Upper and lower airway disease in penicillamine treated patients with rheumatoid arthritis

Four of 133 patients with rheumatoid arthritis suddenly developed progressive respiratory symptoms while receiving penicillamine therapy. None had previous disease. None of 89 patients treated with gold alone and 0 of 380 not taking gold or penicillamine developed respiratory symptoms. Two of the 4 developed simultaneous severe, unresponsive sinusitis. Lung biopsy demonstrated obliterative bronchiolitis (OB) in 2 patients, fibrosing alveolitis in one. A clinical course characteristic of OB was noted in the 4th patient. Sinus biopsy in 2 demonstrated lymphocytic and plasmacytic mucosal infiltration. The high frequency of OB in penicillamine treated patients and its absence in 469 non penicillamine treated patients suggests the possibility of a causal relationship.