Management of celiac disease in children

INTRODUCTION — Celiac disease is a condition in which there is abnormal small intestinal mucosa that improves morphologically when treated with a gluten-free diet and relapses when gluten is reintroduced. The disorder is sometimes referred to as "celiac sprue" or "gluten-sensitive enteropathy." A strict gluten-free diet is the only available treatment and should be continued lifelong for those with a confirmed diagnosis of celiac disease.

The management of celiac disease and its complications are reviewed here. Its pathogenesis, clinical manifestations, and diagnosis are discussed separately. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children" and "Diagnosis of celiac disease in children".)

OVERVIEW OF MANAGEMENT — Treatment of the pediatric patient with celiac disease begins with dietary counseling to establish a gluten-free diet. It also includes addressing micronutrient deficiencies, monitoring the response to gluten elimination, and further evaluating patients who do not respond. Long-term management includes monitoring growth and development, surveillance/counselling for cooccurring autoimmune diseases, and monitoring for other potential celiac complications.

The six key elements in the management of patients with celiac disease can be summarized with the following mnemonic [1]:

●C - Consultation with a skilled dietitian

●E - Education about the disease

●L - Lifelong adherence to a gluten-free diet

●I - Identification and treatment of nutritional deficiencies

●A - Access to an advocacy group and/or health behavior support

●C - Continuous long-term follow-up by a multidisciplinary team

WHOM TO TREAT

Confirmed diagnosis of celiac disease — Treatment with a gluten-free diet is recommended for all children who have a confirmed diagnosis of celiac disease. The diagnosis of celiac disease is reinforced if the child responds to the gluten-free diet, with improvement in clinical symptoms and antibody tests.

In addition, treatment with a gluten-free diet is recommended for patients with dermatitis herpetiformis confirmed by skin biopsy, with or without associated pathology of the small intestinal mucosa. (See 'Dermatitis herpetiformis' below.)

Potential celiac disease — Potential celiac disease refers to patients who have positive tissue transglutaminase-immunoglobulin A antibodies (tTG-IgA) or endomysial antibody but who have a normal small bowel biopsy [2]. These patients are at an increased risk for celiac disease but cannot be formally diagnosed. There are some challenges with this definition because of the variability in the adequacy of the biopsies taken to exclude active celiac disease. They may or may not have celiac disease. For these patients, management decisions are based on the presence of symptoms and patient preference:

●For children who are truly asymptomatic, a gluten-free diet is not necessary. However, these patients should be monitored with repeat serology and undergo repeat small intestinal biopsy if symptoms develop or if there is higher suspicion of active disease over time. Because a child may not effectively communicate about symptoms that may herald active disease, periodic reevaluation for symptoms and appropriate growth is important. Studies suggest that a majority of children with potential celiac disease will not go on to develop celiac disease even when remaining on a gluten-containing diet [3].

●For children with symptoms that might be caused by celiac disease, management is unclear. It is reasonable to do a trial of a gluten-free diet, then monitor the response of symptoms and antibody tests, then continue the gluten-free diet if the child's symptoms improve and antibody tests return to normal. For those who do not respond, there is the possibility of a gluten rechallenge and repeat assessment in the future. Undertaking a gluten-free diet in a child with potential celiac disease should be based on joint decision-making between the provider and family.

Thus, the presence of symptoms remains the primary determinant of the decision to treat for children with potential celiac disease. Risk factors that predict progression from potential celiac disease to celiac disease include the presence and quantity of intraepithelial lymphocytes, positive anti-endomysial antibody tests, high-risk HLA-DQ genotypes, and presence of high-risk comorbidities [4-7]. Risk factors for celiac disease in the general population are discussed separately. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Pathogenesis and risk factors'.)

DIETARY MANAGEMENT

Principles of a gluten-free diet — The cornerstone of treatment of celiac disease is the lifelong elimination of gluten in the diet. Consumption of a gluten-free diet requires a major lifestyle change because gluten is contained in many common foods in a Western diet. It is important to provide written information and dietary counseling to improve compliance, ideally from a registered dietitian with expertise in this area [8]. A number of resources are available for patients with celiac disease, including a variety of cookbooks, gluten-free prepared foods, and online organizations (Celiac Disease Foundation, Beyond Celiac, National Celiac Association, Coeliac UK). (See "Patient education: Celiac disease in adults (Beyond the Basics)".)

