Vasculopathy, hematological, and immune abnormalities associated with levamisole-contaminated cocaine use.

To report 4 cases of cocaine-related purpura and to review previously reported cases of levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy. We describe 4 patients suspected of vasculopathy associated with levamisole-tainted cocaine use. A retrospective review of the literature was performed using the PubMed, PubJet, MD consult, and Cochrane review databases. Four cases (2 females and 2 males), 46 to 55 years of age, presented with cocaine-related purpura, mainly affecting the ears, neutropenia, and autoantibodies. Skin biopsies revealed a mixed pattern of leukocytoclastic vasculitis and microvascular thrombosis in 2 cases, and pure thrombosis in the third case. The mixed vasculopathic pattern in association with neutropenia, both known adverse effects of levamisole, and levamisole positivity in 2 cases point to this compound as the true etiologic agent in our patients. Eleven cases of levamisole-contaminated cocaine-induced vasculopathy have been described in the English literature. Among these, 10 were females. Age range was 22 to 57 years. Urine levamisole positivity was tested and confirmed in 3 of the 11 cases. The clinical characteristics, laboratory features, histology, treatment, and recovery rates were compared for the published cases of levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy. Adulterated cocaine abuse is an increasingly recognized phenomenon in North America. Levamisole is among the many contaminants that have been detected in seized cocaine throughout North America and Europe. Recent reports described an association between levamisole-tainted cocaine and purpuric skin rash, neutropenia, and the presence of autoantibodies.

Khan TA ，Cuchacovich R ，Espinoza LR ，Lata S ，Patel NJ ，Garcia-Valladares I ，Salassi MM ，Sanders CV Jr ... -  《-》

Cocaine-related retiform purpura: evidence to incriminate the adulterant, levamisole.

The term 'cocaine-induced pseudovasculitis' was coined to encompass a constellation of clinical and laboratory findings which mimics a systemic vasculitis but lacks confirmatory evidence of vasculitis on biopsy. Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase (HNE) have been reported to distinguish the cocaine-related syndrome from a true autoimmune vasculitis. Published cases of retiform purpura related to cocaine use are rare and an etiologic role for levamisole, a common adulterant of cocaine, has been postulated. We describe two female patients aged 39 and 49 years with cocaine-related retiform purpura, mainly affecting the legs. The initial clinical and serological profile in case 1 led to a suspicion of anti-phospholipid syndrome and in case 2 to Wegener's granulomatosis with an unexplained associated neutropenia. Skin biopsies revealed a mixed pattern of leukocytoclastic vasculitis and microvascular thrombosis in case 1 and pure microvascular thrombosis in case 2. Identification of anti-HNE antibodies in both patients linked their disease to cocaine. The mixed vasculopathic pattern in case 1 and the associated neutropenia in case 2, both known adverse effects of levamisole, point to this as the true etiologic agent. Urine toxicology shortly after a binge of cocaine use in each case was positive for levamisole.

Walsh NM ，Green PJ ，Burlingame RW ，Pasternak S ，Hanly JG ... -  《-》

Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leukopenia.

We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy. Cases were seen and reviewed in both the inpatient consult service and the outpatient clinics at Rhode Island Hospital from August 2009 to August 2010. Clinical characteristics as well as pertinent laboratory parameters were also reviewed and corroborated with a review of the present literature. We describe 3 cases of cocaine-levamisole-related cutaneous vasculitis with or without associated neutropenia, and 1 case of severe neutropenia with oral mucosal ulceration. Further serologic studies revealed maximum titers of ANCA mostly in a perinuclear pattern. Antimyeloperoxidase tested negative or mildly elevated in our cohort. Three patients with neutropenia had positive antigranulocyte IgM antibody. Nonsteroidal anti-inflammatory drugs were effective as first-line treatment for joint pain. The use of colchicine and systemic corticosteroid was employed to manage severe and persistent skin lesions. Cocaine-levamisole-related cutaneous vasculitis with leukopenia is a diagnosis of exclusion, but this diagnosis should be strongly considered in patients with a history of cocaine abuse who present with a tetrad of cutaneous manifestations consisting of palpable purpura or bullae with ear involvement, arthralgias, leukopenia, and positive ANCA in high titers and negative Antimyeloperoxidase, when other infectious or idiopathic vasculitic entities have been excluded.

Poon SH ，Baliog CR Jr ，Sams RN ，Robinson-Bostom L ，Telang GH ，Reginato AM ... -  《-》

Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine.

To describe the clinical and serologic abnormalities in 6 patients who presented with retiform purpura and extensive cutaneous necrosis after exposure to levamisole-adulterated cocaine. All patients were evaluated at San Francisco General Hospital or the University of California San Francisco Medical Center. Each underwent standard screening for substances of abuse and had urine tested for the presence of levamisole by liquid chromatography tandem mass spectrometry. Routine laboratory, autoantibody, and antiphospholipid antibody testing was performed in the hospitals' clinical or reference laboratories. Testing for atypical antineutrophil cytoplasmic antibodies (ANCAs) was performed separately using commercially available enzyme-linked immunosorbent assay kits. The patients were women ages 39-50 years who presented with retiform purpura and cutaneous necrosis. Skin biopsies revealed a predominantly small-vessel thrombotic vasculopathy with varying degrees of vasculitis. Four patients were neutropenic. All tested positive for lupus anticoagulant, had IgM antibodies to cardiolipin, and tested strongly positive for ANCAs in a perinuclear pattern by immunofluorescence. Each patient had antibodies to multiple components of neutrophil granules, including neutrophil elastase, lactoferrin, cathepsin G, proteinase 3, and myeloperoxidase. Rheumatologists should be aware of this distinctive form of necrotic purpura, its associated autoantibodies, and its link to levamisole-adulterated cocaine.

Graf J ，Lynch K ，Yeh CL ，Tarter L ，Richman N ，Nguyen T ，Kral A ，Dominy S ，Imboden J ... -  《-》

Retiform purpura: a new stigmata of illicit drug use?

Geller L ，Whang TB ，Mercer SE ，Phelps R ... -  《-》