[Evidence of treatment of chronic inflammation in childhood and adolescence with biologics]. / Evidenz der Therapie chronisch-entzündlicher Erkrankungen in Kindheit und Adoleszenz mit Biologika.

BACKGROUND: Biologics, usually monoclonal antibodies or fusion proteins, are thought to specifically interfere with immunopathogenesis of chronic inflammatory diseases. In order to test these substances also in children and adolescents, financial incentives for manufacturers were created and classification of chronic inflammatory diseases and definition of disease activity, improvement, relapse and remission were established and large international research cooperation projects were founded. METHODS: A selective literature search was carried out for treatment of chronic inflammatory diseases in children and adolescents with biologics including current guidelines. RESULTS: Only 7 out of 18 prescribed biologics have been approved for children and mostly within narrow limits. The evidence for efficacy is based on four randomized double blind placebo-controlled studies, seven withdrawal studies and seven observational studies. In spite of the limited evidence in comparison to their use in adult patients these substances are broadly used worldwide and have enlarged and substantially improved the therapeutic choices in children when conventional treatment failed or proved to be toxic. Severe adverse events including infections occasionally occur (0.01-0.03 events per patient year) but the rate of malignancies is not obviously increased; however, only two thirds of patients respond to treatment. Improvement is often incomplete, some patients deteriorate and definite termination of drug treatment is possible in only a few patients. CONCLUSION: As the prescription of biologics has become an important issue of treatment but is based on insufficient evidence data, further studies are necessary in children and adolescents with diseases, such as juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis and inherited fever syndromes. As many drugs are available these studies can be conducted against verum.

[Immunization in children and adolescents with rheumatic and musculoskeletal diseases]. / Sinnvolle Impfprävention bei Kindern und Jugendlichen mit rheumatischen und muskuloskelettalen Erkrankungen.

BACKGROUND: Children and adolescents with inflammatory rheumatic diseases have a disease and treatment-related increased risk of infections. This risk includes vaccine-preventable diseases; therefore, vaccinations represent an important preventive measure against infection in these patients. However, approximately one in three patients with a juvenile rheumatic disease is nowadays still inadequately vaccinated, mostly due to uncertainty regarding the efficacy and safety of vaccination in these patients. OBJECTIVES: This paper summarizes the available evidence regarding the efficacy and safety of vaccinations in children and adolescents with rheumatic diseases and gives recommendations for the clinical practice. RESULTS AND PERSPECTIVES: Almost 2000 children and adolescents with rheumatic diseases were examined in the more than 30 previously published vaccination studies, comprising nearly all standard vaccinations in the immunization schedule. The immunogenicity was usually sufficient and there was no evidence of a relevant aggravation of the underlying disease. Recommendations for the clinical practice are given also considering data beyond pediatric rheumatology; however, a final benefit-risk assessment is not yet possible.

[Diagnosis and treatment of Lyme arthritis. Recommendations of the Pharmacotherapy Commission of the Deutsche Gesellschaft für Rheumatologie (German Society for Rheumatology)]. / Diagnostik und Therapie der Lyme-Arthritis. Empfehlungen der Kommission Pharmakotherapie der DGRh.

These guidelines summarize the current evidence for diagnosis and treatment of Lyme arthritis and the most frequent skin manifestations of Borrelia burgdorferi infections. Lyme arthritis is a monoarticular or oligoarticular form of arthritis that typically involves the knee. A positive enzyme-linked immunosorbent assay (ELISA) for IgG antibodies should be followed by an IgG immunoblot. A positive PCR test from synovial fluid adds increased diagnostic certainty. Serum positivity for antibodies to Borrelia burgdorferi without typical symptoms does not justify antibiotic treatment. Oral antibiotic treatment for erythema migrans is recommended using doxycycline, 200 mg once per day for 10-21 days, alternative choices are amoxicillin, cefuroxime and azithromycin. For children below 8 years of age, amoxicillin is recommended.Lyme arthritis can usually be successfully treated with orally administered antimicrobial agents. Doxycycline, 1 × 200 or 2 × 100 mg for 30 days is the antibiotic agent of choice. Amoxicillin (3 × 500-1000 mg) can be alternatively chosen. Patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy should be treated intravenously. In this situation, ceftriaxone at 2 g per day for 14-21 days is recommended. There is no evidence to recommend long-term and combined treatments.

Prevalence of antibodies against hepatitis A virus among children and adolescents in Germany.

