2. INTRODUCTION
A chronic inflammatory disease
Unknown aetiology
Symmetrical polyarthritis
Chronic inflammation resulting in joint damage
and physical disability
Systemic involvement is common
Fatigue/Anemia
3. Extra Articular features
Sub cutaneous nodules(on knuckles)
Pleural nodules
Pericarditis
Peripheral neuropathy
Vasculitis
Kerato conjunctivitis sicca
Episcleritis
Xerostomia
4. CLINICAL FEATURES
Age : 25 to 55 years
Sex : Female predominance
Early morning joint stiffness lasts for half to one
hour, gets eased with activity
Earliest joints involved :
Small joints of hand and feet
Usually monoarticular
Oligoarticular
Polyarticular
Usually symmetrical
Results in inflammation of joints tendons and
bursae
5. Frequently involved joints
MCP
DIP
PIP
Flexor tendon synovitis(Hallmark of RA)
Decreased ROM
Decreased grip strength
Trigger finger
Irreversible deformities with destruction of joints and
soft tissue
6. Ulnar deviation
Subluxation of MCP joints
Subluxation of proximal phalynx
Subluxation of volar side
Z line deformity
Piano key movement
Flat feet(Pes Plano valgus)
Main target of RA are 14 joint groups
PIP
MCP
Wrist
Elbow
Knees
Ankle
MTP
Does not affect thoracic, lumbar spine and rarely temporo-
mandibular joint.
7. Constitutional
Loss of body weight
Malaise
Fever
Fatigue
Cachexia
Depression
Temperature >101*F
8. Nodules
30-40%
Benign subcutaneous nodules
Common sites
Forearm, sacral prominence, achilles tendon
Lung, Pleura
Pericardium
Peritoneum
Firm, non tender
Adherent to periosteum, tendon, bursae
Sign of increased disease activity
Associated with infection, ulceration and gangrene
11. Heamotological
Anaemia
Correlates well with increased CRP/ESR
Increased platelets(APR)
Thrombocytopaenia
Felty’s
Neutopenia
Spleenomaegaly
Nodular RA
T-LGL with enlarged spleen and neutopenia
Lymphoma: 2-4% incidence
Most common- large B Cell lymphoma
12. Cardiovascular
Common cause of death
Atherosclerosis/CAD
Higher in RA, even after risk factors
CHF- 2 fold higher
Osteoporosis
20-30% incidence
Generalized bone lossimmobility
Fracture hip common
Treatmnert with cortisone
Androgrenism
Old aged male – decreased testosterone
Post menospausal
Note-increased testosterone levels offer protection from RA in
younger males.
13. Epidemiology
RA seen in 0.5 to 1% of population
Varies based on geographical location
0.2-0.4% in africa/asia
7% in native americans tribes in america
Female:male ratio 2-3:1
Incidence more in latin america
Possible role of estrogens in its pathogenesisin
enhancing immune response
As this stimulates TNF-a a major cytokine in RA
pathogenesis
14. Genetic considerations
First degree relatives share RA 2-10 times
Twins upto 60%
Alleles in RA located in MHC
1/3rd genetic risk rests in this locus
In HLA-DRB1 gene
Encodes the MHC-II B chain
Groups of alleles collectively identified as Shared
epitopes
Include HLA-DR4(DRB1:0401, DRB1: 0101)
Genetic susceptibilty in indians to RA with highest risk
with DRB1 0405 DRB1 0401
DQB1:0302-DR4 haplotypes
Certain HLA-DR alleles are protective for RA. Eg:
DRB1:1502, DRB1: 0403
15. Environmental factors
Cigarette smoking: risk increases 1.5-3.5 times,
higher risk in twins
Increased anti CCP antibodies in RA
Recurrent insult to mucosa of airways leads to low
grade inflammation activating innate immune system
Infective: EB virus, parvovirus
Women: 2-4 times higher risk
Role of hormones, pregnancy
16. PATHOLOGY
Synovium-primary site of inflammation
Hypertrophied intima layer(seen as 10 cell layer)
Increase in number of synoviocytes
Microvascular injury/thromvbosis of sub intimal
region
Neovascularization
Hyperplasia and increased cellularity
17. Pannus
Consists of edema of synovium
Overgrowth
Villious projections
Protruding into joint cavity
Cytokines
TNF-a from macrophages of synovium
Triggers inflammation cascade
Inbalance between pro and anti inflammatory cytokines
Chronic inflammatory synovitis
RH Synovitis
Variable number of B-cells
Polyclonal increase in immunoglobulins
Auto antibodies production
Lymphoid aggregates coupled with CD4+Th1, Th17 and t-helper,
memory cells
19. LAB INVESTIGATIONS
• ESR
• CRP
• Reversal of alb/globulin ratio
• Raised serum alkaline phosphartase
• Hepatic enzymes
• RBS
• Renal parameters
• RA factor
• Anti-CCP
• Imaging
• MRI : Periarticular osteopenia
• Narrowing of joint space
• Loss of cartilage of joint
20. TREATMENT OF RA
Damage, disability seen during first few months to
two years
Delay of 3-4 years is disastrous
Plan for early and aggressive treatment
programme
To combine medical, surgical and rehabilitative
procedures.
