Rheumatoid Arthritis - pathogenesis, clinical features and diagnosis

1. RHEUMATOID ARTHRITIS
DR. ROHIT RAJEEVAN C K

2. QUESTIONS

3. 1.
• Which of the following is the most common area affected by
rheumatoid arthritis?
• A. Temporomandibular joints
• B. Metatarsophalangeal joints
• C. Proximal interphalangeal joints
• D. Metacarpophalangeal joints

4. 2.
• Which of the following is not associated with a poor prognosis
in patients with rheumatoid arthritis?
• A. Female Sex
• B. Age > 30 years
• C. Extra articular manifestations
• D. High serum titer of antibodies ( RA factor, Anti – CCP etc)

5. 3.
• Which of the following organ systems is more likely to be
affected by rheumatoid arthritis?
• A. Digestive System
• B. Cardiovascular system
• C. Urinary tract
• D. Lymphatic system

6. 4.
• Which of the following is the first choice for imaging in
rheumatoid arthritis?
• A. CT scan
• B. MRI
• C. USG
• D. Radiography

7. DEFINITION
• Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that
may affect many tissues and organs, but mainly attacks the joints
producing an inflammatory synovitis.

8. EPIDEMIOLOGY
• Affects 0.5% to 1% of the general population worldwide
• Females more frequently than males, F:M ratio of ~ 3:1.
• Most commonly occurs at age 45–65 years ; can occur at any
age

9. Idiopathic
Positive family history
Inherited tissue type major histocompatibility complex
(MHC) antigen (MHC II)s
Smoking
Bacterial and Fungal Infection
Herpes simplex virus infections
Epstein-Barr virus (EBV)
Vitamin D deficiency
Risk Factors

10. IMMUNOPATHOLOGY
• Overproduction of inflammatory cytokines, in particular tumour
necrosis factor-α (TNFα) and interleukin-6 (IL-6), is central to
the pathology of RA.
• Persistent inflammation  increased vascularity and
inflammation of the synovial lining of joints (synovitis) 
secondary cartilage degradation (joint space narrowing) and
bone erosion.

12. PATHOGENESIS
• There is increased synovial vascularity, influx of monocytes and plasma cells,
and activation of tissue macrophages and fibroblasts.
• Synovial plasma cells are numerous and produce antibodies which will have a
proinflammatory local effect.
• Cellular activation of cytokines locally bone resorption activating osteoclasts
bone erosion.
• In severe cases, cellular aggregation can lead to lymphoid follicles forming in
the synovial tissue.
• Extra-synovial inflammation includes rheumatoid nodule formation and
inflammation of lung and cardiac tissue.

14. CLINICAL FEATURES
• Typically affects small joints of hands and feet; but can affect any joint
having synovial tissue
• Wrists, metacarpophalangeal (MCP), and proximal inter-phalangeal (PIP)
joints - most frequently involved
• Early morning stiffness lasting for >30 min
• Movement of affected joints alleviates stiffness and discomfort
• Boggy swelling over the joint line – synovitis
• If larger joints involved – ballotable joint effusion
• Deformities may occur later if untreated/aggressive disease.

15. DEFORMITIES
• Ulnar deviation at wrist.
• Swan neck and boutonniere deformities in fingers
• Lateral deviation of toes
• Limited shoulder movt
• Erosion of atlanto-axial joint  unstable C1-C2 articulation  life
threatening brainstem compression / pain, headache, syncope
• Radicular pains

16. SWELLING DUE TO
SYNOVITIS

18. Mallet finger is asimple
flexion deformity of
the distal
interphalangeal joint
preventing extension.

19. Hammer toes

20. EXTRA - ARTICULAR
MANIFESTATIONS OF RA

22. RHEUMATOID
NODULES

24. DIAGNOSIS

25. INVESTIGATIONS
•Bloodcount- usually a normochromic, normocytic
anaemia; ESR, CRP - elevated
•X-ray- joint narrowing, erosions at thejoint
margins
•Synovialfluid - high neutrophil count in
uncomplicated disease (~ 5,000 – 50,000/ uᶾ)

26. 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%.

