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Overview of Rheumatoid
Arthritis
Naureen Mirza, MDMay 10, 2010
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Epidemiology
An annual incidence of approximately 0.2 per1000 in males and 0.4 per 1000 in females
A prevalence of 0.5-1% is reported in diversepopulations worldwide
Twin studies show the disease to have aheritability of 60%
Hormonal and reproductive factors contribute tothe female excess and parity
Obesity, smoking, coffee consumption, and priorblood transfusion have also been identified aspotential risk factors
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1. Morning stiffnessMorning stiffness in and around the joints, lasting at least 1
h before maximal improvement
2. Arthritis in three or
more joint areas
Soft tissue swelling or fluid (not bony overgrowth) observed
by a physician, present simultaneously for at least 6weeks
3. Arthritis of hand
joints
Swelling of wrist, MCP or PIP joints for at least 6 weeks
4. Symmetric arthritis Simultaneous involvement of the same joint areas (defined
in 2) on both sides of the body (bilateral involvement of
PIP, MCP or MTP joints is acceptable without absolutesymmetry) for at least 6 weeks
5. Rheumatoid nodules Subcutaneous nodules over bony prominences, extensor
surfaces or in juxta-articular regions, observed by a
physician
6. Rheumatoid factor Detected by a method positive in fewer than 5% of normalcontrols
7. Radiographic
changes
Typical of RA on posteroanterior hand and wrist
radiographs; it must include erosions or unequivocal
bony decalcification localized in or most marked
adjacent to the involved joints (OA changes alone do
not qualify)
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New criteria for the diagnosis of RA
Joint involvement
1 med-lg joint
0
2-10 Med-Lg joints 1
1-3 small joints 2
4-10 small joints 3
>10 small joints 5
Serology
Neither RF or Anti ccp
0
At least one + with low titer 2
Atleast one with high titer 3
Duration of synovitis
6 weeks 1
Acute phase reactants
Neither CRP or ESR abnormal
0
Abnormal CRP or abnormal ESR 1
Score >=6 indicates
definite RA
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History In RAChronological account of illness from the onset
Onset: acute or gradual, with detailsLocation of pain (local or referred): precise anatomy,
presence/absence of swelling
Pattern of joint involvement: axial, peripheral, symmetric
Type of pain: quality and character
Severity: pain threshold effects, interference with activities of daily
living, range of joint movement
Radiation of pain: local or deep referred type
Clinical course: duration, frequency, periodicity, persistence
Modifying factors: aggravating, relieving, medication effectsAssociated symptoms: fatigue, other systemic symptoms
Duration of morning stiffness: non-restorative sleep pattern
Present status: regional review of joints, extra-articular features,
functional class, activities of daily living, psychologic state
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Extra-articular features
Record presence of nodules, Raynaud's phenomenon,
digital infarcts, episcleritis, peripheral neuropathy, palmar
erythema, leg ulcers
Note tendon sheath involvement, or tendon nodules,
subluxation or rupture
Check for anemia, splenomegaly, leukopenia, pleuritis or
pericarditis, the sicca syndrome or renal involvement
Articular: measures of inflammatory activity
Check for tenderness, synovial effusion, grip strength
Articular: measures of destruction and deformity
Check for lax collaterals, subluxation, malalignment,
metatarsal prolapse, hammer toes and bone-on-bone
crepitus
Examination
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Articular manifestations
Arthritis : Joint swelling, tenderness,
warmth, limitation of motion, pain in range
of motion,
Morning stiffness
Muscle atrophy
Chronic deformitiesAnkylosis of the joint
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Rheumatoid nodules20% of RA patients with +tests for blood
rheumatoid factors and rarely in RF
most commonly on pressure areas
central fibrinoid necrosis with surrounding
fibroblastsMay occur in any organs as well
May regress with treatment , but has been
reported to increase with Methotrexate use
believed to occur as a result of small vessel
vasculitis with fibrinoid necrosis, which
forms the center of the nodule, and
surrounding fibroblastic proliferation
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Histology of rheumatoid nodule
Rheumatoid nodule with granulomatoustransformation.There is prominent central fibrinoidnecrosis, with surrounding palisading histiocytes and anouter layer of chronic fibrosing connective tissue withinflammatory cells including lymphocytes and fibroblasts.
