| Abstract|| |
The chance of normal survival for patients with inflammatory bowel disease is generally good. There may be a small excess mortality for those with Crohn's disease; however recent studies do not confirm this trend. For those with ulcerative colitis, there may be an excess mortality in the first two years after diagnosis, especially in those who undergo surgery.
The necessity for an operation varies, but at least 50% of patients with Crohn's disease will be an operation in the first 10 years; whereas only about 20% of patients with ulcerative colitis will require a colectomy. Most patients with inflammatory bowel disease are able to lead a normal life and are not disabled by their disease.
The prognosis in the elderly is usually good; however there is an increased mortality over younger patients, which is probably due to the presence of coexistent disease. Children also have a slightly higher mortality; this may be due to the relative frequency of a particularly extensive disease and the development of colorectal cancer. Growth retardation occurs in up to one-third of children with Crohn's disease, but it may be resol" d if remission can be obtained. Pregnancy has not been shown to have an impact on inflammatory bowel disease, but its onset during pregnancy confers a significant risk for both mother and child.
Extensive involvement is a poor prognosis factor in both diseases; conversely, isolated small bowel Crohn's disease and ulcerative proctitis carry particularly good prognoses. A short clinical history, fistulae or abscesses at presentation probably represent an aggressive form of Crohn's disease. Hypoalbuminemia, anemia and raised inflammatory markers are laboratory markers which suggest a worse prognosis in the short and possibly long-term.
|How to cite this article:|
Thompson NP, Wakefield AJ, Pounder RE. Prognosis and prognostic factors in inflammatory bowel disease. Saudi J Gastroenterol 1995;1:129-37
When a diagnosis of either Crohn's disease or ulcerative colitis is made, the patient frequently wishes to know what will happen in the future. What impact will inflammatory bowel disease have on lifestyle? What are the chances of needing an operation? And is it possible to predict lifeexpectancy? We have searched the current literature in an attempt to provide some answers to these often-posed questions. The answers are generally reassuring; although there are some patients who suffer considerable morbidity and premature death. We have not specifically addressed the risk of malignancy in inflammatory bowel disease, particularly ulcerative colitis and colorectal cancer, as there is in an enormous literature concerning this field which has been frequently reviewed.
| Mortality|| |
The mortality rate for patients with Crohn's disease or ulcerative colitis has been described as being either the same as that of the general population or significantly worse [Table - 1] and [Table - 2]. One explanation for the variation in prognosis is that, centers with a particular interest in inflammatory bowel disease are likely to be referred patients with more severe disease, and so provide a biased cohort with a poor prognosis.
Two major studies from Sweden considered patients with either ulcerative colitis or Crohn's disease. The study from Stockholm reviewed 709 patients and found that survival in the first year was only 94% as compared with an expected 99.5%, the mortality rate continued to be 2-3 times that of expected, survival being 77% after 12 years.
A later series from Uppsala revealed a 10-year survival that was 96% of that expected (Standardised Mortality Ratio 1.4) among 2,509 patients with ulcerative colitis and 1,469 with Crohn's disease; inflammatory bowel disease was the cause for the excess mortality and there was no evidence that survival had improved between 1965 and 1983.
Series from Denmark , Japan , South Africa  and the United Kingdom reported a good prognosis for patients with Crohn's disease, with survival similar to that of a matched population. The Danish study followed all 185 patients with Crohn's disease from Copenhagen county for a median period of 5.8 years  The study from Leicestershire, UK also compared mortality among Europeans and South Asians, between whom there was no difference. In contrast, series from Holland, England,,, Wales and Italy have recorded increased mortality. Mayberry et al reported a two-fold relative risk of dying among 513 patients studied for 1-35 years; this risk was most marked in the years immediately after diagnosis . There were similar conclusions from a series from Cardiff. The study by True love and Pena , including patients from a 42-year period, revealed a unique pattern of increasing divergence of expected and observed survival rates, suggesting that the disease became progressively more dangerous. The Dutch series of 671 patients followed-up at Leiden University Hospital from 1934-1984 and a review of 360 patients with colonic Crohn's disease, followed for a mean 14.9 , years revealed an increased mortality; however this had decreased significantly in recent years. Recent improvements in mortality may be attributed to less radical surgery and improved medical care with the use of antibiotics and nutritional support ,.
