Diagnosis of children

Coeliac Disease (CD) has a myriad of clinical features. With this in mind, the first, most important step in diagnosis is to consider these features. And just as there is a clinical spectrum, there is also a range of laboratory and histopathologic results.

Initial screening of suspected cases of CD is usually carried out using serological tests. Those available are:

• Anti gliadin antibodies (AGA)
• Anti endomysial antibodies (EMA)
• Anti tissue transglutaminase (tTG)

As these serological tests are Immunoglobulin-A (IgA) dependent, total serum IgA needs to be checked in order to interpret the results correctly. Human tTG has a high specificity (1)  (equivalent to the EMA test but more accurate than AGA) and because tTG is an enzyme linked immunosorbent assay (ELISA) based method, it has less potential for interpretation error (2) . EMA, however, depends on a subjective assessment of immunofluorescence and so is observer dependent. Recent studies show that quantitative determination of human anti tTG antibodies is a highly sensitive and specific marker and can identify patients with CD better than any other serological test (3,4). However, serologic testing for CD in children less than 5 years of age may be less reliable and requires further study (5) . Approximately 2% of symptomatic children with CD are IgA deficient. Therefore, if testing for CD in children with suspicious symptoms, measurement of quantitative serum IgA can help when the tTG IgA is low.     

A small intestinal (SI) biopsy is still required to confirm the diagnosis. Because histological changes in CD may be patchy, 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 CD 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 CD in children. If the diagnosis remains uncertain, additional strategies can be considered, including determination of the HLA type, repeat biopsy or a trial of a gluten free diet with repeat serology and biopsy. Prior to the biopsy, it must be explained to the parents and child the importance of remaining on a gluten containing diet. It is bad practice to start a GFD prior to the confirmation of the diagnosis (5).

The definitive diagnosis is confirmed when symptoms completely resolve following treatment with a gluten free diet (GFD) in a previously symptomatic individual with characteristic histological changes on SI biopsy. Following treatment with a GFD a previously positive serological test becoming negative further supports the diagnosis. A second biopsy to demonstrate normalized histology following a GFD is no longer recommended (5). However, a gluten challenge should be carried out in children (a) in whom the initial biopsy was performed before 2 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) (b) cases where the initial diagnosis was in doubt or (c) in non-compliant patients who question their diagnosis and wish to discontinue the GFD. The challenges should be avoided before 6 years of age to minimise the risk of dental enamel defects and during periods of rapid growth e.g. puberty. 10-20 grams of gluten powder should be added to the GFD or a regular normal gluten containing diet (equivalent to 2-4 slices of bread daily). The biopsy should be repeated at the onset of clinical relapse or between 6-12 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, Dietitian and one of Coeliac UK's Medical Advisory Council Associates, for providing this information. 

References

1 Lepers S, Soula F, Fily S, Fontaine E, Vuye S, Colombel JF, Guimber D, Prin L, Dubucquoi S. Relevance of anti-tissue transglutaminase antibodies in celiac disease diagnosis. Ann Biol Clin 2003; 61:337-343.  
 

2 Hill ID, Bhatnagar S, Cameron DJS, De Rosa S, Maki M, Russell GJ, Troncone R. Coeliac disease: working group report of the first world congress of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2002; 35: S78-S88.   
 

3 Tesei N, Sugai E, Vazquez H, Smecuol E, Niveloni S, Mazure R, Moreno ML, Gomez JC, Maurino E, Bai JC. Antibodies to human recombinant tissue transglutaminase may detect celiac disease patients undiagnosed by endomysial antibodies. Aliment Pharmacol Ther 2003; 17: 1415-1423.   
 

4 Wolters V, Vooijs-Moulaert AF, Burger H, Brooimans R, de Schryver J, Rijkers G, Houwen R. 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. Eur J Pediatr 2002; 161:284-287.     
 

5 Proceedings of the National Institute of Health Consensus Conference on Celiac Disease. 2004.
 

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, Shmerling DH, Visakorpi JK. Revised criteria for diagnosis of celiac disease: Report of working group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990; 65: 909-911.