Rheumatoid arthritis Dr. Lamiaa Mohammed, lecturer of internal medicine, immunology and rheumatology

1. Dr/ LAMIA MOHAMED, MD

2. DEFINITION
• 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.

5. Epidemiology
• 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

6. Pathophysiology
• 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
• Porphyromonas gingivalis, present in the mouths of
people with periodontal disease, appears to
stimulate the production of ACPA linked to
rheumatoid arthritis

7. 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.

8. 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 to produce proinflammatory
cytokines, including TNF, IL-1, IL-6 and IL-15.

9. 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).

10. 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

11. Clinical Findings
Symptoms and Signs
• Highly variable
• Symmetric swelling of multiple joints with
tenderness and pain is characteristic
• >6 weeks 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.

12. • 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.

13. 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).

14. • Characteristic deformities in hands with
longstanding uncontrolled disease, including
– ‘swan neck’ deformity
– the boutonnière
– Z deformity of the thumb
• Dorsal subluxation of the ulna at the distal
radioulnar 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.

15. RA hands

17. ‘Swan neck’ deformity of the
fingers.

18. 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.

19. EXTRA-ARTICULAR MANIFESTATIONS2
Systemic
• Fever
• Weight loss
• Fatigue
• Susceptibility to infection
Musculoskeletal
• Muscle-wasting
• Tenosynovitis
• Bursitis
• Osteoporosis
Haematological
• Anaemia
• Thrombocytosis

20. Lymphatic
• Felty’s syndrome
• Splenomegaly
Nodules
• Sinuses
• Fistulae
Ocular
• Episcleritis
• Scleritis
• Scleromalacia
• Keratoconjunctivitis sicca

21. Vasculitis
• Digital arteritis
• Ulcers
• Pyoderma gangrenosum
• Visceral arteritis
Cardiac
• Pericarditis
• Myocarditis
• Endocarditis
• Conduction defects
• Coronary vasculitis
• Granulomatous aortitis

22. Pulmonary
• Nodules
• Pleural effusions
• Fibrosing alveolitis
• Bronchiolitis
Neurological
• Cervical cord compression
• Compression neuropathies
• Peripheral neuropathy
• Mononeuritis multiplex

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

24. INVESTIGATIONS
Establish Diagnosis
• Clinical criteria
• ESR and CRP
• Ultrasound or MRI
• Rheumatoid factor and anti-citrullinated
peptide antibodies

25. Rheumatoid Factor (RF)
RF is a specific antibody in the blood.
A negative RF does not rule out RA. The arthritis
is then called seronegative, most common during
the first year of illness and converting to
seropositive status over time.
Anti-citrullinated Protein Antibodies
(ACPAs)
Like RF, this testing is only positive in a
proportion of all RA cases.
Unlike RF, this test is rarely found positive if RA
is NOT present, giving it a specificity of about 95%.

26. Monitor Disease Damage
• X-rays
• Functional assessment
Monitor Drug Safety
• Urinalysis
• Full blood count
• Urea, creatinine and liver function tests

27. Criteria for Diagnosis of Rheumatoid
Arthritis
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

28. 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.

29. IMAGING STUDIES
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.

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

31. Marginal erosions at metatarsal heads

32. MRI

34. MANAGEMENT
• 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

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

36. NSAIDs
• 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

37. Corticosteroids
• 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.

38. • 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.

39. Synthetic DMARDs
• 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)

41. Biological DMARDs

42. *Which Drugs and When???
• 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

45. Other Treatments
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