ulcerative colitis: historical natural · ulcerative colitis: definition, historical background,...

Postgrad. med. J. (September 1968) 44, 684-692.

Ulcerative colitis: definition, historical background,aetiology, diagnosis, natural history and

local complications

F. T. DE DOMBALLecturer in Surgery, University of Leeds

DefinitionIt has recently been argued that, since we do

not know the basic cause of ulcerative colitis,formal definition of the disease is impossible andshould not be attempted (Bargen, 1966). None-theless, the recent recognition that non-infectiouscolitis may be sub-divided into various diseaseentities-such as ulcerative colitis, Crohn'sdisease, ischaemic colitis and so on-has made itimperative to define each of these disease entitiesas closely as possible. The definition adopted inthe present context is as follows:

Ulcerative colitisAn inflammatory disease of unknown origin,

characterized clinically by recurrent attacks ofbloody diarrhoea, and pathologically by a diffuseinflammation of the wall of the large bowel. Theinflammatory changes spread proximally from therectum; and are confined to (or most severe in)the colonic and rectal mucosa.From this it will be apparent that the custom-

ary name by which this disease is known-'ulcerative colitis'-is a thoroughly bad one, sinceulceration is not a 'sine qua non' of the diseaseand since the disease usually involves colonicand rectal mucosa. Undoubtedly 'idiopathicdiffuse mucosal proctocolitis', would be a moreaccurate descriptive term. Unfortunately howeverthe terminology appertaining to various forms ofcolitis 'is already buried under the verbal debrisof several centuries' (Crane, 1927); and since theterm 'ulcerative colitis' possesses the twin meritsof admirable brevity and wide usage, this is theterm which will be adopted in the followingdescription of the disease.

Historical backgroundIn all probability we shall never know who first

described ulcerative colitis; although the diseasewas first referred to by name in 1859 by SirSamuel Wilks. Prior to that date, as far back asRoman times, various forms of non-contagiousdiarrhoea were described freely in the literature

by such physicians as Aretaeus (A.D. 300), andthe curiously aptly named Soranus (A.D. 117); andit has been suggested that in 1745 Prince Charles,the Young Pretender to the throne, suffered fromulcerative colitis and cured himself by adoptinga milk-free diet (Wilson, 1961)!Some years after Wilks (1859) first referred to

the disease by name, the Surgeon General ofthe Union Army (describing the medical historyof the American Civil War), also referreddirectly to 'ulcerative colitis'-and even producedphotomicrographs showing the histologicalappearances, an outstanding technical achieve-ment for the time (Crohn, 1962). Following thesepioneer descriptions the pathological and clinicalfeatures of the disease were closely characterized,notably by Wilks & Moxon (1875), Allchin(1885) and Hale-White (1888). Gradually ulcer-ative colitis became more widely recognized-until in 1909, at a symposium of the RoyalSociety of Medicine, no less than 300 cases hadbeen collected from the various Londonhospitals. Since then the disease has consistentlyincreased in popularity, until recent studies byEvans & Acheson (1965) have suggested that itafflicts roughly 1 in 1000 of the general popula-tion.

AetiologyWhilst it is unfortunately true to say that the

aetiology of ulcerative colitis remains obscure,during the past few decades many attempts havebeen made to unravel this complicated problem.The most popular theories concerning theaetiology of ulcerative colitis can be listed asfollows:

InfectionEven though ulcerative colitis had clearly been

separated from the contagious forms of diarrhoeaby the middle of the nineteenth century, untilrecently many workers refused to believe that thisdisease was not infectious in nature. Perhaps themost widely celebrated of these was Bargen, who

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in 1924 claimed to have isolated a diplococcusfrom the stools of patients suffering from ulcer-ative colitis-and even produced a vaccineagainst this diplococcus, which was claimed tobe effective in such patients. Unfortunately inthe fullness of time it became apparent that theseclaims were not entirely justified. Bargen's'diplococcus' was shown to be almost certainlya harmless type of enterococcus found in thestools of vast numbers of the general popula-tion; and no real convincing evidence was forth-coming to suggest that the vaccine was effectivein preventing attacks of colitis.