A good prognosis for ulcerative colitis with a survival rate essentially similar to that of a matched population has been obtained from studies from Denmark , the USA  and Japan . The Danish study was of 783 patients from the county of Copenhagen who were followed for 8 years; the mortality in women was the same as that of the general population, but there was a slight excess mortality in men over 40 years old for the first 2 years after diagnosis. In contrast with these studies, 1,274 patients identified as having ulcerative colitis over a 25-year period from 1955-1979 from Stockholm County had a worse cumulative survival than expected; the 20year survival probability was 80% for males and 85% for females, compared with 97% for males and 98% for females, expected in the general population . The pattern of increased mortality during the first 2 years after diagnosis, noted in men over 40 years old in the study from Copenhagen , was also reported in another study of prognosis in ulcerative colitis from Japan , this increase in mortality being attributed to postoperative complications.
| Likelihood of surgery and quality of life studies|| |
With regard to Crohn's disease, in a Danish series, 46% of patients had an operation in the first 2 years after a diagnosis was made; but the rate fell subsequently to 3% per year . In the Japanese study, rather fewer required surgery, 26% after 5 years and 47% after 10 years . Similar rates of surgery were found in a German survey of 492 patients  and an Italian survey of 267 patients , although a smaller study, also from Italy, reported an operative rate of 54% .
Although Cooke et al  reported an increased mortality risk associated with Crohn's disease, all but 2 of 121 living patients -a mean 28 years from diagnosis- were leading a normal life free from physical restrictions; all but 14 of 360 patients with Crohn's colitis surviving for a mean period of 14.9 years were well and asymptomatic . A slightly less optimistic picture was obtained from the Danish regional survey which recorded 15-20% as being disabled (however, this was not strictly defined) but 75% were able to work normally in any one year, other than the year of diagnosis. From the same study, in any year 45% of patients were asymptomatic; 30% had low disease activity but in 25%, activity was moderate or high. In a further study of 152 patients in Sweden, only 2.6% had pronounced subjective symptoms and 89% reported a good quality of life .
In those with ulcerative colitis, the reported likelihood of a colectomy being performed in Japanese and Danish studies, varies from 16.524% at 10 years and 31-38.5% at 15 to 18 years ,. A total of 13.5% underwent a proctocolectomy in the series from Minnesota , but a more extensive series from Cleveland revealed a surgical rate of 37% among 1,116 patients followed for a mean 12.7 years . A second Japanese series reported a likelihood of surgical intervention in 34 % of patients with total colitis, but only 10% if the disease was limited to the left side of the colon .
In the regional study from Copenhagen, the probability of maintaining working capacity after 10 years was 93% . In this same cohort it had been reported earlier that at any one time, 50% were asymptomatic, 30% had low disease activity and 20% had moderate or high disease activity. Although in the first year after diagnosis over 50% were described as being partly disabled . The impact of ulcerative colitis on family, emotional, social and professional life was assessed in 122 patients, including 28 who had undergone colectomy, and compared to age and gender matched controls; no difference was detected between the 2 groups . Sexual activity was either improved or unchanged in 32 patients with inflammatory bowel disease, who were followed-up after colectomy and ileostomy had been performed in childhood or adolescence; impotence was not experienced by any male patient . Sexual activity was also studied in 150 patients with inflammatory bowel disease with no difference found between them and matched controls . Quality of life among 113 patients one year after colectomy was found to be high, irrespective of which surgical procedure (conventional ileostomy, ileal reservoir or Kock's pouch) was performed .
| Inflammatory bowel disease in different groups of patients|| |
If the prognosis for inflammatory bowel disease is either unchanged from the general population or carries only a slightly increased risk of mortality, are there subgroups with a worse prognosis particularly the elderly, children and adolescents, or pregnant women?
The course of inflammatory bowel disease in the elderly, on the basis of studies from the 1960s, was felt to be worse than that for younger patients. However, more recent data suggest the differences between the two groups may only be marginal. A review of 244 patients over 60 years old with inflammatory bowel disease found that response to therapy, need for surgery and development of complications was no different than in younger patients under 60 years . The mortality rate was higher, 2.4% compared to 0.8%, although the duration of this study was not stated. The pattern of Crohn's disease was different with colonic disease being relatively more common in the elderly, 52% compared to 28.2%. A similarly high proportion of colonic disease, 20/ 47 patients, was detected in a study from Birmingham, UK, of elderly patients under long-term review between 1944-83. In this study there were 15 deaths (though 9 were unrelated to Crohn's disease). Of those surviving, all but one were alive, well and asymptomatic . Another study of Crohn's disease in the elderly suggested a good prognosis in colonic disease but a worse one in ileal or ileocolonic disease . A study of elderly patients with ulcerative colitis revealed no difference in prognosis compared with younger patients, but they were more likely to be admitted to a hospital or to receive systemic steroids .
