Rheumatoid Arthritis

INTRODCUCTION

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder of unknown etiology characterized by polyarticular symmetric joint involvement and systemic manifestations

CLINICAL PRESENTATION

Nonspecific prodromal symptoms developing over weeks to months include fatigue, weakness, low-grade fever, anorexia, and joint pain. Stiffness and myalgias may precede development of synovitis.

• Joint involvement tends to be symmetric and affect small joints of the hands, wrists, and feet; elbows, shoulders, hips, knees, and ankles may also be affected.
• Joint stiffness typically is worse in the morning, usually exceeds 30 minutes, and may persist all day.
• On examination, joint swelling may be visible or apparent only by palpation. Tissue is soft, spongy, warm, and may be erythematous. Joint deformities may involve subluxations of wrists, metacarpophalangeal joints, and proximal interphalangeal joints (swan neck deformity, boutonnière deformity, and ulnar deviation).

DIAGNOSIS

The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) revised criteria for diagnosis of RA in 2010. These criteria are intended for patients early in their disease and emphasize early manifestations. Late manifestations (bone erosions, subcutaneous nodules) are no longer in the diagnostic criteria. Patients with synovitis of at least one joint and no other explanation for the finding are candidates for assessment. The criteria use a scoring system with a combined score of 6 or more out of 10 indicating that the patient has definite RA.

• Laboratory abnormalities include normocytic, normochromic anemia; thrombocytosis or thrombocytopenia; leukopenia; elevated erythrocyte sedimentation rate and C-reactive protein; positive rheumatoid factor (60%–70% of patients); positive anticitrullinated protein antibody (ACPA) (50%–85% of patients); and positive antinuclear antibodies (25% of patients).
• Aspirated synovial fluid may reveal turbidity, leukocytosis, reduced viscosity, and normal or low glucose relative to serum concentrations.
• Early radiologic findings include soft tissue swelling and osteoporosis near the joint (periarticular osteoporosis). Erosions later in the disease course are usually seen first in the metacarpophalangeal and proximal interphalangeal joints of the hands and metatarsophalangeal joints of the feet.

TREATMENT

Goals of Treatment: The ultimate goal is to induce complete remission or low disease activity. Additional goals are to control disease activity and joint pain, maintain ability to function in daily activities

General Approach

Start disease-modifying antirheumatic drugs (DMARDs) as soon as possible after disease onset because early treatment results in more favorable outcomes.

• DMARDs slow RA disease progression. Common nonbiologic DMARDs include methotrexate (MTX), hydroxychloroquine, sulfasalazine, and leflunomide. The order of selection is not clearly defined, but MTX is often chosen initially because long-term data suggest superior outcomes compared with other DMARDs and lower cost than biologic agents.
• Combination therapy with two or more nonbiologic DMARDs may be effective when single-DMARD treatment is unsuccessful. Recommended combinations include

(1) MTX plus hydroxychloroquine,

(2) MTX plus leflunomide,

(3) MTX plus sulfasalazine, and

(4) MTX plus hydroxychloroquine plus sulfasalazine.

Tab Naprox (Naproxen) 500mg 1 tab PO BD or . Tab Celbexx ( Celecoxib) 100-200mg, 1 tab PO BD Tab Deltacotril ( Prednisolone) 5 mg, 4-6 tabs PO BD for 6 days Tab Cytotrexate (Methotrexate) 2.5mg, 1tab PO TDS in a day once a week

Methotrexate (MTX) inhibits cytokine production and purine biosynthesis, and may stimulate adenosine release, all of which may lead to anti-inflammatory properties. Onset is as early as 2 to 3 weeks, and 45% to 67% of patients remained on it in studies ranging from 5 to 7 years.

• Concomitant folic acid may reduce some adverse effects without loss of efficacy. Monitor liver injury tests periodically, but a liver biopsy is recommended during therapy only in patients with persistently elevated hepatic enzymes. MTX is teratogenic, and patients should use contraception and discontinue the drug if conception is planned.
• MTX is contraindicated in pregnant and nursing women, chronic liver disease, immunodeficiency, pleural or peritoneal effusions, leukopenia, thrombocytopenia, preexisting blood disorders, and creatinine clearance of less than 40 mL/min (0.67 mL/s).
• Lefora (Leflunomide) inhibits pyrimidine synthesis, which reduces lymphocyte proliferation and modulation of inflammation. Efficacy for RA is similar to that of MTX.
• A loading dose of 100 mg/day for 3 days may result in therapeutic response within the first month. The usual maintenance dose of 20 mg/day may be lowered to 10 mg/ day in cases of GI intolerance, alopecia, or other dose-related toxicity.

Tab Salazine (Sulfasalazine) 500mg PO OD use is often limited by adverse effects. Antirheumatic effects should be seen within 2 months.

• GI symptoms may be minimized by starting with low doses, dividing the dose evenly throughout the day, and taking it with food.