Incidence of inflammatory bowel disease in two medical centers in Uruguay, during the period 2007-2011

Beatriz Iade,¹ Gaby Beatriz Buenavida,² Andrea Casañas³

¹ Gastroenterology Clinic, Hospital de Clínicas – Faculty of Medicine UDELAR.
² Centro de Asistencia del Sindicato Médico del Uruguay (CASMU).
³ Sociedad Médica Quirúrgica de Salto/Centro de Asistencia Médica (CAM).

Acta Gastroenterol Latinoam 2018;48(4):263-270
Recibido: 27/09/2017 / Aprobado: 02/07/2018 / Publicado en www.actagastro.org el 17/12/2018

Summary

Incidence of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), seems to be increasing, but data about IBD epidemiology in Latin America remains scarce. This study aimed to determine the incidence of IBD in Uruguay for the period 2007-2011. A retrospective, registry-based study was performed, with data between January 2007 and December 2011 of two medi­cal centers from Uruguay – Montevideo (220,687 members) and Salto (51,235 members). Patients were excluded if the diagnosis occurred outside this period, if it was not confir­med after one year of follow-up or if presenting unclassified IBD. Poisson regression was used to evaluate differences in incidence rates by sex and age at diagnosis. The U Mann Whitney test and Fisher’s exact test were used to compare age at diagnosis and sex distribution between centers and UC vs. CD patients. 67 new IBD cases were identified during 2007-2011. The adjusted IBD incidence was 5.22 /105 person-years with a UC/CD ratio of 7.7. Overall, women presented higher incidence of IBD (3.54 /105 person-years, p-value = 0.028). Incidence was also higher for patients aged 20-44 years (9.12 /105 person-years). Among IBD pa­tients, 65.7% were female, mean age at diagnosis was 37.2 ± 17.25 years and 10.4% had family history of IBD. There were no significant differences between centers regarding sex and age at diagnosis of IBD patients. Despite industrializa­tion, Uruguay continues to be a region of low IBD incidence, with UC being more common than CD. This trend is in line with epidemiological data from other Latin American countries.

Key words. Inflammatory bowel disease, ulcerative colitis, Crohn’s disease, incidence.

Incidencia de la enfermedad inflamatoria intestinal en dos centros médicos en Uruguay durante el período 2007-2011

Resumen

La incidencia de la enfermedad inflamatoria intesti­nal (EII), incluyendo la enfermedad de Crohn (EC) y la colitis ulcerosa (CU), sigue aumentando, pero los datos epidemiológicos de América Latina son escasos. Se reali­zó un estudio retrospectivo (registro de enero de 2007 a diciembre de 2011 de dos centros médicos de Uruguay) para determinar la incidencia de EII en Uruguay entre 2007 y 2011. Los pacientes fueron excluidos si el diag­ nóstico se produjo fuera de este período; si no, se confir­mó después de un año de seguimiento o si presentaban EII no clasificada. Una regresión de Poisson para eva­luar las diferencias en las tasas de incidencia por sexo y edad, al momento del diagnóstico, ha revelado que las mujeres presentaron mayor incidencia de EII (3,54/105 años-persona, p = 0,028). La incidencia también fue ma­yor para los pacientes de 20-44 años de edad (9,12/105 años-persona). Se utilizaron pruebas de Mann Whitney y exacta de Fisher para comparar la edad al diagnóstico y la distribución de sexos entre los centros. No hubo di­ferencias significativas entre los centros. Se identificaron 67 nuevos casos de EII. La incidencia ajustada de EII fue de 5,22/105 años-persona con una proporción CU/EC de 7,7. Entre los pacientes con EII, el 65,7% eran mujeres, la edad promedio al momento del diagnóstico fue de 37,2 ± 17,25 años y el 10,4% tenía antecedentes familiares de EII. Uruguay sigue siendo una región de baja incidencia de EII, y la CU es más frecuente que la EC, en concor­dancia con los datos latinoamericanos.

Palabras claves. Enfermedad inflamatoria intestinal, coli­tis ulcerosa, enfermedad de Crohn, incidencia.

Abbreviations
IBD: inflammatory bowel diseases.
CD: Crohn’s disease.
UC: ulcerative colitis.
RNEII: the National IBD Registry.
UDELAR: la Universidad de la República – Uruguay.
CASMU: Centro de Asistencia del Sindicato Médico del Uruguay.

