Drug Overdose-Induced Coma Blisters: Pathophysiology and Clinical and Forensic Diagnosis

Author(s): Ricardo J. Dinis-Oliveira*.

Journal Name: Current Drug Research Reviews

Volume 11 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Coma blisters or coma bullae are bullous lesions that have been associated with cases of drug overdose-induced coma. Previous history of suicide attempt by administering benzodiazepines, barbiturates, ethanol, antipsychotics, antidepressants or opioids have been particularly implicated. Patients may present also painful deep skin and soft tissue involvement, edema and functional impairment. The pathophysiology remains unknown and lesions are usually self-limited and typically resolve without scarring.

Objective: This work aims to fully review the state of the art regarding the causes pathophysiology, diagnosis and treatment of drug overdose-induced coma blisters.

Conclusion: Coma blisters are a benign, self-limiting condition that should be suspected in patients who develop pressure blisters several hours after an altered state of consciousness.

Keywords: Coma blisters, drug overdose, diagnosis, histopathology, treatment, pathophysiology.

[1]
Larrey DJ. Memoires de chirurgie militaire et campagnes. Smith and Buisson 1812; 3: 13.
[2]
Villaret ML, Bith H, Desoille M. Ulcérations cutanées dues aux barbituriques. Paris Med (Paris) 1932; 2: 340.
[3]
Wenzel FG, Horn TD. Nonneoplastic disorders of the eccrine glands. J Am Acad Dermatol 1998; 38: 1-17.
[4]
Sanchez YE, Requena L, Simon P. Histopathology of cutaneous changes in drug-induced coma. Am J Dermatopathol 1993; 15: 208-16.
[5]
Rocha J, Pereira T, Ventura F, Pardal F, Brito C. Coma Blisters. Case Rep Dermatol 2009; 1: 66-70.
[6]
Branco MM, Capitani EM, Cintra ML, Hyslop S, Carvalho AC, Bucaretchi F. Coma blisters after poisoning caused by central nervous system depressants: Case report including histopathological findings. An Bras Dermatol 2012; 87: 615-7.
[7]
Holden CE. Cutaneous bullae in coma due to poisoning. An association with deep seated ischaemic lesions of muscle. Anaesthesia 1977; 32: 554-5.
[8]
Ruiz-Rivero J, Pulido-Perez A, Suarez-Fernandez RM. Coma blisters with deep soft tissue involvement after drug overdose. Int J Dermatol 2017; 56: 881-3.
[9]
Dinis-Oliveira RJ, Caldas I, Carvalho F, Magalhaes T. Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse. Clin Toxicol (Phila) 2010; 48: 863-4.
[10]
Dinis-Oliveira RJ, Carvalho F, Duarte JA, Proenca JB, Santos A, Magalhães T. Clinical and forensic signs related to cocaine abuse. Curr Drug Abuse Rev 2012; 5: 64-83.
[11]
Dinis-Oliveira RJ, Carvalho F, Moreira R, et al. Clinical and forensic signs related to opioids abuse. Curr Drug Abuse Rev 2012; 5: 273-90.
[12]
Dinis-Oliveira RJ, Carvalho F, Moreira R, et al. Clinical and forensic signs related to chemical burns: A mechanistic approach. Burns 2015; 41: 658-79.
[13]
Dinis-Oliveira RJ, Magalhães T, Moreira R, et al. Clinical and forensic signs related to ethanol abuse: A mechanistic approach. Toxicol Mech Methods 2014; 24: 81-110.
[14]
Dinis-Oliveira RJ, Magalhães T, Queiros O, et al. Signs and Related Mechanisms of Ethanol Hepatotoxicity. Curr Drug Abuse Rev 2015; 8: 86-103.
[15]
Dunn C, Held JL, Spitz J, Silvers DN, Grossman ME, Kohn SR. Coma blisters: report and review. Cutis 1990; 45: 423-6.
[16]
You MY, Yun SK, Ihm W. Bullae and sweat gland necrosis after an alcoholic deep slumber. Cutis 2002; 69: 265-8.
[17]
Keng M, Lagos M, Liepman MR, Trever K. Phenobarbital-induced bullous lesions in a non-comatose patient. Psychiatry (Edgmont Pa) 2006; 3: 65-9.
[18]
Arndt KA, Mihm MC, Parrish JA. Bullae: a cutaneous sign of a variety of neurologic diseases. J Invest Dermatol 1973; 60: 312-20.
[19]
