Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

Abstract

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Detection of Cutting Agents in Drug‐Positive Seized Exhibits within the United States

“…The first cases of toxicity due to the use of levamisole-tainted cocaine were reported in 2009 (39), and some studies already reported deaths as a result of complications secondary to this factor (32,33,(39)(40)(41). Multiple reports link the use of levamisoletainted cocaine to neutropenia, agranulocytosis, methemoglobinemia, and retiform purpura of the face and extremities (27,38,39,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50).…”

Antineutrophil cytoplasmic antibodies negative levamisole‐induced leukocytoclastic vasculitis: a presumed case and literature review

“…When available, the specificity of p‐ANCA may be helpful in differentiating LIV from other vasculitides, as atypical antibody targets like human neutrophilic enolase (HNE) rather than myeloperoxidase (MPO) are more frequently associated with cocaine exposure. Additional laboratory findings in LIV may include neutropenia, leukopenia, agranulocytosis, hypocomplementemia, C‐reactive protein, and elevated sedimentation rate …”

“…As part of the innate immune system, this represents a mechanism to bind and kill extracellular microbes independent of phagocytic uptake. 21,22 A study by Lood and Hughes 22 14,20,21,[28][29][30] There are no established criteria for levamisole-induced vasculitis/vasculopathy, and the diagnosis is based on clinical suspicion and that of exclusion. 14,27,31 Hence, a judicious history and physical exam remain a clinician's strongest diagnostic tool.…”

Bilateral tunnel vision as the first presenting sign of levamisole-induced vasculitis

“…Other recognized manifestations among cocaine abusers are pulmonary-renal syndrome (13), multifocal recurrent leukoencephalopathy with diffuse white matter involvement with sparing of the U fibers, without brain stem or cerebellar involvement (14,15), pyoderma gangrenosum (16), intravascular thrombosis, and less commonly crescentic nephritis, retiform purpura, and pauci-immune glomerulonephritis (17,18). Common side effects are shown in Table 1, while common laboratory values are presented in Table 2.…”