GASTROENTEROLOGY Official Publication of the American Gastroenterological Association

CoPYRIGHT 1975 THE WILLIAMS & WILKINS Co.

Vol68 April 1975 Number 4

ALIMENTARY TRACT

CLINICAL PATTERNS IN CROHN'S DISEASE: A STATISTICAL STUDY OF 615 CASES

RICHARD G. FARMER. M.D., WILLIAM A. HAWK, M.D., AND RUPERT B. TURNBULL, JR., M.D.

The Department of Gastroenterology, the Department of Pathologv, and the Department of Colon and Rectal Surgery, The Cleveland Clinic Foundation and The Cleveland Clinic Educational Foundation, Cleveland, Ohio

Results of a study of 615 consecutive patients with Crohn's disease seen at the Cleveland Clinic from 1966 through 1969 are reported. The thesis evaluated was that initial anatomic involvement bears directly on the clinical course and prognosis. The following clinical patterns were established: (1) ileocolic, 252 patients (41%); (2) small intestine, 176 patients (28.6%); (3) colon, 166 patients (27%); ( 4) anorectal, 21 patients (3.4%). Among symptoms, statistically significant features (P < 0.0001) were: rectal bleeding with colon involvement, and rectal fistulae with ileocolic or colon involvement. Among complications statistically significant (P < 0.0001) were: with ileocolic pattern were perianal fistulae, internal fistulae, and intestinal obstruction; with colon pattern were perianal fistulae, toxic megacolon, and arthritis; with small intestine pattern was intestinal obstruction. Operation was required for 73% of patients with ileocolic pattern and 51% of patients with each of small intestine and colon patterns. Anorectal involvement was rarely the initial manifestation, but frequently accompanied the ileocolic and colon patterns. There were postoperative recurrences in 27% of patients with ileocolic pattern, 21% of the patients with small intestine pattern, and 16% of the patients with colon pattern. Death occurred in 7% of patients with the ileocolic pattern, in 5% with the colon pattern, and in 4% with the small intestine pattern.

Crohn's disease of the intestine has re-ceived much attention and has now been well defined by clinical and pathological criteria. Our findings have been reported in

previous studies, 1- 3 and the natural history and prognosis of the disease have been

land Clinic Foundation, 9500 Euclid Avenue. Cleve-land, Ohio 44106.

Received May 15, 1974. Accepted October 8, 1974. The authors wish to thank J. N. Berrettoni, Ph.D., Address requests for reprints to: Dr. Richard G. Professor of Statistics, Case Western Reserve Univer-

Farmer, Department of Gastroenterology, The Cleve- sity, for his assistance in the statistical study. 627

628 FARMER ET AL. Vnl. 68. No.4

described m other reports. 4- 10 Some of these studies have evoked an editorial comment by Mendeloff, 11 who described the results as "progress confounded." Nevertheless, now there is much less confu-sion in the clinical differentiation between Crohn's disease and ulcerative colitis. 2 12- 14 However, Crohn's disease frequently ap-pears to be regarded as a homogeneous entity and clinical features, complications, and prognosis have been based on entire groups of patients studied, rather than on subdivisions based on anatomic involve-ment of inflammation in different areas of the intestine. The purpose of this study was to explore the thesis that initial ana-tomic involvement in Crohn's disease may directly determine the clinical course and prognosis.

Materials and Methods The case records of all patients for whom a

diagnosis of Crohn's disease (regional enteritis, granulomatous colitis or enteritis, transmural colitis or enteritis, regional colitis or ileitis. and ileocolitis) was originally made at the Cleveland Clinic from January 1966 through December 1969 were reviewed. The diagnosis of Crohn's disease was based on a combination of well recognized clinical features, proctosigmoido-scopic and roentgenographic findings. and. when available, histological data (either biopsy or operative specimens). A total of 615 consecu-tive cases were analyzed and all had docu-mented Crohn's disease. An additional 152 cases were excluded because of insufficient data and lack of adequate documentation of the diagnosis. Most patients in this latter group were seen only once in consultation at the Cleveland Clinic. A presumptive diagnosis of Crohn's disease was made but diagnostic stud-ies were not undertaken, and no continuing clinical relationship was established.

