title: Cross-reactivity in drug hypersensitivity reactions to sulfasalazine and sulfamethoxazole.
abstract: 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.
authors.affiliation: Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Zawodniak
authors.forename: Priska
authors.initials: P
authors.lastname: Lochmatter
authors.forename: Andreas
authors.initials: A
authors.lastname: Beeler
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: 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*
chemical_list: D000890:Anti-Infective Agents; D012460:Sulfasalazine; D013420:Sulfamethoxazole