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Published in: Current Pediatrics Reports 4/2019

Open Access 01-12-2019 | Critical Care (J Giuliano and M Bigham, Section Editors)

Focus on Chronic Variable Immunodeficiency for Primary Care Practitioners, the Gatekeepers to Optimal Health Outcomes for Primary Immunodeficiency Syndromes

Author: William A. Gerber

Published in: Current Pediatrics Reports | Issue 4/2019

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Abstract

Purpose of Review

This review sought to assess the extent and causes of suboptimal healthcare outcomes for chronic variable immunodeficiency (CVID).

Recent Findings

Significant improvements in diagnostic technology and treatment protocols over time were found, leading to reduced morbidity and mortality for those accessing therapies. Treatments continue to be largely non-curative with financing (mainly insurance coverage) an obstacle. Symptom recognition by primary care practitioners (PCP) remains a gating factor to treatment and a widespread and persistent barrier to optimal health outcomes.

Summary

CVID is a subtype of primary immunodeficiency (PIDD) associated with under-diagnosis. It has emerged as a health issue more prevalent than historically known. No symptom-recognition framework for early detection of CVID has been generally accepted; those proposed for primary immunodeficiencies have shown low sensitivity, low specificity or both. Positive trends in cases diagnosed have been aided by awareness campaigns and international collaborations. However, treatments for CVID will not realize full potential without effective, accepted frameworks for timely identification in the clinic.
Literature
1.
go back to reference Ochs HD, Hitzig WH. History of primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol. 2012;12(6):577–87.PubMed Ochs HD, Hitzig WH. History of primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol. 2012;12(6):577–87.PubMed
2.
go back to reference Boyle JM, Buckley RH. Population prevalence of diagnosed primary immunodeficiency diseases in the United States. J Clin Immunol. 2007;27:497–502.PubMed Boyle JM, Buckley RH. Population prevalence of diagnosed primary immunodeficiency diseases in the United States. J Clin Immunol. 2007;27:497–502.PubMed
3.
go back to reference Fudenberg H, Good RA, Goodman HC, Hitzig W, Kunkel HG, Roitt IM, et al. Primary immunodeficiencies, report of a World Health Organization committee. Pediatrics. 1971;47(5):927–46.PubMed Fudenberg H, Good RA, Goodman HC, Hitzig W, Kunkel HG, Roitt IM, et al. Primary immunodeficiencies, report of a World Health Organization committee. Pediatrics. 1971;47(5):927–46.PubMed
4.
go back to reference • Bonilla F, Barlan I, Chapel H, Costa-Carvalho B, Cunningham-Rundles C, de La Morena M, et al. International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38–59 A comprehensive overview of CVID, including epidemiology, clinical manifestations, genetics, diagnosis, treatments and prognosis, resulting from extensive international collaboration. PubMed • Bonilla F, Barlan I, Chapel H, Costa-Carvalho B, Cunningham-Rundles C, de La Morena M, et al. International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38–59 A comprehensive overview of CVID, including epidemiology, clinical manifestations, genetics, diagnosis, treatments and prognosis, resulting from extensive international collaboration. PubMed
5.
go back to reference Bousfiha AA, Jeddane L, Picard C, Ailal F, Gaspar HB, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:128–43. Bousfiha AA, Jeddane L, Picard C, Ailal F, Gaspar HB, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:128–43.
7.
go back to reference Immune Deficiency Foundation, prepared by Schulman, Ronca & Bucuvalas, Inc. Primary immune deficiency diseases in America, the first national survey of patients and specialists, No. IDF0034, Towson, Maryland. 1995. Immune Deficiency Foundation, prepared by Schulman, Ronca & Bucuvalas, Inc. Primary immune deficiency diseases in America, the first national survey of patients and specialists, No. IDF0034, Towson, Maryland. 1995.
