Celiac disease, such as diagnostic tests

Gluten is a complex of proteins that contain prolamins. There are different types of prolamins, including gliadin, secalin and hordein respectively present in wheat, rye and barley, the most toxic cereals for celiac subjects.

In common language, however, it is normal to extend the term gluten also to the proteins of other cereals that must be excluded from the diet of a celiac, such as spelt, oats, kamut, triticale, bulgur, spelt.

What is celiac disease

Celiac disease is the most frequent genetic disease in the population and is estimated to have a prevalence of 1% worldwide. In genetically predisposed subjects, the ingestion of gluten triggers an abnormal immune reaction that determines chronic inflammation of the small intestine with the progressive atrophy of the intestinal villi. These, with the passage of time, “flatten” losing the ability to assimilate nutrients such as iron, vitamins, minerals, proteins, fats and sugars.

According to the 2015 Annual Report to Parliament on celiac disease, in Italy there are about 183,000 celiac individuals, 70% of whom are women. A figure that is increasing compared to past years due to the greater attention to the disease, although probably not corresponding to reality due to the existence of many asymptomatic and not yet diagnosed forms.

Celiacs, in fact, you become. Today it has been established that the disease can also develop during adult life, in conjunction with events that can favor its onset, such as viral infections, acute emotional trauma, pregnancy, surgery. In practice, the development of the disease is the result of the combination of genetic and environmental factors, the latter still unknown. Celiac disease is a benign disease, but if left untreated it can expose the individual to the risk of complications, such as intestinal lymphoma. Celiacs are also at greater risk of developing other autoimmune diseases.

Symptoms

The symptoms of celiac disease are very varied and can affect not only the digestive system, but also other systems. Among the intestinal symptoms, are frequent abdominal pain, intestinal disorders, diarrhea, bloating, constipation.

Less typical symptoms are bone and joint pain, mood changes, alopecia, mouth ulcers, damage to enamel and tooth color. Fatigue, chronic fatigue, muscle cramps and numbness in the legs may also occur. Another uncommon symptom is dermatitis herpetiformis, with itchy redness especially in the elbows, knees and on the back.

Due to insufficient absorption of nutrients, especially if the disease is not diagnosed promptly, anemia, weight loss, osteopenia, osteoporosis may occur.

In children, irritability is a very common symptom; The presence of the disease can also cause growth retardation.

In women, some manifestations can be the indicator of an unrecognized celiac disease: irregularities of the menstrual cycle, amenorrhea, iron deficiency anemia, late menarche or early menopause, infertility, complications in pregnancy such as prematurity or repeated miscarriages. In the presence of some of these situations it is therefore legitimate to suspect celiac disease and undergo appropriate diagnostic tests, provided that they are always under the supervision of the doctor.

How celiac disease is diagnosed

At the moment there is no scientific evidence in favor of population screening; The first step in the diagnosis of celiac disease is therefore clinical suspicion, usually by the general practitioner, following the appearance of symptoms. However, given the extreme variability of these, diagnosing celiac disease can be difficult. The disease can in fact present in an atypical form, with late onset and extra-intestinal symptoms, and silent, that is, without giving obvious signs.

The diagnosis of celiac disease is based on two types of analysis:

• the dosage in the blood of specific anti-gliadin antibodies (IgA and IgG) and anti-transglutaminase antibodies (tTG) that the body produces in response to gluten, perceived as a foreign substance
• biopsy of the duodenal mucosa, to quantify the damage caused by intestinal villi. The examination is carried out by taking small fragments of duodenal mucosa during an esophagogastroduodenoscopy, then viewed under a microscope.

In some doubtful situations, anti-endomysium antibodies (EmA) are also used in response to continuous damage to the intestinal lining.

It is important that both blood tests and histological examination are performed on a free diet, that is, containing gluten. Otherwise the correct diagnosis would be prejudiced: as long as you are on a gluten-free diet, in fact, the tests for celiac disease are negative, even in celiac subjects.

