Adult-onset hypogammaglobulinemia

Related Terms

Acquired agammaglobulinemia, acquired immunodeficiency, adult-onset hypogammaglobulinemia, antibody, B-cell, B-cell defect, Celontin?, CVI, genetic disorder, hypogammaglobulinemia, IgA, IgG, IgM, immune disease, immune disorder, immune system, immunodeficiency, immunoglobulin, immunoglobulin A, immunoglobulin G, immunoglobulin M, infection, late-onset hypogammaglobulinemia, Kapseals?, lymphocytes, lymphoma, primary immunodeficiency, primary immunodeficiency disease, Ridaura?, T-cell, T-cell defect, T lymphocytes, weakened immune system.

Background

Common variable immunodeficiency (CVID), also called hypogammaglobulinemia or adult-onset hypogammaglobulinemia, is a relatively common primary immune deficiency. The disorder is characterized by a lack of antibody-producing B-cells or plasma cells, low levels of most or all immunoglobulin isotypes and recurrent bacterial infections.
CVID is considered the most prevalent type of primary immunodeficiency. Primary immunodeficiencies are disorders that occur because part of the body's immune system does not function properly. Unlike secondary immunodeficiencies, which are caused by factors (like viruses or chemotherapy) outside of the immune system, primary immunodeficiencies are caused by intrinsic or genetic defects in the immune system.
While the exact incidence rate of CVID is unknown, researchers estimate that about one out of 50,000 individuals develop the disorder. Most patients develop the disorder between the ages of 20 and 50. Only about 20% of patients are diagnosed during childhood. CVID affects an equal number of males and females.
CVID is diverse, both in its clinical presentation (signs and symptoms) and in the types of deficiency. Although decreased serum levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) are characteristic of the disorder, about half of CVID patients also have decreased immunoglobulin M (IgM) levels in the blood. In addition, about half of CVID patients experience some T-lymphocyte dysfunction.
The first signs of the deficiency are recurrent bacterial infections, which may occur as early as infancy or as late as the fourth decade of life.
Because of the variable manifestations of CVID, no clear pattern of inheritance has been established. In most cases, there is no family history of immunodeficiency. However, when more than one family member is diagnosed with CVID, researchers believe it is the result of autosomal recessive inheritance. Rheumatoid arthritis, vitiligo (autoimmune disorder that causes white patches on the skin), hemolytic anemia (type of anemia that occurs when blood cells are destroyed prematurely), thrombocytopenia (low levels of platelets) and neutropenia (low levels white blood cells called neutrophils) have all been associated with CVID.
Initially, the disorder was called acquired agammaglobulinemia. This name generally applied to patients who developed the immunodeficiency when they were 20-50 years old. However, today the use of the term is discouraged in order to avoid confusion with the acquired immune deficiency syndrome (AIDS). Instead, CVID that develops later in life is now referred to as adult-onset hypogammaglobulinemia.
Prognosis depends on the extent of damage to the lungs and other organs, as well as how successfully infections are prevented. In general, the expected survival rate for male and female patients is 92% and 94%, respectively. Factors associated with fatality include low levels of IgG, poor T-cell responses to antigens and a low percentage of B cells. Fatalities related to CVID are usually the result of lymphoma (cancer of the lymph nodes). Other potential causes of death include cor pulmonale (right-sided heart failure) secondary to chronic pulmonary infection, liver failure (caused by viral or autoimmune hepatitis) and malnutrition (resulting from gastrointestinal tract disease).
While there is currently no cure for CVID, treatment can help alleviate symptoms and prevent infections that are associated with the disease. Since the cause of CVID is poorly understood, there is currently no known method of prevention.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard: The Authority on Integrative Medicine. .
Primary Immunodeficiency Resource Center. Common Variable Immunodeficiency. .
St. Jude's Children's Research Hospital. Inherited Immunodeficiencies. .
University of Virginia Health System. Common Variable Immunodeficiency (CVID). .

Causes

The primary cause of CVID remains unknown. Part of the problem is the heterogeneity (variation in physical manifestations) of the disease.
Genetics: In most cases, there is no family history of immunodeficiency. However, about 20% of patients who have CVID have a first-degree family member who has a selective IgA deficiency. This suggests that the genes may be linked. Studies have revealed specific localization to the C4A gene and, rarely, to the C2 gene in the class III region of the major histocompatibility complex (MHC), located on chromosome 6.
No clear pattern of inheritance has been observed. Since most CVID cases are sporadic, with no family history of immunodeficiency, different modes of inheritance have been reported. For instance, when more than one family member is diagnosed with CVID, researchers believe it is the result of autosomal recessive inheritance. Autosomal dominant inheritance is also thought to play a role with variable penetrance and X-linked forms.
Antirheumatic or antiepileptic drugs: CVID is associated with the use of antirheumatic drugs, such as auranofin (Ridaura?) or antiepileptic drugs, such as methsuximide (Celontin? or Kapseals?). If this type of association is later proven to be a causal relationship, the actual cause of the disorder may be a genetic predisposition to CVID.

