sign in sign up
<<
Home , Proctocolitis

Tohoku J. exp. Med., 1976, 118 (Suppl.), 97-109

Crohn's Disease, Non-specific Ulcers of the , and Idiopathic Proctocolitis in a Japanese University Hospital from 1954 to 1974

MAKOTO ISHIKAWA,* IIIKARU WATANABE, GORO YAMAGISHI, OSAMU MASAMUNE, TOMOO GOMI, TSUNEO TAKAHASHI,* KENICHI SHOJI, AKIO NAGASAKI and SHOICHI YAMAGATA The Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai

ISHIKAWA, M., WATANABE, H., YAMAGISHI, G., MASAMUNE,0., Gomi, T., TAKAHASHI, T., Snoji, K., NAGASAKI, A. and YAMAGATA,S. Crohn's Disease, Non-Specific Ulcers of the Small Intestine, and Idiopathic Proctocolitis in a Japanese University Hospital from 1954 to 1974. Tohoku J. exp. Med., 1976, 118 (Suppl.), 97-109 - Most of the cases of Crohn's disease reported in Japan were originally treated surgically as acute and, after appendectomy, they were diagnosed as acute terminal or acute Crohn's disease, which should belong to a category different from typical Crohn's disease, according to the international nomenclature by the Council for International Organization of Medical Sciences in 1973. Reviewing our university hopsital records from 1954 to 1974, the incidence of typical Crohn's disease and idiopathic proctocolitis has been increasing, while the patients with intestinal tuberculosis have been decreasing. Clinical and histopathological features of operated three groups of our patients with Crohn's disease of the small intestine, non-specific ulcers of the small intestine and prestomal ileitis were comparatively studied. Futhermore, 9 cases of operated Crohn's disease of the colon and 23 cases of operated idiopathic proctocolitis were similarly evaluated. The importance of diagnosing Crohn's disease as a whole from both clinical and histopathological stand points of view was emphasized, and main differential diagnostic criteria between Crohn's disease and idiopathic proctocolitis were discussed. Crohn's disease; granulomatous ; ; idiopathic proctocolitis

As Schachter and Kirsner (1975) stated in their paper on the definition of the inflammatory bowel disease of unknown etiology, the definition and the true understanding of a disease are not achieved until the exact cause is identified, or the mechanism of the disordered structure or function is established. Although the etiology and pathogenesis of Crohn's disease and ulcerative colitis, which was designated as idiopathic proctocolitis by the Council for International Organiza tion of Medical Sciences in 1973, are not yet clarified and some of the clinical and radiological features overlap, their histopathological features have been regarded as specific for diagnosis.

Received for publication, November 20, 1975. * Present address: The Second Department of Internal Medicine, Yamagata University School of Medicine, Yamagata. 97 99 M. Ishikawa et al.

According to Jones et al. (1973), five attributes seemed most useful in separating patients with Crohn's disease of the colon from those with ulcerative colitis. These are tenesmus, abnormal , abnormal sigmoidoscopic appearance of the rectal mucosa, radiological absence of mucosa] granularity and widening of the mucosal line in ulcerated areas, and histological finding of mucin depletion of the rectal epithelium. In this communication, however, we have classified our patients with ulcerative bowel diseases into Crohn's disease based on histological evidence such as transmural inflammatory changes with non-caseating . If non-specific shallow ulcers are the sole finding and neither transmural nor definite granuloma is found histologically within the submucosa, we have designated them as non-specific ulcer of the small intestine according to Okabe et al. (1965). Patients with so-called prestomal ileitis designated by Marshak and Lindner (1973) had resection of some parts of the previously by some reasons, which were not always certain, and they developed reccurrent abdominal symptoms. The clinical, laboratory, radiological, endoscopical and histopathological features in our patients with the above-mentioned diseases are comparatively studied, and recent situation of these patients in our University Hosptial from 1954 to 1974 as well as discussion about the nomenclature and glossary relating to these diseases will be described.

