[A 34-year-old patient with retropharyngeal tendinitis]. / Ein 34-jähriger Patient mit retropharyngealer Tendinitis.

This article reports the case of a 34-year-old male patient presenting with neck pain, massive pressure pain of the neck muscles and limited cervical rotational mobility. Laboratory tests showed elevated levels for markers of inflammation. Computed tomography (CT) and magnetic resonance imaging (MRI) detected a retropharyngeal tendinitis of the longus cervicis muscle. This rare clinical entity is probably responsible for a high number of unreported cases. A CT scan, which can identify prevertebral edema and light calcification inferior to the ventral aspect of the second cervical vertebra, was previously the gold standard. Meanwhile, MRI scans now show a higher sensitivity in the detection of prevertebral edema. The first line treatment is the administration of non-steroidal anti-inflammatory drugs (NSAIDs).

[Improvement of the diagnostic accuracy in patients with suspected rheumatic disease by preselection in the early arthritis clinic : An alternative to the appointment service point model of the Healthcare Improvement Act]. / Verbesserung der diagnostischen Treffsicherheit bei Patienten mit vermuteter rheumatischer Erkrankung durch Vorselektion in der Früharthritissprechstunde : Eine Alternative zum Termin-Servicestellen-Modell des Versorgungsstärkungsgesetzes?

The diagnosis and treatment of inflammatory rheumatic diseases can be delayed by a long waiting period for an appointment with a rheumatologist. This study investigated whether preselection of patients in an early arthritis clinic is a suitable tool to improve this situation. In 2006 an early arthritis clinic was founded by the Collaborating Center of Rheumatology in Halle (Saale). General practitioners refer patients by using a special registration form that helps to identify patients with an early joint swelling or inflammatory back pain. Patients are then allocated to a pool of participating rheumatologists and are seen by one of them within 2 weeks. For our scientific evaluation the data of 248 patients from the early arthritis clinic and data of 187 regular patients were gathered by means of an additional questionnaire for rheumatologists and patients. In the early arthritis clinic 40.3 % of patients received the diagnosis of an inflammatory rheumatic disease compared with 19.3 % in the control group. In the latter group 51 % were diagnosed as having degenerative joint or spine disorders compared with 22 % in patients from the early arthritis clinic; however, 61 % of patients who were referred to the early arthritis clinic did not fulfill the criteria of the registration form. On the other hand, patients in this group fulfilling these criteria had an inflammatory rheumatic disease in 68.1 % of the cases. The mean duration of symptoms at the time of first rheumatological consultation was significantly shorter in the early arthritis clinic than in the control group (6 vs. 39 months). Our data demonstrate that the preselection of patients can serve as a useful instrument to guide the referral of patients to rheumatologists. The high percentage of patients who did not fulfil the criteria of the registration form indicates that a further improvement of this form is necessary and stresses the need for intensive communication between rheumatologists and general practitioners. Early arthritis clinics may be an alternative to the current efforts of the legislative authorities to improve specialist care by centralized distribution of specialist appointments.

[Therapeutic application of mesenchymal stromal cells in autoimmune disease: rationale and initial clinical experience]. / Therapeutische Anwendung mesenchymaler Stromazellen bei Autoimmunerkrankungen: Rationale und erste klinische Erfahrungen.

Mesenchymal stromal cells (MSC) are characterized by their proliferative capacity, their phenotype and their ability to multipotent differentiation. However, little is known about their function and characteristics in vivo. MSC posses a tropism for injured tissues. Numerous investigations of MSC in different model systems suggest an immunosuppressive potential, although the results are in part contradictory. Apparently, MSC exert these effects on nearly all cells in the immune system. However, the relevance and mechanisms of these phenomena in vivo are not clear. The clinical effectiveness of allogeneic MSC in the treatment of refractory graft-versus-host disease has raised hopes that MSC could offer a new concept for the therapy of other immune-mediated disorders. However, before MSC are introduced in clinical practise, several important questions as to their side effects have to be addressed. This includes the possibility that MSC may contribute to the induction of malignant diseases.

