Case Presentation: A 61-year-old African-American male with a history of hepatitis C virus, syphilis and substance abuse history presented with a 1-day history of painful, blue discoloration of toes, ears, and nose associated with exquisitely tender, hyperpigmented and edematous distal upper and lower extremities. The patient’s urine drug screen was positive for cocaine. The location of the lesions was consistent with levamisole-induced vasculitis (LIV) and the patient was positive for p-ANCA antibodies. The patient was administered a five-day course of high dose prednisone and was discharged to a nursing facility. The patient subsequently returned 3 weeks later with sepsis secondary to osteomyelitis requiring emergent right guillotine below-the-knee amputation, left 2nd and 3rd toe amputations with debridement, as well as bilateral  upper extremity distal digit amputations. Wound cultures were positive for MRSA and Group-B-Streptococci and the patient was placed on IV vancomycin for six weeks. 

Discussion: Initially used as an anthelminthic and antineoplastic agent, Levamisole was withdrawn from the market in 1999 due to its severe immunomodulatory effects, resulting in agranulocytosis, leukopenia, and vasculitis. Levamisole is frequently used as an adulterant in cocaine, and in 2003 the first case of levamisole-induced vasculitis associated with cocaine use was described. By 2009, it was reported that 69% of seized cocaine in the United States was contaminated with levamisole. Patients with levamisole induced vasculitis (LIV) typically present with characteristic purpuric lesions involving distal extremities and may exhibit a broad spectrum of autoantibody findings. The exact pathogenic mechanism of autoantibody formation still remains elusive, however it has been proposed that levamisole may act as a hapten as animal studies have revealed delayed-type-hypersensitivity reactions occurring after injection of the thiol moiety of levamisole as well as the ability to dampen those reactions with prior immunization of a hapten-carrier complex. Steroids are commonly used as part of the management approach, however the efficacy of immune-suppression and the optimal immunosuppressive modality remain unclear given the relative novelty of LIV. Therefore management is largely supportive in nature and fortunately, in the majority of cases, immunologic abnormalities and symptoms typically resolve within months of agent withdrawal. However as this case indicates, in certain instances LIV has the capability of yielding devastating results. 

Conclusions:  This case illustrates the potentially fulminant progression of an increasingly reported disease. Levamisole induced vasculitis is a diagnosis of exclusion, but it should be strongly considered in cases involving neutropenia, leukopenia, palpable purpura of the distal extremities with necrotic centers, and positive ANCA serology.