Inflammatory bowel diseases (IBD) comprise mainly Crohn’s disease (CD) and ulcerative colitis (UC), for which treatment remains challenging.^{1, 2} With episodes of relapse and remission, it is one of the most severe gastrointestinal disorders, with relevant health and economic burden.^3-5

IBD are characterized by chronic inflammation of the digestive mucosa, resulting from the interaction between genetic and environmental factors that triggers an exces­sive mucosal immune response.^6-8 A number of environ­mental risk factors have been explored, including smok­ing, diet, breastfeeding, antibiotics, but the association of some of these factors with IBD is still inconsistent.⁶ Epi­demiological studies may provide relevant information about IBD, its risk factors and clinical management.^{7, 9}

Globally, the prevalence of IBD is estimated to be around 396 per 10⁵ people.¹⁰ The incidence of inflamma­tory bowel disease (IBD) has been increasing in several world regions, namely in developing countries.⁹ Since its first description, IBD was more relevant in developed countries from North America and Europe, but the inci­dence and prevalence of CD and UC are now increasing in other geographical areas with previous low incidence, such as South and Eastern Europe and Asia.^9-13 This trend in reported incidence and prevalence rates may be explained partially by the advances in disease diagnosis, but continued environmental changes may also impact IBD onset.⁴

Data about IBD epidemiology in Latin America is scarce and mostly based on hospital and retrospective re­cords.^14-17 A study conducted by Linares et al. reported incidences of 2.2 per 10⁵ inhabitants in Argentina and 1.2 per 10⁵ in Panama, during 1987-1993 period.¹⁸ Oth­er recent studies in Brazil, Puerto Rico and Colombia have shown an increasing trend, similar to the evolution in high incidence areas.^{16, 17, 19-21}

The National IBD Registry (RNEII, for its Spanish acronym) was created in 2006 and in 2008 it was de­clared of public interest by the Ministry of Health. This order applies to all medical institutions in Uruguay, whether public or private, enabling the collection of data from endoscopy files, pathology, pharmacy and clinical records that are required to identify new cases.²²

Based on this registry, a (crude) incidence rate of 2.63 per 10⁵ inhabitants/year was observed for the period 2007-2008,²² a lower rate in comparison with Puerto Rico, Colombia and Brazil.^{14, 18}

This study aimed to determine the incidence of IBD (CD and UC) in two areas of Uruguay (Salto and Mon­tevideo) for the period 2007-2011, and to compare the results with previous ones from Uruguay and those from other geographical regions.

Methods

A retrospective, registry-based study was performed, with data collection between January 1st 2007 and De­cember 31^st 2011 at two medical centers from Montevi­deo and Salto. Written informed consent was given by all study participants prior to inclusion. The study protocol was approved by the Ethics Committee of the Faculty of Medicine – UDELAR (La Universidad de la República – Uruguay).

Population

Uruguay is a country in South America with 176,215 km2 and a total population of 3.3 million people, of whom 1.8 million live in the metropolitan area of its capital and largest city, Montevideo. Salto region is one department of Uruguay and Salto is the third largest city of Uruguay, with 124.878 inhabitants.23 The majority of Uruguayans have Spanish and Italian origins, followed by French, German and other European origins; 87.4% of the population are Caucasian, 9.1% are Afro-descendants and 2.9% are aborigines. Male/female ratio is 0.93.²⁴

Two medical centers were selected among those with complete information. The Montevideo center (CAS­MU – Centro de Asistencia del Sindicato Médico del Uruguay) is a private medical center with an average of 220,687 members. In Salto, IBD cases were identified among 51.365 patients followed up in a private medi­cal center (CAM – Sociedad Médica Quirúrgica de Salto/ Centro de Asistencia Médica), during the study period. Both centers cover approximately 8% of the population in Uruguay.

Inclusion and exclusion criteria

The study included both outpatients and inpatients, with a new case of IBD (UC or CD) diagnosed between January 1^st, 2007 and December 31^st 2011, that received surgery or not and irrespective of treatment status. Pa­tients were excluded from the study if the disease had started before or after this date, if the diagnosis was not confirmed after one year or if the colitis was unclassified.

The active search included not only endoscopy, pa­thology registries and medical records, but also admin­istrative and pharmacy databases. When a potential case was identified, a medical appointment was scheduled with the patient to obtain the patient’s informed con­sent and fill in a RNEII form that includes data about IBD type, gender, age and place of residence at onset. The case was confirmed according to standard protocol after review by the principal investigators and a one year of follow up.

Statistical methods

The IBD incidence rates and specific incidence rates for UC and CD were calculated as the number of new cases for 100,000 patients-year. Demographic data of the year 2007, retrieved from the Uruguay National Institute of Statistics was assumed for the standardization of inci­dence rates.²⁵ Differences in incidence rates by sex and age at diagnosis (0–19; 20–44; 45 years or older) were evaluated using Poisson regression models. The U Mann Whitney test was used to compare age at diagnosis be­tween CASMU-Montevideo vs. CAM-Salto and UC vs. CD patients. Fisher’s exact test was used to compare sex distribution between CASMU-Montevideo vs. CAM-Salto and UC vs. CD patients.

