426 Gut, 1990,31,426-430 Ulcerative colitis: one disease or two? (Quantitative histological differences between distal and extensive disease) Gut: first published as 10.1136/gut.31.4.426 on 1 April 1990. Downloaded from D Jenkins, A Goodall, B B Scott Abstract tive histological rectal mucosal biopsy changes in Cell counts and measurements of mucosal carefully matched groups of patients with architecture were made on rectal biopsies from proctitis and distal colitis were therefore com- nine patients with total colitis, eight with left pared with the changes in extensive ulcerative sided colitis, 15 with distal colitis, and 11 with colitis. proctitis. The mean total lamina propria cell count in proctitis and distal colitis approached twice that of extensive left sided and total Methods colitis (p<0001) and in distal proctocolitis the cell numbers are further increased in the SUBJECTS chronic over the acute phase. This difference The disease group of43 patients were all primary was not explained by age, duration, activity, or referrals to one district general hospital with treatment. The predominantly increased sigmoidoscopic and biopsy appearances typical lymphoid and mononuclear cell infiltrate in of active ulcerative proctocolitis. In none was distal proctocolitis indicates a different pattern there evidence ofCrohn's disease. All cases were of immune response, suggesting a separate characterised clinically as acutely active, either at process from extensive colitis or a more onset or exacerbation, or as chronic but still intense reaction resulting in localisation of active at the time of the biopsy. Acutely active disease. cases were defined as those with recent (within 12 weeks) onset of diarrhoea either at first onset of disease or during an exacerbation, with Ulcerative colitis may involve varying lengths of endoscopic evidence of inflammation. Chronic http://gut.bmj.com/ large bowel extending from the rectum. The activity was defined as symptoms persisting term idiopathic, or non-specific, proctitis is more than 12 weeks, and all had endoscopic applied to patients with inflamed rectal mucosa abnormality of the mucosa. Patients in com- which has an upper limit in the rectum.' Similar plete clinical and endoscopic remission were changes extending into the sigmoid colon are excluded. The patients were initially divided termed proctosigmoiditis or distal procto- into four groups on the basis of extent of disease colitis.2 Although a proportion of cases with defined by either double contrast barium enema on October 7, 2021 by guest. Protected copyright. distal disease on barium enema will have more and sigmoidoscopy or by colonoscopy performed extensive disease on colonoscopy and biopsy,45 at or about the same time as the rectal biopsy and it is still unclear whether the general view examined. Rectal biopsies were taken during the that all are manifestations of one disease is course of routine management. correct.' The gross and microscopic appear- ances and the medical treatment of localised and TOTAL COLITITIS extensive colitis are similar' 369 although a small Nine patients, seven men, five acute, with con- group ofcases of 'follicular proctitis' with promi- tinuous disease extending into the right side of nent lymphoid follicles,'0 and a group of young the colon, mostly to the caecum. The median age children with allergic proctitis characterised by was 43 years (range 16-70), median duration of large numbers of eosinophils" have been pro- the current active state - that is, since first onset posed as distinct diseases. Suggestions of an IgE or ending of the last remission) was two months mediated basis for other cases of proctitis have (range three weeks to eight years), and median not been confirmed.'2 13 total follow up was 11 years (range three to 35). Although limited extension of proctitis or Four were taking sulphasalazine and none were distal colitis has been reported in 4-45% ofcases, on steroids. Department of only 10-15% extend to the proximal colon.34 9 Histopathology, There is also only a very low risk of malignancy LEFT SIDED COLITIS Whittington Hospital, or systemic complications developing in distal Eight patients, three men, three acute, with London and the Department of colitis.3 9 It is therefore entirely possible that continuous disease extending into the descend- Gastroenterology, those patients with disease which remains ing colon, but not higher than the mid transverse County Hospital, Lincoln localised are a separate group with a different colon. Median age was 35 years (range 19-74), D Jenkins, A Goodall, pathogenesis. duration one month (range one week to one B B Scott We have previously shown the ability of year), and total follow up nine years (range 3 5- Correspondence to: Dr D