Common variable immunodeficiency in children
- Mary Beth Hogan, MD
Mary Beth Hogan, MD
- Vice Chair of Pediatric Research
- Professor of Pediatrics
- University of Nevada School of Medicine
- Nevin W Wilson, MD
Nevin W Wilson, MD
- Professor and Chairman of Pediatrics
- University of Nevada School of Medicine
Common variable immunodeficiency (CVID) is a heterogeneous disorder involving immune dysfunction of B and T lymphocytes and dendritic cells. The characteristic immunologic defect is the inability of B cells to differentiate into plasma cells capable of secreting all immunoglobulin types. While CVID is often regarded as a disease of adults, it does affect children, and diagnosis in young children can be challenging.
Clinical features of CVID and issues in the diagnosis and management of this disorder that are specific to pediatric patients (less than 18 years of age) will be reviewed here. Additional reviews of CVID, which emphasize adult manifestations and management, are found separately. (See "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults" and "Pathogenesis of common variable immunodeficiency" and "Treatment and prognosis of common variable immunodeficiency".)
DEFINITION AND CLASSIFICATION
Definition — Common variable immunodeficiency (CVID) is defined by the following :
●Age-specific reduction in serum concentrations of immunoglobulin G (IgG), in combination with low levels of immunoglobulin A (IgA) and/or immunoglobulin M (IgM)
●Presence of B cells
- Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 1999; 93:190.
- Martín-Nalda A, Soler-Palacín P, Español Borén T, et al. [Spectrum of primary immunodeficiencies in a tertiary hospital over a period of 10 years]. An Pediatr (Barc) 2011; 74:74.
- Urschel S, Kayikci L, Wintergerst U, et al. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. J Pediatr 2009; 154:888.
- Yong PL, Orange JS, Sullivan KE. Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells. Pediatr Allergy Immunol 2010; 21:852.
- Ogershok PR, Hogan MB, Welch JE, et al. Spectrum of illness in pediatric common variable immunodeficiency. Ann Allergy Asthma Immunol 2006; 97:653.
- Rudge P, Webster AD, Revesz T, et al. Encephalomyelitis in primary hypogammaglobulinaemia. Brain 1996; 119 ( Pt 1):1.
- Touw CM, van de Ven AA, de Jong PA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol 2010; 21:793.
- van de Ven AA, van Montfrans JM, Terheggen-Lagro SW, et al. A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. Chest 2010; 138:371.
- Wilson NW, Daaboul J, Bastian JF. Association of autoimmunity with IgG2 and IgG4 subclass deficiency in a growth hormone-deficient child. J Clin Immunol 1990; 10:330.
- Blümel P, Eibl M. [Growth hormone therapy in STH deficiency with immunologic deficiency and chromosome fragility]. Monatsschr Kinderheilkd 1992; 140:223.
- van Bilsen K, Driessen GJ, de Paus RA, et al. Low level IGF-1 and common variable immune deficiency: an unusual combination. Neth J Med 2008; 66:368.
- Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 1999; 92:34.
- Sneller MC, Strober W, Eisenstein E, et al. NIH conference. New insights into common variable immunodeficiency. Ann Intern Med 1993; 118:720.
- Khodadad A, Aghamohammadi A, Parvaneh N, et al. Gastrointestinal manifestations in patients with common variable immunodeficiency. Dig Dis Sci 2007; 52:2977.
- Savaşan S, Warrier I, Buck S, et al. Increased lymphocyte Fas expression and high incidence of common variable immunodeficiency disorder in childhood Evans' syndrome. Clin Immunol 2007; 125:224.
- Filipovich AH, Heinitz KJ, Robison LL, Frizzera G. The Immunodeficiency Cancer Registry. A research resource. Am J Pediatr Hematol Oncol 1987; 9:183.
- Kersey JH, Shapiro RS, Filipovich AH. Relationship of immunodeficiency to lymphoid malignancy. Pediatr Infect Dis J 1988; 7:S10.
- Cunningham-Rundles C, Cooper DL, Duffy TP, Strauchen J. Lymphomas of mucosal-associated lymphoid tissue in common variable immunodeficiency. Am J Hematol 2002; 69:171.
- Sala Cunill A, Soler-Palacín P, Martín De Vicente C, et al. [Common variable immunodeficiency. Prognostic factors for lung damage]. Med Clin (Barc) 2010; 134:64.
- http://cis.execinc.com/edibo/PublicDirectory (Accessed on August 24, 2012).
- http://aaaai.execinc.com/find-an-allergist/ (Accessed on August 24, 2012).
- http://www.acaai.org/allergist/Pages/locate_an_allergist.aspx (Accessed on August 24, 2012).
- van de Ven AA, van Montfrans JM. Clinical complications in pediatric CVID are not restricted to patients with severely reduced class-switched memory B cells. Pediatr Allergy Immunol 2011; 22:347.
- van de Ven AA, van de Corput L, van Tilburg CM, et al. Lymphocyte characteristics in children with common variable immunodeficiency. Clin Immunol 2010; 135:63.
- Kutukculer N, Gulez N. The outcome of patients with unclassified hypogammaglobulinemia in early childhood. Pediatr Allergy Immunol 2009; 20:693.
- Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun 2005; 25:57.
- Mahévas M, Le Page L, Salle V, et al. Efficiency of rituximab in the treatment of autoimmune thrombocytopenic purpura associated with common variable immunodeficiency. Am J Hematol 2006; 81:645.
- El-Shanawany TM, Williams PE, Jolles S. Response of refractory immune thrombocytopenic purpura in a patient with common variable immunodeficiency to treatment with rituximab. J Clin Pathol 2007; 60:715.
- Kim JJ, Thrasher AJ, Jones AM, et al. Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency. Br J Haematol 2007; 138:94.
- Piazza-Waggoner C, Adams CD, Cottrell L, et al. Child and caregiver psychosocial functioning in pediatric immunodeficiency disorders. Ann Allergy Asthma Immunol 2006; 96:298.
- Piątosa B, Pac M, Siewiera K, et al. Common variable immune deficiency in children--clinical characteristics varies depending on defect in peripheral B cell maturation. J Clin Immunol 2013; 33:731.
- DEFINITION AND CLASSIFICATION
- CLINICAL MANIFESTATIONS
- Recurrent infections
- Pulmonary manifestations
- Allergic diseases
- Failure to thrive
- Gastrointestinal problems
- Autoimmune disease
- - Evans syndrome
- Indications for referral
- Immunoglobulin levels
- Antibody function studies
- Other testing at the time of diagnosis
- - B cell studies
- - T cell studies
- - Genetic studies
- - Endocrine studies
- Diagnostic uncertainties
- - Periodic reassessment
- DIFFERENTIAL DIAGNOSIS
- Primary hypogammaglobulinemia
- - Agammaglobulinemia
- - Transient hypogammaglobulinemia of infancy
- Selective antibody deficiency
- IgG subclass deficiency
- Hyperimmunoglobulin M syndromes
- X-linked lymphoproliferative disease
- Combined immunodeficiency disorders
- Immune globulin
- Evaluation of illnesses
- Monitoring pulmonary status
- Autoimmune cytopenias
- Psychosocial and educational issues
- General supportive care