Dr. Scot M. Lewey, DO, FACG, FACP - CELIAC and GLUTEN SENSITIVITY_CME PRESENTATION-ACCREDITED MATERIAL_COPYRIGHT (C) 2014 SCOT M LEWEY
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Celiac & Gluten Sensitivity Scot Michael Lewey, DO, FACG, FASGE, AGAF, FACOI, FACP, FAAP, FACOP Gastroenterologist Peak Gastroenterology Associates Clinical Professor of Medicine Rocky Vista University-College of Osteopathic Medicine & Kansas City University of Medicine and Bioscience www.thefooddoc.com www.peakgastro.com @thefoodgutdoc Facebook.com/thefooddoc Copyright (c) 2014 Scot M. Lewey, DO, FACP, FACG - Peak Gastroenterology Associates, P.C.
• “B lymphocytes” white blood cells produce IgA & IgG class antibodies against tTG, endomysium (EMA), & gliadin
• Increase T-lymphocytes recruited (intraepithelial lymphocytosis) and chemicals released damage occurs to intestinal villi (atrophy/blunting) further increasing leaky gut
• Historically, it has been reported that patients with undetected celiac disease (CD) may present with irritable bowel syndrome (IBS) type symptoms.
• This has led to the recommendation by the American College of Gastroenterology Task force that patients presenting with diarrhea predominant IBS type symptoms should be serologically tested for CD.
• Concurrently speculative media data suggest that the US general public have increased their uptake of a gluten-free diet (GFD) far in excess of the known prevalence of CD.
• This may suggest that individuals with gastrointestinal symptoms are deriving benefit from a GFD even if they do not have CD. This has led to the scientific community considering the evidence for an emerging concept of non-celiac wheat sensitivity.
• There is a significant disparity in our views about what this phenomenon may be. There is also confusion about the nomenclature for this entity and indeed whether patients are suffering due to symptoms related to gluten or perhaps other components of wheat, for example fructans….we see evidence to support the clinical concept of wheat sensitivity or intolerance..
Am. J. Gastroenterol. 2012 (12):1908-12Copyright (c) 2014 Scot M. Lewey, DO, FACP, FACG - Peak Gastroenterology
• All of us have “white blood cell types” based on inherited HLA genes Just like we have a red blood cell types (I’m A positive) we have white blood cell types (I’m DQ2/DQ7)
• Our HLA “white blood cell types” are inherited
• Our HLA protein types determine our risk for certain diseases, especially autoimmune diseases like Celiac disease & type I Diabetes
Great Ormond Street Hospital for Children in the U.K.• Published “On the Coelic
Affliction”• Recognized dietary cause
but mistakenly advised gluten containing foods
• Presented accounts of both children & adults with Coeliac
• “to regulate food is the main part of treatment. The allowance of farinaceous foods must be small, but if the patient can be cured at all, it must be by means of diet”
• 1924 NY Pediatrician Sidney Valentine Haas described treatment banana diet, excluded bread, crackers, potatoes & cereals, later published “The Management of Celiac Disease” in 1951• Described cures of Celiac with diet• Led to many individuals now with untreated
• But these stains are not routinely performed and have to be requested. This can be important in early Celiac disease or in those who have already restricted gluten in their diet. Copyright (c) 2014 Scot M.
Lewey, DO, FACP, FACG - Peak Gastroenterology
Associates, P.C.
Normal biopsies may not be normal
• Pathologists reading the intestinal biopsies have varying degree of experience
• They also may have a negative bias towards “over diagnosing” Celiac disease
Biopsies that are “normal” under routine light microscope have been shown to be abnormal when examined with special stains and research based electron microscopy
• Pathologists reading the intestinal biopsies have varying degree of experience
• They also may have a negative bias towards “over diagnosing” Celiac disease
• Biopsies that are “normal” under routine light microscope have been shown to be abnormal when examined with special stains and research based electron microscopy
New Paradigm: Gluten sensitivity not just a gut disease
• Gluten Sensitivity, Celiac Disease, & Celiac Sprue used synonymously for years but to quote Hadjivassiliou in 2004:
• “the systemic nature of this disease, the overwhelming evidence of an immune pathogenesis and the accumulating evidence of diverse manifestations involving organs other than the gut, such as the skin (dermatitis herpetiformis) and the nervous system (gluten ataxia, gluten neuropathy), necessitates a re-evaluation of the belief that gluten sensitivity is solely a disease of the gut.”
