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RHEUMATOID ARTHRITIS
Semmelweis University
3rd Department of Medicine
György Temesszentandrási MD
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
The progression of rheumatoid synovitis
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).
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
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
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, inter-
stitial 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)
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
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
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
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
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
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 IgG1 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)
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
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.
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
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
__________________________________________________
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
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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