Dr Nanang Sukmana, Sppd-kai - Penyakit Autoimun 5t6s6y

Patofisiologi, jenis-jenis autoimun, faktor risiko, diagnosis, pencegahan ( nutrisi) dan pengelolaan pada penyakit autoimun. NANANG SUKMANA DIVISI ALERGI - IMUNOLOGI KLINIK FKAUI / RSCM

Curriculum vitae Nama: dr. Nanang Sukmana, SpPD-KAI Jenis Kelamin: Laki-laki Agama: Islam Tempat/Tgl. Lahir: Pegaden ( Subang ), 3 Agustus 1948 Status Keluarga: Nikah ( Anak dua ) Alamat Rumah: Jl. Gambang No. 5 Kelapa Gading Bangun Cipta Sarana Jakarta 14250 Telp. 4504683

PENDIDIKAN SD Negeri III di Pagaden: Ijazah Tanggal 14 Juli 1961 SMP Negeri II di Subang: Ijazah Tanggal 4 Juli 1964 SMA Sanjaya di Jakarta: Ijazah Tanggal 20 Nopember 1967 Lulus FKUI di Jakarta: Ijazah Tanggal 18 Juni 1974 Lulus Pasca Sarjana Program Studi I.P.D: Ijazah Tanggal 18 Nopember 1987 Konsultan Alergi-Imunologi Klinis I.P.D: 12 Maret 1999

PENGALAMAN KERJA  1 Februari 1975 – 11 Februari 1980 : Dokter Depkes yang ditempatkan pada RSCM Jakarta  1977 s/d Februari 1980 : Bekerja di Poliklinik Umum Penyakit Dalam RSCM  11 Februari 1980 – 18 Nopember 1987 : Mengikuti Pendidikan Pasca Sarjana Program Studi Ilmu Penyakit Dalam FKUI  18 Nopember 1987 – Sekarang : Bekerja di Subbagian Alergi-Imunologi Klinik Bagian Ilmu Penyakit Dalam FKUI – RSCM.  Wakil Kepala IGD RSCM 28 Februari 1995 s/d 1998  Kepala Instalasi Rawat Jalan RSCM 1998 s/d 2002  Kepala Pelatihan Keperawatan Penata di IGD 21 Desember 1995  Pelatihan di Bidang Vaskulitis di SLE Royal Adelaide Hospital Nopember – Desember 1996  Anggota Koordinator Pengadaan Dana Dies Natalis Universitas Indonesia ke 43 Tingkat FKUI Maret 1992  Tim Dokter Kepresidenan (Anggota Majelis Dokter Ahli) Jakarta, 16 Desember 1995  Tim Penanggulangan Penyalahgunaan Narkotik RSCM.  Penaggung jawab Pendidikan Konsultan Alergi – Imunologi Klinik, 2008 s/d sekarang  Kepala Divisi Alergi-Imunologi Klinik, Departemen Ilmu Penyakit Dalam FKUI/RSCM,  Mei 2008 s/d sekarang  Ketua PB Peralmuni, 2012-2015

Defining Autoimmune Disease An autoimmune disease is a condition in which tissue injury is caused by T-cell or antibody reactivity to self. The immune activation may be initiated by infection, but must persist in the absence of any detectable microbial antigen. (Davidson and Diamond, 2001).

Autoantibodies Precede Disease by Years Some AutoAb before Dx: 80%

ANA: 3 yrs Anti-Ro/La

Arbuckle et al NEJM 2003

Anti-DNA: 2 yrs Anti-PL

Anti-Sm: 1 yr Anti-RNP

EXAMPLES 0F ORGAN-SPECIFIC AND NON ORGAN-SPECIFIC (SYSTEMIC) AUTOIMMUNE DISEASES

Organ-specific  Hashimoto thyroiditis  Thyrotoxicosis  Addison’s disease  Atrophic gastritis  Juvenile diabetes mellitus  Multiple sclerosis

Non organ-specific  Systemic lupus (SLE)  Rheumatoid arthritis (RA)  Scleroderma  Dermatomyositis  Mixed connective tissue disease (MCTD)  Sjögren’s syndrome

DIAGNOSTIC STEPS IN SYSTEMIC LUPUS • • • • • • •

Immunoglobulin level (↑ >90%) Complement components level (↓60%) Anti-nuclear antibodies(ANA)(1:80< 95%) Anti-ds DNA Ab (90-95%) Rheumatoid factor (30%) Immune complex deposits in the skin(60%) „ „ „ in kidney (90%)

Full Blood Count 

Anemia - normochromic

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normocytic, microcytic, macrocytic ?  

