RHEUMATOID
ARTHRITIS
MOGES T(MD,Internist)
Introduction
Chronic multisystem disease of unknown cause.
Affects nearly 1% of the populationworldwide with quite
variable course.
The characteristic feature is persistent inflammatory
synovitis, usually involving peripheral joints in a
symmetric distribution.
The synovial inflammation to cause cartilage
destruction and bone erosions and subsequent changes
in joint integrity is the hallmark of the disease
Introduction (contd.)
Etiology
The exact cause of rheumatoid arthritis is still
obscure.
The interaction of the following factors bring
to the disease process.
Etiology (contd.)
Genetics:
Family studies indicate a genetic predisposition
Monozygotic twins are at least four times more likely
to be concordant for RA than dizygotic twins.
The class II MHC allele HLA-DR4 (DRB1*0401) and
related alleles are known to be major genetic risk
factors for RA.
70% of patients with classic or definite RA express
HLA-DR4.
Etiology (contd.)
Genes outside the HLA complex also contribute.
These include genes controlling the expression of the
antigen receptor on T cells and both immunoglobulin
heavy and light chains, IL -10 and TNF- on
chromosome 3.
Etiology (contd.)
Infectious agents:
A number of possible causative infectious agents
have been suggested.
Mycoplasma, Epstein-Barr virus (EBV),
cytomegalovirus, parvovirus, and rubella virus.
The process by which an infectious agent might cause
chronic inflammatory arthritis with a characteristic
distribution also remains a matter of controversy
Etiology (contd.)
Recent evidence of similarity between products of
certain gram-negative bacteria and EBV and the HLA-
DR4 molecule itself has been identified.
Superantigens produced by a number of
microorganisms, including staphylococci, streptococci
and M. arthritidis have also been identified.
Etiology (contd.)
Other environmental factors
Food allergy
Altered bowel permeability
Altered normal bowel flora
Smoking
Endocrine abnormalities
Heavy metal poisoning
Chronic stress
Etiology (contd.)
HLA DR 4
Other gene
abnormalities
Genetic
Factors
Immunologi
c
Environment abnormaliti
Infection
es
Food allergy
Bowel defect
Smoking
Endocrine
abnormalities
Heavy metal
poisoning
Chronic
Chronic stress
Inflammatio
n
Pathology and pathogenesis
Rheumatoid synovial endothelial cells
express increased amounts of various
adhesion molecules.
Synovial fibroblasts produce a number of
enzymes such as collagenase and
cathepsins that can degrade components of
the articular matrix.
Pathology and pathogenesis
(contd.)
Activated lymphocytes, macrophages, and fibroblasts
produce cytokines and chemokines synovial tissue
inflammation, synovial fluid inflammation, synovial
proliferation, and cartilage and bone damage, as well
as the systemic manifestations of RA
Pathology and pathogenesis
(contd.)
Late:
Synovial exudation: Locally produced immune
complexes can activate complement and generate
anaphylatoxins and chemotactic factors which
increase local vascular permeability.
Enhanced migration of polymorphonuclear leukocytes
into the synovial site.
Bone and cartilage destruction :
The cytokines IL-1 and TNF- play an important role
by stimulating the cells of the pannus to produce
collagenase and other neutral proteases
Pathology and pathogenesis
(contd.)
Generally the propagation of RA is an
immunologically mediated event,
although the original initiating stimulus
has not been characterized fully.
Inflammatory process in the tissue is
driven by the CD4+ T cells infiltrating the
synovium which is then altered/enhanced
by a number of cytokines.
Clinical features
Insidious onset
Increase incidence b/n 25-55yrs then
plateau till 75.
Two third of patients have prodrome.
Symmetrical joint pain is the major
symptoms mainly involving smaller joints
around the wrist and ankle.
Morning stiffness
Swelling, tenderness, and limitation of
motion is evident on examination
Clinical features (contd.)
The fingers are typically deviated towards
the little finger (ulnar deviation) and can
assume unnatural shapes.
Classical deformities in rheumatoid
arthritis are :
Boutonniere deformity
Swan neck deformity
"Z-Thumb" deformity with fixed flexion and
subluxation at the metacarpophalangeal joint,
leading to a "squared" appearance in the
hand.
Clinical features (contd.)
Clinical features (contd.)
Clinical features (contd.)
Extra-articular
manifestations
Pleuropulmonary manifestations
Cardiac-Pericardium C/M occur in<10% of
RA
-CMP,rheumatoid nodule in
[Link].
-increased risk of coronary
atherosclerosis.
Osteoporosis
prevalence is 20-30%
Skin manifestations
Nodules
Rheumatoid nodules
Benign rheumatoid nodules
Linear subcutaneous bands
SC nodule occur 30-40% pf patients
and is
associated with higher disease
activity (+ RF,
+radiologic evidence etc)
o Vascular lesions
Vasculitis and leg ulceration
Raynaud's phenomenon
Felty's syndrome
Is a triad of
Neutropenia,splenomegally& dodular
RA and is seen<1% of patients.
is seen in late stage of severe
disease.
