Primary Immunodeficiency Symptoms: 8 Signs To Watch For

Primary immunodeficiency (PI) is a general term for over 500 different inherited conditions that affect the immune system. All primary immunodeficiency disorders are caused by mutations (changes) in specific genes. Because parts of the immune system aren’t working correctly, or some of the body’s immune defenses are missing, people with PI often have trouble fighting infections.

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PI has many other symptoms beyond frequent infections. Each PI condition is unique, and the impact of someone’s condition on their health and daily life can range from mild to severe. In this article, we’ll cover some key primary immunodeficiency signs.

When Do Symptoms of Primary Immunodeficiency Appear?

People can be diagnosed with PI at any point in their lives. However, many severe PI conditions tend to be diagnosed early because they cause noticeable symptoms. Less severe PI conditions, or those whose symptoms can be confused with other health issues, might be diagnosed later in life. Learning the general symptoms of PI is important if you suspect you or a loved one might have one of these conditions. Sometimes, PI symptoms are mistaken for common childhood illnesses or adult infections. Early diagnosis and treatment can make a big difference in quality of life and symptom management.

Warning Signs of Primary Immunodeficiency

Below, we describe a few of the main signs of primary immunodeficiency conditions. Not every PI will cause them all. If you or your loved one is experiencing some of these signs and are worried about the possibility of having a PI, bring the topic up with a healthcare provider. They’ll be able to order tests that could lead to a diagnosis and help you understand what’s going on.

1. Frequent, Severe Infections

The most well-known symptom of PI is frequent, recurrent, or severe infections. However, it can be hard to tell exactly what this means for an individual. Not everyone with PI has more infections than the general population, but their infections might be deeper or more severe.

The medical community has developed a list of 10 warning signs of PI in children and adults. Nearly all of these warning signs have to do with where and how often infections occur.

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2. Persistent Fatigue

Persistent fatigue (extreme tiredness that doesn’t improve with rest) is a common symptom of many PI conditions that can significantly affect quality of life. In a recent survey of Americans with PI, about 18 percent reported being fatigued. In the general population, only about 7 percent of people report this symptom. Two PI conditions, antibody deficiency disorders and common variable immunodeficiency (CVID), are especially associated with high levels of reported fatigue.

3. Autoimmune Symptoms

Many people with PI also have autoimmune issues, or disorders where the body’s immune system attacks its own cells and tissues. One study of people with CVID found that 26 percent of respondents had at least one autoimmune disorder as well. The autoimmune issues associated with PI can be quite varied.

The most common autoimmune issue related to PI is a blood disorder called autoimmune cytopenia. The symptoms of autoimmune cytopenia include:

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

Other possible autoimmune conditions include skin issues, such as psoriasis, and rheumatoid arthritis, which causes joint pain and swelling.

4. Digestive Issues

Autoimmune disorders can also affect the digestive system, including your mouth, esophagus, stomach, small intestine, liver, and colon. About one-third of people with PI experience digestive issues. When the lining of these organs is attacked, it causes inflammation and pain. Digestive autoimmune disorders can also make it more difficult for your body to absorb nutrients from food and maintain a stable weight.

Some of the symptoms of PI-related digestive issues include:

• Diarrhea that doesn’t go away
• Stomach pain
• Urgent pooping after eating
• Unintentional weight loss

5. Swollen Lymph Nodes

The lymph nodes are small glands that filter fluid called lymph. This lymph fluid picks up germs, dead cells, and waste from your tissues. The lymph nodes contain immune cells. The immune cells act as a security checkpoint to remove damaged cells and foreign substances.

You have hundreds of lymph nodes scattered throughout your organs and tissues. When you’re fighting an infection, lymph nodes near the site of the infection might swell as they work overtime to get rid of the germs. This is a normal process. For example, when you have an upper respiratory infection, you might feel the lymph nodes on either side of your jaw become swollen and tender.

In people with some types of PI, lymph nodes can swell because of a buildup of immune cells, even when they’re not sick. This is particularly common in CVID.

6. Enlarged Spleen

The spleen is another important immune organ. It’s located on the left side of your body above your stomach. It filters toxins and germs from the blood and makes white blood cells and antibodies.

Normally, an adult's spleen is about the size of an avocado. In some types of PI, the spleen becomes enlarged as it fills with immune cells. For example, about 25 percent of people with CVID have an enlarged spleen. An enlarged spleen doesn’t always cause symptoms. However, here are some possible signs and symptoms of a swollen spleen:

• Pain in the upper left side of your stomach
• Loss of appetite or feeling full even if you haven’t eaten
• Ability to feel your spleen when pressing above your stomach

7. Poor Growth in Children

In babies and children, primary immunodeficiency disorders can sometimes lead to poor growth or weight gain for their age. This is also called “failure to thrive.” There are many reasons why a PI condition might make it hard for the body to grow and develop. For example, recurrent infections cause inflammation that interferes with normal growth signals. Autoimmune digestive issues can make it difficult to absorb enough nutrients from food. This can lead to malnutrition, fatigue, and other complications. Additionally, some PI conditions also affect hormones, which can be important for growth.

8. Family History of Immune Disorders

Having a family history of primary immunodeficiency or other immune problems is a strong warning sign of possible PI. This is because the genetic mutations that cause PI can run in families and be passed down to children.

Even if you don’t know if a family member was diagnosed with PI, there are a few signs of a possible undiagnosed PI condition. These include:

• Nonaccidental infant or early childhood death
• Unexplained enlarged spleen, liver, or lymph nodes
• Frequent, recurring, severe, or uncommon infections
• Autoimmune diagnoses like arthritis, inflammatory bowel disease, or lupus
• Blood cancer diagnoses like leukemia or lymphoma

If you notice any of the signs in this article, you may want to talk to your doctor about testing for primary immunodeficiency. They can help you get to the root cause of your symptoms.

Talk With Others Who Understand

On myPIteam, people come together to learn more about life with primary immunodeficiency disorders.

Have you or a loved one been diagnosed with primary immunodeficiency? Which of the signs and symptoms listed here have you experienced? Share your tips and experiences in a comment below.