Hot Topics in Rheumatology Prof. MG Molloy

Overview Rheumatoid Arthritis Psoriatic Arthritis Vasculitides: SLE Osteoarthritis Osteoporosis

Rheumatoid 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 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? –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 disease Extra-articular: –Cardiac coronary heart disease –Pulmonary fibrosis –Haematological Anaemia –Ophthalmology –Dermatology –Renal

Cardiac 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 RA

Medications 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

DMARDs 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

Methotrexate Commonest DMARD 30 year experience Monitoring: monthly FBC, ESR, CRP, Bioprofile, LFTs Complications: –Haem:Neutropenia, thrombocytopenia, ? Leukemia –Liver dysfunction

New 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 RA Indication: Refractory RA Prior to commencing: CXR, Mantoux Contraindications/Precautions: –Previous TB, COPD, Chronic infections, HIV

Biologic 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 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 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

Spondyloarthropathies Ankylosing Spondylitis Psoriatic arthropathy

Ank Spond

Diagnosis: –Clinical: Backpain and stiffness: EMS –Age 20-40yrs male –Xray: late changes Treatment: –Exercises, NSAIDS –Biologics

Gout & Pseudogout Crystal arthropathies

Gout uric acid deposition Clinical –Monoarticular –The most painful arthropathy Treatment –NSAIDS –Allopurinol: prophylaxis –Colchicine: Nausea, vomting, diarrhoea

Pseudo-gout 2 nd, 3 rd MCPs, wrists, shoulders, knees, feet Associations: –Haemochromatosis –Age Treatment –Underlying disease –NSAIDS

Vasculitides SLE

SLE

Management of SLE

Osteoarthritis

Osteoarthritis

Osteoporosis

Osteoporosis Diagnosis

Osteoporosis Management

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