Bullous Lesions, Sweat Gland Necrosis and Rhabdomyolysis in Alcoholic Coma

Abstract

A 42-year-old male developed hemorrhagic bullae and erosions while in alcohol induced coma. The lesions were limited to areas of the body in prolonged contact with the ground in the comatose state. He developed rhabdomyolysis, progressing to acute renal failure (ARF). Histopathological examination of the skin showed spongiosis, intraepidermal vesicles, and necrosis of eccrine sweat glands with denudation of secretory epithelial lining cells. With supportive treatment and hemodialysis, the patient recovered in 3 weeks time. This is the first reported case of bullous lesions and sweat gland necrosis occurring in alcohol-induced coma complicated by rhabdomyolysis and ARF.

Introduction

What was known?

Bullous skin lesions and necrosis of eccrine sweat glands have been described in drug induced coma. The commonest reported cause is barbiturates; alcohol is a rare cause. A previously reported patient with alcohol induced coma and bullous skin lesions had biochemical evidence of rhabdomyolysis.

Bullous lesions may occur in association with unconscious state. Coma due to barbiturate toxicity is perhaps the most widely known setting in which such lesions develop.[1,2,3] Histopathologically, sweat gland necrosis is a characteristic finding in these cases. Other causes include benzodiazepines,[4,5] amitryptyline,[6] theophylline,[7] and anticonvulsants[8]. Though, mostly reported in association with drug induced coma, it has been postulated that bullous lesions associated with sweat gland necrosis can occur in comatose states due to any cause.[9] Rarely, the condition has been reported in non-comatose patients.[10] Earlier, only two cases have been reported in patients with alcoholic coma.[11,12]

Case Report

A 42-year-old male with normal previous medical history was brought to the casualty with altered sensorium and numerous bullae and erosions on the skin. He was found lying unconscious on the floor of a cramped room, after a prolonged bout of alcohol consumption.

On examination, he was drowsy and had multiple, bilateral, asymmetrically distributed vesicles, hemorrhagic bullae and erosions of irregular shapes on the front of trunk, forearms, legs, and face; mostly limited to areas in contact with the floor while he was lying unconscious [Figures 1 and 2]. The vesicles were seen arising from erythematous and edematous skin [Figure 3]. Flexures and mucosae were spared. Nikolsky's sign was negative.

Figure 1.

Irregular and bizarre-shaped bullae and erosions on anterior trunk

Figure 2.

Close-up view of bullous skin lesions

Figure 3.

Vesicles on erythematous and edematous skin on the lateral aspect of forearm

Urine was dark red in colour and showed albuminuria, numerous RBCs, and granular casts. Blood urea was 108 mg/dL and serum creatinine 3.1 mg/dL, which rose to 140 mg/dL and 5.6 mg/dL, respectively on the subsequent days. Prothrombin time (PT) was 15.7 s (control: 11.9) with international normalized ratio (INR) 1.3 and activated partial thromboplastin time (APTT) 35.8 s (control: 30.2). Serum glutamic oxaloacetic transaminase (SGOT) was 450 IU/L (control: 5-40), serum glutamic pyruvic transaminase (SGPT) 295 IU/L (control: 5-50) and serum creatine phosphokinase (CPK) was 14,120 IU/L (control: 40-320). Ultrasonogram of abdomen showed hepatomegaly with coarse parenchyma, hyperechoic kidneys with minimal corticomedullary differentiation, and mild ascites. Tzanck smear from bullae showed a few neutrophils. Culture of bullous fluid, blood, and urine were sterile.

Histopathological examination of the skin on the edge of the erosions using hematoxylin and eosin (H and E) stain showed mild acanthosis, spongiosis, intraepidermal vesiculation; and focal lymphocytic infiltrate particularly around eccrine sweat glands, extravasated erythrocytes, and dilated blood vessels in the dermis [Figures 4 and 5]. There was necrosis of sweat glands with denudation of secretory epithelial lining cells [Figure 6]. Direct immunofluorescence test was negative.

Figure 4.

Spongiosis, intraepidermal vesiculation, and focal dermal lymphocytic infiltrate around eccrine sweat gland and duct. H and E, ×100

Figure 5.

Spongiosis and intraepidermal vesicles. H and E, ×400

Figure 6.

Necrosed eccrine sweat gland with denuded secretory epithelial lining cells. H and E, ×400

Provisional diagnosis was bullous lesions related to coma, alcoholic liver disease, and acute renal failure (ARF) due to rhabdomyolysis. He was treated with parenteral fluids, injections of ceftriaxone, and metronidazole; other supportive measures and four cycles of hemodialysis. Sensorium and renal function recovered to normal over the next 2 weeks. The skin lesions were treated with normal saline compresses and topical mupirocin cream. They healed within 3 weeks with hyperpigmentation and scars.

Discussion

This patient had a sudden onset of hemorrhagic blisters progressing to erosions and necrotic ulcers, strikingly on the areas in contact with the floor in comatose state. These features suggested a diagnosis of bullous lesions associated with comatose state. Sweat gland necrosis is an associated histopathological finding in such cases.[1,4] The skin lesions were not considered to be associated with sepsis as the bullae were hemorrhagic, neither flaccid nor pustular; Nikolsky's sign was negative and the bullous fluid did not grow bacteria on culture. Histopathological examination confirmed the diagnosis of sweat gland necrosis in our patient. Presence of dark coloured urine and elevated CPK levels in the context of ARF suggested the possibility of rhabdomyolysis.

Bullous lesions have been reported in patients with carbon monoxide poisoning as early as in 1865,[13] while such lesions have been associated with barbiturate poisoning from 1950.[14] Both of the previously reported cases of sweat gland necrosis associated with alcoholic coma had bullous lesions on pressure points.[11,12] One of them also had biochemical evidence of muscle damage as in our patient.[11] However, our case is unique in that rhabdomyolysis complicated by ARF was a prominent clinical presentation.

Vesiculobullous lesions seen in unconscious patients are believed to be due to a combined effect of generalized or localized hypoxia or drug toxicity coupled with trauma and friction.[1,2] Impaired vasomotor reflexes in comatose state and associated vasodilatation could also be responsible.[9] The characteristic histopathological finding is coagulative necrosis of the secretory cells of sweat glands. Inflammation is usually minimal or absent in the adjacent dermis. In severe cases, sweat ducts, and the pilosebaceous units may also show necrosis. Epidermis adjacent to sweat ducts may show spongiosis. There can be both intraepidermal and subepidermal vesicles.[1]

This case highlights the need for greater awareness about this relatively uncommon cause of bullous disease on the skin. When one encounters a case of sudden appearance of bullous lesions in a comatose patient, history of ingestion of drugs or toxins including alcohol should be sought for. A skin biopsy showing spongiosis, intraepidermal as well as subepidermal vesicles and necrosis of eccrine sweat glands will confirm the diagnosis. These patients should be evaluated for associated rhabdomyolysis and other life-threatening complications such as ARF.

What is new?

While evaluating comatose patients with bullous skin lesions, history of excessive consumption of alcohol should be sought for. Such patients should be monitored for complications such as rhabdomyolysis and acute renal failure.