Among 70 Scottish young adults, who had had inflammatory bowel disease for a mean of 14 years, 50% had proceeded to higher education and only 6 were involuntarily unemployed . The largest series of patients with Crohn's disease diagnosed in childhood and adolescence suggested that the disease caused a small number of premature deaths; 13 of 513 patients died during a mean follow-up of 7.7 years. There was also a considerable morbidity with 69% undergoing an operation and 67% of survivors considering their health to be sub-optimal . Growth retardation was found in 21 of 67 children followed for a mean of 15 years, but this was only permanent in 10, catch-up occurring in 11, after surgical resection or medical therapy . Mortality in this group was high, 9/67, and occurred particularly in those with diffused intestinal disease (6/14 children). Of the 58 survivors, 38 had no evidence of recurrence and only six were symptomatic. the growth catchup occurring after surgery was examined further in 37 children undergoing resection, of whom 14 had severe growth failure; only two experienced catch-up and this occurred when there was no early recurrence and the child was prepubertal . Very similar long-term results were seen among 14/38 children with Crohn's disease who experienced permanent impaired growth (36). Impaired growth, in a prospective study, was related to disease activity, rather than steroid use . Ileocolitis was found to be the most common pattern of Crohn's disease among 87 children, being present in 52%, and again extensive disease was associated with a worse prognosis ; isolated small bowel involvement carried the best prognosis. Ileocolitis was also identified as carrying a poor prognosis for recurrence after surgical resection in 82 children followed for a mean of 5.3 years . Sixty-eight Scottish children with Crohn's disease were followed for a mean 7 years: five died, 49 underwent at least one operation and the median in-patient stay was 64 days. This compared with 37 children with ulcerative colitis, in which case there were no deaths, 11 had operations and the median in-patient stay was 30 days; none had growth retardation as compared with 10/ 45 with Crohn's disease for whom data were available .
There are fewer studies of ulcerative colitis in children. A large review of 336 patients with ulcerative colitis diagnosed before 21 years of age between 1955-74 revealed a mortality of 5.4% (9/ 18 died due to carcinoma of the colon) and a colectomy rate of 35% . A comparative study of ulcerative colitis in children and adults from Denmark suggested that children have more severe disease, both by clinical and histological criteria, require colectomy more frequently, but have a lower mortality . A review of very young children with ulcerative colitis (onset before age of 10 years) was encouraging with three-quarters of them reporting a good quality of life and only 2/38 had required colectomy .
Fertility has been reported as being lower in those women with inflammatory bowel disease, however, it is not clear whether this is due to patient's choice  or due to the disease itself . A recent survey of 409 women suggested no increase of involuntary infertility . The course of pregnancy is said not to be influenced by either ulcerative colitis or Crohn's disease if the disease is not active, and the chance of relapse is not influenced by the pregnancy . In active disease, however, the prognosis may be worse both for fetus and mother ,. A 1988 review of 11 patients with onset of Crohn's disease in pregnancy revealed that two mothers died and 7/12 infants did not survive . The implications of active disease may not be so severe in ulcerative colitis, with 30/35 pregnancies progressing to normal live births in a series from northern Scotland . As a community-based study, this probably reports patients with less severe disease than most hospital-based studies.
| Site of disease as a prognostic factor|| |
Several studies have shown that extensive Crohn's disease involving both small and large bowel carries a relatively bad prognosis ,. Farmer et al in a review of 592 patients found 91.5% of those with ileocolitis required surgery, compared to 65.5% with only small bowel disease and 58% with colonic /anorectal disease . They further reported that those with segmental involvement of small or large bowel had the best quality of life. Wright also found an increased number of relapses in those with ileocolitis . Conversely, patients with isolated small bowel disease appear to have the best prognosis, reported in reviews of 104 patients  and 93 patients . The Japanese study reports that the Crohn's disease activity index was higher, and a number of laboratory and clinical parameters worse, in those with either ileocolitis or colonic disease compared to small bowel disease only . Crohn's disease confined to the appendix appears to have a particularly favorable prognosis ,; a review of 56 patients with histologicallydiagnosed Crohn's disease isolated to the appendix revealed recurrent disease in only 14% over a mean follow-up of 5.2 years . Duodenal involvement represented extensive disease elsewhere in the alimentary tract and hence carried a particularly poor prognosis, with a mortality of 2/7 in one small series ; duodenal and jejunal disease were found to be a marker of an increased mortality in a recent study from Probert et al . Asymptomatic abnormalities, both endoscopic and histological, of the upper gastrointestinal tract may be more common and less important prognostically, as 23/41 screened patients with Crohn's disease had histological or endoscopic abnormalities . Localized involvement of the small or large bowel carries a good prognosis; confirmed by a review of 80 patients with disease affecting only the rectum and/or sigmoid colon, in whom mortality was found to be less than expected for the cumulative observation period of 655 patients-years .
