RA involves inflammation in the joint synovium, causing an inflammatory state that leads to articular cartilage loss and bony erosion, resulting in irreversible damage and functional impairment. The onset of disease is insidious, most typically presenting with symmetric polyarthritis described as pain, swelling, and inflammation of joints leading to stiffness after a period of inactivity. Some patients present with constitutional symptoms of malaise, fatigue, low-grade fevers, weight loss, and depressed mood. Patients may be anemic. Classically, this symmetrically distributed polyarthritis affects the small joints of the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal joints (MTP) early in disease. Other synovial joints may be involved including the elbows, shoulders, ankles, and knees. Of note, the C1-C2 joints of the spine and temporomandibular, sternoclavicular, or cricoarytenoid joints may be involved. Less common initial presentations include a monarticular or oligoarticular arthritis.
RA is labeled "seropositive" when rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPAs) are present. Seropositive disease tends to be more severe and associated with increased risk of systemic involvement. Rheumatoid nodules occur in up to 20% of RA patients and more frequently among patients with seropositive disease.
Initial evaluation of the patient presenting with joint pain should focus on determining whether the presenting arthritis pain is inflammatory vs. noninflammatory in nature. For example, inflammatory joint symptoms include a joint stiffness that occurs after inactivity – including in the morning after waking (> 30 minutes of stiffness) – and improves with activity. Signs of inflammation such as redness, swelling, and warmth should prompt consideration of inflammatory and infectious arthritides.
Felty syndrome is an uncommon presentation of severe RA with splenomegaly, neutropenia, and sometimes lower extremity ulcerations. A diagnosis of large granular lymphocytic leukemia should be considered in any patient with a Felty-like presentation.
Patients with interstitial lung disease and RA have a genetic promotor variant MUC5B.
Palindromic RA is episodic RA with intervening symptom-free periods. It is not RF seropositive.
It has been reported that exposure to moderate to high levels of silica increases the risk for rheumatoid arthritis. This association is more common in males due to occupational exposure.
Molecular and cellular studies are underway to determine the mechanism of flaring of RA.
Advances in medical therapy have greatly improved prognosis, decreased functional impairment, and increased quality of life for patients with RA.
Related topic: Juvenile idiopathic arthritis
M06.9 – Rheumatoid arthritis, unspecified
69896004 – Rheumatoid arthritis
- Systemic lupus erythematosus / connective tissue disease
- Psoriatic arthritis – Look for the presence of psoriasis on the scalp, posterior auricular regions, intertriginous areas, and intergluteal cleft as well as nail changes to help make this diagnosis.
- Polymyalgia rheumatica (PMR) – Overlap between RA and PMR may exist.
- Fibromyalgia / pain syndrome
- Crystal disease (pseudogout, gout)
- Still disease
- Septic arthritis
- Lyme arthritis (see Lyme disease)
- Acute viral arthritis (parvovirus B19, hepatitis B, hepatitis C, human immunodeficiency virus, chikungunya fever, rubella)
- Inflammatory bowel disease (ulcerative colitis, Crohn disease) – Associated arthritis.
- Reactive arthritis
- Seronegative spondyloarthritis (ankylosing spondylitis, etc)
- Synovial chondromatosis
- Paraneoplastic disease (hypertrophic osteoarthropathy, myelodysplasia)
- Sarcoid arthropathy (see sarcoidosis)
- Multicentric reticulohistiocytosis – Rare.
- Whipple disease – Rare.
Last Updated: 08/12/2020