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GI- celiac disease

Primary Care Corner with Geoffrey Modest MD: Celiac disease and neuropathy

22 May, 15 | by EBM

By: Dr. Geoffrey Modest 

Peripheral neuropathy has been associated with celiac disease in past studies, typically based in referral centers. The current population-based study in Sweden looked more systematically at the association (see doi:10.1001/jamaneurol.2015.0475​). As background, celiac disease is pretty common, with prevalence of about 1%, and peripheral neuropathy is present in 2-7% of the population. Details of the study:

–Data collected on small intestine biopsies performed at Sweden’s 28 pathology departments from 1969-2008

–They compared the risk of neuropathy in 28,232 patients with celiac disease vs 139,473 age- and sex-matched controls (median age at diagnosis of 29: 42% were 0-19 yo, 18% 20-39, 22% 40-59, 18% >60; 62% female; comorbidity of type 1 diabetes in 3.2 vs 0.4% in controls, alcohol use in 2.7 vs 2.6%). Patients had confirmed celiac disease (CD), with villous atrophy, Marsh 3

–CD was associated with a 2.5-fold (2.1-3.0, p<0.001) increased risk of later neuropathy (0.7% vs 0.3% in controls, absolute risk of 64/100K vs 15/100K)

–CD also associated with increased risk of

–chronic inflammatory demyelinating neuropathy: 2.8-fold (1.6-5.1, p<0.001)

–autonomic neuropathy: 4.2-fold (1.4-12.3, p=0.009)

–mononeuritis multiplex: 7.6-fold (1.8-32.4, p=0.006)

–but not with acute inflammatory demyelinating polyneuropathy: 0.8-fold (0.3-2.1, p=0.68)

–No difference in neuropathy by sex, or age. Overall risk decreased minimally from 2.5 fold to 2.3-fold (1.9-2.7) after controlling for educational level, SES, type 1 or 2 diabetes, autoimmune thyroid disease, rheumatologic diseases, pernicious anemia, vitamin deficiencies, and alcoholic disorders.

–Association with neuropathy was pretty consistent in group with <1 yr of followup vs 1-5 yr, vs >5 yr

–There was a positive association between any neuropathy and CD, even when the diagnosis of neuropathy preceded the diagnosis of CD with an odds ratio of  1.8; 1.4-2.2, p<0.001

So, seems like we really should add an evaluation for CD as part of our neuropathy workup. In small studies, it seems that the association of CD with neuropathy is not necessarily associated with CD-related vitamin deficiencies (one study of 18 patients with confirmed CD and neuropathy found that they all had normal vitamin B12 levels). My sense, given the pretty low absolute association as noted above in Sweden, is that screening questions about GI symptoms seem appropriate. It might also be reasonable to perform serologic studies for CD, since there are some data suggesting that a gluten-free diet may either prevent or ameliorate the neuropathy (this is not very robust data), and on the other hand there are data suggesting that there are many people with “asymptomatic” CD who actually do feel better on a gluten-free diet, they might have significant malabsorption issues that should be detected/addressed, and (data not so robust) asymptomatic patients may still be at higher risk of lymphoma or autoimmune diseases which decreases with a gluten-free diet.


Primary Care Corner with Geoffrey Modest MD: Celiac Disease in Kids with Irritable Bowel Syndrome

28 May, 14 | by EBM

article in jama pediatrics looked at kids with functional GI disease and assessed the incidence of concomitant celiac disease  (see doi:10.1001/jamapediatrics.2013.4984). background is that approx 1% of US population has celiac disease (often asymptomatic). adults with IBS have approx 4-fold increased prevalence of celiac disease. the present study is a 6-year prospective cohort study in Italy, where prior large epidemiologic studies have found celiac disease prevalence to be in the 0.5-1% range. 992 kids (43% male, median age 6.8y) referred by their primary care MD for recurrent abdominal pain, 782 of whom had diagnosis of IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine by Rome III criteria. these kids were then assessed for celiac disease, with total IgA, IgA tissue transglutaminase antibody, and endomysial antibodies, then duodenal bx if positive.  results for these 992 children:

–270 had IBS, of whom 12 tested positive for celiac disease = 4.4%
–201 had functional dyspepsia, of whom 2 tested positive for celiac disease = 1%
–311 had functional abdominal pain, of whom 1 tested positive for celiac disease = 0.3%
–210 were excluded from this study because they had some “organic disorder”, mostly GERD, gastritis, lactose intolerance
–of note, there was no difference in wt, ht, iron levels, ferritin, albumin, hemoglobin, or ALT in those diagnosed with celiac disease vs those without the diagnosis

so, recurrent abdominal pain is common (10-15% of school-aged children). one could argue, as the editorialists do, that those who meet criteria for IBS are at high enough risk (4% range) that they should be tested for celiac disease (at the 1% prevalence rate and given the sens and specificity of the serum tests, there would be a 68% false positive rate for celiac disease, suggesting that universal testing is not useful. at the 4.4% prevalence rate, 32% would be false positive). in fact NICE (natl institute for health and clinical excellence in the UK) does recommend celiac testing on all patients meeting criteria for IBS. there are some advantages to an earlier diagnosis (avoiding osteopenia, short stature, delayed puberty, infertility, intestinal lymphoma) in later life, so it seems reasonable to me to test kids and adults with IBS.

fyi, full set of Rome III diagnostic criteria for functional GI disorders — see here.


