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Background Young adults with childhood-onset inflammatory bowel disease (IBD) have increased risks of low areal bone mineral density and low skeletal muscle mass. Volumetric BMD (vBMD), bone geometry and microstructures, in addition to possible associations with skeletal muscle index (SMI) and physical exercise have been scarcely studied in this patient group. Patients and methods In total, 49 young adult male patients with childhood-onset IBD and 245 age- and height-matched young adult male controls were scanned with high-resolution peripheral quantitative computed tomography. Bone geometry, vBMD, and bone microstructures were calculated as median values and compared between the patients and controls. Multivariable linear regression analyses were performed to determine the independent associations among IBD diagnosis, SMI (kg/m2), and physical exercise. Results The group of young adult patients had, in comparison with the controls, significantly smaller median cortical area (126.1 mm2 vs151.1 mm2, P Conclusions Young adult men with childhood-onset IBD are at increased risk of having reduced bone quality in both the cortical and trabecular bone structures compared with normative matched controls.

Background Patients with inflammatory bowel disease (IBD) have an increased risk of compromised bone mineral density (BMD) and body composition. There are limited data on the physical exercise (PE) habits of patients with childhood-onset IBD and on the associations between PE and BMD and body composition. Patients and methods In total, 72 young adults with childhood-onset IBD and 1341 normative young adult controls answered questionnaires regarding PE [hours/week (h/w)] in the last 12 months. BMD and body composition were measured with dual x-ray absorptiometry (DXA) and presented as age- and gender-adjusted Z-scores for BMD, skeletal muscle index (SMI, the weight of lean mass in arms and legs/m2), and percentage body fat (Fat %). Results A total of 41 (57%) patients with IBD engaged in PE during the previous 12 months, as compared to 913 (68%) of the controls (p = .053). Sedentary patients had significantly lower median BMD, SMI, and Fat % Z-scores than the controls with corresponding PE habits (all p 4 h/week) patients had total body BMD, SMI, and Fat % in the same range as the controls with corresponding PE levels (p = .151, p = .992, and p = .189, respectively), albeit with lower BMDs in the spine (p = .007) and femoral neck (p = .015). Using multiple regression analyses, a diagnosis of childhood-onset IBD was independently associated with inferior BMD and body composition, regardless of the amount of PE. Conclusion Physical exercise is associated with beneficial bone mineral density and body composition in patients with IBD despite the negative effects of the disease.

Aim To examine the clinical follow up of paediatric coeliac disease and the rate of loss of follow up during childhood, for which data are scarce. Methods In a cohort of coeliac children diagnosed in 2013–2018 in Gothenburg, Sweden, we retrospectively explored the follow-up practice of paediatric coeliac disease until June 2021. We used medical records from hospital-based paediatric gastroenterology and general paediatric outpatient clinics, laboratory records, and questionnaires. Loss of follow up was defined no coeliac disease-related follow up or tissue transglutaminase test over the past 2 years of study enrolment. Results We included 162 children (58% girls) aged 7.8–18.2 years (average 12.7). Most participants (76%) were followed at general paediatric outpatient clinics rather than hospital-based clinics. After 2.3–8.8 (average 5.3) years since diagnosis, 23 patients (14%; 95% confidence interval, 9%–21%) had been lost to follow up. Patients with loss of follow up were more often boys (61% versus 39%, p = 0.08), with a somewhat longer average disease duration of 5.8 versus 5.2 years (p = 0.11). There were no between-group differences in socio-economic characteristics and patient-reported experience measures of coeliac disease care. Conclusion One in seven coeliac patients may experience loss of follow up during childhood.

INTRODUCTION: Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients.METHODS: Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally.RESULTS: The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient.DISCUSSION: The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).

Background: Patients with inflammatory bowel disease (IBD) often develop alterations in body composition in terms of their proportions of lean mass and fat mass, as well as reduced bone min...

Background: Children who have inflammatory bowel disease (IBD) have increased risk of low bone mineral density (BMD). There is a scarcity of information on BMD development through puberty and into young adulthood in patients with childhood-onset IBD. Methods: We conducted a prospective longitudinal study of BMD in patients with childhood-onset IBD. In total, 74 children with IBD were followed into young adulthood, with a mean follow-up of 8.4 years. The BMD was assessed longitudinally using dual-energy X-ray absorptiometry of the lumbar spine, total hip and whole body, and related to anthropometric measures. Results: Young adult male patients with IBD had lower mean BMD Z-scores for the lumbar spine at −0.8 (±1.1 SD) and total hip at −0.5 (±0.9 SD), as compared to standard references. In young female patients, the BMD Z-scores were within the normal range at all 3 measured sites as compared to the standard references. There were no significant differences in the BMD Z-scores between patients with Crohn's disease and patients with ulcerative colitis. The female and male patients showed significantly improved mean lumbar spine BMD Z-scores during follow-up into young adulthood, indicating that bone accumulation in the lumbar spine continues beyond the expected age for achieving peak bone mass. Conclusions: Male patients with childhood-onset IBD seem to have an increased risk of compromised BMD in young adulthood. Both female and male patients with IBD seem to increase their BMD beyond the age for expected peak bone mass (see Video abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B648).

