There is debate as to the benefits of screening. Some studies suggest that early detection would decrease the risk of osteoporosis and anaemia. In contrast, a cohort study suggested that people with undetected coeliac disease had a beneficial risk profile for cardiovascular disease (less overweight, lower cholesterol levels). There is limited evidence that screen-detected cases benefit from a diagnosis in terms of morbidity and mortality; hence, population-level screening is not presently thought to be beneficial.

The United States Preventive Services Task Force found insufficient evidence to make a recommendation among those without symptoms. In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends testing for coeliac disease in people with newly diagnosed chronic fatigue syndrome and irritable bowel syndrome, as well as in type 1 diabetics, especially those with insufficient weight gain or unexplained weight loss. It is also recommended in autoimmune thyroid disease, dermatitis herpetiformis, and in the first-degree relatives of those with confirmed coeliac disease.

Serology has been proposed as a screening measure, because the presence of antibodies would detect some previously undiagnosed cases of coeliac disease and prevent its complications in those people. However, serologic tests have high sensitivity only in people with total villous atrophy and have very low ability to detect cases with partial villous atrophy or minor intestinal lesions. Testing for coeliac disease may be offered to those with commonly associated conditions.

Although blood antibody tests, biopsies, and genetic tests usually provide a clear diagnosis, occasionally the response to gluten withdrawal on a gluten-free diet is needed to support the diagnosis. Currently, gluten challenge is no longer required to confirm the diagnosis in patients with intestinal lesions compatible with coeliac disease and a positive response to a gluten-free diet. Nevertheless, in some cases, a gluten challenge with a subsequent biopsy may be useful to support the diagnosis, for example in people with a high suspicion for coeliac disease, without a biopsy confirmation, who have negative blood antibodies and are already on a gluten-free diet. Gluten challenge is discouraged before the age of 5 years and during pubertal growth. The alternative diagnosis of non-coeliac gluten sensitivity may be made where there is only symptomatic evidence of gluten sensitivity. Gastrointestinal and extraintestinal symptoms of people with non-coeliac gluten sensitivity can be similar to those of coeliac disease, and improve when gluten is removed from the diet, after coeliac disease and wheat allergy are reasonably excluded.

Up to 30% of people often continue having or redeveloping symptoms after starting a gluten-free diet. A careful interpretation of the symptomatic response is needed, as a lack of response in a person with coeliac disease may be due to continued ingestion of small amounts of gluten, either voluntary or inadvertent, or be due to other commonly associated conditions such as small intestinal bacterial overgrowth (SIBO), lactose intolerance, fructose, sucrose, and sorbitol malabsorption, exocrine pancreatic insufficiency, and microscopic colitis, among others. In untreated coeliac disease, these are often transient conditions derived from the intestinal damage. They normally revert or improve several months after starting a gluten-free diet, but may need temporary interventions such as supplementation with pancreatic enzymes, dietary restrictions of lactose, fructose, sucrose or sorbitol containing foods, or treatment with oral antibiotics in the case of associated bacterial overgrowth. In addition to gluten withdrawal, some people need to follow a low-FODMAPs diet or avoid consumption of commercial gluten-free products, which are usually rich in preservatives and additives (such as sulfites, glutamates, nitrates and benzoates) and which might have a role in triggering functional gastrointestinal symptoms.

GSE, particularly coeliac disease, increases the risk of cancers of specific types. There are two predominant cancers associated with coeliac disease, cancer of the esophagus and lymphoproliferative diseases such as gluten-sensitive enteropathy-associated T-cell lymphoma (EATL). For non-EATL cancers it is thought the mineralemias such as zinc and selenium may play a role in increasing risk. GSE associated cancers are invariably associated with advanced coeliac disease, however, in de-novo EATL, the cancer is frequently detected in advance of the coeliac diagnosis, also EATL is the most common neoplasm.

Fibromyalgia was found in 9% of adult patients relative to 0.03% in the general population with a link common to IBD. Concurrent IBS is found in 30% to 70%. Small intestinal bacterial overgrowth is associated is common with a transient response to antimicrobial therapy.

Evaluating the presence of antigliadin antibodies (AGA) can be a useful complementary diagnostic test. Up to 50% NCGS patients may have elevated AGA IgG antibodies, but rarely AGA IgA antibodies (only 7% of the cases). In these patients, unlike in celiac disease people, the IgG AGA became undetectable within 6 months of using a gluten-free diet.

