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

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

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

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.

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

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)

The Pathogenesis of RA

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)

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

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

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

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

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

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).

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

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

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

Differential Diagnosis of RA

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

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

Rheumatoid factor Are IgM antibodies directed against the Fc portion of immunoglobulin G (IgG) 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 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%) 

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

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

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

SYNOVIAL FLUID:

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

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

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

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

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

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

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

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

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

Biologic disease modifying anti-rheumatic drugs

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

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

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

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

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

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