Background Giant papillae tongue disorder (GPTD) is a newly discovered, long-lasting clinical disorder that may develop in organ-transplanted pediatric recipients. The key feature of this disorder is the unique tongue lesion, which comprises swollen fungiform papillae. The aim of this study was to characterize the immunohistopathology of this novel inflammatory condition. Methods Six organ transplanted children with GPTD were included in the study. Routine histopathology and immunohistochemical stainings for CD3, CD4, CD8, CD25, FOXP3, CD20, CD138, CD68, CD1a, CD15, CD23, and mast cell tryptase were performed. Results Immunohistochemical analyses of the oral lesions revealed a subepithelial infiltrate that was primarily composed of CD3- and CD4-positive T cells, CD20-expressing B cells, macrophages, and CD138-positive plasma cells. The CD20-positive cells did not display the typical B cell morphology, having in general a more dendritic cell-like appearance. The CD138-expressing plasma cells were distinctly localized as a dense infiltrate beneath the accumulation of T cells and B cells. Increased numbers of CD1a-expressing Langerhans cells were detected both in the epithelium and connective tissue. Because no granulomas were observed and only single lesional eosinophils were detected, GPTD does not resemble a granulomatous or eosinophilic condition. Conclusions We describe for the first time the immunopathological characteristics of a novel inflammatory disorder of the oral cavity, which may develop after solid organ transplantation in children.

Background Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric EoE and adult EoE represent different disease entities. The objectives of this study were to determine whether the blood eosinophil molecular pattern of children with EoE is (i) distinct from that of healthy children; and (ii) different from that of adults with EoE. Methods Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3, and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data were analyzed using a multivariate method of pattern recognition. Results An eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers. Conclusions Children with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children vs adults with EoE.

Allergy and other immune-mediated diseases are more frequently reported in children who have undergone liver transplantation. Furthermore, autoantibodies are also prevalent, suggesting a state of immune dysregulation in these patients. Whether or not these processes occur simultaneously in the same individual has not been studied previously.A cohort of 43 children who had undergone liver transplantation for nonautoimmune liver disease at median age of 1.3 years was investigated for allergy and autoimmune disease. Sensitization to food and inhalant allergens was assessed, and autoantibodies were measured.The prevalence of food allergy was 26% and that of respiratory allergy was 23%, whereas 33% and 26% of the subjects were sensitized to food and inhalant allergens, respectively. Autoimmune disease (ie, autoimmune hepatitis) occurred in a single individual (2%), whereas autoantibodies were present in 44% of the children. Food allergy and autoantibodies occurred concomitantly in 19% of the children, which was almost twice the frequency expected by chance (11%, P = 0.04). Respiratory allergy and the presence of autoantibodies were unrelated (12% concurrence versus the expected 10%, P = 0.73). In the logistic regression analysis, autoantibody formation was associated with discontinued immunosuppression and food allergy, with odds ratios of 13 (P = 0.01) and 7.1 (P = 0.03), respectively.In contrast to respiratory allergy, food allergy and autoantibody formation occurred together in the same children who underwent liver transplantation at a frequency higher than would be expected by chance. This may reflect an underlying immune dysregulation that impairs immune tolerance to both food allergens and autoantigens.

The gut microbiota harbor a wide range of bacterial species, but also yeasts may be part of this ecosystem. Infants who are being treated in intensive care units are often colonized by Candida species. However, little is known regarding commensal yeast colonization of healthy infants and young children. Here the acquisition of yeast species was studied in a birth-cohort including 133 healthy Swedish infants. A rectal swab sample was obtained on day 3 of life, and fresh fecal samples were obtained at regular intervals up to 3 years of age; the samples were cultured quantitatively for yeasts. Colonization with yeasts increased rapidly in the first months of life, with 73/133 infants (55%) colonized at 6 months of age. The yeast numbers in positive samples decreased from an average of 105 cfu/g in infants aged 0–2 months to 103.5 cfu/g at 3 years of age. Candida albicans was the most frequently isolated species and reached higher population counts than the other species in culture-positive infants. The yeast colonization rate did not differ between infants who were delivered vaginally and those birthed via Caesarean section, whereas breastfed infants showed a lower colonization rate (p < 0.05 for 1 year of age compared to the other infants). The results demonstrate that yeasts, particularly C. albicans and C. parapsilosis (sensu lato), are common commensals in the gut microbiota of healthy infants and young children.

Summary Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of Tregs, was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in Tregs. To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE.

