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A Definition of the Disease and a Clinical Description Based on a Numerical Study of 293 Patients and Controls

]4-2 Maciej Wiewi6rowski and Julita Graczyk: Methotrexate in treatment of rheumatoid arthritis in some patients resistant to methotrexate received per os. Other reports demonstrate similar effects of methotrexate after oral and parenteral administra- tion (22,32). Mter oral administration methotrexate is absorbed quickly, but not completely; reaching its maximum level after 1-2 h. As the oral dose is increased, the amow1t of absorbed drug decreases because of the saturation of the system of carriers responsible for its absorption. The drug adminis- tered

-4362.2003.01916.x [7] Davis L.S., Sackler M., Brezinschek R.I., Lightfoot E., Bailey J.L., Oppenheimer-Marks N., Lipsky P.E. 2002. Inflammation, immune reactivity and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. American Journal of Pathology, 160, 357–367. [8] Firestein G.S. 2001. Etiology and pathogenesis of rheumatoid arthritis. In: Kelley’s textbook of rheumatology (Eds. S. Ruddy, E.D. Jr. Harris and C.B. Sledge). W.B. Saunders, Philadelphia, 921–966. [9] Forton F., Song M. 1998. Limitation of standardized skin surface biopsy in

Introduction Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints which leads, when left untreated, to bone and cartilage destruction along with other co-morbidities [1, 2]. Inflamed synovium has several hallmarks reminiscent of neoplastic processes including blood vessel formation (angiogenesis) and infiltration of blood-derived cells (i.e., T cells, B cells, monocytes, macrophages). Together with synovial fibroblasts, these cells are responsible for the production of multiple proinflammatory cytokines (e.g., TNFα, IL1β, and

.H., Dundar U., Cetinkaya Z., Kulac M., Kiyildi N., Turel A., Evcik D., Kavuncu V. 2007. Demodex folliculorum in patients with rheumatoid arthritis. Acta Parasitologica, 52, 70–73. DOI: 10.2478/s11686-007-0002-7. [11] Ivy S.P., Mackall C.L., Gore L., Gress R.E., Hartley A.H. 1995. Demodicidosis in childhood acute lymphoblastic leukaemia: an opportunistic infection occurring with immunosuppression. Journal of Pediatrics, 127, 751–754. DOI: 10.1016/S0022-3476(95)70168-0. [12] Jansen T

References 1. Spector, T.D. (1990). Rheumatoid arthritis. Rheum Dis Clin North Am. 16(3), 513 2. Vessey M.P., Villard-Mackintosh L. & Yeates D. (1987). Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception . 35(5),457-464 3. Voigt L.F., Koepsell T.D., Nelson J.L., Dugowson C.E. & Daling J.R. (1994). Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology. 5(5), 525-532. 4. Karlson E.W., Lee J.M. & Cook N.R. (1999). A retrospective cohort study of cigarette smoking and risk of

References 1. Gabriel S. (2001). Epidemiology of rheumatic diseases. In Ruddy S., Harris E., Sledge C., editors. Kelley’s Textbook of Rheumatology. Vol.1. 6th ed. Philadelphia, Pennsylvania: W. B. Saunders Company; 2011. pp. 321-333. 2. Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004;50(10):3085-92. 3. Makrygiannakis D, Hermansson M, Ulfgren AK, Nicholas AP, Zendman AJ, Eklund A, et al. Smoking

. Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study. Arthritis Res Ther. 2009;11:R110. 9. Karimi M, Mazloomzadeh S, Kafan S, Amirmoghadami H. The frequency of metabolic syndrome in women with rheumatoid arthritis and in controls. Int J Rheum Dis. 2011;14:248-254. 10. Karakoca M, Batmaza I, Sariyildiza MA, et al. The Relationship of Metabolic Syndrome With Disease Activity and the Functional Status in Patients With Rheumatoid

ABBREVIATIONS ACR - American College of Rheumatology ACCP - Antibodies against cycled citrullinated peptide bDMARD-s – biolocical Disease-modifying antirheumatic drugs CRP- C reactive protein c DMARD-s – conventional Disease-modifying antirheumatic drugs DAS28 - Disease Activity Score DMARD-s - Disease-modifying antirheumatic drugs EULAR - European League for Rheumatoid Arthritis ICER - Incremental cost-effectiveness ratio IL-1 - Interleukin-1 IL-6 - Interleukin-6 IL-8 - Interleukin 8 HAQ - Health Assessment Questionnaire NICE - National Institute

2010; 6: 417-429. 19. WILAND P., WOJATALA R., GOODACRE J., SZECHINKI J., The prevalence of subclinical amyloidosis in Polish patients with rheumatoid arthritis . Clin Rheumatol 2004; 23: 193-198. 20. GERTZ M.A., KYLE R.A., Secondary systemic amyloidosis: response and survival in 64 patients. Medicine (Baltimore) 1991; 70: 246-256. 21. KNUDSEN K.A., ROSAND J., KARLUK D., GREENBERG S.M., Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston Criteria. Neurology 2001; 56: 537-539. 22. VAN GAMEREN I.I., HAZENBERG B.P.C., BIJZET J., VAN RIJSWIJK