The prevalence of having coeliac disease in children with type 1 diabetes was not significantly higher during the Swedish coeliac epidemic.

AIM: From 1986 to 1996, there was a four-fold increase in coeliac disease among young Swedish children, known as the Swedish coeliac epidemic. Children with type 1 diabetes have an increased risk of developing coeliac disease. We studied whether the prevalence of coeliac disease differed in children with type 1 diabetes born during and after this epidemic. METHODS: We compared national birth cohorts of 240 844 children born in 1992-1993 during the coeliac disease epidemic and 179 530 children born in 1997-1998 after the epidemic. Children diagnosed with both type 1 diabetes and coeliac disease were identified by merging information from five national registers. RESULTS: There was no statistically significant difference in the prevalence of coeliac disease among children with type 1 diabetes between the two cohorts: 176/1642 (10.7%, 95% confidence interval 9.2%-12.2%) in the cohort born during the coeliac disease epidemic versus 161/1380 (11.7%, 95% confidence interval 10.0%-13.5%) in the post-epidemic cohort. CONCLUSION: The prevalence of having both coeliac disease and type 1 diabetes was not significantly higher in children born during, than after, the Swedish coeliac epidemic. This may support a stronger genetic disposition in children who develop both conditions.

Presentation and progression of childhood-onset inflammatory bowel disease in Northern Stockholm County.

BACKGROUND: Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County. METHODS: Medical records for all 280 patients diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification. RESULTS: Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%-20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79-118.68; P = 0.01). CONCLUSIONS: Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.

Increasing incidence of paediatric inflammatory bowel disease in northern Stockholm County, 2002-2007.

OBJECTIVES: A sharp increase in paediatric (younger than 16 years) inflammatory bowel disease (IBD) incidence was observed in northern Stockholm County, Sweden, in 1990-2001. The increasing incidence was primarily explained by a rising incidence of Crohn disease (CD). Here, we present an update on the trends in incidence of paediatric IBD, 2002-2007. METHOD: Medical records of all children diagnosed as having suspected IBD in northern Stockholm County, 2002-2007, were scrutinised using defined diagnostic criteria. Disease extension, localisation, and behaviour at diagnosis were classified within the framework of the Paris classification. RESULT: A total of 133 children were diagnosed as having IBD 2002-2007 corresponding to a sex- and age-standardised incidence (per 10 person-years) for paediatric IBD of 12.8 (95% CI 10.8-15.2). The standardised incidence was 9.2 (95% CI 7.5-11.2) for CD and 2.8 (95% CI 1.9-4.0) for ulcerative colitis (UC). A significant increasing incidence of UC (P < 0.05) was observed during the study period. No temporal trend was observed for the incidence of CD. CONCLUSIONS: The incidence rate of paediatric IBD in northern Stockholm was significantly higher in 2002-2007 than that observed in our earlier study covering 1990-2001. The former sharp increase in incidence of paediatric CD seems, however, to have levelled out, although at a higher rate than reported from most other regions in the world. Although CD was still predominant, the observed increase in incidence of UC during the study period is notable.

Cesarean section and the risk of pediatric Crohn's disease.

BACKGROUND: Crohn's disease (CD) could involve an inappropriate immune response against normal bowel flora. Disrupted or atypical patterns of microbial bowel colonization may impair development of homeostasis between gut flora and the immune system. Perinatal microbial exposures may be particularly important in stimulating intestinal immune recognition. As birth by cesarean section is thought to represent an atypical pattern of early bowel colonization, we examined its association with pediatric CD. METHODS: Some 1536 patients diagnosed with pediatric CD and 15,439 controls matched by delivery unit, week of birth, sex, and born between 1973 and 2006 were identified through Swedish registers. The association of birth by cesarean section with pediatric CD was examined using conditional logistic regression, with stratification by sex and adjustment for parental socioeconomic index and maternal infections during pregnancy. RESULTS: Birth by cesarean section is associated with a modestly increased risk for pediatric CD among boys (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.01-1.54) but not girls, (OR = 0.99, 95% CI 0.76-1.29) and elective cesarean section is associated with a modest increased risk for the entire population (OR = 1.36, 95% CI 1.02-1.80). CONCLUSIONS: This study does not suggest that the delivery procedure should be altered, but the findings may be of etiological significance in CD, indicating a potential role for perinatal exposures associated with delivery mode. Although the sex difference may have arisen by chance, the modestly increased CD risk for boys delivered by cesarean section is consistent with sex-specific differences in susceptibility to some exposures.

