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APDS Symptoms

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APDS, or activated PI3K delta syndrome, is a rare primary immunodeficiency that affects approximately 1 to 2 people per million worldwide. It occurs when there are variations to the PIK3CD or PIK3R1 genes.
While people with APDS may suffer from a wide variety of symptoms, the most common are frequent and severe infections of the ears, sinuses, and upper and lower respiratory tracts. Infections usually begin in infancy. People with APDS are susceptible to swollen lymph nodes or an enlarged spleen (splenomegaly), as well as autoimmunity and inflammatory symptoms. People with APDS may be at higher risk for cancers like lymphoma.
See the below diagram for more information about some typical APDS symptoms.

Typical APDS Symptoms

Fatigue
Persistent painful or swollen lymph nodes
Autoimmune or autoinflammatory conditions such as anemia
Lymphoma (cancer of the immune system)
Enlarged spleen or liver
Developmental delay (speech and growth)
Frequent and severe respiratory tract infections, sinus infections, or ear infections
Coughing phlegm (mucus), wheezing, difficulty breathing, chest pain
Diarrhea, malabsorption (part of the cause of low weight)
Chronic, severe, or recurrent Herpes virus infections, including EBV, CMV, Herpes simplex, and Varicella Zoster (chicken pox or shingles)
Fatigue
Persistent painful or swollen lymph nodes
Autoimmune or autoinflammatory conditions such as anemia
Lymphoma (cancer of the immune system)
Enlarged spleen or liver
Diarrhea, malabsorption (part of the cause of low weight)
2
4
5
7
8
9
Developmental delay (speech and growth)
Frequent and severe respiratory tract infections, sinus infections, or ear infections
Coughing phlegm (mucus), wheezing, difficulty breathing, chest pain
Chronic, severe, or recurrent Herpes virus infections, including EBV, CMV, Herpes simplex, and Varicella Zoster (chicken pox or shingles)

Most Common APDS Symptoms

People with APDS usually suffer from any two or more of the symptoms below.
People with APDS usually suffer from any two or more of the symptoms below.
Ear, Sinus, and Respiratory Tract Infections
Frequent and severe ear, sinus, and/or respiratory tract infections have been reported to affect 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.
Nodules In The Airway or Digestive Tract
An overproduction of B and T cells have been shown to appear as nodules in the airway or digestive tract of people with APDS. In the airways, these nodules make it hard for the lungs to work properly. When the nodules appear in the digestive tract, they can cause gastrointestinal issues like diarrhea and/or the inability to absorb nutrients from food.
Autoimmune And Autoinflammatory Disorders
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 inflammation of the joints (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.
Chronic Cough or Difficulty Breathing
Up to 50% 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) than those with variants in PIK3R1 (called APDS2). Bronchiectasis is a condition that causes the walls of the lungs' airways to thicken and widen. They become inelastic and accumulate easily mucus and bacteria. 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.
Herpes
Infections
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. 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 infection could progress to lymphoma in people with APDS. Your provider may order antibody tests to determine if you have been exposed to or are currently fighting a herpes infection.
Low Numbers Of
Blood Cells
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.
Enlarged Tonsils, Lymph
Nodes, or Spleen
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 people with APDS. Often times, people have undergone surgery to have their tonsils, adenoids, or spleen removed before they are diagnosed with APDS.
Gastrointestinal (Digestive) Tract Issues
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.
Developmental
Delay
Speech delay or other neurological conditions have been reported to affect 19% of APDS1 patients and 28% of APDS2 patients. Struggling to gain weight or to grow has affected 45% of people with APDS2 (caused by variants in the PIK3R1 gene) in particular.
Lymphoma
Has been reported to develop in 13 – 28% of people with APDS. It tended to appear around 18 – 23 years of age, although it can occur even earlier, later, or not at all. In APDS, lymphoma cases can develop 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.
Ear, Sinus, and Respiratory Tract Infections
Frequent and severe ear, sinus, and/or respiratory tract infections have been reported to affect 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.
Nodules In The Airway or Digestive Tract
An overproduction of B and T cells have been shown to appear as nodules in the airway or digestive tract of people with APDS. In the airways, these nodules make it hard for the lungs to work properly. When the nodules appear in the digestive tract, they can cause gastrointestinal issues like diarrhea and/or the inability to absorb nutrients from food.
Autoimmune And Autoinflammatory Disorders
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 inflammation of the joints (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.
Chronic Cough or Difficulty Breathing
Up to 50% 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) than those with variants in PIK3R1 (called APDS2). Bronchiectasis is a condition that causes the walls of the lungs' airways to thicken and widen. They become inelastic and accumulate easily mucus and bacteria. 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.
Herpes
Infections
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. 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 infection could progress to lymphoma in people with APDS. Your provider may order antibody tests to determine if you have been exposed to or are currently fighting a herpes infection.
Low Numbers Of
Blood Cells
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.
Enlarged Tonsils, Lymph
Nodes, or Spleen
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 people with APDS. Often times, people have undergone surgery to have their tonsils, adenoids, or spleen removed before they are diagnosed with APDS.
Gastrointestinal (Digestive) Tract Issues
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.
Developmental
Delay
Speech delay or other neurological conditions have been reported to affect 19% of APDS1 patients and 28% of APDS2 patients. Struggling to gain weight or to grow has affected 45% of people with APDS2 (caused by variants in the PIK3R1 gene) in particular.
Lymphoma
Has been reported to develop in 13 – 28% of people with APDS. It tended to appear around 18 – 23 years of age, although it can occur even earlier, later, or not at all. In APDS, lymphoma cases can develop 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.
Ear, Sinus, and Respiratory Tract Infections
Frequent and severe ear, sinus, and/or respiratory tract infections have been reported to affect 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.
Nodules In The Airway or Digestive Tract
An overproduction of B and T cells have been shown to appear as nodules in the airway or digestive tract of people with APDS. In the airways, these nodules make it hard for the lungs to work properly. When the nodules appear in the digestive tract, they can cause gastrointestinal issues like diarrhea and/or the inability to absorb nutrients from food.
Autoimmune And Autoinflammatory Disorders
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 inflammation of the joints (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.
Chronic Cough or Difficulty Breathing
Up to 50% 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) than those with variants in PIK3R1 (called APDS2). Bronchiectasis is a condition that causes the walls of the lungs' airways to thicken and widen. They become inelastic and accumulate easily mucus and bacteria. 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.
Herpes
Infections
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. 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 infection could progress to lymphoma in people with APDS. Your provider may order antibody tests to determine if you have been exposed to or are currently fighting a herpes infection.
Low Numbers Of
Blood Cells
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.
Enlarged Tonsils, Lymph
Nodes, or Spleen
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 people with APDS. Often times, people have undergone surgery to have their tonsils, adenoids, or spleen removed before they are diagnosed with APDS.
Gastrointestinal (Digestive) Tract Issues
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.
Developmental
Delay
Speech delay or other neurological conditions have been reported to affect 19% of APDS1 patients and 28% of APDS2 patients. Struggling to gain weight or to grow has affected 45% of people with APDS2 (caused by variants in the PIK3R1 gene) in particular.
Lymphoma
Has been reported to develop in 13 – 28% of people with APDS. It tended to appear around 18 – 23 years of age, although it can occur even earlier, later, or not at all. In APDS, lymphoma cases can develop 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.

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