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Gut: first published as 10.1136/gut.24.9.857 on 1 September 1983. Downloaded from

Gut, 1983, 24, 857-862

Case report Crohn's disease and ulcerative in the same patient C L WHITE III, S R HAMILTON, M P DIAMOND, AND J L CAMERON From the Departments ofPathology, Medicine, and Surgery, The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland, USA

SUMMARY A well documented case of a patient with both Crohn's disease and is presented. A 29 year old woman underwent resection of her terminal and ascending colon for typical Crohn's disease with ileocolitis. Eleven years later, an ileoproctocolectomy was performed for typical ulcerative colitis involving the left colon. The resection specimen also showed evidence of colonic Crohn's disease near the anastomotic site. This unusual case shows that Crohn's disease and ulcerative colitis can occur in the same patient. The rarity of such cases supports the concept that Crohn's disease and ulcerative colitis are separate entities, rather than different manifestations of the same disease process.

Crohn's disease and ulcerative colitis are the two healed with conservative measures. Four months well recognised forms of idiopathic inflammatory later she developed rectal . Proctoscopy bowel disease. As the aetiologies (or aetiology) of showed slightly inflamed rectal mucosa, but no idiopathic inflammatory bowel disease are biopsy was performed. Barium showed a unknown, these entities are distinguished on the stricture in the ascending colon; the caecum and basis of their pathologic and resulting clinical, and colon distal to the hepatic flexure were normal. An http://gut.bmj.com/ radiographic features. Some authors have suggested ileocolectomy was performed with primary ileo- that these two forms of idiopathic inflammatory colonic anastomosis in the transverse colon. bowel disease are merely different manifestations of The resection specimen from 1969 consisted of the same disease and represent the ends of a 30 cm of ileum and 25 cm of colon. The gross and histopathologic spectrum. Over the last two histopathologic findings of Crohn's disease were decades, however, reliable pathologic criteria have present in the ileum and ascending colon. Strictures evolved to separate the manifestations of Crohn's with overlying were found 6 cm proximal to disease and ulcerative colitis in the small and large and several centimetres distal to the ileocaecal valve on September 27, 2021 by guest. Protected copyright. bowel.6 Credible reports of patients with both (Figs. la, lb). The mucosa of the terminal ileum Crohn's disease and ulcerative colitis are rare,7-9 showed loss of plicae and small ulcers. Histopatho- although many such cases were described before logic sections from the strictures showed fissuring differential diagnostic criteria were established.1-12 ulceration with transmural and fibrosis We present a patient with well documented (Figs. lc, ld). In addition, non-caseating epithelioid pathologic evidence of Crohn's disease and cell granulomas were present in the pericolonic soft ulcerative colitis. The implications for aetiology and tissue (Fig. ld) and regional lymph nodes. The differential diagnosis of idiopathic inflammatory colonic mucosa between the caecum and the bowel disease are discussed. stricture was normal. Postoperative barium enema showed mild Case report oedema in the left colon, but a repeat study one year later was normal. Thirteen months after the right A 29 year old white woman presented to The Johns ileocolectomy, the patient again developed rectal Hopkins Hospital in 1968 with a fissure in ano which bleeding. revealed diffusely friable, granular rectal mucosa suggesting active ulcerative Address for correspondence: Charles L. White III, MD, Department of colitis, as did the biopsy findings. Over the next two Pathology, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75235. USA. years, the patient was treated with oral steroids and Received for publication 13 October 1982 had periods of remission. 857 Gut: first published as 10.1136/gut.24.9.857 on 1 September 1983. Downloaded from

858 White III, Hamilton, Diamond, and Cameron

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OK|.| http://gut.bmj.com/ on September 27, 2021 by guest. Protected copyright. c'AJ d Fig. 1 Specimenfrom right ileocolectomy for Crohn's disease in 1969. (a) Ileocaecal region ofgross specimen. Ulceration and loss ofplicae are seen in portion ofterminal ileum (TI) immediately proximal to ileocaecal valve (ICV). (b) Ascending colon ofgross specimen. Segmental ulceration with strictureformation (arrow) is present. Colon between the caecum (*) and stricture is grossly uninvolved. (c) Histopathologic section ofabnormal terminal ileum shown in (a). Activefissuring (U) is present. Underlying submucosa shows scarring (*) and aggregates oflymphocytes (arrow) extending to muscularis propria (MP). (H & E, x8). (d) Histopathologic section ofascending colon stricture shown in (b). Activefissuring ulcer (U) is present with underlying transmural inflammation extending into muscularis propria (MP). Non-caseating epithelioid cell granuloma (arrow) with multinucleated giant cell (see inset) is present in the pericolonic soft tissue. (H & E, x8; inset x230).

