Peer Reviewed

Photoclinic

Levamisole Toxicity From Adulterated Cocaine

Volume 59 - Issue 1 - January 2019

  • Levamisole is not detected in routine toxicology screens, but other laboratory abnormalities can include neutropenia/agranulocytosis and positive test results for p-ANCA, lupus anticoagulant antibodies, anti–double-stranded DNA, proteinase-3, and anticardiolipin antibodies.8-10 Some laboratory test result disparities may aid in distinguishing levamisole vasculitis from idiopathic ANCA-associated vasculitis, since patients will have extremely high p-ANCA levels and low (or absent) antibodies to myeloperoxidase, the typical target of p-ANCA.9,10 Additionally, other types of ANCA vasculitis may show lower ANCA titers, with specific antibodies to one neutrophilic antigen rather than several.10 The various immune markers may remain positive from 2 months to up to 1 year after discontinuation.10

    Stellate purpura in the setting of recent cocaine use is becoming a recognizable clinical syndrome.7 Our patient’s recent hospitalization for pneumonia with intravenous antibiotic treatment widened the differential to a possible drug reaction. Such clinical findings also require consideration of autoimmune and inflammatory vasculopathic conditions.10 Levamisole can cause extracutaneous disease secondary to vasculitis involving any organ system—most notably pulmonary vasculopathy, glomerulonephritis, coronary vasculitis, ischemic colitis, ulcers, and rarely pancreatitis.1,11 Renal and pulmonary disease occur more commonly in idiopathic ANCA-associated vasculitis; reports suggest that it is commonly overlooked in levamisole toxicity cases.9,10 Early recognition of levamisole as the offending agent is paramount in avoiding unnecessary aggressive treatments associated with the misdiagnosis of an autoimmune cause of vasculitis.10

    Management. Treatment is primarily supportive following strict abstinence from cocaine. Necrotic plaques may require debridement and prevention of secondary infection.12 Corticosteroids, hyperbaric oxygen, and methotrexate have led to improvement in case reports; however, no evidence-based studies have demonstrated benefit over a conservative approach.3,8 Skin grafting may be necessary; some studies recommend early graft intervention with large body surface area involvement.12

    References:

    1. Lee KC, Ladizinski B, Nutan FNU. Systemic complications of levamisole toxicity. J Am Acad Dermatol. 2012;67(4):791-792.
    2. Drug Enforcement Administration, Office of Diversion Control, Drug & Chemical Evaluation Section. Levamisole (Ergamisol®). https://www.deadiversion.usdoj.gov/drug_chem_info/levamisole.pdf. April 2013. Accessed November 27, 2018.
    3. Bradford M, Rosenberg B, Moreno J, Dumyati G. Bilateral necrosis of earlobes and cheeks: another complication of cocaine contaminated with levamisole. Ann Intern Med. 2010;152(11):758-759.
    4. Mallette JR, Casale JF, Jones LM. The separation of cocaine and phenyltetrahydroimidazothiazole mixtures. Microgram J. 2013;10(2):12-16.
    5. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. Vol 2. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2014:1402-1403.
    6. Chung C, Tumeh PC, Bimbaum MD, et al. Characteristic purpura of the ears, vasculitis, and neutropenia—a potential public health epidemic associated with levamisole adulterated cocaine. J Am Acad Dermatol. 2011;65(4):722-725.
    7. Nolan AL, Jen K-Y. Pathologic manifestations of levamisole-adulterated cocaine exposure. Diagn Pathol. 2015;10:48.
    8. Belfonte CD, Shanmugam VK, Kieffer N, Coker S, Boucree A, Kerr G. Levamisole-induced occlusive necrotizing vasculitis in cocaine abusers: an unusual cause of skin necrosis and neutropenia. Int Wound J. 2013;10(5):590-596.
    9. Álvarez Díaz H, Marińo Callejo AI, García Rodríguez JF, Rodríguez Pazos L, Gómez Buela I, Bermejo Barrera AM. ANCA-positive vasculitis induced by levamisole-adulterated cocaine and nephrotic syndrome. Am J Case Rep. 2013;14:557-561.
    10. Strazzula L, Brown KK, Brieva JC, et al. Levamisole toxicity mimicking autoimmune disease. J Am Acad Dermatol. 2013;69(6):954-959.
    11. Pearson T, Bremmer M, Cohen J, Driscoll M. Vasculopathy related to cocaine adulterated levamisole: a review of the literature. Dermatol Online J. 2012;18(7):1.
    12. Miner J, Gruber P, Perry TL. Early excision and grafting, an alternative approach to surgical management of large body surface area levamisole-adulterated cocaine induced skin necrosis. Burns. 2015;41(3):e34-e40.