Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children

Abstract

The cutaneous side-effects of levamisole include non-specific and lichenoid eruptions, fixed drug eruption and, very rarely, cutaneous vasculitis. We describe a distinctive clinical and histological vasculopathy with immunological abnormalities in children with paediatric nephrotic syndrome receiving long-term levamisole treatment. Four boys and one girl were identified. Their average age was 10 years. Levamisole had been used for an average of 24 months. Purpura of the ears was the most common finding corresponding histologically to a vasculopathic reaction pattern ranging from a leucocytoclastic and thrombotic vasculitis to a vascular occlusive disease without true vasculitis but with associated antinuclear, antiphospholipid and anticytoplasmic antibodies. The eruption resolved in all patients 2-3 weeks after the discontinuation of levamisole, but serum autoantibodies persisted for 2-14 months.

Cutaneous vasculopathy associated with cocaine use

“…Levamisole was previously used as an immunomodulator for certain malignancies and inflammatory conditions. 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).…”

Case 10-2013

“…Necrosis of the earlobe is a common and distinctive finding associated with levamisole-induced vasculopathy and vasculitis. [5][6][7] This patient's fine, erythematous, blanching, reticular, macular rash bears little resemblance to a levamisole-induced lesion.…”

Levamisole Exposure and Hematologic Indices in Cocaine Users

“…Within 2 to 14 months of drug discontinuation, all markers returned to normal. 24 These adjunctive markers may be very helpful to consultants in managing patients with agranulocytosis and urine screens negative for levamisole. Given the prevalence of levamisole adulteration, its short elimination half life, and the rapidity of recovery, those patients with a history of cocaine use, negative levamisole screening, and positive autoimmune markers may not require bone marrow biopsy to evaluate causes of agranulocytosis.…”

“…1 Similarly, the putative pathogenesis of vasculitis may involve levamisole functioning as a hapten with antibody generation and deposition in vessel walls. 24 None of the other imidazothiazole derivatives used in therapeutic settings cause neutropenia. 11 During our review of the levamisole-associated neutropenia literature, a striking number of individuals-52% of all patients-presented to care for oropharyngeal complaints such as pharyngitis, mouth ulcers, or odynophagia.…”