Rheumatoid Arthritis

Systemic chronic inflammatory disease Mainly affects synovial joints Variable expression Prevalence about 3% Worldwide distribution Female:male ratio 3:1 Peak age of onset: 25-50 years

Rheumatoid ArthritisUnknown etiologyGeneticsEnvironmentalPossible infectious component

Autoimmune disorder

THE PATHOLOGY OF RA Serositis 1. Synovitis Joints Tendon sheaths Bursae Nodules Vasculitis

RA Is Characterised by Synovitis and Joint DestructionNORMALRASynovial membraneCartilageCapsuleSynovial fluidInflamed synovial membranePannusMajor cell types:T lymphocytesmacrophagesMinor cell types:fibroblastsplasma cellsendotheliumdendritic cellsMajor cell type:neutrophilsAdapted from Feldmann M, et al. Annu Rev Immunol. 1996;14:397-440.Cartilage thinning

Numerous Cellular Interactions Drive the RA ProcessB cellT cellAntigen-presentingcellsB cell ormacrophageSynoviocytesPannusArticularcartilageProduction of collagenase and other neutral proteasesIL-1 andTNF-ChondrocytesRheumatoidfactorsSoluble factors and direct cellcell contactImmune complexesBacterial productsIL-1, TNF-, etcMacrophageIL-1HLA-DRArend W. Semin Arthritis Rheum. 2001;30(suppl 2):1-6.

IL-1 and TNF- Have a Number of Overlapping Proinflammatory EffectsCOX-2 = cyclo-oxygenase type 2; PGE2 = prostaglandin-E2; NO = nitric oxideCOX-2 PGE2 NO Adhesion molecules Chemokines Collagenases IL-6 Proinflammatory effects of IL-1Proinflammatory effects of TNF-TNF- Osteoclast activation Angiogenic factors IL-1 cell death

Activates monocytes/ macrophages Activates chondrocytes Induces fibroblastproliferationActivates osteoclastsInflammation Synovial pannus formationCartilage breakdown Bone resorptionIL-1IL-1 Plays a Pivotal Role in the Inflammatory and Destructive Processes of RA

Signs and SymptomsJoint inflammationTender, warm swollen jointsSymmetrical patternPain and stiffnessSymptoms in other parts of the bodyNodulesAnemiaFatigue, occasional fever, malaise

JOINT INVOLVEMENT ON PRESENTATION OF RA

Polyarticular 75% Monoarticular 25%

Small joints Knee 50%of hands and feet 60%

Large joints 30% Shoulder } Wrist }Large and Hip } 50%Small joints 10% Ankle } Elbow }

Articular features seen in the Rheumatoid Hand

WRIST: PIPs: SynovitisSynovitis Prominent ulnar styloidFixed flexion or extension Subluxation and collapse of deformities carpus(Swan neck or boutonniere Radial deviation deformity)MCPs: THUMBS: SynovitisSynovitis Ulnar deviationZ deformity Subluxation

Joint Destruction

Extra-articular manifestations

Generalfever, lymphadenopathy, weight loss, fatigueDermatologicpalmar erythema, nodules, vasculitisOcularepiscleritis/scleritis, scleromalacia perforans, choroid and retinal nodules

Extra-articular manifestations

Cardiacpericarditis, myocarditis, coronary vasculitis, nodules on valvesNeuromuscularentrapment neuropathy, peripheral neuropathy, mononeuritis multiplexHematologicFeltys syndrome, large granular lymphocyte syndrome, lymphomas

Extra-articular manifestations

Pulmonarypleuritis, nodules, interstitial lung disease, bronchiolitis obliterans, arteritis, effusionsOthersSjogrens syndrome, amyloidosis

Investigations:Hematology : CBC , ESRBiochemistry : LFT , Renal profileSerology : RF , Anti-CCPRadiography : Joints , Spines ,Chest

Treatment GoalsRelieve pain

Reduce inflammation

Prevent/slow joint damage

Improve functioning and quality of life

Treatment ApproachesLifestyle modifications

Rest

Physical and occupational therapy

Medications

Surgery

Rationale for the Early Treatment of R.A.

Erosions develop early in the disease courseDestruction is irreversibleDisease activity is strongly associated with joint destruction later in the disease courseEarly treatment can slow down radiographic progressDisease activity must be suppressed maximally in its early stages to prevent destruction and preserve function

Drug TreatmentsNonsteroidal anti-inflammatory drugs (NSAIDs)

Disease-modifying antirheumatic drugs (DMARDs)

Biologic response modifiers

Corticosteroids

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)Traditional NSAIDs

Aspirin Ibuprofen KetoprofenNaproxenCOX-2 Inhibitors

CelecoxibRofecoxib

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)To relieve pain and inflammation

Use in combination with a DMARD

Gastrointestinal side effects

Disease-Modifying Antirheumatic Drugs (DMARDs)Hydroxychloroquine

SulfasalazineMethotrexateLeflunomideGoldAzathioprine

Disease-Modifying Antirheumatic Drugs (DMARDs)Control symptomsNo immediate analgesic effectsCan delay progression of the disease (prevent/slow joint and cartilage damage and destruction)Effects generally not seen until a few weeks to months

DMARDs

hydroxychloroquinemild non-erosive diseasecombinations200 mg bideye exams

DMARDs

Sulfasalazine1 gm bid - tidCBC, LFTsonset 1 - 2 monthsMethotrexatemost commonly used drugfast acting (4-6 weeks)po, SQ - weeklyCBC, LFTs

DMARDs

IM Goldslow onset (3-6 months)weekly then monthly injectionsCBC, UA before each injectionOral Goldless effectiveslow acting (4-6 months)dailyCBC, UA

Biologic Response ModifiersEtanercept

Infliximab

Anakinra

Biologic Response ModifiersEtanercept and infliximab target tumor necrosis factor alpha (TNF-)

Anakinra targets interleukin-1 receptor

OSTEOARTHRITIS

MULTIFACTORAL ETIOLOGY OF OA Joint instabilityAgeHormonal factorsTraumaAltered biochemistryInflammationGenetic predisposition? Others

SYMPTOMS AND SIGNS OF OAPain worse on use of jointStiffness mild after immobilityLoss of movementPain on movement/restricted rangeTenderness (articular or periarticular)Bony swellingSoft tissue swellingJoint crepitus

RADIOLOGICAL FEATURES OF OA Narrowing of joint space Osteophytosis Altered bone contour Bone sclerosis and cysts Periarticular calcification Soft-tissue swelling

MANAGEMENT OF OSTEOARTHTITIS Confirm diagnosis Initial Therapy : Pysiotherapy Wt loss Local therapy Paracetamol

MANAGEMENT OF OSTEOARTHTITIScontSecond-line approach: NSAIDS Intra-articular therapy: steroids,hyalurinate Opioids ?glucosamines Arthroscopy Surgery

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