| ORIGINAL PAPERS |
Epidemiology of chronic inflammatory bowel disease in the Northern area of Huelva
A. Garrido, M. J. Martínez1, J. A. Ortega1, A. Lobato1, M. J. Rodríguez1 and F. J. Guerrero2
Department of Gastrointestinal Medicine. 1Family and Community Medicine. 2Department of Internal Medicine. Hospital Comarcal
de Riotinto. Huelva. Spain
ABSTRACT
Objective: to know the different epidemiologic aspects of chronic inflammatory bowel disease (IBD) in the Northern area of the province of Huelva. ]]>
Material and methods: we carried out a retrospective (1980-1996) and prospective (1996-2003) study of all patients diagnosed with IBD in the Northern area of Huelva, with 77,856 inhabitants. The distribution of Crohn's disease (CD) and ulcerative colitis (UC) was analyzed, as well as sex, age and smoking habit at the time of diagnosis, familial aggregation, appendicectomy rate, phenotype (anatomical site and clinical types), extraintestinal manifestations, and immunosuppressive therapy or surgical requirements.
Results: 70 patients with IBD were studied, 40 with UC and 30 with CD. Sex distribution was 39 (55.7%) males (55% with CD vs 56.6% with UC; NS) and 31 (44.3%) females (45% with CD vs 43.3% with UC; NS). Mean age at presentation was 44.7 ± 19.32 years in UC vs 32.3 ± 16.43 in CD; p < 0.001. Familial association was 7.1%. Previous appendicectomy was referred in 2.5% of patients with UC vs 36.7% of those with CD (p < 0.001), and the percentage of smokers was also higher in CD 66.7% vs CU 12.5% (p < 0.001).
Anatomical site in UC was: proctitis, 20%; proctosigmoiditis/left colon, 42.5%; extensive colitis, 25%; and pancolitis, 12.5%; in CD was: terminal ileum, 43.3%; colon, 20%; and ileo-colon, 36.7%. The disease patterns were: inflammatory 56.7%, obstruction 26.7%, and fistulization 16.7%. Extraintestinal manifestations were diagnosed in 7.5% of patients with UC vs 16.6% patients with CD; surgery was performed in one patient with UC vs 10 with CD, and one patient with UC required immunosuppressive treatment vs 12 with CD.
A multivariant analysis showed that younger age and smoking habit were risk factors for CD vs advanced age in UC, in which case, the smoking habit was a protective factor. The mean incidence rate of IBD starting from 1996 and expressed in cases/100.000 inhabitants/year was 5.2 for UC and 6.6 for CD.
Conclusions: the mean incidence of UC in our area was 5.2 cases/100,000/inhabitants/year, and 6.6 for CD. Patients presenting with CD are diagnosed at a significantly younger age that those with UC; the smoking habit is a risk factor for CD while it protects from UC. The characteristics of IBD in our geographical area do not differ substantially from those in other regions of Spain.
Key words: Inflammatory bowel disease. Ulcerative colitis. Crohn's disease. Epidemiology. Incidence.
Garrido A, Martínez MJ, Ortega JA, Lobato A, Rodríguez MJ, Guerrero FJ. Epidemiology of chronic inflammatory bowel disease in the Northern area of Huelva. Rev Esp Enferm Dig 2004; 96: 687-694.
Recibido: 04-12-03.
Aceptado: 17-02-04.
Correspondencia: Antonio Garrido Serrano. C/ Almajarra, 1, Blq. 7, 1º B.Urb. Jard. Sta. Eufemia. 41940 Tomares. Sevilla. e-mail: agarridos@interec.org
]]>INTRODUCTION
IBD comprises three conditions (UC, CD, and indeterminate colitis) that are well defined in their clinical and pathologic aspects (1,2). However, its etiology and pathogenesis remain unknown, and therefore epidemiological investigation to determine disease variability and disease-related risk factors are important, in an attempt to establish the origin of the disease and the way effective treatment may be applied. At present it is thought that an interaction exists between extrinsic (environmental) and intrinsic factors (genetic predisposition) allowing the expression of this disease; epidemiological studies address all extrinsic circumstances potentially involves.
The incidence of IBD in our geographic area has increased in the last decades (3,4), and leveled out around 1980 at 10-15 cases/100,000/year (5); variations according to the different geographical areas have also been documented (6).
Classically, UC and CD are associated with high socio-cultural levels, with a higher economic capacity (7), and with urban and industrialized areas.
