APDS Symptoms

Frequent and severe ear, sinus, and/or respiratory tract infections have been reported to effect 96-100% of patients with APDS. Furthermore, 59% – 85% of patients experienced at least one episode of pneumonia. These infections typically start in infancy or early childhood and can progress to permanent lung or hearing damage.

An overproduction of B and T cells have been shown to appear as nodules in the airway or digestive tract for 24-36% of people with APDS. In the airways, these nodules make it hard for the lungs to work as well as they should. When the nodules appear in the digestive tract, they can cause gastrointestinal issues like diarrhea, abdominal pain or cramping, blood in stool, or the inability to absorb nutrients from food.

In autoimmune and autoinflammatory diseases, the immune system mistakenly attacks the body, which has occurred in around 30% of people with APDS. This can affect nearly every organ system, and can result in conditions such as arthritis, diabetes, eczema, liver or kidney disease, and others. There is no one test to detect these different types of autoimmune and inflammatory disorders, but your provider may order a blood test called ANA that indicates general autoimmunity, and other antibody tests and imaging scans may also be ordered.

Up to 60% of patients with APDS have been reported to have permanent lung damage called bronchiectasis. This results in shortness of breath, coughing up phlegm (mucus) and chest pain. This has occurred more frequently in patients with variants in PIK3CD (called APDS1): 34-60% of patients with APDS1 have been reported to suffer this lung condition, while 13-27% of patients with variants in PIK3R1 (called APDS2) have. The bronchial tubes in your lungs need to be elastic so they can pump oxygen through your lungs. Bronchiectasis is a condition where these tubes widen and thicken. This makes them inelastic, and it becomes difficult to move oxygen through them. It also becomes easy for bacteria and mucus to accumulate in the widened spaces. The result is frequent infections, which along with overproduction of B and T cells in the airways can lead to permanent damage to the lungs.

People with APDS are particularly vulnerable to frequent, severe, or persistent herpesvirus infections, which have affected 36-49% of people with the disease. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can cause mononucleosis and pneumonitis. CMV can also occur in the eye. Herpes simplex can appear as mouth or skin sores and eye infections. Varicella Zoster Virus (VZV) causes chicken pox or shingles. In some cases, EBV and CMV can be present in the blood. This is called “viremia.” EBV has been shown to progress to lymphoma in 6% of people with APDS. Your provider may order antibody tests to determine if you have been exposed to or are currently fighting a herpes infection.

Roughly 1/3 of people with APDS have reported having low numbers of blood cells, called cytopenias (“cyto” means cell; “penia” means deficiency). One type of cytopenia is anemia, which means low numbers of red blood cells. White blood cells (immune cells) and platelets can also be low in some types of cytopenia. These conditions usually have started later in childhood (around 10 years, on average) and can be detected in routine blood work. Cytopenias are usually a form of autoimmunity in APDS. This means immune cells are attacking these blood cells.

Immune cells can build up in certain areas of your body, making them appear enlarged or swollen. This “lymphoproliferation” has occurred in the tonsils, lymph nodes, spleen, and/or liver of 71-89% of people with APDS. Often times, people have undergone surgery to have their tonsils, adenoids, or spleen removed before they are diagnosed with APDS.

51% of people with APDS have been reported to experience digestive tract issues such as bowel inflammation or chronic diarrhea, typically starting around 5 years of age. Another common GI issue for people with APDS is called malabsorption. This means that the food you eat is not properly broken down in the small intestine. When this happens, the nutrients in the food are not absorbed and used, and the person is unable to gain weight, despite eating. This may also lead to fatigue.

Speech delay or other neurological conditions have been reported to affect 10-31% of people with APDS. Struggling to gain weight or to grow has affected 45-62% of people with APDS2 (caused by variants in the PIK3R1 gene) in particular.

Has been reported to develop in 12-25% of people with APDS. It tended to appear around 18-23 years of age, although it can occur even earlier, or not at all. In APDS, about 6% of lymphoma cases developed from chronic Epstein-Barr virus (EBV) infection. In other cases, lymphoma develop from prolonged dysregulation of the B and T cells; this means they grow out of control over an extended period.