Rheumatoid arthritis

Rheumatoid arthritis. causes to treatment

1. RHEUMATOID ARTHRITIS

2. INTRODUCTION A chronic inflammatory disease Unknown aetiology Symmetrical polyarthritis Chronic inflammation resulting in joint damage and physical disability Systemic involvement is common Fatigue/Anemia

3. Extra Articular features Sub cutaneous nodules(on knuckles) Pleural nodules Pericarditis Peripheral neuropathy Vasculitis Kerato conjunctivitis sicca Episcleritis Xerostomia

4. CLINICAL FEATURES Age : 25 to 55 years Sex : Female predominance Early morning joint stiffness lasts for half to one hour, gets eased with activity Earliest joints involved : Small joints of hand and feet Usually monoarticular Oligoarticular Polyarticular Usually symmetrical Results in inflammation of joints tendons and bursae

5. Frequently involved joints MCP DIP PIP Flexor tendon synovitis (Hallmark of RA) Decreased ROM Decreased grip strength Trigger finger Irreversible deformities with destruction of joints and soft tissue

6. Ulnar deviation Subluxation of MCP joints Subluxation of proximal phalynx Subluxation of volar side Z line deformity Piano key movement Flat feet( Pes Plano valgus ) Main target of RA are 14 joint groups PIP MCP Wrist Elbow Knees Ankle MTP Does not affect thoracic, lumbar spine and rarely temporo-mandibular joint.

7. Constitutional Loss of body weight Malaise Fever Fatigue Cachexia Depression Temperature >101*F

8. Nodules 30-40% Benign subcutaneous nodules Common sites Forearm, sacral prominence, achilles tendon Lung, Pleura Pericardium Peritoneum Firm, non tender Adherent to periosteum , tendon, bursae Sign of increased disease activity Associated with infection, ulceration and gangrene

9. COMPLICATIONS Sjogren’s syndrome : 10% of RA patients Kerratoconjunctivitis sicca Xerostomia Pulmonary Pleuritic chest pain Friction rub Effusion- exudative Nodules Interstitial lung disease Symptoms: cough, SOB, Diagnosis:HRCT , Restrictive pattern in PFT Very poor prognosis Bronchiolitis bronchiectasis

10. Cardiac Pericarditis Cardiomyopathy Myocarditis CAD Amyloid infiltration Vasculitis Rare <1% Long standing disease RA positive Cutaneous signs Petechiae Purpura Digital infarcts Gangrene Livedo reticularis Painful ulcerations

11. Heamotological Anaemia Correlates well with increased CRP/ESR Increased platelets(APR) Thrombocytopaenia Felty’s Neutopenia Spleenomaegaly Nodular RA T-LGL with enlarged spleen and neutopenia Lymphoma: 2-4% incidence Most common- large B Cell lymphoma

12. Cardiovascular Common cause of death Atherosclerosis/CAD Higher in RA, even after risk factors CHF- 2 fold higher Osteoporosis 20-30% incidence Generalized bone lossimmobility Fracture hip common Treatmnert with cortisone Androgrenism Old aged male – decreased testosterone Post menospausal Note-increased testosterone levels offer protection from RA in younger males.

13. Epidemiology RA seen in 0.5 to 1% of population Varies based on geographical location 0.2-0.4% in africa / asia 7% in native americans tribes in america Female:male ratio 2-3:1 Incidence more in latin america Possible role of estrogens in its pathogenesisin enhancing immune response As this stimulates TNF-a a major cytokine in RA pathogenesis

14. Genetic considerations First degree relatives share RA 2-10 times Twins upto 60% Alleles in RA located in MHC 1/3 rd genetic risk rests in this locus In HLA-DRB1 gene Encodes the MHC-II B chain Groups of alleles collectively identified as Shared epitopes Include HLA-DR4(DRB1:0401, DRB1: 0101) Genetic susceptibilty in indians to RA with highest risk with DRB1 0405 DRB1 0401 DQB1:0302-DR4 haplotypes Certain HLA-DR alleles are protective for RA. Eg : DRB1:1502, DRB1: 0403

15. Environmental factors Cigarette smoking: risk increases 1.5-3.5 times, higher risk in twins Increased anti CCP antibodies in RA Recurrent insult to mucosa of airways leads to low grade inflammation activating innate immune system Infective: EB virus, parvovirus Women: 2-4 times higher risk Role of hormones, pregnancy

16. PATHOLOGY Synovium -primary site of inflammation Hypertrophied intima layer(seen as 10 cell layer) Increase in number of synoviocytes Microvascular injury/ thromvbosis of sub intimal region Neovascularization Hyperplasia and increased cellularity

