Cutaneous necrotising vasculitis induced by levamisole.

Abstract

Cutaneous necrotising vasculitis induced by levamisoleThe anthelmintic agent levamisole has immunostimulant properties in patients with defective cell-mediated immune responses. We are assessing the drug in patients with breast cancer to see whether it can maintain surgically induced remission. One such patient developed a severe cutaneous necrotising vasculitis, which disappeared once the drug was withdrawn. Case reportA 59-year-old woman had been receiving thrice-weekly levamisole 150 mg/day for three months, when in May 1975 she developed fever and a severe rash. Cutaneous necrotising vasculitis was diagnosed. Biopsy of one of the lesions showed intense neutrophil and eosinophil infiltration of the vessel wall with obliteration of the lumen. There were no other physical abnormalities, and no sign of the original disease was noted. She had not been taking any other drugs.Haemoglobin was 13 g/dl and white cell count 3 0 x 109/1 (3000/mm3; 30 % segmented neutrophils, 8 0o eosinophils, 10 Po monocytes, 52°lymphocytes). Results of complement studies were within normal limits, and other immunological and biochemical values were normal. A bone-marrow aspirate showed a normal distribution of white and red cells but a moderate increase in eosinophils. A chest radiograph was normal.Levamisole was discontinued and the patient given a short course of prednisone 40 mg daily. After two weeks the clinical picture returned to normal, and three months later the skin lesions showed no signs of recurrence and the white cell count was normal. CommentLevamisole-induced vasculitis has not been reported, despite wide use of the drug in various conditions, including malignant and rheumatic diseases.1-3 The pathogenesis of our patient's skin reaction is unknown, though histologically it was similar to an Arthus-type reaction, in which immune-complex formation or complement activation is usually implicated. We found no complement abnormalities in our patient, but the tests did not exclude a local type III reaction.The peripheral blood neutropenia in our patient also implicates levamisole as the causal agent, since neutropenia and agranulocytosis are associated with levamisole treatment.3 The exact mechanism of this reaction is unknown, but the peripheral and central eosinophilia suggest a hypersensitivity reaction. Although we did not challenge the patient (for ethical reasons) we think that levamisole was the likely cause of the vasculitis.

Cutaneous vasculopathy associated with cocaine use

“…In a series of children treated for nephrotic syndrome, levamisole was associated with the development of vasculitic skin lesions particularly involving the ear lobes and the face, as well as positive ANCA, ANA, and aPL (10). In addition, a case of cutaneous necrotizing vasculitis was described in a woman receiving levamisole for breast cancer (11). It is estimated that up to 70% of street cocaine in parts of the US and Canada is contaminated with levamisole (12).…”

Drug-Induced Glomerular Disease

“…Reports exist describing cutaneous vasculitis (13,14) and the presence of autoantibodies, including ANCAs (15,16), in patients exposed to levamisole. Levamisole was withdrawn from the market in the United States in 2000 because of cases of treatment-associated agranulocytosis.…”

Levamisole-Adulterated Cocaine: A Case Series

“…10 As early as the 1970s, case reports of levamisoleinduced skin reactions or neutropenia were documented. 11,12 Recent case reports of patients thought to be affected by cocaine adulterated with levamisole present with a similar clinical picture: urine drug screen positive for cocaine, leukopenia, characteristic cutaneous manifestations, and positive autoimmune serologies. With more severe leukopenia, patients may have infectious complications as well.…”