All the cases studied fit criteria established for diagnosis of Crohn's disease. Clinical fea-tures included symptoms such as diarrhea. rectal bleeding, abdominal pain, weight loss and malnutrition, perianal fistulae, and "sys-temic" manifestations (skin, eye, and mus-culoskeletal). Also included were proctosig-moidoscopic, roentgenographic and histological features of operative or biopsy specimens.

Definition of Criteria Used in Assessment Symptoms and clinical features. (a) Diar-

rhea: many loose bowel movements daily and on a persistent basis for days or weeks. (b) Rectal

bleeding: blood mixed with stool contents oc-curring with most bowel movements for at least several weeks: not simply blood noted on tissue. (c) Rectal fistulae or perianal disease: develop-ment of a perianal fistula or abscess: not simply an anal fissure or hemorrhoids. (d) Abdominal pain: moderate abdominal cramping persisting for several weeks. (e) Malnutrition: loss of 20% of body weight from onset of illness. (f) Sys-temic manifestations: objective evidence of ab-normalities in the skin, joints. or eyes.

Proctosif

Apri/1975 CLINICAL PATTERNS IN CROHN'S DISEASE 629

cation of the anatomic location of inflammatory disease process. The essential feature in deter-mining the clinical pattern was the ability to define the anatomic involvement at the time of the original Cleveland Clinic diagnosis.

Definition of the Clinical Population The 615 cases included in this study all had a

diagnosis of Crohn's disease established at the Cleveland Clinic during the period 1966 through 1969. Many of these patients were referred by other physicians, and for some patients, the diagnosis of Crohn's disease had been either previously established or the presumptive diag-nosis was considered. As indicated, patients who were excluded were those for whom a reasonable clinical diagnosis could not be estab-lished or those felt to have ulcerative colitis rather than Crohn's disease. Clinical data were recorded including predominant symptoms and history prior to establishment of the diagnosis at the Cleveland Clinic. The sex and age at the time of diagnosis were recorded. Racial and ethnic data could not be assessed adequately by the technics used.

Tests of statistical significance were made by the use of x2 , t, and Kolmogorov-Smirnov two-sample statistics.

Presentation of Clinical Data Clinical patterns. The following clinical pat-

terns were established on the basis of anatomic diagnosis of location of inflammation. (a) Ileo-colic pattern: involvement of distal ileum and right colon-252 patients (41%). (b) Small intestine pattern: involvement of small intes-tine without colonic involvement-176 patients (28.6%). This pattern was subdivided into those with ileal involvement only (139 patients) and those with involvement of duodeum and jeju-num as well (37 patients). Only 8 patients had no ileal involvement. (c) Colon pattern: colonic involvement without small intestine involvement-166 patients (27%). This pattern was subdivided into those with total colonic involvement (114 patients) and those with seg-mental involvement (52 patients). (d) Anorectal pattern: anorectal involvement without initial involvement of proximal colon or small intestine-21 patients (3.4%).

There were large numbers of patients in three patterns, and anorectal involvement initially presented in only 3.4% of all patients. The latter was included because of concern that ini'tial anorectal involvement with inflammatory dis-ease by itself might not adequately differentiate ulcerative colitis and Crohn's disease. 15 All cases of Crohn's dise.ase with anorectal and

colonic involvement were analyzed carefully to avoid confusion with ulcerative colitis. The determination was made by the means de-scribed above. Thus. all patients with colonic or rectal involvement were shown to have Crohn"s disease and not ulcerative colitis.

Statistical comparison was made among the three major clinical patterns observed: ileocolic, colon, and small intestine. Data were compared among these three groups and statistically sig-nificant features were ascertained to determine those which characterized the clinical pattern. Thus, all data in these three groups were compared.

