an overview of autoimmune diseases management, focus on LUPUS

1. Rachmat Gunadi Wachjudi
Lahir di Garut 16 Januari 1955
Pendidikan
- Dokter umum FK UNSRI Palembang
-Internist FK UNPAD Bandung
-Subspesialis Reumatologi FK UI Jakarta
- Clinical Rheumatology and Osteoporosis
Training – Perth - WA
Pekerjaan
Ka Div Reumatologi
Departemen Ilmu Penyakit Dalam
Rumah Sakit dr Hasan Sadikin Bandung
Organisasi:
IDI, PAPDI, IRA, PEROSI, PERALMUNI
1

2. Comprehensive Management of
Autoimmune Disorders
in Internal Medicine
Rachmat Gunadi Wachjudi
Perhimpunan Reumatologi Cabang Bandung

3. The Basics
• Autoimmunity occurs when the body is unable
to differentiate “self” from “non-self”
–Results in overactive immune response
against own cells and tissues
• Affects 5%-8% of the population
–78% affected are females
• Over 100 conditions linked to autoimmunity
–15 diseases directly linked to autoimmune
response
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4. 4 4

5. 5 5

6. Pathogenesis of Autoimmunity
• Genetic predisposition and environmental factors relevant
– Immunoglobulins, T cell receptors, major histocompatibilty complex
• T Cell Bypass- The requirement of T cells to activate B cells in order to produce
large amounts of antibodies is bypassed
• Molecular Mimicry- An exogenous antigen shares structural similarities with
host antigen and when an antibody is produced, it can bind to host antigen
• Idiotype Cross Reaction- A cross reaction between the idiotype (molecule
recognized by antigen) on an antiviral antibody and a host cell receptor for the virus
in question
• Cytokine Dysregulation- Certain cytokines have a role in the prevention of
the exaggeration of pro-inflammatory immune response
• Dendritic Cell Apoptosis- Defective dendritic cells can lead to
inappropriate systemic lymphocyte activation and a decline in self tolerance
6

7. Many times there are no symptoms!
Symptoms
Many different symptoms make
autoimmune disorders hard to diagnose
• Tiredness • Swelling
• Depression • Rash
• Weight gain • Body pains
• Weight loss • Tremors
• Muscle weakness • Numbness
• Cramps • Fatigue
• Irritability • Loss of appetite
• Sweating • Insomnia
• Shaky • Coordination loss
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8. Workup
• History and Physical
• Markers of inflammation (ESR, CRP)
• Markers of immune activation (C3/C4)
• Imaging studies (hand/foot radiographs)
• Synovial fluid analysis
• Autoantibody testing
• Diagnostic criteria of 103 AID
8

9. Autoantibody Tests
• ANA • P-ANCA
• DS-DNA • C-ANCA
• RF • Anti-GBM
• CCP • ASCA
• Ro/La • ASMA
• Jo • LKM
• Scl-70 • AMA
• RNP • ACE
• Anti-Histone • TTG 9

10. Dysthyroïdies Arthritis
RA/JIA
Sjögren
PM DM
CBI
Scleroderma vasculitis
SLE
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11. The impact of debiltating diseases
SLE
Scleroderma
Dermatomyositis
Undifferentiated CTD
Polymyositis
Sjogren’s syndrome
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12. The impact of autoimmune
disorders…….
12

13. Clinical Features related to disability
• Constitutional and multisystem effects
• Chronic, no cure
• Exacerbations (flares) and remissions unpredictable
but usually treatable
• Treated with immunosuppressive medications – side
effects
• Comorbidities due to organ damage, to medication
side effects, to long term disease/treatment effects and
to other factors (eg psychological)
13

14. Major Features of Active Autoimmune disease
• Constitutional – fatigue, malaise, fever, arthralgia, myalgia
• Variable organ involvement
– Arthritis, pleurisy, pericarditis
– Raynauds phemomenon, vasculitis, stroke
– Mucocutaneous – rashes, oral ulcers, sicca syndrome,
– Kidney, CKD, NS
– Neuropsychiatric – psychosis, seizures, transverse myelitis
• Variable abnormalities in laboratory testing
– High ESR, CRP, anemia, low WBC, platelets, abnormal urinalysis
– RF, ACPA, Anti Scl-70, anti-DNA, low complement levels (C3, C4)
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15. Stigmatisation
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16. The ritual
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17. Could we have a baby ?
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18. The damages
• Disease damage
– CKD, cognitive dysfunction, ovarial failure
• Drug related
– Obesity, hypertension, diabetes
– osteoporosis, avascular necrosis
– Dyslipidemia
– Striae
• Premature atherosclerotic disease
– heart attack, stroke, heart failure
• Infection … opportunistic
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19. Life threatening
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20. Management principles
• Diagnosis
• Disease activity, severity, damage ?
• Start remission induction  disease control
• Treatment follow up and maintenance
• Non medicinal approaches
• Patient education and family involvement
• The role of support group
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21. The goal of treatment
• Symptoms control
• Disease activity as low as possible
• Less medicinal side effects
• Monitor co-morbidity and infection
• Quality of life maintenance
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22. Disease activity score: SLEDAI
Total score
1st January 2003 15 Urinary casts (4)
Proteinuria (4)
Pyuria (4)
Increased DNA binding (2)
Fever (1)
-> New drug given
1st February 2003 15 Seizure (8)
Proteinuria (4)
Increased DNA binding (2)
Leukopenia (1)
1st March 2003 15 Lupus headache (8)
Arthritis (4)
Increased DNA binding (2)
Leukopenia (1)
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23. 23

