1. Dr. Hanan AL Rayes, MD Consultant Rheumatology
Rheumatoid arthritis
Dr. Hanan AL Rayes, MD
Consultant Rheumatology

2. Outlines Introduction Pathogenesis Clinical manifestation Diagnosis
Symptoms and signs
Clinical course
Diagnosis
Differential diagnosis
Management

3. Rheumatoid arthritis (RA)
RA is a chronic inflammatory autoimmune disease that is characterized by inflammation of the synovium and the destruction of joint cartilage
Chronic multisystem disease of unknown etiology
Onset
May present at any age but more common ( 30-60years)
The prevalence of rheumatoid arthritis in most population
1% among adults >18
Increases with age( 2% in men and 5% in women by age 65)
The incidence also increases with age, peaking between the 4th and 6th decades
Female: Male ratio 3:1

4. Rheumatoid arthritis (RA)
If it is untreated
It will lead to deformity through
Stretching of tendons and ligaments
Destruction of joints through the erosion of cartilage and bone.
Loss of physical function
Inability to carry out daily tasks of living
Difficulties in maintaining employment.

5.  Synovial joint
A synovial joint, also known as a diarthrosis, is a movable type of joint

6. Pathogenesis Exact mechanism unknown
Most likely related to acute and chronic inflammation in the synovium in addition to a proliferate and destructive process of joint tissues
Combination of genetic and environmental factors
HLA-DR4 is associated
An important early event may result the interaction of antigen presenting macrophages with T-cells (helper/inducer)

7. The Pathogenesis of RA

8. Stages:
Proliferative :swelling ,pain with , limited movement ,nerve compression
Destructive: synovial erosion causes irreversible changes ( tendon rupture, capsular weakness and disruption ,bone erosion, joint subluxation and deformity)
Reparative: fibrosis replaces inflammation (adhesions, ankylosis, fixed deformity)

10. Medical history: Articular manifestation
Joint pain(inflammatory)
Swelling
Hotness
Morning Stiffness more than 1 hour
Onset
Rheumatoid arthritis usually has a slow, insidious onset over weeks to months
About 15-20% of individuals have a more rapid onset that develops over days to weeks

11. Acute onset
Hours to a few days
Infectious More commonly
Crystal
Autoimmune (Less commonly)
Insidious onset
several weeks to months
Autoimmune More commonly
Infectious
Other

12. Articular manifestation:
The pattern
poly-articular
Symmetrical
Location
Peripheral joints
Typically small joints PIP, MCP, MTP
wrist, elbow, shoulder, knee , ankle
The axial skeleton is usually spared except Cervical spine
Tempro-mandibular

13. Extra-articular manifestations
Subcutaneous nodules 30 %
Hematological (anemia, thrombocytosis)
Eye
(Episcleritis ,scleritis, kerato-cojuctivitis)
CNS
peripheral neuropathy
entrapment neuropathy (Carpal tunnel syndrome)
Atlanto-axial subluxation
Felty’s syndrome ( splenomegaly and neutropenia)
Sjögren’s syndrome

14. Extra-articular: Constitutional symptoms (fever, fatigue )
Respiratory: Pleural Effusion, pneumonitis, ILD, Rheumatoid nodules
CVS : Pericardial effusion
Rheumatoid Vasculitis
Mononeuritis multiplex
Vasculitic rash
Digital gangrene
Cutaneous ulceration

15. The absence of other conditions or symptoms suggesting an alternative diagnosis
Psoriasis
Inflammatory bowel disease (IBD)
Systemic rheumatic disease such as systemic lupus erythematosus (SLE).

16. A complete physical examination
Assess for synovitis, including the presence and distribution of swollen or tender joints and limited joint motion
In the initial stages of each joint involvement, there is warmth, pain, and redness, with corresponding decrease of range of motion of the affected joint

17. Rheumatoid Arthritis: PIP Swelling
Swelling is confined to the area of the joint capsule
Synovial thickening feels like a firm sponge
Progression of the disease results in muscle
weakness, atrophy and later fixed deformities 5

19. Rheumatoid Arthritis:
Ulnar Deviation and MCP Swelling
Prominent ulnar deviation in the right hand
MCP and PIP swelling in both hands
Synovitis of left wrist 6

20. Differential Diagnosis of RA

21. In a patient with arthritis, consider:
Age of patient
Sex of patient
Mode of onset
Number of joints affected
Symmetry of joint affection
Which regions or joints are affected
Factors that aggravate and ameliorate symptoms
Associated manifestations

22. Diagnosis: Clinical Laboratory
CBC/differrential, Urea and Creatinine , ERS , CRP , Hepatitis screen
Serological test:
Rheumatoid factor
Anti-citrullinated peptide antibodies ( Anti CCP)
X-ray
Synovial fluid aspiration

23. Rheumatoid factor Are IgM antibodies directed against the Fc portion of immunoglobulin G (IgG)
1- Rheumatic disorders
Rheumatoid arthritis – %
Sjögren’s syndrome – 75 to 95 %
Mixed connective tissue disease – 50 to 60%
Mixed cryoglobulinemia %
SLE
Polymyositis or dermatomyositis
2- Non-rheumatic disorders
Chronic infection, as with SBE ,hepatitis B or C virus infection
Inflammatory or fibrosing pulmonary disorders(sarcoidos)
Malignancy, particularly B-cell neoplasms
Primary biliary cirrhosis
3- Healthy individuals ( 4-20%) 