Coeliac disease characteristics, compliance to a gluten free diet and risk of lymphoma by subtype.

OBJECTIVE: Coeliac disease is associated with an increased risk of malignant lymphomas. We investigated the importance of coeliac disease characteristics and diet compliance for risk of lymphoma. METHODS: In a nested case-control design, we identified 59 patients with lymphoma and 137 matched controls from a population-based cohort of 11,650 inpatients with coeliac disease. We assessed coeliac disease characteristics at diagnosis and dietary compliance collected prospectively from medical records during follow-up. RESULTS: Poor compliance was not significantly associated with risk of lymphoma overall (odds ratio 1.83, 95% confidence interval 0.78-4.31) nor of lymphoma subtypes. Risk estimates differed by subtype; risk of T-cell lymphoma (odds ratio 1.01, confidence interval 0.32-3.15) or intestinal lymphoma (odds ratio 0.66, confidence interval 0.17-2.56) was unelevated, whereas there was an indication of a risk increase of B-cell lymphoma (odds ratio 4.74, confidence interval 0.89-25.3) or extraintestinal lymphoma (odds ratio 3.00, confidence interval 0.73-12.3) following poor compliance. History of weight loss (odds ratio 2.89, confidence interval 1.00-8.29) at coeliac disease diagnosis was associated with an increased risk of lymphoma when excluding tumours occurring with short latency (<3 years). CONCLUSIONS: Compliance to a gluten-free diet did not significantly alter lymphoma risk, but a moderate effect cannot be excluded. Weight loss, a potential marker of coeliac disease severity, may be associated with lymphoma risk.

Pediatric inflammatory bowel diseases and the risk of lymphoma: should we revise our treatment strategies?

Inflammatory bowel diseases (IBDs) are lifelong inflammatory gastrointestinal diseases starting in about one third of patients during childhood. Treatment strategies aim to control this chronic inflammatory process. Owing to recent advances in the understanding of IBD, immunosuppressive agents (mainly against TNFalpha directed) as well as biological drugs are more and more often used. This therapeutic approach clearly improved the clinical condition of the majority of patients with IBD. However, with this more aggressive treatment strategy, safety concerns clearly arise. Recently, the description of a series of a particularly severe form of T cell lymphoma in pediatric and young adult patients with IBD under immunomodulator and biological combination therapy raised the question of the risks of treatment-induced side effects or complications. As reviewed in the present article, there is a slightly increased risk of not only lymphoma development in IBD patients, potentially related to the inflammatory process, but also to the use of immunosuppressive therapies. On the basis of the literature data, were analyzed current treatment strategies for children with moderate-to-severe IBD, who are candidates to receive immunomodulator and/or biological agents potentially accelerating the risk of lymphoma development. Comparative clinical studies in IBD are still missing; however, it is prudent to think about adapting immunosuppressive therapies to the inflammatory process of the underlying disorder and if possible to reduce them to monotherapy. Alternative treatment strategies for heavy immunosuppression exist (eg, enteral nutrition in Crohn disease or colectomy in patients with ulcerative colitis) and should be considered whenever appropriate. There is a major need for comparative studies before evidence-based guidelines can be established for safest and best treatment strategies of pediatric patients with IBD.

Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease.

OBJECTIVE: An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease. MATERIAL AND METHODS: Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data. RESULTS: Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04-7.21) and 4.94 (1.83-13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease. CONCLUSIONS: Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.

Guidelines for the management of growth failure in childhood inflammatory bowel disease.

