Hot Topics in Hot Topics in RheumatologyRheumatology

Prof. MG Molloy

OverviewOverview

• Rheumatoid Arthritis

• Psoriatic Arthritis• Vasculitides: SLE• Osteoarthritis• Osteoporosis

Rheumatoid arthritisRheumatoid arthritis

– RA is a condition involving inflammation of the joints• It has the potential to result in serious joint

damage• It may come on suddenly or appear slowly

over time• Its symptoms may include pain, swelling,

stiffness in the joints, and general tiredness

Rheumatoid ArthritisRheumatoid Arthritis• Damage occurs early in most patients

• 50% show joint space narrowing or erosions in the first 2 years

• By 10 years, 50% of young working patients are disabled

• Death comes early• Multiple causes• Compared to general population

• Women lose 10 years, men lose 4 years

Who is affected by RA?Who is affected by RA?

– RA is one of the most common forms of inflammatory arthritis

• Affects about 1% of the world’s population

• Occurs 2 to 3 times more often in women than in men

• In most cases it develops between the ages of 25 and 50

RA: Multisystem diseaseRA: Multisystem disease

• Extra-articular:– Cardiac

• coronary heart disease

– Pulmonary• fibrosis

– Haematological• Anaemia

– Ophthalmology– Dermatology– Renal

Cardiac disease in RACardiac disease in RA

• Mortality in RA is unchanged in 40yrs despite DMARDS

• Patients unlikely to report symptoms of angina

• Not all IHD risk is due to traditional risk factors nor drugs such as Pred use, HRT DM etc

• Control BP, cholesterol etc

• High index of suspicion: cardiology referral

Management RAManagement RA

Medications for RAMedications for RA

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Corticosteroids

• Disease-modifying antirheumatic drugs (DMARDs)

• Biologics

• Combination

DMARD options DMARD options

• Hydroxychloroquine

• Sulphasalazine

• Methotrexate

• Azathioprine • Slow onset, reasonably effective

• Leflunomide• Pyrimidine inhibitor• Effect and side effects similar to those of MTX

DMARDsDMARDs Combination or monotherapy Combination or monotherapy

• No superiority of traditional combination DMARD therapy over monotherapy

• Some trials did not control for glucocorticoid use

• Review of studies since 2000 have shown that step-up therapy of Leflunomide +MTX is superior but, with significant toxicity

MethotrexateMethotrexate

• Commonest DMARD• 30 year experience• Monitoring: monthly FBC, ESR, CRP,

Bioprofile, LFTs• Complications:

– Haem:Neutropenia, thrombocytopenia, ? Leukemia

– Liver dysfunction

New BiologicsNew Biologics

• Infliximab ( chimeric monoclonal antibody to TNF)

• Etanercept (soluble TNF receptor)

• Adalimumab (humanised monoclonal antibody to TNF)

• Rituximab (anti-CD 20 )

• Anti-Interleukin 6 (in clinical trials for JRA)

Biologic agents in RABiologic agents in RA

• Indication: Refractory RA

• Prior to commencing: CXR, Mantoux

• Contraindications/Precautions:– Previous TB, COPD, Chronic infections, HIV

Biologic agents in RABiologic agents in RA• Monitoring:

– Monthly bloods: FBC, ESR, CRP, Bioprofile

– Regular physical examination

– Beware infection

• NB: Normal WCC, ESR, CRP does not exclude infection

New drugs New drugs

• Rituximab (anti- CD 20)- in use• Epratuzumab anti-CD22 – better risk profile than ritux• Anti-CD4 – was good but CD4 counts dropped so low trials

stopped• Efalizumab – anti-CD11a –used in psoriasis, no good in PSA• CTLA4-Ig (in trials)- binds CD80/86 and blocks cell activation• Alefacept- binds LFA-3• Anti-RANKL• SOCS• IL1-trap• Anti-IL6 receptor antibody• Soluble IL-15 receptor antagonist – 62% ACR 20 scores in high

dose group• Other targets – IL-12, IL-17, IL-18, IL-23, IL-27,IFN alpha and

gamma

Summary RA Summary RA RA – early treatment = better outcome MTX good monotherapy in many patients Combo therapy of traditional DMARDs is possibly

superior but conflicting studies

Biologics =higher expectations Currently combo biologics +MTX better than biologic

monotherapy Are biologics capable of inducing remission in early

disease – then do we switch to mainteance therapy with MTX – unknown yet

Anti – CCP antibody - predictor of erosive disease course

SpondyloarthropathiesSpondyloarthropathies

Ankylosing SpondylitisPsoriatic arthropathy

Ank SpondAnk Spond

Ank SpondAnk Spond

• Diagnosis:– Clinical: Backpain and stiffness: EMS– Age 20-40yrs male– Xray: late changes

• Treatment:– Exercises, NSAIDS– Biologics

Gout & PseudogoutGout & PseudogoutCrystal arthropathiesCrystal arthropathies

Gout Gout uric acid depositionuric acid deposition

• Clinical– Monoarticular– The most painful

arthropathy

• Treatment– NSAIDS– Allopurinol:

prophylaxis– Colchicine:

• Nausea, vomting, diarrhoea

Pseudo-goutPseudo-gout

• 2nd, 3rd MCPs, wrists, shoulders, knees, feet

• Associations:– Haemochromatosis– Age

• Treatment– Underlying disease– NSAIDS

VasculitidesVasculitides

SLE

SLESLE

Management of SLEManagement of SLE

OsteoarthritisOsteoarthritis

OsteoarthritisOsteoarthritis

OsteoporosisOsteoporosis

Osteoporosis Osteoporosis

• Diagnosis

Osteoporosis Osteoporosis

• Management

ThankyouThankyou