Rheumatoid Arthritis is a chronic autoimmune disease that causes inflammation of the joints and surrounding tissues. It is characterized by symmetric polyarticular joint involvement and can also affect other body systems. Early, aggressive treatment is important to slow disease progression and prevent joint damage. Treatment involves medications like DMARDs and biologics to reduce inflammation and slow joint destruction, with the goal of achieving remission and preserving joint function.

1. Rheumatoid Arthritis
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2. Introduction
• RA is an autoimmune disorder that causes inflammation
of the lining of the joints. The body tissue is mistakenly
attacked by its own immune system.
• RA may also affect the skin, eyes, lungs, heart, blood, or
nerves.
• Rheumatoid arthritis is a chronic disorder
– early, aggressive treatment is key to slowing or stopping its
progression
• Characterized by polyarticular symmetric joint
involvement and systemic manifestations
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3. • Rheumatoid arthritis is a chronic, progressive
autoimmune disorder. In response to an
unknown trigger, the body makes antibodies
that attack its own tissues. The self-attacks
mostly affect the joints, although they can also
affect other body parts.
• Disease attacks, called flare-ups, occur
periodically, or can be continuous in some
people.
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4. • What is it?
– Chronic: long-term disease, no cure
– Inflammatory: causes swelling of joints
– Auto-immune: body recognizes self as foreign
substance
– Systemic: can affect other organs
– Symmetrical: affects opposite joints equally
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5. Epidemiology
– Affects 1% of U.S. population
 2 million people
– 70% of patients are women
– Men are more severely affected
– Onset between 30 and 50 years old
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6. Pathophysiology
• RA results from a dysregulation of the immune system.
• The pathogenesis of RA is driven by T lymphocytes, but
the initial catalyst causing this response is unknown.
• Most patients produce antibodies called rheumatoid
factors.
• These seropositive pts tend to have a more aggressive
course than pts who are seronegative.
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7. • The characteristics of a synovium affected by RA are:
1. The presence of a thickened, inflamed membrane
lining called pannus
2. The development of new blood vessels
3. An influx of inflammatory cells in the synovial
fluid, majorly T lymphocytes.
• The components of most significance are T
lymphocytes, cytokines, and B lymphocytes.
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8. • Chronic inflammation of the synovial tissue lining the
joint capsule results in tissue proliferation (pannus
formation)
• Pannus invades cartilage and eventually the bone
surface, producing erosions of bone and cartilage and
leading to joint destruction.
• These may lead to loss of joint space, loss of joint
motion, bony fusion (ankylosis) and chronic deformity.
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9. Clinical Presentation
• Nonspecific: fatigue, weakness, low-grade fever,
loss of appetite and joint pain.
• Stiffness and myalgias may precede
development of synovitis.
• Joint involvement tends to be symmetric and
affect the small joints of the hands, wrists, and
feet; elbows, shoulders, hips, knees & ankles.
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10. • Joint stiffness typically is worse in the
morning, > 30 minutes, and may persist all day
• Joint swelling may be visible or may be
apparent only by palpation.
• The tissue feels soft and spongy and may
appear erythematous and warm
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11. • Chronic joint deformities: subluxations of the
wrists, metacarpophalangeal (MCP) joints,
and proximal interphalangeal (PIP) joints
Swan-neck deformity
Boutonniere deformity
Ulnar deviation
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13. Extra-articular involvement:
• Rheumatoid Nodules
• Vasculitis
• Pulmonary
• Ocular
• Cardiac
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18. Diagnosis
1. Morning stiffness
2. Arthritis of three or more joint areas
3. Arthritis of hand joints
4. Symmetric arthritis
5. Rheumatoid nodules
6. Serum rheumatoid factor
7. Radiographic changes
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19. Laboratory:
• Elevated erythrocyte sedimentation rate (ESR)
• Positive rheumatoid factor (most pts)
• Positive antinuclear antibodies (ANA)
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20. Synovial fluid:
• Turbidity, leukocytosis, reduced viscosity, and
normal or low glucose relative to serum
concentrations.
Radiologic findings:
• Soft tissue swelling and osteoporosis near the
joint (periarticular osteoporosis).
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21. Desired Outcome
• To induce a complete remission, although this is
seldom achieved.
• The primary objectives are to:
Reduce joint swelling, stiffness, and pain
Preserve range of motion & joint function
Improve quality of life
Prevent systemic complications; and
Slow destructive joint changes
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22. Treatment
Non-Pharmacologic Therapy
• Adequate rest, weight reduction if obese, occupational
therapy, physical therapy, and use of assistive devices may
improve symptoms and help maintain joint function.
• Surgical procedures such as tendon repair, and joint
replacements.
• Patient education about the disease and the benefits and
limitations of drug therapy
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23. Pharmacologic Therapy
General Approach
• A disease-modifying antirheumatic drug (DMARD)
should generally be started within the first 3 mths of
symptom onset.
• Early use of DMARDs results in a more favorable
outcome and can reduce mortality.
• First-line DMARDs include methotrexate,
hydroxychloroquine, sulfasalazine, and leflunomide.
