Nitrofurantoin-induced acute, subacute and chronic pulmonary reactions

The clinical histories of 81 patients with hypersensitivity reactions to nitrofurantoin, 66 of whom had pulmonary reactions, were studied. Of all patients, 94% were women and of these, 43% were between 40 and 59 years of age. The nitrofurantoin preparation that contained vitamin c caused significantly fewer hypersensitivity reactions than the others. Acute pulmonary reactions appeared a mean of 8.7 days after the start of nitrofurantoin treatment. Typical for these were high fever, dyspnoea, cough, blood eosinophilia, bilateral pneumonic or pleuro-pneumonic infiltrations, a reduced transfer factor of the lung and, as revealed in pulmonary biopsy specimens, vasculitis, interstitial inflammation and alveolar exudation. Symptoms of subacute and chronic pulmonary reactions developed after at least 1 and 6 months of treatment, respectively. Findings of interest were anti-nuclear antibodies in serum, capillary sclerosis, interstitial fibrosis and inflammation in pulmonary tissue. Most patients with an acute pulmonary reaction recovered within 15 days, but in more than half of those with chronic reactions slight signs of pulmonary fibrosis persisted on follow-up. The findings suggest that the interstitial pulmonary changes caused by nitrofurantoin are largely the result of an Arthus-type immune complex-mediated reaction.