CURRENT CLINICAL CONCEPTS

GASTROENTEROLOGY Copyright 1968 by The Williams & Wilkins Co. Vol. 54, No.6 Printed in U.S.A. CURRENT CLINICAL CONCEPTS Thomas R. Hendrix, M.D. Current Clinical Concepts Editor The Johns Hopkins University School of Medicine Baltimore, Maryland CLINICAL AND PATHOLOGICAL DIFFERENTIATION OF CROHN'S DISEASE AND PROCTOCOLITIS J. E. LENNARD-JONES, M.D., F.R.C.P., H. E. LOCKHART-MuMMERY, M.D., M.CHIR., F.R.C.S., AND B. C. MORSON, D.M., F.C.PATH. St. Mark's Hospital, London, England. Gases of regional ileitis! were originally distinguished from ileocecal tuberculosis because they lacked the well defined features associated with tuberculous infection. Regional ileitis itself, however, has typical characteristics but no defining features which are invariably present in this disease and in no other, and which are essential for confirmation of the diagnosis. Further study of typical cases of regional ileitis has widened the description of the clinical behavior and pathological anatomy!? of the disease but any definition has still to be based on a description of characteristics, only some of which may be present in each case. Likewise, proctocolitis (proctocolitis is classified as ulcerative colitis of the rectum by some; however, we prefer "proctocolitis" to the term "ulcerative colitis" as it does not imply ulceration) has many characteristic clinical and pathological features but none by which it can with certainty be recognized. Wells 3 and Brooke 4 were the first to recognize that in certain cases of colitis the illness differed from the usual pattern. It is now apparent that two types of nonspecific colitis can be distinguished on clinical, radiological, and pathological evidence. One has the pathological anatomy usually associated with proctocolitis and the other the anatomical features described first in Address requests for reprints to: Dr. J. E. Lennard-Jones, St. Mark's Hospital, City Road, London. E.C.I., England. 1162 regional ileitis. These two types of colitis differ in their characteristics but neither has defining features, present in every case of the one and absent in every case of the other. The distinction between these two conditions depends therefore on a full consideration of all of the clinical and pathological features in each case and recognition of a characteristic pattern by which the diagnosis can be made. The distinction between proctocolitis and Grohn's disease confined to the colon was originally made after examination of total colectomy specimens. Analysis of the clinical course of the illness in these patients, of the radiological appearances of their colon, and of the pathological features of biopsy material suggested features which might enable the two diseases to be distinguished without operation. At the present time we believe that the correct diagnosis can usually be made on the basis of the clinical history and examination, combined with radiological investigation and the microscopic examination of biopsy material from the rectal mucosa or anus. The following account emphasizes the features which we find most helpful in distinguishing between proctocolitis and Grohn's disease of the colon. 5, 6 Clinical Features ( table 1 ) History. Diarrhea is the most frequent complaint in both diseases, but in Grohn's disease it is more a true diarrhea wit.h loose

J1me 1968 CURRENT CLINICAL CONCEPTS lhi3 stools than the passage of blood and mucus with tenesmus of which the patient with proctocolitis usually complains. In the latter, blood in the stools is almost invariably.. noticed by the patient, while bleedmg IS less common in patients with Grohn's disease, and is only mentioned as a symptom by about one-third of our patients. On the other hand, abdominal pain, usually recurrent episodes of colic, is frequently mentioned in Grohn's disease, whereas this is hardly ever a complaint in cases of proctocolitis. Loss of weight may occur in both diseases but seems to occur earlier and more constantly in patients with Grohn's disease. Specific inquiries should be made in taking the history about any anal infections or operations in the past (see below) and also whether any close relative (parent, sibling, or child) has had intestinal disease, for there is now suggestive evidence that a familial tendency is more common in Grohn's disease. On the whole, the course of Grohn's disease tends to be more continuous than ulcerative colitis, in which the relapses, whether mild or severe, are often followed by long periods of complete remission and perfect health. Physical examination. Both diseases may lead to weight loss and anemia, and both may, in the more acute phases, cause pyrexia and general malaise. Septic skin conditions of a minor sort are rather more frequent in cases of proctocolitis, but are seen in both diseases. Abdominal examination is usually negative in both diseases, apart from some tenderness over the colon in the more acute cases. However, in some patients with Grohn's disease there is sufficient pericolic thickening to cause the bowel to become