Data were analyzed using the Statistical Package for the Social Sciences (version 21.0, SPSS, Chicago, IL) and the statistical package R (version 3.1.2, 2014). Signifi­cance level was set at 0.05.

This study was conducted within the RNEII frame­work. The RNEII was approved by the School of Medi­cine’s Ethics Committee and its public interest was recog­nized by the Uruguay Health Ministry in 2008.

Results

In the two centers, a total of 67 new IBD cases were identified during the period between 2007 and 2011. The crude incidence rate of IBD during the period 2007- 2011 was 4.94 per 10⁵ person-years, 4.35 for UC and 0.59 for CD. After adjustment, the IBD incidence was 5.22 per 10⁵ person-years, 4.62 for UC and 0.60 for CD, with a UC/ CD ratio of 7.7. For each center, the crude incidence rates of IBD were 4.98 per 10⁵ person-years in CASMU-Mon­tevideo, and 4.72 per 10⁵ person-years in CAM-Salto (Ta­ble 1). Regarding, the incidence rates of IBD according to sex (Table 2), the crude incidence rates were 3.54 and 6.22 per 10⁵ person-years, and the adjusted incidence rates were 3.80 and 6.59 per 105 person-years, for male and female sex, respectively. Overall, women presented significantly higher incidence rate of IBD (p = 0.028).

The incidence rates of IBD for patients aged ≤19 years (3.45 per 105 person-years) and for patients aged ≥ _45 years (2.92 per 10⁵ person-years) were significantly lower (p = 0.005 and p < 0.001, respectively) than for patients aged 20- 44 years (9.12 per 10⁵ person-years).

In CASMU-Montevideo, the crude incidence rate by age group was 4.04 per 105 person-years (< 19 years), 9.15 per 10⁵ person-years (for 20-44 years), and 2.89 per 105 person-years (> 45 years). In CAM-Salto, the crude incidence rate by age group was 1.50 (< 19 years), 9.00 (for 20-44 years), and 3.04 (> 45 years) per 10⁵ person-years (Table 2).

Table 3 presents the main characteristics of the IBD pa­tients. No significant differences were found between UC and CD patients regarding sex (p = 0.711) and age at diag­nosis (p = 0.568). The location in the UC was proctitis in 17 patients, left-sided in 20, and extensive in 22 of which 3 required surgery (colectomy). The location on the CD was ileal in 5, colon in 3; there were 0 cases with perineal involve­ment and 1 required surgery during the study period.

There were no statistically significant differences bet­ween centers regarding sex (p = 0.705) and age at diagnosis (p = 0.641) of IBD patients. In CASMU-Montevideo, the location in the UC was proctitis in 14 patients, left-hand side in 16, and extensive in 20 of which 3 required surgery (colectomy). Regarding CD, there were no cases with pe­rineal involvement and none required surgery during the study period.

In CAM-Salto, the location in the UC was proctitis in 3 patients, left-hand side in 4, and extensive in 2; no patient required surgery. There were no CD cases with perineal involvement. One CD patient required surgery during the study period.

Table 1. Incidence rate of IBD in Montevideo and Salto, 2007-2011.

Table 2. Incidence rates of IBD by age and sex, 2007-2011

Table 3. Characteristics of IBD patients in Montevideo and Salto, 2007-2011.

Discussion

The observed IBD incidence was in accordance with a previous RNEII study and confirms Uruguay as one region of low IBD incidence.²² UC was more common than CD, as it has been described in other low incidence countries, including Brazil, Puerto Rico, Colombia, and Chile-^{14, 19, 26-28} In fact, the highest frequency of UC vs. CD is in line with the worldwide epidemiological data which shows that the increase of IBD follows a pattern where the increase of the UC precedes 15 to 20 years the increase of CD.^{10, 26}

In North America and Europe, there has been an increase of IBD incidence, being estimated that the an­nual incidence of CD is higher in North America (20.2 /10⁵ person-years), whereas the annual incidence of UC is higher in Europe (24.3 /10⁵ person-years).^{4, 29} In our study, we have observed cumulative adjusted incidence of 5.22 /105 person-years. This lower IBD incidences are in line with the results from other Latin American coun­tries, that reported incidences of UC ranging from 0.7 up to 6.8 per 10⁵ people, between 1986 and 2008.²⁶

In Brazil^{16, 21} and Mexico,³⁰ the incidence of UC has been increasing. Furthermore, CD seems also to be in­creasing in Brazil.^{16, 21} The situation in Brazil is different from 1993 data from Argentina¹⁸ and from a previous study in Uruguay,²² where the reported incidence of IBD has been lower. Buenavida et al. have reported an adjust­ed incidence rate of 4.01 per 10⁵ people for IBD during the biennial 2007 and 2008, considering 5 geographical areas in Uruguay.²² The higher incidence observed in 2011 in Salto could be related with the few cases identi­fied in the whole period. The incidence in Montevideo did not show remarkable differences during this period.