Since that date other authors have postulatedthat a number of organisms might be partlyresponsible for ulcerative colitis, includingparasites, fungi and various viruses (Fradkin,1937; Dragstedt, Dack & Kirsher, 1941 ; Hender-son, Pinkerton & Moore, 1942; Victor, Kirsner &Palmer, 1950). Unfortunately, however, furthercareful controlled studies have failed to upholdthe claims of these various organisms to be theoffending agents in causing ulcerative colitis.Thus there is little concrete evidence nowadaysin support of any hypothesis proposing an infec-tious aetiology for ulcerative colitis.

MucinasesIn 1947 Meyer and his colleagues (Meyer,

Gellhorn & Prudden, 1947) proposed that ulcer-ative colitis might be due to destruction of themucus lining the surface of the colon by enzymes,(which were termed mucinases), thus renderingthe colon more susceptible to attack by bacterialand other agents. It was shown that stool concen-tration of lysozyme (an enzyme claimed to becapable of digesting colonic mucus), was higherin colitic patients than in normal controls, andthat the stool concentration rose and fell duringexacerbations and relapses of colitis.

It remained, however, far from certain thatlysozyme was the cause of this disease, since thechanges observed in lysozyme titre could verywell have been the result instead. Finally thishypothesis fell into disrepute when it was shown(albeit in vitro) that lysozyme was incapable ofdissolving or digesting human mucus (Glass et al.,1950).

AllergyDespite the fact that some workers have

succeeded in producing a type of delayed hyper-sensitivity reaction in the colon of the experi-mental animal (Rosenberg & Fischer, 1964;Bicks & Rosenberg, 1964), the position of aller-gens in the aetiology of ulcerative colitis is alsosomewhat uncertain at the present time. But it

would be a serious omission to dismiss this sub-ject without dealing in some detail with thepotential allergen which has been most widelydiscussed during the last 40 years, namely cow'smilk.The idea that cow's milk might be in some way

responsible for the development of ulcerativecolitis was first emphasized by Andresen (1925,1942). More recently as a result of studies byTruelove and his colleagues at Oxford, severaladditional facts have come to light which appearto support this hypothesis. These workers haveshown that occasional patients with ulcerativecolitis experience a remission of their diseasewhen milk products are excluded from their diet,and suffer a relapse when they are re-introduced.Also it has been shown that the titre of antibodiesto milk proteins in the circulation is significantlyraised in colitic patients when compared withnormal matched controls, and it has been furthersuggested that a significantly greater proportionof colitis patients have abandoned breast feedingin the 1st month of life than healthy matchedcontrols (Truelove, 1961; Taylor & Truelove,1961; Acheson & Truelove, 1961; Wright & Truelove, 1965a, b).However, in a subsequent controlled trial

(Wright & Truelove, 1965a), the benefit derivedfrom a milk-free diet was only marginallysignificant despite the application of complex andelegant statistical tests; and it would require amuch larger and more prolonged trial to confirmthe value of this diet. As for the claim thatcirculating antibody titre to milk is raised bothin colitic patients and in individuals who areweaned at an early age, this has both been sup-ported and-conversely-denied (Dudek, Spiro &Thayer, 1965), by other careful controlledstudies.There are several other pieces of evidence

which argue that milk may not be the primecause of ulcerative colitis. We in Leeds havetried to repeat Acheson and Truelove's surveyconcerning early weaning; but the majority ofour patients could unfortunately not recallwhether they were breast or bottle fed, and mostof them seemed unable to find out! But we diddiscover that it is the clandestine custom ofmany maternity nurses to administer a feed ofcow's milk every night (so as not to disturb themother), to 'breast fed' infants born in hospital!We may conclude that milk is unlikely to be

the prime aetiological agent responsible for ulcer-ative colitis-although it may possibly play asecondary aetiological role, perhaps determiningthe occurrence of some subsequent relapses ofthe disease as suggested by Truelove (1961).

