Initial assessment
In a child or adolescent with suspected coeliac disease, the first step is to recognize the clinical features that justify investigation. Presentation is heterogeneous and may include gastrointestinal and/or extra-intestinal symptoms, varying widely in frequency and severity, which may make early diagnosis difficult.
Gastrointestinal symptoms
The most frequent gastrointestinal symptoms include chronic or intermittent diarrhoea, often with features of steatorrhoea, and persistent abdominal distension. Less frequently, the child may present with refractory chronic constipation, recurrent nausea and vomiting or abdominal pain with no identified cause.
Extra-intestinal manifestations
A significant proportion of cases present predominantly with extra-intestinal features. The most common include growth delay or short stature. Other possible manifestations include unexplained iron-deficiency anaemia resistant to treatment, delayed puberty and, in females, primary or secondary amenorrhoea. Chronic fatigue, mood changes such as irritability, osteopenia or osteoporosis in childhood, sometimes with recurrent fractures, arthralgia, recurrent aphthous stomatitis, dental enamel defects, persistent elevation of transaminases and mild peripheral neuropathy may also occur.
Dermatitis herpetiformis
A feature considered pathognomonic of coeliac disease is dermatitis herpetiformis, which presents as an intensely pruritic papulovesicular rash, symmetrically distributed over extensor surfaces, buttocks and scalp. It may occur even in the absence of digestive symptoms.
Initial serological testing
When compatible features are present, investigation should begin with measurement of total IgA and IgA anti-tissue transglutaminase antibodies. These tests form the basis of initial screening and guide the subsequent steps of the diagnostic algorithm.
Interpretation of negative serology
If total IgA is normal and IgA anti-tissue transglutaminase is negative, and clinical suspicion is low, coeliac disease becomes unlikely. However, if clinical concerns persist — such as a positive family history, associated autoimmune diseases or persistent symptoms — further investigation should be considered, including possible duodenal biopsy.
False-negative serology
When IgA anti-tissue transglutaminase is negative, the possibility of a false-negative result should always be considered, particularly if the child follows a low-gluten or gluten-free diet, is immunosuppressed or has selective IgA deficiency. In these contexts, additional investigation may be required.
Selective IgA deficiency
When total IgA is reduced, the reliability of IgA-based tests is compromised. In these cases, it is appropriate to use IgG-based serological tests, namely IgG anti-tissue transglutaminase, IgG anti-endomysial antibodies or IgG anti-deamidated gliadin peptide antibodies, which are usually available in hospital settings.
Interpretation of positive serology
If IgA anti-tissue transglutaminase is positive with normal total IgA, the diagnosis of coeliac disease should be considered. Duodenal biopsy may be avoided when two cumulative criteria are met: an IgA anti-tissue transglutaminase value greater than 10 times the upper limit of normal, confirmed in a second sample, and IgA anti-endomysial antibody positivity in a new sample. If either criterion is not met, diagnostic confirmation should be obtained by duodenal biopsy, including samples from the bulb and the second portion of the duodenum.
Treatment after diagnostic confirmation
Once the diagnosis is confirmed, either serologically or histologically, a strict gluten-free diet should be introduced and maintained lifelong. Strict adherence to the diet is essential for symptom resolution, normalization of growth and prevention of long-term complications. HLA typing is not required after diagnostic confirmation and does not change therapeutic management.
Screening in risk groups
Even in the absence of symptoms, screening for coeliac disease should be considered in children at increased risk. This group includes first-degree relatives of patients with coeliac disease and children with type 1 diabetes mellitus, autoimmune hepatitis, autoimmune thyroiditis, Down syndrome, Turner syndrome, psoriasis, epilepsy with occipital calcifications, IgA nephropathy, pulmonary haemosiderosis, asplenia or hyposplenism. In these contexts, early diagnosis is essential to prevent clinical manifestations and avoidable morbidity.
