RHEUMATOID ARTHRITIS. Semmelweis University 3rd Department of Medicine. György Temesszentandrási MD

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1 RHEUMATOID ARTHRITIS Semmelweis University 3rd Department of Medicine György Temesszentandrási MD

2 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting diarthrodial joints and frequently a variety of other organs. The hallmark of the disease is a chronic symmetric polyarthritis (synovitis) causing cartilage destruction, bone erosions and subsequent changes in joint integrity

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6 The progression of rheumatoid synovitis

7 Histology of rheumatoid synovitis. A. The characteristic features of rheumatoid inflammation with hyperplasia of the lining layer (arrow) and mononuclear infiltrates in the sublining layer (double arrow). B. A higher magnification of the largely CD4+ T cell infiltrate around postcapillary venules (arrow).

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9 Radiologic abnormalities 1.) Due to acute inflammation in the soft tissue: periarticular swelling, loss of definition of tissue planes, evidence of joint effusions. Juxtaarticular osteopenia within weeks of onset 2.) Due to articular and periarticular destruction (irreversible changes): erosion (=loss of cortical bone) at bare areas, diffuse joint space narrowing, joint subluxation and dislocation, bony ankylosis

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14 Classification of extraarticular features of RA I. Serositis, vasculitis, nodules (granulomata) II. Anemia, lymphadenopathy, (? Felty syndrome) III. Sicca syndrome, fibrosing alveolitis IV. Amyloidosis, osteopenia V. Drug-induced complications

15 Organ manifestations of extraarticular disease Skin rheumatoid nodules, vasculitis Heart pericarditis (tamponade,constriction), valvulitis coronaritis, arrhythmias, conduction disturb. Lung chronic pleuritis with or without effusion, interstitial pneumonitis and fibrosis, pulmonary HT, bronchiolitis oblit., BOOP, intrapulm. rheumatoid nodules with (Caplan sy) or without pneumoconiosis, cricoarytenoid joint involvement upper airway obstruction Neurologic mononeuritis, nerve entrapment, cervical instability and myelopathy Eye keratoconj. sicca, episcleritis, scleritis ( scleromalacia perforans ), retinal vasculitis Bone osteopenia (juxtaarticular and general)

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18 Laboratory findings Rheumatoid factors (RF): autoaantibodies to Fc portion of IgG in >80% of patients Anti-cyclic citrullinated protein/peptides antibodies: good diagnostic value (over 90% sensitivity and specificity) Other antibodies such as ANA (30 to 40%), ANCA (1/3) etc. may be present * Anemia (chronic, normochromic, normocytic) * Thrombocytosis due to chr. inflammation * Elevated erythrocyte sedimentation rate * Elevated acute phase reactants such as CRP * Synovial fluid analysis: PMNLs predominate

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20 Clinical course and mortality RA is known to result in considerable disability and increased mortality rate most patients experience persistent but fluctuating disease activity; within 10 years approx. 50% of patients become disabled median life expectancy is shortened by 3 to 7 years 2.5 fold increase in mortality rate mortality results from infections, systemic manifestations and GI bleeding or perforation

21 Management (general principles) therapy largely empirical, not curative, directed at nonspecific suppression of the inflammatory and immunologic processes requires interdisciplinary approach graded exercise programs to maintain full range of motion and muscle strength (overexertion is harmful) exercise and physiotherapy loosen the joint stiffness during acute attacks passive range of motion exercises by a physical therapist splinting can reduce unwanted motion of inflamed joints surgery later in the course

22 Medical management I NSAIDs (agents i.e. aspirin, diclofenac - blocking the COX enzymes prostaglandins, prostacyclin and thromboxanes ): exert nonspecific anti-inflammatory, analgesic and antipyretic effects with no true remission wide spectrum of toxic side-effects! DMARDs (disease-modifying antirheumatic drugs, i.e. methotrexate, leflunomide, antimalarials, sulfasalazin, d-penicillamine): exert nonspecific anti-inflammatory and analgesic effects benefit is delayed for weeks or months 2/3 of patients develop clinical improvement, but true remission is unusual improve serologic abnormalities:rf titer, ESR, CRP retarded the development of bone erosions