Many people remove gluten from the diet after a long history of health complaints and unsuccessful consultations with numerous physicians, who simply consider them as suffering from irritable bowel syndrome, or even before seeking medical attention. This fact can diminish the CD serological markers titers and may attenuate the inflammatory changes found in the duodenal biopsies. In these cases, patients should be tested for the presence of HLA-DQ2/DQ8 genetic markers because a negative HLA-DQ2 and HLA-DQ8 result has a high negative predictive value for celiac disease. If these markers are positive, it is advisable to undertake a gluten challenge under medical supervision, followed by serology and duodenal biopsies. However, gluten challenge protocols have significant limitations, because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for many patients. Gluten challenge is also discouraged before the age of 5 years and during pubertal growth.

It remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last. Some protocols recommend eating a maximum of 10 g of gluten per day for 6 weeks. Nevertheless, recent studies have shown that a 2-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven celiac disease. This new proposed protocol has shown higher tolerability and compliance. It has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% of patients referred for suspected NCGS, while the remaining 93% would be confirmed as NCGS; this is not yet universally adopted.

For people on a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify possible celiac disease is an in vitro gliadin challenge of small bowel biopsies; this test is only available at selected specialized tertiary-care centers.

The current gold standard diagnostic test for EE is intestinal biopsy and histological analysis. Histological changes observed include:

- Villous blunting

- Crypt hypertrophy

- Villous fusion

- Mucosal inflammation

However, this procedure is considered too invasive, complex and expensive to be implemented as standard of care. As a result, there are various research efforts underway to identify biomarkers associated with EE, which could serve as less invasive, yet representative, tools to screen for and identify EE from stool samples.

In an effort to identify simple, accurate diagnostic tests for EE, the Bill and Melinda Gates Foundation (BMGF) has established an EE biomarkers consortium as part of their Global Grand Challenges initiative (specifically, the Discover Biomarkers of Gut Function challenge).

So far, various biomarkers have been selected and studied based on the current understanding of EE pathophysiology:

- Gut permeability/barrier function

- Dual sugar permeability (lactose-to-mannitol ratio)

- Intestinal inflammation

- Alpha-1 anti-trypsin

- Neopterin

- Myeloperoxidase

- Exocrine (hormonal) markers

- Bacterial translocation markers

- Endotoxin core antibody

- Markers of systemic inflammation

- Alpha-1 glycoprotein

- C-reactive protein (CRP)

It is postulated that the limited of understanding of EE is partially due to the paucity of reliable biomarkers, making it difficult for researchers to track the epidemiology of the condition and assess the efficacy of interventions.

At least one study suggests that gluten neuropathy can be effectively treated with a gluten-free diet. In the study, 35 patients with gluten neuropathy adhered to a gluten-free diet, where adherence was monitored serologically. After one year, the treatment group had improved significantly compared to the control group. The indicators of improvements were improvements of sural sensory action potential and subjective improvement of neuropathic symptoms. Subgroup analysis suggested that severe neuropathy might imply reduced capacity for recovery of the peripheral nerves or longer recovery.

A literature review of 2014 found that non-coeliac gluten sensitivity diagnosis can be reached only by excluding celiac disease (CD) and wheat allergy.

Persons suspected of having celiac disease may undergo serological testing for IgA anti-tissue transglutaminase antibodies (abbreviated anti-tTG antibodies or anti-TG2 antibodies) and anti-endomysial antibodies (abbreviated EMA) provided the IgA-level is high, and if IgA is low, testing for certain IgG antibodies; in case of positive serological indication, a duodenal biopsy may confirm active celiac disease.

Eliminating the possibility of CD can generally also be done by adding HLA-DQ typing. The absence of HLA-DQ2 and HLA-DQ8 has a very high negative predictive value for CD, and the predictive value can be further enhanced by including HLA-DQ7.5 (HLA-DQ2 and HLA-DQ8 are found in coeliac disease 98% of the time in Caucasians, HLA-DQ7.5 present in the remaining 1.6% and only 0.4% of Caucasians are missed with the combination of these 3). Without serological or HLA-DQ2/8 positivity, celiac disease is likely not present. HLA-DQ typing has a practical advantage in that it is the only diagnostic test that allows to exclude CD when a patient is already on a gluten-free diet; however, as not only celiacs are HLA-DQ2/HLA-DQ8 positive, this method has a higher false positive rate than anti-TG2 and EMA antibody testing.

