Gastrointestinal Manifestations in Patients with Common Variable Immunodeficiency

Document Type: Original Article


1 Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran

2 Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

3 Department of Gastroenterology and Hepatology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

4 Department of Pediatrics, Shahid Bahonar Hospital, Alborz University of Medical Sciences, Karaj, Iran

5 Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran Department of Allergy and Clinical Immunology , Shahid Bahonar hospital, Alborz University of Medical Sciences, Karaj, Iran



Background: Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifest a wide clinical variability such as gastrointestinal (GI) disorder.
Patients and Methods: A total of 240 patients with CVID were enrolled in this study. The patients were evaluated for demographic data, clinical manifestations, and immunologic profile.
Results: In demographic data, the frequency of consanguinity and mortality rate were higher in patients with GI manifestation than those without GI manifestation. History of GI manifestations was evident in 147 patients (61.3%). The most common GI manifestation in patients with CVID was chronic diarrhea (29.6%). The prevalence of GI disease was 59 of 102 (57.8%) in female patients and 88 of 138 (63.8%) in male patients. The frequency of recurrent infection was higher in patients with GI manifestation than in those without GI manifestation. Also, CVID patients with GI manifestations had lower WBC and CD4+ T cells than patients without GI manifestations.
Conclusion: CVID patients are at increased risk of infectious conditions in the GI tract; hence GI manifestations are one of the most important presentations in CVID patients which can appear as a first manifestation or appear during the course of disease.


