Pathogenesis of necrotising enteritis with special reference to intestinal hypersensitivity reactions.

The aetiological aspects of 83 sporadic cases of necrotising enteritis (NE) have been studied. Of 56 cases in which histology of the intestine was possible, eight showed appearances (oedema and local eosinophilia) suggestive of a type I hypersensitivity reaction, while in 37 the appearances were suggestive of a type III reaction. We suggest that these reactions, which were more common in children and young adults, were initiating factors in the intestinal necrosis. The type III reactions (submucosal arteritis, fibrinoid necrosis of arteriolar walls, intramural and perivascular infiltration with polymorphonuclear, mononuclear, and eosinophil cells, and submucous oedema) were in seven cases accompanied by extraintestinal lesions (hypercellularity of glomeruli, amorphous material in the Bowman's capsular space, tubular casts, mononuclear cell infiltration into the hepatic portal tracts, congestion and oedema of the lung) which were compatible with systemic immune complex disease. The mesenteric lymph nodes in 12 out of 15 cases with intestinal arteritis showed appearances indicative of a humoral immune response. We suggest that NE is a two-stage process. In stage 1, a necrotic focus is established in the intestinal mucosa-submucosa by 'initiating' factors of vascular (functional or organic) or microbial (exotoxic, endotoxic, or Shwartzman) origin. Functional circulatory insufficiency in the intestine is of particular relevance to necrotising enteritis in neonates and in adults with traumatic shock or cardiac insufficiency. The jejunal and--to a lesser extent--the ileal microcirculation appear to be particularly vulnerable to microcirculatory insufficiency. Ninety-seven per cent of our cases were of NE of the small intestine of which 76% involved the jejunum alone or as a part of a jejunoileitis. These 'initiating' factors act either singly or synergistically with 'promoting' factors (changes in the volume, composition, or pH of the diet, intestinal stasis, or bacterial factors) in the establishment of necrotic foci in the intestine. Stage 2 results from the colonisation of the necrotic foci by intestinal clostridia, the toxigenic capacity of which will determine the progress of the intestinal lesion. Clinically established NE is essentially gas gangrene of the intestinal wall. Our bacteriological findings (microscopic, cultural, and serological) support a pathogenetic role of Cl. welchii in the established stages of necrotising enteritis. Strains of Cl. welchii from NE cases had significantly higher histidine decarboxylase activity than strains from control sources; it is possible that the resultant histamine production could act as a promoting factor in stage 1. Neutralising antibody against the Wanowrie virus, an Asian arbovirus which produces haemorrhagic enteritis in mice, was absent in the paired sera from 10 cases examined.