Rheumatoid Arthritis Flashcards
Rheumatoid arthritis - definition
A common seropositive inflammatory arthritis causing destructive polyarthritis with some systemic symptoms.
A major cause of disability, it can affect all synovial joints but particularly the small joints of the hands and feet
Rheumatoid arthritis - causes
Cause is unclear and there is some genetic component (15-20%) with a link to HLA DR4/DR1 in whites (65-80%) but others in different ethnic groups
Links to infectious agents or periods of stress have been suggested by evidence is lacking - EBV shares a epitope with type 2 collagen
Rheumatoid arthritis - clinical features
typically insidious onset pain and symmetrical morning stiffness in the small joints sparing the DIP
Patients can also present with subacute systemic symptoms without clear joint involvement
Patients may also show rheumatoid nodules, positive rheumatoid factor and joint erosions radiographically
Rheumatoid arthritis - epidemiology
Prevalence: 3.4/10,000 in women & 1.4/10,000 in men - 0.5-1% overall
Incidence increases with age up to 45, but in women the incidence plateaus at 45 and then decreases at 75
Life expectancy is reduced by 7 in men and 3 years in women
Rheumatoid arthritis - lymph node involvement
Often are found to be enlarged but rarely palpable
RA can rarely present with widespread swollen nodes which mimic hodgkins disease
Rheumatoid arthritis - pregnancy
Pregnancy has a beneficial affect on RA which usually returns 1-2 months post partum but my be more severe
Rheumatoid arthritis - pulmonary disease
Pleuritis, pericarditis and pleural effusions can occur, more likely in older patients
Sero-positive RA can present with asymptomatic pulmonary nodules which may require biopsy to exclude malignancy
Fibrosing alveolitis or diffuse interstitial fibrosis are rare complications, particularly when methotrexate has been used.
Rheumatoid arthritis - cardiovascular complications
RA has been shown to increase the risk of cardiovascular and atherosclerotic disease
1.3 increased risk in men and 1.9 in women
There is also a risk of pericardial effusion and constrictive pericarditis
Rheumatoid arthritis - skin
Palmar erythema is common
There is an association with raynaud’s and associated infarcts and infection risk
Leukocyclastic vasculitis can be seen as a visible purpura but usually spontaneously resolves
Rheumatoid arthritis - ocular complications
Rheumatoid vasculitis an lead to severe scleritis leading to scleromalcia
Associated with sjogren’s syndrome causing dryness
Rheumatoid arthritis - neurological involvement
Peripheral neuropathies can occur secondary to synovitis, particularly median nerve compression.
May be acute onset mononeuritis multiplex or motor neuropathy can indicate aggressive vasculitis
Cervical (atlano-axial) subluxation may also occur with neurological complications (cord compression)
Rheumatoid arthritis - ligament and tendon involvement
Spontaneous tendon rupture is common, most often at the wrist, hand and rotator cuff.
Tenosynovitis and ligament weakening can also often lead to joint instability and subluxation
Rheumatoid arthritis - fracture risk
Circulating Inflammatory cytokines may cause periarticular osteoporosis
This can be compounded by inactivity, nutritional deficiency and steroid/methotrexate use increasing the risk of spontaneous fractures
Rheumatoid arthritis - infection risk
RA patients are particularly at risk of septic arthritis
The risk is also compounded by immunosupressive drug use
This can be dangerous as the usual signs of sepsis will be absent
Rheumatoid arthritis - secondary amyloidosis
A severe but rare complication, most commonly affecting the kidneys
80% five year survival with intensive treatment
Felty’s syndrome
RA + splenomegaly + neutropenia.
RF +ve in ~100%
Initial evaluation of RA
Degree/duration of morning stiffness, joint pain and fatigue
Functional impairment and patient assessment of severity
Number and distribution of swollen, painful and dis-functioning joints - including periodicity and the any extra-articular disease
Radiographic and blood markers
Radiographic features of RA
Marginal erosive changes to the joints – also periarticular oestoporosis
May show early subluxation or distortion of the joints or bones
Joint space narrowing ad subchondral cysts
Blood markers in RA
IgM rheumatoid factor –> only 70-80% of patients are RF positive and a negative result shouldn’t override a clinical diagnosis
Anti-cyclic citrullinated peptide antibodies (anti-CCP) –> surrogate marker for RA (98% specific) 50-60% of early pts will be anti-CCP positive
Blood tests in RA
RF and anti-CCP are useful disease markers
ESR and CRP is also a useful general inflammatory marker
FBC, LFT, U+Es and urinalysis to assess for systemic disease
Pharmacotherapy for RA - Pain relief
analgesia and NSAIDs
Treatments of systemic disease in RA
Anaemia (iron, erythropoietin)
Osteoporosis (oestrogens, bisphosphonates, strontium, teriparatide)
Vasculitis (glucocorticoid, cyclophosphamide)
Amyloidosis (chlorambucil, anti-TNF therapies)
ACR classification criteria for RA
