Chronic urticaria with multiple NSAID intolerance: is tramadol always a safe alternative analgesic?

Mechanisms underlying multiple intolerance to nonsteroidal anti-inflammatory drugs (NSAID) in patients with chronic urticaria (CU) are unclear. One hypothesis is that COX-1 inhibition may play a relevant pathogenic role. If so, drugs that are not active on COX-1 would be expected to be well tolerated by CU patients.

This study aimed at assessing the tolerability of a central analgesic (tramadol) in a group of patients with CU and a history of intolerance to several NSAIDs, asking for a safe, alternative compound.

Twenty-eight patients with CU exacerbated by several, distinct NSAIDs underwent single-blind, placebo-controlled, oral challenges with increasing doses of tramadol (50 mg total dose). Most of them underwent oral challenges with rofecoxib, paracetamol, and/or nimesulide as well.

Twenty-three patients tolerated tramadol, whereas, surprisingly, in 5 (18%) patients tramadol induced urticaria, in one case with laryngeal edema. A similar proportion of CU patients did not tolerate rofecoxib, and higher proportions of patients did not tolerate acetaminophen and nimesulide.

Mechanisms other than COX inhibition may also play a role in drug intolerance in patients with CU. In CU patients intolerant to NSAID, the tolerability of tramadol, as well as of other "alternative" drugs, should be assessed by oral challenge tests.