Causes of hematochezia and hemorrhagic antibiotic-associated colitis in children and adolescents.

Diseases causing hematochezia range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We studied the underlying causes and long-term outcome of hematochezia in children. We further investigated the relevance of antibiotic-associated hemorrhagic colitis in children, especially if caused by Klebsiella oxytoca.Infants, children, and adolescents with hematochezia were recruited prospectively. Patients were grouped according to age (<1 year, 1-5 years, 6-13 years, >14 years). In addition to routine diagnostics, K oxytoca stool culture and toxin analysis was performed. We collected data on history, laboratory findings, microbiological diagnostic, imaging, final diagnosis, and long-term outcome.We included 221 patients (female 46%; age 0-19 years). In 98 (44%), hematochezia was caused by infectious diseases. Endoscopy was performed in 30 patients (13.6%). No patient died due to the underlying cause of hematochezia. The most common diagnoses according to age were food protein-induced proctocolitis in infants, bacterial colitis in young children, and inflammatory bowel disease in children and adolescents. Seventeen (7.7%) had a positive stool culture for K oxytoca. Antibiotic-associated colitis was diagnosed in 12 (5%) patients: 2 caused by K oxytoca and 2 by Clostridium difficile; in the remaining 8 patients, no known pathobiont was identified.Infections were the most common cause of hematochezia in this study. In most patients, invasive diagnostic procedures were not necessary. Antibiotic-associated hemorrhagic colitis caused by K oxytoca was an uncommon diagnosis in our cohort. Antibiotic-associated colitis with hematochezia might be caused by pathobionts other than C difficile or K oxytoca.

B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.

Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase δ (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.

[Allergen-specific Immunotherapy for children and adolescents - a review on available products in Austria]. / Spezifische Immuntherapie bei IgE-vermittelten allergischen Erkrankungen im Kindes- und Jugendalter - eine Ubersicht über in Osterreich zugelassene/registrierte Allergenpräparate : Konsensus Report 2009 der AG Pneumologie und Allergologie der Osterreichischen Gesellschaft für Kinder und Jugendheilkunde.

A pediatric consensus report on allergen-specific immunotherapy for children and adolescents is presented for Austria. Products on the market in Austria are presented and categorised according to studies performed on the target population of children and adolescents, their effectiveness and indication. In general, more clinical studies on children and adolescents are mandatory for most of the available allergen-specific immunotherapeutics. In addition, the use of allergen-specific immunotherapy in general should be promoted as the exclusive treatment with long-lasting effects in type I allergies in particular in children.

Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice.

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1alpha of protein kinase A) mutations in CNC. Mutational analyses of the PRKAR1A gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to PRKAR1A haploinsufficiency. Therefore, we studied the consequences of prkar1a haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in prkar1a(+/-) mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover, prkar1a(+/-) mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from prkar1a(+/-) mice did not exhibit prkar1a loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation.