Pediatric Celiac Disease (Sprue) Workup

Updated: Jul 07, 2023
  • Author: Stefano Guandalini, MD, AGAF; Chief Editor: Carmen Cuffari, MD  more...
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Approach Considerations

The most important first step in the diagnostic workup is definitely to have a high degree of suspicion. In fact, celiac disease needs to be taken into account in many conditions that may not immediately be connected with this entity. This is especially true when "minor" or extraintestinal signs are the only manifestations, such as iron deficiency, headache, short stature, and thyroiditis. Also consider celiac disease in symptom-free children who have a first-degree relative with the disease. In fact, it has been documented that physicians are more likely to miss asymptomatic individuals as well as those whose symptoms do not include overt GI involvement. [52]  

Once the condition is supected, in all cases the first screening test must be the combination of total serum IgA and anti-tissue transglutaminase IgA (tTG-IgA). If tTG-IgA levels are normal, in individuals who are not IgA-deficient, then celiac disease can be ruled out with a high degree of probability.

If the test is positive, the subsequent steps that need to be taken are outined in the next section. 


Laboratory Studies

The discovery of the tissue transglutaminase as the auto-antigen of CD, and the subsequent development of the very sensitive and specific tTG-IgA, allowed for a major simplification of the previous diagnostic guidelines. Thus, in 2020 the European Society for Pediatric Gastroenterology, Hepatology and Nutriion (ESPGHAN) published new evidence-based guidelines allowing a diagnosis to be made without the biopsy previously thought to be fundamental in demonstrating the changes in the duodenal mucosa caused by the immune reaction to gluten. This, however, strictly applies only when tTG-IgA levels are found to be more than 10 times the upper limit of normal and  are coupled with a clearly positive anti-endomysium antibody (EMA-IgA) titer. Of interest, this applies even in asymptomatic children. [2]  It is estimated that this approach actually applies to about 50% of children presenting to a celiac center with suspected CD. Utilizing such an algorithm, it has been estimated that in the United States, “between 4891 and 7738 pediatric endoscopies per year could be avoided,” thus resulting in considerable cost savings. [53]

In cases where biopsies are obtained, as mentioned in previous sections and fully discussed in other chapters, patients with positive celiac serology and normal histology are considered to have potential celiac disease; however, it should be noted that before concluding for such diagnosis, it is imperative to confirm that at the time of biopsy the patient was consuming a sufficient amount of gluten and that the biopsies were adequate in number and position and were well oriented.



Imaging Studies

Radiography of the GI tract with a barium swallow study and a small intestinal follow-through may show nonspecific changes because of the mucosal inflammation and possible concomitant protein-losing enteropathy (edema of the bowel walls, dispersion of the barium column). The findings are clearly nonspecific, and radiographic investigation is not needed for the diagnosis.



As mentioned, obtaining duodenal biopsies for the diagnosis is currently recommened whenever the diagnostic conclusion cannot be already possible with the combination of very high titers of tTG-IgA and positive EMA, a condition expected to involve approximately 50% of pediatric patients at the time of referral. In these cases, duodenal biopsies should be obtained by esophagogastroduodenoscopy (EGD). Obtaining at least four biopsy samples from the distal duodenum and one or two from the bulb is highly recommended because mucosal changes in celiac disease may be patchy. Of note, during the EGD it would be useful to obtain also biopsies from the esophagus in order to exclude the possible coexistence of eosinophilic esophagitis. [54]  

Colonoscopy, on the other hand, may be indicated only if bloody stools are reported or if symptoms of colitis are also present.


Histologic Findings

The typical histologic celiac lesion is characterized by intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. These changes occur in a continuum: from a normal mucosa to a complete flattening of the villi in a slow progression. Marsh described in detail such progression, [55]  and his scoring system is utilized by pathologists to classify duodenal damage in celiac disease as follows:

  • Type 0 or preinfiltrative stage (normal)
  • Type 1 or infiltrative stage (increased IELs)
  • Type 2 or hyperplastic stage (type 1 + hyperplastic crypts)
  • Type 3 or destructive stage (type 2 + villous atrophy of progressively more severe degrees, denominated 3a-partial atrophy, 3b-subtotal atrophy, and 3c-total atrophy)

However, changes referred to as Marsh 1 or even Marsh 2 are nonspecific because they can also be found in food-allergic enteropathies, such as cow's milk allergy or soy allergy (especially in infancy). These changes are also observed in giardiasis and in autoimmune enteropathy.

Although also not pathognomonic for celiac disease, changes referred to as Marsh 3 are usually much more specific, especially if they are associated with supportive serology findings.

Evidence suggests that patients with Marsh type 1 changes who have positive serology findings may develop more severe changes if they continue a gluten-containing diet; this challenges the idea that celiac disease is only observed in those who have more advanced findings. [56]


Other Tests

Additional tests recommended at the time of diagnosis include the following [57] :

  • CBC count
  • Iron studies (including ferritin)
  • Vitamin D
  • Vitamin B12
  • AST, ALT
  • TSH, T4

Although an evaluation of bone mineral density is not routinely recommended in children, this should be performed in patients who have a history of fractures.

Clearly, any abnormal test at the time of diagnosis must be properly followed up.