Rheumatoid Arthritis Disease Process

Rheumatoid arthritis (RA) is a disease defined by seven criteria, with four that should be fulfilled to make the diagnosis (Table 1). These criteria have been useful in harmonizing clinical trials and clinical practice. However, they are not based on what is now known about etiology or pathogenesis, and they are not too helpful in selecting treatment for the single patient. Hence, there are needs to redefine the diagnosis for RA and related diseases, first to define entities more related to distinct etiologies and pathogenetic mechanisms, then to use such new entities for stratification and selection of patients in clinical trials and clinical practice.

Basic features of the immune and inflammatory process in RA are, on the one hand, processes that can be identified in the peripheral circulation, initially

TABLE 1 Classification Criteria for Rheumatoid Arthritis"

1. Morning stiffness in and around joints lasting at least 1 hour before maximal improvement

2. Soft tissue swelling (arthritis) of three or more joint areas observed by a physician

3. Swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints

4. Symmetric swelling (arthritis)

5. Rheumatoid nodules

6. Presence of rheumatoid factor

7. Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints

Source: Arnett FC, Edworthy SM, Bloch DA, et al. (American Rheumatism Association) (1988). The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum, 31:315-324.

"Criteria 1 through 4 must have been present for at least six weeks. Rheumatoid arthritis is defined by the presence of four or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. These criteria demonstrated 91 to 94% sensitivity and 89% specificity for RA compared with non-RA rheumatic disease control subjects.

Synovial fluid

Joint capsule

Synovial membrane

Synovial fluid

Joint capsule

Synovial membrane

Figure 1 Inflamed RA joint. In healthy joints a thin synovial membrane lines the joint capsule and the synovial fluid. In the RA joint both the synovial membrane and the synovial fluid are infiltrated by inflammatory cells, leading to tender and swollen joints. The synovial membrane also "grows" over the cartilage, aiding in the process of cartilage and bone desctruction.

Figure 1 Inflamed RA joint. In healthy joints a thin synovial membrane lines the joint capsule and the synovial fluid. In the RA joint both the synovial membrane and the synovial fluid are infiltrated by inflammatory cells, leading to tender and swollen joints. The synovial membrane also "grows" over the cartilage, aiding in the process of cartilage and bone desctruction.

rheumatoid factors (RFs), and on the other hand, processes in the inflamed tissue, mainly the joints (Figure 1). Rheumatoid factors, identified almost 70 years ago, are part of the diagnostic criteria for RA. Being present in some 50 to 60% on incident RA cases and increasing over time with active disease, these auto-antibodies are also seen in many non-RA conditions and are thus not very specific for the disease.

Rheumatoid factors have never been shown to be pathogenic by themselves, neither in patients nor in experimental models. They are thus seen mainly as biomarkers of importance for diagnosis and prognosis of a more severe disease course, but not necessarily directly involved in disease patho-genesis. Joint inflammation in RA is focused on synovial inflammation, in many cases associated with cartilage destruction and concomitant erosions in bone. This inflammation has been studied in large detail over the years, demonstrating that its features are common to many other types of chronic inflammation in other tissues. No real RA pathognomonic features have yet been identified, the most unique feature identified so far being the way the inflammatory cells and molecules attack and destroy bone and cartilage.

Having the major features of RA, the synovial joint inflammation and presence of RF being typical but by no means unique for RA, there is an obvious need to define more specific features of the disease. The identification of such features would enable us to search for a better understanding of the patho-genesis of RA, a more accurate diagnosis based on biomarkers, and more specific treatments.

Osteoarthritis

Osteoarthritis

Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.

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