Background: Although orofacial granulomatosis (OFG) may present as a separate clinical entity, it often seems in conjunction with various systemic diseases, of which Crohn's disease (CD) is one of the most common. The aim of this study was to investigate whether CD with concomitant OFG represents a distinctive disease subtype. Methods: Twenty-one patients with CD and concomitant OFG (CD+OFG group) were included in the study. As the reference group, a cohort of 39 patients with CD but without OFG (CD-R group) was used. Demographic data and clinical characteristics were recorded at the time of diagnosis. The 2 groups were compared using multivariate analyses. Results: The percentage of patients with intestinal inflammation in the upper gastrointestinal tract was significantly higher in the CD+OFG group, as compared with the CD-R group (81% versus 33%; P < 0.001). Furthermore, ileocolonic inflammation was significantly more common in the CD+OFG patients (81% versus 46%; P = 0.013). In addition, perianal disease was more frequently observed in the CD+OFG group (48% versus 18%; P = 0.033). Significantly more patients showed evidence of granulomas in the primary endoscopy in the CD+OFG group than in the CD-R group (81% versus 38%; P = 0.003). Conclusion: The data from this study suggest that the presence of CD in conjunction with OFG represents a distinctive subphenotype of CD that is characterized by extensive inflammation, perianal disease, and pronounced granuloma formation in the intestine.

Clostridium difficile is a colonizer of the human gut, and toxin-producing strains may cause diarrhea if the infectious burden is heavy. Infants are more frequently colonized than adults, but they rarely develop C. difficile disease. It is not known whether strains of C. difficile differ in the capacity to colonize and persist in the human gut microbiota. Here, we strain typed isolates of C. difficile that had colonized 42 healthy infants followed from birth to ≥12 months of age by using PCR ribotyping of the 16S-23S rRNA intergenic spacer region. The isolates were also characterized regarding carriage of the toxin genes tcdA , tcdB , and cdtA/B and the capacity to produce toxin B in vitro . Most strains (71%) were toxin producers, and 51% belonged to the 001 or 014 ribotypes, which often cause disease in adults. These ribotypes were significantly more likely than others to persist for ≥6 months in the infant micobiota, and they were isolated from 13/15 children carrying such long-term-colonizing strains. Ribotype 001 strains were often acquired in the first week of life and attained higher population counts than other C. difficile ribotypes in newborn infants' feces. Several toxin-negative ribotypes were identified, two of which (GI and GIII) were long-term colonizers, each found in one infant. Our results suggest that the toxin-producing C. difficile ribotypes 001 and 014 have special fitness in the infantile gut microbiota. Toxin-producing strains colonizing young children for long time periods may represent a reservoir for strains causing disease in adults.

OBJECTIVE: Immune stimulation through exposure to commensal microbes may protect against allergy development. Oral microbes may be transferred from parents to infants via pacifiers. We investigated whether pacifier cleaning practices affected the risk of allergy development. METHODS: A birth-cohort of 184 infants was examined for clinical allergy and sensitization to airborne and food allergens at 18 and 36 months of age and, in addition, promptly on occurrence of symptoms. Pacifier use and pacifier cleaning practices were recorded during interviews with the parents when the children were 6 months old. The oral microbiota of the infants was characterized by analysis of saliva samples collected at 4 months of age. RESULTS: Children whose parents “cleaned” their pacifier by sucking it (n = 65) were less likely to have asthma (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.01–0.99), eczema (OR 0.37; 95% CI 0.15–0.91), and sensitization (OR 0.37; 95% CI 0.10–1.27) at 18 months of age than children whose parents did not use this cleaning technique (n = 58). Protection against eczema remained at age 36 months (hazard ratio 0.51; P = .04). Vaginal delivery and parental pacifier sucking yielded independent and additive protective effects against eczema development. The salivary microbiota differed between children whose parents cleaned their pacifier by sucking it and children whose parents did not use this practice. CONCLUSIONS: Parental sucking of their infant’s pacifier may reduce the risk of allergy development, possibly via immune stimulation by microbes transferred to the infant via the parent’s saliva.

OBJECTIVES:: Low bone mineral density (BMD) is recognized as a potential problem in children with inflammatory bowel disease (IBD). We aimed to describe the longitudinal development of BMD in a population of Swedish pediatric patients with IBD. METHODS:: A total of 144 IBD patients (93 males; 83 with ulcerative colitis (UC), 45 with Crohn's disease (CD)) were examined with dual-energy X-ray absorptiometry (DXA) at baseline. At follow-up two years later, 126 of the initial 144 patients were re-examined. BMD values are expressed as Z-scores. RESULTS:: Children with UC and CD had significantly lower mean BMD Z-scores of the lumbar spine (LS) at baseline and after two years. The reduction in BMD was equally pronounced in UC and CD patients, and neither group improved their Z-score during the follow-up period. Furthermore, significantly lower mean BMD Z-scores LS were found at baseline in males (-1.1 SD, ± 2.7 SD, p

Perceptions of living with inflammatory bowel disease (IBD) during adolescence were explored in a cross-sectional study with a multimethod design. The adolescents as a group described general well-being and ability to handle the disease, which was related to their self-reported self-esteem. However, a subgroup of adolescents with a severe disease course reported a more negative view of the impact of IBD in their daily lives. Encouraging adolescents to communicate in different ways may help professionals to identify vulnerable subgroups with impaired health and to provide more appropriate support and treatment for those most in need.

