A population-based study on the incidence of inflammatory bowel disease in Oviedo (Northern Spain)

L. Rodrigo, S. Riestra¹, P. Niño, V. Cadahía, R. Tojo, D. Fuentes, M. Moreno, E. González-Ballina, and E. Fernández²

Service of Digestive Diseases. Hospital Universitario Central de Asturias. 1Section of Digestive Diseases. Hospital Valle del Nalón. Asturias. ²Department of Biochemistry. Hospital de Cabueñes. Gijón. Asturias, Spain

 

ABSTRACT

Objective: to assess the incidence of inflammatory bowel disease in Oviedo (Northern Spain), and to describe the clinical features of new patients.
Patients and methods: a prospective population-based study was made at the Health Area IV, Principality of Asturias (Oviedo, 312,324 inhabitants). All new diagnosed patients with inflammatory bowel disease were registered over a 2-year period.
Results: a total of 85 patients were included, 47 of these with ulcerative colitis (UC), 37 with Crohn's disease (CD), and 1 with undetermined colitis. The overall adjusted incidence rate of UC and CD per 10⁵ inhabitants between 15-64 years was 9.1 (95% CI: 5-13.1) and 7.5 (95% CI: 3.8-11.2), respectively. The global male/female ratio was 0.9, without significant differences between both diseases. CD patients were younger than those with UC (33 ± 15 years vs 45 ± 20 years; p < 0.05). Mostly, CD patients were diagnosed at an age younger than 35 years (65%), while UC patients were diagnosed at an age between 25 and 64 years (81%).
Disease extension in UC was proctitis in 11%, left-side colitis in 53% and extensive colitis in 36%. With respect to CD, the ileo-colonic form predominated (49%), followed by the ileal (40%) and colonic (11%) forms; an inflammatory, stenotic and fistulous pattern was seen in 54, 22 and 24% of patients, respectively.
Conclusions: in our area, the incidence of CD is similar to that in other Northern European countries, while UC has a lower incidence. CD mainly affects young people, while UC predominates in middle-aged patients. At diagnosis, UC is predominantly localized, the ileo-colonic form and an inflammatory pattern being most frequent in CD patients.

Key words: Inflammatory bowel disease. Ulcerative colitis (UC). Crohn's disease (CD). Incidence. Epidemiology. Spain.

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Rodrigo L, Riestra S, Niño P, Cadahía V, Tojo R, Fuentes D, Moreno M, González-Ballina E, Fernández E. A population-based study on the incidence of inflammatory bowel disease in Oviedo (Northern Spain). Rev Esp Enferm Dig 2004; 96: 296-304.

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Recibido: 08-10-03.
Aceptado: 10-11-03.

Correspondencia: Luis Rodrigo. Servicio de Aparato Digestivo. Hospital Universitario Central de Asturias. C/ Celestino Villamil, s/n. 33006 Oviedo. Tel.: +34. (985) 10 80 58. Fax: +34. (985) 27 36 14. E-mail: Irodrigos@terra.es

 

INTRODUCTION

Inflammatory bowel disease (IBD) is a generic term that classically includes Crohn's disease (CD), ulcerative colitis (UC), and undetermined colitis (UC). The causes of these diseases are not well known, but genetic predisposition and environmental factors are involved in their etiology and pathogenesis (1). In general, population studies have shown that the incidence of UC and CD is highest in northern latitudes (2-3); in addition, evidence exists for epidemiologic variability within countries (4). These differences may result from variations in the socio-demographic characteristics of populations (5), rather than from different genetic backgrounds. In Spain, several prospective population-based studies have shown a variable frequency of IBD (8-16 cases per 100.000 inhabitants/year) (6-8). These results are in agreement with the smaller-than-expected difference in North-versus-South incidence of IBD, found by the European Collaborative Study on Inflammatory Bowel Disease (2).

Most incidence-oriented studies of IBD have been made in adults and there have been few population-based, prospective studies in children (9). Contradictory data exist on the time trend of juvenile-onset IBD incidence (9-11). In Spain, the incidence of IBD in children 14 years of age or younger is unknown.

At present, the management of patients with IBD is associated with substantial healthcare costs in terms of medical visits, hospitalization, surgery, chronic treatments, biologic therapies, etc. (12,13). On the other hand, in view of the complexity of these diseases, a multidisciplinary approach (gastroenterologists, surgeons, dieticians,…) has been required, and monographic units have been created to attend to this type of patients. Therefore, in order to schedule health resources, it is of considerable interest that the incidence of IBD be known.

The objective of this study was to determine the incidence of IBD in the general population of Oviedo (Principality of Asturias, Spain), and to record the phenotypic characteristics of newly diagnosed patients during a two-year period. Furthermore, clinical features of IBD in children are described.

PATIENTS AND METHODS

Study design

A prospective and descriptive study was undertaken in the general population (312,324 inhabitants, 75% in urban areas) of Health Area IV, Principality of Asturias (Northern Spain). The referral hospital for this population was "Hospital Universitario Central de Asturias" (Oviedo). The enrolment period spanned from September 2000 to September 2002.

