Lupus is easy with a little practice - Professor ... - Parkside Hospital

Lupus is easyWith a little practiceProfessor John Axford DSc MD FRCP FRCPCHSt George’s University of LondonLondon Rheumatology Clinic

Autoimmune rheumaticdiseases– Rheumatoid arthritis: RhF, anti-CCP Arthritis– Sjogren’s syndrome: anti-Ro/La Dryness– Vasculitis syndromes: c- & p-ANCA– Myositis: Jo-1 Weakness– Systemic sclerosis:SCL-70 scleoderma

Lupus– Multi-systemic disease– Wide spectrum of clinical manifestations– Exacerbations and remissions– Constellation of autoantibodies

Lupus• Epidemiology– 1/1000 - 1/6000– age: 25 - 35 years– Sex: Females 90%– Race: Afro Caribbean are commonlyaffected

What Does Lupus Look Like?

Lupus• Skin– Malar butterfly rash– Patchy alopecia– Oral/vaginal ulceration– Periungual erythema– Angioedema– Cutaneous vasculitis

Lupus• Musculoskeletal– Myalgia– Symmetrical arthritis– Jacoud’s

Lupus• Renal– Lupus Nephritis 50%Broad spectrum of severity–Hypertension–Renal failure

Lupus• Nerves Neuropsychiatric SLE– Peripheral– Central– Diffuse

Comparison Of NPSLE vs MST2 Weighted ImagesCuadadro MJ et al; Medicine (Baltimore) 2000;70:57-68

MR Imaging and Spectroscopy of an NPSLE PatientABmI+37%tCrNAA-16%tCholipids4 3 2 1 0CmI+36%tCrNAA-26%tChoA) T 2 weighted axial image of a 60yr femalepatient with NPSLEB) 1 H spectrum from a parietal white matterlesionC) 1 H spectrum from a region of normalappearing occipital white matter.lipids4 3 2 1 0

Anisotropy Map• Bright pixels - high anisotropy• Shows white matter• Quantitative

Lupus• Blood– Haemolytic anaemia– Neutropenia– Antiphospholipid Syndrome

Lupus• Heart and Circulation– Raynaud’s phenomenon– Pericarditis– Myocarditis– Endocarditis

Lupus• Lungs– Plural Effusion– Loss of lung volume

Lupus• Eyes– Sjögren’s syndrome– Episcleritis– Retinal infarcts– Optic neuritis

Lupus• General management– Sun protection– Diet and nutrition:– Unsaturated fatty acids– Exercise– Smoking cessation:– Increased risk– More active disease– Immunizations:Influenza & Pneumococcal vaccine

Lupus• Immunisation in SLE– Safe and useful– Influenza, Tetanus and pneumococcalvaccine– Prevent infection and associated flare– Live vaccine contraindicated ifimmunosuppressed

LupusImmunosuppressivemedication• Corticosteroid• Hydroxychloroquine

LupusImmunosuppressivemedication• Methotrexate• Cyclophosphamide• Azathioprine• Mycophenolate• Rituximab• Belimumab

Lupus• Belimumab• Monoclonal antibody that inhibits thebiological activity of B cell survival factor– B lymphocyte stimulator or BLyS.• Data indicate may be useful for patients withactive musculoskeletal or cutaneous disease.

LupusTreating co-morbid conditions:• Lupus patients have increased risks of:– accelerated atherosclerosis– pulmonary hypertension– Thrombosis: anti-phospholipid antibodies– osteopenia/osteoporosis

Lupus• Is cancer risk increased in lupus: YES– Non- Hodgkin’s and Hodgkin’s lymphoma– Lung cancer: smoking is a predictor– Breast cancer– Squamous skin cancer– Cervical cancer– Vaginal and vulval cancer

LupusRadiation therapy:• Anecdotal reports of increase toxicity during radiationtherapy• Little data to support• If required radiation therapy may be used to treatmalignant disease

LupusDhydroepiandrosterone (DHEA)• Lupus patients have low levels of DHEA.• Replacement– Data indicates no effect on disease activity– May improve overall well-being.– Side effects: acne, hair growth, menstrual changes.– Not recommended.

Lupus• Avoidance of specific medication:– Sulphur-containing antibiotics may causeexacerbations– Drugs that cause drug-induced lupus• Procainamide, Hydralazine & Minocycline– do not cause exacerbations.

Lupus• SLE in Pregnancy– Not contraindicated– Fertility rate normal– High spontaneous miscarriage 30 - 50%• if antiphospholipid antibodies present– Treatment with Prednisolone safe

Lupus• SLE in PregnancyAdverse outcomes– Neonatal SLE rare• Transient rash• Complete heart block– Prematurity– Still birth– Disease flare

LupusPrognosis• Patient survival with lupus:– five year survival 1950’s 40%, 1980’s 90%.• Death:– 5 times higher in women than men– 3 times higher black compared with to white women– 1 third of deaths between 15 and 44 years

LupusPrognosis• Causes of death:– Heart disease– Non-Hodgkin’s lymphoma– Lung cancer– Infections– Renal disease• Steroid therapy: considerable morbidity

Lupus• Does clinical remission occur– Yes– 25% in one study:• at least one treatment-free clinicalremission lasting for at least one year• Remission however uncommonand frequently not sustained.

The RA Revolution!Professor John Axford DSc MD FRCP FRCPCHThe London Rheumatology Clinic

Rheumatoid Arthritis• The bottom line• It can be cured

Clinical HistoryMCP Destruction Causing UlnarDeviation of the Digits

Clinical HistorySwan Neck Deformity of theForefingers

Clinical HistoryProgresive MCPJ & PIPJ synovitis

Rheumatoid Arthritis• In the last 10 years• Mr Gateley has NOToperated on any ofmy patients

Rheumatoid Arthritis• So what has happened?• Rheumatologists aresmarter• They have biologicdrugs

Rheumatoid ArthritisManagement theory/RA revolution• Joint damage begins early• Longer active disease persists

Rheumatoid Arthritis• So why areRheumatologists smart?