8.
go back to reference Joshi AY, Iyer VN, Hagan JB, St. Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84(1):16–22.PubMedPubMedCentral Joshi AY, Iyer VN, Hagan JB, St. Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84(1):16–22.PubMedPubMedCentral
9.
go back to reference Kobrynski L, Powell RW, Bowen S. Prevalence and morbidity of primary immunodeficiency diseases, United States 2001–2007. J Clin Immunol. 2014;34(8):954–61.PubMedPubMedCentral Kobrynski L, Powell RW, Bowen S. Prevalence and morbidity of primary immunodeficiency diseases, United States 2001–2007. J Clin Immunol. 2014;34(8):954–61.PubMedPubMedCentral
11.
go back to reference Bousfiha AA, Jeddane L, Ailal F, Benhsaien I, Mahlaoui N, Casanova JL, et al. Primary immunodeficiency diseases worldwide: more common than generally thought. J Clin Immunol. 2013;33:1–7.PubMed Bousfiha AA, Jeddane L, Ailal F, Benhsaien I, Mahlaoui N, Casanova JL, et al. Primary immunodeficiency diseases worldwide: more common than generally thought. J Clin Immunol. 2013;33:1–7.PubMed
13.
go back to reference •• Modell V, Quinn J, Orange J, Notarangelo LD, Modell F. Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers global network. Immunol Res. 2016;64:736–53 A unique analysis showing PIDD-related costs for a large patient population prior to and post diagnosis. PubMed •• Modell V, Quinn J, Orange J, Notarangelo LD, Modell F. Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers global network. Immunol Res. 2016;64:736–53 A unique analysis showing PIDD-related costs for a large patient population prior to and post diagnosis. PubMed
14.
go back to reference Rubin Z, Pappalardo A, Schwartz A, Antoon JW. Prevalence and outcomes of primary immunodeficiency in hospitalized children in the United States. J Allergy Clin Immunol in Pract. 2018;6(5):1705–10. Rubin Z, Pappalardo A, Schwartz A, Antoon JW. Prevalence and outcomes of primary immunodeficiency in hospitalized children in the United States. J Allergy Clin Immunol in Pract. 2018;6(5):1705–10.
15.
go back to reference Cunningham-Rundles C, Sidi P, Estrella L, Doucette J. Identifying undiagnosed primary immunodeficiency diseases in minority subjects by using computer sorting of diagnosis codes. J Clin Immunol. 2004;113:747–55. Cunningham-Rundles C, Sidi P, Estrella L, Doucette J. Identifying undiagnosed primary immunodeficiency diseases in minority subjects by using computer sorting of diagnosis codes. J Clin Immunol. 2004;113:747–55.
17.
go back to reference Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, et al. Primary immune deficiency treatment consortium (PIDTC) update. J Clin Immunol. 2016;138(2):375–85. Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, et al. Primary immune deficiency treatment consortium (PIDTC) update. J Clin Immunol. 2016;138(2):375–85.
18.
go back to reference Chapel H, Lucas M, Patel S, Lee M, Cunningham-Rundles C, Resnick E, et al. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J Clin Immunol. 2012;130:1197–8. Chapel H, Lucas M, Patel S, Lee M, Cunningham-Rundles C, Resnick E, et al. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J Clin Immunol. 2012;130:1197–8.
19.
go back to reference • Modell V, Orange JS, Quinn J, Modell F. Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes. Immunol Res. 2018;66:367–80 A comprehensive breakdown of PIDD subtypes within a large patient population. PubMed • Modell V, Orange JS, Quinn J, Modell F. Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes. Immunol Res. 2018;66:367–80 A comprehensive breakdown of PIDD subtypes within a large patient population. PubMed
20.
go back to reference Waltenburg R, Kobrynski L, Reyes M, Bowen S, Khoury MJ. Primary immunodeficiency diseases: practice among primary care providers and awareness among the general public, United States, 2008. Genet Med. 2010;12(12):792–800.PubMed Waltenburg R, Kobrynski L, Reyes M, Bowen S, Khoury MJ. Primary immunodeficiency diseases: practice among primary care providers and awareness among the general public, United States, 2008. Genet Med. 2010;12(12):792–800.PubMed
21.
