Primary Immunodeficiency in Adults: Late-Onset PI Explained

Do you get sick more often than other people? Do colds linger for weeks? Do antibiotics seem to stop working? If so, your immune system might not be working as well as it should. The reason for this could be something called primary immunodeficiency (PI).

Thanks! You've successfully submitted your vote.

Sign up to view the results!

Continue with Facebook

Sign up with your email

By joining, you accept our Terms of Use, and acknowledge our collection, sharing, and use of your data in accordance with our Health Data and Privacy policies.

Already a Member? Log in

PI disorders are often diagnosed in childhood, but not always. Some forms of PI aren’t detected until adulthood. When this happens, it’s called late-onset PI, and it can cause years of health problems before it’s finally found.

In this article, we’ll explain what late-onset PI is, how common it is, what symptoms to watch for, how it’s diagnosed, and what treatments can help.

What Is Primary Immunodeficiency?

Having PI means that your immune system doesn’t work quite right. Your body may have trouble fighting off germs like bacteria, viruses, or fungi. PI isn’t contagious — it’s something you’re born with. It happens because of a genetic mutation (change) that affects how your immune system develops and works.

There are more than 500 PI diseases — also known as “inborn errors of immunity.” While each type is rare, together they affect about 1 in 500 people.

PI can lead to:

• Recurrent (repeated) infections
• An increased risk of certain cancers
• Autoimmune diseases (where the body attacks its own healthy tissue by mistake)

Why Does Late-Onset Primary Immunodeficiency Happen?

Even though most cases of PI are found in children, about 1 in 4 people don’t develop symptoms until the age of 15 or later. This can happen for a few reasons. Sometimes, the symptoms are mild at first or look like other problems, like asthma, allergies, or chronic sinus infections. Other times, the body’s immune system gets weaker with age or stress. This can make the warning signs of PI more obvious or problematic.

Signs and Symptoms of Primary Immunodeficiency in Adults

Living with late-onset PI may mean getting sick more often, taking longer to get better, or not responding well to standard treatments. Some signs may be easy to miss, but knowing what to look for can help you get the right diagnosis and care.

Common signs and symptoms of adult-onset PI include:

• Frequent sinus infections, colds, or bronchitis
• Repeated cases of pneumonia (a lung infection that fills air sacs with fluid or pus, making it harder to breathe)
• Ear infections that keep coming back
• Skin infections or painful abscesses (inflamed pockets of pus)
• Fatigue (exhaustion that doesn’t improve with rest)
• Autoimmune symptoms, like joint pain, rashes, or thyroid problems
• Opportunistic infections (infections from germs that rarely affect healthy people)

If any of these sound familiar, talk to your healthcare provider. They can run tests to help figure out if your symptoms are related to a PI or something else.

Common Types of Primary Immunodeficiency That Can Show Up in Adults

Certain PI conditions can go unnoticed for years and may not be diagnosed until adulthood. Below are some of the most common PI conditions seen in adults.

Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is one of the most common PI conditions diagnosed in adults. Many people with CVID have low levels of antibodies (also called immunoglobulins), which are proteins that help protect your body from infection.

Types of immunoglobulin include:

• Immunoglobulin G (IgG), which helps fight bacteria and viruses
• Immunoglobulin A (IgA), which protects mucous membranes, like those in the nose and gut
• Immunoglobulin M (IgM), which acts as a first responder during new infections

Low antibody levels make it harder for your immune system to fight infections.

Common symptoms of CVID may include:

• Frequent sinusitis, pneumonia
• Digestive problems, such as chronic diarrhea
• Autoimmune symptoms, like joint pain, low blood counts, or thyroid issues
• Swollen lymph nodes (small, bean-shaped glands that help filter germs and support immune responses) or an enlarged spleen (an organ that helps filter blood and fight infection)

Selective IgA Deficiency

Selective IgA deficiency is the most common form of PI overall. It’s also commonly diagnosed in adulthood.

Some people with this condition have no symptoms at all, and the disease may only be discovered during blood tests for unrelated issues. Others may develop recurrent infections, frequent allergies, or other autoimmune diseases.

Although often mild, selective IgA deficiency can sometimes lead to more serious immune challenges over time.

