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

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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

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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