Rheumatoid arthritis

Dr. Hanan AL Rayes, MDConsultant Rheumatology

Introduction Pathogenesis Clinical manifestation

◦ Symptoms and signs◦ Clinical course

Diagnosis Differential diagnosis Management

Outlines

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

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.

Rheumatoid arthritis (RA)

 Synovial joint A synovial joint, also known as

a diarthrosis, is a movable type of joint

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)

Pathogenesis

The Pathogenesis of RA

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)

Stages:

◦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

Medical history:Articular manifestation

Acute onsetHours to a few days

Infectious More commonly

Crystal Autoimmune (Less

commonly)

Insidious onset several weeks to

months

Autoimmune More commonly

Infectious Other

◦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

Articular manifestation:

◦ 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

Extra-articular manifestations

Constitutional symptoms (fever, fatigue ) Respiratory: Pleural Effusion, pneumonitis, ILD,

Rheumatoid nodules

CVS : Pericardial effusion

Rheumatoid Vasculitis Mononeuritis multiplex Vasculitic rash Digital gangrene Cutaneous ulceration

Extra-articular:

◦ 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).

◦ 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

A complete physical examination

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

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

Differential Diagnosis of RA

Mode of onset

In a patient with arthritis, consider:

Number of joints affectedSymmetry of joint affection Which regions or joints are affected

Factors that aggravate and ameliorate symptomsAssociated manifestations

Age of patientSex of patient

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

Diagnosis:

1- Rheumatic disorders◦ Rheumatoid arthritis – 75-80 %◦ Sjögren’s syndrome – 75 to 95 %◦ Mixed connective tissue disease – 50 to 60% ◦ Mixed cryoglobulinemia 40-100%◦ SLE◦ Polymyositis or dermatomyositis

2- Non-rheumatic disordersChronic 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%) 

Rheumatoid factorAre IgM antibodies directed against the Fc portion of immunoglobulin G (IgG)

Prognostic value of RF-positive :◦ More aggressive and erosive joint disease ◦ Extra-articular manifestations

Rheumatoid factor

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

Anti-citrullinated peptide antibodies ( Anti CCP)

X- Ray hand

SYNOVIAL FLUID:

ACR 1987 For RA diagnosis1. Morning stiffness >1h2. Arthritis of 3 or more joints3. Arthritis of hand joints4. Symmetric arthritis5. Rheumatoid nodules6. Serum Rheumatoid factor7. 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

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 pointsHigh positive = 3 points

Elevated acute phase response (ESR or CRP) 1 point

Symptom duration at least six weeks 1 point

Guide line for diagnosis2010 ACR/ EULAR Diagnostic criteria:

Clinical Course of RA

Type 1 = Self-limited—5% to 20%Type 2 = Minimally progressive—5% to 20%Type 3 = Progressive—60% to 90%

0

1

2

3

4

0 0.5 1 2 3 4 6 8 16

Type 1Type 2Type 3

Years

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itis

Pincus. Rheum Dis Clin North Am. 1995;21:619.

Pincus, et al. Rheum Dis Clin North Am. 1993;19:123–151.

• 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

Rheumatoid Arthritis: Typical Course

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

Rheumatoid Arthritis:Treatment Principles

• 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

Critical Elements of a Treatment Plan: Assessment

• 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

Critical Elements of a Treatment Plan: Therapy

• 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

Rheumatoid Arthritis: Drug Treatment Options

Paget. Primer on Rheum Dis. 11th edition. 1997:168.

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

Treatment Options

Biologic disease modifying anti-rheumatic drugs

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

Case 2

Case 2 (cont’d)

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

X-ray hand

ACR Clinical Slide Collection, 1997.

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

• 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

Case 2 (cont’d)

Advice 1: A good history and physical examination Your Eyes and Your Hand

Advice 2: Listen to your patients

QUESTION