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Autoimmunity - Thinking outside of the box

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  1. 1. Thinking Outside the Box - Autoimmunity Glenn Reeves
  2. 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. 3. Antigen Pattern Recognition Receptor “Normal” Immune Response
  4. 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. 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. 6. Autoimmune Conditions occur in clusters
  7. 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. 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. 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. 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. 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. 12. UCTD (Undifferentiated Connective Tissue Disease)
  13. 13. 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
  14. 14. 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
  15. 15. 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