RheumatoidnodulesareaninfrequentmanifestationofRAandtypicallyoccurinsubcutaneoustissueincludingtheforearm,elbows,occiput,andlumbosacralarea.Microscopically,theyresemble necrotizinggranulomas(Fig.21.38 ).Rarely,RAcaninvolvethelungs(rheumatoidnodules,interstitiallungdisease).
TH17 cell TH1 cell Antibodies Lymphocytes, antibodies and immune complexes enter joint
Release of Fibroblasts proteases and
Pannus formation Destruction of bone and cartilage
Fig.21.36Majorprocessesinvolvedinthepathogenesisofrheumatoidarthritis.
be produced during inflammation. Insults such as infection (including periodontitis) and smoking may promote citrullination of self-proteins, creating new epitopes that trigger autoimmune reactions.
The inflammation localizes to the joint, recruiting macrophages and triggering activation and/or proliferation of synovial cells, chondrocytes, and fibroblasts. The production of proteolytic enzymes and cytokines contributes to the destruction of cartilage and, through increased osteoclast activity, bone (
Fig. 21.36 http://ebooksmedicine.net
Fig.21.37Rheumatoidarthritis.(A)Schematicviewofthejointlesion.(B)Lowmagnificationshowsmarkedsynovialhypertrophywithformationofvilli.
(C)Athighermagnification,subsynovialtissuecontainingadenselymphoidaggregate.(A,Modified from Feldmann M: Development of anti-TNF therapy for rheumatoid arthritis. NatRevImmunol2:364, 2002.)
RA can be distinguished from other forms of polyarticular inflammatory arthritis by the presence of ACPA and by characteristic radiographic findings. In about half of patients, RA begins slowly and insidiously with malaise, fatigue, and generalized musculoskeletal pain. After several weeks to months, the joints become involved. The pattern of joint involvement is generally symmetrical and the hands and feet, wrists, ankles, elbows, and knees are most commonly affected. The metacarpophalangeal and proximal interphalangeal joints are frequently involved (in contrast to OA, see earlier).
Involved joints are swollen, warm, and painful. In contrast to OA, the joints are stiff when patient rises in the morning or following inactivity. The typical patient has progressive joint enlargement and decreased range of motion pursuing a chronic waxing and waning course. In a minority of patients, especially those lacking RF and ACPA, the disease may stabilize or even regress.
Fig.21.38Rheumatoidnodulecomposedofcentralnecrosisrimmedbypalisadedhistiocytes.
Inflammation in the tendons, ligaments, and occasionally the adjacent skeletal muscle frequently accompanies the arthritis and produces the characteristic ulnar deviation of the fingers and flexion-hyperextension of the fingers (swan-neck deformity, boutonnière deformity). Radiographic hallmarks are joint effusions and juxtaarticular osteopenia with erosions and narrowing of the joint space and loss of articular cartilage (
Fig. 21.39
The treatment for RA consists of corticosteroids, other immunosuppressants such as methotrexate, and, most notably, TNF antagonists. However, anti-TNF agents are not curative, and patients must be maintained on TNF antagonists to avoid disease flares. Long term treatment with TNF antagonists carries with it increased risk of infections with organisms such as M. tuberculosis.