PATIENTS AND METHODS We have experienced 6 cases of Crohn's ileitis or jejunoileitis and 14 cases of Crohn's colitis, 4 of which were eventually Crohn's ileocolitis , among 98,952 outpatients during a period from 1954 to 1974. During the same period , we have had 10 cases of intestinal tuberculosis and 145 cases of idiopathic proctocolitis , of which 23 cases were operated on (Table 1). Comparative studies on clinical , laboratory, radiological, endo scopical, and histopathological features were conducted among 4 cases of Crohn's disease of the small intestine, 4 cases of non-specific ulcers of the small intestine and 4 cases of so-called prestomal ileitis, and also between 9 cases of Crohn's colitis and 23 cases of idiopathic proctocolitis.

RESULTS

Clinical manifestations of Crohn's disease , non-specific ulcers of the small intestine and so-called prestomal ileitis are summarized in Fig . 1. Abdominal pain was complained of in 3 , in 1, anemia in 3, and loss of weight and in 2 out of 4 cases of Crohn's disease of the small intestine . On the other hand, anemia, and were seen in 3 out of 4 cases of non -specific ulcers of the small intestine, none of which had fever . All cases of prestomal ileitis revealed palpable lower abdominal masses without any of fever , loss of blood in the feces, and edema. Main laboratory findings of these three groups are shown in Fig . 2. A rather remarkable elevation of the blood sedimentation rate was seen only in Crohn's disease. The amount of total serum albumin was lowest in non -specific ulcers of the small intestine and lower in the Crohn's disease of the small intestine , Crohn's Disease 99

TABLE 1. Incidence of Crohn's disease, tuberculosis of the colon and idiopathic proctocolitis in Tohoku University Hospital from 1954 to 1974

Fig. 1. Clinical manifestations of cases of Crohn's disease of the small intestine, so-called " non-specific ulcers of the small intestine" and prestomal ileitis. while remarkable increase of y-globulin was found in all the groups. Instead, the y-globulin level seemed to be decreased in the group of non-specific ulcers. An in- crease of protein loss was found by the Gordon test in 3 cases of non-specific ulcers rather than in Crohn's disease or prestomal ileitis. Main clinical pictures of Crohn's colitis and idiopathic proctocolitis are shown in Fig. 3. Bloody stools or melena and diarrhea were seen in all the cases of idiopathic proctocolitis, while only 2 developed bloody stool or melena and 3 had diarrhea out of 9 cases of Crohn's colitis. In the latter, a palpable abdominal mass in the lower quadrant or fistula was observed 100 M. Ishikawa et al.

Fig. 2. Main laboratory findings. A, Crohn's disease of the small intestine; B, so-called non-specific ulcers of the small intestine; C, prestomal ileitis.

Fig. 3. Clinical differences between Crohn's colitis and idiopathic proctocolitis (1958-74).

Fig. 4. Differences in laboratory findings of Crohn's colitis and idiopathic proctocolitis . CC, Crohn's colitis; IP, idiopathic proctocolitis .

and most of the cases revealed negative tuberculin test . Values of main laboratory examinations including red and white blood cell counts, blood sedimentation rate , total serum protein and ƒÁ-globulin seemed to be lower in patients with idiopathic proctocolitis than in patients with Crohn's colitis. An increase of sedimentation rate was seen in most cases of the above diseases, and anemia, hypoproteinemia and hypo-ƒÁ-globulinemia were seen in a half of cases of idiopathic proctocolitis (Fig . 4). Radiological features of Crohn's disease of the small intestine vs . non-specific ulcers of the small intestine and Crohn's disease of the colon vs . idiopathic Crohn's Disease 101

Fig. 5. Radiological appearances in cases of Crohn's disease of the small intestine and so-called "non-specific ulcers of the small intestine" .

Fig. 6. Radiological differences between Crohn's colitis and idiopathic proctocolitis (1958-74). proctocolitis are summarized in Figs. 5 and 6, respectively. Thickening of the mucosal folds, luminal stricture, spiculae, spikes, fissure-ulcers, and cobblestone appearance were seen in the cases of Crohn's disease (Figs. 7-12), resulting from the proliferative and destructive processes of the desease, while annular strictures were more remarkable in the cases of non-specific ulcers than in the cases of Crohn's disease (Fig. 13). Lesions of Crohn's disease were asymmetric and its ulcers were usually located along the mesenteric attachment (Figs. 7 and 11). Discrete ulcers, longitudinal ulcers (Fig. 14) and lesions were found in Crohn's disease and most of the lesions terminated proximal to the rectosigmoid junction, while continuous and symmetrical lesions as well as rectal involvements were found radiologically in most cases of idiopathic proctocolitis (Fig. 15). Endoscopic findings similar to radiological pictures represent histopathological changes in the bowel. Segmental lesions, discrete and longitudinal ulcers and cobblestone appearance are diagnostic features for Crohn's disease and particularly important in differentiating Crohn's disease from idiopathic proctocolitis. Histopathological features in our cases of Crohn's disease are summarized in Table 2. A tuberculoid reaction like sarcoid, i.e., granuloma, or a cluster of 102 M. Ishikawa et al.

