AgeingandEndingsA-OsteoarthritisandRheumatoidArthritis(TimothyYang)

8/10/2019 AgeingandEndingsA-OsteoarthritisandRheumatoidArthritis(TimothyYang)

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Osteoarthritis andRheumatoid Arthritis

Timothy Yang

New College Village

1. Osteoarthritis


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Epidemiology

Most common joint disease

May be primary or secondary

Males more hip OA, Females

more n sma o n s o an

Native Americans > whites > Chinese

Genetic or lifestyle?

Familial component in certain cases

Risk Factors

For OAAge

Female

Race

Genetic

Major trauma or repetitive joint use

Congenital

Prior inflammatory joint disease

Metabolic/endocrine disorders

For pain & disability in those with OAQuadriceps muscle weakness (knee OA)

Female

On welfare

Divorced


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Classification

PrimaryLocalised

Hands, feet, knee, hip, spine, otherGeneralised (3+)

SecondaryTrauma

Chronic

Congenital/developmentalLocalised slipped epiphysis, congenital hip dislocation

Mechanical valgus/varus deformity

Bone dysplasis

MetabolicOchronosisHaemochromatosis

Wilsons disease

Classification

SecondaryEndocrine

Acromegaly

Hyperparathyroidism

Diabetes mellitusObesity

Hypothyroidism

Calcium deposition diseases

Other bone & joint diseaseLocalised fracture, infection, gout

Diffuse RA, Pagets disease

Neuropathic (Charcot joints)

Endemic

MiscellaneousFrostbite

Haemoglobinopathies


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PathologyProgressive loss of articular cartilage

Whole synovial joint affected

Subchondral bone, synovium, meniscus, ligaments,neuromuscular apparatus

Changes most striking in load bearing areasInitially, thickening of cartilage

Joint cartilage thins, softens, breach of surface vertical clefts (fibrillation)

Attempted repair with fibrocartilage clusters ofchondrocytes

Remodelling & hypertrophy of boneAppositional bone growth sclerosis & osteophytesAbraded bone ivory eburnation

Patchy chronic synovitis + joint capsule thickening

Pariarticular muscle wasting

Pathogenesis

OA occurs in two settingsBiomaterial properties of cartilage normal with excessiveloading

Suboptimal biomaterial properties of cartilage with normal

loadingArticular cartilage

Two redominant macromoleculesProteoglycans

Responsible for compressive stiffness + withstanding loads

Collagen Tensile strength + resistance to shear

Contains MMPs and aggrecanaseLevel of MMPs determined by balance between activation &inhibition

Aggrecanase degrades PG

IL-1 stimulates MMPs and suppresses PG synthesis


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Pathogenesis

Articular cartilage

Inhibitors of matrix degrading enzymes

Tissue inhibitor of MMP (TIMP)

- -

IGH-1 & TGF- may stimulate PG

synthesis

Brief durations of mechanical loading

Pathogenesis

Cartilage Changes in OAIncreased MMP, plasmin & cathepsin mediatedbreakdown of articular cartilage

NO from chondrocytes stimulated by IL-1 & TNFcauses synthesis of MMPs

- - -, , attempts repair process

Initially chondrocytes become moremetabolically active PG synthesiscartilage thickening compensated OA

Repair tissue inferior to normal hyaline cartilage PG synthesis (end-stage OA) with fullthickness loss of cartilage


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Clinical Presentation

Joint pain

Deep ache localised to involved jointAggravated by use, relieved by restEventually persistent with nocturnal pain (interferingwith sleep)

minutes

Source of painSynovial inflammation (marked in advanced OA)

Subchondral bone microfractures & medullary HTN

Osteophyte stretching periosteal nerve endingsLigament stretch

Capsular inflammation & distension

Muscle spasm


Physical Exam

Localised tenderness

Bony or soft tissue swellingBony crepitus

Synovial effusions, if present, are small

May be warm over joint

Periarticular muscle atrophy

Disuse or reflex inhibition

Gross deformity, bony hypertrophy,subluxation, loss of motion (advanced)


