Rheumatology Back to Basics Dr. Doug Smith

Immune Mechanisms of Disease Type I:Anaphylactic IgE eg. asthma Type II: Cytotoxic eg. AIHA Type III: Immune Complex eg. SLE Type IV: Cell-mediated/Delayed Hypersensitivity: T-cells eg. Contact dermatitis

HLA: Disease Associations HLA B27 (MHC Class I) - Ankylosing Spondylitis - Reiter’s - Psoriatic arthritis - IBD arthropathy HLA DR4, DR1 (MHC Class II) - RA HLA DR3 (MHC Class II) - SLE, Sjogren’s, Type I DM…

Rheumatoid Factor Anti-antibodies (Fc domain of IgG) Rheumatoid Arthritis: - sensitivity = 70% - poor prognosis - extra-articular features Non-specific: - other rheumatic diseases eg. Sjogren’s - chronic inflammatory diseases - chronic infections – SBE, Hep C % over age 65

Antinuclear Antibodies SLE: sensitivity = 90% + Specificity low: - other autoimmune dis., - family members - drugs...

Other Autoantibodies Anti-DNA (native, double-stranded) - SLE- sensitivity 60-70% - specificity ~ 100% - correlate with disease activity Anti-SSA, SSB (Ro, La) - Sjogren’s, SLE - congenital complete heart block

Antiphospholipid Antibodies Anticardiolipin antibodies Lupus anticoagulant Associations: - thrombosis - recurrent pregnancy losses - thrombocytopenia SLE, other CTD’s, primary

Anti-Neutrophil Cytoplasmic Antibodies (ANCA) Patients with suspected vasculitis - pulmonary/renal syndromes cANCA: Wegener’s Granulomatosus: - 80% sensitive and specific pANCA: less specific

Osteoarthritis (OA) The most common type of arthritis > 5 million Canadians Disease of cartilage (cf. RA) Characterized by: - Cartilage degradation, loss - hypertrophic bone formation (osteophytes...

Primary (idiopathic) OA Peripheral Joints: - hands- DIP, PIP (cf. RA) - 1st C-MC - feet - 1st MTP - large weight-bearing joints - hips, knees Spine- apophyseal joints - intervertebral discs

OA: Heberden’s (DIP) Bouchard’s (PIP) Nodes

Osteoarthritis: X-ray 1st C-MC Joint Joint space narrowing Subchondral sclerosis Osteophytes

Rheumatoid Arthritis Prevalence 1:100 small joint, symmetric polyarthritis + AM stiffness chronic (>6weeks) Path = synovial inflammation extraarticular features

RA: Extra-articular features Skin - sc nodules, vasculitis... Eyes - sicca, scleritis, episcleritis Lungs - pleurisy/effusion, interstitial fibrosis, nodules Cardiac - pericarditis, nodules Hematologic - anemia, Felty’s Neurologic - peripheral neuropathy...

RA: Factors Associated with Poor Prognosis Rheumatoid factor positivity HLA-DR4 haplotype Degree of disease activity at onset …  Early aggressive therapy

RA: Treatment Symptomatic - rest, education - splints, orthotics - ASA, NSAID’s, Coxibs (???) Disease Modifying Anti-Rheumatic Drugs (DMARDs)

RA: Common DMARD’s Methotrexate Hydroxychloroquine Sulfasalazine New Biologics...

RA: New Therapies - Biologics anti-TNF soluble TNF receptor Interleukin 1 Receptor Antagonist (IL-1RA) Concerns:- cost - parenteral - risk of infections, TB

Lupus Prevalence 1:2000 1:350 young black females 9:1 female: male broad spectrum: skin   systemic

SLE: Classification Criteria 1. Malar Rash 2. Discoid Rash 3. Photosensitivity 4. Oral ulcers 5. Arthritis 6. Serositis Renal Neurologic Hematologic Immunologic ANA

SLE: Clinical Features at Presentation Arthralgia/arthritis55% Skin 20% Nephritis5% Fever 5% Other15%