Around 1 in 4 patients with inflammatory bowel disease (IBD) present in childhood, the majority around the time of their pubertal growth spurt. This presents challenges over and above those of managing IBD in adults as this period is a time of dramatic psychological and physical transition for a child. Growth and nutrition are key priorities in the management of adolescents and young adults with IBD. Growth failure in IBD is characterized by delayed skeletal maturation and a delayed onset of puberty, and is best described in terms of height-for-age standard deviation score (Z score) or by variations in growth velocity over a period of 3-4 months. Growth failure is common at presentation in Crohn's disease (CD), but less common in ulcerative colitis (UC). The etiology of growth failure is multifactorial. Principal determinants, however, include the inflammatory process per se, with proinflammatory cytokines (e.g., IL-1beta, IL-6) being directly implicated. Furthermore, poor nutrition and the consequences of prolonged corticosteroid use also contribute to the significant reduction in final adult height of almost 1 in 5 children. Initially a prompt, where possible steroid-free, induction of remission is indicated. The ideal is then to sustain a relapse-free remission until growth is complete, which is often not until early adulthood. These goals can often be achieved with a combination of exclusive enteral nutrition (EEN) and early use of immunosuppressants. The advent of potent and efficacious biological agents considerably improves the range of growth-sparing interventions available to children around puberty, although well-timed surgery remains another highly effective means of achieving remission and significant catch-up growth. We carried out a systematic review of publications to identify the best available evidence for managing growth failure in children with IBD. Despite the paucity of high-quality publications, sufficient data were available in the literature to allow practical, evidence-based where possible, management guidelines to be formulated. Although there is clear evidence that exclusive enteral nutrition achieves mucosal healing, its effect on growth has only been assessed at 6 months. In contrast to corticosteroids, EEN has no negative effect on growth. Corticosteroids remain the key therapy responsible for medication-induced growth impairment, although the use of budesonide in selected patients may minimize the steroid effect on dividing growth plates. Immunosuppressants have become a mainstay of treatment in children with IBD, and are being used earlier in the disease course than ever before. However, there are currently no long-term data reporting better growth outcome if these agents are introduced very soon after diagnosis. In comparison, recent data from a large prospective trial of infliximab in children with moderate to severe CD suggested significant catch-up growth during the first year of regular infusions. The only other intervention that has documented clear catch-up growth has been surgical resection. Resection of localized CD, in otherwise treatment-resistant children, early in the disease process achieves clear catch-up growth within the next 6 months. There are no data available that growth hormone improves final adult height in children with CD. In conjunction with expert endocrinological support, pubertal delay, more common in boys, may be treated with parenteral testosterone if causing significant psychological problems. The optimal management of children and adolescents requires a multidisciplinary approach frequently available within the pediatric healthcare setting. Dedicated dietetic support, along with nurse-specialist, child psychologist, and with closely linked medical and surgical care will likely achieve the best possible start for children facing a lifetime of chronic gut disease.

The usefulness of magnetic resonance imaging in the diagnosis of anterolateral impingement of the ankle.

The purpose of this study is to assess the sensitivity and specificity of magnetic resonance imaging (MRI) in the diagnosis of anterolateral impingement of the ankle and to assess the most helpful sequence in making the diagnosis. Twenty-four patients who had undergone ankle arthroscopy were chosen. Twelve patients had arthroscopically documented anterolateral impingement, and 12 patients with no impingement on arthroscopy served as controls. Two musculoskeletal radiologists and an orthopedic surgeon, blinded to the operative diagnosis, retrospectively reviewed selective MRI images in the sagittal, axial, and coronal planes. The sensitivities and specificities were calculated for all 3 reviewers. The Kendall coefficient of concordance was calculated for overall agreement among reviewers. Sensitivities varied from 0.75 to 0.83, whereas specificities varied from 0.75 to 1.00. Using the Fisher exact test of contingency, the sensitivities and specificities showed that all reviewers' interpretations were statistically significant with P = .039, .001, and .012, respectively. The axial images were felt to be most helpful in making the diagnosis. The physicians felt that the sagittal images were helpful in 67%, 83%, and 100%, respectively. MRI is a useful tool that can aid the clinician in the diagnosis of anterolateral impingement of the ankle. T1 sagittal images demonstrating displacement of the normal fat signal anterior to the fibula by scar can be useful and help to confirm the diagnosis.