The pathogenesis of idiopathic megacolon

Background Even today, the pathogenesis of idiopathic megacolon is still a subject of controversy. Anomalies of the gastrointestinal autonomous nervous system or of the smooth muscle of the muscularis propria are being considered. Methods Sixty-three idiopathic megacolon resections between 1997 and June 2004 were investigated. The native specimens were coiled caudo-cranially and cryostat-cut. Connective tissue was stained with picric acid/Sirius red after Delauney fixation. Immunohistochemistry was performed for collagen types I, II, III and IV, as well as smooth muscle actin, vimentin, desmin fibronectin and CD117 for interstitial cells of Cajal. The enteric nervous system was examined by enzyme histochemistry for acetylcholine-esterase, lactate dehydrogenase, succinic dehydrogenase and nitroxide synthase. Results Histologically, idiopathic megacolon was characterized by a total atrophy of the collagenous tendinous connective tissue membrane of the myenteric plexus and the tendinous collagen fibre net of the muscularis propria. Immunohistochemically, mainly collagen type III was missing in the muscularis propria. Interestingly, the incidence of idiopathic megacolon in those of the female sex was seven times more frequent than in the male sex. The myenteric plexus was normal in the majority of patients. Interstitial cells of Cajal, collagen II and IV, as well as smooth muscle actin, desmin and fibronectin showed no consistent alteration. Conclusion A normally structured tendinous fibre net of muscularis propria is an essential prerequisite for effective gut peristalsis. Atrophy of the tendinous fibre net abolishes peristalsis and allows for unlimited distension of the colon. A diagnosis of idiopathic megacolon can reliably be made on a collagen stain. The normal findings of myenteric plexus support the hypothesis that a primary metabolic defect of muscularis propria may be the underlying cause of idiopathic megacolon.