Rheumatoid Arthritis
Manish Relan, MD FACP RhMSUS
Arthritis & Rheumatology Care Center.
Jacksonville, FL
(904) 503-6999.
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Disclosures
Speaker Bureau: Abbvie
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Objectives
Better understand the pathophysiology of Rheumatoid Arthritis
Role of Auto antibodies in Rheumatoid Arthritis
Updated treatment guidelines.
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Case
29 year old female comes to Primary care clinic with complaints of right wrist pain, right and left index finger swelling and pain for 4 wks.
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History of RA
First known traces date back as far as 4500 BC
In the Old World the disease is vanishingly rare before the 1600s.
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Epidemiology: RA
Affects 0.5-1% of adults in developed countries.
3x more frequent in women.
Prevalence rises with age and is highest in women older than 65 yrs.
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Epidemiology: RA
Is a chronic inflammatory disease that causes destruction of synovial joints, leading to severe disability and premature mortality.
Is best considered a clinical syndrome spanning several disease subsets.
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RA: Pathophysiology
Genetics
Modifiable Risk Factors
Infectious Disease
Autoantibodies
The Joint
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Pathophysiology of RA: Genetic Factors
Concordance rates
Monozygotic Twins: 15 to 30%.
Dizygotic Twins: 5%.
HLA-DRB1 has been confirmed in patients who are positive for RF or Anti-citrullinated peptide antigen (ACPA)
ACPA negative disease involves a different alleles (HLA-DRB1*03)
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Pathophysiology of RA: Modifiable Risk Factors
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Smoking and RA
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Smoking and RA
Smoking, Smoking Cessation, and Disease Activity in Large Cohort of Patients with RA
16,521 Patients with RA and smoking status.
Results: Current smokers had a worse disease activity than former smokers or never smokers.
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Modifiable Risk Factors: Reproductive and Breast Feeding
Oral Contraceptives (OC)
Hormone replacement therapy (HRT)
Live Birth History
Breastfeeding
Menstrual History
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Pathophysiology: Infectious Agent
EBV, CMV, Proteus species, and E Coli along with their products (example: Heat Shock Protein) have long been associated with RA.
Molecular mimicry
GI microbiome influence the development of autoimmunity in articular models.
Periodontal Diseases?
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Figure 1 Schematic illustration of the etiological hypothesis for P. gingivalis and
citrullinated α-enolase involvement in RA
Lundberg, K. et al. (2010) Periodontitis in RA—the citrullinated enolase connection
Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2010.139 15
RF
Rheumatoid factor (RF), an antibody reactive with the Fc portion of IgG.
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Rheumatoid Factor Positivity in Different Diseases
Rheumatic Conditions (Sensitivity)
Cryoglobulinemia (40%-100%)
Polymyositis and dermatomyositis (5%-10%)
Rheumatoid arthritis (50%-90%)
Sjögren's syndrome (75%-95%)
Systemic lupus erythematosus (15%-35%)
Systemic sclerosis (20%-30%)
Nonrheumatic Conditions Bacterial endocarditis
Infections
• Hepatitis • Leprosy • Parasites • Syphilis • Tuberculosis Malignancy Pulmonary disease
• Interstitial pulmonary fibrosis • Sarcodosis • Silicosis Primary biliary cirrhosis
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Autoantibodies
In very early or undifferentiated arthritis, use of both RF and anti-CCP test can improve diagnostic specificity with a minimal loss of sensitivity.
Anti-CCP Abs speficity 95-97%
RF specificity: 65-75%
Caveat: Upto 30% of RA patients do not have usual biomarkers of RF, anti-CCP, elevated ESR, or CRP.
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Autoantibodies
Do the antibodies have any prognostic value?
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Synovial Immunologic Processes and Inflammation
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Leucocytes infiltrate synovium
Cell migration enabled by endothelial activation in synovial microvessels.
Neoangiogenesis induces local hypoxic condition
Profound synovial architectural reorganization and local fibroblast activation.
Buildup of Synovial inflammatory tissue in RA
Immune Processes within the Joint in RA
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Pathophysiology: Bone Erosion
Occurs rapidly
Affects 80% within 1 year after diagnosis.
Associated with prolonged, increased inflammation.
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—29-year-old woman with pain in her wrist.
Boutry N et al. AJR 2007;189:1502-1509
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Ultrasound German US7 Score:
A new standardized US score based on 7 joints of clinically dominant hand and foot.
Semiquantitative scoring by Gray-scale and Power Doppler US.
Significantly reflected therapeutic response, and was found to be a viable tool for examining RA patients.
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1958 Diagnostic Criteria for RA
Possible RA
Diagnosis requires two of the following criteria, and the total duration of joint symptoms must be at least three weeks.
1. Morning Stiffness
2. Tenderness or pain on motion (observed by a physician) with history of recurrence or persistence for three weeks.
3. History or observation of joint swelling
4. Subcutaneous nodules (observed by a physician)
5. Elevated sedimentation rate or C-reactive protein
6. Iritis
Criteria will continue to change and evolve
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1987 Revised ACR Classification Criteria for RA
Criterion
1. Morning Stiffness lasting >1 hour
2. Swelling of 3 or more joints
3. Swelling of hand joints
4. Symmetric joint involvement
5. Rheumatoid Nodules
6. Serum RF
7. Radiographic Changes
Must satisfy 4 or more of the 7 criteria.
Criteria 1 through 4 must have been present for 6 wks or more.
Patients with 2 clinical diagnoses are not excluded.
Criteria will continue to change and evolve
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2010 ACR/EULAR RA Classification Criteria
2010 RA Classification Criteria
One or more joint with synovitis (excluding the DIP, first MTP and first CMC joints)
Absence of alternative diagnosis that better explains synovitis.
Achievement of total score of ≥6 (of 10) from individual scores in 4 domains:
Joint Involvement
Serologic abnormality
Acute Phase response
Duration of symptoms
Criteria will continue to change and evolve
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2010 ACR/EULAR Classification Criteria for RA
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New Approach to the Treatment of RA?
Explicit goal of ACR/EULAR criteria is to facilitate early identification, referral and treatment.
New paradigm of very early aggressive therapy as standard of care.
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In a study of over 100,000 persons coded as having RA by a non-rheumatologist, only 27.3% consulted a rheumatologist within the next 3.5 years.
Median time to rheumatology consultation was 79 days.
Feldman et al. Delay in consultation with specialist for persons with suspected new-onset RA: a population based
study. Arthritis Rheum. 2007 Dec 15;57(8):1419-25
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The Old Treatment algorithm
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Treatment Guidelines: Limitation
No recommendations regarding use of other anti-inflammatory medications, such as
NSAIDs
Oral and Intraarticular corticosteroids
Use of non pharmacological therapies.
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Are the 2010 ACR/EULAR RA criteria old before their time?
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Conclusion
.
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