Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings

Abstract

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae. Keywords: Coma; Fluorescent antibody technique; Microscopy, fluorescence; Phenobarbital; Toxicology Resumo: Formação de bolhas e necrose de glândula sudoríparas écrinas é uma manifestação cutânea associada com estados de diminuição da consciência, mais frequentemente relatada após superdosagens de depressores do sistema nervoso central, particularmente fenobabital. Relatamos o caso de uma paciente de 45 anos que desenvolveu "bolhas do coma" após tentativa de suicídio por fenobarbital (confirmada laboratorialmente), associada a outros depressores do sistema nervoso central (clonazepam, prometazina, oxcarbazepina e quetiapina). Biópsia da bolha do 1o quirodáctilo esquerdo no 4o dia de internação revelou necrose focal da epiderme e necrose de células epiteliais de glândula sudorípara; a imunofluorescência direta foi fortemente positiva para IgG na parede superficial dos vasos sanguíneos, mas negativa para IgM, IgA, C3 e C1q. A paciente teve alta no 21o dia, sem seqüelas.

Coma blisters with deep soft tissue involvement after drug overdose

“…Coma blisters or coma bullae (CB) are bullous lesions that have been associated with a variety of neurological diseases, especially with drug and nondrug‐induced coma. They are usually related to drug overdose in patients with previous history of suicide attempt (barbiturate, antipsychotics, antidepressants, or opiate overdose) or in the setting of metabolic imbalance (diabetic ketoacidosis, chronic renal failure) . The exact pathogenesis remains unclear .…”

“…They are usually related to drug overdose in patients with previous history of suicide attempt (barbiturate, antipsychotics, antidepressants, or opiate overdose) or in the setting of metabolic imbalance (diabetic ketoacidosis, chronic renal failure) . The exact pathogenesis remains unclear . CB represent a self‐limited disease; however, some patients may develop deep skin and soft tissue involvement presenting as pain, edema, and functional impairment.…”

“…The first description of CB dates back to early XIX century, when Larrey (Napoleon's surgeon) noticed blisters in soldiers who had been comatose from carbon monoxide intoxication . Since then, there is a wide list of drugs and clinical settings that can potentially cause this entity . They consist of tense and flaccid blisters more frequently located distally in the limbs.…”

“…CB are thought to be caused partly by pressure and ischemia in patients with impaired mental status, but their distribution and localization cannot be explained simply by traumatic or vascular damage. On the other hand, while it has been suggested that some toxic effect of drugs may play a role, it has not been proven the relation between CB and any specific drug . Deep seated ischemic lesions of subcutaneous fat and muscle have been poorly reported in the literature since the first description by Holden CE in 1977.…”

“…3 Since then, there is a wide list of drugs and clinical settings that can potentially cause this entity. 1,4 They consist of tense and flaccid blisters more frequently located distally in the limbs. Typically, adjacent skin is spared.…”