23 Medical management II Corticosteroids low dose (<7.5 mg prednisone) corticosteroids are used together with DMARDs also used in acut, rapidly progressive RA or in extraarticular manifestations, vasculitis and as an ultimate therapy in severe drug-refractory disease intraarticular corticosteroid injections in persisting inflammation of limited number of joints

24 Medical management III Biologic response modifiers Rapid onset of action (within days), slowing progression Etanercept: a fusion protein (TNF- receptor fused to the Fc portion of human IgG) Infliximab: a human/mouse monoclonal antibody against TNF- Adalimubab: a humanized IgG 1 anti-tnf- monoclonal ab Rituximab: decreases the B cell count and inhibits B cell functions Abatacept: CTLA4-Ig (blocks activation of autoreactive T cells by inhibiting B7/CD28 pathway)

25 Medical management IV Immunosuppressive therapy (azathioprine, cyclosporine, cyclophosphamide) reserved for patients failing therapies with DMARDs or for patients with extraarticular manifestations (i.e. rheumatoid vasculitis) Combinations MTX+cyclosporine A, MTX+SSA+hydroxychloroquine; MTX+infliximab, etc

26 Algorithm for the medical management of rheumatoid arthritis. Coxib, COX-2 inhibitors; DMARD, disease-modifying anti-rheumatic drug; CCP, cyclic citrullinated polypeptide; MTX, methotrexate; SSA, sulfasalazine; TNF, tumor necrosis factor.

27 Surgery arthroplasties, total joint replacements (hip, knee, shoulder) reconstructive hand surgery cosmetic and some functional benefit open or arthroscopic synoviectomy in persistent monarthritis (especially the knee) for symptom relief, but does not alter the natural history of the disease early tenosynoviectomy of the wrist to prevent tendon rupture

28 Diagnostic criteria for the classification of juvenile RA 1. Age of onset: less than 16 years 2. Arthritis of one or more joints defined as swelling or effusion, or the presence of 2 or more of the following signs: limitation of range of motion, tenderness or pain on motion, or fever 3. Duration of the disease: longer than 6 weeks 4. Type of disease onset during the first 6 months classified as: a) Polyarthritis: 5 or more joints b) Pauciarticular disease (oligoarthritis): <4 joints c) Systemic disease: arthritis with intermittent fever 5. Exclusion of other forms of juvenile arthritis

29 Juvenile rheumatoid arthritis (JRA) 12 to 25% of the RA population are persistently seronegative (RF-). The majority of cases of chronic arthritis beginning in childhood do not resemble adult RA Several subgroups exist: 1.) Arthritis of systemic onset or Still s disease: 20% * RF-, ANA- * fever, evanescent maculopapular, salmon-colored rash a with fever, lymphadenopathy, hepatosplenomegaly, polyserositis, leukocytosis, thrombocytosis, anemia * serum ferritin * self-limited course, chronic polyarthritis and joint deformities occur in only about 10% of patients

30 Juvenile rheumatoid arthritis (continued) 2.) Polyarticular (>5 joints involved) form: 40% *The majority of patients are seronegative, their prognosis is good, seropositive patients have a poor prognosis, their disease is similar to adult RA * Female preponderance in the seronegative form * The temporomandibular joint is often involved micrognathia, inanition, severe headaches 3.) Pauciarticular (<4 joints involved): 40%, 2 subgroups: a) early age of onset, female preponderance, ANA+ (70-75%), RF-, chr. iridocyclitis (ant. uveitis), which may progress to blindness, arthritis resolves without deformity b) strong male preponderance, later age of onset, HLA- B27+, the course is consistent with SPA Adult onset Still s disease: same features as Still s disease

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