Exacerbations characterised by diarrhoea, rectal small bowel contrast studies and barium enema discomfort, and stool blood and mucus occurred showed narrowing and mucosal irregularity in the every few months. Rectal biopsies during exacerba- sigmoid colon and with normal proximal tions repeatedly showed low grade active inflam- colon, interpreted as ulcerative colitis. Repeat matory bowel disease with features suggesting barium enema 22 months later showed development ulcerative colitis. Nine years after the first resection, of shortening of the colon. Because of repeated Gut: first published as 10.1136/gut.24.9.857 on 1 September 1983. Downloaded from

Crohn's disease and ulcerative colitis in the same patient 859 Fig. 2 Specimenfrom ileoproctocolectomyfor ulcerative colitis in 1980. (a) Gross specimen. Haustra are lost and mucosa isfeatureless throughout entire left colon, including rectum. Ileocolonic anastomotic site (ICA) is in transverse colon. (b) Histopathologic section ofrectosigmoid region. Mucosa shows marked generalised atrophy. Chronic inflammation is limited to mucosa, rarely extending deeper than muscularis mucosae (MM). Muscularis propria (MP) andpericolonic tissue is normal. (H & E, x21) (c) Histopathologic section ofrectosigmoid region shown in (b). Marked crypt loss is evident. Remaining crypts show prominent distortion and epithelial mucin depletion. Muscularis mucosae (MM) contains scattered chronic inflammatory cells (H & E, X130). (d) Histopathologic section ofileocolonic anastomotic site (ICA) represented by scar through muscularis propria and transitionfrom small intestinal to colonic mucosa. Focal active inflammation (arrow) ispresentin colonic mucosa. (H & E, x21). (e) Histopathologic section ofcolonic mucosa near region indicated by arrow in (d). Granulomatous inflammation characterised by epithelioid histiocytes (short arrow) and a multinucleted giant

cell (long arrow) ispresent near an http://gut.bmj.com/ erosion. Epithelial mucin is maintained. Although located near the anastomosis site, thesefeatures suggest clinically inapparent Crohn's disease involving this area ofthe colon. (H& E, X310). on September 27, 2021 by guest. Protected copyright. Gut: first published as 10.1136/gut.24.9.857 on 1 September 1983. Downloaded from

