Your Guide to PI: Symptoms, Treatments, and More

Primary Immunodeficiency Symptoms in Children and Adults

Medically reviewed by Marcela Castillo-Rama, MD, PhD

Written by Medeea Popescu, Ph.D.

Updated on July 16, 2026

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Key Takeaways

Primary immunodeficiency, also called inborn errors of immunity, is a group of more than 550 inherited conditions that can be difficult to recognize because its symptoms often look like everyday infections at first.

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Primary immunodeficiency (PI), also called inborn errors of immunity (IEI), can be hard to spot because its symptoms may look like common infections at first. But when infections keep coming back, turn severe, or happen along with other unexplained symptoms, they may be signs that the immune system is not working as it should.

PI includes more than 550 inherited conditions, so symptoms vary widely from person to person and can go well beyond frequent infections. Severe forms are often diagnosed early in life, while milder forms or those that are mistaken for other conditions may not be diagnosed until adulthood. Doctors have identified warning signs — with slightly different lists for children and adults — that can help you know when to ask about testing.

Frequent, Severe Infections

The best-known symptom of primary immunodeficiency is frequent, recurrent, or severe infections. However, not everyone with PI gets sick more often than average.

Researchers and doctors have identified 10 warning signs of PI for children and adults. Most of these warning signs are based on how often infections happen, where they occur, and how severe they are.

10 Warning Signs of Primary Immunodeficiency in Children

If your child has two or more of these warning signs in a year, talk with their pediatrician about testing for primary immunodeficiency:

A family history of primary immunodeficiency
Four or more ear infections in a year
Two or more severe sinus infections in a year
Two or more months of antibiotic treatment that doesn’t clear the infection
Need for IV antibiotics to clear infections
Two or more cases of pneumonia in a year
Repeated deep organ or skin infections
Long-lasting fungal infections in the mouth (called thrush) or on the skin
Two or more severe infections, such as sepsis or meningitis
Failure to gain weight or grow as expected

Some children with PI may not have these exact warning signs. Doctors also consider family history and may use genetic testing to help make a diagnosis.

10 Warning Signs of Primary Immunodeficiency in Adults

Talk to your healthcare provider if you or a loved one has two or more of these warning signs:

A family history of PI
Two or more ear infections in a year
Two or more sinus infections in a year, without known allergies
One case of pneumonia each year for more than one year
Repeated viral infections, such as colds, warts, or herpes
Chronic diarrhea that causes weight loss
Oral thrush or long-lasting fungal skin infections
Recurrent deep skin or organ infections
Infection with tuberculosislike bacteria that usually don’t cause illness
Repeated need for IV antibiotics to clear infections

Adults with PI may also have other problems affecting the skin, lungs, ears, nose, throat, liver, or digestive system, as well as autoimmune illnesses. These can occur even if a person doesn’t get frequent infections.

White, patchy plaques on the inside of the cheek and gums, consistent with oral thrush. — White patches inside the mouth can be a sign of thrush, a fungal infection that people with primary immunodeficiency may be more likely to develop. (CC BY-NC-ND 4.0/DermNet)

Other Symptoms That May Affect Adults and Children

Beyond infections, PI conditions can cause many other symptoms.

Persistent Fatigue

Persistent fatigue (extreme tiredness that doesn’t improve with rest) is a common symptom of many PI conditions and can greatly affect quality of life.

In a 2017 survey of people in the United States with primary immunodeficiency, about 18 percent reported fatigue, compared with about 7 percent of people in the general population.

Fatigue is especially common in antibody deficiency disorders and common variable immunodeficiency (CVID).

Autoimmune Symptoms

Many people with PI also develop autoimmune diseases, in which the immune system attacks the body’s own cells and tissues. In one study of people with CVID, 26 percent had at least one autoimmune disease.

Autoimmune problems linked to PI can affect many parts of the body. One of the most common autoimmune conditions associated with PI is a group of blood disorders called autoimmune cytopenias. Symptoms may include:

Easy bruising
Bleeding that’s slow to stop
Anemia (low red blood cell levels)

Other autoimmune diseases linked to PI include psoriasis and rheumatoid arthritis, which causes joint pain and swelling.

Red, scaly, and thickened plaques with silvery-white scaling on the back of the hand of a person with light skin, characteristic of psoriasis. — Psoriasis is an autoimmune condition that creates scaly patches on the skin. People with primary immunodeficiency may be at a greater risk for psoriasis. (Adobe Stock)

Digestive Issues

About one-third of people with PI have digestive problems, often because autoimmune activity causes inflammation in the lining of the digestive tract. This can cause pain and make it harder for the body to absorb nutrients and maintain a healthy weight.

Common symptoms include:

Ongoing diarrhea
Stomach pain
An urgent need to poop after eating
Unintentional weight loss

Swollen Lymph Nodes

Lymph nodes are small glands that filter germs and waste from lymph, a fluid that circulates throughout the body. They often swell temporarily while your body is fighting an infection — like the tender nodes you might feel in your jaw during a cold.

In some types of PI, lymph nodes can become enlarged because of a buildup of immune cells, even when there isn’t an infection. This is especially common in CVID.

Enlarged Spleen

The spleen, located on the left side of your abdomen above your stomach, filters germs and waste from the blood and helps make white blood cells and antibodies.

Normally about the size of an avocado, the spleen can become enlarged in some types of PI as immune cells build up inside it. For example, about 25 percent of people with CVID have an enlarged spleen.

An enlarged spleen doesn’t always cause symptoms. When it does, symptoms may include:

Pain in the upper left side of your abdomen
Loss of appetite or feeling full after eating only a small amount
The ability to feel your spleen when pressing on the upper left side of your abdomen

Poor Growth in Children

In babies and children, PI can sometimes lead to poor growth or poor weight gain, sometimes called “failure to thrive.” This can happen for several reasons, such as the following:

Frequent infections can cause inflammation that interferes with normal growth.
Autoimmune digestive problems can make it harder to absorb enough nutrients from food, leading to malnutrition, fatigue, and other complications.
Some PI conditions can also affect hormones that are important for growth.

Family History of Immune Disorders

A family history of primary immunodeficiency or other immune disorders is an important warning sign of possible PI. That’s because the genetic mutations (changes) that cause PI can run in families and be passed from parents to children.

Even if no one in your family has been diagnosed with PI, these situations may suggest an undiagnosed PI condition:

An infant or child who died unexpectedly from an illness
An unexplained enlarged spleen, liver, or lymph nodes
Frequent, recurrent, severe, or unusual infections
Autoimmune diagnoses such as arthritis, inflammatory bowel disease (IBD), or lupus
Blood cancers such as leukemia or lymphoma

If you notice any of the signs described in this article, talk with your healthcare provider about whether testing for primary immunodeficiency may be appropriate. They can help identify the cause of your symptoms and determine the next steps.