Hydrochlorothiazide-Induced Pulmonary Edema and Associated Immunologic Changes Carlos Bernal and Roberto Patarca
OBJECTIVE:
To describe a patient with noncardiogenic acute pulmonary edema induced by hydrochlorothiazide and to investigate the possible involvement of an immunologic mechanism in this adverse reaction. CASE SUMMARY: A 66-year-old Hispanic woman developed acute pulmonary edema 30 minutes after the ingestion of one tablet of triamterene 75 mg/hydrochlorothiazide 50 mg. The reaction was associated with hemoconcentration; a decreased white blood cell count with a shift to a predominance of polymorphonuclear cells; decreased serum immunoglobulin (Ig) G, IgG1, and IgG4; and increased serum IgM and complement 3 concentrations. DISCUSSION: Although there have been 35 reports of cases of hydrochlorothiazide-induced pulmonary edema, the etiology of this adverse reaction remains unknown. The observations presented in this case report, along with commonalities with previously reported cases, suggest that granulocytic infiltration into the lungs and IgG deposition in alveolar membranes may play a role in hydrochlorothiazide-induced pulmonary edema. CONCLUSIONS: Noncardiogenic pulmonary edema may be an immunologically mediated rare idiosyncratic reaction to hydrochlorothiazide. KEY WORDS: pulmonary edema, hydrochlorothiazide. Ann Pharmacother 1999;33:172-4.
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oncardiogenic pulmonary edema has been reported1 as a rare idiosyncratic reaction that occurs with some specificity with the thiazide diuretic hydrochlorothiazide. The etiology of this adverse reaction is unknown. We report a case of hydrochlorothiazide-induced pulmonary edema and associated changes at the hematologic and immunologic levels. CASE REPORT
A 66-year-old woman of Hispanic descent had a history of hypertension and non-insulin-dependent type 2 diabetes mellitus for 10 years. She had undergone cholecystectomy, appendectomy, subtotal thyroidectomy, and oophorectomy. Medications at the time of admission included nifedipine extended-release 60 mg Carlos Bernal MD, Instructor, Department of Internal Medicine, and Chief Medical Resident, Miami Veterans Administration Medical Center, Miami, FL Roberto Patarca MD PhD HCLD, Assistant Professor of Medicine, Department of Medicine, and Research Director, EM Papper Laboratory of Clinical Immunology, School of Medicine, University of Miami, Miami, FL Reprints: Roberto Patarca MD PhD HCLD, EM Papper Laboratory of Clinical Immunology (R-42), School of Medicine, University of Miami, RMSB Rm. 8173, 1600 N.W. 10th Ave., Miami, FL 33136, FAX 305/243-4674, E-mail
[email protected]
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qd, glipizide 20 mg bid, lisinopril 10 mg qd, and furosemide 20 mg qd. One day prior to admission, triamterene 75 mg/hydrochlorothiazide 50 mg qd was started by a private physician. The patient was brought to the emergency room with shortness of breath, sweating, nausea, and three episodes of diarrhea, which started 30 minutes after the ingestion of the first tablet of triamterene/hydrochlorothiazide. She stated that five years before in a different city, she had a similar episode after ingestion of hydrochlorothiazide alone in a dose she did not recall. At that time, she required hospitalization in a medical intensive care unit for severe pulmonary edema and a workup that included a coronary angiogram and an echocardiogram. The results of the tests were normal and she improved after three days of hospitalization. She had failed to report this event to the physician who prescribed the triamterene/hydrochlorothiazide tablets on the current occasion. The physical examination on admission revealed a diaphoretic, cyanotic woman with BP 140/70 mm Hg, HR 130 beats/min, RR 38 breaths/min, and T 39 ˚C. Neck veins were flat; heart sounds were normal without murmurs, rubs, or gallops; and chest auscultation revealed diffuse bilateral inspiratory crackles. The abdomen was benign and examination of the extremities revealed bilateral +2 pitting edema up to the knees with a negative Homan’s sign, which, if present, would have suggested deep venous thrombosis. Arterial blood gas analysis yielded pH 7.37, pCO2 32 mm Hg, pO2 40 mm Hg, bicarbonate 20 mEq/L, oxygen saturation 86% on room air, and an arterial–alveolar gradient of 60. An electrocardiogram showed sinus tachycardia at 130 beats/min with no ST segment–T wave changes that would have suggested ischemia. A chest X-ray showed a normal heart size and bilateral interstitial infiltrates suggestive of pulmonary edema. An echocardiogram was immediately done and, although a poor window was obtained, it documented a normal ventricular ejection fraction and no areas of hypokinesis. The pulmonary artery could not be assessed. A ventilation–perfusion scan was reported as low probability for pulmonary embolism. Cardiac enzymes, liver function tests, and coagulation studies were within normal limits. Blood cultures yielded no growth. Hematologic assessment showed a white blood cell count of 3.8 × 103/mm3 with a left shift in the differential (polymorphonuclear cells 86%, lymphocytes 12%, monocytes 1%, and eosinophils