ARe and sex of patients. In the total group of 615 patients were 332 males and 283 females. The age range at the time of diagnosis was from 5 years to 83 years (mean 32 years); 169 patients were younger than 20 (only 8 were age 10 or younger) and 26 were older than 60. Next, these data were analyzed according to the clincal patterns (tables 1 through 4). The only pattern in which there was significant male preponder-ance was the colon pattern (97 males and 69 females); otherwise, the sex distribution was roughly equal. With regard to mean age at time of diagnosis, the distribution among the four groups was similar. Furthermore, the mean duration of symptoms was 5 years prior to the time of diagnosis of Crohn's disease at the

TABLE 1. Age and duration of symptoms at diagnosis: ileocolic pattern in 252 patients-131 male, 121

femalea

Age (yr) 0-20 67 (26)

21-30 81 (32) 31-40 47 (18) 41-50 33 (13) 51-60 16 (6) Over61 8 (3)

Mean age 30.9 yr Duration of symptoms

Less than 6 mo 44 (17) 6-12 mo 32 (13) 1-2 yr 45 (18) 3-4yr 50 (20) 5-7 yr 32 (13) 8-10 yr 19 (7) Over 10 yr 30 (12)

Mean duration 5 yr 68% had symptoms

from 0-4yr

a Numbers are numbers of patients. Numbers in parentheses are percentages.

630 FARMER ET AL. Vol. 68, No.4

TABLE 2. Age and duration of symptoms at diagnosis: small intestine pattern in 176 patients-90 male, 86

female Ileal Other"' % involvementa

Age (yr) 0-20 38 16 31

21-30 29 8 20 31-40 20 5 14 41-50 28 5 19 51-60 16 2 10 Over61 8 1 5

Total 139 37 Mean age 32.9 yr

Duration of symptoms Less than 6 mo 19 3 13 6-12 mo 28 11 22 1-2 yr 30 6 20 3-4yr 27 9 20 5-7yr 10 3 7 8-10 yr 12 2 8 Over 10 yr 13 3 9

Total 139 37 Mean duration, 4 yr 76% had symptoms

from0-4yr

a Numbers are numbers of patients. Other: involvement of duodenum and jejunum,

with or without ileal disease.

Cleveland Clinic with relatively little variation among the four groups.

Symptoms. The predominant symptoms at the time of diagnosis were analyzed by clinical pattern (table 5). The three major groups of clinical patterns were then compared to deter-mine statistically significant percentage differ-ences in symptomatology. Virtually all patients had diarrhea in various degrees, but this symp-tom did not differentiate one clinical pattern from another. Also, the frequency and episodes of diarrhea described by the patients varied widely from 'time to time and could not be distinguished to enable differences to be made among the groups. Rectal bleeding, rectal fis-tulae, abdominal pain, and malnutrition were defined as noted previously.

It was statistically significant (P < 0.0001) that patients with colonic disease had more rectal bleeding, 46% compared with 22% for ileocolic and 10% for small intestine patterns. Those with ileocolic and colonic disease had more rectal fistulae (21 and 19%) than those with small-intestine involvement (5%). There were no statistically significant percentage dif-

TABLE 3. Age and duration of symptoms at diagnosis: colon pattern in 166 patients-97 males, 69 female

Entire Seg- % colona mental0 (J

Age (yr) 0-20 34 9 26

21-30 36 12 30 31-40 19 10 15 41-50 12 8 12 51-60 8 10 11 Over 61 5 3 5

Total 114 52 Mean age 32.6 yr

Duration of symptoms Less than 6 mo 27 15 25 6-12 mo 17 11 17 1-2 yr 14 6 12 3-4 yr 25 10 21 5-7 yr 15 4 11 8-10 yr 6 3 5 Over lOyr 10 3 8

Total 114 52 Mean duration, 4 yr 75% had symptoms

from0-4yr

a Numbers are numbers of patients. Segmental: involvement of a portion or portions

of the colon, but not the entire colon.