palpable, or a localized mass may have formed as a result of a pericolic abscess. Palpable bowel thickening and localized masses do not occur in cases of proctocolitis in the absence of carcinoma, and so these findings on abdominal examination are very suggestive of Grohn's disease. Similarly, Grohn's disease occasionally leads to a spontaneous fistula from the diseased colon to the skin surface, usually on the abdomen, although such fistulae may track to the loin or even to the but- TABLE 1. Clinical distinctions between prociowlitis and Crohn's disease - - - - ----;-----1 --- - Proctocolitis Crohn's disease Bleeding Very common Unusmt! Abdominal pain None Common Abdominal mass Never Sometimes Spontaneous fis - Never Sometimes tulae Perianal infections Unusual Common Undermining anal Never Sometimes ulceration Anal lesion pre- Never Sometimes ceding bowel upset Rectum involved 95% 50% Sigmoidoscopic Uniformly hy- Ederm., ul - appearances peremic and cers, 1101'- granular mal patches tock. Spontaneous fistulae of this type never occur in proctocolitis, although rectovaginal fistulae occur in both diseases. Anal lesions. The association between Grohn's disease in the intestine and anal fistulae has been known for many years.7 However, increased experience has shown that not only fistulae but other anal lesions may occur in cases of Grohn's disease' that these anal lesions are of more,. frequent occurrence when the dsease i Involves the large bowel; that the anal lesion may precede any other symptoms or manifestations of the disease 7 8; and that the characteristic histological changes of Grohn's disease may often be found in the tissue around these lesions. We regard the anal abnormalities as such an important part of the clinical picture of Grohn's disease of the large bowel that it worth discussing these points in greater detail. Many anal and perianal abnormalities may be seen in association with Grohn's disease. Probably the most common form is some ulceration of the anal canal, leading to one or more anal "fissure". However, these differ from the common nonspecific dorsal anal fissure in that they may occur in any part of the anal canal, are seldom very painful, and may be multiple. In appearance, they are often broad and shallow and look indolent and undermined, sometimes with a little surface

1164 CURRENT CLINICAL CONCEPTS Vol. 54, No.6 pus. Most are accompanied by an unusual amount of edema, leading to soft anal tags around the base of the fissure. In some patients, these ulcers of the anal canal extend out on to the perianal skin, and in a few cases very extensive ulcers are seen, with destruction of the perianal skin, ischiorectal fat, and the anal sphincters. In most of these patients with perianal ulceration, the skin around and between the ulcers has a curious dusky cyanotic appearance with some edema; the ulcers have undermined edges, and may communicate with each other, leaving undermined strips of blue unhealthy skin; and there seems to be a tendency for such ulcers and fistulae to track forward to the vulva and groins. Other patients develop perineal infections which, after bursting spontaneously or after surgical incision, lead to persisting anal fistulae; many of these are complex in their multiplicity of tracks, but most lead to induration around the track and are not usually clinically distinguishable from ordinary pyogenic anal fistulae. They may lead to continuing discharge or may heal only to flare into activity again later. In our experience anal lesions have occurred in about 80% of cases of Grohn's disease of the large bowel, being particularly common when the sigmoid colon and rectum are involved. On the other hand, only a small proportion of patients with proctocolitis has an anal lesion at any time during the course of the illness. The patients with proctocolitis may have soreness and excoriation of the perianal skin when their diarrhea is severe, and a few of them may develop perianal and ischiorectal abscesses which may in turn lead to fistulae. However, such complications are unusual in proctocolitis, and the undermining anal ulceration, dusky cyanosis, and edema described above are never seen. We have therefore come to regard the presence of an anal lesion as suggestive of Grohn's disease and the presence of undermining anal ulceration with edema as practically diagnostic, whereas extensive colonic disease without anal abnormality is, in our experience, less likely to be Grohn's disease. Yarnis and Grohn 7 pointed out that anal infections may precede abdominal symptoms in cases of Grohn's disease, sometimes by many years. Most of the cases in which a long interval occurred between the anal fistula and later abdominal symptoms have had disease of the terminal ileum. However, nonetheless, in about onequarter of our patients with Grohn's disease of the colon, an anal abnormality was the first clinical manifestation of the disease. H ence careful inquiry into the past history and careful anal examination are essential parts of the clinical evaluation. Rectal examination