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Differential Diagnoses

Soft tissue rheumatism

Anserine bursitis of knee, trochanteric bursitisof hip

Radiculopathy

Referral from another joint

Knee pain referred from hip

Entrapment neuropathy

Vascular disease

Other arthritis

Investigations

X-ray (disparity between radiographic changes &symptoms)

Joint space narrowing

Subchondral bone sclerosis

Subchondral cysts

s eop y os s

Change in joint contour

Subluxation

Synovial fluidMild leukocytosis (< 2000/L), predominant mononuclear

Exclude CPDD, gout, septic arthritis

Arthroscopy


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Specific Joints

Interphalangeal joints

Heberdens nodes (DIP)

Bouchards nodes (PIP)

May present with pain, redness, swelling

Erosive OA

DIP, PIP prominently affected

Subchondral plate collapse + bony ankylosis

Severe deformity & functional impairment

Specific joints

Thumb base

2nd most frequently involved area

SwellingTenderness

Crepitus

Loss of motion & strength

Osteophytes squared appearance

Contracted 1st web space

Adduction of thumb, due to pain with pinching


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Specific joints

Hip

Congenital & developmental defectspredispose to OA at hip

Referred pain to inguinal areaAlso buttocks, proximal thigh, or knee

Provoked by movement esp. internal rotation

Loss of internal rotation initially, followed

by extension, adduction, flexionCapsular fibrosis and/or buttressingosteophytes

Specific joints

Knee3 compartments

Medial femorotibial varusLateral femorotibial valgus

Patellofemoral Positive shrug sign: pain with movement of

patella against femur during quad contraction

Osteophytes & tenderness on palpation

Effusions, if present, are small

Crepitus


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Specific joints

Spine

May involve apophyseal joints, IV disks(spondylosis) & paraspinous ligaments

Diagnosis must involve apophyseal jointsease

Localised pain & stiffness

Radicular pain & weakness 2 to nerveroot compression

Osteophyte blocking neural foramina,prolapsed IV disk, subluxation of apophyseal

joint

Management

Non-pharmacological measures

Reduce joint loading

Patellar taping (patellofemoral knee OA)Wedged insoles or orthoses (medial

compartment knee OA)

Thermal modalities

Exercise

Patient education

Tidal irrigation of kneeArthroscopic debridement & lavage


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Management

Pharmacological

NSAIDs & Paracetamol

COX-2 inhibitors

Intrarticular injection of hyaluronan

Opioids

Topical Rubefacients/capsaicin

Management

Other

Glucosamine, chondroitin sulfate

Orthopaedic surgery


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2. Rheumatoid Arthritis

Epidemiology

F:M, 3:1

Prevalence increases with age

Affects all races and is prevalent

Incidence & severity less in rural sub-Saharan Africa & in Caribbean blacks

Onset most frequent from 40s-50s


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Genetics

Genetic predisposition4X expected rate in 1st-degree relatives of those withRF+ RA10% of RA patients have an affected 1st degree relative

HLA-DR4 is major genetic risk factors in certaingroups

HLA-DR1, DR3, DR9, DR10 in other populations

Other HLA-DR & HLA-DQ genes may be protective

Genes outside HLA complex may also contribute

Environmental factors also play a role in aetiology

Aetiology

RA may be a manifestation of the response to aninfectious agent in a genetically susceptible host

Possible processes of chronic inflammatory

arthritisPersistent infection or retention of microbial antigenwithin articular structures

Induction of immune response revealing hiddenantigens within joint

Cross reactivity between microorganism & joint antigens(molecular mimicry)

Superantigen products of microorganisms may inducethe disease

Environmental risk factorsSmoking


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Pathology & Pathogenesis

Chronic inflammatory process in

synoviumInitially, hyperplasia of synovial liningcells + erivascular infiltration withmononuclear cells