Fig. 7. Crohn's disease of the small intestine. Note the asymmetrical involvement of Crohn's disease. Arrows indicate discrete ulcers.

Fig. 8. Barium meal in cases of Crohn's ileitis shows a longitudinal ulcer (indicated by an arrow) and relief convergence in the ileum. An ascaris lumbricoides, which is rarely seen nowadays in Japan, is unexpectedly demon strated as an elongated filling defect in the adjacent loop of the ileum.

Fig. 9. Barium meal study in another case of Crohn's disease shows a longitudinal ulcer (thick arrow) as well as nodular pattern or cobblestone appearance (thin arrows) in the ileum. Crohn's Disease 103

Fig. 10. Barium study in the same case as shown in Fig. 8 demonstrates the lesions distributed in the caecum and ascending colon. An arrow indicates a fistula. Fig. 11. Barium enema study in the same case as Figs. 8 and 10 shows a longitudinal ulcer (thick arrow), cobblestone appearance (thin arrows) and fistulae (arrows with open circle) in the descending colon. epithelioid cells encircled by a variable number of lymphocytes and other mono nuclear cells, often including Langhans giant cells, was found in the cases of Crohn's disease. When present in the bowel and/or lymph nodes, non-caseatinggranulomas are characteristic but not pathognomonic of Crohn's disease (Figs. 16 and 17). Fissure-ulcers,i.e., extentions of ulcerations deep into or beyond the bowel wall, usually bordered by acute or chronic inflammationwhich might include granuloma, were usually found in both Crohn's disease and idiopathic proctocolitis. When these ulcers were bordered by nearly normal mucosa,the diagnosisof Crohn's disease was supported.

DISCUSSION Yanase et al. (1967) reviewed 548 cases of regional in the Japanese literature from 1950 to 1966. Approximately 70% of those cases were treated within 7 days and about half of them received operation under the diagnosisof ap pendicitis within the first 24 hr. Most of those acute cases might be different from 104 M. Ishikawa et al.

Fig. 12a and b. Films taken after evacuation of barium. Fig. 12a shows a longitudinal ulcer (thick arrow) and cobblestone appearance (thin arrow) after evacuation of barium in the same case as shown in Figs. 8 and 10. Fig. 12b was taken by the double contrast method after more air was inserted immediately after the film of Fig. 12a was taken.

Fig. 13. Non-specific multiple ulcers of the small intestine . Arrows indicate multiple small ulcers and remarkable annular strictures are seen . Fig. 14. A probe specimen, resected four years ago , of the ileum in the same case as shown in Figs. 8, 10, 11 and 12 has a longitudinal ulcer along mesenteric attachment . Crohn's Disease 105

Fig. 15. Macroscopic differences in pathology of Crohn's colitis and idiopathic proctocolitis (1958-74).

TALE 2. Histological findings of surgically resected specimens in cases of Crohn's disease of the small intestine and Crohn's colitis

typical Crohn's disease and they should have belonged to a category of acute termi nal ileitis according to the nomenclature of the Council for International Organization of Medical Sciences in 1973. The incidence of Crohn's disease is increasing in Sweeden, U.S.A., England and Denmark, while not yet so high in Finland, Norway, parts of Germany, France, and southern and eastern Europe. Krause (1971) speculated that a great consumption of synthetically manufactured food products and also an addition of different chemical substances to the natural food (often unabsorbable or perhaps causing an allergic reaction in the gut) might be reasons for such high incidences of Crohn's disease in these countries. We have been taking a good deal of fresh and natural products in Japan and, therefore, we still have a low incidence of Crohn's disease although it seems to have increased recently (Ishikawa et al. 1972, 1975). Farmer et al. (1975) studied 615 patients with Crohn's disease consecutively seen at the Cleaveland Clinic from 1966 to 1969. Operation was required for 73% of the patients with ileocolic pattern and 51% each of the patients with small intestine and colonic patterns. 106 M. Ishikawa et al.