and sigmoidoscopy. In 95% of patients with proctocolitis the disease starts in the rectum and spreads proximally in continuity, so that in nearly every patient there are abnormal sigmoidoscopic appearances. In only about 50% of patients with large bowel Grohn's disease, however, is the rectum involved, so that findings on digital and sigmoidoscopic examination of the rectum may be normal. In some of these patients the rectum itself may be quite normal, but the presence of pus in the lumen indicates active diseasp more proximally. In cases of Grohn's disease in which the rectum is involved the findings usually differ from those in ulcerative colitis. On palpation the lower rectum may feel rough and nodular, or actual ulcers may be felt, and sometimes there may be considerable narrowing of the lumen with thickening of the wall. On sigmoidoscopy, the patient with proctocolitis shows loss of normal vascular pattern with a uniformly granular mucosa, which may be pink or red and angry, according to the degree of activity of the disease, and which bleeds easily on touch; there is usually some blood-stained mucus in the lumen, which is somewhat reduced in caliber. It is rare to see ulcers, but inflammatory polyps may be seen in cases of some duration. The appearance is usually different in Grohn's disease, in which the main feature is edema of the mucosa. In the more severe cases, edematous and congested mucosal folds can be seen, with scattered irregular ulcers between them and frank pus in the lum en.

June 1968 CURRENT CLINICAL CONCEPTS 1165 In milder cases, the slight edema of the mucosa may only lead to an appearance of shiny congestion, and tiny petechiae or pinpoint ulcers may be seen on the congested mucosa. This mucosa may also bleed on touching with the end of the instrument, but not so readily as in ulcerative colitis, and the mucosa does not have the granularity of the latter disease. Patches of completely normal mucosa may be seen between the involved areas in some cases of Grohn's disease, whereas the changes are uniform and diffuse in cases of proctocolitis. The differences between the sigmoidoscopic appearances of proctocolitis and Grohn's disease are in some cases obvious and in others only slight and subtle, and it is not always possible for the observer to make a certain diagnosis on sigmoidoscopy. Complications. Severe acute cases of proctocolitis may lead to paralysis and distension of the colon, the so-called toxic megacolon, which may lead on to perforation of the bowel unless vigorously treated. It is sometimes stated that this state of toxic dilation of the colon does not occur in cases of Grohn's disease, but this is not entirely true. It is seen less often in Grohn's disease than in proctocolitis, but nonetheless occasional patients present with severe toxemia, colonic dilation leading to abdominal distension, and deep ulceration of the colonic mucosa and muscle. Such patients may perforate just as in cases of proctocolitis, and require energetic treatment in hospital and perhaps urgent surgery. In the same way, Grohn's disease of the colon in an acute or subacute phase may lead to a severe hemorrhage, sometimes necessitating colectomy for its control. Of the systemic disorders that may complicate these colonic diseases, we get the impression that erythema nodosum is more commonly a complication of Grohn's disease than of proctocolitis, while we have never seen pyoderma gangrenosum in association with Grohn's disease. Synovitis, iritis, and minor septic skin lesions may occur in both diseases, but are more usually seen in cases of long standing proctocolitis. TABLE 2. Radiological distinctions between proctocolitis and Crohn's disease Distribution of disease Rectum Anal fistulae or blind track Internal fistulae Strictures Mucosa Small intestine Proctocolitis Continuous with rectum Usually involved Occasional Granular, shallow ulceration In continuity if involved; dilated Investigation Crohn's disease Often discontinuous along and around colon Often normal Common May occur Often present Fissuring; deep undermined ulcers; cobblestone appearance May be discontinuous lesion ; contracted and irregular Laboratory investigations. No hematological or biochemical distinctions between proctocolitis and Grohn's disease are at present known. The Mantoux reaction is not helpful because the frequency of positive reactions in Grohn's disease is the same as in the general population. Radiology. Examination of plain abdominal X-rays is not helpful in distinguishing the two diseases unless a small bowel lesion or primarily right-sided colonic lesion suggests Grohn's disease. Dilation of the colon may occur in both conditions but is more common in proctocolitis. The main points of differentiation on barium examination 9 10 are shown in table 2. In proctocolitis the rectum is usually involved with narrowing, granularity of the mucosa, and an increased rectosacral distance. The disease extends proximally and continuously from the rectum to involve part or the whole of the colon. In Grohn's disense the rectum is often normal, although an anal lesion may be present distally in addition to a colonic lesion proxi-