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Hematologic abnormalities
Anemia
Thrombocytosis
Thrombocytopenia ( rare )
Eosinophilia(esp related to gold)
Lymphadenopathy ( concomitant Sjogrens syndrome may
increase the risk of Lymphoma)Splenomegaly ( clinically in 5-10 % with active RA and upto
58% by radionuclide scanning)
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Feltys syndrome
RA in combination with splenomegaly and leukopenialong-standing, seropositive, nodular, deforming RA
33%do not have active synovitisLower extremity ulcers, hyperpigmentation, bacterial
infections, ANAs, Also may have thrombocytopenia,hypocomplementemia,
an increased risk for the development of lymphomas
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Neutropenia
Anemia
Thrombocytopenia
Splenomegalylarge granularlymphocytes in thesepatients represent in
vivoactivatedcytotoxic T cells andclonality is present.
Large granular lymphocytes
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Pulmonary manifestations
Pulmonary nodules
Pleural effusions (50%)
Caplans syndrome
Diffuse interstitial
pulmonary fibrosis (28%)
Bronchiolitis obliteransorganizing pneumonia
(BOOP)
Obliterative bronchiolitis
Drug induced
Isolated pul. Arteritis (rare)
Pulmonary hypertension
(rare)
Airway obstruction (38%)
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Caplans
syndrome
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Cardiac disease in RA
Pericarditis (50%)
Premature cardiovascular disease(TNF- is produced by cardiacmyocytes and resident macrophages during cardiac stress and may help trigger andperpetuate atherosclerosis)
Myocardial and endocardial disease (clinically insignificant)
Coronary arteritis
Valvular abnormalities
Rheumatoid nodule in the aortic valve cusp
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Ocular InvolvementMost common : Keratoconjuctivitis sicca (10-35%)
Episcleritis: nodular or diffuse, appears acutely andcauses eye redness and pain
Scleritis is less common than episcleritis, but is more obviously correlatedwith vasculitis, long-standing arthritis and active joint inflammation.
Untreated scleritis may progress to scleromalacia
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Other uncommon manifestation of RA in the
eyeUveitis
Episcleral nodulosis
Corneal filamentary keratitis
Peripheral ulcerative keratitis
Retinal detachments
Macular edema
Glucocorticoids, Gold and Chloroquine
Brown's syndrome, which is defined as diplopia upon
upward and inward gaze and is believed to be the result of
inflammation and thickening of the superior tendons, and
optic neuritis
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Neurological manifestations
Nerve compressions
(Carpal tunnel, tarsal tunnel, atlantoaxial subluxation, subaxial
c-spine involvement, extradural nodules)
Stroke, seizure, hemorrhage, encephalopathy and
meningitis as a result of cerebral vasculitis, amyloidosis orrheumatoid nodules, or both, in the dura and choroid plexus
of the brain
Most patients have long-standing RA with other extra-
articular disease
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Renal Involvement
The kidneys are usually spared in RA, although a low-grade
membranous nephropathy, glomerulitis, vasculitis and secondary
reactive amyloidosis have all been described
Renal abnormalities frequently result from the agents used intreating RA, notably gold, D-penicillamine, cyclosporin and NSAIDs,
and usually manifest as membranous nephropathy and acute
interstitial nephritis, often the result of a drug hypersensitivity
reaction
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Amyloidosis
0.7-5.8% of patients with RA
Virtually every organ system may be involved in the secondary
amyloidosis that complicates RA, including the heart, kidney, liver,
spleen, intestines and skin.
Renal manifestations of amyloidosis are the most common onesPoor prognosis : 4-year survival rates of about 58% are reported
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Rheumatoid vasculitisSystemic vasculitis uncommon, usually with longstanding,
poorly controlled disease
pANCA
More in patients with feltys
Skin: Nail fold infarcts . Leg ulcers, gangrene
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Baker's popliteal cyst
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Diagnosis
CBC
RF
Anti ccpESR
X rays of affected joints
Musculoskeletal ultrasoundMRI
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Additional testing
PPD
Chest X ray
Hep B and C serologiesANA
Joint aspiration
Synovial biopsyLyme serology
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More aggressive disease
TNF inhibitors
Abatacept (CTLA 4 IgG)
Rituximab (Anti CD 20)