Variable Immunodeficiency Syndrome: Causes, Symptoms & Treatment

Variable immunodeficiency syndrome, also known as common variable immunodeficiency – CVID, is a congenital immunodeficiency. As part of the defect, immunoglobulin synthesis, especially immunoglobulin G, is extremely low.

What is variable immunodeficiency syndrome?

CVID, or variable immunodeficiency syndrome, is a congenital disorder in which affected individuals have very few or no antibodies. The lack of antibodies leads to an increased susceptibility to infections. In particular, affected individuals suffer more frequently from gastrointestinal tract complaints and respiratory tract infections; the triggers are bacteria. The defect is therefore called “variable” because the defects do not always have to occur at the same point in the immune system. For this reason, the clinical picture of CVID can vary, which complicates treatment on the one hand and diagnosis on the other. In many cases, CVID does not appear until between the ages of 16 and 25; the disease is relatively rare, making it 1 in 25,000.

Causes

In variable immunodeficiency syndrome, B cells are often present but nonfunctional. For this reason, a necessary number of antibodies cannot form to protect the body from any infections. Patients therefore unfortunately suffer from a (sometimes greater, sometimes lesser) reduction in the antibody classes IgA, IgM as well as IgG. So far, the genetic causes for which the defect may arise have not yet been clarified. However, physicians are of the opinion that women as well as men are equally affected by the variable immunodeficiency syndrome. Familial clusters have already been observed, although medical experts are currently still of the opinion that CVID is not inherited.

Symptoms, complaints, and signs

Symptoms are divided into the following groups: Disorders or problems with the gastrointestinal tract, infections, skin symptoms, granulomas, chronic respiratory infections, changes in lymphoid tissue, and tumors and autoimmune phenomena. Infections include respiratory infections caused by bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), inflammation of the brain caused by the enteroviruses (encephalitides), and infections of the urinary tract (mycoplasmas). Diarrhea as well as insufficient nutrient absorption are possible as well as chronic respiratory diseases (bronchiectasis). As part of the changes in lymphoid tissue, enlargement of the spleen and an enlarged liver have been documented (hepato-splenomegaly). Granulomas are also symptoms and signs of CVID; those are manifested by inflammatory foci in the body, predominantly affecting the organs (lungs, spleen, liver) as well as the bone marrow. The term autoimmune phenomena is used by physicians to describe reactive joint inflammation as well as the immunologically caused lack of blood platelets; about 20 percent of all those affected complain of immune thrombocytopenia. Immunologically induced and pernicious anemia may also occur. Further symptoms are hair loss, granulomas of the skin as well as white spot disease. Furthermore, tumors (thymomas, stomach cancer, malignant lymphomas) can also form.

Diagnosis and course of the disease

The physician will probably suspect, based on recurrent respiratory infections, that it could sometimes be a variable immunodeficiency syndrome. However, a so-called incidental finding can also lead to the physician making the diagnosis. After the suspected diagnosis, the physician determines the immunoglobulins in the blood. In the context of CVID, immunoglobulin G is always low; as a rule, the value is below 3 g/l. In many cases, however, the immunoglobulins A and M are also reduced. The antibody deficiency is the essential component and also the indication that a variable immunodeficiency syndrome is present. However, in order for a definitive diagnosis to be made, the physician must rule out any other diseases that may well cause an antibody deficiency. These include monoclonal proliferation of so-called immunoglobulin light chains (also known as Bence-Jones myeloma). Nephrotic syndrome (protein loss via the kidneys) and exudative enteropathy (protein loss via the intestines) must also be completely ruled out in advance. Special immunological tests are also performed; for example, the subclasses of immunoglobulin B levels are measured.The prognosis and the course of the disease are relatively difficult to assess. Due to IVIG therapy, which has been offered for some time, the prognosis has improved significantly. However, individuals with variable immunodeficiency syndrome develop severe diseases (such as autoimmune phenomena or tumors) over time, which can sometimes drastically shorten life expectancy.

Complications

A wide variety of complications can occur in the setting of variable immunodeficiency syndrome, which overall contribute to a reduction in life expectancy. Precise statistical data on this are not available. However, it has been observed that regular infusion with immunoglobulins leads to an improvement in prognosis. The most important complications are severe bacterial inflammation of the respiratory tract, viral encephalitis, diarrheal diseases caused by lamblia or infections of the urinary tract caused by mycoplasma. Chronic respiratory diseases may cause bronchiectasis, characterized by irreversible bronchial dilatation with chronic suppurative bacterial infections of the bronchial wall. There is constant tissue death (necrosis) on the bronchial wall. Without adequate antibiotic treatment, these infections often lead to early death. Further complications are caused by various autoimmune reactions of the immune system. These may include reactive joint inflammation, platelet deficiency, hemolytic anemia, pernicious anemia, or multiple sites of inflammation in the internal organs. Platelet deficiency (thrombocytopenia) inhibits blood clotting and leads to frequent bleeding. Hemolytic and pernicious anemias are characterized by severe blood deficiency due to increased blood breakdown or deficient hematopoiesis. Both thrombocytopenias and the anemias can lead to death in severe cases. Foci of inflammation in the liver, lungs, spleen, or bone marrow become apparent as granulomas. Finally, malignant lymphoma, thymoma, or gastric cancer may develop in some cases as part of the variable immunodeficiency syndrome.