go back to reference Verbsky JW, Routes JR. Recurrent fever, infections, immune disorders, and autoinflammatory diseases. In: Kliegman RM, Lye PS, Bordini BJ, Toth H, Basel D, editors. Nelson pediatric symptom-based diagnosis. Amsterdam: Elsevier; 2018. p. 746–73. Verbsky JW, Routes JR. Recurrent fever, infections, immune disorders, and autoinflammatory diseases. In: Kliegman RM, Lye PS, Bordini BJ, Toth H, Basel D, editors. Nelson pediatric symptom-based diagnosis. Amsterdam: Elsevier; 2018. p. 746–73.
22.
go back to reference Abolhassani H, Sagvand B, Shokuhfar T, Mirminachi B, Rezaei N, Aghamohammadi A. A review on guidelines for management and treatment of common variable immunodeficiency. Expert Rev Clin Immunol. 2013;9(6):561–75.PubMed Abolhassani H, Sagvand B, Shokuhfar T, Mirminachi B, Rezaei N, Aghamohammadi A. A review on guidelines for management and treatment of common variable immunodeficiency. Expert Rev Clin Immunol. 2013;9(6):561–75.PubMed
23.
go back to reference Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013;174:203–11.PubMedPubMedCentral Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013;174:203–11.PubMedPubMedCentral
24.
go back to reference Urschel S, Kayikci L, Wintergerst U, Notheis G, Jansson A, Belohradsky B. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. J Pediatr. 2009;154(6):888–94.PubMed Urschel S, Kayikci L, Wintergerst U, Notheis G, Jansson A, Belohradsky B. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. J Pediatr. 2009;154(6):888–94.PubMed
26.
go back to reference Chapel H. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.PubMed Chapel H. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.PubMed
27.
go back to reference Grundling K. Common variable immunodeficiency in the very old. J Allergy Clin Immunol. 2014;133(2):AB9. Grundling K. Common variable immunodeficiency in the very old. J Allergy Clin Immunol. 2014;133(2):AB9.
28.
go back to reference Cunningham-Rundles C. The many faces of common variable immunodeficiency, vol. 2012: Hematology Am Soc Hematol Educ Program; 2012. p. 301–5. Cunningham-Rundles C. The many faces of common variable immunodeficiency, vol. 2012: Hematology Am Soc Hematol Educ Program; 2012. p. 301–5.
29.
go back to reference Kardar GA, Oraei M, Shahsavani M, Namdar Z, Kazemisefat GE, Haghi Ashtiani MT, et al. Reference intervals for serum immunoglobulins IgG, IgA, IgM and complements C3 and C4 in Iranian healthy children. Iran J Public Health. 2012;41(7):59–63.PubMedPubMedCentral Kardar GA, Oraei M, Shahsavani M, Namdar Z, Kazemisefat GE, Haghi Ashtiani MT, et al. Reference intervals for serum immunoglobulins IgG, IgA, IgM and complements C3 and C4 in Iranian healthy children. Iran J Public Health. 2012;41(7):59–63.PubMedPubMedCentral
30.
go back to reference Welch K, Resnick E, Cunningham-Rundles C. Genetic basis of CVID-like disease. J Allergy Clin Immunol. 2014;133(2) supplement. Welch K, Resnick E, Cunningham-Rundles C. Genetic basis of CVID-like disease. J Allergy Clin Immunol. 2014;133(2) supplement.