Since hepatitis A virus (HAV) infection during childhood is mostly asymptomatic, only seroprevalence studies can provide reliable information on incidence of HAV infection in children. The prevalence of anti-HAV antibodies was determined in sera taken in 2008 to 2010 from 1,645 children aged 0-17 years and in sera taken in 2010-2011 from 400 adult blood donors in Germany. For examination of trend over time, 715 sera collected between 1999 and 2006 from children at the age of 0-17 years within the federal state Thuringia were included. Antibody testing was carried out using the test kits ETI-AB-HAVK PLUS and ETI-HA-IGMK PLUS from DiaSorin. In children, the overall prevalence of antibodies was 10.8 %. After the seroprevalence declined from 8.8 % among the 0-2 year-olds to 2.4 % among the 3-4 year-olds, there was a significant increase to 20.5 % in the group of the 15-17 year-olds. Boys had with 12.7 % a significantly higher seroprevalence of anti-HAV antibodies compared to 8.8 % among girls. In adult blood donors, there was a HAV seroprevalence of 19.3 %. The likelihood of past infection or immunization within the age groups of children from 0 to 12 years differed significantly from that of adults. In conclusion, in Germany, only a small number of HAV infections occur in children, especially up to the age of 12 years. The proportion of susceptible children is greater than the proportion of susceptible adults. Thus, during outbreaks, the rate of infection among children would usually be higher than the rate among adults.

Rational diagnostic strategies for Lyme borreliosis in children and adolescents: recommendations by the Committee for Infectious Diseases and Vaccinations of the German Academy for Pediatrics and Adolescent Health.

The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high-titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations.

[Biologicals for children and adolescents in the treatment of rheumatic diseases]. / Biologika bei Kindern und Jugendlichen zur Behandlung rheumatischer Erkrankungen.

Following pharmacolegal measures several biologic agents have been tested in children and adolescents with rheumatic diseases, mainly juvenile idiopathic arthritis (JIA), in controlled trials and have been introduced into treatment algorithms. This was achieved by international research cooperation and after introduction of well-defined criteria for disease entities, disease activity, improvement and deterioration. Etanercept, adalimumab, abatacept, tocilizumab and canakinumab have obtained limited licenses. Etanercept is the longest available biologic agent. Etanercept or adalimumab are the treatment of choice when methotrexate is not sufficient or toxic in children with polyarthritis. Tocilizumab is given to patients with systemic JIA when glucocorticoids fail or become toxic. These and other biologic agents including anakinra and rituximab are effectively applied also off label; however, there is a lack of long-term studies. These drugs should be prescribed only by pediatric rheumatologists.

[Henoch-Schönlein purpura : most frequent form of vasculitis in childhood and adolescence]. / Purpura Schönlein-Henoch : Häufigste Vaskulitis des Kindes- und Jugendalters.

Henoch-Schönlein purpura is the most common form of vasculitis in childhood and adolescence. It is manifested as palpable purpuras in the region of position-dependent extremities with otherwise good clinical general condition. The expression on the skin can, however, be variable so that sometimes other differential diagnoses must be included. In typical cases an extensive diagnostic procedure is unnecessary but the short-term complications of abdominal symptoms as well as the long-term complications of nephritis should be pursued. If musculoskeletal symptoms occur paracetamol or non-steroidal anti-inflammatory drugs are effective as are steroids for reducing the duration of abdominal pain. The effectiveness of steroid prophylaxis of renal damage is still controversial.

[Updated statement by the German Society for Pediatric and Adolescent Rheumatology (GKJR) on the FDA's report regarding malignancies in anti-TNF-treated patients from Aug. 4, 2009]. / Aktualisierte Stellungnahme der GKJR zur Meldung der FDA über Fälle von Malignomen bei Anti-TNF-behandelten Patienten vom 04.08.2009.

TNF inhibitors and other biologicals have greatly expanded the therapeutic options for juvenile idiopathic arthritis (JIA). While the efficacy of etanercept and adalimumab has been proven in randomized controlled clinical trials, their long-term safety remains the subject of ongoing investigations. Reports of leukaemia and tumours in children and adolescents treated with etanercept, infliximab and adalimumab have raised questions about an increased risk for malignancies, with lymphoma accounting for the largest group at 50% of all 48 malignancies reported by the FDA.Consequently, TNF inhibitors should be indicated under careful consideration of individual risk factors, such as increased family occurrence of malignancies, or pre-treatment with carcinogenic substances such as cyclophosphamide. This is particularly true for non-approved substances, and non-approved indications, and for combination therapy of TNF inhibitors with immunosuppressive drugs. On the other hand, however, treatment should not be stopped or started in any patient in whom treatment is necessary due to the current knowledge. Adequate patient information, surveillance and documentation of treatment in the registry of the GKJR is strongly recommended.

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004.

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries.