RESPONSI DERMATITIS MEDIKAMENTOSA
Pembimbing dr. Firdausi Nurharini, SpKK
Disusun Oleh : Annisa Bunga Nafara, S.ked 201720401011137
SMF KULIT DAN KELAMIN RSU HAJI SURABAYA FAKULTAS KEDOKTERAN UNIVERSITAS MUHAMMADIYAH MALANG 2018
i
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LEMBAR PENGESAHAN RESPONSI DERMATITIS MEDIKAMENTOSA
Responsi dengan judul “ Dermatitis Medikamentosa” telah diperiksa dan disetujui sebagai salah satu tugas dalam rangka menyelesaikan studi kepaniteraan Dokter Muda di bagian Kulit dan Kelamin.
Surabaya, Februari 2018 Pembimbing
dr. Firdausi Nurharini, SpKK
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KATA PENGANTAR
Segala puji syukur Alhamdulillah penulis panjatkan kehadirat Allah SWT, atas rahmat dan hidayah-Nya penulis dapat menyelesaikan responsi ini dengan judul Dermatitis Medikamentosa . Penyusunan tugas ini merupakan salah satu tugas yang penulis laksanakan selama mengikuti kepaniteraan di SMF Kulit dan Kelamin RSU Haji Surabaya. Penulis mengucapkan terima kasih kepada dr. Firdausi Nurharini, SpKK selaku dokter pembimbing dalam penyelesaian tugas responsi ini, terima kasih atas bimbingan dan waktunya, sehingga penulis dapat menyelesaikan tugas ini. Akhirnya, penulis berharap semoga responsi ini dapat memberikan manfaat pada pembaca. Penulis menyadari bahwa penyusunan tugas ini ma sih jauh dari kesempurnaan. Dalam kesempatan ini penulis mengharapkan kritik dan saran yang dapat membangun demi kesempurnaan responsi ini.
Surabaya, Februari 2018
Penulis
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DAFTAR ISI HALAMAN JUDUL ………………………...………………………….....i LEMBAR PENGESAHAN ……………………………………………....ii KATA PENGANTAR ……………………………………………………iii DAFTAR ISI ……………………………………………………………...iv DAFTAR GAMBAR ……………………………………………………..v BAB I TINJAUAN PUSTAKA …..……………………………………....1
1.1
Pendahuluan ...………………………………… ...……………………………………………………….1 …………………….1
1.2
Definisi ………..…………………… ………..………………………………………………… ………………………………..1 …..1
1.3
Sinonim………………………………………………………………1
1.4
Epidemiologi …………..……………… …………..……………………………………………. …………………………….1 1
1.5
Etiologi …………..………………… …………..……………………………………………… ………………………………..2 …..2
1.6
Jenis…….……………………………………………………………. 4
1.7
Patogenesis.. …………..………………… …………..…………………………………………….. …………………………..6 6
1.8
Gejala Klinis …………..………………………………………….…. …………..………………………………………….….8 8
1.9
Diagnosis …………..……………………… …………..………………………………………………... ………………………...9 9
1.10 Diagnosis Banding Banding …………..……………………… …………..………………………………...… ………...…....11 ....11 1.11 Penatalaksanaan …………..…………………… …………..……………………………………...…1 ………………...…15 5 1.12 Prognosis …………..…………………… …………..………………………………………………..1 …………………………..15 5 …………………..........…………………...……....16 6 DAFTAR PUSTAKA…………………..........…………………...……....1 BAB II TINJAUAN KASUS …….………………………………………1 8
2.1
Identitas Penderita …………..…………………… …………..……………………………………. ………………....18 ...18
2.2
Anamnesis …………..………………… …………..……………………………………………… ……………………………1 18
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2.3
Pemeriksaan Fisik …………..………………… …………..……………………………………....1 …………………....19 9
2.4
Pemeriksaan Penunjang ……………………………………………. …………………………………………….20 20
2.5
Resume …………..……………… …………..………………………………………… ………………………………… ………21 21
2.6
Diagnosis Diagnosis …………..……………………………………………….21 …………..………………………………………………. 21
2.7
Diagnosis Banding …………..…………………… …………..…………………………………..…. ……………..….21 21
2.8
Planning …………..………………… …………..…………………………………………...…… ………………………...……21 21
2.9
Edukasi………………………………………………………………22 Edukasi……………………………………………………………… 22
2.10 Prognosis …………..…………………… …………..……………………………………………….. …………………………..22 22 ………………..………………………...……...23 23 BAB III FOTO KASUS ………………..………………………...……... LAMPIRAN SUMBER ……………………………………………… .…24
