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PendidikanPendidikan

- - Dokter umum FK UNSRI PalembangDokter umum FK UNSRI Palembang

-Internist FK UNPAD BandungInternist FK UNPAD Bandung

-Subspesialis Reumatologi FK UI Subspesialis Reumatologi FK UI JakartaJakarta

- Clinical Rheumatology and - Clinical Rheumatology and Osteoporosis Training – Perth - WAOsteoporosis Training – Perth - WA

Rachmat Gunadi WachjudiRachmat Gunadi WachjudiLahir di Garut 16 Januari 1955Lahir di Garut 16 Januari 1955

PekerjaanPekerjaan

Ka Div ReumatologiKa Div Reumatologi

Departemen Ilmu Penyakit Dalam Departemen Ilmu Penyakit Dalam Rumah Sakit dr Hasan Sadikin Rumah Sakit dr Hasan Sadikin BandungBandung

Organisasi: IDI, PAPDI, IRA, PEROSI, PERALMUNI

Comprehensive Management of

Autoimmune Disordersin Internal Medicine

Rachmat Gunadi WachjudiPerhimpunan Reumatologi Cabang Bandung

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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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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

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Symptoms

• Tiredness

• Depression

• Weight gain

• Weight loss

• Muscle weakness

• Cramps

• Irritability

• Sweating

• Shaky

• Swelling

• Rash

• Body pains

• Tremors

• Numbness

• Fatigue

• Loss of appetite

• Insomnia

• Coordination loss

Many different symptoms make autoimmune disorders hard to diagnose

Many times there are no symptoms!

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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

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Autoantibody Tests

• ANA

• DS-DNA

• RF

• CCP

• Ro/La

• Jo

• Scl-70

• RNP

• Anti-Histone

• P-ANCA

• C-ANCA

• Anti-GBM

• ASCA

• ASMA

• LKM

• AMA

• ACE

• TTG

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Dysthyroïdies Arthritis RA/JIA

Sjögren

PM DM CBI

Scleroderma vasculitis

SLE

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The impact of debiltating diseases SLE

Dermatomyositis

PolymyositisUndifferentiated CTD

Sjogren’s syndrome

Scleroderma

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The impact of autoimmune disorders…….

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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)

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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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Stigmatisation

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The ritual

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Could we have a baby ?

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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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Life threatening

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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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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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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)

Disease activity score: SLEDAI

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Remission induction Immunosuppression

• Reduce the activation or efficacy of the immune system

• Leaves body very vulnerable to opportunistic infections

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Immunosuppression

• Steroid

• Azathioprine

• Cyclosporine

• Mycophenolic acid

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Treatments- Anti-Inflammatory

• Remedy pain by reducing inflammation

• Steroidal

• Nonsteroidal

–Cox 1 selective, Cox 2 selective

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Disease Modifying Drugs

• Improve symptoms

• Alter disease course --- disease activity

• Improve radiographic outcomes

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Disease Modifying Drugs

• Methotrexate

• Chloroquine

• Sulfasalazine

29FcR

FcRI

Ib

IIb

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

• anti-BAFF, TACI-Ig• anti-IL-10, anti-IL-6• anti-IFNB Cell inhibitor• anti-TNF , LTaB• anti-CXCL13• proteasome inhibition

DC

CD

22

TACI BCMA BAFFR

CD40CD40B-cell

CD20CD20

CD40LT-cellT-cell

B7B7 CTLA4

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Other treatmentsOther treatments Helminthic therapyHelminthic therapy inoculation of the patient with specific parasitic

intestinal nematodes

Radiation of the lymph nodes and plasmapheresis

Treatment for the deficiency Treatment for the deficiency - for example, insulin injections in the case of for example, insulin injections in the case of

diabetes. diabetes.

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Features of autoimmune disorderswhich can lead to disability

• Related to disease activity

– constitutional

– structural organ effects

• Related to medication effects

• Functional changes “related to AID” but not to active disease**

**common

malaise, fatigue, fever

renal insufficiency/failure, deforming arthritis, disfiguring skin rash

acute and chronic infections, bone and joint damage, mood swings, weight gain, hypertension, diabetes

chronic fatigue, chronic muscle and joint pains, neurocognitive dysfunction, depression

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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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Social Aspects in SLEExtent 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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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

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Emotional and Spiritual support

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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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Orchestration

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The journey to the ‘remission land’

Thank you

We cordially invite you to participate in

Reumatologi Klinik Bandung

9-10 Feb 2013