – Dermatologists are often on the frontline when it comes to diagnosing polycystic ovary syndrome (PCOS), which is one reason they should be up to date and aware of the changing diagnostic criteria for the condition, according to Kanade Shinkai, MD.

About one-quarter of patients who are diagnosed with PCOS are seen first by a dermatologist. That’s because skin conditions may be more concerning than reproductive issues in young women.

“Sometimes, people don’t see [irregular menstruation] as a problem,” explained Dr. Shinkai of the department of dermatology at the University of California, San Francisco. “Maybe they’re young, or they’re not trying to get pregnant. But if their hair is falling out, they see that as a problem, or if they have bad acne, or they’re becoming hirsute, they see that as a problem. So, they present to a dermatologist.”

Early recognition of PCOS is important, because many women with the condition go on to develop diabetes, impaired glucose intolerance, hyperlipidemia, hypertension, fertility problems, and obesity.

SAN FRANCISCO – Dermatologists are often on the frontline when it comes to diagnosing polycystic ovary syndrome (PCOS), which is one reason they should be up to date and aware of the changing diagnostic criteria for the condition, according to Kanade Shinkai, MD.

About one-quarter of patients who are diagnosed with PCOS are seen first by a dermatologist. That’s because skin conditions may be more concerning than reproductive issues in young women.

“Sometimes, people don’t see [irregular menstruation] as a problem,” explained Dr. Shinkai of the department of dermatology at the University of California, San Francisco. “Maybe they’re young, or they’re not trying to get pregnant. But if their hair is falling out, they see that as a problem, or if they have bad acne, or they’re becoming hirsute, they see that as a problem. So, they present to a dermatologist.”

Early recognition of PCOS is important, because many women with the condition go on to develop diabetes, impaired glucose intolerance, hyperlipidemia, hypertension, fertility problems, and obesity.

SAN FRANCISCO – Dermatologists are often on the frontline when it comes to diagnosing polycystic ovary syndrome (PCOS), which is one reason they should be up to date and aware of the changing diagnostic criteria for the condition, according to Kanade Shinkai, MD.

About one-quarter of patients who are diagnosed with PCOS are seen first by a dermatologist. That’s because skin conditions may be more concerning than reproductive issues in young women.

“Sometimes, people don’t see [irregular menstruation] as a problem,” explained Dr. Shinkai of the department of dermatology at the University of California, San Francisco. “Maybe they’re young, or they’re not trying to get pregnant. But if their hair is falling out, they see that as a problem, or if they have bad acne, or they’re becoming hirsute, they see that as a problem. So, they present to a dermatologist.”

Early recognition of PCOS is important, because many women with the condition go on to develop diabetes, impaired glucose intolerance, hyperlipidemia, hypertension, fertility problems, and obesity.

The Diagnosis: Lichen Aureus

The clinicopathological findings were diagnostic of lichen aureus (LA). Microscopic examination revealed a relatively sparse, superficial, perivascular and interstitial lymphohistiocytic infiltrate with scattered siderophages in the upper dermis. Extravasation of red blood cells also was noted (Figure 1). An immunohistochemical stain for Melan-A highlighted a normal number and distribution of single melanocytes at the dermoepidermal junction with no evidence of pagetoid scatter. A Perls Prussian blue stain for iron demonstrated abundant hemosiderin in the dermis (Figure 2).

Pigmented purpuric dermatosis (PPD) describes a group of cutaneous lesions that are characterized by petechiae and pigmentary changes. These lesions most commonly present on the lower limbs; however, other sites have been reported.1 This group includes several major clinical forms such as Schamberg disease, LA, purpura annularis telangiectodes of Majocchi, eczematidlike purpura of Doucas and Kapetanakis, and lichenoid PPD of Gougerot and Blum. Lesions typically demonstrate a striking golden brown color clinically and by definition occur in the absence of platelet defects or vasculitis.¹

Factors implicated in the pathogenesis of pigmented purpura include gravitational dependency, venous stasis, infection, and drugs.² It is suggested that cellular immunity may play a role in the development of the disease based on the presence of CD4⁺ T lymphocytes in the infiltrate and the expression of HLA-DR by these lymphocytes and the keratinocytes.³ Lichen aureus differs in that it relates to increased intravascular pressure from an incompetent valve in an underlying perforating vein.⁴

Lichen aureus, also referred to as lichen purpuricus, is one major variant of PPD. The name reflects both the characteristic golden brown color and the histopathologic pattern of inflammation.¹ Lichen aureus usually presents as a unilateral, asymptomatic, confined single lesion located mainly on the leg,¹ though it can develop at other sites or as a localized group of lesions. Extensive lesions have been reported⁵ and cases with a segmental distribution have been described.⁶ In contrast, Schamberg disease demonstrates pinhead-sized reddish lesions giving the characteristic cayenne pepper pigmentation. These lesions coalesce to form thumbprint patches that progress proximally.¹ Majocchi purpura is annular and telangiectatic, while lichenoid purpura of Gougerot and Blum presents with flat-topped, polygonal, violaceous papules that turn brown over time.

