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 recommended for both diagnostic and therapeutic purposes in individuals with a provisional diagnosis of celiac disease. If celiac disease is confirmed, the diet should be continued lifelong.

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 patient with celiac disease begins with dietary counseling to establish a gluten-free diet. Management also includes addressing nutritional needs (including the prevention of bone loss), monitoring the response to gluten elimination, and further evaluating patients who do not respond.

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

●Consultation with a skilled dietitian

●Education about the disease

●Lifelong adherence to a gluten-free diet

●Identification and treatment of nutritional deficiencies

●Access to an advocacy group

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

WHOM TO TREAT

Provisional diagnosis of celiac disease — Treatment with a gluten-free diet is recommended for both diagnostic and therapeutic purposes for all children who have a provisional diagnosis of celiac disease. The diagnosis of celiac disease is confirmed if the child responds to the gluten-free diet, with improvement in clinical symptoms and antibody tests. It is important to perform serologic testing for celiac disease before initiating a gluten-free diet because these tests may be falsely negative if performed while on a gluten-free diet.

A provisional diagnosis of celiac disease can be made in:

●Children with characteristic findings on intestinal biopsy and symptoms consistent with celiac disease (including nonspecific symptoms such as constipation or abdominal pain).

●Children with characteristic findings on intestinal biopsy who belong to a high-risk group (eg, relatives of patients with established celiac disease or patients with type 1 diabetes), whether or not there are associated symptoms (table 1).

●Selected patients who are diagnosed with celiac disease because of very high results of tissue transglutaminase-immunoglobulin A antibodies (tTG-IgA) testing (>10 times the upper limit of normal) and positive results of anti-endomysial-IgA antibody, as well as symptoms typical for celiac disease. (See "Diagnosis of celiac disease in children", section on 'Is biopsy necessary for all patients?'.)

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 are diagnosed with gluten sensitivity by a positive tTG-IgA or endomysial antibody but who have a normal small bowel biopsy. For these patients, management decisions are based on the presence of symptoms:

●For children who are truly asymptomatic, a gluten-free diet is not recommended. However, these patients should be monitored and rebiopsied if symptoms develop. Because a child may not effectively communicate about symptoms that may herald active disease, periodic reevaluation for symptoms and appropriate growth is important. An additional endoscopy with biopsies should be performed when appropriate in high-risk patients (eg, those who develop gastrointestinal symptoms and/or have rising titers of celiac serologic tests).

●For children with symptoms attributable to 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 to continue the gluten-free diet if the child's symptoms improve and antibody tests return to normal.

Before considering a patient to have potential celiac disease, it is important to repeat the antibody testing and to make certain that the intestinal biopsies were adequate. The histologic abnormalities of celiac disease can be patchy, so multiple biopsies must be taken from both the distal duodenum and duodenal bulb, and these should be evaluated by an expert pathologist [2]. In addition, we generally recommend further serologic testing using a second specific antibody (eg, anti-endomysial IgA antibodies). HLA testing may also be helpful; if the patient has neither the DQ2 nor DQ8 genotype, the likelihood of having celiac disease is extremely low.

PRINCIPLES OF A GLUTEN-FREE DIET — The cornerstone of treatment of celiac disease is the lifelong elimination of gluten in the diet. The principle sources of dietary gluten are wheat, rye, and barley. Pure oats are probably safely tolerated by patients with celiac disease, but there is some controversy on this issue. (See 'Oats' below.)

Cereal chemistry — Gluten refers to the protein fraction of wheat flour, also known as "prolamins" due to the high content of the amino acids proline and glutamine. Gluten consists of an alcohol-soluble fraction, gliadin, and an alcohol-insoluble fraction, glutenin. Prolamins from other cereals are secalins from rye and hordeins from barley. The term gluten is often used loosely to refer to all prolamins found in wheat, rye, and barley.

The taxonomic relationship among the major cereal grains predicts their relative toxicity in celiac disease (figure 1). Wheat, rye, and barley belong to the tribe known as Triticeae, while oats belong to a neighboring tribe (Aveneae). Thus, the prolamins in wheat, barley, and rye (gluten, hordein, and secalin, respectively), are genetically and structurally more similar to each other than they are to the prolamin in oats (avenin). Nonetheless, there is some immunologic cross-reactivity between oats and these other grains. However, despite the greater genetic difference, the oat prolamins have some immunologic cross-reactivity with those from wheat, barley, and rye that reflects their common ancestry [3,4].