Symptoms

Infections: Common symptoms include, recurrent infections of the ears, bronchi, sinuses and lungs. Infections are usually caused by Hemophilus influenzae, pneumococci, staphylococci and Mycoplasma pneumoniae bacteria. Bronchiectasis (widening and scarring of the bronchial tubes) infections of the bronchi are severe. Patients with bronchiectasis may have a regular morning cough that produces yellow or green sputum. Many CVID patients have an enlarged spleen and lymph nodes.
Inflammation: Other patients, who may not receive sufficient gammaglobulin replacement during treatment, may develop painful inflammation of the ankle, knee, elbow or wrist joints. These symptoms may disappear after gammaglobulin therapy (blood products containing human antibodies) is administered.
Gastrointestinal problems: Gastrointestinal complaints occur frequently in CVID patients, and symptoms may include abdominal pain, bloating, nausea, vomiting, diarrhea or weight loss. These symptoms may suggest malabsorption of certain sugars or fats, or they may indicate the presence of the Giardia lamblia parasite (protozoan parasite that infects the intestines). Serious gastrointestinal symptoms may include nodular lymphoid hyperplasia (excessive lymphatic tissue), giardiasis (protozoan disease), a sprue-like (gastrointestinal) disorder, pernicious anemia, atrophic (tissue wasting) gastritis, aphthous stomatitis (ulcerous mouth inflammation), inflammatory bowel disease and malignancy (cancerous tumor).
Autoimmunity: Some patients develop autoantibodies (antibodies that mistakenly attack the body's tissues). Autoantibodies can destroy one or more types of body tissues, cause abnormal organ growth or impair organ function. Autoantibodies commonly affect blood components (like red blood cells, connective tissues and blood vessels), endocrine glands (like the thyroid or pancreas), as well as muscles, joints and the skin.

Diagnosis

General: Diagnostic criteria for CVID include significantly decreased IgG and IgA levels in the blood, which are sometimes associated with decreased IgM levels.
Blood test: A blood test can be performed to determine whether there are significantly decreased levels of IgG and IgA in the patient's blood.
The number of T-lymphocytes and their function may be tested in samples of the patient's blood. Normally, about 60-70% of the blood lymphocytes are T-lymphocytes, and about 5-10% are B-lymphocytes. Patients who have cryoglobulinemia may have a low level of B-lymphocytes, which fail to develop into antibody-producing cells, or the B-lymphocytes may be normal in number, but fail to fully mature. T-lymphocytes that either suppress or fail to promote B-lymphocyte development may also be present.
Tissue culture: A tissue culture can help determine if the B-lymphocytes produce antibodies, and if T-lymphocytes help the B-lymphocytes in this task.