As general rules, the following advice can be given to all patients:

●Foods to avoid – Avoid all foods containing wheat, rye, and barley and any food that contains gluten (table 1). Read labels on prepared foods and condiments carefully, paying particular attention to additives such as stabilizers or emulsifiers that may contain gluten.

●Foods that are safe – Alternate starches containing rice, corn, buckwheat, and potatoes can be safely eaten, as can foods with soybean or tapioca flours.

Gluten-free labeling may vary in different countries. In the United States and Canada, manufacturers are permitted to label a product "gluten-free" if gluten levels are <20 ppm. This is also the standard set by the international Codex Alimentarius Commission. Accordingly, manufacturers that use this label on their products are responsible for using the claim in an accurate and not misleading manner. In the United States, a "Certified Gluten-Free" label denotes that the product has been tested by a third-party laboratory and meets the criteria, but the US Food and Drug Administration does not specifically endorse or accredit this labeling.

A review of the literature by an expert panel concluded that the lower threshold of gliadin intake that can cause mucosal damage is between 10 and 100 mg daily [9].

●Oats – Pure oats, ie, uncontaminated by the other three grains, appear to be safely tolerated by most people with celiac disease, although tolerance varies among patients and depends on the quantity of oats consumed [8]. Our clinical approach is as follows:

•New diagnosis – For newly diagnosed patients, practice varies among experts. In our practice, we permit certified gluten-free oats from the start and only eliminate oats if patients do not show improvement. Some other experts recommend avoiding oats (including certified gluten-free oats) during the first 6 to 12 months of a gluten-free diet, until the disease is clearly in remission.

•In remission – For patients whose disease is in remission after a stringent gluten-free diet, there is no restriction for gluten-free oat consumption. However, it is critical that any oats be certified gluten-free because contamination with even small amounts of other cereals can lead to damage to the intestinal tract [10]. For example, mills that are not dedicated to processing oats alone may cross-contaminate oats with gluten from other grains.

•Unresponsive or relapsed – For patients who do not respond as anticipated to a gluten-free diet or who relapse after gluten-free oats are reintroduced, we eliminate oats or limit their quantity. This is because there is some uncertainty about the role of oats in a gluten-free diet. First, most studies that examined the safety of oats have included patients with relatively mild disease or whose disease was in remission upon reinstitution of oats in the diet. Second, some patients may have heightened sensitivity to oat prolamins. Third, a few studies suggest that daily intake above 40 to 60 g per day may be associated with disease recurrence, although this is controversial [11,12].

●Medications – Medications (pills) generally contain minimal gluten and do not need to be avoided. Information about gluten-free drugs is available on the internet (eg, glutenfreedrugs.com).

While trace gluten exposures are inevitable, it is also important not to promote hypervigilance, as this may increase child and parental anxiety and disordered eating [13].

Rationale for strict gluten avoidance — A strict gluten-free diet is recommended for all patients with established celiac disease. This is because of the benefit of reducing symptoms for many patients, restoration of normal growth, as well as reduction in long-term adverse health risks. However, it should be recognized that a strict gluten-free diet represents a substantial lifestyle burden. Therefore, in addition to implementing a strict gluten-free diet, dietary counseling should include strategies to minimize the burden of this diet.

●Benefits for reducing symptoms – Many patients experience significant improvement of symptoms on a gluten-free diet. For these patients, the benefit is sufficient to outweigh the burden of adhering to a strict gluten-free diet.

However, patients with mild symptoms may feel that the burden of fastidiously avoiding gluten-containing foods outweighs the burden of their symptoms. The perception may be even greater among asymptomatic patients in whom celiac disease was diagnosed based upon antibody screening (ie, testing of first-degree relatives). These patients may be inclined to include small amounts of gluten in their diet. In this case, it is particularly important to discuss the evidence for long-term health risks, as outlined below, so that they can make a fully informed decision.

