[Intersectoral patient care in rheumatology: concept and preliminary experiences with a model project]. / Sektorenübergreifende Versorgung in der Rheumatologie: Konzept und erste Erfahrungen in einem Modellprojekt.

In October 2006 the Rheumaklinik Ostbayern was founded as a clinic for acute rheumatology patient care, carried by Landkreis Passau Krankenhaus GmbH. The clinic operates in close professional cooperation with the Orthopädiezentrum Bad Füssing, an adjacent rehabilitation clinic carried by Deutsche Rentenversicherung Bayern Süd. The close constructional and personnel network between the two institutions creates optimal conditions for an interdisciplinary and intersectoral approach. The authors report their first experiences since foundation of the clinic and completion of a cooperation contract.

Antibiotic treatment of Lyme borreliosis: what is the evidence?

Antibiotic treatment of all disease manifestations after infection with Borrelia sensu lato spp aims at resolving the presenting disease manifestation and preventing late stage disease. The goals are resolution of the preventing manifestation and prevention of the spread of bacteria to prevent late disease like arthritis. Different borrelial species prevail in Europe. The natural disease course of European borreliosis is not well defined and the effect of antibiotic treatment is unclear.

Anti-tumour necrosis factor (TNF)-alpha therapy in undifferentiated spondyloarthropathy.

The cytokine tumour necrosis factor (TNF)-alpha plays a major role in the spinal inflammatory process of spondyloarthropathy. In contrast to rheumatoid arthritis, disease modifying antirheumatic drugs have not been proved effective against inflammation and progressive ankylosis. Initial studies on TNFalpha inhibitors in ankylosing spondylitis are promising and raise the question as to whether early stages of the disease, mostly classified as "undifferentiated spondyloarthropathy" (uSpA), should also be treated with TNFalpha inhibitors. This article summarises the preliminary results of 11 uSpA patients in 4 different trials treated with TNFalpha inhibitors.

Nodular fasciitis, erythema migrans, and oligoarthritis: manifestations of Lyme borreliosis caused by Borrelia afzelii.

We describe a 35-year old patient with nodular fasciitis, erythema migrans, and gonarthritis four months after a bite of a Borrelia afzelii infected tick. The Borrelia afzelii infection was identified by a polymerase chain reaction and direct sequencing of the amplification product. Borrelia-specific DNA was also detectable in nodular fasciitis tissue. We therefore conclude that Borrelia afzelii can be a causative agent of nodular fasciitis and Lyme arthritis in a highly endemic region of Northern Germany.

Evaluation of amplicor chlamydia PCR and LCX chlamydia LCR to detect Chlamydia trachomatis in synovial fluid.

OBJECTIVES: PCR has been successfully used in research for the detection of C. trachomatis DNA in synovial samples. However, each research laboratory has developed its own PCR, making inter-laboratory comparisons difficult. To allow for standardization we evaluated two commercially available amplification systems originally designed for the examination of urogenital samples (Roche Amplicor Chlamydia PCR and Abbott LCX Chlamydia LCR), using them to analyse spiked and clinical synovial fluid (SF) samples from reactive arthritis (ReA), undifferentiated arthritis (UA), and rheumatoid arthritis (RA) patients. We compared their sensitivity in assays of clinical SF samples with our in-house developed C. trachomatis specific nested PCR. METHODS: SF was spiked with purified C. trachomatis elementary bodies (EB) and analyzed by the commercial assays. Clinical SF samplesfrom ReA (n=21), UA (n=79) and RA (n=50) patients were examined by the two commercial assays and our in-house PCR. RESULTS: Using SF samples spiked with defined numbers of C. trachomatis EB, the sensitivity of the commercial tests was high and similar to published PCR sensitivity. In clinical SF specimens the commercial assays was also able to detect CT; however, the in-house PCR was more sensitive. Out of 10 PCR-positive SF samples Amplicor tested positive in only 4/10 and LCX in only 3/10. The in-house PCR detected chlamydial DNA in synovialfluidfrom 5/21 ReA (24%), 5/79 UA (6%) and in none of the 50 RA patients. CONCLUSION: Commercial amplification assays allow the detection of C. trachomatis in clinical specimens, although with a lower sensitivity than optimized PCR. Potential explanations are discussed.

Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study.

