CROHNS-00936; No of Pages 7 Journal of Crohn's and Colitis (2014) xx, xxx–xxx
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The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry J. Martín-de-Carpi a,⁎, A. Rodríguez b , E. Ramos c , S. Jiménez d , M.J. Martínez-Gómez e , E. Medina f , V.M. Navas-López g , On behalf of the SPIRIT-IBD Working Group of SEGHNP (Sociedad Española de Gastroenterología Hepatología Nutrición Pediátrica) a
Unidad para el Cuidado Integral de la Enfermedad Inflamatoria Intestinal Pediátrica, Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Déu, Barcelona, Spain b Hospital Virgen del Rocío, Sevilla, Spain c Hospital La Paz, Madrid, Spain d Hospital Central de Asturias, Oviedo, Spain e Hospital Niño Jesús, Madrid, Spain f Hospital Doce de Octubre, Madrid, Spain g Hospital Materno-Infantil, Málaga, Spain
Received 4 July 2013; received in revised form 27 December 2013; accepted 5 January 2014 KEYWORDS Pediatric inflammatory bowel disease; Crohn's disease; Ulcerative colitis; IBD unclassified; Incidence; SPIRIT registry; EXPERIENCE registry
Abstract Objectives: A growing incidence of pediatric IBD (PIBD) in southern Europe has been recently reported. The SPIRIT registry (1996–2009) confirmed these tendencies in Spain. Our aim is to obtain data from 1985 to 1995 and describe the complete picture of PIBD presentation changes in Spain in the last 25 years. Methods: A retrospective survey of incident PIBD in the period 1985–1995 was performed. Patients' data were obtained from the hospitals' databases and compared with the published data from the 1996 to 2009 period. Seventy-eight IBD reference centers took part in this survey. Results: Data from 495 patients were obtained: 278 CD (56.2%), 198 UC (40%), and 19 IBDU (3.8%); 51.7% were female, with higher predominance both in UC (58.6%) and in IBDU (57.9%), but not in CD (46.4%). Median (IQR) age at diagnosis was 12.9 (10.0–15.7) years, with significant differences among
⁎ Corresponding author at: Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Déu Paseo Sant Joan de Déu, 2, 08950 Barcelona, Spain. Tel.: + 34 93 600 61 03; fax: + 34 93 203 39 59. E-mail address: [email protected] (J. Martín-de-Carpi). 1873-9946/$ - see front matter © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.crohns.2014.01.005
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
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J. Martín-de-Carpi et al. IBD subtypes: CD: 13.1 (10.8–16.0) vs UC: 12.4 (9.4–15.1) vs IBDU: 7.5 (3.0–13.0) (p ≤ 0.001). These results are significantly different to the ones in the SPIRIT registry, with a higher proportion of IBDU, younger age and male predominance. The data from both periods taken together give a complete picture of a 25–year period. An annual increase of incident patients was observed, with a ten-fold increase over this period. Conclusion: These data extend the epidemiological trends to a full 25–year period (1985–2009). PIBD incidence in Spain has experienced a sixteen-fold increase. The IBD subtype, localization of the affected segment, age- and sex distribution observed are in accordance with our previously published ones of 1996–2009. © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction A growing incidence of pediatric inflammatory bowel disease (PIBD; diagnosed below 18 years of age) worldwide has been reported.1–6 Although the highest incidence figures have been found in the northern parts of North America7 and in Scandinavia,8 recent studies have also showed this trend in southern Europe and other Mediterranean countries.9 The exhaustive systematic review by Benchimol et al. on international epidemiological trends of pediatric IBD10 concludes a globally rising trend of pediatric IBD both in developed and developing countries, although most of these countries lacked accurate estimates. The recently published SPIRIT registry by the IBD working group of the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition) offered for the first time robust data on the increase of PIBD incidence in Spain in the period 1996–2009, and constitutes the most extensive nationwide incidence study from a Mediterranean country.11 According to its results, overall IBD incidence increased from 0.97/105 inhabitants under 18 years in 1996 (95% CI 0.8–1.2) to 2.8 in 2009 (95% CI 2.4–3.2) (p b 0.001), Crohn's disease (CD) from 0.53 (95% CI 0.3–0.7) to 1.7 (95% CI 1.45–2.03) (p b 0.001) and ulcerative colitis (UC) from 0.39 (95% CI 0.27–0.55) to 0.88 (95% CI 0.69–1.1) (p b 0.001). Both overall IBD and CD incidence at the end of the studied period were found to be three fold higher than baseline, whereas UC experienced a two-fold increase in the same period.
2. Objectives Our aim is to extend our epidemiological data of PIBD in Spain with information about children and adolescents diagnosed between January 1985 and December 1995 and to compare these data with those previously obtained from the period 1996–2009. This new study contributes to the complete description of changes in PIBD presentation in Spain in the last 25 years.
3. Material and methods This is a collaborative, retrospective, multicenter study called EXPERIENCE (EXtended PEdiatric Registry of IBD Epidemiological Nationwide ChangEs). The study was planned and performed inside the IBD working group of the
Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP). A retrospective survey of incident PIBD (below 18 years at diagnosis) in the “early period” of 1985–1995 was performed. IBD diagnosis was made according to standard clinical, endoscopic, histological, and radiological criteria.12,13 Patients' data at diagnosis were obtained from the different hospitals' own databases. Both pediatric and adult IBD Units were contacted in order to avoid missed PIBD patients being followed from the beginning in adult services and to obtain the most reliable data. The same seventy-eight reference IBD centers that had previously participated in the SPIRIT registry, both pediatric and general, took part in this new survey (see Appendix A). All the 35 referral PIBD Units from tertiary centers in Spain participated, plus 31 small pediatric Gastroenterology Units in regional hospitals (representing 90% of these hospitals in which PIBD patients can be followed and that usually work in a shared care network with referral IBD Units), and lastly 12 adult hospitals without pediatric services. Distribution of all these centers, spread all over the nation, guarantees that the data collected are representative of the whole country and included mostly all pediatric patients with IBD diagnosed throughout this 25-year period. Every patient was identified in the registry with three letters (initial letter of the name and the two surnames used in Spain) and the date of birth indicated as ddmmyy. Patient's epidemiological and clinical data at diagnosis were obtained: sex, age, type (CD, UC, IBD type unclassified — IBDU) and location of the disease according to the Montreal classification.14 We decided not to include data from possible upper involvement or perianal involvement in CD (L4 and p variants of the Montreal classification) as we considered these could be not very reliable due to the retrospective nature of the study and the period reviewed starting before the Porto Criteria publication, which emphasized the need for upper GI endoscopy as well as colonoscopy at PIBD diagnosis.12 We assumed many patients diagnosed before 2005 would only have had an upper endoscopy with significant upper GI symptoms present. These data were compared to our previously published data of incidence changes from the “later period” of the SPIRIT registry (1996–2009).11
3.1. Ethics The study was approved by the Ethics Committee of the first author's center, as representative of the rest of the hospitals.
