1. RHEUMATOID ARTHRITIS (RA) Gergely Péter dr RHEUMATOID ARTHRITIS (RA) Gergely Péter dr Definition: Chronic destructive diseases characterized by joint inflammation with pain and swelling. In a considerable proportion of patients, the arthritis is progressive, resulting in joint destruction and ultimately incapacitation and increased mortality. Relatively common, prevalence: 0.3-1.5 %, the male:female ratio cca. 1:3. Typical case: woman aged 30-40 years with polyarthritis and early joint deformities. RHEUMATOID ARTHRITIS (RA)

2. Endogenous factorsExogenous factors MHC genes, hormon milieu)cross-reacting antigenes, bacteria, viruses Synovial vasculitis Adhesion molecule expressioncellular infiltration Macrophages, T cells, B cells, granulocytes Cytokines (TNF- , IL-1, IL-6), RF, free-radicals, enzymes Synovial proliferation, angiogenesis, chondrocyte-, osteoclast- activation Pannus, cartilage destruction, bone resorption Pathogenesis of RA

3. Cytokinek interakciói Cytokine interactions Cytokine interactions

4. Picture

5. Classification criteria of RA (ARA, 1987) 1.Morning stiffness – for at least 1 hr and present for at least 6 weeks 2.Swelling of 3 or more joints for at least 6 weeks 3.Swelling of wrist, metacarpophalangeal (MCP) or proximalinterphalangeal (PIP) joints for at least 6 weeks 4.Symmetric joint swelling 5.Typical radiologic changes in hands (erosions or unequivocal bony decalcification) 6.Rheumatoid nodules 7.Serum rheumatoid factor (RF) positivity Diagnosis is made by the presence of 4 or more criteria

6. Differential diagnosis of polyarthritis RA should be differentiated from: - Other autoimmune diseases (SLE, primary Sjögren’s syndrome, MCTD, PM/DM, PSS, PAN, gian cell vasculitis, polymyalgia rheumatica, adult onset Still’s disease) - Viral diseases (parvovirus B19 infection, rubella, hepatitis B & C infection) - Bacterial infections (tbc, rheumatic fever, Jaccoud’s arthritis, septic endocarditis, mycoplasma arthritis) - Seronegative spondylarthritides (erosive psoriatic arthitis, reactive arthritis, enteropathic arthritis) - Paraneoplastic arthritis - Other diseases (e.g. hyperthrophic osteoarthropathy, erythema nodosum, agammaglobulinemia, acromegaly, diabetes mellitus) - Other rheumatic diseases (chronic gout, inflamed erosive osteoarthritis) Differential diagnosis of polyarthritis

7. Signs of early RA (=undifferentiated arthritis) In the early stage (within the first 3-6 months) (ARA) classification criteria cannot be used. The patient should be referred to a rheumatologist, if the patient has 3 or more swollen joints the metacarpophalangeal (MCP) and/or metatarsophalangeal (MTP) joints are involved; the squeeze test is positive morning stiffness is 30 min or more.

8. Squeeze test

9. Joint involvement in RA The most specific sign of RA is arthritis. It is progressive and deforming in the majority (2/3) of cases (= erosive polyarthritis)

10. RA early stage

11. Early assymmetric RA

12. PIP joint involvement in RA

13. RA: swan neck deformity

14. RA: ulnar deviation

15. Ulnar deviation in RA with severe atrophy of interosseal muscles Ulnar deviation in RA with severe atrophy of interosseal muscles

16. RA: Boutonnière deformity

17. RA: arthritis mutilans

18. Involvement of joints of feet in RA

19. Severe destruction of ankles in RA

20. Periarticular osteoporosis (decalcification)

21. Erosions and sclerosis (in late stage)

22. Erosion in RA

23. Early erosions (MRI)

24. Scinti- graphy of the hands Scinti- graphy of the hands

25. Baker’s cyst

26. Bursitis in the shoulder

27. Bursitis and rheumatoid nodule

28. Rheumatoid nodules

29. Atlantoaxial subluxation Atlantoaxial subluxation

30. RA – end stage

31. Extraarticular manifestations of RA rheumatoid nodules – subcutaneous - in internal organs (lung, aortic valve) pleuritis/pericarditis fibrotizing alveolitis Felty’s syndrome vasculitis amyloidosis