Diagnosing asthma is difficult in infants and preschool children because wheezing is common in this age group and it is not synonymous with asthma. Some children outgrow the tendency to wheeze during colds in a few years’ time, whereas other develop asthma. Efforts have been made to find ways to identify the subgroup of preschool children with wheeze who are most likely to develop asthma (1,2). However, the different asthma predictive indexes mainly aim to predict children who will have a persistent wheeze or asthma, not necessarily the subgroup who will outgrow their symptoms. This article is protected by copyright. All rights reserved.

Staphylococcus aureus is a pathogen and a skin commensal that is today also common in the infant gut flora. We examine the role of S. aureus virulence factors for gut colonization. S. aureus isolated from quantitative stool cultures of 49 Swedish infants followed from birth to 12 months of age were assessed for 30 virulence-associated genes, spa type, and agr allele by serial polymerase chain reaction (PCR) assays. Strains carrying genes encoding collagen-binding protein, and the superantigens S. aureus enterotoxin O/M (SEO/SEM) had higher stool counts than strains lacking these genes, whereas genes for S. aureus enterotoxin A (SEA) were associated with low counts. A cluster of strains belonging to agr allele I and the spa clonal cluster 630 (spa-CC 630) that carried genes encoding SEO/SEM, SEC, collagen-binding protein, and elastin-binding protein were all long-time colonizers. Thus, certain S. aureus virulence factors might promote gut colonization.

Background and Aim: Low bone mineral density (BMD) has recently been recognized as a potential health problem in children with inflammatory bowel disease (IBD). Our aim was to investigate the familial resemblance of BMD in pediatric patients with IBD. Patients and Methods: In this population-based study from western Sweden, we assessed 144 children with IBD, 83 with ulcerative colitis, 45 with Crohn disease, 16 with indeterminate colitis, and their parents (136 mothers and 130 fathers) with dual-energy X-ray absorptiometry (DEXA). After adjustment for sex, age, weight, height, and parental IBD, we correlated the BMD of the patients to the BMD of their mothers, fathers, and the midparent value ([mother's BMD + father's BMD]/2) at different skeletal sites and calculated the Pearson correlation coefficient (r) to evaluate the extent of familial resemblance. Results: The BMD of the children with IBD was clearly related to the BMD of their parents. The strongest correlation was found in the femoral neck with r = 0.55 (P < 0.001, 95% CI 0.41―0.66) between BMD of the children and the midparent value. The group of children with IBD had an odds ratio of 5.96 for decreased BMD (lumbar spine z score < ―1 standard deviation) given that decreased BMD was diagnosed in both parents. Conclusions: We conclude that BMD in children and adolescents with IBD is significantly related to that of their parents. In a clinical setting, it may be helpful to assess the parents of children with IBD with DEXA to interpret the children's DEXA measurements.

Objective: To investigate if the development of allergic diseases during the child’s first 18 months of life is influenced by the time at which different food items were introduced into the child’s diet. Method: A birth cohort of 184 children was followed to 18 months of age. Diaries were used to document feeding practices, and parental interviews were performed at 6 and 12 months of age, probing for symptoms suggesting allergic disease, general health-related issues and food introduction regimes. Symptoms promoted prompt clinical examination, and all children were examined clinically, and tested for sensitization to common airborne and food allergens at 18 months of age. Results: The earlier the fish was introduced into the child’s diet the lower was the frequency of eczema. This association remained after control for confounding factors. The timing of fish introduction and asthma development showed a similar pattern, but did not reach statistical significance. Sensitization was not influenced by the timing of fish introduction. Other food items or feeding practices did not seem to influence allergy development. Conclusion: Early introduction of fish into the child’s diet was associated with less eczema development, and a tendency to less asthma. Sensitization was not associated with the timing of fish introduction.

Summary Background Epidemiological studies point to an inverse relationship between microbial exposure and the prevalence of allergic diseases. The underlying mechanism for this observation remains largely unknown, as well as the nature of the microbes involved. Objective To investigate the effects of early infection with human herpesviruses (HHVs) on IgE formation and T-helper type 2 (Th2) development in infants. Methods Serum was collected from children aged 18 months and assessed for IgE to common allergens and IgG to five common herpesviruses. Cord blood plasmacytoid dendritic cells (pDC) were exposed to HHV type 6 in vitro and mixed with allogeneic cord blood CD4+ T cells. Cytokine levels were determined by ELISA and by flow cytometry. Results We found that children seropositive at 18 months of age to HHV type 6 were significantly less often IgE sensitized than seronegative children [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.009–0.68]. HHV type 6 also decreased the production of the Th2-associated cytokines IL-5 and IL-13 by CD4+ T cells when co-cultured with allogeneic cord blood pDC. This was associated with an increased production of IFN-α by pDC exposed to HHV type 6. Conclusion These data indicate that an early childhood infection with HHV type 6 could down-regulate Th2 responses and reduce IgE formation to common allergens in a young child.