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Psychological factorsThe controversy concerning Bargen's bacillus

and the role of milk is as nothing compared withthe polemic which has raged concerning thepossible significance of psychological factors inthe aetiology of ulcerative colitis. Indeed thereis powerful evidence to suggest that emotionalfactors may be of some importance in maintain-ing or prolonging an existing attack of colitis.It is well known that feelings of anxiety or resent-ment may be accompanied by several changes inthe colonic mucosa, comprising an increase intone, in lysozyme secretion, and in intracolonicpressures; furthermore the mucosa may becomehyperaemic and secrete a thick tenacious mucus(Grace, Wolf & Wolff, 1951). These physiologicalstudies have extreme importance, in that theyprovide powerful evidence in favour of the con-tention that attacks of colitis are more prolongedand severe in the presence of an adverse psycho-logical reaction; and they provide powerful sup-port for the inclusion in conservative manage-ment of this disease of a 'common sense' formof psychotherapy during an acute, troublesomeattack (see p. 698).However, there is very little evidence to suggest

that the majority of patients suffering from ulcer-ative colitis have an inherently differentemotional make-up from the remainder of thepopulation. Of our own series of patients inLeeds less than 5% were attending or had atten-ded a psychiatrist at any time time during theirlife. A further 9% when questioned about theirreaction to colitis admitted that they consideredtheir relapses of the disease to be related toemotional trauma-usually adding that they hadpreviously been told that their colitis was causedby 'nerves'. The remainder of our patientsseemed to us to be normal well-adjustedindividuals who showed a natural interest intheir disease. This finding has been supported bya similar carefully controlled study recentlyreported from the United States of America(Feldman et al., 1967).Undoubtedly there are changes in the attitude

to life of patients during severe attacks of colitis.They become depressed, morose and dependentupon their clinical attendants. But who wouldnot be depressed at the prospect of ten or twelvebowel actions a day; and who would not becomedependent upon a medical attendant whom oneconsidered to be capable of alleviating this dis-tressing symptom? If such depression and depen-dence are to be accepted criteria for a 'psycho-somatic' disease, then one must carefully considerthe claims of diseases such as peripheral arterio-sclerosis, colonic cancer, hiatal hernia, congestive

cardiac failure, and food poisoning to be psycho-somatic diseases also!AutoimmunityThe first studies suggesting that ulcerative

colitis might be an autoimmune disease arewidely attributed to Broberger & Perlmann(1959)-although Cornelis (1958) had alreadysuggested such a possibility. Broberger & Perl-mann (1959), using an extract of foetal colon intissue culture, were able to show haemagglutinat-ing antibodies to the colonic mucosa in no lessthan twenty out of thirty children with ulcerativecolitis. It was still possible to argue that thechanges which Broberger & Perlmann hadobserved were occurring as a totally independentphenomenon, and were unrelated to the diseaseprocess of ulcerative colitis. But this argumentwas in part refuted by their further studies(Perlmann & Broberger, 1963) showing that theleucocytes from patients with ulcerative colitishad a cytotoxic effect upon the foetal coloncells in tissue culture, an effect which was inhib-ited by pre-treatment with colon antigen. Brober-ger & Perlmann's pioneer work has recently beenconfirmed and extended (Fink, Donnelly &Jablokow, 1967; Watson, Quigley & Bolt, 1966;de Dombal, 1967).However, recent studies by Harrison (1965)

and by Wright & Truelove (1966) have shown thatautoantibodies to colon can be demonstrated inonly 15 or 20% of patients with ulcerative colitis;and moreover there is little correlation betweenthe clinical course of colitis and the incidenceof circulating antibodies to colon. Thus it seemsclear that some patients with ulcerative colitis docertainly develop circulating antibodies to theircolonic mucosa cytoplasm; but the experimentalevidence available has largely failed to showwhether these antibodies arise as a cause or asan effect of the pathological changes which areoccurring in the colon.

DiagnosisHistory and general examination

It is surprising what scant attention is paid inthe literature to this aspect of ulcerative colitis,presumably because the symptoms and thegeneral physical findings are considered to beonly too well known. The principal symptoms ofulcerative colitis are rectal bleeding and diarrhoea-which are present in nearly every case seen inan acute attack of the disease. Not so generallyrecognized is the fact that nearly two-thirds ofpatients during acute attacks suffer from acolicky type of abdominal pain; whilst lesscommon symptoms are fever, weight loss, vomit-

