Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Its multifactorial etiopathogenesis includes altered gastrointestinal motor function, enhanced perception of visceral stimuli, and psychosocial factors. Recently, mucosal immune activation has been implicated. While routine histologic examinations often show no mucosal abnormalities, advanced histological, immunohistochemical, and ultrastructural analyses have revealed subtle morphologic changes involving lymphocytes, mast cells, enterochromaffin cells, and enteric nerves. These findings suggest new links between the central and enteric nervous systems and immune processes.
IBS Diagnosis and Subtypes
IBS affects 10-20% of adolescents and adults in Western societies, and is the most common cause of recurrent abdominal pain in children. Diagnosed based on symptomatology, several criteria, including the Manning, Rome I, Rome II, and Rome III criteria, have been developed. These criteria have shown reasonable sensitivity and specificity, with the Rome criteria having a positive predictive value of approximately 98%.
IBS is subclassified into diarrhea-predominant, constipation-predominant, and mixed subtypes. Some patients experience extraintestinal symptoms such as fatigue, fibromyalgia, urinary frequency, and headache. A subset of IBS patients report symptom onset following acute gastroenteritis, known as post-infectious IBS (PI-IBS).
Histological Findings in IBS
Routine histologic examinations often reveal no significant colonic mucosal abnormalities. However, recent studies have shown:
- Chronic Inflammatory Cells: Increased numbers of T-lymphocytes in the lamina propria and epithelial layers.
- Mast Cells: Increased mast cell density, particularly in diarrhea-predominant IBS, with mast cells often located near enteric nerves.
- Enterochromaffin Cells (EC): Increased EC cell numbers, especially in PI-IBS.
- Enteric Nerves: Increased nerve fibers staining for neuron-specific enolase, substance P, and 5-HT, with closer proximity to mast cells and lymphocytes in IBS patients.
Pathophysiological Implications
The modest increases in inflammatory cells and their potential for cytokine production suggest immune activation in IBS. The proximity of chronic inflammatory cells to enteric nerves provides an interface for direct interaction, potentially linking immune and nervous system processes. Reports of increased mast cell numbers and degranulation, along with increased spontaneous release of mast cell mediators, indicate a role for mast cells in disturbed sensorimotor functions in IBS.
Clinical Relevance
While the precise relationship between these histopathologic changes and IBS pathogenesis remains unclear, recognizing these subtle changes enhances our understanding of IBS. Quantitative analyses have uncovered significant mucosal abnormalities, suggesting that routine histopathological assessment may underestimate the extent of changes present.
Conclusion
IBS involves a complex symptomatology with multifactorial etiopathogenesis. Recent studies highlight the role of immune activation and neuro-immune interactions in IBS. Although routine pathology practices may not yet incorporate these findings, understanding the subtle histopathologic changes in IBS patients can provide valuable insights into its pathophysiology and potential treatment strategies.
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