Celiac disease treatment: gluten-free diet and beyond.

The basis for celiac disease (CD) treatment is a strict lifelong gluten-free diet. On the diet, the small intestinal mucosal injury heals and gluten-induced symptoms and signs disappear. The mucosal healing is a prerequisite for sustaining health and is also obtained with a diet containing oats and trace amounts of gluten, industrially purified wheat starch-based gluten-free products. The small intestinal mucosa does not heal in noncompliant people, nor when a patient is inadvertently ingesting gluten. Development of adjunctive or alternative therapies is on its way. There are several novel treatment pipelines within academy and industry. Examples are the ideas of using glutenases as a drug to degrade the ingested gluten, polymers to bind and sequester the gluten to the feces, and also vaccine development for an immunotherapy to induce tolerance towards gluten. Clinical drug trials are to be foreseen in CD, soon also in children.

[Fiber, food intolerances, FODMAPs, gluten and functional gastrointestinal disorders--update 2014]. / Fiber, food intolerances, FODMAPs, gluten und funktionelle darmerkrankungen--update 2014.

The controversial effects of dietary fiber on symptoms in functional gastrointestinal disorders are summarized. Studies concerning adverse reaction to foods are mentioned and the possible role of food allergy and food intolerances, especially pseudoallergic reactions to biogenes amines, in symptom provocation is discussed. The known effects of lactose deficiency and fructose malabsorption are reviewed. The FODMAP concept (fermentable oligo-, di-, monosaccharides and polyols) is presented in more detail and recent studies on pathophysiological effects of FODMAP constituents and of therapeutic effects of a low FODMAP diet on symptoms in patients with irritable bowel syndrome are discussed. Finally, studies on the new disorder non-celiac gluten sensitivity (NCGS) are summarized and the state of the discussion whether wheat intolerance is due to gluten or the grains is given.

The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study.

BACKGROUND: Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS). METHODS: This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale [VAS]) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E+) or gluten-free (E-) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G+) or gluten-free (G-) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended. FINDINGS: Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to E+G+ (n=21), E+G- (n=21), E-G+ (n=20), or E-G- (n=22). One person in the E+G+ group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for E+G+ (16·6 mm [95% CI 13·1 to 20·0]) than for E-G+ (6·9 mm [3·5 to 10·4]; difference 9·6 mm [95% CI 3·0 to 16·2], p=0·0010) and E-G- (7·4 mm [4·2 to 10·7]; difference 9·1 mm [2·7 to 15·6], p=0·0016), but not for E+G- (11·7 mm [8·3 to 15·1]; difference 4·9 mm [-1·7 to 11·5], p=0·28). There was no difference between E+G- and E-G+ (difference 4·7 mm [-1·8 to 11·3], p=0·33), E+G- and E-G- (difference 4·2 mm [-2·2 to 10·7], p=0·47), and E-G+ and E-G- (difference -0·5 mm [-7·0 to 5·9], p=1·0). Adverse events were reported by two participants in the E+G- group (itching jaw [n=1]; feeling lightheaded and stomach rumbling [n=1]) and one participant in the E-G+ group (vomiting). INTERPRETATION: The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS. FUNDING: Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.

Recognition and management of coeliac disease in children.

Coeliac disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten (found in wheat, rye, and barley) in genetically susceptible individuals. It affects around 1% of children and leads to proximal small bowel enteropathy, although many cases may remain undiagnosed. CD classically presents with gastrointestinal symptoms of diarrhoea, abdominal pain and weight loss, although other symptoms such as iron deficiency anaemia, faltering growth, dental enamel defects, short stature, liver disease, arthropathy, mouth ulcers, etc may be the presenting feature. Breastfeeding is considered to have a beneficial role in preventing CD or at least delays onset. Community practitioners should remain aware of the classical gastrointestinal and other features of CD and make an early referral to medical professionals. Suspicion of CD should lead to antibody screening tests and the diagnosis is confirmed by an intestinal biopsy. A gluten-free diet (GFD) should always be started by paediatric dietitians and they play a vital role in educating and supporting families. Strict adherence to a GFD is essential to maintain good health and to prevent development of long-term complications.

The effect of low FODMAP diet with and without gluten on irritable bowel syndrome: A double blind, placebo controlled randomized clinical trial.

