Mysterious Purpura & Neutropenia in a Cocaine User

Introduction:
The following clinical presentation is increasingly being seen in urban hospitals throughout the country. The main findings are:

• Purpuric skin lesions
  
• Severe neutropenia
  
• High fever
• Swollen glands
• Painful sores on the mouth or anus
• Lingering infections, including sore throat, mouth sores, skin infections, abscesses, thrush, or pneumonia

It's diagnosis is challenging given that this condition has many shared exam and laboratory findings as many vasculitides. In particular, these patients often have lupus anticoagulant and c- or p-ANCA positivity.

Case:
Ms. F is a 38-year-old woman with hepatitis C, remote miscarriage, and active polysubstance abuse who was admitted for MRSA endocarditis. A toxicology screen performed on admission was positive for cocaine, opiates, and benzodiazepines. She developed a deep venous thrombosis on her right lower extremity that was initially treated with heparin and an appropriate bridge to warfarin. On day 27 (day 12 of warfarin), she developed multiple discrete, stellate, purpuric macules, papules, and plaques with a bright erythematous border on her pinna, earlobes, cheeks, right breast, and bilateral proximal upper and lower extremities. Concomitant unexplained episodic tachycardia and neutropenia were noted. Skin biopsy specimens revealed leukocytoclastic vasculitis with mural fibrin deposition, neutrophilic infiltrate, nuclear dust, and extravasated erythrocytes involving superficial small vessels with pauciinflammatory luminal thrombosis in a few vessels. Synchronous tests revealed positive platelet factor IV antibody (but negative serotonin release assay), mixing studies (noncorrecting), lupus anticoagulant, and Russell viper venom time. Antineutrophil cytoplasmic antibodies (ANCAs) directed against proteinase-3 (PR-3) were 39.2 EU/mL (normal, <4.0>9/L). A subsequent urine toxicology screen on hospital day 33 was positive for cocaine, confirming in-hospital cocaine use.

Diagnosis:
This is a case of levamisole toxicity. Levamisole is an antihelmithic drug that has increasingly been used as a cutting agent for cocaine. In July 2009, the Substance Abuse and Mental Health Services Administration (SAMHSA) found the drug in over 70% of cocaine analyzed. Another recent analysis in Seattle, WA found individuals who tested positive for cocaine also tested positive for levamisole nearly 80% of the time.The Drug Enforcement Agency says it has seen a steady increase in the amount of the medication found in cocaine since 2002. Complete clinical resolution of skin lesions occurs 2 to 3 weeks after stopping levamisole and serologies normalize within 2 to 14 months. Detection of levamisole is challenging, because specific testing is necessary but not routinely available; levamisole's half-life is so short (5.6 hours) that only 2% to 5% of the parent drug is detected in urine; and the sensitivity of available testing is low. However, the clinical constellation of retiform purpura, neutropenia, lupus anticoagulant and ANCA positivity, and temporal association with cocaine use is nearly pathognomonic for levamisole toxicity. So, next time you're in the ED and you see a patient with purpura and neutopenia in the context of a positive utox for cocaine, add this to your differential!

Reference: Trimarchi et al. Cocaine-induced midline destructive lesions: clinical, radiographic, histopathologic, and serologic features and their differentiation from Wegner granulomatosis. Medicine (Baltimore) 2001; 80:391-404.