Hereditary angioedema (HAE) is a rare genetic disorder characterized by episodes of sudden and widespread swelling of affected areas of the skin, subcutaneous tissue, and mucous membranes. Unlike an allergic reaction, the swelling is not associated with an increase in histamine levels and is not amenable to traditional treatment with antihistamines. The underlying cause of HAE is C1 inhibitor deficiency, which leads to excess kallikrein activity and the formation of broncokinin, which causes vasodilation and increased vascular permeability. Episodes of swelling may involve various anatomical sites, including the face, arms, legs, and internal organs, which may lead to life-threatening conditions such as laryngeal edema and collapse.
History of the disease and interesting historical facts
The history of hereditary angioedema goes back more than a hundred years. The first descriptions of this disease date back to the beginning of the 20th century, when in 1888 the Austrian dermatologist Victor van Hirschpraun documented cases of sudden swelling that did not respond to antihistamines. In 1963, studies conducted by the University of Sheffield showed this pathology as a genetically inherited disease. In parallel, in the 1970s, scientists began actively studying the molecular mechanisms of the disorder, which led to the identification of a deficiency of C1 inhibitor. This protein, involved in normal blood clotting and inflammatory processes, has become a key object of study for understanding the pathogenesis of HAE.
Epidemiology
Hereditary angioedema occurs with a frequency of approximately 1 in 50,000 to 1 in 150,000 population worldwide. The disease is inherited in most cases in an autosomal dominant manner, which means that having one copy of the mutated gene is enough to cause its symptoms. According to statistics, NAO is diagnosed more often in countries with a high level of medical development, since there are more opportunities for genetic testing. The disease occurs with equal frequency in men and women, but clinical manifestations in women may be more pronounced due to hormonal factors such as menstruation and pregnancy, which can be triggers for exacerbations.
Genetic predisposition to this disease
The main cause of hereditary angioedema is a mutation in the SERPING1 gene, which codes for the synthesis of C1 inhibitor. Depending on the nature of the mutation, three types of the disease are distinguished. The first type is classical, caused by a complete loss of function of C1 inhibitor, while the second is associated with its partial loss. The third type, the last one, includes genes that code for a mutated form of C1 inhibitor, which, however, is present in sufficient quantities. Genetic tests can be useful for diagnosis and predisposition to the disease, since 20% cases remain differentially unclear. It is important to emphasize that increased awareness of the genetic aspects of HAE helps in the development of prognosis and treatment methods.
Risk factors for the development of this disease
Risk factors for hereditary angioedema include:
- Genetic heredity – the presence of close relatives with a previously diagnosed disease.
- Hormonal changes – menstrual cycles, pregnancy and hormone treatments can increase the severity of the disease.
- Infections – Some viral infections precede the onset of HAE.
- Physical factors – injuries, surgeries, and even stress can be triggers for attacks.
- Chemical factors – the impact of certain intoxicants or medications, realized through allergic mechanisms.
Diagnosis of this disease
Diagnosis of hereditary angioedema involves both clinical evaluation and laboratory testing. The main symptoms occur suddenly and include:
- Swelling of the skin and subcutaneous tissues, especially the face and extremities.
- Swelling of the mucous membranes, which can lead to difficulty breathing.
- Abdominal pain, which may be the result of swelling of the abdominal organs.
Laboratory tests include:
- Measurement of C1 inhibitor levels and its function.
- Analysis for the presence of kallikrein and other components of the complement system.
- Genetic tests to confirm mutation in the SERPING1 gene.
Radiological examinations such as abdominal ultrasound may be used to exclude other causes of abdominal pain. Differential diagnosis with other forms of edema such as allergic angioedema or drug-induced edema is also important.
Treatment
Treatment of hereditary angioedema requires an individual approach and may include pharmacological therapy, surgical correction and the use of other methods. General treatment involves:
- Timely identification of triggers.
- Teaching the patient self-care, including administering medications at the first signs of swelling.
Pharmacological treatment includes the following drugs:
- C1 inhibitors - concentration from normal human plasma.
- Epsilon-aminocaproic acid - used to prevent attacks.
- Octagam is a replacement therapy for immunoglobulin deficiency.
Surgical treatment may be considered in cases of recurrent edema that causes significant impairment of the patient's quality of life, by performing surgical correction or removal of the affected areas. Other treatments include immunotherapy and supportive therapy.
List of medications used to treat this disease
The main drugs used in the treatment of hereditary angioedema include:
- C1 inhibitor (Zomak, Heylian, etc.)
- Epsilon-aminocaproic acid.
- Bradykenin antagonists (eg, Icatibant).
- Recombinant forms of C1 inhibitor.
Disease monitoring
Monitoring the condition of a patient with hereditary angioedema includes regular medical observation with assessment of the frequency and severity of attacks, as well as analysis of the effectiveness of the therapy. Control stages may include:
- Regular laboratory testing of C1 inhibitor levels.
- Assessing the patient's quality of life by indexing the manifestations of the disease.
- The forecast based on the number of participants includes promising areas for improvement.
Complications resulting from uncontrolled attacks can be serious, including life-threatening laryngeal edema and intestinal obstruction, highlighting the critical importance of patient monitoring.
Age-related features of the disease
Hereditary angioedema can manifest at any age, but the clinical picture often develops in childhood or adolescence. In children, rare cases may have more pronounced symptoms, while in adults, symptoms can vary significantly depending on hormonal levels and physical activity levels. In older patients, the course is milder, but there is a high probability of mixed forms of the disease and masking under other conditions.
Questions and Answers
- How is hereditary angioedema inherited? The disease is inherited in an autosomal dominant manner, with only one abnormal copy of the gene required to cause symptoms.
- What provokes exacerbations of the disease? Flare-ups can be triggered by infections, injuries, stress, and hormonal changes.
- What is the prognosis for hereditary angioedema? The prognosis varies, but with proper treatment, patients can lead full lives.
- What are the main symptoms of HAE? The main symptoms include sudden swelling of the skin, mucous membranes and abdominal pain.
- How is HAE diagnosed? Diagnosis includes clinical examination, laboratory tests of C1 inhibitor levels, and genetic testing.
Dr. Oleg Korzhikov recommends taking preventive measures and being vigilant to symptoms. "If you have a predisposition to hereditary angioedema, always keep the medications prescribed by your doctor on hand. Do not neglect regular check-ups and monitor changes in your health."
