Pathophysiology treatment of Hereditary Angioedema

Hereditary angioedema is an autosomic dominant disease that is characterized by recurrent angioedema and effected by a defective enzyme known as C1 inhibitor. There are three types of the disease, the first one related to a decrease in the production of the enzyme, the second one characterized by an altered function of the enzyme and the third one due to an altered factor xiI gene. The recurrent angioedema may localized in the periphery, in the gastrointestinal system or laryngeal, the last one being life threatening. For the treatment there are a many drugs available, such as attenuated androgens, fresh frozen plasma, tranexamic acid or the enzyme substitution by a C1 inhibitor concentrate purified from plasma, nanofiltered or recombinant. Recently, treatment has directed to the avoidance of baradykinin production or its action through its B2 receptor.

Introduction

HAE is a rare disease, but it has a great impact on the quality of life of the patient, both due to the recurrence of symptoms and the risk to life in certain circumstances.
It is a disease of genetic origin, transmitted with an autosomal dominant pattern. It is characterized by the presence of recurrent episodes of non-pruritic angioedema that can affect any part of the body; it typically involves the lower and upper extremities, the digestive system, the face, and the airway.

Historical background

The first description of the disease is located in 1586 when Donati described patients with angioedema, without association with urticaria. In 1883 Quincke reported cases of the disease, calling it angioneurotic edema. It was up to Sir William Osler, in 1888, to comment on the hereditary nature of the disease and its autosomal dominant pattern. 1 Improvement in laboratory techniques allowed Virginia Donaldson to identify the C1 Inhibitor molecular defect in 1963. https://wearehae.co.uk/ .

Epidemiology

The prevalence of this disease, based on the bibliography, has been determined at 1:10 000 and up to 1:50 000, without finding gender differences or race predominance. 1 There are no data regarding the Mexican population. In the Allergy and Clinical Immunology service of the General Hospital of Mexico, in the last five years a patient has been managed. Seven cases are published in the national bibliography, published in the Allergy Magazine. 4,5 The disease begins in childhood, around two to three years of age. 1 More than half of the cases present symptoms at 10 years. The disease has been observed to worsen during adolescence and persist throughout life, with an unpredictable course.

Genetics

Genetic studies have identified more than 150 different mutations without finding a clear correlation between the genetic defect and the severity of the disease so far. 1 Although mutations that produce truncated proteins or alteration in protein processing have been related and are related to type I. Mutations in the active site, generally in exon 8, are related to a defective protein that is produced in normal or increased quantity, which is found in type II.

It should be considered that despite the identification of an autosomal dominant inheritance pattern, in a quarter of the patients there will be no family history of the disease because they are spontaneous mutations.