31.
go back to reference Schouwenburg PA, Davenport EE, Kienzler AK, Marwah I, Wright B, Lucas M, et al. Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders. Clin Immunol. 2015;160:301–14.PubMedPubMedCentral Schouwenburg PA, Davenport EE, Kienzler AK, Marwah I, Wright B, Lucas M, et al. Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders. Clin Immunol. 2015;160:301–14.PubMedPubMedCentral
32.
go back to reference de Valles-Ibáñez G, Esteve-Solé A, Piquer M, González-Navarro EA, Hernandez-Rodriguez J, Laayouni H, et al. Evaluating the genetics of common variable immunodeficiency: monogenetic model and beyond. Front Immunol. 2018;9(636):1–15. de Valles-Ibáñez G, Esteve-Solé A, Piquer M, González-Navarro EA, Hernandez-Rodriguez J, Laayouni H, et al. Evaluating the genetics of common variable immunodeficiency: monogenetic model and beyond. Front Immunol. 2018;9(636):1–15.
33.
go back to reference Li J, Wei Z, Li YR, Maggadottir SM, Chang X, Desai A, et al. Understanding the genetic and epigenetic basis of common variable immunodeficiency disorder through omics approaches. Biochim Biophys Acta. 2016;1860:2656–63.PubMed Li J, Wei Z, Li YR, Maggadottir SM, Chang X, Desai A, et al. Understanding the genetic and epigenetic basis of common variable immunodeficiency disorder through omics approaches. Biochim Biophys Acta. 2016;1860:2656–63.PubMed
34.
go back to reference Westh L, Mogensen TH, Dalgaard LS, Bernth Jensen JM, Katzenstein T, Hansen ABE, et al. Identification and characterization of a nationwide Danish adult common variable immunodeficiency cohort. Scand J Immunol. 2017;85:450–61.PubMed Westh L, Mogensen TH, Dalgaard LS, Bernth Jensen JM, Katzenstein T, Hansen ABE, et al. Identification and characterization of a nationwide Danish adult common variable immunodeficiency cohort. Scand J Immunol. 2017;85:450–61.PubMed
35.
go back to reference Orange JS, Grossman W, Navickis R, Wilkes M. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137(1):21–30.PubMed Orange JS, Grossman W, Navickis R, Wilkes M. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137(1):21–30.PubMed
36.
go back to reference Cinetto F, Scarpa R, Rattazzi M, Agostini C. The broad spectrum of lung diseases in primary antibody deficiencies. Eur Respir Rev. 2018;27(149):180019.PubMed Cinetto F, Scarpa R, Rattazzi M, Agostini C. The broad spectrum of lung diseases in primary antibody deficiencies. Eur Respir Rev. 2018;27(149):180019.PubMed
37.
go back to reference • Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European society for immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(201):1–17 A large and unique study analyzing individual and society disease burden of CVID. • Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European society for immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(201):1–17 A large and unique study analyzing individual and society disease burden of CVID.
38.
go back to reference Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2011;119(7):1650–7.PubMed Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2011;119(7):1650–7.PubMed
39.
go back to reference Quinti, I., Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. (2007). Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol, 27(3), 308–316.PubMed Quinti, I., Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. (2007). Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol, 27(3), 308–316.PubMed
40.
go back to reference Blaese R, Stiehm E, Bonilla F, Younger M, editors. Immune Deficiency Foundation patient & family handbook for primary immunodeficiency diseases. 5th ed. Baltimore: Immune Deficiency Foundation; 2013. Blaese R, Stiehm E, Bonilla F, Younger M, editors. Immune Deficiency Foundation patient & family handbook for primary immunodeficiency diseases. 5th ed. Baltimore: Immune Deficiency Foundation; 2013.
41.
go back to reference Maarschalk-Ellerbroek LJ, Hoepelman AIM, van Montfrans JM, Ellerbroek PM. The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital. J Clin Immunol. 2012;32:907–21.PubMedPubMedCentral Maarschalk-Ellerbroek LJ, Hoepelman AIM, van Montfrans JM, Ellerbroek PM. The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital. J Clin Immunol. 2012;32:907–21.PubMedPubMedCentral
42.
