Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation of the joints. It affects around 1% of the global population and is three times more common in women than men. While the exact cause is unknown, genetic and environmental factors are believed to play a role. RA results in painful swelling of the joints, stiffness, and over time can cause permanent joint damage and deformity. Diagnosis involves physical exam, blood tests to check for inflammatory markers and autoantibodies, and x-rays. Treatment aims to reduce inflammation and prevent further joint damage through medications, exercise, and assistive devices. While there is no cure, early and aggressive treatment can help control symptoms and minimize disability.

1. RHEUMATOID
ARTHRITIS
Ashwini Somayaji
1ST M.Pharm
Pharmacology

2. INTRODUCTION
Rheumatoid arthritis (RA) is a chronic systemic
inflammatory disorder that may affect many
tissues and organs-skin, blood vessels, heart,
lungs and muscles. But principally attacks the
joints, producing a non-suppurative proliferative
and inflammatory synovitis that often progresses
to destruction of the articular cartilage and
ankylosis of the joints.
2

3. Rheumatoid arthritis affects approximately
1% of world population, with women
developing the condition three times more
than men.
Juvenile rheumatoid arthritis (JRA) causes
joint inflammation and stiffness for more
than six weeks in a child aged 16 or
younger.
Even though infectious agents such as
viruses, bacteria, and fungi have long been
suspected, the cause of rheumatoid
arthritis is unknown. 3

4. An example showing the differences
between a normal, healthy joint, a
joint affected by osteoarthritis, and one
affected by rheumatoid arthritis.
4

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6. 1. Initiating factor therapy:
An initiating factors causes joint
inflammation
It does not switch off after acute episode
2. Infectious theory:
Infection from diphtheroids & mycoplasms
or from the viruses – rubella, harpes zoster
3. Genetic predisposition:
Relative of people with RA are more prone
to develop the disease than rest of
population.
HYPOTHISED CAUSES
6

7. 7

8. •Highly variable
•Symmetric swelling of multiple joints with
tenderness and pain is characteristic
•>6 wk of pain, swelling, warmth in one or more
peripheral joints, frequently with symmetric joint
involvement involving wrists, hands, and/or feet,
and often associated with >1 hr of morning
stiffness.
Clinical Findings
Symptoms and Signs
8

9. •Characteristic deformities in hands with long-
standing uncontrolled disease, including
•‘swan neck’ deformity
•The boutonnière or ‘button hole’ deformity
•Z deformity of the thumb
•Dorsal subluxation of the ulna at the distal
radio-ulnar joint is common and may
contribute to rupture of the fourth and fifth
extensor tendons.
•Triggering of fingers may occur because of
nodules in the flexor tendon sheaths.
9

10. ‘Swan neck’ deformity of the fingers
10

11. ‘button hole’ deformity 11

12. Z- deformity of Thumb
12

13. Ulnar deviation of the fingers with wasting of the small muscles of
the hands and synovial swelling at the wrists, the extensor tendon
sheaths, the metacarpophalangeal and proximal interphalangeal
joints. 13

14. 1987 AMERICAN COLLEGE OF RHEUMATOLOGY
CRITERIA FOR RA
• Patients must have 4 of the 7 criteria:
1. Morning stiffness lasting at least 1 hour*
2. Swelling in three or more joints*
3. Swelling in hand joints*
4. Symmetric joint swelling*
5. Erosions or decalcification on x-ray of
hand
6. Rheumatoid nodules
7. Abnormal serum rheumatoid factor.
[*Must be present at least six weeks]
14

15. Progressive changes in joints
Stage I:
•Inflammation of the synovial membrane
spreads to articular cartilage & other soft
tissues.
•Limitation of joint movment with pain &
muscle spasm
15

16. •Granulation tissue formation within synovial
membrane & spread to periarticular tissue.
•Cartilage disintegration & joint filled with
granulation
•Thickening of joint capsule, tendon (with
sheaths) & impaired joint movt permanently.
Stage II:
16

17. •Granulation tissue converted into fibrous
tissue with adhesion formation between
tendon, joint capsule & articular surface.
•Articular surface cover partly by cartilage &
partly by fibrous tissue.
Stage III:
17

