Drugs & Aging

, Volume 30, Issue 7, pp 503–512 | Cite as

Therapeutic Management of Primary Immunodeficiency in Older Patients

  • Nisha Verma
  • Anthony Thaventhiran
  • Benjamin Gathmann
  • for the ESID Registry Working Party
  • James Thaventhiran
  • Bodo Grimbacher
Review Article

Abstract

Primary immunodeficiency disease (PID) has traditionally been viewed as a group of illnesses seen in the paediatric age group. New advances in diagnosis and treatment have led to an increase in the number of elderly PID patients. However, there is lack of research evidence on which to base clinical management in this group of patients. Management decisions often have to be based therefore on extrapolations from other patient cohorts or from younger patients. Data from the European Society for Immunodeficiencies demonstrates that the vast majority of elderly patients suffer from predominantly antibody deficiency syndromes. We review the management of PID disease in the elderly, with a focus on antibody deficiency disease.

Notes

Acknowledgments

Statistics from the ESID Online Database (http://www.esid.org/research-database) are presented in this paper.

Conflict of interest

Bodo is a Consulting Physician in the Royal Free Hospital, London, and Scientific Director of CCI, University Hospital Freiburg; remaining authors have no conflict of interest.

References

  1. 1.
    Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, Conley ME, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124(6):1161–78.PubMedCrossRefGoogle Scholar
  2. 2.
    McEwan WA, Mallery DL, Rhodes DA, Trowsdale J, James LC. Intracellular antibody-mediated immunity and the role of TRIM21. BioEssays. 2011;33(11):803–9. doi: 10.1002/bies.201100093. (Epub 2011 Aug 29).PubMedCrossRefGoogle Scholar
  3. 3.
    Cowan MJ, Neven B, Cavazanna-Calvo M, Fischer A, Puck J. Hematopoietic stem cell transplantation for severe combined immunodeficiency diseases. Biol Blood Marrow Transpl. 2008;14(1 Suppl 1):73–5.CrossRefGoogle Scholar
  4. 4.
    Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med. 1993;86(1):31–42.PubMedGoogle Scholar
  5. 5.
    Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34–48.PubMedCrossRefGoogle Scholar
  6. 6.
    Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine. 2006;85(4):193–202.PubMedCrossRefGoogle Scholar
  7. 7.
    Bruton OC. Agammaglobulinemia. Pediatrics. 1952;9(6):722–8.PubMedGoogle Scholar
  8. 8.
    Kornfeld SJ, Haire RN, Strong SJ, Tang H, Sung SS, Fu SM, et al. A novel mutation (Cys145–>Stop) in Bruton’s tyrosine kinase is associated with newly diagnosed X-linked agammaglobulinemia in a 51-year-old male. Molecular Med. 1996;2(5):619–23.Google Scholar
  9. 9.
    Plebani A, Soresina A, Rondelli R, Amato GM, Azzari C, Cardinale F, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. 2002;104(3):221–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Schaffer AA, Salzer U, Hammarstrom L, Grimbacher B. Deconstructing common variable immunodeficiency by genetic analysis. Current Opin Genet Dev. 2007;17(3):201–12.CrossRefGoogle Scholar
  11. 11.
    Di Renzo M, Pasqui AL, Auteri A. Common variable immunodeficiency: a review. Clin Exp Med. 2004;3(4):211–7.PubMedCrossRefGoogle Scholar
  12. 12.
    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(2):306–12.PubMedCrossRefGoogle Scholar
  13. 13.
    De Santis W, Esposito A, Conti V, Fantauzzi A, Guerra A, Mezzaroma I, et al. Health care and infective aspects in patients affected by common variable immunodeficiency assisted in the Lazio Regional Authority Reference Centre for Primary Immunodeficiencies. Infez Med. 2006;14(1):13–23.PubMedGoogle Scholar
  14. 14.
    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(3):190–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005;94(5 Suppl 1):S1–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Dhalla F, da Silva SP, Lucas M, Travis S, Chapel H. Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme. Clin Exp Immunol. 2011;165(1):1–7. doi: 10.1111/j.1365-2249.2011.04384.x. (Epub 2011 Apr 6).PubMedCrossRefGoogle Scholar