go back to reference Gathmann, B., & Mahlaoui N., , Gérard L., Oksenhendler E., Warnatz K., Schulze I., Kindle G., Kuijpers T.W., van Beem R., Guzman D., Workman S., Soler-Palacín P., de Gracia J., Witte T., Schmidt R.E., Litzman J., Hlavackova E., Thon V., Borte M., Borte S., Kumararatne D., Feighery C., Longhurst H., Helbert M., Szaflarska A., Sediva A., Belohradsky B.H., Jones A., Baumann U., Meyts I., Kutukculer N., Wågström P., Galal N.M., Roesler J., Farmaki E., Zinovieva N., Ciznar P., Papadopoulou-Alataki E., Bienemann K., Velbri S., Panahloo Z., Grimbacher B., CEREDIH., Dutch WID, European Society for Immunodeficiencies Registry Working Party (2014). Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol, 134(1), 116–126.PubMed Gathmann, B., & Mahlaoui N., , Gérard L., Oksenhendler E., Warnatz K., Schulze I., Kindle G., Kuijpers T.W., van Beem R., Guzman D., Workman S., Soler-Palacín P., de Gracia J., Witte T., Schmidt R.E., Litzman J., Hlavackova E., Thon V., Borte M., Borte S., Kumararatne D., Feighery C., Longhurst H., Helbert M., Szaflarska A., Sediva A., Belohradsky B.H., Jones A., Baumann U., Meyts I., Kutukculer N., Wågström P., Galal N.M., Roesler J., Farmaki E., Zinovieva N., Ciznar P., Papadopoulou-Alataki E., Bienemann K., Velbri S., Panahloo Z., Grimbacher B., CEREDIH., Dutch WID, European Society for Immunodeficiencies Registry Working Party (2014). Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol, 134(1), 116–126.PubMed
43.
go back to reference Modell V, Quinn J, Ginsberg G, Gladue R, Orange J, Modell F. Modeling strategy to identify patients with primary immunodeficiency utilizing risk management and outcome measurement. Immunol Res. 2017;65:713–20.PubMed Modell V, Quinn J, Ginsberg G, Gladue R, Orange J, Modell F. Modeling strategy to identify patients with primary immunodeficiency utilizing risk management and outcome measurement. Immunol Res. 2017;65:713–20.PubMed
44.
go back to reference Bjelac JA, Yonkof JR, Fernandez J. Differing performance of the warning signs for immunodeficiency in the diagnosis of pediatric versus adult patients in a two-center tertiary referral population. J Clin Immunol. 2018. Bjelac JA, Yonkof JR, Fernandez J. Differing performance of the warning signs for immunodeficiency in the diagnosis of pediatric versus adult patients in a two-center tertiary referral population. J Clin Immunol. 2018.
45.
go back to reference Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7–14.PubMed Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7–14.PubMed
46.
go back to reference Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127(5):810–6.PubMed Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127(5):810–6.PubMed
47.
go back to reference Lankisch P, Schiffner J, Ghosh S, Babor F, Borkhardt A, Laws HJ. The Dusseldorf warning signs for primary immunodeficiency: is it time to change the rules? J Clin Immunol. 2015;35:273–9.PubMed Lankisch P, Schiffner J, Ghosh S, Babor F, Borkhardt A, Laws HJ. The Dusseldorf warning signs for primary immunodeficiency: is it time to change the rules? J Clin Immunol. 2015;35:273–9.PubMed
48.
go back to reference de Vries E, et al. Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic protocol designed for non-immunologists: 2011 update. Clin Exp Immunol. 2011(167):108–19. de Vries E, et al. Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic protocol designed for non-immunologists: 2011 update. Clin Exp Immunol. 2011(167):108–19.
49.
go back to reference Orange JS, Seeborg FO, Boyle M, Scalchunes C, Hernandez-Trujillo V. Family physician perspectives on primary immunodeficiency diseases. Front Med. 2016;3(12). Orange JS, Seeborg FO, Boyle M, Scalchunes C, Hernandez-Trujillo V. Family physician perspectives on primary immunodeficiency diseases. Front Med. 2016;3(12).
