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RHEUMATOID ARTHRITIS (RA)

RHEUMATOID ARTHRITIS (RA). RHEUMATOID ARTHRITIS ( RA ) Gergely Péter dr. Definition: Chro ni c destru ctive diseases characterized by joint inflammation with pain and swelling. In a considerable proportion of patients, the arthritis is progressive, resulting in joint destruction and

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RHEUMATOID ARTHRITIS (RA)

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  1. RHEUMATOID ARTHRITIS (RA) RHEUMATOID ARTHRITIS (RA) Gergely Péter dr Definition: Chronic destructivediseases 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 %, themale:femaleratiocca. 1:3. Typical case: womanaged 30-40 years with polyarthritis and early joint deformities.

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

  3. Cytokineinteractions Cytokine interactions Cytokinek interakciói

  4. Picture

  5. Classification criteria of RA (ARA, 1987) • Morning stiffness – for at least 1 hr and present for atleast 6 weeks • Swelling of 3 or more joints for at least 6 weeks • Swelling of wrist, metacarpophalangeal (MCP) orproximal interphalangeal (PIP) joints for at least 6weeks • Symmetric joint swelling • Typical radiologic changes in hands (erosions orunequivocal bony decalcification) • Rheumatoid nodules • 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’sdisease) • Viral diseases (parvovirus B19 infection, rubella, hepatitis B &Cinfection) •  Bacterial infections (tbc, rheumatic fever, Jaccoud’s arthritis, septicendocarditis, mycoplasma arthritis) • Seronegative spondylarthritides(erosive psoriatic arthitis, reactivearthritis, 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 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 RA early stage

  11. Early assymmetric RA Early assymmetric RA

  12. PIP joint involvement in RA PIP joint involvement in RA

  13. RA: swan neck deformity RA: swan neck deformity

  14. RA: ulnar deviation RA: ulnar deviation

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

  16. RA: Boutonnière deformity RA: Boutonnière deformity

  17. RA: arthritis mutilans RA: arthritis mutilans

  18. Involvement of joints of feet in RA Involvement of joints of feet in RA

  19. Severe destruction of ankles in RA Severe destruction of ankles in RA

  20. Periarticular osteoporosis (decalcification) Periarticular osteoporosis (decalcification)

  21. Erosions and sclerosis (in late stage) Erosions and sclerosis (in late stage)

  22. Erosion in RA Erosion in RA

  23. Early erosions (MRI) Early erosions (MRI)

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

  25. Baker’s cyst Baker’s cyst

  26. Bursitis in the shoulder Bursitis in the shoulder

  27. Bursitis and rheumatoid nodule Bursitis and rheumatoid nodule

  28. Rheumatoid nodules Rheumatoid nodules

  29. Atlantoaxialsubluxation Atlantoaxial subluxation

  30. RA – end stage 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 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 Rheumatoid nodules in the lungs

  36. Episcleritis in RA Episcleritis in RA

  37. Scleritis in RA Scleritis in RA

  38. Scleromalacia perforans Scleromalacia perforans

  39. Vasculitis in RA Vasculitis in RA

  40. Vasculitis in RA Vasculitis in RA

  41. Leg ulcers in Felty’s syndrome Leg ulcers in Felty’s syndrome

  42. Large granular lymphocytes in Felty’s syndrome Large granular lymphocytes in Felty’s syndrome

  43. Disease modifying antirheumatic drugs (DMARD) Disease modifying antirheumatic drugs (DMARD): Drug Adverse effects Dose 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-penicillamine proteinuria, myasthenia, 125-750 mg/day stomatitis Owing to low tolerability it is not used any more azathioprine hepatitis, bone marrow depression 50-150 mg/day Scarcely given in RA methotrexatehepatotoxicity, pulmonary fibrosis, 7,5-25 (MTX) bone marrow depression mg/week most frequently used therapy

  44. sulfasalazine sulfasalazine nausea, vomiting 1,5-2 g/day diarrhea, bone marrow depression cyclosporine A nephrotoxicity, tremor 1,5-4 mg/kg/day creatinineand blood pressure should be checked regularly leflunomidehepatotoxicity, GI 10-20 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)

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

  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. Hematologicdiseases g. Psychogenic arthralgia h. Other (sarcoidosis, hyperthrophicosteoarthropathy, villonodular synovitis, chronic aktive hepatitis, familial Mediterraneanfever)

  47. Child with advanced polyarticular JIA Child with advanced polyarticular JIA

  48. Micrognathia in JIA Micrognathia in JIA

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

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

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