860 White III, Hamilton, Diamond, and Cameron

bowel disease. The accepted pathologic criteria for the differentiation of these two patterns of idopathic inflammatory bowel disease in the colon were emphasised by Warren and Sommers in 19543 and Lockhart-Mummery and Morson in 1960.4 The criteria were expanded subsequently by others.5 6 Briefly, ulcerative colitis is characterised by continuous loss of haustra and mucosal atrophy on gross examination. The findings consistently involve the left colon, including the rectum. The histopatho- logic features of ulcerative colitis include diffuse and chronic inflammation generally limited to the mucosa, mucosal atrophy with crypt loss and distortion, and epithelial mucin depletion. The gross pathologic features of colonic Crohn's disease, on the other hand, include discontinuous gross involve- sl ment with intervening normal areas ('skip lesions'), a more frequent right sided distribution and relative rectal sparing. The ileum is involved also in a exacerbations of her inflammatory bowel disease, 11 majority of the cases with colonic involvement. The years after her first resection she underwent ileo- histopathologic features of Crohn's disease include proctocolectomy at age 41. fissuring ulceration; transmural extension of The resection specimen (Fig. 2a) showed aggregates of lymphocytes into the deep layers of continuous, uniform loss of haustra and mucosal the bowel wall and pericolonic soft tissue; and atrophy involving the entire left colon including the discontinuous or focal mucosal inflammation. The rectum. These features and their distribution are most characteristic feature, of course, is the non- those of ulcerative colitis. Histopathologic examina- caseating epithelioid cell granuloma, which has been tion confirmed the mucosal atrophy characterised by reported in up to 63% of Crohn's disease cases.'3 marked crypt loss with distortion of those crypts the Despite development of reliable differential http://gut.bmj.com/ remaining, distributed uniformly throughout the left criteria, difficulty still arises in the clinical, radio- colon. In addition, acute and chronic inflammation graphic, and occasionally the pathologic distinction was present in the mucosa without involvement of between ulcerative colitis and Crohn's disease. Such the submucosa or deeper layers (Fig. 2b). The acute difficulties continue to raise questions regarding the inflammation was confined largely to the rectum and nosology and ultimately the aetiology of these was accompanied by generalised mucin depletion diseases. Historically, as pathologic criteria began to (Fig. 2c). The distal predominance of the active evolve for the separation of colonic Crohn's disease inflammation, destruction of crypt architecture, and from ulcerative colitis, series of cases were reported on September 27, 2021 by guest. Protected copyright. mucin depletion are histopathologic features of describing coexistence of the two entities in ulcerative colitis. No anal or perirectal inflammation individual patients.11 12 These early reports, was present. Granulomas, which were easily however, greatly overestimated the proportion (up identified in the previous resection, were not found to 12.8%1) of cases which showed such coexistence. in the left colon despite examination of histologic The confusion in terminology which existed in the sections from 16 areas. The colon in the mid-portion older literature contributed to this overestimation. of the specimen was normal in three tissue blocks. In Counsell,11 for example, pointed out the term the colonic mucosa near the anastomotic site (Fig. 'ileocolitis' was used variously by different authors 2d), however, focal non-specific inflammation and to mean involvement of terminal ileum and colon by granulomatous inflammation with epithelioid histio- Crohn's disease, retrograde (or 'backwash') in cytes and multi-nucleated giant cells (Fig. 2e) were ulcerative colitis, or the actual coexistence of present, suggesting clinically inapparent recru- Crohn's disease and ulcerative colitis in an descent Crohn's disease. The ileum was uninvolved individual patient. Secondly, many of the older in two tissue blocks. reports were published before the establishment of differential criteria. For example, French and Discussion Vander,"' and Counsell 11 described the presence of granulomas in the colonic wall of specimens said to Crohn's disease and ulcerative colitis are the two show ulcerative colitis, but almost certainly well recognised forms of idiopathic inflammatory representing Crohn's disease of the colon. Gut: first published as 10.1136/gut.24.9.857 on 1 September 1983. Downloaded from

