Rheumatoid arthritis is a complex multisystem disease characterized by a symmetrical polyarthropathy, predominantly affecting small joints. However, varying patterns of arthritis may occur. It occurs in 0.5-1% of the adult population and is 2-3 times commoner in women.
Patients with RA demonstrate auto-immunity; the most characteristic being anti-citrullinated protein antibodies (ACPA), which are more specific for RA than rheumatoid factor (an antibody to the Fc component of IgG. Other antibodies have also been described. Citrullination is a post-transcriptional protein modification in which arginine is deimination to citrulline – this is promoted by smoking, which accounts for the relation between smoking and RA.
Patients with RA have synovitis infiltrated by B lymphocytes, monocytes and macrophages. Macrophages produce proinflammatory cytokines, especially TNF-α, IL-6 and IL-17. Rheumatoid fibroblast-like synoviocytes also elaborate inflammatory cytokines and are important in promoting cartilage destruction through activation of osteoclasts through receptor activator of NF-κB (RANK) ligand, producing joint erosions and the formation of inflammatory pannus over the damaged joint surface.
Several possible infective causes have been suggested for RA. Recent research has focused on Porphyromonas gingivalis, an oral commensal often involved in periodontitis. However, as with other organisms, evidence is inconclusive.
RA has a strong genetic element. Monozygotic twins have an incidence of 12-15%. Patients with RA commonly share an amino-acid sequence in the major histocompatibility complex, the "shared epitope". This is coded for by the HLA-DRB1 gene, at the HLA-DRw4 locus. The shared epitope is common in ACPA-positive but not ACPA-negative disease. Over 20 other genetic factors have been described, some of which are associated with ACPA-negative disease (HLA-DR3), or are protective against RA (different alleles at HLA-DRB1). There is some evidence that the shared epitope binds citrulline but not arginine and thus can present citrullinated proteins as antigens to T-cells.
A systemic disease
The inflammatory process may also affect extra-articular sites (Turesson 1999). 40% of patients will suffer extra-articular manifestations of RA, of which the commonest are rheumatoid nodules (30%) and keratoconjunctivitis sicca (10%). 1/100 patient-years will suffer a severe extra-articular manifestation such as vasculitis. The presence of extra-articular rheumatoid disease increases mortality by five times.
Rheumatoid nodules are present mainly in seropositive RA and occur mainly over extensor surfaces. They often improve with treatment of the RA, except that methotrexate may make them worse.
Many patients with RA have a normochromic normocytic anaemia of chronic disease with depressed erythropoietin levels and low responsiveness to erythropoietin. More serious is Felty’s syndrome (leukopenia with splenic and sometimes liver enlargement), which predisposes to severe infection. Patients with RA have a higher than average risk of lymphoid malignancies.
Patients with RA have a higher than normal rate of cardiovascular disease and cardiac death. More rarely they may have a small vessel vasculitis with digital infarcts. RA itself can cause pulmonary fibrosis and it is also a side-effect of methotrexate. Nodules may occur in the lungs; solitary nodules may be difficult to distinguish from lung carcinoma.
Peripheral neuropathy is relatively common (Wilson 2006) but rarely causes neuropathic ulceration (Firth 2008).
Other extra-articular manifestations include skin atrophy, episcleritis, amyloidosis and renal disease.
The complex nature of the condition requires a multidisciplinary team approach, including
- Orthopaedic specialists in other sites such as hip, knee and upper limb
- And the patient themself!
A changing disease
There is some evidence that the severity of RA has diminished over the past 50 years, quite apart from the effects of treatment (Verstappen 2011). In addition, changes in treatment over the last decade have also changed the problems that present to the surgeon, and have extended the reconstructive options available. It remains to be seen whether medical treatment will eventually prevent the need for surgical treatment in RA, as has happened in peptic ulcer disease.
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