- Email: [email protected]
Scleroderma-like changes in cutaneous eruption of rhabdomyolysis
J AM ACAD DERMATOL
Letters 177
VOLUME 53, NUMBER 1
Scleroderma-like changes in cutaneous eruption of rhabdomyolysis To the Editor: A 66-year-old man presented with peculiar skin lesions on the right side of his face, chest wall, and scrotum of 2 days’ duration. He had been a chronic alcohol abuser for the past 40 years. Three days before admission, he went mountain hiking, had an alcoholic binge, and slept in a right lateral decubitus position. The next morning, he awoke to find the skin lesions and admitted himself to the emergency department. He had been taking diltiazem and nitrate for stable angina. Physical examination revealed well-demarcated, erythematous, swollen plaques on the right side of the cheek, neck, chest wall, arm, and scrotum. Bullous eruptions with local heating sensation and tenderness were noted on the right anterior chest wall (Fig 1, A). Histopathologic examination of the specimen from a bullous lesion showed severe eosinophilic necrosis of the epidermis with intraepidermal blister (Fig 1, B). Dermal eccrine ducts and glands showed varying degrees of necrosis (Fig 1, C ). There were mild inflammatory infiltrates consisting of neutrophils around the vessels in the dermis. He was diagnosed as having rhabdomyolysis on the basis of laboratory findings of elevated serum myogenic enzymes (creatine kinase, 970 U/L; lactate dehydrogenase, 277 U/L) and myoglobinuria. Tissue hypoxia and pressure were considered to be causative factors for his skin eruption. Treatment with topical and systemic corticosteroids resulted in clearing most of the skin lesions except those on the anterior chest wall. The bullous lesion on the chest changed into stony hard sclerodermoid plaques during the seventh week of treatment (Fig 2, A). A skin biopsy specimen showed thickened, sclerotic collagen fibers in the dermis (Fig 2, B). The laboratory findings for rheumatic factor, anti-centromere antibody, anti-Scl70 antibody, and antinuclear antibody were negative or within normal range. The patient has responded favorably to intralesional injection of corticosteroid, although the sclerodermoid plaques have persisted. Rhabdomyolysis usually occurs because of massive damage to the skeletal muscles, but muscle compression attributable to prolonged positioning, as was the case in our patient, may lead to this syndrome.1,2 Cutaneous eruptions in nontraumatic rhabdomyolysis are infrequent, but have been described as well-demarcated erythema, violaceous plaques and petechiae, bulla and ulcers, typically occurring in the pressure areas several hours or days after application of pressure.1,3 These skin eruptions can be important symptoms of nontraumatic rhabdomolysis, especially in mild cases, that are usually
Fig 1. A, Well-demarcated, erythematous, swollen plaques and bullae over right anterior chest wall. B, Eosinophilic necrosis of epidermis with intraepideramal blister. C, Dermal eccrine ducts and glands showing varying degrees of necrosis. (B and C, Hematoxylin-eosin stain; original magnifications: B, 3200; C, 3100.)
Fig 2. A, Scleroderma-like plaque after 7 weeks. B, Thickened, sclerotic collagen fibers in dermis. (Hematoxylin-eosin stain; original magnification 3100.)