Other Humoral Deficiencies

Humoral immune deficiencies affect the body’s ability to make antibodies. These include conditions like CVID, hypogammaglobulinemia, and selective IgA deficiency, among others.

Humoral deficiencies are the most common group of PI conditions. Because symptoms can be mild, vague, or resemble other health problems, many people are not diagnosed right away.

In fact, about half of all humoral deficiencies are first identified in adulthood, often after years of recurrent infections or unexplained health concerns.

Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare immune disorder that affects how certain white blood cells — called phagocytes — destroy germs. Normally, these cells “eat” bacteria and fungi, but in CGD, they can’t finish the job. This can lead to severe infections, especially in the skin, lungs, and gut.

While CGD is often found in childhood, milder cases may not be diagnosed until adulthood. People may have abscesses, lung infections, or digestive symptoms that look similar to the inflammatory bowel disease Crohn’s disease.

Other PI disorders that may not be found until adulthood include:

• Severe combined immunodeficiency (SCID) — SCID is a serious condition in which both the T-cell and B-cell components of the immune system are missing or not working, so the body can't fight infections at all.
• X-linked agammaglobulinemia (XLA) — XLA is a genetic disorder where the body can’t make antibodies, making it hard to fight bacteria and viruses.
• Familial hemophagocytic lymphohistiocytosis — This is a rare disease where the immune system becomes overactive and attacks the body’s own tissues and organs.
• Autoimmune lymphoproliferative syndrome — In this condition, immune cells don’t die when they should, leading to swelling of organs and a risk of autoimmune problems.

Diagnosing Primary Immunodeficiency in Adults

If your doctor suspects you might have immune dysregulation related to a type of PI, you’ll likely be referred to an immunologist (immunology specialist). Diagnosis usually starts with:

• A full medical and family history
• A physical exam to check for symptoms or signs, such as lymph node swelling or features of autoimmune disease.
• Complete blood count (CBC) to measure different types of blood cells, including lymphocytes, T cells, B cells, and neutrophils
• Blood tests to check levels of immunoglobulins

You may also be tested to see how your immune system responds to vaccines. If your body can’t make antibodies after vaccination, it could signal a PI.

Sometimes, genetic testing is needed to look for a mutation linked to a specific type of PI. This is especially helpful if there’s a family history or signs of immune dysregulation, autoimmune disorders, or malignancy like lymphoma.

Treating Primary Immunodeficiency in Adults

Treatment for PI depends on the specific type and severity. However, the goal is to keep infections under control and support the immune system.

One of the main treatments is immunoglobulin replacement therapy. This gives your body the antibodies it may be missing. It can be given intravenously (through a vein), known as IVIG, or subcutaneously (under the skin), called SCIG. This can help reduce infections and hospital visits. Your doctor will check your IgG levels regularly to make sure you’re getting the right dose and that it’s working.

Some people may also need antibiotic prophylaxis. This means taking low-dose antibiotics regularly to help prevent bacterial infections. Others may need antiviral or antifungal medications, depending on their type of PI.

If you have autoimmune symptoms, you may be treated with immunosuppressant drugs or biologics under close medical supervision. For certain conditions, more advanced treatments may include stem cell transplantation or gene therapy. These are usually offered at specialized centers. Your healthcare provider will help coordinate your care if these options are chosen.

Treatment plans are often lifelong and require regular check-ins with your immunologist. However, with the right care, most people with PI can live active and fulfilling lives.

Living With Late-Onset Primary Immunodeficiency

Being diagnosed with PI as an adult can feel overwhelming, especially if you’ve spent years feeling sick without knowing why. However, getting a diagnosis is the first step toward feeling better.

It might help to take some time to learn about your specific condition and seek support groups for others living with the same thing. The immune system is complicated, and most people without a medical or scientific background won’t understand all of the terminology. Don’t be afraid to ask questions — your doctor can help you understand what terms mean and how they relate to you.

If you think you might have PI, or you’ve already been diagnosed, talk to your healthcare team about the next steps. Together, you can create a care plan that fits into your life.

Join the Conversation

On myPIteam, people share their experiences with primary immunodeficiency, get advice, and find support from others who understand.

Were you diagnosed with PI as an adult? Share your story in a comment below.