Hereditary angioedema (HAE) is a rare genetic disease that affects around 1,500 people in France. It is mainly linked to the deficiency of a protein in the blood (C1 inhibitor). Symptoms, photos, treatment: discovery.
I’hereditary angioedema (HAE) is a rare genetic disease responsible for a protein deficiency (the C1 Inhibitor). The number of patients in France is estimated at around 1,500 cases. It’s a disease hereditary which can begin early in childhood and is characterized by the unpredictable and sudden onset of edema (transient swellings) in the skin or mucous membranes. What are the different types of angioedema? What are the typical symptoms of an HAE? The causes ? How is the disease diagnosed? What treatment to treat it?
What is the definition of angioedema?
“The term “angioedema” refers to a frequent symptom which corresponds to transient and limited swelling that can reach different parts of the body (skin and mucous membranes)“, defines Pr Laurence Bouillet, national coordinator of the Reference Center for Angioedema (CREAK). several types of angioedema:
► Mast cell angioedema (or histamines) spontaneous (the most frequent) or allergic (commonly called Quincke’s edema)
► Bradykinic angioedema of which is part hereditary angioedema (HAE)who is his rare (about 1,500 people are affected in France). In the past, hereditary angioedema (HAE) was called “angioedema“.
What are the typical symptoms of hereditary angioedema?
The disease is characterized by the appearance unpredictable and unexpected ofedema that can be located on any part of the body like hands, feet, face (lips, eyelids), genitals, throat, abdomen… The disease can occur at any age, including in children or adolescents. These edemas persist for about 2 to 5 days then disappear. These edemas can be bothersome and painful (tightness or painful tension). Due to their location, some edemas can be serious, in particular those of the throat which can obstruct the airways and lead to deadly asphyxiation in the absence of appropriate treatment. Their care is a vital emergency. Those located on the abdomen can cause severe pain with vomiting and may require emergency hospitalization. Angioedema attacks are often spontaneous but can be triggered by physical trauma, even minimal medical procedures (such as scaling-type dental care), infections, medication, etc.
Pictures of hereditary angioedemas
What causes hereditary angioedema?
HAEs are secondary to a deficiency or malfunction of a protein blood called the C1 inhibitor (C1Inh). This protein plays a regulatory role the kallikrein-kinin pathway (sets of proteins responsible for the synthesis of bradykinin). When the C1 inhibitor runs out, these proteins activate in excess and generate a transient and localized increase in bradykinin. Bradykinin increases the permeability of blood vessels, which leads to a liquid leak in the tissues, responsible for oedemas. “Note that there are other types of hereditary angioedema which are not linked to a deficiency of the C1 inhibitor but to other genetic mutations“, specifies our interlocutor. It is said that the transmission of the disease is autosomal dominant and that most cases are heterozygousthat is to say thatit can be passed on to the child if only one parent is affected.
What is type 1 or 2 HAE?
► Type 1 is the most common hereditary angioedema (85% of patients) and is characterized by a deficiency of the C1 inhibitor protein.
► Type 2 is rarer and represents 15% of patients. It is characterized by a normal rate of C1 inhibitor but this one does not function correctly.
What is a normal C1 Inhibitor HAE?
This type of HAE is not associated with C1 inhibitor deficiency. It is secondary to an imbalance of the kallikrein-kinin pathway due to various mutations of the proteins composing it. The effect is the same as in the case of C1 Inhibitor deficiency, i.e. a transient and localized increase in bradykinin. The main mutations involved affect the F12, plasminogen and kininogen genes. Other mutations are being characterized.
“The diagnosis of HAE with C1Inh deficiency is based on a simple blood test to assess the concentration and functioning of the C1 inhibitor. The diagnosis is more complex for HAE without C1Inh deficiency. In this case, it is necessary to proceed to genetic analysis, explains Professor Bouillet. As with all genetic diseases, it is imperative to carry out family screening (parents and siblings), even if family members do not have symptoms. Indeed, people can carry the mutation but have no symptoms.
The treatments usually used in mast cell angioedema (anti
► Emergency treatment in the event of a crisis: the Icatibant by subcutaneous injection is the preferred one because “in case of severe attack or risk of serious edema (at the throat for example), the patient can quickly perform a subcutaneous injection themselves (the patient has the product at home).
The risk of death exists in a patient who is not diagnosed or who does not have his treatment on him.
► Basic treatment: “When patients have a lot of seizures, we can offer them a disease-modifying treatment to prevent the occurrence of a seizure. Currently, patients have 2 new, effective and well-tolerated treatments (either orally or by subcutaneous injection every month“), details our expert. A dozen other treatments are under development.
The management of hereditary angioedema requires regular follow-up by a CREAK referring doctor. Patients must have a care and emergency card for the rare disease with them and have access to emergency treatment at home due to the potential seriousness of the disease.
Does it impact life expectancy?
“No, if the patient has been diagnosed and has the crisis treatment at home (“on him”). The risk of death exists in an undiagnosed patient or in a patient who does not have his specific treatment on him. Well taken care of, patients have the same life expectancy as the general population. However, the unpredictability of seizures can significantly alter the quality of life of patients. This is why he does not hesitate to prescribe a basic treatment to restore a good quality of life.“, concludes our interlocutor.
Thanks to Professor Laurence Bouillet, national coordinator of the Angioedema Reference Center (CREAK)
Sources:
– Hereditary angioedema: diagnosis and management in adults and children, Haute Autorité de Santé, 2021
– Hereditary angioedema, Ministry of Health sheet
– International Association of Patients with C1 Inhibitor Deficiency (AHEI)
– Associations of patients suffering from C1 inhibitor deficiency angioedema (AMSAO)