Synovium becomes oedematousprojects into joint cavity


On light microscopy:Hyperplasia & hypertrophy of synovial lining cells

Focal or segmental vascular changes microvascular

injury, thrombosis, neovascularisationOedema

Mononuclear infiltration

Rheumatoid synovial endothelial cells expressincreased adhesion molecules

Predominant cell in infiltrate is CD4+ Tlymphocytes

Also CD8+ T cells, B cells, plasma cells macrophages,dendritic cells


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Polyclonal immunoglobulin & autoantibody

RF produced within synovial tissue

localformation of immune complexesAntigen to synovial tissue also form

S novial fibroblasts roduce enz mes(collagenase, cathepsins) which degradearticular matrix

Osteoclasts & activated mesenchymalstromal cells also present


Cytokines & chemokines secreted bylymphocytes, macrophages, fibroblasts &other cells account for many pathological &

clinical manifestations of RASynovial tissue inflammation

Synovial fluid inflammation

Synovial proliferation

Cartilage & bone damage

Systemic manifestations

Other factors (TGF-) may inhibit such

features, slowing inflammation


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Inflammatory process mainly driven by CD4+ T

cellsCD4+ T cells in synovium differentiatepredominantly into TH1 cells producing IFN-

Relatively deficient in IL-4 producing TH2 cells

IFN- activates macrophages IL-1, TNF + increasedexpression of HLA molecules

Also stimulate B cells Ig & RF production immune-complexes complement activation inflammation dueto anaphylatoxins (C3a, C5a) & chemotactic factor C5a


On top of the chronic inflammatory process in thesynovial tissue, is an acute inflammatory processin the synovial fluid

Exudative synovial fluid contains more PMNs thanmononuclear cellsLocall roduced antibodies com lexes chemokinescytokines can be activate complement or be directlychemotactic for neutrophils

They can also enhance endothelial cells of venules tobind cells more efficiently

Net result: enhanced PMN migration into synovial site synovial fluid

Mast cells (histamine) & prostaglandin E2 also facilitate

exudation of inflammatory cells to site


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Bone & cartilage destruction occurs

where inflamed synovium or pannusspreads to cover articular cartilage

Panus a vascular granulation tissuewith blood vessels & cells capable ofproducing degradative enzymes &cytokines which cause bonedemineralisation (osteoclast activation)


Systemic manifestations are a result

of inflammatory mediators into serum

IL-1, TNF-, IL-6

-

due to immune complex deposition

within circulation


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Characteristically, RA is a chronic

polyarthritisOnsetInsidious onset with fatigue, anorexia, mildfever, generalised weakness, vaguemuscu os e eta symptoms

Specific. symmetrical joint symptoms followprodrome (weeks-months later)

10% have an acute onset of rapidly developingpolyarthritis + fever, lymphadenopathy, splenomegaly

33% may have initial symptoms may be confined toone or few joints


Articular diseasePain aggravated by movement

Stretching of joint capsule

Swelling, tendernessAccumulation of synovial fluid, synovial hypertrophy, joint

Stiffness, most apparent after period of inactivity

Morning stiffness >1 hr

Warmth over joint

Disability

Initially due to pain

Later due to fibrous or bony ankylosis or soft tissue

contractures


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Articular disease

Characteristic joints involvedPIPs, MCPs

Wrists limited motion, deformity, carpal tunnel

Knee joint Bakers cyst, ligamentous laxity

Forefoot, ankles, subtalar joints severe pain on

ambulation, deformities

Upper cervical spine atlantoaxial subluxation

(occiput pain)


Characteristic joint changesRadial deviation at wrist, ulnar deviation of digits +/-palmar subluxation of proximal phalanges

Swan-neck deformity: hyperextension of PIP, flexion ofDIP

,extension of DIP

Z-thumb: hyperextension of 1st interphalangeal, flexion of1st MCP

Feet changes: eversion of hindfoot, plantar subluxation ofmetatarsal heads, widening of forefoot, hallux valgus,lateral deviation & dorsal subluxation of toes


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Extra-articular manifestations (occur mainly

in those with high RF titre)Rheumatoid nodules (20-30%)

Usually on periarticular, extensor & other surfaces

Olecranon bursa, proximal ulna, Achilles tendon,

occiput

May form in non-skin sites pleura, meninges

Central zone of fibrinoid necrosis: necrotic collagen

fibrils, filaments, cellular debris

Extra-articular Manifestations

Weakness & atrophy of skeletal

muscle (common)

