Siddiqui AN, Hafsa R, Karmani VK, Rehan Z, Chowdhary R. Cronkhite-Canada syndrome: An elusive gastrointestinal disorder with multisystem involvement-pathogenesis, diagnosis, and therapeutic strategies. World J Gastrointest Pathophysiol 2026; 17(3): 121535 [DOI: 10.4291/wjgp.121535]
Corresponding Author of This Article
Rishi Chowdhary, MD, Department of Medicine, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109, United States. rxc822@case.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Araj Naveed Siddiqui, Rabia Hafsa, Vikash Kumar Karmani, Zainab Rehan, Department of Medicine, Jinnah Sind Medical University, Karachi 75510, Pakistan
Rishi Chowdhary, Department of Medicine, MetroHealth Medical Center, Cleveland, OH 44109, United States
Author contributions: Siddiqui AN, Chowdhary R, Karmani VK designed the research study; Siddiqui AN, Hafsa R, Rehan Z investigated and curated data; Siddiqui AN, Hafsa R edited the figures; Siddiqui AN, Hafsa R, Rehan Z wrote the original draft; Siddiqui AN, Hafsa R, Rehan Z, Chowdhary R, Karmani VK reviewed and edited the manuscript; Chowdhary R supervised the study.
AI contribution statement: No AI tool was involved in the generation of research concepts, interpretation of results, or formulation of conclusions. All results were critically reviewed and revised by the authors, who take full responsibility for the accuracy, originality, and integrity of the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Corresponding author: Rishi Chowdhary, MD, Department of Medicine, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109, United States. rxc822@case.edu
Received: March 27, 2026 Revised: May 25, 2026 Accepted: June 25, 2026 Published online: September 22, 2026 Processing time: 165 Days and 22.7 Hours
Abstract
Cronkhite-Canada syndrome (CCS) is a rare, non-hereditary gastrointestinal (GI) disorder characterized by diffuse polyposis in the GI tract, ectodermal abnormalities, and nutritional deficiencies. It is a multisystem disorder with a multifactorial origin, particularly autoimmune, with only about 500 cases reported from around the world. This narrative review aims to consolidate current knowledge on CCS, focusing on its epidemiology, clinical features, pathogenesis, diagnostic techniques, and treatment strategies. Clinically, patients with CCS present with chronic diarrhea, abdominal pain, protein-losing enteropathy, alopecia, onychodystrophy, and hyperpigmentation. These symptoms often overlap with other prevalent GI conditions like ulcerative colitis, leading to misdiagnosis of CCS in earlier stages of the disease. Diagnosis of CCS requires a combination of laboratory analyses facilitated with endoscopic visualization of characteristic polyps, histopathological evaluation, and exclusion of other polyposis syndromes. Treatment remains non-standardized, with corticosteroids being the mainstay of management. Other therapeutic regimens include immunosuppressants, biologic agents, non-steroidal anti-inflammatory drugs, and proton pump inhibitors, which are often used as adjunctive therapy with steroids and paired with nutritional supplementation. On the other hand, malignant polyps need to be surgically resected. The prognosis of CCS is improving owing to improved treatment strategies and better patient outcomes. Further research is crucial to enhance our understanding of the pathologic mechanisms of CCS, ultimately aiming to improve early detection and reduce long-term morbidity and mortality.
Core Tip: Cronkhite-Canada syndrome is a rare, non-hereditary gastrointestinal (GI) polyposis disorder with multisystem involvement and significant diagnostic challenges due to its overlap with more common GI diseases. This review provides a comprehensive synthesis of current evidence, highlighting emerging insights into its multifactorial pathogenesis, including immune dysregulation, microbiome alterations, and potential infectious triggers. It also emphasizes the evolving role of immunosuppressive and biologic therapies alongside nutritional support. By integrating clinical features, diagnostic strategies, and therapeutic approaches, this article proposes a structured framework to improve early recognition, guide management, and reduce long-term complications, including malignancy.
