kuliah erupsi obat
DESCRIPTION
VGFFTRANSCRIPT
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ERUPSI OBATERUPSI OBAT
LAB / SMF Ilmu Kesehatan Kulit dan Kelamin
FK U.J / RSU Dr SoebandiJEMBER
Bambang Suhariyanto
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Toxic Epidermal Necrolysis disebabkan oleh antikonvulsan Hidantoin
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Obat(Dx, Px, Tx)
Adverse Drug Reaction(ADR)
Adverse Drug Reaction(ADR)
kulit organ
drug eruption(erupsi obat) - ringan - berat
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IDENTIFIKASI ERUPSI OBAT
1. Riwayat penggunaan obat-obat yang dicurigai / reaksi silang
2. Penyebab lain selain obat-obatan3. Waktu kejadian4. Kadar obat / dosis5. Reaksi terhadap penghentian obat6. Reaksi terhadap pemberian ulang
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ERUPSI OBATERUPSI OBAT
Metabolisme obat Status imunologi penderita Penyakit lain Obat lain yang diberikan
bersamaan
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OBATOBAT
DetoksikasiDetoksikasi ExkreasiExkreasi
Toxic / Reactive metabolite
Toxic / Reactive metabolite
Immunogenic hapten
Immunogenic hapten Non Toxic /
Non ReactiveNon Toxic /
Non Reactive
Phase I(CyP450)
Phase I(CyP450)
Phase IIAsetilasi
Conjungasidsb
Phase IIAsetilasi
Conjungasidsb
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• Tidak diketahui• Non imunologis• Imunologis
– Respon imun (immune response) terhadap• obat• metabolit• kontaminan
– Human Leukocyte Antigen (HLA)– Kondisi klinis– Abnormalitas metabolisme obat
Respon imun reaksi hipersensitivitas
– sensitisasi o.k. paparan obat sebelumnya– reaksi silang
PATOGENESIS ERUPSI OBAT
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REAKSI TIPE I(IgE dependent))
• Histamine• Eosinophil chemotactic factor of anaphylaxis• Leukotriene C4• Prostaglandin D2• Cytokines
Mast cellBasophil
Mast cellBasophil
Kulit Respiratory Tract Cardiovascular
PruritusUrticaria
Kontraksi- Smooth muscle- Sekresi mocous- Laryngeal edema
Dilatasi / permeabilitas - Edema- Hypotension
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REAKSI TIPE II(Ab mediated)
Contoh: thrombocytopenic purpura
obatobat
selsel
Ig Complement(IgG, IgM)
Cell damage(cytolysis)
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aktivasi complement
anaphylatoxin(C3a, C5a)
mast cellbasophil
mediatorsrelease
REAKSI TIPE III(Immune complex)
Contoh :- Serum sickness- Vasculitis- Arthus Reaction
Immune complex
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REAKSI TIPE IV(cell mediated)
Contoh: Erythema Multiforme
T lymphocytes / CMI
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Bentuk Klinis Erupsi Obat
1. Exanthems2. Hypersensitivity Syndrome3. Urticaria / Angioedema4. Red man syndrome5. Reaksi fotosensitivitas6. Pustular Reaction7. Drug Induced Pigmentation8. Vasculitis & serum sickness like reactions9. Fixed drug reaction10. Lichenoid reactions11. Bullous drug reactions
Bentuk Klinis Erupsi Obat
1. Exanthems2. Hypersensitivity Syndrome3. Urticaria / Angioedema4. Red man syndrome5. Reaksi fotosensitivitas6. Pustular Reaction7. Drug Induced Pigmentation8. Vasculitis & serum sickness like reactions9. Fixed drug reaction10. Lichenoid reactions11. Bullous drug reactions
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• Paling sering dijumpai• Etiologi
- Penisillin- Sulfa methoxazole / Trimetoprim
• Masa awitan: - 1 mg – 2 mg sesudah Tx - sesudah stop Tx
• Pathogenesis: T cell Dermatitis Kontak Alergi ?• Klinis:
- maculopapular (erithema + papula) pada inguinal / aksila
menyebar dalam 1 – 2 hari - pruritus: ++ DD viral infections
Berat Complex exanthems (Hypersensitivity Syndromes)- demam + rash- hepatitis- nephritis - dsb
• Paling sering dijumpai• Etiologi
- Penisillin- Sulfa methoxazole / Trimetoprim
• Masa awitan: - 1 mg – 2 mg sesudah Tx - sesudah stop Tx
