Understanding RA Stages and Progression
How RA progresses and expresses itself varies widely from patient to patient. This variability can be seen in patterns of joint involvement, as well as the degree of disease involvement outside of the joints, including development of rheumatoid nodules, lung involvement, and other RA-related complications. One patient may experience RA symptoms that affect only small joints, while another may have symptoms that affect only large joints. Still other patients will experience more generalized disease that affects a range of joints, regardless of size. There is also wide variation among patients in how active the disease is and how quickly structural damage in the joints develops.1
Are the symptoms of RA constant throughout the disease?
For the majority of patients with RA, disease activity will fluctuate over time. For instance, most patients will experience periods lasting from weeks to months when symptoms increase or worsen. For many patients, a predictable long-term pattern of disease activity may develop that lasts over the entire course of the disease.1
For a minority of patients, around 10% to 20%, active disease may persist throughout the entire course of the disease.1
What is the likelihood of disease remission?
Lasting disease remission will occur in a small percentage of patients with RA and is linked to appropriate early treatment. In one study that included 191 patients with RA who received treatment with disease-modifying anti-rheumatic drugs (DMARDs) within the first year following diagnosis, one quarter experienced disease remission after receiving treatment for three years and this remission lasted through 5 years with continued treatment in 16% (30 out of 191) of patients.2
In this study, there were several factors that predicted the likelihood of experiencing lasting remission (through 5 years). In general, patients with milder disease at diagnosis had a greater chance for remission with treatment. Factors including having low disease activity (as measured by a standard score used to rate disease activity), a more favorable health assessment (as measured by the Health Assessment Questionnaire or HAQ), a low C-reactive protein (CRP) level (<14.5 mg/l), low joint tenderness (measured by Ritchie score), as well as less morning stiffness predicted a greater likelihood of remission.2
Predictors of likelihood of remission with early treatment
CRP=C reactive protein; DAS=disease activity score; HAQ=health assessment questionnaire.
Stages of RA
Early detection and treatment to control inflammation is of critical importance in RA, given the potential for rapid destruction of joint and other tissue and impairment of functioning. Although how RA progresses in individual patients and the pattern of joint involvement varies widely from patient to patient, in the majority of patients with RA (70%) some degree of joint erosion in the hands and feet is detectable by x-ray within the first two years of the disease.1
Without adequate treatment, at 20 years after diagnosis, more than 60% of patients with RA may develop significant functional impairment (stage III), including need of mobility aids, loss of ability for self-caring, and requirement of joint replacement, or experience loss of independence and require daily care (stage IV).1
Early stage RA (stage I) is characterized by synovitis, or an inflammation of the synovial membrane, causing swelling of involved joints and pain upon motion. During this stage, there is a high cell count in synovial fluid as immune cells migrate to the site of inflammation. However, there is generally no x-ray evidence of joint destruction, with the exception of swelling of soft tissues and possibly evidence of some bone erosion.3
In moderate RA, stage II, there is a spread of inflammation in synovial tissue, affecting joint cavity space across joint cartilage. This inflammation will gradually result in a destruction of cartilage, accompanied by a narrowing of the joint.3
Severe RA, stage III, is marked by formation of pannus in the synovium. Loss of joint cartilage exposes bone beneath the cartilage. These changes will become evident on x-ray, along with erosions around the margins of the joint. Joint deformities may also become evident.3
Stage IV is called terminal or end stage RA. The inflammatory process has subsided and formation of fibrous tissue and/or fusing of bone results in ceased joint function. This stage may be associated with formation of subcutaneous nodules.3
Stages of RA
Synovitis characterized by:
- Swelling of synovial membrane with excess of blood
- Small areas of lymphocyte infiltration in membrane
- Synovial fluid with high cell counts (5,000 to 60,000 per mm3)
- X-ray shows soft tissue swelling and possibly osteoporosis, but no evidence of joint destruction
- Proliferation of inflammation in joint tissue, spreading into joint cavity across joint cartilage
- Joint cartilage shows signs of gradual destruction
- Loss of joint cartilage results in a narrowing of joint
- Synovial pannus forms
- Joint cartilage becomes eroded and bone beneath cartilage is exposed
- X-ray shows extensive loss of cartilage, joint erosion (around margins), and possible deformities
- Disease reaches end stage with inflammatory process subsiding
- Loss of joint function
- Subcutaneous nodules form
- Venables PJW, Maini RN. Clinical features of rheumatoid arthritis. In: O'Dell JR, Romain PR, eds. UptoDate. Wolters Kluwer Health. Accessed at: www.uptodate.com. 2013.
- Gossec L, Dougados M, Goupille P, et al. Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study. Ann Rheum Dis 2004;63:675-80.
- Wheeless CR. Rheumatoid arthritis. In Wheeless CR, Nunley JA, Urbaniak JR, eds. Wheeless' Text of Orthopaedics. Data Trace Internet Publishing, LLC; Available at: www.wheelessonline.com: 2012.