A four-of-five rule was proposed 2010 for confirming celiac disease, with the disease confirmed if at least four of the following five criteria are satisfied:

- typical symptoms of celiac disease;

- positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer;

- human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes;

- celiac enteropathy at the small bowel biopsy; and

- response to the gluten-free diet.

For diagnosis of wheat allergy, allergy tests are available.

There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE.

- The MAL-ED project

- The Alive and Thrive nutrition project

- The Sanitation, Hygiene and Infant Nutrition Efficacy (SHINE) Trial (ClinicalTrials.gov identifier: NCT01824940)

- The WASH Benefits Study

There is a diagnostic test for AIE that looks for an antibody against the enterocyte. The diagnostic test contains the Western Blot which can identify the antibody IgG or IgA and with the immunohistochemistry can localize these antibodies. Endoscopy with biopsies of the colon, small colon, stomach, and other locations may be helpful in diagnosing. This test is done to look at the stomach and small intestines and to see what cells are infiltrating the digestive tract. There are also documented cases of autoimmune enteropathy where the auto-antibodies were undetectable and the diagnosis was made on the basis of clinical presentation and response to treatment.

For patients with celiac disease, a lifelong strict gluten-free diet is the only effective treatment to date; for patients diagnosed with NCGS, there are still open questions concerning for example the duration of such a diet; for patients with wheat allergy, the individual average is six years of gluten-free diet, excepting persons with anaphylaxis, for whom the diet is to be wheat-free for life.

A gluten-free diet should not be started before the tests for excluding celiac disease have been performed, for the reason that the serological and biopsy tests for celiac disease are reliable only if the patient is consuming gluten.

Preferably, newly diagnosed celiacs seek the help of a dietician to receive support for identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. Knowledge of hidden sources of gluten is important for celiac disease patients as they need to be very strict regarding eating only gluten-free food; for NCGS patients, it is not certain how strict the diet needs to be. Balanced eating is important because unless particular care is taken, a gluten-free diet can be lacking in vitamins, minerals, and fiber, and be too high in fat and calories.

The inclusion of oats in gluten-free diets remains controversial. Avenin present in oats may also be toxic for coeliac sufferers. Its toxicity depends on the cultivar consumed. Furthermore, oats are frequently cross-contaminated with gluten-containing cereals.

Diagnosis of gluten-sensitive neuropathies without a clear cause is on the rise. These "idiopathic" neuropathies were first identified by screening for anti-gliadin IgG (AGA). The criteria have been critiqued because of the large misdiagnosis rate of coeliac disease (CD), and because AGA exists in the normal population at over 12%, far more abundant than cases of neuropathy. The problem in diagnosis arises because there are precursor states prior to coeliac disease. These are called coeliac disease and early gluten-sensitive enteropathy and are defined as Marsh grade 1 and 2 coeliac disease. Coeliac disease was diagnosed by duodenal biopsy, often misinterpreted as negative as high as grade 3 on the Marsh scale. Anti-gliadin antibodies may precede or lag the appearance of coeliac disease. Studies in Scandinavia found an increase of pathologies as much as 10 years before coeliac disease. These included gastrointestinal symptoms, anemia or other autoimmune disease. In addition IgG and IgA responses sometimes accompany allergic responses to proteins. Gliadin is exceptional in that it has several proteins which remain peptides of considerable length after digestion, and migrate into systemic circulation.

A subset of people with idiopathic neuropathies have only anti-gliadin antibodies but none of the other enteropathic criteria. About 1/3 have no DQ2 or DQ8 and an apparent abundance of HLA-DQ1. One percent of coeliacs in Europe have no DQ2 and DQ8 but have DQ1. The DQ1 serotype is very common in the normal population, over 65% of Americans have one copy, therefore the linkage is speculative.