• Pathogenesis: T cell Dermatitis Kontak Alergi ?• Klinis:
- maculopapular (erithema + papula) pada inguinal / aksila
menyebar dalam 1 – 2 hari - pruritus: ++ DD viral infections
Berat Complex exanthems (Hypersensitivity Syndromes)- demam + rash- hepatitis- nephritis - dsb
1. EXANTHEMS (morbiliform / Scarlatiniform)
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ERUPSI EKSANTEMERUPSI EKSANTEM
Erupsi Makulopapular
Erupsi Morbiliformis
Histopatologi anatomi erupsi obat eksantem Infiltrat inflamasi perivaskular superfisial dengan sejumlah eosinofil
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• Insidens : 1 : 5000 Px• Masa awitan : 2 mg – 6 mg febris• Klinis:
- morbiliformis - eczema (fase awal) - bullae
- purpura - mengelupas
- tanda lain : - mukosa - pharingitis - lymphadenopathy - hepatosplenomegali
- Lab: - eosinophilia - lymphocytosis - LFT - nephritis
2. HYPERSENSITIVITY SYNDROME
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• Contoh : Anti convulsant Hypersensitivity Syndrome
- Dilantin Hypersensitivity Syndrome- Phenobarbital Hypersensitivity Syndrome- Carbamazepine Hypersensitivity Syndrome
Sulfonamide Hypersensitivity Syndrome
Allopurinol Hypersensitivity Syndrome
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Sindroma Hipersensitivitas Obat Disebabkan Karbamazepin
Sindroma Hipersensitivitas Obat Disebabkan Karbamazepin
Histopatologi anatomi SHOHistopatologi anatomi SHOKulit menunjukkan dermatitis limfositik superfisial Kulit menunjukkan dermatitis limfositik superfisial
dan dermal perivaskular dengan skuama, krusta dan dan dermal perivaskular dengan skuama, krusta dan sejumlah eosinofilsejumlah eosinofil
Sindroma Hipersensitivitas Obat disebabkan Karbamazepin
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Etiologi : Penisilin / lactam Aspirin / NSAID Angiotensin Converting Enzym (ACE) inhibitor
Patogenesis: - Non imunologi - Imunologi
Penisilin / lactam reaksi tipe IAspirin / NSAID urtikaria non imunologi
merubah metabolisme prostaglandin
degranulasi mast cell
ACE inhibitor Angioedema (Quincke’s edema)
3. URTICARIA / ANGIOEDEMA
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URTIKARIAURTIKARIA
Lesi kulit Urtikaria setelah pemberian Vaksin Influenza
Histopatologi anatomi urtikariaCampuran infiltrat inflamatori perivaskular dengan eosinofil,
khas ditemukan pada urtikaria yang diinduksi oleh obat.
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ANGIOEDEMA
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Etiologi : Vancomycin iv histamin
Klinis:
- makula pada umumnya pada leher belakang menyebar ke badan, muka dan lengan- angioedema- pruritus- hipotensi
4. RED MAN SYNDROME
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RED MAN SYNDROMERED MAN SYNDROME
Eritema difus dan skuama pada tungkai setelah mendapat terapi Vancomycin
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Fotosensitivitas - Reaksi Foto toksik - Reaksi Likenoid - ReaksiFoto alergik - Pseudoporfiria
Etiologi : - Tetrasiklin- Amiodaron- NSAID
Mekanisme - absorbsi obat terhadap UV- penetrasi UV pada kulit
Reaksi Foto toksik : - dose related obat / UV- beberapa jam – hari sesudah paparan- menetap sesudah stop Tx
Reaksi Foto alergik: - tidak dipengaruhi dosis- terjadi sesudah beberapa kali paparan- hipersensitivitas pruritus / eksematosa- menetap sesudah stop Tx
5. REAKSI FOTOSENSITIVITAS (Photosensitive Drug Reaction)
Obat photosensitizer
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REAKSI FOTOTOKSIK & FOTOALERGIKREAKSI FOTOTOKSIK & FOTOALERGIK
Eritema dorsum manus setelah mengkonsumsi demetilklortetrasiklin untuk terapi acne
Dermatitis ekzematus dengan hiperpigmentasi area terpapar matahari. Penderita mengkonsumsi trimetoprim-sulfame.toksazol sebagai profilaksis
primer Pneumocystis carinii pneumonia