Some authors have championed a role for dermoscopy in diagnosis of LA.⁷ By dermoscopy, LA demonstrates a diffuse copper background reflecting the lymphohistiocytic dermal infiltrate, red dots and globules representing the extravasated red blood cells and the dilated swollen vessels, and grey dots that reflect the hemosiderin present in the dermis.⁸

Histologically, LA demonstrates a superficial perivascular infiltrate composed mainly of CD4⁺ lymphocytes surrounding the superficial capillaries. Over time, red cell extravasation leads to the formation of hemosiderin-laden macrophages, which can be highlighted with Perls Prussian blue stain. A bandlike infiltrate with thin strands of collagen separating it from the epidermis also may be noted.⁹

An important consideration in the differential diagnosis of PPD is mycosis fungoides (MF). Mycosis fungoides is a cutaneous T-cell lymphoma that clinically presents as a single or multiple hypopigmented or hyperpigmented patches or as erythematous scaly lesions in the patch or plaque stage. These lesions eventually may evolve into tumor stage.¹⁰ Mycosis fungoides may mimic PPD clinically and/or histopathologically, and rarely PPD also may precede MF.¹¹ Involvement of the trunk, especially the lower abdomen and buttock region, favors a diagnosis of MF. Typically, histopathologic examination of MF demonstrates an epidermotropic lymphocytic infiltrate composed of atypical cerebriform lymphocytes overlying papillary dermal fibrosis. Although classic MF would be difficult to confuse with PPD, the atrophic lichenoid pattern of MF may show remarkable overlap with PPD.¹² Such cases require clinicopathologic correlation, immunophenotyping of the epidermotropic lymphocytes, and occasionally T-cell clonality studies.

Lichen aureus is a chronic persistent disease unless the underlying incompetent perforator vessel is ligated. Various treatments have been used for other forms of pigmented purpura including topical corticosteroids, topical tacrolimus, systemic vasodilators such as prostacyclin and pentoxifylline, and phototherapy.¹ Clinical follow-up is recommended for lesions that show some clinical or histopathological overlap with MF. Additional biopsies also may prove useful in establishing a definitive diagnosis in ambiguous cases.

The Diagnosis: Lichen Aureus

The clinicopathological findings were diagnostic of lichen aureus (LA). Microscopic examination revealed a relatively sparse, superficial, perivascular and interstitial lymphohistiocytic infiltrate with scattered siderophages in the upper dermis. Extravasation of red blood cells also was noted (Figure 1). An immunohistochemical stain for Melan-A highlighted a normal number and distribution of single melanocytes at the dermoepidermal junction with no evidence of pagetoid scatter. A Perls Prussian blue stain for iron demonstrated abundant hemosiderin in the dermis (Figure 2).

Pigmented purpuric dermatosis (PPD) describes a group of cutaneous lesions that are characterized by petechiae and pigmentary changes. These lesions most commonly present on the lower limbs; however, other sites have been reported.1 This group includes several major clinical forms such as Schamberg disease, LA, purpura annularis telangiectodes of Majocchi, eczematidlike purpura of Doucas and Kapetanakis, and lichenoid PPD of Gougerot and Blum. Lesions typically demonstrate a striking golden brown color clinically and by definition occur in the absence of platelet defects or vasculitis.¹

Factors implicated in the pathogenesis of pigmented purpura include gravitational dependency, venous stasis, infection, and drugs.² It is suggested that cellular immunity may play a role in the development of the disease based on the presence of CD4⁺ T lymphocytes in the infiltrate and the expression of HLA-DR by these lymphocytes and the keratinocytes.³ Lichen aureus differs in that it relates to increased intravascular pressure from an incompetent valve in an underlying perforating vein.⁴

Lichen aureus, also referred to as lichen purpuricus, is one major variant of PPD. The name reflects both the characteristic golden brown color and the histopathologic pattern of inflammation.¹ Lichen aureus usually presents as a unilateral, asymptomatic, confined single lesion located mainly on the leg,¹ though it can develop at other sites or as a localized group of lesions. Extensive lesions have been reported⁵ and cases with a segmental distribution have been described.⁶ In contrast, Schamberg disease demonstrates pinhead-sized reddish lesions giving the characteristic cayenne pepper pigmentation. These lesions coalesce to form thumbprint patches that progress proximally.¹ Majocchi purpura is annular and telangiectatic, while lichenoid purpura of Gougerot and Blum presents with flat-topped, polygonal, violaceous papules that turn brown over time.