asymptomatic (no muscle pain and swelling).3 The pathologic findings were compatible with hypoxic skin injury showing necrosis of the epidermis and eccrine glands, consistent with the suggested pathogenesis of skin lesions of rhabdomyolysis.1 Prolonged right decubitus positioning after alcohol abuse might be the course of tissue hypoxia in our patient.4 It is noteworthy that the bullous lesions later changed into scleroderma-like indurations. This scleroderma-like change is different from bullous morphea in which subepidermal bullae and lymphatic dilatations are the characteristic histologic findings.5 We believe that the scleroderma-like changes were induced by previous tissue hypoxia. Hypoxic modulation of collagen metabolism appears related to fibrosis of connective tissue after injury and scleroderma.6 Recently, it was reported that tissue hypoxia may induce extracellular
178 Letters
J AM ACAD DERMATOL JULY 2005
matrix overproduction by fibroblasts.7 Altogether, we believe that hypoxic events in skin may induce bullae via direct epidermal necrosis, which can evolve into sclerodermoid induration via collagen remodeling. Sung Kwon Kim, MD You Chan Kim, MD Bang Jin Lee, MD Hee Young Kang, MD Department of Dermatology Ajou University School of Medicine Suwon, Korea Correspondence to: Hee Young Kang, MD 5 Wonchon-dong, Yeongtong-ku Suwon, 443-721, Korea (South)
Fig 1. Multiple indurated, slightly erythematous plaques with nondiscrete borders located bilaterally on the dorsal surfaces of the hands and fingers. Note the discretely elevated dusky-red plaques and papules between the first and second fingers on the dorsal surface of the left hand.
E-mail: [email protected] REFERENCES 1. Szewczyk D, Ovadia P, Abdullah F, Rabinovici R. Pressure-induced rhabdomyolysis and acute renal failure. J Trauma 1998;44:384-8. 2. Mathes DD, Assimos DG, Donofrio PD. Rhabdomyolysis and myonecrosis in a patient in the lateral decubitus position. Anesthesiology 1996;84:727-9. 3. Miyamoto T, Ikehara A, Kobayashi T, Kitada S, Hagari Y, Mihara M. Cutaneous eruptions in coma patients with nontraumatic rhabdomyolysis. Dermatology 2001;203:233-7. 4. Singh S, Sharma A, Sharma S, Sud A, Wanchu A, Bambery P. Acute alcoholic myopathy, rhabdomyolysis and acute renal failure: a case report. Neurol India 2000;48:84-5. 5. Daoud MS, Su WP, Leiferman KM, Perniciaro C. Bullous morphea: clinical, pathologic, and immunopathologic evaluation of thirteen cases. J Am Acad Dermatol 1994;30:937-43. 6. Silverstein JL, Steen VD, Medsger TA Jr, Falanga V. Cutaneous hypoxia in patients with systemic sclerosis (scleroderma). Arch Dermatol 1988;124:1379-82. 7. Tamby MC, Chanseaud Y, Guillevin L, Mouthon L. New insights into the pathogenesis of systemic sclerosis. Autoimmun Rev 2003;2:152-7.
Fig 2. Erosive lesions on the lower lip mucosa.
doi:10.1016/j.jaad.2005.01.096
Neutrophilic fixed drug eruption caused by naproxen: A real entity or a stage in the histopathologic evolution of the disease?
Fig 3. Epidermal spongiosis, very prominent neutrophilic exocytosis, intraepidermal micropustule formation, upper dermal slight edema, and inflammatory infiltration with perivascular neutrophils and scattered leucocytoclasia. (Hematoxylin-eosin stain; original magnification: 3100.)
