Morning Report: Levamisole Toxicity

Thanks to Dr. Nordstrom for today’s Morning Report!

The Case:

A 45 y.o female presents to the ED with a chief complaint of leg pain. She says the rash started 1 week ago and is located on both of her legs and also both ears. The rash has been increasingly painful, and is most painful when touched. She denies fever or chills. She denied any travel, hiking, or camping. All review of systems were otherwise negative.

She reports that approx 1 year ago she had a similar episode, and a doctor told her that she ‘may’ have Lupus. She has never seen or followed with a Rheumatologist.

All: none

Meds: none

SocHx: uses cocaine regularly.

Exam:

BP: 114/68 HR: 95 Temp: 98.4 RR: 18

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Levamisole Toxicity

Brief History:

– 1966 compound is Developed at Jassen Pharmaceutical in Belgium. As an Anti-biologic / Anti-Helminthic.

– First used as an Anti-Helminthic to de-worm livestock.

– In 1970’s – 80’s: the medication was used for the treatment of inflammatory conditions (UC, RA, nephrotic syndrome in children) and in the treatment of cancer as an adjunct (Colon Ca, head and neck cancer, melanoma).

– 1970’s – 80’s: Case reports of Levamisole causing fatal agranulocytosis, cutaneous vasculitis (with prediliction for the earlobes), and neurologic side effects (multifocal leukoencephalopathy) also reports of ‘mood elevating properties’ as a side effect.

– 2000 taken off the market due to severe agranulocytosis.

– 2003 Levamisole is identified as a cocaine adulterant.

– 2009 First case reports of a cutaneous vasulitis in patients using levamisole contaminated cocaine.

-2014 Levamisole associated vasculopathy, agraulocytosis associated with cocaine abuse.

Pharmacology:

– Structurally a Phenethylamine (typically these compounds are known for there psychoactive and CNS stimulatory effects.

– Immune system: immune modulator, enhances T cells response, increase neutrophil and potentiates monocyte and macrocyte function.

– Anti-helminthic: targets nematode Nicotinic Acetylcholine receptor

– CNS: stimulant, decreases noradrenergic reuptake, metabolized into amphetamine like compound

– Adverse effects: agranulocytosis, vasculitis, multifocal leukoencephalopathy (mechanism unknown).

Clinical Syndrome:

– Levamisole associated vasulopathy: stellate pupuric rash with bright red border, non blanching, can be severe and cause bullae or central necrosis. Has a prediliction for the ears and extremities.

– ANCA positive (p-anca, c-anca, anti-mpo with other auto Ab’s negative.

– Unique from other systemic vasculidities in that there is no systemtc involvement., isolated to the skin. But there have been case reports of severe involvement involving deeper skin structures with extensive necrosis and requiring skin grafting.

– Levamisole assocated neutropenia, agranulocytosis. Can occur in isolation or preceding cutaneous vasculopathy. Case reports of pt’s with neutropenia and sepsis who later developed typical rash.

Cocaine Contamination:

– 2010: US DEA reported approx 74% of all cocain bricks entering the US were contaminated with Levamisole.

– 2011 Studies in SF and Denver showing 78%, 88% of people testing positive for cocaine also had Levamisole in the urine.

Economics:

– 1 gram = $7.5 USD

Reference:

Vasculopathy related to cocaine adulterated with levamisole: A review of the literature
Timothy Pearson BS, Matthew Bremmer MD, Jared Cohen BS, Marcia Driscoll MD Pharm D
Dermatology Online Journal 18 (7): 1