1. Janeway CA, Apt L, Gitlin D. Agammaglobulinemia. Transactions of the Association of American Physicians. 1953;66:200. 2. Tam JS, Routes JM. Common variable immunodeficiency. American journal of rhinology & allergy. 2013;27(4):260-5. 3. Bonilla F. Antibody deficiency. Pediatric AllergyPrinciple and Practice. 2010;88:97. 4. Pikkarainen S, Martelius T, Ristimäki A, Siitonen S, Seppänen MR, Färkkilä M. A High Prevalence of Gastrointestinal Manifestations in Common Variable Immunodeficiency. The American journal of gastroenterology. 2019;114(4):648. 5. Picard C, Gaspar HB, Al-Herz W, Bousfiha A, Casanova J-L, Chatila T, et al. International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. Journal of clinical immunology. 2018;38(1):96-128. 6. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. The Journal of Allergy and Clinical Immunology: In Practice. 2016;4(1):38-59. 7. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clinical immunology. 1999;92(1):34-48. 8. Oksenhendler E, Gérard L, Fieschi C, Malphettes M, Mouillot G, Jaussaud R, et al. Infections in 252 patients with common variable immunodeficiency. Clinical Infectious Diseases. 2008;46(10):1547-54. 9. Kalha I, Sellin JH. Common variable immunodeficiency and the gastrointestinal tract. Current gastroenterology reports. 2004;6(5):377- 83. 10. Daniels JA, Lederman HM, Maitra A, Montgomery EA. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. The American journal of surgical pathology. 2007;31(12):1800-12. 11. Kienzler AK, Hargreaves C, Patel S. The role of genomics in common variable immunodeficiency disorders. Clinical & Experimental Immunology. 2017;188(3):326-32. 12. Uzzan M, Ko HM, Mehandru S, CunninghamRundles C. Gastrointestinal disorders associated with common variable immune deficiency (CVID) and chronic granulomatous disease (CGD). Current gastroenterology reports. 2016;18(4):17. 13. Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277-86. 14. 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. Journal of Allergy and Clinical Immunology. 2012;130(5):1197-8. e9. 15. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650-7. 16. 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. The American journal of gastroenterology. 2010;105(10):2262. 17. Pecoraro A, Nappi L, Crescenzi L, D’Armiento FP, Genovese A, Spadaro G. Chronic diarrhea incommon variable immunodeficiency: a case series and review of the literature. Journal of clinical immunology. 2018;38(1):67-76. 18. Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Current allergy and asthma reports. 2009;9(5):347. 19. Agarwal S, Cunningham-Rundles C. Gastrointestinal Manifestations and Complications of Primary Immunodeficiency Disorders. Immunology and Allergy Clinics. 2019;39(1):81- 94. 20. Urschel S, Kayikci L, Wintergerst U, Notheis G, Jansson A, Belohradsky BH. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. The Journal of pediatrics. 2009;154(6):888-94. 21. Notarangelo L, Day N, Fleisher T. 2nd Conference of the Robert A. Good immunology society primary immune deficiencies and immune reconstitution Harvard Medical Boston, November 16th, 17th. Immunologic research. 2009;44(1-3):1- 3. 22. Khodadad A, Aghamohammadi A, Parvaneh N, Rezaei N, Mahjoob F, Bashashati M, et al. Gastrointestinal manifestations in patients with common variable immunodeficiency. Digestive diseases and sciences. 2007;52(11):2977-83. 23. Mohammadinejad P, Pourhamdi S, Abolhassani H, Mirminachi B, Havaei A, Masoom S, et al. Primary Antibody Deficiency in a Tertiary Referral Hospital: A 30-Year Experiment. Journal of investigational allergology & clinical immunology. 2015;25(6):416-25. 24. Rodríguez-Negrete EV, Mayoral-Zavala A, Rodríguez-Mireles KA, de León-Salazar OED, Hernández-Mondragón O, Gómez-Jiménez LM, et al. Prevalence of gastrointestinal disorders in adults with common variable immunodeficiency at Specialty Hospital Dr. Bernardo Sepulveda. Revista Alergia México. 2015;62(1):1-7. 25. Chapel H, Cunningham‐Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. British journal of haematology. 2009;145(6):709-27. 26. Agarwal S, Smereka P, Harpaz N, Cunningham-Rundles C, Mayer L. Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease. Inflammatory bowel diseases. 2010;17(1):251-9. 27. Abolhassani H, Sagvand BT, Shokuhfar T, Mirminachi B, Rezaei N, Aghamohammadi A, et al. A review on guidelines for management and treatment of common variable immunodeficiency. Expert review of clinical immunology. 2013;9(6):561-75. 28. Hosseini AH, Mesdaghi M, Sayyari AA, Chavoshzadeh Z. Case Report: Chronic Diarrhea as a Presenting Manifestation of Common Variable Immunodeficiency. 2013. 29. Cunningham‐Rundles C. Common variable immune deficiency: Dissection of the variable. Immunological reviews. 2019;287(1):145-61. 30. McCabe RP. Gastrointestinal manifestations of non-AIDS immunodeficiency. Current treatment options in gastroenterology. 2002;5(1):17-25.31. Odetola O, Ananthanarayanan V. Gastrointestinal presentations of common variable immunodeficiency: hiding in plain sight. Archives of pathology & laboratory medicine. 2018;143(4):525-30. 32. Resnick ES, Cunningham-Rundles C. The many faces of the clinical picture of common variable immune deficiency. Current opinion in allergy and clinical immunology. 2012;12(6):595- 601. 33. Patuzzo G, Barbieri A, Tinazzi E, Veneri D, Argentino G, Moretta F, et al. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimmunity reviews. 2016;15(9):877- 82. 34. Gathmann B, Mahlaoui N, Gérard L, Oksenhendler E, Warnatz K, Schulze I, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. Journal of Allergy and Clinical Immunology. 2014;134(1):116-26. e11. 35. Boileau J, Mouillot G, Gérard L, Carmagnat M, Rabian C, Oksenhendler E, et al. Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study. Journal of autoimmunity. 2011;36(1):25-32. 36. Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term followup and outcome of a large cohort of patients with common variable immunodeficiency. Journal of clinical immunology. 2007;27(3):308-16. 37. Pensieri MV, Pulvirenti F, Schiepatti A, Maimaris S, Lattanzio S, Quinti I, et al. The high mortality of patients with common variable immunodeficiency and small bowel villous atrophy. Scandinavian journal of gastroenterology. 2019;54(2):164-8. 38. Eren M, SALTIK‐TEMIZEL IN, YÜCE A, ÇAĞLAR M, Kocak N. Duodenal appearance of giardiasis in a child with selective immunoglobulin A deficiency. Pediatrics International. 2007;49(3):409-11. 39. Oraei M, Aghamohammadi A, Rezaei N, Bidad K, Gheflati Z, Amirkhani A, et al. 2 Naïve CD4+ T cells and Recent Thymic Emigrants in Common Variable Immunodeficiency. Journal of Investigational Allergology and Clinical Immunology. 2012;22(3):160. 40. Rezaei N, Aghamohammadi A, Nourizadeh M, Kardar G, Pourpak Z, Zare A, et al. Cytokine production by activated T cells in common variable immunodeficiency. J Investig Allergol Clin Immunol. 2010;20(3):244-51. 41. Khan R, Habbal M, Scaffidi MA, Bukhari AA, Rumman A, Al Ghamdi S, et al. Gastrointestinal Disease in Patients with Common Variable Immunodeficiency: A Retrospective Observational Study. Journal of the Canadian Association of Gastroenterology. 2019.