Rheumatoid arthritis is a chronic inflammatory disease that affects about 0.8-2.1% of the population. It is characterized by symmetric inflammation of joints that can lead to joint damage over time. While the exact cause is unknown, genetics and autoimmunity are thought to play a role. Treatment involves medications like NSAIDs for symptom relief and DMARDs like methotrexate to slow disease progression. Left untreated, rheumatoid arthritis can cause pain, deformities, and loss of function in joints as well as increase the risk of other health issues.

1. Rheumatoid
arthritis
DR. D. ANANDADURAI M.D (GEN MED)

2. Rheumatoid Arthritis (RA):
Epidemiology
 Prevalence of - 0.8% to 2.1% of the population
 Gender predilection ratio – Women: Men – 3:1
 About 40-60% have severe disease – 3 fold 
mortality
 Median life expectancy is shortened by 3 to 7 years
 Onset mostly between ages of 35 – 60 years
 Genetic – HLA-DR1 – Class II HCA
 Exact etiology is not known

3. Features
 Chronic inflammatory disease of unknown etiology
marked by a symmetric, peripheral polyarthritis
 Systemic disease
 Cigarette smoking is associated with increased risk

4. Pathophysiology
 Not completely elucidated!
 Autoimmune
Trigger Synovial cell
hyperplasia and endothelial cell
activation  uncontrolled
inflammation  bone destruction
 Genetics

8. Synovial PANNUS

9. How dose RA affect all
these organ systems ?
By causing…
1. Synovitis
2. Serositis
3. Nodules
4. Vasculitis
5. Autoantibodies

10. Rheumatoid Arthritis: Key
Features
• Symptoms >6 weeks’ duration
• Often lasts the remainder of the patient’s life
• Inflammatory synovitis
• Palpable synovial swelling
• Morning stiffness >1 hour, fatigue
• Symmetrical and polyarticular (>3 joints)
• Typically involves wrists, MCP, and PIP joints
• Typically spares certain joints
Thoracolumbar spine, Sacroiliac
DIPs of the fingers and IPs of the toes

11. Rheumatoid Arthritis: Key Features (cont’d)
• Rheumatoid nodules: subcutaneous or periosteal at
pressure points (elbow)
• Rheumatoid factor
• 45% positive in first 6 months
• 85% positive with established disease
• Not specific for RA, high titer early is a bad sign
• Marginal erosions and joint space narrowing on x-ray

12. Rheumatoid
arthritis

13. Osteoarthritis

14. RA Vs. OA
Features Rheumatoid Arthritis Osteoarthritis
Age of onset Can happen at any age Usually later in life
Speed of onset Rapid- weeks to months Slow- over years
Distribution Symmetrical polyarthritis Initially asymmetrical
monoarthritis polyarthritis
Joints affected Small joints of hands and
feet
Weight bearing joints- knees,
hips
Duration of morning
stiffness
Stiffness worse in the
morning >1hour
Stiffness <1hour and worse at
the end of the day (after
activity)
Systemic symptoms Fatigue, fever, night sweats -

15. Pathology

16. Radiology
Bony erosions and joint space narrowing

17. Deformities
 Ulnar drift
 Wrist subluxation
 Swan-neck deformity
 Boutonniere deformity
 Z deformity
 Flat feet
 Trigger finger

20. Rheumatoid Arthritis: PIP Swelling
 Swelling is confined to the area of the joint capsule

21. Rheumatoid Arthritis:
Ulnar Deviation and MCP Swelling
 Prominent ulnar deviation in the right hand
 MCP and PIP swelling in both hands
 Synovitis of left wrist

23. Cockup toes
 Feet are involved 90% / MTP’s
 ( Although patients get Hallux valgus – the 1st MTP is spared in RA)

24. Rheumatoid nodule
•These are small subcutaneous nodules
present at the extensor surfaces of hand,
wrist, elbow and back in rheumatoid
arthritis patients.
•Characteristics feature of rheumatoid
arthritis
•A marker of disease activity

25. Nodules

26. Systemic
Disease

27.  Constitutional symptoms ( most common)
 Rheumatoid nodules(30%)
 Hematological-
 normocytic normochromic anemia
 leucocytosis /leucopenia
 thrombocytosis
 Felty’s syndrome-
 Chronic nodular Rheumatoid Arthritis
 Splenomegaly
 Neutropenia
Extraarticular Involvement