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ing, tenesmus-and occasionally symptoms whichoccur as the result of systemic complications suchas joint pain, iritis, or nodose skin lesions.General physical examination of the colitic

patient is usually unrewarding, but during severeacute attacks the patient may be emaciated, sallowin complexion, and showing evidence of anaemiaand dehydration. Abdominal examination mayreveal tenderness, localized muscular guardingand rigidity, and occasionally distension. How-ever, it must be pointed out that there are consid-erable discrepancies in authoritative opinionregarding the reliability of these physical findingsin severe acute ulcerative colitis; and this diffi-culty is increased by the widespread use ofcorticosteroids, which tend to mask the moreflorid signs of severe ulcerative colitis (and evenon occasion to breed a false sense of security inthe unwary physician). For this reason, in ulcer-ative colitis additional diagnostic procedures suchas sigmoidoscopy and radiological studies assumean increased importance.

Rectal examination including sigmoidoscopyIt is difficult to over-rate the value of this ex-

amination in dealing with ulcerative colitis. Afull rectal examination should be carried out onevery new case of ulcerative colitis and certainlyin any case in which the diagnosis is in doubt;sigmoidoscopy then being repeated from time totime to assess the progress of this disease. Thefacets of rectal examination which are relevantin this situation are several. First digital andproctoscopic examination is carried out, followedby a full and careful sigmoidoscopy. For anypatient with new, or doubtful disease, rectalbiopsy may then be performed; and a specimenof the patient's stools should be sent for culture.

Sigmoidoscopic appearances. The appearancesgenerally accepted as being typical of ulcerativecolitis are shown in Table 1. However, there hasrecently been considerable dispute as to the easeand reliability with which these various signs canbe recognized. Indeed in a recent survey fromLeeds, Watts, Thompson & Goligher (1966c)were able to identify only four characteristics ofthe rectal mucosa which could be recognizedwith any reliability, namely:

(1) The overall impression of normality orabnormality.

(2) The presence or absence of a vascular pat-tern.

(3)The presence or absence of contact bleed-ing.

(4)The presence or absence of oedema.Moreover, as Matts (1961) has shown, quies-

cent ulcerative colitis is perfectly compatible with

a normal sigmoidoscopic appearance showingnone of these changes. His study emphasizes theneed for additional rectal biopsy to be performedin any case where the diagnosis is in doubt, orwhere the sigmoidoscopic appearances indicatequiescent disease.

TABLE 1Sigmoidoscopic appearances of ulcerative colitis

Rectal wall Lumen of bowel

Red (or very pale) mucosa MucopusAbsent vessel pattern Free bloodContact bleeding Liquid faecesGranularityOedemaUlcerationAbsent or distorted valvesRigidityPolypsStrictureCarcinoma

Radiological examinationThe classical method of radiological examina-

tion of the colon is undoubtedly by the bariumenema technique; although more recently thevalue of plain X-ray plates of the abdomen hasbeen emphasized, and selective mesentericarteriographic method have been tried.Barium enema examination. As long ago as

1912 the barium enema appearances of ulcerativecolitis were described by Stierlin. Unfortunately,though there have been many additions sincethen to our knowledge of the abnormal findingsin the colitic bowel on X-ray examination, therehave been very few worth while attempts toevaluate the reliability and practical value of thevarious radiological signs described in thisdisease. In has, therefore, seemed relevant to usto examine our own experience in this respect ina highly critical manner, initially by means ofcareful 'observer variation' studies (Geffen et al.,1968; de Dombal et al., 1968). The findings inour own survey were somewhat disconcerting, inthat although thirty or forty signs were listed forstudy at the start of the proceedings, there wasno single radiological sign about which completeagreement could be reached between twoindependent observers!A small group of radiological signs (Table 2)

were, however, both frequently seen and reliablyinterpreted. These signs include many of the'classical appearances' of ulcerative colitis, suchas shortening and narrowing of the colon,absence of haustration, ulceration, and so on.We regard these signs as reliable; and wouldsuggest that the diagnosis of ulcerative colitis

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made on a radiological basis should be deter-mined on the presence or absence of these tenor eleven signs.

TABLE 2Frequent, reliable radiological signs of ulcerative

colitis seen on barium enema

Narrowing of bowelShortening of bowelDecreased distensibilityDecreased bowel toneUlcerationLoss of haustrationFine serration of bowel wallPolypsAbnormal haustra After evacuationLongitudinal folds JDouble contour

From Geffen et al. (1968).

