dommr rheumatoid arthritis

8/7/2019 DOMMR Rheumatoid Arthritis

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Rheumatoid Arthritis

DOM MR Week of 9/8/2008Rozina Mithani


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Goals

General Approach to Arthritis


Diagnostic Criteria

Pathophysiology

Therapeutic Approach

Disease Severity and Course


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Approach to

Arthritis


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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)


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Number ofJoints Affected

Inflammatory vs. Non-Inflammatory


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Number ofJoints Affected

Monoarticular Crystal-induced

Infection

Reactive Arthritis

Hemarthrosis

OA: joint effusions

Autoimmune disease

Psoriasis, IBD, AS,Behet's

Oligo/Polyarticular Monoarticular causes

RA

SLE

Viral infection

B19

Acute Serum Sickness

Untreated Crystal-induced

Vasculidities


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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


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Arthrocentesis

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

Labs: cell count w/diff crystal analysis Gram stain & Culture

WBC >2000/L indicates inflammatory arthritis

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


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Rheumatoid

Arthritis


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RA

Systemic inflammatory autoimmune disorder ~1% of population

Onset: 52 years

40-70 years of age


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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


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Pathophysiology


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Immunology

Macrophages: Produce cytokines Cytokines (TNF-) cause

systemic features Release chemokines recruit

PMNs into synovialfluid/membrane

TNF- & 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


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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


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Bottom Line

Proliferation Destruction of joints

Disability


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Disease Trigger

Subclinical vs. Viral trigger Lab manifestations up to 10 yrs before clinical

RF & anti-CCP (anticyclic 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


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Clinical Presentation

Gradual onset Stiffness & Swelling

Intermittent or Migratory involvement

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

loss, depression


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Stiffness & Swelling

Pain with pressure to joint Pain with movement of joint

Swelling due to hypertrophy

Effusion Heat

Redness


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Physical Exam

Decreased grip strength Boxing glove edema

Carpal tunnel

Ulnar deviation Boutonniere/Swan neck deformities

Extensor tendon rupture


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Extraarticular Involvement

Anemia Rheumatoid nodules

Pleuropericarditis

Neuropathy

Episcleritis, Scleritis Splenomegaly

Sjogrens

Vasculitis


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Differential

Seronegative polyarthritis Psoriatic arthritis

Crystal-induced Tophaceous gout

Pseudogout

Erosive inflammatory OA Reiters

Enteropathic arthritis

SLE

Paraneoplastic syndrome


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Diagnostic

Criteria


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Diagnostic Criteria

Symmetric peripheral polyarthritis AM Stiffness >1 hour

Rheumatoid nodules

Laboratory features Radiographic bone erosions


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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 ofJoints Erosion of cartilage and bone


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Stiffness

AM or after Prolonged Inactivity Bilateral

In/Around Joints

> 1 hours Reflects severe joint inflammation

Better with movement

Present >6 weeks


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Rheumatoid Nodules

Extensor surfaces elbows

Very Specific

Only occur in ~30%

Late in Disease


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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


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Rheumatoid Factor

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

Non-specific

SLE, Sjgren's, Sarcoidosis, Chronic infections


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Anti-CCP

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

Sensitivity (65%) & Specificity (95%)

Predictive of Erosive Disease Disease severity Radiologic progression Poor functional outcomes


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Other Lab Abnormalities

AOCD Thrombocytosis

Leukocytosis

ANA 30-40%

Inflammatory synovial fluid

Hypoalbuminemia


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Radiology

Evaluate disease activity & joint damage Bony decalcification

Baseline AP views

Initiation of DMARDs


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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


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Disease

Severity


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Arthralgias >3 inflamed joints

Mild functional limitation

Minimally elevated ESR & CRP

No erosions/cartilage loss No extraarticular disease i.e. anemia

Mild Disease


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Moderate Disease

6-20 Inflamed joints Moderate functional limitation

Elevated ESR/CRP

Radiographic evidence of inflammation

No extraarticular disease


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Severe Disease

>20 persistently inflamed joints Rapid decline in functional capacity

Radiographic evidence of rapid progessionof bony erosions & loss of cartilage

Extraarticular disease:

AOCD, Hypoalbuminemia


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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


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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 = Decreasedatherosclerosis/morbidity Lipid screening & treatment Control of obesity, Hyperhomocystinemia, DM, HTN ASA


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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


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Staging

Early


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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


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Treatment

Strategies


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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


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Pharmacologic Therapy

Analgesics NSAIDs

Glucocorticoids

SAARD/DMARD

Anticytokine therapy


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Analgesics

Topical Capsaicin

Diclofenac

Oral Tylenol

Opiods


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NSAIDs

Pros: Analgesic, Antipyretic, Anti-

inflammatory

Cons: Dont alter disease progression Ineffective in Erosive disease

GI/Ulcers Hepatotoxicity

Nephrotoxicity

AIN

Bleeding antiplatelet

Rash Aseptic meningitis


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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


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Disease modification

SAARD slow acting antirheumatic drugs

DMARD disease modifying antirheumatic drugs


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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


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Leflunomide

Inhibits dihydrooratatedehydrogenase

Dec. activated T-cells

Onset: rapid

Efficacy: 6 weeks

Monitoring:

CBC, LFTs

Derm - rash, alopecia

Diarrhea

BM toxicity

Hepatotoxicity


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Azathioprine

Corticosteroid-sparing

Monitoring: CBC Q1-2 months

AST/ALT

Infection BM Toxicity

Hepatitis

Malignancy


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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 withacrolein

Oral more toxic than IV


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Anticytokine therapy

Anti-TNF alpha agents Etanercept

Infliximab

Adalimumab

IL-1 receptor antagonist (Anakinra)


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TNF-a Inhibitors

Anti-inflammatory

Block TNF-(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


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More aggressive approach Combo therapy

Adjunctive therapy: TNF- antagonist


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Disease Course

Long Remission 10%

Intermittent Disease

15-30%

Progressive Disease


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Summary

Approach to Arthritis Number ofJoints Affected



Diagnostic Criteria Pathophysiology

Therapeutic Approach

Disease Severity and Course


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Questions?

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