Levamisole-Laced Cocaine May Unmask Autoimmune Process

Kate Johnson

March 23, 2012

March 23, 2012 (San Diego, California) — Levamisole-contaminated cocaine is a growing cause of retiform purpura and vasculitis, and might be responsible for unmasking certain autoimmune conditions in genetically predisposed individuals, according to reports presented here at the American Academy of Dermatology 70th Annual Meeting.

"Levamisole is increasingly being discovered in street cocaine as an adulterant," said Mark Jackson, MD, clinical professor of medicine and dermatology at the University of Louisville, Kentucky, during a Hot Topics session on drug reactions.

In addition to adding bulk to cocaine, the alkaline phosphatase inhibitor "has the ability to potentiate dopaminergic pathways, contributing to a euphoria," said Anthony Rossi, MD, from St. Luke's-Roosevelt Hospital in New York City, where he has treated several cases.

Levamisole is primarily used in veterinary medicine as an antihelminthic agent. Before it was taken off the market because of its numerous adverse effects, it was used as an immunomodulating agent in people with colon cancer and nephritic diseases, said Dr. Jackson.

"It can cause rash and nausea, abdominal cramps, taste alteration, alopecia, and flu-like symptoms, but its worst effects are causing life-threatening agranulocytosis and vasculitis," he said.

It was estimated that in 2009, 69% of the cocaine seized at the American border was mixed with levamisole. A recent analysis from Seattle, Washington, found it in 80% of patients who tested positive for cocaine (Semin Arthritis Rheum. 2011;41:445-454).

In 2010, prompted by several cases of retiform purpura with cutaneous necrosis induced by levamisole-contaminated cocaine, St. Luke's-Roosevelt Hospital alerted New York City authorities, who issued a public health warning, said Dr. Rossi, who described 2 patients who were admitted because of a suspected cellulitis-like presentation.

The 2 women had used cocaine in the previous week and presented with painful violaceous purpuric patches with well-delineated dusky necrotic centers and a bright erythematous rim, he said. Both had involvement of the earlobes and helices bilaterally, as well as the abdomen and upper and lower extremities.

Trunk with multiple tender purpuric patches with an erythematous rim and central necrosis.

"On both, punch biopsies from the erythematous border showed small-vessel vasculopathy with organizing thrombus and a mixed-cell infiltrate," he said.

Although these findings are not specific to levamisole toxicity, the real clue is their combination with the cutaneous presentation, especially the ears, "which is one of the clinical pearls," said Dr. Jackson.

Lobe and superior and midanterior helix with purpuric tender necrotic patches surrounded by an erythematous border.

Both of Dr. Rossi's patients were leukopenic and neutropenic on admission, and blood work revealed positive D-dimers, antidouble-stranded DNA antibodies, antineutrophil cytoplasmic antibodies (ANCA), decreased protein S levels, and lupus anticoagulant antibodies.

The presence of autoantibodies has been reported fairly consistently in the small but increasing literature about this phenomenon, said Dr. Rossi.

Although Dr. Jackson advised that autoimmune conditions should be ruled out in such situations, he explained that a positive autoantibody test "does not mean they actually have those conditions. Levamisole can induce that."

Dr. Rossi said it is debatable whether the autoimmunity is actually drug-induced or simply triggered in genetically predisposed individuals.

Although drug-induced autoimmunity is a recognized phenomenon and has been associated with levamisole, "we're thinking that an underlying genetic predisposition may be unmasked by exposure to this new agent through the phenomenon known as epitope spreading," he explained.

"What I have been researching and suggesting is that autoantibody production to a variety of 'self' antigens is produced secondary to levamisole exposure, as a result of an underlying genetic predisposition to developing a type of autoimmune syndrome/diathesis," he told Medscape Medical News.

"What we're proposing is a possible synergistic role between the cocaine and levamisole, with a possible underlying genetic predisposition to the antiphospholipid antibody syndrome, a protein C or S deficiency, or an ANCA-associated vasculitis." He therefore recommends that these patients receive long-term monitoring.

"Antibodies are not formed against the levamisole itself, but rather against certain parts of the cell that can cause autoimmune syndromes, such as the ANCA-associated vasculitis, or antiphospholipid antibody syndrome," he added.

In support of this theory, he said one patient still had positive autoantibodies 7 months after her initial presentation, despite testing negative for cocaine. "If it was drug-induced, this should have gone away," he said. The second patient, and subsequently a third, were lost to follow-up.

Although Dr. Rossi's theory is reasonable, "I think it is too early to tell what will happen in the majority of cases," Dr. Jackson told Medscape Medical News. "Antibodies are not the same in every patient and do resolve with time. Since these reactions usually resolve with cessation of the use of the tainted cocaine, it [supports] a link to levamisole being the culprit...in the absence of the underlying condition being present. There must be, however, some genetic predisposition or the presence of epitope spreading that allows the condition to occur, as the reports of this condition are very rare compared to the use of cocaine."

Dr. Rossi and Dr. Jackson have disclosed no relevant financial relationships.

American Academy of Dermatology (AAD) 70th Annual Meeting: Hot Topics report, presented March 16, 2012; abstract 4808, presented March 18, 2012.

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