50.
go back to reference Hernandez-Trujillo VP, Scalchunes C, Hernandez-Trujillo HS, Boyle J, Williams P, Boyle M, et al. Primary immunodeficiency diseases: an opportunity in pediatrics for improving patient outcomes. Clin Pediatr. 2015;54(13):12652015–1275. Hernandez-Trujillo VP, Scalchunes C, Hernandez-Trujillo HS, Boyle J, Williams P, Boyle M, et al. Primary immunodeficiency diseases: an opportunity in pediatrics for improving patient outcomes. Clin Pediatr. 2015;54(13):12652015–1275.
52.
go back to reference Reust CE. Evaluation of primary immunodeficiency disease in children. Am Fam Physician. 2013;87(11):773–8.PubMed Reust CE. Evaluation of primary immunodeficiency disease in children. Am Fam Physician. 2013;87(11):773–8.PubMed
53.
go back to reference Orange JS, Glessner JT, Resnick E, Sullivan KE, Lucas M, Ferry B, et al. Genome-wide association identifies diverse causes of common variable immunodeficiency. J Allergy Clin Immunol. 2011;127(6):1360–7.PubMedPubMedCentral Orange JS, Glessner JT, Resnick E, Sullivan KE, Lucas M, Ferry B, et al. Genome-wide association identifies diverse causes of common variable immunodeficiency. J Allergy Clin Immunol. 2011;127(6):1360–7.PubMedPubMedCentral
54.
go back to reference Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139:S1–S46.PubMed Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139:S1–S46.PubMed
55.
go back to reference Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin N Am. 2008;28:413–37. Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin N Am. 2008;28:413–37.
56.
go back to reference Pulvirenti F, Cinetto F, Pecoraro A, Carrabba M, Crescenzi L, Neri R, et al. Health-related quality of life in patients with CVID under different schedules of immunoglobulin administration: prospective multicenter study. J Clin Immunol. 2019;39:159–70.PubMedPubMedCentral Pulvirenti F, Cinetto F, Pecoraro A, Carrabba M, Crescenzi L, Neri R, et al. Health-related quality of life in patients with CVID under different schedules of immunoglobulin administration: prospective multicenter study. J Clin Immunol. 2019;39:159–70.PubMedPubMedCentral
57.
go back to reference Eades-Perner AM, Gathmann B, Knerr V, Guzman D, Veit D, Kindle G, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2004–06. Clin Exp Immunol. 2007;147:306–12.PubMedPubMedCentral Eades-Perner AM, Gathmann B, Knerr V, Guzman D, Veit D, Kindle G, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2004–06. Clin Exp Immunol. 2007;147:306–12.PubMedPubMedCentral
58.
go back to reference Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Clin Immunol. 2008;122:210–2. Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Clin Immunol. 2008;122:210–2.
59.
go back to reference Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah M, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125(6):1354–60.PubMed Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah M, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125(6):1354–60.PubMed
60.
go back to reference Langereis JD, van der Flier M, de Jonge MI. Limited innovations after more than 65 years of immunoglobulin replacement therapy: potential of IgA- and IgM-enriched formulations to prevent bacterial respiratory tract infections. Front Immunol. 2018;9(1925):1–8. Langereis JD, van der Flier M, de Jonge MI. Limited innovations after more than 65 years of immunoglobulin replacement therapy: potential of IgA- and IgM-enriched formulations to prevent bacterial respiratory tract infections. Front Immunol. 2018;9(1925):1–8.
