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Gastrointestinal Disease
Published in Praveen S. Goday, Cassandra L. S. Walia, Pediatric Nutrition for Dietitians, 2022
Justine Turner, Sally Schwartz
Typically, children who are suspected of having celiac disease undergo blood testing for aTTG. If it is positive, the child should undergo an upper endoscopy and small intestinal biopsy while on a diet containing gluten. Accurate diagnostic serology and histopathology depend on contemporary consumption of gluten. Furthermore, if a gluten-free diet (GFD) is commenced, the duration and amount of gluten intake required to trigger the autoimmune response and develop enteropathy is not known. The gluten challenge most often recommended is 4–6 weeks of 5–10 g of gluten/day. More recently, protocols have been developed whereas a small subset of patients can be diagnosed with celiac disease based solely on blood testing.
Celiac disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
The diagnosis of celiac disease in a person on a gluten-free diet is problematic, because in the absence of gluten ingestion, the clinical signs, serology, and morphology return to normal. Thus, several months of gluten ingestion are required for a proper diagnosis. Many patients are reluctant to engage in a prolonged gluten challenge, but such a challenge may not be necessary in the future. After oral gluten consumption for 3 days, most celiac disease patients have T cells specific to deamidated gluten peptides in their peripheral blood. Such T cells can be detected by ELISPOT (enzyme-linked immunospot assay) or by staining with HLA-DQ2–gliadin peptide tetramers. Anti-TG2 antibodies can be detected in patients with extraintestinal diseases, such as dermatitis herpetiformis, but biopsy is required when the levels of anti-TG2 antibodies are low.
Celiac Disease in Infancy and Childhood
Published in Tadeusz P. Chorzelski, Ernst H. Beutner, Vijay Kumar, Tadeusz K. Zalewski, Serologic Diagnosis of Celiac Disease, 2020
Thomas Rossi, Tadeusz Zalewski
Although the ESPGAN criteria have served as the “gold standard” for establishing the diagnosis of celiac disease, there is considerable controversy regarding the necessity for strict adherence to the criteria. The controversy centers about the cumbersome requirement for three biopsies as well as the timing of the biopsies and length of time for the gluten withdrawal and challenge. The intestinal mucosa of celiacs may require months or years to recover and also to become reinjured following gluten challenge.72 In those patients who exhibit a normal biopsy following challenge one always questions whether the duration of the challenge period was sufficiently long. In those patients who relapse following challenge one usually questions whether their condition is permanent or only temporary. One also usually experiences an aversion to gluten challenge mainly because the objective is to reinduce illness, mucosal damage, and perhaps deceleration in growth in a child who has recovered from his initial problem. Consideration is currently being given for the revision of the criteria to include immunological evidence of disease so that the above concerns can be circumvented (see Chapter 3).
Emergence of an adaptive immune paradigm to explain celiac disease: a perspective on new evidence and implications for future interventions and diagnosis
Published in Expert Review of Clinical Immunology, 2022
Persistent symptomatology is reported to be common in celiac disease and has attracted the attention of drug developers although it remains unclear how much is attributable to gluten versus irritable bowel syndrome [39]. Acute symptoms attributed to gluten are a major cause of lifestyle restriction and impaired quality of life in celiac disease. Understanding the mechanistic basis for acute and chronic gluten-induced symptoms will support novel therapies but also help resolve the relationship between patient-reported symptoms, gluten-specific immunity, and the objective endpoints of histology and serology. Whilst protection against gluten-induced symptoms may be regarded a major regulatory endpoint for novel celiac disease therapies, patient-reported outcome measures are subjective and contextual, and none have been validated to assess gluten-challenge induced symptoms. Recent insights linking acute gluten-specific T-cell activation with IL-2 release and symptomatology provide important clues implicating a central role for T cells that provides a rational starting point for mechanistic studies.
Investigational drug therapies for coeliac disease – where to from here?
Published in Expert Opinion on Investigational Drugs, 2018
James Haridy, Diana Lewis, Evan D. Newnham
The ‘hygiene hypothesis’ postulates the rise in autoimmune and immune-mediated diseases in developed countries is in part related to the reduction in infectious disease exposure, particularly in childhood [52]. Epidemiologic studies suggest that a major factor includes the dramatic reduction in helminth infections [53]. Animal and human models have demonstrated reduced autoantigen-specific responses and attenuated response in both autoimmune liver disease and IBD [54–56]. An initial Phase 2 double-blinded placebo-controlled study of 20 patients infected with necator americanus for 21 weeks did not improve histological or patient-reported outcomes [57]. Immunological data this study was encouraging, displaying suppression of intestinal inflammatory cytokine production and possibly modulating T-helper cell responses [58]. This led to a second non-blinded nor placebo-controlled 52-week study of 12 of the same subjects with lower levels of gluten challenge. The study noted a paradoxical decline in mean TG2 IgA titers upon exposure to 3g of gluten daily, and there was no alteration in villous height to crypt depth ratio in those exposed to 1g gluten daily. Patient-reported outcomes were not significantly improved [59]. It is difficult to draw sufficient conclusions based on current data. However, a further Phase 2 trial is currently underway with necator americanus on a larger sample population.
Insight in the diagnosis and treatment of coeliac disease in general practice: A survey and case vignette study among 106 general practitioners
Published in European Journal of General Practice, 2021
Maxine D. Rouvroye, Pauline Slottje, Tom van Gils, Chris J. Mulder, Jean W. Muris, Dick Walstock, Marcel Reinders, Gerd Bouma
The second case dealt with the dilemma of diagnostic testing in a patient on a self-initiated strict GFD. One percent would perform HLA-DQ typing and 39% would opt for a gluten challenge (reintroduction of gluten in the diet and a tTGA test after a period of gluten intake). The median time suggested by participants for the gluten challenge was 6.1 ± SD4.5 weeks. Twelve percent would refer the patient to a gastroenterologist. Remarkably, 33% would opt for a tTGA test or a gastroduodenoscopy, while neither is appropriate in a patient following a GFD for a more extended period. Four percent would choose not to perform any tests since the patient does not experience symptoms.