1166 CURRENT CLINICAL CONCEPTS mally. Predominantly right-sided colonic involvement should always suggest the possibility of Grohn's disease. The lesions in Grohn's disease tend to be discontinuous along the length of the bowel and separated by areas which appear normal. The lesions also tend to be discontinuous around the circumference of the gut so that one side may be normal and the opposite side abnormal. Anal fistulae in Grohn's disease may be filled with barium and sometimes a blind barium-filled track may be seen passing at right angles from the anal canal into the surrounding tissues. Enterocutaneous or internal fistulae do not occur in proctocolitis but may occur in Grohn's disease. The discontinuous lesions of Grohn's disease often take the form of strictures which may be long or short and eccentric or concentric. The strictures tend to taper from the normal bowel on either side. Gonstant strictures are most uncommon in colitis in the absence of carcinoma. The mucosal lesions in proctocolitis cause thickening and fine irregularity of the mucosal line in the double contrast enema. Shallow ulceration may be seen or, in the severe case, widespread stripping of the mucosa leaving surviving islands of mucosa which appear as filling defects. In Grohn's disease ulceration tends to take the form of sharp fissures passing outward from the lumen into the bowel wall or deep undermining "collar stud" ulceration. N odularity of the mucosa may be seen in Grohn's disease. This nodularity, particularly if the nodules are separated by linear ulcers, produces the so-called "cobblestone" appearance. The small intestine is involved in proctocolitis only when the disease involves the whole colon. In these circumstances the ileocecal valve may be incompetent, the terminal ileum is dilated, and its mucosa appears featureless. In Grohn's disease there may be a small intestinal lesion discontinuous from the colonic lesion. Involvement of the terminal ileum produces contraction and irregularity of the lumen, possibly with fissuring and evidence of a surrounding inflammatory mass. Biopsy. In rectal biopsy specimens ot' proctocolitis the superficial distribution 01 the inflammation is apparent. Even in severe, active, and chronic cases it is primarily the mucous membrane that is involved, the submucosa being normal or showing only a little inflammatory cell illfiltration just deep to the muscularis mucosae. If there is substantial involvement of submucosa by inflammation with relatively intact, although inflamed overlying mucous membrane, then a diagnosis of Grohn's disease is more likely. Focal mucosal inflammation with normal intervening areas is also suggestive of Grohn's disease. However, this diagnosis is most readily established by finding sarcoid-like granulomas in the mucosa or submucosa Multiple sections through the biopsy make the detection of granulomas more likely. The presence of sarcoid granulomas in the anal lesions of Grohn's disease can in some cases be detected by biopsy or examination of tissue removed during "lay open" operations. s, 11 Pathology Macroscopic differences. The distinction between proctocolitis and Grahn's disease can, in many cases, be made solely on the macroscopic pathology. However, the 8a"e which which this can be achieved does depend on the way the surgical specimen ha,; been prepared. It is important that the fresh colectomy specimen should be promptly fixed in formalin solution in a way that preserves the pathological anatomy and in particular allows close in1'peetion of the mucosal surface. Black and white photography of all fixed specimens is, in our experience, better than color for illustrating pathological differences. In Table 3 the main points of difference in the macroscopic pathology of these two diseases are compared. However, it must be emphasized that these differences are not rigid ones and in some cases there is considerable overlap. Proctocolitis is an inflammatory disease primarily affecting the mucous membrane of the colon and rectum. It spreads from the rectum in continuity to involve part or

June 1968 CURRENT CLINICAL CONCEPTS 1167 TABLE 3. Macroscopic differences in the pathology of proctocolitis and Crohn's disease of the large intestine Proctocolitis Crohn '5 disease Distribution Rectum In continuity Usually involved D iscon tinuous Often normal Terminal ileum Involved 10%; normal or Illcreased Involved 30%; thickened, stenosed, caliber ulcerated Mucosa Granular, ulcerated, no fissuring Discrete ulcers, cobblestone appearance, fissuring. Vascularity Often intense Seldom pronounced Serosa Normal (except III fulminating Serositis common colitis) Shortening Due to muscle thickening Due to fibrosis Fibrous strictures Very rare Common Spontaneous fistulae Never Enterocutaneous or internal fistulae 10% Inflammatory polyposis Often prominent ltnd extensive Less prominent and extensive Malignant change Occurs Doubtful Anal lesions Less than 