Immunodeficiency

Immunodeficiency is a condition where your body’s defense system cannot fight infections as it should. When you have immunodeficiency, you get sick more often and your infections may be more serious, last longer, or be harder to treat than in people with a healthy immune system.

Table of contents

• What is immunodeficiency?
• Types of immunodeficiency
• Signs and symptoms
• Causes and risk factors
• Diagnosis
• Treatment options
• Living with immunodeficiency

What is immunodeficiency?

Your immune system is made up of organs and cells that work together to protect your body from harmful invaders like bacteria, viruses, fungi, and parasites. The immune system includes your bone marrow, lymph nodes, spleen, tonsils, thymus, and white blood cells^[1][2].

When you have immunodeficiency, also called immunocompromise, your immune system’s ability to defend your body against foreign or abnormal cells is reduced or absent. This makes you more likely to get infections and become seriously ill from germs that would not normally cause severe problems in people with healthy immune systems^[4][5].

Immunodeficiency disorders can affect different parts of your immune system. The affected parts may be missing, reduced in number, or not working properly. Problems can occur with B cells (which produce antibodies), T cells (which help identify and destroy harmful cells), phagocytes (cells that swallow and destroy germs), or complement proteins (which help immune cells kill bacteria)^[2][4].

Types of immunodeficiency

There are two main types of immunodeficiency: primary and secondary^[4][5].

Primary immunodeficiency

Primary immunodeficiency disorders, also called inborn errors of immunity, are conditions you are born with. They are caused by genetic changes that affect how your immune system develops and works^[1][9].

There are more than 400 types of primary immunodeficiency. Some are so mild they are not noticed until adulthood, while others are severe enough to be discovered soon after birth. About 60% of people with primary immunodeficiency are male^[1][4][6].

Primary immunodeficiencies are classified based on which part of the immune system is affected. Problems with B cells are the most common, accounting for more than half of all cases. Other types involve T cells, both B and T cells together, phagocytes, or complement proteins^[3][4].

Some examples of primary immunodeficiency diseases include common variable immunodeficiency, X-linked agammaglobulinemia, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, and chronic granulomatous disease^[3][9].

Secondary immunodeficiency

Secondary immunodeficiencies are more common than primary types. They develop later in life and are caused by other factors that weaken the immune system^[4][9].

Many conditions and factors can cause secondary immunodeficiency, including HIV/AIDS, malnutrition (especially if you do not eat enough protein), diabetes, cancer, and serious illnesses that require long hospital stays. Medications can also cause secondary immunodeficiency, including corticosteroids, immunosuppressants used after organ transplants, chemotherapy, and radiation therapy^[2][9].

People who have had their spleen removed also have a higher risk of certain infections. As you get older, your immune system naturally becomes less effective, which also increases your risk of infections^[2].

Signs and symptoms

The most common sign of immunodeficiency is getting infections more frequently than most people. When you do get sick, your infections may be more severe, last longer, or be harder to treat than usual^[1][4].

You should talk to your healthcare provider if you or your child have any of these warning signs^[1][6][17]:

• Eight or more ear infections within one year
• Two or more serious sinus infections within one year
• Two or more cases of pneumonia within one year
• Two or more deep-seated infections, such as meningitis or blood infections (sepsis)
• Infections that require intravenous antibiotics to clear up
• Two or more months on antibiotics with little effect
• Recurrent, deep skin or organ abscesses (pus-filled infections)
• Persistent thrush (a fungal infection) in the mouth or on the skin after age one
• Failure of an infant to gain weight or grow normally
• A family history of immunodeficiency

Infections can occur anywhere in the body, including the ears, sinuses, lungs, throat, skin, brain, spinal cord, and digestive system. You may also develop infections from unusual organisms that do not normally cause illness in people with healthy immune systems. These are called opportunistic infections^[1][5][6].

Other symptoms can include swollen lymph nodes, enlarged spleen or liver, digestive problems like chronic diarrhea, unexplained weight loss or poor growth in children, blood disorders such as low platelet count or anemia, and autoimmune problems where the immune system attacks the body’s own tissues^[1][4][9].

Most people with primary immunodeficiency experience symptoms before turning 20, although they can develop at any point in life^[9].

Causes and risk factors

Causes of primary immunodeficiency

Primary immunodeficiency disorders are caused by genetic changes or mutations that happen before you are born. These genetic changes prevent your immune system from developing or working correctly. If the mutated gene is on the X chromosome, the disorder occurs more often in boys. The genetic changes that cause primary immunodeficiencies often run in biological families^[4][9].

Causes of secondary immunodeficiency

Secondary immunodeficiency develops when something damages or weakens the immune system after birth. Common causes include chronic illnesses like HIV/AIDS, diabetes, and cancer, as well as medications such as steroids, chemotherapy drugs, and medicines used to prevent organ transplant rejection^[2][9].

Malnutrition, especially severe protein deficiency, can also cause secondary immunodeficiency. People who are very ill for long periods, particularly those who are older or hospitalized in intensive care, are at higher risk^[2].

