Pediatric Inflammatory Bowel Disease in Finland: Incidence and Long-term Outcomes

Abstract

Kroonisten tulehduksellisten suolistosairauksien (IBD) kaksi pääryhmää ovat haavainen paksusuolen tulehdus (UC) ja Crohnin tauti (CD). Haavaisen paksusuolen tulehduksen yleisin oire on veriripuli. Vastaavasti Crohnin taudin tyyppioireita ovat vatsakipu ja ripuli. Nämä etiologialtaan tuntemattomat suoliston krooniset tulehdussairaudet ovat lisääntyneet viimeisten vuosikymmenten aikana etenkin länsimaissa. Geneettisen alttiuden lisäksi sairauden puhkeamiseen vaikuttavat esimerkiksi ympäristötekijät. Etenkin lapsilla kroonisiin tulehduksellisiin suolistosairauksiin sairastuminen voi vaikuttaa laajalti kehitykseen aina pituuskasvusta elämänlaatuun.

Tämän väitöskirjatutkimuksen tavoitteena oli selvittää lasten IBD:n ilmaantuvuus Suomessa vuosien 1987 ja 2003 välillä. Tavoitteena oli lisäksi tutkia ympäristötekijöiden vaikutusta ilmaantuvuuden alueellisiin eroihin. Lasten kroonisten suolistosairauksien taudinkuvaa, käytettyjä hoitomuotoja ja sairauden vaikutusta elämänlaatuun selvitettiin sairauskertomusten ja kyselytutkimuksen perusteella.

Tulehduksellisten suolistosairauksien ilmaantuvuus kolminkertaistui suomalaisen lapsiväestön keskuudessa tutkimusjakson aikana. Alueilla, joissa on matala lapsiväestöntiheys, havaittiin suuremmat ilmaantuvuusluvut verrattuna alueisiin, joissa lapsiväestöntiheys on korkea. Maanviljelijöiden määrällä, merenrannan läheisyydellä, paperitehtaiden sijainnilla tai vesijohtoveden kemikaalipitoisuuksilla ei todettu olevan merkittävää vaikusta ilmaantuvuuden alueellisiin eroihin. Lapsilla taudinkuva on usein aggressiivinen; jopa joka viides lapsipotilas joutui leikkaukseen. Elämänlaadun havaittiin olevan alentunut varhaisaikuisuudessa verrattuna terveisiin ikätovereihin. Tulevaisuudessa onkin tärkeää selvittää lasten tulehduksellisten suolistosairauksien ilmaantuvuuden nopean kasvun taustalla olevia tekijöitä.

Background: The incidence of inflammatory bowel disease (IBD) has been increasing among children especially in Western countries over the past decades. Crohn’s disease (CD) predominates over ulcerative colitis (UC) in most countries. The factors behind this increase are mainly unknown. Environmental factors influence, however, unquestionably the pathogenesis of IBD. The disease course in pediatric IBD is suggested to be more severe compared to adults which may have particularly impact on child development. The possible long-term sequelae of pediatric onset disease include growth impairment, risk of surgery and reduced quality of life.

Objectives: This epidemiological study aimed to evaluate the incidence of IBD among Finnish children between the years 1987-2003. The role of environmental determinants (pediatric population density, agricultural industry, paper mills or sea shore close to the place of residence, north-south gradient and chemical concentrations of tap water) in the spatial variations of pediatric IBD was explored. Further, medical record data were applied in the characterization of the clinical picture. The long-term outcome of pediatric IBD patients was assessed by conducting a questionnaire survey among the patients diagnosed at Helsinki and Tampere university hospitals between years 1987-2003.

Materials and methods: All children aged 0-17 years diagnosed with IBD in Finland between years 1987-2003 were identified through the Social Insurance Institution special reimbursement database. Information on residence was obtained from the Population Register Centre and population size data from Statistics Finland. Annual incidence rates per 100,000 pediatric population and 95% confidence intervals (CI) were calculated assuming a Poisson distribution. The surface area of Finland was divided into squares of 250 x 250 m and regional differences were assessed. The databases of the two largest university hospitals in Finland were searched to collect the information on the clinical picture of the pediatric IBD diagnosed between years 1987-2003. In addition, a questionnaire on the health status was sent to the patients identified from the hospital files and to age- and sex-matched controls randomly selected from the Population Register Centre.

Results: In total, 1880 children at the age of <18 years were diagnosed with IBD in Finland during the 17-year study period. The incidence of pediatric IBD increased three-fold from 4.8/100,000 in 1987 to 15.0/100,000 in 2003. The annual increase was on average 6.5% (95% CI 5.4%-7.5%). The analysis by IBD subtype was conducted only for years 1992-2003 due to incompleteness of the earlier data. The annual incidence of UC increased from 4 to 9 per 100,000 and that of CD from 2 to 5 per 100,000 during years 1992-2003. UC was more common than CD during the entire period. The average annual increase in CD was, however, higher compared to UC (8.4% versus 5.2%). There was no statistically significant north-south gradient in the incidence rates. In addition, chemical concentrations of tap water, agricultural industry and the closeness of the paper mill or seaside were not associated the incidence rates of pediatric IBD within the geographic units. Nevertheless, the incidence rates were significantly higher in the districts with sparse compared to dense child population.

Of the patients identified from the hospital databases, the majority (52%, n=317) was diagnosed with UC. The proportion of CD was 34% (n=203) and IBD-unclassified 14% (n=83) respectively. Altogether 45% of these children with IBD had received glucocorticoids as primary medication and 21% were operated before age 18. Participation proportion of the questionnaire survey was 67% (368/550) among patients and 37% (646/1760) among controls. As much as 83% of these patients had received systemic glucocorticoids during the disease course. The most common extraintestinal manifestation among the patients was a joint disease (in 5% of the patients who completed the questionnaire). According to questionnaire responses, the patients with pediatric onset IBD had lower scores in all four questions assessing quality of life compared to the healthy controls although the difference was statistically significant only in overall quality of life and physical functioning. Moreover, the male patients were shorter and weighted less than the healthy controls.

Conclusions: The incidence of pediatric IBD has substantially increased in Finland during 1987-2003. Moreover, the incidence rate of pediatric IBD was higher in the areas with low density of child population than in areas with high density of child population. The disease course of IBD among children is aggressive; systemic glucocorticoid therapy and surgical operations are frequent. In consequence, pediatric onset IBD reduces overall quality of life even in early adulthood when compared to overall quality of life in their healthy peers.