rhumatoid arthritis def,symptoms,diagnosis,ttt.

1. Rheumatoid arthritis
Dr. Reda Elbastwesy

2. Rheumatoid Arthritis
 Def
• Chronic inflammatory disease that affects the joints, characterized by
progressive destruction of symmetric joints.
 Risk factors
• Genetics
• Infection
• Smoking
• All these factors lead to mutation in structure of synovial membrane and
morphological change in the joint.

3. Morphological changes in joint
• Hyperplasia in synovial membrane (Pannus)
• Bone resorption
• Cartilage damage
• Edema in joint

4. Pathophysiology
• APC recognize cetrullinated protein in structure of synovial membrane and starts to attack it
and exposing it on its surface
• APC activate both T cells and B cells
• B cells differentiate into plasma cells which produce 2 types of Ab one is Rf which is an IGm
that form immune complex. The other is ACPA which is IGg
• T cells activate macrophage which secret various cytokines like Interleukine 1,6 and TNF
• These cytokines activate synoviocytes to proliferate to form Pannus
• FLS responsible for activation of osteoclasts for bone resorption and produce protease which
digest cartilage

6. Symptoms & Complications
 RA is a chronic disease marked by symptoms of inflammation and pain in joints.
 These symptoms and signs occur during periods:
• Flares (Sudden worsening),
• Remission (when symptoms disappear completely).
 Joint symptoms
• Symmetrical.
• Multiple joints ≥ 5.
• Pain, swelling, redness & warmth.
• Stiffness mainly at morning (after inactivity

7. Commonly affected joints
 Small joints
• Metacarpophalangeal joints (MCP),
• Proximal Interphalangeal (PIP),
• Metatarsophalangeal joints (MTP).
 As disease worsens..
Shoulders, elbows, knees, ankles.

8. SIGNS, SYMPTOMS & Complications
Specific deformities
• Ulnar deviation.
• Boutonniere deformity.
• Swan neck deformity.

9. Extra-articular problems
Whole body
• Low grade fever, muscle aches, poor appetite; weight loss, malaise.
Organ specific
• Rheumatoid nodules (Skin, lung, heart, sclera).
• Increased risk of atherosclerosis ,Heart attack, stroke.
• Ocular Keratoconjunctivitis sicca , cataract & scleritis .
• Liver ↑ hepcidin (↓ serum iron).
• Anemia.
• Blood vessels; Vasculitis.

10. Extra-articular problems
• Felty syndrome (triad):
RA
Splenomegaly Life-threatening infections
Neutropenia
• Carpal tunnel syndrome.
• Interstitial lung fibrosis, Pleural effusion (rare)
Progressive shortness of breath.

11. rheumatoid arthritis and osteoarthritis
Like RA, people with osteoarthritis (OA) can experience painful and stiff joints that make moving around difficult.

12. Diagnosis
• Rheumatoid arthritis can be difficult to diagnose in its early stages because the
early signs and symptoms mimic those of many other diseases.
• There is no one blood test or physical finding to confirm the diagnosis .
• During the physical exam, your doctor will check your joints for swelling, redness
and warmth. He or she may also check your reflexes and muscle strength

13. Blood tests
• elevated ESR or C-reactive protein (CRP), which may indicate the presence of an
inflammatory process in the body.
• Also look for Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies
• The anti-CCP Ab is more specific for RA than the RF test

15. Imaging tests
 X-rays & ultrasound to help track the progression of rheumatoid arthritis in joints over time.
 MRI and ultrasound tests can help your doctor judge the severity of the disease in your body

16. Treatment
• The main treatment goals with rheumatoid arthritis are to control inflammation, relieve pain,
and reduce disability associated with RA..
• In the treatment of rheumatoid arthritis, many factors come into play. Factors include severity
of disease and disability, the location of the joint injury, comorbidities, patient preferences
(including cost and frequency of monitoring).
• either monotherapy or a combination of therapies.
DRUGS
SURGERY
PHYSICAL
THEARPY

17. Drugs for Rheumatoid
Arthritis
NSAIDS Streoids DMARDS Biologics

18. NSAIDS
• These medications reduce pain and inflammation but do not slow down RA
• EX-ibuprofen and naproxen
• Long term use risk of :
 heart attack and stroke
 raise blood pressure
 stomach irritation, ulcers, and bleeding.