  17. 17.
    Correa P, Houghton JM. Carcinogenesis of Helicobacter pylori. Gastroenterology. 2007;133:659–72.PubMedCrossRefGoogle Scholar
  18. 18.
    Zullo A, Romiti A, Rinaldi V, Vecchione A, Tomao S, Aiuti F, Frati L, Luzi G. Gastric pathology in patients with common variable immunodeficiency. Gut. 1999;45(1):77–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Cunnigham-Rundles C, Cooper DL, Duffy TP, Strauchen J. Lymphomas of mucosal associated lymphoid tissue in common variable immunodeficiency. Am J Hematol. 2002;69(3):171–8.CrossRefGoogle Scholar
  20. 20.
    Aghamohammadi A, Parvaneh N, Tirgari F, Mahjoob F, Movahedi M, Gharagozlou M, Mansouri M, Kouhi A, Rezaei N, Webster D. Lymphoma of mucosa-associated lymphoid tissue in common variable immunodeficiency. Leuk Lymphoma. 2006;47(2):343–6. (Review).PubMedCrossRefGoogle Scholar
  21. 21.
    Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS. Common variable immunodeficiency: a new look at an old disease. Lancet. 2008;372(9637):489–502.PubMedCrossRefGoogle Scholar
  22. 22.
    Mellemkjaer L, Hammarstrom L, Andersen V, Yuen J, Heilmann C, Barington T, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol. 2002;130(3):495–500.PubMedCrossRefGoogle Scholar
  23. 23.
    Spector BD, Perry GS, 3rd, Gajl-Peczalska KJ, Coccia P, Nesbit ME, Kersey JH. Malignancy in children with and without genetically-determined immunodeficiencies. Birth Defects Orig Artic Ser. 1978;14(6A):85–9.PubMedGoogle Scholar
  24. 24.
    Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 1999;104(5):1031–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Sodickson A, Baeyens PF, Andriole KP, Prevedello LM, Nawfel RD, Hanson R, Khorasani R. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009;251(1):175–84.PubMedCrossRefGoogle Scholar
  26. 26.
    Yong PF, Tarzi M, Chua I, Grimbacher B, Chee R. Common variable immunodeficiency: an update on etiology and management. Immunol Allergy Clin N Am. 2008;28(2):367–86, ix-x.Google Scholar
  27. 27.
    Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16.PubMedCrossRefGoogle Scholar
  28. 28.
    Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25(1):57–62.PubMedCrossRefGoogle Scholar
  29. 29.
    Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debré P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85 (Epub 2007 Sep 26).Google Scholar
  30. 30.
    Sordet C, Cantagrel A, Schaeverbeke T, Sibilia J. Bone and joint disease associated with primary immune deficiencies. Joint Bone Spine. 2005;72(6):503–14.PubMedCrossRefGoogle Scholar
  31. 31.
    Wang LJ, Yang YH, Lin YT, Chiang BL. Immunological and clinical features of pediatric patients with primary hypogammaglobulinemia in Taiwan. Asian Pac J Allergy Immunol. 2004;22(1):25–31.PubMedGoogle Scholar
  32. 32.
    Kelesidis T, Yang O. Good’s syndrome remains a mystery after 55 years: a systematic review of the scientific evidence. Clin Immunol. 2010;135(3):347–63.PubMedCrossRefGoogle Scholar
  33. 33.
    Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. International Union of Immunological Societies. Clin Exp Immunol. 1999;118(Suppl 1):1–28.Google Scholar
  34. 34.
    Kaveri SV, Maddur MS, Hegde P, Lacroix-Desmazes S, Bayry J. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011;164(Suppl 2):2–5.PubMedCrossRefGoogle Scholar
  35. 35.
    de Gracia J, Vendrell M, Alvarez A, Pallisa E, Rodrigo MJ, de la Rosa D, et al. Immunoglobulin therapy to control lung damage in patients with common variable immunodeficiency. Int Immunopharmacol. 2004;4(6):745–53.PubMedCrossRefGoogle Scholar
  36. 36.
    Chapel HM, Spickett GP, Ericson D, Engl W, Eibl MM, Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol. 2000;20(2):94–100.PubMedCrossRefGoogle Scholar
  37. 37.
    Stein MR, Koterba A, Rodden L, Berger M. Safety and efficacy of home-based subcutaneous immunoglobulin G in elderly patients with primary immunodeficiency diseases. Postgrad Med. 2011;123(5):186–93.PubMedCrossRefGoogle Scholar
