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Ulcerative Colitis: Definition, Historical Background, Aetiology, Diagnosis, Natural History and Local Complications

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Ulcerative Colitis: Definition, Historical Background, Aetiology, Diagnosis, Natural History and Local Complications Postgrad. med. J. (September 1968) 44, 684-692. Postgrad Med J: first published as 10.1136/pgmj.44.515.684 on 1 September 1968. Downloaded from Ulcerative colitis: definition, historical background, aetiology, diagnosis, natural history and local complications F. T. DE DOMBAL Lecturer in Surgery, University of Leeds Definition by such physicians as Aretaeus (A.D. 300), and It has recently been argued that, since we do the curiously aptly named Soranus (A.D. 117); and not know the basic cause of ulcerative colitis, it has been suggested that in 1745 Prince Charles, formal definition of the disease is impossible and the Young Pretender to the throne, suffered from should not be attempted (Bargen, 1966). None- ulcerative colitis and cured himself by adopting theless, the recent recognition that non-infectious a milk-free diet (Wilson, 1961)! colitis may be sub-divided into various disease Some years after Wilks (1859) first referred to entities-such as ulcerative colitis, Crohn's the disease by name, the Surgeon General of disease, ischaemic colitis and so on-has made it the Union Army (describing the medical history imperative to define each of these disease entities of the American Civil War), also referred as closely as possible. The definition adopted in directly to 'ulcerative colitis'-and even producedProtected by copyright. the present context is as follows: photomicrographs showing the histological appearances, an outstanding technical achieve- Ulcerative colitis ment for the time (Crohn, 1962). Following these An inflammatory disease of unknown origin, pioneer descriptions the pathological and clinical characterized clinically by recurrent attacks of features of the disease were closely characterized, bloody diarrhoea, and pathologically by a diffuse notably by Wilks & Moxon (1875), Allchin inflammation of the wall of the large bowel. The (1885) and Hale-White (1888). Gradually ulcer- inflammatory changes spread proximally from the ative colitis became more widely recognized- rectum; and are confined to (or most severe in) until in 1909, at a symposium of the Royal the colonic and rectal mucosa. Society of Medicine, no less than 300 cases had From this it will be apparent that the custom- been collected from the various London ary name by which this disease is known- hospitals. Since then the disease has consistently 'ulcerative colitis'-is a thoroughly bad one, since increased in popularity, until recent studies by ulceration is not a 'sine qua non' of the disease Evans & Acheson (1965) have suggested that it and since the disease usually involves colonic afflicts roughly 1 in 1000 of the general popula- http://pmj.bmj.com/ and rectal mucosa. Undoubtedly 'idiopathic tion. diffuse mucosal proctocolitis', would be a more accurate descriptive term. Unfortunately however Aetiology the terminology appertaining to various forms of Whilst it is unfortunately true to say that the colitis 'is already buried under the verbal debris aetiology of ulcerative colitis remains obscure, of several centuries' (Crane, 1927); and since the during the past few decades term 'ulcerative colitis' possesses the twin merits many attempts have been made to unravel this complicated problem. on September 30, 2021 by guest. of admirable brevity and wide usage, this is the The most popular theories concerning the term which will be adopted in the following aetiology of ulcerative colitis can be listed as description of the disease. follows: Historical background Infection In all probability we shall never know who first Even though ulcerative colitis had clearly been described ulcerative colitis; although the disease separated from the contagious forms of diarrhoea was first referred to by name in 1859 by Sir by the middle of the nineteenth century, until Samuel Wilks. Prior to that date, as far back as recently many workers refused to believe that this Roman times, various forms of non-contagious disease was not infectious in nature. Perhaps the diarrhoea were described freely in the literature most widely celebrated of these was Bargen, who Ulcerative colitis 685 Postgrad Med J: first published as 10.1136/pgmj.44.515.684 on 1 September 1968. Downloaded from in 1924 claimed to have isolated a diplococcus would be a serious omission to dismiss this sub- from the stools of patients suffering from ulcer- ject without dealing in some detail with the ative colitis-and even produced a vaccine potential allergen which has been most widely against this diplococcus, which was claimed to discussed during the last 40 years, namely cow's be effective in such patients. Unfortunately in milk. the fullness of time it became apparent that these The idea that cow's milk might be in some way claims were not entirely justified. Bargen's responsible for the development of ulcerative 'diplococcus' was shown to be almost certainly colitis was first emphasized by Andresen (1925, a harmless