Severe Allergic Reaction to Hydrochlorothiazide Mimicking Septic Shock

Abstract

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.

Sulfonamide cross-reactivity: Is there evidence to support broad cross-allergenicity?

“…The literature search revealed a retrospective chart review and five case reports involving thiazides or related diuretics and sulfonamide allergies. [62][63][64][65][66][67] In one case, reported by Mineo and Cheng, 65 a woman with septic shock due to pneumonia was discharged from the hospital and started on furosemide. Her current drug therapy included hydrochlorothiazide, and she had a documented history of allergy to penicillin and sulfamethoxazole.…”

“…The manufacturer indicated that abacavir was being taken concurrently during the clinical trials and could have contributed to the rash seen in 2 of the patients. In another study cited in the prescribing information for amprenavir, 71 65 patients who had previously received a sulfonamide took amprenavir; 19 of the patients had a history of rash due to sulfonamides. Seven (37%) of those 19 patients developed a rash while taking amprenavir compared with 10 of 46 patients (22%, p = 0.208; not significant) without a history of sulfonamide-induced rash; 13 of the 17 patients who developed a rash were also receiving efavirenz, abacavir, or both.…”

Reacción grave e infrecuente con hidroclorotiazida

“…La paciente descrita presentó tres reacciones adversas graves que simulaban choque séptico tras la toma de hidroclorotiazida. En la literatura existe un caso que describe una reacción similar asociada con infi ltrados pulmonares, 9 así como otros casos de edema agudo de pulmón. 5,6 Se desconoce el mecanismo inmunológico implicado en la reacción, sin embargo, el corto periodo de latencia entre la toma del fármaco y la aparición de síntomas sugiere un mecanismo de hipersensibilidad inmediato, si bien las características del cuadro clínico indican un mecanismo tipo enfermedad del suero, mediado por inmunocomplejos e hipersensibilidad tipo III Gell y Coombs.…”

Life-threatening idiopathic reaction to hydrochlorothiazide treated with veno-venous extracorporeal membrane oxygenation

“…1 HCTZ has rarely been shown to cause idiopathic, non-cardiogenic, pulmonary edema, with or without shock, in over 60 case reports since the first publication in 1968. [2][3][4] We describe a case report of a patient transferred to our facility for life-sustaining veno-venous extracorporeal membrane oxygenation (VV-ECMO) secondary to presumed septic shock and acute respiratory distress syndrome (ARDS). It was later concluded that the patient had an allergic reaction to HCTZ, representing the first case report to our knowledge of such a severe reaction to this medication supported by ECMO therapy.…”