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Reaksi Likenoid(Lichenoid photo eruption)
• Etiologi : Thiazide (diuretic)
Quinidine
NSAID
• Lokasi sun exposed / photo distribution• Effloresensi papula eritematus
plakat
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Erupsi LikenoidErupsi Likenoid akibat Quinidinakibat Quinidin
Erupsi LikenoidErupsi Likenoid akibat Garam Emasakibat Garam Emas
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Reaksi pseudoforpiria(Pseudophorphyria reaction)
• Etiologi : Naproxene
Furosemide
Tetracycline
Dapsone
• Effloresensi : bulla (~ Porfiria cutanea tarda)
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Histopatologi Anatomi PseudoporfiriaBula dengan sedikit inflamasi
Pseudoporfiria disebabkan Tetrasiklin
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(1) Acute Generalized Exanthematous Pustulosis (AGEP – PEGA)
Sin : Pustular Drug Eruption, Toxic PustulodermaEtiologi : - merkuri
- beta lactam - macrolide
Insidens : Ax Psoriasis vulgaris (+) pada 17% kasusMasa awitan : + 5 hari sesudah TxKlinis : - Scarlatiniform erythema
menyebar pustulasi < 5 mm(Nikolsky sign: dapat + )desquamasi
- febris (+)Lab : Neutrofilia; Eosinofilia
6. ERUPSI PUSTULAR
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PUSTULAR EKSANTEMATOUS GENERALISATA AKUT (PEGA)
Pustul dengan dasar eritem setelah penggunaan Azitromicin
Pustul spongioform pada dasar epidermis dengan oedem dan neutrofil pada papillary
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(2) Acneiform Eruption
Etiologi : glucocorticoid, isoniazid,
androgen, phenitoin dsb
Klinis :lokasi pada area yang atipikal
- monomorfisme (Comedone -)
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Etiologi : - minosiklin- chloroquine / hydroxy chloroquine- quinacrine- quinidine
- clofazimine- zidovudine
- chlorpromazine
Pathogenesis:- Post Inflammatory Hyperpigmentation ( Hiperpigmentasi Pasca Inflamasi)- timbunan obat pada kulit
Etiologi : - minosiklin- chloroquine / hydroxy chloroquine- quinacrine- quinidine
- clofazimine- zidovudine
- chlorpromazine
Pathogenesis:- Post Inflammatory Hyperpigmentation ( Hiperpigmentasi Pasca Inflamasi)- timbunan obat pada kulit
7. DRUG INDUCED PIGMENTATION
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Drug Induced Pigmentation
Pigmentasi AmiodaronPigmentasi Minosiklin
HPA : Makrofag terisi granul pigmen
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klinis menyerupai, immune complex (-)
Etiologi : CefaclorMasa awitan : + 7 hariKlinis :
urtikaria dengan warna lebih gelap pada sentralpruritusedema / bengkak pada akralnyeri sendi kaki / tangan
8. VASCULITIS & SERUM SICKNESS LIKE REACTIONS
8. VASCULITIS & SERUM SICKNESS LIKE REACTIONS
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VASCULITIS
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SERUM SICKNESS LIKE REACTIONSERUM SICKNESS LIKE REACTION
Reaksi serupa serum sickness disebabkan oleh Amoksisilin
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Obat / erupsi di tempat yang samaReaksi silang + (50% sekitar mulut / genitalia)
Etiologi : - NSAID - mefenamic acid - sulfonamide - trimethoprim - barbiturate - tetracyclin - dsb
Pathogenesis : ( HLA ) ?Klinis : bercak merah iris / target lesion blister
erosi prolonged / permanent Post Inflammatory Hyperpigmentation
9. FIXED DRUG REACTION (Fixed Eruption)
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Fixed Drug EruptionFixed Drug Eruption Non Pigmented Fixed Drup EruptionNon Pigmented Fixed Drup Eruption
Histopatologi Anatomi Histopatologi Anatomi Non Pigmented Fixed Drug EruptionNon Pigmented Fixed Drug Eruption
Fixed Drug Eruption
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Bullous Fixed Drug Eruption
Fixed Drug Eruption Bullosa disebabkan Pseudoefedrin. patch eritematous oval. Beberapa plak yang lebih besar
dengan bula yang flaccid (mudah pecah).