type of enterococcus found in the 1942). More recently as a result of studies by stools of vast numbers of the general popula- Truelove and his colleagues at Oxford, several tion; and no real convincing evidence was forth- additional facts have come to light which appear coming to suggest that the vaccine was effective to support this hypothesis. These workers have in preventing attacks of colitis. shown that occasional patients with ulcerative Since that date other authors have postulated colitis experience a remission of their disease that a number of organisms might be partly when milk products are excluded from their diet, responsible for ulcerative colitis, including and suffer a relapse when they are re-introduced. parasites, fungi and various viruses (Fradkin, Also it has been shown that the titre of antibodies 1937; Dragstedt, Dack & Kirsher, 1941 ; Hender- to milk proteins in the circulation is significantly son, Pinkerton & Moore, 1942; Victor, Kirsner & raised in colitic patients when compared with Palmer, 1950). Unfortunately, however, further normal matched controls, and it has been further careful controlled studies have failed to uphold suggested that a significantly greater proportion the claims of these various organisms to be the of colitis patients have abandoned breast feeding offending agents in causing ulcerative colitis. in the 1st month of life than healthy matched Thus there is little concrete evidence nowadays controls (Truelove, 1961; Taylor & Truelove, Protected by copyright. in support of any hypothesis proposing an infec- 1961; Acheson & Truelove, 1961; Wright & True tious aetiology for ulcerative colitis. love, 1965a, b). However, in a subsequent controlled trial Mucinases (Wright & Truelove, 1965a), the benefit derived In 1947 Meyer and his colleagues (Meyer, from a milk-free diet was only marginally Gellhorn & Prudden, 1947) proposed that ulcer- significant despite the application of complex and ative colitis might be due to destruction of the elegant statistical tests; and it would require a mucus lining the surface of the colon by enzymes, much larger and more prolonged trial to confirm (which were termed mucinases), thus rendering the value of this diet. As for the claim that the colon more susceptible to attack by bacterial circulating antibody titre to milk is raised both and other agents. It was shown that stool concen- in colitic patients and in individuals who are tration of lysozyme (an enzyme claimed to be weaned at an early age, this has both been sup- capable of digesting colonic mucus), was higher ported and-conversely-denied (Dudek, Spiro & in colitic patients than in normal controls, and Thayer, 1965), by other careful controlled that the stool concentration rose and fell during studies. http://pmj.bmj.com/ exacerbations and relapses of colitis. There are several other pieces of evidence It remained, however, far from certain that which argue that milk may not be the prime lysozyme was the cause of this disease, since the cause of ulcerative colitis. We in Leeds have changes observed in lysozyme titre could very tried to repeat Acheson and Truelove's survey well have been the result instead. Finally this concerning early weaning; but the majority of hypothesis fell into disrepute when it was shown our patients could unfortunately not recall (albeit in vitro) that lysozyme was incapable of whether they were breast or bottle fed, and most on September 30, 2021 by guest. dissolving or digesting human mucus (Glass et al., of them seemed unable to find out! But we did 1950). discover that it is the clandestine custom of many maternity nurses to administer a feed of Allergy cow's milk every night (so as not to disturb the Despite the fact that some workers have mother), to 'breast fed' infants born in hospital! succeeded in producing a type of delayed hyper- We may conclude that milk is unlikely to be sensitivity reaction in the colon of the experi- the prime aetiological agent responsible for ulcer- mental animal (Rosenberg & Fischer, 1964; ative colitis-although it may possibly play a Bicks & Rosenberg, 1964), the position of aller- secondary aetiological role, perhaps determining gens in the aetiology of ulcerative colitis is also the occurrence of some subsequent relapses of somewhat uncertain at the present time. But it the disease as suggested by Truelove (1961). 686 F. T. de Dombal Postgrad Med J: first published as 10.1136/pgmj.44.515.684 on 1 September 1968. Downloaded from Psychological factors cardiac failure, and food poisoning to be psycho- The controversy concerning Bargen's bacillus somatic diseases also! and the role of milk is as nothing compared with Autoimmunity the polemic which has raged concerning the The first studies suggesting that ulcerative possible significance of psychological factors in colitis might be an autoimmune disease are the aetiology of ulcerative colitis. Indeed there widely attributed to Broberger & Perlmann is powerful evidence to suggest that emotional (1959)-although Cornelis (1958) had already factors may be of some importance in maintain- suggested such a possibility. Broberger & Perl- ing or prolonging an existing attack of colitis.
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