CORRECT DIAGNOSIS:

Cocaine levamisole toxicity

DISCUSSION:

The woman described in this case presents with signs and symptoms suggestive of cocaine levamisole toxicity. Cutaneous manifestations of levamisole toxicity can range from exanthems, urticarial, angioedema, lichenoid eruptions to vasculitis and Stevens-Johnson syndrome. A distinguishing feature are the characteristic necrotic and purpuric skin eruptions that preferentially involve the ear lobes and cheeks.

Stellate purpura in the setting of recent cocaine use is becoming a recognizable clinical syndrome. Our patient’s recent hospitalization for pneumonia with intravenous antibiotic treatment opens up the differential to a possible drug reaction. The clinical findings also require consideration of autoimmune and inflammatory vasculopathic conditions. However in our case, the history served an important clue in the setting of stellate purpura. Levamisole can cause extra-cutaneous disease secondary to vasculitis involving any organ system; most notably pulmonary vasculopathy, glomerulonephritis, coronary vasculitis, ischemic colitis, GI ulcers and rarely pancreatitis. Renal and pulmonary disease occurs more commonly in idiopathic ANCA associated vasculitis; reports suggest it is commonly overlooked in levamisole toxicity cases. Early recognition of levamisole as the offending agent is pinnacle in avoiding any unnecessary aggressive treatments associated with the misdiagnosis of an autoimmune cause for vasculitis.

Levamisole is not detected in routine toxicology screens, but other laboratory abnormalities can include positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), neutropenia/agranulocytosis, lupus anticoagulant, anti-dsDNA, proteinase-3 (PR3) and anti-cardiolipin antibody. Some laboratory disparities may aid in distinguishing levamisole vasculitis from idiopathic ANCA- associated vasculitis as patients will result with extremely high p-ANCA and low (or absent) antibodies to myeloperoxidase (MPO), the typical target of p-ANCA. Additionally other types of ANCA vasculitis may show lower ANCA titers with specific antibodies to one neutrophilic antigen rather than several. The various immune markers may remain positive from 2 months to up to 1 year after discontinuation.

Levamisole was withdrawn from in the U.S. market in 1999 due to serious side effects related to agranulocytosis along with development of safer alternative antihelminths. It is still currently in use as a deworming agent in livestock and aquariums, thus it’s availability as a cutting agent in cocaine. Approximately 70% if cocaine in the U.S. is contaminated with levamisole. It adds bulk and a purity factor due to its color, weight and white powdery consistency. There may also be an added stimulant effect of levamisole making it ideal for passing street tests by users and dealers.

TREATMENT:

Treatment is primarily supportive following strict abstinence from cocaine. Necrotic plaques may require debridement and prevention of secondary infection. Corticosteroids, hyperbaric oxygen, and methotrexate have shown improvement in case reports, no evidence based studies demonstrate benefit over a conservative approach. Skin grafting may be necessary, some studies recommend early graft intervention with large BSA involvement.

REFERENCES:

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Bolognia, JL, Jorizzo JL, Schaffer, JV. Dermatology. 3rd Edition. Vol 2.Elsevier, 2014 p 1403

Drug Enforcement Agency. Drug & Chemical Evaluation Section. Levamisole. April 2013

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Belfonte, CD, Shanmugam, VK, et al. Levamisole-induced occlusive necrotizing vasculitis in cocaine abusers: An unusual cause of skin necrosis and neutropenia. Int Wound J. 2013 Oct; 10(5)590-596

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Chung, C, Tumeh, PC, Bimbaum, MD, et al. Characteristic purpura of the ears, vasculitis, and neutropeniae- a potential public health epidemic associated with levamisole adultered cocaine. J Am Acad Dermatol. 2011 Oct; 65(4): 722-725

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Strazzula, L, Brown, KK, Brieva, JC, et al. Levamisole Toxicity mimicking autoimmune disease. J Am Acad Dermatol. 2013 Sept 24.

Michaud, K, Grabherr, S, Shiferaw, K, et al. Acute coronary syndrome after levamisole-adultered cocaine abuse. J Forensic and Leg Med. Jan 2014; 21:48-52