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chronic inflammation or illness blood loss – e.g. NSAIDs, pulmonary haemorrhage Hemolysis

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SLE (lymphopenia <1500/mm3) Sjogren’s syndrome side effect of medications

Thrombocytosis * *

Leucocytosis 

Leucopenia

blood loss e.g. GI, lung other inflammatory arthritis or systemic vasculitis

infection

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Thrombocytopenia * * *

SLE anti-phospholipid syndrome side effect of therapy

Urine and protein Active urinary sediments always indicate active SLE – rbc, granular or rbc casts.  Proteinuria indicates renal involvement but not necessarily active renal disease.  Proteinuria may be due to other causes such as renal vein thrombosis from secondary APS. 

Clinical interpretation of ANA staining pattern

Role of the ANA test in diagnosis of SLE Highly sensitive for SLE.  ANA is present in 95-99% of SLE population.  A negative test argues strongly against a diagnosis of SLE.  Lacks specificity: should only be ordered if the pre-test probability of SLE is high. 

Value of ANA test titer 

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Presence of very high concentrations of antibody (titer >1:640) should arouse suspicion of an autoimmune disorder. However, its presence alone is not diagnostic of disease. If no initial diagnosis can be made, watch the patient carefully over time to exclude ANA associated diseases. The combination of very low titers of antibody (1:80 or lower) and no signs or symptoms of disease suggest a much less ominous prognosis. Need reevaluation far less frequently than those with extremely high antibody titers.

Anti-double stranded DNA (dsDNA)  

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Is relatively specific (97%) for SLE. Helps in diagnosis but not useful as screening test for SLE since positive in only about 60% of SLE patients. Often used to monitor response to therapy of lupus. Some patients have elevated titers of anti-dsDNA antibodies in the setting of inactive or minimally active lupus. Found at low frequency (generally less than 5%), and usually in low titer and with low avidity, in patients with rheumatoid arthritis, Sjögren's syndrome, scleroderma, Raynaud phenomenon, mixed connective tissue disease, discoid lupus, myositis, uveitis, juvenile arthritis, antiphospholipid syndrome, Grave's disease, Alzheimer's disease, and in autoimmune hepatitis. Has also been reported in patients receiving minocycline, etanercept, infliximab and penicillamine.

Autoantibodies in SLE2 Autoantibody

Frequency

Clinical Associations

Anti - Sm

30%; very specific for SLE

Lupus nephritis

Anti – Ro Anti - La

15-35% Anti Ro in ANA

SjÖgren’s/SLE overlap Neonatal lupus Photosensitivity Subacute cutaneous lupus

Anti-U1-RNP

40%

MCTD;Raynaud’s Tend not to have nephritis

Anti-histone

Drug-induced lupus (DLE), SLE

Mild arthritis and serositis

Sabatine, S Marc : Pocket Medicine Second Edition ; 2004

Indications for ordering anti-Ro/SSA 

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Women with SLE planning to or who have become pregnant. Women who have a history of giving birth to a child with heart block or myocarditis. Patients with a history of unexplained photosensitive skin eruptions. Patients suspected of having a systemic connective tissue disease in whom the screening ANA test is negative. Patients with symptoms of xerostomia, keratoconjunctivitis sicca and/or salivary and lacrimal gland enlargement. Patients with unexplained small vessel vasculitis or atypical multiple sclerosis.

Drugs In Pregnancy and Lactation Pregnancy

Lactation

NSAIDs

Yes (avoid after 32 weeks)

Yes

Antimalarials

Yes

Yes

Corticosteroids

Yes

Yes

Azathioprine

Yes

Yes?

Mycophenolate

No

No

Methotrexate

No

No

Cyclophosphami de

No

No

Anti-TNF

No

No

Warfarin

No (with caution after first trimester)

Yes

Heparin

Yes

Yes

AAS (low dose)

Yes

Yes

NSAIDS, non-steroidal anti-inflammatory drugs; AAS, aspirin Lupus and Pregnancy : ten questions and some answers. Gruiz-Irastorza and MA Khamashta. Lupus (2008)17, 416-420

Looking for environmental factors at the right time

Multiple environmental exposures

Genetically susceptible individual Early life infectious exposure may programme a “plastic” immune system

Disease Clinical disease Threshold

Edwards CJ and Cooper C. Early environmental exposure and the development of lupus. Lupus 2006 ; 15 : 814-819.

Hip Fracture

Scleroderma