Rheumatoid arthritis (RA) is a chronic multisystemic disease of unknown cause, in which persistent synovitis symmetrically involving peripheral joints is the characteristic manifestation. Despite the destructive nature of RA, the clinical course varies widely, with some patients experiencing only a transient oligoarthritic process, while others may have a persistently progressive polyarthritic process with significant joint dysfunction. The prevalence of RA is 0.8% of the population, with female patients being three times more likely than male patients, and 80% of cases starting between the ages of 35 and 50. Familial studies have shown a genetic susceptibility to RA. In first-degree relatives of patients with rheumatoid factor-related disease, the prevalence of severe RA is approximately four times the expected value. The type II major histocompatibility allele and related alleles are considered to be the major genetic risk factors for RA. Based on the genetic susceptibility to RA, it has been proposed that RA may be a manifestation of a genetically susceptible host’s response to an infectious agent, including chronic inflammation caused by microbial products trapped in synovial tissue and an immune response against joint components induced by exposure to joint antigen peptides. Because RA is globally distributed, it is envisioned that if an infectious agent exists, then this pathogen must be ubiquitous. Presumably possible pathogens include mycoplasma, EBV virus, cytomegalovirus, rubella virus, etc. Clinical presentation: Approximately 2/3 of patients have an insidious onset of malaise, anorexia, generalized weakness, and vague musculoskeletal symptoms before the onset of overt synovitis, with gradual onset of joint symptoms, often with morning stiffness. Nearly 10% of patients with RA have an acute onset and present with rapidly developing polyarthritis, often accompanied by systemic symptoms such as fever, enlarged lymph nodes, and splenomegaly. The characteristic joints involved are the proximal interphalangeal and metacarpophalangeal joints. The wrist, elbow, knee and ankle joints can be involved. Synovial inflammation leads to swelling, pressure and limitation of motion. Pain originates primarily in the joint capsule, which is rich in painful fibers and is particularly sensitive to traction and pain. Swelling of the joint is due to accumulation of joint fluid, synovial hyperplasia and thickening of the joint capsule. Initial limitation of motion is caused by pain, followed by cartilage destruction, fibrosis, bony ankylosis and soft tissue contracture leading to joint deformity and limitation of motion. Persistent inflammation causes a series of characteristic joint changes, such as radial deviation of the wrist with ulnar deviation of the fingers (Z-deformity), proximal interphalangeal joint oversubscription with compensatory flexion of the distal interphalangeal joint (swan neck deformity), talocrural joint exostosis of the heel, lateral deviation of the toes and distal subluxation. Extra-articular manifestations: Extra-articular manifestations are common and sometimes they are important evidence of disease activity and disability. These extra-articular manifestations are usually seen in those patients with high titers of rheumatoid factor. Rheumatoid vasculitis, which can affect almost any organ system, is seen in patients with severe RA or with high titers of rheumatoid factor and can lead to sensory neuropathy, multiple mononeuritis, skin ulceration and necrosis, gangrene of the fingers, and organ infarction. Pulmonary pleural manifestations, which can lead to interstitial pulmonary fibrosis, pleurisy, and pneumonia. Rheumatoid nodules, commonly found in the periarticular and extensor surfaces, but can also occur elsewhere, including the pleura and cerebrospinal membranes. Felty’s syndrome, including chronic RA, splenomegaly, leukopenia, anemia, and thrombocytopenia. Skeletal muscle weakness and atrophy, usually more prominent in the muscle tissue around the joints. Laboratory tests: There are no specific tests that can diagnose RA. About 2/3 of patients can have a positive rheumatoid factor, but this is not specific because rheumatoid factor positivity is seen in 5% of the healthy population, in transient positivity after vaccinations and blood transfusions, and in other diseases (systemic lupus erythematosus, desiccation syndrome, chronic liver disease, hepatitis B, tuberculosis, interstitial lung fibrosis, syphilis, etc.). Therefore, the rheumatoid factor test is not used as a screening test, but it can be used to assess the condition and prognosis of patients with high titers of rheumatoid factor because they have more severe, more rapidly progressive joint disease and are more likely to have extra-articular systemic damage. Anti-citrullinated protein antibodies (Anti-CCP) are more specific for RA, so testing for Anti-CCP can help in the early differential diagnosis of RA. In addition, anemia and elevated platelets, sedimentation, and C-reactive protein are also associated with disease activity and progression. Imaging: The main value is to clarify the extent of cartilage destruction and bone erosion caused by the disease, to assess the aggressiveness of the disease, to test the efficacy of disease-modifying drugs (DMARDS) or to decide whether surgical intervention is needed. Diagnosis and treatment: Diagnosis relies on characteristic clinical manifestations and exclusion of other inflammatory processes. Treatment, because the etiology of RA is not clear and the pathogenesis is not fully understood, is empirical in its treatment. There is no therapeutic intervention that can cure RA, and the goal of treatment is to relieve pain, reduce inflammation, protect joint structures, maintain function, and control system involvement. The main drugs are non-steroidal anti-inflammatory drugs (used to relieve local inflammation and symptoms), anti-rheumatic drugs that improve the condition DMARDS (slowly bring clinical improvement), glucocorticoids (rapidly control systemic inflammation and systemic damage), immunosuppressive drugs (similar in efficacy to DMARDS, available when DMARDS is ineffective) biologics (effective in controlling symptoms and slowing the process of joint destruction).