Levamisole Adulterated In Cocaine Causing Agranulocytosis, Vasculopathy and Acquired Protein S Deficiency
Authors: Dy Irene , Pokuri Venkata , Gamboa Eric O. , Olichney John 
Published: October 2019

Abstract
Abstract 1421
More than 2 million Americans use cocaine each month. Levamisole is a veterinary antihelminthic agent that has been used as a cutting agent in cocaine and adds bulk to powdered cocaine. It has been used for the treatment of colon cancer, rheumatoid arthritis and nephrotic syndrome. According to the Drug Enforcement Administration (DEA) as of July 2009, 69% of seized cocaine lots coming into the United States contained levamisole as an added agent. Levamisole has recently been reported to cause neutropenia in cocaine abusers. We report a case of a severe cutaneous necrotizing vasculopathy, agranulocytosis with acquired protein S deficiency caused by tainted cocaine in an active abuser.
A 44-year-old active cocaine abusing woman presented with a day of acute worsening cutaneous lesions, subjective fever and arthralgias. She last inhaled three bags of cocaine the day prior to admission. On examination, she had multiple tender palpable purpuric plaques with central necrosis on her thighs, lower extremities, chest, abdomen, arms, and bilateral ear helices. Urine toxicology screen was positive for cocaine. Laboratory data showed neutropenia of 1.4 × 103/uL with mild anemia (haemoglobin 12g/dl) and normal platelet count. She had anemia of chronic disease with negative Coombs test. She also has normal kidney and liver functions. Vasculitides and rheumatological workup showed positive antineutrophil cytoplasmic antibodies (ANCAs) directed against proteinase-3 (PR-3) and myeloperoxidase (MPO) but negative for ANA or rheumatoid factor and normal complement levels. Assays for syphilis, hepatitis B and C, and the human immunodeficiency virus were negative. A skin biopsy showed small vessel thrombo-vasculopathy with organizing thrombus and mixed cell infiltrate. Subsequent workup for hypercoagulable states revealed a positive lupus anticoagulant and a low protein S activity. The patient was treated with steroids. Her skin lesions and neutropenia improved gradually in two weeks.Figure 1.Palpable purpuric plaques on bilateral lower extremities.Figure 1. Palpable purpuric plaques on bilateral lower extremities.Figure 2.Necrotic ear helix.Figure 2. Necrotic ear helix.Figure 3.Skin biopsy showing small vessel thrombovasculopathy, organizing thrombus and mixed cell infiltrate.Figure 3. Skin biopsy showing small vessel thrombovasculopathy, organizing thrombus and mixed cell infiltrate.
The acute onset of necrotic skin lesions following cocaine use, ANCA positivity, histopathology and neutropenia strongly suggest levamisole-induced vasculopathy. Although levamisole levels were not obtained, exposure from cocaine contamination is very likely. Levamisole is known to have immunostimulating effects with the production of autoantibodies like ANCA. Life-threatening agranulocytosis and a positive lupus anticoagulant have been reported in a few cases of prolonged levamisole use. The pathogenesis of agranulocytosis is hypothesized to either be a direct toxin effect or immune-mediated. Lupus anticoagulant has also been reported to cause a similar pattern of cutaneous necrosis. Clinicians should be aware of this kind of clinical presentation in active cocaine abusers and consider it as a significant emerging public health problem.

Disclosures:
No relevant conflicts of interest to declare.