Common Variable Immunodeficiency (CVID)

What is common variable immunodeficiency (CVID)?

Common variable immunodeficiency (CVID) is a group of genetic disorders that affect your immune system. People with CVID have low levels of antibodies (proteins that fight infections) in their blood.

When you don’t have enough antibodies, you can get sick more often and more severely than other people. People with CVID have frequent respiratory, ear and sinus infections. Vaccines are also ineffective because your immune system can’t respond to them by making antibodies.

How serious is CVID?

In addition to frequent infections — which are sometimes hard to treat — CVID increases your risk of developing other life-threatening conditions. This includes severe lung disease and certain cancers.

How common is CVID?

About 1 in 25,000 people have CVID. It’s the most common primary immunodeficiency in adults. Most people are diagnosed as adults, but symptoms can start in childhood.

What are the symptoms of common variable immunodeficiency (CVID)?

The most common sign of CVID is frequent infections — most commonly, sinusitis, pneumonia, bronchitis, ear infections and shingles.

Other symptoms of CVID can include:

• Chronic rhinitis (runny nose or nasal congestion).
• Enlarged lymph nodes.
• Gastrointestinal (GI) symptoms. This includes abdominal pain, nausea, vomiting and diarrhea.
• Unintended weight loss.
• Joint pain.
• Finger clubbing.

What causes CVID?

Genetic variations (changes in your DNA, the instructions that make your body work) cause CVID. No single change causes CVID — many different gene changes are associated with it and experts think it takes more than one change to cause CVID. The most commonly found mutations are in the TNFRSF13B gene.

These changes mean that your B-cells — a type of immune cell — don’t work properly. They don’t develop into plasma and memory B-cells, which make antibodies (also called immunoglobulins). Specifically, people with CVID have low levels of IgG, IgA and IgM antibodies.

Low levels of antibodies mean your body can’t fight off infections as easily. And since your body’s way of making antibodies doesn’t work, vaccines aren’t effective at helping your body create immunity to diseases.

The gene variations that lead to CVID are inherited in about 10% of cases. Experts don’t know what causes them in the other 90% of people with CVID. They think epigenetic changes (changes in the way your body interprets DNA, caused by environmental or lifestyle factors) could contribute to developing CVID. But researchers need more studies to understand this theory better.

What are the complications of CVID?

Damage from infections and CVID’s effects on your immune system can lead to additional diseases and conditions. These include:

• Autoimmune disorders.
• Cancers. Lymphoma and cancers that affect your GI tract are the most common cancers in people with CVID.
• Chronic lung diseases.
• Enlarged spleen (splenomegaly).
• Granulomas.

People with CVID are also at a higher risk of developing depression.

CVID and autoimmune disorders

People with CVID are at a higher risk for developing autoimmune disorders, including:

• Antiphospholipid syndrome.
• Autoimmune hemolytic anemia.
• Autoimmune hepatitis.
• Celiac-like diseases.
• Hashimoto’s Disease.
• Immune thrombocytopenia purpura (ITP).
• Inflammatory bowel disease (IBD).
• Rheumatoid arthritis.
• Vasculitis.

CVID and chronic lung diseases

Damage from infections and inflammation in your lungs can lead to chronic lung and airway diseases. People with CVID are at risk for developing:

• Asthma.
• Bronchiectasis.
• COPD (chronic obstructive pulmonary disease).
• Emphysema.
• Granulomatous–lymphocytic interstitial lung disease (GLILD). GLILD is a condition that damages your lungs and causes nodules of immune cells to form.

How is CVID diagnosed?

Healthcare providers diagnose CVID with blood tests. They’ll measure the amount of IgG, IgA and IgM antibodies in your blood. If test results show a low level of antibodies, your provider might order genetic testing to look for DNA changes.

Providers also look at your health history and might perform other tests or imaging to rule out other conditions.

How is CVID treated?

CVID can be managed with replacement immunoglobulin therapy (RIgG). This provides your body with antibodies that it can’t make on its own. This can either be:

• Intravenous immunoglobulin therapy (IVIg). Your provider gives you antibodies directly into a vein every three to four weeks.
• Subcutaneous immunoglobulin therapy (SCIg). Your provider gives you antibodies under your skin (subcutaneous injections) every one to four weeks.

Replacement therapy isn’t a cure for CVID — you’ll need to be on this treatment for the rest of your life. Your provider may also give you antibiotics to prevent bacterial infections or to treat them at the first sign of infection.

What can I expect if I have CVID?

If you have CVID, you’ll need treatment for the rest of your life to protect yourself from infectious diseases. You’ll need to work closely with a healthcare provider to treat any illnesses as soon as possible. You may have regular screening for cancer, lung diseases or other complications.

You should avoid getting vaccinations unless your provider recommends them. Live vaccinations can be dangerous for people with CVID.

Does CVID ever get better?

There’s no cure for CVID. But immunoglobulin replacement treatments (IVIg and SCIg) have increased survival rates in the past few decades. They’ll reduce your risk of getting a life-threatening infection.

What is CVID life expectancy?

Studies suggest that most people with CVID (over 75%) are alive 25 years after diagnosis. About half live 45 years or more after their diagnosis. The most common cause of death is lung disease.

How do I take care of myself?

The best way to take care of yourself with CVID is to prioritize your care. Keep appointments with your provider, and make sure you can recognize signs of an infection or other diseases. Ask your provider what to do if you have symptoms of an infection.

People with CVID are at a higher risk for depression. Talk to a provider if you have symptoms of depression, or if you just don’t feel like yourself. Addressing your mental health is as important as managing any other aspect of your well-being.

When should I see my healthcare provider?

Talk to a healthcare provider if you:

• Get sick from a live vaccine.
• Get sick frequently with bacterial infections.
• Have other long-lasting symptoms, like lung or GI issues.

They can tell you whether they need to look into it more.

What questions should I ask my doctor?

It might be helpful to ask a healthcare provider:

• What signs and symptoms of infection should I look for?
• What should I do if I think I have an infection?
• What are my treatment options?
• How often do I need treatment?
• What vaccinations are safe to get?

A note from Cleveland Clinic

A CVID diagnosis might bring about a mix of emotions. While the future might feel uncertain, having a diagnosis means you can start treatment to keep yourself healthy. People with CVID are now living longer lives — decades after their diagnosis — thanks to the use of immunoglobulin replacement therapy. If you’ve been diagnosed with CVID, have honest conversations with your provider about what to expect. Along with a personal support system, they can help you navigate ongoing care that’s right for you.