BACKGROUND & AIM: Although the effects of low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet on amelioration of irritable bowel syndrome (IBS) symptoms have been reported previously, it has not yet been elucidated whether the gluten of wheat and barley induces the symptoms or only their fructans lead to aggravation of the symptoms. The aim of this study was to assess the effect of low FODMAPs diet with vs. without gluten on clinical symptoms in IBS patients. METHODS: In this double-blind, placebo-controlled randomized trial, forty nine IBS patients were randomly assigned to placebo and/or intervention group. Patients in the intervention group received 5 gr/day of gluten powder with low FODMAP diet, while placebo group received 5 gr of rice flour as placebo, with low FODMAP diet. Quality of life (QoL) and IBS-SSS (symptom severity score) were measured before and after the intervention using a valid QoL questionnaire and a standard visual analog scale, respectively. RESULTS: Significant improvements were observed in total scores of IBS-SSS (-32% vs. - 49%), abdominal pain intensity (-45% vs. -52%), and frequency (-26 vs. -46%), abdominal distension (-29% vs. -63%), Interference with community function (-14% vs. -45%) and quality of life (+23 vs. +32%) in both gluten and placebo groups respectively (P < 0.05). Only 5 patients in the gluten-containing diet reported exacerbation of their symptoms. CONCLUSION: Exacerbation of IBS symptoms after wheat and barley consumption is due to their fructan, and not related to their gluten content in most of the patients. CLINICAL TRIAL REGISTRATION NO: IRCT20100524004010N29.

Implications of gluten exposure period, CD clinical forms, and HLA typing in the association between celiac disease and dental enamel defects in children. A case-control study.

BACKGROUND: The association between coeliac disease (CD) and dental enamel defects (DED) is well known. AIM: The aim of this study was to investigate the prevalence of DED in children with CD and to specifically find the association of DED and gluten exposure period, CD clinical forms, HLA class II haplotype. DESIGN: This study was designed as a matched case-control study: 250 children were enrolled (125 coeliac children - 79 female and 46 male, 7.2 +/- 2.8 years and 125 healthy children). Data about age at CD diagnosis, CD clinical form, and HLA haplotype were recorded. RESULTS: Dental enamel defects were detected in 58 coeliac subjects (46.4%) against seven (5.6%) controls (P < 0.005). We found an association between DED and gluten exposure period, as among CD subjects the mean age at CD diagnosis was significantly (P = 0.0004) higher in the group with DED (3.41 +/- 1.27) than without DED (1.26 +/- 0.7). DED resulted more frequent (100%) in atypical and silent CD forms than in the typical one (30.93%). The presence of HLA DR 52-53 and DQ7antigens significantly increased the risk of DED (P = 0.0017) in coeliac children. CONCLUSIONS: Our results confirmed a possible correlation between HLA antigens and DED.

Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity?

The gluten-free diet (GFD) has gained increasing popularity in recent years, supported by marketing campaigns, media messages and social networks. Nevertheless, real knowledge of gluten and GF-related implications for health is still poor among the general population. The GFD has also been suggested for non-celiac gluten/wheat sensitivity (NCG/WS), a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of celiac disease (CD) or wheat allergy (WA). NCG/WS should be regarded as an "umbrella term" including a variety of different conditions where gluten is likely not the only factor responsible for triggering symptoms. Other compounds aside from gluten may be involved in the pathogenesis of NCG/WS. These include fructans, which are part of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA) and glyphosate. The GFD might be an appropriate dietary approach for patients with self-reported gluten/wheat-dependent symptoms. A low-FODMAP diet (LFD) should be the first dietary option for patients referring symptoms more related to FODMAPs than gluten/wheat and the second-line treatment for those with self-reported gluten/wheat-related symptoms not responding to the GFD. A personalized approach, regular follow-up and the help of a skilled dietician are mandatory.

Evaluation of Non-Celiac Gluten Sensitivity in Patients with Previous Diagnosis of Irritable Bowel Syndrome: A Randomized Double-Blind Placebo-Controlled Crossover Trial.

Background. To date, there is no reliable marker for the diagnosis of non-celiac gluten sensitivity (NCGS), which benefits from a gluten-free diet (GFD). This condition is characterized by functional gastrointestinal symptoms similar to those occurring in the course of irritable bowel syndrome (IBS). However, IBS has a higher prevalence, and often benefits from the administration of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. The overlap of symptoms between these two pathologies has led to an overestimation of self-made diagnosis NCGS. Aims. To better identify NCGS in subjects with a previous diagnosis of IBS. Methods. All subjects received a low FODMAP diet that was also gluten-free (low FODMAP-GFD), and those presenting an improvement of symptoms were exposed to gluten or placebo (double-blind challenge with wash-out and crossover). The response to dietary treatments was evaluated by visual analogue scale (VAS). Results. Of 30 patients (23 women, seven men, aged 42.2 ± 12.5 years, body mass index (BMI ) 24.7 ± 4.1 kg/m2), 26 benefited from the administration of low FODMAP-GFD and were exposed to the gluten/placebo challenge. After the challenge, using an increase of visual analogue scale VAS (Δ-VAS) ≥30%, 46.1% of the patients were NCGS+. However, this percentage became only 19.2% using a different method (mean ∆-VAS score plus two standard deviations). Conclusions. FODMAP intolerance could hide the response to a challenge test with gluten for the identification of NCGS in IBS patients. A low FODMAP-GFD followed by gluten/placebo challenge is able to identify patients with NCGS better. ClinicalTrials.gov registration number NCT04017585.

Enamel hypoplasia in coeliac children: a potential clinical marker of early diagnosis.

AIM: To assess at the scansion electron microscope (SEM) the structural aspects of enamel hypoplasia (EH) in coeliac disease (CD) with the aim to investigate our hypothesis of a possible significant difference between structural characteristics of EH in CD affected patients and EH of non-coeliac patients. If the presence of specific features of the EH associated with CD were demonstrated, these findings would represent for the dentist early non-invasive clinical markers of diagnosis of CD in case of suspected disease. METHODS: We analysed at SEM two samples of enamel fragments from hypoplasic teeth, both deciduous and permanent, harvested from 10 coeliac children (18 permanent teeth, 6 deciduous teeth; study group) and 10 non-coeliac children (16 permanent teeth, 4 deciduous teeth; control group) treated for dental caries, dental extractions for extensive caries lesions or deciduous teeth exfoliation. RESULTS: Significant structural differences were noted between EH of non-coeliac patients and same dental ? lesion in the group with CD. In the study group, EH defects were predominantly located on the central and lateral incisors, upper and lower, both deciduous and permanent, and on the first permanent molars, and were always simmetrical. EH of permanent teeth of CD affected patients was characterised by prisms more irregularly distributed with irregular margins and less interprismatic substance than observed in non-coeliac EH. The deciduous teeth of the study group showed shorter enamel prisms with a non-parallel direction up to convergence and less interprismatic substance than observed in the control group. CONCLUSION: This morphological analysis at SEM of the hypoplasic enamel defects of a group of coeliac children, the first published in literature, demonstrates that the EH of deciduous and permanent teeth in CD is highly hypomineralised with shorter prisms, more irregularly distributed and less interprismatic substance than observed in the non-coeliac EH. More data are needed to validate the significance OF our observations with the aim to assess if this simple, non-invasive microscopic analysis can be considered effective for the early identification of silent cases of CD that otherwise would not be diagnosed in the paediatric age.

Wheat-based foods and non celiac gluten/wheat sensitivity: Is drastic processing the main key issue?

While gluten and wheat must be absolutely avoided in coeliac disease and allergy, respectively, nutritional recommendations are largely more confused about non-coeliac wheat/gluten sensitivity (NCWGS). Today, some even recommend avoiding all cereal-based foods. In this paper, the increased NCWGS prevalence is hypothesized to parallel the use of more and more drastic processes applied to the original wheat grain. First, a parallel between gluten-related disorders and wheat processing and consumption evolution is briefly proposed. Notably, increased use of exogenous vital gluten is considered. Drastic processing in wheat technology are mainly grain fractionation and refining followed by recombination and salt, sugars and fats addition, being able to render ultra-processed cereal-based foods more prone to trigger chronic low-grade inflammation. Concerning bread, intensive kneading and the choice of wheat varieties with high baking quality may have rendered gluten less digestible, moving digestion from pancreatic to intestinal proteases. The hypothesis of a gluten resistant fraction reaching colon and interacting with microflora is also considered in relation with increased inflammation. Besides, wheat flour refining removes fiber co-passenger which have potential anti-inflammatory property able to protect digestive epithelium. Finally, some research tracks are proposed, notably the comparison of NCWGS prevalence in populations consuming ultra-versus minimally-processed cereal-based foods.

