A 57-year-old Caucasian female was admitted with a 3-day history of fever up to 39 C, non-productive cough, and progressive shortness of breath. Dyspnea worsened 12 h before admission. The patient had no relevant occupational exposure, known allergies, travel history, or previous lung disease. She was a smoker (10 pack-year) and her medical history included hypertension, hypothyroidism, depression, and recurrent UTIs which were treated with nitrofurantoin, 100 mg/day, for the previous 23 days.
On the day of admission, the patient was afebrile, blood pressure was 120/70 mmHg, pulse rate was 120/min and respiratory rate was 28/min. Auscultation of the chest revealed fine inspiratory crackles on the middle and lower lung zones bilaterally. The rest of physical examination did not reveal noteworthy findings. Arterial blood gas (ABG) on room air showed type I acute respiratory failure (pH = 7.46, partial pressure of carbon dioxide (PaCO2) = 26 mmHg, partial pressure of oxygen (PaO2) = 49 mmHg, bicarbonate (HCO3 -) = 21 mEq/L), while the clinical indicator of hypoxemia, the ratio of partial pressure arterial oxygen, and fraction of inspired oxygen (PaO2/FiO2) was 233 and the alveolar-arterial PO2 difference ([A-a]PO2) was 63. The electrocardiogram revealed sinus tachycardia without any other abnormalities. Laboratory results showed increased leucocytes (15.500 K/muL) and eosinophils (2.260 K/muL), with mildly increased inflammatory markers. Chest X-ray showed reticular changes bilaterally on the mid and lower lung zones and bilateral pleural effusions (Fig. 1). High resolution computerized tomography (HRCT) scan of the chest showed bilateral inter and intralobular septal thickening mainly involving the mid and lower lung zones, centrilobular nodules bilaterally, bilateral small pleural effusions, and patchy ground glass opacities (Fig. 2). On the day of admission, computerized tomography-pulmonary angiogram ruled out pulmonary embolism and the echocardiogram showed no structural or functional abnormalities.
Differential diagnosis included diseases presenting with type I acute respiratory failure and reticulo-nodular opacities on HRCT, such as respiratory infections, pulmonary edema, acute respiratory distress syndrome (ARDS) and interstitial lung diseases with rapid onset and worsening (acute interstitial pneumonia, acute hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug reaction, cryptogenic organizing pneumonia, connective tissue disease and diffuse alveolar hemorrhage).
The patient was supported with supplemental oxygen. Treatment with ceftriaxone and macrolide was administered pending the results of the laboratory tests. Nitrofurantoin was suspected to be the cause and it was discontinued immediately.
The patient's condition rapidly improved within 24 h: she had no shortness of breath, auscultation of the chest revealed fine inspiratory crackles only on the lower lung zones, the chest X-ray improved with reticular shadowing on the lower lung zones and ABG's on room air showed pH = 7,42, PaCO2 = 36 mmHg, PaO2 = 73 mmHg, and HCO3 - = 24 mEq/L.
As part of the investigational process, bronchoscopy with bronchoalveolar lavage (BAL) was performed and the results showed 12% eosinophilia and CD+ 4/CD+ 8 ratio of 1.26 (normal). Microscopic examination and cultures of BAL for Mycobacterium tuberculosis, Pneumocystis jirovecii, bacteria and fungi were negative. Polymerase chain reaction of BAL for influenza and P. jirovecii was negative. Cytology test of BAL and sputum showed no malignant cells. Cultures of sputum, blood, and urine were sterile. Nasopharyngeal swab specimen testing for influenza was negative. Urine antigens for Legionella pneumophila and S Streptococcus pneumoniae were negative. Serology tests for Human Immunodeficiency Virus, Hepatitis C virus, Hepatitis B virus, chlamydia, mycoplasma, rickettsia, aspergillus, and common viruses were also negative. Complement factors, quantitative immunoglobulin levels, thyroid hormones, and serum angiotensin converting enzyme were within normal limits. Mantoux test was 0 mm. Rheumatoid factor and antinuclear antibodies were negative. Total Immunoglobulin (Ig)E of the blood was increased (203.54 UI/mL). Microscopic examination of peripheral blood smear showed eosinophilia.
Five days after admission, pulmonary function tests were performed and showed the ratio Forced expiratory volume in 1 sec to Forced vital capacity (FEV1/FVC) = 81%, FEV1 = 2.31(99%), FVC = 2.86(104%), Total lung capacity = 4.27(89%), Residual volume = 1.19(67%), Diffusing capacity of the lungs for carbon monoxide (DLCO) = 91%, DLCOadj = 99%.
The patient was diagnosed with pulmonary toxicity due to nitrofurantoin use.
High resolution computerized tomography (HRCT) image of the chest. A reticulonodular pattern is demonstrated with bilateral inter- and intralobular septal thickening, centrilobular nodules and associated patchy ground glass opacities.