25%; acute fissures, excoriation Occur in 75%; anal fistula (often m u l ~ and rectovaginal fis tiple), anal ulceration or chronic tulae fissure, edematous tags the whole of the large intestine. In contrast, Crohn's disease is nearly always a discontinuous process. Even with extensive involvement there are usually small patches of uninvolved bowel. Commonly there are diseased areas widely separated by normal tissue. A segmental colitis with normal bowel on either side is never true proctocolitis. The rectum is almost always involved in proctocolitis. Indeed, it is doubtful whether it is ever normal in this disease as judged by both sigmoidoscopic and biopsy examination. It must be emphasized that sigmoidoscopy alone is not enough, for occasionally a diseased mucosa may be found histologically when the sigmoidoscopic appearances reveal no abnormality. The presence of a colitis with a normal rectum is highly suggestive of Crohn's disease. The terminal ileum is involved in about 10% of colectomy specimens for proctocolitis. Often this involvement is for a very short distance, but uncommonly it may affect as much as 30 cm. There is a granular hemorrhagic appearance of the mucous membrane in continuity with disease in the cecum, sometimes with patchy superficial ulceration. The transverse caliber of the involved ileum is normal or increased with minimal thickening of the bowel wall. The appearance is greatly in contrast to the terminal ileitis of Crohn's disease which shows a thickened wall, stenosis of the lumen, and serpiginous mucosal ulceration, often with a cobblestone appearance. Discontinuous disease may be present which is not seen in the ileitis of proctocolitis. In proctocolitis the involved mucosa is, typically, granular and hemorrhagic with or without areas of full thickness mucosal ulceration. In Crohn's disease discrete, serpiginous ulcers surrounded by normal mucosa are common. A cobblestone pattern is characteristic and fissuring can frequently be demonstrated. The latter is not seen in proctocolitis. Fresh operation specimens of proctocolitis are often intensely vascular and congested, especially in very active disease. This is not a prominent feature of Crohn's disease in which edema is a better index of activity. Inspection of the serosal surface of a colectomy specimen for colitis will show a normal shiny peritoneum except in fulminating disease with toxic megacolon. Serositis, with or without "tubercle" formation, is a regular feature of Crohn's disease. A striking shortening of the large intes-

1168 CURRENT CLINICAL CONCEPTS Vol. 54, No.6 tine is a feature of proctocolitis. This is never due to fibrosis. It is the result of a muscle abnormality which is sometimes reversible. 12 This muscle abnormality also accounts for the loss of the haustral pattern which is such a valuable sign in the radiographic diagnosis. Crohn's disease does produce fibrous strictures. If a stricture is present in the colon in chronic proctocolitis then it is likely to be malignant unless proved otherwise. Spontaneous internal or enterocutaneous fistulae are a feature of Crohn's disease and never occur in colitis. They are caused by a fissure penetrating right through the bowel wall and causing a serosal reaction which then leads to adherence to neighboring bowel or anterior abdominal wall. For the same reason chronic pericolic abscess formation only occurs in Crohn's disease. Extensive inflammatory or pseudopolyposis is common in colectomy specimens for colitis and involves the colon more than the rectum. These polyps are really mucosal tags. In Crohn's disease polyposis is a much less prominent and extensive feature. The cobblestoning of Crohn's disease is wrongly referred to as polyposis. Microscopic differences. Sections should be taken from all parts of the colectomy specimen, especially from those areas which may be most productive of the important microscopic signs of fissuring and transmural inflammation. All lymph nodes should be removed for microscopic examination in order to detect any sarcoid granulomas. Twelve principle microscopic differences between these two diseases are given in table 4. Proctocolitis is essentially a superficial inflammation of the mucous membrane of the rectum and colon, with involvement of the submucosal layer only in the presence of full thickness mucosal ulceration. Even in very chronic, long standing cases the muscularis propria and serosa remain completely free of inflammatory infiltration. The exception to this general rule is in fulminating colitis with toxic megacolon when the intense inflammatory reaction causes separation of the muscle fibers of the muscularis propria by edematous fluid with eventual perforation through the greatly thinned bowel wall. In contrast Crohn's disease is a transmural inflammation spreading right across the bowel wall. In colitis the width of the submucosal layer is normal or reduced, whereas it is characteristically widened in Crohn's disease to a variable extent by edema, fibrosis, and inflammatory cell infiltration. There are other