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
The complete picture of changing pediatric inflammatory bowel disease incidence in Spain
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3.2. Statistical analysis A chi-square test was applied for category data; t-Student, U-Mann Whitney and 1-way analysis of variance (ANOVA) were performed to compare continuous variables. Significance was set at p b 0.05. SPSS v. 19.0 (Chicago, IL) was used for statistical analysis.
4. Results From 1985 to 1995, 495 new patients were diagnosed: 278 CD (56.2%), 198 UC (40.0%) and 19 IBDU (3.8%). Due to a lower proportion of IBDU, this disease distribution in this “early period” was significantly different to the data obtained from 2107 patients in the “later period” (1996–2009) which were 55.3%, 37.4%, and 7.3% respectively (p b 0.01). The majority of our patients were Caucasian (98.2%), 4 were of gypsy ethnicity (0.8%), and 1% were immigrants born abroad (mainly form northern Africa). A slightly higher proportion of immigrants (4.6%) were observed in our SPIRIT registry, in accordance with the migration changes that took place at the beginning of the XXI century. Regarding sex distribution, 51.7% of PIBD patients in the early period were female, with a higher female predominance in the UC (58.6%) and IBDU groups (57.9%), but this proportion changed for CD, with 53.6% male. A general male predominance had been observed in the later period (56.4%), more striking for CD (59.3%) than UC (52.8%) and IBDU (53.2%) (p = 0.012). Therefore, sex distribution between both periods was also significantly different (p b 0.001). Global median (IQR) age at diagnosis was 12.9 years (10.0– 15.7) in the early period (Fig. 1). Median (IQR) age for CD was 13.1 years (10.8–16.0), for UC 12.4 (9.4–15.1) and for IBDU 7.5 (3.0–13.0). We have observed significant differences between CD and IBDU (p b 0.001), between CD and UC (p b 0.001), and between UC and IBDU (p b 0.001). By comparison, the global median (IQR) age at diagnosis in the later period was significantly different: 12.3 years (9.7–14.6) (p b 0.028). Comparisons between both periods regarding disease and sex distribution, and age at diagnoses are shown in Table 1. Distribution of the diseases according to age at diagnosis in the early period showed a small proportion diagnosed below 5 years of age and a similar proportion of patients diagnosed in the second (6–12) and in the third (13–17) age groups (43.2% and 48.0% respectively). We have observed a predominance of UC and IBDU in the first 5 years of life (48.8% and 20.9%), whereas in groups 2 and 3, CD was the most frequent disease (54.7% and 62.2% respectively). The total amount of colonic-only IBD in group 1 (UC + IBDU + L2 group of CD) was 81.3%, similar to the results in the SPIRIT registry (83%). There was a relationship between IBDU diagnosis and younger age at presentation (20.9% in group 1, 2.3% in group 2 and 2.1% in group 3) (p b 0.001). A similar pattern of disease distribution had been communicated in our previous publication regarding the period 1996–2009. Disease location phenotype according to Montreal classification in the early period was the following: - Crohn's disease: L1 (isolated ileal or ileo-cecal involvement) 27.1%, L2 (isolated colonic involvement) 16.8%, and L3 (ileo-colonic disease) 56.1%.
Figure 1 Age distribution of the diagnosed cases in the 1985–1995 period.
- Ulcerative colitis: E1 (procto-sigmoiditis) 9.1%, E2 (leftsided colitis) 31.3%, and E3 (extensive colitis) 59.6%. These results are not significantly different to the data obtained from the later period, both for CD (L1: 26.5%, L2: 16.6%, L3: 56.9%) and for UC (E1: 10.3%, E2: 26%, E3 63.7%). The important increase of the diagnosed cases per year we reported in the SPIRIT registry has also been found in this earlier period; in 1985, 22 new cases of IBD in children below 18 years were recognized, whereas in 1995, 88 new cases were diagnosed. This represents a 4-fold increase. This increase was observed both for CD (11 cases in 1985, 49 in 1995), for UC (10 cases in 1985, 34 in 1995), and also for IBDU (1 case/year for the first years of the period, 5 cases in 1995). Finally, these new data obtained from 1985 to 1995 were added to those from the later period showing a complete picture of the changing pattern of PIBD in Spain for a 25-year period (the EXPERIENCE registry). In total, as a result of the two registries we obtained data from 2602 incident PIBD Table 1 Comparisons between both periods regarding disease and sex distribution, and age at diagnosis. 1985–1995 Disease distribution CD UC IBDU Sex distribution Male Female Median age (years) at diagnosis (IQR)
1996–2009
p b 0.018
278 (56.2%) 198 (40.0%) 19 (3.8%)
1165 (55.3%) 788 (37.4%) 154 (7.3%)
b 0.001 49.3% 56.4% 51.7% 43.6% 12.9 (10–15.7) 12.4 (9.7–14.6) b 0.028
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
J. Martín-de-Carpi et al.
Group 2 (6–12 years)
(62.4%) (35.0%) (2.6%) (44.5%) 722 405 30 1157 652 (55.1%) 451 (38.1%) 81 (6.8%) 1184 (45.5%) (26.4%) (49.8%) (23.8%) (10%) 69 130 62 261 (62%) (35%) (3%) (43.7%) 574 320 25 919 (55.2%) (37%) (7.8%) (46.0%) 535 359 76 970 56 (25.7%) 109 (50%) 53 (24.3%) 218 (10.3%) 148 (62.2%) 85 (35.7%) 5 (2.1%) 238 (48.1%) 117 (54.7%) 92 (43.0%) 5 (2.3%) 214 (43.2%) 13 (30.2%) 21 (48.8%) 9 (20.9%) 43 (8.7%) CD (% within age group) UC (% within age group) IBDU (% within age group) Total
Group 2 (6–12 years) Group 1 (0–5 years) Group 1 (0–5 years) Group 1 (0–5 years)
Group 3 (13–17 years)
SPIRIT (1996–2009)
The recently published SPIRIT registry constituted the first attempt to describe nationwide recent incidence of PIBD in Spain and its evolution over a long period of time.11. The investigators decided to focus in the period from which incidence data could be obtained (1996–2009). In Spain it is not feasible to get reliable pediatric age-stratified epidemiological data before 1996, as the results of the source that provides official population figures of all municipalities standardized at 1st January each year and classified by age (the municipal register),15 are available only from that year. The results of that registry showed a three-fold increase of PIBD for the studied period (1996–2009), with a three-fold increase in CD diagnosis and a parallel two-fold increase of UC. Once this first robust data were published, we decided to extend the analysis to the early years of a 25-year period (1985–1995) in order to obtain a complete figure of PIBD evolution (the EXPERIENCE registry). We have obtained data from 495 new incident patients diagnosed between 1985 and 1995. We have observed significant differences between the two studied periods; in the early period there were a lower proportion of IBDU
“Early period” (1985–1995)
5. Discussion
Table 2
For CD, L3 was the most frequent localization in age groups 2 and 3 (61.5% and 54.2% respectively) and L2 was predominant in younger children. We also found the highest frequency of isolated ileal or ileo-cecal disease in group 3 (31.3%) in comparison with group 1 (21.7%) and group 2 (21.9%) (p b 0.001). Regarding UC, we found that a predominance of extensive colitis presentation in group 1 (73.8%) as compared to group 2 (67%) and group 3 (54.8%). CD and UC distribution according disease localization and extension in the different periods can be observed in Tables 3 and 4 respectively.