TABLE 4. Age and duration of symptoms at diagnosis: anorectal pattern in 21 patients-12 male, 9 female" Age (yr)

0-20 5 (24) 21-30 4 (19) 31-40 4 (19) 41-50 1 (5) 51-60 5 (24) Over 61 2 (9)

Mean age 38.6 yr Duration of symptoms

Less than 6 mo 7 (33) 6-12 mo 3 (14) 1-2 yr 7 (33) 3-4 yr 3 (14) Over 5 yr 1 (5)

q Numbers are numbers of patients. Numbers in parentheses are percentages.

ferences associated with symptoms of abdomi-nal pain, malnutrition, or diarrhea. Thus, sig-nificant differences in symptoms included a higher incidence of 'rectal bleeding with the

April 1975 CLINICAL PATTERNS IN CROHN'S DISEASE 631

TABLE 5. Symptoms by clinical pattern Statistical

Symptoms Ileocolic" Small intestine" Colon" significance of o/c differences among patterns by symptoms

Rectal bleeding . 56 (22) 18 (10) 77 (46) p < 0.0001 Rectal fistula .. . . . . ...... 54 21) 9 (5) 32 (19) p < 0.0001 Abdominal pain 164 (65) 109 (62) 93 (55) NS" Malnutrition 53 12) 33 (19) 37 (22) NS

a Numbers are numbers of patients. Numbers in parentheses are percentages. NS, not statistically significant.

colon pattern and perianal fistulae with colon and ileocolic patterns. Analysis of the sub-groups of the small intestine and colon patterns did not reveal any data which would enable differentiation by symptoms alone. Of the 139 patients with ileal involvement only, 12 had rectal bleeding, and 6 had rectal fistulae. Of the 37 patients with more proximal small intestine involvement, 6 had rectal bleeding, and 3 had rectal fistulae. Among patients with colon dis-ease, 55 of the 114 who had involvement of the entire colon had rectal bleeding as a predomi-nant symptom. Among those with segmental involvement of the colon, 22 of the 52 had rectal bleeding. Rectal fistulae were present as an initial manifestation among 22 of the 114 with entire colon involvement and 10 of the 52 with segmental involvement; features were not sta-tistically significant for purposes of differentia-tion.

Complications. The case records were then analyzed for complications which had occurred after the initial diagnosis of Crohn's disease at the Cleveland Clinic. The over all mean dura-tion of follow-up in this series of patients was 3.6 years, with a range from a few months to 8 years (table 6). (All patients were first seen after January 1, 1966.) Complications are shown in table 7. Perianal fistulae which occurred after the original diagnosis, and enterocutaneous or enteroenteric fistulae frequently were associ-ated with abscess formation. Intestinal obstruc-tion was diagnosed only when associated with significant clinical symptoms (increasing ab-dominal pain) and objective demonstrations of abdominal distention with roentgenographic documentation. Growth retardation was based on standard growth curves, and applied to children whose growth was presumably im-paired by the disease. The diagposis of arthritis and spondylitis included objective evidence of synovitis or roentgenographic evidence of bone destruction and/or disease as opposed to symp-toms of arthralgia or fibrositis. Megacolon was defined as an acute illness characterized by

TABLE 6. Follow-up; frequency distributions Pattern

Months Small Ileocolic" Colon"

intestine"

1-24 81 (32) 79 (46) 61 (37) 25-48 82 (32) 57 (33) 53 (32) 49-72 52 (21) 28 (16) 28 (17) 73-100 37 (14) 8 (4) 24 (14)

Total 252 173 166 Average 4yr 3yr 4yr Lost None 3 None

a Numbers are numbers of patients. Numbers in parentheses are percentages.

dilation of the transverse colon over 7 em in its widest diameter.

Complications occurring during the period of observation were tabulated and percentage dif-ference among the three major clinical patterns were compared (table 7). Internal fistulae oc-curred in 34% of the patients with ileocolic Crohn's disease in contrast to 17 and 16% of those with small intestine and colon patterns (P < 0.0001). Perianal fistulae occurred in 38 and 36% of patients with the ileocolic and colon patterns, respectively, but with only a fre-quency of 14% with the small intestine pattern (P < 0.0001). The frequencies of intestinal obstruction are 44, 35, and 17% for ileocolic, small intestine, and colon patterns, respectively (P < 0.0001). Arthritis was documented in 16% of the colon pattern patients, and in 3.6 and 4% of ileocolic and small intestine disease, respec-tively. Megacolon rarely appeared with ileocolic and small intestine pattern but was found in 11% of the patients with colon pattern. Pyo-derma gangrenosum and growth retardation were unusual complications in all three groups.