To the Editor: We herein report a rare case of neutrophilic fixed drug eruption (FDE) with naproxen as a novel causative agent. A 51-year-old white woman presented with multiple indurated pruritic plaques on her hands (Fig 1) and erosions on the lower lip mucosa (Fig 2) following the ingestion of a 275 mg tablet of naproxen (Apranax; Roche, Basel, Switzerland). This was her fourth attack during the last 5 years. Histopathology of the skin lesions revealed intense neutrophilic exocytosis resulting in intraepidermal pustule formation, similar to another recently reported case.1 Occlusive topical
patch testing using 10% naproxen gel (Naprosyn; Roche Laboratories Inc, Nutley, NJ) in a Finn Chamber, performed 4 weeks after the subsidence of the lesions, remained negative both in previous FDE sites and in the unaffected back skin. Four weeks later, skin lesions flared up within 1 to 2 hours following an oral challenge with one tablet of naproxen. Histopathology again showed a neutrophilic reaction (Fig 3). A history of 4 site-specific attacks, a lack of fever, leukocytosis and other systemic illnesses, and the
Letters 177
VOLUME 53, NUMBER 1
Scleroderma-like changes in cutaneous eruption of rhabdomyolysis To the Editor: A 66-year-old man presented with peculiar skin lesions on the right side of his face, chest wall, and scrotum of 2 days’ duration. He had been a chronic alcohol abuser for the past 40 years. Three days before admission, he went mountain hiking, had an alcoholic binge, and slept in a right lateral decubitus position. The next morning, he awoke to find the skin lesions and admitted himself to the emergency department. He had been taking diltiazem and nitrate for stable angina. Physical examination revealed well-demarcated, erythematous, swollen plaques on the right side of the cheek, neck, chest wall, arm, and scrotum. Bullous eruptions with local heating sensation and tenderness were noted on the right anterior chest wall (Fig 1, A). Histopathologic examination of the specimen from a bullous lesion showed severe eosinophilic necrosis of the epidermis with intraepidermal blister (Fig 1, B). Dermal eccrine ducts and glands showed varying degrees of necrosis (Fig 1, C ). There were mild inflammatory infiltrates consisting of neutrophils around the vessels in the dermis. He was diagnosed as having rhabdomyolysis on the basis of laboratory findings of elevated serum myogenic enzymes (creatine kinase, 970 U/L; lactate dehydrogenase, 277 U/L) and myoglobinuria. Tissue hypoxia and pressure were considered to be causative factors for his skin eruption. Treatment with topical and systemic corticosteroids resulted in clearing most of the skin lesions except those on the anterior chest wall. The bullous lesion on the chest changed into stony hard sclerodermoid plaques during the seventh week of treatment (Fig 2, A). A skin biopsy specimen showed thickened, sclerotic collagen fibers in the dermis (Fig 2, B). The laboratory findings for rheumatic factor, anti-centromere antibody, anti-Scl70 antibody, and antinuclear antibody were negative or within normal range. The patient has responded favorably to intralesional injection of corticosteroid, although the sclerodermoid plaques have persisted. Rhabdomyolysis usually occurs because of massive damage to the skeletal muscles, but muscle compression attributable to prolonged positioning, as was the case in our patient, may lead to this syndrome.1,2 Cutaneous eruptions in nontraumatic rhabdomyolysis are infrequent, but have been described as well-demarcated erythema, violaceous plaques and petechiae, bulla and ulcers, typically occurring in the pressure areas several hours or days after application of pressure.1,3 These skin eruptions can be important symptoms of nontraumatic rhabdomolysis, especially in mild cases, that are usually
Fig 1. A, Well-demarcated, erythematous, swollen plaques and bullae over right anterior chest wall. B, Eosinophilic necrosis of epidermis with intraepideramal blister. C, Dermal eccrine ducts and glands showing varying degrees of necrosis. (B and C, Hematoxylin-eosin stain; original magnifications: B, 3200; C, 3100.)
Fig 2. A, Scleroderma-like plaque after 7 weeks. B, Thickened, sclerotic collagen fibers in dermis. (Hematoxylin-eosin stain; original magnification 3100.)