Other radiological signs, described in the liter-ature as being typical of ulcerative colitis, wereshown on a detailed analysis to be almost cert-ainly unreliable, since our two observersdisagreed about their presence or absence moreoften than they were able to agree. Indeed therewere a few signs in this category, such as spicula-tion, eccentric contour and the presence of acoarse reticular mucosal pattern, which werenever agreed to be present at all! Occasionallyone or other observer would claim that he sawsuch a sign; but in view of the failure to reachagreement in a single instance concerning thepresence of these signs we must regard them asbeing utterly unreliable.

Plain X-ray abdominal examination. Simpleradiological examination of the abdomen oftenreveals useful information in cases of ulcerativecolitis. The gas ordinarily present in the largeintestine is evident on a plain X-ray plate, andfunctions as an opaque medium to give an out-line of the colon which may be recognized tobe abnormal. The changes are most usually seenin the transverse colon if the plain film is takenwith the patient lying supine. Occasionally fur-ther information is available, as when a cobble-stone appearance indicates the presence of poly-posis, or where a great widening of the colonicshadow indicates the occurrence of acute dilata-tion of the bowel. Hence the main value of plainabdominal X-ray examination is in the severeacute attack, both in the detection of the presenceof colitis, and in the detection of the develop-ment of complications such as acute colonicdilatation. To be of use for this purpose it shouldbe carried out both on admission of suchpatients, and thereafter every day or so untiltheir acute attack has undergone remission.

Pathological diagnosisIt is not proposed to deal in any great detail

with this difficult problem at this juncture; forconsiderable controversy exists concerning thepathological diagnosis of ulcerative colitis, andin particular the differentiation between ulcer-ative colitis and Crohn's disease involving thelarge bowel. Indeed this fascinating pathologicaldistinction is worthy of discussion in its ownright, and this has been undertaken elsewhere(Morson, 1968). Suffice it to say at this stage thatulcerative colitis almost without exceptioninvolves the rectum and spreads diffusely fromthe rectum for a variable distance proximallyaround the large bowel-whereas Crohn's diseaseis more apt to affect the colon and rectum on asegmental basis, the rectum frequently beingcompletely normal in this latter complaint. Theother cardinal pathological feature of ulcerativecolitis is that the disease primarily involves therectal and colonic mucosa; again in completecontra-distinction to classical Crohn's disease,which affects all coats of the bowel wall.

In the vast majority of cases on clinical andpathological grounds the two diseases can be dis-tinguished from one another with little difficulty.However, most authorities would agree that asmall percentage of patients cannot be allocatedwith confidence to either category; and perhapsfor the moment whilst this difficult problem isunresolved these occasional few cases would bethe best categorized as 'unclassifiable colitis'.

Natural historyThe natural history of ulcerative colitis has

provoked a number of important studies in thelast 100 years, two of the most recent being thosereported by Edwards & Truelove from Oxford(1963) and that of our own group in Leeds(Watts et al., 1966a, b). From these studies it hasemerged that the most logical way to deal withthe course and prognosis of ulcerative colitis isinitially to investigate the first attack of thedisease suffered by the patient; and then toassess the long-term prognosis by a careful con-sideration of the subsequent course of the disease.

First attackSince it is widely recognized that the first attack

of ulcerative colitis is perhaps the most danger-ous of all from the patient's point of view, it isastonishing that so little attention was paid tothis important aspect of the disease prior to 1963.Our own findings (Watts et al., 1966a) confirmthose of Edwards & Truelove (1963), namely thatthe factors which affect the outcome of the firstattack are:

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(1)The severity of the attack.(2) The extent of disease.(3) The age of the patient.The effect of these factors upon the

of our own patientsshown in Fig. 1.

during their first attack

loo- (a) (b) (c)

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40

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240 __ _2 3 2 3 2 .3

FIG. 1. The factors which modify the outcome of thefirst attack of ulcerative colitis; (a) the severity ofdisease, (b) the extent of involvement, and (c) the ageof the patient. Severity: 1, mild; 2, moderate; 3, severe.Extent: 1, rectum; 2, substantial; 3, total. Age: 1,

under 20; 2, 20-59; 3, over 60. (From Watts et al.,1966a.)

