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RESEARCH: Morten Frisch, Bo V Pedersen, and Roland E Andersson Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark BMJ 2009; 338: b716 [Abstract] [Full text]

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Might immunization against endotoxin prevent ulcerative colitis and peptic ulceration?

Richard G Fiddian-Green   (12 March 2009)

Appendicitis, ulcerative colitis and aberrant reinnervation

MJ Quinn MB ChB MD MRCOG LLM   (4 April 2009)

Might immunization against endotoxin prevent ulcerative colitis and peptic ulceration? 12 March 2009
Richard G Fiddian-Green, FRCS, FACS None Send response to journal: Re: Might immunization against endotoxin prevent ulcerative colitis and peptic ulceration?	This interesting study has shown that, "appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis" (1). Might the protection have been conferred by the development of antibodies to endotoxin? Both appendicitis and ulcerative colitis were extremely uncommon in the Zulu population when I worked at the KEVIII hospital in Durban a few decades ago and yet amoebic and bacillary dysentery were extremely common. The late Professor Wilmot, on whose amoebiasis unit I worked as an HP, used to say that he had never seen a case of ulcerative colitis in his Zulu and Indian patients that had not had an antecedent attack of dysentery. Might that mean that dysentery protects Zulus and Indians from developing ulcerative colitis in the same way that appendicitis protected patients in Sweden and Denmark in this study? The mortality risk in fulminant colitis is said to be greatest with the first attack and to be far less in subsequent attacks. If true might the risk of dying from ulcerative colitis also be reduced by developing an immunity to the systemic effects of endotoxin during the first attack? The systemic effects of endotoxin are well known. It is also common to experience difficulty in cross-matching blood for patients requiring surgery for ulcerative colitis because of all the funny antibodies these patients tend to have developed. The endotoxin in H pylori has been implicated in the pathogenesis of peptic ulceration (2). Might endotoxin have a similar effect upon colonic mucosa which is exposed to very much large amounts of endotoxin produced by E coli? But the endotoxin does not damage healthy colonic mucosa and so some degree of antecedent cellular dysfunction must be required for it to do so [Virchow's cell theory](3). There are gaps in this line of thinking but if the underlying hypotheses are correct then immunizing healthy people against endotoxin should reduce the risk both gastric and colonic mucosal ulceration in addition to reducing the risk of death from acute abdominal catastrophes including fulminant ulcerative colitis. 1. Morten Frisch, Bo V Pedersen, and Roland E Andersson Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark BMJ 2009; 338: b716. 2. Richard G. Fiddian-Green. Helicobacter pylori eradication and L- dopa absorption in patients with PD and motor fluctuations. Neurology. 2007 Mar 27;68(13):1085. 3. Virchow's Cell Theory vs Pasteur's Germ Theory Richard G Fiddian-Green (3 September 2004) eLetter re: Nosocomial infections: What needs to be done? CMAJ 2004; 171: 421 Competing interests: None declared
Appendicitis, ulcerative colitis and aberrant reinnervation 4 April 2009
MJ Quinn MB ChB MD MRCOG LLM, Consultant in Gynaecology London SW6 4PH Send response to journal: Re: Appendicitis, ulcerative colitis and aberrant reinnervation	Appendicitis and ulcerative colitis often result from injuries to the autonomic nervous system. In "neuroimmune" appendicitis three different patterns of aberrant reinnervation result in visceral dysmotility and inflammation (1). Different expressions of similar injuries in Meissner's plexus occur in ulcerative colitis (2). Neither occurs in non-Westernised, Third World communities (3). DP Burkitt identified the differences in daily stool weights (110g v 450g), and bowel transit times (80 hours v 34 hours). He did not identify the primary source of aberrant reinnervation which are persistent physical efforts during defaecation (4). Resulting autonomic denervation takes place at different sites in the mesenteric and hypogastric nerve plexi with different disease phenotypes. The morphology of autonomic nerves has disappeared with their post-war preservation in formalin (5). Both "neuropathic" forms of these diseases are entirely preventable by better diets and better bowel habits - as are many other "phenotypes" of Western diseases at different ages of onset (4). (1) Guller U, Oertli D, Trracciano L, Harder F. Neurogenic appendicopathy: a frequent, almost unknown, disease picture. Evaluation of 816 appendices and review of the literature. Chirurg 2001; 72(12): 1508-09 (2) Geboes K, Collins S. Structural abnormalities of the nervous system in Crohn’s disease and ulcerative colitis. Neurogastroenterol Motil 1998; 10:1189-192 (3) Burkitt DP. Some diseases characteristic of modern Western civilization. BMJ 1973; 1:274-8. (4) Quinn MJ Perivascular nerve fiber proliferation. J Obstet Gynaecol 2007; 27(2):185-8. (5) Spackman R, Wrigley B, Roberts A, Quinn M. The inferior hypogastric plexus: a different view. J Obstet Gynecol 2007; 27(2) 130-3 Competing interests: None declared