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. 2026 Jan 2;15(1):353.
doi: 10.3390/jcm15010353.

Clinical, Endoscopic, and Histological Characteristics of Severe Immune Checkpoint Inhibitor-Induced Colitis

Diego Casas Deza  1 , Cristina Polo Cuadro  1 , Marta Gascón Ruiz  2 , Manuel Barreiro-de Acosta  3 , Míriam Mañosa  4 , Francisco Rodríguez-Moranta  5 , Yamile Zabana  6 , Elena Céspedes Martínez  7 , Ingrid Ordás  8 , José Miranda Bautista  9 , María José García  10 , Irene García de la Filia Molina  11 , Cristina Roig Ramos  12 , Alexandra Ruiz Cerulla  13 , José Xavier Segarra-Ortega  14 , Virginia Matallana Royo  15 , Esther Rodríguez González  16 , Fernando Martínez de Juan  17 , Noemí Manceñido Marcos  18 , Lucía Madero Velázquez  19 , Elena Betoré Glaría  20 , Begoña Álvarez Herrero  21 , Gerard Suris  22 , Alejandro Garrido Marín  23 , Eduard Brunet Mas  24 , Inmaculada Alonso Abreu  25 , Javier Santos Fernández  26 , María Vaamonde Lorenzo  27 , Cristina Almingol Crespo  28 , Carla Folguera  29 , Patricia Sanz Segura  30 , Óscar Moralejo Lozano  31 , Laura López Couceiro  32 , Coral Tejido Sandoval  33 , Raquel Mena Sánchez  34 , Empar Sainz  35 , Miquel Marquès-Camí  36 , Rocío Ferreiro-Iglesias  3 , Silvia Patricia Ortega Moya  37 , Pablo Miles Wolfe García  38 , Pere Borras Garriga  39 , Belén Herreros Martínez  40 , María Calvo Iñiguez  41 , Santiago Frago Larramona  42 , Pablo Ladrón Abia  43 , Xavier Serra-Ruiz  7 , Luis Menchén  9 , Coral Rivas Rivas  10 , Francisco Mesonero Gismero  11 , Raquel Vicente Lidón  1 , Ana Gutierrez  44 , Santiago García López  1 ; GETECCU
Affiliations

Clinical, Endoscopic, and Histological Characteristics of Severe Immune Checkpoint Inhibitor-Induced Colitis

Diego Casas Deza et al. J Clin Med. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. They can cause immune-mediated colitis (IMC), a potentially severe adverse event. Current data on severe IMC (grade 3-4) are limited, particularly regarding clinical, endoscopic, and histological features. Methods: We conducted a multicenter, retrospective observational study promoted by GETECCU, including adults with solid tumors who developed grade 3-4 IMC requiring hospitalization and systemic therapy. Clinical symptoms, endoscopic findings (Mayo and UCEIS indices), and histological features were systematically collected and analyzed. Results: A total of 196 patients were included. Diarrhea was universal (median 8 bowel movements/day), with 76% reporting abdominal pain and 39% rectal bleeding. Endoscopy (n = 139) revealed vascular pattern loss (80%), mucosal lesions (69%), and Mayo scores ≥2 in 69%. Histopathology (n = 141) showed abnormalities in 85%, including cryptitis (50%), lymphocytic infiltration (48%), and crypt abscesses (37%). Notably, 72% of patients with normal endoscopy had histological inflammation. Endoscopic severity correlated with bleeding and impaired general condition but not with stool frequency or pain intensity. Histological and endoscopic severity were modestly associated. Conclusions: Severe IMC presents with heterogeneous clinical, endoscopic, and histological features, with limited correlation between these domains. Endoscopic findings were often ulcerative and inflammatory, yet histological abnormalities were frequently present even in endoscopically inactive disease. These findings highlight the importance of biopsy in all suspected IMC cases and underscore the need for validated multidimensional assessment tools for accurate diagnosis and management of severe IMC.

Keywords: endoscopy; histology; immune checkpoint inhibitors; immune-mediated colitis.

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Conflict of interest statement

DCD has served as speaker, consultant, advisory member or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Taked, Janssen, Ferring, Faes Farma and Alfasigma. EBM has served as a speaker and consultant for Janssen and Chiesi, Kern, Takeda and Alfasigma. VMR has served as a speaker or consultant for Abbvie, Allergan, Casen Recordati, Italfármaco S.A., Janssen Cilag S.A., Merck Sharp & Dohme Española S.A., Pfizer, Schwabe Farma Ibérica S.A.U., and Takeda. MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, SunRock and Oncostellae. MMC has served as speaker, consultant or has received research funding from Abbvie, Janssen, GSK and Ferring. CR has received support for conference attendance and education funding from Kern Pharma, Ferring, Alfasigma, Faes Farma, Pfizer and Takeda. JMB has received support for conference attendance, speaker fees, and consulting and advisory fees from AbbVie, Lilly, Adacyte, Dr Falk Pharma, FAES Pharma, Ferring, Janssen, Pfizer, Takeda, Galapagos and Tillots. YZ has received financial support for travelling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Alfasigma, Almirall, Amgen, Boehringer Ingelheim, Dr Falk Pharma, Faes Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen, Johnson&Johnson, Kern, Lilly, MSD, Otsuka, Pfizer, Sanofi, Shire, Takeda, and Tillotts Pharma. IO has received financial support for traveling and educational activities from or has served as an advisory board member or speaker for Abbvie, MSD, Pfizer, Takeda, Janssen, Kern Pharma, Chiesi, Falk Pharma, and Faes Farma. Research support from Abbvie and Faes Farma.

Figures

Figure 1
Figure 1
Correlation (Spearman) matrix between clinical and endoscopic indices.
Figure 2
Figure 2
Comparison of histological findings in patients with and without endoscopic activity.
See this image and copyright information in PMC

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