Joint in rheumatoid arthritis

Olszewski WL, Pazdur J, Kubasiewicz E, Zaleska M, Cooke CJ, Miller NE. Lymph draining from foot joints in rheumatoid arthritis provides insight into local... 

Mecfianism of Action A monoclonal antibody that binds specifically to tumor necrosis factor (TNF) alpha, blocking its interaction with cell surface TNF receptors, Tfier-apeutic Effect Reduces inflammation, tenderness, and swelling of joints slows or prevents progressive destruction of joints in rheumatoid arthritis. 

Inflammation of the synovial joints in rheumatoid arthritis includes this change in the synovial fluid. 

Hyaluronic acid acts as a lubricant in the synovial fluid of joints. In rheumatoid arthritis, inflammation breaks down hyaluronic acid to smaller molecules. Under these conditions, what happens to the lubricating power of the synovial fluid ... 

Grassi W, Tittarelli E, Pirani O et al (1993). Ultrasound examination of metacarpophalangeal joints in rheumatoid arthritis. Scand J Rheumatol 22 243-247 Grassi W, Lamanna G, Farina A et al (1999) Sonographic imaging of normal and osteoarthritic cartilage. Semin Arthritis Rheum 28 398-403... 

Grass W, Tittarelli E, Pirani O et al (1993) Ultrasound examination of metacarpophalangeal joints in rheumatoid arthritis. 

In rheumatoid arthritis the damage that is found in joints may also be a result of the inactivation of a-1-PI due to the oxidation of an essential methionine(s) residue in this protein. It has been found that a-l-PI purified from the synovial fluid of patients with rheumatoid arthritis contained four Met(O) residues and was not able to form a binary complex with elastase89. It is probable that the presence of the Met(Oj residues in a-l-PI from these patients results from a high level of oxidants produced by neutrophils in the inflammed joint. 

Jason, M.I.V. and Dixon, A. St. J. (1970a). Intra-articular pressures in rheumatoid arthritis of the knee. I. Pressure changes during passive joint distention. Ann. Rheum. Dis. 29, 261-265. 

FIGURE 54-1. Patterns of joint involvement in rheumatoid arthritis. (From DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy. 6th ed. New York McGraw-Hill 2005, Figure 89-3, p. 1673, with permission.)... 

Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001 344( 12) 907—916. Cronstein BN. Low-dose methotrexate A mainstay in the treatment of rheumatoid arthritis. Pharmcol Rev 2005 57(2) 163—172. 

Fournier C. Where do T cells stand in rheumatoid arthritis Joint Bone Spine 2005 72(6) 527-532. 

Ellingsen T, Buus A, Stengaard-Pedersen K. Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis. J Rheumatol... 

Articulated joints between bones, for example at the knee, are covered in a capsule enclosing a space, which contains synovial fluid. The lining of the capsule is composed by the synovial membrane it is this synovium that becomes inflamed in rheumatoid arthritis (RA). Secretions produced by inflammatory cells (lymphocytes, macrophages... 

Ospelt C, Kyburz D, Pierer M, Seibl R, Kurowska M, Dis-tler O et al. ToU-hke receptors in Rheumatoid arthritis joint destruction mediated by two distinct pathways. Ann Rheum Dis 2004 63 Suppl 11 90-1. 

Aspirin and related salicylates are the primary treatment for mild to moderate pain, such as that associated with headache, joint and muscle pain, and dysmenorrhea. At higher doses aspirin is an effective analgesic in rheumatoid arthritis (see Chapter 36). The analgesic effects of salicylates are thought to be due to the inhibition of prostaglandin synthesis in the periphery and to a less well documented mechanism at cortical areas. 

Acute phase react ant s for efficacy in rheumatoid arthritis pain, stiffness, number of swollen joints, range of motion, functional capacity, structural damage fecal occult... 

In rheumatoid arthritis, immune complexes are deposited in the affected joints, causing an inflammatory response that is amplified by eicosanoids. Lymphocytes and macrophages accumulate in the synovium, whereas leukocytes localize mainly in the synovial fluid. The major eicosanoids produced by leukocytes are leukotrienes, which facilitate T-cell proliferation and act as chemoattractants. Human macrophages synthesize the COX products PGE2 and TXA2 and large amounts of leukotrienes. 

Although antimalarials improve symptoms, there is no evidence that these compounds alter bony damage in rheumatoid arthritis at their usual dosages (up to 6.4 mg/kg/d for hydroxychloroquine or 200 mg/d for chloroquine). It usually takes 3-6 months to obtain a response. Antimalarials are often used in the treatment of the skin manifestations, serositis, and joint pains of systemic lupus erythematosus, and they have been used in Sjogren s syndrome. 

Cytokines play a central role in the immune response (see Chapter 56) and in rheumatoid arthritis. Although a wide range of cytokines are expressed in the joints of rheumatoid arthritis patients, TNF-a appears to be particularly important in the inflammatory process. 

Kavanaugh A (2007) Current treatments for rheumatoid arthritis. Am J Orthop 236(3) 4-7 Kirwan JR (1995) The effect of glucocorticoids on joint destruction in rheumatoid arthritis the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 333(3) 142-146... 

Muller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S (2005) Mechanisms of disease the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol 1 (2) 102—110... 

IL-18 augments T- and NK-cell maturation, cytotoxicity and cytokine production. It stimulates TH differentiation, promotes secretion of TNF-a, IFN-y and GM-CSF and enhances NK cell cytotoxicity by increasing FasL expression. IL-8-mediated neutrophil chemotaxis is promoted by IL-18 via its effects on TNF-a and IFN-y, which are stimulatory in action. It plays an important role in maintaining synovial inflammation and inducing joint destruction in rheumatoid arthritis. In synovium of patients with rheumatoid arthritis, enhanced levels of TNF-a and IL-1 are associated with augmented expression of IL-18. 

Choy EH, Pnaayi GS. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. NEJM. 344 907-916. 

Several agents are now available that inhibit the action of tumor necrosis factor-alpha (TNF-a). TNF-a is a small protein (cytokine) that is released from cells involved in the inflammatory response. TNF-a seems to be a key chemical mediator that promotes inflammation and joint erosion in rheumatoid arthritis.83 Drugs that inhibit this chemical will therefore help delay the progression of this disease by decreasing TNF-a s destructive effects.70... 

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