Piede J, Wallace E. Coma bullae: Associations beyond medications. Mayo Clin Proc 2011; 86: e5.
[20]
Mehregan DR, Daoud M, Rogers RS III. Coma blisters in a patient with diabetic ketoacidosis. J Am Acad Dermatol 1992; 27: 269-70.
[21]
Chang KS, Su YJ. Coma blister in nontraumatic rhabdomyolysis. Am J Emerg Med 2016; 34: 1324.e1-2.
[22]
Chacon AH, Farooq U, Choudhary S, et al. Coma blisters in two postoperative patients. Am J Emerg Med 2013; 35: 381-4.
[23]
Bosco L, Schena D, Colato C, Biban P, Girolomoni G. Coma blisters in children: case report and review of the literature. J Child Neurol 2013; 28: 1677-80.
[24]
Agarwal A, Bansal M, Conner K. Coma blisters with hypoxemic respiratory failure. Dermatol Online J 2012; 18: 10.
[25]
Holten C. Cutaneous phenomena in acute barbiturate poisoning. Acta Derm Venereol 1952; 32: 162-8.
[26]
Beveridge GW, Lawson AA. Cccurrence of bullous lesions in acute barbiturate intoxication. BMJ 1965; 1: 835-7.
[27]
Vazquez-Osorio I, Gonzalvo-Rodriguez P, Rodriguez-Diaz E. Coma Blisters after an Overdose of Central Nervous System Depressants. Actas Dermosifiliogr 2017; 108: 81-3.
[28]
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 Dermatol 1979; 115: 499.
[29]
Reilly GD, Harrington CI. Positive immunofluorescence in bullous lesions in drug-induced coma. Br J Dermatol 1983; 109: 720.
[30]
Fogarty BJ, Khan K. Drug induced blistering and the plastic surgeon: a case of amitriptyline induced skin necrosis. Burns 1999; 25: 768-70.
[31]
Maguiness S, Guenther L, Shum D. Coma blisters, peripheral neuropathy, and amitriptyline overdose: A brief report. J Cutan Med Surg 2002; 6: 438-41.
[32]
Dahlin KL, Bohlin K, Strindlund J, Ryrfeldt A, Cotgreave IA. Amitriptyline-induced loss of tight junction integrity in a human endothelial--smooth muscle cell bi-layer model. Toxicology 1999; 136: 1-13.
[33]
Tsokos M, Sperhake JP. Coma blisters in a case of fatal theophylline intoxication. Am J Forensic Med Pathol 2002; 23: 292-4.
[34]
Bas A, Brown S, Kirkham N, Ramesh V, Leech S, Devlin A. Coma blisters in 2 children on anticonvulsant medication. J Pediatr Neuroradiol 2009; 24: 1021-5.
[35]
Setterfield JF, Robinson R, MacDonald D, Calonje E. Coma-induced bullae and sweat gland necrosis following clobazam. Clin Exp Dermatol 2000; 25: 215-8.
[36]
Wiegand TJ, Gorodetsky RM, Peredy TR. Coma blisters in the setting of quetiapine overdose: case report and review of literature. Asia Pac J Med Toxicol 2013; 2: 153-6.
[37]
Leavell UW. Sweat gland necrosis in barbiturate poisoning. Arch Dermatol 1969; 100: 218-21.
[38]
Branco MM, Capitani EMD, Cintra ML, Hyslop S, Carvalho AC, Bucaretchi F. Coma blisters after poisoning caused by central nervous system depressants: Case report including histopathological findings. An Bras Dermatol 2012; 87: 615-7.
[39]
Kashiwagi M, Ishigami A, Hara K, et al. Immunohistochemical investigation of the coma blister and its pathogenesis. J Med Invest 2013; 60: 256-61.
[40]
Caulín C, Salvesen GS, Oshima RG. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. J Cell Biol 1997; 138: 1379-94.
[41]
Melrose E, Laageide L, Mutgi K, Stone MS, Wanat KA. Pressure-induced necrosis can mimic retiform purpura. JAAD Case Rep 2018; 4: 365-7.
[42]
Ankrom MA, Bennett RG, Sprigle S, et al. Pressure-related deep tissue injury under intact skin and the current pressure ulcer staging systems. Adv Skin Wound Care 2005; 18: 35-42.
[43]
Varma AJ, Fisher BK, Sarin MK. Diazepam-induced coma with bullae and eccrine sweat gland necrosis. Ann Intern Med 1977; 137: 1207-10.
[44]
Waring WS, Sandilands EA. Coma blisters. Clin Toxicol (Phila) 200(45): 808-9.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 11
ISSUE: 1
Year: 2019
Page: [21 - 25]
Pages: 5
DOI: 10.2174/1874473711666180730102343
Price: $58

Article Metrics

PDF: 56
HTML: 3