24. Remission induction 
Immunosuppression
• Reduce the activation or efficacy of the immune
system
• Leaves body very vulnerable to opportunistic
infections
24

25. Immunosuppression
• Steroid
• Azathioprine
• Cyclosporine
• Mycophenolic acid
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26. Treatments- Anti-Inflammatory
• Remedy pain by reducing inflammation
• Steroidal
• Nonsteroidal
–Cox 1 selective, Cox 2 selective
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27. Disease Modifying Drugs
• Improve symptoms
• Alter disease course --- disease activity
• Improve radiographic outcomes
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28. Disease Modifying Drugs
• Methotrexate
• Chloroquine
• Sulfasalazine
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29. Biologic therapies
• B cell elimination:
• B cell depleting: anti-CD20
• B cell depleting/modulating: anti-CD22
• Specific autoreactive B cell depletion: LJP394
• Co-stimulatory blockade:
• anti-CD40L, CTLA4-Ig, anti-ICOSL
• Other: anti-cytokine, anti-survival factors, factors up-stream
and down-stream of B cells
DC
• anti-BAFF, TACI-Ig
CD
CD
• anti-IL-10, anti-IL-6
20
20
TACI
• anti-IFNB Cell inhibitor BCMA B-cell
CD40CD40L T-cell
• BAFFR
anti-TNF , LTaB B7 CTLA
CD2
IIb
4
• anti-CXCL13
Rγ
2
Fc 29
• proteasome inhibition

30. Other treatments
 Helminthic therapy
inoculation of the patient with specific parasitic
intestinal nematodes
 Radiation of the lymph nodes and
plasmapheresis
 Treatment for the deficiency
- for example, insulin injections in the case of
diabetes.
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31. Features of autoimmune disorders
which can lead to disability
• Related to disease activity
– constitutional malaise, fatigue, fever
– structural organ effects renal insufficiency/failure,
deforming arthritis, disfiguring
skin rash
• Related to medication effects
acute and chronic infections, bone
and joint damage, mood swings,
weight gain, hypertension,
diabetes
• Functional changes “related
to AID” but not to active chronic fatigue, chronic muscle
disease** and joint pains, neurocognitive 31
**common dysfunction, depression

32. Comorbidities
(various causes, independent of disease activity)
• Organ damage (prior activity)
– kidney, brain (neurocognitive, stroke-extremity weakness)
• Medication effects (corticosteroids)
– obesity, hypertension, diabetes
– osteoporosis, avascular necrosis
• Premature atherosclerotic disease
– heart attack, stroke, heart failure
• Other
– Fibromyalgia
– Cognitive dysfunction
– Depression
– Chronic fatigue
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33. Social Aspects in SLE
Extent of the Problem
• Cohort of 159 patients with SLE working since diagnosis (Partridge et al:
Arthritis Rheum 1997; 40:2199)
– 40% quit work completely average of 3.4 years after diagnosis
– substantial job modifications
– predictors of early work disability – lower education status (no
college), health insurance status, physical rather than mental job,
low income, greater disease activity at time of diagnosis
• Inception cohort of 273 SLE patients
(Bertoli et al: Ann Rheum Dis 2007; 66:12)
- 19% self-report of disability at 5 years (25% in AA)
- predictors – age*, longer disease duration, male, poverty*, less
social support, higher disease activity and damage index
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34. Summary
• Confirm the diagnosis if possible
• Disease activity, severity, chronicity (damage)
assessment
• Co-morbidity ? Infection…
• Induction of remission
• Tight follow in a while, treatment maintenance
• See if there is any psycho-socio-economic burden
 patient educations, relatives and support group
involvement 34

35. Emotional and Spiritual support
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36. Role of the Physician
Can help with elucidation of diagnostic features and severity of
organ involvement, medications used, comorbidities
• Better to ask to support group help than to handle it one man
show
• Invite close relatives to participate in supporting the patients
• Emotional, spiritual and continuous educational approach
Please be respectful of physician’s limited time
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37. Orchestration
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38. The journey to the ‘remission land’
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39. Thank you
We cordially invite you to
participate in
Reumatologi Klinik Bandung
9-10 Feb 2013