32. Systemic manifestations of RA: pulmonary fibrosis Systemic manifestations of RA: pulmonary fibrosis

33. Interstitial pneumonitis in RA

34. Systemic manifestations of RA: Caplan’s syndrome Systemic manifestations of RA: Caplan’s syndrome

35. Rheumatoid nodules in the lungs

36. Episcleritis in RA

37. Scleritis in RA

38. Scleromalacia perforans

39. Vasculitis in RA

41. Leg ulcers in Felty’s syndrome

42. Large granular lymphocytes in Felty’s syndrome

43. Disease modifying antirheumatic drugs (DMARD) Disease modifying antirheumatic drugs (DMARD) : DrugAdverse effectsDose gold (i.m.) dermatitis, stomatitis, 25-50 mg /2-4 proteinuria, enterocolitis, weeks thrombocytopenia gold (p.o.)less frequently used, brecause of lower tolerability chloroquine (hydroxy-retinopathia, pigment-250 mg/day chloroquine)anomalies Regular ophthalmology check is required d-penicillamineproteinuria, myasthenia, 125-750 mg/day stomatitis Owing to low tolerability it is not used any more azathioprinehepatitis, bone marrow depression50-150 mg/day Scarcely given in RA methotrexatehepatotoxicity, pulmonary fibrosis, 7,5-25 (MTX)bone marrow depressionmg/week most frequently used therapy Disease modifying antirheumatic drugs (DMARD)

44. sulfasalazinenausea, vomiting1,5-2 g/day diarrhea, bone marrow depression cyclosporine Anephrotoxicity, tremor1,5-4 mg/kg/day creatinine and blood pressure should be checked regularly leflunomidehepatotoxicity, GI10-20 mg/day complaints TNF-  blockers: local reaction, autoimmune disease (SLE, SM) (etanercept, infection (tbc) infliximab, and abatacept) etanercept: 25 mg 2x weekly s.c. infliximab: 3 mg/kg every 8 week i.v. Other: anakinra (IL-1 blocker) rituximab (anti-CD20 antibody) abatacept (T cell activation blocker antibody) sulfasalazine

45. Diseases related to RA: 1)Juvenile forms (= juvenile RA, juvenile idiopathic arthritis (JIA) Subgroups: a)systemic (Still’s disease) b)pauciarticular (<4 joints) c)polyarticular (similar to adult RA) 2) Seronegative (RF negative) forms (seronegative spondarthropathies = SNSA) a)Ankylosing spondylarthritis (Mo Bechterew) b)Psoriatic arthritis c)Reiter’s disease - postinfectious arthritis d)Enteropathic arthritis Diseases related to RA:

46. Classification criteria of JIA (ARA, 1982) 1. Persistent arthritis of at least 6 weeks duration in one or more joints 2. Exclusion of other causes of arthritis (in particular): a. other systemic autoimmune diseses (SLE, rheumatic fevers, vasculitis, PSS, SS, MCTD, Behçet’s syndrome, PM/DM, SPA, Reiter’s syndroma, psoriatic arthritis) b. Infectious arthritis c. Inflammatory bowel diseases d. Neoplasms (e.g. leukaemia) e. Nonrhematic conditions f. Hematologic diseases g. Psychogenic arthralgia h. Other (sarcoidosis, hyperthrophic osteoarthropathy, villonodular synovitis, chronic aktive hepatitis, familial Mediterranean fever)

47. Child with advanced polyarticular JIA

48. Micrognathia in JIA

49. Typical skin rash in Still’s disease Typical skin rash in Still’s disease

50. Inflamed joints with diffuse edema in SNSA (‘sausage-like’ fingers)

51. Involvement of DIP joint in SNSA

52. Asymmetric (MTP) arthritis in SNSA

53. Skin and nails in psoriasis Skin and nails in psoriasis

54. Exanthema in the rare adult onset Still’s disease Exanthema in the rare adult onset Still’s disease