Rheumatoid arthritis: Treatment

Non-Pharmacologic Therapy:

Adequate rest, weight reduction if obese, occupational therapy, physical therapy, and use of assistive devices may improve symptoms and help maintain joint function.

Patients with severe disease may benefit from surgical procedures such as tenosynovectomy, tendon repair, and joint replacements.

Patient education about the benefits and limitations of drug therapy is important.

Pharmacologic Therapy:

General Approach:

A disease-modifying antirheumatic drug (DMARD) should generally be started within the first 3 months of symptom onset. DMARDs should be used in all patients except those with limited disease or those with class IV disease in whom little reversibility is expected. Early use of DMARDs results in a more favorable outcome and can reduce mortality.

First-line DMARDs include methotrexate, hydrochloroquine, sulfasalazine, and leflunomide. The order of agent selection is not clearly defined. Hydroxychloroquine or Sulfasalazine may be used initially in mild disease, but methotrexate is often chosen initially in more severe cases because of long-term data suggesting superior outcomes than other DMARDs and lower cost than biologic agents. Leflunomide appears to have long-term efficacy similar to methotrexate.

Rheumatoid arthritis: Desired outcome

The ultimate goal of RA treatment is to induce a complete remission, although this is seldom achieved. The primary objectives are to reduce joint swelling, stiffness, and pain; preserve range of motion and joint function; improve quality of life; prevent systemic complications; and slow destructive joint changes.

Rheumatoid arthritis: Diagnosis

The American Rheumatism Association criteria for classification of RA are (1987 revision):

Sr. no.	Criteria	Definintion
1.	Morning stiffness	Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement.
2.	Arthritis of three or more joint areas	At least three joint areas simultaneously have soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible joints are (right or left): PIP, MCP, wrist, elbow, knee, ankle,and MTP joints.
3.	Arthritis of hand joints	At least one joint area swollen as above in wrist, MCP, or PIP joint.
4.	Symmetric arthritis	Simultaneous involvement of the same joint areas (as in 2) on both sides of the body (bilateral involvement of PIP, MCP, or MTP joints is acceptable without absolute symmetry).
5.	Rheumatoid nodules	Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician.
6.	Serum rheumatoid factor	Demonstration of abnormal amounts of serum rheumatoid factor by any method that has been positive in less than 5% of normal control subjects.
7.	Radiographic changes	Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist x-rays, which must include erosions or uniequivocal bony decalcification localized to or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify).

For classification purposes, a patient is said to have rheumatoid arthritis if he or she has satisfied at least four of these seven criteria. Criteria 1 through 4 must be present for at least 6 weeks. Patients with two clinical diagnosis are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is not to be made.

PIP: proximal interphalangeal

MCP: metacarpophalandeal

MTP: metatarsophalangeal

Laboratory abnormalities that may be seen include normocytic, normochromic anemia; thrombocytopenia; leukopenia;elevated erythrocye sedimentation rate (ESR);positive rheumatoid factor (60% to 70% of patients); and positive antinuclear antibodies (ANA) (25% of patients).

Examination of aspirated synovial synovial fluid may reveal turbidity,  leukocytosis, reduced viscosity, and normal or low glucose relative to serum concentrations.

Radiologic findings include soft tissue swelling and osteoporosis near the joint (periarticular osteoporosis). Erosions occurring later in the disease course are usually seen first in the MCP and PIP joints of the hands and metatarsophalangeal (MTP) joints of the feet.

Rheumatoid arthritis: Clinical Presentation

Nonspecific prodromal symptoms that develop insidiously over weeks to months may include fatigue, weakness, low-grade fever, loss of appetite, and joint pain. Stiffness and myalgias may precede development of synovitis.

Joint involvement tends to be symmetric and affect the small joints of the hands, wrists, and feet; the 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 may be apparent only by palpation. The tissue feels soft and spongy and may appear erythematosus and warm, especially early in the course of the disease.

Chronic joint deformities commonly involve subluxations of the wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints (swan-neck deformity, boutonniere deformity, ulnar deviation).

Extra-articular involvement may include rheumatoid nodules, vasculitis, pleural effusions, pulmonary fibrosis, ocular manifestations, pericarditis, cardiac conduction abnormalities, bone marrow suppression, and lymphadenopathy.

Rheumatoid arthritis: Pathophysiology

Rheumatoid arthritis (RA) results from dysregulation of the humoral and cell-mediated components of the immune system. Most patients produce antibodies called rheumatoid factors; these seropositive patients tend to have a more aggressive course than patients who are seronegative.

Immunoglobulins can activate the complemet system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. The processed antigen is recognized by the major histocompatibility comples (MHC) proteins on the lymphocyte surface, resulting in activation of T and B cells.

Tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are proinflammatory cytokines important in the initiation and continuance of inflammation.

Activated T cells produce cytotoxins, which are directly toxic to tissues, and cytokines, which stimulate further activation of inflammatory processes and attract cells to areas of inflammation. Macrophages are stimulated to release prostaglandins and cytotoxins.

Activated B cells produce plasma cells, which form antibodies that, in combination with complement, result in accumulation of polymorphonuclear leukocytes (PMNs). PMNs release cytotoxins, oxygen free radicals, and hydroxyl radicals that promote cellular damage to synovium and bone.

Vasoactive substances (histamine, kinins, and prostaglandins) are released at sites of inflammation, increasing blood flow and vascular permeability. This causes edema, warmth, erythema, and pain and makes it easier for granulocytes to pass from blood vessels to sites of inflammation.

Chronic inflammation of the synovial tissue lining the joint capsule results in tissue proliferation (pannus formation). Pannus invades cartilage and eventually the bone surface, producing erosions of bone and cartilage and leading to joint destruction. The end results may be loss of joint space, loss of joint motion, bony fusion (ankylosis), joint subluxation, tendon contractures, and chronic deformity.

Rheumatoid arthritis - Definition

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