Otolaryngologic Manifestations of Levamisole-Induced Vasculitis | Laryngology | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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March 2016

Otolaryngologic Manifestations of Levamisole-Induced Vasculitis

Author Affiliations
  • 1Department of Otolaryngology—Head and Neck Surgery, University of California, San Francisco, San Francisco.
JAMA Otolaryngol Head Neck Surg. 2016;142(3):299-300. doi:10.1001/jamaoto.2015.3565

Levamisole is a synthetic imidazothizole derivative that was introduced in the 1970s for the treatment of rheumatalogic conditions and cancer owing to its immunomodulatory effects.1 Although withdrawn from the market in 2000 because of severe adverse reactions,2 levamisole is commonly found in cocaine. Adverse effects of levamisole include neutropenia, agranulocytosis, and vasculitis. Patients with levamisole-induced vasculitis (LIV) typically present with necrotic cutaneous lesions, secondary to microvascular thrombosis and small-vessel vasculitis, arthralgias, and malaise.3 Necrosis of the ears, malar eminence, and nose are among the most common findings of LIV. Despite increasing incidence, the full spectrum of otolaryngologic manifestations of LIV has yet to be delineated. Herein we report the first case, to our knowledge, of laryngeal involvement in LIV.

Report of a Case

An adult patient with a history of crack cocaine abuse presented with several days of malaise, painful violacious pupura, and necrosis of bilateral cheek and ear skin. Lesions were nonblanching centrally, with a rim of erythema. Similar lesions were present on the thighs and hard palate (Figure 1). The patient's voice was rough and breathy. Endoscopy revealed normal hypopharyngeal and supraglottic mucosa, but bilateral ulcerative lesions of the true vocal folds with surrounding edema were detected (Figure 2). There were no mucosal stigmata to suggest burn injury. Complete blood cell count findings were normal while results of antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA) testing were positive. Results of urine toxicology testing was positive for cocaine metabolites, which was in concordance with the presumed diagnosis of LIV. The facial lesions were treated with oral steroids and petroleum jelly ointment, and the patient was counseled to cease cocaine use. When seen at follow-up visits at 1, 8, and 16 weeks, the patient's facial lesions had healed with minimal scaring. The patient’s voice remained rough and breathy, with stiffening of the bilateral vocal folds observed on videostroboscopy.

Figure 1.  Levamisole-Induced Vasculitic Lesions of the Thigh
Levamisole-Induced Vasculitic Lesions of the Thigh

Patient with history of crack cocaine abuse presented with painful violacious pupura and necrosis of the skin.

Figure 2.  Levamisole-Induced Vasculitis of the Vocal Folds
Levamisole-Induced Vasculitis of the Vocal Folds

Laryngoscopy revealed ulcerative lesions of the true vocal folds with surrounding edema.


The differential diagnoses for a patient with retiform purpura is extensive, and includes small- and medium-sized vessel vasculitis, infectious, embolic, and rheumatologic phenomena.4 In LIV, p-ANCA, c-ANCA, anti-PR3, anti-MPO, and anti-HNE are variably positive. Definitive diagnosis is by liquid chromatography–tandem mass spectrometry from a urine sample. However, this is infrequently available in the clinical setting, and must be performed soon after exposure because of the short half-life of levamisole. Thus, diagnosis is dependent on the typical features of diffuse purpuric lesions, including the helical rims of the ears, serological testing, and the appropriate epidemiologic context.5

Workup should include a drug use history and physical examination of the skin, oral cavity, and larynx. Complete blood cell count should be obtained to rule out agranulocytosis. Urine toxicology, ANA, and ANCA should be performed and, if available, liquid chromatography–tandem mass spectrometry for the presence of levamisole. Laboratory testing to rule out other entities should be pursued on a case-by-case basis and requires consultation with rheumatology specialists. Biopsy, if performed, reveals thrombotic microvascular angiopathy, which is similarly nonspecific. Treatment is supportive and resolution of lesions is seen with cessation of cocaine use.

Recent estimates suggest that more than 70% of cocaine in the United States is contaminated with levamisole.3 The addition of levamisole to cocaine likely occurs because of its physical similarity to cocaine, allowing it to be used as a bulking agent, and because it appears to potentiate the desired effects in all forms of use. Recent work suggests that levamisole enhances the rewarding and locomotor-activating effects of cocaine and displays modest rewarding and locomotor-stimulant effects of its own.6 Herein we describe the first case to our knowledge of laryngeal involvement in LIV. Knowledge of the cutaneous and mucosal patterns of involvement is key to making the diagnosis. Prompt identification of this diagnosis is paramount because cessation of use of levamisole-adulterated cocaine is requisite for resolution of symptoms.

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Article Information

Corresponding Author: A. Sean Alemi, MD, Department of Otolaryngology—Head and Neck Surgery, University of California, 2233 Post St, 3rd Floor, San Francisco, CA 94115 (sean.alemi@ucsf.edu).

Published Online: January 28, 2016. doi:10.1001/jamaoto.2015.3565.

Conflict of Interest Disclosures: None reported.

Previous Presentation: This case report was presented as an abstract at the Combined Otolaryngology Spring Meeting; April 24, 2015; Boston, Massachusetts.

Popovic  M, Stefanovic  D, Pejnovic  N,  et al.  Comparative study of the clinical efficacy of four DMARDs (leflunomide, methotrexate, cyclosporine, and levamisole) in patients with rheumatoid arthritis.  Transplant Proc. 1998;30(8):4135-4136.PubMedGoogle ScholarCrossref
Lee  KC, Ladizinski  B, Federman  DG.  Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge.  Mayo Clin Proc. 2012;87(6):581-586.PubMedGoogle ScholarCrossref
Centers for Disease Control and Prevention (CDC).  Agranulocytosis associated with cocaine use—four States, March 2008-November 2009.  MMWR Morb Mortal Wkly Rep. 2009;58(49):1381-1385.PubMedGoogle Scholar
Tran  H, Tan  D, Marnejon  TP.  Cutaneous vasculopathy associated with levamisole-adulterated cocaine.  Clin Med Res. 2013;11(1):26-30.PubMedGoogle ScholarCrossref
Hahn  E, Bogoch  II.  Levamisole-induced vasculitis in a cocaine user.  J Rheumatol. 2015;42(10):1924-1925.PubMedGoogle ScholarCrossref
Tallarida  CS, Tallarida  RJ, Rawls  SM.  Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats.  Drug Alcohol Depend. 2015;149:145-150.PubMedGoogle ScholarCrossref