Association between interleukin 6 gene polymorphisms and Behçet ’ s disease in Korean people

T he paper of Mohr discussing the development of rice bodies with apatite crystals in fibrinous debris synovitis in rheumatoid arthritis 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. 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. 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. 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. 6 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. 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. VEGF-C and D were shown to stimulate lymphangiogenesis. Recently, mature VEGF-C was found in rheumatoid arthritis synovial tissue.