Rheumatoid ArthritisRheumatoid Arthritis

Dr ahad azamiDr ahad azami

Rheumatoid ArthritisRheumatoid Arthritis

SystemicSystemic

ChronicChronic

InflammatoryInflammatory

Primarily targets the synovium of diarthrodial jointsPrimarily targets the synovium of diarthrodial joints

Etiology likely combination genetic and Etiology likely combination genetic and

environmentalenvironmental

Diarthrodial JointDiarthrodial Joint

Rheumatoid ArthritisRheumatoid Arthritis

Female: male 3:1Female: male 3:1

44thth-6-6thth decades of life decades of life

Symmetric polyarthritis Symmetric polyarthritis

Extra-articular manifestationsExtra-articular manifestations Subcutaneous nodules/lung nodulesSubcutaneous nodules/lung nodules ScleritisScleritis VasculitisVasculitis Felty’s syndromeFelty’s syndrome

Stages of RA PathogenesisStages of RA Pathogenesis

StageStage SymptomsSymptoms FindingsFindings

1.1. AntigenAntigen NoneNone None None PresentationPresentation Normal X-rayNormal X-ray

to T Cellsto T Cells

2.2. T and B CellT and B Cell Malaise, Mild,Malaise, Mild, Swelling or PainSwelling or PainProliferation,Proliferation, Joint StiffnessJoint Stiffness of Small Jointsof Small JointsAngiogenesisAngiogenesis SwellingSwelling Wrists, KneesWrists, Kneesin Synoviumin Synovium Normal, X-rayNormal, X-ray

ACR

Stages of RA Pathogenesis Stages of RA Pathogenesis (Continued)(Continued)

StageStage SymptomsSymptoms FindingsFindings

3.3. SFPMNSFPMN Joint Pain,Joint Pain, Warm, SwollenWarm, SwollenAccumulationAccumulation SwellingSwelling Joints, Inc SFJoints, Inc SFSynovial CellSynovial Cell AM Stiffness,AM Stiffness, Soft TissueSoft TissueProliferationProliferation Malaise,Malaise, Proliferation,Proliferation,

WeaknessWeakness Limited ROM,Limited ROM,Nodules, SoftNodules, SoftTissue Tissue

SwellingSwellingon X-rayon X-ray

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Stages of RA Pathogenesis Stages of RA Pathogenesis (continued)(continued)

StageStage Symptoms Symptoms FindingsFindings

4.4. PannusPannus Same as Same as Same asSame as

Invasion,Invasion, Stage 3 Stage 3 Stage 3Stage 3

ChondrocyteChondrocyte PeriarticularPeriarticular

Activation,Activation, Osteopenia,Osteopenia,

EnzymeEnzyme Proliferative Proliferative

ActivationActivation Pannus on MRIPannus on MRI

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Stages of RA Pathogenesis Stages of RA Pathogenesis (continued)(continued)

StageStage Symptoms Symptoms FindingsFindings

5.5. SubchondralSubchondral Same as Same as Same as stage 3Same as stage 3Bone Erosion,Bone Erosion, Stage 3 Stage 3 Plus InstabilityPlus InstabilityPannusPannus Plus Loss Plus Loss FlexionFlexionInvasion ofInvasion of of Function of Function Contractures,Contractures,Cartilage Cartilage Deformity Deformity Extra-ArticularExtra-ArticularStretchedStretched Disease, EarlyDisease, EarlyLigamentsLigaments Erosions and JointErosions and Joint

Space Space NarrowingNarrowing

on X-Rayon X-Ray

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Synovium in RASynovium in RA

PIP SwellingPIP Swelling

Ulnar Deviation, MCP Swelling, Ulnar Deviation, MCP Swelling, Left Wrist SwellingLeft Wrist Swelling

Joints involved in RAJoints involved in RA

Joints involved in RAJoints involved in RA

Don’t forget the cervical spine!! Instability Don’t forget the cervical spine!! Instability there can lead to impingement of the spinal there can lead to impingement of the spinal cordcord

