Autoimmunity - Thinking outside of the box

1. Thinking Outside the Box -
Autoimmunity
Glenn Reeves

2. The Autoimmune Spectrum
 “Mischief” cells with autoimmune potential are in
everyone
 These cells are usually controlled by immune “regulator”
cells
 When circumstances conspire to impair this regulation,
autoimmunity turns into an autoimmune condition
 Autoimmune conditions are common
 Autoimmune conditions occur in clusters, extending
across many systems
 Labels are often misleading – think of a spectrum of
autoimmune processes

3. Antigen
Pattern
Recognition
Receptor
“Normal” Immune Response

4. Auto-Immune Disease:
Commoner Than You Think
Number 3 cause of illness (after vascular
disease and cancer)
Autoimmune diseases affect 1:20 people:
Coeliac
Diabetes (Type I)
Lupus
Scleroderma
Vasculitis
etc.
Chronic Urticaria
Thyroid disease
Pernicious anaemia
Sjögren’s
Inflammatory bowel
disease
etc.
Organ-Specific and Systemic Conditions

5. Autoimmune Burden: Facts 1.6 million Australians [21 million total],
 More than 100 interrelated diseases
 75% of those afflicted are women with most cases
occurring during the childbearing years.
 More than half of those with an autoimmune disease
suffered for 4 years and visited 4 doctors before
obtaining a diagnosis, and
 Half of women were told they were chronic complainers
or too concerned with their health prior to being
diagnosed.
 A close genetic relationship exists among autoimmune
diseases, explaining clustering in individuals and families
as well as common pathways for disease development.
 Epigenetic analysis has shown that environmental factors
can cause genes to be ‘‘turned on’’ or ‘‘turned off’’.
Differing exposures to environmental factors can result
in differing patterns of autoimmune expression.
 Understanding how to modulate immune system activity
will benefit transplant recipients, cancer patients, AIDS
patients, and infectious disease patients.
 Lack of awareness on the part of the public and health
care professionals contributes to patients’ extreme
difficulty in obtaining a correct diagnosis, and lack of
effective treatments.
 only 5.5 percent of Australians can even name an
autoimmune disease and 29 percent incorrectly identify
AIDS as an autoimmune disease.
Lupus
• affects at least 100,000 Australians
• About 1 out of 5 lupus sufferers receives
disability payments, costing the
Government several billion dollars each
year for Social Security disability benefits,
lost taxes, and medical care provided
through Medicare
• The average annual cost of medical
treatment for an individual with lupus is
$7,000 to $12,000; for some people,
medical costs may exceed several
thousand dollars every month.
Other Autoimmune Conditions:
• Multiple sclerosis - 28,000 individuals
• Sjogren’s syndrome - 250000 Australians
• Rheumatoid arthritis - 150000 people
• Systemic sclerosis - 20000 individuals
• Myasthenia gravis - ~2500 cases.
• Wegener’s granulomatosis (WG) strikes 1
in every 20,000 to 30,000 people.
• Alopecia areata, alopecia totalis, or
alopecia universalis > 310000 Australians,
• Pemphigus and pemphigoid - 100000
• Myositis - ~ 3500 Australians.
• Psoriasis or psoriatic arthritis - 345000
people in Australia
• Sarcoidosis - ~ 2000 cases in Australia.
Indigenous Australians++
• Vitiligo - 200000 to 400000 Australians

6. Autoimmune Conditions occur in clusters

7. Holistic Concept of Autoimmunity
Sleep
Energy
Immunity
Mood
Pain
Autoimmune
“Mischief”
Cells
Regulator
CellsSerotonin
Noradrenaline
Stress
Imbalance
Bereavement
Sleep ∆
Chronic Illness SkinBody
Joints
Organs
Glands
We’ll come back to stress later