Some authors have championed a role for dermoscopy in diagnosis of LA.⁷ By dermoscopy, LA demonstrates a diffuse copper background reflecting the lymphohistiocytic dermal infiltrate, red dots and globules representing the extravasated red blood cells and the dilated swollen vessels, and grey dots that reflect the hemosiderin present in the dermis.⁸

Histologically, LA demonstrates a superficial perivascular infiltrate composed mainly of CD4⁺ lymphocytes surrounding the superficial capillaries. Over time, red cell extravasation leads to the formation of hemosiderin-laden macrophages, which can be highlighted with Perls Prussian blue stain. A bandlike infiltrate with thin strands of collagen separating it from the epidermis also may be noted.⁹

An important consideration in the differential diagnosis of PPD is mycosis fungoides (MF). Mycosis fungoides is a cutaneous T-cell lymphoma that clinically presents as a single or multiple hypopigmented or hyperpigmented patches or as erythematous scaly lesions in the patch or plaque stage. These lesions eventually may evolve into tumor stage.¹⁰ Mycosis fungoides may mimic PPD clinically and/or histopathologically, and rarely PPD also may precede MF.¹¹ Involvement of the trunk, especially the lower abdomen and buttock region, favors a diagnosis of MF. Typically, histopathologic examination of MF demonstrates an epidermotropic lymphocytic infiltrate composed of atypical cerebriform lymphocytes overlying papillary dermal fibrosis. Although classic MF would be difficult to confuse with PPD, the atrophic lichenoid pattern of MF may show remarkable overlap with PPD.¹² Such cases require clinicopathologic correlation, immunophenotyping of the epidermotropic lymphocytes, and occasionally T-cell clonality studies.

Lichen aureus is a chronic persistent disease unless the underlying incompetent perforator vessel is ligated. Various treatments have been used for other forms of pigmented purpura including topical corticosteroids, topical tacrolimus, systemic vasodilators such as prostacyclin and pentoxifylline, and phototherapy.¹ Clinical follow-up is recommended for lesions that show some clinical or histopathological overlap with MF. Additional biopsies also may prove useful in establishing a definitive diagnosis in ambiguous cases.

The Diagnosis: Lichen Aureus

The clinicopathological findings were diagnostic of lichen aureus (LA). Microscopic examination revealed a relatively sparse, superficial, perivascular and interstitial lymphohistiocytic infiltrate with scattered siderophages in the upper dermis. Extravasation of red blood cells also was noted (Figure 1). An immunohistochemical stain for Melan-A highlighted a normal number and distribution of single melanocytes at the dermoepidermal junction with no evidence of pagetoid scatter. A Perls Prussian blue stain for iron demonstrated abundant hemosiderin in the dermis (Figure 2).

Pigmented purpuric dermatosis (PPD) describes a group of cutaneous lesions that are characterized by petechiae and pigmentary changes. These lesions most commonly present on the lower limbs; however, other sites have been reported.1 This group includes several major clinical forms such as Schamberg disease, LA, purpura annularis telangiectodes of Majocchi, eczematidlike purpura of Doucas and Kapetanakis, and lichenoid PPD of Gougerot and Blum. Lesions typically demonstrate a striking golden brown color clinically and by definition occur in the absence of platelet defects or vasculitis.¹

Factors implicated in the pathogenesis of pigmented purpura include gravitational dependency, venous stasis, infection, and drugs.² It is suggested that cellular immunity may play a role in the development of the disease based on the presence of CD4⁺ T lymphocytes in the infiltrate and the expression of HLA-DR by these lymphocytes and the keratinocytes.³ Lichen aureus differs in that it relates to increased intravascular pressure from an incompetent valve in an underlying perforating vein.⁴

Lichen aureus, also referred to as lichen purpuricus, is one major variant of PPD. The name reflects both the characteristic golden brown color and the histopathologic pattern of inflammation.¹ Lichen aureus usually presents as a unilateral, asymptomatic, confined single lesion located mainly on the leg,¹ though it can develop at other sites or as a localized group of lesions. Extensive lesions have been reported⁵ and cases with a segmental distribution have been described.⁶ In contrast, Schamberg disease demonstrates pinhead-sized reddish lesions giving the characteristic cayenne pepper pigmentation. These lesions coalesce to form thumbprint patches that progress proximally.¹ Majocchi purpura is annular and telangiectatic, while lichenoid purpura of Gougerot and Blum presents with flat-topped, polygonal, violaceous papules that turn brown over time.

