Transcript Diagnosis and Investigation of Arthritis

Rheumatoid Arthritis
VTS Course 6.4.2010
Dr Daniel Fishman
Consultant Rheumatologist
Luton and Dunstable
• Arthritis
– Inflammation of a joint
• Pain, redness, heat, swelling, loss of function
– Is it ‘inflammatory’ arthritis i.e. RA?
– Is it ‘degenerative’ arthritis i.e. OA?
35 year old female
• Previously well: 8 weeks of
– pain, swelling, stiffness all small joints of
fingers of both hands, progressive
– 2 hours morning stiffness; Generally unwell
• O/e puffy sts mcp and pip j’s, metatarsalgia
• U&E normal, Hb 10.9. ESR 58, CRP 37
• RF Latex Pos; RW Pos 1/320, AA’s Neg
• RA
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Held ‘protected’
Soft tissue swelling
Symmetrical
Longer EMS
Eased by rest
MCPs
78 year old female
• Mild T2 DM; stable angina; cholecystectomy
• 2~3 years of progressive, deforming small
joint swelling, occ. Painful, esp. base of left
thumb and DIPjs
• Knees ache, occ. swell, difficulty with stairs.
• FBC, U&E, LFT all normal,
• RA Latex pos, RW neg.
• OA
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‘Massaged’
Bony swelling
DIP and 1st CMCj
Heberden’s Nodes
Brief EMS
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‘Good days/bad days’
Movement/weight bearing
<15 mins EMS/gelling
Oligoarticular
Associated knee OA
Frequency of finger joints
affected in GNOA
22 year old male
• 8 years of moderately severe plaque
Psoriasis
• Swelling 3rd toe left foot, right index finger
DIP joint, left middle finger DIP joint, right
thumb
• ESR 28, RF neg, AA negative.
Psoriatic arthropathy
63 year old female
• 6 years ago L beast lump – malignant, local
DxT, Tamoxifen,. No nodes
• 3 weeks swelling mcps,
• Extreme morning stiffness in shoulders and
thighs
• ESR 82, CRP 76, RF Latex Pos, RW 1/80
PET scan in active PMR/GCA
Image courtesy of Dr G Clunie, Consultant Rheumatologist, Ipswich.
34 year Asian Female
• 3 months widespread polyarthralgia,
photosensitive rash, migraines, 4
miscarages, right pleuritic chest pain (Ix by
Physicians, no cause found),
• Presents with anaemia and Creat 144
– Hb 7.4, WCC 5, Lymphs 0.2, plts 100
– ESR 76, CRP <5
– ANA 1/2560
52 year female
• 2 years menopausal, declines HRT (FH of
Breast ca)
• Polyarthralgia, tired, sleep disturbed by
widespread pain, depressed, marital
difficulties.
• O/E NAD, joints OK
• All Baseline tests normal, RF Latex pos,
RW 1/160
Fibromyalgia
• Diffuse symptoms
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Widespread pain and tenderness
Sleep disturbance
Depression
Lethargy
Associated IBS/Migraines/Food intolerance's
etc.
• General screening indicated
– FBC, ESR, Biochemistry with TFTs
Rheumatoid Arthritis:
Prevalence and Incidence
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Worldwide 0.5~1% of the population
250~500,000 patients in England and Wales
F ~2.5:1 M; until over 75yrs
12 to 80 years of age
Overall incidence
• 0.14~0.2/1000 males
• 0.36~0.5/1000 females
Risk factors for RA -1
• Sex hormones
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Female preponderance
Remits in pregnancy, flares soon after
Nulliparity increases risk
OCP protects/postpones development of
severe RA
• Low socio-economic status
• Poor education
• Stress
Risk factors for RA -2
• Genetic factors
– Relatives of patients with seropositive RA are 4x
more likely to develop RA
– ~10% of RA patients have an affected 1st degree
relative
– MZ twins 4x concordance for RA compared to DZ
• But only 15~20% of MZ twins are concordant
• Therefore: environmental factors also important
Risk factors for RA -3
• Class II MHC product: HLA-DR4
– 70% of classic/definite RA are DR4 +ve
– 28% of normal individuals are DR4 +ve
– Worldwide association
• Except:
Israeli Jews/Asian Indians - DR1
Yakima Indians (USA) – Dw16
‘Shared Epitope’ theory
Tri-Molecular Complex in RA
• Arthritogenic peptide
presented to T-cell in
association with riskconveying HLA-DR
molecule
• Specific T-cells
activated
Activation of T-cells
• Activated T-cells
initiate cellular and
humoral mechanisms
of disease and tissue
damage
• Potential sites for
therapeutic
intervention
1987 ARA Criteria for RA
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Morning stiffness
Arthritis of 3 or more areas
Arthritis of hand joints
Symmetric arthritis