8. Case 1: Mrs JH 35F
 Previously healthy
 3 month history
inflammatory small joint
polyarthropathy
 Fatigue ++
 Photosensitive rash
 Mild alopecia
 Recurrent oral ulceration
 Dry eyes and mouth
 Raynaud’s phenomenon
 OE: Tender across MCPs
FBC Normal
ESR 35 CRP 20
UEC LFT Urine Microscopy
Normal
ANA 1:320 Homogeneous
DNA 9
ENA: SSA Positive
Diagnosis: Lupus
Rx: Photoprotection;
Plaquenil; PRN Panadol

9. Sm
(“Smith”)
 95% specific for lupus, but only seen in 15-30% of patients
RNP  In a range of autoimmune conditions (rheumatoid, lupus, scleroderma,
Sjogren’s)
 In lupus, it is associated with milder, non-renal disease
 Isolated RNP (without other ENAs) associated with “mixed connective
tissue disease” ( Raynaud’s, swollen digits, arthropathy, serositis,
myopathy & oesophageal dysfunction)
SSA  Associated with photosensitive lupus skin disease (“subacute cutaneous
lupus”), neonatal lupus syndrome, and Sjogren’s syndrome
SSB  More specific for Sjogren’s than SSA
Ribosomal-P  95% specific for lupus
 Argument over its association with psychosis & renal disease
Scl-70  Highly specific for diffuse scleroderma, but only has a sensitivity of 30%
for the disease
 Associated with interstitial lung disease as well as severe skin and
musculoskeletal involvement in scleroderma
Jo-1  Highly specific for polymyositis, but only has a sensitivity of 30%
 Associated with development of interstitial lung disease

10. Autoimmune Features on History
 Fatigue
 Arthritis/EMS
 Rash (photosensitive)
 Alopecia
 Sicca (+dyspareunia)
 Raynaud’s
 Oral ulcers
 Serositis
• Reflux
• “IBS” (?CD)
• Neuropathy
• Nephritis
• Clots & miscarriages
• Myalgia/myopathy
• SOB / Palpitations
• Nocturia
• Blood problems
• Thyroid, other organ-
specific autoimmunity
• FHx organ-specific or
systemic autoimmunity

11. SLE Criteria (I)
74 clinical features reduced to 14 for
1971 ARA criteria
Further reduced to 11 in 1982
 Four out of 11 criteria required for diagnosis:
Malar rash Malar erythema, flat or rasied
Discoid rash Erythematous raised patches with keratotic scaling and follicular plugging
Photosensitivity Rash as an unusual reaction to sunlight
Oral ulcers Oral/nasopharyngeal ulcers, usually painless, observed by physician
Arthritis Nonerosive arthritis involving >=2 peripheral joints with tenderness, swelling or effusion
Serositis Pleuritis or pericarditis
Renal Proteinuria or cellular casts
Neurological Seizures or psychosis
Haematological Haemolysis, leucopaenia, lymphopaenia or low plateletes
Immunological LE cells, DNA, Sm or False positive VDRL
ANA No drugs known to cause DIL

12. UCTD
(Undifferentiated
Connective
Tissue Disease)

14. Names Can Distract
 Symptoms such as arthralgias, myalgias, fatigue,
Raynaud’s, alopecia, sicca etc. may be shared
between all conditions – lupus, scleroderma
 Sjogren’s may be “primary” or “secondary”
 Other features are more specific, but overlaps still
occur:
 Skin thickening – scleroderma
 Malar photosensitivity - lupus

15. Immunity &
Stress
 “Stress”  two major paths:
HPA (GCs) and SNS (CAs)
 Bidirectional links brain 
immune
 Chronic stress  cellular &
humoral immunosuppression
 Th2 > Th1
 Associated infection,
inflammation, cancer, wound
problems
 Holistic approach to patient
care most fruitful

16. Key Points
 When circumstances conspire to impair normal
regulation of “mischief” cells, autoimmunity occurs
 Autoimmunity is common & occurs in clusters, organ-
specific and systemic
 Labels are often misleading – think of a spectrum of
autoimmune processes