OBJECTIVE: More than 50% of patients with synovitis involving 1-4 joints remain classified as having undifferentiated oligoarthritis (UOA) after 1 year of disease. The clinical presentation is often similar to that of reactive arthritis (ReA) and other spondylarthropathies or to Lyme arthritis. We therefore determined how often Chlamydia trachomatis (Ct) and Borrelia burgdorferi (Bb) can be identified in patients with UOA, by using an extensive laboratory approach. METHODS: We prospectively studied 52 patients with UOA who presented at an early synovitis clinic in a region highly endemic for Lyme disease. Patients were examined by standardized clinical and immunoserologic procedures. Synovial fluid was screened for the presence of Ct and Bb DNA by polymerase chain reaction (PCR). Urine was tested for Ct DNA by ligase chain reaction, and serum was tested for Ct antibodies by enzyme-linked immunosorbent assay and Bb antibodies by hemagglutination test and Western blotting. PCR results in the UOA patients were compared with the results in cohorts of patients with definite rheumatoid arthritis (RA), Lyme arthritis, and Chlamydia-induced arthritis (CIA). RESULTS: In the synovial fluid of 9 of 52 patients with UOA (17%), we found Ct DNA, and in 6 of the 52 patients (12%), Bb DNA was found. The frequency of bacteria-specific DNA was 50% (7 of 14) in CIA patients and 69% (11 of 16) in patients with Lyme arthritis. No Bb or Ct DNA was found in the synovial fluid of the 31 RA patients. CONCLUSION: With optimized PCR protocols, it is possible to detect considerable levels of Bb and Ct DNA in the synovial fluid of patients with UOA. Although the presence of bacterial DNA does not unequivocally prove its etiologic significance, we suggest that at least one-third of patients with UOA may have a form of ReA that involves asymptomatic primary infection.

Intra-articular co-infection by Borrelia burgdorferi and Chlamydia trachomatis.

OBJECTIVE: Chlamydia trachomatis and Borrelia burgdorferi infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis. METHODS: Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from C trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to C trachomatis and B burgdorferi were determined. RESULTS: Six patients (8%) had DNA from both C trachomatis and B burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm(3), 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydia only. CONCLUSIONS: DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

[Detection of Borrelia DNA in urine using polymerase chain reaction in rheumatologic laboratory diagnosis of Lyme borreliosis]. / Nachweis von Borrelien-DNA im Urin mittels Polymerase-Kettenreaktion in der rheumatologischen Labordiagnostik der Lyme-Borreliose.

Borrelia burgdorferi specific DNA has been detected by polymerase chain reaction (PCR) in different specimens of patients with Lyme disease (LD). The aim of the present study is to evaluate PCR-diagnostic of urine specimens regarding rheumatologic diagnosis of Lyme disease. Urine specimens of 77 patients (LD, n = 34; undifferentiated arthritis (UA), n = 25; arthralgia/myalgia (AM), n = 18) and 15 controls were investigated. Flagellin gene (60 specimens) or OspA-plasmid (32 specimens) were used as targets. Sensitivity of the flagellin-nested-PCR was 27%, by OspA-nested-PCR only one positive PCR result was found. Despite of low sensitivity PCR enabled the correct diagnosis of LD in two patients classified as UA. Therefore, PCR can give valuable hints in single cases if LD is clinically suspected.

Bacterial antigens in reactive arthritis and spondarthritis. Rational use of laboratory testing in diagnosis and follow-up.

An aetiological diagnosis of reactive arthritis is based on the demonstration of recent or ongoing infection with the causative bacterium. This may be done by serological demonstration of antibacterial antibodies, demonstration of the causative microorganism at an extra-articular site or by identification of bacterial nucleic acids or antigens in joint material from patients with aseptic arthritis. The finding of elevated titres of bacteria-specific IgG- and IgA-class antibodies may indicate recent or persistent infection, but has some limitations due to the prevalence of such antibodies among apparently healthy individuals and the persistence of such antibodies after the infection. While Chlamydia can be demonstrated in urogenital specimens in at least one-third of patients with Chlamydia-induced arthritis, the triggering microorganisms are usually no longer detectable in post-dysenteric reactive arthritides. Assays involving molecular amplifications have been successfully used to demonstrate bacterial nucleic acids in joint specimens from patients with reactive arthritis. In addition, bacterial antigens have been detected by immunofluorescence tests. Even though examination of synovial fluid and synovial membrane specimens for bacterial DNA by the polymerase chain reaction is increasingly used to diagnose reactive arthritis, such assays have not been standardized and are not generally available. While some problems remain, these techniques will facilitate the exact diagnosis of reactive arthritides in the near future.

Early ontogeny of the central benzodiazepine receptor in human embryos and fetuses.

The early ontogeny of the central benzodiazepine receptor (BZR) was investigated in human embryos and fetuses between 7 and 26 weeks of gestation. Brain tissue was gained from terminated pregnancies or spontaneous abortions. Binding studies, which were performed with 3H-flunitrazepam (FNZ), revealed that specific benzodiazepine binding is already detectable at an embryonal age of 7 weeks post conceptionem. Binding at this early stage can be displaced potently by clonazepam and the inverse agonist beta-CCE. Additionally, 3H-FNZ binding is enhanced by GABA. Thus, benzodiazepine binding is of the central type. Receptor density increases steeply in whole brain between weeks 8 and 11 of gestation. In frontal cortex receptor density increases gradually between weeks 12 and 26 of gestation. No specific fetal disease entity (including trisomy 21) was consistently associated with exceptionally high or low Bmax-values.