• Hadjivassiliou et.al. in Trends in Immunology 2004 Nov; 25(11):578-582
Diagnosis and classification of celiac disease and gluten sensitivity.
Autoimmun Rev 2014 • Celiac disease is a complex disorder, the development of which is controlled by a
combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. • New diagnostic guidelines developed by ESPGHAN emphasize the crucial role of
serological tests in the diagnostic process of symptomatic subjects, and of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic subjects belonging to at-risk groups.
• The serological diagnosis of CD is based on the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti-deamidated gliadin peptide antibody assays of the IgG class are used.
• When anti-tTG antibody levels are very high, antibody specificity is absolute and CD can be diagnosed without performing a duodenum biopsy.
• Non-celiac gluten sensitivity is a gluten reaction in which both allergic and autoimmune mechanisms have been ruled out.
• Diagnostic criteria for NCGS include the presence of symptoms similar to those of celiac or allergic patients; negative allergological tests and absence of anti-tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of the symptoms with a gluten-free diet; relapse of the symptoms when gluten is reintroduced.
New Paradigm: Gluten Sensitivity Is Not Just a Disease
of the Gut “the systemic nature of this disease, the
overwhelming evidence of an immune pathogenesis and the accumulating evidence of diverse manifestations involving organs other than the gut, such as the skin (dermatitis herpetiformis) and the nervous system (gluten ataxia, gluten neuropathy), necessitates a re-evaluation of the belief that gluten sensitivity is solely a disease of the gut.”
• Celiac disease is common but non-celiac gluten sensitivity is much more common
• Though abnormal specific blood tests and an abnormal biopsy can confirm celiac disease, normal biopsies neither exclude celiac nor gluten sensitivity
• Abnormal specific blood tests likely confirm celiac disease even if biopsy is “normal”
Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity. Clin. Gastroenterol. Hepatol.
2013
• Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage.
• There is no evidence for mucosal or serologic modifications in those individuals. • Investigation of immunologic responses of duodenal mucosa samples and peripheral
blood basophils, isolated from NCGS patients, after exposure to gliadin. Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy.
• Patients were considered to have NCGS based on their symptoms and the current definition of the disorder.
• Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34)
• Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers).
• There were no significant increases in the levels of CD63 and CD203c in NCGS patients.• Unlike the duodenal mucosa from patients with celiac disease, upon incubation with
gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin.
• In vitro gliadin challenge therefore should not be used to diagnose NCGS.Copyright (c) 2014 Scot M. Lewey, DO, FACP, FACG - Peak Gastroenterology
Associates, P.C.
Non-coeliac gluten sensitivity: hype, or new epidemic?
Ned Tijdschr Geneeskd 2013 (21)• Coeliac disease is an immune-mediated inflammation of the
small intestine caused by sensitivity to dietary gluten and related proteins in genetically sensitive individuals.
• Recently, a novel gluten-related disorder has gained significant interest from the scientific community and mass media. This condition, known as non-coeliac gluten sensitivity, is characterised by gastrointestinal or extra-intestinal symptoms that respond to gluten withdrawal without evidence of underlying coeliac disease.
• Its symptoms overlap considerably with those of irritable bowel syndrome and the number of individuals embracing a gluten-free diet is rapidly growing.
• No discriminative markers to support a diagnosis of gluten sensitivity have been identified; the perceived response to a gluten-free diet after exclusion of coeliac disease is currently the best diagnostic and therapeutic marker.
• Its pathogenesis remains obscure but may be related to non-gliadin molecules in grains that stimulate the innate immune system of the intestine.
Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the Continuous National Health and Nutrition
Examination Survey 2009-2010Scand. J. Gastroenterol. 2013
• Clinical inference suggests the prevalence of non-celiac gluten sensitivity is substantially higher than that of celiac disease in the USA.
• Unfortunately, there are currently no data supporting these claims. The authors analyzed nationally representative data to estimate the prevalence of adherence to a gluten-free diet among participants without celiac disease and also to characterize the demographics and general health status of these participants.
• The Continuous National Health and Nutrition Examination Survey (NHANES) 2009-2010 enrolled 7762 individuals representing the civilian, non-institutionalized, US population free of celiac disease. Participants responded to interviewer administered questionnaires regarding current adherence to a gluten-free diet. Prevalence estimates were computed using SAS survey procedures.
• There were 49 individuals who reported current adherence to a gluten-free diet reflecting a weighted prevalence of 0.548% (95% CI 0.206-0.889).
• The prevalence of a gluten-free diet was higher in females (0.58%) than males (0.37%), although this was not statistically significant (p = 0.34).
• \Participants reporting a gluten-free diet were older (46.6 vs. 40.5 years, p = 0.005), had higher high-density lipoprotein, lower iron and lower body mass index
• The estimated national prevalence of non-celiac gluten sensitivity is 0.548%, approximately half that of celiac disease.
• Future studies are merited in order to better understand the population burden of non-celiac gluten sensitivity
Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness
Cell. Mol. Immunol. 2013 • Recently, the increasing number of patients worldwide who are sensitive to dietary gluten
without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity.
• Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota.
• Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%.
• From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced.
• Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy.
• Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.
Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity.Am. J. Gastroenterol. 2013
(5):842-50• Celiac disease (CD), gluten induces both adaptive and innate immune
responses. • Non-celiac gluten sensitivity (NCGS) is another form of gluten intolerance
where the immune response is less characterized. • Comparison of early mucosal immunological events in CD and NCGS by
challenging 30 HLA-DQ2(+) NCGS and 15 CD patients, all on a gluten-free diet, with four slices of gluten-containing bread daily for 3 days. Duodenal biopsy specimens were collected before and after challenge.
• In CD patients, tumor necrosis factor alpha (P=0.02) and interleukin 8 (P=0.002) mRNA increased after in vivo gluten challenge. The interferon gamma (IFN-γ) level of treated CD patients was high both before and after challenge and did not increase significantly (P=0.06). Four IFN-γ-related genes increased significantly.
• Treated and untreated CD patients had comparable levels of IFN-γ. Increased expression of MxA in treated CD patients after challenge suggested that IFN-α was activated on gluten challenge. In NCGS patients only IFN-γ increased significantly (P=0.03)
• Importantly, we found that the density of IELs was higher in NCGS patients compared with disease controls, independent of challenge, although lower than the level for treated CD patients.CD patients mounted a concomitant innate and adaptive immune response to gluten challenge.
• NCGS patients had increased density of intraepithelial CD3(+) T cells before challenge compared with disease controls and increased IFN-γ mRNA after challenge.
Non-celiac gluten sensitivity: clinical relevance and recommendations for future research.
Neurogastroenterol. Motil. 2013
• There has been increasing interest in the entity of Non-Celiac Gluten Sensitivity (NCGS) in recent years; however, it still remains a controversial topic and its pathogenesis is not well understood.
• Celiac Disease, in contrast, is a well-studied condition that has become increasingly recognized as a prevalent condition arising from a heightened immunological response to gluten
• Wheat allergy is an IgE-mediated condition capable of causing a variety of gastrointestinal symptoms.
• However, the number of patients who have neither celiac disease nor wheat allergy, but appear to derive benefit from a gluten-free diet, is also increasing substantially.
• The use of the term NCGS as a way of describing this condition has become increasingly prevalent in recent years.
• There is evidence for the condition but it’s putative pathogenesis is in dispute.
• There are areas of controversy and areas for potential future research.Copyright (c) 2014 Scot M. Lewey, DO, FACP, FACG - Peak Gastroenterology
Associates, P.C.
Is gluten a cause of gastrointestinal symptoms in people without celiac disease?
Curr Allergy Asthma Rep 2013
• The avoidance of wheat- and gluten-containing products is a worldwide phenomenon.
• While celiac disease is a well-established entity, the evidence base for gluten as a trigger of symptoms in patients without celiac disease (so-called 'non-celiac gluten sensitivity' or NCGS) is limited.
• The problems lie in the complexity of wheat and the ability of its carbohydrate as well as protein components to trigger gastrointestinal symptoms, the potentially false assumption that response to a gluten-free diet equates to an effect of gluten withdrawal, and diagnostic criteria for coeliac disease.
• Recent randomized controlled re-challenge trials have suggested that gluten may worsen gastrointestinal symptoms, but failed to confirm patients with self-perceived NCGS have specific gluten sensitivity.
• Furthermore, mechanisms by which gluten triggers symptoms have yet to be identified but there is recent scientific evidence supporting the entity of NCGS.
Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.Nutrients 2013
• Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a "re-discovered" disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA).
• Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem.
• Clinical studies further defined the identity of NCGS and implications in human disease.
• An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria.
• Several studies suggest a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia.
• The first case reports of NCGS in children have been described. • Lack of biomarkers is still a major limitation of clinical studies, making it
difficult to differentiate NCGS from other gluten related disorders. • Recent studies raised the possibility that, beside gluten, wheat amylase-
trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients.
A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to
secondary care.Eur J Gastroenterol Hepatol 2014
• Reports suggest that gluten sensitivity (GS) exists in the absence of coeliac disease (CD). • This clinical entity has been termed noncoeliac gluten sensitivity (NCGS).• To determine the population prevalence of self-reported GS and referral characteristics to
secondary care.A UK population-based questionnaire screened for GS and related symptoms.
• Diagnostic outcomes were also analyzed in patients referred to secondary care with GS. CD diagnosis entailed a positive coeliac serology (endomysial and/or tissue transglutaminase antibodies) plus Marsh 1-3 on duodenal biopsies. NCGS diagnosis was based on exclusion of CD.
• Clinical comparisons were made between NCGS and CD.A total of 1002 adults in the population (female 55%, mean age 39 years).
• The self-reported prevalence for GS was 13% (female 79%, mean age 39.5 years, P<0.0001), with 3.7% consuming a gluten-free diet and 0.8% known to have a doctor diagnosis of CD. Individuals with GS had an increased prevalence of fulfilling the Rome III criteria for irritable bowel syndrome, in comparison with those without GS (20 vs. 3.89%, odds ratio 6.23, P<0.0001).
• In secondary care 200 GS patients (female 84%, mean age 39.6 years) were investigated, in whom 7% were found to have CD and 93% to have NCGS. All CD patients were human leucocyte antigen DQ2 or DQ8 positive compared with 53% of NCGS cases (P=0.0003).
• Nutritional deficiencies (P≤0.003), autoimmune disorders (23.1 vs. 9.7%, P=0.0001) and a lower mean BMI (23.7 vs. 25.8, P=0.001) were significantly associated with CD compared with NCGS.
• GS is commonly self-reported with symptoms suggesting an association with irritable bowel syndrome. The majority of patients have NCGS, an entity which demonstrates clinical and immunologic difference to CD.
Clinical, Serologic, and Histologic Features of Gluten Sensitivity in Children.
J. Pediatr. 2013 • Study to describe the clinical, serologic, and histologic characteristics of children with
gluten sensitivity (GS).• 15 children (10 males and 5 females; mean age, 9.6 ± 3.9 years) with GS who were
diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease (CD) and wheat allergy, along with 15 children with active CD (5 males and 10 females; mean age, 9.1 ± 3.1 years) and 15 controls with a functional gastrointestinal disorder (6 males and 9 females; mean age, 8.6 ± 2.7 years).
• All children underwent CD panel testing (native antigliadin antibodies IgG and IgA, anti-tissue transglutaminase antibody IgA and IgG, and anti-endomysial antibody IgA), hematologic assessment (hemoglobin, iron, ferritin, aspartate aminotransferase, erythrocyte sedimentation rate),
• HLA typing, and small intestinal biopsy (on a voluntary basis in the children with GS).Abdominal pain was the most prevalent symptom in the children with GS (80%), followed by chronic diarrhea in (73%), tiredness (33%), bloating (26%), limb pain, vomiting, constipation, headache (20%), and failure to thrive (13%).
• Native antigliadin antibodies IgG was positive in 66% of the children with GS. No differences in nutritional, biochemical, or inflammatory markers were found between the children with GS and controls. HLA-DQ2 was found in 7 children with GS.
• Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in the children with GS.
• Our findings support the existence of GS in children across all ages with clinical, serologic, genetic, and histologic features similar to those of adults.Copyright (c) 2014 Scot M.
Lewey, DO, FACP, FACG - Peak Gastroenterology
Associates, P.C.
Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar
disorder.Bipolar Disord 2013
• Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder.
• Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder.
• We measured a marker of GI inflammation, anti-Saccharomyces cerevisiae antibodies (ASCA), in non-psychiatric controls (n = 207), in patients with bipolar disorder without a recent onset of psychosis (n = 226), and in patients with bipolar disorder with a recent onset of psychosis (n = 38).
• We compared ASCA levels to antibodies against gluten, casein, Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), influenza A, influenza B, measles, and Toxoplasma gondii.
• Elevated ASCA conferred a 3.5-4.4-fold increased odds ratio of disease association (age-, race-, and gender-corrected multinomial logistic regressions, p ≤ 0.00001) that was independent of type of medication received. ASCA correlated with food antibodies in both bipolar disorder groups (R(2) = 0.29-0.59, p ≤ 0.0005), and with measles and T. gondii immunoglobulin G (IgG) in the recent onset psychosis bipolar disorder group (R(2) = 0.31-0.36, p ≤ 0.004-0.01)
• Elevated seropositivity of a GI-related marker and its association with antibodies to food-derived proteins and self-reported GI symptoms suggest a GI comorbidity in at least a subgroup of individuals with bipolar disorder.
• Marker seroreactivity may also represent part of an overall heightened activated immune state inherent to this mood disorder.
Reactivity to dietary gluten: new insights into differential diagnosis among gluten‑related gastrointestinal disorders.
Pol. Arch. Med. Wewn. 2013
• The ingestion of dietary gluten sometimes may trigger allergic, autoimmune or nonallergic and nonautoimmune response.
• The typical gluten‑related allergic disorder is the wheat allergy (WA). • Celiac disease (CD) is a well‑known gluten‑related autoimmune
condition. • The clinical expression of a gluten‑related nonallergic and
nonautoimmune response is nonceliac gluten sensitivity (NCGS), an emerging condition whose framework is yet unclear and whose diagnosis is suggested only by demonstration of gluten‑dependency in patient' symptoms after exclusion of WA and CD.
• This review discusses the current tools to identify patients suffering from WA, CD, and NCGS, as well as the most recent insights in the differential diagnosis among these gluten‑related gastrointestinal disorders .
Biomarkers of gluten sensitivity in patients with non-affective psychosis: A meta-analysis.
Schizophr. Res. 2013
• Dohan first proposed that there may be an association between gluten sensitivity and schizophrenia in the 1950s.
• Since then, this association has been measured using several different serum biomarkers of gluten sensitivity.
• At this point, it is unclear which serum biomarkers of gluten sensitivity are elevated in patients with schizophrenia.
• However, evidence suggests that the immune response in this group is different from the immune response to gluten found in patients with Celiac disease.
• A systematic literature review was performed to identify all original articles that measured biomarkers of gluten sensitivity in patients with schizophrenia and non-affective psychoses compared to a control group. Three databases were used dating back to 1946 and a meta-analysis was performed of specific biomarkers and reported according to MOOSE guidelines.
• 17 relevant original articles were identified, and 12 met criteria for the meta-analysis.• Five biomarkers of gluten sensitivity were found to be significantly elevated in patients
with non-affective psychoses compared to controls. • The pooled odds ratio and 95% confidence intervals were Anti-Gliadin IgG OR=2.31
[1.16, 4.58], Anti-Gliadin IgA OR=2.57 [1.13, 5.82], Anti-TTG2 IgA OR=5.86 [2.88, 11.95], Anti-Gliadin (unspecified isotype) OR=7.68 [2.07, 28.42], and Anti-Wheat OR=2.74 [1.06, 7.08]. Four biomarkers for gluten sensitivity, Anti-EMA IgA, Anti-TTG2 IgG, Anti-DGP IgG, and Anti-Gluten were not found to be associated with schizophrenia.
• Not all serum biomarkers of gluten sensitivity are elevated in patients with schizophrenia.
• However, the specific immune response to gluten in this population differs from that found in patients with Celiac disease.
Non-celiac gluten sensitivity. Is it in the gluten or the grain?
J Gastrointestin Liver Dis 2013 • Celiac disease is an immune-mediated inflammatory disorder of the
small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals.
• Over the past several years, the concept of non-celiac gluten sensitivity (NCGS) has gained significant interest from the scientific community and mass media and the number of individuals embracing a gluten-free diet is rapidly growing.
• This condition is characterized by gastrointestinal or extraintestinal symptoms that respond to gluten withdrawal without evidence for underlying celiac disease or wheat allergy.
• Symptoms display significant overlap with the irritable bowel syndrome.
• Many important factors regarding this relatively novel condition remain to be elucidated; no discriminative markers to support a diagnosis of gluten sensitivity have been identified yet and its pathogenesis remains obscure.
• Here we review the current knowledge on NCGS, and outline potential pathogenic pathways of different gluten related disorders in order to gain clues about the pathophysiology of this novel condition.
• Leonardo da Vinci's face symmetry derives from 3 equal craniofacial segments
• It has been reported that adult subjects with celiac disease (CD) can be identified on the basis of a greater extension of the forehead in comparison to the medium third of the face.
• 126 biopsy-proven patients with CD (76 children and 50 adults) and 102 healthy controls (43 children and 59 adults). Their faces were photographed; the pictures were edited using a software program to calculate the facial segments.
• The tn length was significantly different between adult celiac and adult controls (7.43 ± 1.46 cm vs 6.38 ± 1.73 cm, P = 0.001)
• 43 of 50 patients (sensitivity 86%), but 34 of 59 controls were positive (specificity 54.2%). The positive predictive value was 56%. Neither the tn length nor the tn/ns ratio in celiacs correlated to the time of gluten exposure.
• Adults, but not children, with celiac disease show a forehead extension significantly greater than controls, but this test's specificity appears too low to be used in the screening of CD.
• Food intolerance is a common complaint amongst patients with functional gastrointestinal (GI) disorders (FGIDs), including those with irritable bowel syndrome (IBS), functional dyspepsia, as well as gastroesophageal reflux disease.
• Although there has been a longstanding interest in the possible role of food allergy in IBS, there are limited data supporting the association.
• However, the prevalence of food allergy is sufficiently high that patients with FGID may also have food allergies or hypersensitivities.
• Food intolerances or sensitivities are reactions to foods, which are not due to immunological mechanisms. Lactose intolerance is common in the general population and can mimic symptoms of FGID or coexist with FGID.
• Other carbohydrate intolerances may be responsible for symptom generation in patients with IBS and perhaps other FGIDs.
• There is a great interest in the role of a major dietary protein, gluten, in the production of symptoms that are very similar to those of patients with celiac disease without the enteropathy that characterizes celiac disease.
• Emerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS..
• Dietary proteins and functional gastrointestinal disorders.Am. J. Gastroenterol. 2013 (5):728-36
