Pediatric Common Variable Immunodeficiency Differential Diagnoses

  • Author: C Lucy Park, MD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: Sep 28, 2010
 
 

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

C Lucy Park, MD  Head, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago

C Lucy Park, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Medical Association, Chicago Medical Society, Clinical Immunology Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Ann O'Neill Shigeoka, MD †  Former Clinical Associate Professor, Department of Pediatrics, Division of Immunology-Rheumatology, University of Utah School of Medicine

Ann O'Neill Shigeoka, MD † is a member of the following medical societies: American Federation for Medical Research, Clinical Immunology Society, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

John Wilson Georgitis, MD  Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. [Guideline] Piqueras B, Lavenu-Bombled C, Galicier L, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. Sep 2003;23(5):385-400. [Medline].

  2. [Guideline] Warnatz K, Denz A, Drager R, et al. Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. Mar 1 2002;99(5):1544-51. [Medline].

  3. Wehr C, Kivioja T, Schmitt C, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. Jan 1 2008;111(1):77-85. [Medline].

  4. Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. Jun 2009;145(6):709-27. [Medline].

  5. Olerup O, Smith CI, Bjorkander J, Hammarstrom L. Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc Natl Acad Sci U S A. Nov 15 1992;89(22):10653-7. [Medline].

  6. Bates CA, Ellison MC, Lynch DA, et al. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. Aug 2004;114(2):415-21. [Medline].

  7. Ballow M. Clinical and investigational considerations for the use of IGIV therapy. Am J Health Syst Pharm. Aug 15 2005;62(16 Suppl 3):S12-8; quiz S19-21. [Medline].

  8. Carsetti R, Rosado MM, Donnanno S, et al. The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency. J Allergy Clin Immunol. Feb 2005;115(2):412-7. [Medline].

  9. Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. Aug 2005;37(8):829-34. [Medline].

  10. Chapel H, Lucas M, Lee M, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. Jul 15 2008;112(2):277-86. [Medline].

  11. Conley ME, Park CL, Douglas SD. Childhood common variable immunodeficiency with autoimmune disease. J Pediatr. Jun 1986;108(6):915-22. [Medline].

  12. Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. May 2008;28 Suppl 1:S42-5. [Medline].

  13. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. Jul 1999;92(1):34-48. [Medline].

  14. Cunningham-Rundles C, Kazbay K, Hassett J, Zhou Z, Mayer L. Brief report: enhanced humoral immunity in common variable immunodeficiency after long-term treatment with polyethylene glycol-conjugated interleukin-2. N Engl J Med. Oct 6 1994;331(14):918-21. [Medline].

  15. Durandy A, Wahn V, Petteway S, Gelfand EW. Immunoglobulin replacement therapy in primary antibody deficiency diseases--maximizing success. Int Arch Allergy Immunol. Mar 2005;136(3):217-29. [Medline].

  16. Eijkhout HW, van Der Meer JW, Kallenberg CG, at el. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. Aug 7 2001;135(3):165-74. [Medline].

  17. Elenitoba-Johnson KS, Jaffe ES. Lymphoproliferative disorders associated with congenital immunodeficiencies. Semin Diagn Pathol. Feb 1997;14(1):35-47. [Medline].

  18. Fevang B, Mollnes TE, Holm AM, et al. Common variable immunodeficiency and the complement system; low mannose-binding lectin levels are associated with bronchiectasis. Clin Exp Immunol. Dec 2005;142(3):576-84. [Medline].

  19. Giannouli S, Anagnostou D, Soliotis F. Autoimmune manifestations in common variable immunodeficiency. Clin Rheumatol. Oct 2004;23(5):449-52. [Medline].

  20. Heeney MM, Zimmerman SA, Ware RE. Childhood autoimmune cytopenia secondary to unsuspected common variable immunodeficiency. J Pediatr. Nov 2003;143(5):662-5. [Medline].

  21. IUIS Scientific Group. Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. International Union of Immunological Societies. Clin Exp Immunol. Oct 1999;118 Suppl 1:1-28. [Medline].

  22. Johnson ML, Keeton LG, Zhu ZB, Volanakis JE, Cooper MD, Schroeder HW Jr. Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID). Clin Exp Immunol. Jun 1997;108(3):477-83. [Medline].

  23. Kainulainen L, Varpula M, Liippo K, et al. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. Nov 1999;104(5):1031-6. [Medline].

  24. Knight AK, Cunningham-Rundles C. Inflammatory and autoimmune complications of common variable immune deficiency. Autoimmun Rev. Feb 2006;5(2):156-9. [Medline].

  25. Lin JH, Liebhaber M, Roberts RL, et al. Etanercept treatment of cutaneous granulomas in common variable immunodeficiency. J Allergy Clin Immunol. Apr 2006;117(4):878-82. [Medline].

  26. Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS. Common variable immunodeficiency: a new look at an old disease. Lancet. Aug 9 2008;372(9637):489-502. [Medline].

  27. Quinti I, Soresina A, Agostini C, Spadaro G, Matucci A, Sfika I, et al. Prospective study on CVID patients with adverse reactions to intravenous or subcutaneous IgG administration. J Clin Immunol. May 2008;28(3):263-7. [Medline].

  28. Roifman CM, Schroeder H, Berger M, et al. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial. Int Immunopharmacol. Sep 2003;3(9):1325-33. [Medline].

  29. Rosen FS, Cooper MD, Wedgwood RJ. The primary immunodeficiencies. N Engl J Med. Aug 17 1995;333(7):431-40. [Medline].

