Common variable immunodeficiency (CVID): recurrent infections, diagnosis and treatment

Immunodeficiency UK explains that common variable immune deficiency disorders are the name for a group of conditions that affect how the immune system makes antibodies and fights infections. Antibodies are proteins called immunoglobulins, found in blood and body fluids. The charity describes three major types: IgG, the most abundant and common, which works mainly against bacteria and some viruses; IgM, which works similarly but is formed earlier in an immune response; and IgA, found in blood, tears and saliva, which protects the lining of the respiratory, reproductive, urinary and digestive systems.

In CVID the body is unable to make protective antibodies, so people become susceptible to infection. The charity says that those affected have low levels of immunoglobulin or none at all, that all are unable to make functional IgG or IgA antibodies, and that some do make IgM antibodies.

CVID is one type of primary immunodeficiency (PID), a term the charity uses for a large number of different conditions that affect how the immune system works and leave people with reduced or no natural defence against germs such as bacteria, fungi and viruses. Primary means the cause is within the immune system itself, as opposed to secondary immunodeficiency, which is caused by something else such as a medicine or illness.

Immunodeficiency UK lists features that, if repeated, persistent or severe, may lead a clinician to a diagnosis of CVID. A hallmark is recurring infection, but because infections are common at any age, the charity notes that even when low immunoglobulins are found it may take time for the significance to be determined, and that doctors can find it hard to recognise when a person has too many infections.

• Sinusitis, ear infections such as otitis media, and throat infections such as tonsillitis.

• Chest infections such as bronchitis, pneumonia or pleurisy.

• Stomach and intestinal infections causing persistent diarrhoea or weight loss.

• Skin infections such as abscesses and boils, oral ulcers, and eye infections such as conjunctivitis.

• Enlarged lymph nodes, an enlarged spleen found on examination, bleeding or bruising from low platelets, or severe anaemia from destruction of red cells.

• Autoimmune disease, joint problems and bowel problems.

Immunodeficiency UK says a clinical immunologist usually makes the diagnosis, and that tests may be intensive at the beginning. Diagnosis is confirmed by blood tests that check for low levels of serum IgG and IgA, and usually IgM. The doctor will also test for antibodies to previous immunisations or known infections. If antibodies are absent, the charity says the person may have to be immunised again and blood taken 3 to 4 weeks later, to be sure that the earlier result was significant.

Other tests may include a CT scan of the chest, because people who have had multiple chest infections may have permanent damage to the airways known as bronchiectasis, samples of infected body fluids to find which germs are present and which antibiotics might work, and an ultrasound scan of organs such as the spleen. Some centres offer genetic testing as part of studies, and the charity notes that genetic testing sometimes reveals a related primary immunodeficiency in people with more severe or unusual forms.

The charity warns that delay in diagnosis can be serious if infections are severe, and gives the example of pneumonia causing structural scarring of the lungs. Many affected people feel frustrated and angry when a diagnosis is finally made after a long time without recognition of the cause.

In most cases of CVID the causes are unknown, according to Immunodeficiency UK. It usually occurs in people with no apparent history of the disorder in their family, and the charity says only 5% have a close relative who is also affected. It describes CVID as a multi-gene disorder with many causes and says that for the vast majority of patients the cause is not known.

The charity says most diagnoses are made in adulthood, with the condition most often diagnosed between 20 and 40, but that it can occur at any age. It notes that the few people (under 10%) whose antibody failure presents in childhood are called CVID but may have a more severe primary immunodeficiency.

The charity also explains that many medicines can cause low antibody levels (hypogammaglobulinaemia), but that CVID is a distinct diagnosis made after other causes such as medicines have been ruled out; where medicines are the cause it is classed as secondary rather than primary immunodeficiency.

The main treatment is immunoglobulin replacement therapy. Immunodeficiency UK says this replaces missing antibodies with purified immunoglobulins from the blood of healthy donors, given either intravenously, usually every 2 to 4 weeks, or subcutaneously, usually every day or week, depending on the person. Many people are taught to give the treatment themselves at home. The dose is monitored by how well it protects against infections, and blood tests are done periodically, typically every 3 to 6 months, to check safety and IgG levels.

Antibiotics are used for breakthrough infections and some people take them as a preventative. The charity says treatment for infections should start promptly at the first sign of infection. More specialist treatments such as haematopoietic stem cell transplant and gene therapy may be suitable for certain primary immunodeficiencies; for CVID, the charity says the suitability of bone marrow transplant depends on the type of CVID, its genetic basis and the person's health problems.

Because not all vaccines are safe for people with CVID, the charity says any recommended vaccination should be discussed with your clinical immunology team before you receive it.

Some people with CVID, but not all, have or develop other health problems. Immunodeficiency UK lists chronic lung disease such as bronchiectasis, autoimmune problems such as very low platelet counts or severe anaemia from antibodies attacking blood cells, thyroid failure, vitiligo, arthritis, and gut problems such as abdominal pain, bloating and diarrhoea, which can lead to weight loss or poor growth.

The charity says autoimmunity and inflammation are the most frequent complications of CVID. Monitoring is usually by infrequent blood tests and, for some people, annual scans or breathing tests, and the immunologist will work with other specialists. If lung disease has developed, the charity says physiotherapy and specific exercises may be recommended to clear mucus from the airways.

The charity says that immunoglobulin therapy combined with antibiotics for breakthrough infections means that people with CVID can live relatively normal lives with no restrictions on employment. The outlook depends on how much damage has occurred to the lungs or other organs before diagnosis and how successfully infections can be prevented in future.

Fatigue is common. Immunodeficiency UK says fatigue in CVID should prompt a doctor to look for associated autoimmune conditions such as low thyroid function or anaemia, and complications. It says that if nothing else is found, management is similar to chronic fatigue, including graded exercise and psychological support. It also notes that exercise that gets the lungs moving and breathing deeply is good physiotherapy and helps keep lungs healthy.

If you plan a family, the charity says familial cases exist but are a small proportion, and that unless a genetic cause has been identified it is unlikely a child would be affected. It suggests discussing this with your immunologist.

CVID is managed by clinical immunology teams, and immunoglobulin replacement is arranged through hospital services as part of NHS care in the UK. If you see an immunologist privately for an opinion, make sure results are shared with your NHS team so that treatment and monitoring are not duplicated and your records stay complete.