Hereditary Angio-Oedema for Dermatologists

Abstract

Among angio-oedema patients, hereditary angio-oedema (HAE) should not be overlooked. Besides skin swellings, these patients might have very painful abdominal attacks and potentially life-threatening angio-oedema of the upper airway. They will not respond to traditional anti-allergic therapy with antihistamines, corticosteroids, and adrenaline, and instead need specific drugs targeting the kallikrein-kinin pathway. Classically, patients with HAE have a quantitative or qualitative deficiency of the C1 inhibitor (C1INH) due to different mutations in SERPING1, although a new subtype with normal C1INH has been recognised more recently. This latter variant is diagnosed based on clinical features, family history, or molecular genetic testing for mutations in F12, ANGPT1,or PLG.The diagnosis of HAE is often delayed due to a general unfamiliarity with this orphan disease. However, undiagnosed patients are at an increased risk of unnecessary surgical interventions or life-threatening laryngeal swellings. Within the last decade, new and effective therapies have been developed and launched for acute and prophylactic therapy. Even more drugs are under evaluation in clinical trials. It is therefore of utmost importance that patients with HAE are diagnosed as soon as possible and offered relevant therapy with orphan drugs to reduce morbidity, prevent mortality, and improve quality of life.

C1-inhibitor Deficiency Induces Myositis-like Symptoms Via the Deposition of the Membrane Attack Complex in the Muscle

“…In particular, certain HAE patients experience EM as a prodromal symptom, and the administration of plasma-derived C1-inhibitor concentrate during EM is reported to be effective as prophylaxis for HAE attacks ( 19 ). Regardless of the presence of skin lesions, four different types of drugs (plasma-derived or recombinant C1-inhibitor concentrates, kallikrein inhibitors, or bradykinin B2 inhibitors) are selected for the treatment of acute attacks ( 20 , 21 ); the administration of C1-inhibitor concentrate is effective for long-term prophylaxis ( 21 ).…”

Recognition and Management of Hereditary Angioedema: Best Practices for Dermatologists

“…HAE typically manifests during childhood or young adulthood, with symptoms often worsening around the time of puberty [9]. Attacks are recurrent and generally unpredictable, with severity and frequency variable between patients and also within individual patients at different stages of life [14]. Common sites of HAE swelling include the face (Fig.…”

“…Attack frequency can range from almost never to multiple attacks per week, with a frequency of 1 to 3 attacks per month being the average in the absence of prophylaxis [9]. Many HAE attacks happen spontaneously, but about half of attacks are triggered by factors such as hormones (e.g., during menstrual cycle, pregnancy, or birth control use), emotional stress, and physical trauma, including medical and dental surgeries and procedures [9,14]. Some attacks are preceded by prodromal symptoms such as a transient reticular rash [erythema marginatum (Fig.…”

“…Some attacks are preceded by prodromal symptoms such as a transient reticular rash [erythema marginatum (Fig. 3)], skin tingling, or vague complaints such as nausea, anxiety, fatigue, or flu-like symptoms [14].…”

“…C1INH C1 inhibitor, HMW high molecular weight, IgE Immunoglobulin E, NSAIDs nonsteroidal anti-inflammatory drug. *E.g., tryptase, chymase, heparin, prostaglandins, cysteinyl leukotrienes, and anaphylatoxins may have more rapid onset [8,14]. Abdominal attacks can be excruciatingly painful and can result in unfortunate consequences such as narcotic dependency or unnecessary surgery [9,15].…”