• Acquired hypogammaglobulinemia
• Adult-onset hypogammaglobulinemia
• Dysgammaglobulinemia
• Common variable hypogammaglobulinemia

• The primary immunologic defect(s) leading to this syndrome is (are) unknown.
• Most patients have impaired immunoglobulin and specific antibody production despite normal B-lymphocyte numbers.
• Functional defects of both B and T lymphocytes occur.

• Usually, no clear inheritance patterns
• Some families have a pattern consistent with autosomal recessive inheritance.
• Increased prevalence of two rare MHC Class III haplotypes in a large number of CVID kindreds
• Family members of patients with CVID have an increased incidence of other immunologic defects, including IgA deficiency and autoimmune disease.

• Incidence is estimated to be 1 in 100,000 in the general population.
• Can present at any age, but usually seen in the second to third decade of life. CVID has been described in patients as young as 6 months.
• Diagnosis is usually made several years after the onset of recurrent infections.
• A subgroup of children has been described in which the onset of disease was most often before 5 years of age. This group was characterized by a relapsing and remitting course in which autoimmune disease predominated.

• Autoimmune disease in 20% of CVID patients. Most common are autoimmune hemolytic anemia and thrombocytopenia.
• GI complications include chronic diarrhea and malabsorption.
• Lymphoproliferative disease: Overall risk is 8% to 10%. The most common are lymphomas and leukemia.
• Chronic sinusitis and lung disease with abnormal PFTs
• Progressive decline in T-lymphocyte function

• Other primary antibody-deficiency disorders: X-linked agammaglobulinemia and transient hypogammaglobulinemia of infancy
• Severe malabsorption with protein-losing enteropathy
• HIV infection
• Chronic lung disease: cystic fibrosis, immotile cilia syndrome, and a₁-antitrypsin deficiency
• Primary autoimmune diseases: immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), systemic lupus erythematosus (SLE), and thyroiditis

• Recurrent sinopulmonary infections, especially sinusitis and pneumonias, with encapsulated bacteria
• Autoimmune diseases such as AIHA, ITP, thyroid disease, and chronic active hepatitis
• Persistent diarrhea of infectious (e.g., Giardia lamblia) or noninfectious etiologies
• Severe or unusual viral infections with herpes simplex, cytomegalovirus (CMV), and varicella, such as pneumonitis, hepatitis, or encephalitis. Chronic meningoencephalitis can be seen with enteroviral infection.

• Evaluation should focus on the presence of infection.
• Thirty percent of patients will have lymphadenopathy and/or splenomegaly.

• IgG, IgA, IgM, and IgE below age-appropriate norms
• CBC with differential: Examine smear for evidence of hemolysis in AIHA.
• Autoimmune antibody screen: ANA, autoantibody panel
• Stool culture for bacteria and ova/parasites to evaluate chronic diarrhea
• Isohemagglutinins as well as functional antibody titers to bacterial antigens such as tetanus, diphtheria, and pneumococcus are usually low to absent.
• Spirometry may be helpful in following chronic lung disease.
• Mitogen/antigen stimulation studies will help assess lymphocyte function.
• T- and B-lymphocyte enumeration by flow cytometry
• Absent B lymphocytes suggests X-linked agammaglobulinemia (XLA) rather than CVID.
• Appropriate cultures based on site of infection

• GI endoscopy with biopsies for cases of idiopathic persistent diarrhea
• Lymph node biopsy in suspected malignancy

• Appropriate antibiotics for acute infections. Prophylactic antibiotics may be helpful in chronic/recurrent infections.
• Monthly IV immunoglobulin (IVIG) replacement: Nadir IgG levels should be greater than 300 mg/dL.
• Cautious use of corticosteroids may be necessary in the treatment of GI and autoimmune manifestations.

• Close and frequent follow-up is warranted for patients with severe, recurrent symptoms. It may be as frequent as monthly, depending on symptoms.
• Signs and symptoms suggesting malignancy (e.g., persistent adenopathy in absence of infection, significant weight loss, or abdominal mass) should be evaluated expeditiously.

Q: What is the life expectancy of patients with the diagnosis of CVID?
A: Since the clinical presentations and symptoms are variable, it is difficult to predict the life expectancy in individual patients. The availability of IVIG, in addition to antibiotic therapy, has greatly improved the outlook for these patients. However, despite adequate therapy, a large percentage of patients with CVID have a progressive decline in immune function. Major morbidity and mortality usually result from the associated complications of malignancy, chronic lung disease, and severe autoimmune disease.

Q: Do children differ in their presentation compared with adults?
A: In a subgroup of children with CVID, autoimmune disease may be the major clinical problem rather than infections.

Q: Should patients with CVID receive live viral vaccines?
A: In general, patients receiving IVIG therapy do not require any vaccinations. Live viral vaccines should be avoided in these patients, especially if they have deteriorating immune function.

Q: Can CVID be diagnosed prenatally?
A: Since there are no clear genetic inheritance patterns, prenatal diagnosis is unavailable.

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