Lupus: Arthritis (80-90%) Migratory Non-Erosive Deformities (10%)

Lupus : Skin (70%) Butterfly rash Discoid rash plaques Photosensitive

Lupus: Treatment Sunprotection, sunscreens ASA, NSAIDs Antimalarial drugs Steroids Immunosuppressants

Scleroderma Disorder of: - small blood vessels = SPASM, ischemia + - overproduction of connective tissue (collagen) = FIBROSIS

Scleroderma: Types Systemic - Diffuse - Limited (CREST) Localized- morphea - linear scleroderma

Scleroderma: Antibodies ANA: common Systemic - Diffuse: anti-topoisomerase(Scl-70) - Limited (CREST): anti-centromere Localized: none

Scleroderma: Systemic Vascular: Raynaud’s telangiectasias Skin: swelling, thickening, tightening Esophagus: reflux, strictures… Lungs: - Pulmonary fibrosis - Pulmonary hypertension Kidneys: - hypertension, renal failure - esp. Diffuse

Raynaud’s phenomenon Triggers: cold, stress 3 phases: white  blue  red 8-10% of normals 90% - scleroderma

Scleroderma: kidneys Patients with diffuse disease Usually in first few years of disease Hypertension, renal failure Treatable/reversible! - ACE inhibitors

Limited Scleroderma (CREST) Calcinosis Telangiectasias

Acute Inflammatory Monoarthritis Infections Spondyloarthropathies Crystals

Synovial Fluid Testing Cell count, differential WBC: = non-inflammatory ,000 = inflammatory >75,000 = septic Gram stain, C&S Crystals

Spondyloarthropathies 1. Ankylosing Spondylitis 2. Reiter’s/reactiv e arthritis 3. Psoriatic arthritis 4. Inflammatory Bowel Disease Axial and/or peripheral joints HLA-B27 Path = enthesopathy Inflammatory back pain Extra-articular: - uveitis etc. RF negative

Reiter’s Syndrome

HLA-B27: Disease Associations Ankylosing Spondylitis>90% Reiter’s syndrome/ reactive 80% Inflammatory bowel disease 50% Psoriatic Arthritis - with spondylitis 50% - with peripheral arthritis 15% Caucasians 8% Inuit25%

Gout Acute monoarthritis - lasts days - recurrent attacks Uncontrolled hyperuricemia  tophi  polyarthritis

Gout: uric acid crystals Needle-shaped Strong negative bireringence Phagocytosed by PMN’s

Gout: Treatment Asymptomatic hyperuricemia  none Acute attack- NSAID’s - colchicine - steroid’s Indications to lower uric acid - allopurinol - renal stones - frequent attacks - tophi

Pseudogout - CPPD Acute monoarthritis Knees, wrists Chondrocalcinosis Pyrophosphate crystals: - rhomboid - weak positive birefringence

Vasculitis: Classification Small Vessel Hypersensitivity Medium Vessel: - necrotizing = Polyarteritis nodosa - granulomatous = Wegener’s Large Vessel: - Giant Cell (Temporal) arteritis - Takayasu’s (Aortic Arch Syndrome)

Giant Cell Arteritis (GCA) Age >50 years - mean = 70 years Symptoms related to arteries: - headache, scalp tenderness - visual loss - jaw claudication

Giant Cell (Temporal) Arteritis

Diagnosis: - CBC - anemia of chronic disease - ESR - markedly elevated, often >100 - Biopsy temporal artery Treatment: URGENT! (prevent visual loss) - steroids - prednisone 60mg daily...

Toxicity: ASA and NSAIDs GI renal CNS platelet effects contraindicated ASA hypersensitivity avoid if possible - pregnancy and lactation

Cox-2 “specific” Inhibitors (coxibs) improved GI safety no effect on platelets efficacious in RA, OA, pain X ?? Increased risk MI, stroke X renal effects like other NSAID’s  caution!- elderly - hypertension - cardiac disease - renal disease