These findings in our own patients, coveringthe period 1952-63, emphasized that despite recentimprovements in treatment, severe attacks ofcolitis, (particularly in those with extensivedisease, or in those aged over 60 at the time),remained a formidable clinical problem with ahigh mortality. We, therefore, decided in 1964,as a result of our studies, that we would infuture invoke the aid of radical surgery at anearly stage of all severe attacks (including firstattacks), unless there was unequivocal evidenceof rapid improvement upon a conservativeregime. A more recent publication (Goligheret, al., 1967) has shown considerable initial successfor this policy. No patient has died in a firstattack of ulcerative colitis since 1963; and theoverall mortality in all severe attacks of thedisease (assessed according to the criteria ofTruelove & Witts, 1955) has been only 1-3%-as against 11-3% in the previous decade.

In summary it may be fairly said, therefore,that there is a large measure of agreement con-cerning the initial attack of colitis. The mortalityis highest during severe attacks, with extensivedisease, and in elderly patients; and this mortalitymay be sharply reduced by the early use ofsurgery where intensive medical treatment failsto produce an improvement.Subsequent course and long term prognosisEdwards & Truelove (1963) claimed that the

influence of the first attack of colitis extendedc

throughout the course of the disease-in thatthose with severe initial attacks and total initialinvolvement subsequently tended to fare badly.In view of this we also attempted to relate thesubsequent course of disease to the initial sever-ity and extent of colitis; but it soon becameapparent that in our patients what really influ-enced the subsequent prognosis in each individualpatient during each year of followup was theseverity and extent of involvement at that time.Our own results are summarized in Fig. 2. Thisshows the factors which modify the outcome(after the first referred attack) for each individualpatient in each year of their disease. The markedill effect of severe attacks, total involvement, andold age on the overall mortality can be wellseen.

C (a) (b) (c)

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1 2 3 1 2 3 2 3 4FIG. 2. The factors which modify the outcome ofulcerative colitis in each year after the first attack isover: (a) the severity and (b) extent of disease, and(c) age of the patient at the time (see Fig. 1). Age:1, 0-19; 2, 20-39; 3, 40-59; 4, 60-79. (From Wattset al., 1966b.)

High-risk patientsWe have already dealt with patients who suffer

from severe attacks of ulcerative colitis, and havecommented that these severe attacks are besttreated by radical surgery at an early stage. Ourstudies have also taught us, however, that patientswith total colonic involvement are at a consider-able risk; the mortality from the effects of thedisease in such patients being less than 2-7% ineach year of individual follow-up. This appliesnot only to patients with total involvement duringbut also to any patient who may develop totalinvolvement during the subsequent course of theirdisease. Moreover (see p. 711), there is consider-able evidence that this high cumulative mortalityin patients with total involvement may be re-duced by the use in such patients of electiveproctocolectomy. Since our studies have shownthat half such patients come to surgery anyway,many of them in desperate straits, it is not un-reasonable to argue that it would be better to

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bring all of them to surgery at a time when theyare relatively fit. Certainly the results of such apolicy (see p. 711) would seem at this earlystage to bear out such a contention.

ConclusionsTo sum up, ulcerative colitis is always likely

to re-assert itself at any time after the firstattack is over, but in any large group of coliticpatients just over half spend each year in remis-sion. The initial severity and extent of colitis givea poor guide to subsequent prognosis (partlybecause the disease shows a tendency to extendproximally with the passage of time in manypatients). Further analysis shows, however, thatthe severity and extent in the individual patientat any particular time profoundly influence thecourse and outcome of disease during that year.In our own group of patients those with totalinvolvement carry a risk to life of around 3%each year-and this mortality could almost cer-tainly be cut sharply by the use of electiveproctocolectomy for all patients with totalinvolvement.

Local complicationsThe complications of ulcerative colitis are be-

wildering in their complexity; and it was neces-sary as early as 1954 for Brooke to subdividethese into 'local' and 'systemic' complications.Local complications are those which are directlyrelated to the pathological changes in the bowel;and a list of these local complications togetherwith their frequency in our own group of 465patients in Leeds is shown in Table 3. Onceagain these fascinating complications meritdetailed individual study which is clearly notfeasible within the present context. However, itmay be appropriate to say a few words abouttwo of the most lethal complications-namelyperforation of the colon and large bowel cancer.