There are several studies which suggest that patients with pancolitis have a worse prognosis than those with more limited disease ,,,. In a survey from Japan, 34% of patients with total colitis, required surgery as opposed to 10% with left-sided disease and whereas relapses gradually became less frequent with left-sided colitis, this pattern was not seen in those with total colitis . In the survey of 1,274 patients from Stockholm County, those with total colitis had a greater mortality in the first years after diagnosis . In contrast, those presenting with disease limited to the rectum and sigmoid colon appear to have a particularly good prognosis. In only 10% of 359 such patients did the disease become more - extensive and only 8% required an operation over a mean of 11 years . A smaller study (reported in abstract form only) suggested that disease progression may be more common, 16% after 5 years and 37% after 11 years; again surgery was required in relatively few, 11% . A comparison between those with and without rectal sparing was made in a group of 30 patients, observed for at least 5 years; atypical ulcerative colitis with rectal sparing had a higher relapse rate and apparently had disease which was more difficult to control .
| Clinical prognosis factors|| |
Indicators, both clinical and laboratory, have been studied to a greater degree in Crohn's disease than ulcerative colitis. A short history of symptoms prior to surgery appears to indicate a more aggressive disease pattern with two studies showing more frequent disease recurrence after surgery ,. Another showed an increased risk of a first operation in such patients  but no such relationship was detected in two other studies ,. To cause further confusion, two retrospective studies of disease recurrence postoperatively among 82 children  and 90 adults  revealed increased recurrence rates in those with longer symptomatic periods prior to surgery. Disease which results in fistulae and abscesses has been postulated as being more aggressive, requiring reoperation more frequently. Not surprisingly, in a review of 55 patients over 60 years old, delayed diagnosis, malnutrition and other associated diseases were all poor prognostic factors . As might be expected, a delayed diagnosis and severe first episode of ulcerative colitis were found to be poor prognostic indicators among 124 patients followed for 10 years or more . Fifty-six clinical features were correlated with the need for surgery in 181 patients admitted for treatment of acute colitis to one specialist center; a patient with a temperature greater than 38°C and bowel frequency of more than 8 during the first day had an 80% chance of surgery, while if neither of these criteria were fulfilled, then only 4% required surgery. Oral monilia was also a poor prognostic indicator but less selective than stool frequency, pyrexia and hypoalbuminemia . Severe diarrhea during relapses requiring admission, in a group of 89 patients, was confirmed as a prognostic indicator for surgery .
| Laboratory prognostic indicators|| |
Confusion exists as to the prognostic relevance of granulomas in histological specimens of Crohn's disease; their presence has been found to be a favorable indicator in colonic and anal disease , to be associated with more extensive and aggressive disease [76[, and to bear no relation to prognosis . The presence of ulceration or fissuring on histological examination of either rectal biopsy or resection specimens has however been associated with more severe disease in two studies ,. Laboratory markers associated with a poor prognosis for Crohn's disease at the time of diagnosis have included anemia, hypoalbuminemia (albumin below 40 g/dl), a raised ESR (above 30 mm/first hr); when one of these was present, the probability of surgery over a 10-year period was increased by 3 times . Hypoalbuminemia was also a prognostic indicator for surgery during a relapse in ulcerative colitis ,. Lymphopenia, with counts less than 1 X 10 9 /liter preoperatively, was shown in one study to be associated with a higher rate of disease recurrence . Preoperative blood transfusion was found to have no effect on disease recurrence in 104 patients .
| Conclusions|| |
Every gastroenterologist must know of the occasional patient who has died from a complication of inflammatory bowel disease. Indeed, in England and Wales, between 1987 and 1992, about 400 people/year died from ulcerative colitis or Crohn's disease (data from death certificates, Office of Population Censuses and Surveys). Yet, it is difficult to prove from the literature that there is a clear decrease in life expectancy for patients with inflammatory bowel disease. It is possible that the hazards of inflammatory bowel disease are compensated by long-term health monitoring and access to expert medical care. Corticosteroid, 5 aminosalicylic acid-containing preparations and immunosuppressives are of proven clinical efficacy; they should improve the prognosis of present-day patients, yet all can cause serious clinical adverse events. We must hope that modern medical treatment (including parenteral nutrition and potent antibiotics) and conservative surgery, will reduce morbidity and mortality for the present generation of patients with inflammatory bowel disease.
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Roy E Pounder
University Department of Medicine. Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2]