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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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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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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Editor's Notes
Joint pain and stiffness of more than 6 weeks’ duration