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24. • Hydroxychloroquine or sulfasalazine may be
used initially in mild disease,
• But methotrexate is often chosen initially in more
severe cases because of superior outcomes than
other DMARDs and lower cost than biologic
agents.
• Leflunomide appears to have long-term efficacy
similar to methotrexate.
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25. • Biologic agents with disease-modifying
activity include the anti-TNF agents
(etanercept, infliximab, adalimumab) and the
interleukin-1 receptor antagonist anakinra.
• Biologic agents are effective for pts who fail
treatment with other DMARDs.
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26. • DMARDs that are less frequently used include
– Azathioprine, penicillamine, minocycline,
cyclosporine, and cyclophosphamide.
• These agents have either less efficacy or high
toxicity, or both.
• Combination therapy with two or more
DMARDs may be effective when single-
DMARD treatment is unsuccessful.
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27. Combinations therapies:
1. Methotrexate plus hydroxychloroquine,
2. Methotrexate plus leflunomide, or
3. Methotrexate plus sulfasalazine or
4. Triple DMARDs (sulfasalazine,
hydroxychloroquine, and methotrexate)
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28. • NSAIDs and/or corticosteroids may be used
for symptomatic relief if needed.
• They provide relatively rapid improvement
compared with DMARDs, which may take wks
to months before benefit is seen.
• However, NSAIDs have no impact on disease
progression, and corticosteroids have the
potential for long-term complications.
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29. NSAIDs
• Possess both analgesic and anti-inflammatory
properties and reduce stiffness but do not slow
disease progression or prevent bony erosions or joint
deformity.
• They should seldom be used as monotherapy for
rheumatoid arthritis.
• COX-2 selective NSAIDs have a better GI safety profile
and similar efficacy as conventional NSAIDs.
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30. Methotrexate
• MTX inhibits cytokine production and purine
biosynthesis, which may be responsible for its
anti-inflammatory properties.
• Its onset is relatively rapid (as early as 2 to 3 wks)
• Toxicities are GI, hematologic, pulmonary, and
hepatic.
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31. • Concomitant folic acid may reduce some
adverse effects without loss of efficacy.
• AST or ALT should be monitored periodically
• MTX is teratogenic, and pts should use
contraception and discontinue the drug if
conception is planned
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32. Leflunomide
• Leflunomide inhibits pyrimidine synthesis,
which reduces lymphocyte proliferation and
modulation of inflammation.
• Its efficacy for RA is similar to that of MTX.
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33. • The drug may cause liver toxicity and is
contraindicated in pts with preexisting liver dx.
• The ALT should be monitored monthly initially
and periodically thereafter.
• It is teratogenic:- avoid during pregnancy.
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34. Hydroxychloroquine
• lacks the myelosuppressive, hepatic, and renal
toxicities seen with some other DMARDs, which
simplifies monitoring.
• Its onset may be delayed for up to 6 wks, but the
drug should not be considered therapeutic
failure until after 6 mths of therapy with no
response.
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35. • Short-term toxicities include GI, ocular,
dermatologic, and neurologic effects.
• Periodic ophthalmologic examinations are
necessary for early detection of reversible
retinal toxicity.
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36. Sulfasalazine
• Sulfasalazine use is often limited by adverse effects.
• Antirheumatic effects should be seen in 1-2 mths.
• Adverse effects include GI, dermatologic, hematologic,
and hepatic effects
• GI symptoms may be minimized by starting with low
doses, dividing the dose more evenly throughout the
day, and taking the drug with food.
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37. Azathioprine
• Azathioprine is a purine analog that is converted
to 6-mercaptopurine and is thought to interfere
with DNA and RNA synthesis
• Antirheumatic effects may be seen in 3 - 4 wks.
• It should be discontinued if no response is
observed after 12 wks at maximal doses.
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38. • Its major adverse effects are bone marrow
suppression, stomatitis, GI intolerance,
infections, drug fever, hepatotoxicity, and
oncogenic potential.
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39. Ethiopia STG 2010
Drug Treatment
First line
• Aspirin, 600-1200mg P.O. TID,
Alternatives
• Ibuprofen, 400-800 mg P.O. TID
OR
• Indomethacin, 25-50 mg P.O. TID
OR
• Indomethacin, 100 mg rectal at night, as part of the total
daily dose of NSAID, may be needed in some pts for severe
nocturnal pain.
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40. For non-responders
A. DMARD:
• After 4- 6 wks, monitor toxicity
• Chloroquine phosphate, 150-300 mg P.O. as base QD
Alternatives
• Methotrexate, 7.5 mg P.O. weekly,
N.B. Pts on methotrexate should be placed on
supplementary folic acid, P.O. 5 mg QD
• OR Azathioprine, 50-100 mg P.O QD
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41. B. Oral Corticosteroids
• Prednisone, 30-40 mg/day P.O. for 1-2 wks with
rapid tappering to minimize side effects.
• Use for longer duration at doses of 5-7.5mg/day.
OR
C. Intra-articular Corticosteroids
• Methylprednisolone acetate, 20-80 mg intra-
articular depending on the joint
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