Background. Acute oral angioedema is well documented in young pediatric liver-transplanted patients. This is a report of an identified novel entity of long-standing oral mucosal lesions (OML) in children who had undergone solid organ transplantation. Methods. In conjunction with routine medical follow-ups, all solid organ-transplanted children were examined annually for OML. Results. Eight children developed a novel entity of long-standing OML after solid organ transplantation. Seven of the eight children had undergone liver transplantation whereas one child was kidney transplanted. The children received tacrolimus immunosuppression after transplantation. All recipients presented with multiple spherical nodules on the dorsum of the tongue, which later on displayed a fissured appearance. Most patients also presented with mucosal tags or ridges and swollen lips similar to those found in patients with orofacial granulomatosis. In addition, most patients had a clinical history of immediate-onset food-induced allergic reactions, including transient angioedema, after transplantation, but this clinical manifestation appeared separately from the long-standing lesions. Conclusion. A novel entity of long-standing OML that share some features with orofacial granulomatosis has been identified in children after solid organ transplantation.

Background: Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD. Methods: To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine. BMD values were expressed as Z-scores using normative pediatric data from Lunar (GE Medical Systems). Results: In this population-based study, the lowest BMD values were found in the lumbar spine. The entire IBD group showed significantly lower BMD Z-scores of the lumbar spine (L2–L4) in comparison to healthy references (−0.8 standard deviation [SD], range −5.9 to 3.7 SD, P < 0.001). Decreased BMD with a Z-score < −1 SD occurred in 46.7% of the individuals with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low BMD with a Z-score ≤ −2 SD was present in 26.7% of the patients with CD and in 24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as the depending variable, possible factors associated with lower BMD were male gender, low body mass index (BMI), and treatment with azathioprine. Conclusions: Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk factors for lower BMD are male gender, low BMI, and treatment with azathioprine, as a probable marker of disease course severity. (Inflamm Bowel Dis 2009)

AIM: To compare the self-esteem of adolescents suffering from inflammatory bowel disease (IBD) with that of healthy adolescents, and to identify factors affecting self-esteem in the presence of IBD. METHODS: A self-assessment questionnaire, 'I think I am' (ITIA), was completed by 71 (41 boys) out of 77 adolescents (10-16 years) with IBD. Of the participating adolescents, 23 had Crohn's disease, 44 had ulcerative colitis and 4 had indeterminate colitis. The self-esteem of adolescents with IBD was compared with that of 1037 school children. RESULTS: In this population-based study, children with IBD estimated their self-esteem in the same range as healthy adolescents. Using a multiple regression analysis, the self-esteem of adolescents with IBD was related to disease course severity and cohabitation status of parents. Children with severe disease and children of single parents were found to be most at risk of low self-esteem. CONCLUSION: This study shows that, as a group, adolescents with IBD have self-esteem in the same range as their healthy peers, but that there are some adolescents with IBD who are at risk of low self-esteem. Special attention should be given to adolescents with a severe disease course and to those with separated parents.

This is a grounded theory study to identify concepts for describing how adolescents with inflammatory bowel disease (IBD) respond to their parents' concern for them. Ten adolescent boys and seven girls were interviewed. In the analysis four main categories emerged: ambivalence, ability/inability, compliance/resistance and trust/distrust. We found ambivalence to be the most distinctive theme to appear in the way in which these young people described how they felt about their parents' response to their disease. The core category ambivalence was expressed as an oscillation between seeking close contact with one's parents or, sometimes, staving them off, one moment feeling anxiously dependent upon them or turning to them for protection and support and the next, trying to achieve a dialogue with them. The core category comprised three subcategories, ability/inability, compliance/resistance and trust/distrust. The clinical support for young individuals with IBD should include an awareness of the simultaneous existence of conflicting attitudes, reactions and emotions.

Background: Stimulation of the immune system by gut microbes might prevent allergy development. Objective: The present study examined the hypothesis that sensitization to food allergens and atopic eczema are influenced by the infantile intestinal colonization pattern. Methods: Infants were recruited perinatally in Goteborg (n = 116), London (n = 108), and Rome (n = 100). Commensal bacteria were identified to the genus or species level in rectal (3 days) and quantitative stool cultures (7, 14, and 28 days and 2, 6, and 12 months of age). At 18 months of age, atopic eczema and total and food-specific IgE levels were assessed. These outcomes were modeled in relation to time to colonization with 11 bacterial groups and to ratios of strict anaerobic to facultative anaerobic bacteria and gram-positive to gram-negative bacteria at certain time points. Study center, mode of delivery, parity, and infant diet were included as covariates. Results: Neither atopic eczema nor food-specific IgE by 18 months of age were associated with time of acquisition of any particular bacterial group. Cesarean section delayed colonization by Escherichia coli and Bacteroides and Bifidobacterium species, giving way to, for example, Clostridium species. Lack of older siblings was associated with earlier colonization by Clostridium species and lower strict anaerobic/facultative anaerobic ratio at 12 months. Conclusions: This study does not support the hypothesis that sensitization to foods or atopic eczema in European infants in early life is associated with lack of any particular culturable intestinal commensal bacteria. Clinical implications: The nature of the microbial stimulus required for protection from allergy remains to be identified.