28.  Respiratory- pleural effusion, pneumonitis , pleuro-
pulmonary nodules, ILD
 CVS-asymptomatic pericarditis , pericardial effusion,
cardiomyopathy
 Rheumatoid vasculitis- mononeuritis multiplex,
cutaneous ulceration, digital gangrene, visceral
infarction
 CNS- peripheral neuropathy, cord-compression from
atlantoaxial/midcervical spine subluxation,
entrapment neuropathies
 EYE- kerato-conjunctivitis sicca, episcleritis, scleritis

29. RA Systemic disease—Sicca
syndrome – dry eye and mouth
 Major cause of
Secondary
Sjogren’s
disease

30. Scleromalacia- thinning of
sclera
Blue choroid coming through thinned sclera

31. Rheumatoid lung - most serious visceral
organ affected by Rheumatoid arthritis
**LUNG
 Most common small
bilateral pleural effusions
 Cause of lung fibrosis
 Pulmonary vasculitis
 Caplan’s syndrome
Rheumatoid nodules

32. Caplan’s syndrome
 First reported in coal
miners (Pneumoconiosis)
with RA
 RA nodules

33. Neurologic
Entrapment Carpal tunnel
Wrist Synovitis in RA
C1 C2 subluxation synovial
involvement of the ligament
over the odontoid

34. Rheumatoid vasculitis
 Digital infarcts
warning sign of small
vessel vasculitis in RA or
impending digital
gangrene
 Small vessel Vasculitis
Result in Lung
hemorrhage or GI
bleeding

35. ACR-
EULAR
criteria

36. Clinical Course of RA
Type 1 = Self-limited—5% to 20%
Type 2 = Minimally progressive—5% to 20%
Type 3 = Progressive—60% to 90%
0
1
2
3
4
0 0.5 1 2 3 4 6 8 16
Type 1
Type 2
Type 3
Years
Severity
of
Arthritis

37. Rheumatoid Arthritis: Typical Course
• Damage occurs early in most patients
• 50% show joint space narrowing or erosions in
the first 2 years
• By 10 years, 50% of young working patients are
disabled
• Death comes early
• Multiple causes
• Compared to general population
Women lose 10 years, men lose 4 years

38. Critical Elements of a Treatment
Plan: Assessment
• Assess current activity
• Morning stiffness, synovitis, ESR
• Document the degree of damage
• Restriction of movt and deformities
• Joint space narrowing and erosions on x-ray
• Document extra-articular manifestations
• Nodules, pulmonary fibrosis, vasculitis

39. Diagnosis
 Blood investigation
 X-Ray of involved joints
 CT/MRI scans
 Direct arthroscopy
 Synovial/Fluid aspirate
 Synovial membrane biopsy
 Arthrocentesis
No single test is specific to Rheumatoid Arthritis

40. Inflammatory Markers: ESR and
CRPTest
ESR rates for men: 0-15mm/hr
ESR rates for women: 0-20mm/hr
The level of CRP in the blood is normally low
Increasing amount
suggests inflammation

41. Antibody Tests:
Rheumatoid Factor and Anti CCP Ab
Other blood tests check for the presence of antibodies
that are not normally present in the human body

42. Rheumatoid Factor (RF)
 IgM antibodies Fc portion of IgG
 Positive in 5% of normal persons and in only 70-80% of RA /
negative in 30% cases of RA – Sero negative RA
 85% of patients with RA over the first 2 years become RF+
• A negative RF may be repeated 4-6 monthly for the first two year of
disease, since some patients may take 18-24 months to become
seropositive.
• PROGNOSTIC VALUE- Patients with high titres of RF, in general,
tend to have POOR PROGNOSIS, MORE EXTRA ARTICULAR
MANIFESTATION.

43. Causes of positive test for RF
 Rheumatoid arthritis
 Sjogrens syndrome
 Vasculitis such as polyarteritis nodosa
 Sarcoidosis
 Systemic lupus erythematosus
 Cryoglobulinemia
 Chronic liver disease
 Infections- tuberculosis , bacterial endocarditis,
infectious mononucleosis, leprosy, syphilis, leishmaniasis.
 Malignancies
 Old age(5% women aged above 60)

44. Anti-CCP
Anti Cyclic Citrulinated Peptide Ab
IgG against synovial membrane
peptides damaged via inflammation
Sensitivity (65%) & Specificity (95%)
Both diagnostic & prognostic value
Predictive of Erosive Disease
Disease severity
Radiologic progression
Poor functional outcomes

45. Acute Phase Reactants
Positive acute phase reactants () Negative acute phase reactants ()
Mild elevations
– Ceruloplasmin
– Complement C3 & C4
Moderate elevations
– Haptoglobulin
– Fibrinogen (ESR)
– 1 – acid glycoprotein
– 1 – proteinase inhibitor
Marked elevations
– C-reactive protein (CRP)
– Serum amyloid A protein
– Albumin
– Transferrin

