Patofisiologi, jenis-jenis Patofisiologi, autoimun, faktor risiko, diagnosis, pencegahan ( nutrisi) dan pengelolaan pada penyakit autoimun. NANANG SUKMANA DIVISI DIV ISI ALE ALERG RGII - IMU IMUNO NOLOG LOGII KLI KLINIK NIK FKAUI / RSCM
Curriculum vitae Nama: dr. Nanang Sukmana, SpPD-KA SpPD-KAII Jenis Kelamin: Laki-laki Agama: Islam Tempat/Tgl. Lahir: Pegaden ( Subang ), 3 Agustus 1948 Status Keluarga: Nikah ( Anak dua ) Alamat Rumah: Rumah: Jl. Gambang No. 5 Kelapa Gading Gading Bangun Cipta Sarana Jakarta 14250 Telp. 4504683
PENDIDIKAN SD Negeri III di Pagaden: Ijazah Tanggal Tanggal 14 Juli 1961 SMP Negeri II di Subang: Ijazah Tanggal Tanggal 4 Juli 1964 SMA Sanjaya di Jakarta: Ijazah Tanggal Tanggal 20 Nopember 1967 1967 Lulus FKUI FKUI di Jakarta: Ijazah Tanggal 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 Februari 1980 : Bekerja di Poliklinik Umum Penyakit Dalam RSCM 11 Februari 1980 – 1980 – 18 Nopember 1987 : Mengikuti Pendidikan Pasca Sarjana Program Studi Ilmu Penyakit Dalam FKUI 18 Nopember 1987 – 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 – Nopember – Desember 1996 Anggota Koordinator Koordinator Pengadaan Pengadaan Dana Dies Natalis Universitas Universitas Indonesia Indonesia ke 43 Tingkat FKUI Maret 1992 Tim Dokter Kepresidenan Kepresidenan (Anggota Majelis Majelis Dokter Ahli) Jakarta, Jakarta, 16 Desember 1995 Tim Penanggulangan Penyalahgunaan Penyalahgunaan Narkotik RSCM. Penaggung jawab Pendidikan Konsultan Alergi – Alergi – Imunologi Klinik, 2008 s/d sekarang Kepala Divisi Alergi-Imunologi Klinik, Departemen Ilmu Penyakit Dalam FKUI/RSCM, Mei 2008 s/d sekarang
Defining Autoimmune Disease An autoimmune disease is a condition in which tiss tissue ue in inju jury ry is 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 ORGAN-SPECIF IC (SYSTEMIC) AUTOIMMUNE DISEASES
Organ-specific
Non org org ann-ss peci cific fic
Hashimoto thyroiditis Thyrotoxicosis Addison’s disease Atrophic gastritis Juvenile diabetes mellitus Multiple sclerosis
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%) •
„
„
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in kidney (90%)
Full Blood Count
normo mochr chrom omic ic Anemia - nor
normocytic, microcytic, macrocytic ?
chronic inflammation or illness blood loss – loss – e.g. NSAIDs, pulmonary haemorrhage Hemolysis
* * *
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
Thrombocytopenia * * *
SLE anti-phospholipid syndrome side effect of therapy
Urine and protein
Active urinary urinary sediments sediments always always indicate indicate active SLE – 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 i n diagnosis of SLE Highly sensitive for SLE. of SLE ANA is present in 95-99% of population. A negative test argues 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
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. 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)
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. patients. Often used to monitor response to therapy of o f 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%), 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 Alzh eimer's disease, and in autoimmune hepatitis. Has also been reported in patients receiving minocycline, etanercept, infliximab and penicillamine.
A utoantibodi utoantib odies es i n S L E 2 A utoantibody utoantibo dy A nti - S m A nti – R o A nti - L a
F r equency equenc y 30%; ver v eryy s pec pecii fificc for S L E 15-35% A nti R o in A NA
A nti nti-U1-U1-R R NP
40%
A nti nti-hi -hiss tone
D r ug -i -indu nducc ed lupus ( D L E ) , S L E
C lini lin i c al A s s oci oc i ati ati ons L upu upuss nephr nephrii tis SjÖgren’s/SLE SjÖgren’s/S LE overlap N eonata eonatall lupus Photosensitivity S ubacu ubacute te c utaneous lupus MCTD;Raynaud’s Tend not no t to to have nephritis Mild Mi ld ar thr thrii tis and s er eros os i tis
Sabatine, S Marc : Pocket Medicine Second Edition ; 2004
Indications for ordering anti-Ro/SSA
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
Yes (avoid after 32 weeks)
Yes
Yes
Yes
Y es
Yes
Yes
Yes?
Mycophenolate
No
No
Methotrexate
No
No
Cyclophosphami de
No
No
No
No
Warfarin
No (with caution after first trimester)
Yes
Heparin
Y es
Y es
Yes
Yes
NSAIDs Antimalarials Corticosteroids Azathioprine
Anti-TNF
AAS (low dose)
NSAIDS, non-steroidal anti-inflammatory drugs; AAS, aspirin
Looking for environmental factors at the right time Multiple environmental exposures
Genetically susceptible individual Early life infectious exposure may programme a “plastic” immune immune system
Disease Clinical disease Threshold
Edwards CJ and Cooper C. Early environmental environmental exposure and the development of lupus. Lupus 2006 ; 15 : 814-819.
Hip Fracture
Scleroderma
