Cocaine levamisole toxicity
Pyoderma gangrenosum has also been reported to be associated with levamisole-adulterated cocaine, and almost always involves the lower extremities and often the upper extremities, while lacking the ear involvement and arthralgias that are common with levamisole-associated purpura. Case reports also exist of pulmonary hemorrhage or acute renal failure associated with levamisole-induced vasculopathy.
Levamisole is a synthetic imidazothiazole antihelminthic agent with immunomodulatory properties, and was previously used for various inflammatory or neoplastic diseases until its removal from the United States market in 2000 due to side effects of agranulocytosis and vasculitis. However, it is still widely used as a veterinary antihelminthic drug and cocaine-bulking agent. The Centers for Disease Control and Prevention (CDC) estimate that approximately 70% of cocaine in the United States may be contaminated with levamisole. Toxicity induced by levamisole seems to affect all ages and both sexes equally depending on cocaine use. The cocaine can be either smoked as crack cocaine or snorted.
Because levamisole is difficult to test for and because other treatable causes of vasculitis may be present, levamisole-induced vasculopathy is a diagnosis of exclusion. Several published cases have had concurrent or preceding medical histories that involve both chronic and acute infections as well as signs of chronic autoimmune disease. Other cases have had absolutely no preceding medical history. Cannabis has also been associated with vascular disease, but that finding may be confounded by the frequent presence of a smoking history. Levamisole has also been found to be a contaminant in heroin, although heroin-related levamisole vasculopathy has not yet been reported.
Since neutropenia is a common presenting sign of this toxicity, bacterial or fungal infections may be presenting features of levamisole toxicity.
Related topics: Cocaine Use Disorder, Cocaine Mucosal Ulcer, Cocaine-Related Cardiomyopathy
F14.188 – Cocaine abuse with other cocaine-induced disorder
L95.8 – Other vasculitis limited to the skin
9982009 – Poisoning by cocaine
Differential Diagnosis & Pitfalls
- Cryoglobulinemia – check for serum IgM and IgG cryoglobulins, hepatitis C virus infection.
- Bacterial sepsis
- Coumadin necrosis
- Heparin necrosis
- Purpura fulminans
- Acute meningococcemia – the patient is usually systemically ill, but since cocaine use may complicate the neurologic exam, this diagnosis should be considered carefully.
- Vasculitis secondary to viral infections such as hepatitis A, B, C, varicella-zoster virus, parvovirus B19, and cytomegalovirus, or to medications.
- Arthropod bites
- Erythema multiforme minor (EM) – characteristic findings on histology will assist in differentiating EM. Systemic involvement is rare.
- Toxic epidermal necrolysis (TEN) – usually larger areas of skin are involved with more skin pain and resulting bullae.
- Frostbite or chilblains (perniosis) – history of recent cold exposure.
- Microscopic polyangiitis is ANCA positive and has palpable purpura and constitutional symptoms; look for evidence of pulmonary and renal involvement.
- Granulomatosis with polyangiitis is ANCA positive and has necrotizing granulomatous inflammation of the upper and lower respiratory tracts and glomerulonephritis.
- Eosinophilic granulomatosis with polyangiitis is ANCA positive and is associated with eosinophilia and asthma.
- Polyarteritis nodosa – medium vessel vasculitis with subcutaneous nodules, livedo reticularis, ulcers, and gangrene as cutaneous manifestations.
- Immune thrombocytopenic purpura – look for isolated thrombocytopenia.
- Over-anticoagulation with Coumadin (warfarin) or heparin
- Early disseminated intravascular coagulation
Drug Reaction Data