Diagnosis of children

Coeliac diseaseA condition where a person is unable to eat gluten as it makes their body attack itself. has a wide spectrum of clinical features. Children can present with a wide range of signs and symptoms and with this in mind, the first, most important step in diagnosis is to consider these. If the child is suspected of having coeliac disease or there is a first degree relative with the condition (1) then it is recommended that initial screening is carried out using serological testing.

Serological testing should not be used in infants before glutenA protein that is found in the cereals wheat, barley and rye. has been introduced into the diet. It is important for children to continue having a normal gluten containing diet before considering diagnostic tests for coeliac disease.

Coeliac disease serology includes:                    

• tissue transglutaminase antibody (tTGA)
• endomysial antibodiesExist in the blood and are used by the immune system to attack viruses or bacteria. (EMAEndomysial antibody - an antibody that is measured in the blood as part of the diagnosis process for coeliac disease. Depending on the laboratory performing the test, one or more antibodies may be measured (see Tissue Transglutaminase))
• total serum IgA.

Tissue transglutaminase antibody is a highly sensitive and specific marker and can identify patients with coeliac disease better than any other serological test (2,3). Endomysial antibodies can be used if the test is equivocal.

IgA deficiency 

Although most negative results suggest that someone does not have coeliac disease, it is possible to have false negative results. Further investigations should be carried out in patients whose symptoms are strongly suggestive of coeliac disease.

Some research shows that patients with coeliac disease are more likely to be IgA deficientSomeone who does not produce the specific antibodies used to identify coeliac disease than the general population (4). People with IgA deficiency will have a false negative result if IgA-based serological tests are used in the diagnosis of coeliac disease.

The NICENational Institute for Health and Clinical Excellence - an independent organisation responsible for providing national guidance on promoting good health and preventing and treating ill health. NICE had produced a clinical guideline on the recognition and assessment of coeliac disease. guideline recommends using IgG antibody blood tests in those who are IgA deficient.

Biopsy

Prior to the biopsy, it must be explained to the parents and child, the importance of remaining on a normal diet which contains gluten in at least one meal a day for at least six weeks prior to testing (1). It is bad practice to start a gluten-freeWhen a food has less than 20 parts per million (ppm) of gluten so it is safe for people with coeliac disease to eat. diet prior to the confirmation of the diagnosis (5).

A small intestinal biopsy is still required to confirm the diagnosis of coeliac disease in children. Histological changes in coeliac disease may be patchy; therefore multiple biopsy
specimens should be obtained from the distal duodenum (6). The characteristic histological features are partial/total villous atrophy. An infiltrative change, with crypt hyperplasia, is compatible with coeliac disease but less clear. In this case, a diagnosis needs to be strengthened by the presence of positive serological tests. Infiltrative changes alone are not specific for coeliac disease in children.  

The definitive diagnosis is confirmed when symptoms completely resolve following treatment with a gluten-free diet in a previously symptomatic individual with characteristic histological changes on small intestinal biopsy. Following treatment with a gluten-free diet a previously positive serological test becoming negative further supports the diagnosis. A second biopsy to demonstrate normalised histology, following a gluten-free diet, is no longer recommended (5). 

Gluten challenge

A gluten challenge after diagnosis is not usually necessary; however, it can be carried out in children:

• in whom the initial biopsy was performed before two years of age (7)  (because of the risk of confusion with many other conditions such as cow's milk sensitive enteropathy, postenteritis enteropathy and giardiasis)
• in cases where the initial diagnosis was in doubt
• in non-compliant patients who question their diagnosis and wish to discontinue the gluten-free diet.

Gluten challenge should be avoided before six years of age to minimise the risk of dental enamel defects and during periods of rapid growth, such as puberty. A normal diet should be followed which contains gluten in more than one meal every day (equivalent to two to four slices of bread daily). Gluten powder can also be added for those who do not wish to add gluten containing foods back into the diet. At least 10-15 grams of gluten powder should be added to the gluten-free diet each day.

The biopsy should be repeated at the onset of clinical relapse or between six and twelve months in the absence of symptoms. Monitoring of the antibody status may help to determine when to undertake the biopsy.     

Thank you to Jacqui Lowdon, DietitianAn expert in food and nutrition. and one of Coeliac UK's Medical Advisory Council Associates, for providing this information. 

References

1. National Institute for Health and Clinical Excellence (NICE) guidelines (2009) Recognition and assessment of coeliac disease http://www.nice.org.uk/nicemedia/pdf/CG86FullGuideline.pdf

2. Tesei N, Sugai E, Vazquez H, et al (2003) Antibodies to human recombinant tissue transglutaminase may detect celiac disease patients undiagnosed by endomysial antibodies. Alimentary Pharmacology and Therapeutics 17: 1415-1423.    

3. Wolters V, Vooijs-Moulaert AF, Burger H, et al (2002) Human tissue transglutaminase enzyme linked immunosorbent assay outperforms both the guinea pig based tissue transglutaminase assay and anti-endomysium antibodies when screening for celiac disease. European Journal of Paediatrics 161:284-287.

4.Lenhardt A, Plebani A, Marchetti F et al (2004) Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency. Digestive & Liver Disease. 36(11): 730-4      

5. Catalodo F, Marino V, Ventura A, Bottaro G, Corazza GR (1998) Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study. Gut 42: 363-365 

6. Guideline for the Diagnosis and Treatment of Celiac Disease in Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. 2004.

7. Walker-Smith JA, guandalini S, Schmitz J, et al (1990) Revised criteria for diagnosis of celiac disease: Report of working group of European Society of Paediatric Gastroenterology and Nutrition. Archives of Disease in Childhood 65: 909-911.