Infectious Complications in Patients with Common Variable Immunodeficiency (CVID) in Iran

Document Type : Original Article

Authors

1 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran

2 Department of Basic Science and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran

10.22034/igj.2020.222234.1032

Abstract

Background: Common variable immunodeficiency (CVID) is a common primary immunodeficiency disease defined by a failure in B cell differentiation and impaired immunoglobulin production. Subsequently CVID patients are remarkably susceptible to recurrent and multiple infections with bacterial, viral or fungal agents. In the present study, we aimed to provide an update report on different infectious complications of patients with CVID in Iran.
Methods: Demographic, clinical and immunologic data as well as history of infections with related microbial pathogens were obtained from records of patients diagnosed with CVID and followed up at Children’s Medical Center. Based on presence of meningitis, osteomyelitis and sepsis, 2 groups of severe infections and non-severe infections were defined for further investigations.
Results: Among the enrolled 301 CVID patients, 15 (5%) had severe and 286 (95%) had non-severe infections. Respiratory followed by gastrointestinal tract problems (83.1 and 71.4%, respectively) were the most common involved organs. Among the infectious complications, lower and upper respiratory tract infection, followed by mucocutaneous and gastrointestinal tract were the most frequent (76.1, 64.8, 21.6 and 19.6%, respectively). Candida followed by Giardia lamblia were the most common detected pathogens, respectively in those with opportunistic infections and infectious diarrhea.
Conclusion: Recurrent infections of various parts of body are the most prevalent manifestation among patients with CVID playing an important role in the morbidity and even mortality in those with prolonged and untreated infections. Recurrent infections initiating early in childhood should be paid attention and trigger further immunological work up for a possible underlying immunodeficiency especially in families with consanguineous marriage and/or a positive family history of primary immunodeficiency.

Keywords

References

1. Gupta S, Pattanaik D, Krishnaswamy G. Common Variable Immune Deficiency and Associated Complications. Chest. 2019;156(3):579-593 2. Emmaneel EE, Bogaert D, Van Gassen S, Tavernier S, Dullaers M, Haerynck F, et al. A computational pipeline for the diagnosis of CVID patients. Front immunol. 2019;10:2009. 3. Li R, Zheng Y, Li Y, Zhang R, Wang F, Yang D, et al. Common variable immunodeficiency with genetic defects identified by whole exome sequencing. Biomed Res Int. 2018;2018:3724630 4. Edgar D, Ehl S. ESID Registry-Working definitions for clinical diagnosis of PID, 2014. 5. 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. 6. Bousfiha A, 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(1):129-43. 7. Smith T, Cunningham-Rundles C. Primary B-cell immunodeficiencies. Hum immunol. 2019;80(6):351-62. 8. Saikia B, Gupta S. Common variable immunodeficiency. Indian J Pediatr. 2016;83(4):338-44. 9. Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, et al. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol 2017;13(2):101-15. 10. Cunningham-Rundles C. The many faces of common variable immunodeficiency. The Am Soc Hematol Educ Book. 2012;2012(1):301-5. 11. Tam JS, Routes JM. Common variable immunodeficiency. Am J Rhinol Allergy. 2013;27(4):260-5. 12. 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. 13.Knight AK, Cunningham-Rundles C. Inflam-matory and autoimmune complications of common variable immune deficiency. Autoimmun Rev. 2006;5(2):156-9. 14. 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. 15. Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract. 2019. 16.Aghamohammadi A, Moein M, Farhoudi A, Pourpak Z, Rezaei N, Abolmaali K, et al. Primary Immunodeficiency in Iran: First Report of the National Registry of PID in Children and Adults. J Clin Immunol. 2002;22(6):375-80. 17. Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis. J Clin Immunol. 2018;38(7):816-32. 18. Aghamohammadi A, Farhoudi A, Moein M, Pourpak Z, Rezaei N, Abolmaali K, et al. A 20- year survey of infectious complications in 64 patients with common variable immunodeficiency. Medical Journal of The Islamic Republic of Iran (MJIRI). 2002;16(3):123-8. 19. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin immunol. 1999;92(1):34-48. 20. Oksenhendler E, Gérard L, Fieschi C, Malphettes M, Mouillot G, Jaussaud R, et al. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis. 2008;46(10):1547-54. 21. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood, Am. J. Hematol.. 2012;119(7):1650-7. 22. Aydogan M, Eifan A, Gocmen I, Ozdemir C, Bahceciler N, Barlan I. Clinical and immunologic features of pediatric patients with common variable immunodeficiency and respiratory complications. J Investig Allergol Clin Immunol. 2008;18(4):260-5. 23. Cunningham-Rundles C, Warnatz K. Chapter 14- Hypogammaglobulinemia and Common Variable Immunodeficiency. In: Sullivan KE, Stiehm ER, editors. Stiehm’s Immune Deficiencies. Amsterdam: Academic Press; 2014. p. 347-65. 24. 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(3):315-22. 25. Martínez MG, Nauffal MM, Muñoz MP, Compte LT, Macián V, Perpiñá MT. Respiratory disorders in common variable immunodeficiency. Respir med. 2001;95(3):191-5. 26. Busse PJ, Farzan S, Cunningham-Rundles C. Pulmonary complications of common variable immunodeficiency. Ann Allergy Asthma Immunol . 2007;98(1):1-9. 27. Favre O, Leimgruber A, Nicole A, Spertini F. Intravenous immunoglobulin replacement prevents severe and lower respiratory tract infections, but not upper respiratory tract and non-respiratory infections in common variable immune deficiency. Allergy. 2005;60(3):385-90. 28. Atarod L, Raissi A, Aghamohammadi A, Farhoudi A, Khodadad A, Moin M, et al. A review of gastrointestinal disorders in patients with primary antibody immunodeficiencies during a 10-year period (1990-2000), in children hospital medical center. Iran J Allergy Asthma Immunol. 2003;2(2):75-9. 29. Onbasi K, Gunsar F, Sin AZ, Ardeniz O, Kokuludag A, Sebik F. Common variable im-munodeficiency (CVID) presenting with malabsorption due to giardiasis. Turk J Gastroenterol. 2005;16(2):111-3. 30. Agarwal S, Mayer L. Gastrointestinal manifestations in primary immune disorders. Inflamm Bowel Dis. 2010;16(4):703-11. 31. Luzi G, Zullo A, Iebba F, Rinaldi V, Sanchez Mete L, Muscaritoli M, et al. Duodenal pathology and clinical-immunological implications in common variable immunodeficiency patients. Am J Gastroenterol. 2003;98(1):118-21. 32. Malamut G, Verkarre V, Suarez F, Viallard J-F, Lascaux A-S, Cosnes J, et al. The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease. Am J Gastroenterol. 2010;105(10):2262-75. 33. Daniels JA, Lederman HM, Maitra A, Montgomery EA. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol. 2007;31(12):1800-12. 34. Malphettes M, Gérard L, Carmagnat M, Mouillot G, Vince N, Boutboul D, et al. Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin Infect Dis. 2009;49(9):1329-38. 35. Kaczmarski RS, Webster AD, Moxham J, Davison F, Sutherland S, Mufti GJ. CD4+ lymphocytopenia due to common variable immunodeficiency mimicking AIDS. J Clin Pathol. 1994;47(4):364-6.
Immunology and Genetics Journal
Volume 3, Issue 1
March 2020
Pages 41-53

Files

Share

How to cite

Statistics