Leukocytoclastic Vasculitis Associated with Anti-tumor Necrosis Factor (TNF) Therapy

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Leukocytoclastic Vasculitis Associated with Anti-tumor Necrosis Factor (TNF)

Therapy

Category:  17 RA‹treatment

Niveditha Mohan1, e T 2, R Cupps1, R Slifman2, M

Miles Braun2, Jong-Hoon Lee2, N Siegel2

1town University Medical Center, Washington, DC;2Center for Biologics

Evaluation and Research, US Food and Drug Administration, Rockville, MD

Presentation Number: 354

Poster Board Number: 354

Keywords: leukocytoclastic vasculitis, anti-TNF therapy, adverse event

Objective: To describe the occurrence and clinical features of

leukocytoclastic vasculitis (LCV) during the use of anti-tumor necrosis

factor a (TNFa) therapy.

Methods: The Adverse Events Reporting System of the US Food and Drug

Administration (FDA), a postmarketing database of spontaneously reported

adverse events associated with drugs and biological products, was queried

following literature reports of patients with inflammatory arthritides who

developed LCV, during or after anti-TNFa therapy. Limitations of this method

of data collection include underreporting and incomplete case report forms.

Events observed after a product exposure are not necessarily due to that

exposure. Reports received by the FDA from August 1998 through April 2002

were reviewed.

Results: Twenty-eight cases were identified, 16 following etanercept

administration and 12 following infliximab administration. Sixteen of the 28

(57.1%) were biopsy-proven cases, and the others showed skin lesions that

were reported to be clinically typical for LCV (i.e., palpable purpura,

distribution on the lower extremities). Twenty-one of 28 (75%) patients had

complete resolution or marked improvement of skin lesions upon stopping

anti-TNFa therapy; lesions in 2 patients who continued on the agent did not

improve. There is no information available on the status of the skin lesions

in the other 5 patients. Concomitant medications in 21 of 28 patients (this

information was unavailable in the other 7 patients) included drugs that

have been reported to cause LCV such as methotrexate, sulfasalazine,

azathioprine, quinine, famotidine, lisinopril, losartan, furosemide and

naproxen. Eight patients experienced recurrence (positive rechallenge

phenomenon) of LCV upon restarting anti-TNFa therapy. Biopsies were not

reported in the 2 patients whose LCV did not recur when anti-TNFa therapy

was reintroduced. Ten patients were treated with glucocorticoids to hasten

recovery.

Conclusion: Anti-TNFa therapy may be associated with the development of LCV.

Skin lesions improved on discontinuation of anti-TNFa therapy in the

majority of patients, though they remained on concomitant medications that

have also been reported to cause LCV, suggesting their non-etiologic role in

this clinical setting.

Discontinuation of anti-TNFa therapy should be seriously considered if a

biopsy confirms the diagnosis in patients who develop skin lesions

suggestive of LCV while being treated with anti-TNFa therapy. Other causes

of LCV such as infection should be excluded, and the patient should be

evaluated for possible systemic involvement, based on presenting clinical

signs and symptoms. Therapy with glucocorticoids may be useful in causing

resolution of LCV.