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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 andultimately 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.
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Endogenous factors Exogenous factorsMHC genes, hormon milieu) cross-reacting antigenes,
bacteria, viruses
Synovial vasculitis
Adhesion molecule expression cellular 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
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CytokinekinterakcióiCytokineinteractions
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Classification criteria of RA (ARA, 1987)
1. Morning stiffness – for at least 1 hr and present for atleast 6 weeks
2. Swelling of 3 or more joints for at least 6 weeks3. Swelling of wrist, metacarpophalangeal (MCP) or
proximal interphalangeal (PIP) joints for at least 6weeks
4. Symmetric joint swelling5. Typical radiologic changes in hands (erosions or
unequivocal bony decalcification)6. Rheumatoid nodules7. Serum rheumatoid factor (RF) positivity
Diagnosis is made by the presence of 4 or more criteria
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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 & Cinfection)- 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)
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Signs of early RA (=undifferentiated arthritis)
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.
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Squeeze test
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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)
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RA early stage
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Early assymmetric RA
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PIP joint involvement in RA
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RA: swan neck deformity
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RA: ulnar deviation
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Ulnar deviation in RA with severe atrophy of interossealmuscles
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RA: Boutonnière deformity
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RA: arthritis mutilans
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Involvement of joints of feet in RA
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Severe destruction of ankles in RA
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Periarticular osteoporosis (decalcification)
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Erosions and sclerosis (in late stage)
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Erosion in RA
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Early erosions (MRI)
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Scinti-graphy ofthe hands
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Baker’s cyst
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Bursitis in the shoulder
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Bursitis and rheumatoid nodule
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Rheumatoid nodules
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Atlantoaxialsubluxation
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RA – end stage
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Extraarticular manifestations of RA
• rheumatoid nodules – subcutaneous
- in internal organs (lung, aortic valve)
• pleuritis/pericarditis• fibrotizing alveolitis• Felty’s syndrome• vasculitis• amyloidosis
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Systemic manifestations ofRA:pulmonary fibrosis
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Interstitial pneumonitis in RA
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Systemic manifestations ofRA:Caplan’s syndrome
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Rheumatoid nodules in the lungs
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Episcleritis in RA
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Scleritis in RA
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Scleromalacia perforans
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Vasculitis in RA
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Vasculitis in RA
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Leg ulcers in Felty’s syndrome
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Large granular lymphocytes in Felty’s syndrome
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Disease modifying antirheumatic drugs (DMARD)Disease modifying antirheumatic drugs (DMARD): Drug Adverse effects Dosegold (i.m.) dermatitis, stomatitis, 25-50 mg /2-4
proteinuria, enterocolitis, weeksthrombocytopenia
gold (p.o.) less frequently used, brecause of lower tolerability
chloroquine (hydroxy- retinopathia, pigment- 250 mg/daychloroquine) anomalies
Regular ophthalmology check is requiredd-penicillamine proteinuria, myasthenia, 125-750 mg/day
stomatitisOwing to low tolerability it is not used any more
azathioprine hepatitis, bone marrow depression 50-150 mg/day
Scarcely given in RAmethotrexate hepatotoxicity, pulmonary fibrosis, 7,5-25 (MTX) bone marrow depression mg/week
most frequently used therapy
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sulfasalazine nausea, vomiting 1,5-2 g/daydiarrhea, bone marrow depression
cyclosporine A nephrotoxicity, tremor 1,5-4 mg/kg/daycreatinine and blood pressure should bechecked regularly
leflunomide hepatotoxicity, GI 10-20 mg/daycomplaints
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)
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Diseases related to RA:
1) Juvenile forms (= juvenile RA, juvenile idiopathicarthritis (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 arthritisc) Reiter’s disease - postinfectious arthritisd) Enteropathic arthritis
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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 arthritisc. Inflammatory bowel diseasesd. Neoplasms (e.g. leukaemia)e. Nonrhematic conditionsf. Hematologic diseasesg. Psychogenic arthralgiah. Other (sarcoidosis, hyperthrophic osteoarthropathy, villonodular synovitis, chronic aktive hepatitis, familial Mediterranean fever)
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Child with advanced polyarticular JIA
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Micrognathia in JIA
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Typical skin rash inStill’s disease
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Inflamed joints with diffuse edema in SNSA (‘sausage-like’ fingers)
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Involvement of DIP joint in SNSA
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Asymmetric (MTP) arthritis in SNSA
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Skin and nails in psoriasis
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Exanthema in the rare adult onset Still’s disease