Rheumatoid Arthritis

Goals

General Approach to Arthritis

Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course

Approach to Arthritis

Joint Pain

most common symptom Pain (arthralgia) vs. Inflammation (arthritis)

Inflammation: heat, redness, pain, swelling, loss of

function inflammatory arthritis (RA, SLE) vs. pain

syndrome (fibromyalgia)

Number of Joints Affected

Inflammatory vs. Non-Inflammatory

Number of Joints Affected

Monoarticular Crystal-induced Infection Reactive Arthritis Hemarthrosis OA: joint effusions Autoimmune

disease Psoriasis, IBD, AS,

Behçet's

Oligo/Polyarticular Monoarticular causes RA SLE Viral infection

B19 Acute Serum Sickness Untreated Crystal-

induced Vasculidities

Inflammatory vs. Non-Inflammatory

Inflammatory: i.e. RA Generalized AM

stiffness > 30 min Resolves with

movement Classic signs of

inflammation

Non-Inflammatory: i.e. Osteoarthritis Localized AM

stiffness < 30 min

Arthrocentesis

Confirm diagnoses Differentiate between inflammatory & noninflammatory Therapeutic/Adjunct to Antibiotics Labs:

cell count w/diff crystal analysis Gram stain & Culture WBC >2000/µL indicates inflammatory arthritis

Arthroscopy Evaluate ligamentous & cartilaginous integrity Biopsy Infectioun: aspirate thick or loculated fluid

RheumatoidArthritis

RA

Systemic inflammatory autoimmune disorder

~1% of population Onset: 52 years

40-70 years of age <60 - 3-5:1 female predominance

Genetics

Increased incidence among Pima & Chippewa Native American tribes (5%) Genetic & Environmental

HLA-DRB1*0401 & HLA-DRB1*0404 Increased risk Increased joint damage Increased joint surgery

Pathophysiology

Immunology

Macrophages: Produce cytokines Cytokines (TNF-α) cause

systemic features Release chemokines

recruit PMNs into synovial fluid/membrane

TNF-α & IL-1: Proliferation of T cells Activation of B cells Initiates

proinflammatory/joint-damaging processes

TH-1 cells: Mediate disease processes Activate B cells

B cells: Release cytokines Plasma cells that produce

Ab

Osteoclasts: Bone erosion Juxta-articular & Systemic

osteoporosis

Pathophysiology

Swelling of Synovial lining Angiogenesis

Rapid division/growth of cells = Pannus Synovial thickening/hyperplasia Inflammatory vascularized tissue Generation of Metalloproteinases

Cytokine release Infiltration of leukocytes Change in cell-surface adhesion molecules & cytokines Destruction of bone & cartilage

Bottom Line

Proliferation Destruction of joints Disability

Disease Trigger

Subclinical vs. Viral trigger Lab manifestations up to 10 yrs before clinical RF & anti-CCP (anti–cyclic citrullinated peptide) Ab Increased CRP subclinical inflammatory disease

ADLs: > 50% of pts stop working w/i 5-10 years of disease

onset ~ 80% disabled to some degree > 20 years Life expectancy: decreased by 3-18 years

Clinical Presentation

Gradual onset Stiffness & Swelling Intermittent or Migratory

involvement Extraarticular manifestations Myalgia, fatigue, low-grade fever, wt

loss, depression

Stiffness & Swelling

Pain with pressure to joint Pain with movement of joint Swelling due to hypertrophy Effusion Heat Redness

Physical Exam

Decreased grip strength Boxing glove edema Carpal tunnel Ulnar deviation Boutonniere/Swan neck deformities Extensor tendon rupture

Extraarticular Involvement

Anemia Rheumatoid

nodules Pleuropericarditis Neuropathy

Episcleritis, Scleritis

Splenomegaly Sjogren’s Vasculitis

Differential

Seronegative polyarthritis

Psoriatic arthritis Crystal-induced

Tophaceous gout Pseudogout

Erosive inflammatory OA

Reiter’s Enteropathic arthritis SLE Paraneoplastic

syndrome

DiagnosticCriteria

Diagnostic Criteria

Symmetric peripheral polyarthritis AM Stiffness >1 hour Rheumatoid nodules Laboratory features Radiographic bone erosions

Symmetric Peripheral Polyarthritis 3 or more Joints for >6 weeks

Small Joints Hands & Feet Peripheral to Proximal

MCP and PIP Joints SPARES DIP

MTP & Plantar subluxation

Leads to Deformity & Destruction of Joints Erosion of cartilage and bone

Stiffness

AM or after Prolonged Inactivity Bilateral In/Around Joints > 1 hours

Reflects severe joint inflammation Better with movement Present >6 weeks

Rheumatoid Nodules

Extensor surfaces elbows

Very Specific Only occur in ~30% Late in Disease

Laboratory Features

RF 70-80% of pts Overlap with HCV/Cryoglobulinemia

Anti-Cyclic Citrulline Peptide (anti-CCP) Rare overlap with HCV

Acute Phase reactants ESR, CRP monitoring disease activity

Rheumatoid Factor

IgM against IgG IgM+ pts: more severe disease & poorer

outcome Non-specific

SLE, Sjögren's, Sarcoidosis, Chronic infections

Anti-CCP

IgG against synovial membrane peptides damaged via inflammation Value in IgM-RF negative

Sensitivity (65%) & Specificity (95%)

Predictive of Erosive Disease Disease severity Radiologic progression Poor functional outcomes