[Severe, non-infectious mitral valve endocarditis after mitral valve reconstruction in a 32-year old female with primary antiphospholipid syndrome]. / Schwere, nicht-infektiöse Mitralklappenendokarditis nach Klappenrekonstruktion bei einer 32-jährigen Patientin mit primärem Antiphospholipid-Syndrom.

BACKGROUND: A 32-year old female with primary antiphospholipid syndrome presented 8 months after mitral valve reconstruction with progressive exertional dyspnea and echocardiographically demonstrable critical mitral stenosis and regurgitation. Tachycardia, weight loss, sleep disturbances and increasing nervosity led to the diagnosis of concomitant hyperthyroidism. After the patient stopped the oral anticoagulation by herself, a 'catastrophic antiphospholipid syndrome' with multiple microthromboembolic events in several organs developed rapidly within a few weeks. Severe respiratory failure was observed 14 days after admission at our hospital because of a pulmonary edema. TREATMENT: Removal of the annuloplasty ring and alloplastic mitral valve replacement with a 25 mm bilifleat valve. Postoperatively, the patient was placed on oral anticoagulation. Several pre- and postoperative plasmaphereses lowered the level of antiphospholipid antibodies. The patient additionally underwent radioiodtherapy 5 months postoperatively. RESULTS: While hemodynamics and diuresis remained sufficient, ventilatory support with tracheostomy was necessary for 16 postoperative days to achieve stable respiration. Thirty months later, the patient is well and without further cardiac and neurological dysfunction. CONCLUSION: Secondary cardiac valve operations on patients with primary antiphospholipid syndrome may be successfully performed within a multidisciplinary approach. Oral anticoagulation remains the treatment of choice to prevent further thromboembolic events.

[MR angiography in diagnosis of vasculitis and benign angiopathies of the central nervous system]. / MR-Angiographie in der Diagnostik von Vaskulitiden und benignen Angiopathien des Zentralnervensystems.

PURPOSE: To evaluate TOF 3D magnetic resonance angiography (MRA) of the intracranial arteries in patients with vasculitis or vasculitis-like benign angiopathy of the central nervous system (CNS). METHOD: The results of MRA in 20 patients with clinically and radiographically proven vasculitis (17/20) or vasculitis-like benign angiopathy (3/20) of the CNS were retrospectively analysed. Patients with hyperintense lesions of more than 3 mm on T2-weighted MRI images were included in this trial. An inflammatory, embolic, neurodegenerative or metastatic origin of these lesions was excluded by extensive clinical studies. For the MR-examination a TOF 3D FISP sequence was used on a 1.5 T imager. RESULTS: MRA showed characteristic changes for vasculitis or angiopathy in 15 of 20 patients (75%). CONCLUSIONS: In patients suspected of having a vasculitis or vasculitis-like angiopathy, MRA is recommended as a non-invasive modality. If the results of MRI and extensive clinical studies are carefully correlated, MRA may substitute conventional angiography in cases with typical vascular changes.

A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study.

OBJECTIVE: To study the efficacy of combination therapy with etanercept and methotrexate in patients with refractory juvenile idiopathic arthritis. METHODS: Seven children with active juvenile idiopathic arthritis refractory to at least combination therapy with methotrexate and sulfasalazine or cyclosporin A were studied. Concomitant treatment, consisting of non-steroidal drugs, corticosteroids, and methotrexate, remained unchanged. RESULTS: Six patients continued the treatment for at least 24 weeks. In the child with systemic arthritis, etanercept was stopped because of persisting spiking fever, joint pain, and rash. In the remaining children an immediate significant decrease in joint pain (p<0.05), disappearance of morning stiffness, and regression of joint swelling (p<0.05) were observed. Improvement was apparent after two injections. An immediate significant (p<0.05) decrease in erythrocyte sedimentation rate, C reactive protein, and interleukin 6 was observed. Side effects consisted of mild reactions at the injection site in two children. CONCLUSIONS: In this observational study, etanercept in combination with methotrexate was well tolerated and highly effective in treating juvenile polyarthritis but not in the patient with systemic arthritis. Combination treatment appears to be feasible in terms of toxicity and may enhance efficiency.

Insights from a novel three-dimensional in vitro model of lyme arthritis: standardized analysis of cellular and molecular interactions between Borrelia burgdorferi and synovial explants and fibroblasts.