Disease distribution of IBD types according age groups in the different periods.
- CD L1 26.6%, L2 16.4%, and L3 57% - UC E1 10%, E2 27.1%, and E3 62.9%.
Group 2 (6–12 years)
Group 3 (13–17 years)
EXPERIENCE (1985–2009)
Group 3 (13–17 years)
Total
patients diagnosed in Spain: 1443 CD (55%), 986 UC (38%) and 173 IBDU (7%). Regarding sex distribution, we observed a male predominance in the IBD population (53%), with a higher predominance for CD (58.3%) as compared to UC (50.9%) and IBDU (52%) (p = 0.002). Mean age at diagnosis (years) was 11.8 years, and we observed significant differences between IBD subtypes (CD: 12.7 vs UC: 11.5 vs IBDU: 8.2; p b 0.001). If we focus on the distribution of the diseases according to age at diagnosis, we can observe a small proportion diagnosed below 5 years of age and a similar proportion of patients diagnosed in the second (6–12) and in the third (13–17) age groups (45.5% and 44.4% respectively). We have observed a predominance of UC and IBDU in the first 5 years of life (49.8% and 23.8%), whereas in groups 2 and 3, CD was the most frequent disease (55.1% and 62.4% respectively). The total amount of colonic-only IBD in group 1 was 82.6% and there was a relationship between IBDU diagnosis and younger age at presentation (23.8% in group 1, 6.8% in group 2 and 2.6% in group 3) (p b 0.001). Disease distribution according to age at diagnosis in the different periods is described in Table 2. CD and UC location phenotype according to Montreal classification in this whole period was:
1443 (55%) 986 (38%) 173 (7%) 2602
4
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
Location of intestinal involvement in pediatric CD (ileum and colon only) according to age group in the different periods. “Early period” (1985–1995)
SPIRIT (1996–2009)
EXPERIENCE (1985–2009)
Total
Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 (0–5 years) (6–12 years) (13–17 years) (0–5 years) (6–12 years) (13–17 years) (0–5 years) (6–12 years) (13–17 years) L1 (ileal or ileo-cecal) 1 (7.7%) (% within age group) L2 (colonic) (% within age group) 5 (38.5%) L3 (ileo-colonic) 7 (53.8%) (% within age group) Total 13 (4.7%)
Table 4
22 (18.8%)
52 (35.1%)
14 (25%)
121 (22.6%)
174 (30.3%)
15 (21.7%)
143 (21.9%)
226 (31.3%)
384 (26.6%)
21 (17.9%) 74 (63.2%)
18 (12.2%) 78 (52.7%)
19 (33.9%) 23 (41.1%)
87 (16.3%) 327 (61.1%)
87 (15.2%) 313 (54.5%)
24 (34.8%) 30 (30%)
108 (16.6%) 401 (61.5%)
105 (14.5%) 391 (54.2%)
237 (16.4%) 822 (57.0%)
117 (42.1%)
148 (53.2%)
56 (4.8%)
535 (45.9%)
574 (49.3%)
69 (4.0%)
652 (45.0%)
722 (51%)
1443 (100%)
Extent of UC amongst different age groups in the different periods. “Early period” (1985–1995) Group 1 (0–5 years)
E1 (procto-sigmoiditis) (% within age group) E2 (left-sided colitis) (% within age group) E3 (extensive colitis) (% within age group) Total
Total
Group 2 (6–12 years)
Group 3 (13–17 years)
Group 1 (0–5 years)
Group 2 (6–12 years)
Group 3 (13–17 years)
8 (9.4%)
7 (6.4%)
27 (7.5%)
47 (14.7%)
8 (6.2%)
36 (8.0%)
55 (13.6%)
99 (10.0%)
23 (25%)
32 (37.6%)
19 (17.4%)
90 (25.1%)
96 (30.0%)
26 (20.0%)
113 (25.1%)
128 (31.6%)
267 (27.1%)
13 (61.9%)
60 (65.2%)
45 (52.9%)
83 (76.1%)
242 (67.4%)
177 (55.3%)
96 (73.8%)
302 (67.0%)
222 (54.8%)
620 (62.9%)
21 (10.6%)
92 (46.5%)
85 (42.9%)
109 (13.8%)
359 (45.6%)
320 (40.6%)
130 (13.1%)
451 (45.7%)
405 (41.1%)
986 (100%)
7 (33.3%)
9 (9.8%)
Group 3 (13–17 years)
EXPERIENCE (1985–2009)
Group 1 (0–5 years)
1 (4.8%)
Group 2 (6–12 years)
SPIRIT (1996–2009)
The complete picture of changing pediatric inflammatory bowel disease incidence in Spain
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
Table 3
5
6
J. Martín-de-Carpi et al.
patients, a higher female predominance and an older age at diagnosis. We could theorize that a better definition of IBDU, together with a wider availability of diagnostic tools, and the publication of the Porto Criteria recommendation of not classifying as CD or UC those entities that do not fit strictly in CD or UC criteria respectively, could have contributed to the increase of IBDU cases in the later period. This fact, although seems paradoxical (improvement of diagnostic criteria should have lead to a higher proportion of patients with a definite and accurate diagnosis), makes the proportion of IBDU patients in this second period more similar to the previously described in other pediatric series (10–20%).16 We could think that clinicians previously tended to classify an IBD patient as having CD or UC based only in endoscopic and histological findings, without considering the possibility of “indeterminate” cases. The extension of our retrospective registry of incident PIBD patients gives a clear picture of the evolution of the disease in Spain over 25 years. We have observed that the results of this 25-year period are equivalent to the ones from the SPIRIT registry.11 Similarities and differences between our global national data and those from previous international series regarding disease subtypes, localization and age and sex distribution are equivalent to the ones reported and exhaustively analyzed in the SPIRIT publication.11 PIBD diagnosis in Spain has dramatically increased over this long period, experiencing a ten-fold increase of diagnosed cases. Although it could be postulated that this sharp increase could represent a greater awareness by pediatric gastroenterologists, all PIBD patients presenting with rectal bleeding or moderate to severe IBD would undoubtedly have proceeded to colonoscopy regardless of when they presented. We do not think that there would have been enough mild PIBD cases whose diagnosis was delayed to adult life to account for the dramatically fewer cases in 1985–1995. We believe that a real increase of IBD in the Spanish population has also played an unquestionable role, as IBD diagnosis in pediatric hospitals in the 1980s was quite rare. Fig. 2 shows the number of new diagnoses of CD, UC and IBDU/year. The total number of new diagnoses/year was in continuous increase. 150 Crohn's disease Ulcerative Colitis IBD unclassified
Frequency
100
50
0 1985
1990
1995
2000
2005
2010
Year of diagnosis
Figure 2 Evolution of the diagnosed cases in the whole studied period (1985–2009).
