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Sections Pediatric Celiac Disease (Sprue)
Overview
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Workup
Treatment
Guidelines
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Guidelines

Guidelines Summary

The American College of Gastroenterology (ACG), the European Society for the Study of Coeliac Disease (ESsCD), and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) have published guidelines for the diagnosis and management of celiac disease (sprue). These guidelines are summarized below.

American College of Gastroenterology

In January 2023, the American College of Gastroenterology (ACG) published guidelines for the diagnosis and management of celiac disease.^[63]

Esophagogastroduodenoscopy (EGD) with multiple duodenal biopsies is recommended for confirmation of diagnosis in both children and adults suspected to have celiac disease (CD).

Combination of high-level tissue transglutaminase (TTG) IgA (>10× upper limit of normal) with a positive endomysial antibody (EMA) in a second blood sample is a reliable test for diagnosing CD in children.

Immunoglobulin IgA anti-TTG antibody (TTG-IgA) is the preferred single test for the detection of CD in children younger than 2 years who are not IgA-deficient.

Testing for CD in children with IgA deficiency should be performed using IgG-based antibodies.

Intestinal healing is recommended as the goal of gluten-free diet (GFD) therapy in CD patients.

Use of gluten detection devices in food or biospecimens among patients with CD is not recommended.

Consumption of gluten-free oats in the diet of those with CD is recommended.

Vaccination to prevent pneumococcal disease is recommended in patients with CD.

Diagnosis of celiac disease

In 2020, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published guidelines for the diagnosis of celiac disease (sprue).^[64]

There is no need for HLA-DQ2 and HLA-DQ8 typing in patients with positive transglutaminase immunoglobulin A (TGA-IgA) if they qualify for celiac disease (CD) diagnosis with biopsies or if high serum TGA-IgA (≥10 times the upper limit of normal [ULN]) and endomysial antibody (EMA)-IgA positivity exist. While patients testing negative for HLA-DQ2 and HLA-DQ8 have a very low CD risk, the diagnosis is not confirmed with a positive result.

If serum IgA values are normal for age, TGA-IgA should serve, regardless of patient age, as the initial serologic test.

Children with suspected CD should undergo total IgA and TGA-IgA testing as an initial screen. If total IgA concentrations are low, the second step should consist of an IgG-based test (deamidated gliadin peptide [DGP], EMA, or TGA). Testing for EMA, DGP, or AGA antibodies (IgG and IgA) is not recommended as an initial screen in clinical practice.

The TGA-IgA serum concentration should be at least 10x ULN for a diagnosis of CD made without biopsies. Antibody tests should be used only if they have proper calibration curve–based calculation and their measurement range accommodates a 10x ULN value. In patients in whom IgA is deficient but IgG-based serologic tests are positive, biopsies should not be omitted.

If the parents/patient have agreed to a no-biopsy approach to CD diagnosis, a positive EMA-IgA test performed on a second blood sample should be used to confirm the diagnosis in children with TGA ≥10x ULN.

While the patient is on a gluten-containing diet, histologic evaluation should be carried out using at least four biopsies from the distal duodenum and at least one from the duodenal bulb. Optimally orientated biopsies should be assessed. The presence of mucosal lesions is indicated by a villous-to-crypt ratio of less than 2. If the TGA results are discordant with the histopathology, the biopsies should be recut and/or a second opinion should be obtained from an experienced pathologist.

It is not necessary to consider that other pathologies or diagnoses may have been missed if the CD diagnosis omits upper endoscopy with biopsies.

Treatment and follow-up of celiac disease

In September 2022, ESPGHAN published guidelines for the management and follow-up of children and adolescents with celiac disease (sprue).^[57]

Regular follow-up is recommended for children and adolescents with celiac disease. The first follow-up visit should be scheduled about 3-6 months after the diagnosis is made. Subsequent visits should occur every 6 months until IgA-TGA levels return to normal, and then every 12-24 months.

Adherence to the gluten-free diet should be assessed at follow-up visits.

If IgA-TGA levels fail to decrease after 6-12 months on a gluten-free diet if or IgA-TGA levels are persistently positive, a careful review of dietary compliance and measurement of IgA-TGA levels with the same test from the same manufacturer are recommended.