The antibodies that are raised against gluten proteins are discussed in detail separately. (See "Diagnosis of celiac disease in children", section on 'How to test'.)

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 [5]. Our clinical approach is as follows:

●For patients with newly diagnosed celiac disease, avoid oats during the first 6 to 12 months of a gluten-free diet, until the disease is clearly in remission as indicated by improvement in symptoms and celiac-specific antibody testing.

●For patients whose disease is in remission after a stringent gluten-free diet or for those with mild disease in presentation, permit consumption of oats but limit the quantity to 50 to 60 g/day (approximately 2 oz). The patients should be followed carefully for clinical or serologic evidence of disease recurrence after reintroducing oats [5].

●Oats also should be avoided if the purity cannot be guaranteed because contamination with even small amounts of other cereals can cause damage to the intestinal tract [6]. For example, mills that are not dedicated to processing oats alone may cross-contaminate oats with gluten from other grains.

This approach is supported by several randomized studies in adults that suggested that oats caused no differences in nutritional status, symptoms, or laboratory or histologic measures after one or five years [7-9], and a meta-analysis of 10 studies concluded that there is no good evidence that consumption of oats causes mucosal damage in patients with celiac disease [10]. Among 165 patients included in the studies, only one developed histologic changes. Similarly, several randomized trials in children with celiac disease in remission suggest that oat consumption is tolerated [7,11,12]. There were no significant differences in clinical, histologic, or biochemical markers of disease activity during long-term follow-up.

It is possible that tolerance of oats depends on the quantity consumed. Oats contain a sequence homology (ie, QQQPF) with gliadin peptides, which have been shown to be disease-activating [8,9]. However, oats contain a small proportion of this homologous sequence, and this homology may not be relevant since T-cell activation requires larger epitopes. Indeed, some clinical studies suggest that tolerance to oats depends at least in part on the total amount consumed [10]. Daily oats consumption less than 40 to 60 g/day by patients whose celiac disease is in remission appears to be well tolerated, while larger daily intake is associated with disease recurrence [10].

Despite these observations, the long-term safety of oat consumption in patients with celiac disease is uncertain, and 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. Furthermore, some patients may be exquisitely sensitive to oat prolamins. Thus, our approach is to offer oats only to patients whose disease is in remission, and only in limited quantities, as described above.

NUTRITIONAL CONSIDERATIONS

Dietary counseling — Consumption of a gluten-free diet requires a major lifestyle change because gluten is contained in many common foods in a Western diet (table 2). It is important to provide written information and dietary counseling to improve compliance, ideally from a registered dietitian with expertise in this area [5]. A number of resources are available for patients with celiac disease, including a variety of cookbooks, gluten-free prepared foods, and online organizations (The National Celiac Association, The Celiac Disease Foundation, Coeliac UK, Celiac.com). (See "Patient education: Celiac disease in adults (Beyond the Basics)".)

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

●Avoid all foods containing wheat, rye, and barley.

●Rice, corn, buckwheat, and potatoes can be safely eaten, as can foods with soybean or tapioca flours.

●Advice regarding consumption of oats is discussed above. (See 'Oats' above.)

●Read labels on prepared foods and condiments carefully, paying particular attention to additives such as stabilizers or emulsifiers that may contain gluten.

●Avoid dairy products initially since many patients with celiac disease have secondary lactose intolerance. Lactose may be added back to the diet after three to six months (when mucosal healing can be expected) and continued as tolerated. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)

●Medications (pills) generally contain minimal gluten and do not need to be avoided. An exception is that certain antacid medications use wheat flour as an excipient. Information about gluten-free drugs is available on the internet (eg, glutenfreedrugs.com).

●A gluten-free diet is low in fiber and may induce troublesome constipation. This usually responds to the addition of dietary rice bran and ispaghula husks; psyllium fiber or methylcellulose supplements are also generally gluten-free.

In addition, each patient's overall nutritional status should be considered so that nutritional and caloric deficiencies can be adequately supplemented.