Thoracolumbar, sacroiliac, and distal Thoracolumbar, sacroiliac, and distal interphalangeal joints of the hand are not interphalangeal joints of the hand are not involvedinvolved

Extra-articular SymptomsExtra-articular Symptoms

Patients that are more likely to get are:Patients that are more likely to get are:

RF+RF+

HLA DR4+HLA DR4+

Male Male

Corneal MeltCorneal Melt

NodulesNodules

Pulmonary NodulesPulmonary Nodules

Felty’s SyndromeFelty’s Syndrome

Seropositive Rheumatoid ArthritisSeropositive Rheumatoid Arthritis SplenomegalySplenomegaly GranulocytopeniaGranulocytopenia

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Large Granular LymphocytesLarge Granular Lymphocytes

LabsLabs

Can also see nonspecific abnormalitiesCan also see nonspecific abnormalities

High sedimentation rateHigh sedimentation rate

AnemiaAnemia

HypergammaglobulinemiaHypergammaglobulinemia

ThrombocytosisThrombocytosis

Rheumatoid FactorRheumatoid Factor

Antibodies that recognize Fc portion of Antibodies that recognize Fc portion of IgGIgG

Can be IgM, IgG, IgA, IgECan be IgM, IgG, IgA, IgE

85% of patients with RA over the first 2 85% of patients with RA over the first 2 years become RF+years become RF+

Anti-ccpAnti-ccp

Radiographic FeaturesRadiographic Features

Peri-articular osteoporosisPeri-articular osteoporosis Uniform joint space narrowingUniform joint space narrowing Marginal erosionsMarginal erosions Soft tissue swellingSoft tissue swelling Subluxations Subluxations Symmetric Symmetric CystsCysts

Synovial FluidSynovial Fluid

InflammatoryInflammatory

WBCs 5000-50,000WBCs 5000-50,000

≥ ≥ 50% neutrophils50% neutrophils

No crystalsNo crystals

Negative CulturesNegative Cultures

Noninflammatory on leftNoninflammatory on leftInflammatory on rightInflammatory on right

ACR CriteriaACR Criteria

Morning Stiffness ≥1 hourMorning Stiffness ≥1 hour

Soft tissue swelling of ≥ 3 joints observed by Soft tissue swelling of ≥ 3 joints observed by

physicianphysician

Swelling of proximal interphalangeal (PIP), Swelling of proximal interphalangeal (PIP),

metacarpophalangeal (MCP), or wrist jointsmetacarpophalangeal (MCP), or wrist joints

These signs and symptoms must be present ≥ 6 weeksThese signs and symptoms must be present ≥ 6 weeks

ACR Criteria ContinuedACR Criteria Continued

Symmetric Arthritis present for ≥ 6 weeksSymmetric Arthritis present for ≥ 6 weeks Subcutaneous nodulesSubcutaneous nodules Positive Rheumatoid FactorPositive Rheumatoid Factor Radiographic Erosions or periarticular Radiographic Erosions or periarticular

osteopenia in hand or wrist jointsosteopenia in hand or wrist joints

Must have ≥4 criteria to meet diagnosis of RA

Criteria for Progression of RACriteria for Progression of RA

Stage I – Stage I – EarlyEarlyNo Destructive ChangesNo Destructive Changes

Osteoporosis on X-RayOsteoporosis on X-Ray

Stage II – Stage II – ModerateModerateOsteoporosis and Slight Subchondral Bone or Osteoporosis and Slight Subchondral Bone or Cartilage DestructionCartilage Destruction

No Joint Deformaties, Mobility May be LimitedNo Joint Deformaties, Mobility May be Limited Adjacent Muscle AtrophyAdjacent Muscle Atrophy

Nodules or Tenosynovitis May be PresentNodules or Tenosynovitis May be PresentACR

Criteria for Progression of RA Criteria for Progression of RA (continued)(continued)