There is a great deal of conflicting information regarding the inclusion of oats in a gluten-free diet. Although cross-contamination in the field and during processing partially explains the different reactions that celiacs can have to oats, a recent study indicates that there are also different amounts of avenin present in different cultivars of oat. The G12 antibody used in the study is currently the only one that can reliably distinguish between varieties of oat. Previous studies have indicated both children and adult coeliacs are largely tolerant of oats. Other studies have followed both children and adults for one, two, and five years on the "uncontaminated" oat containing gluten-free diet. These studies failed to show significant changes in intestinal morphology indicative of a relapse of celiac disease. Anti-gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) did not differ significantly between oat-eating celiacs and non-oat-eating controls in remission. Invitro tests that are sensitive to wheat gluten found that tryptic peptides of avenin could not induce EMA production in supernatant fluid from cultured duodenal mucosa specimen from celiac patients.

Algorithms that successfully predict T cell stimulatory peptides in gluten identified many similar peptides in hordeins and secalins, but not in oat avenins.

The Canadian Celiac Association suggests that adults can consume up to 70g of oats per day, and children up to 25g. However, two studies indicated that celiac adults could consume 93 grams (3.3 ounces) of oats per day. There is no evidence that oats can trigger GSE, only that in a small number of celiacs disease can be sustained or reinitiated by oats once triggered by wheat. A recent paper examining the IEL levels of celiac patients in remission showed a significantly higher number of IELs in oat-eating celiacs. In addition, antibodies to avenin remain low as long as the diet is gluten-free, but higher anti-avenin antibodies can increase with a diet containing wheat.

Some coeliacs respond adversely to oats. Estimates range from 0.5 to 20% of the GSE population. With coeliac disease, non-compliance in attempting to achieve normal intestinal morphology is a risk factor for refractory disease and cancer.

Common clinical signs and symptoms of Whipple's disease include diarrhea, steatorrhea, abdominal pain, weight loss, migratory arthropathy, fever, and neurological symptoms. Weight loss and diarrhea are the most common symptoms that lead to identification of the process, but may be preceded by chronic, unexplained, relapsing episodes of non-destructive seronegative arthritis, often of large joints.

Diagnosis is made by biopsy, usually by duodenal endoscopy, which reveals PAS-positive macrophages in the lamina propria containing non-acid-fast gram-positive bacilli. Immunohistochemical staining for antibodies against "T. whipplei" has been used to detect the organism in a variety of tissues, and a PCR-based assay is also available. PCR can be confirmatory if performed on blood, vitreous fluid, synovial fluid, heart valves, or cerebrospinal fluid. PCR of saliva, gastric or intestinal fluid, and stool specimens is highly sensitive, but not specific enough, indicating that healthy individuals can also harbor the causative bacterium without the manifestation of Whipple's disease, but that a negative PCR is most likely indicative of a healthy individual.

Endoscopy of the duodenum and jejunum can reveal pale yellow shaggy mucosa with erythematous eroded patches in patients with classic intestinal Whipple's disease, and small bowel X-rays may show some thickened folds. Other pathological findings may include enlarged mesenteric lymph nodes, hypercellularity of lamina propria with "foamy macrophages", and a concurrent decreased number of lymphocytes and plasma cells, per high power field view of the biopsy.

A D-Xylose test can be performed, which is where the patient will consume 4.5g of D-xylose, a sugar, by mouth. The urine excretion of D-Xylose is then measured after 5 hours. The majority of D-Xylose is absorbed normally, and should be found in the urine. If the D-Xylose is found to be low in the urine, this suggests an intestinal malabsorption problem such as bacterial overgrowth of the proximal small intestine, Whipple's Disease, or an autoimmune with diseases such as Celiac's Disease (allergy to gluten) or Crohn's Disease (autoimmune disease affecting the small intestine). With empiric antibiotic treatment after an initial positive D-Xylose test, and if a follow-up D-Xylose test is positive (decreased urine excretion) after antibiotic therapy, then this would signify it is not bacterial overgrowth of the proximal small intestine. Since Whipple's disease is so rare, a follow-up positive D-Xylose test more likely indicates a non-infectious etiology and more likely an autoimmune etiology. Clinical correlation is recommended to rule out Whipple's disease.

Dermatitis herpetiformis is often misdiagnosed, being confused with drug eruptions, contact dermatitis, dishydrotic eczema (dyshidrosis), and even scabies.