21. Goals of Treatment
To suppress joint inflammation
To maintain joint function
To prevent deformities
To repair damage
To relieve pain
To improve function/mobility of joint
22. Basic principles
Early diagnosis for better outcome
Accurate objectified assessment of disease
activity
Aggressive treatment with disease modifying
drugs
As monotherapy or in combination
Step-up, step-down, saw tooth strategy
Methotrexate is the anchor drug which prevents
damage to joints or any other complications
Judicious use of corticosteroids is better
23. Methotrexate
Initial choice of DMARD
Indicated in RA with
Synovitis
Myositis
Felty’s with leukopenia
Evidence of increased disease activity
A purine inhibitor and folic acid antagonist
Clinical response in 4-8 weeks
Start with 7.5 mg to 10mg weekly once and increment of 2.5-5mg every month to
be followed
Contraindicated in pregnancy, hepatic and renal impairment
1-2mg folic acid to reduce toxicity
Side effects
GI intolerance
Stomatitis/Headache
Rash/Alopecia
BM suppresion with higher doses
Cirrhosis of liver
24. OTHER DRUGS
NSAIDS SULFASALAZINE HCQ
•Non selective
•Acetic acid deriviative
•Indomethican
•Etodolac
•Anthranilic acid
•Mefanemic acid
•Aryl propionic acid
•Ibuprofen
•Naproxen
•Ketoprofen
•Enolic acid
•Piroxicam
•Meloxicam
•Good in seronegative
•500mg orally
•Weekly increments by
500mg upto 2-3 months
•Response in 6-10
weeks
•Avoid in sulpha allergy,
G6PD defeciency
•High toxicity
•Nausea
•Frequent monitoring of
CBP and LFT required
•Anti malarial used in
RA, SLE
•4-6mg/kg/daily
•Response in 4-8
weeks i.e 200-400mg
once daily
•Safe in pregnancy
25. LEFLUNOMIDE TNF-A INHIBITORS INTERLEUKIN
INHIBITORS
•Pyrimidine inhibitor
•Used in RA treatment
•10-20 mg daily
•Response in 4-8 weeks
•Contraindicated in
pregnancy and hepatic
dysfunction
•GI side effects common
•Diarrhoea in 20% cases
•Loperamide or dose
reduction
•Expensive
•Good in seronegative RA
•In those with poor
response to DMARD’s
•Reduces joint damage
•Monoclonal antibodies with
suffix MAB
•Fusion proteins with suffix
CEPT
•Etenarcept – 50 mg/ week
SC
•Infliximab- 3mg/kg initially
at 2 month/ 6th or 8th weekly
therafter, IV infusin with
methotrexate
•Adalimumab- 40 mg SC
every other week, specific
to TNF-a
•Gulimumab-once a month
•Certolimab- pegylated
humanized FAB fragment of
TNF-a, monthly once
•Anakinra
•Recombinant IL-1
receptor antagonist
•Immunomodulation of
IL-1, inhibits pro-
inflammation
•100mg SC daily
•Not for sepsis
•Tocilizumab
•IL-6 receptor
antagonist
•IV infusion
26. CONTRAINDICATIONS
Serious infections/Sepsis
In active/latent tuberculosis
CHF or LVEF<30%
Those for elective surgery
Local infection site reactions
Common with SC administration
Generally self limited
Serious systemic effects rare
Other side effects
Lupin like illness
Demylienating disorder
Exacerbations of pre existing multiple sclerosis
Lymphoma
27. Combine therapy
DMARD’s with two biological agents
Contraindicated in view of increased infective complications
NSAID’s selective COX-2 inhibitors as adjunct to DMARD
Glucocorticoids
Not curative
Delays erosions of joints
Uses
Patients with constitutional symptoms
Weight ;loss
Extra articular features
Vasculitis
Episcleritis
Pleurisy
Persistent synovitis
Dose
5-20 mg daily – prednisolone
If severe- 1mg/kg body weight
28. NON PHARMACOLOGICAL
Acute care of inflamed joint
Pain relief
Joint protection
Keep joint in proper position
SplintinG if necessary
Local heat application
Subacute
Passive and active joint movement
Chronic
Adaptive equipment
Splints
Orthoptics
Mobility aids
Specific exercises
Overall cardiac conditioning