Clinical presentation of hereditary angioedema

Abstract

Hereditary angioedema (HAE) is a rare, autosomal dominant disease caused by a deficiency in the C1-inhibitor protein. It is characterized by recurrent episodes of nonpruritic, nonpitting, subcutaneous or submucosal edema that typically involves the extremities or the gastrointestinal tract. However, the genitourinary tract, face, oropharynx, and/or larynx may be affected as well. Symptoms often begin in childhood, worsen at puberty, and persist throughout life, with unpredictable severity. Patients who are untreated may have frequent attacks, with intervals that can range from every few days to rare episodes. Minor trauma and stress are frequent precipitants of swelling episodes, but many attacks occur without clear triggers. HAE attacks may be preceded by a prodrome and/or be accompanied by erythema marginatum. The swelling typically worsens over the first 24 hours, before gradually subsiding over the subsequent 48 to 72 hours. Although oropharyngeal swelling is less frequent, more than half of patients have had at least one episode of laryngeal angioedema during their lifetime. Attacks may start in one location and spread to another before resolving. HAE attacks that involve the abdomen or oropharynx have been associated with significant morbidity and mortality. Abdominal attacks can cause severe abdominal pain, nausea, and vomiting. Bowel sounds are often diminished or silent, and guarding and rebound tenderness may be present on physical examination. These findings may lead to unnecessary abdominal imaging and procedures. Fluid shifts into the interstitial space or peritoneal cavity can cause clinically significant hypotension. Laryngeal edema poses the greatest risk for patients with HAE. Although prompt diagnosis and treatment improves outcomes, the variable presentation of HAE can make it difficult to diagnose.