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The opioid epidemic: Coma blisters and beyond

DII small banner By Warren R. Heymann, MD
Aug. 4, 2017

The opioid crisis in the United States is responsible for at least 90 fatalities every day. This dire situation has been aggravated by the increased availability of very potent synthetic opioids such as fentanyl and carfentanil, which are 50 and 5000 times as potent as heroin, respectively. According to Volkow and Collins, “Misuse of or accidental exposure to these drugs (e.g., laced in heroin) is associated with very high overdose risk.” (1)
Unfortunately, it is time to review the clinical manifestations of coma blisters (CBs).

CBs are associated with prolonged impairment of consciousness. Napoleon’s surgeon Larrey, who noticed blisters in soldiers who had been comatose from carbon monoxide intoxication, initially described them. (2) Subsequent associations include overdoses of barbiturates, benzodiazepines, tricyclic antidepressants, heroin, and alcohol. CBs may also be observed in patients with central nervous system diseases such as tumors, strokes, hemorrhages, trauma, infectious meningoencephalitis, and metabolic disorders (e.g., diabetic ketoacidosis, hypoglycemia). CBs characteristically occur in pressure areas of the extremities and trunk 48 to 72 hours after the onset of unconsciousness (3). Lesions present with an erythematous base that evolves into tense bullae and vesicles, occasionally appearing as erosions or violaceous plaques. (4) CBs are self-limiting and usually heal spontaneously in 1 to 2 weeks (3). Histologic findings include epidermal and eccrine sweat gland necrosis, subepidermal bullae, and thrombi in dermal vessels. (3)
The pathogenesis is probably multifactorial, involving localized and generalized hypoxia and tissue ischemia, direct toxicity of the overdose medication, local pressure effects, friction, immune mechanisms, and changes in vasomotor control related to a comatose state. (4) The characteristic sweat gland necrosis appears to be due to apoptotic processes, as recently demonstrated by immunohistochemical analysis. (5)

It is essential that dermatologists recognize CBs and question the possibility of pathology beyond the skin, especially if lesions are painful (assuming the patient is conscious enough to admit that). Ruiz-Rivero et al presented the case of a 49-year-old man who was admitted with a progressive loss of consciousness following an attempted suicide with a tricyclic antidepressant, opiates, and benzodiazepine overdose. Laboratory tests revealed positive urine toxic levels, leukocytosis, renal dysfunction with rhabdomyolysis, and a chest X-ray consistent with aspiration pneumonia. His leg was edematous and slightly erythematous; this was initially (incorrectly) interpreted as bacterial cellulitis. An MRI demonstrated edema of the subcutaneous fat with increased volume along the distal part of the long peroneal muscle and with signs of muscle necrosis. (2) Chang and Su reported the case of a 40 year-old man, who was unconscious for a day, who developed palmar blisters with digital cyanosis. He was diagnosed with a compartment syndrome accompanied by rhabdomyolysis, necessitating an emergent faciotomy. (6)
Although dermatologists must recognize CBs and appreciate their complications, the root issue is the opioid crisis itself. I encourage you to read the enlightening manuscript by Dr. Robert L. DuPont, who was the first Director of the National Institute on Drug Abuse. The following is the abstract of the commentary (7):

The current narrative describing the national opioid epidemic as the result of overprescribing opioid pain medicines fails to capture the full dimensions of problem and leads to inadequate and even confounding solutions. Overlooked is the fact that polysubstance use is nearly ubiquitous among overdose deaths, demonstrating that the opioid overdose death problem is bigger than opioids. The foundation of the nation’s opioid overdose crisis – and the totality of the nation’s drug epidemic — is widespread recreational pharmacology, the use of drugs for fun or “self-medication.” The national focus on the opioid overdose deaths provides important new opportunities in both prevention and treatment to make fundamental changes to the way that substance use disorders and related problems are understood and managed. The first-ever US Surgeon General’s report on addiction provides a starting point for systemic changes in the nation’s approach to preventing, treating and managing substance use disorders as serious, chronic diseases. New prevention efforts need to encourage youth to grow to adulthood not using alcohol, nicotine, marijuana or other drugs for reasons of health. New addiction treatment efforts need to focus on achieving long-term recovery including no use of alcohol, marijuana and other drugs.

The opioid epidemic extends to every community, socioeconomic group, and physician. A coma blister is only a sign of a far greater problem that must be addressed. There are no easy solutions to the current opioid epidemic — improving the situation will require societal focus and commitment.

1. Volkow ND, Collins FS. The role of science in addressing the opioid crisis. N Engl J Med 2017; 377: 391-4.
2. Ruiz-Rivero J, et al. Coma blisters with deep soft tissue involvement after drug overdose. Int J Dermatol 2017; 56: 881-3.
3. Bosco L, et al. Coma blisters in children: Case report and review of the literature. J Child Neurol 2013; 28: 1677-80.
4. Chacon AH, et al. Coma blisters in two postoperative patients. Am J Dermatopathol 2013; 35: 381-4.
5. Kashiwagi M. et al. Immunohistochemical investigation of the coma blister and its pathogenesis. J Med Invest 2013; 60: 256-61.
6. Chang KS, Su YJ. Coma blister in nontraumatic rhabdomyolysis. Am J Emerg Med 2016; 34: 1324.
7. Dupont RL. The opioid epidemic is an historic opportunity to improve both prevention and treatment. Brain Res Bull 2017 June 13 [Epub ahead of print].

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