Cross-Reactivity in Drug Hypersensitivity Reactions to Sulfasalazine and Sulfamethoxazole

• Published in: International archives of allergy and immunology Vol. 153; no. 2; pp. 152 - 156
• Main Authors: Zawodniak, Anna, Lochmatter, Priska, Beeler, Andreas, Pichler, Werner J.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2010; S. Karger AG
• Subjects: Adult; Aged; Allergies; Anti-Infective Agents - immunology; Antibiotics; Biological and medical sciences; Cross Reactions; Drug Hypersensitivity - etiology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunology; Immunopathology; Male; Medical sciences; Middle Aged; Pharmacology; Prescription drugs; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Short Communication; Side effects; Sulfamethoxazole - adverse effects; Sulfamethoxazole - immunology; Sulfasalazine - adverse effects; Sulfasalazine - immunology; Sulfasalazine; Sulfamethoxazole; Sulfonamide allergy; Aromatic sulfonamides; Cross-reactivity; Allergy; Immunopathology; Sulfonamide; Toxicity; Hypersensitivity; Immunology; Sulfonamides; Cross reaction; Salicylates
• ISSN: 1018-2438; 1423-0097
• DOI: 10.1159/000312632

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.