Cross-reactivity in drug hypersensitivity reactions to sulfasalazine and sulfamethoxazole.
BACKGROUND
Sulfonamides are generally classified into 2 groups: antibiotics and non-antibiotics. Recent studies showed that patients allergic to sulfonamide antibiotics do not have a specific risk for an allergy to sulfonamide non-antibiotic. However, the anti-inflammatory drug sulfasalazine represents an important exception. Used in rheumatic diseases, it is classified as a non-antibiotic sulfonamide, but is structurally related to antibiotic sulfonamides. Therefore, we aimed to analyze in vitro the cross-reactivity between the antimicrobial sulfamethoxazole and the anti-inflammatory drug sulfasalazine.


METHODS
PBMC from 2 patients with severe hypersensitivity syndrome to sulfasalazine, 3 patients with sulfamethoxazole allergy and 5 healthy donors were isolated and incubated with medium only (negative control), 2 concentrations (10, 100 μg/ml) of sulfapyridine, 2 concentrations (100, 200 μg/ml) of sulfamethoxazole, and tetanus toxoid (10 μg/ml) as a positive control. After 6 days of culture, (3)H-thymidine was added and cell proliferation was measured.


RESULTS
In all patients tested, the lymphocyte transformation tests were positive for both sulfapyridine and sulfamethoxazole, suggesting a strong cross-reactivity to these drugs. None of the healthy donors reacted to any of the drugs tested. We refrained from provoking our patients with either sulfasalazine or sulfamethoxazole, as they had a clear, typical history, severe symptoms and were positive on in vitro tests to both compounds.


CONCLUSIONS
We demonstrate that in the case of sulfamethoxazole and sulfasalazine, cross-reactivity is dependent on chemical features rather than the indication of the drugs. Therefore, patients with hypersensitivity to sulfasalazine or sulfamethoxazole should be specifically advised to avoid both drugs.
Zawodniak
Anna
A
Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, Bern, Switzerland.
Lochmatter
Priska
P
Beeler
Andreas
A
Pichler
Werner J
WJ
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000276:immunology*; D003429:Cross Reactions; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013420:Sulfamethoxazole / Q000009:adverse effects / Q000276:immunology*; D012460:Sulfasalazine / Q000009:adverse effects / Q000276:immunology*
D000890:Anti-Infective Agents; D012460:Sulfasalazine; D013420:Sulfamethoxazole