●Benefits for long-term health risks – The benefit of rigid gluten avoidance has not been conclusively proven, since the natural history of celiac disease in patients who are asymptomatic or have only mild symptoms is unclear. Several arguments favor encouraging strict adherence to a gluten-free diet in most patients with established celiac disease regardless of clinical symptoms:

•Multiple reports have suggested increased overall mortality (mostly from gastrointestinal malignancies) in patients with celiac disease compared with the general population [14-16]. Several studies have suggested that the risk is decreased in patients who adhere to a gluten-free diet [17-20]. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults".)

•Ongoing celiac disease activity even without symptoms may still result in the development other long-term complications. For example, patients may have micronutrient deficiencies that may ultimately have clinical consequences (such as bone loss due to vitamin D deficiency) [21]. (See 'Screening and prevention of micronutrient deficiencies' below.)

•The association between duration of gluten exposure and risk of development of other autoimmune disorders is controversial. While celiac disease is associated with autoimmune diseases such as type 1 diabetes mellitus, Hashimoto thyroiditis, and Graves disease [22-24], the data are discordant and coexistence of autoimmunity may be related to shared genetic predisposition rather than triggered by gluten itself. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'High-risk groups'.)

•Mothers with untreated celiac disease are at increased risk for having low birth weight newborns and preterm births [25,26].

Other dietary counseling

●General nutrition – Each patient's overall nutritional status should be considered so that nutritional and caloric deficiencies can be adequately supplemented. Patients with the classic presentation of celiac disease may be malnourished; their nutritional status typically improves rapidly after a gluten-free diet is initiated. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on '"Classical" gastrointestinal symptoms'.)

●Dairy – For some patients, avoiding dairy products initially may provide symptomatic relief because many patients with celiac disease have secondary lactose intolerance. Lactose can usually be added back to the diet by three to six months (when mucosal healing can be expected) and continued as tolerated. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)

●Fiber – A gluten-free diet may be low in fiber and may induce troublesome constipation. This usually responds to the addition of dietary fiber such as from psyllium or inulin.

●Bone health – Bone loss (principally osteopenia and less often osteoporosis) is common in celiac disease and can occur in patients without gastrointestinal symptoms [21,27-29]. Much of the bone loss is related to secondary hyperparathyroidism, which is probably due to vitamin D deficiency. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Non-gastrointestinal manifestations'.)

Children with celiac disease have reduced bone mass at the time of diagnosis, similar to adults with newly diagnosed celiac disease. However, children are more likely than adults to have fully restored bone mass after 6 to 12 months of a gluten-free diet [30-33]. Nutritional counseling should include instruction on age-appropriate intake of calcium and vitamin D [34].

Screening and prevention of micronutrient deficiencies — Patients with newly diagnosed celiac disease should undergo laboratory evaluation for iron deficiency anemia (using a complete blood count and ferritin) and vitamin D deficiency, and any deficiency should be corrected (table 2) [8]. Routine laboratory testing for other nutritional deficiencies is unnecessary, except in patients with very low body weight or other evidence of malnutrition [35].

We suggest a daily multivitamin for patients with newly diagnosed celiac disease, as suggested by an expert panel [35]. We also encourage patients to continue the supplement indefinitely because a gluten-free diet is associated with certain micronutrient deficiencies [36].

MONITORING THE RESPONSE TO A GLUTEN-FREE DIET — The rapidity of the response to a gluten-free diet is variable. Approximately 70 percent of patients have noticeable clinical improvement within two weeks [37]. Clinical tools to monitor celiac disease activity and response to the gluten-free diet are rather limited; symptom monitoring and autoantibody decline/resolution are commonly used. Periodic assessment by a skilled dietitian is also necessary to gauge dietary adherence.

Symptoms generally improve faster than do antibody levels or histology, especially when biopsies are obtained from the proximal intestine. While historical data indicate that mucosal healing rates are 95 percent in children [38], more recent evidence hints that mucosal healing on a gluten-free diet in pediatrics may not be as complete as previously thought [39,40].

Antibody testing — Celiac-specific antibodies levels can be measured to monitor the response to a gluten-free diet as a surrogate for celiac disease activity [8]. Antibody levels will decline on a gluten-free diet but may remain abnormal for up to two years, although this may vary based on the assay used for monitoring and the baseline elevation of the antibody level [41,42].

