Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurrent, unpredictable episodes of severe swelling. This swelling can affect various body parts, including the face, limbs, gastrointestinal tract, and airways, potentially becoming life-threatening if the throat is involved. While the condition is inherited, specific events or conditions can initiate these attacks, making understanding these triggers a key aspect of managing HAE.
The Body’s Internal Mechanism
HAE attacks stem from a malfunction involving a protein called C1-inhibitor (C1-INH). Most HAE cases involve insufficient or dysfunctional C1-INH. C1-INH normally regulates several biological pathways, including the contact system. When C1-INH is deficient or dysfunctional, it cannot properly inhibit plasma kallikrein and coagulation factor XIIa, leading to an uncontrolled increase in bradykinin production.
Bradykinin causes fluid to leak from blood vessels into surrounding tissues, resulting in the characteristic swelling. The genetic basis for HAE often involves mutations in the SERPING1 gene for Type I and Type II HAE. However, HAE with normal C1-INH levels can result from mutations in other genes, such as F12, PLG, ANGPT1, and KNG1, which also lead to bradykinin overproduction.
Everyday Triggers
Many factors can initiate HAE attacks, varying from person to person. Physical trauma is a common trigger, encompassing minor injuries, surgical procedures, and dental work. Repetitive physical activities, such as typing, hammering, or prolonged standing, can also trigger swelling.
Emotional stress and anxiety are common triggers for HAE attacks. The fear of an attack itself can create a cycle of stress, potentially leading to more episodes. Illnesses and infections, including common colds, flu, or dental infections, can also provoke an attack.
Certain medications are known to trigger HAE attacks. Angiotensin-converting enzyme (ACE) inhibitors, used for high blood pressure, are contraindicated for HAE patients as they can increase attack frequency and severity. Estrogen-containing medications, such as oral contraceptives and hormone replacement therapy, can also increase the number and intensity of attacks.
Hormonal changes, particularly those experienced during puberty, menstruation, and pregnancy, can influence attack frequency and severity in women with HAE. While less common, some individuals report certain foods, extreme temperatures, or alcohol as potential triggers. Understanding these diverse triggers helps individuals and their healthcare providers anticipate and manage potential attacks.
Tracking and Avoiding Triggers
Identifying personal triggers is an important step in managing Hereditary Angioedema. Keeping a detailed trigger journal can help individuals recognize patterns between their activities, circumstances, and HAE attacks. This record should include the attack’s severity, possible triggers, and the effectiveness of any treatment used.
Working closely with healthcare providers is important for developing a personalized management plan. Physicians can help interpret journal entries, refine trigger identification, and advise on avoidance strategies. General avoidance strategies include stress management techniques, careful planning for medical procedures, and avoiding known personal triggers.
For unavoidable triggers, such as necessary surgeries or dental procedures, prophylactic measures may be implemented. This often involves taking pre-procedure medication to prevent an attack. Maintaining good dental hygiene can also reduce the need for dental interventions that might act as triggers.
HAE Versus Allergic Swelling
Distinguishing HAE from more common forms of angioedema, particularly allergic swelling, is important for proper management. HAE attacks are mediated by bradykinin, not histamine, which is the primary mediator in allergic reactions. Consequently, standard allergy medications like antihistamines, corticosteroids, and epinephrine are ineffective for HAE attacks.
HAE swelling typically presents without itching or hives, often appearing deeper and sometimes affecting the airways or gastrointestinal tract. In contrast, allergic angioedema is frequently accompanied by itching, redness, and hives, and responds to allergy medications. The swelling in HAE can last for several days, whereas allergic angioedema tends to resolve more quickly with appropriate treatment. A correct diagnosis is important because misdiagnosing HAE as an allergic reaction can lead to inappropriate and ineffective treatments, delaying proper care for a potentially life-threatening condition.