A study protocol was established and sent to all general practitioners, pediatricians and Internal Medicine, Gastroenterology and Surgery specialists in Health Area IV. In addition, several informative meetings were held, before and during the period of the study. The objective was that all new patients with a suspected diagnosis of IBD, were sent to the referral center, for confirmation and registration.

IBD patients

All cases were evaluated at Hospital Universitario Central de Asturias in an outpatient clinic, devoted to patients with IBD (outpatients). Furthermore, patients who had been hospitalized for the first time because of suspected IBD, and were then diagnosed as new cases during the study period, were also included (inpatients). There was no age restriction.

At baseline, all subjects underwent a complete evaluation, including a collection of demographic and clinical data, physical examination and laboratory studies (blood cell count, coagulation tests, and biochemistry). Acute-phase reactants such as erythrocyte sedimentation rate, reactive C protein and orosomucoid acid, were also measured. A colonoscopy and/or barium examination of the small bowel was performed, and intestinal biopsies were collected, in order to confirm the diagnosis and to assess disease extension. Based on the results of these studies, patients were registered as having or not IBD; the classical Lennard-Jones criteria for CD (14) and Truelove-Witts criteria for UC (15) were strictly applied. Follow-up visits were individually scheduled according to the each patient's clinical status.

In order to assess the intensity of symptoms, specific activity indexes were calculated at baseline and during each visit (15,16). With the aim of describing the phenotypic expression of CD, we used the Vienna classification (17), which includes age at diagnosis (A1 = below 40 years; A2 = equal to or above 40 years), location (L1 = terminal ileum; L2 = colon; L3 = ileocolon; L4 = upper gastrointestinal tract), and behavior (B1 = inflammatory; B2 = stricturing; B3 = penetrating).

Statistical analysis

One patient with undetermined colitis was excluded from the study. Mean annual CD and UC incidence rates were calculated as the number of new cases per 100,000 inhabitants per year. We used the direct method of standardization (European standard population) to adjust incidence rates for different ages (ten-year intervals) and genders. Confidence intervals (CI) for incidence rates were assessed with a 95% level of probability, by using a Poisson distribution or normal distribution. Truncated (15-64 yr) age-standardized incidence rates were used to compare our results with those in the European standard population. Proportions were compared using Fisher's exact test. Differences between groups were examined using a two-sided approach, with p < 0.05 considered as significant.

RESULTS

A total of 85 new patients were diagnosed as having IBD during the 2-year enrolment period, of whom 47 had UC, 37 CD and 1 undetermined colitis. The ratio UC/CD was 1.3. Overall, 28 patients (33%) were diagnosed during hospitalization as having severe gastrointestinal symptoms (inpatients), without differences between both processes. Forty patients were male (M) and 44 female (F), with a M/F ratio of 0.9. Mean age was 39 ± 18 years (range 12-91 years), without significant differences when comparing the mean age of males (36 ± 17) versus females (32 ± 17). The baseline general characteristics of patients with IBD are shown in table I; on comparing patients with UC and CD, differences were only found for age (CD patients were younger than UC patients) (p <0.05).

The mean annual incidence rates of UC and CD were 7.5 and 5.9 per 10⁵ inhabitants, respectively. Figure 1 shows overall age and gender-specific incidence rates for both diseases. CD was diagnosed mostly in subjects younger than 35 years (65%), with rates for both genders declining with increasing age; a small increase in incidence was observed in women at 45-54 years and in men at 55-64 years. For UC, different patterns of incidence were observed for both men and women, with an incidence peak at 25-34 years for women, whereas for men there were two incidence peaks, at 25-34 and 45-64 years. Table II shows the adjusted UC and CD incidence rate per 10⁵ inhabitants at 15-64 years reported for the Spanish study (6,7), European Collaborative study (2), and present study.

At diagnosis, the extension and disease activity index of UC patients is shown in table III. In 53% of cases, the disease was located in the left colon. Regarding CD, the most frequent phenotype according to the Vienna classification was A1L3B1 (Table IV). Four cases of CD (3 male/1 female) and 1 case of UC were registered during the study period among the population under the age of 15; thus, the mean incidence of CD and UC per 100,000 among these individuals was 5.7 and 1.4, respectively. The clinical characteristics of children with CD were as follows: ileum (L1) and ileocolon (L3) location in 3 (75%) and 1 (25%), respectively; inflammatory (B1) and penetrating (B3) behavior in 1 (25%) and 3 (75%), respectively; CDAI was 209 ± 11.

In this study, we have shown that the incidence of IBD in Oviedo, Spain, is similar to that recently described in other Spanish areas (6-8). The adjusted incidence rate per 10⁵ at ages between 15 and 64 years was 9.1 for UC and 7.5 for CD. UC was diagnosed as frequently as in other Southern European countries, whereas the incidence of CD was similar to that described in Northern European countries (2).

