Rheumatoid Arthritis

1
Overview
Definition of Rheumatoid Arthritis and prevalence

What is the pathogenesis of RA?

What clinical manifestations ?

How do you diagnose RA?

Current treatment principles

Prognosis
2
Introduction
Rheumatoid arthritis (RA) is a systemic , chronic
inflammatory disease characterized by joint
inflammation and destruction in association with
serological evidence of autoreactivity.
⬢ Affects 1% of the population
⬢  Peak incidence in the 30 to 50 years
⬢  Female-to-male ratio 3:1
⬢  Familial predisposition, with HLA-DR4 association

3
4
5
A 40-year-old woman presents with bilateral hand and
knee pain that has slowly been getting worse over the
last 6 weeks. Her hands feel tight in the morning and she
has to wait 45 minutes to an hour for them to "warm up."
Her past medical history is significant for vitiligo that
began about 4 years ago and is limited to her face and
upper thorax. She also had pericarditis about 1 year ago
that resolved with NSAIDs. Physical examination reveals
swelling of the MCP and PIP, but sparing of the DIP
● Most likely diagnosis
● Single most specific test
● Best long-term therapy
Clinical presentation
⬢ Additive, symmetrical polyarthritis affecting both small and
large joints
⬢ Presentation is often suggested by its inflammatory Character
⬢ Fatigue, fever, and weight loss may be present reflecting
systemic nature of the disease
⬢ Joint pain, swelling, erythema, heat, and tenderness may
develop acutely or insidiously
⬢ Morning stiffness lasts more than 1 hour, and “gel”
phenomenon present after inactivity

6
Overview of joints affected
● Joints most frequently affected in RA
include:
✓The proximal interphalangeal
(PIP) and metacarpophalangeal
(MCP) joints of the hands
✓The wrists
✓The shoulders
✓The elbows
✓The knees
✓The ankles, and
✓The metarsophalangeal (MTP)
joints of the feet
● Distal interphalangeal (DIP)
joints are typically spared
in RA.
7
⬢ Untreated, RA can cause joint destruction and disability,
beginning in the first year of disease
⬢ Ulnar deviation and subluxation of the fingers at the MCP
joints, with radial deviation at the wrist
⬢ Swan neck deformity (hyperextension of the PIP and
flexion of the DIP joints , Boutonnière deformity (flexion
of the PIP and hyperextension of the DIP joints.

8
9
10
11
12
Extra-articular manifestations

✓  Rheumatoid nodules
⬢  Typically appear on extensor surfaces and pressure
points (e.g., olecranon process and Achilles tendon) but
may also affect internal organs
⬢  Occur in approximately 25% of patients with RA
⬢  Associated with rheumatoid factor (RF) seropositivity
and more severe disease
⬢  Nodules are not specific for RA and can occur in other
rheumatic diseases
⬢   Methotrexate can worsen nodulosis, even as
inflammatory joint disease improves


13
Ocular
⬢  Episcleritis, scleritis, and scleromalacia perforans
⬢ Keratoconjunctivitis sicca (secondary Sjogren syndrome)
 Pulmonary
⬢  Pleural disease (effusions exudative and pleural fluid
glucose typically low)
⬢ Interstitial lung disease and fibrosis
⬢  Bronchiolitis obliterans
⬢  Pulmonary nodules
●  Single or multiple
●  Nodules may cavitate and pleural nodules cause
bronchopleural fistulae
●  Caplan disease (nodules with underlying RA and pneumoconiosis)

14
Cardiac
⬢  Pericarditis and effusions are common but rarely
symptomatic
⬢  Constrictive pericarditis, myocarditis, and conduction
defects develop rarely
 Hematologic
⬢  Anemia due to iron deficiency (NSAID-associated GI
loss) and “chronic disease”
⬢  Felty syndrome (RA associated with splenomegaly,
⬢ neutropenia, and leg ulcers)
⬢  Thrombocytosis or thrombocytopenia
⬢  Increased risk for non-Hodgkin lymphoma independent
of tumor necrosis factor (TNF) inhibitor use