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Etiologi : HydrochlorothiazideNSAIDsd-penicillamineCaptoprilQuinidine
Klinis : Lichenoid photo eruption UV generalized
Klinis : - papula - plakat - exfoliative erythema
10. LICHENOID REACTION
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Erupsi LikenoidErupsi Likenoid akibat Quinidinakibat Quinidin
Erupsi LikenoidErupsi Likenoid akibat Garam Emasakibat Garam Emas
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- Erythema multiforme
- Stevens Johnson Syndrome
- Toxic Epidermal Necrolysis
11. BULLOUS DRUG REACTION
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Sifat : - self limited - Gx ringan / exanthems - berulangEtiologi : HSV 1 & HSV 2 Herpes Simplex Associated Erythema Multiforme (HAEM) (Erythema multiforme minor)Pathogenesis T lymphocyt – HLAKlinis : prodrome : minimal s/d ringan
lesi kulit : makula eritema batas jelas meninggi papula edematus dlm 24-48 jam ring erythematous
central flat purpuric3 zones target (iris) lesion:
- central purpura- elevated / edematous pale ring- macular erythema
ERYTHEMA MULTIFORME
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ERITEMA MULTIFORMEERITEMA MULTIFORME
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• EM HSV EM minor ( HAEM )
• SJS
TEN
• True EM :
EM minor
EM with mucosa involvement
Drugs EM major
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<10%(SJS)
>30%TEN
Body Surface Area (BSA)
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STEVENS JOHNSON SYNDROME
Lesi pada tungkai dan proksimal ekstremitasDaerah gelap merupakan tempat nekrosis ‘
EpidermisMakula purpura tipikal dari SJS
Makula bergabung membentuk Bula
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SJS / TEN
SJS TENInsidens per tahun 1,2 – 1,6 / 1 juta 0,4 – 1,2 / 1 juta
Area tubuh < 10% > 30%
Lesi awal Atypical targetoid lesion
Erythema + nyeriepidermolysis
Ethiology Obat-obatan(50%)
Obat-obatan(80%)
Obat-obatan - trimethoprim / sulfamethoxazole- sulfadexine- anti biotika – penisillin- carbamazepine- NSAID
Pathogenesis Type III / IV Type III / IV
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1. Identifikasi penyebab / eliminasi obat penyebab
2. Pengobatan aktif- supressi proses penyakita) Steroid
methyl prednisolon p.o.1-2 mg/kg BB/hari tap. offb) mempertahankan hemodinamika, elektrolit dan proteinc) Antibiotika
3. Supportive therapy- kulit – perawatan luka- mata- pernafasan- nutrisi
PENATALAKSANAAN SJS / TEN
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Definisi : - keradangan - bukan karena infeksi - gatal
Klasifikasi1. Dermatitis Endogen
- Dermatitis atopik- Dermatitis numularis- Dermatitis seboroika
2. Dermatitis Eksogen (Dermatitis kontak)- Dermatitis kontak iritan- Dermatitis kontak alergik- Dermatitis kontak sinar
(Photo contact dermatitis)
DERMATITIS(ECZEMA – EKSIM)
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Dermatitis KontakDermatitis Kontak
Insiden DK Insiden DK
Pengenalan DK sangat perlu
Pengenalan DK sangat perlu
Sehari-hariSehari-hari
PekerjaanPekerjaan
Me paparanMe paparan
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DKIDKI DKADKA
Iritan AlergenBAHAN
KONTAK
DAKDAKPekerjaanKosmetik
DKSDKS
S.M.
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SINGKATANSINGKATAN
1. DKI : Dermatitis Kontak Iritan2. DKA : Dermatitis Kontak Alergik3. DKS : Dermatitis Kontak Sinar4. DAK : Dermatitis Akibat Kerja5. APC : Antigen Presenting cell6. TEWL : Trans Epidermal Water
Loss
1. DKI : Dermatitis Kontak Iritan2. DKA : Dermatitis Kontak Alergik3. DKS : Dermatitis Kontak Sinar4. DAK : Dermatitis Akibat Kerja5. APC : Antigen Presenting cell6. TEWL : Trans Epidermal Water
Loss
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T LymfositT Lymfosit
APC
TEWLIRITANAlergen
TEWL : Trans Epidermal Water Losses
APC : Antigen Presenting Cell
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- karena sifat kimiawi kerusakan sel- dapat terjadi pada paparan pertama
Pembagian : - Dermatitis kontak iritan akut
- Dermatitis kontak iritan kronis ditentukan oleh : - konsentrasi
- pH
DERMATITIS KONTAK IRITAN
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- karena reaksi hypersensitivitas tipe lambat- fase sensitisasi fase elisitasi
Etiologi - Nikel - pewarna - Chrom - pewangi - Cobalt - dsb
Klinis : - gatal - eritema, eksudasi, likenifikasi
DERMATITIS KONTAK ALERGIKDERMATITIS KONTAK ALERGIK
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ANAMNESISANAMNESIS
Riwayat Alergi Riwayat kontak
• Sehari-hari• Pekerjaan
Jenis Bahan Predisposisi
Riwayat Alergi Riwayat kontak
• Sehari-hari• Pekerjaan
Jenis Bahan Predisposisi Dx. Atopik
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Prinsip:
Kontak Alergen baca 48 jam 72 jam
- Standard Patch Test- Bahan yang dicurigai
PATCH TEST(UJI TEMPEL)
PATCH TEST(UJI TEMPEL)
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Dx
Dx. Banding
KESIMPULANKESIMPULAN
Efloresensi Distribusi lesi Riwayat kontak
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ERUPSI OBAT_ Bambang SuhariyantoERUPSI OBAT_ Bambang Suhariyanto