In children with celiac disease who are following a gluten-free diet, routine assessment of mucosal healing with small-bowel biopsies is not recommended.

A trial of a lactose-reduced diet is recommended only for patients with celiac disease who have symptoms that suggest lactose intolerance (eg, ongoing diarrhea, abdominal pain, gassiness) despite adherence to the gluten-free diet.

European Society for the Study of Coeliac Disease

In June 2019, the European Society for the Study of Coeliac Disease (ESsCD) released updated guidelines for the management of celiac disease (CD) and other gluten-related disorders in adults and children.^{[65, 66]}Their recommendations are outlined below.

Who should be tested for celiac disease?

Adult patients with symptoms, signs, or laboratory evidence suggestive of malabsorption: Test with serology for CD.

Patients with unexplained elevation of serum aminotransferase levels: Exclude CD.

Patients with type 1 diabetes: Screen regularly for CD.

Workup

Serology

IgA-TG2 (immunoglobulin A-tissue transglutaminase 2) antibody is the preferred single test for CD detection at any age. Concurrently measure total IgA level with serology testing to determine whether IgA levels are sufficient.

At diagnosis and follow-up, perform IgG-based testing (IgG-DGPs [deamidated gliadin peptides] or IgG-TG2) in patients with selective total IgA-deficiency.

Perform all diagnostic serologic testing while patients are on a gluten-containing diet.

Antibodies directed against native gliadin (AGA) are not recommended for primary CD detection.

Endoscopy and histopathology

When CD is suspected, obtain biopsies even with a normal endoscopic appearance of the duodenum.

Duodenal biopsy is an essential component of the diagnostic evaluation for adults with suspected CD and is recommended to confirm the diagnosis. Multiple duodenal biopsies (at least four of the second part of duodenum) are recommended for confirmation.

An increase in intraepithelial lymphocyte (IEL) infiltration in the absence of villus atrophy (VA) in duodenal biopsies (Marsh 1) is not specific for CD; exclude other causes.

Helicobacter pylori infection is often associated with Marsh 1 histology; its eradication may normalize the duodenal IEL count. Obtain concomitant gastric biopsies or perform serology when H pylori is suspected.

If CD is highly suspected, perform duodenal biopsy even if the serology is negative.

HLA-DQ2/8 typing

Avoid routine use of HLA-DQ2/DQ8 testing in the initial diagnosis of CD. Include the results of such testing with a caution that patients at risk should be serologically tested for CD without changing their diet.

Use HLA-DQ2/DQ8 testing to rule out CD in selected clinical situations, including: (a) Marsh 1-2 histology in seronegative patients; (b) evaluation of patients not tested for CD before initiation on a gluten-free diet (GFD); (c) discrepant results of celiac-specific serology and histology.

Other diagnostic tests

Video capsule endoscopy (VCE) is not used for the initial diagnosis of CD except for patients with positive celiac-specific serology who are unwilling/unable to undergo endoscopy with biopsy. VCE is important in detecting complications associated with CD.

Intestinal-permeability tests are neither sensitive nor specific and are not recommended for CD diagnosis.

Serum intestinal fatty acid binding protein (I-FABP) might be useful in identifying dietary nonadherence and unintentional gluten intake.

Diagnostic confirmation

Diagnostic confirmation of CD in adults and in some children should be based on clinical data, positive serology, and duodenal histology.

Improvement of symptoms or exacerbation after gluten re-introduction has a very low predictive value for CD and should not be used for diagnosis in the absence of other supportive evidence.

A positive CD-specific serology in patients with VA confirms the CD diagnosis.

In case of an elevated TG2-titer and normal histology, a pathologist familiar with CD should review the biopsies. Repeat the biopsy after gluten challenge if the patient was not on gluten-containing diet before testing. HLA-DQ2/8 typing is mandatory. Testing for other antibodies (eg, DGP and/or endomysium [EMA]) may be of added value.

Seronegative CD requires careful assessment with HLA-DQ2/8 testing and a response to a GFD after excluding other causes of seronegative VA. Coeliac serology, both IgA- and IgG-based, should be negative.

In patients who are already following GFD prior to testing, serology and HLA typing are needed. If serology is positive, then biopsy is the next step. Perform a gluten challenge when serology is negative but HLA DQ2/DQ8 is positive.

