Rachmat Gunadi Wachjudi  Lahir di Garut 16 Januari 1955Pendidikan- Dokter umum FK UNSRI Palembang-Internist FK UNPAD Bandu...
Comprehensive Management of   Autoimmune Disorders    in Internal Medicine      Rachmat Gunadi Wachjudi    Perhimpunan Reu...
The Basics• Autoimmunity occurs when the body is unable to differentiate “self” from “non-self”  –Results in overactive im...
4   4
5   5
Pathogenesis of Autoimmunity• Genetic predisposition and environmental factors relevant    – Immunoglobulins, T cell recep...
Many times there are no symptoms!                     Symptoms   Many different symptoms make   autoimmune disorders hard ...
Workup• History and Physical• Markers of inflammation (ESR, CRP)• Markers of immune activation (C3/C4)• Imaging studies (h...
Autoantibody Tests• ANA                     • P-ANCA• DS-DNA                  • C-ANCA• RF                      • Anti-GBM...
Dysthyroïdies             Arthritis                      RA/JIA                 Sjögren                                   ...
The impact of debiltating diseases                           SLEScleroderma                                     Dermatomyo...
The impact of autoimmune      disorders…….                           12
Clinical Features related to disability• Constitutional and multisystem effects• Chronic, no cure• Exacerbations (flares) ...
Major Features of Active Autoimmune disease• Constitutional – fatigue, malaise, fever, arthralgia, myalgia• Variable organ...
Stigmatisation                 15
The ritual             16
Could we have a baby ?                         17
The damages• Disease damage   – CKD, cognitive dysfunction, ovarial failure• Drug related   – Obesity, hypertension, diabe...
Life threatening                   19
Management principles• Diagnosis• Disease activity, severity, damage ?• Start remission induction  disease control• Treat...
The goal of treatment• Symptoms control• Disease activity as low as possible• Less medicinal side effects• Monitor co-morb...
Disease activity score: SLEDAI                    Total score1st January 2003        15        Urinary casts           (4)...
23
Remission induction            Immunosuppression• Reduce the activation or efficacy of the immune system• Leaves body ver...
Immunosuppression• Steroid• Azathioprine• Cyclosporine• Mycophenolic acid                               25
Treatments- Anti-Inflammatory• Remedy pain by reducing inflammation• Steroidal• Nonsteroidal  –Cox 1 selective, Cox 2 sele...
Disease Modifying Drugs• Improve symptoms• Alter disease course --- disease activity• Improve radiographic outcomes       ...
Disease Modifying Drugs• Methotrexate• Chloroquine• Sulfasalazine                                   28
Biologic therapies• B cell elimination:   • B cell depleting: anti-CD20   • B cell depleting/modulating: anti-CD22   • Spe...
Other treatments Helminthic therapy  inoculation of the patient with specific parasitic  intestinal nematodes Radiation ...
Features of autoimmune disorders         which can lead to disability• Related to disease activity   – constitutional     ...
Comorbidities     (various causes, independent of disease activity)• Organ damage (prior activity)    – kidney, brain (neu...
Social Aspects in SLE                      Extent of the Problem• Cohort of 159 patients with SLE working since diagnosis ...
Summary• Confirm the diagnosis if possible• Disease activity, severity, chronicity (damage) assessment• Co-morbidity ? Inf...
Emotional and Spiritual support                                  35
Role of the PhysicianCan help with elucidation of diagnostic features and severity of organ involvement, medications used,...
Orchestration                37
The journey to the ‘remission land’                                      38
Thank you We cordially invite you to      participate inReumatologi Klinik Bandung      9-10 Feb 2013
Upcoming SlideShare
Loading in …5
×

