Volume 27 Number 2, Part 1 August 1992

Brief communications 269

Coma blisters in a patient with diabetic ketoacidosis Darius R. Mehregan, MD, Mazen Daoud, MD, * and Roy S. Rogers III, MD Rochester, Minnesota Bullae, erosions, and violaceous plaques at sites of pressure have been described in comatose patients. The lesions generally occur within 24 hours of the onset of coma and resolve in 10 to 14 days. I Histologic examination of the lesions shows epidermal necrosis with formation of intraepidermal and subepidermal vesicles and necrosis of eccrine glands and ducts. 2 The pilosebaceous units may also be involved. 3 Bullous lesions associated with coma were described originally in 1812 by L arrey4 in soldiers of Napoleon's army who were exposed to carbon monoxide. Since that time, many authors have reported cases of "coma blisters" associated with exposure to barbiturates, opioids, benzodiazepines, and tricyclic antidepressants. 1-3, 5 Similar lesions have also been reported in patients with non-drug-induced coma. Bullous lesions on areas of pressure have been reported in patients with coma resulting from head trauma, cerebrovascular accidents, viral encephalitis, and hypoglycemia. 3, 6-8 Pressure-associated bullae have also been reported in noncomatose patients with severe neurologic disease. 3, 8-11 We report a case of coma bullae in a girl with coma caused by diabetic ketoacidosis. To our knowledge this is the first report of diabetic ketoacidosis associated with coma bullae.

CASE REPORT A 12-year-old girl had polydipsia, polyphagia, polyuria, and a 4.5 kg weight loss the month before admission. Malaise and progressive weakness developed I week earlier. On the morning of admission to a local emergency room, she was unresponsive. Her pulse was 136 beats/ min, blood pressure was 86/44 mm Hg, and respiratory rate was 28 breaths/min. Blood glucose concentration was 1909 mg/dl. Six units of insulin was administered intravenously and an insulin drip (4 U/hr) was initiated. From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Reprint requests: R. S. Rogers III, MD, Mayo Clinic, 200 FirstSt. SW, Rochester, MN 55905. *Visiting Clinician at the Department of Dermatology.

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Fig. 1. Eroded ecchymotic bullae with area of necrotic eschar over the buttocks.

At admission to the hospital, she was febrile and no skin lesions were noted. Within 12 hours, she became arousable. Within 24 hours of admission, violaceous, ecchymotic, curvilinear plaques were noted on her right upper and mid back. There were also bullae and erosions on ecchymotic bases on the buttocks (Fig. 1) and tense bullae on the temple and the dorsal aspect of the right hand. Macular erythema was noted in the popliteal fossa bilaterally. A biopsy specimen of the erythematous border of a bulla revealed superficial to complete epidermal necrosis (Fig. 2). Necrosis of the papillary dermis, with hemorrhage and focal necrosis of the panniculus, was noted. The eccrine glands and duct showed focal areas of degeneration. Necrotic cells with pyknotic nuclei and vacuolated cytoplasm were seen among normal-appearing eccrine cells. There was minimal inflammation. At 6-week follow-up, the cutaneous lesions had almost completely healed and the largest sacral erosions had residual crusting. Hyperpigmentation was noted in the previously involved areas. No new lesions had developed.

DISCUSSION Coma blisters were first described in persons exposed to carbon monoxide. The histologic findings included necrosis of the sweat glands with formation ofintraepidermal and subepidermal vesicles. 12 However, coma blisters now are associated most often with toxic coma from drug overdose. Beveridge 13

Journal of the American Academy of Dermatology

270 Briefcommunications

injuries caused by compression of the limb. Our patient showed areas of erythema overlying the peroneal nerve at the level of nerve blockage, but bullae did not develop at these sites. At 6-week follow-up after her initial evaluation, our patient still had evidence of a peroneal nerve palsy bilaterally. The cause of the nerve damage may have been compression or infarction of the nerve, similar to that reported by Holden. 15 REFERENCES 1. Varma AJ, Fisher BK, Sarin MK. Diazepam-induced

2. 3. 4.

Fig. 2. Epidermal necrosis, basal cell regeneration, eccrine duct necrosis, and dermal hemorrhage with minimal inflammation. (Hematoxylin-eosin stain; X40.)

reported bullous lesions in 6.5% of patients with barbiturate overdosage. The cause is unclear, but a toxic drug effect, pressure, friction, and local hypoxia have been implicated. 2, 3 Bullae have occurred on the penis and uvula without evidence of local trauma. I In addition, common friction blisters occur between the granular and malpighian layers, whereas coma blisters tend to occur intraepidermally and subepidermally. Therefore factors other than local tissue hypoxia may be involved. Immunofluorescence studies have shown intercellular staining with IgG, IgA, and C3, which implies the immune system may be involved in the induction of 1esions. 14 In addition to coma bullae, compression neuropathy developed bilaterally while our patient was in coma. Holden l5 also reported on two patients with coma bullae and infarction ofunderlying muscle and nerve. Shields et a1. 16 reported a series of eight patients in unattended coma who had peripheral nerve

5.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

coma with bullae and eccrine sweat gland necrosis. Arch Intern Med 1917;137:1207-10. Mandy S, Ackerman AB. Characteristic traumatic skin lesions in drug-induced coma. JAMA 1970;213:253-6. Arndt KA, Mihm MC Jr, Parrish JA. Bullae: a cutaneous sign of a variety of neurologic diseases. J Invest Dermatol 1973;60:312-20. Larrey DJ. Memoires de chirurgie militaire et campagnes; vol 3. Paris: Smith and Buisson, 1812:13. Herschthal D, Robinson MJ. Blisters of the skin in coma induced by amitriptyline and clorazepate dipotassium: report of a case with underlying sweat gland necrosis. Arch Dermatol1979;115:499. Raymond LW, Cohen AB. "Barbiturate blisters" in a case of severe hypoglycaemic coma. Lancet 1972;2:764. Freeman DM, Raza M. Bullous lesions in acute barbiturate intoxication. Br Med J 1965;1:1495-6. Judge TG, Nisbet NH. Trophoneurotic blisters in elderly hemiplegics. Lancet 1967;1:811-2. McLardy T. Uraemic and trophic deaths following leucotomy: neuro-anatomical findings. J Neural Neurosurg Psychiatry 1950;13:106-14. Metz RJS, Cooper W. Salt retention and uraemia in brain injury. Br Med J 1958;1:435-8. Robertson EE. Skin lesions in organic brain disease. Br Med J 1953;1:291-5. Leavell UW, Farley CH, McIntyre JS. Cutaneous changes in a patient with carbon monoxide poisoning. Arch Dermato11969;99:429-33. Beveridge GW. Bullous lesions in poisoning. Br Med J 1971;4:116-7. Reilly GD, Harrington CI. Positive immunofluorescence in bullous lesions in drug-induced coma [Letter]. Br J Dermatol 1983;109:720. Holden CEA. Cutaneous bullae in coma due to poisoning: an association with deep seated ischaemic lesions of muscle. Anaesthesia 1977;32:554-5. Shields RW Jr, Root KE Jr, Wilbourn AJ. Compartment syndromes and compression neuropathies in coma. Neurology 1986;36:1370-4.