submucosal signs such as lymphangiectasia, neuromatous hyperplasia, and focal arteritis which are features of Crohn's disease and are not seen in proctocolitis. TABLE 4. Microscopic differences in the pathology of proctocolitis and Crohn's disease of the large intestine Inflammation Submucosa Vascularity Focal lymphoid hyperplasia Crypt abscesses Mucus secretion Paneth cell metaplasia Sarcoid foci "Fissuring', Precancerous epithelial changes Lymph nodes Anal lesions Proctocolitis Mucosal and submucosal (except in fulminating colitis) Width normal or reduced Often intense Restricted to mucosa and submucosa Very common Grossly impaired Common Occur Reactive hyperplasia Nonspecific Transmural Crohn's disease Width normal or increased Seldom prominent Mucosa, submucosa, serosa and pericolic tissues Fewer Slightly impaired Rare 60-70% Very common Often sarcoid foci Often sarcoid foci

June 1 68 CURRENT CLINICAL CONCEPTS 1169 Intense congestion and dilation of the blood supply to the bowel wall (particularly, capillaries and veins) is more prominent in proctocolitis, particularly with very active disease. Focal hyperplasia of lymphadenoid tissue is restricted to the mucosa and superficial submucosa in proctocolitis and is most common in the rectum. In Grohn's disease such focal collections of lymphocytic cells are characteristically distributed right across the bowel wall, particularly in the submucosa and just outside the muscularis propria. They may also be found quite some way out in the pericolic fat. Grypt abscesses have been regarded in the past as specific for proctocolitis. In fact, they can be found in a wide variety of inflammations of gut including simple appendicitis, the dysenteries, infected carcinomas, and Crohn's disease. However, they are a particularly prominent feature of colitis because of the great extent of the mucosal inflammation. Because the main impact of proctocolitis falls on the mucous membrane of the rectum and colon there is much epithelial destruction with loss of goblet cells and corresponding impairment in the amount of mucin secretion. 13 This is not true of Grohn's disease in which areas of involved gut will often retain what is an almost normal population of goblet cells. This is a useful histological sign which can be detected in both hematoxylin and eosin sections as well as with special stains. The cycles of epithelial destruction and repair in proctocolitis may lead to Paneth cell metaplasia, especially in very long standing disease. Much Paneth cell metaplasia is rarely seen in Grohn's disease. The two most reliable histological signs of Grohn's disease are the presence of sarcoid granulomas and the phenomenon of " fissuring." Neither are found in proctocolitis. The granulomas of Grohn's disease consist of collections of epithelioid cells and giant cells of the Langhans type without any central caseation. They may be found anywhere in the affected bowel wall as well as in the regional lymphatic glands. Their numbers vary greatly from specimens in which they are very sparse indeed to others in which the tissues of the bowel wall are riddled with granulomas. In about 30 to 40% of cases of Grohn's disease no granulomas can be found. They are never, in our opinion, found in the regional lymph glands without also being present in the bowel wall. The sarcoid granulomas can also be found in the anal lesions of Grohn's disease, sometimes widely involving the tissues of the perianal region. Fissuring is a most important sign of Crohn's disease and can be found in most cases if looked for carefully. These knifelike linear ulcers are lined by a layer of necrotic inflammatory cells. They may also appear in histological sections as intramural or submucosal abscesses but their shape depends on the way the section has been cut. Precancerous epithelial changes occur in proctocolitis but have not been observed in Crohn's disease. They take the form of neoplastic polyps or more commonly of precancerous change in a flat mucosa.14 The main impact of proctocolitis is on the mucosa of the large bowel leading to repeated cycles of diffuse epithelial destruction and repair which may, at least partly, explain the proneness to malignant change. In contrast the intestinal epithelium is relatively unaffected by this process in Grohn's disease. Conclusion Crohn's disease of the colon may be distinguishable from proctocolitis by the clinician, radiologist, or pathologist. 15 In a particular patient distinguishing features may be more apparent by one method of examination than by another. For example, it is occasionally impossible on pathological evidence alone, either macroscopic or microscopic, to make a distinction between the two conditions. In these patients clinical or radiological features may be more helpful in suggesting the diagnosis. Conversely, in other patients, the clinical and radiological features may be equivocal, whereas the pathological features are diagnostic. It is thus necessary to consider all features of the illness in distinguishing between these two types of colitis.