Fig. 16. Histological findings of the specimen resected from the case shown in Figs. 8, 10-12 and 14. An ulcer and an abscess in the muscle layer surrounded by non- caseating granuloma are seen. Fig. 17. Enlargement of a part of Fig. 16 shows a non-caseating granuloma containing multinucleated giant cells.

There were postoperative recurrences in 27% of the patients with ileocolic pattern, 21% of those with small intestine pattern , and 16% of those with colonic pattern. Korelitz and Janowitz (1973) criticized the productivity in colitis surgery of the groups of Cleaveland Clinic and Lahey Clinic, warning the high recurrence rate (46%) of true granulomatous colitis as compared with the low recurrence rate (5%) of ulcerative colitis after ileostomy. The term prestomal ileitis probably should be limited to the well-known "ulcerative" variety which may result from mechanical stomal obstruction. These instances of Crohn's disease occurring proximal to a stoma are designated as recurrent Crohn's disease of the prestomal ileum (Schachter and Kirsner 1975). Considering these facts , our cases of so-called prestomal ileitis might have included Crohn's disease of the colon. We feel a necessity to follow up these patients for a long period of time . As for so-called non- specific ulcers of the small intestine by Okabe et al. (1966), whether this is one of the new disease entities or an atypical type of Crohn's disease still remains to be resolved in the future. According to Okabe et al., an ulcerative, non-prolifierative disease of the intestine is clinically seen in young adults , and its cardinal symptoms i nclude persistent occult blood in the stool of many year's duration , and marked anemia and hypoproteinemia due to the overt bleeding . Usually, it is not accompanied with diarrhea, fever or . Relapse is mostly common Crohn's Disese 101 with re-bleeding even after surgical correction, but none of perforation, fistuliza tion, intestinal obstruction or abscess is seen in spite of its long lasting course. Basic macroscopic pictures of ulcerative, non-proliferative disease of the intestine are multiple shallow ulcers developing crosswise or obliquely on the intestinal mucosa. The terminal ileum remains free from ulceration. Its microscopic features are multiple shallow ulcers mostly confined within the submucosa. Accompanying inflammation is also of a slight degree. Features seen in Crohn's disease, such as severe edema, thick proliferation of connective tissue and granuloma, cannot be observed. Our cases of non-specific ulcers of the small intestine included in the present study may be the same as described by Okabe et al., or may be different. Again we feel a necessity to repeat periodic diagnostic review for those patients. Secondary involvement of the colon in primary Crohn's disease of the ileum was first described by Colp (1934) and subsequently confirmed by other workers. Wells (1952) described a form of regional colitis with fibrosis, non-caseating tubercles and multinucleated giant cells, and designated it as "Crohn's disease of the colon" This name has become generally accepted in the British literature (Dukes and Lockhart-Mummery 1952; Lockhart-Mummery and Morson 1960). Radiological ly, the typical appearances of "segmental colitis" and "granulomatous colitis" have been described by Wolf and Marshak (1962). However, a number of patients with a granulomatous histological lesion exhibiting a clinical picture suggestive of Crohn's disease of the large bowel are symptomatically indistinguishable from ulcerative colitis (Lewin and Swales 1966). Ulcerative colitis usually starts distally as a proctocolitis and spreads towards the caecum. There are no skip areas. The out- standing histological features are mucosal erosion or ulceration, marked vascular dilatation, and a non-specific chronic inflammation limited to the mucosa and the superficial submucosa. The mucosal destruction varies from superficial erosion to full thickness ulceration. The re-epithelization of the mucosal tags produces pseudo polyps. Crohn's disease is frequently segmental although the whole colon may be affected. Skip areas are common. Microscopically, in contrast to ulcerative colitis, two distinguishing features of Crohn's disease are transmural inflammation and thickening of the bowel wall. The latter is initially due to submucosal edema but later due to fibrosis. The inflammatory consists of lymphocytes, often with prominent follicle formation, plasma cells and sarcoid-like granulomata. The latter two are probably the most useful features in the diagnosis of Crohn's disease, but they are not always found. Sometimes the granulomata are poorly formed and consist of loose follicles made up of epithelioid cells only (Lewin and Swales 1966). The of Crohn's disease, however, may be identical in the appearances with the granulomas in a minority of the cases of non-caseating tuberculosis. In the latter condition, the granulomas are usually larger and the rim of lymphocyte infiltration is more prominent. The giant cells and epithelioid cells also appear bigger. Morson (1971) pointed out in pathology of intestinal tuberculosis and Crohn's disease that "caseation, if present, is pathognomonic of tuberculosis, but a little 108 Mr Ishikawa et al.

