rheumatology back to basics dr. doug smith. immune mechanisms of disease type i:anaphylactic ige eg....
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Rheumatology
Back to Basics
Dr. Doug Smith
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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
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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…
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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- 10-20% over age 65
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Antinuclear Antibodies
SLE: sensitivity = 90% + Specificity low:
- other autoimmune dis.,- family members- drugs...
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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
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Antiphospholipid Antibodies
Anticardiolipin antibodies Lupus anticoagulant
Associations:- thrombosis- recurrent pregnancy losses- thrombocytopenia
SLE, other CTD’s, primary
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Anti-Neutrophil Cytoplasmic Antibodies
(ANCA) Patients with suspected vasculitis
- pulmonary/renal syndromes
cANCA: Wegener’s Granulomatosus:
- 80% sensitive and specific
pANCA: less specific
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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...
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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
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OA: Heberden’s (DIP) Bouchard’s (PIP) Nodes
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Osteoarthritis: X-ray 1st C-MC Joint
Joint space narrowing
Subchondral sclerosis
Osteophytes
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Rheumatoid Arthritis
Prevalence 1:100 small joint,
symmetric polyarthritis
+ AM stiffness chronic (>6weeks) Path = synovial
inflammation extraarticular
features
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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...
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RA: Factors Associated with Poor Prognosis
Rheumatoid factor positivity HLA-DR4 haplotype Degree of disease activity at
onset …
Early aggressive therapy
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RA: Treatment
Symptomatic- rest, education- splints, orthotics- ASA, NSAID’s, Coxibs (???)
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
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RA: Common DMARD’s
Methotrexate Hydroxychloroquine Sulfasalazine New Biologics...
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RA: New Therapies - Biologics
anti-TNF soluble TNF receptor Interleukin 1 Receptor
Antagonist (IL-1RA) Concerns: - cost
- parenteral- risk of infections,
TB
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Lupus
Prevalence 1:20001:350 young
black females
9:1 female: male
broad spectrum: skin systemic
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SLE: Classification Criteria1. Malar Rash2. Discoid Rash3. Photosensitivi
ty4. Oral ulcers
5. Arthritis
6. Serositis
7. Renal
8. Neurologic
9. Hematologic
10. Immunologic
11. ANA
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SLE: Clinical Features at Presentation Arthralgia/arthritis 55%
Skin 20%
Nephritis 5%
Fever 5%
Other 15%
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Lupus: Arthritis (80-90%)
Migratory
Non-Erosive
Deformities (10%)
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Lupus : Skin (70%)
Butterfly rashDiscoid rash plaquesPhotosensitive
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Lupus: Treatment
•Sunprotection, sunscreens•ASA, NSAIDs•Antimalarial drugs•Steroids•Immunosuppressants
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Scleroderma
Disorder of:- small blood vessels = SPASM,
ischemia
+- overproduction of connective
tissue(collagen) = FIBROSIS
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Scleroderma: Types
Systemic - Diffuse
- Limited (CREST)
Localized - morphea- linear scleroderma
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Scleroderma: Antibodies
ANA: common
Systemic - Diffuse: anti-topoisomerase
(Scl-70)- Limited (CREST): anti-centromere
Localized: none
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Scleroderma: Systemic
Vascular: Raynaud’stelangiectasias
Skin: swelling, thickening, tightening Esophagus: reflux, strictures… Lungs: - Pulmonary fibrosis
- Pulmonary hypertension Kidneys: - hypertension, renal failure
- esp. Diffuse
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Raynaud’s phenomenon
Triggers: cold, stress
3 phases:white blue red
8-10% of normals
90% - scleroderma
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Scleroderma: kidneys
Patients with diffuse disease Usually in first few years of
disease Hypertension, renal failure Treatable/reversible!
- ACE inhibitors
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Limited Scleroderma (CREST)
Calcinosis
Telangiectasias
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Acute Inflammatory Monoarthritis
Infections
Spondyloarthropathies
Crystals
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Synovial Fluid Testing
Cell count, differential
WBC: 200-2000 = non-inflammatory 2000-100,000 = inflammatory >75,000 = septic
Gram stain, C&S
Crystals
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Spondyloarthropathies
1. Ankylosing Spondylitis
2. Reiter’s/reactive 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
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Reiter’s Syndrome
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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% Inuit 25%
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Gout
Acute monoarthritis- lasts days- recurrent attacks
Uncontrolled hyperuricemia tophi polyarthritis
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Gout: uric acid crystals
Needle-shaped
Strong negative bireringence
Phagocytosed by PMN’s
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Gout: Treatment
Asymptomatic hyperuricemia none Acute attack - NSAID’s
- colchicine- steroid’s
Indications to lower uric acid - allopurinol- renal stones- frequent attacks- tophi
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Pseudogout - CPPD
Acute monoarthritis Knees, wrists Chondrocalcinosis
Pyrophosphate crystals:
- rhomboid
- weak positive birefringence
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Vasculitis: Classification
Small Vessel Hypersensitivity
Medium Vessel:- necrotizing = Polyarteritis nodosa- granulomatous = Wegener’s
Large Vessel: - Giant Cell (Temporal) arteritis- Takayasu’s (Aortic Arch Syndrome)
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Giant Cell Arteritis (GCA)
Age >50 years - mean = 70 years Symptoms related to arteries:
- headache, scalp tenderness- visual loss- jaw claudication
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Giant Cell (Temporal) Arteritis
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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...
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Toxicity: ASA and NSAIDs
GI renal CNS platelet effects contraindicated ASA
hypersensitivity avoid if possible - pregnancy and
lactation
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Cox-2 “specific” Inhibitors (coxibs)
improved GI safety no effect on platelets efficacious in RA, OA, pain
X ?? Increased risk MI, strokeX renal effects like other NSAID’s
caution! - elderly - hypertension- cardiac disease- renal disease