Cronkhite-Canada Syndrome: A Comprehensive Review of Its Pathophysiology, Clinical Manifestations, and Current Therapeutic Approaches

Abstract

Cronkhite-Canada Syndrome (CCS) is a rare, non-hereditary gastrointestinal polyposis syndrome characterized by a complex constellation of clinical features, including diffuse gastrointestinal polyposis, ectodermal abnormalities, and profound malabsorption. Although its exact etiology remains elusive, an autoimmune pathogenesis has been increasingly suspected, with reports of immune-mediated damage contributing to epithelial dysfunction. Patients with CCS typically present with chronic diarrhea, weight loss, protein-losing enteropathy, and alopecia, in addition to nail dystrophy and cutaneous hyperpigmentation. Histopathological examination of intestinal polyps reveals hamartomatous and inflammatory characteristics, with a predilection for the stomach and colon.

The diagnosis of CCS relies on a combination of endoscopic findings, histopathological analysis, and the exclusion of other polyposis syndromes. Given the high morbidity and potential for malignant transformation, early recognition and intervention are crucial. Treatment strategies are primarily supportive, aiming to manage nutritional deficiencies and control inflammation. Glucocorticoids, immunosuppressive agents, and proton pump inhibitors have been utilized with varying success, while emerging therapies targeting immune dysregulation offer potential novel avenues for management. Despite therapeutic advancements, the prognosis remains guarded, with a substantial risk of relapse and complications such as gastrointestinal bleeding and malignancy.

This review aims to provide a detailed analysis of the pathophysiology, clinical spectrum, diagnostic modalities, and therapeutic strategies for CCS, emphasizing recent insights into its immunopathogenesis and emerging treatment options.