Complications were also analyzed for the subgroups of small intestine and colon patterns. Among those in the small intestine pattern with

632 FARMER ET AL. Vol. 68, No.4

TABLE 7. Complications by clinical patterns

Statistical Pattern significance of

Complications % differences Ileocolic" Small intestine" Colon" among patterns

by complications

Perianal fistulae 97 (38) 25 (14) 59 (36) p < 0.0001 Internal and cutaneous

fistulae .. .... 85 (34) 30 (17) 26 (16) p < 0.0001 Intestinal obstruction 111 (44) 62 (35) 29 (17) p < 0.0001 Growth retardation ...... 8 (3) 5 (3) 5 (3) NS" Pyoderma .. .... 4 (1.6) 0 (0) 5 (3) NS Arthritis ..... . . . . . 9 (3.6) 7 (4) 27 (16) p < 0.0001 Spondylitis 4 (1.6) 1 (0.6) 8 (5) NS Megacolon 5 (2) 0 (0) 18 (11) p < 0.0001

Total no. of patients . 252 176 166

"Num hers are numbers of patients. Numbers in parentheses are percentages. NS, not statistically significant.

predominant ileal involvement (139 patients), 18 had perianal complications. 23 had other fistulae, and 42 had intestinal obstruction. Of the other 37 patients with more proximal small intestine involvement, 7 had perianal complica-tions, 7 had internal fistulae, and 20 had intestinal obstruction.

Of the 114 patients who had involvement of the entire colon, 44 had perianal fistulae, 16 had other fistulae, 15 had toxic megacolon, and 21 had intestinal obstruction. Five patients had significant growth retardation, 5 others had pyoderma gangrenosum, 23 had definite evi-dence of arthritis or spondylitis. Of the 52 patients with segmental involvement of the colon, 15 had perianal fistulae, 10 had internal fistulae, only 3 had toxic megacolon, and 8 had intestinal obstruction. No patient had signifi-cant growth retardation or pyoderma gan-grenosum; 12 had significant arthritis or spon-dylitis.

Clinical course and operations. The mean duration follow-up was 3.6 years, and only 3 of the 615 patients were lost to follow-up (table 6). A total of 370 patients underwent operation (60.2% of the entire group). The indications for operation are listed in table 8; generally, indica-tions reflected complications which had oc-curred in the course of the disease. The major indications for surgical intervention at the Cleveland Clinic Hospital were perianal dis-ease, internal fistulae with or without abscess formation, intestinal obstruction, and toxic megacolon (table 8). A smaller number of pa-tients required operation because of severity and chronicity of disease, poor response to medical therapy, and growth retardation. For

the ileocolic pattern, the primary indications for surgery were internal fistulae. 38%; intestinal obstruction, 37%; and perianal disease, 15%. For the small intestine pattern, the indications for surgery were intestinal obstruction, 54%; and internal fistulae, 29%. For colonic disease, the indications were more varied and included all of the major categories, although less so for intestinal obstruction. As can be further noted in table 8, many patients underwent intestinal operation before the original diagnosis at the Cleveland Clinic. These included 75 patients in the ileocolic group, 38 of whom required a subsequent operation at the Cleveland Clinic, 36 in the small intestine pattern, of whom 29 underwent an additional surgical procedure. and 19 in the colon pattern, of whom 9 under-went a second procedure at the Cleveland Clinic. Interestingly, none of the 21 patients with anorectal involvement as a primary mani-festation had undergone operation prior to that done at the Cleveland Clinic.

