Case Presentation: A 70-year-old man with a history of hypertension presented to the emergency department with a rapid onset of laryngeal edema preceded by abdominal pain. Physical exam revealed extensive lip, tongue, and supraglottic swelling, stridor, and abdominal tenderness, but no urticaria. Initial labs were significant for leukocytosis and respiratory acidosis. The anesthesia team performed an emergency fiberoptic nasal intubation, and he was transferred to the intensive care unit. He was given empiric histamine-mediated angioedema treatment with Solumedrol, Benadryl, and famotidine. Fresh frozen plasma was also given due to concern for possible bradykinin-mediated angioedema. He was extubated on hospital day three and transferred to the medicine service. The patient later reported two similar episodes in the past year, the most recent of which was also associated with hypotension and syncope. No specific foods or medications were identified as triggers. He had been taking lisinopril for hypertension, but discontinued it after the episode of hypotension three months prior. He has a known penicillin allergy, but no history of airway compromise, nor a family history of similar symptoms. A form of bradykinin-mediated angioedema was suspected. He improved to baseline by day four and was discharged home with a pending workup, which later revealed low C1 esterase inhibitor function (6%), low quantitative C1q (5.8 U/mL), and undetectable C4 level (< 8 mg/dL), suggesting acquired angioedema in the setting of C1 esterase inhibitor deficiency (C1-INH). Additional labs were notable for elevated lymphocytes (54%) and bradykinin. He was notified of the results and advised to follow up with an allergist and his primary care physician for further workup of underlying causes, such as lymphoproliferative disorder. He was prescribed an injectable rescue medication, icatibant, and a daily preventive medication, berotralstat. The patient is currently being evaluated by hematology.
Discussion: Acquired angioedema (AAE) is a rare condition characterized by recurrent episodes of edema of the face, extremities, upper respiratory tract, and gastrointestinal tract without urticaria. AAE resembles hereditary angioedema, but instead develops after the fourth decade of life and is often linked to lymphoproliferative disorders, plasma cell disorders, or autoimmune conditions. The prevalence is estimated to be 1:100,000 to 1:500,000 in the general population, with just over 100 cases reported in the literature. However, this may be an underestimation as AAE often goes unrecognized before diagnosis, despite the significant risk of morbidity and mortality if untreated. Obstacles to diagnosis include: lack of awareness of an acquired form of C1-INH deficiency, lack of family history and therefore asymptomatic screening, and misattribution to drug reactions due to polypharmacy at the typical age of AAE diagnosis.
Conclusions: The purpose of this case is to raise awareness of AAE, as lack of early recognition can lead to life-threatening complications and delays in the diagnosis of an underlying malignancy. In our patient’s case, suspecting and testing for acquired C1-INH deficiency led to a preliminary diagnosis that led to an allergy referral, eventual access to life-saving rescue treatments, and the start of a comprehensive hematologic work-up. On discharge, extensive patient education and communication with the healthcare team is key to prevention and proper treatment of future episodes.