Rheumatoid nodules
Serum rheumatoid factor
Radiographic changes
– 1-4 for > 6 weeks
– RA if 4 or more criteria
Mode of Onset
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Gradual/Insidious
Slow, monoarticular
Abrupt, acute polyarthritis
Acute Monoarthritis
Palindromic rheumatism
Local extra-articular
Polymyalgic
Disease Course
• Monocyclic: single cycle of ~1 year: 20%
• Polycyclic: intermittent/continuous: 70%
• Progressive: increasing joint damage: 10%
• Poor Prognostic Factors:
– DR4/DR4
– gradual onset/severe at presentation
– high inflammatory markers
Pathology of Rheumatoid
Arthritis
• Chronic synovial inflammation
• Progressive erosion of cartilage and bone by
Pannus – inflammatory cells/synovial
proliferation
• Monocytes/macrophages
• Neutrophils
• Lymphocytes
• Cytokine ‘soup’ in synovial fluid
Important clinical points
• Diffuse, symmetrical small joint pain and
swelling
• Reduced fist; early morning stiffness
• Non-restorative sleep
– General malaise, lethargy
• Family history
• Psychological stress
Clinical evaluation of RA - 1
• Articular: measures of inflammation
– Tenderness, pain, effusion, grip, EMS
• Articular: measures of destruction
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Lax collateral ligaments
Subluxation
Malalignment
Metatarsal prolapse
Hammer toes
Bone-on-bone crepitus
Clinical evaluation of RA - 2
• Extra-articular complications
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Raynaud’s Phenomenon
Digital Infarcts
Episcleritis
Peripheral neuropathy
Leg ulcers
• Bursitis and nodulosis
•Pressure Ulcers
Clinical evaluation of RA - 3
• Ocular complications
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Sicca
Episcleritis
Scleritis
Scleromalacia
Clinical evaluation of RA - 4
Tendon sheath nodules,
subluxation or rupture
Clinical evaluation of RA - 5
• Extra-articular features:
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Anaemia
Splenomegaly
Leukopaenia
Pleuropericarditis
Sicca syndrome
Renal impairment
Interpreting blood tests
• Why do a test?
– What are you looking for
– How do you interpret the result
• What is a ‘titre’?
Rheumatoid Factor
• An autoantibody directed against the Fc
portion of human IgG
• Any subclass
– Commonly IgM
– RAHA-screen
• Polystyrene beads coated with human IgG
• Sensitive
– Rose-Waaler
• Sheep red cells
• More specific for pathogenic RFs
• >1/80 significant
• Sensitivity 80%, specificity >95%
• Positive predictive value low because RA is
rare in population
– Only 20-30% who are RF+ve will really have
RA
– Lots of other causes of a +ve RF:
Anti-CCP antibodies
• Citrullination – incorporation of the amino acid
Citrulline into proteins
– E.g.. Keratin, fillagrin and vimentin
• Vimentin is secreted and citrullinated by
macrophages in response to apoptosis, or by proinflammatory cytokines, such as TNF-alpha
• Close to a ‘diagnostic test for RA
– sensitivity between 69.6% and 77.5% and a specificity
between 87.8% and 96.4%
– Markers for progressive or severe disease
Rheumatoid disease management
• Multi-disciplinary approach
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Physiotherapy
Occupational Therapy
Nurse Practitioner
Dietician
Orthopaedic Surgeon
Podiatry
Orthotics
Psychology
Complementary therapy
NSAIDs
• Generally more beneficial than paracetamol
• Risk of adverse effects
– co-morbidity
– elderly
– other drugs
• Consider use with PPI
• Start with ibuprofen, etc.
Cox-II Inhibitors
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Safer than non-Cox-specific
Equally effective
Not free of adverse effects
More expensive
Less long term data, but more recent
evaluation
Older DMARDs
• Hydroxychloroquine
• Gold
• D-penicillamine
• Sulfasalazine
• Methotrexate
• Ciclosporin
Steroids
New DMARDs
• Leflunamide
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first ‘specific’ anti-rheumatoid arthritis drug
inhibits lymphocyte dihydro-orate reductase
activity as good as methotrexate
expensive
more side effects
more dangerous in combination?
Biological Therapies
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Etanercept
Infliximab
Adalimumab
Rituximab
Certolizumab
Golimumab
Monitoring
• Regular blood tests recommended for
traditional DMARDS
• Protocols vary
• Does it matter?
Thank You
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