46. Other Lab Abnormalities
Elevated APRs( ESR, CRP )
Thrombocytosis
Leukocytosis
ANA
30-40%
Inflammatory synovial fluid
Hypoalbuminemia

47. Direct arthroscopy
Benefits
•Minimally invasive
•Less tissue damage
•Fewer complications
•Reduced pain
•Quicker recovery time
•Outpatient basis

48. Synovial/Fluid aspirate
Synovial membrane biopsy
Arthrocentesis
Athrocentesis: synovial fluid is aspirated and analysed for inflammatory components
Abnormal synovial fluid: cloudy, milky, or dark yellow containing leukocytes

49. X-Ray
X-rays are an important diagnostic test for monitoring the disease progression
Patients may reveal NO changes on an X-ray in the early stages

50. Arthography
A radiopaque substance or air is injected
into the joint, which outlines soft tissue
structures surrounding the joint

51. CT/MRI scans
MRI is particularly sensitive for the early and subtle features of RA
(Radiopaedia, 2010; Dat et al., 2010)
Used for better visualization of soft tissue
Can detect changes of Rheumatoid Arthritis prior to an X-Ray

52. Management
Medical
management
 NSAIDs
 Glucocorticoids
 Conventional DMARDs
 Biologics (Biologic
Response Modifiers)
Surgical
management
 Arthroplasty

53. RA: Drug Treatment Options
• NSAIDs
• Symptomatic relief, improved function
• No change in disease progression
• Low-dose prednisone (10 mg OD)
• Used as bridge therapy, For extra-articular RA like
rheumatoid vasculitis and interstitial lung disease
• If used long term, consider prophylactic treatment
for osteoporosis
• Intra-articular steroids
• Useful for flares

54. NSAIDS
Non-Steroidal anti-inflammatories (NSAIDS) / Coxibs for symptom control
1) Reduce pain and swelling by inhibiting COX
2) Do not alter course of the disease.
3) Chronic use should be minimised.
4) Most common side effect related to GI tract.

55. DMARDs
Conventional
 Methotrexate
 Sulfasalazine
 Leflunomide
 Hydroxychloroquine
Biological
 TNF- inhibitors
infliximab,
etanercept,
adalimumab,
golimumab and
certolizumab
 Anakinra
 Abatacept
 Rituximab
 Tocilizumab

56. DMARDs
Commonly used Less commonly used
Methotrexate Chloroquine
Hydroxychloroquine Gold(parenteral & oral)
Sulphasalazine Cyclosporine A
Leflunomide D-penicillamine/bucillamine
Minocycline/Doxycycline
Levamisole
Azathioprine,cyclophosphami

57. 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/Steroids must be continued with them
until true remission is achieved .
 Induction of true remission is unusual .

58. Clinical information about DMARDs
NAME DOSE SIDE EFFECTS MONITORING ONSET OF
ACTION
1) Hydroxycloro
quine
200mg twice
daily x 3 months,
then once daily
Skin
pigmentation ,
retinopathy
,nausea,
psychosis,
myopathy
Fundoscopy &
perimetry yearly
2-4 months
2) Methotrexate 7.5-25 mg once a
week orally
GI upset,
hepatotoxicity,
Bone marrow
suppression,
Pulmonary
fibrosis
Blood counts,LFT
6-8 weekly,Chest
x-ray annually,
urea/creatinine 3
monthly;
Liver biopsy
1-2 months

59. Clinical information about DMARDs contd..
NAME DOSE SIDE EFFECTS MONITORING ONSET OF
ACTION
3)Sulphasalazine 2gm daily p.o Rash,
myelosuppressio
n, may reduce
sperm count
Blood counts ,LFT
6-8 weekly
1-2 months
4)Leflunomide Loading 100 mg
daily x 3 days,
then 10-20 mg
daily p.o
Nausea,diarrhoe
a,alopecia,
hepatotoxicity
LFT 6-8 weekly 1-2 months

60. Methotrexate
 First used in 1947 for childhood leukaemia
 Probably the most effective DMARD
 Convenient ONCE weekly dosing
 Faster onset of action (6 weeks to 3 months)
(compared to other DMARDs)
 Mode of action - unclear!!
 Dose – 7.5 mg per week
 Remember – Folic acid

62. Side Effects of MTX
 Nausea, stomatitis
 Haematological toxicity
 Hepatic toxicity
LFTs, cirrhosis, hepatic fibrosis
 Pulmonary toxicity
Pneumonitis, Fibrosis
 Teratogenic (ova and sperm)

63. Limitations of conventional DMARDs
1) The onset of action takes several months.
2) The remission induced in many cases is partial.
3) There may be substantial toxicity which
requires careful monitoring.
4) DMARDs have a tendency to lose effectiveness
with time-(slip out).
 These drawbacks have made researchers look
for alternative treatment strategies for RA- The
Biologic Response Modifiers.

