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Summary for primary care

European Society for the Study of Coeliac Disease (ESsCD) Guideline for Coeliac Disease and Other Gluten-related Disorders


This Guidelines summary covers European Society for the Study of Coeliac Disease recommendations on managing coeliac disease (CeD) and other gluten-related disorders in adults and children.

Recommendations in this summary are on serology, diagnosis, dietary management, follow up, slow responders and refractory CeD (RCeD), special issues, non-coeliac gluten sensitivity (NCGS), and CeD-related skin and orodental disorders. For more detail on each of these areas, refer to the full guideline.

The GRADE system was used to evaluate the quality of supporting evidence. A strong recommendation is made when the benefits clearly outweigh the negatives and the result of no action. Conditional is used when some uncertainty remains about the balance of benefit/potential harm. For more information on the GRADE system, refer to the full guideline.


  • Gluten ingestion has been linked with a range of clinical disorders, collectively called gluten-related disorders
  • CeD is a chronic, multiorgan autoimmune disease precipitated by the ingestion of gluten that affects the small bowel in genetically predisposed persons
  • Depending on certain clinical, immunological, and histopathological characteristics, CeD may be subdivided into different categories, such as seronegative, slow-responding, and refractory
  • Dermatitis herpetiformis (DH) is a cutaneous manifestation of CeD characterised by herpetiform clusters of pruritic urticated papules and vesicles on the skin and granular Immunoglobulin (Ig) A deposits in the dermal papillae. The skin lesions usually clear with gluten withdrawal, but not in all adults
  • Gluten ataxia is defined as an otherwise idiopathic sporadic ataxia in association with positive coeliac serology with or without enteropathy. Other alternative explanations of ataxia, such as genetic disorders, ischaemia, and paraneoplastic phenomena, need to be excluded
  • NCGS is a condition characterised by irritable bowel syndrome (IBS)-like symptoms and extra-intestinal manifestations, occurring in a few hours or days after ingestion of gluten-containing food, improving rapidly with gluten withdrawal, and relapsing soon after gluten challenge
  • A prerequisite for suspecting NCGS is the exclusion of both CeD and wheat allergy (WA) when the patient is still on a gluten-containing diet.

Serology in Coeliac Disease Diagnosis


Who Should be Tested for Coeliac Disease? 

  • Adult patients with symptoms, signs, or laboratory evidence suggestive of malabsorption should be tested with serology for CeD [strong recommendation]
  • Screening of an asymptomatic first-degree family member of the patient with CeD is recommended. If available, human leukocyte antigen (HLA) typing may be offered as the first-line test; if negative, no further work up is needed [conditional recommendation]
  • CeD should be excluded in patients with unexplained elevation of serum aminotransferase levels [strong recommendation]
  • People with type 1 diabetes should be screened regularly for CeD [strong recommendation].

Role of Serology in Coeliac Disease Diagnosis

  • IgA-transglutaminase 2 (TG2) antibody is the preferred single test for detection of CeD at any age [strong recommendation]
  • Total IgA level needs to be measured concurrently with serology testing to determine whether IgA levels are sufficient [strong recommendation]
  • In patients with selective total IgA deficiency, IgG-based testing (IgG-deamidated gliadin peptides [DGPs] or IgG-TG2) should be performed at diagnosis and follow up [strong recommendation]
  • All diagnostic serological testing should be done while the patient is on a gluten-containing diet [strong recommendation]
  • Antibodies directed against native gliadin (antigliadin antibodies) are not recommended for the primary detection of CeD [strong recommendation].
For information and recommendations on endoscopy and histopathology, and other issues related to CeD diagnosis, refer to the full guideline.

