Epidemiology

• Used in the treatment of inflammatory bowel disease, rheumatoid arthritis, Sjogren’s syndrome, etc

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Pharmacology

• Sulfonamide (see Sulfonamides)
• Sulfasalazine is metabolized to 5-aminosalicylic acid (5-ASA) and sulfapyridine
  • Sulphapyridine is probably responsible for most of the hypersensitivity reactions that occur, although the salicylate component may also be implicated since aspirin has been implicated in the development eosinophilic pneumonia

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Adverse Effects

Pulmonary Adverse Effects

• Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia)
  • Epidemiology: typically begins 1-8 months after start of continuous therapy (ranging in dose from 1.5-8g per day)
  • Clinical
    • Cough
    • Dyspnea
    • Fever (50% of cases)
  • Diagnosis
    • CXR/Chest CT: ranges from upper lobe alveolar to diffuse interstitial infiltrates -> none have migratory infiltrates
    • CBC: peripheral eosinophilia (50% of cases)
    • OLB: fibrosing alveolitis, interstitial pneumonitis, eosonophilic pneumonitis, and desquamative intersitial pneumonia have all been reported
  • Treatment/Prognosis
    • Withdraw drug -> resolution within 1-6 wks
    • Corticosteroids: may be necesaary in some cases
• Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome) (see Drug Rash with Eosinophilia and Systemic Symptoms)
• Cryptogenic Organizing Pneumonia (see Cryptogenic Organizing Pneumonia)
  • Epidemiology: most cases have been reported when sulfasalazine was used to treat ulcerative colitis (few cases have been reported when sulfasalazine was used to treat rheumatoid arthritis)
  • Diagnosis: upper lobe-predominant
  • Treatment: withdraw drug + corticosteroids -> pulmonary infiltrates usually regress
• Pleural Effusion (see Pleural Effusion-Exudate)
  • Diagnosis
    • Pleural Fluid: eosinophilia
• Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage)
  • May mimic presentation of Wegener’s Granulomatosis (see Wegeners Granulomatosis)
  • ANCA: c-ANCA may be positive
• Drug-Induced SLE (see Systemic Lupus Erythematosus)

Renal Adverse Effects

• Acute Kidney Injury (see Acute Kidney Injury): due to intratubular deposition and obstruction

Hematologic Adverse Effects

• Possible Risk of Hemolysis in Patient with G6PD Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency and Hemolytic Anemia)
• Blood Dyscrasias

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References

• Sulfasalazine Pulmonary Toxicity in Ulcerative Colitis Mimicking Clinical Features of Wegener’s Granulomatosis. Chest 1996;110;556-559
• Pleuropericardial effusion after 37 years of sulfasalazine therapy. J Cardiovasc Med (Hagerstown). 2011 Jan 11
• Sulfasalazine-induced lupus erythematosus. Am J Med. 1988 Mar;84(3 Pt 1):535-8
• Sulphasalazine and lung toxicity. Eur Respir J 2002; 19: 756–764