  30. Salzer U, Grimbacher B. TACItly changing tunes: farewell to a yin and yang of BAFF receptor and TACI in humoral immunity? New genetic defects in common variable immunodeficiency. Curr Opin Allergy Clin Immunol. Dec 2005;5(6):496-503. [Medline].

  31. Schaffer AA, Pfannstiel J, Webster AD, et al. Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q. Hum Genet. Feb 2006;118(6):725-9. [Medline].

  32. Schejbel L, Marquart H, Andersen V, et al. Deficiency of somatic hypermutation of immunoglobulin G transcripts is a better predictor of severe respiratory tract infections than lack of memory B cells in common variable immunodeficiency. J Clin Immunol. Jul 2005;25(4):392-403. [Medline].

  33. Spickett GP, Webster ADB, Farrant J. Cellular abnormalities in common variable immunodeficiency. In: Rosen FS, Seligmann M, eds. Immunodeficiencies. Philadelphia: Harwood Academie;1993:111-26.

  34. Stiehm ER. Human intravenous immunoglobulin in primary and secondary antibody deficiencies. Pediatr Infect Dis J. Jul 1997;16(7):696-707. [Medline].

  35. Stiehm ER, Casillas AM, Finkelstein JZ, et al. Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product. J Allergy Clin Immunol. Jun 1998;101(6 Pt 1):848-9. [Medline].

  36. Stray-Pedersen A, Abrahamsen TG, Froland SS. Primary immunodeficiency diseases in Norway. J Clin Immunol. Nov 2000;20(6):477-85. [Medline].

  37. Taubenheim N, von Hornung M, Durandy A, et al. Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J Immunol. Oct 15 2005;175(8):5498-503. [Medline].

  38. Viallard JF, Camou F, Andre M, et al. Altered dendritic cell distribution in patients with common variable immunodeficiency. Arthritis Res Ther. 2005;7(5):R1052-5. [Medline].

  39. Vorechovsky I, Zetterquist H, Paganelli R, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol. Nov 1995;77(2):185-92. [Medline].

  40. Watts WJ, Watts MB, Dai W, et al. Respiratory dysfunction in patients with common variable hypogammaglobulinemia. Am Rev Respir Dis. Oct 1986;134(4):699-703. [Medline].

  41. Wright JJ, Birx DL, Wagner DK, et al. Normalization of antibody responsiveness in a patient with common variable hypogammaglobulinemia and HIV infection. N Engl J Med. Dec 10 1987;317(24):1516-20. [Medline].

  42. Zhang L, Radigan L, Salzer U, et al. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol. Nov 2007;120(5):1178-85. [Medline].

 
Previous
Next
 
Table 1. Genetic Defects in Common Variable Immunodeficiency
Genetic defectChromosomal locationInheritancePhenotypeB cells
TNFRSF13B (TACI); approximately 10% of cases17p11.2Autosomal dominantCommon variable immunodeficiency, selective immunoglobulin A deficiency (SIgAD)< 5% of cases involve absent TACI expression; 95% of cases have normal TACI expression on B cells; low-to-absent IgA levels; autoimmune disease; lymphoproliferative disease; splenomegaly; reduced class-switched memory B cells
TNFRSF13C (BAFF-R); < 1% of cases22q13.2Autosomal recessiveLate-onset, incomplete penetranceAbsent BAFF-R on B-cell surface; reduced class-switched and non–class-switched memory B cells; increased transitional B cells
ICOS; approximately 2% of cases2q33Autosomal recessiveEarly and late onsetAbsent ICOS on activated T cells; reduced class-switched memory B cells; nodular lymphoid hyperplasia; autoimmunity; predisposition to neoplasm
CD19; < 1% of cases16p11.2Autosomal recessiveEarly and late onsetLow-to-absent CD19 on B cells; reduced class-switched memory B cells; low CD21+ expression on B cells; normal number of CD20+ cells in peripheral blood
Table 2. Immune Globulin, Intravenous
Brand (Manufacturer)Virus Inactivation processpH/ Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors (eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].) Osmolality (mOsm/kg)Parenteral Form & Final ConcentrationsIgA Content mcg/mL
Carimune NF



(CSL Behring)



Fractionation and depth filtration, pH 4 and pepsin treatment, nanofiltration6.4-6.8; SucroseIn normal saline: 498-1074; in 5% dextrose: 444-1020; in sterile water: 192-768Lyophilized powder 3%, 6%, 9%, 12%720
Flebogamma



(Grifols)



PEG precipitation, ion-exchange chromatography, pasteurization5.1-6; Sorbitol240-350Liquid 5%< 50
Gammagard Liquid



(Baxter)



Solvent detergent (S/D) treatment, nanofiltration, low pH incubation at elevated temp4.6-5.1; Glycine240-300Liquid 10%37
Gamunex



(Talecris)



Caprylate-chromatography purification, cloth and depth filtration,



pH 4 incubation



4-4.5; Glycine258Liquid 10%46
Gammaplex



(Bio Products)



Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation 4.8-5.1; Contains sorbitol (40 mg/mL); do not administer if fructose intolerant420-500Ready-for-use liquid 5%< 10
Gammagard S/D



(Baxter)



Ultrafiltration, ion exchange chromatography, solvent detergent (S/D) treatment6.4-7.2;



Albumin,



Glycine,



Glucose, PEG



5%: 636; 10%:1250Lyophilized powder



5%, 10%



< 1.6 (5% solution)
Octagam



(Octapharma)



9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events



Ultrafiltration, pH 4 incubation; S/D treatment5.1-6;



Maltose



310-380Liquid 5%£200
Privigen



(CSL Behring)



pH 4 incubation, nanofiltration, depth filtration4.6-5;



L-proline



240-440Liquid 10%< 25
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.