Case Presentation:

A 49–year–old male with diabetes mellitus presented with jaw pain and an absolute neutrophil count (ANC) of 200 cells/mm³. He denied drug use. A periodontal abscess seen on computerized tomogram was treated by incision, drainage, and antibiotics. Incidental proteinuria and microscopic hematuria were noted. Neutropenia was attributed to glipizide toxicity. As an outpatient neutropenia persisted; bone marrow biopsy and peripheral blood flow cytometry were normal. HIV, anti–nuclear antibodies, rheumatoid factor, hepatitis B and C serologies, cytomegalovirus IgM, and Epstein–Barr IgM were negative. Three months later he represented to our care with malaise, arthralgias and pustules on the dorsum of his fingers, right nasal ala and axilla. The ANC was 60 cells/mm³. Microhematuria with proteinuria persisted, and urine microscopy demonstrated abundant acanthocytes. Anticardiolipin IgM was positive. Anti–neutrophil cytoplasmic antibodies were strongly positive with a perinuclear staining pattern and both proteinase 3 and myeloperoxidase reactivity. Drug–induced vasculitis was suspected, and after urine toxicology revealed cocaine, the patient admitted to several years of daily use. Gas chromatography/mass spectrometry at a Food and Drug Administration lab confirmed the presence of urinary levamisole. After 2 months of abstinence, the ANC and the hematuria normalized.

Discussion:

Originally introduced as an antihelminthic in the 1960s, levamisole’s immunomodulating effects were later applied to a variety of diseases, including rheumatoid arthritis (RA), colorectal cancer, and nephrotic syndrome. First detected in cocaine in 2005, levamisole now contaminates over 70% of seized samples in the USA for unclear reasons. The complications of previous levamisole pharmacotherapy predict the clinical effects of levamisole–tainted cocaine use. Agranulocytosis is a common complication of both clinical and illicit levamisole exposure. Reports exist of a retiform purpuric rash with underlying vasculitis affecting pediatric patients who took levamisole for nephrotic syndrome, as well as modern cocaine users. Regardless of the mode of exposure, levamisole can induce ANA, ANCA, and anti–phospholipid antibodies, though their pathophysiologic role is unclear. Our patient had proteinuria and abundant urinary acanthocytes. The latter finding is highly specific for glomerulonephritis and cannot be otherwise explained by his past medical history. Resolution following reported cocaine abstinence implicates levamisole as a culprit. Levamisole has been associated with biopsy–proven glomerulonephritis in a patient with RA who later fully recovered following drug cessation. We propose a similar glomerulonephritis may manifest in patients using levamisole–tainted cocaine.

Conclusions:

Hospitalists should be aware of an associated autoimmune vasculitic syndrome in patients exposed to levamisole–tainted cocaine. To our knowledge, this is the first reported association with possible glomerulonephritis.