Summary Background Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown. Methods We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age. Results Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non-colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development. Conclusions Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.

OBJECTIVE: Intestinal and multivisceral transplantation have gained acceptance as treatment modalities for patients with: intestinal failure and life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and selected cases of low-grade neoplastic tumors such as neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The aim was to describe the survival and nutritional outcome in the transplanted Nordic patients and the complications attributed to this procedure.METHOD: The authors included all Nordic patients transplanted between January 1998 and December 2013. Information on patients transplanted outside the Nordic region was collected through questionnaires.RESULTS: A total of 34 patients received different types of intestinal allografts. Currently, there are two Nordic transplant centers (n = 29) performing these procedures (Gothenburg, Sweden n = 24, Helsinki, Finland n = 5). The remaining five patients were transplanted in the USA (n = 3) and the UK (n = 2). Most patients were transplanted for life-threatening failure of PN (70%) caused primarily by intestinal motility diseases (59%). Allograft rejection was the most common complication and occurred in 79% of the patients followed by post-transplantation lymphoproliferative disorders (21%) and graft-versus-host disease (18%). The 1- and 5-year survival was 79% and 65% respectively for the whole cohort and nutritional autonomy was achieved in 73% of the adults and 57% of the children at 1 year after transplantation.CONCLUSION: This collective Nordic experience confirms that intestinal transplantation is a complex procedure with many complications, yet with the possibility to provide long-term survival in selected conditions previously considered untreatable.

Effective immunosuppression has improved the results following liver transplantation, but also increased the risk for opportunistic infections. Epstein-Barr virus (EBV) infection in transplant patients can cause various symptoms including the life-threatening premalignant condition, post-transplantation lymphoproliferative disorder (PTLD). Serum specimens from 24 consecutive children (mean 7.6 specimens/patient), who had undergone liver transplantation in Göteborg from January 1995 to May 2002, were analyzed retrospectively for EBV DNA by real-time TaqMan polymerase chain reaction (PCR). The results were related to clinical picture, immunosuppression, graft rejection and infections with other agents. Eleven patients (46%) developed primary EBV infection at a mean time of 4.8 months after transplantation, and six (25%) reactivated EBV infection at a mean of 4.0 months after transplantation. Four of the 11 patients with primary infection had symptomatic EBV infection: two had PTLD and two hepatitis. One patient in the group with reactivated infection developed PTLD. EBV DNA levels were significantly higher in the group with primary symptomatic infection compared with the patients with primary asymptomatic infection (mean 65 500 copies/mL; range 14 200-194 300 vs. 3700 copies/mL; range 100-9780). In patients with symptomatic infection EBV DNA levels did not differ between PTLD and hepatitis patients. The data suggest that quantitative analysis of EBV DNA in serum by real-time PCR is useful for identification of EBV-related disease.

Colonization by Escherichia. coli in infants might have decreased in the last decades, owing to changes in hospital routines and family lifestyle. In this study, the E. coli flora was characterized in 70 healthy Swedish infants followed for the first year of life. E. coli was isolated from rectal swabs obtained at 3 d of age and quantified in fecal samples collected at 1, 2, 4, and 8 wk of age and at 6 and 12 mo of age. Strains were typed using random amplified polymorphic DNA, and their virulence factor genes were identified by multiplex PCR. Colonization by E. coli occurred late; only 61% of the infants were positive by 2 mo of age. The turnover of individual strains in the microflora was slow (1.5 strains per infant during 6 mo, 2.1 during 1 y). Environmental factors, such as siblings, pets, or feeding mode, did not influence colonization kinetics or strain turnover rate. Genes encoding type 1 fimbriae, P fimbriae, and hemolysin were significantly more common in E. coli strains persisting for at least 3 wk in the microflora than in transient strains. The P-fimbrial class III adhesin gene was more common in E. coli from children who had a cat in their homes than in E. coli from children without pets (p = 0.01); this adhesin type is common in E. coli from cats. The late colonization and low E. coli strain turnover rate suggest limited exposure of Swedish infants to E. coli. Our results confirm that P fimbriae and other virulence factors facilitate persistence of E. coli in the human colonic microflora.