Comprehensive autoimmune disease management gunadi

884 views

Published on

an overview of autoimmune diseases management, focus on LUPUS

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
884
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
10
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide
  • Disease appears without warning or cause Hormone levels have been shown the affect severity of disease Low level autoimmunity- aid in recognition of neoplastic cells by T cells, reducing incidence of cancer - allows rapid immune response in early stages on infection when the availability of foreign antigens limits the response
  • Systemic autoimmune diseases affect skin, joints, kidney & muscle. Individual organs are more affected in some diseases than others.
  • Autoimmune diseases (AIDs) may be classified as organ-specific or systemic (non-organ-specific). There is a spectrum of AIDs including some that exhibit intermediate features.
  • Genetic factors- The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocytes , which are capable of self-reactivity. strong evidence to suggest that certain MHC class II allotypes are strongly correlated with specific autoimmune diseases: Inverse relationship between infectious and autoimmune disease Antigen- molecule that stimulates an immune response, proteins or polysaccharides, may have entered from outside the body, or have been generated within the cell Antibody- proteins found in body that are used by the immune system to identify and neutralize foreign objects, produced by B cells, bind to antigens tcell bypass- Molec mimicry- this amplifies the immune response Idiotype cross rxn- - Idiotypes are antigenic epitopes (molecule recognized by immune system found in the antigen-binding portion (Fab) of the immunoglobulin molecule. In this case, the host-cell receptor is envisioned as an internal image of the virus, and the anti-idiotype antibodies can react with the host cells. Cytokine dysreg- Cytokines (signaling proteins used in cell communication) have been recently divided into two groups according to the population of cells whose functions they promote: Helper T-cells type 1 or type 2. The second category of cytokines, which include IL-4, IL-10 and TGF-β (to name a few), seem to have a role in prevention of exaggeration of pro-inflammatory immune responses. Dendritic cell apoptosis - immune system cells called dendritic cells present antigens to active lymphocytes . Dendritic cells that are defective in apoptosis can lead to inappropriate systemic lymphocyte activation and consequent decline in self-tolerance
  • Pain at injections site lasts 24-48 hours
  • Comprehensive autoimmune disease management gunadi

    1. 1. Rachmat Gunadi Wachjudi Lahir di Garut 16 Januari 1955Pendidikan- Dokter umum FK UNSRI Palembang-Internist FK UNPAD Bandung-Subspesialis Reumatologi FK UI Jakarta- Clinical Rheumatology and OsteoporosisTraining – Perth - WAPekerjaanKa Div ReumatologiDepartemen Ilmu Penyakit Dalam Rumah Sakit dr Hasan Sadikin Bandung Organisasi: IDI, PAPDI, IRA, PEROSI, PERALMUNI 1
    2. 2. Comprehensive Management of Autoimmune Disorders in Internal Medicine Rachmat Gunadi Wachjudi Perhimpunan Reumatologi Cabang Bandung
    3. 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 3
    4. 4. 4 4
    5. 5. 5 5
    6. 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. 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 7
    8. 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. 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. 10. Dysthyroïdies Arthritis RA/JIA Sjögren PM DM CBI Scleroderma vasculitis SLE 10
    11. 11. The impact of debiltating diseases SLEScleroderma Dermatomyositis Undifferentiated CTD Polymyositis Sjogren’s syndrome 11
    12. 12. The impact of autoimmune disorders……. 12
    13. 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. 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) 14
    15. 15. Stigmatisation 15
    16. 16. The ritual 16
    17. 17. Could we have a baby ? 17
    18. 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 18
    19. 19. Life threatening 19
    20. 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 20
    21. 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 21
    22. 22. Disease activity score: SLEDAI Total score1st January 2003 15 Urinary casts (4) Proteinuria (4) Pyuria (4) Increased DNA binding (2) Fever (1)-> New drug given1st 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)22 22
    23. 23. 23
    24. 24. Remission induction  Immunosuppression• Reduce the activation or efficacy of the immune system• Leaves body very vulnerable to opportunistic infections 24
    25. 25. Immunosuppression• Steroid• Azathioprine• Cyclosporine• Mycophenolic acid 25
    26. 26. Treatments- Anti-Inflammatory• Remedy pain by reducing inflammation• Steroidal• Nonsteroidal –Cox 1 selective, Cox 2 selective 26
    27. 27. Disease Modifying Drugs• Improve symptoms• Alter disease course --- disease activity• Improve radiographic outcomes 27
    28. 28. Disease Modifying Drugs• Methotrexate• Chloroquine• Sulfasalazine 28
    29. 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. 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. 30
    31. 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. 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 32
    33. 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 33
    34. 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. 35. Emotional and Spiritual support 35
    36. 36. Role of the PhysicianCan 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 36
    37. 37. Orchestration 37
    38. 38. The journey to the ‘remission land’ 38
    39. 39. Thank you We cordially invite you to participate inReumatologi Klinik Bandung 9-10 Feb 2013

    ×