Tissue transglutaminase-immunoglobulin A antibodies (tTG-IgA) are usually used for this purpose; alternatives include anti-endomysial antibodies or deamidated gliadin peptide-immunoglobulin G antibodies (DGP-IgG). One study suggests that DGP may be slightly more sensitive to gluten exposure [43]. In IgA-deficient patients, tTG-IgG or DGP-IgG antibodies should be used to monitor dietary exposure to gluten [44]. (See "Diagnosis of celiac disease in children", section on 'Pretesting diet'.)

Monitoring should be performed as follows:

●For all patients, measure levels at three to six months after the start of treatment, then at approximately six month-intervals until normalized after beginning a gluten-free diet. A decrease in the antibody titer, with eventual disappearance in most individuals, is an indirect indicator of dietary adherence and recovery. In one series, 35 percent of children with celiac disease became seronegative for tTG-IgA within six months of beginning a gluten-free diet and 55 percent were seronegative within 12 months [45].

●If symptoms persist or recur after starting a gluten-free diet, repeat the antibody test. A significant rise in antibody levels may indicate that the individual is ingesting gluten (either knowingly or inadvertently) and should prompt careful review of the diet.

●For surveillance, measure levels approximately annually to monitor adherence to the gluten-free diet.

Although antibody testing is typically used to monitor response to a gluten-free diet, it may not be a reliable predictor of mucosal recovery. In one study of children who had been on a gluten-free diet for at least one year and underwent follow-up intestinal biopsies, approximately one in five (19 percent) had persistent enteropathy (defined by villous blunting or Marsh stage 3 damage), despite good adherence to the diet [39]. tTG-IgA was elevated in 43 percent of children who had persistent enteropathy and 32 percent of children who had mucosal recovery. Approximately one-half of the children with persistent enteropathy were asymptomatic, and the presence of symptoms did not predict enteropathy.

Very rarely, a patient is diagnosed with celiac disease on the basis of an abnormal intestinal biopsy despite negative results for all celiac-specific antibody tests; the diagnostic steps for such patients are discussed separately (see "Diagnosis of celiac disease in children", section on 'Pretesting diet'). In such cases, the response to a gluten-free diet could be monitored by changes in symptoms and/or repeat intestinal biopsy. (See 'Follow-up biopsy' below and "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Pathogenesis and risk factors'.)

Monitoring of nutrition and autoimmune disease — For all patients, we monitor the following, as indicated in the table (table 2) [35]:

●Monitoring of growth (height, weight, and body mass index)

●Complete blood count

●Iron status (by measuring ferritin)

●Thyroid-stimulating hormone – Patients with celiac disease have substantially increased risk of autoimmune thyroiditis that increases with age (see "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'High-risk groups')

●Aspartate and alanine aminotransferases – Patients with celiac disease have an increased risk of autoimmune hepatitis [46]

●Vitamin D status (by measuring 25-hydroxyvitamin D)

Laboratory testing for type 1 diabetes is not routinely needed but is appropriate for selected patients based on individual risk factors, clinical signs or symptoms, or prior test results. We counsel patients on the signs and symptoms of type 1 diabetes and perform screening if they develop symptoms.

FOLLOW-UP TESTING FOR SELECTED PATIENTS

Follow-up biopsy — There is ongoing controversy about the need for a follow-up biopsy in patients with clinical improvement, especially with new data to suggest lower rates of mucosal healing in children. (See "Diagnosis of celiac disease in children", section on 'Diagnosis'.)

We and many other clinicians do not routinely perform a repeat intestinal biopsy in patients with a definite diagnosis of celiac disease. This practice pattern is consistent with guidelines from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition [44]. However, the study cited above raises concerns about this monitoring approach since neither tissue transglutaminase-immunoglobulin A antibodies (tTG-IgA) nor symptoms were predictors of mucosal healing [39]. (See 'Antibody testing' above.)

For children who do not respond as anticipated to the gluten-free diet, we suggest a repeat endoscopy to evaluate for mucosal healing. The timing of repeat endoscopy will vary based on symptoms, gluten-free diet adherence, and antibody patterns. Although histologic improvement is usually seen within two years of being on a gluten-free diet, persistent abnormalities have been described, even in patients with symptomatic improvement [40,47,48]. After checking for dietary noncompliance or inadvertent ingestion of gluten, other causes of villous atrophy should be considered in these patients. (See 'Nonresponders' below.)