Objective To compare oral manifestations in a Swedish cohort of patients with orofacial granulomatosis with or without Crohn′s disease and to assess NOD2 polymorphisms in the two groups. Methods Twenty-nine patients with orofacial granulomatosis were included. Demographics, disease history, clinical features and concurrent Crohn′s disease were recorded. DNA was extracted from buccal swabs and examined for NOD2 variants Arg702Trp, Gly908Arg and Leu1007fsinsC, all previously linked to gastrointestinal Crohn′s disease. Results Twelve of 29 patients were diagnosed with coexisting gastrointestinal Crohn′s disease, and of whom 21 were males. Symptom duration was significantly longer for the orofacial granulomatosis group com-pared to the group with coexisting Crohn′s disease (P

Objectives: The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn’s disease (OFG+CD). Study Design: Biopsy specimens with granulomas were obtained from patients with OFG-S (n=11) and OFG+CD (n=11) and immunostained with antibodies against CD1a, CD3, CD4, CD8, CD11c, CD20, CD68 and mast cell tryptase, followed by quantitative analysis. Results: Analyses of the connective tissue revealed a significantly higher number of CD3-expressing T cells and CD11c-expressing dendritic cells in the connective tissue of patients with OFG-S compared to patients with OFG+CD. Mast cells displayed a high level of activation, although no significant difference was detected when comparing the two groups. Conclusions: The results show a different composition of the inflammatory infiltrate in patients with OFG-S compared to patients with OFG+CD. The present observations support that partly divergent immune mechanisms are involved in these two different subcategories of OFG. Key words:Granulomas, autoimmunity, T cells, B cells, dendritic cells, children, adults.

Recently, sera from children with active coeliac disease were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) of gliadin-coated cells. In the present study, the subclass profile of immunoglobulin (Ig)G antigliadin antibodies in sera from young children, with or without coeliac disease, was determined and related to the ADCC-mediating capacity of the same sera. In addition, IgG subclasses were selectively depleted from sera and the effect on ADCC-mediating was studied. Children with untreated coeliac disease had high antigliadin antibody activities of all four IgG subclasses. However, they had a particularly high proportion of IgG1 antigliadin antibodies (ratio IgG1/IgG) compared with healthy references or coeliac children in remission. In contrast, children who had high serum antigliadin antibody activity but no histological signs of enteropathy (disease references), showed significantly lower proportions of antigliadin antibodies of the IgG1 as well as the IgG3 subclass compared with healthy references or untreated coeliac children. Regression analysis showed that IgG1 and IgG3 antigliadin antibody activity correlated positively to ADCC-mediating capacity, and depletion of IgG1 from sera profoundly diminished ADCC. The results suggest that gliadin-specific antibodies of predominantly the IgG1 subclass mediate tissue-damaging immune reactions like ADCC, and may, thus, contribute to the disease process of coeliac disease.

One of the characteristic features of celiac disease is an increase in anti-gliadin antibodies (Abs). Recently we found that some of the monoclonal Abs to gliadin cross-react with molecules on rat enterocytes. One of these cross-reacting molecules was identified as rat calreticulin. This study shows that the levels of serum IgA Abs to gliadin, rat, and human enterocytes; purified enterocyte antigens; and calreticulin in sera from patients with active disease were significantly higher than in patients on a gluten-free diet and healthy controls (P < 0.001). Anti-gliadin Abs were isolated by affinity chromatography from the sera of six active celiac patients. The reactivity of these anti-gliadin Abs was demonstrated to be significantly higher (P < 0.05) with human enterocytes and human calreticulin than with other antigens tested. Furthermore, using isolated patients' anti-gliadin Abs bound to Sepharose 2B, two main proteins of molecular mass 62 and 66 kDa were purified from a lysate of human enterocytes. The 62-kDa enterocyte antigen was identified as human calreticulin. These findings suggest that anti-gliadin Abs may play a pathogenic role in celiac disease by cross-reacting with enterocytes. Calreticulin in enterocytes may be one of the putative targets for autoimmune reactions.

The rate of PTLD can be reduced by weaned IS guided by monitoring of EBV DNA. In this single-center retrospective case series study, we analyzed how reduction in IS influenced EBV DNA levels in whole blood and serum in 30 children during the first year after liver transplantation, and how these levels were related to symptoms putatively due to EBV. Primary and reactivated EBV infection was seen in 18 (60%) and eight patients (27%), respectively. Thirteen patients (42%) developed chronic high load the first year post-transplant. IS was successfully discontinued in six patients the first year post-transplant and in another two patients within 3 years. EBV DNA levels were reduced, but persisted long term in all the eight patients who had IS completely withdrawn. There was no case of PTLD. In summary, EBV DNAemia and chronic high load were very common after pediatric liver transplantation. Liver graft tolerance facilitates radical reduction in IS treatment, which may prevent PTLD, but EBV DNAemia may persist long term after discontinued IS.

Background The aim was to investigate whether young children with drug-refractory nausea and vomiting can be treated with gastric electrical stimulation (GES) in a similar way as adults and to evaluate whether temporary percutaneous gastric electrical stimulation (TPGES) can be used in the pediatric population to select the patients who are responders to GES treatment. We report the clinical results in 3 children between 2 and 3 years of age. To the best of our knowledge, these are the youngest patients treated with GES. Methods Three patients younger than 3 years with intractable vomiting underwent TPGES. Custom-made leads were percutaneously implanted in the gastric wall under gastroscopic guidance. Symptoms were recorded daily during the TPGES stimulation time (12-40 days). Responders were offered permanent GES treatment. Results There were no technical problems. All 3 patients were responders to TPGES. They are now treated with surgically implanted permanent GES and reported greater than 50% vomiting reduction at last visit. Conclusion Children younger than 3 years can be treated with GES in a similar way as adolescents and adults. Temporary percutaneous GES is a safe, feasible technique even in small children, with the possibility to perform the test over several weeks to select responders to GES treatment.