15
Neurologic
⬢  Atlantoaxial (C1-C2) instability and subluxation may
produce a cervical myelopathy
⬢  Peripheral neuropathy Compression associated with
synovitis (e.g., carpal tunnel syndrome)
⬢  Ischemic associated with vasculitis (e.g., mononeuritis
multiplex)
 Vasculitis
⬢  cutaneous ulcers, visceral involvement, and
mononeuritis multiplex
⬢  Associated with high-titer RF and severe disease

1
6
Diagnosis RA

17
⬢  Clinical presentation highly suggestive in classic cases
⬢  History characterized by insidious onset
 Inflammatory manifestations
⬢  Physical examination reveals
⬢  Synovitis , Symmetrical polyarthritis
⬢  Renal and hepatic function normal unless the result of
drug toxicity
⬢  Normochromic normocytic anemia
⬢  Elevated sedimentation rate and C-reactive protein

18
Rheumatoid factor (RF)
❖ Antibody reactive against Fc fragment of IgG

❖ 70-85% of RA patients are ever seropositive for RF, and

is associated with:

• More radiological abnormalities

• More disease activity
• Worse functional ability
• More extra-articular manifestations
• More treatment with second line drugs

❖ Not specific for RA: chronic infections, cirrhosis, malignancies, other

rheumatic diseases. 1
9
Anti–cyclic citrullinated peptide (anti-CCP) antibodies
⬢  Anti-CCP antibody is 68% to 80% sensitive and 98%
specific for RA
⬢  Anti-CCP is more likely to be present in early RA than is
RF
Radiographic findings
⬢ Only soft tissue swelling in early disease
⬢  Periarticular osteopenia
⬢  Uniform joint space narrowing
⬢  Joint margin erosions
⬢  Ulnar styloid erosions
⬢  Atlantoaxial (C1-C2) instability and subluxation

20
Radiographic findings
2010 ACR/EULAR classification criteria for RA
A score of ≥6/10 is needed to classify
RA
A. Joint involvement Score
❖1 large joint 0
❖2-10 large joints 1
❖1-3 small joints (with or without involvement of large joints) 2
❖4-10 small joints (with or without involvement of large joints) 3
❖>10 joints (at least 1 small joint) 5

B. Serology (at least 1 test result is needed)

❖Negative RF and negative ACPA 0
❖Low-positive RF or low-positive ACPA 2
❖High-positive RF or high-positive ACPA 3

C. Acute-phase reactants (at least 1 test result is needed)

❖Normal CRP and normal ESR 0
❖Abnormal CRP or abnormal ESR 1

D. Duration of symptoms
❖<6 weeks 0
❖≥6 weeks 1

22
 Assessing Disease
Activity in RA
Level of Disease
Instrument Remission Low Activity
Moderate High

DAS28 < 2.6 ≥ 2.6 to < ≥ 3.2 to ≥ ≥ 5.1

(range, 3.2 5.1
0-9.4)
PAS or PAS- 0 to 0.25 0.26 to 3.7 3.71 to < ≥ 8.0
II (range, 8.0
0-10)
CDAI ≤ 2.8 > 2.8 to > 10.0 to > 22.0
(range, 10.0 22.0
0-76)
RAPID 3 0 to 3.0 > 3.0 to 6.0 > 6.0 to > 12.0 to
(range, 12.0 30.0
0-30)
26
SDAI ≤ 3.3 > 3.3 to ≤ > 11.0 to ≤ > 26.0
25
RA: Current Pharmacologic therapy

⬢ Agents that are effective in controlling the signs and symptoms of RA, but
have no effect on disease progression

⬢ NSAIDs reduce inflammation and pain

⬢ COX-2 inhibitors are similar to NSAIDs, but with improved GI safety and
tolerability and higher cardiac side effects

