Cocaine contaminated with levamisole has been detected in the United States since 2003, and the incidence of toxicity caused by this contamination has been increasing rapidly since 2008. Use of levamisole-adulterated cocaine most often leads to a syndrome of levamisole-associated vasculopathy or vasculitis. Symptoms appear within days to several weeks after use, including agranulocytosis, neutropenia, and a vasculitis-like purpuric tender skin eruption. The most common sites of purpura are the external ears and cheeks. Arthralgias (the most common systemic manifestation), persistent rhinorrhea, fever, and mouth pain can also be present. The purpura is generally followed by skin necrosis, but resolves several weeks after cessation of cocaine use. Purpura associated with levamisole occurs in approximately 0.5% to 3% of all exposed patients. Recurrent use of contaminated cocaine generally results in recurrent skin eruptions.
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
Cocaine levamisole toxicity
Alerts and Notices
Synopsis
Codes
ICD10CM:
F14.188 – Cocaine abuse with other cocaine-induced disorder
L95.8 – Other vasculitis limited to the skin
SNOMEDCT:
9982009 – Poisoning by cocaine
F14.188 – Cocaine abuse with other cocaine-induced disorder
L95.8 – Other vasculitis limited to the skin
SNOMEDCT:
9982009 – Poisoning by cocaine
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
The differential diagnosis for cocaine levamisole toxicity includes many of the same diagnoses as for leukocytoclastic vasculitis (LCV) or drug toxicities. Secondary causes of LCV such as infection, medication reactions, neoplasms, and autoimmune connective tissue disorders should be sought out.
- Cryoglobulinemia – check for serum IgM and IgG cryoglobulins, hepatitis C virus infection.
- Cryofibrinogenemia
- 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.
- Calciphylaxis
- 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
Best Tests
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Management Pearls
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
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References
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Last Reviewed:05/25/2017
Last Updated:06/06/2017
Last Updated:06/06/2017
Cocaine levamisole toxicity