Lymphoma
Increased risk 2-4 fold. Esp the DLBCL
The risk is also higher if the disease
activity is high or if there is feltys
syndrome.
Clinical features (contd.)
Clinical features (contd.)
Laboratory features
No tests are specific for diagnosing RA
Rheumatoid factors are found in more
than two-thirds of adults with the disease.
The presence of rheumatoid factor is not
specific for RA and is found in 5% of
healthy persons.
A number of conditions besides RA are
associated with the presence of
rheumatoid factor.
Serum anticycliccitrrullinated
pepitides(Anti-ccp) specificity reaches
Laboratory features
(contd.)
Normochromic, normocytic anemia.
Thrombocytopenia
Increased ESR
Mild leukocytosis or leukopenia
ANA
Synovial fluid analysis
white blood cell count >2000/uL with more
than 75% polymorphonuclear leukocytes.
Usually range 5,000-50,000.
Imaging features
Plain radiography,MRI& ultrasound.
Changes occur late in the course of the
disease.
Juxtaarticular osteopenia
Loss of articular cartilage
Bone erosions
X-ray features (contd.)
X-ray features (contd.)
Diagnosis
The ACR has defined the following criteria
for the diagnosis of rheumatoid arthritis:
Morning stiffness of >1 hour.
Arthritis and soft-tissue swelling of >3 of joints
Arthritis of hand joints
Symmetric arthritis
Subcutaneous nodules
Rheumatoid factor positive
Radiological changes suggestive of joint
erosion
Classification Criteria for R A
2010
Score
Joint involvement 1 large joint (shoulder, elbow, hip, knee, ankle) 0
2–10 large joints 1
1–3 small joints (MCP, PIP, Thumb IP, MTP, wrists) 2
4–10 small joints 3
>10 joints (at least 1 small joint) 5
Serology Negative RF and negative ACPA 0
Low-positive RF or low-positive anti-CCP antibodies (3 times 2
ULN)
High-positive RF or high-positive anti-CCP antibodies (>3 times 3
ULN)
Acute-phase reactants Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
Duration of symptoms <6 weeks 0
6 weeks
Treatment
The goals of therapy of RA are
1. Relief of pain,
2. Reduction of inflammation,
3. Protection of articular structures,
4. Maintenance of function, and
5. Control of systemic involvement
These goals are achieved mainly by
pharmacological treatments, also
physiotherapy as well as surgery play
significant role in achieving them.
Principle of treatment
Early ,aggressive therapy to prevent joint
damage and disability.
Frequent modification of therapy with utilization
of combination therapy where appropriate
Individualization of therapy in an attempt to
maximize response and minimize side effects.
Achieving, whenever, possible remission of
clinical disease activity.
Methotrixate is the DMARD of choice.(Mod to
severe)
Combination of Rx if mono RX with
methotrexate fails.
possible combinations are…
triple treatment with MTX,sulfasalazine
and
hydroquinolone
MTX plus Lefunomide
MTX plus biological agent
Treatment (contd.)
Pharmacological treatment
Analgesics and antiinflammatory agents
[Link]
Treatment (contd.)
Glucocorticoids: used alone or in
conjunction with other medications to
reduce symptoms and inflammation.
Can be given at low doses daily for
maintenance or in large doses pulsed
over 3 days for a rheumatoid flare.
Prednisolone:
Maintenance: 5-10 mg PO qd (0.1mg/kg/d)
Flare: 20-50 mg PO qd for 1-3 doses
2-5mg/kg/d)
Treatment (contd.)
Disease modifying agents:
Methtrexate - 0.2-0.4 mg/kg (10-15
mg/m2/wk) PO each wk as a single dose is
given.
Azathioprine - 1 mg/kg/d PO for 6-8 wk;
increase by 0.5 mg/kg q4wk until response
or dose reaches 2.5 mg/kg/d
Sulfasalazine - 0.5-1g/d PO; increase qwk to
maintenance dose of 2 g/d PO divided bid;
increase to 3 g/d if response not
satisfactory after 12 wk of treatment; not to
exceed 3 g/d
Treatment (contd.)
Other xenobiotic DMARDs include
Cyclosporin, D-penicillamine, Gold
salts, Hydroxychloroquine,
Leflunomide, Minocycline.
Treatment (contd.)
Biological agents:
TNF- blockers
IL-1 receptor inhibitors
Anti CD20 antibody.
Acr/Eular Provisional Definition of Remission in Rheumatoid
Arthritis
At any time point, patient must satisfy all of the following:
Tender joint count 1
Swollen joint count 1
C-reactive protein 1 mg/dL
Patient global assessment 1 (on a 0–10 scale)
OR
At any time point, patient must have a Simplified Disease
Activity Index score of 3.3
Also consider
Physical therapy & assistive devices.
Surgical correction & or arthroplasty
Special precaution in pregnancy and
elderly
THANK YOU!!