When should you see a doctor?

Treatment by a physician is usually always needed for this disease. Only early diagnosis with subsequent treatment can prevent further complications or discomfort. The affected person should therefore contact a medical professional at the first signs and have an examination performed. A doctor should be consulted if the affected person suffers from chronic respiratory problems. This usually results in a severe cough and therefore a very low exercise tolerance. An enlarged liver may also indicate this disease. Many patients also suffer from hair loss or white patches that spread all over the body on the skin. If these symptoms occur permanently, a doctor must be consulted. Since the disease also significantly increases the likelihood of tumors, regular examinations of the internal organs should also be performed to detect them at an early stage. Usually, the disease can be detected by a general practitioner or by an internist. However, further treatment depends on the exact manifestation of the symptoms, so no general prediction can be made. In many cases, however, the life expectancy of the affected person is reduced.

Treatment and therapy

Treatment is given only if it is necessary or if the patient suffers from symptoms or other diseases that have arisen due to the variable immunodeficiency syndrome. Patients who are free of symptoms are not treated. Some time ago a new method of treatment was found, which is based on subcutaneous or intravenous infusion of immunoglobulins. The medical profession refers to this treatment as IVIG therapy. In IVIG therapy, the physician administers – every two to six weeks – a dosage of 200 to 600 mg, depending on body weight. If the physician opts for a subcutaneous infusion, a lower dosage is administered, which is, however, administered weekly. The goal of IVIG therapy is to keep the level of immunoglobulin G above 5 g/L. Furthermore, if diseases typical of the variable immunodeficiency syndrome occur, the bacterial infections are treated with antibiotics. The dosage is higher; the intake takes much longer than in healthy persons.

Prevention

Due to the fact that no reasons that have caused an outbreak of immunodeficiency have been found so far, no preventive measures are known.

Follow-up

Variable immunodeficiency syndrome is one of the rare immunodeficiencies. It is hereditary and caused by mutated chromosomes. The defect triggers various secondary diseases that require treatment. For this reason, follow-up care is necessary. The immunodeficiency syndrome as such cannot be treated. Therefore, treatment and follow-up care extends to the resulting diseases. On the one hand, the aim is to cure the present disease, on the other hand, to avoid a relapse and to prevent further physical complaints. The quality of life of the affected person is in the foreground. If the patient does not exhibit any symptoms, neither therapies nor aftercare checks are necessary. The form of aftercare depends on the disease in the affected organs. The patient is treated with appropriate drugs, and the tolerance and healing are checked during the aftercare. The aftercare ends with the successful elimination of the symptoms. Special caution is required when administering antibiotics, as they must not be taken for a certain period of time. If the immunodeficiency syndrome represents a considerable psychological burden for the affected person, psychotherapy is recommended in addition to medical care. Depression or affective disorders must be prevented, and the patient’s quality of life should be maintained despite chronic hereditary disease.

What you can do yourself

Immunodeficiency syndrome, due to the weakening of the immune system, especially to viral and bacterial infections, is always a challenge in the life of patients. The gamma globulins of affected individuals make up the bulk of all antibodies in the blood plasma. These are each directed at a very specific pathogen by which the immune system has already been attacked and shows the appropriate immune response via the immunoglobulins M . The adaptation of everyday behavior as well as effective self-help measures presuppose that causative factors of this disease are already known. The disease may be genetically caused or it may be triggered due to certain circumstances such as severe protein deficiency or even chemotherapy. If the disease is caused by genetic factors, self-help measures consist of keeping well away from all sources of infection. This means that contact with fellow human beings who have a cold, for example, must be avoided, as the immune system is unable to fight off the infectious germs that are picked up. The same behavior is also useful in the case of acquired immunodeficiency syndrome in order not to worsen the condition. In cases where other serious health disorders, such as autoimmune diseases or cancer, can be considered as the cause of the immunodeficiency syndrome, these must be clarified as quickly as possible. Because only then can efficient treatment against immunodeficiency syndrome be started as early as possible.