The widening spectrum of celiac disease.

Celiac disease is a permanent intolerance to ingested gluten that results in immunologically mediated inflammatory damage to the small-intestinal mucosa. Celiac disease is associated with both human leukocyte antigen (HLA) and non-HLA genes and with other immune disorders, notably juvenile diabetes and thyroid disease. The classic sprue syndrome of steatorrhea and malnutrition coupled with multiple deficiency states may be less common than more subtle and often monosymptomatic presentations of the disease. Diverse problems such as dental anomalies, short stature, osteopenic bone disease, lactose intolerance, infertility, and nonspecific abdominal pain among many others may be the only manifestations of celiac disease. The rate at which celiac disease is diagnosed depends on the level of suspicion for the disease. Although diagnosis relies on intestinal biopsy findings, serologic tests are useful as screening tools and as an adjunct to diagnosis. The treatment of celiac disease is lifelong avoidance of dietary gluten. Gluten-free diets are now readily achievable with appropriate professional instruction and community support. Both benign and malignant complications of celiac disease occur but these can often be avoided by early diagnosis and compliance with a gluten-free diet.

Celiac disease--a worldwide problem.

Celiac disease and dermatitis herpetiformis are caused by the alcohol soluble fractions of wheat, barley, and rye. Reliable serological tests are available for both mass and risk group screening and recent epidemiological studies on celiac disease suggest that the prevalence varies between 1:100-300 in different continents. The clinical manifestations of the disease has changed in the West and the classical symptomatic cases represent only approximately 1/7th of all diagnosed cases. Symptoms such as, anemia, short stature, dental enamel defect or osteoporosis can be the only manifestations of the atypical disease. There is an increased prevalence of celiac disease in patients with autoimmune diseases. Recent data suggest that there is a correlation between the prevalence of autoimmune diseases and the number of years that an individual consumes gluten-containing foods. Genetic studies revealed a high prevalence of certain HLA antigens in celiac patients, however, there is likelihood that non-HIA genes are also important in the pathomechanism. An interesting new development is the recognition of tissue transglutaminase (tTG), an enzyme that probably forms an autoantigen with gluten. It is generally accepted that antibodies to tTG are identical to the previously described antiendomysium antibodies. Whether or not tTG is responsible for the initiation of an immunoreaction against prolamines or just exacerbates the immune response is a subject of further investigations.

The management of coeliac disease.

One hundred children put on a gluten free diet because of suspected coeliac disease were followed for a mean period of 9.9 years. The diagnosis was eventually confirmed in 53. Under the age of two, 35 children showed subtotal villous atrophy in their initial biopsy but nine of these on subsequent gluten challenge and rebiopsy were found to tolerate gluten normally. Challenge and rebiopsy are also necessary for children over the age of two where the initial biopsy changes are less severe than subtotal villous atrophy. Such challenges can probably be carried out earlier than the recommended age of six given in the 1990 ESPGAN (European Society for Paediatric Gastroenterology and Nutrition) report with little risk of serious dental damage.

Celiac disease: a review.

Triggered by the ingestion of gluten in genetically predisposed individuals, celiac disease is the most common genetically based food intolerance in the world, with a prevalence among approximately 1% of the general population. This enteropathy may appear at any age and is characterized by a wide variety of clinical signs and symptoms that go well beyond the gastrointestinal tract. In young children, gastrointestinal presentations are common and include chronic diarrhea, failure to thrive, and abdominal distention; however, extraintestinal manifestations are becoming increasingly more common. They include numerous conditions such as dermatitis herpetiformis, anemia, dental enamel hypoplasia, recurrent oral aphthae, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminase levels, and female infertility. Therefore, diagnosing celiac disease requires a high degree of suspicion, followed by correct screening and a confirmatory test with an intestinal biopsy. After diagnosis, a strict gluten-free diet must be followed, which in most cases will bring a marked improvement of symptoms. However, there are important compliance and quality-of-life problems, especially in adolescents.

