CASE
An 89-year-old white female presented to the emergency department (ED) with a 1-month history of fatigue, nonproductive cough, and weakness, progressing over the previous 3 days to the point where she was unable to attend meals in her assisted living facility's cafeteria. Her cough was exacerbated with deep inspiratory effort. The patient denied fever, chills, night sweats, dyspnea, nausea, vomiting, weight loss, syncope, or chest pain.
The medical history included gastroesophageal reflux, grade 3 cystocele, hypertension, macular degeneration, mild to moderate dementia, osteoarthritis, osteopenia, recurrent urinary tract infection (UTI), and vertigo secondary to acoustic neuroma. The surgical history included an appendectomy and total abdominal hysterectomy with bilateral oophorectomy several years earlier. The patient could not remember all of her home medications, but she reported taking metoprolol, a sulfa agent for the UTIs, nitrofurantoin in the past, and an NSAID whose name she could not recall. She was allergic to penicillin. She denied tobacco and alcohol intake. She typically walked without assistance. Review of systems was significant for joint pain, back pain, anxiety, cough, constipation, reflux disease, and chronic UTI.
Physical examination On admission, the patient was alert and oriented. Pulse was 74 beats per minute; respiration, 20 breaths per minute; BP, 153/70 mm Hg; and oxygen saturation on room air (by pulse oximetry), 90%. Pupils were equal, round, and reactive to light. Extraocular movements were intact. The neck was supple and without lymphadenopathy. Cardiovascular examination demonstrated a regular rhythm with a rate in the 70s without murmur, rub, or heave. Chest auscultation revealed bilateral rales and cough with deep inspiratory effort. The abdomen was soft, nontender, and nondistended. The extremities were without clubbing or cyanosis, and 1-cm pedal edema with tenderness to palpation was present on the left.
Testing Abnormal laboratory test results included sodium, 130 mEq/L; and albumin, 2.0 g/dL; other laboratory results were within normal limits. Arterial blood gas analysis results were a pH of 7.46, PCO2 of 38 mm Hg, and PO2 of 57 mm Hg. A chest radiograph demonstrated extensive interstital changes with bilateral cyst formation or possible cavitation. These findings were not present on previous chest radiographs obtained 3 years earlier.
Hospital course The patient was placed in isolation for a workup for tuberculosis. She was initially treated empirically with furosemide and supplemental oxygen. A brain natriuretic peptide level and echocardiography findings were within normal limits. Collection of sputum culture was unsuccessful. A purified protein derivative test was negative.
Because of inconsistencies among the medication histories documented in the various patient records (ED, admission, nursing, and consultant records), nursing contacted the patient's assisted living facility to reconcile the home medication list. On day 2 of hospitalization, the patient was restarted on these home medications, including acetamino phen (500 mg every 6 hours prn for pain), galantamine (12 mg twice daily), metoprolol (125 mg once daily), nitrofurantoin (100 mg once daily), and an oyster shell calcium supplement (500 mg) plus vitamin D (3 times daily).
On day 3 of hospitalization, during unrelated medication monitoring, a clinical staff pharmacist recognized the possibility that nitrofurantoin could be the cause of the pulmonary symptoms and alerted the pulmonologist. The nitrofurantoin was discontinued, but corticosteroids were not administered. Diagnostic tests were continued to rule out other causes. High-resolution chest CT was ordered, which demonstrated extensive septal thickening and periseptal areas of infiltrate throughout all lung fields. Flexible bronchoscopy was performed. Visual inspections of the airways were normal. Bronchoalveolar lavage (BAL) was performed, and three transbronchial biopsies were obtained of the left lower lobe. Cultures were sent for cytology, acid-fast bacilli, fungi (Pneumocystis), viruses (cytomegalovirus), Legionella, and Mycoplasma. No malignant cells were identified, and all cultures were negative. BAL pathology showed a mild cellular specimen with macrophages and reactive bronchoepithelial cells. Transbronchial biopsy revealed chronic interstitial pneumonia, thickened alveolar septa, and increased alveolar macrophages. No acute inflammatory cells were identified. The injury pattern was nonspecific but, when combined with the clinical history, thought to be compatible with nitrofurantoin toxicity.