Ulrika L Fagerberg

Uppsala University, Uppsala, Uppsala, Sweden

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Publications (11)37.37 Total impact

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    ABSTRACT: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.
    Inflammatory Bowel Diseases 02/2014; 20(2):291-300. · 5.12 Impact Factor
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    ABSTRACT: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.
    Journal of pediatric gastroenterology and nutrition 07/2012; 55(3):340-61. · 2.18 Impact Factor
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    ABSTRACT: We report the manifestations of Crohn's disease (CD) observed on magnetic resonance enterography (MRE) in a pediatric population at the time of CD diagnosis. MRE of 95 consecutive pediatric patients with inflammatory bowel disease (IBD) examined in 2006-2009 were retrospectively analyzed, with documentation of findings based on type and location of the small bowel (SB) disease. In all, 51 were boys and 44 girls. 54 had CD, 31 non-CD IBD, and 10 no IBD. The most common site of SB involvement in CD was the terminal ileum seen in 29 (53.7%) patients, followed by ileum in 10 (18.5%) and jejunum in 9 (16.7%) patients. Solitary jejunal inflammation (3.7%), SB stenoses (1.9%), fistula formation (0.95%), and abscess (0.95%) were much less common. Perienteric lymphadenopathy was seen in 30 (55.6%) patients and fatty proliferation in 9 (16.7%). The most common manifestation of SB inflammation was increased contrast enhancement of bowel wall (93.5%), thickening of the bowel wall (90.3%), and derangement of bowel shape with saccular formations (25.8%). MRE in the pediatric population often demonstrates increased contrast uptake, bowel wall thickening, and perienteral lymphadenopathy in CD. More chronic small bowel changes seen commonly in adults and solitary jejunal involvements are less commonly seen.
    Inflammatory Bowel Diseases 04/2011; 18(3):520-8. · 5.12 Impact Factor
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    ABSTRACT: Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). During 1999-2008, CD patients were monitored for disease activity by Harvey-Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey-Bradshaw index decreased with infusions during the first year of treatment (P < 0.0001), whereas hemoglobin (P < 0.01) and albumin (P <0.001) increased, C-reactive protein (P < 0.01) decreased, platelets (P <0.001) increased, and leukocytes (P< 0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P < 0.0001), and nitrite (P < 0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.
    European journal of gastroenterology & hepatology 10/2009; 21(10):1168-76. · 1.66 Impact Factor
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    ABSTRACT: Introduction: Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. Aim: To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). Methods: During 1999-2008, CD patients were monitored for disease activity by Harvey-Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. Results: A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey-Bradshaw index decreased with infusions during the first year of treatment (P<0.0001), whereas hemoglobin (P<0.01) and albumin (P<0.001) increased, C-reactive protein (P<0.01) decreased, platelets (P<0.001) increased, and leukocytes (P<0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P<0.0001), and nitrite (P<0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Conclusion: Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.
    European Journal of Gastroenterology & Hepatology 09/2009; 21(10):1168-1176. · 1.92 Impact Factor
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    ABSTRACT: The protein calprotectin (S100 A8/A9) is present in neutrophils, monocytes, and macrophages. Colorectal inflammation can be detected by increased excretion of fecal calprotectin (FC). The aim of this study was to evaluate FC as a quantitative marker of inflammatory activity in children with inflammatory bowel disease (IBD). Thirty-nine children with IBD delivered a fecal spot sample and underwent colonoscopy. The samples were examined with an enzyme-linked immunosorbent assay for FC (Calprest, Eurospital, Trieste, Italy). The concentrations were correlated to macroscopic and microscopic assessments of extent and severity of inflammation in 8 colonic segments for each patient. FC correlated significantly to the macroscopic extent (Spearman rho = 0.61) and the severity (Spearman rho = 0.52) of colonic inflammation and to a macroscopic, combined extent and severity score (Spearman rho = 0.65). Significant correlations also were found to the microscopic extent (Spearman rho = 0.71) and severity (Spearman rho = 0.72) of colonic inflammation and to a microscopic, combined extent and severity score (Spearman rho = 0.75). The median FC was 392 mug/g (95% confidence interval [CI], 278-440) in children with clinical IBD symptoms (n = 23) and 32.9 mug/g (95% CI, 9.4-237) in asymptomatic IBD patients (n = 16). Of the asymptomatic children, 56% had a complete microscopic mucosal healing, and their median FC was 9.9 mug/g (95% CI, 5.9-41.9). FC can be used as a surrogate marker for estimation of colonic inflammation in pediatric IBD. Normalized FC concentration seems to indicate complete mucosal healing. FC is simple to obtain and analyze; this should facilitate objective assessment and monitoring of IBD activity.