TABLE 3Local complications of ulcerative colitis

Ano-rectal complications 17-6 %*(a) Abscess 6-0%(b) Fistula in ano 5 4%(c) Recto Vaginal fistula 2-2%(d) Fissue in ano 12-3 %

Pseudopolyposis 12 5%Stricture 11-2%'Toxic megacolon' 3-0%Perforation 2-8%Carcinoma 1-7%Massive haemorrhage 1-5 %

*Percentage incidence is that found in 465 Leeds patients1963 series).

Perforation of the colonIntraperitoneal perforation of the colon is

without a doubt the most lethal complication ofulcerative colitis. It is apt to occur primarily inthe first attack of the disease. In patients withsevere first attacks and/or total colonic involve-ment, the risk of intraperitoneal perforation isabout 15-20% (de Dombal et al., 1965). Suchperforations in our own experience are mostlikely to occur in the sigmoid colon.

Considerable controversy has raged concerningthe influence of corticosteroid therapy on thedevelopment of perforations in the colitic patient.Many authorities, such as Bargen (1955) andBrooke (1956) are of the opinion that cortico-steroid therapy predisposes in some way to thedevelopment of colonic perforation. However,our own experience is contrary to this; for theoverall incidence of perforation in all severeattacks of the disease seem to be around 4%whether or not corticosteroids are used.The treatment of established perforation is un-

doubtedly emergency colectomy; for whereaswithout such a procedure the mortality mayreach 100% (Jankelson, McClure & Sweetsir,1945), the mortality after emergency colectomyeven in these desperate circumstances is usuallysomewhat less than 25% (de Dombal et al., 1965).Nonetheless, whilst it is true to say that estab-lished perforation is best treated by surgery, it isoften untrue to say that it is an indication forsurgery, since established perforation is exceed-ingly difficult to diagnose in the acutely illcolitic patient. Frequently a perforation of thecolon presents not with the classical clinical pic-ture of the silent, tender, rigid abdomen, butwith a more general picture of catastrophe, thepatient's general condition rapidly deterioratingdespite intensive treatment. For this reason sud-den deterioration of a patient during a severeattack-despite intensive treatment-is in ourview an indication for emergency surgery.

Large bowel cancerRecent studies (Edwards & Truelove, 1964;

MacDougall, 1964; de Dombal et al., 1966; Hin-ton, 1966); have emphasized that in patients withtotal or near-total colonic involvement by ulcer-ative colitis, the risk of development of largebowel cancer is indeed a serious one. Our ownstudies have enabled us to make some sort ofquantitative assessment of the cancer risk in thesepatients (Figs. 3 and 4). The annual risk even inpatients with total involvement of the large bowelby colitis is small during the first 10 years oftheir disease (Fig. 3); but after that it begins torise alarmingly until after 20 years of bowel

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symptoms the annual cancer risk is no less than6 %. Moreover this 6 % is an annual risk; andif the risk over a period of 20, 25 or 30 yearsis estimated, we find (Fig. 4) that this cumulativerisk in patients with total involvement over aperiod of 30 years is no less than 56%! Such adisturbing finding underlines the remarks madepreviously about the need for prophylactic sur-gery in patients with total involvement; for itshows that not only do they face risks whichare serious enough in all conscience from theircolitis, but in addition nearly half of such patientscan be expected to develop large bowel cancerwhilst still at a relatively young age.

a 5-8%>, 0

0-9 10-19 20-29Duration of colitic symptoms (years)

FIG. 3. The yearly incidence of large bowel cancerin 210 patients with total or near total involvement,related to the duration of colitic symptoms. (Fromde Dombal et al., 1966.)

60 o

50 - 56-8%o 0/40~~~~~40

. 30 _C

20 -

E

I0 20 30Durotion of colitic syptoms (years)

FIG. 4. The cumulative expected incidence of largebowel cancer over 30 years in patients with totalinvolvement by colitis. (From de Dombal et al., 1966.)

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ANDRESEN, A.F.R. (1942) Ulcerative colitis-an allergicphenomenon. Amer. J. dig. Dis. 9, 91.

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