1170 CURREN T CLIN ICAL CONCEPTS Vol. 54, No.6 Future Problems, This description of the features which distinguish between Crohn's disease of the colon and proctocolitis summarizes the present state of our knowledge. Further analysis is still required to assess which clinical, radiological, or pathological features give the greatest discrimination in separating the two conditions. For example, the typical anal lesions on clinical examination, the strictures and fissures on X-ray, and the sarcoid reaction on microscopy all tend to be found only in Crohn's disease and thus have very high discriminant value. Further advance in discrimination will be limited until more becomes known about the cause of colitis. It may then be possible to say whether these two disease patterns represent different reactions of the body to a singje cause or whether they are the result of quite different disease processes. Such studies may also reveal defining characteristics which would enable the type of colitis to be determined with certainty on the result of one or more tests. Even though the cause of these two types of colitis is not at present known it is important to see whether they respond differently to treatment in order to decide whether the distinction between them is of therapeutic importance. Now that diagnosis is possible, without operation the effects of medical treatment in the two conditions can be assessed and compared. Similarly, it is important to compare the results of different surgical procedures in the two types of disease. These important distinctions concerning etiology and treatment should now be our main concern. REFERENCES 1. Crohn, B. B., L. Ginzburg, and G. D. Oppenheimer. 1932. Regional ileitis: a pathologic and clinical entity. J. A. M. A. 90: 1323-1329. 2. Hadfield, G. 1939. The primary histological l e sion of regional ileitis. Lancet 2: 773-775. 3. Wells, C. 1952. Ulcerative colitis and Crohn's disease. Ann. Roy. Coli. Surg. Eng. 11: 105-120. 4. Brooke, B. N. 1959. Granulomatous diseases of the intestine. Lancet 2: 745-749. 5. Lockhart-Mummery, H. E., and B. C. Morson. 1960. Crohn's disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut 1: 87-105. 6. Lockhart-Mummery, H. E., and B. C. Morson. 1964. Crohn's disease of the large intestine. Gut 5: 493-509. 7. Yarnis, H., and B. B. Crohn. 1960. Segmental (ulcerative) colitis. Gastroenterology 38: 721-728. 8. Gray, B. K., H. E. Lockhart-Mummery, and B. C. Morson. 1965. Crohn's disease of the anal region. Gut 6: 515-524. 9. Wolf, B. S., and R. H. Marshak. 1962. Granulomatous colitis (Crohn's disease of the colon): roentgen features. Amer. J. Roentgen. 88:' 662-670. 10. Young, A. C. 1968. In S. C. Shanks, and P. J. Kerley [ed.], Textbook of X-ray diagnosis H. K. Lewis and Company, London. 11. Morson, B. C., and H. E. Lockhart-Mummery. 1959. Anal lesions in Crohn's disease. Lancet 2: 1122-1123. 12. Kirsner, J. B., W. L. Palmer, and A. P. Klotz. 1951. Reversibility in colitis: clinical and roentgenologic observations. Radiology 57: 1- l4. 13. H ellstrom, H. R., and E. R. Fisher. 1967. Estimation of mucosal mucin as aid in the differentiation of Crohn's disease of the colon and chronic ulcerative colitis. Amer. J. Clin. Path. 48: 259-268. 14. Morson, B. C., and L. S. C. Pang. 1967. Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut 8: 423-434. 15. Janowitz, H. D., A. E. Lindner, and R. H. Marshak. 1965. Granulomatous colitis: Crohn's disease of the colon. J. A. M, A. 191: 825-828.