RHEUMATOID ARTHRITIS

Dr. Syed Muhammad Ali ShahRMO

Dept. of Medicine

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.

Epidemiology2,3

• Prevalence of 1%

• More common in women than men (female:maleratio 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

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

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.

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 proinflammatorycytokines, including TNF, IL-1, IL-6 and IL-15.

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 chondrocytesdrives destruction of bone and cartilage

• The RA joint is hypoxic and this promotes new blood vessel formation (neoangiogenesis).

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

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.

• 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.

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

• 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.

‘Swan neck’ deformity of the fingers.

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.

• 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 tibialisposterior tendon.

Cock Up Toe Deformity

EXTRA-ARTICULAR MANIFESTATIONS2

Systemic• Fever• Weight loss• Fatigue• Susceptibility to infectionMusculoskeletal• Muscle-wasting• Tenosynovitis• Bursitis• OsteoporosisHaematological• Anaemia• Thrombocytosis

• EosinophiliaLymphatic• Felty’s syndrome• SplenomegalyNodules• Sinuses • FistulaeOcular• Episcleritis• Scleritis• Scleromalacia• Keratoconjunctivitis sicca

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

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

INVESTIGATIONS2

Establish Diagnosis• Clinical criteria• ESR and CRP• Ultrasound or MRI• Rheumatoid factor andanti-citrullinated peptideantibodies

Monitor Disease Damage• X-rays • Functional assessment

Monitor Drug Safety• Urinalysis• Full blood count• Urea, creatinine and

liver function tests

*Criteria for Diagnosis ofRheumatoid Arthritis2,7

Criterion Score

Joints affected1 large joint 02–10 large joints 11–3 small joints ` 24 -10 small joints 34–10 small joints 5

SerologyNegative RF and ACPA 0Low positive RF or ACPA (<3 times ULN) 2High positive RF or ACPA (>3 times ULN) 3

Duration of symptoms< 6 wks 0> 6 wks 1

Acute phase reactantsNormal CRP and ESR 0Abnormal CRP or ESR 1

Patients with a score ≥ 6 are consideredto have definite RA.

*European League Against Rheumatism/American College of Rheumatology 2010 Criteria.

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.

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

Marginal erosions at metatarsal heads

Disease Activity Score 285

• 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

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

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

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

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.

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.

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)

Biological DMARDs2

*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 AntirheumaticDrugs and Biologic Agents in the Treatment of Rheumatoid Arthritis

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

Bibliography

1. Ferri's Clinical Advisor 20142. Davidsons Principles and Practice of Medicine 22ed3. Current Medical Diagnosis and Treatment 2014 4. 2012 Update of the 2008 American College of Rheumatology

Recommendations for the Use of Disease-Modifying AntirheumaticDrugs 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/DAS286. http://www.medscape.com/viewarticle/8345847. 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