Muscle atrophy apparent within weeks of

Most apparent in musculature of affected

joints

Disuse atrophy + muscle fibre necrosis

+/- mononuclear infiltrate


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Rheumatoid vasculitis

Affects any organ system

Polyneuropathy, mononeuritis multiplex

Mild, distal sensory neuropathy

Cutaneous vasculitis, ulceration, dermal

necrosis

Small brown spots in nail beds, nail folds, digital pulp

Digital gangrene

Visceral infarction


Pleuropulmonary manifestationsPleural disease

Interstitial fibrosisPleuro ulmonar nodules

Pneumonitis

Arteritis

Heart

Pericarditis (usually asymptomatic)


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Nervous system

Neurologic manifestations from atlanto-

axial, cervical subluxation

Median, ulnar, radial, anterior tibial nerves

Eye

Episcleritis, scleritis


GastrointestinalFeltys syndrome

Chronic RA, splenomegaly, neutropenia +/- anaemia,thrombocytopenia

Increased susceptibility to infection due to dysfunctional &decreased number of PMNs

OsteoporosisRA causes a modest reduction in mean bone mass

Aggravated by glucocorticoid treatment

Increased risk of fractures

Lymph nodesRA associated with an increased incidence of lymphoma,

especially large B cell lymphoma


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Investigations

Rheumatoid factor

IgM autoantibodies to Fc portion of IgG (>66%)

5% of healthy persons are RF+

Also associated with SLE, Sjogrens, chronic

liver disease, sarcoidosis, interstitial pulmonary

fibrosis, infectious mononucleosis, TB etc

Good prognostic factor

RF+ more severe disease, extra-articular

manifestations

Investigations

FBC

Normochromic, normocytic anaemia

Chronic disease ineffective erythropoiesis

Normal or mild leukocytosis

Leukopenia with Feltys syndrome

ESR, CRP


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Investigations

Synovial fluid aspirate

Turbid, reduced viscosityProtein, normal or glucose

WCC: 5 50 000/ L PMNspredominate

>2,000/L, >75% PMNs characteristic ofinflammatory arthritis

Markedly diminished C3, C4 (activationof classic complement pathway)

Investigations

X-ray

Early soft tissue swelling, joint effusion

Juxta-articular osteopenia (weeks)

,

(months)

MRI

Bone scan


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Clinical Course & Prognosis

Most patients experience persistent, but

fluctuating disease activityVariable joint abnormalities & functional

impairment

15% have remitting, short-lived

inflammation with no major disability

Median life expectancy shortened by 3-7

years

Clinical Course & Prognosis

Poor prognostic factors>20 inflamed joints

Markedly ESR

Radiographic evidence of bone erosions

Rheumatoid nodules

g serum t tre

Functional disability

Persistent inflammation

Advanced age

Comorbid condition

Low socioeconomic status or education level

HLA-DR4


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Diagnosis

Mean delay to diagnosis from disease onset: 9months

Early symptoms are non-specific

American College of Rheumatology criteria (4+criteria for classification as RA, but failure to meetcriteria does not exclude dia nosis

Morning stiffness >1hr

Arthritis of 3+ joints

Arthritis of hand joints

Symmetric arthritis

Rheumatoid nodules

Serum RF

Radiographic changes

Management

GoalsPain relief

Reduce inflammation

Protect articular structures

Maintain functionControl systemic involvement

Medicals, - n tors

DMARDsMethotrexate, gold, D-penicillamine, antimalarials, sulfasalazine

Glucocorticoids

Anti-cytokine agentsEtarnercept (TNF receptor fused to IgG1), infliximab (monoclonal Ig to TNF),adalimumab (recombinant human Ig to TNF)

ImmunosuppressionAzathioprine, leflunomide, cyclosporine, cyclophosphamide

Surgery

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AgeingandEndingsA-OsteoarthritisandRheumatoidArthritis(TimothyYang)