Two patients with substance-use disorder present to an ED in the United States with a new rash. Which of the following is the most likely exposure?

  1. Krokodil (desomorphine)
  2. Levamisole-adulterated cocaine
  3. Methamphetamine-induced allergic reaction
  4. Wound botulism secondary to heroin use

Levamisole-Adulterated Cocaine

These rashes are typical for the leukocytoclastic vasculitis produced by levamisole exposure. As of 2015, the U.S. Drug Enforcement Agency identified levamisole in over 90% of seized cocaine.1 Levamisole is an antihelminthic and immunomodulatory agent used in veterinary medicine. Previously used as therapy for rheumatoid arthritis and some cancers, levamisole was withdrawn from the U.S. market for human use in 2000 due to adverse effects including rash, leukopenia, and agranulocytosis.2–4

Levamisole is physically similar to cocaine and its postulated mechanisms of action include:2,3,5

  1. Decreased catecholamine degradation in the synapse
  2. Independent stimulatory effects
  3. Potentiate and prolong the action of cocaine via anticholinesterase activity

Levamisole exposure is associated with multiple cutaneous manifestations including:

  • Vasculitis
  • Purpuric lesions
  • Skin necrosis
  • Urticaria
  • Bullae
  • Dermatitis

The face and ears are commonly affected, although lesions can appear anywhere. Patients may describe fevers, malaise, fatigue, sore throat, oral ulcers, and joint pain.

Bedside Pearls

Patients presenting with rash, oropharyngeal complaints, abscesses, and fever should be asked about cocaine use to assess for levamisole exposure. In patients with any of these symptoms and a history of cocaine use, consider obtaining a

  • Complete blood count
  • Electrolytes
  • Renal function

Additional studies may include:

  • Antineutrophil cytoplasmic antibody (ANCA)
  • Antineutrophil antibody (ANA)
  • Antiphospholipid antibody
  • Cryoglobulin
  • Lupus anticoagulant
  • Complement levels
  • Anti-human elastase antibody

Levamisole can be detected in blood and urine; however, the window of detection is fairly short. Drug paraphernalia can also be assessed for levamisole contamination.2,3,5

Cessation of the exposure is the mainstay of therapy with targeted care indicated for dermatologic and/or infectious features.2–4 While the clinical course is typically benign, debridement and skin grafting has been necessary in some cases, and necrosis and auto-amputation have been reported. Filgrastim has been used for levamisole-associated leukopenia and sepsis. Since leukopenia frequently resolves with cessation of exposure alone, supportive care can be considered for this finding unless the patient is critically ill.4 Patients should also be advised of the dangers of continued cocaine use, including the risk of recurrent levamisole-related complications, with future exposure.4,5

This post was expert peer-reviewed by Dr. Bryan Judge and Dr. Kavita Babu.


2017 National Drug Threat Assessment Summary. Drug Enforcement Administration. Published 2017. Accessed August 20, 2018.
Larocque A, Hoffman R. Levamisole in cocaine: unexpected news from an old acquaintance. Clin Toxicol (Phila). 2012;50(4):231-241. [PubMed]
Lee K, Ladizinski B, Federman D. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc. 2012;87(6):581-586. [PubMed]
Chai P, Bastan W, Machan J, Hack J, Babu K. Levamisole exposure and hematologic indices in cocaine users. Acad Emerg Med. 2011;18(11):1141-1147. [PubMed]
Brunt T, van den, Pennings E, Venhuis B. Adverse effects of levamisole in cocaine users: a review and risk assessment. Arch Toxicol. 2017;91(6):2303-2313. [PubMed]
Jennifer S. Love, MD

Jennifer S. Love, MD

Chief Resident
Department of Emergency Medicine
University of Pennsylvania
Jennifer S. Love, MD

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Louise Kao, MD, FACMT

Louise Kao, MD, FACMT

Associate Professor of Clinical Emergency Medicine
Indiana University School of Medicine
Louise Kao, MD, FACMT

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