Hereditary Angioedema (HAE) is a very rare and potentially life-threatening genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE symptoms include episodes of edema (swelling) in various body parts including the hands, feet, face and airway.
In addition, patients often have bouts of excruciating abdominal pain, nausea and vomiting that is caused by swelling in the intestinal wall. Airway swelling is particularly dangerous and can lead to death by asphyxiation.
HAE patients have a defect in the gene that controls a blood protein called C1 Inhibitor. The genetic defect results in production of either inadequate or non-functioning C1-Inhibitor protein. Normal C1-Inhibitor helps to regulate the complex biochemical interactions of blood-based systems involved in disease fighting, inflammatory response and coagulation. Because defective C1-Inhibitor does not adequately perform its regulatory function, a biochemical imbalance can occur and produce unwanted peptides that induce the capillaries to release fluids into surrounding tissue, thereby causing edema.
HAE is called hereditary because the genetic defect is passed on in families. A child has a 50 percent chance of inheriting this disease if one of his or her parents has it. The absence of family history does not rule out the HAE diagnosis, however. Scientists report that as many as 20 percent of HAE cases result from patients who had a spontaneous mutation of the C1-Inhibitor gene at conception. These patients can pass the defective gene to their offspring.
Because the disease is very rare, it is not uncommon for patients to remain undiagnosed for many years. Many patients report that their frequent and severe abdominal pain was inappropriately diagnosed as psychosomatic, resulting in referral for psychiatric evaluation. Unnecessary exploratory surgery has been performed on patients experiencing gastrointestinal edema, because abdominal HAE attacks mimic a surgical abdomen. Before therapy became available, the mortality rate for airway obstruction was reportedly as high as 30 percent.
FDA-approved medication for treating the symptoms of HAE became available in the US for the first time in late 2008.
Symptoms, Diagnosis, Treatment & Management
According to the leading experts in immunology, when part of the immune system is either absent or not functioning properly, it can result in an immune deficiency disease. When the cause of this deficiency is hereditary or genetic, it is called a primary immunodeficiency disease (PIDD). Researchers have identified more than 150* different kinds of PIDD.
The immune system is composed of white blood cells. These cells are made in the bone marrow and travel through the bloodstream and lymph nodes. They protect and defend against attacks by “foreign” invaders such as germs, bacteria and fungi.
In the most common PIDDs, different forms of these cells are missing. This creates a pattern of repeated infections, severe infections and/or infections that are unusually hard to cure. These infections may attack the skin, respiratory system, the ears, the brain or spinal cord, or in the urinary or gastrointestinal tracts.
In some instances, PIDD targets specific and/or multiple organs, glands, cells and tissues. For example, heart defects are present in some PIDDs. Other PIDDs alter facial features, some stunt normal growth and still others are connected to autoimmune disorders such as rheumatoid arthritis.
Primary Immunodeficiency Disease Symptoms & Diagnosis
Serious PIDDs typically become apparent in infancy. In milder forms, it often takes a pattern of recurrent infections before PIDD is suspected. In some cases, a PIDD is not diagnosed until people reach their 20s and 30s.
Important signs that may indicate a PIDD include:
• Recurrent, unusual or difficult to treat infections
• Poor growth or loss of weight
• Recurrent pneumonia, ear infections or sinusitis
• Multiple courses of antibiotics or IV antibiotics necessary to clear infections
• Recurrent deep abscesses of the organs or skin
• A family history of PIDD
• Swollen lymph glands or an enlarged spleen
• Autoimmune disease
Some immunodeficiency disorders are not primary (hereditary or genetic). A secondary immune deficiency disease occurs when the immune system is compromised due to an environmental factor. Examples of these external causes include HIV, chemotherapy, severe burns or malnutrition.
Primary Immunodeficiency Disease Treatment & Management
Research in primary immunodefeciency is making great strides, improving treatment options and enhancing the quality of life for most people with these complex conditions.
If you or your child have symptoms of these sometimes critical conditions, you want the best care available. An allergist / immunologist or a clinical immunologist has specialized training and expertise to accurately diagnose and coordinate a treatment plan for PIDD.
* Geha R, Notarangelo L, Casanova JL, Conley ME, Chapel ME, Fischer A, Hammerstrom L, Nonoyama S, Ochs H, Puck J, Roifman C, Seger R, Wedgwood J. Primary Immunodeficiency Diseases: An Update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting. Journal of Allergy and Clinical Immunology 2007; 120(4):776-794.