Some authors have championed a role for dermoscopy in diagnosis of LA.⁷ By dermoscopy, LA demonstrates a diffuse copper background reflecting the lymphohistiocytic dermal infiltrate, red dots and globules representing the extravasated red blood cells and the dilated swollen vessels, and grey dots that reflect the hemosiderin present in the dermis.⁸

Histologically, LA demonstrates a superficial perivascular infiltrate composed mainly of CD4⁺ lymphocytes surrounding the superficial capillaries. Over time, red cell extravasation leads to the formation of hemosiderin-laden macrophages, which can be highlighted with Perls Prussian blue stain. A bandlike infiltrate with thin strands of collagen separating it from the epidermis also may be noted.⁹

An important consideration in the differential diagnosis of PPD is mycosis fungoides (MF). Mycosis fungoides is a cutaneous T-cell lymphoma that clinically presents as a single or multiple hypopigmented or hyperpigmented patches or as erythematous scaly lesions in the patch or plaque stage. These lesions eventually may evolve into tumor stage.¹⁰ Mycosis fungoides may mimic PPD clinically and/or histopathologically, and rarely PPD also may precede MF.¹¹ Involvement of the trunk, especially the lower abdomen and buttock region, favors a diagnosis of MF. Typically, histopathologic examination of MF demonstrates an epidermotropic lymphocytic infiltrate composed of atypical cerebriform lymphocytes overlying papillary dermal fibrosis. Although classic MF would be difficult to confuse with PPD, the atrophic lichenoid pattern of MF may show remarkable overlap with PPD.¹² Such cases require clinicopathologic correlation, immunophenotyping of the epidermotropic lymphocytes, and occasionally T-cell clonality studies.

Lichen aureus is a chronic persistent disease unless the underlying incompetent perforator vessel is ligated. Various treatments have been used for other forms of pigmented purpura including topical corticosteroids, topical tacrolimus, systemic vasodilators such as prostacyclin and pentoxifylline, and phototherapy.¹ Clinical follow-up is recommended for lesions that show some clinical or histopathological overlap with MF. Additional biopsies also may prove useful in establishing a definitive diagnosis in ambiguous cases.

The Diagnosis: Incontinentia Pigmenti

The infant's mother was noted to have diffuse hypopigmented patches over the trunk, arms, and legs (present since adolescence) with whorled cicatricial alopecia of the vertex scalp and peg-shaped teeth (Figure). Together, these findings suggested incontinentia pigmenti (IP), which the mother revealed she had been diagnosed with in childhood. The infant's characteristic lesions in the setting of her mother's diagnosed genodermatosis confirmed the diagnosis of IP.

Incontinentia pigmenti is an X-linked dominant disorder that presents with many classic dermatologic, dental, neurologic, and ophthalmologic findings. The causative mutation occurs in IKBKG/NEMO (inhibitor of κ polypeptide gene enhancer in B-cells, kinase γ/nuclear factor-κB essential modulator) gene on Xq28, disabling the resultant protein that normally protects cells from tumor necrosis factor family-induced apoptosis.¹ Incontinentia pigmenti usually is lethal in males and causes an unbalanced X-inactivation in surviving female IP patients. Occurring at a rate of 1.2 per 100,000 births,² IP typically presents in female infants with skin lesions patterned along Blaschko lines that evolve in 4 stages over a lifetime.³ Stage I, presenting in the neonatal period, manifests as vesiculobullous eruptions on the limbs and scalp. Stages II to IV vary in duration from months to years and are comprised of a verrucous stage, a hyperpigmented stage, and a hypopigmented stage, respectively.³ All stages of IP can overlap and coexist. 

The vesiculobullous findings in infants with IP may be mistakenly attributed to other diseases with prominent vesicular or bullous components including herpes simplex virus, epidermolysis bullosa, and infantile acropustulosis. With neonatal herpes simplex virus infection, vesicular skin or mucocutaneous lesions occur 9 to 11 days after birth and can be confirmed by specimen culture or qualitative polymerase chain reaction, while stage I of IP appears within the first 6 to 8 weeks of life and can be present at birth.⁴ The hallmark of epidermolysis bullosa, caused by mutations in keratins 5 and 14, is blistering erosions of the skin in response to frictional stress,¹ thus these lesions do not follow Blaschko lines. Infantile acropustulosis, a nonheritable vesiculopustular eruption of the hands and feet, rarely occurs in the immediate newborn period; it most often appears in the 3- to 6-month age range with recurrent eruptions at 3- to 4-week intervals.⁵ Focal dermal hypoplasia is another X-linked dominant disorder with blaschkolinear findings at birth that presents with pink or red, angular, atrophic macules, in contrast to the bullous lesions of IP.⁶

