Sulfasalazine lung toxicity

Sulfasalazine lung toxicity is a rare and poorly understood entity, usually taking the form of eosinophilic pneumonia, for which only a handful of case reports can be found in the literature.

Epidemiology

Unknown but probably very rare. Occurred twice in a series of 774 patients treated with sulfasalazine monitored for 11 years ².

Clinical presentation

Overlap with that of eosinophilic pneumonia. In a 2002 case series comprising of 50 patients ³, the symptoms were distributed as follows:

• classic triad of breathlessness, fever and cough: 42%
  • breathlessness: 80%
  • fever: 70%
  • cough: 64%
  • crackles/crepitations/rales: 52%
• less commonly:
  • weight loss: 22%
  • chest pain: 20%
  • rash: 7%

Pathology

Sulfasalazine is a compound of 5-aminosalicylic acid (5-ASA) and sulfapyridine joined by an azo bond, used in the treatment of chronic inflammatory bowel disease. Fatal toxicity of sulfasalazine is related to blood dyscrasias due to its effects on the bone marrow. 

As with eosinophilic pneumonia, a high eosinophil count in bronchoalveolar lavage is characteristic of the condition ³. There is an overlap with other pathological entities, such as organising pneumonia and acute interstitial pneumonia.

Interestingly, old reports seem to imply that patients with sulfasalazine lung disease also have aspirin allergy ^4,5.

Radiographic features

Plain radiograph

• pulmonary infiltrates are the dominant feature

CT

• interstitial infiltrates and ground glass opacities, possibly with upper lobe preference
• can show peripheral nodules, and those can cavitate
• pleural thickening is also reported in a few cases

Treatment and prognosis

It is important to recognise sulfasalazine as the cause of the lung condition as recovery is possible either with sulfasalazine withdrawal or with a corticosteroid course. In a 2002 case series ³, all five deaths due to lung toxicity were patients with ulcerative colitis and it is possible there are unknown factors contributing to these deaths.