For the time being no epidemiological studies on IBD are being carried out in our sanitary area; thus, with the present paper we want to know the distribution and variability of IBD in the Northern area of the province of Huelva, with a rural population and a poor socioeconomic level.
MATERIAL AND METHODS
This is an epidemiological, descriptive and population-based study carried out from 1980 to 2003, in a retrospective way from 1980 to 1996 and prospectively from 1996 to 2003, which includes the group of patients with IBD in the Northern area of Huelva. This geographic area has a total population of 77,856 inhabitants who exclusively depend on one hospital located in Riotinto. This sanitary area comprises three districts: a) "Andévalo": next to the county capital, with its population mainly employed in the area of services; b) "Cuenca Minera": population traditionally employed in mines and nowadays in absolute economic regression; and c) "Sierra": with a marked rural character, dedicated to agriculture and cattle raising.
Inclusion criteria: all patients diagnosed with IBD in our area were included, 40 with UC and 30 with CD, who met the diagnostic criteria established by Truelove (8) and Lennard-Jones (9), respectively. All of them are followed up in the usual way at Hospital de Riotinto on an outpatient basis or in a hospitalization regimen.
Patients were identified in the retrospective study by reviewing endoscopies, the Unit of Gatroenterology, and the general records in our hospital, and in the prospective study by means of the detection of incident cases. In all patients a clinical follow-up was carried out to the closing of the study.
]]> Demographic data were analyzed for all cases in a protocolized way: sex, age at the time of diagnosis, and district the patient originates from; members affected in the same family were also analyzed to calculate the percentage of familial association, as well as the rate of previous appendicectomy and smokers at the time of diagnosis.In UC, involvement extent was estimated according to the most recent and deeply penetrating endoscopic exploration, with the following definitions: proctitis with involvement of 15 cm from the anal margin; proctosigmoiditis with involvement of the rectum and sigmoid; left colitis with alterations distal to the splenic flexure; extensive colitis up to the hepatic flexure; and pancolitis with lesions throughout the entire colon. Extraintestinal manifestations as well as the requirements for immunosuppressive agents and/or surgical therapy were also evaluated.
Anatomical site in CD was subdivided as follows: terminal ileitis, ileocolic, colon, and other. For disease behavior the classification by Lennard-Jones (10) -inflammatory, fibrostenotic, and fistulizing types- was used. Extraintestinal manifestations as well as the requirements for immunosuppressive or biologic agents and/or surgical therapy were also evaluated.
The incidence rate (number of new cases every year/100,000 inhabitants) was calculated.
Statistical analysis: the statistical study was made using an R-SIGMA program. Results were expressed as mean ± standard deviation or as percentage, both with a 95% confidence interval. The chi-square test was used for the analysis of qualitative variables.
In the two logistic multivariant regression analyses, 5 variables of clinical interest were included (age, sex, region, cigarette smoking, and previous appendicectomy), taking as a dependent variable the presence of CD versus UC, or vice versa, according to cases. Regions lacking statistical significance in the multivariate analysis were not included in the tables. Age was considered a continuous variable, and the rest dicotomic variables.
All values of p < 0.05 were considered statistically significant.
RESULTS
Seventy patients fulfilled the diagnostic criteria of IBD in our area: 40 (57%) with UC and 30 (43%) with CD. The mean incidence of IBD starting from 1996 and expressed in cases/100.000 inhabitants/year was 5.2 for UC and 6.6 for CD.
Table I shows the general characteristics of patients in our sample, and highlights the younger age at diagnosis of those with CD, as well as their higher percentage of previous appendicectomies and smokers. The male/female ratio (22 men/18 women in UC and 17 men/13 women in CD) and extraintestinal manifestations were similar between CD and UC, although the indication of immunosuppressive or biologic therapy, as well as of surgical procedures, was lower in patients with UC.
]]>
Anatomical sites, expressed as percentage with 95% CI, were for UC as follows: proctitis 20% (9.6-36.1), proctosigmoiditis/left colitis 42.5% (27.4-59), extensive colitis 25% (13.2-41.5), and pancolitis 12.5% (4.7-27.6); in CD, 43.3% (26-62.3) had terminal ileum involvement, 20% (8.4-39.1) colic involvement, and 36.7% (20.5-56.1) colon and small bowel involvement, with the disease being inflammatory in 56.7% (37.7-74) of patients, fibrostenotic in 26.7% (13-46.2) of patients and fistulizing in 16.7% (6.3-34.5) of patients.
