Celiac Disease and Increased Risk of Pneumococcal Infection: A Systematic Review and Meta-Analysis

  • Malorie Simons
    Requests for reprints should be addressed to Malorie Simons, MD, Alpert Medical School of Brown University and Rhode Island Hospital, Division of Internal Medicine, Providence, RI 02903.
    Division of Internal Medicine, Alpert Medical School of Brown University and Rhode Island Hospital, Providence
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  • Lori A.J. Scott-Sheldon
    Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI

    Department of Psychiatry and Human Behavior, Alpert School of Medicine, Brown University, Providence, RI

    Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI
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  • Yesenia Risech-Neyman
    Division of Gastroenterology, Alpert Medical School of Brown University and Rhode Island Hospital, Providence
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  • Steven F. Moss
    Division of Gastroenterology, Alpert Medical School of Brown University and Rhode Island Hospital, Providence
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  • Jonas F. Ludvigsson
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Department of Pediatrics, Örebro University Hospital, Sweden

    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, United Kingdom

    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY
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  • Peter H.R. Green
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY
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      Celiac disease has been associated with hyposplenism, and multiple case reports link celiac disease and pneumococcal infections; however, increased risk of pneumococcal infection in celiac disease has not been confirmed. The purpose of this study was to conduct a systematic review to determine the risk of pneumococcal infections in celiac disease.


      Relevant studies were identified using electronic bibliographic searches of PubMed, OVID, Medline, and EMBASE (1980 to February 2017) and reviewing abstracts from major conferences in gastroenterology. Using number of events in celiac patients and referent patients, we calculated a summary relative risk of pneumococcal infections. All analyses were conducted in Comprehensive Meta-Analysis software using random-effects assumptions.


      Of a total of 156 articles, 3, representing 3 large databases (the Swedish National Inpatient Register; the Oxford Record Linkage Study; and the English National Hospital Episode Statistics) were included. Each compared patients with celiac disease and confirmed pneumococcal infection to a specific reference group: inpatients and/or the general population. Overall, the odds of pneumococcal infection were higher among hospitalized celiac patients compared with controls (odds ratio 1.66; 95% confidence interval 1.43-1.92). There was no evidence of heterogeneity (Q[1] = 1.17, P = .56, I2 = 0%).


      Celiac disease is associated with an increased risk of pneumococcal infection. Preventive pneumococcal vaccination should be considered for those with celiac disease, with special attention to those aged 15-64 years who have not received the scheduled pneumococcal vaccination series as a child.


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