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Rheumatoid arthritis
Dr. Hanan AL Rayes, MDConsultant Rheumatology
Introduction Pathogenesis Clinical manifestation
◦ Symptoms and signs◦ Clinical course
Diagnosis Differential diagnosis Management
Outlines
RA is a chronic inflammatory autoimmune disease that is characterized by inflammation of the synovium and the destruction of joint cartilage
Chronic multisystem disease of unknown etiology Onset
◦ May present at any age but more common ( 30-60years)◦ The prevalence of rheumatoid arthritis in most population
1% among adults >18 Increases with age( 2% in men and 5% in women by age
65)◦ The incidence also increases with age, peaking between
the 4th and 6th decades Female: Male ratio 3:1
Rheumatoid arthritis (RA)
If it is untreated◦ It will lead to deformity through
Stretching of tendons and ligaments
Destruction of joints through the erosion of cartilage and bone.
◦ Loss of physical function◦ Inability to carry out daily
tasks of living◦ Difficulties in maintaining
employment.
Rheumatoid arthritis (RA)
Synovial joint A synovial joint, also known as
a diarthrosis, is a movable type of joint
Exact mechanism unknown Most likely related to acute
and chronic inflammation in the synovium in addition to a proliferate and destructive process of joint tissues
Combination of genetic and environmental factors
HLA-DR4 is associated An important early event
may result the interaction of antigen presenting macrophages with T-cells (helper/inducer)
Pathogenesis
The Pathogenesis of RA
Proliferative :swelling ,pain with , limited movement ,nerve compression
Destructive: synovial erosion causes irreversible changes ( tendon rupture, capsular weakness and disruption ,bone erosion, joint subluxation and deformity)
Reparative: fibrosis replaces inflammation (adhesions, ankylosis, fixed deformity)
Stages:
◦Joint pain(inflammatory) Swelling Hotness Morning Stiffness more than 1
hour◦Onset
Rheumatoid arthritis usually has a slow, insidious onset over weeks to months
About 15-20% of individuals have a more rapid onset that develops over days to weeks
Medical history:Articular manifestation
Acute onsetHours to a few days
Infectious More commonly
Crystal Autoimmune (Less
commonly)
Insidious onset several weeks to
months
Autoimmune More commonly
Infectious Other
◦The pattern poly-articular Symmetrical
◦ Location Peripheral joints Typically small joints PIP,
MCP, MTP wrist, elbow, shoulder, knee ,
ankle The axial skeleton is
usually spared except Cervical spine
Tempro-mandibular
Articular manifestation:
◦ Subcutaneous nodules 30 %
◦ Hematological (anemia, thrombocytosis)
◦ Eye (Episcleritis ,scleritis, kerato-cojuctivitis)
◦ CNS peripheral neuropathy entrapment neuropathy (Carpal tunnel syndrome) Atlanto-axial subluxation
◦ Felty’s syndrome ( splenomegaly and neutropenia)
◦ Sjögren’s syndrome
Extra-articular manifestations
Constitutional symptoms (fever, fatigue ) Respiratory: Pleural Effusion, pneumonitis, ILD,
Rheumatoid nodules
CVS : Pericardial effusion
Rheumatoid Vasculitis Mononeuritis multiplex Vasculitic rash Digital gangrene Cutaneous ulceration
Extra-articular:
◦ The absence of other conditions or symptoms suggesting an alternative diagnosis Psoriasis
Inflammatory bowel disease (IBD) Systemic rheumatic disease such as systemic lupus
erythematosus (SLE).
◦ Assess for synovitis, including the presence and distribution of swollen or tender joints and limited joint motion
◦ In the initial stages of each joint involvement, there is warmth, pain, and redness, with corresponding decrease of range of motion of the affected joint
A complete physical examination
Rheumatoid Arthritis: PIP Swelling
Swelling is confined to the area of the joint capsule
Synovial thickening feels like a firm sponge
◦ Progression of the disease results in muscle
weakness, atrophy and later fixed deformities
Rheumatoid Arthritis:
Ulnar Deviation and MCP Swelling
Prominent ulnar deviation in the right hand
MCP and PIP swelling in both hands
Synovitis of left wrist
Differential Diagnosis of RA
Mode of onset
In a patient with arthritis, consider:
Number of joints affectedSymmetry of joint affection Which regions or joints are affected
Factors that aggravate and ameliorate symptomsAssociated manifestations
Age of patientSex of patient
Clinical Laboratory CBC/differrential, Urea and Creatinine , ERS , CRP , Hepatitis screen Serological test:
◦ Rheumatoid factor◦ Anti-citrullinated peptide antibodies ( Anti CCP)
X-ray Synovial fluid aspiration
Diagnosis:
1- Rheumatic disorders◦ Rheumatoid arthritis – 75-80 %◦ Sjögren’s syndrome – 75 to 95 %◦ Mixed connective tissue disease – 50 to 60% ◦ Mixed cryoglobulinemia 40-100%◦ SLE◦ Polymyositis or dermatomyositis
2- Non-rheumatic disordersChronic infection, as with SBE ,hepatitis B or C virus infection
Inflammatory or fibrosing pulmonary disorders(sarcoidos) Malignancy, particularly B-cell neoplasms Primary biliary cirrhosis
3- Healthy individuals ( 4-20%)
Rheumatoid factorAre IgM antibodies directed against the Fc portion of immunoglobulin G (IgG)
Prognostic value of RF-positive :◦ More aggressive and erosive joint disease ◦ Extra-articular manifestations
Rheumatoid factor
IgG against synovial membrane peptide Detected by Enzyme-linked immunosorbent assays (ELISA)
for antibodies against cyclic citrullinated peptides (CCP) More specific for RA (90 %) Positive patients with early RA are at increased risk of :
◦ Progressive joint damage ◦ Predict erosive disease ◦ Poor functional outcome
Anti-citrullinated peptide antibodies ( Anti CCP)
X- Ray hand
SYNOVIAL FLUID:
ACR 1987 For RA diagnosis1. Morning stiffness >1h2. Arthritis of 3 or more joints3. Arthritis of hand joints4. Symmetric arthritis5. Rheumatoid nodules6. Serum Rheumatoid factor7. Radiographic changes(X- ray erosive changes0
A person shall be said to have RA if he or she has satisfied 4 of 7 criteria, with criteria 1-4 present for at least 6 weeks
SCORE
Large joints 2 to 10 (shoulders, elbows, hips, knees, and ankles)
1 point
Small joints 1 to 3 (metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists)
2 points
Small joints 4 to 10 3 points
Greater than 10 joints 5 points
Serological abnormality (rheumatoid factor or anti-citrullinated peptide/protein antibody)
Low positive = 2 pointsHigh positive = 3 points
Elevated acute phase response (ESR or CRP) 1 point
Symptom duration at least six weeks 1 point
Guide line for diagnosis2010 ACR/ EULAR Diagnostic criteria:
Clinical Course of RA
Type 1 = Self-limited—5% to 20%Type 2 = Minimally progressive—5% to 20%Type 3 = Progressive—60% to 90%
0
1
2
3
4
0 0.5 1 2 3 4 6 8 16
Type 1Type 2Type 3
Years
Sev
erity
of A
rthr
itis
Pincus. Rheum Dis Clin North Am. 1995;21:619.
Pincus, et al. Rheum Dis Clin North Am. 1993;19:123–151.
• Damage occurs early in most patients • 50% show joint space narrowing or erosions in the first 2
years• By 10 years, 50% of young working patients are disabled
Rheumatoid Arthritis: Typical Course
Confirm the diagnosis Determine where the patient stands in the
spectrum of disease When damage begins early, start aggressive
treatment early Use the safest treatment plan that matches
the aggressiveness of the disease Monitor treatment for adverse effects Monitor disease activity, revise Rx as needed
Rheumatoid Arthritis:Treatment Principles
• Assess current activity • Morning stiffness, synovitis, fatigue, ESR
• Document the degree of damage • ROM and deformities• Joint space narrowing and erosions on x-ray• Functional status
• Document extra-articular manifestations • Nodules, pulmonary fibrosis, vasculitis
• Assess prior Rx responses and side effects
Critical Elements of a Treatment Plan: Assessment
• Education • Build a cooperative long-term relationship• Use materials from the Arthritis Foundation
and the ACR• Assistive devices
• Exercise• ROM, conditioning, and strengthening
exercises• Medications
• Analgesic and/or anti-inflammatory• Immunosuppressive, cytotoxic, and biologic• Balance efficacy and safety with activity
Critical Elements of a Treatment Plan: Therapy
• NSAIDs • Symptomatic relief, improved function• No change in disease progression
• Low-dose prednisone (£10 mg qd)• May substitute for NSAID • Used as bridge therapy• If used long term, consider prophylactic treatment
for osteoporosis• Intra-articular steroids
• Useful for flares
Rheumatoid Arthritis: Drug Treatment Options
Paget. Primer on Rheum Dis. 11th edition. 1997:168.
Disease modifying anti-rheumatic drugs
◦ Methotrexate has been one of the mainstays of RA treatment Action: Inhibits dihydrofolate reductase
◦ Sulfasalazine◦ Luflonamide ◦ hydroxychloroquine
Biologic disease modifying anti-rheumatic drug◦ Over the past 16 years biologic disease
modifying anti-rheumatic drugs have been developed
◦ These drugs target select aspects of the immune response so as to decrease inflammation
Treatment Options
Biologic disease modifying anti-rheumatic drugs
34-year-old woman with 1-year history of symmetrical poly arthritis
Morning stiffness = 90 minutes Synovitis: 1+ swelling of MCP, 2+ PIP, wrist, knee, and MTP
joints Normal joint alignment
RF positive
Case 2
Case 2 (cont’d)
A. Soft-tissue swelling, no erosions
B. Thinning of the cortex on the radial side and minimal joint space narrowing
C. Marginal erosion at the radial side of the metacarpal head with joint space narrowing
X-ray hand
ACR Clinical Slide Collection, 1997.
Case 2 (cont’d)Early erosion at the tip of the ulnar styloid
• Assessment of case 2• Moderate-severe disease activity• Many joints involved• Clear radiologic signs of joint destruction early in disease
course• Progressive course with poor prognostic factors
• Treatment should be more aggressive• NSAID, MTX, SSZ, and hydroxychloroquine would be a
good choice
Case 2 (cont’d)
Advice 1: A good history and physical examination Your Eyes and Your Hand
Advice 2: Listen to your patients
QUESTION