Gluten rechallenge — In the past, a gluten rechallenge was recommended for all patients to confirm the diagnosis of celiac disease. This is no longer required to confirm the diagnosis of celiac disease, consistent with many society guidelines [8,44,49,50]. (See "Diagnosis of celiac disease in children".)

A gluten rechallenge is usually reserved for cases in which the initial diagnosis of celiac disease remains in doubt. This includes children already on a gluten-free diet either without any prior testing for celiac disease or where there is a discrepancy between the antibody testing and the histologic findings on biopsies.

If the decision is made to perform a gluten rechallenge, a common protocol is to have the patient ingest at least 10 g of gluten per day (an amount contained in four slices of regular bread) for 8 to 12 weeks, followed by endoscopic biopsies. The biopsy should be performed earlier in patients who develop severe symptoms and are unable to tolerate the full duration of rechallenge. This approach also varies among practitioners, with some rechallenges involving as little as 3 g of gluten per day and for as little as two weeks [51]. Some clinicians will also avoid a gluten rechallenge during high-risk periods such as growth spurts. More research is needed to standardize the gluten rechallenge in pediatrics.

A rare hazard in a gluten rechallenge is the development of fulminant diarrhea, with resulting dehydration, acidosis, and other metabolic disturbances (a condition known as "gliadin shock" or "celiac crisis") [52]. Such patients should be treated with corticosteroids.

IMMUNIZATIONS — Patients with celiac disease should follow routine immunization schedules, with the following special considerations:

●Hepatitis B vaccine – It was previously believed that patients with celiac disease may not respond to the hepatitis B vaccine if administered prior to treatment with a gluten-free diet [35,53]. More recent studies have shown that individuals with celiac disease are not at higher risk of nonresponse than is the general population and, more importantly, are not at higher risk of hepatitis B virus infection [54]. However, some clinicians still perform serologic screening to determine the hepatitis B immune status. If found to be nonimmune to the hepatitis B virus, it is recommended that children undergo repeat immunization once they are on a gluten-free diet and are felt to have achieved mucosal healing. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Postvaccination serology'.)

●Pneumococcal vaccines – Indirect evidence from studies in adults showed that celiac disease is associated with hyposplenism and an increased risk for invasive pneumococcal disease [55-57]. Children with celiac disease have similarly been shown to have increased risk of pneumococcal infection, although the mechanism of this increased risk is less clear [57,58]. Therefore, it is particularly important to ensure that children with celiac disease receive the standard pneumococcal vaccine series during infancy. It might also be reasonable to screen affected children for evidence of hyposplenism with a complete blood count and peripheral smear (eg, "pitted" erythrocytes, Howell-Jolly bodies, and/or thrombocytosis) and to offer the additional vaccine booster to those with evidence of hyposplenism. Such patients also should receive additional meningococcal vaccination, as for other patients with functional asplenia. (See "Pneumococcal vaccination in children" and "Prevention of infection in patients with impaired splenic function".)

●Coronavirus disease 2019 (COVID-19) – Individuals with celiac disease are not considered to be at higher risk for COVID-19 infection or for more severe disease [59,60]. Recommendations for COVID-19 vaccination should follow governmental agency guidelines, and there are no contraindications for COVID-19 vaccination in celiac disease. (See "COVID-19: Vaccines".)

NONRESPONDERS — The majority of patients with celiac disease respond to a gluten-free diet. Patients who do not respond fall into four main categories:

●Ongoing gluten ingestion due to poor adherence or inadvertent gluten ingestion

●Concurrent gastrointestinal disorders that are causing similar symptoms

●Diseases that mimic the clinical and histologic features of celiac disease

●Refractory celiac disease (adults)

Another consideration in incomplete responders or nonresponders is that not all clinical features of celiac disease respond at the same rate. Furthermore, bone loss caused by secondary hyperparathyroidism and peripheral neuropathy may improve only partially despite a gluten-free diet [30]. Complete catch-up growth may not occur in affected children. (See 'Dermatitis herpetiformis' below and "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children".)