There is some disagreement over the strict definition and product labeling of gluten-free foods. Foods must contain no more than 20 ppm of gluten to be considered gluten-free [13]. A review of the literature by an expert panel concluded that the lower threshold of gliadin intake that causes mucosal damage is between 10 and 100 mg daily [14].

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 want 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 [15-17]. Several studies have suggested the risk is decreased in patients who adhere to a gluten-free diet [18-21]. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults".)

•Despite feeling clinically well, patients may have micronutrient deficiencies that may ultimately have clinical consequences (such as bone loss due to vitamin D deficiency) [22]. (See 'Prevention of bone loss' below.)

•The duration of gluten exposure may be associated with increased risk for other autoimmune disorders, such as type 1 diabetes mellitus, connective tissue diseases, Hashimoto thyroiditis, and Graves disease. This association was reported in some studies [23,24], although discordant data have also been reported [25]. (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 [26,27].

Management of micronutrient deficiencies — We suggest a daily multivitamin for patients with newly diagnosed celiac disease, as suggested by an expert panel [28]. Long-term vitamin supplementation is not needed after full recovery on a gluten-free diet. Patients with newly diagnosed celiac disease should undergo laboratory evaluation for iron deficiency anemia (using a complete blood count, ferritin, and serum iron levels), and vitamin D deficiency, and any deficiency should be corrected (table 3) [5]. Routine laboratory testing for other nutritional deficiencies is unnecessary except in patients with very low body weight or other evidence of malnutrition [28].

Prevention of bone loss — Bone loss (principally osteopenia and less often osteoporosis) is common in celiac disease and can occur in patients without gastrointestinal symptoms [22,29-31]. 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 'Metabolic bone disease'.)

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 [32-34]. Nutritional counseling should include instruction on age-appropriate intake of calcium (700 mg for ages 1 to 3 years, 1000 mg for ages 4 to 8 years, and 1300 mg for 9 to 18 years) and vitamin D (15 micrograms [600 international units] daily) [35].

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 [36]. As a general rule, symptoms improve faster than histology, especially when biopsies are obtained from the proximal intestine. The reason is incompletely understood; however, a likely explanation is that the proximal intestine, which typically is affected more severely because of relatively increased exposure to gluten, recovers more slowly than the less severely damaged distal small intestine [37].

The diagnosis of celiac disease is confirmed if a patient with presumptive celiac disease responds to a gluten-free diet. A positive response to a gluten-free diet is based on symptom resolution and a decrease and eventual disappearance of celiac-specific antibodies. In general, follow-up biopsy and gluten rechallenge are not necessary if patients have shown clinical improvement. (See 'Biopsy' below and 'Gluten rechallenge' below.)

Antibody testing — Celiac-specific antibodies levels should be measured to monitor the response to a gluten-free diet [5]. 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 [38]. In IgA-deficient patients, tTG-IgG or DGP-IgG antibodies should be used to monitor dietary exposure to gluten [39]. (See "Diagnosis of celiac disease in children", section on 'Antibody testing'.)

Monitoring should be performed as follows:

●For all patients, measure levels 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 CD became seronegative for tTG-IgA within six months of beginning a gluten-free diet and 55 percent were seronegative within 12 months [40]. Once the levels are normalized, measure antibody levels annually.

●Test patients with persistent or recurrent symptoms at any time after starting a gluten-free diet. A rise in antibody levels may indicate that the individual is knowingly or inadvertently ingesting gluten and should prompt careful review of the diet.

●For asymptomatic patients, 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 3 damage), despite good adherence to the diet [41]. 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.

Biopsy — The need for a follow-up biopsy in patients with clinical improvement has been debated, especially since serologic testing can be used to monitor recovery and compliance with the diet. (See "Diagnosis of celiac disease in children", section on 'Diagnosis'.)

We and many other clinicians do NOT perform a repeat intestinal biopsy in patients with a definite diagnosis of celiac disease who have all of the following characteristics:

●Symptoms suggestive of celiac disease and elevated tTG-IgA, or anti-endomysial antibodies at presentation.

●Initial intestinal biopsy with histologic changes characteristic of celiac disease (Marsh type 3 villous atrophy).

●Complete resolution of symptoms on a gluten-free diet and progressive decrease in tTG-IgA antibodies, with eventual normalization.

