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Published byBarrie Dorsey Modified over 9 years ago
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Rheumatoid Arthritis Systemic chronic inflammatory disease
Mainly affects synovial joints Variable expression Prevalence about 3% Worldwide distribution Female:male ratio 3:1 Peak age of onset: years
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Rheumatoid Arthritis Unknown etiology Genetics Environmental
Possible infectious component Autoimmune disorder
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THE PATHOLOGY OF RA • Serositis 1. Synovitis • Nodules • Vasculitis
Joints Tendon sheaths Bursae • Nodules • Vasculitis
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Inflamed synovial membrane
RA Is Characterised by Synovitis and Joint Destruction NORMAL RA Inflamed synovial membrane Synovial membrane Major cell types: T lymphocytes macrophages Pannus Cartilage Minor cell types: fibroblasts plasma cells endothelium dendritic cells Synovial fluid Major cell type: neutrophils Capsule Cartilage thinning Adapted from Feldmann M, et al. Annu Rev Immunol. 1996;14:
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Numerous Cellular Interactions Drive the RA Process
Rheumatoid factors Immune complexes Bacterial products IL-1, TNF-, etc B cell IL-1 Soluble factors and direct cell–cell contact T cell HLA -DR Antigen- presenting cells Macrophage B cell or macrophage IL-1 and TNF- Synoviocytes Chondrocytes Pannus Articular cartilage Production of collagenase and other neutral proteases Arend W. Semin Arthritis Rheum. 2001;30(suppl 2):1-6.
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IL-1 and TNF- Have a Number of Overlapping Proinflammatory Effects
Proinflammatory effects of IL-1 Proinflammatory effects of TNF- COX-2 PGE2 NO Adhesion molecules Chemokines Collagenases IL-6 TNF- Osteoclast activation Angiogenic factors IL-1 cell death COX-2 = cyclo-oxygenase type 2; PGE2 = prostaglandin-E2; NO = nitric oxide
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IL-1 Plays a Pivotal Role in the Inflammatory and Destructive Processes of RA
Activates monocytes/ macrophages Induces fibroblast proliferation Activates chondrocytes Activates osteoclasts Inflammation Synovial pannus formation Cartilage breakdown Bone resorption
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Signs and Symptoms Joint inflammation Pain and stiffness
Tender, warm swollen joints Symmetrical pattern Pain and stiffness Symptoms in other parts of the body Nodules Anemia Fatigue, occasional fever, malaise
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JOINT INVOLVEMENT ON PRESENTATION OF RA
Polyarticular % Monoarticular % Small joints Knee % of hands and feet % Large joints % Shoulder } Wrist } Large and Hip } % Small joints % Ankle } Elbow }
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Articular features seen in the Rheumatoid Hand
WRIST: PIPs: Synovitis Synovitis Prominent ulnar styloid Fixed flexion or extension Subluxation and collapse of deformities carpus (Swan neck or boutonniere Radial deviation deformity) MCPs: THUMBS: Ulnar deviation ‘Z’ deformity Subluxation
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Joint Destruction
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Extra-articular manifestations
General fever, lymphadenopathy, weight loss, fatigue Dermatologic palmar erythema, nodules, vasculitis Ocular episcleritis/scleritis, scleromalacia perforans, choroid and retinal nodules
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Extra-articular manifestations
Cardiac pericarditis, myocarditis, coronary vasculitis, nodules on valves Neuromuscular entrapment neuropathy, peripheral neuropathy, mononeuritis multiplex Hematologic Felty’s syndrome, large granular lymphocyte syndrome, lymphomas
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Extra-articular manifestations
Pulmonary pleuritis, nodules, interstitial lung disease, bronchiolitis obliterans, arteritis, effusions Others Sjogren’s syndrome, amyloidosis
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Investigations: Hematology : CBC , ESR
Biochemistry : LFT , Renal profile Serology : RF , Anti-CCP Radiography : Joints , Spines ,Chest
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Treatment Goals Relieve pain Reduce inflammation
Prevent/slow joint damage Improve functioning and quality of life
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Treatment Approaches Lifestyle modifications Rest
Physical and occupational therapy Medications Surgery
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Rationale for the Early Treatment of R.A.
•Erosions develop early in the disease course •Destruction is irreversible •Disease activity is strongly associated with joint destruction later in the disease course •Early treatment can slow down radiographic progress •Disease activity must be suppressed maximally in its early stages to prevent destruction and preserve function
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Drug Treatments Nonsteroidal anti-inflammatory drugs (NSAIDs)
Disease-modifying antirheumatic drugs (DMARDs) Biologic response modifiers Corticosteroids
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Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Traditional NSAIDs Aspirin Ibuprofen Ketoprofen Naproxen COX-2 Inhibitors Celecoxib Rofecoxib
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Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
To relieve pain and inflammation Use in combination with a DMARD Gastrointestinal side effects
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Disease-Modifying Antirheumatic Drugs (DMARDs)
Hydroxychloroquine Sulfasalazine Methotrexate Leflunomide Gold Azathioprine
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Disease-Modifying Antirheumatic Drugs (DMARDs)
Control symptoms No immediate analgesic effects Can delay progression of the disease (prevent/slow joint and cartilage damage and destruction) Effects generally not seen until a few weeks to months
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DMARDs hydroxychloroquine mild non-erosive disease combinations
200 mg bid eye exams
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DMARDs Sulfasalazine Methotrexate 1 gm bid - tid CBC, LFTs
onset months Methotrexate most commonly used drug fast acting (4-6 weeks) po, SQ - weekly
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DMARDs IM Gold Oral Gold slow onset (3-6 months)
weekly then monthly injections CBC, UA before each injection Oral Gold less effective slow acting (4-6 months) daily CBC, UA
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Biologic Response Modifiers
Etanercept Infliximab Anakinra 36
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Biologic Response Modifiers
Etanercept and infliximab target tumor necrosis factor alpha (TNF-) Anakinra targets interleukin-1 receptor 36
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OSTEOARTHRITIS
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MULTIFACTORAL ETIOLOGY OF OA
● Joint instability ● Age ● Hormonal factors ● Trauma ● Altered biochemistry ● Inflammation ● Genetic predisposition ● ? Others
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SYMPTOMS AND SIGNS OF OA
Pain – worse on use of joint Stiffness – mild after immobility Loss of movement Pain on movement/restricted range Tenderness (articular or periarticular) Bony swelling Soft tissue swelling Joint crepitus
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RADIOLOGICAL FEATURES OF OA
Narrowing of joint space Osteophytosis Altered bone contour Bone sclerosis and cysts Periarticular calcification Soft-tissue swelling
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MANAGEMENT OF OSTEOARTHTITIS
Confirm diagnosis Initial Therapy : Pysiotherapy Wt loss Local therapy Paracetamol
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MANAGEMENT OF OSTEOARTHTITIS cont
Second-line approach: NSAIDS Intra-articular therapy: steroids,hyalurinate Opioids ?glucosamines Arthroscopy Surgery
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