Lung toxicity and Nitrofurantoin: the tip of the iceberg?

A 56-year-old female was referred to the respiratory clinic by her general practitioner with a 3-month history of dyspnoea and cough. She was a non-smoker. Her cough persisted despite several trials of medication, including antibiotics and inhaled bronchodilator and steroid therapy. Her past medical history included cervical cancer in 1997 with vault relapse in 1999, treated by hysterectomy, chemotherapy and radiotherapy; breast cancer in 2001 treated with wide local excision, chemother-apy and radiotherapy subsequently troubled with leg and arm lymph oedema. Following her gynae-cological illnesses, she had been troubled with recurrent urinary tract infections and for the last 12 months she had been treated with prophylactic Nitrofurantoin. On examination, she was tachypnoeic at rest. Room air saturations were 88%, falling to 76% on minimal exertion. Chest auscultation revealed bilateral inspiratory crackles. Spirometry showed an FEV1 1.38 (59%), FVC 1.54 (57%) with a ratio of 89%. Transfer factor was significantly reduced at 49% predicted. Chest radiograph showed diffuse air space shadowing most prominent at the right base. The working diagnosis was of Nitrofurantoin-induced lung injury with a differential diagnosis to include interstitial lung disease, atypical infection or lymphangitis. Nitrofurantoin was discontinued and she was commenced on Trimethoprim as an alternative. A high resolution CT (HRCT) showed widespread patchy areas of ground glass shadowing in both lung fields with minor peripheral sub-pleural interlobular septal thickening. The differential diagnosis included hypersensitivity or chemical pneu-monitis, atypical pneumonia and acute interstitial pneumonia. At review, 4 months later, the patient's symptoms had resolved, there was normalization of her lung function (transfer factor 94%) and there had been a marked improvement in the interstitial changes on her HRCT. Her recurrent urinary tract infections were controlled on Cefradine. Discussion Nitrofurantoin is an antibiotic commonly prescribed for urinary tract infections. It has a very valued place in the treatment of urinary infections, not least in light of its efficacy against ESBL coliforms. Since the early 1960's, significant side effects from its use have been reported. 1 These include a spectrum of lung disease presenting as acute, sub-acute and chronic interstitial lung disease. The acute and sub-acute reactions are thought to represent a hypersensitive pneumonitis and often resolve after withdrawal of the drug. In the chronic form, Nitrofurantoin has been reported to cause diffuse interstitial pneumonitis and bronchiolitis obliterans organizing pneumonia, 2 thought to reflect an allergic or toxic response. Those patients most likely to develop Nitrofurantoin-induced pneumonitis also reflect …