Incontinentia pigmenti may encompass a wide range of systemic symptoms in addition to the classic dermatologic findings. Notably, central nervous system defects are concurrent in up to 40% of IP cases, with seizures, mental retardation, and spastic paresis being the most common sequelae.⁷ Teeth defects, seen in 35% of patients, include delayed primary dentition and peg-shaped teeth. Many patients will experience ophthalmologic defects including vision problems (16%) and retinopathy (15%).⁷

The cutaneous eruptions of IP may be treated with topical corticosteroids or topical tacrolimus, and vesicles should be left intact and monitored for signs of infection.^8,9 Seizures, if present, should be treated with anticonvulsants, and regular neuropsychiatric monitoring and physical rehabilitation may be warranted. Patients should be regularly monitored for retinopathy beginning at the time of diagnosis. Retinal fibrovascular proliferation is treated with xenon laser photocoagulation to reduce the high risk for retinal detachment in this population.^10,11 Older and younger at-risk relatives must be evaluated by genetic testing or thorough physical examination to clarify their disease status and determine the need for additional genetic counseling.

The Diagnosis: Incontinentia Pigmenti

The infant's mother was noted to have diffuse hypopigmented patches over the trunk, arms, and legs (present since adolescence) with whorled cicatricial alopecia of the vertex scalp and peg-shaped teeth (Figure). Together, these findings suggested incontinentia pigmenti (IP), which the mother revealed she had been diagnosed with in childhood. The infant's characteristic lesions in the setting of her mother's diagnosed genodermatosis confirmed the diagnosis of IP.

Incontinentia pigmenti is an X-linked dominant disorder that presents with many classic dermatologic, dental, neurologic, and ophthalmologic findings. The causative mutation occurs in IKBKG/NEMO (inhibitor of κ polypeptide gene enhancer in B-cells, kinase γ/nuclear factor-κB essential modulator) gene on Xq28, disabling the resultant protein that normally protects cells from tumor necrosis factor family-induced apoptosis.¹ Incontinentia pigmenti usually is lethal in males and causes an unbalanced X-inactivation in surviving female IP patients. Occurring at a rate of 1.2 per 100,000 births,² IP typically presents in female infants with skin lesions patterned along Blaschko lines that evolve in 4 stages over a lifetime.³ Stage I, presenting in the neonatal period, manifests as vesiculobullous eruptions on the limbs and scalp. Stages II to IV vary in duration from months to years and are comprised of a verrucous stage, a hyperpigmented stage, and a hypopigmented stage, respectively.³ All stages of IP can overlap and coexist. 

The vesiculobullous findings in infants with IP may be mistakenly attributed to other diseases with prominent vesicular or bullous components including herpes simplex virus, epidermolysis bullosa, and infantile acropustulosis. With neonatal herpes simplex virus infection, vesicular skin or mucocutaneous lesions occur 9 to 11 days after birth and can be confirmed by specimen culture or qualitative polymerase chain reaction, while stage I of IP appears within the first 6 to 8 weeks of life and can be present at birth.⁴ The hallmark of epidermolysis bullosa, caused by mutations in keratins 5 and 14, is blistering erosions of the skin in response to frictional stress,¹ thus these lesions do not follow Blaschko lines. Infantile acropustulosis, a nonheritable vesiculopustular eruption of the hands and feet, rarely occurs in the immediate newborn period; it most often appears in the 3- to 6-month age range with recurrent eruptions at 3- to 4-week intervals.⁵ Focal dermal hypoplasia is another X-linked dominant disorder with blaschkolinear findings at birth that presents with pink or red, angular, atrophic macules, in contrast to the bullous lesions of IP.⁶

Incontinentia pigmenti may encompass a wide range of systemic symptoms in addition to the classic dermatologic findings. Notably, central nervous system defects are concurrent in up to 40% of IP cases, with seizures, mental retardation, and spastic paresis being the most common sequelae.⁷ Teeth defects, seen in 35% of patients, include delayed primary dentition and peg-shaped teeth. Many patients will experience ophthalmologic defects including vision problems (16%) and retinopathy (15%).⁷

The cutaneous eruptions of IP may be treated with topical corticosteroids or topical tacrolimus, and vesicles should be left intact and monitored for signs of infection.^8,9 Seizures, if present, should be treated with anticonvulsants, and regular neuropsychiatric monitoring and physical rehabilitation may be warranted. Patients should be regularly monitored for retinopathy beginning at the time of diagnosis. Retinal fibrovascular proliferation is treated with xenon laser photocoagulation to reduce the high risk for retinal detachment in this population.^10,11 Older and younger at-risk relatives must be evaluated by genetic testing or thorough physical examination to clarify their disease status and determine the need for additional genetic counseling.

