Sulfasalazine-induced pulmonary disease is a rare entity. We describe the first patient with psoriatic arthritis to develop pulmonary toxicity with unique pathology and an interesting clinical course.
A 38 year old Caucasian woman with psoriatic arthritis presented with a five month history of progressively worsening dyspnea on exertion and dry cough. Of note, her psoriatic arthritis was initially diagnosed in September 2000, and sulfasalazine (3 grams/day) was started in October 2000. She was evaluated in February 2002, 17 months after her initial diagnosis, and 16 months after initiation of therapy. Initial pulse oximetry on room air was 95%, however with ambulation, desaturation to 91% was noted. Physical examination revealed bibasilar inspiratory crackles in the posterior lung fields and psoriatic plaques over the extensor surfaces of the elbows. Chest radiograph displayed bilateral patchy infiltrates in the lower lobes. Pulmonary function tests demonstrated restrictive lung disease with a significantly reduced diffusion capacity (44% of predicted). Subsequent chest computed tomography showed bilateral lower lobes ground glass alveolar opacities. Transbronchial biopsy revealed pulmonary parenchyma with the interstitium fraught with granulomas. Several granuloma giant cells contained refractile and calcified material, resembling Schaumann bodies. Stains and culture for acid fast bacilli and fungi were negative. Given the possibility of sulfasalazine toxicity, the medication was discontinued. Significant improvement of symptoms was noted within four days after cessation of the drug. Repeat pulmonary function tests two months after intervention demonstrated improvement of the total lung capacity and diffusion capacity (69% predicted). Repeat chest computed tomography also showed clearing of the ground glass opacities. Pulmonary function tests obtained three years after intervention showed a near normal diffusion capacity (74% of predicted).
Review of the literature between 1972 and 1999 identified 50 patients with possible sulfasalazine-induced lung toxicity. The daily dose of sulfasalazine ranged from 1 to 8 grams (mean of 3 grams). The average duration of exposure to sulfasalazine was 17.8 months with a range of 0.5 to 120 months. Sulfasalazine toxicity may present in a variety of distinct forms including: subacute cellular interstitial pneumonitis, pulmonary infiltrates with eosinophilia, desquamative interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, pulmonary fibrosis, acute pulmonary edema, eosinophilic pleural effusion, pleural/pericardial thickening or effusion with positive antinuclear/antihistone antibodies, and vasculitis. The majority of patients recovered after termination of the drug. Clinical improvement usually occurs between 1 and 32 weeks, with an average time of 6.5 weeks. In contrast, our patient rapidly improved in only four days after termination of the drug. Sequential pulmonary function tests up to three years after intervention clearly exhibited improvement and stabilization of lung function and diffusion capacity. More importantly, pathology demonstrating well formed granulomas and Schaumann bodies mimicking sarcoidosis has not previously been described.
Sulfasalazine-induced pulmonary disease may masquerade in different forms. The importance of early recognition remains paramount. Proper identification may not only spare the patient from severe lung damage, but also prevent an untimely death and unnecessary complications from other drug therapies. Prompt recognition of the disease, followed by immediate cessation of the drug, should result in an excellent prognosis.
Rosa Estrada-Y-Martin, None.