Bringing Your “A” Game to Urticaria and Angioedema

Abstract

Urticaria and angioedema are common conditions encountered by the practicing allergist. Although we lack epidemiologic data of the accurate prevalence of urticaria and angioedema in the United States, there is a general perception among practicing allergists that we are seeing more patients with both chronic urticaria (CU) and angioedema. Whether this is due to a true increase in prevalence of CU and angioedema or that other specialists are managing these patients less frequently is unclear. In this issue of the Journal of Allergy and Clinical Immunology: In Practice, 3 review articles discuss the topics of urticaria and 2 different forms of angioedema. The most common form of angioedema is due to histamine release and may or may not be associated with urticaria. Hereditary nonhistamine-mediated angioedema has been recognized for more than a century as a different entity. Recently, there has been an explosion of literature on hereditary angioedema (HAE), partly due to newer HAE-specific therapies. For many years, investigators have noted patients with HAE-like presentations but who had normal C1INH. This condition has been referred to by several names, including HAEIII and estrogen-dependent HAE. In this issue, Riedl tackles this perplexing subject of hereditary angioedema with normal C1 inhibitor, which he has termed HAE-nmlC1INHdef. Riedl points out the clinical manifestations of this rare condition, which have many similarities with other forms of C1INH deficiency, eg, recurrent angioedema, including gastrointestinal angioedema, and the absence of urticaria. Key differentiating features of HAE-nmlC1INHdef are that the age of onset is later, some patients may develop hemorrhage into areas of angioedema, and the disease predominately affects women. Estrogen has been noted to exacerbate this condition in many patients, which potentially could be related to estrogen’s effects on bradykinin degradation. Unfortunately, the pathophysiology of this condition remains unknown, and various hypotheses are discussed by Riedl. Diagnostic criteria for HAE-nmlC1INHdef are also reviewed, including the requirement for a demonstration of either a factor XII mutation (rare in the United States) or a positive family history of angioedema. As discussed, this