When to Perform Endoscopy or Radiological Tests in Patients with Unresponsive Celiac Disease

In general, celiac disease patients with unresponsive or worsening GI symptoms are the ones at higher risk of complicated disease or complications such as EATL (lymphoma), AdenoCa, ulcerative enteritis (1). 

In patients with persistent symptoms one should perform capsule endoscopy or deep enteroscopy or radiological imaging (small bowel follow through-enteroclysis), MR enterography (2). 

Alerting findings on endoscopy are ulcerations, polypoid or tumors lesions, raised discoid (round) type lesions. 

On x-ray the following are signs: reversed fold pattern (more Kerckring folds in ileum than in jejunum), small bowel dilation, small bowel wall thickening, cavitations mesenteric lymphadenopathy, mesenteric hypervascularization and splenic atrophy.

Indeed, splenic atrophy is more common in RCD II (refractory celiac disease), but not in celiac disease and lymphoma (likely because the lymphoma brought the spleen size back to „normal“) (3). 

Because of both functional hyposplenism and spleen atrophy, patients with celiac disease are prone to infections with encapsulated organisms such as Klebsiella, Staphylooccus aureus and Streptococcus pneumonia (penumococcus) pneumoniae.  Vaccination against Streptococcus pneumonia is indicated.

References:

1. Al-Toma A, Branchi F, Zingone F, Schiepatti A, Malamut G, Canova C, Rosato I, Ocagli H, Trott N, Elli L, Popp A, Gianfrani C, Auricchio R, Neefjes-Borst A, Sanders DS, Cellier C, Mulder CJ, Bouma G, Lundin KEA, Sollid LM, Schumann M. European Society for the Study of Coeliac Disease (ESsCD) 2025 Updated Guidelines on the Diagnosis and Management of Coeliac Disease in Adults. Part 2: Management, Follow-Up, and Complex Disease Courses. United European Gastroenterol J. 2026 Mar;14(2):e70195. doi: 10.1002/ueg2.70195. PMID: 41831197; PMCID: PMC13097674.
2. Al-Toma A, Zingone F, Branchi F, Schiepatti A, Malamut G, Canova C, Rosato I, Ocagli H, Trott N, Elli L, Popp A, Gianfrani C, Auricchio R, Neefjes-Borst A, Sanders DS, Cellier C, Mulder CJ, Bouma G, Lundin KEA, Sollid LM, Schumann M. European Society for the Study of Coeliac Disease 2025 Updated Guidelines on the Diagnosis and Management of Coeliac Disease in Adults. Part 1: Diagnostic Approach. United European Gastroenterol J. 2025 Dec;13(10):1855-1886. doi: 10.1002/ueg2.70119. Epub 2025 Sep 26. PMID: 40999951; PMCID: PMC12704582.
3. van Gils T, Nijeboer P, van Waesberghe JHT, Coupé VM, Janssen K, Zegers JA, Nurmohamed SA, Kraal G, Jiskoot SC, Bouma G, Mulder CJ. Splenic volume differentiates complicated and non-complicated celiac disease. United European Gastroenterol J. 2017 Apr;5(3):374-379. doi: 10.1177/2050640616663571. Epub 2016 Aug 17. PMID: 28507749; PMCID: PMC5415212.