asymptomatic (no muscle pain and swelling).3 The pathologic findings were compatible with hypoxic skin injury showing necrosis of the epidermis and eccrine glands, consistent with the suggested pathogenesis of skin lesions of rhabdomyolysis.1 Prolonged right decubitus positioning after alcohol abuse might be the course of tissue hypoxia in our patient.4 It is noteworthy that the bullous lesions later changed into scleroderma-like indurations. This scleroderma-like change is different from bullous morphea in which subepidermal bullae and lymphatic dilatations are the characteristic histologic findings.5 We believe that the scleroderma-like changes were induced by previous tissue hypoxia. Hypoxic modulation of collagen metabolism appears related to fibrosis of connective tissue after injury and scleroderma.6 Recently, it was reported that tissue hypoxia may induce extracellular
178 Letters
J AM ACAD DERMATOL JULY 2005
matrix overproduction by fibroblasts.7 Altogether, we believe that hypoxic events in skin may induce bullae via direct epidermal necrosis, which can evolve into sclerodermoid induration via collagen remodeling. Sung Kwon Kim, MD You Chan Kim, MD Bang Jin Lee, MD Hee Young Kang, MD Department of Dermatology Ajou University School of Medicine Suwon, Korea Correspondence to: Hee Young Kang, MD 5 Wonchon-dong, Yeongtong-ku Suwon, 443-721, Korea (South)
Fig 1. Multiple indurated, slightly erythematous plaques with nondiscrete borders located bilaterally on the dorsal surfaces of the hands and fingers. Note the discretely elevated dusky-red plaques and papules between the first and second fingers on the dorsal surface of the left hand.
E-mail: [email protected] REFERENCES 1. Szewczyk D, Ovadia P, Abdullah F, Rabinovici R. Pressure-induced rhabdomyolysis and acute renal failure. J Trauma 1998;44:384-8. 2. Mathes DD, Assimos DG, Donofrio PD. Rhabdomyolysis and myonecrosis in a patient in the lateral decubitus position. Anesthesiology 1996;84:727-9. 3. Miyamoto T, Ikehara A, Kobayashi T, Kitada S, Hagari Y, Mihara M. Cutaneous eruptions in coma patients with nontraumatic rhabdomyolysis. Dermatology 2001;203:233-7. 4. Singh S, Sharma A, Sharma S, Sud A, Wanchu A, Bambery P. Acute alcoholic myopathy, rhabdomyolysis and acute renal failure: a case report. Neurol India 2000;48:84-5. 5. Daoud MS, Su WP, Leiferman KM, Perniciaro C. Bullous morphea: clinical, pathologic, and immunopathologic evaluation of thirteen cases. J Am Acad Dermatol 1994;30:937-43. 6. Silverstein JL, Steen VD, Medsger TA Jr, Falanga V. Cutaneous hypoxia in patients with systemic sclerosis (scleroderma). Arch Dermatol 1988;124:1379-82. 7. Tamby MC, Chanseaud Y, Guillevin L, Mouthon L. New insights into the pathogenesis of systemic sclerosis. Autoimmun Rev 2003;2:152-7.
Fig 2. Erosive lesions on the lower lip mucosa.
doi:10.1016/j.jaad.2005.01.096
Neutrophilic fixed drug eruption caused by naproxen: A real entity or a stage in the histopathologic evolution of the disease?
Fig 3. Epidermal spongiosis, very prominent neutrophilic exocytosis, intraepidermal micropustule formation, upper dermal slight edema, and inflammatory infiltration with perivascular neutrophils and scattered leucocytoclasia. (Hematoxylin-eosin stain; original magnification: 3100.)
To the Editor: We herein report a rare case of neutrophilic fixed drug eruption (FDE) with naproxen as a novel causative agent. A 51-year-old white woman presented with multiple indurated pruritic plaques on her hands (Fig 1) and erosions on the lower lip mucosa (Fig 2) following the ingestion of a 275 mg tablet of naproxen (Apranax; Roche, Basel, Switzerland). This was her fourth attack during the last 5 years. Histopathology of the skin lesions revealed intense neutrophilic exocytosis resulting in intraepidermal pustule formation, similar to another recently reported case.1 Occlusive topical
patch testing using 10% naproxen gel (Naprosyn; Roche Laboratories Inc, Nutley, NJ) in a Finn Chamber, performed 4 weeks after the subsidence of the lesions, remained negative both in previous FDE sites and in the unaffected back skin. Four weeks later, skin lesions flared up within 1 to 2 hours following an oral challenge with one tablet of naproxen. Histopathology again showed a neutrophilic reaction (Fig 3). A history of 4 site-specific attacks, a lack of fever, leukocytosis and other systemic illnesses, and the