17. Pannus Consists of edema of synovium Overgrowth Villious projections Protruding into joint cavity Cytokines TNF-a from macrophages of synovium Triggers inflammation cascade Inbalance between pro and anti inflammatory cytokines Chronic inflammatory synovitis RH Synovitis Variable number of B-cells Polyclonal increase in immunoglobulins Auto antibodies production Lymphoid aggregates coupled with CD4+Th1, Th17 and t-helper, memory cells

18. CLASSIFICATION OF RA

19. LAB INVESTIGATIONS ESR CRP Reversal of alb/globulin ratio Raised serum alkaline phosphartase Hepatic enzymes RBS Renal parameters RA factor Anti-CCP Imaging MRI : Periarticular osteopenia Narrowing of joint space Loss of cartilage of joint

20. TREATMENT OF RA Damage, disability seen during first few months to two years Delay of 3-4 years is disastrous Plan for early and aggressive treatment programme To combine medical, surgical and rehabilitative procedures.

21. Goals of Treatment To suppress joint inflammation To maintain joint function To prevent deformities To repair damage To relieve pain To improve function/mobility of joint

22. Basic principles Early diagnosis for better outcome Accurate objectified assessment of disease activity Aggressive treatment with disease modifying drugs As monotherapy or in combination Step-up, step-down, saw tooth strategy Methotrexate is the anchor drug which prevents damage to joints or any other complications Judicious use of corticosteroids is better

23. Methotrexate Initial choice of DMARD Indicated in RA with Synovitis Myositis Felty’s with leukopenia Evidence of increased disease activity A purine inhibitor and folic acid antagonist Clinical response in 4-8 weeks Start with 7.5 mg to 10mg weekly once and increment of 2.5-5mg every month to be followed Contraindicated in pregnancy, hepatic and renal impairment 1-2mg folic acid to reduce toxicity Side effects GI intolerance Stomatitis /Headache Rash/Alopecia BM suppresion with higher doses Cirrhosis of liver

24. OTHER DRUGS NSAIDS SULFASALAZINE HCQ Non selective Acetic acid deriviative Indomethican Etodolac Anthranilic acid Mefanemic acid Aryl propionic acid Ibuprofen Naproxen Ketoprofen Enolic acid Piroxicam Meloxicam Good in seronegative 500mg orally Weekly increments by 500mg upto 2-3 months Response in 6-10 weeks Avoid in sulpha allergy, G6PD defeciency High toxicity Nausea Frequent monitoring of CBP and LFT required Anti malarial used in RA, SLE 4-6mg/kg/daily Response in 4-8 weeks i.e 200-400mg once daily Safe in pregnancy

25. LEFLUNOMIDE TNF-A INHIBITORS INTERLEUKIN INHIBITORS Pyrimidine inhibitor Used in RA treatment 10-20 mg daily Response in 4-8 weeks Contraindicated in pregnancy and hepatic dysfunction GI side effects common Diarrhoea in 20% cases Loperamide or dose reduction Expensive Good in seronegative RA In those with poor response to DMARD’s Reduces joint damage Monoclonal antibodies with suffix MAB Fusion proteins with suffix CEPT Etenarcept – 50 mg/ week SC Infliximab - 3mg/kg initially at 2 month/ 6 th or 8 th weekly therafter , IV infusin with methotrexate Adalimumab - 40 mg SC every other week, specific to TNF-a Gulimumab -once a month Certolimab - pegylated humanized FAB fragment of TNF-a, monthly once Anakinra Recombinant IL-1 receptor antagonist Immunomodulation of IL-1, inhibits pro- inflammation 100mg SC daily Not for sepsis Tocilizumab IL-6 receptor antagonist IV infusion

26. CONTRAINDICATIONS Serious infections/Sepsis In active/latent tuberculosis CHF or LVEF<30% Those for elective surgery Local infection site reactions Common with SC administration Generally self limited Serious systemic effects rare Other side effects Lupin like illness Demylienating disorder Exacerbations of pre existing multiple sclerosis Lymphoma

27. Combine therapy DMARD’s with two biological agents Contraindicated in view of increased infective complications NSAID’s selective COX-2 inhibitors as adjunct to DMARD Glucocorticoids Not curative Delays erosions of joints Uses Patients with constitutional symptoms Weight ;loss Extra articular features Vasculitis Episcleritis Pleurisy Persistent synovitis Dose 5-20 mg daily – prednisolone If severe- 1mg/kg body weight

28. NON PHARMACOLOGICAL Acute care of inflamed joint Pain relief Joint protection Keep joint in proper position SplintinG if necessary Local heat application Subacute Passive and active joint movement Chronic Adaptive equipment Splints Orthoptics Mobility aids Specific exercises Overall cardiac conditioning

29. SURGICAL Synovectomy Total joint replacement Joint fusion

30. Thank you