OBJECTIVE: To develop a novel 3-dimensional (3-D) in vitro model of Lyme arthritis to use in the study of the interactions between Borrelia burgdorferi (Bb) and human synovial host cells with respect to phagocytosis and potential persistence of Bb as well as the induction of proinflammatory cytokines and chemokines. METHODS: Two distinct culture systems, consisting of synovial membrane explants or interactive synovial cells embedded in 3-D fibrin matrices, were chosen. Both systems were artificially infected with Bb, and the interactions between Bb and synovial tissue/cells were studied by histology, immunohistochemistry, and electron microscopy. Functional analyses included the induction/secretion of cytokines by Bb in the model system. RESULTS: Both culture systems proved to be stable and reproducible. The host cells and spirochetes showed high levels of viability and maintained their physiologic shape for >3 weeks. Bb invaded the synovial tissue and the artifical matrix in a time-dependent manner. Host cells were activated by Bb, as indicated by the induction of interleukin-1beta and tumor necrosis factor alpha. Electron microscopic analysis revealed Bb intracellularly within macrophages as well as synovial fibroblasts, suggesting that not only professional phagocytes, but also resident synovial cells are capable of phagocytosing Bb. Most interestingly, the uptake of the spirochetes appeared to cause severe damage of the synovial fibroblasts, since the majority of these cells displayed ultrastructural features of disintegration. CONCLUSION: A novel 3-D in vitro model has been established that allows the study of distinct aspects of Lyme arthritis under conditions that resemble the pathologic condition in humans. This reproducible, standardized model supplements animal studies and conventional 2-D cultures. The disintegration of synovial fibroblasts containing Bb or Bb fragments challenges the concept of an intracellular persistence of Bb and may instead reflect a mechanism that contributes to the inflammatory processes characteristic of Lyme arthritis.

Treatment of refractory rheumatoid arthritis with low-dose cyclophosphamide. Long-term follow-up of 108 patients.

Although cyclophosphamide (CYC) is an effective drug in the treatment of refractory rheumatoid arthritis (RA), the application of this drug in RA has largely been abandoned, due to potentially life-threatening adverse events such as myelosuppression and cancer development. However, the question remains open, whether it is possible to balance the toxicity and the efficacy of CYC with low-dose therapy. 108 patients with refractory RA or with vasculitic organ involvement were treated with 50 mg CYC per day. Joint indices and laboratory parameters were gathered prospectively and the occurrence of serious side effects was monitored over a median of 10 years. The efficacy was surveyed in six months intervals. A 50% improvement of the swollen joint count was required to continue therapy. A long-term follow-up was performed to survey the incidence of malignancies. 85 patients dropped out within the first year. Only four patients were treated for longer than 4 years. In the total cohort, 50 patients were withdrawn due to the lack of efficacy, 34 patients had to discontinue because of adverse events, and 9 patients dropped out for both reasons. Gastrointestinal intolerance was the most frequent adverse event that led to the discontinuation of the drug, followed by myelosuppression. Five patients suffered from 6 malignancies occurring after a median of 4.5 years after cessation of treatment. Treatment of RA patients with 50 mg CYC per day resulted in a more favorable rate of serious adverse events and a markedly lower incidence of tumors compared to the treatment with 75 to 150 mg per day described in the literature. However, the long-term efficacy of this regimen was poor in our cohort.

[Innovative approaches in therapy of chronic polyarthritis]. / Innovative Ansätze in der Therapie der chronischen Polyarthritis.

New approaches to the treatment of chronic polyarthritis are based on recent insights into the pathogenesis of this disease, in particular the involvement of cytokines and adhesion molecules in the process of joint destruction. These experimental approaches have been made possible by the development of monoclonal antibodies and recombinant fusion proteins, with the aid of which, cytokines such as TNF-alpha or IL-6 can be neutralized, or adhesion molecules and receptors on the cell surface blocked. Other therapeutic strategies include the induction of a specific tolerance to hypothetical disease-relevant antigens and autoantigens. Despite the good results seen in the pilot projects, however, the efficacy of most of these newly developed forms of treatment still need to be confirmed in long-term trials involving adequate numbers of patients.