Establishing a Diagnosis of Coeliac Disease

Requirements for Coeliac Disease Diagnosis


  • The confirmation of a CeD diagnosis should be based on clinical data, positive serology, and duodenal histology [strong recommendation]
  • Improvement of symptoms or exacerbation after reintroduction of gluten has a very low predictive value for CeD, and should not be used for diagnosis in the absence of other supportive evidence [strong recommendation]
  • A positive CeD-specific serology in patients with villus atrophy (VA) confirms the diagnosis of CeD [strong recommendation]
  • In asymptomatic patients with positive (but low titre) coeliac serology, the decision to perform biopsy may be preceded by repeating the serology test at 3–6 months [conditional recommendation]
  • In the case of elevated TG2 titre and normal histology, biopsies should be reviewed by a pathologist familiar with CeD [strong recommendation]
  • Seronegative CeD requires careful assessment with HLA-DQ2/8 testing and a response to a gluten-free diet (GFD) after excluding other causes of seronegative VA. Coeliac serology, both IgA and IgG based, should be negative [strong recommendation]
  • In patients who are already following a GFD prior to testing, serology and HLA typing are needed. If serology is positive, then biopsy is the next step. Gluten challenge should be undertaken when serology is negative, but HLA DQ2/DQ8 is positive [strong recommendation].

Dietary Management

Gluten-Free Diet

  • The mainstay of treatment for CeD is a GFD. Patients with CeD should be educated to avoid cereals and food products derived from wheat, barley, or rye, and food made from gluten-contaminated cereals that are normally gluten-free, such as maize and oats
  • Oats uncontaminated by gluten are safe for almost all patients with CeD. A small percentage of patients with CeD may be sensitive to oats and develop symptoms or even mucosal damage
  • Patients should be instructed on using separate cooking utensils, cooking surfaces, and toasters. However, this may not be necessary if these shared items are thoroughly cleaned with soap and water between use in the case of the first two items, and toaster bags can avoid the need for two toasters
  • Food labelling is important; available lists should be checked for allowable foodstuffs
  • Patients should be advised to eat a high-fibre diet
  • There is evidence that compliance with a GFD is improved in those who are more knowledgeable about CeD and the diet, and support from health providers and families has a positive impact. In most countries, high-quality gluten-free products are available in supermarkets, specialised health food stores, and on the internet
  • GFD foodstuffs are generally more expensive than the equivalent wheat-based foods, and some countries reimburse patients on this diet. Coeliac support groups may be of help, especially for underprivileged and migrant populations.

Safe Gluten Intake

  • The susceptibility to gluten contamination of food varies among patients with CeD. A calculated daily intake of 30 mg seems not to harm the mucosa. Therefore, at present, a safe limit could be set at between 10 and 100 mg.

Benefits of Gluten-Free Diet

  • Poor dietary adherence is negative for specific health problems, such as the risk of lymphoma and adverse pregnancy outcomes. Poor fetal outcomes in pregnant women with undiagnosed CeD compared with those with CeD on a GFD has been reported
  • Adherence to a GFD typically leads to a vast improvement in symptomatology and mucosal healing associated with decreased risks of cardiovascular disease and malignancy
  • Untreated CeD is associated with an increased prevalence of low bone mineral density (BMD), which improves on a GFD in both adults and children. A GFD reduces the risk of infertility, spontaneous abortions, preterm deliveries, and delivery of low-birth-weight infants.

Nutritional Deficiencies/Excess in Coeliac Disease and Gluten-Free Diet

Micronutrient Deficiencies

  • Adherence to a GFD usually leads to improvement in nutrient absorption. However, a GFD itself has limitations in nutrient value, and vigilant dietary monitoring is necessary
  • Iron deficiency is present in 7–80% of patients with CeD at diagnosis. CeD is present in 2–5% of patients with iron deficiency anaemia. With a strict GFD, iron stores typically improve. Eating foods rich in iron is necessary
  • Folate deficiency improves as the underlying enteropathy improves. A GFD is typically low in folate
  • Supplementation of folate and vitamin B12 can help improve anxiety and depression and may be needed for years, especially in slow responders
  • Vitamin B12 deficiency is present in 5–41% of untreated cases of CeD. B12 deficiency is typically corrected with a GFD, but should be treated with B12 supplementation in the short term
  • Vitamin D absorption is decreased as a result of fat malabsorption. Further, elimination of milk products in CeD with concomitant lactose intolerance will also lead to vitamin D deficiency. Several studies report that vitamin D and calcium levels can normalise within 1–2 years of a strict GFD and, in some patients, reverse bone loss
  • Calcium and vitamin D should be supplemented in patients with CeD and documented low serum levels, those with loss of BMD, or those who cannot achieve adequate intake via diet
  • Zinc deficiency can lead to growth arrest and diminished protein synthesis. With a strict GFD, zinc deficiencies resolve, and long-term supplementation is not needed
  • Malabsorption may lead to deficiency of copper in CeD. With copper repletion, the haematological manifestations typically resolve, but the neurological deficits can be irreversible. Screening for copper deficiency needs to be considered at diagnosis of CeD, especially when any associated deficiency symptoms are identified
  • Screening for pyridoxine (vitamin B6) is indicated
  • In general, these deficiencies are more common in adults than in children.

Other Nutritional Deficiencies in the GFD

  • Macronutrients and energy intake are usually imbalanced, both at the diagnosis of CeD and also with adherence to a GFD
  • The GFD is usually low in fibre. This can lead to constipation, as well as removal of other health benefits of soluble and insoluble fibre
  • Many processed gluten-free products have an increased glycaemic index, with increased fat and lower proteins compared with gluten-containing meals.


  • Patients with CeD should adhere to a lifelong GFD [strong recommendation]
  • Oats are safely tolerated by the majority of patients with CeD; introduction into the diet should be cautious and patients should be monitored for possible adverse reactions [strong recommendation]
  • Patients with CeD should be referred to a dietitian who is well-trained concerning CeD in order to get a detailed nutritional assessment, education on the GFD, and subsequent monitoring [strong recommendation]
  • A newly diagnosed adult patient with CeD should undergo testing to uncover deficiencies of essential micronutrients—for example, iron, folic acid, vitamin D, and vitamin B12 [strong recommendation]
  • Patients should be advised to eat a high-fibre diet supplemented with whole-grain rice, maize, potatoes, and ample vegetables [strong recommendation].
For information and recommendations on the management of severe presentations of CeD, refer to the full guideline.

Follow Up of Coeliac Disease in Adults

Systemised Follow Up

  • Patients should be encouraged to join national coeliac societies or other disease-specific patient support groups
  • In the first year after establishing the diagnosis, follow up needs to be frequent to optimise the chance of dietary adherence, provide psychological support, and to optimally motivate the patient to adapt to the new situation
  • Once the disease is stable and the patient manages their diet without problems, annual or biennial follow ups should be initiated. The physician should check the integrity of small bowel absorption, associated autoimmune conditions (in particular, thyroid disorders and type 1 diabetes), liver disease, and dietary adherence by measuring coeliac-specific antibodies (anti-TG2 or EMA/DGP)
  • Liver enzyme abnormalities, if present at presentation, need to be followed up. If these abnormalities are persistent, then further assessment (immunological, radiological, and/or histopathological) is needed
  • Key endpoints at follow up of patients with CeD are absence of symptoms and achieving mucosal healing.

Assessment of Adherence to a GFD

  • There are four complementary steps to assess dietary adherence:
    • clinical assessment: a strict adherence to the GFD is a prerequisite to control symptoms, improve quality of life, and decrease the risk of complications. Nutritional status, height, and weight need to be assessed
    • dietetic review: there is extensive evidence to support the central role of a dietitian in slow-responder patients or if gluten contamination is suspected. A dietetic review supported by questionnaires evaluating self-reported GFD adherence and food frequency is a useful tool to rule out inadvertent gluten intake and to provide education for a balanced and adequate, but not excessive, nutrient intake
    • serology and other markers: all coeliac-associated antibodies are gluten-dependent. A decrease from baseline values is expected within months of strict adherence to the GFD. Lack of declining values and/or persistently positive serology 1 year after starting a GFD strongly suggests gluten contamination. It is reasonable to assume that positive antibody titres indicate some gluten intake. A significant decrease (or normalisation) of markers of malabsorption, such as steatorrhea, should be expected after a GFD
    • follow-up biopsy: in adults, neither symptoms nor serology are reliable to predict small bowel damage. Serum antibodies have poor sensitivity for persistent VA. Early biopsy (at 6 months) is not considered to be optimal.
  • Currently, there are no studies indicating an absolute necessity for performing routine follow-up biopsy for all patients. However, there is a need for distinguishing asymptomatic patients with negative serology from symptomatic patients who need repeated biopsies to rule out RCeD or malignancies
  • It may be reasonable to do a follow-up biopsy in adults after 1–2 years of starting a GFD to assess for mucosal healing, especially in patients older than 40 years or in those having initially severe presentations. It seems logical to perform a follow-up biopsy in patients with serology-negative coeliac disease because this is the only way possible to confirm response to a GFD.

