New Insights in Celiac Disease

David Branski

doi:10.5041/rmmj.10073

Abstract

Celiac disease (CD) is an autoimmune disorder occurring in genetically susceptible subjects. The incidence of CD is around 1%, and it is much more common in first-degree relatives of CD patients, 10%–18%. However, the pattern of the genetic inheritance is still obscure. Environmental factors are undoubtedly affecting the disease’s clinical presentation, time at presentation, and may have an effect on the characteristics of the disease. The clinical presentation of CD has shifted during the previous decades from the classical presentation in which the toddler suffers from diarrhea, constipation, vomiting, failure to thrive, abdominal distension, etc., to the child with a monosymptomatic presentation, such as anemia, as well as an enlarged list of extra-intestinal disorders. The diagnosis of CD is being established by symptoms consistent with CD and positive serology. The ultimate diagnosis should be made upon histological evaluation of the small bowel mucosa. The treatment of CD is a lifelong, strict gluten-free diet (GFD). Compliance with a GFD is quite difficult. Therefore, new strategies for prevention and treatment modalities other than GFD are greatly needed. Recently several promising therapeutic modalities have been developed; these include resuming traditional baking techniques. Another methodology is using probiotic-driven prolylendopeptidase. Another pathway to tackle the therapeutic option in CD is by down-regulation of the activity of zonulin—the active pump enabling gluten to enter the enterocytes. We are facing an era where other modalities beyond a GFD might allow CD patients to be able to tolerate occasionally a small amount of gluten in their diet.

Highlights

Celiac disease (CD) is an autoimmune disorder occurring in genetically susceptible subjects
We have demonstrated elevated prostaglandin E2 and thromboxane B2 levels in the mucosa obtained from CD patients as compared with controls.[10]
The clinical presentation of CD has shifted during the previous decades from the classical presentation in which the toddler suffers from diarrhea, constipation, vomiting, failure to thrive (FTT), abdominal distension, etc., to the child with a monosymptomatic presentation, such as anemia, bone disorders, and arthritis, as well as an enlarged list of extra-intestinal disorders (Table 1).[12]

Summary

ENVIRONMENTAL FACTORS

Environmental factors are undoubtedly affecting the disease’s clinical presentation, time at presentation, and may affect the characteristics of the disease. Several studies towards the end of the previous century demonstrated that breastfeeding reduced the incidence of developing CD. Adherence of bacterial agents to the small bowel intestinal mucosa was found in CD patients, but not in control subjects.[8] Nieuwenhuizen et al.[9] demonstrated that the virulent factor of Candida albicans—hyphal wall protein 1—shares similar sequence homology of amino acids with gliadin. The most important is the TH1 response by which proinflammatory mediators such as transforming growth factor beta (TGF-β) and tumor necrosis factors gamma (TNF-γ) are secreted The latter activates matrix methyl proteinases, which degrade the matrix, eventually culminating in destruction of enterocyte villi, characteristic of CD. We have reported increased apoptosis in CD patients while on a glutencontaining diet, in comparison to controls.[11]

CLINICAL PRESENTATION

Connective tissue disorders