Although it is not possible to calculate consistent incidence rates for the period 1985–1995, due to the lack of appropriate and reliable pediatric age-stratified annual epidemiological data before 1996, we could hypothesize an approximate incidence rate based on the estimative population between the demographic census of 1981 and 1991. Estimated population below 18 years at 1st January of 1985 was 10,992,440.15 Therefore, the estimated PIBD incidence rate at the beginning of the 25-year period would be around 0.17/105 inhabitants under 18 years. This would mean an estimated sixteen-fold increase of PIBD incidence rate in Spain between 1985 and 2009, one of the highest PIBD increases described all around the world. However, this estimation is not completely reliable, as population data between census could not be verified. In conclusion, this extended registry constitutes one of the few attempts to describe PIBD evolution over a long period of time (25 years) based on nationwide incidence data. Although PIBD incidence in Spain is remarkably lower than those reported in other European countries17–20 as well as in North America,7 incidence trends observed in our studies seem equivalent to the ones observed in those countries.
Conflict of interest The authors declare no conflict of interest.
Acknowledgments We thank Vicente Varea MD, PhD, for his persistent dedication to Pediatric IBD, and without whom this study could not have been possible. We also thank Victoria Trenchs MD, PhD, for her contributions to the statistical analyses and Prof. David Wilson MD, PhD, for their priceless help.
Appendix A The following investigators participated in the SPIRIT study: Juliana Serrano (H. Carlos Haya, Málaga), Elena Ricart (H. Clínic, Barcelona), Félix Sánchez-Valverde (H. Virgen del Camino, Pamplona), Luis Peña-Quintana (H. Maternoinfantil, Las Palmas de Gran Canaria), Rafael González de Caldas (H. Reina Sofía, Córdoba), Alfonso Solar (H. A. Coruña), Oscar Segarra (H. Vall d'Hebrón, Barcelona), Lucrecia Suárez (H. Ramón y Cajal, Madrid), Carolina Gutiérrez (H. Puerta de Hierro, Madrid), Pilar Pavón, Manuel Barreiro-de-Acosta (H. Santiago de Compostela), César Sánchez (H. Gregorio Marañón, Madrid), José Ignacio García Burriel (H. Xeral-Cíes, Vigo), Ignacio Ros (H. Miguel Servet, Zaragoza), Mª Jesús Balboa (H. Juan Ramón Jiménez, Huelva), Pilar Guallarte (H. Parc Taulí, Sabadell), María Chaparro (H. La Princesa, Madrid), Daniel Carpio (H. Pontevedra), Antoni Rosell (H. Son Espases, Palma de Mallorca), Ricardo Torres (H. Salamanca), Iñaki Irastorza (H. Cruces, Bilbao), Cristina Iglesias (H. León), Montserrat Montraveta (H. Germans Trias I Pujol, Badalona), Antonio Pereda (H. La Fe, Valencia), Elena Lorenzo (H. Basurto, Bilbao), Honorio Armas (H. Canarias, Tenerife), Elena Balmaseda (H. Albacete), Ana Echarri (H. El Ferrol), Pablo Sáez (H. Josep Trueta, Girona), Josefa Barrio (H. Fuenlabrada, Madrid), Luis Ortigosa (H. Virgen de la Candelaria, Tenerife),
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
The complete picture of changing pediatric inflammatory bowel disease incidence in Spain Andrés Bodas (H. Clínico San Carlos, Madrid), José Manuel Marugán (H. Clínico, Valladolid), Miguel Angel López (H. Virgen de las Nieves, Granada), Mireia Peñalva (H. Bellvitge, Barcelona), Mercedes Juste (H. San Juan, Alicante), David Gil (H. Virgen de la Arrixaca, Murcia), Manuel Martín (H. Torrecárdenas, Almeria), Gonzalo Galicia (H. Guadalajara), Francisco Javier Eizaguirre (H. Donostia, San Sebastián), Javier Rubio (H. Jerez de la Frontera), Raquel Simó (H. Dr. Peset, Valencia), Juan Manuel Bartolomé (H. Palencia), Rosa Solaguren (H. Virgen de la Salud, Toledo), Carlos Rodríguez (H. Vega Baja, Orihuela, Alicante), Zuriñe García (H. Txagorritxu, Vitoria), Alfonso Barrio (H. Alcorcón, Madrid), Oscar Manrique (H. General, Alicante), Roger García (H. Mútua de Terrasa), Carlos Ochoa (H. Virgen de la Concha, Zamora), Mª Lluisa Masiques (H. Granollers, Barcelona), Amadeo Roca (H. Calella, Barcelona), Míriam Blanco (Fundación Jiménez Díaz, Madrid), Belén Botella (H. Infanta Cristina, Parla, Madrid), Alfonso Rodríguez (Instituto Hispalense de Pediatría, Sevilla), José Antonio Blanca (H. Puerta del Mar, Cádiz), Eduardo Ubalde (H. San Jorge, Huesca), Enrique Salcedo (H. Getafe, Madrid), Benjamín Martín (H. Terrasa), Rosmarí Vázquez (H. Elche, Alicante), Jesús Carnicer (H. Sant Pau, Barcelona), Patricia Barros (H. San Pedro de Alcántara, Cáceres), Pilar Sánchez (H. General, Ciudad Real), Esperanza Llorens (H. Barcelona), Begoña Perez-Moneo (H. Infanta Leonor, Vallecas, Madrid), Neus Pociello (H. Arnau de Vilanova, Lérida), Ana Fernández (H. General Yagüe, Burgos), Javier Torrecillas (H. Virgen de la Luz, Cuenca), Alfredo Lucendo (H. Tomelloso, Ciudad Real), Nuria Maroto (H. Manises, Valencia), and Margarita Pich (Cínica Teknon, Barcelona).
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tive population-based study in northern France (1988–1999). J Pediatr Gastroenterol Nutr 2005;41:49–55. Malaty HM, Fan X, Opekun AR, Thibodeaux C, Ferry G. Rising incidence of inflammatory bowel disease among children: a 12-year study. J Pediatr Gastroenterol Nutr 2010;50:27–31. Benchimol EI, Guttmann A, Griffiths AM, Rabeneck L, Mack DR, Brill H, et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence form health administrative data. Gut 2009;58:1490–7. Olafsdottir EJ, Fluge G, Haug K. Chronic inflammatory bowel disease in children in western Norway. J Pediatr Gastroenterol Nutr 1998;8:454–8. Castro M, Papadatou B, Baldassare M, Balli F, Barabino A, Barbera C, et al. Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996–2003). Inflamm Bowel Dis 2008;14:1246–52. Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis 2011;17:423–39. Martín-de-Carpi J, Rodríguez A, Ramos E, Jiménez S, Martínez-Gómez MJ, Medina E, et al. Increasing incidence of pediatric inflammatory bowel disease in Spain (1996–2009): the SPIRIT registry. Inflamm Bowel Dis 2013;19:73–80. Espghan I.B.D. working group. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis — the Porto criteria. J Pediatr Gastroenterol Nutr 2005;41:1–7. Chong SK, Blackshaw AJ, Boyle S, Williams CB, Walker-Smith JA. Histological diagnosis of chronic inflammatory bowel disease in childhood. Gut 1985;26:55–9. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19:5A–36A. Population figures and demographic censuses from the municipal register, Instituto Nacional de Estadística. http://www.ine.es/ en/inebmenu/indice_en.htm accessed September 4, 2013 at. Prenzel F, Uhlig HH. Frequency of indeterminate colitis in children and adults with IBD—a metaanalysis. J Crohns Colitis 2009;3:277–81. Cosgrove M, Al-Atia RF, Jenkins HR. The epidemiology of paediatric inflammatory bowel disease. Arch Dis Child 1996;74:460–1. Barton JR, Gillon S, Ferguson A. Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease. Gut 1989;30:618–22. Armitage E, Drummond HE, Wilson DC, Ghosh S. Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland. Eur J Gastroenterol Hepatol 2001;13: 1439–47. Henderson P, Hansen R, Cameron FL, Gerasimidis K, Rogers P, Bisset WM, et al. Rising incidence of pediatric inflammatory bowel disease in Scotland. Inflamm Bowel Dis 2012;18:999–1005.