19. Steroids
• Ease the pain and stiffness of affected joints
• Used temporarily to calm a symptom flare
• Some people need to take steroids for a longer time to control pain and inflammation
• Shot directly into an inflamed joint or take them as a pill .
Side effects of long-term steroid
 High blood pressure, osteoporosis, and diabetes.
Ex: Prednisone

20. DMARDs
• Slow the progression of rheumatoid arthritis and save the joints and other tissues
from permanent damage.
• Slow-acting and can take several weeks to work
• IMMUNOSUPRESSION [ anti TNF-α ]
Traditional DMARDs
• Methotrexate (Trexall)
• Leflunomide (Arava)
• Hydroxychloroquine (Plaquenil)
• Sulfasalazine (Azulfidine).

21. bwm
 Methotrexate
 mainly as chemotherapy for cancer treatment
• the most commonly used as an initial treatment.
• Folic acid antagonist
• Given once a week
Side effect : Hepatotoxicity- Bone marrow depression- Anemia
 Hydroxychloroquine & Sulfasalazine
• mild rheumatoid arthritis
• Suppression of T lymphocyte cells
Side effect: Neutropenia, hemolytic anemia and Thrombocytopenia

22. Comparison between NSAIDs & DMARDs
• Slow onset of action used in
chronic cases when deformity or
damage is exciting
• Arrest progression of the disease
• Prevent formation of new
deformity
• Rapid onset of action used in
acute cases to relief
inflammation & pain
• No effect
• Can not stop formation of new
deformity
NSAIDSDMARDs

23. Biologic DMARDs
• Came to market in the early 1990s and are usually prescribed after
evidence of disease progression and structural joint damage despite
treatment with steroids and conventional therapy.
• Genetically engineered protein (monoclonal antibodies) molecules that
work by blocking specific inflammatory pathways made by immune cells.
• Very selective in their mechanism of action.
• They are administered either intravenously or subcutaneously.

24. Biologic DMARDs
Classification of biologic disease modifiers
 TNF-α blocking agents (Etanercept, Infliximab, Rituximab)
 T-cell modulating drug ( Abatacept )
 B-cell cytotoxic agent ( Rituximab )
 Anti-IL-6 agents (Tocilizumab)
 Anti-IL-8 agents (Anakinra)
 Janus kinase inhibitors (JAK Inhibitors)
(tyrosine kinase essential for signaling of cytokines ) E.g. (Tofacitinib).

25. Biological DMARDs
Precautions
- Risk of infection.
- Recent malignancies: lymphoproliferative cancer.
- Congestive heart failure.
- Demyelinating disease: multiple sclerosis.
- Avoid vaccination with live vaccines.

26. Prosorba (Column Apheresis Therapy)
Blood passed through apparatus (plasma filtering device)
contain sand like coated with a special material called
protein A binds to IgG and circulating immune complexes
in plasma.
The procedure takes approximately 2.5 hours one a week for 12weeks.
Patients with active disease should be monitored every 3 months, and
treatment should be adjusted if there is no improvement at 6 months.

27. Biological DMARDs
RecommendationsDisease activity
Administer DMARD monotherapy in patient with
low-high disease activity.
If disease activity remains moderate /high despite
DMARD monotherapy, use combination DMARDs or
a TNF inhibitor or a non-TNF biologic.
Early RA < 6 months
If disease activity remains moderate or high despite
DMARD monotherapy, ACR guidelines recommend
one of the following:
- Combination DMARDs,
- Add an anti-TNF biologic,
- Non-TNF biologic or
- Tofacitinib.
Established RA =6 months