Neuronal hypertrophy in acute appendicitis

Objective.-The pathogenesis of appendicitis remains poorly understood. Howe ver, there is increasing evidence of involvement of the enteric nervous sys tem in immune regulation and in inflammatory responses. This study was set up to characterize the status of the enteric nervous system in normal and i n inflamed appendixes. Methods;-S100- and 2',2'-cyclic nucleotide 3' phosphodiesterase-positive Sc hwann cells, synaptophysin, and neuron-specific, enolase-positive nerve fib ers and tryptase-positive mast cells were evaluated with immunohistochemica l staining in surgically resected appendixes from 20 children with histolog ically proven acute appendicitis (HA), 10 histologically normal appendixes (HN) from patients with a clinical diagnosis of appendicitis, and 10 normal appendixes from patients undergoing elective abdominal surgery. Immunostai ned sections were subjected to quantitative image analysis. The number and size of ganglia and the number of nerve fibers, Schwann cells, and mast cel ls in each tissue compartment was quantitatively or semiquantitatively meas ured. Results.-Increased numbers of fibers, Schwann cells, and enlarged ganglia, widely distributed in the muscularis externa and submucosa, were seen in al l HA appendixes and in 4 of 10 HN appendixes. The number and size of gangli a in muscularis externa and in the submucosa of appendixes with HA were sig nificantly greater compared with those in control appendixes (P < .001). A significantly increased number of individually stained nerve fibers and Sch wann cells (P < .05) were present in the muscularis externa in HA appendixe s compared with control appendixes. Significantly increased numbers of tryp tase-positive mast cells (P < .05) were present in the submucosa, musculari s, and especially in the lamina propria in HA specimens, compared with that of control tissue. Conclusions.-The significant increase in neural components and mast cells i n acute appendicitis is unlikely to develop during a single acute inflammat ory episode. This suggests an underlying chronic abnormality as a secondary reaction to repeated bouts of inflammation, obstruction, or both. These re sults challenge our current understanding of the pathophysiological process es that give rise to acute appendicitis.