Sulfasalazine (Azulfidine)

Epidemiology

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

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

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)
  • 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


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