central necrosis is rarely seen in what is otherwise Crohn's disease." Regional lymph node involvement is almost the rule in intestinal tuberculosis, whereas it is often absent in Crohn's disease (Morson 1971; Tandon 1972). No specimens of lymph nodes were examined in our cases of this study. In diagnosing intestinal tuberculosis by radiology, Maruyama (1974) described the importance to detect linear ulcers vertical to the longitudinal axis of the intestine, accompanied by mucosal convergence and pseudopolyps. Although the incidence of intestinal tuberculosis is reduced recently in Japan, we have still several cases every year. Therefore, it is very important to differentiate tuberculosis from Crohn's disease and idiopathic proctocolitis in daily practice. Brahme (1971) stated that there are two dominating histopathological features in Crohn's disease. One is the proliferative changes manifested by edema, inflammation and fibrosis, and the other is the tissue destruction in the form of ulcers, fissures and fistulae. These changes also form the morphological basis of alterations seen at roentgenography. The proliferative changes cause thicken ing of the bowel wall with subsequent narrowing of its lumen, and separation of the lumina of adjacent bowel loops. Shallow ulcers, which become deep and undermining later, and "fiord-like" fissures protrude from the bowel lumen as spiculae, spikes or "collarbutton" ulcers when filled with constrast medium. Discrete ulcers tend to become confluent and linear , and in advanced cases, multiple, parallel longitudinal ulcers are intersected by deep transverse fissures. Small areas of inflammation and edema "cobblestone" , separated by the ulcers, form polypoid , which appear as more or less regular rows of broad-based polypoid lesions in the roentgenograms . In Crohn's disease of the and proximal or midileum, areas of strictures interchange with plump areas secondary to the mural edema. In the terminal ileum, the classic "string sign" of Kantor appears in combination with decreased motility; a thin irregular stream of barium is seen to trickle through the diseased segment . In Crohn's disease, the lesions do not often involve the whole circumference of the colon , but are confined to one aspect of its wall, thereby rendering the colon characteristically asymmetric . However, the distinction of Crohn's disease from ulcerative colitis is sometimes impossible, as radiological and histopathological features can overlap (Lewin and Swales 1966; Schachter et al. 1970; Kirsner 1970; Thayer 1970; Schachter and Kirsner 1975; Marshak and Lindner 1975) . By recent progress of fibercolonoscopy, it has b een made possible to diagnose endoscopicall y the diseases of the colon, and e ven granulomas can be demonstrated in the biopsied specimens (Watanabe et al. 1975).

References 1) Brahme, F . (1971) Roentgenology . In: Regional Enteritis . Crohn's Disease, edited by A. Engel & T . Larsson, Nordiska Bokhandelns Forlag -99 . , Stockholm, pp. 81 2) Colp, R. (1934) A case of non -specific granuloma of the terminal ileum and the caecum. Surg . Clin. N. Amer ., 140, 443-449. Crohn's Disease 109