64. Immunosuppresive therapy
Agent Usual dose/route Side effects
Azathioprine 50-150 mg orally GI side effects ,
myelosuppression, infection,
Cyclosporin A 3-5 mg/kg/day Nephrotoxic , hypertension ,
hyperkalemia
Cyclophosphamide
(used in Vasculitis)
50 -150 mg orally Myelosuppression , gonadal
toxicity ,hemorrhagic cystitis ,
bladder cancer
.
.

66. Agent Usual dose/route Side effects Contraindications
Infliximab
(Anti-TNF)
3 mg/kg i.v infusion at
wks 0,2 and 6 followed
by maintainence dosing
every 8 wks
Has to be combined
with MTX.
Infusion reactions,
increased risk of
infection, reactivation
of TB ,etc
Active infections,
uncontrolled DM,
surgery(with hold for 2 wks
post op)
Etanercept
(Anti-TNF)
Active infections,
uncontrolled DM,
surgery(with hold for 2 wks
post op)
Adalimumab
(Anti-TNF)
40 mg s/c every 2
wks(fornightly)
May be given with MTX
or as monotherapy
Same as that of
infliximab
Active infections
.
25 mg s/c twice a wk
May be given with MTX
or as monotherapy.
Injection site
reaction,URTI ,
reactivation of
TB,development of
ANA,exacerbation
of demyelenating
disease.

67. Abatacept
(CTLA-4-IgG1
Fusion protien)
Co-stimulation
inhibitor
10 mg/ kg body wt.
At 0, 2 , 4 wks &
then 4wkly
Infections, infusion
reactions
Active infection
TB
Concomittant with other
anti-TNF-α
Rituximab
(Anti CD20)
1000 mg iv at
0, 2, 24 wks
Infusion reactions
Infections
Same as above
Tocilizumab
( Anti IL-6)
4-8 mg/kg
8 mg/kg iv monthly
Infections, infusion
reactions,dyslipidemia
Active infections
Agent Usual
dose/route
Side effects
.
Anakinra 100 mg s/c once
daily
May be given with
MTX or as
monotherapy.
Injection site
pain,infections,
neutropenia
Active infections
Contraindications
(Anti-IL-1)

68. Biologics: Relative
Contraindications
 Active Hepatitis B Infection
 Multiple sclerosis, optic neuritis
 Active serious infections
 Chronic or recurrent infections
 Current neoplasia
 History of TB or evidence of Koch’s
 Congestive heart failure (Class III or IV)

69. These targeted therapies have
changed the course of RA…
 No deformities
 No synovectomies
 No splinting
 No small vessel vasculitis
 Resolution of nodules
 Less RA lung
 Less Mortality from CVD
 Decreased incidence of
Non Hodgkin’s
Lymphoma

70. 2012 ACR Update

71. Recent developments
Emergence of
methotrexate as the
DMARD of choice for
early disease
1
Development of
novel highly
efficacious
biologicals
2
Proven superiority of
combination DMARD
regimens over
methotrexate alone
3

72. How to measure Rheumatoid Arthritis?
28 Joint Count

73. DAS (28) Score
Swollen and Tender Joint Count
ESR
Global health assessment by patient
DAS28 =
0.56 x sqrt(tender28) + 0.28 x
sqrt(swollen28) + 0.70 x ln(ESR) +
0.014 x GH

74. DAS in Practice
“An objective method for measuring
disease activity”
>5.1 = Active disease
<3.2 = low disease activity
<2.6 = Remission

75. Surgical Approaches
 Synovectomy is ordinarily not recommended for patients
with rheumatoid arthritis, primarily because relief is only
transient.
However, an exception is synovectomy of the wrist, which is
recommended if intense synovitis is persistent despite medical
treatment over 6 to 12 months. Persistent synovitis involving the
dorsal compartments of the wrist can lead to extensor tendon
sheath rupture resulting in severe disability of hand function.
 Total joint arthroplasties , particularly of the knee, hip,
wrist, and elbow, are highly successful.
 Other operations include release of nerve entrapments
(e.g., carpal tunnel syndrome), arthroscopic procedures,
and, occasionally, removal of a symptomatic rheumatoid
nodule.

76. Thank you!