  38. 38.
    Moore ML, Quinn JM. Subcutaneous immunoglobulin replacement therapy for primary antibody deficiency: advancements into the 21st century. Ann Allergy Asthma Immunol. 2008;101(2):114–21. (Quiz 22–3, 78).PubMedCrossRefGoogle Scholar
  39. 39.
    Wood PM. Primary antibody deficiency syndromes. Current Opin Hematol. 2010;17(4):356–61.CrossRefGoogle Scholar
  40. 40.
    Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson RP Jr, Patel DD, Secord E, Sorensen RU, Wasserman RL, Cunningham-Rundles C, Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006;117(4 Suppl):S525–53.Google Scholar
  41. 41.
    Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. Int Immunopharmacol. 2006;6(4):535–42.PubMedCrossRefGoogle Scholar
  42. 42.
    Caress JB, Kennedy BL, Eickman KD. Safety of intravenous immunoglobulin treatment. Expert Opin Drug Safety. 2006;9(6):971–9.CrossRefGoogle Scholar
  43. 43.
    Cheng MJ, Christmas C. Special considerations with the use of intravenous immunoglobulin in older persons. Drugs Aging. 2011;28(9):729–36.PubMedCrossRefGoogle Scholar
  44. 44.
    Paran D, Herishanu Y, Elkayam O, Shopin L, Ben-Ami R. Venous and arterial thrombosis following administration of intravenous immunoglobulins. Blood Coagul Fibrinolysis. 2005;16(5):313–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Caress JB, Hobson-Webb L, Passmore LV, Finkbiner AP, Cartwright MS. Case-control study of thromboembolic events associated with IV immunoglobulin. J Neurol. 2009;256(3):339–42.PubMedCrossRefGoogle Scholar
  46. 46.
    Hoiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros. 2005;4(Suppl 2):49–54.PubMedCrossRefGoogle Scholar
  47. 47.
    Cullen M, Steven N, Billingham L, Gaunt C, Hastings M, Simmonds P, et al. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med. 2005;353(10):988–98.PubMedCrossRefGoogle Scholar
  48. 48.
    Hoiby N. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis. BMC Med. 2011;9:32.PubMedCrossRefGoogle Scholar
  49. 49.
    Green H, Paul M, Vidal L, Leibovici L. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. 2007(3):CD005590.Google Scholar
  50. 50.
    Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, 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.e4. (Epub 2010 May 14).Google Scholar
  51. 51.
    Longhurst HJ, Taussig D, Haque T, Syndercombe-Court D, Cavenagh J, Edgar JD, et al. Non-myeloablative bone marrow transplantation in an adult with Wiskott–Aldrich syndrome. Br J Haematol. 2002;116(2):497–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Rizzi M, Neumann C, Fielding AK, Marks R, Goldacker S, Thaventhiran J, et al. Outcome of allogeneic stem cell transplantation in adults with common variable immunodeficiency. J Allergy Clin Immunol. 2011;128(6):1371–4.e2.Google Scholar
  53. 53.
    Marodi L, Notarangelo LD. Immunological and genetic bases of new primary immunodeficiencies. Nat Rev. 2007;7(11):851–61.CrossRefGoogle Scholar
  54. 54.
    Yong PF, Thaventhiran JE, Grimbacher B. “A rose is a rose is a rose,” but CVID is not CVID common variable immune deficiency (CVID), what do we know in 2011? Adv Immunol. 2011;111:47–107.PubMedCrossRefGoogle Scholar
  55. 55.
    Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010;363(4):355–64.PubMedCrossRefGoogle Scholar
  56. 56.
    Alcais A, Quintana-Murci L, Thaler DS, Schurr E, Abel L, Casanova JL. Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity? Ann N Y Acad Sci. 2010;1214:18–33.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Nisha Verma
    • 1
  • Anthony Thaventhiran
    • 1
  • Benjamin Gathmann
    • 2
  • for the ESID Registry Working Party
  • James Thaventhiran
    • 1
  • Bodo Grimbacher
    • 1
    • 2
  1. 1.Department of Immunology and Molecular PathologyRoyal Free Hospital and University College LondonLondonUK
  2. 2.Centre of Chronic Immunodeficiency (CCI)University Medical Center Freiburg and University of FreiburgFreiburgGermany

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