Risk factors

You are more likely to have a primary immunodeficiency if your biological parents or siblings have one. These disorders are also more common in males. For secondary immunodeficiency, risk factors include having chronic diseases, taking immune-suppressing medications, being older, and having poor nutrition^[4][9].

Diagnosis

If your healthcare provider suspects you have an immunodeficiency, they will start by asking about your medical history, including how often you get infections, which infections you have had, and whether anyone in your family has an immune system disorder. They will also perform a physical examination^[1][10].

Blood tests are the main tool for diagnosing immunodeficiency. These tests can measure the levels of infection-fighting proteins called immunoglobulins (antibodies) in your blood. Blood tests also count different types of blood cells and immune system cells. Having too many or too few of certain cells can indicate an immune system problem. Blood tests can also show whether your immune system is responding properly by producing antibodies when needed^[1][10].

Your healthcare provider may refer you to a clinical immunologist, a specialist who focuses on diseases of the immune system. Additional testing may be needed to identify the specific type of immunodeficiency you have^[1][9].

For families with a child who has a primary immunodeficiency, genetic testing during future pregnancies may be available. This allows parents to prepare for treatment soon after birth if necessary^[10].

Treatment options

Treatment for immunodeficiency focuses on preventing infections, treating infections when they occur, and boosting the immune system. The specific treatment depends on the type of immunodeficiency you have^[10][14].

Preventing and treating infections

Preventing infections is a high priority. Your healthcare provider may prescribe antibiotics, antifungals, or antiviral medications to prevent infections before they start. This is called prophylactic treatment. When infections do occur, they need to be treated quickly and aggressively, often with longer courses of antibiotics than usual^[10][12].

Immunoglobulin replacement therapy

For people with antibody deficiencies, immunoglobulin replacement therapy is the main treatment. This therapy provides the antibodies your body cannot make on its own. Immunoglobulin is a blood product derived from thousands of healthy donors^[11][15].

Immunoglobulin can be given through an intravenous (IV) line into a vein, usually every three to four weeks. It can also be given as an injection under the skin (subcutaneous), typically once or twice a week. Some people can learn to give themselves subcutaneous injections at home^[11][15].

This treatment significantly reduces the frequency and severity of infections and helps people with immunodeficiency lead fuller lives^[15].

Stem cell transplantation

For some severe primary immunodeficiencies, hematopoietic stem cell transplantation, also known as bone marrow transplant, may offer a cure. This procedure replaces the faulty immune system with healthy stem cells from a donor^[11][14].

Gene therapy

Gene therapy is a newer treatment option that is being tested in clinical trials for several types of primary immunodeficiency. It involves correcting the genetic defect that causes the disorder. Gene therapy may be an option when a suitable donor for stem cell transplant is not available^[11][14].

Other treatments

Some types of immunodeficiency can be treated with specific medications that target the affected immune pathway. For example, certain drugs can help control autoimmune or autoinflammatory symptoms that sometimes occur with immunodeficiency^[14].

Living with immunodeficiency

While immunodeficiency requires lifestyle changes and ongoing medical care, most people with these conditions can live full and active lives^[20][24].

Preventing infections

Good hygiene is essential for preventing infections. Wash your hands frequently with soap and water for at least 20 seconds, especially before meals and after contact with other people. Use hand sanitizer when soap and water are not available. Take care of your teeth by brushing and flossing regularly and visiting your dentist for routine checkups^[19][23].

Avoid close contact with people who are sick. During flu season or disease outbreaks, consider avoiding crowded public places. Wearing a mask can provide additional protection^[19][20].

Prepare food safely by keeping utensils and work surfaces clean. Avoid eating raw or undercooked foods, as they may increase your risk of foodborne illness^[22][23].

Diet and exercise

Eating a nutritious, balanced diet helps keep your body strong. Most people with immunodeficiency do not need special diets or supplements unless they have another condition. However, you should generally avoid raw or undercooked dishes like meats, eggs, and cheeses to reduce infection risk^[23][24].

Stay hydrated by drinking enough water daily. Regular exercise helps you stay fit and can reduce stress. Low-impact activities like walking, cycling, or yoga are good options. Most people with immunodeficiency can exercise and play sports, though some may need to avoid certain activities. Ask your healthcare provider for specific recommendations^[22][23].

Medical care

Regular visits to your healthcare provider are essential. Take all medications and treatments as prescribed. Keep track of your symptoms and infections in a health diary to share with your doctor, who can adjust your treatment as needed^[19][22].

Contact your doctor whenever you suspect an infection. Early treatment can prevent complications^[23].

Support and mental health

Living with immunodeficiency can affect your mental health. Finding a support group where you can connect with others who understand what you are going through can provide comfort and encouragement. Do not hesitate to share your concerns with your healthcare team, and seek support from family and friends^[20][22].

Most importantly, do not let your condition prevent you from participating in activities like work, school, and social events. With proper care and precautions, you can live a full, happy, and productive life^[22].