Unraveling the Complexity of Celiac Disease: A Narrative Review of Its Multisystem Nature

Celiac disease is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible individuals, primarily those carrying <i>HLA-DQ2</i> or <i>HLA-DQ8</i> and, in rare cases, <i>HLA DQ7</i> alleles. Although traditionally regarded as a gastrointestinal condition, celiac disease is now recognized as a multisystem disorder with a wide range of clinical presentations. It has been described as a “clinical chameleon” due to its variable manifestations, which may include non-specific symptoms, extraintestinal involvement, or even an asymptomatic course, often identified only through screening of high-risk groups. This narrative review provides a comprehensive overview of celiac disease, highlighting recent insights into its pathogenesis, including genetic predisposition, immune mechanisms, and the role of environmental and microbial factors. It emphasizes the importance of recognizing extraintestinal features, outlines current diagnostic approaches and their limitations, and discusses management strategies centered around the gluten-free diet. Furthermore, it explores emerging therapies aimed at improving patient outcomes and reducing dependence on dietary restriction. By synthesizing the latest developments, this review aims to present a fresh perspective on a condition with significant clinical relevance that is evolving.