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Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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Page 1: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Rheumatoid Arthritis

Manish Relan, MD FACP RhMSUS

Arthritis & Rheumatology Care Center.

Jacksonville, FL

(904) 503-6999.

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Page 2: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Disclosures

Speaker Bureau: Abbvie

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Page 3: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Objectives

Better understand the pathophysiology of Rheumatoid Arthritis

Role of Auto antibodies in Rheumatoid Arthritis

Updated treatment guidelines.

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Page 4: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 5: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 6: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 7: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 8: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

RA: Pathophysiology

Genetics

Modifiable Risk Factors

Infectious Disease

Autoantibodies

The Joint

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Page 9: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 10: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Pathophysiology of RA: Modifiable Risk Factors

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Page 11: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Smoking and RA

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Page 12: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 13: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Modifiable Risk Factors: Reproductive and Breast Feeding

Oral Contraceptives (OC)

Hormone replacement therapy (HRT)

Live Birth History

Breastfeeding

Menstrual History

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Page 14: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 15: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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

Page 16: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

RF

Rheumatoid factor (RF), an antibody reactive with the Fc portion of IgG.

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Page 17: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 18: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 19: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Autoantibodies

Do the antibodies have any prognostic value?

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Page 20: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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

Page 21: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Immune Processes within the Joint in RA

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Page 22: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Pathophysiology: Bone Erosion

Occurs rapidly

Affects 80% within 1 year after diagnosis.

Associated with prolonged, increased inflammation.

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Page 23: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

—29-year-old woman with pain in her wrist.

Boutry N et al. AJR 2007;189:1502-1509

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Page 24: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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Page 25: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 26: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 27: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 28: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 29: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

2010 ACR/EULAR Classification Criteria for RA

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Page 30: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 31: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 32: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

The Old Treatment algorithm

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Page 33: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

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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Page 34: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Are the 2010 ACR/EULAR RA criteria old before their time?

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Page 35: Rheumatoid Arthritis: New Genie in an Old Bottle · Rheumatoid Arthritis Manish Relan, MD FACP RhMSUS Arthritis & Rheumatology Care Center. Jacksonville, FL (904) 503-6999. 1

Conclusion

.

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