Rheumatology

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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- 10-20% 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 1:20001:350 young

black females

9:1 female: male

broad spectrum: skin systemic

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

SLE: Clinical Features at Presentation Arthralgia/arthritis 55%

Skin 20%

Nephritis 5%

Fever 5%

Other 15%

Lupus: Arthritis (80-90%)

Migratory

Non-Erosive

Deformities (10%)

Lupus : Skin (70%)

Butterfly rashDiscoid rash plaquesPhotosensitive

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’stelangiectasias

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: 200-2000 = non-inflammatory 2000-100,000 = inflammatory >75,000 = septic

Gram stain, C&S

Crystals

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

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% Inuit 25%

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

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, strokeX renal effects like other NSAID’s

caution! - elderly - hypertension- cardiac disease- renal disease