Common Variable Immunodeficiency
Common Variable Immunodeficiency: Excerpt from The 5-Minute Pediatric Consult
Elena Elizadeth Perez, MD, PhD
Common Variable Immunodeficiency - BASICS
Common Variable Immunodeficiency - description
- A heterogeneous immunodeficiency syndrome characterized by:
- Hypogammaglobulinemia
- Recurrent infections
- A wide spectrum of immunologic abnormalities, including autoimmune disease, inflammatory conditions, and the development of lymphomas
- A common primary immunodeficiency
- Other terminology for this disease includes:
- Acquired hypogammaglobulinemia
- Adult-onset hypogammaglobulinemia
- Dysgammaglobulinemia
- Common variable hypogammaglobulinemia
- Diagnosis of exclusion, requiring variable reduction in one or more immunoglobulin classes (IgG, IgA, and/or IgM), impaired specific antibody responses, and in some cases reduction of B cell number
Common Variable Immunodeficiency - epidemiology
- Incidence is estimated to be 1 in 25,000 to 1 in 66,000 in the general population.
- Can present at any age, but usually seen in the 2nd–3rd decade of life. Common variable immunodeficiency has been described in patients as young as 6 months.
- Diagnosis is usually made several years after the onset of recurrent infections (pneumonia, sinusitis, otitis).
- A subgroup of children has been described in which the onset of disease was most often <5 years of age. This group was characterized by a relapsing and remitting course in which autoimmune disease predominated.
- About 20%–25% of patients with common variable immunodeficiency have one or more autoimmune conditions at the time of diagnosis.
- Affects males and females equally.
Common Variable Immunodeficiency - risk factors
Common Variable Immunodeficiency - genetics
- Some evidence for potential susceptibility locus on 6p21 (proximal part of MHC locus)
- Some families have a pattern consistent with autosomal recessive inheritance. TACI mutation may be autosomal dominant.
- IgA deficiency more likely in offspring of parents with common variable immunodeficiency
- Incidence of IgA deficiency, autoimmune disease, malignancies increased in family members of patients with common variable immunodeficiency
Common Variable Immunodeficiency - pathophysiology
- Hypogammaglobulinemia is the main characteristic.
- Most patients have impaired immunoglobulin and specific antibody production despite normal B-lymphocyte numbers. An increased proportion of immature B cells is often present.
- Functional defects of both B and T lymphocytes occur.
Common Variable Immunodeficiency - etiology
- The primary immunologic defect(s) leading to this syndrome is unknown: Multiple defects have been associated with common variable immunodeficiency including:
- Lack of somatic mutation within variable region genes
- Lack of memory B cells
- Some genetic defects have been described, but do not yet account for the majority of cases. These include:
- Inducible costimulatory receptor (ICOS) deficiency, <1% of patients
- Mutations in TNF receptor family member transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) (10%–20% of patients). TACI is involved in isotype switching of B cells. Only 1 TACI allele is mutated in majority of patients studied.
- Mutation in TACI has also been observed in relatives of CVID patients who have IgA deficiency:
- B cell defects include inability to secrete antibodies, and impaired upregulation of CD70 and CD86 (co-stimulatory molecules), and reduction of switched CD27+ B cells.
- Impaired maturation, IL-12 secretion, and upregulation of costimulatory molecules by antigen presenting cells may impair T cells which are important for providing help to B cells for antibody production.
- Toll like receptor 9 (TLR9) response and expression by B cells may also be impaired. TLR signaling pathways are being investigated for their potential role in pathogenesis of CVID.
Common Variable Immunodeficiency - DIAGNOSIS
Common Variable Immunodeficiency - signs & symptoms
Common Variable Immunodeficiency - history
- Recurrent sinopulmonary infections, especially sinusitis and pneumonias, with encapsulated bacteria
- Autoimmune diseases such as autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, thyroid disease, and chronic active hepatitis
- Persistent diarrhea of infectious (e.g., Giardia lamblia) or noninfectious causes
- Severe or unusual viral infections with herpes simplex, cytomegalovirus, and varicella, such as pneumonitis, hepatitis, or encephalitis. Chronic meningoencephalitis can be seen with enteroviral infection.
Common Variable Immunodeficiency - physical exam
- Evaluation should focus on the presence of infection.
- 30% of patients will have lymphadenopathy and/or splenomegaly.
Common Variable Immunodeficiency - tests
Common Variable Immunodeficiency - common variable-immunodeficiency_diagnosis_tests_imaging
Chest and sinus x-ray studies/CT scans may be warranted for evaluation of chronic disease.
Common Variable Immunodeficiency - diag proced-surgery
- GI endoscopy with biopsies for cases of idiopathic persistent diarrhea
- Lymph node biopsy in suspected malignancy
Common Variable Immunodeficiency - differencial diagnosis
- 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 αPrimary autoimmune diseases: Immune idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, systemic lupus erythematosus, thyroiditis
Common Variable Immunodeficiency - TREATMENT
Common Variable Immunodeficiency - general measures
- Monthly IV immunoglobulin replacement: Nadir IgG levels should be >500 mg/dL
- Starting dose is usually 400 mg/kg/month IV
- FDA recently approved formulation for SC administration, which is given weekly.
- Appropriate antibiotics for acute infections. Prophylactic antibiotics may be helpful in chronic/recurrent infections.