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DAFTAR GAMBAR
Gambar 1:Jenis Adverse Cutaneous drug reaction ………………………. ……………………… . 2 Gambar 2: Erupsi obat morbiliformis morbiliformis (eksantema) (eksantema) akibat antibiotic ……..9 ……..9 Gambar 3: Measles. Morbiliformis Morbiliformis eksantema klasik ……………………11 …………………… 11 Gambar 4: Ebstain barr Virus mononucleosis …………………………… ……………………………12 12 Gambar 5: Eksantema subitum pada bayi …………………….……….…. …………………….……….….13 13 Gambar 6: Erupsi papuloskuamosa disseminate disseminate pada syphilis syphilis sekunder …14 Gambar 7: eksantema pada pitriasis rosea dengan herald patch………….. patch………….. 14 14
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1
BAB I TINJAUAN PUSTAKA
1.1 Pendahuluan
Sebuah obat dapat mengandung kandungan kimia atau kombinasi dari substansi, di konsumsi untuk penilaian, pencegahan atau pengobatan penyakit maupun gejala. Dermatitis medikamentosa termasuk dalam golongan adverse drug reaction (ADR), yaitu manifestasi klnis yang tidak di inginkan dari penggunaan obat tertentu, termasuk reaksi overdosis, efek samping s amping yang telah di prediksi, dan manifestasi tidak di inginkan yang tidak dapat di antisipasi. Terkadang, ADR terjadi akibat kesalahan manusia . (1) Dermatitis kontak alergi pada Dermatitis medikamentosa merupakan
tipe “dermatitis kontak sistemik medikamentosa”. Pasien yang pada dasarnya sensitive terhadap sebuah obat dapat mengalami reaksi eksema dengan saat obat dikonsumsi secara sistemik. Erupsi pada kulit terjadi simetris, biasa muncul di satu lokasi sebelum akhirnya tergeneralisata. sering di akibatkan oleh antibiotic 1.2 Sinonim
(2)
(1)
. Erupsi Erupsi obat obat jenis ini paling
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ACDR, paling banyak berupa morbilliform rash (51,2%), urticatia (12,2%), erythema multiforme (4,9%). Kejadian dermatitis medikamentosa/ morbilliform rash terhadap obat antituberkulosis terjadi pada kurang dari 1% pasien.. (1)
1.4 Etiologi
Pasien yang pada dasarnya sensitive terhadap sebuah obat dapat mengalami reaksi eksema dengan saat obat dikonsumsi secara sistemik. (1) di r eaction beserta bawah ini merupakan tabel jenis Adverse Cutaneous drug reaction
obat penyebab nya.
(2)
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3
Efek samping dari obat tuberculosis tuberculosis lini pertama (isoniazid, rifampisin, pirazinamid, etambutol dan streptomisin) sangat umum terjadi, meliputi hepatitis, reaksi kutan, intoleransi gastrointestinal, dan multiple drug reaction. Obat-obatan anti tuberkulosa di bawah ini dilaporkan menyebabkan dermatitis kontak yaitu: isoniazid, rifampicin, ethambutol, p-aminosalicylic acid, streptomycin dan kanamycin. Insiden obat lainnya susah untuk dinilai karena biasanya obat tersebut digunakan secara kombinasi. (1) 1. Isoniazid Lesi berbentuk erupsi acneiform yang biasanya terjadi perlahan setelah penggunaan obat. Urticaria, purpura, dan LE-like syndrome, erupsi likenoid fotosensitive, steven Johnson syndrome dan dermatitis exfoliatif juga dilaporkan. (1) 2. Rifampicin Reaksi hipersensitif pada kulit jarang terjadi. Jenis efloresensi yang dilaporkan antara lain LE, eritema nodusum leprosum-like, eksaserbasi bula eritema multiforme dan pemfigus (beberapa pemphigus dapat terjadi eksaserbasi). (1) 3. Ethambutol
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4
4. Streptomycin dan kanamycin Erupsi exanthema umum terjadi pada penggunaan streptomisin. Penggunaan yang diteruskan dapat mengakibatkan dermatitis exfoliative meski jarang terjadi. Urtikaria, makulo popular rash, febris, dan eosinophilia mudah dikenali sebagai reaksi obat golongan ini (aminoglikosida).