Dietary management

Patients with CD should adhere to a lifelong GFD. The majority of CD patients safely tolerate oats; introduction of oats into the diet should be cautious, and monitor patients for possible adverse reaction.

Refer patients with CD to a dietitian who is well-trained concerning CD to get a detailed nutritional assessment, education on the GFD, and subsequent monitoring.

Newly diagnosed adult CD patients should undergo testing to uncover deficiencies of essential micronutrients (eg, iron, folic acid, vitamins D and B12).

Advise patients to eat a high-fiber diet supplemented with whole-grain rice, maize, potatoes, and ample vegetables.

Follow-up

Monitor CD patients regularly for persistent or new symptoms, adherence to GFD, and assessment for complications. Base monitoring of GFD adherence on a combination of history and serology. Monitoring of CD patients should include verification of the normalization of laboratory abnormalities detected during the initial investigation.

Dietary revision should be performed by a dietitian with special expertise in CD especially in slow-responders to exclude gluten contamination.

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.

CD patients who are known to be hyposplenic should receive the pneumococcal vaccine.

Measure bone density in those at high risk of osteoporosis 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 age 30-35 years and then to be repeated at 5-year intervals. Use a shorter interval (2-3 years) in case of low bone density on index measurement, evidence of ongoing VA, or poor dietary adherence.

Slow-responders and refractory CD (RCD)

Carefully evaluate patients showing slow response to exclude dietary inconsistencies and also identify other specific etiologies. The evaluation should include review of the initial diagnosis, celiac serology, a dietary review, and a follow-up duodenal biopsy.

Distinguish RCD-I from RCD-II to select appropriate management and determine the prognosis. T-cell flow cytometry is the most reliable method to make a distinction between RCD-I and RCD-II.

Closely monitor the nutritional status of RCD patients. Nutritional support including parenteral nutrition forms an essential part of the management.

Confidently exclude enteropathy-associated T cell lymphoma (EATL) before initiating pharmacotherapy in RCD-II. RCD-II patients need to be treated in referral centers by an experienced gastroenterologist in CD with a hematologist.

Exclude EATL in any CD patient with abdominal pain, fever, obstruction, anemia, gastrointestinal bleeding, or unexplained weight loss.

In EATL, debulking surgery for large ulcerated small bowel tumors is recommended for limiting the risk of perforation or bleeding during chemotherapy.

Special issues about children and adolescents

Duodenal histology in some children is recommended to confirm the diagnosis of CD.

Introduce a GFD only when the CD diagnosis has been made conclusively.

A gradual, structured transfer of medical care of an adolescent with CD to adult care is recommended. Include as the minimum written information on the base of diagnosis, follow-up, anthropometric data, comorbidities, and dietary adherence.

Resources

For more information, please go to Celiac Disease (Sprue) and Genetics of Celiac Disease (Sprue).

For more Clinical Practice Guidelines, please go to Guidelines.

Medication

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Media Gallery

Potbelly and muscle wasting in a child with celiac disease.
The celiac iceberg.
Presentations of celiac disease.
Extraintestinal manifestations of celiac disease.
GI signs and symptoms of celiac disease.
Approximate prevalence of celiac disease in other autoimmune disorders.

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Author

Stefano Guandalini, MD, AGAF Founder and Director Emeritus, Celiac Disease Center, University of Chicago; Former Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medicine; Professor Emeritus, The University of Chicago Pritzker School of Medicine

Stefano Guandalini, MD, AGAF is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, North American Society for the Study of Celiac Disease

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Imaware.health.

Coauthor(s)

Phyllis A Vallee, MD Associate Program Director, Department of Emergency Medicine, Henry Ford Hospital

Phyllis A Vallee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, Michigan State Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Additional Contributors

Jorge H Vargas, MD Professor of Pediatrics and Clinical Professor of Pediatric Gastroenterology, University of California, Los Angeles, David Geffen School of Medicine; Consulting Physician, Department of Pediatrics, University of California at Los Angeles Health System

Jorge H Vargas, MD is a member of the following medical societies: American Liver Foundation, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Ginette V Busschots, MD, to the writing and development of this article.