Ongoing gluten ingestion — The most common reasons for a lack of response are poor compliance or inadvertent gluten ingestion (table 1). Thus, a meticulous dietary history should be obtained and dietary counseling pursued with an experienced dietitian in patients who have continued symptoms, persistent histologic abnormalities, or persistently elevated serum antibody titers.

Preliminary studies suggest that monitoring of fecal gluten immunogenic peptides is a sensitive marker for recent (up to six days) gluten exposure and may be useful for monitoring adherence to a gluten-free diet, although commercially available assays do not provide quantitative results [61,62].

Trace amounts of gluten may be contained in products that are labeled as gluten-free. One study examined gluten exposures by testing foods for gluten and monitoring fecal and urine gluten immunogenic peptides and demonstrated that many adults with excellent adherence still had inadvertent gluten exposures [63]. However, the small amount of gluten contained in these products does not necessarily translate into refractory disease. A study evaluating occult gluten intake (from grain contaminants) among 76 patients on a gluten-free diet estimated that gluten contamination of up to 100 parts per million (up to a total of 30 mg per day) did not result in histologic injury [64]. Interestingly, 13 of 59 naturally gluten-free products and 11 of 24 wheat starch-based gluten-free products contained gluten ranging from 20 to 200 mg/kg. Gluten is a common additive in plastics. In one case report, remission was prevented by exposure to gluten from an orthodontic retainer [65].

If children have ongoing symptoms and persistent features of celiac disease on repeat biopsies despite apparent good adherence to a gluten-free diet, a time-limited trial of a gluten contamination elimination diet for up to 12 weeks should be considered. This is a very restrictive diet that is intended to eliminate any inadvertent exposures and not for long-term management of celiac disease [66].

Concurrent gastrointestinal disorders — Other diagnoses should be considered in patients who, despite apparent compliance, continue to have symptoms or do not have histologic improvement.

●Concomitant or secondary lactose intolerance is a possible cause of continued diarrhea and flatulence. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)

●Patients with celiac disease are susceptible to common bowel disturbances such as irritable bowel syndrome, which affects a large proportion of the general population and is characterized by chronic abdominal pain and altered bowel habits. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)

●A small percentage of patients with celiac disease develop small bowel bacterial overgrowth, which may respond to antibiotics [67]. (See "Small intestinal bacterial overgrowth: Management".)

Diseases that mimic celiac disease — A number of diseases associated with small bowel villous atrophy also should be excluded in patients with persistent symptoms who do not show histologic improvement (table 3) [68,69]. (See "Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma".)

Refractory celiac disease — Refractory celiac disease occurs almost exclusively in adults and very rarely in children. These patients meet all the diagnostic criteria for celiac disease but either no initial response to a gluten-free diet or have an initial response but subsequently develop refractory disease despite rigorous gluten abstinence [70]. The diagnostic workup and management of patients with refractory celiac disease in adults are discussed in detail separately. (See "Management of celiac disease in adults", section on 'Refractory sprue'.)

DERMATITIS HERPETIFORMIS — Dermatitis herpetiformis is a skin disorder that is closely associated with celiac disease. It is characterized by an itchy papular vesicular eruption usually located symmetrically on the elbows, knees, buttocks, sacrum, face, neck, trunk, and, occasionally, within the mouth (picture 1) [71]. The predominant symptoms are itching and burning that are rapidly relieved with rupture of the blisters. The vast majority of patients with dermatitis herpetiformis have associated celiac disease (gluten-sensitive enteropathy), but many of these patients have few or no gastrointestinal symptoms. (See "Dermatitis herpetiformis", section on 'Clinical findings'.)

Improvement in dermatitis herpetiformis following withdrawal of gluten may be considerably delayed (6 to 12 months) compared with the response of the intestinal manifestations of the disease [72]. As a result, treatment usually includes medical therapy (such as dapsone) in addition to gluten avoidance [71]. (See "Dermatitis herpetiformis", section on 'Treatment' and "Dermatitis herpetiformis", section on 'Treatment of children'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Celiac disease" and "Society guideline links: Dermatitis herpetiformis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Gluten-free diet (The Basics)")

●Beyond the Basics topic (see "Patient education: Celiac disease in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Whom to treat – Celiac disease is a genetically determined sensitivity to dietary gluten. Treatment depends on whether the diagnosis is serologically and histologically confirmed and whether the patient has symptoms attributable to the disease. (See 'Whom to treat' above.)