Primary care corner with Dr Geoffrey Modest: Non-celiac gluten sensitivity?

25 Nov, 13 | by EBM

It is not uncommon to see patients who have typical symptoms of celiac disease who seem to respond to a gluten-free diet but have negative workup for celiac disease. These patients are said to have nonceliac gluten sensitivity (NCGS), which is characterized by irritable bowel-type symptoms after the ingestion of gluten, improvement after gluten withdrawal from the diet, and negative celiac serologies/biopsies. they can have both intestinal sx (diarrhea, abd discomfort/pain, bloating, flatulence) and extra-abdominal ones (headache, lethargy, poor concentration, ataxia, oral ulceration). Additionally (and previously unknown to me), there are some food items which can also cause these symptoms, called FODMAPs (fermentable, oligo-, di-, monosaccharides and polyols) which are poorly absorbed short-chain carbohydrtates. Presumably, FODMAPs lead to luminal gut distension via osmotic effects and gas production from bacterial fermentation in the gut. A small Australian study was done with a double-blind cross-over methodology of 37 patients with NCGS meeting the criteria for IBS (subjects aged 21-64, 6 men, fulfilling Rome III criteria), continued on their gluten-free diet but also given a 2-week diet of reduced FODMAPs, then randomly placed on diets with high-gluten (16g/d), low-gluten (2 g/d) or control (16 g whey protein isolate/d), with a washout period of 2 weeks, then crossed over to the other diets (see  results:


–several of the patients who stated that they were gluten-responsive did have mild to moderate symptoms on a gluten-free diet, with at least 50% of the patients showing significant improvement on the low FODMAP diet during the run-in period of the study, with decrease in both GI symptoms and fatigue (see their figure 1)

–subsequent addition of the high gluten, low-gluten, or control diet was associated equally with worsening of their symptoms. only 8% had gluten-specific effects. 30% had a significant symptom response to the placebo diet (nocebo effect: patients who have symptoms on placebo meds — i will send around again an interesting article on nocebo effect)

–22 subjects returned  8-17 months later for a 3-day rechallenge trial, already on gluten-free diet, then given FODMAPs reduced diet and additionally elimination of other putative symptom triggers in some patients (salicylates, amines, MSG, and preservatives benzoates, priopionate, sultfites, nitrites, and sorbic acid, as well as added antioxidants and food colors). finding — no gluten-specific differences in response to the addition of gluten vs placebo to the meals. of note, in both of these studies there was a consistent difference by the order of the trial: the first intervention induced more symptoms independent of what the intervention was…


so…. what are these things they call FODMAPs???  there is a good website with a one-page handout for patients (and for us) at basically,

–fructose (honey, fruit, high fructose cornsyrup (HFCS)


–fructans (wheat, onion, garlic)

–galactans (beans, lentils, legumes such as soy)

–polyols (sweeteners containing sorbitol, mannitol, xylitol; fruits such as avocado, apricots, cherries, nectarines, peaches, plums)


therefore, you may ask, what can one eat???

–meat, poultry, eggs, fish

–dairy — lactose-free, or small amounts of cream cheese, 1/2 and 1/2, hard cheeses, sherbet

–grains — gluten-free grains, (ie, no wheat)

–fruits — bananas, berries, cantaloupe, grapes, grapefruit, melons, kiwi, lemon, lime

–veges — bamboo shoots, bell peppers, cukes, carrots, celery, corn, eggplant, lettuce, potatoes, squash, tomatoes, zukes

–beverages — none with HFCS, but other fruit/vege juices (1/2 cup at a time), coffee, tea

–seasonings — most spices and herbs. not garlic, honey, onions, molasses, jams, jellies, coconut


bottom line: from my experience, i think it is pretty common for patients to have abdominal bloating, pain, etc. my first approach is to give fiber, make sure bowel movements are regular and soft. but symptoms may well persist. sometimes low gluten diet works in spite of negative workup for celiac dz. and, if so, that’s an easier solution than the above FODMAPs diet. but i will now try using this diet if the patient continues to have symptoms in spite of regular bowel movements and nonresponse to low gluten diet.




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