18. Permanent joint damage and deformity  disability
Stage IV:
18

19. EXTRA-ARTICULAR MANIFESTATIONS
Systemic
• Fever
• Weight loss
• Fatigue
• Susceptibility to infection
Musculoskeletal
• Muscle-wasting
• Tenosynovitis
• Bursitis
• Osteoporosis
Haematological
• Anaemia
• Thrombocytosis
• Eosinophilia
Lymphatic
• Felty’s syndrome
• Splenomegaly
Nodules
• Sinuses
• Fistulae
Ocular
• Episcleritis
• Scleritis
• Scleromalacia
• Keratoconjunctivitis
sicca
19

20. Rheumatoid nodules
20

21. PATHOPHYSIOLOGY
21

22. Immune deficiency of T-lymphocyte system which is triggered by some
internal and external factors
Leads to uncontrolled synthesis of antibodies (IgG) by B-lymphocytes
Plasmatic cells & lymphocytes of synovium percepts IgG as heterogenous
antigens & starts to produce rheumatoid factors against IgG
Immune complexes formation begins, this process stimulates different
reactions, activation of complement system which triggers immigration of
polymorphonuclear leukocytes to the synovial fluid
Macrophages (neutrophils) engulfs the immune complexes with further
release of lysosomal enzymes and other mediators of inflammation
This results to lesion of microcirculatory vessels and development of
inflammatory changes in synovium
Continuous inflammation stimulates synovial membrane proliferation with
formation of pannus, which is rambling on joint cartilage. The outer joint lesion
appear because of destruction of microcirculatory vessels of visceral organs by
immune complexes
PATHOGENESIS SCHEME
22

23. 23
Rheumatoid arthritis is
autoimmune disorder in which Immune system
identifies the synovial membrane as "foreign" and
begins attacking it.
With long-term or intensive exposure to the
antigen, normal antibodies become auto-
antibodies that target self-antigens in the
synovial membrane.
Once the antigen or immune complex reaches
the synovial membrane .The antigen presenting
cell deals with it.

24. 24
First, the APC usually a macrophage in
synovium engulfs the antigen.
Enzymes (peroxides) inside the APC break
down the antigen into smaller particles.
The processed antigens are transported to
the surface of the APC, where it binds with
MHC (major histocompatibility complex)
This complex (part of a foreign substance and
MHC) is now presented to T-cells (CD4 cells ie
T-helper cell ) or CD8 (cytotoxic T cells) which
the T-cell receptor (TCR) recognizes and binds
to.

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26. 26
Once the T-cell binds to the Antigen / MHC
complex, the APC then secrete cytokines like
 Interleukin-1 (IL-1)
 Interferon-alpha (IFN-a)
 Interferon-gamma (IFN-g)
 Tumor necrosis factor (TNF)
And other factors that activate lymphocytes and
other immune cells to respond to the antigens.

27. 27

28. DIAGNOSIS OF RA
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29. 29
How Is Rheumatoid Arthritis
Diagnosed?
•There is not a singular test to diagnose
rheumatoid arthritis.
• First, the patient will meet with a
rheumatologist who will perform a physical
and take a history of symptoms.
• The joints will be examined to determine if
there is inflammation and tenderness, and
the skin may be examined to look for
rheumatoid nodules.

30. 30
•The doctor may order
blood tests or X-rays to
help diagnose the
condition.
•Many other diseases
such as gout,
fibromyalgia, and lupus
may resemble rheumatoid
arthritis.
•So the doctor will rule out
these conditions before
making a diagnosis of RA

31. 31
RA Diagnostic Test: Citrulline Antibody
Test
Blood tests are usually run to help make a
diagnosis of rheumatoid arthritis.
These tests check for certain antibodies
including anti-cyclic citrullinated peptide
antibodies (ACPA), rheumatoid factor (RF),
and antinuclear antibodies (ANA), which are
present in a majority of RA patients.

32. 32
•Rheumatoid factor (RF) is present in about
75% to 80% of RA patients, and a high RF
may indicate a more aggressive for of the
disease.
•An advantage of anti-cyclic citrullinated
peptide antibody (ACPA) tests is that they can
often detect the disease earlier on, and the
sooner treatment begins the better patients
can manage the disease.
The presence of antinuclear antibodies
(ANA) is not a definitive diagnosis for RA, but
their presence can indicate to the doctor that
an autoimmune disorder may be present.