•Confirmed diagnosis – For patients with serologically and histologically confirmed celiac disease, treatment is as follows (see 'Confirmed diagnosis of celiac disease' above):

-Symptomatic patients – For patients with symptoms attributable to celiac disease, we recommend a lifelong gluten-free diet (Grade 1B). A gluten-free diet reduces or eliminates symptoms for most patients, restores normal growth, and may reduce long-term adverse health risks. The diet should be guided by in-depth consultation with an expert dietitian. (See 'Rationale for strict gluten avoidance' above.)

-Asymptomatic patients – For patients with few or no symptoms but with histologic evidence of celiac disease, we suggest a gluten-free diet (Grade 2C). The rationale for this weak recommendation is that a gluten-free diet may reduce the risk of long-term complications. However, the certainty of this benefit in asymptomatic patients is low and the dietary regimen may impair quality of life. Thus, some patients may choose to delay initiating a strict gluten-free diet, but this decision should be made in consultation with a gastroenterologist. (See 'Confirmed diagnosis of celiac disease' above.)

•"Potential" celiac disease – "Potential" celiac disease refers to patients who have positive serologic tests for celiac disease (tissue transglutaminase-immunoglobulin A antibodies [tTG-IgA] or endomysial antibody) but have normal small bowel biopsy. A gluten-free diet is not necessary in such patients if they are asymptomatic. However, it is important to ensure that the evaluation included multiple intestinal biopsies since histologic abnormalities can be patchy. These patients should be carefully monitored for growth failure and other symptoms that might suggest active celiac disease, and they should be rebiopsied if symptoms develop. (See 'Potential celiac disease' above.)

•Avoid premature initiation of a gluten-free diet – A gluten-free diet should not be initiated prior to serologic testing for celiac disease, because these tests may be falsely negative if performed while on a gluten-free diet. Moreover, a clinical response to a gluten-free diet is not sufficient to establish the diagnosis of celiac disease or of nonceliac gluten-sensitivity. (See 'Whom to treat' above and "Diagnosis of celiac disease in children".)

●Gluten-free diet – A gluten-free diet requires strict avoidance of wheat, rye, and barley (table 1). Patients require detailed dietary counseling to improve compliance and avoid common pitfalls in maintaining a gluten-free diet.

Pure oats (ie, uncontaminated by the other three grains) appear to be safely tolerated by most people with celiac disease, but tolerance varies. We generally advise that gluten-free oats are safe, and only eliminate oats for patients who do not respond as anticipated to the gluten-free diet. (See 'Principles of a gluten-free diet' above.)

●Monitoring the response

•Antibody testing – After establishing a gluten-free diet, specific serologic testing (tTG-IgA) should be repeated approximately every six months until it normalizes. A decrease in the antibody titer indicates adherence to the diet and supports the diagnosis of celiac disease. (See 'Antibody testing' above.)

●Additional testing (selected patients)

•Repeat biopsy – A repeat biopsy is generally not indicated in individuals with an established diagnosis of celiac disease. However, in some situations, a follow-up biopsy to evaluate for mucosal healing may be warranted. (See 'Follow-up biopsy' above.)

•Gluten rechallenge – Rechallenging the patient with gluten is not required to establish a diagnosis of celiac disease. However, gluten rechallenge may be helpful for selected patients in whom the diagnosis remains ambiguous after a trial of a gluten-free diet. (See 'Gluten rechallenge' above.)

●Follow-up – All patients with celiac disease should be reevaluated periodically. The evaluation should include assessment of growth, assessment of gastrointestinal and other symptoms associated with celiac disease, and review of the patient's understanding of and compliance with the gluten-free diet (table 2). We repeat tTG-IgA approximately every six months, then annually after it normalizes. We also repeat tTG-IgA in patients with recurrent or persistent symptoms. (See 'Monitoring the response to a gluten-free diet' above.)

●Nonresponders – The majority of patients with celiac disease respond to a gluten-free diet. The most common reasons for lack of response are poor compliance or inadvertent gluten ingestion. (See 'Nonresponders' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Ivor D Hill, MD who contributed to earlier versions of this topic review.