The type and number of operations were analyzed and related to the clinical pattern (table 9). Among those patients with ileocolic disease. 183 (72.6o/r) underwent operation, with colonic disease 85 (51.2%) underwent operation, and 90 patients (51.1;'l'cl with small intestine disease had operation. With anorectal disease. 12 (57.1%) had an operation. When a statistical comparison is made as to the percentage of operations of ileocolic pattern (73%) with the percentage for the total of operations for the colon, small intestine, and anorectal (52%), the difference is significant (P < 0.0001). In the entire group, ileostomy was performed with or without resection in 232 of the 370 patients who

April1975 CLINICAL PATTERNS IN CROHN'S DISEASE 633

TABLE 8. Primary indication for initial operation at Cleveland Clinic Hospital Pattern

Ileocolic" Small intestine" Colon" Anorectal"

Indication for operation Perianal disease 22 (15) 6 (7) 17 (23) 8 Internal fistulae and abscess . 56 (38) 24 (29) 19 (25) Toxic megacolon ... ...... . . . . . . 5 (3) 0 14 (19) Intestinal obstruction .. .... . . . .. 54 (37) 45 (54) 9 (12) Other (including severe disease;

poor response to therapy; growth retardation) . . . ........ . .... 9 (6) 8 (9) 16 (21) 4

Total in group . . .. . . . . . .... 252 176 166 21 Patients with operation 183 90 85 12 Operations at Cleveland Clinic .... 146 83 75 12 Operations before Cleveland Clinic . 75 36 19 0 Elsewhere . . .. .... 37 7 10 Both . .. . . . .. . . .. . .. . .. . .. .. ........ 38 29 9

"Numbers are numbers of patients. Numbers in parentheses are percentages.

TABLE 9. Number and types of operations performed Pattern

Ileocolic" Small intestine" Colon"

Patients with operation . 183 (72.6) 90 (51.1) 85 (51.2) No. of operations . 430 159 226

Heostomy 121 18 88 Resection 263 110 107 Bypass .. 37 27 9 Ileorectal anastomosis 9 4 22

More than one operation . . ......... 61 18 22 Recurrence postoperative ........... 50 (27) 19 (21) 14 (16)

Total in group .. . .......... 252 176 166

"Numbers are numbers of patients. Numbers in parentheses are percentages.

underwent operation. In the 183 patients with the ileocolic pattern who underwent operation, 263 resections were performed (usually resection of the terminal ileum and right colon with anastomosis). Among the 85 patients with the colon pattern who underwent operation, resec-tion (usually subtotal colectomy with ileos-tomy) was performed 107 times. Ileorectal anas-tomosis was constructed for 22 patients. For the 90 patients with small intestine pattern who required operation, 110 resections were per-formed. Additional operations were frequently necessary, and more than 100 patients under-went a second surgical procedure.

A subsequent concern was that of recurrent disease after the original operation. The mean duration of follow-up (3.6 years) is too short to obtain definitive data, but to date 83 patients have required additional operations for recur-

rent disease. Fifty patients (27%) of the 183 in the ileocolic group who underwent operation had a recurrence requiring another operation. Of the 90 patients with the small intestine pattern, 19 (21%) underwent a second operation for recurrences after initial resection. For pa-tients with colonic involvement, 85 had initial operations and 14 (16%) had operations after recurrence.

Of particular interest was the development of postcolectomy ileitis. This condition is defined as clinical and roentgenographic evidence of inflammatory disease involving the distal seg-ment of ileum, anastomosed to either the rectal segment or, more usually, just proximal to the ileostomy stoma. The cases were reviewed for histological documentation of this condition and postcolectomy ileitis was identified in 31 patients. Among these were 18 with original

634 FARMER ET AL. Vol. 68, No.4

ileocolic pattern involvement and subsequent colectomy because of inflammatory disease and its complications. In addition to these patients, there were 13 among the colon pattern in whom postcolectomy ileitis developed. Of these, all but 1 were in the category in which the entire colon was originally involved.

Thirty-two patients (5.2%) in this series of 615 died. Seventeen deaths (7%) occurred among the 252 patients in the ileocolic group (one-half of all deaths). Of 176 patients with small intestine involvement, 7 (4%) died, and of 166 patients with colonic pattern of disease, 8 (5%) died. There were no deaths among the 21 patients with the anorectal pattern. Among the deaths were 7 who died postoperatively at the Cleveland Clinic Hospital (5 in the ileocolic pattern and 2 in the colon pattern). Usually death occurred as a result of sepsis and pro-longed illness. Other factors, such as malab-sorption, were often associated with sepsis.