This recommendation is consistent with guidelines from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) [39]. However, the study cited above raises concerns about this monitoring approach since neither tTG-IgA antibodies nor symptoms were predictors of mucosal healing [41]. A study in children suggested that a combination of tTG-IgA and DGP-IgG is a more reliable indicator of mucosal healing [42]. Larger and prospective studies are needed to further investigate these findings and to establish the optimal monitoring strategy, which might include use of combinations of antibodies for follow-up serologic testing or use of follow-up biopsies in all patients.

For children who do not meet one or more of the above characteristics, we suggest a second small intestinal biopsy 9 to 12 months after beginning a gluten-free diet to demonstrate histologic improvement. Although histologic improvement is usually seen by this time, persistent abnormalities have been described, even in patients with symptomatic improvement [43,44]. The significance of this finding is unclear, but in many cases the abnormalities do not appear to be linked with dietary indiscretion. 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 — For patients who respond to a gluten-free diet with improvement in symptoms and antibodies, a gluten rechallenge (a traditional approach to diagnosis of celiac disease) is generally not required to confirm the diagnosis of celiac disease, consistent with many society guidelines [5,39,45,46]. (See "Diagnosis of celiac disease in children".)

A gluten challenge 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.

To perform a gluten rechallenge, the patient should ingest at least 10 g of gluten per day (an amount contained in four slices of regular bread) for four to six weeks, followed by endoscopic biopsies. The biopsy date should be advanced in patients who develop severe symptoms.

A rare hazard in giving 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") [47]. Such patients should be treated with corticosteroids.

OTHER ASPECTS OF MANAGEMENT — In addition to monitoring celiac serologies as outlined above, we suggest the following procedures in routine follow-up:

Monitoring of nutrition and autoimmune disease

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

●Complete blood count

●Thyroid-stimulating hormone

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

We perform this periodic monitoring for thyroid disease because patients with celiac disease have substantially increased risk of autoimmune thyroiditis, and that risk increases with age (see "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Autoimmune thyroiditis'). Testing for other autoimmune diseases is not routinely needed but is appropriate for selected patients based on individual risk factors, clinical signs or symptoms, or prior test results (table 3) [28].

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

●Hepatitis B vaccine – Patients with celiac disease may not respond to the hepatitis B vaccine if administered prior to treatment with a gluten-free diet [28,48]. Therefore, patients should undergo serologic screening to determine their hepatitis B immune status. If found to be nonimmune to the hepatitis B virus, it is recommended that they 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 – Because patients with celiac disease may be at increased risk for invasive pneumococcal disease, it is particularly important to ensure that they receive the standard pneumococcal vaccine series (13-valent pneumococcal conjugate vaccine [PCV13], four doses during infancy), as for healthy children. In addition, we suggest that children with celiac disease receive the additional series of polysaccharide vaccine as appropriate for their age (23-valent pneumococcal polysaccharide vaccine [PPSV23], after two years of age), as is recommended for children with functional asplenia [49,50]. Alternatively, it would be reasonable to screen affected children for evidence of hyposplenism (eg, by counting "pitted" erythrocytes by interference contrast microscopy) and to offer the additional vaccine series 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".)

The rationale for additional attention to pneumococcal vaccination is based on indirect evidence from studies in adults that showed that celiac disease is associated with hyposplenism and with an increased risk for invasive pneumococcal disease [51-53]. As an example, one study found that one-third of adults with untreated celiac disease had laboratory evidence of hyposplenism [51]. In children with celiac disease, hyposplenism appears much less commonly [54] and it may be reversible on a gluten-free diet [55]. Thus, it remains unclear whether children with celiac disease have a significantly increased risk for pneumococcal disease compared with healthy children, especially after treatment with a gluten-free diet. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children".)

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 sprue

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 [32]. (See 'Dermatitis herpetiformis' below and "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children".)

Investigation for ongoing gluten ingestion — The most common reasons for a lack of response are poor compliance or inadvertent gluten ingestion (table 2). 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 [56,57].

Trace amounts of gluten may be contained in products that are labeled as gluten-free. 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 [58]. 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 [59].

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 [60]. (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 4) [61]. (See "Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma".)

Refractory sprue — Refractory sprue (also referred to as "unclassified sprue") occurs almost exclusively in adults and very rarely in children. Adults have either no initial response to a gluten-free diet or initial response followed by subsequent development of refractory disease despite gluten abstinence [62].

