Am J Surg Pathol. 2024 Feb 1;48(2):212-220. doi: 10.1097/PAS.0000000000002150.Epub 2023 Nov 23.

Natalie Patel ¹, Daniel A Leffler ², Abdulbaqi Al-Toma ³, Chris J Mulder ⁴, Luca Elli ⁵, Geliang Gan ¹, Pallavi Patil ¹, Amporn Atsawarungruangkit ², Karel C Kuijpers ³, Alessandro Del Gobbo ⁶, Jeffrey Goldsmith ⁷, Zach Hintze ⁷, M Cristina Pacheco ⁸, Michael Vieth ⁹, Balint Melcher ⁹, Marcela Salomao ¹⁰, Rish Pai ¹⁰, John Hart ¹¹, Andrea Olivas ¹¹, Bita Naini ¹², Cherise Meyerson ¹², Won-Tak Choi ¹³, Sanjay Kakar ¹³, Maria Westerhoff ¹⁴, Jerome Cheng ¹⁴, Purva Gopal ¹⁵, Suntrea Hammer ¹⁵, Mariana Moreno Prats ¹⁶, Mary P Bronner ¹⁶, Marie E Robert ¹

Author information

¹Yale School of Medicine, New Haven, CT.

²Beth Israel Deaconess Medical Center.

³St. Antonius Hospital, Nieuwegein.

⁴Amsterdam University Medical Center, Amsterdam, The Netherlands.

⁵Center for Prevention and Diagnosis of celiac disease, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Italy.

⁶Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Italy.

⁷Boston Children's Hospital, Boston, MA.

⁸Seattle' Children's Hospital, Seattle, WA.

⁹Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany.

¹⁰Mayo Clinic, Scottsdale, AZ.

¹¹University of Chicago Medical Center, Chicago, IL.

¹²UCLA Medical Center, Los Angeles.

¹³Department of Pathology, University of California, San Francisco, CA.

¹⁴Department of Pathology, University of Michigan, Ann Arbor, MI.

¹⁵University of Texas Southwestern Medical Center, Dallas, TX.

¹⁶University of Utah Health Sciences Center and ARUP Labs, Salt Lake City, UT.

Abstract

Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal recovery has been incompletely evaluated. The aim of this study was to rigorously assess patterns of histologic mucosal recovery at follow-up in celiac disease and to correlate findings with clinical data. Gastrointestinal pathologists from 13 centers evaluated initial and follow-up duodenal biopsies from 181 celiac disease patients. Marsh scores and intraepithelial lymphocytes (IELs)/100 enterocytes were assessed blindly. Histology at follow-up was correlated with symptoms, immunoglobulin A anti-tissue transglutaminase titers and gluten-free diet adherence. Fifty-six/181 (31%) patients had persistent villous blunting and 46/181 (25%) patients had just persistently elevated IELs at follow-up, with only 79/181 (44%) patients having complete histologic remission. IEL normalization (82/181; 45%) lagged villous recovery (125/181;69%). In a minority of patients, villous blunting was limited to proximal duodenal biopsies. No correlation was found between Marsh scores and symptoms, normalization of immunoglobulin A anti-tissue transglutaminase serology, or diet adherence. Children showed greater recovery of Marsh score ( P <0.001) and IELs ( P <0.01) than adults. Persistent mucosal injury is common in celiac disease, with discordant villous/IEL normalization. Pathologist awareness of expected findings in celiac disease follow-up biopsies, including their frequent lack of correlation with clinical data, is important for patient management, and has implications for eligibility criteria for therapeutics currently in development.