Rheumatoid Arthritis

1. Rheumatoid Arthritis Dr. Kimme Hyrich Consultant Rheumatologist

2. Learning Objectives • Review the epidemiology and clinical presentation of RA • Appreciate the nature of the disease course and complications • Understand the basics of diagnosis • Review the basic pathophysiology behind joint manifestations • Briefly review current approach to treatment

3. Pre-talk Quiz - True or False • Rheumatoid arthritis is very rare with only 1 in 10000 people affected • Smoking may cause rheumatoid arthritis • Diet is important • Only 50% of patients with RA will be positive for RF • RA is characterised by an erosive arthritis • Most patients will have an excellent response to NSAIDs • The underlying cause of RA in thought to be infection • RA rarely affects the eyes • The most common cause of death in RA is infection • Patients with RA do not experience premature death

4. Epidemiology Of RA Worldwide disease, affects all ethnic groups Females > males 3:1 Age onset - peak 35-45 years Can effect children and the elderly Occurs in about 1% of adult population (UK/US)

17. MCP 90-95% PIP 65-90% Temporomandibular 20-30% What joints are commonly affected? Cervical spine 40-50% Shoulder 50-60% Elbow 40-50% Wrist 80-90% Hip 40-50% Knee 60-80% Ankle 50-80% MTP 50-90%

18. Rheumatoid Arthritis is an Erosive Arthritis

19. What is actually going on in the joint?

20. Established Rheumatoid Arthritis

24. The Aetiology of Rheumatoid Arthritis Remains Unknown

25. Environmental Trigger in Genetically Susceptible Person?

26. Genetic Risk Factors • Background risk: 1% • Children have 3x increased risk if parent affected • Siblings have 2-4x risk if sibling affected • Concordence in twins • Monozygotic 15% vs Dizygotic 4% • Strongest gene: HLA-DRB1

27. Gender • Females >> Males • Difference most apparent premenopausal • Pregnancy – no affect on incidence although first onset not uncommon in first 12 months postpartum • Studies of exogenous hormone therapy inconclusive

28. Lifestyle risk factors Smoking Obesity Diet?? Alcohol

29. Infection • Lots studied: EBV, parvovirus • No convincing evidence to support role of infection in aetiology of RA

30. Rheumatoid arthritis is a systemic disease

32. Nodule

34. Extra-articular Manifestations • Sicca syndrome • Pericarditis • Pleuritis/ Pulmonary Fibrosis • Ocular Inflammation • Neuropathies • Vasculitis

35. Rheumatoid Arthritis isa Clinical Diagnosis

36. 1987 Classification Criteria • Morning stiffness lasting at least one hour • Arthritis (swelling) of 3 or more joint areas • Arthritis (swelling) of hand joints • Symmetric arthritis • Subcutaneous nodules • Positive rheumatoid factor • Erosions on x-rays of hands and wrists To qualify as RA, need 4 of 7 for at least 6 weeks

37. 2010 Classification Criteria

38. Antibodies in Rheumatoid Arthritis • Rheumatoid factor (RF) • Anti-citrullinated protein antibody (ACPA) • Anti-CCP

39. Rheumatoid Factor • An autoantibody • Directed against Fc of other antibodies • Present in 50% of patients at presentation • Present in 60-80% of patients with chronic disease • Role in RA unknown but associated with more severe disease

40. Rheumatoid Factor • Not unique to RA • Other connective tissue diseases • Chronic infections e.g. TB, SBE • Chronic liver disease • Cryoglobulinaemia • Neoplasms • Old age • NOT A BLOOD TEST FOR RHEUMATOID ARTHRITIS

41. Anti-citrullinated protein antibody (ACPA) Peptidyl arginine deaminase (PAD)

42. ACPA • Anti-Cyclic Citrullinated peptide (anti-CCP) • Association with HLA-DRB1 and smoking • Limited evidence for direct pathogenic role • Diagnostic and prognostic marker • Sensitivity – 50% early, 75% established • Specificity – 98% • High overlap with RF

43. Other Blood Tests • Anaemia of chronic disease • Thrombocytosis • Increased ESR • Increased CRP • Increased ALP

44. Results: Pain Disability Loss of work Mortality

45. Mortality • RA can reduce life expectancy by 10 to 15 years • Mortality may approach 50% over 5 years in cases of severe disability • Patients with extra-articular involvement are twice as likely to die as those with joint involvement only • Co-morbidity and drug toxicity account for the majority of deaths

46. Mortality – All Cause 3 2 SMR 1 UK UK 0.8 Sweden Finland USA/ Canada

47. Cardiac Disease and RA • Increased risk of myocardial infarction Watson. J Rheum 2003 RR: 1.6 (95% CI 1.5-1.7) Solomon. Circulation 2003 RR: 2.0 (95% CI 1.23,3.29) female

48. Malignancy SIR Finland, 1978 5 5 5 5 Sweden, 1993 Denmark, 1996 3 3 3 3 Scotland, 2000 2 2 2 2 1 1 1 1 0.5 0.5 0.5 0.5 All cancers NHL Lung cancer Colorectal cancer

49. Psychosocial Impact • Depression affects up to 40% of patients and may impact compliance and reporting of symptoms • The divorce rate among people with RA is 70% higher than the national US average • Up to 50% of patients report changes in social roles; 75% decrease leisure activities

50. Goals of RA Treatment • No constitutional symptoms (fever, malaise) • Returning to a normal work schedule • Minimizing the impact on activities of daily living • Changing the course of disease progression (slowing or stopping the disease) • A multidisciplinary approach