Rheumatoid ArthritisComplexity• Most common ARD• Multi-system• Immunological abnormalities• Symmetrical joint inflammation• Extra-articular complications

RA looks different in each patient

Rheumatoid ArthritisTypical referral letter:Dear DoctorPlease see Gwyneth……..• Clientele: Pleasant• RA: 3:1 Female• Age 25-35 yearsIe: Childbearing age

Rheumatoid ArthritisThey can do two things at the same time• Academic– Think and do tests• Practical– Treat the patient

Academic RheumatoidArthritisBlood Investigations for Polyarthritis• FBC• Acute Phase Reaction• Immunology: RhFactor, CCP antibodies• Viruses: Parvovirus B19• Biochemistry: Iron, Urate, ACE• Physiology: Renal, Liver

Academic RheumatoidArthritisImaging in Polyarthritis– Xray– MRI• Sometimes required– Ultrasound– Scintigraphy– CT

Practical RheumatoidArthritisManagement practiceWeek oneDiagnose and treat• Analgesia: Paracetamol, Codydramol, Tramadol• Modify inflammatory events :Diclofenac,Naproxen, Celebrex, Etoricoxib• Corticsteroid: IM and oral• Education: ie talk, booklet, website

Practical Rheumatoid ArthritisNon Drug & Preventative Treatments• Patient education and counselling• Physical Therapy• Occupational Therapy• Nutrition and Dietary Therapy• Modifying Risk Factors for Atherosclerosis• Bone Protection• Vaccinations

Practical RheumatoidArthritisManagement practiceWeek twoConfirm diagnosis and treatModify immunological events• Disease modifying drugs• Biological immunosuppression

Chemical Disease Modifying Drugs• Affect disease process• May not have immediate therapeutic affect• Should be discontinued at < 6 months if notbeneficial• Examples– Methotrexate, Leflunomide, Sulphasalazine,Hydroxychloroquine

Rheumatoid ArthritisBiological treatment strategies• TNF inhibition– Soluble receptor antagonists:• Etanercept• Fusion proteins comprised of the p75 TNF receptor linked tothe Fc portion of the human IgG1– Monoclonal antibodies:• Infliximab• Adalimumab• Golimumab• Certolizumab– polyethylene glycolated Fab fragment. No Fc portion)

Rheumatoid ArthritisBiological treatment strategies• IL1 inhibition– Cell surface receptor antagonists:– Recombulent antagonist of IL1 receptor– Anakinra• IL6 inhibition– Cocilizumab – humanized anti-human IL6 receptor antibody• Co-stimulation blockade– Abatacept (CTLA-4 – Ig)– soluble fusion protein comprising CTLA – 4 and the Fc portion of IgG.Inhibitory signal.• B cell depletion.– Rituximab– Monoclonal anti-CD20 antibody

Rheumatoid ArthritisTB & not TB: latent TB• Anti-TNF therapy associated withincreased risk of a variety ofinfections including reactivation oflatent TB.• QuantiFeron testPositive– Anti-TB therapy for one month andthen treatment with anti-TNF therapy

Rheumatoid ArthritisRA researchScaling new heights…..Now it’s time for a ……

Thank you for your attentionThe London Rheumatology Clinicwww.londonrheumatology.co.uk

Lupus• Do you want more?• Or do you want a….

Lupus• Antiphospholipid Syndrome– Primary– Secondary: SLE or other autoimmunerheumatic diseases

Lupus• Antiphospholipid Syndrome– Vascular Thrombosis– Thrombocytopenia– Recurrent spontaneous miscarriage– Emboli– Stroke– Bleeding tendency

Lupus• Specific Investigations– Antiphospholipid Antibody– Lupus anticoagulant (coagulation assay)

Lupus• Clinical Management– Low dose Aspirin - 75mg daily– Warfarin - serious thrombolic events– Special attention needs to be given toAPS positive mothers

Lupus• Drug Induced Lupus– More problem in Women– Uncommon in Afro Caribbean– 25-70% ANA– 25% SLE

Lupus• Drug Induced Lupus - continued– Procainamide for heart arrhythmias– Phenytoin for hypertension– Primidone for epilepsy– Minocycline for acne

Lupus• Lupus researchScaling new heights…..No it’s time for a ……

Thank you for your attentionThe London Rheumatology Clinicwww.londonrheumatology.co.uk

Thank you for your attention…

Audience exhaustion!

Thank you for yourattention

Understanding the science(Auto?-) AntigenMonocytes/MacrophagesAutocrineGrowthB&T cells and othersMigrationPannus TissueSynovialFibroblastsTarget:B&T cellsTarget:Cell Adhesion Molecules(CAMs)Target:Inflammatory Cytokines

What sort of arthritis?

More Osteoarthritis ResearchRequired

Please Meet Gwyneth

OsteoarthritisPatient ManagementEvidence based•Importance of a Patient-centredmultidisciplinary approach•Conservative non-drug interventions•Judicious use of drugs•Appropriate surgical referral

………and all the complications

Academic RheumatoidArthritisTo Make a Diagnosis• History• Examination– Symmetrical Arthritis– Rheumatoid Nodules• Investigations– Rheumatoid Factor– Radiography

Lupus• SLE in PregnancyAdverse outcomes– Neonatal SLE rare• Transient rash• Complete heart block