Rheumatoid Arthritis

Epidemiology

Rheumatoid arthritis affects 0.3% of the population worldwide, with no racial predilection

Women are affected 2-3 times as often as men (0.2-0.6% of men, 0.4-0.8 %of women)

Peak incidence is between 30 and 55 years old

Symptoms

Initial Presentation – joint stiffness (esp. in morning), joint pain, swelling, limitation of motion; also fatigue, depression

75% begin as polyarticular (60% small joints of hands and feet, 30% large joints, 10% both)
25% begin as monoarticular (50% knee, 50% shoulder, wrist, hip, ankle, or elbow)

Later Disease (within 1 yr of onset) – symmetrical polyarthritis of small joints of hands and feet caused by inflammation

pain, stiffness, limitation of motion
most commonly affected: metacarpophalangeal, proximal interphalangeal, wrist – almost never distal interphalangeal
prolonged disease can produce deformity (e.g., flexors become extensors) so that muscle contraction worsens disability
also palmer erythema, muscular atrophy, joint contractures, weight loss (these are more common with older patients)

Extra-articular manifestations:

direct sequella of joint disease – spinal cord compression due to C1-C2 subluxation

rheumatoid nodules – not diagnostic (can get nodules without disease or disease without nodules)

probably results from microvasculitis; removal does not cure (they tend to recur)
can occur on skin, eye (scleritis and scleromalacia), lung (pulmonary fibrosis)
composed of fibril necrosis center, histiocytes, inflammation on periphery

organ specific manifestations of RA (eg. pericarditis, also vasculitis leading to infarction)
caused by multisystem disorders known to occur with RA (eg. Sjorgen syndrome)

Felty’s syndrome – rheumatoid arthritis along with splenomegaly, lymphadenopathy, lympho/thrombocytopenia

Disease severity is highly variable

15-25% of patients have monocyclic or bicyclic course with prolonged remissions (may not be "true" rheumatic arthritis)
50-70% have intermittent polycyclic waxing and waning of symptoms
10-15% have persistent and progressive disease – no treatment really works for these patients

Outcome is generally poor, with shortened lifespan and 25% severely disabled after 25 years with the disease

worse outcome is associated with insidious rather than acute onset, eosinophilia, immune complexes, thrombocytosis, presence of extra-articular manifestations (especially rheumatoid nodules), perhaps also gender

Diagnosis

symptoms are so variable that there is no set of diagnostic symptoms

Classification criteria exist (e.g. by American Collage of Rheumatology) but these describe dozens of other diseases too

Rheumatic Factor – IgM antibody against IgG present in 33% of rheumatic arthritis patients at three months, 80% after 1year

other diseases also cause presence of Rheumatic Factor, so this test is neither sensitive nor specific

Diagnosis is made by exclusion of other diseases that cause arthritis (infections, drug-induced illness, metabolic, etc.)

Pathology and Etiology

Erosion of cartilage and bone is caused by proliferation of synovial cells, tendons, and bursae (almost like cancer in situ)

fluid phase acute inflammatory response (PMN’s)
tissue phase granulomatous response (activated macrophages, synoviocytes, lymphocytes)

But what causes the inflammation? – probably involves the immune system – immunological response to either:

(1) persistent exogenous antigen – virus or environmental substance absorbed into cartilage

lyme disease arthritis can develop into chronic rheumatoid arthritis long after spirochete is eliminated

(2) endogenous immunogen – type II collagen or an IgG (rheumatoid factor?) to which the patient has become sensitized

humoral and cellular immunity to type II collagen observed in rheumatoid arthritis – but is this cause or effect?

Genetic predisposition – increased prevalence among 1^st degree relatives and monozygotic over dizygotic twins

also increased prevalence among certain closed populations; there are variants unique to certain ethnic groups
one gene identified in MHC locus 9 linked with HLA-DR4

Hormonal factors – female predominance, remission during pregnancy, lower levels of testosterone in male patients

does estrogen therapy (oral contraceptives) reduce risk? – controversial – probably only in severe disease

Treatment

must prevent progression and minimize disability

Drugs–NSAIDs, glucocorticoids (very effective), slow acting anti-rheumatoid drugs (SAARDs), immunosuppressive agents

Physical therapy – application of heat or cold, exercises, splints/orthoses/devices, environmental modification

Surgery (total joint replacement, metatarsal head resection, selected arthrodeses) used only in advanced cases