33. 33
RA Diagnostic Test: Sedimentation Rate
(Sed Rate)
Other blood tests that may be run can help the
doctor determine the extent of the inflammation
in the joints and elsewhere in the body.
The erythrocyte sedimentation rate (ESR, or
"sed rate") measures how quickly red blood
cells fall to the bottom of a test tube.
Usually, the higher the sed rate, the more
inflammation there is in the body.
Another blood test that measures inflammation
is the C-reactive protein (CRP) test. If the CRP
is high, inflammation levels are usually high as
well, such as during a flare

34. 34
RA Diagnostic Test: Joint X-rays
Another test used to diagnose rheumatoid
arthritis is X-ray.
Early in the disease X-rays are not as helpful
because they do not show soft tissue damage,
but they can be useful in later stages to monitor
how the disease progresses over time because
they show bone erosion.
Other imaging tests used may include bone
density scans (DXA or DEXA scans),
ultrasound, and magnetic resonance imaging
(MRI).

35. 35
A Diagnostic Test: Arthrocentesis
A joint aspiration procedure (arthrocentesis)
may be performed to obtain joint fluid to test
in the laboratory.
A sterile needle and syringe drain fluid from
the joint, which is then analyzed to detect
causes of joint swelling such as arthritis.
Removing this joint fluid can also help
relieve joint pain. In some cases, cortisone
may be injected into the joint during the
aspiration procedure for more immediate
pain relief.

36. MANAGEMENT OF RA
36

37. 37
•Focused on relieving pain
•Preventing damage/disability
•Patient education about the disease
•Physical Therapy for stretching and range
of motion exercises
•Occupational Therapy for splints and
adaptive devices
•Treatment should be started early and
should be individualised .
Goals of management

38. 38
How Is Rheumatoid Arthritis Treated?
Currently, there is no cure for rheumatoid
arthritis, but there are a number of
medications that can ease symptoms.
Most treatments are aimed at remission,
where the patient has few to no symptoms of
RA.
When treatment is started early on in the
disease process, this can help minimize or
slow damage to the joints and improve
quality of life for patients.

39. 39
Treatment usually involves a combination of
medication, exercise, rest, and protecting the
joints.
In some cases, surgery may be needed

40. 40
DRUGS USED
NSAIDs
IMMUNOSUPRESSIVES
CORTICOSTEROIDS
DMARDs
SYNTETIC
BIOLOGICAL

41. 41
•Some symptomatic relief
in RA - do not prevent
erosions or alter disease
progression.
•They are not appropriate
for monotherapy.
•Used in conjunction with
DMARDs.
•A large number of NSAIDs
are available; all appear
equivalent in terms of
efficacy
NSAIDs

42. 42
Examples of NSAIDs
include:
Aspirin
Indomethacin
Ibuprofen
Naproxen
Piroxicam
Nabumetone
Diclofenac
All NSAIDs should be taken
with meals to prevent
stomach upset.

43. 43
Are powerful medications that suppress the
body's immune system.
A number of immunosuppressive drugs are
used to treat rheumatoid arthritis.
They include :
Methotrexate
Azathioprine
Cyclophosphamide
Chlorambucil and
Cyclosporine
Immunosuppressive Medicines

44. 44
Because of potentially serious side effects,
immunosuppressive medicines (other than
methotrexate) are generally reserved for
those who have very aggressive disease or
those with serious complications of
rheumatoid inflammation, such as blood
vessel inflammation (vasculitis).
Methotrexate may be taken with or without
food.7.5 mg dose weekly.
Thinning of the bones due to osteoporosis
may be prevented by calcium and vitamin D
supplements.

45. 45
Corticosteroids
Medications can be given orally or injected
directly into tissues and joints.
They are more potent than NSAIDs in reducing
inflammation and in restoring joint mobility and
function.
Corticosteroids are useful for short periods
during severe flares of disease activity or when
the disease is not responding to NSAIDs.
However, corticosteroids can have serious
side effects, especially when given in high
doses for long periods of time .
Safe dose like Prenisolone is 5-10 mg daily.

