Hereditary angioedema
Hereditary angioedema (HA) is a disorder characterised by recurrent episodes of severe swelling (angioedema). Commonly this affects the limbs, face, GI tract and airway and may be caused by minor trauma or stress. The angioedema often occurs with pain, nausea and vomiting, and can be life threatening in the case of airway swelling, note how patients are not itchy (no histamine) as will be explained by the pathophysiology later.
Image: “Swollen hand during a hereditary angioedema attack.” by LucyHAE, CC BY-SA 3.0, via Wikimedia Commons.
Symptoms begin in childhood and worsen during pregnancy, if untreated, attacks occur every 1-2 weeks and last 3-4 days.
HA is a very rare disease, affecting 1 in 50,000 patients. There are three types, type I, II and III. Type I is the most common (85%), type II next (15%) and type III is very rare (<1%). Type I and II are caused by mutations in the SERPING1 gene that codes for the C1 inhibitor protein, an important protein in controlling inflammation, where it blocks the activity of inflammatory proteins. Reduced C1 inhibitor levels (type I) or function (type II) in the blood due to SERPING1 mutation lead to excessive bradykinin production allowing for angioedema. Type III HA is associated with mutations in F12 gene which codes for coagulation factor XII.
Inheritance is AD, although many cases are De Novo. HA is commonly misdiagnosed as an allergy, and ineffectively treated with steroids or epinephrine. HA should be considered in patients with recurrent angioedema (without urticaria), recurrent episodes of abdominal pain and vomiting, laryngeal edema and/or positive family history of angioedema. Once there is suspicion, a blood test can measure serum complement factor 4 (C4) and C1 inhibitor level and function, which will help with a diagnosis.
Prevention of attacks is with C1 inhibitor concentrate, lanadelumab, berotralstat, danazol or tranexamic acid; ACE inhibitors are contraindicated (they block bradykinin breakdown). Management in acute treatment is to halt the edema, this can be with C1 inhibitor concentrate from donor blood (IV), but if this is not available, then fresh frozen plasma can be used as an alternative. Other treatments include synthesised C1 inhibitors.
25% of those affected die in the first two decades of life, often from misdiagnosis and lack of treatment.