Conspicuous synovial lymphatic capillaries in juvenile idiopathic arthritis synovitis with rice bodies

Abstract

T he paper of Mohr discussing the development of rice bodies with apatite crystals in fibrinous debris synovitis in rheumatoid arthritis 1 prompted us to describe our recent morphological findings.During synovectomy in a 33 year old woman with a longlasting systemic form of juvenile idiopathic arthritis (JIA) a large number of rice bodies and numerous synovial villi connected to the synovial membrane (SM) by very thin stalks were visible in the joint space (JS). Light microscopy of paraffin sections showed that the villi contained fibrin and had degenerated. In the SM, mononuclear infiltration, neoangiogenesis, intimal layer hyperplasia, and fibrin at the synovial surface were found. Light microscopy of serial semithin resin sections enabled a distinction to be made between lymphatic capillaries (LC). Prominent LC were found under villous fibrin ( fig 1A). In connective tissue around the LC, macrophages were seen. Cells and debris were rarely seen inside the lumina of the LC ( fig 1B). LC were also seen in areas of the SM not covered with fibrin ( fig 1C). These LC were situated in the subintimal connective tissue and were often surrounded by numerous mononuclear cells. In some of these LC, cells (mostly lymphocytes) were found.Kuhns presented a detailed morphological study of lymphatic drainage of synovial joints in rabbits.2 He discovered that inflammation in the synovial tissue decreased the ability of LC to absorb material larger than that of molecular size and presumed that persistent inflammation was, to a certain extent, dependent on the non-functioning of the lymphatic vessels. Later, Pullinger and Florey proved that LC proliferated in acute inflammation and repair.3 They demonstrated that LC proliferated also in chronic inflammation induced in the skin of mice, and emphasised that debris was removed from the damaged areas by the LC, either directly or by phagocytic cells. Recently, in rheumatoid arthritic synovium, debris and cells were seen inside the lumina of LC and, moreover, endothelial microvalves were visualised in the walls of the LC by transmission electron microscopy. 4 Endothelial microvalves of LC probably have an important role in drainage of excessive tissue fluid, allowing cells and debris to be removed from SM connective tissue spaces into the lymph. The LC are an integral part of connective tissue, in which prelymphatic tissue channels have been described. In the patient reported in this paper, fibrin deposition and mononuclear infiltration may have blocked part of the prelymphatic tissue channels in the SM, thus reducing the drainage of the JS. This might have contributed to the formation of rice bodies in synovial fluid (SF).Rice bodies in rheumatoid SF contain mononuclear cells, mostly macrophagic in appearance.7 Accumulation of rice bodies in the JS may contribute to increased cytokine levels in the SF. It is known that SF cytokines can modulate the level of vascular endothelial growth factor (VEGF) secretion. Our observation of conspicuous LC suggests that lymphangiogenesis ma...

Treatment of Rat Adjuvant Arthritis with Flavonoid (Detralex®), Methotrexate, and Their Combination

“…A generalized abnormality in capillary function (an increase in capillary filtration rate) and some obstruction of lymphatic clearance are associated with rheumatoid arthritis 10,11 . Microscopic changes of postcapillary venules were also found in RA, 12,13 and structural changes of lymphatic vessels in synovial membrane were observed in RA and juvenile idiopathic arthritis 14–16 …”

“…10,11 Microscopic changes of postcapillary venules were also found in RA, 12,13 and structural changes of lymphatic vessels in synovial membrane were observed in RA and juvenile idiopathic arthritis. [14][15][16] Adjuvant arthritis, an experimentally induced inflammatory disorder in rats, bears some features of rheumatoid arthritis. In both diseases edema and inflammation appear in synovial joints.…”

Oedema, infiltration and drainage of connective tissue in rheumatoid arthritis – a preliminary report

“…Istnieją doniesienia o namnażaniu się naczyń limfatycznych błony maziowej u pacjentów z RZS po leczeniu przeciwciałami anty-TNF [5]. W 2005 r. opisano wyraźnie widoczne włosowate naczynia limfatyczne w błonie ma ziowej [28]. Wilkinson i Edwards [7] dostarczyli zdjęcia naczyń limfatycznych zlokalizowanych w pobliżu głęboko położonych tętniczek i małych naczyń żylnych ludzkiej błony maziowej przy użyciu lektyny z kolcolistu zachodniego (lectin Ulex europaeus agglutinin I -UEAAI); jednak przy zastosowaniu tej metody u pacjentów z RZS badane próbki nie wykazały obecności naczyń limfatycznych.…”

“…treatment with anti-TNF antibody [5]. Conspicuous LC were described in synovial membrane in 2005 [28]. Wilkinson and Edwards [7] provided visualisation of lymphatic vessels situated in the proximity of deep arterioles and venules of the human synovial membrane using lectin Ulex europaeus agglutinin I (UEAI); however, using this method in RA patients, the samples did not show any lymphatic vessels.…”

Intra-articular Injection of a B Cell Depletion Antibody Enhances Local Exposure to the Joint-Draining Lymph Node in Mice with Collagen-Induced Arthritis

“…In recent years, B cells have been found to play a critical role in the pathology of RA and thus provide a new target for treatment. , B cells are primarily involved in propagating the autoimmune response in rheumatoid arthritis through autoantibody generation, T cell and myeloid cell activation, and pro-inflammatory cytokine production. , In addition to promoting immune activation and inflammation, B cells also appear to play a role in promoting lymphatic dysfunction that, in turn, exacerbates joint inflammation. Studies over the last two decades have demonstrated a range of structural and functional changes to the synovial and prenodal joint-draining lymphatics in experimental inflammatory arthritis, − osteoarthritic (OA) mouse models, and humans with arthritis. − These experiments collectively report disease severity-related changes in (1) the density and size of lymphatic vessels within the synovium, (2) the composition of joint-draining lymph, (3) the drainage kinetics of joint-draining lymph, and (4) the morphology of the joint-draining lymph node (jdLN).…”