Jenkins, Department of histological measurements of cell populations 15). Four were taking sulphasalazine and three Histopathology, Whittington and mucosal architecture to otherwise were also on steroids. Hospital, Highgate Hill, identify London N19 5NF. undetectable minor changes of inflammatory Accepted for publication 27 bowel disease, and to distinguish inflammatory DISTAL COLITIS June 1989 bowel disease from infective colitis.'4 '5 Quantita- Fifteen patients, seven men, six acute, with Ulcerative colitis: one disease or two? (quantitative histological differences between distal and extensive disease) 427 continuous disease extending into the sigmoid been described previously;'4 the variables are colon but not into the descending colon. Median shown in Table I. age was 35 years (range 19-55), duration seven months (range two weeks to two years), and total STATISTICAL ANALYSIS follow up nine years (range 3-5-14-5). None of Variables were transformed where necessary to Gut: first published as 10.1136/gut.31.4.426 on 1 April 1990. Downloaded from these patients was known to have progressed to normalise the distribution. The Mann-Whitney more extensive disease during this time as judged U test was used to compare age and duration of by repeat double contrast barium enema or disease, and X2 numbers on drug treatment, with colonoscopy. Six were taking sulphasalazine and colonoscopy and with acute and chronic disease three were also on steroids. in each group. All other analyses were carried out using the PROCTITIS BMDP computer package (University of Eleven patients, four men, four acute, with California) on the Amdahl computer at the continuous disease confined to the rectum. Mean University College, London, Computer Centre. extent was 8 5 cm and the maximum 15 cm. A one-way analysis of variance (ANOVA) was Median age was 34 years (range 24 75), duration carried out across the four groups using the four months (range eight weeks to 2 5 years), and program BMDP7D, which also performs pair- total follow up 12 years (range eight to 20). Only wise Student's t tests. When multiple groups one patient was known to have progressed to left were compared, the appropriate Bonferroni sided colitis on repeat colonoscopy and this significance values were used to compensate for patient's biopsy was used only as a test case. Six the number of groups, to reduce the probability patients were taking sulphasalazine and three of detecting spurious differences. Groups were were also on steroids. only regarded as not showing significant differ- The control group comprised 23 patients, nine ences, however, when the nominal probability of men, median age 38 years (range 20-73) who had each significance test was greater than 0.05.16 no evidence of organic gastrointestinal disease Student's t tests were also used in the program and were considered to have irritable bowel BMDP3D to compare the means for each vari- syndrome. able in the combined groups, and to examine the effects of drug treatment within each group. PROCEDURE Stepwise discriminant analysis was carried out Rectal biopsies were immediately fixed in using the program BMDP7M with a 'jack knife' formalin. Well oriented biopsies ofadequate size procedure to reduce any bias resulting from were cut at lu thickness perpendicular to the classifying a data set with a discriminant function mucosal surface, and sections were stained with produced from the same set. http://gut.bmj.com/ haematoxylin and eosin for counts of poly- morphs and total cellularity and for architectural measurements. IgA, IgM, and IgG plasma cells Results were shown using a peroxidase-antiperoxidase There were no significant differences between technique. Measurements were carried out using the four groups for age, duration of disease, a MOPPET image analyser. The method has number of patients receiving drug treatment, investigated by colonoscopy, or degree ofdisease on October 7, 2021 by guest. Protected copyright. activity. Variables for which the one way TABLE I Variables measured or computed and used in the analyses ANOVA was significant (p<005) are shown in Table II, with the Bonferroni significance values IGM Plasma cells/mm mucosal length IGG Plasma cells/mm mucosal length for the t tests made between each pair of groups. IGA Plasma cells/mm mucosal length There were no significant differences between SIE Surface intraepithelial polymorphs/mm mucosal length CIE Crypt intraepithelial polymorphs/10 crypts biopsies from patients with total colitis and those CLUM Crypt lumen polymorphs/10 crypt lumens with left sided colitis for any of the variables. LPP Lamina propria polymorphs/mm mucosal length CELLEN Total lamina propria cells/mm mucosal length Similarly there were no significant differences CARE Total lamina