61.
go back to reference Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125(202):S41–52.PubMedPubMedCentral Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125(202):S41–52.PubMedPubMedCentral
62.
go back to reference Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31:315–22.PubMed Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31:315–22.PubMed
63.
go back to reference Kuruvilla M, de la Morena MT. Antibiotic prophylaxis in primary immune deficiency disorders. J Allergy Clin Immunol Pract. 2013;1:573–82.PubMed Kuruvilla M, de la Morena MT. Antibiotic prophylaxis in primary immune deficiency disorders. J Allergy Clin Immunol Pract. 2013;1:573–82.PubMed
64.
go back to reference Sperlich JM, Grimbacher B, Workman S, Haque T, Seneviratne SL, Burns S, et al. Respiratory infections and antibiotic usage in common variable immunodeficiency. J Allergy Clin Immunol. 2018;6:159–68. Sperlich JM, Grimbacher B, Workman S, Haque T, Seneviratne SL, Burns S, et al. Respiratory infections and antibiotic usage in common variable immunodeficiency. J Allergy Clin Immunol. 2018;6:159–68.
65.
go back to reference Wehr, C., Gennery AR, Lindemans C, Schulz A, Hoenig M, Marks R, et al. (2014). Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency. J Allergy Clin Immunol, 135(4), 988–997. Wehr, C., Gennery AR, Lindemans C, Schulz A, Hoenig M, Marks R, et al. (2014). Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency. J Allergy Clin Immunol, 135(4), 988–997.
68.
go back to reference Shapiro RS, Boyle M. Payor issues: barriers to optimal management of patients with primary immunodeficiency. J Clin Immunol. 2012;32(Supplement 2):S410–4.PubMed Shapiro RS, Boyle M. Payor issues: barriers to optimal management of patients with primary immunodeficiency. J Clin Immunol. 2012;32(Supplement 2):S410–4.PubMed
69.
go back to reference Lyles CA, Scalchunes C, Boyle M, Henderson T, LaMotte L. Health insurance & primary immunodeficiency diseases: a 2014 Immune Deficiency Foundation survey (Survey. Towson, Maryland: Immune Deficiency Foundation. (Primary immunodeficiency health insurance survey). 2014. Lyles CA, Scalchunes C, Boyle M, Henderson T, LaMotte L. Health insurance & primary immunodeficiency diseases: a 2014 Immune Deficiency Foundation survey (Survey. Towson, Maryland: Immune Deficiency Foundation. (Primary immunodeficiency health insurance survey). 2014.
70.
go back to reference Wasserman RL, Ito D, Xiong V, Ye XL, Bonnet P, Li-McLeod J. Impact of site of care on infection rates among patients with primary immunodeficiency diseases receiving intravenous immunoglobulin therapy. J Clin Immunol. 2017;37:180–6.PubMedPubMedCentral Wasserman RL, Ito D, Xiong V, Ye XL, Bonnet P, Li-McLeod J. Impact of site of care on infection rates among patients with primary immunodeficiency diseases receiving intravenous immunoglobulin therapy. J Clin Immunol. 2017;37:180–6.PubMedPubMedCentral
71.
go back to reference Menzin J, Sussman M, Munsell M, Zbrozek A. Economic impact of infections among patients with primary immunodeficiency disease receiving IVIG therapy. Clinicoecon Outcomes Res. 2014;6:297–302.PubMedPubMedCentral Menzin J, Sussman M, Munsell M, Zbrozek A. Economic impact of infections among patients with primary immunodeficiency disease receiving IVIG therapy. Clinicoecon Outcomes Res. 2014;6:297–302.PubMedPubMedCentral
go back to reference Baris S, Ercan H, Cagan H, Ozen A, Karakoc-Aydiner E, Ozdemir C, et al. Efficacy of intravenous immunoglobulin treatment in children with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2011;21(7):514–21.PubMed Baris S, Ercan H, Cagan H, Ozen A, Karakoc-Aydiner E, Ozdemir C, et al. Efficacy of intravenous immunoglobulin treatment in children with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2011;21(7):514–21.PubMed
go back to reference Bonilla FA, Khan DA, Ballas ZK, Chinen JC, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186–205.PubMed Bonilla FA, Khan DA, Ballas ZK, Chinen JC, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186–205.PubMed
go back to reference Buckley RH, editor. Immune Deficiency Foundation diagnostic & clinical care guidelines for primary immunodeficiency diseases. 3rd ed. Towson: Immune Deficiency Foundation; 2015. Buckley RH, editor. Immune Deficiency Foundation diagnostic & clinical care guidelines for primary immunodeficiency diseases. 3rd ed. Towson: Immune Deficiency Foundation; 2015.