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
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The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry J. Martín-de-Carpi a,⁎, A. Rodríguez b , E. Ramos c , S. Jiménez d , M.J. Martínez-Gómez e , E. Medina f , V.M. Navas-López g , On behalf of the SPIRIT-IBD Working Group of SEGHNP (Sociedad Española de Gastroenterología Hepatología Nutrición Pediátrica) a
Unidad para el Cuidado Integral de la Enfermedad Inflamatoria Intestinal Pediátrica, Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Déu, Barcelona, Spain b Hospital Virgen del Rocío, Sevilla, Spain c Hospital La Paz, Madrid, Spain d Hospital Central de Asturias, Oviedo, Spain e Hospital Niño Jesús, Madrid, Spain f Hospital Doce de Octubre, Madrid, Spain g Hospital Materno-Infantil, Málaga, Spain
Received 4 July 2013; received in revised form 27 December 2013; accepted 5 January 2014 KEYWORDS Pediatric inflammatory bowel disease; Crohn's disease; Ulcerative colitis; IBD unclassified; Incidence; SPIRIT registry; EXPERIENCE registry
Abstract Objectives: A growing incidence of pediatric IBD (PIBD) in southern Europe has been recently reported. The SPIRIT registry (1996–2009) confirmed these tendencies in Spain. Our aim is to obtain data from 1985 to 1995 and describe the complete picture of PIBD presentation changes in Spain in the last 25 years. Methods: A retrospective survey of incident PIBD in the period 1985–1995 was performed. Patients' data were obtained from the hospitals' databases and compared with the published data from the 1996 to 2009 period. Seventy-eight IBD reference centers took part in this survey. Results: Data from 495 patients were obtained: 278 CD (56.2%), 198 UC (40%), and 19 IBDU (3.8%); 51.7% were female, with higher predominance both in UC (58.6%) and in IBDU (57.9%), but not in CD (46.4%). Median (IQR) age at diagnosis was 12.9 (10.0–15.7) years, with significant differences among
⁎ Corresponding author at: Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Déu Paseo Sant Joan de Déu, 2, 08950 Barcelona, Spain. Tel.: + 34 93 600 61 03; fax: + 34 93 203 39 59. E-mail address: [email protected] (J. Martín-de-Carpi). 1873-9946/$ - see front matter © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.crohns.2014.01.005
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
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J. Martín-de-Carpi et al. IBD subtypes: CD: 13.1 (10.8–16.0) vs UC: 12.4 (9.4–15.1) vs IBDU: 7.5 (3.0–13.0) (p ≤ 0.001). These results are significantly different to the ones in the SPIRIT registry, with a higher proportion of IBDU, younger age and male predominance. The data from both periods taken together give a complete picture of a 25–year period. An annual increase of incident patients was observed, with a ten-fold increase over this period. Conclusion: These data extend the epidemiological trends to a full 25–year period (1985–2009). PIBD incidence in Spain has experienced a sixteen-fold increase. The IBD subtype, localization of the affected segment, age- and sex distribution observed are in accordance with our previously published ones of 1996–2009. © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction A growing incidence of pediatric inflammatory bowel disease (PIBD; diagnosed below 18 years of age) worldwide has been reported.1–6 Although the highest incidence figures have been found in the northern parts of North America7 and in Scandinavia,8 recent studies have also showed this trend in southern Europe and other Mediterranean countries.9 The exhaustive systematic review by Benchimol et al. on international epidemiological trends of pediatric IBD10 concludes a globally rising trend of pediatric IBD both in developed and developing countries, although most of these countries lacked accurate estimates. The recently published SPIRIT registry by the IBD working group of the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition) offered for the first time robust data on the increase of PIBD incidence in Spain in the period 1996–2009, and constitutes the most extensive nationwide incidence study from a Mediterranean country.11 According to its results, overall IBD incidence increased from 0.97/105 inhabitants under 18 years in 1996 (95% CI 0.8–1.2) to 2.8 in 2009 (95% CI 2.4–3.2) (p b 0.001), Crohn's disease (CD) from 0.53 (95% CI 0.3–0.7) to 1.7 (95% CI 1.45–2.03) (p b 0.001) and ulcerative colitis (UC) from 0.39 (95% CI 0.27–0.55) to 0.88 (95% CI 0.69–1.1) (p b 0.001). Both overall IBD and CD incidence at the end of the studied period were found to be three fold higher than baseline, whereas UC experienced a two-fold increase in the same period.
2. Objectives Our aim is to extend our epidemiological data of PIBD in Spain with information about children and adolescents diagnosed between January 1985 and December 1995 and to compare these data with those previously obtained from the period 1996–2009. This new study contributes to the complete description of changes in PIBD presentation in Spain in the last 25 years.
3. Material and methods This is a collaborative, retrospective, multicenter study called EXPERIENCE (EXtended PEdiatric Registry of IBD Epidemiological Nationwide ChangEs). The study was planned and performed inside the IBD working group of the
Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP). A retrospective survey of incident PIBD (below 18 years at diagnosis) in the “early period” of 1985–1995 was performed. IBD diagnosis was made according to standard clinical, endoscopic, histological, and radiological criteria.12,13 Patients' data at diagnosis were obtained from the different hospitals' own databases. Both pediatric and adult IBD Units were contacted in order to avoid missed PIBD patients being followed from the beginning in adult services and to obtain the most reliable data. The same seventy-eight reference IBD centers that had previously participated in the SPIRIT registry, both pediatric and general, took part in this new survey (see Appendix A). All the 35 referral PIBD Units from tertiary centers in Spain participated, plus 31 small pediatric Gastroenterology Units in regional hospitals (representing 90% of these hospitals in which PIBD patients can be followed and that usually work in a shared care network with referral IBD Units), and lastly 12 adult hospitals without pediatric services. Distribution of all these centers, spread all over the nation, guarantees that the data collected are representative of the whole country and included mostly all pediatric patients with IBD diagnosed throughout this 25-year period. Every patient was identified in the registry with three letters (initial letter of the name and the two surnames used in Spain) and the date of birth indicated as ddmmyy. Patient's epidemiological and clinical data at diagnosis were obtained: sex, age, type (CD, UC, IBD type unclassified — IBDU) and location of the disease according to the Montreal classification.14 We decided not to include data from possible upper involvement or perianal involvement in CD (L4 and p variants of the Montreal classification) as we considered these could be not very reliable due to the retrospective nature of the study and the period reviewed starting before the Porto Criteria publication, which emphasized the need for upper GI endoscopy as well as colonoscopy at PIBD diagnosis.12 We assumed many patients diagnosed before 2005 would only have had an upper endoscopy with significant upper GI symptoms present. These data were compared to our previously published data of incidence changes from the “later period” of the SPIRIT registry (1996–2009).11
3.1. Ethics The study was approved by the Ethics Committee of the first author's center, as representative of the rest of the hospitals.
