A Rare Cause of Angioedema - A Novel Case Report

ABSTRACT

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well described as an etiology to severe acute respiratory distress syndrome (ARDS). However, rare immunologic and allergic manifestations may also occur from this infection. We report a novel case of angioedema occurring in the setting of COVID-19 infection in a fully vaccinated patient. Case Report A 61-yearold COVID-19 vaccinated female with hypertension presented to the emergency department with tongue and lip swelling, odynophagia, dysphonia, and difficulty breathing. She denied personal or family history of allergies, anaphylaxis, or angioedema. Her home medications included Aspirin, methadone, Seroquel, and Klonopin, with no recent changes reported. Physical exam was notable for significant lip and tongue edema, audible dysphonia, and bilateral end-inspiratory wheezing. She was hypoxemic and placed on nasal cannula. Laboratory findings revealed lymphopenia, elevated inflammatory proteins, including C-reactive protein (57), Lactate dehydrogenase (LDH) (238), and D-dimer (11.52). Functional C1 esterase inhibitor levels (>91) were normal. Nasal PCR swab returned positive for SARS-CoV-2. Ear, nose, and throat specialist was consulted given concern for angioedema, and flexible nasolaryngoscopy was performed revealing uvular, epiglottic, and bilateral arytenoid edema concerning for impending airway compromise. The patient was initiated on intravenous methylprednisolone, epinephrine, antihistamines, tranexamic acid and admitted to the medical intensive care unit (ICU). She was monitored closely in the ICU with subsequent improvement of the angioedema and resolution of the hypoxemia. She was discharged with an oral steroid regimen and scheduled for a follow-up appointment with an allergist. Discussion: There exists only a handful of case reports describing angioedema in patients with COVID-19 infection. In those reports, patients also had normal C1 esterase inhibitor levels and no personal or family history of inherited angioedema. Interestingly, our patient was vaccinated six months prior to her presentation. The association between SARS-CoV-2 and angiotensinconverting enzyme 2 (ACE-2), the primary receptor for viral entry into the epithelial cells of the lungs, could be a potential explanation for the occurrence of angioedema. ACE-2 plays a pivotal role in inhibiting a potent ligand of bradykinin receptor 1, Arginine bradykinin. It has been postulated that SARS-CoV-2 downregulation of ACE-2 leads to elevated angiotensin II levels and subsequent activation of the bradykinin pathway. Excessive bradykinin production generates high levels of nitric oxide and prostaglandins, resulting in vasodilation, increased vascular permeability, and angioedema. This case highlights the importance of recognizing atypical and rare presentations of COVID-19 infection, especially angioedema, given its sudden onset and life-threatening complications.