Case Presentation: A 73-year-old male with a past medical history of hypertension and benign prostatic hyperplasia presented to the emergency department (ED) with acute onset generalized weakness, nausea, emesis, diarrhea, fever, and dyspnea approximately 2.5 hours after taking a combination pill of losartan-hydrochlorothiazide (HCTZ). The patient reported that he had been prescribed losartan-HCTZ 50-12.5 mg seven months earlier but had self-discontinued the medication due to the onset of mouth sores and generalized weakness after taking the combination pill. He subsequently returned to his clinic in hypertensive urgency and was counseled to resume the combination pill. Upon resumption, he developed his current symptoms and presented to the ED. His vital signs on presentation were notable for a temperature of 39.3 °C, blood pressure of 137/66 mmHg, heart rate of 131 beats per minute, respiratory rate of 33 breaths per minute, and oxygen saturation of 88% on room air. Physical exam was notable for the presence of bilateral lung crackles and diaphoresis. Point-of-care ultrasound revealed B-lines in bilateral lung fields and a normal ejection fraction. Chest x-ray showed mild bilateral interstitial opacities. Labs were notable for leukopenia (with a white blood cell count of 2.0 K/cumm) and elevated procalcitonin (58.70 ng/mL), and an unremarkable comprehensive metabolic panel, respiratory viral panel, and pro-brain natriuretic peptide. The patient was placed on nasal cannula with improvement in oxygenation. He was admitted to the hospital for acute hypoxic respiratory failure and started on antibiotics for possible community-acquired pneumonia. The patient’s tachycardia, tachypnea, fever, pulmonary crackles, and oxygen requirement resolved within five hours of presentation and he was discharged the following morning. He was counseled to discontinue HCTZ indefinitely.
Discussion: Several cases of HCTZ-induced noncardiogenic pulmonary edema have been observed and described in the literature. Symptoms develop within minutes to hours of medication ingestion and can occur on first exposure to the medication or with intermittent use. Symptoms include dyspnea, wheezing, and cough (90%); and less frequently, fever, chills, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Presentations of anaphylaxis such as hypotension and urticaria or flushing are notably absent, and eosinophilia is also notably absent. Symptoms usually resolve within three days. The pathophysiologic mechanism by which HCTZ causes pulmonary edema remains unknown and is considered idiosyncratic, though some reports implicate neutrophil-mediated pulmonary injury. Our patient’s case had many features consistent with previous reports of HCTZ-associated pulmonary edema, including fever and hypoxia, but also had features not previously described; namely, the outbreak of mouth sores with previous use of HCTZ.
Conclusions: HCTZ is generally a well-tolerated treatment for hypertension with the most common side effects being orthostatic hypotension, electrolyte abnormalities, hyperglycemia, hyperuricemia, and hyperlipidemia. Noncardiogenic pulmonary edema has been reported as a rare but life-threatening adverse reaction to HCTZ. This case highlights the importance of considering medications as a cause of noncardiogenic pulmonary edema, as noncardiogenic pulmonary edema may have life-threatening clinical presentations that require prompt supportive care and treatment of the underlying etiology.