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
The complete picture of changing pediatric inflammatory bowel disease incidence in Spain
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3.2. Statistical analysis A chi-square test was applied for category data; t-Student, U-Mann Whitney and 1-way analysis of variance (ANOVA) were performed to compare continuous variables. Significance was set at p b 0.05. SPSS v. 19.0 (Chicago, IL) was used for statistical analysis.
4. Results From 1985 to 1995, 495 new patients were diagnosed: 278 CD (56.2%), 198 UC (40.0%) and 19 IBDU (3.8%). Due to a lower proportion of IBDU, this disease distribution in this “early period” was significantly different to the data obtained from 2107 patients in the “later period” (1996–2009) which were 55.3%, 37.4%, and 7.3% respectively (p b 0.01). The majority of our patients were Caucasian (98.2%), 4 were of gypsy ethnicity (0.8%), and 1% were immigrants born abroad (mainly form northern Africa). A slightly higher proportion of immigrants (4.6%) were observed in our SPIRIT registry, in accordance with the migration changes that took place at the beginning of the XXI century. Regarding sex distribution, 51.7% of PIBD patients in the early period were female, with a higher female predominance in the UC (58.6%) and IBDU groups (57.9%), but this proportion changed for CD, with 53.6% male. A general male predominance had been observed in the later period (56.4%), more striking for CD (59.3%) than UC (52.8%) and IBDU (53.2%) (p = 0.012). Therefore, sex distribution between both periods was also significantly different (p b 0.001). Global median (IQR) age at diagnosis was 12.9 years (10.0– 15.7) in the early period (Fig. 1). Median (IQR) age for CD was 13.1 years (10.8–16.0), for UC 12.4 (9.4–15.1) and for IBDU 7.5 (3.0–13.0). We have observed significant differences between CD and IBDU (p b 0.001), between CD and UC (p b 0.001), and between UC and IBDU (p b 0.001). By comparison, the global median (IQR) age at diagnosis in the later period was significantly different: 12.3 years (9.7–14.6) (p b 0.028). Comparisons between both periods regarding disease and sex distribution, and age at diagnoses are shown in Table 1. Distribution of the diseases according to age at diagnosis in the early period showed a small proportion diagnosed below 5 years of age and a similar proportion of patients diagnosed in the second (6–12) and in the third (13–17) age groups (43.2% and 48.0% respectively). We have observed a predominance of UC and IBDU in the first 5 years of life (48.8% and 20.9%), whereas in groups 2 and 3, CD was the most frequent disease (54.7% and 62.2% respectively). The total amount of colonic-only IBD in group 1 (UC + IBDU + L2 group of CD) was 81.3%, similar to the results in the SPIRIT registry (83%). There was a relationship between IBDU diagnosis and younger age at presentation (20.9% in group 1, 2.3% in group 2 and 2.1% in group 3) (p b 0.001). A similar pattern of disease distribution had been communicated in our previous publication regarding the period 1996–2009. Disease location phenotype according to Montreal classification in the early period was the following: - Crohn's disease: L1 (isolated ileal or ileo-cecal involvement) 27.1%, L2 (isolated colonic involvement) 16.8%, and L3 (ileo-colonic disease) 56.1%.
Figure 1 Age distribution of the diagnosed cases in the 1985–1995 period.
- Ulcerative colitis: E1 (procto-sigmoiditis) 9.1%, E2 (leftsided colitis) 31.3%, and E3 (extensive colitis) 59.6%. These results are not significantly different to the data obtained from the later period, both for CD (L1: 26.5%, L2: 16.6%, L3: 56.9%) and for UC (E1: 10.3%, E2: 26%, E3 63.7%). The important increase of the diagnosed cases per year we reported in the SPIRIT registry has also been found in this earlier period; in 1985, 22 new cases of IBD in children below 18 years were recognized, whereas in 1995, 88 new cases were diagnosed. This represents a 4-fold increase. This increase was observed both for CD (11 cases in 1985, 49 in 1995), for UC (10 cases in 1985, 34 in 1995), and also for IBDU (1 case/year for the first years of the period, 5 cases in 1995). Finally, these new data obtained from 1985 to 1995 were added to those from the later period showing a complete picture of the changing pattern of PIBD in Spain for a 25-year period (the EXPERIENCE registry). In total, as a result of the two registries we obtained data from 2602 incident PIBD Table 1 Comparisons between both periods regarding disease and sex distribution, and age at diagnosis. 1985–1995 Disease distribution CD UC IBDU Sex distribution Male Female Median age (years) at diagnosis (IQR)
1996–2009
p b 0.018
278 (56.2%) 198 (40.0%) 19 (3.8%)
1165 (55.3%) 788 (37.4%) 154 (7.3%)
