Is it Evans syndrome or could it be APDS?

Activated PI3K delta syndrome (APDS) and Evans syndrome are both rare chronic conditions. Evans syndrome is an autoimmune condition that causes a lower than normal level of blood cells known as cytopenia. People with Evans syndrome can have two forms of cytopenia at the same time, or they may occur sequentially. APDS is a rare primary immunodeficiency (PI) that causes immune deficiency and immune dysregulation. Immune dysregulation can cause autoimmune complications. In around 30% of cases, people with APDS have autoimmune conditions, with cytopenia being the most common manifestation.

APDS is complex and difficult to diagnose

APDS has a wide variety of symptoms which can make it difficult to recognize. It has been reported that the median delay to diagnosis of APDS is seven years. Sometimes people can be diagnosed with other conditions, like Evans syndrome, until APDS is confirmed through a genetic test.

In a study of children (n=80) with Evans syndrome who underwent genetic testing, 40% had
abnormalities in certain genes that are known to cause PI, including PIK3CD, which causes APDS.
How do Evans syndrome & APDS affect the body?
  • In Evans syndrome the body’s immune system produces antibodies that mistakenly destroy the blood cells, platelets and sometimes certain white blood cells known as neutrophils, resulting in cytopenia.
  • The two common forms of cytopenia in Evans syndrome are autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP).
  • In Evans syndrome the body’s immune system produces antibodies that mistakenly destroy the blood cells, platelets and sometimes certain white blood cells known as neutrophils, resulting in cytopenia.
    • In people with APDS, the process of making white blood cells is
      disrupted; this can result in too many underdeveloped white blood
      cells and not enough functioning white blood cells in the body.
      When the white cells are not functioning as they should, this is
      called immune dysregulation and can cause autoimmune
      conditions.
    • The most common autoimmune manifestation in APDS is
      cytopenia.
  • If you have experienced a lack of response to standard Evans
    syndrome treatments, or have cytopenia plus some of the symptoms outlined below, discuss with your doctor if you are a candidate for genetic testing for APDS.

APDS can be diagnosed with a genetic test.

Most Common APDS Signs & Symptoms

The most common, and often earliest reported APDS symptoms include frequent and severe infections of the ears, sinuses, and upper and lower respiratory tracts which begin in infancy.

Common APDS signs & symptoms include:

Ear, Sinus, and Respiratory Tract Infections - 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.

96-100% of cases

Ear, Sinus, and Respiratory Tract Infections

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 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.

71-89% of cases

Enlarged Tonsils, Lymph Nodes, or Spleen

Chronic Cough or Difficulty Breathing - 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.

51% of cases

Chronic Cough

- 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.

51% of cases

Gastrointestinal (Digestive Tract) Issues

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. 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.

36-49% of cases

Herpes Infections

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 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.

~30% of cases

Autoimmune and Autoinflammatory Disorders

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.

~30% of cases

Low Numbers of Blood Cells

Developmental Delay - 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.

27-31% of cases

Developmental Delay

Lymphoma - 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 for a long time.

12-25% of cases

Lymphoma

People who suffer from any two or more of the above conditions, should consider APDS.

A genetic test may shorten the diagnostic journey.

  • Before patients are correctly diagnosed with APDS, they often have a lengthy wait for a diagnosis involving multiple visits to various specialists. Symptoms are treated without identifying the underlying cause.
  • The goal of a quick diagnosis and treatment is to interrupt disease progression to permanent damage or malignancy.
  • As primary immunodeficiencies are inherited, family members of a confirmed patient should be genetically tested. While family members may not have the same symptoms or any symptoms, they may still carry the genetic condition and pass it onto their biological children.
  • Stop the never-ending swirl of doctor visits and specialist appointments as you look for answers. Talk with your doctor about getting a no-charge genetic test from the navigateAPDS program*.

Every year new genetic variants are picked up by the latest genetic tests.

Five years ago we had only identified 200 genes, and by 2019 we had identified 407.

If you have had a genetic test in the past, speak to your doctor to see if retesting is appropriate for you.

Download this information sheet about our no-charge genetic testing program navigateAPDS* to share with your doctor.

Download Now

*This program is currently available in the US and Canada only.

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