Why Doctors Must Biopsy the Duodenal Bulb in Children—Or Risk Missing Celiac Disease

Doctors are missing celiac disease in children because they’re not biopsying the right part of the intestine. A new study published in the Journal of Pediatric Gastroenterology and Nutrition found that when intestinal damage is confined to the duodenal bulb—the first curve of the small intestine just past the stomach—children with low antibody levels are being misdiagnosed as having only “potential” celiac disease instead of active celiac disease requiring immediate dietary intervention.

The findings expose a diagnostic blind spot. Current European guidelines call for taking biopsies from the duodenal bulb, but not all doctors follow this protocol. When they skip the bulb and sample only the descending duodenum further downstream, they miss a distinct pattern called ultra-short celiac disease where intestinal damage stops before it reaches the areas being sampled.

What This Means for You

If your child is being evaluated for celiac disease and has low or borderline antibody levels, you need to ask a specific question: “Will you be taking biopsies from the duodenal bulb?” The answer matters because your child could have active celiac disease that a standard biopsy misses entirely.

The Italian researchers found that among 59 children with low antibody levels (below 10 times the upper limit of normal), 34% had ultra-short celiac disease—villous atrophy isolated to the duodenal bulb with normal tissue in the descending duodenum. Without a bulb biopsy, every one of these children would have been classified as having only “potential celiac disease” and sent home without clear guidance to start the gluten-free diet.

This matters because potential celiac disease and active celiac disease require different approaches. A child with potential celiac disease has positive antibodies but no visible intestinal damage—doctors often recommend continued gluten consumption with periodic monitoring. A child with active celiac disease has intestinal damage and needs to start the gluten-free diet immediately to prevent complications like nutrient deficiencies, growth delays, and bone density loss.

For families like mine, this diagnostic gap is maddening. The gluten-free diet is already exhausting work. The idea that a child could be living with untreated intestinal damage because the endoscopy protocol missed a crucial sampling site adds another layer of anxiety to an already stressful diagnostic process.

Key Takeaways

Ultra-short celiac disease occurs when intestinal damage is confined to the duodenal bulb—the first curve of the small intestine.
One in three children with low celiac antibody levels had this pattern in the Italian study.
Skipping the duodenal bulb biopsy means these children get misdiagnosed as “potential” celiac disease instead of active disease.
European guidelines already call for bulb biopsies, but compliance varies by center and physician.
If your child is undergoing endoscopy for celiac evaluation, confirm that the doctor will sample the bulb.

The Science

Want to understand how this actually works? We’ll walk you through the technical details below and define every term. No medical degree required.

What Is Ultra-Short Celiac Disease?

Ultra-short celiac disease is a phenotype—a distinct pattern of how the disease presents—where villous atrophy (flattening of the finger-like projections that absorb nutrients in the small intestine) occurs only in the duodenal bulb, the rounded first portion of the duodenum immediately after the stomach. In typical celiac disease, damage extends throughout the duodenum and often into the jejunum further downstream. In ultra-short celiac disease, the damage stops at the bulb.

Why does this happen? Researchers aren’t entirely sure, but one theory involves the unique environment of the bulb. It sits at the crossroads where acidic stomach contents meet alkaline digestive secretions from the pancreas and bile ducts. The bulb also experiences more mechanical stress from stomach contractions. These factors may create conditions where gluten exposure triggers localized immune damage without spreading distally (further down the intestinal tract).

The Diagnostic Problem

Standard endoscopy protocols have historically focused on the descending duodenum—the second and third portions of the duodenum past the bulb. The bulb was often skipped because it’s technically harder to biopsy (it moves more, the angle is awkward, and the tissue can be friable) and because older teaching suggested the bulb was prone to false positives from gastric metaplasia (stomach-type tissue growing in the intestine) or peptic damage from stomach acid.

The 2020 European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines changed this, explicitly recommending that at least one biopsy be taken from the bulb in addition to four or more biopsies from the descending duodenum. The Italian study examined what happens when centers follow this protocol versus when they don’t.

Study Design and Findings

The researchers conducted a retrospective analysis of 248 pediatric patients evaluated for celiac disease at a tertiary care center in Turin, Italy, between June 2017 and December 2024. All patients underwent endoscopy with biopsies following the ESPGHAN protocol, including bulb sampling.