The diagnostic workup and management of patients with refractory sprue is discussed in detail separately. (See "Management of celiac disease in adults", section on 'Refractory sprue'.)

DERMATITIS HERPETIFORMIS — Celiac disease is associated with a number of skin disorders of which dermatitis herpetiformis is the most common (table 5) [63]. Dermatitis herpetiformis 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 1A-B). 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 to the response of the intestinal manifestations of the disease [64]. As a result, treatment usually includes medical therapy (such as dapsone) in addition to gluten avoidance [63]. (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

●Celiac disease is a genetically determined sensitivity to dietary gluten, which causes intestinal inflammation and loss of villous surface area with consequent macro- and micronutrient malabsorption. Most cases respond to treatment with a strict gluten-free diet.

●It is important to perform serologic testing for celiac disease before initiating a gluten-free diet 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 non-celiac gluten-sensitivity. (See 'Whom to treat' above and "Diagnosis of celiac disease in children".)

●Patients with serologically and histologically confirmed celiac disease and compatible clinical or laboratory manifestations should adhere to a gluten-free diet for life. For patients with symptoms, we recommend strict avoidance of gluten (Grade 1A). For patients with few or no symptoms but with histologic evidence of celiac disease, we also suggest strict gluten avoidance (Grade 2C). This suggestion recognizes that there are no controlled trials examining the long-term effects of a gluten-free diet in asymptomatic patients or comparing a low-gluten diet to a gluten-free diet and also that quality of life may be adversely affected by the dietary regimen. The diet should be guided by in-depth consultation with an expert dietitian. (See 'Rationale for strict gluten avoidance' above.)

●A gluten-free diet requires strict avoidance of wheat, rye, and barley. Although pure oat products appear to be safely included in a gluten-free diet for up to five years, the long-term safety remains unknown. For patients with disease that is in remission, we suggest permitting oat consumption limited in quantity to 50 to 60 g/day (approximately 2 oz) (Grade 2C). These patients should be followed carefully for clinical or serologic evidence of disease recurrence after reintroducing oats. (See 'Oats' above.)

●Patients with positive tests for tissue transglutaminase-immunoglobulin A antibodies (tTG-IgA) or anti-endomysial antibodies but normal small bowel histology are considered to have "potential" celiac disease. We suggest not treating such patients with a gluten-free diet if they are truly asymptomatic (Grade 2C). However, it is important to ensure that such patients were fully evaluated with multiple intestinal biopsies since the histologic abnormalities can be patchy. These patients should also be carefully monitored for growth failure and other symptoms that might suggest active celiac disease and should be rebiopsied if symptoms develop. (See 'Potential celiac disease' above.)

●Celiac disease is associated with hyposplenism, albeit more so in adults than in children. We suggest that patients with celiac disease receive supplemental pneumococcal vaccine as indicated for other patients with increased risk for invasive pneumococcal disease (Grade 2C). (See 'Immunizations' above.)

●We use the following approach to monitor a patient with celiac disease after establishment of a gluten-free diet. (See 'Monitoring the response to a gluten-free diet' above.)

•Specific serologic testing should be repeated approximately every six months until normalized on a gluten-free diet. A decrease in the antibody titer indicates adherence to the diet and supports the diagnosis of celiac disease. Once the serologic test has normalized, it can be measured annually. (See 'Antibody testing' above.)

•When patients present with typical symptoms, have characteristic laboratory and histologic findings, and respond well to a gluten-free diet, as measured by symptoms and antibodies, the diagnosis of celiac disease is clearly established. For these patients, we do not repeat the duodenal biopsy after beginning a gluten-free diet. (See 'Biopsy' above.)

•For patients who do not meet all of the criteria above, the diagnosis of celiac disease is less firmly established. For these patients, we generally perform a second biopsy after 9 to 12 months of a strict gluten-free diet. (See 'Biopsy' above.)

•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.)

●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 (table 2). All patients with celiac disease should be reevaluated periodically. The evaluation should include assessment of growth, gastrointestinal and other symptoms associated with celiac disease, and review of the patient's understanding of and compliance with the gluten-free diet (table 3). We measure tTG-IgA or other specific antibodies annually and in patients with persistent or recurrent symptoms. (See 'Monitoring the response to a gluten-free diet' above.)