Biology of Disease

AUTOIMMUNE DISORDERS

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Joint capsule

Synovial fluid

Synovial membrane

Bone

Bone

Bone

Bone

Cartilage

Inflammatory cells

Joint swelling

Invasion of the bone

by the synovial

capsule

Worn cartilage

A) B)

Figure 5.7 Schematics showing (A) a normal synovial joint and (B) the characteristic changes associated with rheumatoid arthritis.

MG patients is currently around 10%, which is a significant improvement on
previous decades.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, painful and debilitating condition
characterized by symmetrical arthritis and radiological changes to the
bone. The revised classification of rheumatoid arthritis (1988) is shown in
Table 5.8. Autoantibodies are present in the plasma of patients with RA. The
commonest, occurring in 70% of cases, is an IgM class antibody directed
against IgG, called rheumatoid factor (RF). However, RFs belonging to the
IgA and IgG classes have also been detected. The presence of RF causes large
amounts of immune complexes to be formed, since IgG is present at relatively
high concentrations in the blood. The complexes may adhere to blood vessel
walls, activating complement and initiating an inflammatory reaction. While
a minority of patients suffer a single episode of joint inflammation with long-
term remission, most have a progressive illness characterized by intermittent
‘flares’. In periods of active joint inflammation, the affected joints (Figure
5.7) are painful, swollen, red and warm to the touch; all characteristics of the
inflammation within them. The presence of RF and subsequent inflammatory
disease does not, however, adequately explain the pathogenesis of RA. Cell-
mediated immunity is known to be heavily involved in joint destruction. The
synovial membranes of affected joints are infiltrated with small lymphocytes,
especially TH1 cells, monocytes and macrophages so that the membranes
themselves become thickened. Activated macrophages within the synovial
fluid produce cytokines, such as IL-1 and tumor necrosis factor @ (TNF @),
which mediate erosion of bone. The accumulation of inflammatory
neutrophils within the synovial fluid also contributes to the damage to the
cartilage. Patients may also suffer inflammation of blood vessels or vasculitis
and about 20% have subcutaneous rheumatoid nodules, often on the elbows
and forearms but which may also occur in internal organs. The nodules
consist of a mass of monocytes, lymphocytes and plasma cells surrounding a
necrotic core, and probably represent the progression of vasculitis.

The etiology of RA remains unknown, despite numerous infectious agents
having been implicated over the years. However, RA remains one of the most
common autoimmune disorders, with an incidence of one to two per 100. The
female to male ratio is approximately 3 : 1 and the disease manifests maximally
between the ages of 40 and 60, although juvenile forms also exist.

Rheumatoid factor can be detected in plasma or serum by using the Rose-
Waaler test, which determines the ability of the serum to agglutinate sheep

Criteria for diagnosis

1. Stiffness of the joints in the morning


2. Arthritis in three or more joints


3. Arthritis of the joints in the hand


4. Symmetrical arthritis


5. Rheumatoid nodules


6. Serum rheumatoid factor


7. Radiological changes to the bone

Table 5.81988 Revised classification for rheumatoid

arthritis. To be diagnosed with RA, the patient must

have four or more of these symptoms and symptoms

one to four for at least six weeks.