go back to reference Busse P, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109(6):1001–4.PubMed Busse P, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109(6):1001–4.PubMed
go back to reference Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145:709–29.PubMedPubMedCentral Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145:709–29.PubMedPubMedCentral
go back to reference Llobet M, Soler-Palacin P, Detkova D, Hernández M, Caragol I, Espanol T. Common variable immunodeficiency: 20-yr experience at a single centre. Pediatr Allergy Immunol. 2009;20(2):113–8.PubMed Llobet M, Soler-Palacin P, Detkova D, Hernández M, Caragol I, Espanol T. Common variable immunodeficiency: 20-yr experience at a single centre. Pediatr Allergy Immunol. 2009;20(2):113–8.PubMed
go back to reference Modell F, Puente D, Modell V. From genotype to phenotype. Further studies measuring the impact of a physician education and public awareness campaign on early diagnosis and management of primary immunodeficiencies. Immunol Res. 2009;38:132–49. Modell F, Puente D, Modell V. From genotype to phenotype. Further studies measuring the impact of a physician education and public awareness campaign on early diagnosis and management of primary immunodeficiencies. Immunol Res. 2009;38:132–49.
go back to reference Orange J, Ballow M, Stiehm R, Ballas Z, Chinen J, De La Morena M, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the basic and clinical immunology interest section of the American Academy of Allergy, Asthma & Immunology. The J Allergy Clin Immunol. 2012;130(3):S1–S24.PubMed Orange J, Ballow M, Stiehm R, Ballas Z, Chinen J, De La Morena M, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the basic and clinical immunology interest section of the American Academy of Allergy, Asthma & Immunology. The J Allergy Clin Immunol. 2012;130(3):S1–S24.PubMed
go back to reference Samples S, Sharma N, Ownby D. New diagnosis of common variable immunodeficiency in a 12-year-old with pneumonia: an illustrative case. Hospital Pediatrics. 2014;4(4):251–5.PubMed Samples S, Sharma N, Ownby D. New diagnosis of common variable immunodeficiency in a 12-year-old with pneumonia: an illustrative case. Hospital Pediatrics. 2014;4(4):251–5.PubMed
go back to reference Shapiro RS, Wasserman R, Bonagura V, Gupta S. Emerging paradigm of primary immunodeficiency disease: individualizing immunoglobulin dose and delivery to enhance outcomes. J Clin Immunol. 2017;37:190–6.PubMed Shapiro RS, Wasserman R, Bonagura V, Gupta S. Emerging paradigm of primary immunodeficiency disease: individualizing immunoglobulin dose and delivery to enhance outcomes. J Clin Immunol. 2017;37:190–6.PubMed
go back to reference Shehata N, Palda V, Bowen T, Haddad E, Issekutz T, Mazer B, et al. The use of immunoglobulin therapy for patients with primary immune deficiency: an evidence-based practice guideline. Transfus Med Rev. 2010;24(1):S28–50.PubMed Shehata N, Palda V, Bowen T, Haddad E, Issekutz T, Mazer B, et al. The use of immunoglobulin therapy for patients with primary immune deficiency: an evidence-based practice guideline. Transfus Med Rev. 2010;24(1):S28–50.PubMed
Metadata
Title
Focus on Chronic Variable Immunodeficiency for Primary Care Practitioners, the Gatekeepers to Optimal Health Outcomes for Primary Immunodeficiency Syndromes
Author
William A. Gerber
Publication date
01-12-2019
Publisher
Springer US
Published in
Current Pediatrics Reports / Issue 4/2019
Electronic ISSN: 2167-4841
DOI
https://doi.org/10.1007/s40124-019-00202-8

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