Flashcards in Rheumatology - RA Deck (26)
What is RA?
RA is a chronic and common inflammatory joint condition. Its aetiology is multifactorial and the clinical course is variable with exacerbations and remissions of activity.
Joint inflammation leads to joint damage and erosion.
What are the clinical features of RA?
RA is a small joint inflammatory polyarthropathy - joints are swollen, warm/ red, and tender to palpation. There is also prolonged early morning stiffness of >2 hours.
Extra articular manifestations are common and affect multiple systems. Raynauds and sicca symptoms (dry eyes and mouth) being very common.
The disease often starts in the small joints and spread to other joints occurs over months to years.
What are the classical findings on examination of rheumatoid hands?
RA affects the MCPJ and PIPJ's predominantly with sparing of the DIPs. The findings are also symmetrical, with the same joints involved in both hands.
Other findings include MCP subluxation, ulnar deviation, Z thumb and rheumatoid nodules.
Swan neck and Boutonniere deformities are also characteristic of RA. The joints are warm, swollen and tender.
- Swan neck = hyper-extension of the PIPJ and hyper-flexion of the DIPJ
- Boutonniere = hyper-flexion of the PIPJ and hyper-extension of the DIPJ
What investigations are important in RA?
FBC - anaemia (normochromic normocytic), high platelets (rise due to inflammatory process)
Raised ESR and CRP
RhF and anti-CCP positive - RhF is positive in 80% of patients and is an antibody directed against the Fc portion of IgG
- soft tissue swelling
- periarticular osteopenia
- loss of joint space
What are the pathological features of RA?
RA is a synovitis (inflammation of the synovial membrane)
Macroscopically - joints are painful, swollen and tender. The synovial membrane is thickened with villous overgrowth, increased vascularity and a pannus or plate which grows over and replaces the articular cartilage.
Microscopically - synovial membrane shows villous proliferation with a large lymphocyte and plasma cell infiltration of the oedematous villous fronds. The proliferated synovial tissue extends over the surface of the articular cartilage as a pannus of fibrous tissue containing lymphocytes. This gradually erodes the cartilage and replaces it with a fibrous mass.
What is the immunopathology of RA?
The synovial membrane undergoes infiltration by lymphocytes causing villous hypertrophy. Release of IL-1 and TNFalpha by activated T cells and plasma cells is implicated strongly in the inflammatory process as blocking these molecules often causes remission of symptoms.
What patients are typically at risk of extra-articular manifestations of RA?
Patients who are HLA-DR1 and DR4 positive and smokers.
What is a common cutaneous extra-articular manifestation of RA?
Subcutaneous rheumatoid nodules are very common and are more likely to occur in patients that are RhF positive (they are rare in RhF negative patients).
They tend to occur at pressure points - e.g. the elbows - and are believed to result from a small vessel vasculitis with fibrinoid necrosis forming at the centre of the nodule.
Nailfold infarcts and splinter haemorrhages are also common.
What type of pleural effusion is encountered in RA?
Transudates - low protein, low [glucose]
Why can pulmonary nodules in RA be problematic?
They are usually asymptomatic and often accompany nodules elsewhere. They are usually in the peripheral lung but can cavitate and cause effusions or fistulae leading to a pneumothorax.
What is Caplan's syndrome?
This is the combination of rheumatoid nodules and coal miners pneumoconiosis. There are typically multiple nodules of >1cm diameter.
Other than effusion and nodules, give some other pulmonary manifestations of RA?
1) Fibrosing alveolitis - more common in men; inflammatory (alveolitic) phase usually precedes scarring (fibrotic) phase, diagnosis by HRCT; clinically, basal late inspiratory fine crepitations
2) Bronchiolitis obliterans - may be secondary to therapy
3) Pulmonary arteritis (rare)
4) Drug toxicity - pulmonary fibrosis caused by methotrexate, infection with PCP secondary to immunosuppression
What are the neurological features of RA?
- peripheral neuropathy caused by entrapment or vasculitis (tends to cause mononeuritis multiplex)
- atlanto-axial subluxation may cause compression of the cervical cord leading to a myelopathy
Why can anaemia occur in RA?
This may not simply be to anaemia of chronic disease (normocytic). It could also be caused by:
- iron deficiency - NSAID induced blood loss
- bone marrow suppression - DMARD induced
- hypersplenism - Felty's syndrome
What is Felty's syndrome?
This is RA + splenomegaly + leukopenia. 1/3 have no active synovitis at the time of development of Felty's.
May be associated with leg ulceration and hyperpigmentation.
Bacterial infections in these patients are common.
How is the eye involved in RA?
Inflammation of the blood vessels in the eye can lead to scleritis. If this is not treated it can progress to scleromalacia perforans where the sclera becomes perforated and vision is lost.
Drug toxicity affecting the eyes may also occur:
- steroids - cataracts
- chloriquine - retinopathy
How is the kidney involved in RA?
The kidney may rarely be involved due to the disease process causing a membranous glomerulonephritis. More commonly, drug treatment affects the kidneys. NSAIDs can cause an interstitial nephritis or pre renal failure.
What are the cardiac manifestations of RA?
Pericarditis is common but not usually symptomatic. Coronary artery disease occurs fairly commonly and accounts for the increased mortality in patients with RA. It may be related to endothelial dysfunction.
What is the differential diagnosis for RA?
1) Post viral (parvovirus, rubella)
2) Reactive arthritis (GI or GU infection)
4) Polyarticular gout
5) Polyarticular OA
What is the classification criteria for RA?
ACR classification states that patients must have 4/7 of the following features:
1) Morning stiffness >1hr
2) Arthritis of at least 3 areas (> 6wks)
3) Arthritis of hand joints
4) Symmetrical arthritis
5) Rheumatoid nodules
6) Serum RhF
7) Radiographic changes
The first 5 criteria can be found on clinical examination alone and do not require testing.
What biologic agents are most commonly used in RA?
Biologics are monoclonal antibodies that target pro-inflammatory cytokines or cells involved in the immunopathology of RA.
Anti-TNF therapies are the most common and include:
Tocilizumab (IL-6 receptor antagonist) and Rituximab (anti-B cell therapy) are also used.
What initial therapy is recommended by NICE for RA?
NICE recommend patients with newly diagnosed RA start with a combination of DMARDs (including methotrexate and at least one other DMARD) plus short term steroids.
What are the DMARDs?
Methotrexate is the most commonly used DMARD. These are Disease Modifying Anti Rheumatic Drugs. Other examples include sulfasalazine, leflunomide, and hydroxychloriquine.
Methotrexate requires monitoring of FBC and LFTs due to the risk of myelosuppression and liver cirrhosis. Other effects include pneumonitis.
Under what circumstances can patients be considered for TNF alpha therapy?
Current guidance is following failure of 2 or more DMARDs including methotrexate. Examples include:
- etanercept: recombinant human protein, acts as a decoy receptor for TNF a, sub cutaneous administration, can cause demyelination, risks include reactivation of TB
- infliximab: monoclonal antibody, binds to TNF alpha and prevents it binding to TNF a receptor, i.v. administration, risks include reactivation of TB
- adalimumab: monoclonal antibody, sub cut administration
What is rituximab?
Anti-CD20 monoclonal antibody that results in B cell depletion. Two Ig i.v. infusions are given 2 weeks apart. Infusion reactions are common.