musculoskeletal and connective tissue disorders
Rheumatoid Arthritis (RA)
Diagnosis of Rheumatoid Arthritis
Clinical criteria Serum rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP), and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) X-rays Rheumatoid arthritis should be suspected in patients with polyarticular, symmetric arthritis, particularly if the wrists and 2nd and 3rd metacarpophalangeal joints are involved. Classification criteria serve as a guide for establishing the diagnosis of rheumatoid arthritis and are helpful in defining standardized treatment populations for study purposes. Criteria include laboratory test results for RF, anti-CCP, and ESR or CRP (see table). However, diagnosis requires documented joint inflammation and should not be based on laboratory testing alone. Other causes of symmetric polyarthritis, particularly hepatitis C, must be excluded. Obtaining baseline x-rays of affected joints should be considered to help document progression of disease (erosive changes, joint space narrowing) over time. In patients who have prominent lumbar symptoms, alternative diagnoses should be investigated. RFs, antibodies to human gamma-globulin, are present in about 70% of patients with rheumatoid arthritis. However, RF, often in low titers (levels can vary between laboratories), occurs in patients with other diseases, including Other connective tissue diseases (eg, Systemic Lupus Erythematosus (SLE) ) Granulomatous diseases Chronic infections (eg, Overview of Acute Viral Hepatitis , Cancers Low RF titers can also occur in 3% of the general population and 20% of older patients. Very high RF titers can occur in patients with hepatitis C infection and sometimes in patients with other chronic infections. An RF titer measured by latex agglutination of>1:80 or a positive anti-CCP test supports the diagnosis of rheumatoid arthritis in the appropriate clinical context, but other causes must be excluded. Anti-CCP antibodies have high specificity (90%) and sensitivity (about 77 to 86%) for rheumatoid arthritis and, like RF, predict a worse prognosis. RF and anti-CCP values do not fluctuate with disease activity. Anti-CCP antibodies are notably absent in patients with hepatitis C who may have a positive RF titer and joint swelling related to the viral infection. X-rays show only soft-tissue swelling during the first months of disease. Subsequently, periarticular osteoporosis, joint space (articular cartilage) narrowing, and marginal erosions may become visible. Erosions often develop within the first year but may occur any time. MRI seems to be more sensitive and detects earlier articular inflammation and erosions. In addition, abnormal subchondral bone signals (eg, bone marrow lesions, bone marrow edema) around the knee suggest progressive disease. If rheumatoid arthritis is diagnosed, additional tests help detect complications and unexpected abnormalities. Complete blood count with differential should be obtained. A normochromic (or slightly hypochromic)-normocytic anemia occurs in 80%; hemoglobin is usually>10 g/dL (100 g/L). If hemoglobin is≤10 g/dL (100 g/L), superimposed iron deficiency or other causes of anemia should be considered. Neutropenia occurs in 1 to 2% of cases, often with splenomegaly (Felty syndrome). Acute-phase reactants (eg, thrombocytosis, elevated ESR, elevated CRP) reflect disease activity. A mild polyclonal hypergammaglobulinemia often occurs. ESR is elevated in 90% of patients with active disease. Validated measures of disease activity include the Rheumatoid Arthritis Disease Activity Score DAS-28 and Rheumatoid Arthritis Clinical Disease Activity Index. Synovial fluid examination is necessary with any new-onset effusion to rule out other disorders and differentiate rheumatoid arthritis from other inflammatory arthritides (eg, septic and crystal-induced arthritis). In rheumatoid arthritis, during active joint inflammation, synovial fluid is turbid, yellow, and sterile, and usually has white blood cell counts 10,000 to 50,000/mcL (10.0 x109/L to 50.0 x109/L); polymorphonuclear leukocytes typically predominate, but>50% may be lymphocytes and other mononuclear cells. Crystals are absent. Many disorders can simulate rheumatoid arthritis: Overview of Crystal-Induced Arthritides None Systemic Lupus Erythematosus (SLE) None Sarcoidosis (rarely causes a polyarticular arthritis) Reactive Arthritis None Psoriatic Arthritis None Ankylosing Spondylitis None Infectious causes such as Hepatitis C, Chronic , Osteoarthritis (OA) None Some patients with crystal-induced arthritis, especially Calcium Pyrophosphate Arthritis , may meet criteria for rheumatoid arthritis; however, synovial fluid examination should clarify the diagnosis. The presence of crystals makes rheumatoid arthritis unlikely, although calcium pyrophosphate crystal disease and rheumatoid arthritis may coexist in the same patient. Joint involvement and subcutaneous nodules can result from SLE, gout, cholesterol, and Systemic Lupus Erythematosus (SLE) usually can be distinguished if there are skin lesions on light-exposed areas, hair loss, oral and nasal mucosal lesions, absence of joint erosions in even long-standing arthritis, joint fluid that often has white blood cell counts Arthritis similar to rheumatoid arthritis can also occur in other rheumatic disorders (eg, Polyarteritis Nodosa (PAN) , Sarcoidosis , Reactive Arthritis can be differentiated by antecedent gastrointestinal or genitourinary symptoms; asymmetric involvement and pain at the Achilles insertion of the heel, sacroiliac joints, and large joints of the leg; conjunctivitis; iritis; painless buccal ulcers; balanitis circinata; or keratoderma blennorrhagicum on the soles and elsewhere. Psoriatic Arthritis tends to be asymmetric and is not usually associated with RF, but clinical differentiation may be difficult in the absence of nail or skin lesions. Distal interphalangeal joint involvement and severely mutilating arthritis (arthritis mutilans) is strongly suggestive, as is the presence of a diffusely swollen (sausage) digit. Psoriatic arthritis may involve the sacroiliac joints and lower spine. Distinguishing between psoriatic arthritis and rheumatoid arthritis is important because response to some specific drugs differs. Ankylosing Spondylitis may be differentiated by spinal and axial joint involvement, absence of subcutaneous nodules, and a negative RF test. The HLA-B27 allele is present in 90% of White patients with ankylosing spondylitis. Osteoarthritis (OA) can be differentiated by the joints involved; the absence of rheumatoid nodules, systemic manifestations, or significant amounts of RF; and by synovial fluid white blood cell counts 