Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents.
OBJECTIVE
To describe the clinical features of leukocytoclastic vasculitis (LCV) associated with the use of tumor necrosis factor-alpha (TNF-alpha) blockers.


METHODS
The Adverse Events Reporting System (AERS) of the US Food and Drug Administration (FDA) was queried for reports of patients who developed LCV during or after starting etanercept or infliximab from date of approval of each agent through September 6, 2002.


RESULTS
Thirty-five cases of LCV were identified, 20 following etanercept administration and 15 following infliximab administration. Seventeen of the 35 (48.5%) were biopsy-proven cases and the others had skin lesions that were clinically typical for LCV. Twenty-two of 35 (62.8%) patients had complete or marked improvement of skin lesions upon stopping the TNF-alpha blocker. Three patients who had received etanercept had continuing lesions despite discontinuation of the drug; one of these patients improved when switched to infliximab. One patient who received infliximab was reported to have continuing lesions despite discontinuation of the drug and treatment with prednisone and antihistamines. Six patients experienced a positive rechallenge (recurrence of LCV on restarting therapy with a TNF-alpha blocker) and 3 patients a negative rechallenge phenomenon. LCV lesions improved in patients despite continuing use of concomitant medications reportedly associated with LCV.


CONCLUSIONS
Therapy with TNF-alpha blocking agents may be associated with the development of LCV. Skin lesions improved on discontinuation of anti-TNF-alpha therapy in most patients. Other causes of LCV should be excluded, and evaluation for systemic involvement with appropriate investigations is recommended.
Avera Research Institute, Sioux Falls, South Dakota 57105, USA. nmohan@pol.net
Niveditha
N
Mohan
Evelyne T
ET
Edwards
Thomas R
TR
Cupps
Nancy
N
Slifman
Jong-Hoon
JH
Lee
Jeffrey N
JN
Siegel
M Miles
MM
Braun
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012216:Rheumatic Diseases / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States; D014486:United States Food and Drug Administration; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept