Clinical Reviews in Allergy & Immunology

, Volume 57, Issue 2, pp 226–243 | Cite as

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies

  • Brian P. McAllister
  • Emmanuelle Williams
  • Kofi ClarkeEmail author


Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and “at risk” populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease. Simple algorithms for care based on a comprehensive multidisciplinary approach are proposed. Refractory and non-responsive celiac diseases in the setting of a gluten-free diet are examined as are novel non-dietary therapies. Finally, the association of other disease states including psychiatric illness, infertility, lymphoproliferative malignancy, and mortality is explored with special attention paid to autoimmune and atopic disease.


Celiac disease Gluten intolerance Gluten sensitivity Wheat intolerance Vitamin deficiencies Food intolerance/allergies 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest. However, for full disclosure, Dr. Clarke is on the speakers bureau for AbbVie, Takeda, and Janssen. In addition, he has served on an Ad Board for Pfizer.

Ethical Approval and Informed Consent

This is a review article, no patients were involved and informed consent was not required. Permission was obtained for all images used and appropriate attribution/acknowledgement stated.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Brian P. McAllister
    • 1
  • Emmanuelle Williams
    • 1
  • Kofi Clarke
    • 1
    Email author
  1. 1.Department of Medicine, Division of Gastroenterology and HepatologyPenn State Health Milton S. Hershey Medical CenterHersheyUSA

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