When gluten is ingested and the body shows increased immunological responsiveness in someone who is genetically susceptible, cheap it is defined as gluten sensitive enteropathy or coeliac disease. The prevalence of coeliac disease in Europe is about 1% in the adult population., this , look ,
NON-RESPONSIVE Coeliac Disease (NRCD)
When the subject does not respond to a gluten-free diet (GFD), or while still on GFD the subject has recurrence of symptoms or laboratory abnormalities, after 6-12 months adherence. In 7-30% of cases symptomatic or histological improvement fails with a presumed GFD. If no response to GFD has been seen after twelve moths, it can be defined as primary, and secondary despite adherence to GFD with symptom relapse after initial response., It is important to be sure of the relevance of the initial diagnosis. Serology, FHx, hyposplenism etc. has to be ruled out. Biopsies have to be reviewed and could there be another reason of villous atrophy, look for HLA-DQ2/DQ8 tissue type. Initial response to GFD is not enough to diagnose CD.
CAUSES – Non-Adherence to GFD
The most common cause of NRCD is non-adherence to GFD (estimated adherence is 42-91%).,, Complete non-adherence is not so common and only about 5% according to the literature, with a range of 0-32%. Gluten contamination happens either deliberately or inadvertently and a study by Abdulkarim et al 25/49 subjects had persisting symptoms in spite of the intention on following GFD. Persistent symptoms should be taken seriously and call for re-evaluation, even with histological improvements. Duodenal biopsies do not always reflect improvement as the distal small bowel heals faster than the proximal small bowel., In some cases, very small amount of gluten can prevent mucosal healing and some subjects react to 10 mg per day and that can lead to mucosal abnormalities in the intestines. Most individuals are unlikely to react to <10 mg per day. Serology is a marker of gluten exposure but not villous atrophy. In some cases, subjects do react to oats. An input from dietetic as well as to write food-diary is helpful to try to find the cause for NRCD.
Coeliac disease cannot be diagnosed only on the cause of initial response to gluten as recent evidence show that symptoms can be induced in non-coeliac subjects. Histological evaluation has to be correct to be a diagnostic tool, family history can be supportive evidence and HLA genotyping as well, as the absence of HLA DQ2/HLA DQ8 underline unlikelihood of CD.,,
OTHER Causes of Small Bowel Villous Atrophy
Diagnosing CD is by duodenal villous atrophy (DVA) but villous atrophy can be found in noncoeliac enteropathy (NCE) and misdiagnosing coeliac disease is not so uncommon according to Pallav et al. The most common aetiologies for small bowel villous atrophy are the following; collagenous sprue, small bowel bacterial overgrowth, peptic duodenitis, non-specific immune mediated enteropathy, chohn´s disease, AIDS enteropathy, tropical sprue, common variable immunodeficiency (CVID) and adult autoimmune enteropathy.
OTHER Causes for Symptoms/Diarrhea
Lactose malabsorbtion, irritable bowel syndrome (IBS), exocrine pancreatic insufficiency and small bowel bacterial overgrowth are all conditions that are associated with NRCD.10 Whipples disease, sphincter dysfunction and protein losing enterophaties as well as dietary allergy are also associated with NRCD. One of the known direct cause of villous atrophy is exocrine pancreatic insufficiency in GFD adherent patients. Fructose/lactose intolerance can also occur because of the damage of the mucosal surface. Microscopic colitis (MC) is easy to treat and there is strong evidence on association to CD. Small bacterial overgrowth and small bowel aspirates are known in CD, and IBS is common.
REFRACTORY Coeliac Disease (RCD)
RCD can be diagnosed when all other causes have been ruled out, for the ongoing symptoms. RCD is a rare condition; subjects often have nutritional deficiencies and are underweight as a result of severe malabsorption. Malabsroptive symptoms are persistent, diarrhea/steatorrhea is apparent and micronutrient loss e.g. zinc, copper, selenium etc. Prevalence is from 8-18 % and according to Roshan et al in a North American population, the cumulative incidence of RCD in CD diagnosed patients was 1.5%. Weight loss was high, or 76.5% (unintentional). Rubio-Tapia et al17 define RCD as the following: “Refractory coeliac disease (RCD) is defined by persistent or recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a GFD for at least 6–12?months in the absence of other causes of non-responsive treated coeliac disease and overt malignancy.”
RCD can be subdivided as primary or secondary. Primary – strict adherence to GFD but persisting symptoms. Secondary – recurrence of symptoms after apparent response to GFD for at least one year. Further division can be made, type 1 (polyclonal expansion of IESs and villous atrophy) or type 2 (includes ulcerative jejunitis, colonal expansion of aberrant IESs) RCD, depending on intraepithelial T-cell populations phenotypic appearance. Subjects diagnosed with type 2 RCD do have poorer response to treatment and are therefore more prone to develop lymphoma and have about 50% chance of 5-year survival compared to 90-100% in those with type 1 RCD diagnosis. Mortality can be traced to malabsorption and progression to enteropahy associated T-cell lymphoma (EATL).,, Investigation in RCD is to rule out malignancy, think about CT or PET-CT, small bowel imaging and double-balloon enteroscopy (DBE), OGD – histology for IEL population analysis.
Coeliac disease affects about 1% of the European population. Non-Responsive coeliac disease affects 7-30% of CD diagnosed subjects and the most common cause is non-adherence to GFD. If the initial diagnosis is true, it is important to investigate what is the underlying cause of histological changes as persisting symptoms. In some cases, 8-18%, refractory coeliac disease can be diagnosed and if presented as type 2 there are high chances of lymphoma and survival chances are 5 years in 50% of the cases.
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