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: %, the male:female ratio cca. 1:3. Typical case: woman aged years with polyarthritis and early joint deformities. RHEUMATOID ARTHRITIS (RA)

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

Cytokinek interakciói Cytokine interactions Cytokine interactions

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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

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

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.

Squeeze test

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)

RA early stage

Early assymmetric RA

PIP joint involvement in RA

RA: swan neck deformity

RA: ulnar deviation

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

RA: Boutonnière deformity

RA: arthritis mutilans

Involvement of joints of feet in RA

Severe destruction of ankles in RA

Periarticular osteoporosis (decalcification)

Erosions and sclerosis (in late stage)

Erosion in RA

Early erosions (MRI)

Scinti- graphy of the hands Scinti- graphy of the hands

Baker’s cyst

Bursitis in the shoulder

Bursitis and rheumatoid nodule

Rheumatoid nodules

Atlantoaxial subluxation Atlantoaxial subluxation

RA – end stage

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

Systemic manifestations of RA: pulmonary fibrosis Systemic manifestations of RA: pulmonary fibrosis

Interstitial pneumonitis in RA

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

Rheumatoid nodules in the lungs

Episcleritis in RA

Scleritis in RA

Scleromalacia perforans

Vasculitis in RA

Leg ulcers in Felty’s syndrome

Large granular lymphocytes in Felty’s syndrome

Disease modifying antirheumatic drugs (DMARD) Disease modifying antirheumatic drugs (DMARD) : DrugAdverse effectsDose gold (i.m.) dermatitis, stomatitis, 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, mg/day stomatitis Owing to low tolerability it is not used any more azathioprinehepatitis, bone marrow depression 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)

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

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:

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)

Child with advanced polyarticular JIA

Micrognathia in JIA

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

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

Involvement of DIP joint in SNSA

Asymmetric (MTP) arthritis in SNSA

Skin and nails in psoriasis Skin and nails in psoriasis

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