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Abstract: B-cell depleting therapy (BCDT) is effective in suppressing synovitis and erosions in rheumatoid arthritis suggesting that a cell of the B-lymphocyte lineage is critical in the pathogenesis of this disease. Non-Hodgkins lymphoma (NHL) also responds to BCDT but multiple myeloma (MM), does not as cells have differentiated beyond the CD20-bearing stage. However, there are similarities between B-NHL, MM and RA that suggest all 3 conditions could be initiated and perpetuated by the same cellular players. Numerous plasma cells and B cells are present within rheumatoid synovial membrane, and subarticular bone where they contribute to osteitis. On MRI scans this appears as bone oedema, which has been demonstrated to precede the development of bone erosions. Plasma cell clonality has been detected within RA synovial membrane and bone marrow. It is proposed that RA could represent a “forme fruste” of a B cell neoplastic condition, with production of autoantibodies that target a self-antigen within the joint. The activation of rheumatoid bone osteoclasts by anticitrullinated protein antibodies supports this theory. The erosions of RA would have parallels with the lytic lesions of MM but autoantigen targeting dictates that erosions occur at joint margins. This theory is discussed from rheumatologic and haematologic perspectives. [Copyright &y& Elsevier]

Summary: The JAK2 [V617F] mutation has recently been recognised as critical to the pathogenesis of the myeloproliferative disorders (MPDs). Thus, a common mutation affecting a haematopoietic precursor stem cell is capable of giving rise to diverse clinical phenotypes. In this hypothesis paper, we propose that a similar mutation affecting a stem cell precursor, most likely of the B cell lineage, could underlie the development of the connective tissue disorders which could be regarded as “lymphoproliferative” disorders. Consistent with this hypothesis is the observation that there are similarities between the myeloproliferative disorders and the connective tissue disorders in terms of their biological behaviour. Diseases within each family can transform into each other and sometimes into haematological malignancies (most often B cell origin non-Hodgkins lymphoma for the connective tissue disorders and acute myeloid leukemia for the myeloproliferative disorders). The timecourse for development of the connective tissue disorders involves a long latent period when autoantibodies are present (anti-CCP and ANA) possibly reflecting production by a B cell clone. A similar time-dependent increase in clonal dominance has been described in erythroblastic clones taken from the bone marrow of polycythemia vera patients, long before the onset of clinical disease. Evidence of B cell clonality has been described in bone marrow samples from rheumatoid arthritis patients and from glandular biopsies from those with Sjogren’s syndrome. Moreover, pseudofollicles containing activated B cells are features of rheumatoid synovial membrane and have also recently been described in subchondral bone where they are associated with macrophages, T cells and osteoclasts. The success of B cell depletion therapy in rheumatoid arthritis and systemic lupus erythematosus is also strong circumstantial evidence for this hypothesis. [Copyright &y& Elsevier]

Abstract: Objectives: Despite the predilection of gout to the feet, the impact of gout on foot function and biomechanics is currently unknown. The aim of this study was to describe the effects of chronic gout upon function and selected biomechanical parameters associated with gait. Methods: Twenty-five patients with a history of gout were compared with 25 age and gender matched control participants with no history of gout or other forms of arthritis. General function, foot specific disease activity and lower limb activities were determined using the Health Assessment Questionnaire, Foot Function Index (pain domain), and Leeds Foot Impact Scale respectively. Each patient also underwent a gait assessment that included plantar pressure measurements and an evaluation of temporal–spatial gait parameters. Findings: Patients with chronic gout had higher levels of general and foot-specific disability, pain and impairment (P ≤0.001). Significantly lower peak plantar pressures were observed in the hallux of patients with chronic gout (P ≤0.05). Significantly higher pressure–time integrals were observed in the cases at the midfoot (P ≤0.05), but lower values were observed at the hallux (P ≤0.05). Patients with chronic gout walked slower, with longer step and stride lengths compared to the controls. Interpretation: Patients with chronic gout experience pain and disability associated with their feet. Different toe-off strategies may account for functional changes and pain associated with foot problems in chronic gout. [Copyright &y& Elsevier]