Biomechanical properties of the mandible, as assessed by bending test, in rats fed a low-quality protein.

OBJECTIVE: The present study describes the effects of feeding growing rats with diets containing increasing concentrations of wheat gluten (a low quality protein, G) on both the morphometrical and the biomechanical properties of the mandible. DESIGN: Female rats were fed one of six diets containing different concentrations (5-30%) of G between the 30th and 90th days of life. Control rats were fed a diet containing 20% casein (C), which allows a normal growth and development of the bone. Mandibular growth was estimated directly on excised and cleaned bones by taking measurements between anatomical points. Mechanical properties of the right hemimandibles were determined by using a three-point bending mechanical test to obtain a load/deformation curve and estimate the structural properties of the bone. Bone material properties were calculated from structural and geometric properties. The left hemimandibles were ashed and the ash weight obtained. Calcium content was determined by atomic energy absorption. Results were summarised as means±SEM. Comparisons between parameters were performed by ANOVA and post-test. RESULTS: None of the G-fed groups could achieve a normal growth performance as compared to the C-fed control group. Like body size, age-related increments in mandibular weight, length, height and area (index of mandibular size) were negatively affected by the G diets, as was the posterior part of the bone (posterior to molar III). The cross-sectional geometry of the mandible (cross-sectional area and rectangular moment of inertia) as well as its structural properties (yielding load, fracture load, and stiffness) were also severely affected by the G diets. However, material properties (Young's modulus and maximum elastic stress) and calcium concentration in ashes and the degree of mineralisation were unaffected. CONCLUSIONS: The differences in strength and stiffness between treated and control rats seemed to be the result of an induced loss of gain in bone growth and mass, in the absence of changes in the quality of the bone mineralised material.

Immunoblotting analysis of antigliadin antibodies in the sera of patients with dermatitis herpetiformis and gluten-sensitive enteropathy.

Antigliadin antibodies (AGA) were analyzed by immunoblotting from the sera of 30 patients with dermatitis herpetiformis (DH) and of 13 patients with gluten-sensitive enteropathy (GSE). The results were correlated to the jejunal morphology and to the serum AGA values as quantified with an enzyme-linked immunosorbent assay (ELISA). Immunoblotting analysis disclosed a distinct pattern of AGA which was similar in patients with DH and GSE. In both diseases individual variation in IgG class AGA patterns was large, suggesting that several antigenic determinants are involved in the AGA response. The IgA class AGA pattern was clearly more homogeneous. The sera with several bands in immunoblotting had the highest AGA levels in ELISA. Strong staining in the main gliadin area (bands from 31 to 38 kd) indicated severely damaged intestinal mucosa whereas the serum of DH patients with partial villous atrophy or normal mucosa showed usually weaker staining. The immunoblotting pattern of sera from healthy controls was even weaker but was directed against the same polypeptides as in the patients suggesting a quantitative rather than qualitative difference between healthy and diseased subjects. This difference was, however, more obvious in the IgA than in the IgG class AGA pattern possibly indicating a more fundamental defect in the regulation of synthesis of IgA isotype in DH and GSE.

Coeliac disease in adults.

Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.

Dermatite herpetiforme: manifestações cutâneas e bucais / Dermatitis herpetiformis: cutaneous and oral manifestations

Os autores realizaram uma revisão da literatura sobre dermatite herpetiforme (DH), apresentando os acometimentos cutâneos e bucais. Tal enfermidade, de provável etiologia auto-imune, consiste de uma doença crônica vesicobolhosa caracterizada clinicamente por pápulas e vesículas pruriginosas. Microscopicamente, através de fluorescência, pode ser observada a presença de depósito granular de IgA ao longo de membrana basal. Há associação entre pacientes portadores de DH e a sensibilidade ao glúten, esse achado também encontrado na doença celíaca. O tratamento recomendado para essa enfermidade é medicamentoso associado a uma dieta livre de glúten. Neste artigo discorre-se sobre etiologia, relações com enteropatia, influência do glúten, tratamento e diagnósticos diferenciais.