3) Dukes, C,E. & Lockhart-Mummery, H.E. (1957) Practical points in the pathology and surgical treatment of ulcerative colitis. Brit. J. Surg., 45, 25-36. 4) Farmer, R.G., Hawk, W.A. & Turnbull, R.B. (1975) Clinical patterns in Crohn's disease. Statistical study of 616 cases. , 68, 627-635. 5) Jones, J. Hywel, Lermard-Jones, J.E., Morson, B.C., Chapman, M., Sackin, M.J., Sneath, P.H.A., Spicer, C.C. & Card, W.I. (1973) Numerical taxonomy and discriminant analysis applied to nonspecific colitis. Quart. J. Med., 42, 715-732. 6) Ishikawa, M., Gomi, T, Masamune, 0., Takahashi, T. & Tsukamoto, C. (1972) Ulcerative disease of the intestines with special reference to Crohn's disease. Stomach and Intestine (Jap.), 7, 1593-1603. 7) Ishikawa, M., Watanabe, H., Yamagishi, G., Gomi, T., Masamune, 0., Shoji, K. & Yamagata, S. (1975) Clinical aspects of Crohn's disease. Stomach and Intestine (Jap.), 10, 1027-1037. 8) Kirsner, J.B. (1970) Ulcerative colitis 1970. Recent developments. Scand. J. Gastroenterology, 5, Suppl. 6, 165-185. 9) Korelitz, B.I. & Janowitz, H.D. (1973) Controversy on recurrent ileitis after ileostomy: background and speculation. Gastroenterology, 65, 498-501. 10) Krause, U. (1971) Epidemiology in Sweden. In: Regional Enteritis. Crohn's Disease, edited by A. Engel & T. Larsson, Nordiska Bokhandelns Forlag, Stockholm, pp. 142-151. 11) Lewin, K. & Swales, J.D. (1966) Granulomatous colitis and atypical ulcerative colitis. Gastroenterology, 50, 211-223. 12) Lockhart-Mummery, H.E. & Morson, B.C. (1960) Crohn's disease (regional enteritis) of the and its distinction from ulcerative colitis. Gut, 1, 87-105. 13) Marshak, R.H. & Lindner, A.E. (1973) Ulcerative and granulomatous colitis. In: Alimentary Tract Roentgenology, edited by A.R. Margulis & H.J. Burhenne, 2nd ed., The C.V. Mosby Co., Saint Louis, pp. 1009-1010. 14) Marshak, R.H. & Lindner, R.H. (1975) Radiologic diagnosis of chronic ulcerative colitis and Crohn's disease of the colon. In: Inflammatory Bowel Disease, edited by J.B. Kirsner & R.G. Shorter, Lea & Febiger, Philadelphia, pp. 241-276. 15) Maruyama, H. (1974) Diagnosis of ileocecal tuberculosis. A clinicopathological study on 12 operated cases. Stomach and Intestine (Jap.), 9, 880-881. 16) Morson, B.C. (1971) Histopathology. In: Regional Enteritis. Crohn's Disease, edited by A. Engel & T. Larsson, Nordiska Bokhandelns Forlag, Stockholm, pp. 15-33. 17) Okabe, H., Sakimura, M., Okayama, M., Noutomi, A. & Yamanaka, M. (1966) Three cases of nonspecific primary ulcer of the small intestine. Jap. J. Med. (Jap.), 55, 215. 18) Schachter, H. & Kirsner, J.B. (1975) Definitions of inflammatory bowel disease of unknown etiology. Gastroenterology, 68, 591-599. 19) Schachter, H., Goldstein, M.J. & Rappaport, H. (1970) Ulcerative and "granulo matous" colitis - validity of differential diagnostic criteria: a study of 100 patients treated by total colectomy. Ann. intern. Med., 72, 841-851. 20) Tandon, H.D. (1972) Pathology of intestinal tuberculosis and its distinction from Crohn's disease. Gut, 13, 260-269. 21) Thayer, W.R., Jr. (1970) Crohn's disease (regional enteritis), a look at the last four years. Scand. J. gastroenterology, 5, Suppl. 6, 165-185. 22) Watanabe, H., Narasaka, T., Imai, H., Uezu, J.M., Numazawa, M., Shoji, K., Ishikawa, M. & Yamagata, S. (1975) Fibercolonoscopy for the diagnosis of granulo matous colitis. Tohoku J. exp. Med., 115, 285-296. 23) Wells, C. (1952) Ulcerative colitis and Crohn's disease. Ann. Roy. Coll. Surg., 11, 105-120. 24) Wolf, B.S. & Marshak, R.H. (1962) Granulomatous colitis (Crohn's disease of the colon) : roentgen features. Amer. J. Roentgenol., 88, 662-670. 25) Yanase, K., Masuda, K., Shinada, S. & Yamada, Y. (1967) Regional enteritis in Japan: a review of 548 cases. Int. J. Surg., 47. 497-502.