Rheumatoid arthritis is an autoimmune disease characterized by inflammation of the joints, especially in the hands and feet. It affects around 1% of the population and is more common in women. If left untreated, chronic inflammation can lead to joint damage and disability. Management involves reducing inflammation and pain with medications like NSAIDs, corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), with the goal of achieving remission and preventing long-term joint damage and deformity.

1. RHEUMATOID ARTHRITIS
Dr. Syed Muhammad Ali Shah
RMO
Dept. of Medicine

2. DEFINITION1
• Rheumatoid arthritis (RA) is a systemic
autoimmune disease characterized by
inflammatory polyarthritis, which affects
peripheral joints, especially the small joints of
the hands and feet.
• Chronic untreated inflammation may lead to
joint erosions and joint destruction.

3. Epidemiology2,3
• Prevalence of 1%
• More common in women than men (female:male
ratio of 3:1)
• Peak onset is in the fourth or fifth decade for
women and the sixth to eighth decades for men
• 40% of RA patients are registered as disabled
within 3 years of onset, and around 80% are
moderately to severely disabled within 20 years

4. Pathophysiology3,6
• Genetic, epigenetic and environmental factors
• The MHC class II gene, HLA-DR4, is the major
susceptibility haplotype in 50–75% of Caucasian
patients with RA
• DR1 is more important in Indians and Israelis, and
DW15 in Japanese
• Porphyromonas gingivalis, present in the mouths
of people with periodontal disease, appears to
stimulate the production of ACPA linked to
rheumatoid arthritis7

5. Pathophysiology
• The clinical onset – infiltration of the synovial
membrane with
– Lymphocytes
– Plasma cells
– Dendritic cells
– Macrophages.
• CD4+ T lymphocytes, including Th1 cells and Th17
cells play a central role by interacting with other cells
in the synovium.

6. Pathophysiology
• Lymphoid follicles form within the synovial
membrane in which T cell–B cell interactions
lead B cells to produce cytokines and
autoantibodies, including RF and ACPA.
• Synovial macrophages - activated by immune
complexes - produce proinflammatory
cytokines, including TNF, IL-1, IL-6 and IL-15.

7. Pathophysiology
• Proinflammatory cytokines act on synovial
fibroblasts, to promote swelling of the
synovial membrane and damage to soft
tissues and cartilage.
• Activation of osteoclasts and chondrocytes
drives destruction of bone and cartilage
• The RA joint is hypoxic and this promotes new
blood vessel formation (neoangiogenesis).

8. Pathophysiology
• The inflammatory granulation tissue (pannus)
formed by the above sequence of events
spreads over and under the articular cartilage,
which is progressively eroded and destroyed.
• Later, fibrous or bony ankylosis may occur.
• Muscles adjacent to inflamed joints atrophy
and may be infiltrated with lymphocytes

9. Clinical Findings1,2
Symptoms and Signs
• 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.

10. • Most common joints involved include MCP,
PIP, wrists, MTP, ankles, elbows, shoulders,
hips, and knees.
• DIP joints, Sacroiliac and vertebral joints are
spared except for C1 to C2.
• Atlantoaxial (C1–C2) subluxation can lead to
myelopathy.

11. Subluxation of cervical spine. Flexion, showing
widening of the space (arrow) between the odontoid
peg of the axis (behind) and the anterior arch of the
atlas (in front).

12. • 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.

13. ‘Swan neck’ deformity of the fingers.

14. 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.

16. • Dorsal subluxation of the MTP joints - ‘cock-
up’ toe deformities leading to secondary
adventitious bursae and callosities.
• In the hindfoot, calcaneovalgus (eversion) -
damage to the ankle and subtalar joint.
• Associated with loss of the longitudinal arch
(flat foot) due to rupture of the tibialis
posterior tendon.

17. Cock Up Toe Deformity

18. EXTRA-ARTICULAR MANIFESTATIONS2
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. EXTRA-ARTICULAR MANIFESTATIONS2
Vasculitis
• Digital arteritis
• Ulcers
• Pyoderma gangrenosum
• Visceral arteritis
Cardiac
• Pericarditis
• Myocarditis
• Endocarditis
• Conduction defects
• Coronary vasculitis
• Granulomatous aortitis
Pulmonary
• Nodules
• Pleural effusions
• Fibrosing alveolitis
• Bronchiolitis
Neurological
• Cervical cord compression
• Compression neuropathies
• Peripheral neuropathy
• Mononeuritis multiplex

20. Rheumatoid nodules and olecranon bursitis. Nodules
were palpable within as well as outside the bursa.

21. INVESTIGATIONS2
Establish Diagnosis
• Clinical criteria
• ESR and CRP
• Ultrasound or MRI
• Rheumatoid factor and
anti-citrullinated peptide
antibodies
Monitor Disease Damage
• X-rays
• Functional assessment
Monitor Drug Safety
• Urinalysis
• Full blood count
• Urea, creatinine and
liver function tests