A hybrid condition, called “non-celiac gluten sensitivity“, concerns an increasing proportion of people who experience intestinal and non-intestinal symptoms (stomach pain, headache, feeling of fatigue and depression) following the ingestion of gluten and for whom both celiac disease and wheat allergy have already been excluded. These individuals, who are often diagnosed with irritable bowel syndrome, benefit from a gluten-free diet. It is a condition that has now lost the connotation of psychological disorder that had been attributed to it until a few years ago and that is the subject of growing interest by the scientific community, committed to identifying diagnostic markers.

Tests to diagnose celiac disease

In adults, the first step in the diagnostic process is the measurement of anti-transglutaminase tTG antibodies and total IgA in the blood. Values within the limits normally exclude the presence of celiac disease. If, on the other hand, the results are above the limits with a high titer, the next step is the duodenal biopsy, which will establish with certainty the possible presence of the disease. Finally, when the same antibodies are higher than normal but with low titer, it is necessary to resort to the evaluation of anti-endomysium antibodies. A positive result of the latter test involves performing duodenal biopsy, while a negative result excludes the possibility of the disease.

Similar path in pediatric age. The first step is the assay of total anti-tTg and IgA antibodies. Celiac disease is excluded if both evaluations give normal results. If, on the other hand, transglutaminases are normal and total IgA is less than 5, it is necessary to proceed with the evaluation of IgG: normal values indicate the absence of celiac disease; in other cases, duodenal biopsy is used. For children under two years of age, anti-gliadin deamidata antibodies (anti-dGP IgG) are also diagnosed. In the intermediate situation, characterized by alteration of anti-transglutaminase antibodies and total IgA values in the norm, the diagnosis path is less invasive as it is possible to avoid biopsy.

Following the indications of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the new Guidelines published in 2015 (Protocol for the diagnosis and follow-up of celiac disease) have in fact established that the diagnosis of celiac disease can be separated from duodenal biopsy in children with:

• Clinical picture of malabsorption and symptoms related to gluten intake
• anti-tTG IgA antibodies at least 10 times higher than the threshold value
• positivity for anti-endomysium EmA IgA antibodies
• compatible genetic profile (HLA-DQ2 and/or DQ8).

Attention to family members

Given the genetic nature of the disease, for each new diagnosis it is advisable to carry out an antibody screening in all first-degree relatives of the patient: parents, brothers and sisters, children are considered at risk of celiac disease. Possessing an HLA-DQ2 and HLA-DQ8 genotype is a prerequisite for the development of the disease. This does not mean that those who possess these genes are necessarily celiac, but simply that they have the predisposition to become so.

In a family with a high prevalence of celiac disease, the requirement for genomic typing of HLA could be a tool to establish the need for periodic checks of anti-transglutaminase antibodies, which in asymptomatic subjects should be repeated every two years.

The same applies to people with autoimmune diseases, such as thyroiditis and diabetes, as well as Down syndrome, Turner syndrome and Williams syndrome, where the prevalence of celiac disease can exceed 10%.

Treatment

Celiac disease is a chronic disease, which once manifested does not regress and for which there is no definitive cure to date. The only treatment that allows celiacs to maintain a good state of health is the complete elimination of gluten from their diet.

Celiac subjects must therefore avoid all cereal-based foods that contain it, such as bread, pasta, pizza, crackers, breadsticks, and those where gluten is contained because it is added during production processes, for example cold cuts, ice cream, ready meals, beer. It is an elimination diet that can however count on many naturally gluten-free foods. Not only legumes, vegetables, fruit, potatoes, milk and derivatives, but also numerous varieties of cereals: rice, corn, millet, quinoa, sesame, amaranth, buckwheat, sorghum.

The gluten-free diet should be strictly followed throughout life and allows you to gradually eliminate the symptoms, normalize the duodenal mucosa and prevent complications. The recovery of well-being will require a variable time depending on the starting conditions: according to clinical experience it is generally 6-12 months.