Rheumatoid arthritis is the most common systemic inflammatory disease characterized by symmetrical joint involvement. Extraarticular involvement, including rheumatoid nodules, vasculitis, eye inflammation, neurologic dysfunction, cardiopulmonary disease, lymphadenopathy, and splenomegaly, can be manifestations of the disease.

1. RHEUMATOID ARTHRITIS
PATHOGENESIS AND THERAPY
Dr. S P Srinvas Nayak,
Assistant Professor, SUCP
Hyderabad

2. RHEUMATOID ARTHRITIS
• Rheumatoid arthritis is the most common
systemic inflammatory disease characterized
by symmetrical joint involvement.
• Extraarticular involvement, including
rheumatoid nodules, vasculitis, eye
inflammation, neurologic dysfunction,
cardiopulmonary disease, lymphadenopathy,
and splenomegaly, can be manifestations of
the disease.
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3. EPIDEMIOLOGY
Rheumatoid arthritis is estimated to have a
prevalence of 1% to 2%
• It can occur at any age.
• The disease is three times more common in
women. In people ages 15 to 45 years, women
predominate by a ratio of 6:1
• A majority of patients with rheumatoid
arthritis have HLA-DR4, HLADR1 antigens,
antigens on T-lymphocytes
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4. AETIOLOGY AND PATHOPHYSIOLOGY
• The cause of rheumatoid arthritis remains
unclear with hormonal, genetic and
environmental factors playing a key role.
• Rheumatoid arthritis is characterised by the
infiltration of a variety of inflammatory cells into
the joint.
• The synovial membrane, which is normally
acellular, becomes highly vascularised and
hypertrophied, creating a so-called pannus
formation
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5. INFLAMATORY CELLS
• The inflammatory cells involved in rheumatoid
arthritis include T-cells (predominantly CD4
helper cells), B-cells, macrophages and plasma
cells. Cytokines are released by these cells which
cause the synovium to release proteolytic
enzymes, resulting in the destruction of bone and
cartilage.
• Key cytokines involved in rheumatoid arthritis
include tumour necrosis factor (TNF)-α,
interleukin-1, interleukin- 6 and granulocyte
macrophage colony-stimulating factor (GM-CSF).
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11. CLINICAL PRESENTATIONS
Symptoms
■ Joint pain and stiffness of more than 6 weeks’ duration. May also
experience fatigue, weakness, low-grade fever, loss of appetite.
Muscle pain and afternoon fatigue may also be present. Joint
deformity is generally seen late in the disease.
Signs
■ Tenderness with warmth and swelling hands and feet. frequently
symmetrical. Rheumatoid nodules may also be present.
Laboratory Tests
■ Rheumatoid factor (RF) detectable in 60% to 70%.
■ Anticyclic citrullinated peptide (anti-CCP) antibodies have similar
sensitivity to RF (50% to 85%) but are more specific (90% to 95%)
and are present earlier in the disease.
■ Elevated erythrocyte sedimentation rate and C-reactive protein are
markers for inflammation.
■ Normocytic normochromic anemia is common as is thrombocytosis.
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13. EXTRA ARTICULAR INVOLVEMENT
• Rheumatoid Nodules
• Vasculitis
• Pulmonary Complications
• Ocular Manifestations
• Cardiac Involvement
• Felty’s Syndrome
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14. TREATMENT
NONPHARMACOLOGIC THERAPY
• Rest, occupational therapy, physical therapy, use
of assistive devices, weight reduction, and
surgery are the most useful types of
nonpharmacologic therapy used in patients with
rheumatoid arthritis.
• Rest is an essential component of a
nonpharmacologic treatment plan. It relieves
stress on inflamed joints and prevents further
joint destruction.
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15. PHARMACOTHERAPY
• There are four main categories of drugs
employed in the management of rheumatoid
arthritis:
• non-steroidal antiinflammatory drugs (NSAIDs)
including cyclo-oxygenase (COX)-2 inhibitors,
glucocorticoids, DMARDs and biological
therapies.
• (DMARD) should be started within the first 3
months of symptom onset.
• NSAIDs and/or corticosteroids may be used for
symptomatic relief if needed
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16. DMARDs
• All DMARDs inhibit the release or reduce the
activity of inflammatory cytokines, such as
TNF-α, interleukin-1, interleukin-2 and
interleukin-6.
• Activated T-lymphocytes have been implicated
in the inflammatory process, and these are
inhibited by methotrexate, leflunomide and
ciclosporin.
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17. Glucocorticoids
• Glucocorticoids can be given via the oral,
intramuscular or intraarticular routes. They act by
inhibiting cytokine release and give rapid relief of
symptoms and decrease inflammation.
• Prednisolone is the most commonly used oral
steroid.
• Intra-articular injections, such as triamcinolone or
methylprednisolone, are administered into
inflamed joints for local anti-inflammatory action,
pain relief and to reduce deformity.
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19. Biologic Agents
• Biologic agents are genetically engineered
protein molecules that block the
proinflammatory cytokines TNF-α (infliximab,
etanercept, adalimumab) and IL-1 (anakinra),
deplete peripheral B cells (rituximab), or bind to
CD80/86 on T-cells to prevent the costimulation
needed to fully activate T cells (abatacept).
• These drugs may be effective when other
DMARDs fail to achieve adequate responses but
are considerably more expensive to use.
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21. Rheumatoid arthritis and pregnancy
• The management of rheumatoid arthritis during
pregnancy is a common challenge, with disease activity
improving in approximately 70–80% of patients.
• Disease activity usually decreases in the first trimester,
and this lasts for a number of weeks to months into the
postpartum period. Subsequently, 90% of patients will
then experience a flare usually during the first 3
months.
• None of the available drug treatments for rheumatoid
arthritis are absolutely safe in pregnancy.
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22. THANK YOU
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