The Diagnosis: Incontinentia Pigmenti

The infant's mother was noted to have diffuse hypopigmented patches over the trunk, arms, and legs (present since adolescence) with whorled cicatricial alopecia of the vertex scalp and peg-shaped teeth (Figure). Together, these findings suggested incontinentia pigmenti (IP), which the mother revealed she had been diagnosed with in childhood. The infant's characteristic lesions in the setting of her mother's diagnosed genodermatosis confirmed the diagnosis of IP.

Incontinentia pigmenti is an X-linked dominant disorder that presents with many classic dermatologic, dental, neurologic, and ophthalmologic findings. The causative mutation occurs in IKBKG/NEMO (inhibitor of κ polypeptide gene enhancer in B-cells, kinase γ/nuclear factor-κB essential modulator) gene on Xq28, disabling the resultant protein that normally protects cells from tumor necrosis factor family-induced apoptosis.¹ Incontinentia pigmenti usually is lethal in males and causes an unbalanced X-inactivation in surviving female IP patients. Occurring at a rate of 1.2 per 100,000 births,² IP typically presents in female infants with skin lesions patterned along Blaschko lines that evolve in 4 stages over a lifetime.³ Stage I, presenting in the neonatal period, manifests as vesiculobullous eruptions on the limbs and scalp. Stages II to IV vary in duration from months to years and are comprised of a verrucous stage, a hyperpigmented stage, and a hypopigmented stage, respectively.³ All stages of IP can overlap and coexist. 

The vesiculobullous findings in infants with IP may be mistakenly attributed to other diseases with prominent vesicular or bullous components including herpes simplex virus, epidermolysis bullosa, and infantile acropustulosis. With neonatal herpes simplex virus infection, vesicular skin or mucocutaneous lesions occur 9 to 11 days after birth and can be confirmed by specimen culture or qualitative polymerase chain reaction, while stage I of IP appears within the first 6 to 8 weeks of life and can be present at birth.⁴ The hallmark of epidermolysis bullosa, caused by mutations in keratins 5 and 14, is blistering erosions of the skin in response to frictional stress,¹ thus these lesions do not follow Blaschko lines. Infantile acropustulosis, a nonheritable vesiculopustular eruption of the hands and feet, rarely occurs in the immediate newborn period; it most often appears in the 3- to 6-month age range with recurrent eruptions at 3- to 4-week intervals.⁵ Focal dermal hypoplasia is another X-linked dominant disorder with blaschkolinear findings at birth that presents with pink or red, angular, atrophic macules, in contrast to the bullous lesions of IP.⁶

Incontinentia pigmenti may encompass a wide range of systemic symptoms in addition to the classic dermatologic findings. Notably, central nervous system defects are concurrent in up to 40% of IP cases, with seizures, mental retardation, and spastic paresis being the most common sequelae.⁷ Teeth defects, seen in 35% of patients, include delayed primary dentition and peg-shaped teeth. Many patients will experience ophthalmologic defects including vision problems (16%) and retinopathy (15%).⁷

The cutaneous eruptions of IP may be treated with topical corticosteroids or topical tacrolimus, and vesicles should be left intact and monitored for signs of infection.^8,9 Seizures, if present, should be treated with anticonvulsants, and regular neuropsychiatric monitoring and physical rehabilitation may be warranted. Patients should be regularly monitored for retinopathy beginning at the time of diagnosis. Retinal fibrovascular proliferation is treated with xenon laser photocoagulation to reduce the high risk for retinal detachment in this population.^10,11 Older and younger at-risk relatives must be evaluated by genetic testing or thorough physical examination to clarify their disease status and determine the need for additional genetic counseling.

To the Editor:

Erythema ab igne (EAI) is a reticular erythematous hyperpigmentation of skin repeatedly exposed to moderate heat.¹ It usually is asymptomatic, though some patients report itching or burning at the site.² Historically caused by exposure to coal stoves or open fires, EAI has become increasingly common among individuals using space heaters, heating pads, or laptop computers near bare skin.^2,3 Although EAI itself is benign and usually resolves with the removal of the exposure, it remains of clinical importance because of its association with underlying chronic disease, as chronic pain often is managed with frequent heating pad or hot water bottle use.² Additionally, accurate diagnosis is important given the future risk for malignancy, as chronic changes of EAI have been reported to lead to squamous cell carcinoma or rarely Merkel cell carcinoma.² Erythema ab igne is not traditionally associated with the formation of bullae; however, we present a case of bullous EAI that we believe highlights the importance of including this condition in the differential diagnosis of bullous disorders.