- Cautious use of corticosteroids may be necessary in the treatment of gastrointestinal (GI) and autoimmune manifestations.
Common Variable Immunodeficiency - diet
Normally no restriction
Common Variable Immunodeficiency - activity
Normally no restriction
Common Variable Immunodeficiency - nursing
- Supervision during IVIG administration
- Monitor for side effects of therapy
- Have anaphylaxis medications available
Common Variable Immunodeficiency - medication
Common Variable Immunodeficiency - first line
Immunoglobulin replacement therapy
Common Variable Immunodeficiency - second line
Antibiotics as needed for infection, may also be used as adjunct to immunoglobulin replacement as prophylaxis.
Common Variable Immunodeficiency - FOLLOW UP
- 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. Abdominal pain may indicate infection or lymphoid hyperplasia.
Common Variable Immunodeficiency - disposition
Common Variable Immunodeficiency - admission criteria
- Acute illness such as pneumonia requiring IV antibiotics
- Any acute illness requiring inpatient level of care.
- Respiratory compromise.
Common Variable Immunodeficiency - issues for referral
- Autoimmune manifestations
- GI: Chronic abdominal pain or signs of possible lymphoid hyperplasia
Common Variable Immunodeficiency - prognosis
Good, as long as receiving immunoglobulin replacement therapy and follow up by immunology.
Common Variable Immunodeficiency - complications
- Autoimmune disease in 20% of common variable immunodeficiency patients. Most common are autoimmune hemolytic anemia and idiopathic thrombocytopenia purpura.
- GI complications include chronic diarrhea, malabsorption, and weight loss. Inflammatory bowel disease and Helicobacter pylori infection have also been observed.
- Granulomatous infiltrations may mimic sarcoidosis.
- Lymphoproliferative disease: Overall risk is 8%–10%. The most common are lymphomas, usually non-Hodgkin lymphoma, well differentiated, mostly Epstein-Barr virus negative.
- Chronic sinusitis and lung disease with abnormal pulmonary function tests
- Progressive decline in T-lymphocyte function
Common Variable Immunodeficiency - patient monitoring
CBC with differential, ALT, Creatinine, IgG level
Common Variable Immunodeficiency - bibliography
- Ballow M. Primary immunodeficiency disorders: Antibody deficiencies. J Allergy Clin Immunol. 2002;109:581–591.
- Brant D., Gershwin M. Common variable immune deficiency and autoimmunity. Autoimmunity reviews 5. (2006) 465–470.
- Castigli E., Geha R. Molecular basis of common variable immunodeficiency. J Allergy Clin Immunol. Nov 2005.
- Cunningham-Rundles C. Common variable immunodeficiency. Curr Allergy Asthma Rep. 2001;1:421–429.
- Cunningham-Rundles C. Immune deficiency: Office evaluation and treatment. Allergy Asthma Proc. 2003;24:409–415.
- de Asis ML, Iqbal S, Sicklick M. Analysis of a family obtaining three members with common variable immunodeficiency. Ann Allergy Asthma Immunol. 1996;76:527–529.
- Moratto D., et al. Combined decreased of defined B and T cell subsets in a group of common variable immunodeficiency patients. Clinical Immunology. (2006) 121, 203–214.
- Salzer U, Grimbacher B. Common Variable immunodeficiency: The power of costimulation co-stimulation. Seminars in Immunology 18. (2006) 337–346.
- Simonte S, Cunningham-Rundles C. Update on primary immunodeficiency: Defects of lymphocytes. Clin Immunol. 2003;109:109–118.
Common Variable Immunodeficiency - CODES
Common Variable Immunodeficiency - icd9
279.06 Common variable immunodeficiency
Common Variable Immunodeficiency - PATIENT TEACHING-MED
- Several websites available to patients and families:Immune deficiency Foundation: www.primaryimmune.org
- International Patient Organization for Primary Immunodeficiencies: www.ipopi.org
- The Jeffrey Modell Foundation: www.jmfworld.org
- National Institute of Allergy and Immunology: www.niaid.nih.gov
Common Variable Immunodeficiency - FAQ
- Q: What is the life expectancy of patients with the diagnosis of common variable immunodeficiency?
- A: Because the clinical presentations and symptoms are variable, it is difficult to predict the life expectancy in individual patients. Intravenous immunoglobulin replacement, in addition to antibiotic therapy, has greatly improved the outlook for these patients. However, despite adequate therapy, a large percentage of patients with common variable immunodeficiency 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. In one study, the mortality is estimated at 23%–27% over a median follow-up of 7 years (0–25 years). The 20-year survival after diagnosis for males is 64% and for females 67% versus 92% and 94%, respectively, for the general population.
- Q: Do children differ in their presentation compared with adults?
- A: In a subgroup of children with common variable immunodeficiency, autoimmune disease may be the major clinical problem rather than infections.
- Q: Should patients with common variable immunodeficiency receive live viral vaccines?
- A: In general, patients receiving intravenous immunoglobulin replacement therapy do not require any vaccinations. Live viral vaccines should be avoided in these patients, especially if they have deteriorating immune function.
- Q: Can common variable immunodeficiency be diagnosed prenatally?
- A: Because there are no clear genetic inheritance patterns, prenatal diagnosis is unavailable.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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