b 0.001 49.3% 56.4% 51.7% 43.6% 12.9 (10–15.7) 12.4 (9.7–14.6) b 0.028
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
J. Martín-de-Carpi et al.
Group 2 (6–12 years)
(62.4%) (35.0%) (2.6%) (44.5%) 722 405 30 1157 652 (55.1%) 451 (38.1%) 81 (6.8%) 1184 (45.5%) (26.4%) (49.8%) (23.8%) (10%) 69 130 62 261 (62%) (35%) (3%) (43.7%) 574 320 25 919 (55.2%) (37%) (7.8%) (46.0%) 535 359 76 970 56 (25.7%) 109 (50%) 53 (24.3%) 218 (10.3%) 148 (62.2%) 85 (35.7%) 5 (2.1%) 238 (48.1%) 117 (54.7%) 92 (43.0%) 5 (2.3%) 214 (43.2%) 13 (30.2%) 21 (48.8%) 9 (20.9%) 43 (8.7%) CD (% within age group) UC (% within age group) IBDU (% within age group) Total
Group 2 (6–12 years) Group 1 (0–5 years) Group 1 (0–5 years) Group 1 (0–5 years)
Group 3 (13–17 years)
SPIRIT (1996–2009)
The recently published SPIRIT registry constituted the first attempt to describe nationwide recent incidence of PIBD in Spain and its evolution over a long period of time.11. The investigators decided to focus in the period from which incidence data could be obtained (1996–2009). In Spain it is not feasible to get reliable pediatric age-stratified epidemiological data before 1996, as the results of the source that provides official population figures of all municipalities standardized at 1st January each year and classified by age (the municipal register),15 are available only from that year. The results of that registry showed a three-fold increase of PIBD for the studied period (1996–2009), with a three-fold increase in CD diagnosis and a parallel two-fold increase of UC. Once this first robust data were published, we decided to extend the analysis to the early years of a 25-year period (1985–1995) in order to obtain a complete figure of PIBD evolution (the EXPERIENCE registry). We have obtained data from 495 new incident patients diagnosed between 1985 and 1995. We have observed significant differences between the two studied periods; in the early period there were a lower proportion of IBDU
“Early period” (1985–1995)
5. Discussion
Table 2
For CD, L3 was the most frequent localization in age groups 2 and 3 (61.5% and 54.2% respectively) and L2 was predominant in younger children. We also found the highest frequency of isolated ileal or ileo-cecal disease in group 3 (31.3%) in comparison with group 1 (21.7%) and group 2 (21.9%) (p b 0.001). Regarding UC, we found that a predominance of extensive colitis presentation in group 1 (73.8%) as compared to group 2 (67%) and group 3 (54.8%). CD and UC distribution according disease localization and extension in the different periods can be observed in Tables 3 and 4 respectively.
Disease distribution of IBD types according age groups in the different periods.
- CD L1 26.6%, L2 16.4%, and L3 57% - UC E1 10%, E2 27.1%, and E3 62.9%.
Group 2 (6–12 years)
Group 3 (13–17 years)
EXPERIENCE (1985–2009)
Group 3 (13–17 years)
Total
patients diagnosed in Spain: 1443 CD (55%), 986 UC (38%) and 173 IBDU (7%). Regarding sex distribution, we observed a male predominance in the IBD population (53%), with a higher predominance for CD (58.3%) as compared to UC (50.9%) and IBDU (52%) (p = 0.002). Mean age at diagnosis (years) was 11.8 years, and we observed significant differences between IBD subtypes (CD: 12.7 vs UC: 11.5 vs IBDU: 8.2; p b 0.001). If we focus on the distribution of the diseases according to age at diagnosis, we can observe a small proportion diagnosed below 5 years of age and a similar proportion of patients diagnosed in the second (6–12) and in the third (13–17) age groups (45.5% and 44.4% respectively). We have observed a predominance of UC and IBDU in the first 5 years of life (49.8% and 23.8%), whereas in groups 2 and 3, CD was the most frequent disease (55.1% and 62.4% respectively). The total amount of colonic-only IBD in group 1 was 82.6% and there was a relationship between IBDU diagnosis and younger age at presentation (23.8% in group 1, 6.8% in group 2 and 2.6% in group 3) (p b 0.001). Disease distribution according to age at diagnosis in the different periods is described in Table 2. CD and UC location phenotype according to Montreal classification in this whole period was:
1443 (55%) 986 (38%) 173 (7%) 2602
4
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
Location of intestinal involvement in pediatric CD (ileum and colon only) according to age group in the different periods. “Early period” (1985–1995)
SPIRIT (1996–2009)
EXPERIENCE (1985–2009)
Total
Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 (0–5 years) (6–12 years) (13–17 years) (0–5 years) (6–12 years) (13–17 years) (0–5 years) (6–12 years) (13–17 years) L1 (ileal or ileo-cecal) 1 (7.7%) (% within age group) L2 (colonic) (% within age group) 5 (38.5%) L3 (ileo-colonic) 7 (53.8%) (% within age group) Total 13 (4.7%)
Table 4
22 (18.8%)
52 (35.1%)
14 (25%)
121 (22.6%)
174 (30.3%)
15 (21.7%)
143 (21.9%)
226 (31.3%)
384 (26.6%)
21 (17.9%) 74 (63.2%)
18 (12.2%) 78 (52.7%)
19 (33.9%) 23 (41.1%)
87 (16.3%) 327 (61.1%)
87 (15.2%) 313 (54.5%)
24 (34.8%) 30 (30%)
108 (16.6%) 401 (61.5%)
105 (14.5%) 391 (54.2%)
237 (16.4%) 822 (57.0%)
117 (42.1%)
148 (53.2%)
56 (4.8%)
535 (45.9%)
574 (49.3%)
69 (4.0%)
652 (45.0%)
722 (51%)
1443 (100%)
Extent of UC amongst different age groups in the different periods. “Early period” (1985–1995) Group 1 (0–5 years)
E1 (procto-sigmoiditis) (% within age group) E2 (left-sided colitis) (% within age group) E3 (extensive colitis) (% within age group) Total
Total
Group 2 (6–12 years)
Group 3 (13–17 years)
Group 1 (0–5 years)
Group 2 (6–12 years)
Group 3 (13–17 years)
8 (9.4%)
7 (6.4%)
27 (7.5%)
47 (14.7%)
8 (6.2%)
36 (8.0%)
55 (13.6%)
99 (10.0%)
23 (25%)
32 (37.6%)
19 (17.4%)
90 (25.1%)
96 (30.0%)
26 (20.0%)
113 (25.1%)
128 (31.6%)
267 (27.1%)
13 (61.9%)
60 (65.2%)
45 (52.9%)
83 (76.1%)
242 (67.4%)
177 (55.3%)
96 (73.8%)
302 (67.0%)
222 (54.8%)
620 (62.9%)
21 (10.6%)
92 (46.5%)
85 (42.9%)
109 (13.8%)
359 (45.6%)
320 (40.6%)
130 (13.1%)
451 (45.7%)
405 (41.1%)
986 (100%)
7 (33.3%)
9 (9.8%)
Group 3 (13–17 years)
EXPERIENCE (1985–2009)
Group 1 (0–5 years)
1 (4.8%)
Group 2 (6–12 years)
SPIRIT (1996–2009)
The complete picture of changing pediatric inflammatory bowel disease incidence in Spain
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
Table 3
5
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J. Martín-de-Carpi et al.