22. *Criteria for Diagnosis of
Rheumatoid Arthritis2,7
Criterion Score
Joints affected
1 large joint 0
2–10 large joints 1
1–3 small joints ` 2
4 -10 small joints 3
4–10 small joints 5
Serology
Negative RF and ACPA 0
Low positive RF or ACPA (<3 times ULN) 2
High positive RF or ACPA (>3 times ULN) 3

23. Duration of symptoms
< 6 wks 0
> 6 wks 1
Acute phase reactants
Normal CRP and ESR 0
Abnormal CRP or ESR 1
Patients with a score ≥ 6 are considered
to have definite RA.
*European League Against Rheumatism/American College of Rheumatology 2010 Criteria.

24. IMAGING STUDIES2,1
Plain radiography:
• Radiographic changes are the most specific for
rheumatoid arthritis.
• Earlier changes include soft tissue swelling, joint space
narrowing, and periarticular osteopenia.
• Later changes include periarticular erosions, especially
in MCPs, PIPs, MTPs, and wrist.
• This reflects cartilage and bone destruction secondary
to pannus.
• MRI and musculoskeletal ultrasound are more sensitive
for detecting erosive disease and joint effusion /
synovitis.

25. Periarticular osteopenia and marginal erosions in MCP and a PIP
joint (arrows).

26. Marginal erosions at metatarsal heads

27. Disease Activity Score 285

28. • DAS28 score of higher than 5.1 is indicative of
high disease activity
• DAS28 below 3.2 indicates low disease
activity.
• Remission if they have a DAS28 lower than 2.6
• Disease flare is an increase in DAS28 of >1.2 or
an increase in DAS28 of 0.6–1.2 if this resulted
in DAS28 >5.1

29. MANAGEMENT2,4
• Primary Objectives
– Target is low disease activity or remission
– Reduction of inflammation and pain
– Preservation of function
– Prevention of deformity
DRUGS USED
– NSAIDs
– CORTICOSTEROIDS
– DMARDs
• SYNTETIC
• BIOLOGICAL

30. General Measures3
The general aims of management are to:
• Educate the patient
• Control pain
• Optimise function
• Modify the disease process where this is
possible
• Identify and treat related comorbidity

31. NSAIDs2
• 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

32. Corticosteroids2
• Prompt anti-inflammatory effect in RA and slow
the rate of articular erosion.
• Multiple side effects limit their long term use.
• Low-dose corticosteroids - a “bridge” to reduce
disease activity until the slower acting DMARDs
take effect
• Adjunctive therapy for active disease that persists
despite treatment with DMARDs.
• 10 mg of prednisone or equivalent per day is
appropriate for articular disease.

33. Corticosteroids2
• Higher doses are used to manage serious
extra-articular manifestations (eg, pericarditis,
necrotizing scleritis).
• Intra-articular corticosteroids may be helpful if
one or two joints are the chief source of
difficulty.
– Intra-articular triamcinolone, 10–40 mg
depending on the size of the joint
– Not more than four times a year.

34. Synthetic DMARDs2
• Methotrexate is usually the initial synthetic
DMARD of choice.
• Beneficial effect in 2–6 weeks.
• The usual initial dose is 7.5 mg of methotrexate
orally once weekly.
• Gastric irritation, stomatitis, cytopenias, and
hepatotoxicity
• Either daily folate (1 mg orally) or weekly
leucovorin calcium (2.5–5 mg taken orally 24
hours after the dose of methotrexate)

36. Biological DMARDs2

37. *Which Drugs and When???4
• Early RA - RA disease duration <6 months
• Established RA - RA disease duration >6 months or meeting the
classification criteria
• Disease activity - Categorized as low, moderate, and high as per validated
common scales
• Poor prognosis - Presence of 1 or more of the following features:
– functional limitation
– extraarticular disease (e.g., presence of rheumatoid nodules, RA
vasculitis, Felty’s syndrome)
– positive rheumatoid factor or anti–cyclic citrullinated peptide
antibodies
– bony erosions by radiograph
*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

40. Other Treatments2
Surgery
• Synovectomy of the wrist or finger tendon
sheaths of the hands may be required for pain
relief or to prevent tendon rupture when
medical interventions have failed.
• In later stages when joint damage has
occurred, osteotomy, arthrodesis or
arthroplasty may be required

42. Bibliography
1. Ferri's Clinical Advisor 2014
2. Davidsons Principles and Practice of Medicine 22ed
3. Current Medical Diagnosis and Treatment 2014
4. 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
5. www.4s-dawn.com/DAS28
6. http://www.medscape.com/viewarticle/834584
7. 2010 Rheumatoid Arthritis Classification Criteria
ARTHRITIS & RHEUMATISM Vol. 62, No. 9, September 2010, pp 2569–
2581 DOI 10.1002/art.27584 © 2010, American College of
Rheumatology