DISCUSSION

Temporal trends in the incidence rate of IBD have been documented. In Spain, a clear tendency towards increased incidence of UC and CD has been described during the last two decades. Various factors such as public access to quality medicine, the generalisation of endoscopic techniques and a better design of epidemiological studies may have influenced this. Thus, the first studies carried out in Spain were mainly based on registers of hospitalised patients and had a retrospective character, demonstrating a low incidence of IBD (1-4.8/10⁵/ year) (18-21). More recent prospective, population-based studies have demonstrated higher incidences (8-16/10⁵/ year) (6-8); the importance of the type of study is emphasized by Saro et al. (8), in whose work cases of IBD in Gijon (Spain) are collected both retrospectively (1957-1993) and prospectively (1994-1997), obtaining an incidence of 5.06 and 16.49 respectively, for these periods.

Nevertheless, in spite of the methodology previously commented, we think that the increase in the number of patients with IBD in Spain is mainly related to the socioeconomic development reached by this country in recent years. In general, there is a relationship between the incidence of IBD and the standard of life in a given country, which suggests that environmental factors may be involved, such as diet, industrialization, pollution, and economic development (1).

On using the standard European population as the reference for adjusting incidence rates we have been able to compare our results with those published using a similar methodology (2,6,7); thus, we observed that the incidence of UC (9.1/10⁵) is similar to that described in other areas of Spain and in Southern European countries, but that it is smaller than that in countries of Northern Europe. With regard to CD, we found an adjusted incidence rate of 7.5/10⁵ inhabitants, which is similar to that reported in Northern Europe and higher than in Southern areas. These data are in agreement with the existence of a European North-South gradient for UC, but no for CD.

The UC/CD ratio in our series was 1.3, which is slightly smaller than that reported in other Spanish studies (1.4-2) (2,6-8). In Europe, this ratio is high in Scandinavian countries, given their high incidence of ulcerative proctitis (22), and in the Mediterranean area (Italy, Greece), due to their very low incidence of CD (23,24). A possible explanation of the low UC/CD ratio found in our study may be that ulcerative proctitis amounted to only 11%, which is clearly less than the 30% communicated throughout Europe (25); we believe that the characteristics of our "health area", have been the cause that mild forms of IBD be underreported, amongst which proctitis stands out.

The overall male/female ratio in our series was 0.9, without significant differences between UC [1] and CD [0.8]. In this respect, we wish to emphasize that the onset of CD was earlier in men, although the illness was more frequent in women. The age at diagnosis of patients with UC was greater than that of patients with CD, similarly to reports in the medical literature (3). Regarding UC, the peak of incidence was at 25-34 years, a progressive decrease in the frequency of this disease being seen later in females, while incidence remained high in males, due to the existence of a second peak at 45-64 years; this different pattern according to gender was first demonstrated by the European Collaborative Study of IBD (2). As regards CD, there are no large variations in the incidence according to gender, with a maximum peak of incidence at 15-34 years, and a progressive decrease with age, with a small incidence peak at 45-64 years that was previously observed in other studies (6,7); on the other hand, we have already emphasized that CD develops ten years earlier in males than in females, a fact that explains the predominance IBD has in male children in our series.

From a clinical point of view, UC presents at diagnosis with a mild index of activity, requiring that 32% of patients are hospitalised for management; left colitis is the most frequent form of presentation, similarly to what is found by other studies (25). In 1999, the Spanish Epidemiological and Economic Study Group on Crohn's Disease published the clinical features of 635 patients with CD (26). The mean age of these patients was 33 years, 52% were women, a family history was identified in 10%, and the most frequent localization of the disease was ileo-colonic involvement; our results are similar to the previous ones, with phenotype A1 (< 40 years), L3 (ileocolon location) and B1 (inflammatory behavior) being most common. Thirty-five percent of patients with CD in the Spanish epidemiological study were hospitalised during the year prior to their inclusion in the study, due to the consequences of complications (26); in our series, 32% of patients with CD were diagnosed during hospitalization.

To our knowldge, this is the first Spanish study in which the incidence of IBD has been investigated in children. Even though the number of cases diagnosed is too small to draw definite conclusions, we deem it interesting to provide the incidence of CD and UC, which was 5.7 and 1.4/10⁵ inhabitants younger than 15 years, respectively. One hundred percent of children with IBD were diagnosed between 12 and 14 years of age, which is in accord with other series in which the maximum incidence has been shown to be in this age group. Thus, Bentsen et al. (9) reported an incidence of 0.9 /10⁵ in the 0-12 years age group, and of 7.2/10⁵ in children of 13-15 years of age. A predominance of males among children with CD has also been reported by other authors (11). Even with such a small sample size we observed a predominance of ileal and penetrating forms in children with CD.

In summary, IBD has evolved from being a rare disease to become a relatively frequent one, with UC being slightly more common than CD. Our incidence of UC is similar to that of other countries in Southern Europe, while CD is diagnosed as frequently as in Northern countries. Clinical behaviour at diagnosis, both in terms of dis-ease activity and disease extension and localization, is similar to that observed in the rest of Europe. IBD in Spanish children is relatively frequent, this having been most commonly observed in males. Nevertheless, larger studies are necessary in order to assess the epidemiology of IBD in this population group. With the results obtained in the present study, a better scheduling of health resources to treat this frequent gastrointestinal disease is now possible.

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