Treatment

While there is currently no cure for CVID, various treatments may help relieve symptoms and infections associated with the disease. Immunoglobulin concentrates are used most often to treat CVID patients.
Immunoglobulin concentrates: Immunoglobulin concentrates (like Gamimune?, Gammar-P?, Sandoglobulin? or Gammagard S/D?) may be administered intravenously (injected into the vein) or subcutaneously (injected below the skin). Solutions of 3-12% intravenous immunoglobulin (IVIG) have been used on a regular basis to maintain a trough level of 400-500mg/dL in adults. A dose of 400-600mg/kg every two to four weeks is usually required. In patients with structural lung damage, a trough level of 700-800mg/dL is generally required.
Most patients respond well to immunoglobulin therapy, according to research. The therapy has been shown to reduce the recurrence of infections, arthritic symptoms, and the severity of CVID. However, gastrointestinal disease shows little improvement with immunoglobulin concentrates. In some patients who have a severe autoimmune disease, the concurrent use of steroids or other immunosuppressive drugs may be needed.
The patient should be monitored during therapy for side effects. The most common reactions include backache, nausea, vomiting, chills, low-grade fever, myalgia (muscle pain) and fatigue. Side effects typically occur 30 minutes after the infusion and usually last for several hours. Slowing the rate of infusion or interrupting the infusion for a few minutes may help prevent side effects. Antipyretics, diphenhydramine or corticosteroids are often used to treat side effects such as flushing (reddening of the cheeks), headache, chills, dizziness, increased sweating, leg cramps, pain and tenderness at the injection site. Although anaphylactic reactions to immunoglobulin concentrates are rare, patients who have IgA deficiency have an increased risk for these effects.
There have been reports in the past of transmitted infectious diseases through infusion. While no cases of HIV infection have been linked to immunoglobulin therapy, the transmission of hepatitis C virus has been reported with blood transfusions. However, current methods of viral inactivation help prevent transmission. These methods include treatment with organic solvents and detergents, pasteurization and storage at a low pH. In the United States, immunoglobulin products are derived from donated human plasma, which undergoes a manufacturing process that includes cold ethanol fractionation and viral inactivation steps.
Antibiotics: Patients who have chronic sinusitis or lung disease may need long-term treatment with broad spectrum antibiotics like tetracycline, cephalosporin, trimethoprim/sulfmethoxazole (Bactrim? or Septra?), ciprofloxacin (Cipro?) or others.
Surgery: Surgery may be required to treat the complications of CVID. For instance, chronic sinusitis may require endoscopic sinus surgery to drain the sinus cavities. Severe autoimmune thrombocytopenia or hemolytic anemia can be treated with splenectomy (surgical removal of the spleen). Biopsy should be considered to exclude infection or malignancy in enlarging lymph nodes.

Integrative therapies

Probiotics: Antibiotics are the main treatment to eradicate Helicobacter pylori, the cause of most stomach ulcers. Side effects commonly include bloating, diarrhea and taste disturbances. Probiotics reduce these side effects and generally help people tolerate the treatment. They may also reduce levels of H. pylori in children and adults. Yogurt containing probiotics suppresses H. pylori infection and may lead to more complete eradication during antibiotic treatment.
Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Lactose-sensitive people may develop abdominal discomfort from dairy products containing probiotics.
Probiotics: Limited evidence with daycare children suggests supplementation with Lactobacillus GG may reduce number of sick days, frequency of respiratory tract infections and frequency of related antibiotic treatments.
Fermented milk (with yogurt cultures and L. casei DN-114001) may reduce the duration of winter infections (gastrointestinal and respiratory), as well as average body temperature, in elderly people.
Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Lactose-sensitive people may develop abdominal discomfort from dairy products containing probiotics.
Blessed thistle: Laboratory studies report that blessed thistle (and chemicals in blessed thistle such as cnicin and polyacetylene) has activity against several types of bacteria and no effects on some types. Reliable human study is lacking. Further evidence is necessary in this area before a firm conclusion can be drawn.
Cranberry: Study results of cranberry as an antibacterial in other conditions show conflicting results. Further study is needed before a conclusion can be drawn.
Probiotics: As a bacterial reservoir, the nose may harbor many varieties of potentially disease-causing bacteria. There is limited evidence that probiotic supplementation may reduce the presence of harmful bacteria in the upper respiratory tract. More studies are needed to establish this relationship and its implications for health.
Results are mixed regarding the ability of probiotics to reduce infective complications of medical treatment. Reduced incidence of infection has been seen in patients treated for brain injury, abdominal surgery and liver transplantation. Other studies have shown no such reduction in elective abdominal surgery and critical care patients.
Propolis: Animal and laboratory studies suggest activity of propolis in the treatment of various types of infections. Initial human studies suggest possible benefits against oral/dental bacteria, genital herpes, urine bacteria, intestinal giardia infections or H. pylori. Additional research is needed before a recommendation can be made.
Seaweed, kelp and bladderwrack: Laboratory study suggests antifungal and antibacterial activity of bladderwrack. However, there are no reliable human studies to support use as an antibacterial or antifungal agent.
Selenium: Preliminary research reports that selenium can be beneficial in the prevention of several types of infection, including recurrence of erysipelas (bacterial skin infection associated with lymphedema) or Mycoplasma pneumonia. Further research is needed to confirm these results before a clear recommendation can be made.
Sorrel: There are no well-conducted published studies that demonstrate sorrel to possess activity against viruses or bacteria that are important human pathogens. In an in vitro study, sorrel did not demonstrate activity against herpes simplex virus-1, herpes simplex virus-2, HIV, B. subtilis, E. coli, Proteus morganii, Pseudomonas aeruginosa, P. vulgaris, Serratia marcescens or Staphylococcus aureus.

Prevention

There is currently no known method of prevention.