RECURRENT ANGIOEDEMA FOLLOWING ANGIOTENSIN CONVERTING ENZYME INHIBITOR DISCONTINUATION

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEIs) are guideline recommended first-line treatment for hypertension. Angioedema is a recognized side effect of ACEI therapy, yet clinicians are often unaware that limited case reports describe recurrent angioedema following ACEI discontinuation. This is a case of ACEI-induced angioedema occurring after discontinuing ACEI therapy. CASE PRESENTATION: An elderly male with medical history of hypothyroidism, hypertension, and heart failure presented from his long-term care facility complaining of face, tongue, and throat swelling with dysphagia and voice changes starting 24 hours prior. Examination showed normal vital signs and edema of aforementioned areas. He denied family history of similar occurrences. It was reported 12 days prior he was seen for unilateral lip swelling and his enalapril was discontinued without further treatment. Medication administration record review showed ACEI was appropriately discontinued by his care facility. He was given methylprednisolone, diphenhydramine, intramuscular epinephrine, C1 esterase inhibitor, and 2 units of fresh frozen plasma prior to admission. The patient was monitored in the intensive care unit due to mild airway compromise but did not require invasive airway protection. A serum complement factor 4 level was checked and returned normal. He was discharged after 5 days in stable condition with resolution of symptoms. DISCUSSION: ACEIs are the most common cause of drug induced angioedema in the United States. ACEI-induced angioedema is a self-limiting swelling that may involve the lips, tongue, upper airway, and rarely intestinal wall. Swelling is said to occur because of ACEI inhibition on the angiotensin converting enzyme preventing degradation of vasoactive substances such as bradykinin (1). Recurrence of angioedema after ACEI discontinuation was reported in 46% of cases in one retrospective study (2). The precise etiology of this delayed reaction is not well described, though it is reasonable to hypothesize in part, a drug washout period must occur. The adverse drug reaction probability scale score was 5 (probable) in this patient (3). Recurrence has been documented more commonly in elderly male patients (2). The mainstay of treatment for non-allergic angioedema caused by ACEIs is discontinuation of the offending drug and acute airway management if needed. No drug therapy has been proven effective in the treatment of this condition (1). CONCLUSIONS: Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important among health care providers for appropriate diagnosis and monitoring. While self-limiting without a known effective treatment, close airway monitoring is critical for patient survival. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence early following drug discontinuation. REFERENCE #1: Erickson DL, Coop CA. Angiotensin-converting enzyme inhibitor-associated angioedema treated with c1-esterase inhibitor: A case report and review of the literature. Allergy Rhinol (Providence). 2016;7(3):168-171. REFERENCE #2: Beltrami L, Zanichelli A, Zingale L, Vacchini R, Carugo S, Cicardi M. Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor-related angioedema. J Hypertens. 2011 Nov;29(11):2273-7. REFERENCE #3: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. DISCLOSURES: No relevant relationships by Mark Malesker, source=Web Response No relevant relationships by Shraddha Narechania, source=Web Response No relevant relationships by Bryton Perman, source=Web Response