Rheumatoid Arthritis(RA)

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may affect many tissues and organs—skin, blood vessels, heart, lungs, and muscles—but principally attacks the joints, producing a non-suppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints.

Although the cause of RA remains unknown, autoimmunity plays a pivotal role in its chronicity and progression. About 1% of the world's population is afflicted by RA, women two to three times more often than men. It is most common in those age 40 to 70, but no age is immune.

:* Pathophysiology Unknown antigen stimulates CD4+ T lymphocytes. Active CD4+ T lymphocytes; stimulates macrophages to release IL1 and TNF. Release RANKL which stimulates osteoclasts leading to bone destruction. IL-1 and TNF stimulates synovial cells leading to: Synovial cell proliferation and formation of pannaus. Production of prostaglandins (pain sensation) and matrix metalloproteinases that cause cartilage destruction.

* Sequence of events : Proliferation of synovial membrane cells with inflammatory cell infiltrate Destruction of joints Disability

* Diagnosis: 1. Clinical manifestations. 2. Investigations.

1. Clinical manifestations

Articular manifestations: Symmetric peripheral polyarthritis Morning Stiffness >1 hour Extra-articular manifestations:

Symmetric peripheral polyarthritis: 3 or more Joints for >6 weeks Small Joints Hands & feets Peripheral to Proximal Leads to deformity & destruction of Joints.

Morning stiffness: Morning or after Prolonged Inactivity. Bilateral > 1 hour. Better with movement Pain with movement of joint

Physical Examination: Decreased grip strength Carpal tunnel syndrome(condition characterized by pain and numbing or tingling sensations in the hand and caused by compression of a nerve in the carpal tunnel at the wrist. Ulnar deviation

* Extra-articular manifestations: Myalgia, fatigue, low-grade fever, weight loss, depression. Anemia Rheumatoid nodules Pleuropericarditis Neuropathy Scleritis Splenomegaly Vasculitis

Rheumatoid Nodules Extensor surfaces especially elbows Very Specific Only occur in ~30% Late in Disease

2. Investigations

1. Arthrocentesis. 2. Arthroscopy. Evaluate ligamentous & cartilaginous integrity Biopsy

Rheumatoid arthritis showing inflammatory cell infiltrate in the synovium

3. Laboratory investigations: Rhumatoid Factor: Positive in 70-80% of patients. - - IgM or IgG - If IgM+ve : more severe disease & poorer outcome. Acute Phase reactants: ESR, CRP  monitoring disease activity

4. Radiology: Evaluate disease activity & joint damage. Plain Films. Color Doppler U/S & MRI

Disease Severity

Mild case Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated ESR & CRP No erosions/cartilage loss No extra-articular manifestations.

Moderate case 6-20 Inflamed joints Moderate functional limitation Elevated ESR/CRP Radiographic evidence of inflammation No extra-articular manifestations.

Severe case >20 persistently inflamed joints Rapid decline in functional capacity Radiographic evidence of rapid progression of bony erosions & loss of cartilage Extra-articular manifestations.

Bad prognostic Features RF +ve Early development of multiple inflamed joints. Severe functional limitation Lower socioeconomic status & Less education Persistent joint inflammation for >12 weeks