Crohn's disease and ulcerative colitis in the same patient 861 Aside from problems of terminology, overlap in The frequent overlap of ulcerative colitis and the pathologic features of Crohn's disease and Crohn's disease in earlier series of cases1' 12 was ulcerative colitis can occur in the occasional patient. cited as evidence that these two forms of idiopathic Mucosal changes like those in ulcerative colitis are inflammatory bowel disease merely represented the sometimes present in some areas of a ends of a spectrum, as various manifestations of a specimen showing otherwise typical Crohn's disease could occur together frequently in a disease. The greatest overlap, however, is observed particular patient with that disease. Most of such in specimens from patients who undergo urgent cases with 'overlap', however, were based on loosely surgery for fulminant colitis ('toxic '). applied criteria and therefore spurious. The actual Specifically, deep ulceration with transmural inflam- rarity of patients with both ulcerative colitis and mation is common in fulminant ulcerative colitis,. Crohn's disease supports the alternative concept and may be interpreted as evidence of Crohn's that these two types of idiopathic inflammatory disease. Price5 and Morson14 referred to such bowel disease are separate entities, as the chances of difficult cases as 'colitis indeterminate', indicating a given patient having two uncommon and unrelated that final classification cannot be determined in the diseases are small. Indeed, Eyer has pointed out specimen under conside'ration. Review of sequential that the calculated rate of coincidence of ulcerative pathologic material from such patients, including colitis and Crohn's disease based on prevalence data pre- and post-operative biopsies, will allow a large for each entity would predict between 15 and 60 proportion of these cases to be classified as either patients in the United States with both diseases.9 ulcerative colitis or Crohn's disease. Furthermore, The number of reported bona fide cases of Crohn's difficulty in the pathologic distinction between disease and ulcerative colitis is far fewer than these ulcerative colitis and Crohn's disease in a particular data would suggest. Although such cases of specimen does not imply an overlapping form of ulcerative colitis and Crohn's disease in the same inflammatory bowel disease in the patient. Rather, patient are, therefore, of considerable interest, the it signifies a lack of findings strongly favouring either final answer to the question of the relationship ulcerative colitis or Crohn's disease in the particular between these two forms of idiopathic inflammatory biopsy or resection specimen under consideration. bowel disease depends on the answer to the question In contrast with apparent overlap between of aetiology. Crohn's disease and ulcerative colitis based upon insufficient distinguishing features, some authors Dr Hamiliton was supported by a Senior Fellowship http://gut.bmj.com/ have reported that overlap exists because Crohn's Award from the National Foundation for Ileitis and disease and ulcerative colitis may actually represent Colitis. The photomicrographs were taken by the same disease.' Also, Shorter et all suggested Raymond E Lund, RBP. Assistance in preparing that, while ulcerative colitis and Crohn's disease are the illustrations was provided by Ms Jo Ann not necessarily the same nosologic entity, they may Hoffman. The manuscript was typed by Ms Nancy merely represent separate responses to different Folker and Mrs Nancy Lambert. The authors thank antigenic challenges, or individualised responses to Dr Basil Morson and Dr John Yardley for reviewing similar antigenic stimuli. the case. on September 27, 2021 by guest. Protected copyright. As knowledge of the pathologic manifestations of ulcerative colitis and Crohn's disease has evolved, recent case reports of coexistent ulcerative colitis and Crohn's disease7-9 have provided acceptable pathologic documentation. As a report of References synchronous ulcerative colitis and Crohn's disease 1 Lewin K, Swales JD. Granulomatous colitis and by Voitk et a18 illustrates, however, emergency atypical ulcerative colitis: histological features, colectomy performed for fulminant colitis behaviour, and prognosis. 1966; 50: complicates interpretation. By contrast, we present 21 1-23. a patient with Crohn's disease and ulcerative colitis 2 Margulis AR, Goldberg HI, Lawson TL, et al. The whose course is well documented pathologically in overlapping spectrum of ulcerative and granulomatous two resection specimens and serial biopsies. colitis: a roentgenographic-pathologic study. Am J Roent Rad Ther Nucl Med 1971; 113: 325-34. Furthermore, our case was not complicated by 3 Warren S, Sommers SC. Pathology of regional fulminant colitis and was evaluated with strictly and ulcerative colitis. JAMA 1954; 154: 189-93. applied pathologic criteria in numerous histopatho- 4 Lockhart-Mummery HE, Morson BC. Crohn's disease logic sections. This case, therefore, provides strong (regional enteritis) of and its distinction evidence that Crohn's disease and ulcerative colitis from ulcerative colitis. Gut 1960; 1: 87-105. can occur in the same patient. 5 Price AB. Overlap in the spectrum of non-specific Gut: first published as 10.1136/gut.24.9.857 on 1 September 1983. Downloaded from

862 White III, Hamilton, Diamond, and Cameron inflammatory bowel disease - 'colitis indeterminate'. correlation. Am J Roent Rad Ther Nucl Med 1955; 74: J Clin Pathol 1978; 31: 567-77. 977-88. 6 Yardley JH, Donowitz M. Colorectal biopsy in inflam- 11 Counsell B. Lesions of the ileum associated with matory bowel disease. In: Yardley JH, Morson BC, ulcerative colitis. Br J Surg 1957; 44: 276-90. Abell MR, eds. The . Inter- 12 Colcock BP, Vansant JH, Contreras 0. Surgical national Academy of Pathology Monograph No. 18. treatment of coexisting regional enteritis and ulcerative Baltimore: Williams & Wilkins, 1977: 66-75. colitis. Surg Gynecol Obst 1961; 112: 96-100. 7 von Shima E. Coincidence of Crohn's regional enteritis 13 Cook MG. The size and histological appearances of and ulcerative colitis. Munch Med Wochenschr 1970; mesenteric lymph nodes in Crohn's disease. Gut 1972; 45: 2026-8. 13: 970-2. 8 Voitk AJ, Owen DR, Lough J. Coexistent regional 14 Morson BC, Dawson IMP, eds. Gastrointestinal enteritis and ulcerative colitis. Int Surg 1976; 61: 535-7. Pathology, 2nd ed. Oxford: Blackwell Scientific 9 Eyer S, Spadaccini C, Walker P, Ansel H, Schwartz M, Publications; 1979: 512-74. Sumner HW. Simultaneous ulcerative colitis and 15 Shorter RG, Huizenga KA, Spencer RI. A. working Crohn's disease. Am J Gastroenterol 1980; 73: 345-9. hypothesis for the etiology and pathogenesis of 10 French AJ, Vander SA. Idiopathic chronic ulcerative nonspecific inflammatory bowel disease. Dig Dis 1972; colitis and regional : clincopathologic 17: 1024-32. http://gut.bmj.com/ on September 27, 2021 by guest. Protected copyright.