At-Risk Family Members

  • It is advisable to follow up these individuals with serology. The time interval is not defined, but 3–5 years would be reasonable. Those who get positive serology or develop symptoms should have a duodenal biopsy examination.

Who Needs to be Vaccinated?

  • Hyposplenism or functional asplenia in association with CeD may result in impaired immunity to encapsulated bacteria, and an increase in such infections has been demonstrated in CeD
  • Hyposplenism is considered to be present if the size of the spleen is small at imaging, or in the presence of circulating Howell–Jolly bodies, mild degrees of thrombocytosis, and leucocytosis
  • Those patients who are known to be hyposplenic should receive the pneumococcal vaccine. However, it is unclear whether vaccination with the conjugated vaccine is preferable in this setting and whether additional vaccination against Haemophilus, meningococcus, and flu should be considered if not previously given.

Bone Disease

  • This manifests as osteopenia and early onset of osteoporosis and osteomalacia
  • Rickets is also frequently reported, especially in children from developing countries
  • The risk of osteoporosis and bone fracture is increased in CeD patients. The excess risk is reduced with good dietary adherence and reduction in VA
  • Bone density increases during the first year of GFD adherence.


  • Patients with CeD should be monitored regularly for persistent or new symptoms, adherence to a GFD, and assessment for complications [strong recommendation]
  • Periodic medical follow up should be performed by a gastroenterologist or physician with special expertise in CeD [moderate recommendation]
  • Dietary revision should be performed by a dietitian with special expertise in CeD, especially in slow responders, to exclude gluten contamination [strong recommendation]
  • Monitoring of adherence to a GFD should be based on a combination of history and serology [strong recommendation]
  • A normal anti-TG2 level at follow up does not predict recovery of VA
  • A follow-up duodenal biopsy is recommended for monitoring in cases of lack of clinical response or relapse of symptoms despite a GFD [strong recommendation]
  • Monitoring of coeliacs should include verification of normalisation of laboratory abnormalities detected during initial investigation [strong recommendation]
  • It is advisable to follow up at-risk family members with serology. Those who have positive serology or develop symptoms should have duodenal biopsy examination [conditional recommendation]
  • CeD patients who are known to be hyposplenic should receive the pneumococcal vaccine [strong recommendation]
  • Dual X-ray absorptiometry should be measured in those at high risk of osteoporosis. It may be performed at diagnosis, especially in those with malabsorption or those at high risk if there is a long delay in diagnosis or there are clinical presentations suggestive of bone disease. In others, not later than the age of 30–35 years and then to be repeated at 5-year intervals. A shorter interval (2–3 years) is needed in case of low bone density on index measurement, evidence of ongoing VA, or poor dietary adherence [strong recommendation].

Slow Responders and Refractory Coeliac Disease

  • A considerable percentage of adult patients with CeD (between 7% and 30%) continue to have persistent symptoms, signs, or laboratory abnormalities of CeD despite at least 6–12 months of a GFD
  • These patients are regarded as slow responders. Use of the term 'nonresponsive CeD' to denote these patients is strongly discouraged, because most of them will improve over time on a strict GFD or they have another treatable cause for their complaints
  • RCeD may be defined as persistent or recurrent symptoms and signs of malabsorption with VA despite a strict GFD for more than 12 months and in the absence of other disorders, including overt lymphoma
  • Currently, two types of RCeD are recognised depending on the presence or absence of aberrant intraepithelial lymphocytes.


