Rareshare would like to acknowledge Hassan Abolhassani, MD, PhD, Division of Clinical Immunology at the Department of  Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge for reviewing this content.

CVID prevalence is estimated to be in between 1:50,000 to 1:25,000, however in regions with a high rate of related marriage can increase to 1:10,000 to 1:5,000.

The most common cause is a failure in the development of certain white blood cells called B lymphocytes. These are the immune cells in charge of producing antibodies. But this is not the case in all of the patients and defects in other immune cell types and non-immune organs have been described. In order for the body to be able to defend itself from infectious agents, all the different cells and components within the immune system need to be functional to bring about a proper immune response. A defect in any of these different components could ultimately cause a defective immune system.

The failure in the antibody production in CVID patients is believed to be caused by a combination of genetic and environmental factors. So far, in only a few cases of the affected individuals, the genetic cause has been identified. Approximately 10% of the patients present a mutation in the TNFRSF13B (also known as TACI) gene, but the alteration of this gene does not determine the development of CVID given that there are family members of patients that are healthy even though they present the alteration. This underscores the multifactorial genetic and environmental component of this disease.

Since CVID refers to a group of diseases, the symptoms and their severity differ from person to person. The severity and specific symptoms also vary among CVID patients within the same family. The onset of the symptoms also varies greatly, from the early childhood to the adulthood. Most patients do not present symptoms until their 20-40s.
The deficiency of antibodies leads to recurrent bacterial infections, especially in the respiratory tract. If these infections are not prevented or treated, a complication known as chronic lung disease (the irreversible damage of the lung tissue) can be developed. Some individuals also present complications in the gastrointestinal tract due to infections or inflammation. This might provoke abdominal pain, bloating, nausea, diarrhea and weight loss.

The abnormal B lymphocyte maturation can induce an increased accumulation of these cells in the lymph nodes, liver or spleen, a condition known as lymphadenopathy, hepatomegaly or splenomegaly, respectively. 
People with CVID are more prone to develop certain types of cancer, especially lymphomas (uncontrolled proliferation of lymphocytes).

Some patients will present a complication known as an autoimmune disorder. These disorders are another problem of the immune system. In these disorders the immune cells do not recognize the healthy tissues of the body and mistakenly attacks them as if they were foreign. That those patients with CVID, with a not fully functional immune system, are able to yet develop an autoimmune disorder is something counterintuitive and not well understood.

The diagnosis is made by the presence of very low amounts of antibodies in the context of an unknown B-cell dysfunction; it is essentially a diagnosis by the process of elimination. A genetic test could potentially be helpful for treatment adjustment and family consulting.

There is not a single test to determine if a person has CVID, the diagnosis is made after a thorough examination. When a person presents the characteristic symptoms, the first step is to confirm a lower amount of antibodies than age specific normal range in a blood test. Then the CVID diagnosis is confirmed by both analyzing the family history of the disease and the determination of additional symptoms by running additional tests.

The primary therapy for CVID patients is immunoglobulin replacement therapy, which consists of the regular administration of antibodies either intravenously or subcutaneously. Immunoglobulin is another word for the antibody. This therapy replaces the missing antibodies and can help to prevent recurrent infections. However it mildly helps with non-infectious symptoms of the disease. If this therapy is unable or ineffective to control infections, antibiotics should be prescribed to get rid of the infections when they appear. It should be noted that the increased dose of immunoglobulin or the prophylactic (preventive) use of antibiotics may be considered only in special condition. If other complications arise, those should also be treated. In the case of severe autoimmune disease, steroids or other immunoregulatory drugs might be administered.
 

The prognosis depends on the complications associated with the disorder, being poor prognosis factors the development of severe autoimmune disease, tissue damage in the lung caused by the recurrent infections and the development of cancer. If there are no associated complications, the prevention of the recurrent bacterial infections by immunoglobulin replacement therapy provides an almost normal life expectancy.
 

• http://emedicine.medscape.com/article/1051103
• https://rarediseases.org/rare-diseases/common-variable-immune-deficiency
• https://rarediseases.info.nih.gov/diseases/6140/common-variable-immunodeficiency
• Kienzler, A. K., et al. (2017). "The role of genomics in common variable immunodeficiency disorders." Clin Exp Immunol 188(3): 326-332.