Rheumatoid Arthritis

dr Putra Hendra SpPDUNIBA

Rheumatoid ArthritisChronic, systemic inflammatory diseaseincidence 40-60 th Females 2-3X > MalesPathogenesis unknown

Endogenous factorsExogenous factors : rokokMHC genes, genetik,hormon milieu)cross-reacting antigenes, bacteria, virusesSynovial vasculitisAdhesion molecule expressioncellular infiltrationMacrophages, T cells, B cells, granulocytesCytokines (TNF-a, IL-1, IL-6), RF, free-radicals, enzymesSynovial proliferation, angiogenesis, chondrocyte-, osteoclast-activation Pannus, cartilage destruction, bone resorption

Pathogenesis of RAPathogenesis of RA

Choy, E. H.S. et al. N Engl J Med 2001;344:907-916Cytokine Signaling Pathways Involved in Inflammatory Arthritis

Classification Criteria for RA 4 criteria present > 6 wksMorning stiffness > 1 hourArthritis of 3 joints areas (PIP, MCP, wrist, elbow, knee, ankle, and MTP)Arthritis of hand joints (wrist, MCP, PIP)Symmetric arthritis5) Rheumatoid nodules6) RF+7) RadiographicchangesErosionsUnequivocal periarticular osteopenia

Sites affected

RA: Joint distribution

Progression of RA..Stage 1: - no destructive changes. - Osteoporosis.Stage 2: - periarticular osteoporosis w/wo slight subchondral bone destruction. - joint mobility limit but no destruction. - adjacent muscle atrophy. - extra-articular soft tissue lesions.

Progression of RA..Stage 3 - cartilage and bone destruction in addition to periarticular osteoporosis. - joint deformity w/wo fibrous or bony ankylosis. - extensive muscle atrophy. - extra-articular soft tissue lesions.Stage 4 - criteria of stage 3. - fibrous or bony ankylosis.

RAEarly RAIntermediate RALate RACourtesy of J. Cush, 2002.

RA Hand DeformityUlnar deviation at MCPsRadial deviation at wristsSwan-neck deformitiesBoutonniere deformitiesTendon nodulesTendon rupture3rd, 4th, and 5th extensor tendonsCarpal tunnel syndromeUlnar neuropathy

Swan neck and Boutonniere

Ulnar Deviation

RA- extensor tendon rupture

Carpal Tunnel Syndrome

Deformities..

Rheumatoid nodules

RA - KneesSymmetric lateral and medial joint space lossEffusionsSynovial proliferationBakers cystPosterior herniation of joint capsuleMay ruptureHx and U/S can distinguishCrescent-sign on exam

Popliteal Cyst

Cock-up deformity

RA - Cervical SpineApophyseal joint destruction C4-5 and C5-6 most commonAtlantoaxial InstabilityC1-C2Tenosynovitis of transverse ligament of C1Erosion of odontoid process of C2Cranial settlingNeck/Occiput pain, Paresthesias, Pathologic reflexes

RA: Other Features

RA - Vasculitis

RA - Vasculitis

Extraarticular RA -- OcularSicca symptomsEpiscleritisScleritis

Scleromalacia perforans

RA: Pulmonary nodules

Laboratory ..Hematologic parametersAnaemiaThrombocytosis Serum iron & IBC Serum globuline ALP Acute phase reactantImmunological parameters Synovial fluid analysis

HematologicAnemia of chronic diseaseLow Fe, Low TIBC, Ferritin > 40 - 100Feltys syndromeTriadRASplenomegalyNeutropeniaFrequent infections/Leg ulcersIron deficiency anemia (NSAIDs)

Lab Evidence of InflammationSynovial Fluid WBC > 2000/mm3Serum Acute phase responseAcute phase proteinsCRP, ceruloplasmin, complement, serum amyloid A, fibrinogen, alpha-1-antitrypsin, haptoglobin, and ferritinNegative APPs = albumin, transferrinErythrocyte sedimentation rate

Laboratory RF Rheumatoid FactorAntibody against the Fc fragment of IgNot sensitive80% of RA patientsRF+ patients more likely to haveMore severe diseaseExtraarticular manifestations

RF is not specific for RA.Other autoimmune diseaseSjogrens syndrome , Systemic LupusChronic infectionHep B/C, SBE, Viral, Parasites, TBPulmonary inflammation Sarcoid, IPF, Silicosis, AsbestosisMalignancyHealthy 4% young; 5-25% > age 60

Anti-CCPAnti-cyclic citrullinated peptideSpecificity = 90%Sensitivity = 50-80%

RadiographyPeriarticular osteopeniaSymmetric joint space lossMarginal erosionsAbsence of productive changesBest films for diagnosis:Bilateral Hand Arthritis SeriesBilateral Foot SeriesLarger joints may not show erosions early due to thicker cartilage.

RA - Erosions

RA - imaging

Differential DiagnosisViral polyarthritisConnective tissue diseaseFibromyalgiaSpondyloarthropathyPsoriatic arthritisCrystalline arthritisSeptic arthritisOsteoarthritisParaneoplastic diseaseMulticentric reticulohistiocytosis

RA -- TreatmentAggressive treatment early!DMARDs = disease modifying anti-rheumatic drugsCombinationsBiologics TNF- inhibitors, IL-1 antagonists, Anti-CD20, CTLA4 IgNSAIDsSteroidsOsteoporosis prophylaxis

Rheumatoid Arthritisprognosis

10% improve60% intermittent, slowly worsening20% severe joint erosion, multiple surgery10% completely disabled

*Primarily involves joints but extraarticular involvement5% in some Native American populations5% in females over 65 years oldPathogenesis still unclear but progress being made*Figure 1. Cytokine Signaling Pathways Involved in Inflammatory Arthritis.

The major cell types and cytokine pathways believed to be involved in joint destruction mediated by TNF-{alpha} and interleukin-1 are shown. Th2 denotes type 2 helper T cell, Th0 precursor of type 1 and type 2 helper T cells, and OPGL osteoprotegerin ligand.

Pathogenesis is unknown: 1st step is probably antigen dependent activation of T cells and microvascular changes in the synovium leading to angiogenesis and migration of cells into synoviuma and ultimately a self perpetuating inflammatory cascade in a susceptible host.Inciting Agunknown Type II collagen, heat shock protein, cartilage Ag gp39, citrullinated peptides G6Pisomerase*cricoarytenoid*Stages of RAEarly rheumatoid arthritis (RA) is characterized by symmetric swelling of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. Typical fusiform or spindle-shaped enlargement of the PIP joints is usually seen, accompanied by tenderness and limited range of motion.Later on, massive diffuse swelling is seen, together with deformities such as the boutonnire, the swan neck, and the unstable PIP joint that is caused by synovitis in that joint.Long-standing RA is characterized by severe deformities resulting from joint destruction. Ulnar deviation and MCP joint subluxation are typical deformities, as are rheumatoid nodules.*Tx: Corticosteroid injection into knee joint (not cyst)*No significant Sacro/Lumbar/Thorax involvement***MRI and U/S increasingly being used*Goals: relieve pain and inflammation, maximize function, limit joint destruction*