  • Patients showing slow response should be evaluated carefully to exclude dietary inconsistencies and identify other specific aetiologies [strong recommendation]
  • Evaluation of slow responders should include review initial diagnosis, coeliac serology, a dietary review, and follow-up duodenal biopsy [strong recommendation]
  • Distinction should be made between RCeD-I and RCeD-II to select appropriate management and determine the prognosis [strong recommendation]
  • T-cell flow cytometry is the most reliable method to make a distinction between RCeD-I and RCeD-II [strong recommendation]
  • The nutritional status of RCeD patients should be monitored closely. Nutritional support, including parenteral nutrition, forms an essential part of the management [strong recommendation]
  • Enteropathy-associated T-cell lymphoma (EATL) should be confidently excluded before starting treatment with medications in RCeD-II [strong recommendation]
  • RCeD-II patients need to be treated in referral centres by an experienced gastroenterologist in CeD in collaboration with a haematologist [strong recommendation]
  • EATL needs to be excluded in any patient with CeD with abdominal pain, fever, obstruction, anaemia, gastrointestinal bleeding, or unexplained weight loss [strong recommendation].

Special Issues in Childhood and Adolescence


  • The confirmation of a CeD diagnosis in some children should be based on a combination of clinical data, positive serology, and duodenum biopsies [strong recommendation]
  • Duodenal histology in some children is recommended to confirm the diagnosis of CeD [strong recommendation]
  • CeD diagnosis may be made without duodenal biopsy in symptomatic children with high TG2 levels (>10 times the upper limit of normal) and EMA in the presence of HLA-DQ2/8. The diagnosis is confirmed by an antibody decline and preferably a clinical response to a GFD [conditional recommendation]
  • Gluten challenge is indicated when the CeD diagnosis in doubt with negative serology before starting a GFD. It should not be performed before the child is 5 years old or during the pubertal growth spurt [conditional recommendation]
  • A GFD should be introduced only when a CeD diagnosis has been made conclusively [strong recommendation]
  • The duration of breastfeeding and/or gluten introduction while the infant is still breastfed has no impact on the risk of developing CeD [moderate recommendation]
  • There is currently no evidence to recommend avoiding either an early (at 4 months of age) or a late (at or after 6 or even 12 months) gluten introduction in children at risk of CeD [moderate recommendation]
  • A gradual transfer of medical care of an adolescent with CeD to adult care is recommended. The transfer should be structured and include, as the minimum, written information on the base of diagnosis, follow up, anthropometric data, comorbidities, and dietary adherence.

Non-Coeliac Gluten Sensitivity

  • NCGS is characterised by IBS-like symptoms and extra-intestinal manifestations, occurring in a few hours or days after gluten ingestion, improving rapidly with gluten withdrawal, and relapsing soon after gluten challenge.


  • NCGS may be considered in patients with gluten-related intestinal and/or extra-intestinal complaints showing a normal result of the CeD and WA serological markers on a gluten-containing diet [strong recommendation]
  • Serology and small-bowel histology (while the patient is on a gluten-containing diet) and HLA-DQ typing (to rule out CeD if negative) are needed to differentiate between CeD and NCGS [strong recommendation]
  • The diagnosis of NCGS is excluded in subjects failing to show symptomatic improvement after 6 weeks of a GFD [strong recommendation]
  • A less-stringent GFD may be enough compared with those with CeD [conditional recommendation]
  • Patients showing a negative gluten challenge should be investigated for other possible causes of IBS-like symptoms [conditional recommendation].

Coeliac Disease-Related Skin and Orodental Disorders


  • The diagnosis of DH should always be confirmed by direct immunofluorescence (DIF) examination of perilesional skin showing granular IgA deposits in the papillary dermis [strong recommendation]
  • In case of typical results from DIF and positive anti-TG2, the diagnosis of DH and CeD can be confirmed [strong recommendation]
  • If the patient is on a GFD, a gluten-containing diet should be administered, and the biopsy taken after at least 1 month [strong recommendation]
  • A GFD is essential in the management of DH [strong recommendation]
  • Dapsone is considered an essential therapeutic option for patients with DH during the 6–24-month period until the GFD is effective [strong recommendation]
  • A GFD should be considered in patients with psoriasis and serological evidence of gluten intolerance even in the absence of clinical signs of CeD [conditional recommendation].

For information on neuropsychiatric manifestation related to gluten, quality of life, and novel therapies for CeD, refer to the full guideline.