24. Rheumatoid factor Prognostic value of RF-positive :
More aggressive and erosive joint disease
Extra-articular manifestations

25. Anti-citrullinated peptide antibodies ( Anti CCP)
IgG against synovial membrane peptide
Detected by Enzyme-linked immunosorbent assays (ELISA) for antibodies against cyclic citrullinated peptides (CCP)
More specific for RA (90 %)
 Positive patients with early RA are at increased risk of :
Progressive joint damage
Predict erosive disease
Poor functional outcome

26. X- Ray hand
Radiograph showing erosions of the distal ulna.

27. SYNOVIAL FLUID:

28. ACR 1987 For RA diagnosis
Morning stiffness >1h
Arthritis of 3 or more joints
Arthritis of hand joints
Symmetric arthritis
Rheumatoid nodules
Serum Rheumatoid factor
Radiographic changes(X- ray erosive changes0
A person shall be said to have RA if he or she has satisfied 4 of 7 criteria, with criteria 1-4 present for at least 6 weeks

29. Guide line for diagnosis 2010 ACR/ EULAR Diagnostic criteria:
SCORE
Large joints 2 to 10 (shoulders, elbows, hips, knees, and ankles)
1 point
Small joints 1 to 3 (metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists)
2 points
Small joints 4 to 10
3 points
Greater than 10 joints
5 points
Serological abnormality (rheumatoid factor or anti-citrullinated peptide/protein antibody)
Low positive = 2 points
High positive = 3 points
Elevated acute phase response (ESR or CRP)
Symptom duration at least six weeks

30. Clinical Course of RA Severity of Arthritis Years
Type 1 = Self-limited—5% to 20%
Type 2 = Minimally progressive—5% to 20% Type 3 = Progressive—60% to 90%
Pincus. Rheum Dis Clin North Am. 1995;21:619. 7

31. Rheumatoid Arthritis: Typical Course
Damage occurs early in most patients
50% show joint space narrowing or erosions in the first 2 years
By 10 years, 50% of young working patients are disabled
Pincus, et al. Rheum Dis Clin North Am. 1993;19:123–151. 8

32. Rheumatoid Arthritis: Treatment Principles
Confirm the diagnosis
Determine where the patient stands in the spectrum of disease
When damage begins early, start aggressive treatment early
Use the safest treatment plan that matches the aggressiveness of the disease
Monitor treatment for adverse effects
Monitor disease activity, revise Rx as needed 10

33. Critical Elements of a Treatment Plan: Assessment
Assess current activity
Morning stiffness, synovitis, fatigue, ESR
Document the degree of damage
ROM and deformities
Joint space narrowing and erosions on x-ray
Functional status
Document extra-articular manifestations
Nodules, pulmonary fibrosis, vasculitis
Assess prior Rx responses and side effects 11

34. Critical Elements of a Treatment Plan: Therapy
Education
Build a cooperative long-term relationship
Use materials from the Arthritis Foundation and the ACR
Assistive devices
Exercise
ROM, conditioning, and strengthening exercises
Medications
Analgesic and/or anti-inflammatory
Immunosuppressive, cytotoxic, and biologic
Balance efficacy and safety with activity 12

35. Rheumatoid Arthritis: Drug Treatment Options
NSAIDs
Symptomatic relief, improved function
No change in disease progression
Low-dose prednisone (£10 mg qd)
May substitute for NSAID
Used as bridge therapy
If used long term, consider prophylactic treatment for osteoporosis
Intra-articular steroids
Useful for flares
Paget. Primer on Rheum Dis. 11th edition. 1997:168. 13

36. Treatment Options Disease modifying anti-rheumatic drugs
Methotrexate has been one of the mainstays of RA treatment Action: Inhibits dihydrofolate reductase
Sulfasalazine
Luflonamide
hydroxychloroquine
Biologic disease modifying anti-rheumatic drug
Over the past 16 years biologic disease modifying anti-rheumatic drugs have been developed
These drugs target select aspects of the immune response so as to decrease inflammation

37. Biologic disease modifying anti-rheumatic drugs

38. Case 2
34-year-old woman with 1-year history of symmetrical poly arthritis
Morning stiffness = 90 minutes
Synovitis: 1+ swelling of MCP, 2+ PIP, wrist, knee, and MTP joints
Normal joint alignment
RF positive 24

39. Case 2 (cont’d) A. Soft-tissue swelling, no erosions
X-ray hand
A. Soft-tissue swelling, no erosions
B. Thinning of the cortex on the radial side and minimal joint space narrowing
C. Marginal erosion at the radial side of the metacarpal head with joint space narrowing
ACR Clinical Slide Collection, 1997. 26

40. Case 2 (cont’d)
Early erosion at the tip of the ulnar styloid 25

41. Case 2 (cont’d) Assessment of case 2 Moderate-severe disease activity
Many joints involved
Clear radiologic signs of joint destruction early in disease course
Progressive course with poor prognostic factors
Treatment should be more aggressive
NSAID, MTX, SSZ, and hydroxychloroquine would be a good choice 27

42. A good history and physical examination Your Eyes and Your Hand
Advice 1:
A good history and physical examination
Your Eyes and Your Hand
Advice 2:
Listen to your patients

43. QUESTION