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.

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

CytokinekinterakcióiCytokineinteractions

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

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)

 

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.

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 interossealmuscles

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 ofthe hands

Baker’s cyst

Bursitis in the shoulder

Bursitis and rheumatoid nodule

Rheumatoid nodules

Atlantoaxialsubluxation

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 ofRA:pulmonary fibrosis

Interstitial pneumonitis in RA

Systemic manifestations ofRA:Caplan’s syndrome

Rheumatoid nodules in the lungs

Episcleritis in RA

Scleritis in RA

Scleromalacia perforans

Vasculitis in RA

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): 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

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) 

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

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)

Child with advanced polyarticular JIA

Micrognathia in JIA

Typical skin rash inStill’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

Exanthema in the rare adult onset Still’s disease