Diagnosis and screening of patients with hereditary angioedema in primary care

Abstract

Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients.

Hereditary Angio-Oedema for Dermatologists

“…Patients with an early symptom onset tend to have a more severe outcome [37, 38]. The majority of patients will present before the age of 20 years, while only approximately 4% of patients experience their first attack after the age of 40 years [39]. The disease is, however, lifelong and there is a growing number of affected individuals aged ≥65 years.…”

“…Swelling of the skin causes temporary disability, whereas oedema of the bowel wall can result in bowel occlusion with pain, vomiting, or diarrhoea. Historically, one-third of patients with abdominal attacks received unnecessary surgery and other patients became dependent on morphine [10, 12, 39, 40]. The most serious manifestation is laryngeal oedema, which occurs at least once in a lifetime for 50% of patients and can cause asphyxiation [12, 13, 41].…”

“…In our centre, we find it rational to screen for C4, C1INH protein concentration, and C1INH function at the same time. Blood samples should be handled with care, since decay of functional C1INH can produce ambiguous results [39, 86], and low values should be repeated to confirm the diagnosis [82]. The measurement of complement C1q differentiates HAE from AAE, since C1q is typically decreased in the latter [87, 88].…”

“…Four different types of drugs have shown effectiveness and safety in double-blind and observational studies in HAE patients: plasma-derived C1INH concentrates (trade names Berinert® and Cinryze®), recombinant C1INH concentrate (conestat alfa with trade name Ruconest®), a kallikrein inhibitor (ecallantide with trade name Kalbitor®) launched in the USA, and a competitive BK2R inhibitor (icatibant with trade name Firazyr®) [39, 109]. These drugs have been marketed for approximately 10 years and Berinert® has been available with special permission in many countries for approximately 40 years [56].…”

An ABC of the Warning Signs of Hereditary Angioedema

“…Furthermore, gastrointestinal involvement is quite common and it can lead to unnecessary surgery. Laryngeal edema and airway obstruction are more rare [1,27,28]. Unlike HAE, the main site of the swelling in ACEI-AAE tends to be the face and not the abdomen [8,9,29,30].…”