Other Lab Abnormalities

AOCD Thrombocytosis Leukocytosis ANA

30-40% Inflammatory synovial fluid Hypoalbuminemia

Radiology

Evaluate disease activity & joint damage

Bony decalcification Baseline AP views Initiation of DMARDs

Radiological Studies

Plain Films Bilateral hands & feet Only 25% of lesions Less expensive Through bone cortex around joint margins

Color Doppler U/S & MRI Early signs of damage i.e. Erosions Bone Edema - even with normal findings on

radiography

DiseaseSeverity

Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated ESR & CRP No erosions/cartilage loss No extraarticular disease i.e. anemia

Mild Disease

Moderate Disease

6-20 Inflamed joints Moderate functional limitation Elevated ESR/CRP Radiographic evidence of

inflammation No extraarticular disease

Severe Disease

>20 persistently inflamed joints Rapid decline in functional capacity Radiographic evidence of rapid

progession of bony erosions & loss of cartilage

Extraarticular disease: AOCD, Hypoalbuminemia

Prognostic Features

RF & Anti-CCP antibodies Early development of multiple inflamed joints

and joint erosions Severe functional limitation Female HLA epitope presence Lower socioeconomic status & Less education Persistent joint inflammation for >12 weeks

CV Disease

Leading cause of death ~50%

2x more likely to develop MI chronic, inflammatory vascular burden premature

atherosclerosis MTX: elevated homocysteine levels

Control inflammatory process = Decreased atherosclerosis/morbidity Lipid screening & treatment Control of obesity, Hyperhomocystinemia, DM, HTN ASA

Other diseases

70% more likely to have a stroke

70% higher risk for developing infection Likely 2/2 treatment

44x more likely to develop NHL

Staging

Early <3 months

Established/Persistent 6-12 months

End-stage Significant joint destruction Functional disability

Management

Early and aggressive disease control Rheumatologist Referral

Early/Undiagnosed: NSAIDs, short course Corticosteroids

Late/Uncontrolled: DMARD therapy depends on the presence or absence of joint damage,

functional limitation, presence of predictive factors for poorer prognosis

Goals achieve NED & inflammation no treatment to resolve erosions once they occur

TreatmentStrategies

Therapy

Non-Pharmacologic: Referral to PT/OT Evaluate ADLs Assistive

devices/splints Weight loss Smoking cessation

Pharmacologic: Anti-inflammatory Interrupt progression

Development of erosions

Joint space narrowing

Pharmacologic Therapy

Analgesics NSAIDs Glucocorticoids SAARD/DMARD Anticytokine therapy

Analgesics

Topical Capsaicin Diclofenac

Oral Tylenol Opiods

NSAIDs

Pros: Analgesic, Antipyretic,

Anti-inflammatory

Cons: Don’t alter disease

progression Ineffective in Erosive disease

GI/Ulcers Hepatotoxicity Nephrotoxicity AIN Bleeding – antiplatelet Rash Aseptic meningitis

Corticosteroids

Decrease cytokines

Slow Joint Inflammation

Insomnia Emotional lability Fluid retention Weight gain HTN Hyperglycemia Osteoporosis

Bisphosphonates: >5mg/d for >3months

Cataracts Avascular necrosis Myopathy Psychosis

Disease modification

SAARD – slow acting antirheumatic drugs

DMARD – disease modifying antirheumatic drugs

Methotrexate

Dihydrofolate reductase inhibitor

Well tolerated, Mono/Combo

Onset: 6-12 weeks

Metabolism: LiverClearance: Kidneys

Monitoring: Baseline:CXR, PFTs, HIV,

HBV/HCV CBC, LFTs Q4-8 weeks Caution with CRI

Nausea Mucosal ulcerations Fatigue & Flu-like symptoms BM Toxicity Hepatotoxicity

Treat with Folic acid, 1 mg/d

Leflunomide

Inhibits dihydrooratate dehydrogenase Dec. activated T-

cells Onset: rapid

Efficacy: ≤6 weeks

Monitoring: CBC, LFTs

Derm - rash, alopecia Diarrhea BM toxicity Hepatotoxicity

Azathioprine

Corticosteroid-sparing

Monitoring: CBC Q1-2 months AST/ALT

Infection BM Toxicity Hepatitis Malignancy

Cyclophosphamide

Alkylating agent

Monitoring: CBC, UA monthly Yearly UA +/- Cytology

Alopecia Nausea Infection BM suppression

pancytopenia Infertility – pretreat women

with Leuprolide Renal: hemorrhagic cystitis,

bladder malignancy – treat with acrolein

Oral more toxic than IV

Anticytokine therapy

Anti-TNF alpha agents Etanercept Infliximab Adalimumab IL-1 receptor antagonist (Anakinra)

TNF-a Inhibitors

Anti-inflammatory Block TNF-α

(proinflammatory cytokine)

Etanercept, Adalimumab (SQ), Infliximab (IV) Very expensive:

> $15,000/patient Combo therapy with MTX

Injection site reaction Infection Reactivated TB Infliximab

infusion reaction

Pancytopenia Autoantibody/SLE-like Exacerbate CHF Malignancy –

lymphoma

More aggressive approach Combo therapy Adjunctive therapy: TNF-α

antagonist

Disease Course

Long Remission 10%

Intermittent Disease 15-30%

Progressive Disease

Summary

Approach to Arthritis Number of Joints Affected Inflammatory vs. Non-Inflammatory

Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course

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