The Diagnosis Journey: Primary Immunodeficiency (PI)

A long and difficult road may face people with primary immunodeficiency, also known as PI. It is not always easy to diagnose someone with PI. This article will help you understand how doctors find the condition and what you can expect during the diagnostic process.

What is primary immunodeficiency?

Primary immunodeficiency means that your body's immune system does not work correctly. The immune system is like your body's army. It fights off germs, like bacteria and viruses, that can make you sick. When you have PI, your immune system is weak. This means you can get sick more often, including infections that are hard to treat.^1,2

Recognizing the clues: When to suspect primary immunodeficiency

It can be hard to know if someone has PI. Many common illnesses, like colds, can happen to anyone. But there are some signs that might make a doctor suspect PI.

Here are some important signs that may indicate primary immunodeficiency:^1,2

• Frequent infections – Getting sick a lot is a big clue. People with PI may have more ear infections, sinus infections, skin infections, thrush, etc.
• Serious infections – Some infections are more serious than others. These include pneumonia, a lung infection, sepsis, or meningitis, an infection in the brain and spinal cord.
• Infections that do not go away – Sometimes infections do not get better with regular medicine. They might keep coming back.
• Slow growth – Infants with PI sometimes do not grow as fast as other infants. They might also lose weight.
• Family history – PI is often genetic and can run in families. If someone in your family has PI, you might be more likely to have it.

If you or a family member has any of these signs, tell your doctor. The earlier primary immunodeficiency is diagnosed, the sooner you or a loved one can start treatment.¹

Diagnosing primary immunodeficiency in infants

There are some specific things doctors look for in very young children:^1,3,4

• Serious or unusual infections – Babies with PI might get very severe infections. These infections might be caused by germs that do not usually make healthy babies sick. Examples include severe thrush (a yeast infection in the mouth) or skin infections that are hard to clear.
• Failure to thrive – This means the baby is not gaining weight or growing as expected.

Newborn screening

In the United States, all hospitals now screen all newborn babies for serious health conditions, including a very serious type of PI called severe combined immunodeficiency (SCID). This test is done within 24 to 48 hours after birth using a few drops of blood from the baby's heel, as well as testing for hearing and the heart.^2,3

Finding SCID early is very important because SCID can be fatal, and early treatment can save a baby's life. This screening looks for a problem with T-cells, which are a very important part of the immune system. If test results show a low level of T-cells, an infant will need more testing to confirm a diagnosis.^2,3

The diagnostic journey: What to expect

Finding out if you have primary immunodeficiency can take time. It is often a journey with many steps.

Step 1: Talk to your doctor

The first step is to talk to your doctor about your or a loved one’s symptoms. They will ask you many questions about your healthcare, including how often you get sick and what kind of infections you get. This is called taking a medical history. They will also ask about your family's health history. Your doctor will also do a physical exam to look for signs of illness.⁵

Step 2: Screening and more specialized testing

If your doctor suspects you may have PI, they will order blood tests to help them learn more about your immune system. If the first blood tests show problems, your doctor might order more tests. These tests look closer at how your immune cells work. These tests can be more complex. They help doctors pinpoint exactly what part of your immune system is not working. These tests may include:^5,6

• Complete blood count (CBC) – This test counts your blood cells, including white blood cells. White blood cells are important for fighting infections.
• Immunoglobulin levels – Immunoglobulins are also called antibodies. They are like special proteins that fight germs. This test checks how much of these proteins you have. Low levels can be a sign of PI.
• Vaccine serology tests – After getting certain vaccines, your body should make antibodies. This test checks if your body makes enough antibodies after a vaccine.
• Flow cytometry – This test looks at different types of lymphocytes, which are different white blood cells such as B-cells and T-cells. Each type has a special job in fighting germs. This test counts how many of each type you have.

Step 3: Genetic testing

PI is often caused by a problem with your genes. Genes are like instructions inside your body. They tell your body how to grow and work. If there is a mistake in a gene, it can lead to PI.⁵

Genetic testing looks for these mistakes in your genes. Finding a gene mistake may give a clear answer for why someone has PI. It can also help doctors know the best way to treat the PI. It can also help families understand if other family members might have PI or be carriers.^5,7

The waiting game and emotional impact

Waiting for a diagnosis can be very stressful. You might feel worried, scared, or frustrated. It is important to remember that you are not alone. Many people with PI go through a similar diagnosis journey.

Talk to your doctor. Ask questions so that you understand what is happening and what you can expect. It is also very important to find support. Support groups for people with PI and their families can offer comfort and understanding.

What happens after diagnosis?

Getting a diagnosis of PI can be a relief. It means you finally have an answer. It also means your doctor can start to make a plan to help you. Treatment for PI often involves:^1,2,8

• Preventing and treating infections – This might mean taking special medicines or getting certain vaccines. Also, getting quick and strong treatment for infections is very important.
• Immunoglobulin replacement therapy – Some people with PI need to get regular infusions of immunoglobulin. This helps give your body the antibodies it needs to fight off germs.
• Treating the underlying condition – In rare occasions, certain treatments like stem cell transplant and gene therapy may be available for certain types of PI.

Living with PI can be challenging. But with a diagnosis and the right treatment, people with PI can live full and active lives. The journey to diagnosis may be long, but it is an important step toward better health.