27. RADIOGRAPHY
• Hands and Feet – Erosions, Peri articular osteopenia, soft tissue
swelling
• C Xray – To assess for pulmonary fibrosis prior to initiation of
DMARDs
• Other – C- spine Xray to assess C1-C2 instability

28. RADIOLOG
Y

29. FEET

30. ULTRASOUND
• Assessing for synovitis, hypervascularity , effusion, early erosion
• Can provide dynamic imaging
• MRI
• To assess for cervical myelopathy
• Joint MRI to confirm tendon/joint synovitis , identify pre erosions ,
erosions, rule out other musculo-skeletal lesions

32. CLINICAL COURSE:
• Complex natural history, affected by a number of factors
• As many as 10% individuals – spontaneous remission within 6m
( particularly seroneg.)
• Majority – persistent and progressive disease, waxing and
waning over time.
• Overall mortality rate in RA - two times greater than the
general population

33. • Ischemic heart disease – M/C cause of death followed by
infection.
• Median life expectancy - shortened by avg of 7 years for men
and 3 years for women
• Patients at higher risk for shortened survival - systemic
extraarticular involvement, low functional capacity, low
socioeconomic status, low education, and chronic prednisone
use.

34. ANSWERS

35. 1.
• Which of the following is the most common area affected by
rheumatoid arthritis?
• A. Temporomandibular joints
• B. Metatarsophalangeal joints
• C. Proximal interphalangeal joints
• D. Metacarpophalangeal joints

36. 1.
• Which of the following is the most common area affected by
rheumatoid arthritis?
• A. Temporomandibular joints
• B. Metatarsophalangeal joints
• C. Proximal interphalangeal joints
• D. Metacarpophalangeal joints

37. COMMENT:
• Joint involvement is the characteristic feature of rheumatoid
arthritis. In general, the small joints of the hands and feet are
affected in a relatively symmetric distribution. In decreasing
frequency, the metacarpophalangeal joints, wrist, proximal
interphalangeal joints, knee, metatarsophalangeal joints,
shoulder, ankle, cervical spine, hip, elbow, and
temporomandibular joints are most commonly affected.

38. 2.
• Which of the following is not associated with a poor prognosis
in patients with rheumatoid arthritis?
• A. Female Sex
• B. Age > 30 years
• C. Extra articular manifestations
• D. High serum titer of antibodies ( RA factor, Anti – CCP etc)

39. 2.
• Which of the following is not associated with a poor prognosis
in patients with rheumatoid arthritis?
• A. Female Sex
• B. Age > 30 years
• C. Extra articular manifestations
• D. High serum titer of antibodies ( RA factor, Anti – CCP etc)

40. COMMENT
Unfavorable prognosis in terms of joint damage and disability is seen in:
• HLA-DRB1*04/04 genotype
• High serum titer of autoantibodies (eg, rheumatoid factor, anti–citrullinated protein
antibodies)
• Extra-articular manifestations
• Large number of involved joints
• Age younger than 30 years
• Female sex
• Systemic symptoms
• Insidious onset

41. 3.
• Which of the following organ systems is more likely to be
affected by rheumatoid arthritis?
• A. Digestive System
• B. Cardiovascular system
• C. Urinary tract
• D. Lymphatic system

42. 3.
• Which of the following organ systems is more likely to be
affected by rheumatoid arthritis?
• A. Digestive System
• B. Cardiovascular system
• C. Urinary tract
• D. Lymphatic system

43. COMMENT
• Cardiovascular morbidity and mortality are increased in
patients with rheumatoid arthritis.
• Myocardial infarction, myocardial dysfunction, and
asymptomatic pericardial effusions are common;
• Symptomatic pericarditis and constrictive pericarditis are rare.
• Myocarditis, coronary vasculitis, valvular disease, and
conduction defects are occasionally observed.

44. 4.
• Which of the following is the first choice for imaging in
rheumatoid arthritis?
• A. CT scan
• B. MRI
• C. USG
• D. Radiography

45. 4.
• Which of the following is the first choice for imaging in
rheumatoid arthritis?
• A. CT scan
• B. MRI
• C. USG
• D. Radiography

46. COMMENT
• Radiography remains the first choice for imaging in rheumatoid
arthritis
• Inexpensive, readily available, and easily reproducible + allows easy
serial comparison for assessment of disease progression.
• MRI provides a more accurate assessment and earlier detection of
lesions than radiography does; however, the cost of the examination
and the small size of the joints involved militate against its
widespread use.
• Ultrasonography of joints can detect small effusions that are not
clinically apparent, and its use is increasing in clinical practice;
however, its use is not presently the standard of care for rheumatoid
arthritis.

47. Thank You

48. REFERENCES
• Harrison’s Rheumatology 3rd ed
• Oxford Handbook of Rheumatology 4th ed 2018
• Davidsons’ Principles and Practice of Medicine 23rd ed