    Journal of pediatric gastroenterology and nutrition 11/2007; 45(4):414-20. · 2.18 Impact Factor
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    Elisabeth Fernell, Ulrika L Fagerberg, Per M Hellström
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    ABSTRACT: Due to parental concern regarding the child's bowel habits and the ongoing discussion whether there might be an association between autism and intestinal inflammation, two inflammatory markers were analysed in a group of children with autism. Twenty-four consecutive children with autism (3-13 years) of unknown aetiology were investigated with respect to faecal calprotectin and rectal nitric oxide (NO). One child who previously had a severe Clostridium difficile infection displayed raised levels of both these inflammatory markers and one child with extreme constipation for whom only calprotectin was possible to measure had raised levels. The remaining children displayed results that did not indicate an active inflammatory status in the intestine when the two inflammatory markers were combined. By the use of two independent markers of inflammatory reactions in the gut, i.e. rectal NO and faecal calprotectin we were not able to disclose evidence of a link between the autistic disorder and active intestinal inflammation.
    Acta Paediatrica 08/2007; 96(7):1076-9. · 1.97 Impact Factor
  • Ulrika Lorentzon Fagerberg, Lars Lööf, Urban Myrdal, Lars-Olof Hansson, Yigael Finkel
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    ABSTRACT: The protein calprotectin is mainly derived from neutrophils. Increased fecal excretion of calprotectin has been reported in inflammatory bowel disease. The recommended cut-off level in adults (<50 microg/g feces) seems to be applicable in children aged 4 to 17 years. The aim of this study was to evaluate the use of fecal calprotectin to detect colorectal inflammation in children with gastrointestinal symptoms. We obtained stool samples on thirty-six children with gastrointestinal symptoms and suspected inflammation of the colon before they underwent colonoscopy. The samples were examined with an improved fecal calprotectin enzyme-linked immunosorbent assay method (Calprest, Eurospital). The results were correlated with the histopathologic findings in the colon. In children with colorectal inflammation (n = 22) the median fecal calprotectin concentration was 349 microg/g (range, 15.4-1860 microg/g). The most common diagnosis in this group was inflammatory bowel disease. Median fecal calprotectin was 16.5 microg/g (range, 5.0-65 microg/g) in children with no inflammation (n = 14). When <50 microg/g was used as upper reference limit the fecal calprotectin test had a sensitivity of 95%, specificity 93%, positive predictive value 95% and negative predictive value 93% to detect colorectal inflammation. The improved fecal calprotectin enzyme-linked immunosorbent assay is a simple test with potential use in children. Increased fecal calprotectin strongly predicted the presence of colorectal inflammation in children with gastrointestinal symptoms. Fecal calprotectin can be used to select patients who should undergo diagnostic colonoscopy for investigation of colorectal inflammation, including inflammatory bowel disease.
    Journal of Pediatric Gastroenterology and Nutrition 04/2005; 40(4):450-5. · 2.20 Impact Factor
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    ABSTRACT: Calprotectin is a protein abundant in neutrophils. Fecal calprotectin can be used as a marker of gastrointestinal inflammation, and an improved assay has recently been developed. The aim of this study was to establish reference values for fecal calprotectin in healthy children aged between 4 and 17 years. Fecal samples were obtained from 117 healthy children classified into four age groups: 4 to 6 years, 7 to 10 years, 11 to 14 years, and 15 to 17 years. A health questionnaire was used to ensure that these children fulfilled the inclusion criterion and did not have intercurrent disease, nasal or menstrual bleeding, or nonsteroidal anti-inflammatory drug medication before the sampling period. Calprotectin was analyzed using a quantitative enzyme-linked immunosorbent assay (Calprest, Eurospital SpA, Trieste, Italy). Children with fecal calprotectin values >50 microg/g were asked to deliver an additional sample. The overall median fecal calprotectin concentration was 13.6 microg/g (95% confidence interval, 9.9-19.5 microg/g) in the 117 children. In the different age groups, 4 to 6 years, 7 to 10 years, 11 to 14 years, and 15 to 17 years, the median calprotectin concentrations were 28.2, 13.5, 9.9, and 14.6 microg/g, respectively. Of these children, 104 (89%) had a concentration <50 microg/g. The remaining 13 children with a calprotectin concentration >50 microg/g delivered one additional fecal sample. All showed a lower concentration in the second sample except for one teenager who later proved to have proctitis. The suggested cutoff level for adults (<50 microg/g) can be used for children aged from 4 to 17 years regardless of sex. A fecal calprotectin concentration >50 microg/g warrants follow-up.
    Journal of Pediatric Gastroenterology and Nutrition 11/2003; 37(4):468-72. · 2.20 Impact Factor
  • Gastroenterology 01/2003; 124(4). · 12.82 Impact Factor
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    Ulrika Lorentzon Fagerberg