A 55-year-old man was admitted for presumed cellulitis of the bilateral legs. The patient had developed hyperpigmented discoloration of the medial surface of both legs with subsequent formation of tense bullae over the last 2 months. The dermatology department was consulted, as there was concern for bullous pemphigoid. The patient’s medical history was notable for hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, and hepatitis C virus with cirrhosis. The patient denied pruritus, pain, or known exposure of the legs to potential irritants prior to developing the lesions; however, with additional questioning he did report frequently sitting in front of a space heater with bare legs. Physical examination revealed multiple areas of reticulated erythematous hyperpigmentation with several overlying bullae (Figure 1). Many of the bullae were unroofed with full-thickness ulceration. Biopsies were taken for hematoxylin and eosin staining (Figure 2) and direct immunofluorescence.

Basic hematologic and metabolic laboratory test results as well as blood cultures were negative. Wound culture was positive for methicillin-resistant Staphylococcus aureus. Histologic examination showed interface dermatitis with subepidermal vesicle (Figure 2). Scattered necrotic keratinocytes were present in the adjacent epidermis, and focal subtle vacuolar alteration of the dermoepidermal junction was seen (Figure 3). Sparse perivascular mononuclear cells and scattered melanophages were present in the dermis. Direct immunofluorescence showed no diagnostic immunopathologic abnormality. Focal weak nonspecific vascular positivity for IgG and C3 was seen, but IgA and IgM were negative. Although not specific, these changes were compatible with EAI in the clinical context provided. The diagnosis of bullous EAI with superimposed staphylococcal infection was made.

Although rare, there have been reports of a bullous variant of EAI. Flanagan et al⁴ described 3 cases of bullous EAI with histopathology similar to our case. All 3 biopsies showed subepidermal separation with a mild perivascular dermal lymphocytic infiltrate. Direct immunofluorescence was negative in 2 cases but showed nonspecific weak patchy deposition of IgM along the dermoepidermal junction.⁴ Although our case was negative for IgM, there was a similar weak nonspecific distribution of IgG. Kokturk et al⁵ described a case of bullous EAI in a man with repeated exposure to a space heater. The lesions showed subepidermal separation of the epidermis; increased elastic fibers; dilated dermal capillaries; melanophages in the upper dermis; and a mild, superficial, perivascular-lymphocytic infiltrate. Direct immunofluorescence showed no immune deposits.⁵ Several earlier cases of bullae associated with EAI have been reported in the literature but were thought to be bullous lichen planus superimposed on EAI.⁶ Our case, which exhibited similar historical, physical, and histopathologic findings, strengthens the argument for a defined bullous variant of EAI.

To the Editor:

Erythema ab igne (EAI) is a reticular erythematous hyperpigmentation of skin repeatedly exposed to moderate heat.¹ It usually is asymptomatic, though some patients report itching or burning at the site.² Historically caused by exposure to coal stoves or open fires, EAI has become increasingly common among individuals using space heaters, heating pads, or laptop computers near bare skin.^2,3 Although EAI itself is benign and usually resolves with the removal of the exposure, it remains of clinical importance because of its association with underlying chronic disease, as chronic pain often is managed with frequent heating pad or hot water bottle use.² Additionally, accurate diagnosis is important given the future risk for malignancy, as chronic changes of EAI have been reported to lead to squamous cell carcinoma or rarely Merkel cell carcinoma.² Erythema ab igne is not traditionally associated with the formation of bullae; however, we present a case of bullous EAI that we believe highlights the importance of including this condition in the differential diagnosis of bullous disorders.

A 55-year-old man was admitted for presumed cellulitis of the bilateral legs. The patient had developed hyperpigmented discoloration of the medial surface of both legs with subsequent formation of tense bullae over the last 2 months. The dermatology department was consulted, as there was concern for bullous pemphigoid. The patient’s medical history was notable for hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, and hepatitis C virus with cirrhosis. The patient denied pruritus, pain, or known exposure of the legs to potential irritants prior to developing the lesions; however, with additional questioning he did report frequently sitting in front of a space heater with bare legs. Physical examination revealed multiple areas of reticulated erythematous hyperpigmentation with several overlying bullae (Figure 1). Many of the bullae were unroofed with full-thickness ulceration. Biopsies were taken for hematoxylin and eosin staining (Figure 2) and direct immunofluorescence.

Basic hematologic and metabolic laboratory test results as well as blood cultures were negative. Wound culture was positive for methicillin-resistant Staphylococcus aureus. Histologic examination showed interface dermatitis with subepidermal vesicle (Figure 2). Scattered necrotic keratinocytes were present in the adjacent epidermis, and focal subtle vacuolar alteration of the dermoepidermal junction was seen (Figure 3). Sparse perivascular mononuclear cells and scattered melanophages were present in the dermis. Direct immunofluorescence showed no diagnostic immunopathologic abnormality. Focal weak nonspecific vascular positivity for IgG and C3 was seen, but IgA and IgM were negative. Although not specific, these changes were compatible with EAI in the clinical context provided. The diagnosis of bullous EAI with superimposed staphylococcal infection was made.