Previous appendicectomy was more frequent among patients with CD and fistulizing disease (80%; 95% CI 29.9-98.9) that among those with fibrostenotic disease (25%; 95% CI 4.5-64.4) or inflammatory disease (29%; 95% CI 11.4-56; p < 0.02; odds ratio = 16.7).
As for the region of origin, table II shows a lower incidence of CD in the "Sierra" district.
A multivariate logistical regression analysis showed that factors associated with UC included older age, non-smoking status, and origin in the "Sierra" district, while younger age, smoking status, and origin in the "Cuenca Minera" district were associated with CD (Tables III and IV).
One patient in our series died during the study as a consequence of fatal infectious mononucleosis; he was a 25 year-old male with Crohn's ileitis who was receiving immunosuppressive treatment with azathioprine (11).
The prevalence of IBD in the last year of the study was 95 cases/100.000 inhabitants.
DISCUSSION
Numerous epidemiological studies have been published on IBD; nevertheless, information regarding the incidence of IBD in Spain is still scarce. A systematic review shows a progressive increase in UC incidence -ranging from 0.6 to 8 cases/100,000 inhabitants/year with a mean value of 3.8- and in CD -ranging from 0.4 to 5.5 cases/100,000 inhabitants/year with a mean value of 0.9- (12). This study reported an increased association with urban life and more economically developed geographic regions.
Our data, coming from a region located in Southern Europe that has a marked rural character and poor economic development, are similar to those described for other geographical areas (13-19), indicating that differences are not significant according to geographical regions; therefore, IBD incidence rates in developing countries will probably be equal to those of developed countries in a near future, and the so-called North-South gradient, which was documented by the European epidemiological collaborative study (20), in which four Spanish healthcare areas participated (Vigo, Sabadell, Mallorca, and Motril), will disappear, although whether this effect was due to the technological development of medicine, which allows a better diagnosis of patients with chronic diarrhea, and an easier access of the population to quality medicine, or to factors such as industrialization, variations in dietary habits, etc., was not elucidated.
As in our paper, most Spanish studies do not find differences in the distribution of the disease regarding sex (21-23), but the diagnosis of CD is made at a younger age, with a peak incidence of diagnosis at 15-40 years, and a mean age of 33,53 years (17,18), similar to patients in our series.
Disease behavior and anatomical site in patients with IBD varies much among individuals; in our area, the involvement distal to the splenic flexure is prevalent, and CD shows an inflammatory behavior in approximately half of cases, results that are similar to those of other compared series.
Another conclusion of this paper that appears broadly accepted in the scientific literature is that the smoking habit is one of the more notable environmental factors in CD, with at least a two-fold risk increase among smokers versus non-smokers, and up to a five-fold increase in smoking women (24). It also has a deleterious effect on the development of the disease and its outcome, thus worsening prognosis (25). Similarly, the duration of the smoking habit, as well as the number of cigarettes smoked, has been associated with CD localization and clinical course. There is a predilection for the small intestine in heavy smokers, who also have a higher frequency of fistula and abscess, and an increased risk of surgical procedures after 5-10 years (26). Likewise, there are increased risks of endoscopic and clinical recurrence, and need of a second surgical procedure (27). Because of that we must inform of these risks to patients in an attempt to persuade them to give up smoking.
]]> On the other hand, a higher frequency among non-smokers has been reported in UC (28) as in our study, where smoking cigarettes was a protective factor; other authors have also described a beneficial effect of smoking on UC (29). However, therapeutic studies using oral nicotine or nicotine patches have not reported the expected beneficial results, as the role of the smoker's anxiety in the triggering of disease activity is usually overlooked. Because of these reasons, and keeping in mind the deleterious effects of tobacco on health (risk factor for malignant neoplasms, respiratory or cardiovascular diseases, etc.), start smoking or renew a smoking habit should not be recommended to patients with UC.With respect to the relationship between appendicectomy and IBD, Rutgeerts et al. (30) pointed out that appendicectomy is a protective factor for UC. Later studies come to similar conclusions, thus establishing the hypothesis that the appendix may represent a risk factor for UC because of its role on the intestinal immune system (31).
As for the smoking habit, the opposite has been described in CD, with a positive relationship between appendicectomy and CD (32). However, in their wide case-control study, Russel et al. (31) demonstrated that previous appendicectomy in this disease was probably due to a false appendicitis diagnosis in missdiagnosed CD.
