Fleeting but often pronounced episodes of swelling, predominantly in the face, but also in the hands, feet, or respiratory tract: such symptoms are indicative of angioedema. This usually occurs in the context of an allergic reaction; much more rarely, it is caused by a congenital disorder. In this case, however, additional gastrointestinal complaints usually occur. The swelling is caused by water accumulation (edema) in the subcutaneous tissue; in the past, angioedema of the face was also called Quincke’s edema.
Forms of angioedema
First, two forms of angioedema must be distinguished, as these two require principally different treatments:
- Angioedema is caused either by the neurotransmitter histamine (histamine-mediated angioedema), which is released in increased amounts during an allergy or intolerance reaction, for example, to drugs. This mechanism is similar to that which occurs in hives (urticaria).
- Much rarer is the insufficient function of a specific molecule underlying – the C1 inhibitor (angioedema by C1 inhibitor deficiency – short: AAE), which normally slows down the immune system in uncontrolled reactions. This form is mostly inherited and thus congenital (hereditary angioedema – in short: HAE). The acquired forms of this C1 inhibitor deficiency arise either in the context of cancers of the lymphatic system or as a result of autoimmune diseases.
What are the causes of hereditary angioedema?
In patients with hereditary angioedema, the level of a protein called C1 esterase inhibitor is decreased in blood plasma. This protein inhibits the first component of the complement system. The complement system, in turn, consists of a cascade of serum proteins that play an important role in the human body’s immune and inflammatory response. This disorder is inherited – if one parent is affected, there is a 50 percent risk that a child will inherit the disorder.
Who is affected and why?
The age of onset of HAE symptoms varies widely, but a peak in frequency is found in the first decade of life and a second in the second. Approximately 75% of patients are symptomatic by the time they reach 20 years of age. Attacks seem to occur more frequently during puberty and early adulthood. For example, taking birth control pills has been reported to trigger the first HAE attack in previously unremarkable female patients. Another triggering factor may be an infection, for example the not uncommon viral infection mononucleosis (Pfeiffer glandular fever). The attacks can also occur without any apparent external causes; stress, anxiety, or minor injuries can provoke them. Dental treatments, for example, can contribute to mucosal swelling in the airways. In addition, other triggers (for example, hand swelling after lawn mowing, writing, hammering, etc.) have been described.
Hereditary angioedema during menstruation and pregnancy.
In women, menstruation and pregnancy appear to have an effect on disease activity. Some women report an increase in the number of attacks during their menstrual period. During pregnancy, some patients report an increased frequency of attacks, while others report a decreased frequency. Use of oral contraceptives (birth control pills, especially those high in estrogen) or hormone-containing intrauterine devices appears to increase the frequency and severity of mucosal swelling.
Hereditary angioedema: symptoms.
The typical symptoms for HAE disease are the transient appearance of painful, nonpruritic swellings that are colorless and located in the subcutaneous tissues or acute abdominal pain with no apparent other cause. Patients often report a feeling of tightness at the site where the edema appears about 30 minutes to a few hours later. The swelling lasts for at least four hours – between 24 and 72 hours on average – but may last longer in isolated cases.
Frequency of hereditary angioedema.
The frequency of HAE attacks varies enormously. Some patients are symptom-free for a long time, then swelling occurs at short intervals. Other sufferers experience attacks at shorter, regular intervals.
Complications of hereditary angioedema.
The attacks are particularly dangerous when they occur in the respiratory tract.In this case, the mucosa may close the airway and require the performance of an emergency tracheotomy (windpipe incision). Untreated mucosal swelling in the trachea is a leading cause of death in HAE patients. If HAE was previously unrecognized, mortality 25 to 30 percent of patients has been observed in the past. Therefore, in the event of mucosal swelling in the larynx, immediate administration of C1-esterase inhibitor concentrate and medical treatment are essential.
