Hereditary angioedema - rare but painful

Swelling, like fever, can occur in different situations and for different reasons - so it can be difficult to diagnose. Symptoms of this type are often mild but annoying, for example if they are caused by an insect bite. Sometimes they can also be a sign of serious cardiovascular or kidney disease. However, there are other dangerous swellings whose occurrence can acutely threaten the patient's life and which almost always cause severe pain and discomfort due to their extent.

Such painful, large swellings that do not respond to conventional treatment methods can be a symptom of hereditary angioedema, also known as HAE. Although the diagnosis process itself is not very complicated, it takes an average of twelve years from the first symptoms to the correct diagnosis. This is mainly due to the low awareness of the disease due to its rarity. The frequency of occurrence is between 1:50,000 and 1:100,000, which means that in Germany alone there are probably well over a thousand people affected who are predominantly undiagnosed, which makes more accurate estimates difficult.

The first symptoms of HAE usually appear in the second or third decade of life, but there are also patients in whom they begin earlier, even in infancy, or later. The symptoms of this disease are often mistaken for allergic reactions, but conventional antihistamines or glucocorticosteroids do not bring any improvement in such cases.

"In connection with hereditary angioedema, we speak of swelling attacks that grow continuously and quite quickly within a few hours to enormous sizes. Apart from the lack of response to the usual treatment with antihistamines and glucocorticosteroids, the swelling usually differs from that characteristic of allergies in that it is not accompanied by itching and urticaria or skin irritation. It is also typical that the swelling in HAE subsides on its own within 3 to 5 days. Swelling attacks in hereditary angioedema can affect the skin or the subcutaneous tissue. In the latter case, they are often very dangerous for the patient due to the involvement of the pharynx, larynx, digestive tract or urinary tract - they can cause complete obstruction of the airways as well as severe abdominal pain and vomiting due to intestinal obstruction or partial intestinal obstruction and can even lead to kidney failure," says Dr Aleksandra Kuch, MD. Aleksandra Kucharczyk, MD, a specialist in internal medicine and allergology who works with Saventic Care, an organisation that deals with the diagnosis of rare diseases.

Although it is not possible to predict in which situation and when swelling will occur in a patient, patients name some factors that favour attacks. These include, for example, surgical or dental procedures, infections, minor injuries, psychological factors (stress) and, in women, hormonal changes.

Hereditary angioödem - When should a diagnosis be checked?

HAE is a rare disease that affects around 1 in 50,000 people worldwide. The probability that there are sick people in our environment or that we ourselves become ill is therefore low, but cannot be ruled out. Many patients are still undiagnosed.

"Hereditary angioedema is a disease that is genetically determined in around 80 per cent of patients, which is why the symptoms often occur in other family members as well. In the majority of cases, it is caused by a new mutation in the gene. Characteristic symptoms (the appearance of massive swelling) are caused by increased permeability of the blood vessels, which is caused by increased bradykinin levels. The low production of this protein results in turn from a deficiency or abnormal function of the C1 esterase inhibitor - an important protein involved in coagulation processes, the formation of kinins and the activation of the complement system. Hereditary angioedema was first described by Heinrich Quincke in 1882, but it was not until the 1960s that researchers Donaldson and Evans elucidated the pathogenesis of the disease described here. Understanding the causes of the disease has led to the development of many effective drugs," explains Dr Aleksandra Kucharczyk, MD.

HAE should be suspected in patients with the symptoms described above, i.e. recurrent massive swelling in various parts of the body, unexplained abdominal pain or sore throat that persists for 3 to 5 days despite conventional treatment and then resolves spontaneously. This is particularly true if the symptoms first appeared before the age of 40 and are also observed in other family members. Laboratory tests are required to confirm the diagnosis. Hereditary angioedema can be diagnosed in patients in whom a reduction in the C1 inhibitor level (type I HAE) or its activity (type II HAE) and frequently a reduction in the C4 complement component is detected.

Due to the rarity of HAE, symptoms or test results will not always draw a physician's attention to this diagnosis. In such cases, patients can turn to organisations that help diagnose rare diseases and analyse symptoms more comprehensively.

When to see a doctor and is HAE treatable?

If you have swelling or abdominal pain whose causes are unknown, it is definitely always advisable to consult a doctor. Although HAE attacks do not pose a threat to health in most cases, they can end tragically in the abdomen or throat. Instead of ignoring the symptoms, it is therefore better to have a thorough diagnosis carried out.

"Although the disease cannot be cured, many medications are currently available that not only quickly relieve the swelling, but also prevent it from occurring. Diagnosis of the disease therefore enables appropriate treatment, improves patient comfort and often saves their lives. A rapid response is particularly important in severe, life-threatening seizures. Long-term prophylaxis, which is now available, is particularly important for people with frequent life-threatening seizures. In this case, the regular intake of medication every 2-4 weeks leads to the complete elimination of all symptoms of the disease," explains Dr Aleksandra Kucharczyk, MD.

The early diagnosis of HAE patients is the key to ensuring their safety and quality of life. So it is definitely not worth ignoring worrying symptoms in yourself or loved ones, but starting the diagnostic process and getting answers to your burning questions. Organisations that specialise in identifying some rare conditions include Saventic Care, who will assess your medical records for symptoms that match HAE.

Article from "Saventic Health" from 16/05/2023"