⬢ Corticosteroids have anti-inflammatory and immunoregulatory activity, but

nominal disease-modifying capability

⬢ DMARDs impact the signs, symptoms, and disease progression of RA, as

well as improve the quality of life and functionality of the patient

27
RA: Disease Modifying therapies

Cs DMARDs Biological DMARDS

For example For example

❖ Methotrexate ❖ TNF antagonists

● Etanercept (Enbrel®)
❖ Leflunomide ● Adalimumab (Humira®)
❖ Sulfasalazine ● Infliximab (Remicade®)
● Certolisumab pegol
(Cimzia®)
❖ Hydroxychloroquine ● Golimumab (Simponi®)
❖ Abatacept
❖ Azathioprine, ❖ Rituximab
cyclosporine
❖ Tocilizumab (Actemra®)

❖ Tofacitinib
(Xeljanz®)
2
8
TNF antagonists
❖ 5 currently approved agents:
❖ Etanercept, adalimumab, infliximab, certolizumab pegol, golimumab.

❖ Subcutaneous (etanercept, adalimumab, certolizumab pegol, golimumab) and

intravenous administration (infliximab and golimumab.)

❖ Administration in combination with MTX is superior to monotherapy.

❖ Time to onset: rapid (weeks)

❖ Adverse events:
❖ Infection, TB, multiple sclerosis/demyelination, lupus-like syndrome.
❖ Malignancy: higher rates as compared with normal population but not
higher than the background of lymphoma and solid tumors in RA
population. Increased risk of non melanoma skin cancers.

❖ Monitoring:
❖ TB screening including PPD prior to therapy.
❖ Hepatitis screeing
❖ Periodic CBC, LFTs.
❖ Infection. 29
Prognosis

⃝ up to 10% of cases suffering severe disability.

⃝ Cardiovascular disease, infection and secondary

amyloidosis are major causes of morbidity and mortality.

⃝ Young age at onset, severe disease/disability at

presentation, extra-articular manifestations and high RF
titres all predict a worse prognosis.

30
1. Clinical:
● Insidious rather than explosive onset
● Early development of rheumatoid nodule
● Extra-articular manifestations
● Severe functional impairment
● One year active disease without remission
● Increasing number of peripheral joints involvement
● Level of disability at the onset
● Female sex.
2. Blood tests:
● High titers of anti-CCP antibodies and RA test
● High CRP
● Normochromic normocytic anemia.
3. X-rays:
● Early erosive damage (Note: Ultrasound and MRI can show cartilage and bone damage prior
to conventional X-rays).
1. Rheumatoid factor in Rheumatoid Arthritis
is positive in:
A. 20% cases
B. 95% cases
C. 50% cases
D. 85% cases
E. 100% cases
1. Rheumatoid factor in Rheumatoid Arthritis
is positive in:
A. 20% cases
B. 95% cases
C. 50% cases
D. 85% cases
E. 100% cases
All are extra-articular manifestations of rheumatoid
arthritis except:
A. Fibrosing alveolitis
B. Pericarditis
C. Mononeuritis multiplex
D. Ulcerative colitis
E. Vasculitis
All are extra-articular manifestations of rheumatoid
arthritis except:
A. Fibrosing alveolitis
B. Pericarditis
C. Mononeuritis multiplex
D. Ulcerative colitis
E. Vasculitis
A 40-year-old woman presents with bilateral hand and
knee pain that has slowly been getting worse over the
last 6 weeks. Her hands feel tight in the morning and she
has to wait 45 minutes to an hour for them to "warm up."
Her past medical history is significant for vitiligo that
began about 4 years ago and is limited to her face and
upper thorax. She also had pericarditis about 1 year ago
that resolved with NSAIDs. Physical examination reveals
swelling of the MCP and PIP, but sparing of the DIP
● Most likely diagnosis
● Single most specific test
● Best long-term therapy