46. 46
These side effects include weight gain,
facial puffiness, thinning of the skin and
bone, easy bruising, cataracts, risk of
infection, muscle wasting, and
destruction of large joints, such as the
hips.
Indications for systemic steroids are:-
1. For treatment of rheumatoid flares.
2. For extra-articular RA like rheumatoid
vasculitis and interstitial lung disease.
3. As bridge therapy for 6-8 weeks before
the action of DMARDs begin.
4. Maintainence dose of 10mg or less of
predinisolone daily in patients with active
RA.
5. Sometimes in pregnancy when other
DMARDs cannot be used.

47. 47
Disease Modifying Anti-rheumatic Agents
Drugs that actually alter the disease course .
Should be used as soon as diagnosis is made.
Appearance of benefit delayed for weeks to
months.
NSAIDS must be continued with them until true
remission is achieved .
Induction of true remission is unusual

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EXAMPLES:
METHOTREXATE;HYDROXYCHLOROQUINE
;SALFASALAZINE;LEFLUNAMIDE .
other DMARDS
GOLD;CYCLOSPORINE-A;
AZATHIOPRINE;CYCLOPHOSPHAMIDE;
CHLORAMBUCIL;
D-PENICILLAMINE;
MINOCYCLINE ,DOXYCYCLINE.

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50. 50
Biological DMARDs

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Other Treatments for Rheumatoid Arthritis
While there is no special diet people with
rheumatoid arthritis should follow, eating a
healthy, balanced diet is always recommended,
and some foods may help ease inflammation.
Omega-3 fatty acids found in fish oil may offer
anti-inflammatory benefits, so fish such as
herring, mackerel, trout, salmon, and tuna may
be a part of a healthy diet. If you choose to take
fish oil supplements, check with your doctor for
the proper dosage.
Extra fiber from fruits, vegetables, and whole
grains can result in a lower C-reactive protein
(CRP) in the blood. High levels of CRP indicate
inflammation.

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Many people with RA have low levels of the
mineral selenium.
This can be found in whole-grain wheat
products and shellfish. Consult your doctor
before taking selenium supplements for the
proper dosage as it can increase your risk for
developing diabetes.
Vitamin D may help lower the risk for RA in
women. Eggs, fortified breads and cereals, and
low-fat milk contain Vitamin D.
While some foods can ease inflammation,
others may trigger it. Fried foods, grilled meats,
margarine, egg yolks, and certain oils may
contribute to inflammation and should be eaten
in moderation or avoided if possible

53. 53
Why Are Rest and Exercise Important?
A balance of physical activity and rest periods
are important in managing rheumatoid arthritis.
Exercise more when your symptoms are
minimal, rest more when your symptoms are
worse.
Exercise helps maintain joint flexibility and
motion.
There are therapeutic exercises, such as
physical therapy that is prescribed, that can
help with strength, flexibility, and range of
motion of specific joints or body parts affected
by your RA.

54. 54
Many recreational activities such as walking
swimming are helpful because allow
movement with little to no impact on the joints.
Just as physical activity is important, so is rest.
When you have an RA flare and your
symptoms are worse, it is best to rest to help
reduce joint inflammation and pain, and to
cope with the fatigue that may accompany it.

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Is Surgery an Option for Rheumatoid
Arthritis?
In severe cases of rheumatoid arthritis,
surgery may be needed to reduce pain and
improve joint function.
Some surgeries include joint replacement,
fusion of joints (arthrodesis), tendon
reconstruction, and removal of inflamed
tissues (synovectomy).

56. REFERENCES
• PK Pispati. Manual of Rhrumatology
• Michael L Snaith. ABC of rheumatology;
London; BMJ publishing group; 1996
• Hillary chappel et al. management of early
rheumatoid arthritis. Scottish Intercollegiate
Guideline; 2000; 13-14
• 2012 Update of the 2008 American College of
Rheumatology Recommendations for the Use of
Disease-Modifying Antirheumatic Drugs and
Biologic Agents in the Treatment of Rheumatoid
Arthritis Arthritis Care & Research Vol. 64, No. 5,
May 2012, pp 625–639 DOI 10.1002/acr.21641 ©
2012, American College of Rheumatology
56

57. • Tripathi K D .Essentials of Medical
Pharmacology .Fifth edition;186-88
• Internet sources
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