CTD objectives

1
CTD objectives

• Know why CTDs are considered autoimmune diseases
• Know what the epidemiology of CTDs implies about
  their pathophysiology
• Understand the concept of disease criteria
• Know the criteria for SLE and SSc
• Consider the role of immune pathways in
  autoimmune disease pathogenesis
• Review principals of therapy for SLE and PSS

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Recommended reading

• Primer on Rheumatic Diseases,
• 12Ed p335-352 and p357-367
• Lange Current Medical Dx and TX 2001- p841-849.
  844-846
• LeRoy EC, Lomeo R The spectrum of scleroderma.
  (parts 1 and 2) Hosp Pract 24(1989).
• Systemic Lupus Erythematosus. Science Medicine
  Jul-Aug, 1999, p 18-27.

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Connective Tissue Disease

• Definitions
• Connective tissue diseases are those syndromes
  manifest as multiple organ system involvement in
  which the pathogenesis is heavily dependent on
  self-directed immune mechanisms
• Examples
• SLE, MCTD, SS, PSS, polymyositis

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Connective tissue diseases (CTD) are
characterized by specific properties

• General systemic features-malaise, fever, weight
  loss
• Evidence for multiple organ system involvement
• Musculoskeletal involvement-arthritis, myalgia
• Immune alterations-lead to pathologic
  inflammation
• Therapeutic response to immunosuppression

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1997 update of the 82 revised criteria for SLE

• Malar rash
• Discoid rash
• Photosensitivity
• Oral ulcers
• Nonerosive arthritis
• Serositis

• Renal disorder
• Neurologic disorder
• Hematologic disorder
• Immunologic disorder
• Antinuclear antibody(ANA)

Must have 4 criteria
Modified from the Primer
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SLE CRITERIA DEFINITIONS
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SLE criteria definitions
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SLE criteria definitions
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SLE criteria definitions
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Antinuclear antibodies (ANA)

• 99 of SLE patients
• 5 of normals
• Prevalence is approximately 1/1000 women
• Hence- if 1000 women are tested 51 are ANA
  positive of which only 1 has SLE

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ANA Pattern associations
12
ANA testing
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ANA profiles in connective tissue disease
14
Malar rash of SLE
15
Subacute cutaneous lupus
16
Discoid rash
17
SLE-nonerosive arthritis
18
SLE onset by sex and age
19
SLE by race
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LE disease triggers

• Definite
• Ultraviolet light
• Drugs
• Sulfa antibiotics
• Probable
• Chemicals
• Hydralazine
• Procainamide
• Anti-TNF
• Hair dyes
• Lipstick
• Infections
• EBV

• Possible
• Smoke
• Vinyl chloride
• Asbestos
• Silicone
• Foods
• Hydrazines
• L-Canavanine

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Survival by decade
Modified from Wallace
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Serious or life-threatening consequences of SLE
23
SLE treatment
Modified from Wallace
24
Cytotoxic medications
25
Preliminary criteria for Scleroderma (PSS or SSc)

• Major criteria
• Proximal scleroderma
• Minor criteria
• Sclerodactyly
• Digital pitting
• Bibasilar pulmonary fibrosis

1 Major or two or more minor must be met.
Modified from the Primer
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Clinical subsets of scleroderma
27
Scleroderma antibodies
28
SclerodermadSSc lSSc
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Sclerodactyly of hands
30
Calcinosis cutis
31
Survival of dSSc vs normals
Normal
PSS
32
Scleroderma survival-Effect of Lung Disease
No lung dx
UIP
PAH
33
Diseased organ system or event leading to death
in patients with systemic sclerosis (dSSc).
34
Scleroderma lung
35
dSSc GI Renal
36
Treatment of sclerodermarenal crisis
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Treatment of scleroderma

• Focus on symptoms
• Antibiotics for bowel motility
• Gloves for Raynaud's
• Treat responsive syndromes
• PAH with bosentan, flolan, Rovatio
• Renal crisis with ACE inhibitors

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Summary

• CTD are multi-system diseases
• Immune mechanisms are key to their pathogenesis
  and therapy
• Diagnosis are clinically based using criteria
• Treatment is non-specific-aimed instead at
  specific manifestations
• A move toward prevention of key complications
  like CAD and renal crisis is in progress

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Case 1
A 23 year old female went hiking at Zion park
last week. Now, she presents with rash on her
chest and face, arthritis of her right knee and
severe chest pain that worsens with deep
inspiration or twisting movements of her back.
Further, she relates a history of her hands
looking as if they had frostbite every time she
failed to wear her gloves while skiing last
winter.
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Heliotrope and photosensitivity rash of
dermatomyositis
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Case 1
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Whats up Doc?
As her physician, you are convinced she has a CTD
and feel a diagnostic workup is in order. This
should include which of the following tests?

• ANA
• EMG
• Skin biopsy
• Muscle biopsy

• CXR
• Urinalysis
• CBC
• Head MRI

Be able to explain why each answer was offered,
even if it is not correct.