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Keywords:

  • anaphylactic reaction;
  • celecoxib;
  • cotrimoxazole;
  • cross reaction;
  • sulfamethoxazole;
  • sulfonamides

We have previously reported on anaphylactic reactions to celecoxib (Celebrex®) which was confirmed by a controlled oral provocation test with 50 mg of the particular drug. The allergological investigation revealed a positive lymphocyte stimulation test (LTT) with Celebrex® (1). Here we report a patient (female, 47 years) who experienced vomiting, flushing, shivering and loss of consciousness 30 min after ingestion of a 200-mg tablet, celecoxib. She was admitted to the emergency where hypotension (50/35 mmHg) was documented. One year previously she had regularly been taking celecoxib for the treatment of whiplash trauma.

The patient was referred for diagnostic work-up to the Allergy Unit of the University Hospital of Zurich, Switzerland. Her drug history revealed an episode of vomiting and vertigo after taking Bactrim® (sulfamethoxazole and trimethoprim). Although scratch and patch tests were negative to all substances, the lymphocyte proliferation tests (LTT, performed by W. Pichler, Division of Allergology, Bern, Switzerland), however, were clearly positive for sulfamethoxazole [stimulation index (SI): 5.9] and for celecoxib (SI: 10.2). The patient refused further oral provocation tests.

Only very few anaphylactic reactions to celecoxib have been reported in the literature. Our previous patient experienced an anaphylactic reaction after an oral provocation with 50 mg Celebrex® and his LTT was found to be positive (1). In another patient with anaphylactic reaction to Celebrex®, oral provocation was positive but LTT and skin tests were negative (2). In the third report, laboratory analysis using an enzyme-linked immunosorbent assay failed to demonstrate IgE (3). More reports exist about patients with delayed-type hypersensitivity reactions, documented by positive skin patch test and LTT (4).

Cross reactions between sulfonamides and the sulfur moiety of a celecoxib is discussed controversially. The product labelling of Celebrex® contains a warning that patients with ‘sulfa’-allergies should avoid using this drug. To date, no clinically relevant cross reactions have been reported. The Canadian pharmacovigilance centre has received 220 unconfirmed reports of probable and 562 reports of possible adverse events to celecoxib. Seventy-four of these reports included cutaneous symptoms, of which 16 reported an allergy to sulfonamides (5).

Due to the great structural differences amongst the various sulfonamides, cross reactivity has been disputed (6). Celecoxib contains a nonaromatic amine (Fig. 1). In sulfamethoxazole the sulfonamide is bound to a methylated heterocyclic ring and a benzole ring. The adverse side-effects are attributed either to the aromatic amine group or the heterocyclic ring (6). Both of these chemical structures are not found in celecoxib.

image

Figure 1. Structural formulas. Celecoxib (upper panel): non aromatic amine, Sulfamethoxazole (lower panel): aromatic amine.

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The exact mechanism that ultimately caused sensitization in our patient remains unresolved: either an independent (coincidental) sensitization to the two drugs or a real cross reactivity might have been responsible for this unusual observation. Until further investigations are available, patients with a known sulfonamide allergy should avoid using celecoxib.

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