Natural history of celiac disease-associated antibodies and progression to overt disease in children at increased genetic risk

Background: Celiac disease is a lifelong, gluten-sensitive, autoimmune-mediated chronic enteropathy, tightly associated with risk alleles at the HLA class II genes. Aims: This study was carried out as a part of the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Project. The first aim was to study the natural history of celiac disease-associated antibodies before the diagnosis of celiac disease was made. The second aim was to describe when and in which order celiac disease-associated and type 1 diabetes-associated antibodies appeared in children with genetic risk for both diseases. Subjects and Methods: Antibodies against tissue transglutaminase (TGA) and other celiac disease-associated antibodies were measured in serum samples collected at 3- to 12-month intervals of children at genetic risk for celiac disease who participated in the DIPP project. Celiac disease was confirmed by duodenal biopsy. Type 1 diabetes-associated antibodies were measured in all samples that had been collected. Overt disease was diagnosed according to World Health Organization criteria. Follow-up continued until a diagnosis of type 1 diabetes or until the end of a defined follow-up period. Results: TGA appeared in children at genetic risk for celiac disease only after the first year of life, but anti-gliadin antibodies often emerged significantly earlier, at age 6 months. The data show that spontaneous disappearance of celiac disease-associated antibodies, transient or persisting, is a common phenomenon, at least in prepubertal children. In children with genetic susceptibility to type 1 diabetes and celiac disease, celiac disease-associated antibodies usually develop earlier than the type 1 diabetes-associated antibodies. Conclusions: The transient nature of celiac disease-associated antibodies emphasizes the significance of establishing seropositivity repeatedly in screening detected celiac disease before gastroscopy and duodenal biopsy are considered and emphasized the importance of duodenal biopsy for diagnosing celiac disease.

Burden of Influenza in Children

Background: Most children with influenza are treated as outpatients but, especially among young children, influenza-attributable illnesses often result in hospitalization. However, relatively scarce data exist on the clinical picture and the full disease burden of pediatric influenza. Prompt diagnosis of influenza could enable the institution of antiviral therapy and adequate cohorting of patients. Data are needed to help clinicians correctly suspect influenza at the time of hospital admission. Aims and methods: We conducted a prospective 2-year cohort study of respiratory infections in children aged ≤13 years to determine the incidence of influenza in outpatient children and to assess the clinical presentation of influenza in various age groups seen in primary care. We also determined the rates of different complications attributable to influenza and the absenteeism of the children and their parents due to the child’s influenza infection. We then conducted a further 16-year retrospective study of children ≤16 years of age, hospitalized with virologically confirmed influenza. We estimated the population-based rates of hospitalizations and determined the primary admission diagnoses of the hospitalized children in different age groups. Results: The average annual rate of influenza was highest (179 / 1000) among children <3 years old. In this age group, acute otitis media was diagnosed as a complication of influenza in 40% of children. High fever was the most prominent sign of influenza, and 20% of children <3 years of age had a fever ≥40oC. Most children had rhinitis already during the first days of the illness. The average annual incidence of influenzarelated hospitalization was highest (276 / 100,000) among infants <6 months of age, of whom 52% were primarily admitted due to sepsis-like illnesses. Respiratory symptoms accounted for 38% of the hospitalizations. Conclusions: Influenza causes a substantial burden of illness on outpatient children and their families. The clinical presentation of influenza is most severe in children <3 years of age. The high incidence of influenza-associated hospitalizations among infants aged <6 months calls for more effective ways to prevent influenza in this age group. The clinical manifestations of influenza vary widely in different age groups of children at the time of hospital admission. Awareness of this phenomenon is important for the early recognition of the illness and the potential initiation of effective antiviral treatment of these patients.