The cohort was divided into two groups based on anti-tissue transglutaminase IgA (anti-tTG IgA) antibody levels—the primary blood test for celiac disease screening:

High antibody group: 189 children with levels ≥10 times the upper limit of normal
Low antibody group: 59 children with levels <10 times the upper limit of normal but still positive

In the high antibody group, 93% had villous atrophy in both the bulb and descending duodenum—the typical widespread pattern. Only 7% had ultra-short celiac disease.

In the low antibody group, the picture flipped dramatically. Only 27% had the typical widespread pattern. A striking 34% had ultra-short celiac disease—damage confined to the bulb with completely normal descending duodenum biopsies. The remaining 39% had no villous atrophy anywhere and were classified as potential celiac disease.

Here’s the critical point: if the doctors had skipped the bulb biopsy and relied only on descending duodenum samples, all 20 children with ultra-short celiac disease would have been misclassified as potential celiac disease. Their biopsies would have come back normal, despite active intestinal damage occurring just millimeters upstream.

Clinical Implications

The study reinforces that antibody levels correlate with disease extent but not with disease presence. A child with low antibodies can still have active celiac disease—it’s just more likely to be localized rather than widespread. This finding echoes patterns we’ve discussed in earlier coverage of artificial intelligence-driven histomorphometry and sub-phenotyping research, both of which point toward celiac disease as a spectrum rather than a single uniform condition.

The practical takeaway: bulb biopsy is not optional. It’s a necessary component of celiac diagnostic workup, especially in children with low or borderline antibody levels who are at highest risk for ultra-short disease patterns.

What About the Non-Biopsy Diagnosis Pathway?

ESPGHAN guidelines allow diagnosis without biopsy in children with anti-tTG IgA levels ≥10 times the upper limit of normal, confirmed by positive endomysial antibodies (EMA) and compatible symptoms. This pathway is designed to spare children an invasive procedure when the diagnosis is nearly certain.

The Italian study supports this approach for high antibody cases—93% had widespread villous atrophy, making the diagnosis clear-cut. But it also highlights why the pathway excludes low antibody cases: the 34% prevalence of ultra-short celiac disease in that group means tissue confirmation is essential to distinguish active disease from potential disease.

Unanswered Questions

The study raises several questions that future research needs to address:

Do children with ultra-short celiac disease progress to more extensive intestinal damage if left untreated, or does the disease remain localized?
Are there genetic or immunologic markers that predict ultra-short versus typical patterns?
Does ultra-short celiac disease respond differently to the gluten-free diet in terms of symptom resolution and mucosal healing?
How common is this pattern outside pediatric populations—do adults show similar rates of bulb-confined disease?

What to Do If Your Child Is Being Evaluated

If your child is scheduled for an endoscopy to evaluate possible celiac disease, have a conversation with the gastroenterologist beforehand. Ask explicitly: “Will you be taking biopsies from the duodenal bulb?” If the answer is no or if the doctor seems uncertain, reference the 2020 ESPGHAN guidelines and this study. Print the abstract if it helps.

This isn’t about questioning your doctor’s expertise—it’s about ensuring adherence to current best practices. Guidelines change, and not every center updates protocols at the same pace. Your advocacy ensures your child gets the most accurate diagnostic workup possible.

If your child was previously biopsied without a bulb sample and was diagnosed with potential celiac disease based on positive antibodies and normal descending duodenum biopsies, consider discussing repeat endoscopy with bulb sampling. This is especially worth considering if your child has ongoing symptoms, growth concerns, or nutrient deficiencies despite a gluten-containing diet.

The Bigger Picture

This study is part of a broader push toward diagnostic precision in celiac disease. Researchers are working to identify distinct disease phenotypes, refine biopsy protocols, develop non-invasive biomarkers like urinary microRNAs, and use artificial intelligence to standardize histopathology interpretation. Each advance brings us closer to a future where no child slips through diagnostic cracks because of where a biopsy forceps happened to land.

For now, the message is simple: biopsy the bulb. It’s a small change in procedure with potentially life-changing implications for children who would otherwise be misdiagnosed.

References

Pizzol A, Saraceno E, Opramolla A, Giugliano L, Chiadò C, Manetta T, Canavese G, Falco E, Pinon M, Calvo PL. High prevalence of ultra-short celiac disease in children with low anti-tissue transglutaminase immunoglobulin A levels: The risk of misdiagnosis without bulb biopsy. J Pediatr Gastroenterol Nutr. 2026 May 25. doi: 10.1002/jpn3.70464. https://pubmed.ncbi.nlm.nih.gov/42179344/