Severe allergic reaction to hydrochlorothiazide mimicking septic shock.

Hydrochlorothiazide (HCTZ) is a sulfonamide-containing drug with commonly reported adverse effects that include electrolyte abnormalities, orthostatic hypotension, hyperglycemia, and photosensitivity. A few reports have described rare but serious drug complications such as interstitial pneumonitis, angioedema, and aplastic anemia. We describe a patient who experienced a serious HCTZ-induced adverse event that, to our knowledge, has not yet been reported in the literature. A 78-year-old woman came to the emergency department with dyspnea and severe fatigue; her signs and symptoms were suggestive of septic shock from pneumonia. She was treated accordingly, her condition improved, and she was discharged home. During the next 2 months, the patient returned to the emergency department 2 more times and was hospitalized each time with the same diagnosis. During her third admission, it was discovered that the patient's primary care physician had restarted her HCTZ for hypertension after it had been discontinued during each of the first two hospitalizations. The patient's symptoms began within hours of the first and second hospitalizations and almost immediately after taking a dose of HCTZ on the day of the third hospitalization. Her medical history revealed documented allergic reactions to sulfonamide drugs and penicillin; thus a hypersensitivity reaction to HCTZ was suspected. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's hypersensitivity reactions and HCTZ therapy. Because of a lack of evidence showing cross-reactivity among the different classes of sulfonamides, the mechanism of the allergic reaction to HCTZ was unlikely to be cross-sensitivity between sulfonamide antibiotics and sulfonamide nonantibiotic drugs. Although the mechanism is not clear, evidence shows that the allergy to the HCTZ (sulfonamide nonantibiotic) may be due to a predisposition to drug allergies rather than sulfonamide cross-sensitivity. Clinicians should be aware of the potential for these types of allergic reactions.

Hydrochlorothiazide-induced angioedema in a patient allergic to sulfonamide antibiotics: evidence from a case report and a review of the literature.

BACKGROUND: Hypersensitivity reactions in patients receiving sulfonamide antibiotics have been frequently documented in the literature, but cross-reactivity with sulfonamide non-antibiotics rarely has been reported. CASE SUMMARY: An 82-year-old woman with a history of hypersensitivity reactions to sulfamethoxazole-trimethoprim resulting in angioedema and rash presented to the emergency department (ED) with angioedema and severe dysphagia, shortness of breath, and rash after receiving valsartan and hydrochlorothiazide (HCTZ) for 4 months. Valsartan was identified as the most likely cause of the symptoms and was discontinued; however, the patient continued to have weekly episodes of angioedema and eventually returned to the ED. HCTZ was discontinued at the second ED visit, and the angioedema disappeared. However, it reappeared after reinitiation of HCTZ, and the patient returned to the ED again; this time with more severe symptoms. After the third ED visit and second hospitalization, HCTZ was permanently discontinued, and the angioedema has not returned. HCTZ was the definite cause of angioedema in this patient based on a score of 9 on the 10-point Naranjo adverse drug reaction probability scale. CONCLUSIONS: Although the probability of true cross-reactivity is not known, clinicians should be aware that an allergic-like reaction to sulfonamide-containing non-antibiotics may occur in patients with known allergies to sulfonamide-containing antibiotics. These patients should be monitored closely when receiving these drugs. Further evaluation is needed to determine whether angioedema should be added to the list of adverse events associated with HCTZ.

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia.

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.

Ex vivo antigen preparation for the serological detection of drug-dependent antibodies in immune haemolytic anaemias.

Two patients with severe, intravascular haemolysis due to drug-dependent antibodies are described. The antibodies were directed against presumptive metabolites of buthiazide (International Non-proprietary Name, butizide) and nomifensine. Their detection was possible only in the presence of ex vivo antigens (i.e. fresh serum of volunteers after ingestion of the drugs) while in vitro antigen preparations yielded inconclusive results. Both antibodies lysed normal red cells in the presence of ex vivo antigens and complement. The buthiazide-related antibody was IgG (subclass IgG1), the nomifensine-related antibody was IgM. We conclude that the use of ex vivo antigens is of great importance in the serological evaluation of cases with suspected drug-dependent immune haemolysis.

Fatal intravascular immune hemolysis induced by hydrochlorothiazide.

A patient receiving antihypertensive therapy developed acute intravascular hemolysis and died. Hemolysis was due to an immune process associated with antibody to thiazide. Only two other cases have been reported. Thiazide-induced hemolysis appears to be confined to those patients treated concommitantly with methyldopa.

[Lung edema after administration of hydrochlorothiazide. A rare and life-threatening side effect]. / Lungenödem nach Einnahme von Hydrochlorothiazid. Eine seltene, vital bedrohliche Nebenwirkung.

Recurrent pulmonary oedema occurred in a 62-year-old woman after repeated intake of hydrochlorothiazide-triamterene tablets. Eight similar reports in the medical literature suggested it to be a rare case of intolerance to hydrochlorothiazide. The lymphocyte transformation test proved an allergic genesis: there was significant stimulation of patient lymphocytes by active agent/metabolite serum of hydrochlorothiazide but not triamterene.

Acute immune intravascular hemolysis due to hydrochlorothiazide.

Acute near-fatal intravascular hemolysis and renal failure developed in a patient after he had ingested 15 to 20 tablets of both methyldopa (Aldomet) nd hydrochlorothiazide (HydroDiuril). Serologic test results were inconsistent with those associated with methyldopa-induced hemolytic anemia and suggested that hemolysis was caused by hydrochlorothiazide antibodies reacting by an immune complex mechanism.

Anti-drug-related antibodies in nonthrombocytopenic cardiac patients.

Drug-related antibodies (quinidine, hydrochlorothiazide, and digoxin) were studied using the 51Cr platelet lysis test and a recently introduced simplified platelet factor 3 assay in a total of 109 patients admitted to a coronary care unit. Quinidine antibodies were found in 16 (14.7%), hydrochlorothiazide antibodies in six (5.5%) and digoxin antibodies in two (1.8%) of 109 patients. All patients had normal hematologic data, including platelet counts. There was a significantly high incidence of quinidine antibodies in male patients (p less than 0.02), despite the previous report that quinidine-induced purpura was seen predominantly in female patients. Ten patients (9.2%) had antiplatelet antibodies. The simplified platelet factor 3 assay can easily be done in most laboratories and appears as sensitive as the 51Cr platelet lysis test. The high incidence of drug-related or antiplatelet antibodies in hematologically asymptomatic patients may indicate the presence of an insidious, compensated thrombolytic state in many patients.