Aim: The aim of this study was to explore parents' views and agreement of their child's current and future health, as well as the family's functioning in daily life with inflammatory bowel disease (IBD). Methods: In this study, 119 parents (65 mothers and 54 fathers) of 66 adolescents (11-16 years) with IBD completed a questionnaire regarding their views of their child's IBD and health-related behaviour. Results: The majority of the parents held a positive view of their child's current health status. However, the parents voiced a range of worries about their children's future health and life situation such as fear about the side effects of medication, concerns for future schooling, social life and employment options. Within the families, the parental pairs had more similar views about their child's current health status than about their future health. Factors that affected the parents' views consisted of cohabitation status, i.e. parents not living together, and severe disease course, both correlated with a more negative view of the child's current health and family functioning. Conclusion: The majority of the parents in this study had a largely positive view of their child's current health status, but they expressed concerns about their child's future health. Knowledge about parents' thoughts may be of importance for healthcare teams supporting families with IBD.

Aim: Orofacial granulomatosis (OFG) is a rare clinical entity with orofacial swelling in association with oral lesions such as mucosal oedema, ulcerations and mucosal tags. The aim of this prospective study was to evaluate the connection between OFG in childhood and systemic disease. Methods: During a 3-year period, eight children (9–16 years old) who had been referred to the clinic of oral medicine were diagnosed solely with OFG. Thus, none of them had any known systemic disease or gastrointestinal symptoms at the time of referral. The children were then medically examined and followed up for 6–8 years at the department of paediatrics for systemic disease with specific emphasis on inflammatory disorders elsewhere in the gastrointestinal tract. Results: During follow-up, four patients were diagnosed with Crohn's disease (CD). Further, one girl was found to have a food allergy-induced OFG, with delayed-type hypersensitivity to oats. One boy developed both diabetes and celiac disease during the follow-up. Only two patients had no diagnosis of systemic disease at the end of the observation period. Conclusion: OFG in childhood seems to be frequently related to systemic disease, and children with OFG should be referred to a paediatrician for examination and follow-up.

Summary Background Intestinal bacteria trigger IgA production and delayed maturation of mucosal IgA response is linked to allergy development. Objective Our aim was to investigate if plasma levels of IgA or APRIL (a proliferation inducing ligand), an important factor for IgA class switch recombination, in infancy correlates with intestinal colonization by any specific bacteria or yeast. We also examined if plasma IgA or APRIL levels are related to sensitization and the development of eczema. Methods IgA was quantified in plasma obtained from infants at birth and at 4 and 18 months of age and APRIL was measured at 4 months of age. Colonization by major bacterial groups and yeast was followed in the first 8 weeks of life by quantitative culture of stool samples. A clinical evaluation regarding the presence of allergen-specific IgE or eczema and eosinophil counts in blood was performed at 18 months of age. Results In multiple linear regression analysis, only colonization by Staphylococcus aureus strains producing toxins with superantigen function (SEA-D or TSST-1) made an independent contribution to plasma IgA levels at 4 months of age. Further, increased levels of APRIL in plasma at 4 months were negatively associated with sensitization while IgA plasma levels were inversely correlated to eczema development and blood eosinophil counts at 18 months of age. Conclusion Early intestinal colonization by toxigenic S. aureus strains seems to promote systemic IgA responses. Furthermore, high levels of APRIL and IgA in the circulation at 4 months of age seem to correlate negatively with allergy development.

Background It might be that early intestinal colonization by bacteria in westernized infants fails to give rise to sufficient immune stimulation to support maturation of regulatory immune mechanisms. Objective The purpose of the present study was to characterize the very early infantile microbiota by using a culture-independent approach and to relate the colonization pattern to development of atopic eczema in the first 18 months of life. Methods Fecal samples were collected from 35 infants at 1 week of age. Twenty infants were healthy, and 15 infants were given diagnoses of atopic eczema at the age of 18 months. The fecal microbiota of the infants was compared by means of terminal restriction fragment length polymorphism (T-RFLP) and temporal temperature gradient gel electrophoresis (TTGE) analysis of amplified 16S rRNA genes. Results By means of T-RFLP analysis, the median number of peaks, Shannon-Wiener index, and Simpson index of diversity were significantly less for infants with atopic eczema than for infants remaining healthy in the whole group and for the Swedish infants when Alu I was used for digestion. The same was found when TTGE patterns were compared. In addition, TTGE analysis showed significantly less bands and lower diversity indices for the British atopic infants compared with those of the control subjects. Conclusion There is a reduced diversity in the early fecal microbiota of infants with atopic eczema during the first 18 months of life.