Transcript RHEUMATOID ARTHRITIS (RA) Definition: Chronic destructive diseases characterized

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: 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
MHC genes, hormon milieu)
Exogenous factors
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-, osteoclastactivation
Pannus, cartilage destruction, bone resorption
Pathogenesis of RA
Cytokine
Cytokinek
interakciói
interactions
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
proximal interphalangeal (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)
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
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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
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)
Scintigraphy of
the hands
Baker’s cyst
Bursitis in the shoulder
Bursitis and rheumatoid nodule
Rheumatoid nodules
Atlantoaxial
subluxation
RA – end stage
Extraarticular manifestations of RA
• rheumatoid nodules
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pleuritis/pericarditis
fibrotizing alveolitis
Felty’s syndrome
vasculitis
amyloidosis
– subcutaneous
- in internal organs (lung,
aortic valve)
Systemic
manifestations of
RA:
pulmonary fibrosis
Interstitial pneumonitis in RA
Systemic
manifestations of
RA:
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):
Drug
gold (i.m.)
Adverse effects
Dose
dermatitis, stomatitis,
25-50 mg /2-4
proteinuria, enterocolitis,
weeks
thrombocytopenia
gold (p.o.)
less frequently used, brecause of lower
tolerability
chloroquine (hydroxy- retinopathia, pigment250 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
methotrexate
hepatotoxicity, pulmonary fibrosis, 7,5-25
(MTX)
bone marrow depression
mg/week
most frequently used therapy
sulfasalazine
cyclosporine A
leflunomide
TNF-a blockers:
(etanercept,
infliximab, and
abatacept)
nausea, vomiting
1,5-2 g/day
diarrhea, bone marrow depression
nephrotoxicity, tremor
1,5-4 mg/kg/day
creatinine and blood pressure should be
checked regularly
hepatotoxicity, GI
10-20 mg/day
complaints
local reaction, autoimmune disease (SLE, SM)
infection (tbc)
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 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
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
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