Clinical, histopathologic, and immunofluorescence findings in levamisole/cocaine‐induced thrombotic vasculitis
Year: 2013
Type: article
Study design: Case Report
Abstract: The addition of inexpensive agents to cocaine in order to increase the mass of marketable product is common practice. Because it potentiates the pharmacologic effects of cocaine,1 the addition of levamisole allows for the adulteration of cocaine with minimal impact on its perceived potency. Levamisole has been found in an estimated 80% of cocaine in the USA.2,3 We present a case of levamisole-induced thrombotic vasculitis. A 49-year-old African-American man presented with a 1-week history of a painful eruption consisting of retiform purpura of the trunk and extremities and necrotic palpable purpura of the earlobes, cheeks, and nasal tip (Fig. 1). Two skin biopsies, one from each upper arm, revealed necrotizing vasculitis of the reticular dermal vessels with mural infiltration by neutrophils and luminal occlusion with fibrinous material (Fig. 2a–c). Direct immunofluorescence demonstrated granular deposition of immunoglobulin M (IgM), C3, and fibrin in the superficial reticular dermal vessel walls (Fig. 2d). (a, b) Multiple tender, dusky, macular and palpable purpura of the nose, cheeks and ears (a) Histopathology demonstrates (a) the occlusion of superficial blood vessels and diffuse extravasation of red cells, (b) the occlusion of blood vessels by fibrin-red cell thrombi, and (c) fibrin thrombus in a blood vessel. [Hematoxylin and eosin stain; original magnification (a) ×10, (b) ×20, (c) ×40.] (d) Direct immunofluorescence showing the deposition of C3 in blood vessel walls in the superficial reticular dermis (×10) Cytoplasmic (c-ANCA) and atypical perinuclear (p-ANCA) anti-neutrophil cytoplasmic antibodies were detected. Levels of antibodies to myeloperoxidase and proteinase-3 were 14.7 U/ml (normal range: 0–9 U/ml) and 82.5 U/ml (normal range: 0–3.5 U/ml), respectively. Lupus anticoagulant and anticardiolipin IgM and IgG antibodies were present. A urine toxicology screen was positive for cocaine. The patient experienced marked improvement with a short taper of oral prednisone and cessation of cocaine use. Levamisole-induced thrombotic vasculitis typically manifests as retiform purpura of the extremities and tender palpable purpura of the nose, cheeks, and ears that may be accompanied by leukopenia and agranulocytosis.3,4 The reason for the predominance of clinical lesions on the face and earlobes is not known and may relate to the fact that vascular blood flow in the face and earlobes is relatively sluggish as a result of both the small-caliber vessel size and the cooler body temperature at locations such as the earlobes and nose. Histopathology reveals a thrombotic vasculopathy with a variable neutrophilic infiltrate similar to that of leukocytoclastic vasculitis. At the time the patient was evaluated, direct immunofluorescence findings were not generally reported. Patients typically have both p- and c-ANCAs,5–9 and antibodies to human neutrophil elastase (HNE) may be a specific marker for this entity.9 Anticardiolipin antibody and lupus anticoagulant are variably present.5–9 The presence of levamisole is difficult to confirm as a result of its short half-life (5.6 h), the lack of widespread access to testing, and the low sensitivity of urine and blood assays.10 Management is supportive. Lesions resolve within weeks of discontinuing levamisole, and associated antibodies clear in 2–14 months.7 Cocaine-induced midline destructive lesions (CIMDL) represent an entity that may be related to levamisole-induced thrombotic vasculitis. Patients with CIMDL present with necrotic midline nasal and perinasal lesions mimicking Wegener’s granulomatosis. Histopathology may reveal a dense mixed perivascular infiltrate, leukocytoclastic vasculitis, vascular mural microabscesses, or thrombosis of venules and/or medium-sized arterioles.11,12 Positivity for ANCA is common, and HNE antibodies have been reported to occur in as many as 56% of subjects in a case series of 25 CIMDL patients.12 The similarities between CIMDL and levamisole-induced thrombotic vasculitis are striking, and these disorders may be part of the same disease process.9 ANCA-associated vasculitis (AAV) is an entity that may also be related to levamisole-induced thrombotic vasculitis. It refers to a group of vasculitides that are highly associated with ANCA positivity and may be idiopathic or drug induced.13,14 Causes of drug-induced AAV include intake of propylthiouracil, minocycline, allopurinol, and levamisole. Drug-induced AAV manifests as retiform purpura, painful subcutaneous nodules, and palpable purpura13,14 (with a predilection for the face and earlobes in propylthiouracil- and levamisole-induced cases),15,16 commonly with neutropenia. Direct immunofluorescence of cutaneous lesions reveals immune complex deposition in blood vessel walls.17 Identification and cessation of the causative drug often result in rapid improvement. We believe that the vasculitis caused by levamisole-containing cocaine is a form of drug-induced AAV. The presence of multiple autoantibodies, including antiphospholipid antibodies, has also been reported in other cases.5–9 In the histopathologic presence of vascular occlusion, it is tempting to consider that these antibodies play a role in the pathogenesis. Because other biopsy findings have shown features of vasculitis in addition to thrombosis, it is difficult to determine the primary event, and more detailed evaluation of future cases will be needed. This case not only serves to remind us that levamisole can induce thrombotic vasculitis, but is also, to our knowledge, the first report to include direct immunofluorescence findings. As the majority of cocaine at present is processed with levamisole, clinicians need to be aware of this entity and its unique clinicopathologic and immunologic manifestations.
Authors: David R. Crowe, Pamina S. Kim, Diya F. Mutasim
Institutions: MetroHealth Medical Center, University of Cincinnati
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2095623455