Because of that, further studies are necessary to clarify the relationship between appendicectomy and IBD. In our study we have found a higher percentage of appendicectomy in patients diagnosed with CD in comparison with those with UC. This association was especially marked in patients in the fistulizing group. This association was statistically significant in the univariate analysis but of less value in the multivariate analysis. This is due to the effect of the smoking habit and the small number of patients. If this number had been higher, this percentage would have maintained statistical significance as an independent risk factor for CD. Thus, these results need to be confirmed by new studies including a greater number of cases.
In this study, we also found a percentage of family association in IBD similar to that in other series in our environment, as well as a higher morbidity in CD compared with UC that is based on the increased requirements these patients have regarding immunosuppressive and biologic therapies and/or surgical procedures. Nevertheless, mortality among our patients during follow-up has been practically nil -with the exception of the complication pointed out in the results (11)- which translates into an excellent lifelong prognosis for these patients.
In conclusion, with this study we tried to communicate our results and experience regarding IBD in our sanitary area, highlighting the uniformity of distribution of the disease in connection with types and sex, and with incidence rates similar to those in other more urban, more economically developed regions. Our study, we also show an incidence of UC below that of CD in spite of the rural character of our area. Therefore, the North-South gradient is not really so important, which has deeply relevant epidemiological implications; since it makes mandatory a restatement of geographical situation as an epidemiological factor, despite it is accepted by many authors.
REFERENCES
1. Evans JG, Acheson ED. An epidemiological study of ulcerative colitis and regional enteritis in the Oxford area. Gut 1965; 6: 311-24. [ Links ]
2. Price Ashley B. Overlap in the spectrum of non-specific inflammatory bowel disease "Colitis Indeterminate". J Clinic Pathol 1978; 31: 567-77. [ Links ]
3. Cella Lanau J, López Zaborras J, Gomollón García F, Sáinz Samitier R. Enfermedad inflamatoria en Aragón: un diagnóstico cada vez más frecuente. Rev Esp Enferm Dig 1995; 87: 363-7. [ Links ]
4. Brullet E, Bonfill X, Urrutia G, Ruiz Ochoa V, Cueto M, Clofent J, et al. Estudio epidemiológico sobre la incidencia de enfermedad inflamatoria intestinal en cuatro áreas españolas. Med Clin (Barc) 1998; 110: 651-6. [ Links ]
5. Maté Jiménez J, Pajares García JM. Epidemiología de la Enfermedad Inflamatoria Intestinal: distribución geográfica y factores ambientales. Rev Esp Enferm Dig 1994; 86: 533-9. [ Links ]
6. Sonnenberg A, Mc Carty D, Jacobsen S. Geographic variation of inflammatory bowel disease within the United States. Gastroenterology 1991; 100: 143-9. [ Links ]
7. Sonnenberg A. Occupational distribution of inflammatory bowel disease among German employees. Gut 1990; 31: 1037-42. [ Links ]
8. Truelove SC, Witts C. Cortisone in ulcerative colitis. Br Med J 1955; 2: 1041-8. [ Links ]
9. Lennard-Jones JE. Regional enteritis (Crohn's disease): definition and diagnosis. Skandia International Symposia. Regional Enteritis. Estocolmo: Nordiska Bolchandelns Forlag, 1970. p. 108-9. [ Links ]
10. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol 1989; 24: 2-4. [ Links ]
11. Garrido Serrano A, Pérez Martín F, Guerrero Igea FJ, Galbarro Muñoz J, Palomo S. Mononucleosis infecciosa mortal durante el tratamiento con azatioprina en la enfermedad de Crohn. Gastroenterol Hepatol 2000; 23: 7-8. [ Links ]
12. Pajares JM, Gisbert JP. Epidemiología de la enfermedad inflamatoria intestinal en España. Una revisión sistemática. Rev Esp Enferm Dig 2001; 93: 9-14. [ Links ]