Similar to what was reported by Buenavida et al., IBD was more frequent among women than among men.^{10, 22}

The same trend was observed in data from Colombia,¹⁴ Brazil^{16, 27} and Chile²⁸ and for UC patients in Puerto Rico.¹⁹

Age at diagnosis were similar between centers and somewhat lower than what was reported by Buenavida et al. (40.7 years), but within the range reported in other Latin American countries.²² For instance, a single cen­ter study in Brazil has reported a mean age at diagnosis of 35.2 years, while in Colombia the mean age was 40 years.^{14, 31} The two centres provided age data grouped into different classes. For this reason, data was reclassified to en­able comparisons, which could have partially explained why the group of highest incidences were aged between 20 and 44 years. Nevertheless, Yepes Barreto et al. also observed that 49.9% of IBD patients were aged 20-44 years.¹⁴ Of notice, this study included pediatric patients (aged ≥ 7years) and the decrease in age at diagnosis seems to be aligned with the increase incidence of pediatric IBD worldwide.³²

It is not expected that the low IBD incidence may have resulted from a detection bias, since the included centers were well equipped for the diagnosis and multiple data sources were used. The small number of cases, espe­cially in Salto, may have affected the accuracy of the results, although the sample characteristics are similar to those de­scribed by others.²² The included centers are representative of the two regions, and no selection bias is expected since 94% of the population in Uruguay has access to health care. Furthermore, adjusted and crude incidence rates were simi­lar, underlining that population from these two centers had a similar age and sex distribution.³³

With growing industrialization, it is likely that, over the next years, there will be an increase of IBD in some areas of Central and South America, including Uru­guay.²⁶ In fact, IBD seems to occur most often in urban areas than in rural areas. The industrialization and ur­banization of societies are associated with changes in mi­crobial exposure, sanitation, occupations, diet, lifestyle, medications, and exposure to pollution, which have been implicated as possible risk factors environmental IBD.⁶ Additional follow-up of IBD epidemiology is required in Uruguay, to follow-up the impact of industrialization. This study provides insight about the evolution of IBD epidemiology in two main regions in Uruguay, with re­sults confirming this country as a low incidence region. In the future, the analysis of data from RNEII could pro­vide more evidence about the time trends of IBD and etiology of IBD, supporting the development of health care resources.

Acknowledgements. The authors wish to thank to Ale­jandro Noria (Quantitative Methods Department – Faculty of Medicine UDELAR) for the statistical analysis and as­sistance, Sergio Dotta (responsible for medical archive) at CASMU and to the staff from medical archive at CAM, Gustavo Burroso et al. (pharmacy services – CASMU), Ceci­lia Vazquez, Sabrina Villarroya, Adrian Canavesi, Marlene Faust for the data collection at CASMU, the collaboration of José Pedro Ibargoyen and Prof. Carlos Ketzoian (research coordinator at Hospital de Clínicas). The authors wish to thank for the acknowledgement of the medical writing assis­tance Milene Fernandes (Eurotrials, Scientific Consultants) and the financial support of AbbVie Inc. (Argentina).

Financial support. AbbVie Inc. (Argentina) support­ed medical writing services through Eurotrials, Scientific Consultants. AbbVie was not involved in the development of content of the manuscript and the authors maintained a complete control over the content. The authors had no other additional financial support.

Institutional review board statement. The study pro­tocol was approved by the Institutional Review Board (Eth­ics Committee of the Faculty of Medicine UDELAR, Exp. Nº 071140-000236-06).

Informed consent statement. Written informed con­sent was given by all participants of the study prior to inclu­sion. The study protocol was approved by the Institutional Review Board (Ethics Committee of the Faculty of Medicine UDELAR, Exp. Nº 071140-000236-06).

Biostatistics statement. The statistical methods of this study were reviewed by Alejandro Noria, from the Quantita­tive Methods Department – Faculty of Medicine UDELAR, Montevideo, Uruguay. Statistical methods in this study are adequate and appropriate for the objectives and results studies.

Conflict-of-Interest statement. BI has received speaker fees from AbbVie and project grants from AbbVie and Janssen. The remaining authors have no conflicts of interest to report.

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Correspondencia: Beatriz Iade
Gastroenterology Clinic, Hospital de Clínicas – Faculty of Medicine UDELAR. Av. Italia SN. Montevideo, Uruguay
Tel.: (5982) 4808472/ (5982) 9081818 / Tel. Cel.: (5989) 962 1367
Correo electrónico: beatriz.iade@gmail.com

Acta Gastroenterol Latinoam 2018;48(3): 154-158