Although rare, there have been reports of a bullous variant of EAI. Flanagan et al⁴ described 3 cases of bullous EAI with histopathology similar to our case. All 3 biopsies showed subepidermal separation with a mild perivascular dermal lymphocytic infiltrate. Direct immunofluorescence was negative in 2 cases but showed nonspecific weak patchy deposition of IgM along the dermoepidermal junction.⁴ Although our case was negative for IgM, there was a similar weak nonspecific distribution of IgG. Kokturk et al⁵ described a case of bullous EAI in a man with repeated exposure to a space heater. The lesions showed subepidermal separation of the epidermis; increased elastic fibers; dilated dermal capillaries; melanophages in the upper dermis; and a mild, superficial, perivascular-lymphocytic infiltrate. Direct immunofluorescence showed no immune deposits.⁵ Several earlier cases of bullae associated with EAI have been reported in the literature but were thought to be bullous lichen planus superimposed on EAI.⁶ Our case, which exhibited similar historical, physical, and histopathologic findings, strengthens the argument for a defined bullous variant of EAI.

To the Editor:

Erythema ab igne (EAI) is a reticular erythematous hyperpigmentation of skin repeatedly exposed to moderate heat.¹ It usually is asymptomatic, though some patients report itching or burning at the site.² Historically caused by exposure to coal stoves or open fires, EAI has become increasingly common among individuals using space heaters, heating pads, or laptop computers near bare skin.^2,3 Although EAI itself is benign and usually resolves with the removal of the exposure, it remains of clinical importance because of its association with underlying chronic disease, as chronic pain often is managed with frequent heating pad or hot water bottle use.² Additionally, accurate diagnosis is important given the future risk for malignancy, as chronic changes of EAI have been reported to lead to squamous cell carcinoma or rarely Merkel cell carcinoma.² Erythema ab igne is not traditionally associated with the formation of bullae; however, we present a case of bullous EAI that we believe highlights the importance of including this condition in the differential diagnosis of bullous disorders.

A 55-year-old man was admitted for presumed cellulitis of the bilateral legs. The patient had developed hyperpigmented discoloration of the medial surface of both legs with subsequent formation of tense bullae over the last 2 months. The dermatology department was consulted, as there was concern for bullous pemphigoid. The patient’s medical history was notable for hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, and hepatitis C virus with cirrhosis. The patient denied pruritus, pain, or known exposure of the legs to potential irritants prior to developing the lesions; however, with additional questioning he did report frequently sitting in front of a space heater with bare legs. Physical examination revealed multiple areas of reticulated erythematous hyperpigmentation with several overlying bullae (Figure 1). Many of the bullae were unroofed with full-thickness ulceration. Biopsies were taken for hematoxylin and eosin staining (Figure 2) and direct immunofluorescence.

Basic hematologic and metabolic laboratory test results as well as blood cultures were negative. Wound culture was positive for methicillin-resistant Staphylococcus aureus. Histologic examination showed interface dermatitis with subepidermal vesicle (Figure 2). Scattered necrotic keratinocytes were present in the adjacent epidermis, and focal subtle vacuolar alteration of the dermoepidermal junction was seen (Figure 3). Sparse perivascular mononuclear cells and scattered melanophages were present in the dermis. Direct immunofluorescence showed no diagnostic immunopathologic abnormality. Focal weak nonspecific vascular positivity for IgG and C3 was seen, but IgA and IgM were negative. Although not specific, these changes were compatible with EAI in the clinical context provided. The diagnosis of bullous EAI with superimposed staphylococcal infection was made.

Although rare, there have been reports of a bullous variant of EAI. Flanagan et al⁴ described 3 cases of bullous EAI with histopathology similar to our case. All 3 biopsies showed subepidermal separation with a mild perivascular dermal lymphocytic infiltrate. Direct immunofluorescence was negative in 2 cases but showed nonspecific weak patchy deposition of IgM along the dermoepidermal junction.⁴ Although our case was negative for IgM, there was a similar weak nonspecific distribution of IgG. Kokturk et al⁵ described a case of bullous EAI in a man with repeated exposure to a space heater. The lesions showed subepidermal separation of the epidermis; increased elastic fibers; dilated dermal capillaries; melanophages in the upper dermis; and a mild, superficial, perivascular-lymphocytic infiltrate. Direct immunofluorescence showed no immune deposits.⁵ Several earlier cases of bullae associated with EAI have been reported in the literature but were thought to be bullous lichen planus superimposed on EAI.⁶ Our case, which exhibited similar historical, physical, and histopathologic findings, strengthens the argument for a defined bullous variant of EAI.