patients, a higher female predominance and an older age at diagnosis. We could theorize that a better definition of IBDU, together with a wider availability of diagnostic tools, and the publication of the Porto Criteria recommendation of not classifying as CD or UC those entities that do not fit strictly in CD or UC criteria respectively, could have contributed to the increase of IBDU cases in the later period. This fact, although seems paradoxical (improvement of diagnostic criteria should have lead to a higher proportion of patients with a definite and accurate diagnosis), makes the proportion of IBDU patients in this second period more similar to the previously described in other pediatric series (10–20%).16 We could think that clinicians previously tended to classify an IBD patient as having CD or UC based only in endoscopic and histological findings, without considering the possibility of “indeterminate” cases. The extension of our retrospective registry of incident PIBD patients gives a clear picture of the evolution of the disease in Spain over 25 years. We have observed that the results of this 25-year period are equivalent to the ones from the SPIRIT registry.11 Similarities and differences between our global national data and those from previous international series regarding disease subtypes, localization and age and sex distribution are equivalent to the ones reported and exhaustively analyzed in the SPIRIT publication.11 PIBD diagnosis in Spain has dramatically increased over this long period, experiencing a ten-fold increase of diagnosed cases. Although it could be postulated that this sharp increase could represent a greater awareness by pediatric gastroenterologists, all PIBD patients presenting with rectal bleeding or moderate to severe IBD would undoubtedly have proceeded to colonoscopy regardless of when they presented. We do not think that there would have been enough mild PIBD cases whose diagnosis was delayed to adult life to account for the dramatically fewer cases in 1985–1995. We believe that a real increase of IBD in the Spanish population has also played an unquestionable role, as IBD diagnosis in pediatric hospitals in the 1980s was quite rare. Fig. 2 shows the number of new diagnoses of CD, UC and IBDU/year. The total number of new diagnoses/year was in continuous increase. 150 Crohn's disease Ulcerative Colitis IBD unclassified
Frequency
100
50
0 1985
1990
1995
2000
2005
2010
Year of diagnosis
Figure 2 Evolution of the diagnosed cases in the whole studied period (1985–2009).
Although it is not possible to calculate consistent incidence rates for the period 1985–1995, due to the lack of appropriate and reliable pediatric age-stratified annual epidemiological data before 1996, we could hypothesize an approximate incidence rate based on the estimative population between the demographic census of 1981 and 1991. Estimated population below 18 years at 1st January of 1985 was 10,992,440.15 Therefore, the estimated PIBD incidence rate at the beginning of the 25-year period would be around 0.17/105 inhabitants under 18 years. This would mean an estimated sixteen-fold increase of PIBD incidence rate in Spain between 1985 and 2009, one of the highest PIBD increases described all around the world. However, this estimation is not completely reliable, as population data between census could not be verified. In conclusion, this extended registry constitutes one of the few attempts to describe PIBD evolution over a long period of time (25 years) based on nationwide incidence data. Although PIBD incidence in Spain is remarkably lower than those reported in other European countries17–20 as well as in North America,7 incidence trends observed in our studies seem equivalent to the ones observed in those countries.
Conflict of interest The authors declare no conflict of interest.
Acknowledgments We thank Vicente Varea MD, PhD, for his persistent dedication to Pediatric IBD, and without whom this study could not have been possible. We also thank Victoria Trenchs MD, PhD, for her contributions to the statistical analyses and Prof. David Wilson MD, PhD, for their priceless help.
Appendix A The following investigators participated in the SPIRIT study: Juliana Serrano (H. Carlos Haya, Málaga), Elena Ricart (H. Clínic, Barcelona), Félix Sánchez-Valverde (H. Virgen del Camino, Pamplona), Luis Peña-Quintana (H. Maternoinfantil, Las Palmas de Gran Canaria), Rafael González de Caldas (H. Reina Sofía, Córdoba), Alfonso Solar (H. A. Coruña), Oscar Segarra (H. Vall d'Hebrón, Barcelona), Lucrecia Suárez (H. Ramón y Cajal, Madrid), Carolina Gutiérrez (H. Puerta de Hierro, Madrid), Pilar Pavón, Manuel Barreiro-de-Acosta (H. Santiago de Compostela), César Sánchez (H. Gregorio Marañón, Madrid), José Ignacio García Burriel (H. Xeral-Cíes, Vigo), Ignacio Ros (H. Miguel Servet, Zaragoza), Mª Jesús Balboa (H. Juan Ramón Jiménez, Huelva), Pilar Guallarte (H. Parc Taulí, Sabadell), María Chaparro (H. La Princesa, Madrid), Daniel Carpio (H. Pontevedra), Antoni Rosell (H. Son Espases, Palma de Mallorca), Ricardo Torres (H. Salamanca), Iñaki Irastorza (H. Cruces, Bilbao), Cristina Iglesias (H. León), Montserrat Montraveta (H. Germans Trias I Pujol, Badalona), Antonio Pereda (H. La Fe, Valencia), Elena Lorenzo (H. Basurto, Bilbao), Honorio Armas (H. Canarias, Tenerife), Elena Balmaseda (H. Albacete), Ana Echarri (H. El Ferrol), Pablo Sáez (H. Josep Trueta, Girona), Josefa Barrio (H. Fuenlabrada, Madrid), Luis Ortigosa (H. Virgen de la Candelaria, Tenerife),
Please cite this article as: Martín-de-Carpi J, et al, The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985–2009): The EXPERIENCE registry, J Crohns Colitis (2014), http://dx.doi.org/10.1016/j.crohns.2014.01.005
The complete picture of changing pediatric inflammatory bowel disease incidence in Spain Andrés Bodas (H. Clínico San Carlos, Madrid), José Manuel Marugán (H. Clínico, Valladolid), Miguel Angel López (H. Virgen de las Nieves, Granada), Mireia Peñalva (H. Bellvitge, Barcelona), Mercedes Juste (H. San Juan, Alicante), David Gil (H. Virgen de la Arrixaca, Murcia), Manuel Martín (H. Torrecárdenas, Almeria), Gonzalo Galicia (H. Guadalajara), Francisco Javier Eizaguirre (H. Donostia, San Sebastián), Javier Rubio (H. Jerez de la Frontera), Raquel Simó (H. Dr. Peset, Valencia), Juan Manuel Bartolomé (H. Palencia), Rosa Solaguren (H. Virgen de la Salud, Toledo), Carlos Rodríguez (H. Vega Baja, Orihuela, Alicante), Zuriñe García (H. Txagorritxu, Vitoria), Alfonso Barrio (H. Alcorcón, Madrid), Oscar Manrique (H. General, Alicante), Roger García (H. Mútua de Terrasa), Carlos Ochoa (H. Virgen de la Concha, Zamora), Mª Lluisa Masiques (H. Granollers, Barcelona), Amadeo Roca (H. Calella, Barcelona), Míriam Blanco (Fundación Jiménez Díaz, Madrid), Belén Botella (H. Infanta Cristina, Parla, Madrid), Alfonso Rodríguez (Instituto Hispalense de Pediatría, Sevilla), José Antonio Blanca (H. Puerta del Mar, Cádiz), Eduardo Ubalde (H. San Jorge, Huesca), Enrique Salcedo (H. Getafe, Madrid), Benjamín Martín (H. Terrasa), Rosmarí Vázquez (H. Elche, Alicante), Jesús Carnicer (H. Sant Pau, Barcelona), Patricia Barros (H. San Pedro de Alcántara, Cáceres), Pilar Sánchez (H. General, Ciudad Real), Esperanza Llorens (H. Barcelona), Begoña Perez-Moneo (H. Infanta Leonor, Vallecas, Madrid), Neus Pociello (H. Arnau de Vilanova, Lérida), Ana Fernández (H. General Yagüe, Burgos), Javier Torrecillas (H. Virgen de la Luz, Cuenca), Alfredo Lucendo (H. Tomelloso, Ciudad Real), Nuria Maroto (H. Manises, Valencia), and Margarita Pich (Cínica Teknon, Barcelona).
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