13. Ruiz Ochoa V. Estudio epidemiológico de la Enfermedad de Crohn en Galicia en el periodo 1976 a 1983. Rev Esp Enferm Dig 1984; 66: 273-9. [ Links ]
14. Pajares García JM, Rodríguez Muñoz S, Maté Jiménez J. Prevalencia de la Enfermedad de Crohn en la zona central de España. Estudio epidemiológico colaborativo de la asociación Castellana de Aparato Digestivo. Rev Esp Enferm Dig 1987; 71: 313-7. [ Links ]
15. Martínez Salmerón JF, Rodrigo Moreno M, De Teresa J, Nogueras F, García Montero M, de Sola C et al. Epidemiology of inflammatory bowel disease in the province of Granada, Spain; a retrospective study from 1979 1988. Gut 1993; 34: 1207-9. [ Links ]
16. Hinojosa J, Princo J, Lledó S, López A, Roig JV, Fernández J. Incidencia de la Enfermedad Inflamatoria Intestinal en Sagunto. Rev Esp Enferm Dig 1990; 78: 283-7. [ Links ]
17. Brullet E, Bonfil X, Urrutia G, Ruiz Ochoa V, Cueto M, Clofent J, et al. Estudio epidemiológico sobre la incidencia de la enfermedad inflamatoria intestinal en cuatro áreas españolas. Med Clin (Barc) 1998; 110: 651-6. [ Links ]
18. Saro Gismera C, Lacort Fernández M, Arguelles Fernández G, Antón Magarzo J, Navascues CA, García López R, et al. Epidemiología de la enfermedad inflamatoria intestinal crónica en Gijón. Asturias. Gastroenterol Heopatol 2001; 24: 228-35. [ Links ]
19. Pozzati L, Cabanillas A. Estudio hospitalario de incidencia de la enfermedad inflamatoria intestinal en el Área Sanitaria de Mérida. Gastroenterol Hepatol 2002; 9: 541-4. [ Links ]
20. Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, et al. Incidence of inflammatory bowel disease across Europe: Is there a difference between north and south? Results of the European collaborative study on inflammatory bowel disease (EC-IBD). Gut 1996; 39: 690-7. [ Links ]
21. Solá Lamoglia R, García-Pugues AM, Monés Xiol J, Badosa Gallart C, Badosa Gallart J, Casellas F et al. Enfermedad inflamatoria intestinal crónica en Cataluña (Barcelona y Gerona). Rev Esp Enferm Dig 1992; 81: 7-14. [ Links ]
22. Brullet E, Rue M, Monserrat A, Gil M, Malet A, Mas P, et al. Estudio epidemiológico descriptivo de la colitis ulcerosa en un hospital comunitario (1985-1989). Med Clin (Barc) 1991; 97: 45-9. [ Links ]
23. Maté Jiménez J, Muñoz S, Vicent D, Pajares JM. Incidence and prevalence of ulcerative colitis and Crohn's disease in urban and rural areas of Spain from 1981 to 1988. J Clin Gastroenterol 1994; 18: 27-31. [ Links ]
24. Rhodes J, Thomas GAO. Smoking: Good or bad for Crohn's disease? Gastroenterology 1994; 106: 807-10. [ Links ]
25. Spanish Epidemiological and Economic Study Group on Crohn's Disease. Epidemiological and clinical features of Spanish patients. Eur J Gastroenterol Hepatol 1999; 11: 1121-7. [ Links ]
26. Lindberg F, Varnesot G, Huitfeld B. Smoking in Crohn's disease: effect on localisation and clinical course. Gut 1992; 33: 779-82. [ Links ]
27. Cosner J, Carbonell F, Blaugerie L, Quintrec Y, Gendre GP. Effects of cigarette smoking on the long term course of Crohn's disease. Gastroenterology 1996; 110: 424-31. [ Links ]
28. Harries AD, Baird A, Rhodes J. Non-smoking: a feature of ulcerative colitis. Br Med J 1982; 284: 706. [ Links ]
29. Calkins BM. A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci 1989; 34: 1841-54. [ Links ]
30. Rutgeerts P, D'Haens G, Hiele M, Geboes K, Vantrappen G. Appendicectomy protects against ulcerative colitis. Gastroenterology 1994; 106: 1251-3. [ Links ]
31. Russel MG, Dorant E, Brummer RJM, Van de Kruijis M, Murin J, Bergers JM, et al. Appendicectomy and the risk of developing ulcerative colitis or Crohn's disease: results of a large case-control study. Gastroenterology 1997; 113: 377-82. [ Links ]
32. Gent AE, Hellier DM, Grace RH, Swarbrick ET, Coggon D. Inflammatory bowel disease and domestic hygiene in infancy. Lancet 1994; 343: 766-7. [ Links ] ]]>