Fibroblast activation protein (FAP), as described so far, is a type II cell surface serine protease expressed by fibroblastic cells in areas of active tissue remodelling such as tumour stroma or healing wounds. We investigated the expression of FAP by fibroblast-like synoviocytes (FLSs) and compared the synovial expression pattern in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Synovial tissue from diseased joints of 20 patients, 10 patients with refractory RA and 10 patients with end-stage OA, was collected during routine surgery. As a result, FLSs from intensively inflamed synovial tissues of refractory RA expressed FAP at high density. Moreover, FAP expression was co-localised with matrix metalloproteinases (MMP-1 and MMP-13) and CD44 splice variants v3 and v7/8 known to play a major role in the concert of extracellular matrix degradation. The pattern of signals appeared to constitute a characteristic feature of FLSs involved in rheumatoid arthritic joint-destructive processes. These FAP-expressing FLSs with a phenotype of smooth muscle actin-positive myofibroblasts were located in the lining layer of the synovium and differ distinctly from Thy-1-expressing and non-proliferating fibroblasts of the articular matrix. The intensity of FAP-specific staining in synovial tissue from patients with RA was found to be different when compared with end-stage OA. Because expression of FAP by RA FLSs has not been described before, the findings of this study highlight a novel element in cartilage and bone destruction of arthritic joints. Moreover, the specific expression pattern qualifies FAP as a therapeutic target for inhibiting the destructive potential of fibroblast-like synovial cells.
Polymyalgia rheumatica (PMR) occurs almost exclusively in persons aged 50 years or older and it is the second most common inflammatory rheumatic disease in older people after rheumatoid arthritis. Since there are no specific tests for PMR, the exclusion of clinically similar differential diagnoses is essential to ascertain the diagnosis. These recommendations for the management of PMR assume an already established diagnosis of PMR. It is recommended to initiate treatment with glucocorticoids immediately after diagnosis and to provide appropriate patient information and education about the impact of the disease and its treatment. Methotrexate should be considered in patients at high risk for relapse and/or glucocorticoid-related adverse events. These guidelines have been elaborated because there is significant heterogeneity in the management of PMR in clinical practice in Germany (but also Europe and worldwide), despite the large number of patients with this disease. These guidelines are primarily based on the 2015 EULAR-ACR recommendations for the management of PMR, which were updated by the guideline committee and adapted to the German speaking countries.
The wrists are affected in the long-term in 90% of people with rheumatism and are often (42%) the first manifestation of a destructive disease. The functionality of the wrist and the whole hand is of great importance because in many cases loss of function of the wrists leads to severe limitations. Local and operative treatment of the wrist in rheumatoid arthritis (RA) is one of the main duties in rheuma-orthopaedics. For operative treatment there is a finely tuned differential therapeutic spectrum available. The diagnostic indications take the local and total pattern of affection, the current systemic therapy as well as patient wishes and patient compliance into consideration. In the early stages according to LDE (Larsen, Dale, Eek), soft tissues operations such as articulo-tenosynovectomy (ATS) are most commonly carried out. In further advanced stages osseus stabilisation must often be performed. At this point a smooth transition from partial arthrodesis to complete fixation is possible. After initial euphoria, arthroplasty of the wrist is being increasingly less used for operative treatment due to the unconvincing long-term results and high complication rate. With reference to the good long-term results of all operative procedures, in particular early ATS with respect to pain, function and protection of tendons, after failure of medicinal treatment and persistence of inflammatory activity in the wrist, patients should be transferred to an experienced rheuma-orthopaedic surgeon.
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