Stage III – Stage III – SevereSevere

Osteoporosis and ErosionsOsteoporosis and Erosions

Deformity Without AnkylosisDeformity Without Ankylosis

Extensive Muscle AtrophyExtensive Muscle Atrophy

Nodules and TenosynovitisNodules and Tenosynovitis

Stage IV – Stage IV – TerminalTerminal

Fibrous or Bony AnkylosisFibrous or Bony Ankylosis

Features of Stage IIIFeatures of Stage III

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ManagementManagement

Focused on relieving pain and preventing Focused on relieving pain and preventing damage/disabilitydamage/disability

Patient education about the disease is keyPatient education about the disease is key Physical Therapy for stretching and range of motion Physical Therapy for stretching and range of motion

exercisesexercises Occupational Therapy for splints and adaptive Occupational Therapy for splints and adaptive

devicesdevices SurgerySurgery

Rheumatoid Arthritis: Rheumatoid Arthritis: Classification of FunctionClassification of Function

Class I:Class I: No LimitationsNo Limitations

Class II:Class II: Adequate for Normal Activities DespiteAdequate for Normal Activities Despite

Joint Discomfort of Limitation of MovementJoint Discomfort of Limitation of Movement

Class III: Class III: Inadequate for Most Self-Care andInadequate for Most Self-Care and

Occupational ActivitiesOccupational Activities

Class IV: Class IV: Largely or Wholly Unable to Manage Self-Largely or Wholly Unable to Manage Self-

Care; Restricted to Bed or ChairCare; Restricted to Bed or Chair

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MedicinesMedicines

Non-Steroidal anti-inflammatories (NSAIDS) Non-Steroidal anti-inflammatories (NSAIDS) for symptom controlfor symptom control

Prednisone for quick control of joint Prednisone for quick control of joint inflammation but cannot use long term due to inflammation but cannot use long term due to side effectsside effects

Osteoporosis, cataracts, weight gain, insulin Osteoporosis, cataracts, weight gain, insulin resistance, dyslipidemiasresistance, dyslipidemias

Disease Modifying Anti-Disease Modifying Anti-rheumatic Agentsrheumatic Agents

Drugs that actually control the disease and not Drugs that actually control the disease and not just treat symptomsjust treat symptoms

Should be used early on in patientsShould be used early on in patients

Erosions can develop in the joints of patients Erosions can develop in the joints of patients within the first two years of diseasewithin the first two years of disease

Disease Modifying Anti-Disease Modifying Anti-rheumatic Agentsrheumatic Agents

Hydroxychloroquine-for mild disease, takes a Hydroxychloroquine-for mild disease, takes a long time to reach steady state, very benign in long time to reach steady state, very benign in side effect profileside effect profile

Sulfasalazine-for mild disease, toxicities Sulfasalazine-for mild disease, toxicities include GI upsetinclude GI upset

Azathioprine-for moderate disease, not as Azathioprine-for moderate disease, not as modifying as other drugs, cytopeniasmodifying as other drugs, cytopenias

Disease Modifying Anti-Disease Modifying Anti-rheumatic Agentsrheumatic Agents

Methotrexate-moderate to severe disease, very Methotrexate-moderate to severe disease, very successful in preventing erosions, liver successful in preventing erosions, liver toxicitiestoxicities

Anti-TNFAnti-TNFαα agents-used for mod-severe agents-used for mod-severe disease, but moving up as first line drug, TB disease, but moving up as first line drug, TB reactivation a concern reactivation a concern

PrognosisPrognosis

RA can shorten the life span 3-18 yearsRA can shorten the life span 3-18 years

Most die from cardiovascular disease, infection or Most die from cardiovascular disease, infection or lymphoproliferative disorderslymphoproliferative disorders

Overall RA patients are much better off than at any Overall RA patients are much better off than at any other time in history due to ongoing research and new other time in history due to ongoing research and new meds!!meds!!