Four or more for >6wks: Radiographic changes
Morning stiffness >1hr Arthritis in 3 or more joints
Arthritis in hand joints Symmetrical arthritis
Rheumatoid nodules Serum Rheumatoid factor
Articular complications of RA
Subluxation or destruction of joints
Fibrous or bony Ankylosis
Infection
Systemic complications of RA
Anaemia (iron loss or chronic disease) Weight loss Amyloidosis: kidney, liver, gut Felty's syndrome Increased mortality generally (CVS etc)
Rheumatoid nodules in RA
Rheumatoid nodules occur in 30% of pts on the extensor surface of the forearm, and correlate with disease progression & sero-positivity
Can lead to pain, ulceration or infection
Have a necrotic core and surrounded by fibroblasts and immune cells
Pharmacotherapy for RA - DMARDs
glucocorticoids (IV, oral or intra-articular rarely)
Common:methotrexate, sulfasalazine, hydroxychloroquine, leflunomide
Less common:D-penicillamine, cyclosporin, azothioprine & IM gold
Pharmacotherapy for RA - Biologics
anti-TNF (etanercept, influximab, adalimunab),
anti-B cell (rituximab) – used on named patient basis
IL-1R antagonist (anakinra) – not as effective and not recommended
SEs:infection, TB reactivation, worsening HF
Quantifying the severity of RA
Joint counts – how many swollen and tender joints (out of 66 or 28)
Radiographic – how many erosions can be seen
Disability – Health Assessment Questionnaire scores
Composite score – DAS-28 (combines tender, swollen, ESR and general health) - >5.1 is severe, 3.2-5.1 is medium, <3.2 is low
Rheumatoid factor
a IgM autoantibody to the Fc portion of IgG which leads to the immune complex formation leading to further joint damage and vasculitis
80% of RA patients and some without symptoms – not central to pathogenesis
Pannus
Inflammatory fibrocellular mass of synovium, stroma and granulation tissue which erodes into underlying cartilage and bone – may form a fibrous bridge which can later ossify
Methotrexate in RA
A weekly dose taken on the same day – Oral or IM
Requires monitoring because of Immunosuppresion, liver toxicity, pneumonitis . Also very teratogenic
Slows the development of erosions
Sulphasalazine in RA
Twice a day oral – slows the development of eroisons
SEs: Bone marrow suppression, liver toxicity and oligospermia, rashes, oral ulcers and Heinz body anaemia
Leflunomide in RA
Developed specifically for RA – once daily oral
Slows the development of erosions
SEs: Bone marrow suppression, liver toxicity, HTN and teratogenic
Hydroxychloroquine in RA
Relatively safe but very effective alone – does not slow erosion development
SEs: ophthalmic toxicity (maculopathy, retinopathy, corneal opacities) (annual ophthalmology r/v) and may aggravate psoriasis
Gold in RA
IM, high incidence of side effects: rashes, marrow suppression, proteinuria
Cyclosporin in RA
Oral
SEs: hypertrichosis, gingival hypertrophy, HTN, renal and hepatic dysfunction
Azathioprine in RA
Oral and causes very significant bone marrow suppression
DMARD monitoring
Methotrexate – baseline CXR, monthly FBC, U+Es, LFTs
Leflunomide – monthly FBC, U+Es, LFTs, monitor BP
Sulphasalazine – monthly FBC, U+Es, LFTs
Hydroxychloroquine – baseline and yearly reading charts
Treatment strategies in RA
Combine DMARDs aggressively (Methotrexate+Hydroxychloroquine+Sulphasalazine) or (Methotrexate+cyclosporin) with early corticosteroids to control symptoms
Using anti-TNF drugs in RA
In active disease (>5.1) where 2 DMARDs have been tried -
Infliximab – monoclonal Ab – IV infusion every 8 weeks
Etanercept – Receptor fusion protein – SC injection once/twice weekly
Adalimumab – humanised monoclonal Ab – SC injection every 2wks
Future biologic therapies
Anti -IL6 receptor (tocilizumab) – monoclonal Ab - being trailed on pts
Anti -CTL4Ig (Abatacept) – co-stimulation blocker - used in US
Hand joint deformities in RA
Boutonnieres – flexion of PIP and extension of DIP
Swan neck – hyperextension PIP and flexion of DIP
Ulnar deviation of the finger MCPs
Radial deviation of the wrist
‘Z’ thumb deformity
Spine Involvement in RA
50% will have cervical spine involvement but the rest of the spine is spared
Osteoporosis, odontoid peg erosions and subluxation
Juvenile Rheumatoid\idiopathic arthritis
affects 1/1000 children under 16yrs – features early closure of growth plates and overgrowth of epiphyses
Periosteal reaction in the proximal phalanges/metacarpals
Joint ankylosis in the wrist, IP joints and cervical spine
Side effects of Biologics
Rituximab can cause infusion reactions.
Etanercept (also demylination), infliximab and adalimumab can all cause reactivation of tuberculosis
Caplan’s syndrome
Rheumatoid arthritis, pneumoconiosis and pulmonary rheumatoid nodules
Side effects of methotrexate
Myelosuppression
Liver cirrhosis
Pneumonitis
Side effects of sulfasalazine
Rashes
Oligospermia
Heinz body anaemia
Side effects of leflunomide
Liver impairment
Interstitial lung disease
HTN
Side effects of hydroxychloroquine
Retinopathy
Corneal deposits
Side effects of Gold
Proteinuria
Side effects of D penicillamine
Proteinuria
Exacerbation of myasthenia gravis
Side effects of infliximab
Reactivation of TB