The medical therapy prescribed for these 615 patients varied, and no identifiable pattern could be established or related statistically to course and prognosis. Most of the patients received some form of systemic steroid, either adrenocorticotrophic hormone or a corticoste-roid agent. Among those who received im-munosuppressive therapy (14 with the ileocolic pattern, 8 with the small intestine pattern, and 6 with the colonic pattern), no features could be identified which appeared to alter the clinical course.

Among this group of 615 patients several unusual features associated with inflammatory bowel disease were encountered. These included 2 cases of epidermolysis bullosa of the acquired type, both with an ileocolic pattern. One pa-tient with colon disease also had Behcet's syn-drome and toxic megacolon subsequently devel-oped. Ceroidosis was found in 1 patient and was confirmed histologically by a jejunal biopsy. One patient died of renal amyloidosis after colonic Crohn's disease. One patient with ileal Crohn's disease subsequently had chronic ag-gressive hepatitis and died after gastrointestinal hemorrhage in hepatic coma. Two patients had intestinal malignancies. An adenocarcinoma of the jejunum associated with ileal Crohn's dis-ease, in which there had been long-standing partial obstruction of the ileum, developed in 1 patient. Another patient was found to have an adenocarcinoma of the sigmoid colon with Crohn's disease of the ileum. In that particular patient, at the operation for ileal disease, the carcinoma was found and there was no evidence of inflammatory disease of the colon.

Discussion

Recent reports on the natural history of Crohn's disease 6 - 10 have mentioned ana-tomic areas of disease, but the observa-tions were not based on anatomic involve-ment at the time of initial evaluation, as was done in this study. Furthermore, these reports included smaller numbers of pa-tients (ranging from 75 to 186) rather than the large series (615) presently described. This large number of patients may allow a clearer picture of the natural history of Crohn's disease to emerge from this study. Location of the disease is a major determi-nant in symptomatology, clinical course, and prognosis. An identifiable clinical pat-tern occurs and can be related to prog-nosis. Among the 252 ( 41% of the total) patients with ileocolic Crohn's disease, perianal and rectal fistulae (38%), internal fistulae (34%), abscess, and intestinal obstruction (44%) were frequent (P

April 1975 CLINICAL PATTERNS IN CROHN'S DISEASE 635

short total follow-up period. However, in contrast to the study by Nugent and co-workers, 17 and in support of the conclu-sions of Korelitz and Janowitz, 18 our group of patients included 31 in whom subse-quent postcolectomy ileitis has developed.

Another area of controversy relates to the association between Crohn's disease and intestinal cancer, reemphasized by Wee-don and co-workers. 19 Our previous study did not indicate an association between Crohn's disease of the colon and subse-quent development of carcinoma. 20 As re-ported at that time, we have seen 2 pa-tients with ileal Crohn's disease in whom small intestine cancer developed subse-quently; we are reporting a 3rd case.

Finally, we feel that this study provides statistical validity to the thesis that ana-tomic involvement at the time of diagnosis of Crohn's disease bears directly on the clinical course, type of complications, and prognosis. Thus, one may anticipate a certain clinical pattern based on initial intestinal location of Crohn's disease and direct diagnostic and therapeutic proce-dures toward possible prevention of com-plications. This study further emphasizes and provides data to support the concept that Crohn's disease is not a homogeneous entity and should be considered as a pro-tean disease with certain definable pat-terns.

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14. Kirsner JB: Ulcerative colitis; "puzzles within puzzles." N Eng! J Med 282:625-627, 1970

15. Farmer RG, Brown CH: Emerging concepts of proctosigmoiditis. Dis Col Rectum 15:142-146, 1972

16. Lennard-Jones JE, Stalder GA: Prognosis after resection of chronic regional ileitis. Gut 8:332-336, 1967

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