The diagnosis can be confirmed by a simple blood test for IgA antibodies against tissue transglutaminase (which cross-react with epidermal transglutaminase), and by a skin biopsy in which the pattern of IgA deposits in the dermal papillae, revealed by direct immunofluorescence, distinguishes it from linear IgA bullous dermatosis and other forms of dermatitis. These tests should be done before the patient starts on a gluten-free diet, otherwise they might produce false negatives. Like in ordinary celiac disease, IgA against transglutaminase disappears (often within months) when patients eliminate gluten from their diet. Thus, for both groups of patients, it may be necessary to restart gluten for several weeks before testing can be done reliably. In 2010, "Cutis" reported an eruption labelled "gluten-sensitive dermatitis" which is clinically indistinguishable from dermatitis herpetiformis but lacks the IgA connection, similar to gastrointestinal symptoms mimicking coeliac disease but without the diagnostic immunological markers.

The first line of treatment are corticosteroids and other medicines used to suppress the immune system such as tacrolimus and sirolimus.

A intravenous nutrition such as total parenteral nutrition and/or a special diet may be necessary. Hematopoietic stem cell transplantation may be curative.

The diagnosis of protein losing enteropathy is made by excluding other causes of protein loss. Endoscopy can be used to localize the cause of the protein loss in the bowel. Different methods include faecal excretion of alpha 1-antitrypsin which is a marker of protein losing enteropathy, as well as, viral serologies which may be useful to detect PLE.

The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.

Talley et al. suggested 3 diagnostic criteria which is still widely used:

1. the presence of gastrointestinal symptoms,

2. histological demonstration of eosinophilic infiltration in one or more areas of the gastrointestinal tract or presence of high eosinophil count in ascitic fluid (latter usually indicates subserosal variety),

3. no evidence of parasitic or extraintestinal disease.

Hypereosinophilia, the hallmark of allergic response, may be absent in up to 20% of patients, but hypoalbuminaemia and other abnormalities suggestive of malabsorption may be present.

CT scan may show nodular and irregular thickening of the folds in the distal stomach and proximal small bowel, but these findings can also be present in other conditions like Crohn's disease and lymphoma.

The endoscopic appearance in eosinophilic gastroenteritis is nonspecific; it includes erythematous, friable, nodular, and occasional ulcerative changes.

Sometimes diffuse inflammation results in complete loss of villi, involvement of multiple layers, submucosal oedema and fibrosis.

Definitive diagnosis involves histological evidence of eosinophilic infiltration in biopsy slides. Microscopy reveals >20 eosinophils per high power field. Infiltration is often patchy, can be missed and laparoscopic full thickness biopsy may be required.

Radio isotope scan using technetium (Tc) exametazime-labeled leukocyte SPECT may be useful in assessing the extent of disease and response to treatment but has little value in diagnosis, as the scan does not help differentiating EG from other causes of inflammation.

When eosinophilic gastroenteritis is observed in association with eosinophilic infiltration of other organ systems, the diagnosis of idiopathic hypereosinophilic syndrome should be considered.

Treatment is primarily through diet. Dietary fiber and fat can be increased and fluid intake, especially fruit juice intake, decreased. With these considerations, the patient should consume a normal balanced diet to avoid malnutrition or growth restriction. Medications such as loperamide should not be used. Studies have shown that certain probiotic preparations such as "Lactobacillus rhamnosus" (a bacterium) and "Saccharomyces boulardii" (a yeast) may be effective at reducing symptoms.

Patients show markedly low immunoglobulin levels of IgG, IgA, and IgM.

The appearance of microvillous inclusion disease on light microscopy is similar to celiac sprue; however, it usually lacks the intraepithelial lymphocytic infiltration characteristic of celiac sprue and stains positive for carcinoembryonic antigen (CEA).

The definitive diagnosis is dependent on electron microscopy.

There is no single, specific test for malabsorption. As for most medical conditions, investigation is guided by symptoms and signs. A range of different conditions can produce malabsorption and it is necessary to look for each of these specifically. Many tests have been advocated, and some, such as tests for pancreatic function are complex, vary between centers and have not been widely adopted. However, better tests have become available with greater ease of use, better sensitivity and specificity for the causative conditions. Tests are also needed to detect the systemic effects of deficiency of the malabsorbed nutrients (such as anaemia with vitamin B12 malabsorption).

The differential diagnosis of chronic and intractable diarrhea is:

- Intestinal epithelial dysplasia

- Syndromatic diarrhea

- Immunoinflammatory enteropathy