Eritema
toksik
dengan
folikular
pustulosis
generalisata dilaporkan terhadap peggunaan streptomisin (1). 1.5 Jenis
Berikut adalah jenis-jenis manifestasi klinis pada Cutaneous Adverse Drug Reaction (ACDR) yang dapat terjadi pada penggunaan anti-
tuberkulosis. (4) 1. Maculopapular exanthema Maculopapular exanthema adalah CADR yang paling sering terjadi, yaitu 95% dari kasus CADR anti tuberculosis (4,7). Ditandai dengan eritema macula dan papula simetris seluruh tubuh kadang disertai rasa gatal yang intensif dan sensasi rasa terbakar. Dapat juga disebut dengan morbiliform rash. Pada kasus yang berat. (4)
2. Leukocytoclastic Vasculitis
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membedakan apakah penyebab vasculitis ini CADR antituberkulosis atau bukan. (4) 3. Photodermatitis Photodermatitis jarang muncul pada paparan cahaya matahari. Biasnaya di tandai dengan abu-abu-coklat perifolikuler dan relikuler hiperpigmentasi pada area yang telah terpapar caha ya. (4,7) 4. Fixed Drug Eruption Ditandai dengan macula eritematosa berbatas tegas terlokalisir pada telapak tangan, telapak kaki, regio genitalis, dan membrane mukosa. Lesi ini sembuh bila sembuh akan meninggalkan hiperpigmentasi yang permanen. Bila mengkonsumsi obat yang yang sama akan terjadi rekuren pada lesi yang sama seperti sebelumnya. se belumnya. Fixed drug eruption banyak banyak terjadi pada rifampicin dan fluoroqionolon.(4,7) 5. Lichenoid Drug Eruption Ditandai dengan rasa gatal yang polygonal, papula eritema yang berlokasi dominan di fleksor ekstrimitas.(4) juga macula dan plakke unguanBiasanya berdampak pada mukosa seperti buccal, be rupa warna
putih, sisik retikuler (Wickham’s (Wickham’s striae). Banyak Banyak disebabkan disebabkan oleh
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6
muncul 3 minggu setelah paparan obat. Pada sedikit kasus, obat isoniazid, rifampisin, streptomisin(4) dan pirazinamid (5) dilaporkan berhubungan dengan DRESS.
(4,7)
dan etambutol
(5)
7. Toxic epidermal necrolysis (TEN) dan Steven Johnson syndrome (SJS) Ditandai dengan eritema yang tersebar, pengelupasan epidermis nekrosis yang intensif, flaccid blister, eksfoliasi kulit. Diperkirakan reaksi ini muncul akibat destruksi keratinosit dan apoptosis. Ethambutol, isoniazid, rifampicin, pyrazinamide, streptomycin and thiacetazone diketahui berhubungan dengan dengan TEN dan SJS namun jarang terjadi. (4,7) 8. Acute generalized exanthematous pustulosis (AGEP) Ditandai dengan pustule kecil dengan dasar eritema yang tersebar dan muncul dengan cepat, disertai dengan demam, neutrofilia signifikan. Onsetnya beberapa hari setelah penggunaan obat. (4) 1.6 Patofisiologi
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7
cemokin yang menarik/merangsang sel efektor (eosinophil, atau neutrofil). Pada akut exantematosa generalisata pustulosis set T mensekresi IL-8 dan mengaktifkan neutrophil. Akibat dari peran aktivasi sel T, memori sel T akan terbentuk sehingga penggunaan obat sejenis di kemudian hari mengakibatkan ADR rekuren.
(2)
Pada reaksi obat dermatitis medikamentosa terjadi destruksi
pada sel Langerhans epidermis.(1) Saat sel T teraktifasi, terdapat 4 mekanisme yang dapat terjadi. 1. Sel T menstimulasi produksi IFN- γ yang menstimulasi terjadinya kontak dermatitis. Tipe reaksi ini dapat membentuk bula tetapi tanpa nekrosis epidermal. (2) 2. Sel T mengaktivasi Th2 manner dan menstimulasi eosinophil (pada morbiliformis dan urtikaria) (2) 3. Sel T mengakivasi sitotoksik CD8+ yang dapat mensekresi perforin/granenzym B dan fas ligand, mengakibatkan apoptosis
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1.7 Gejala klinis
1.
“baboon syndrome” dikenal sebagai ciri khas dermatitis kontak sistemik, yaitu eritema(1,2,8) difuse di pantat bagian atas dalam paha dan ketiak. tersering di batang tubuh dan extrimitas
(1)
,
(3)
2. Erupsi pada kulit terjadi simetris(1,3,9), biasa muncul di satu lokasi l okasi sebelum akhirnya tergeneralisata (di seluruh tubuh).
(1)
3. Eritema polisiklik (3) 4. Makula berukuran sekitar 1 cm, berwarna merah ke ungunan
(3)
5. Papul kecil yang menyebar (3,2,9) 6. Bisa disertai demam (3) 7. Seringkali muncul 2 minggu pertama setelah penggunaan obat (2,3), atau lebih, bahkan hingga 10-14 hari setelah obat di hentikan. (2) 8. Lesi muncul di bagian proksimal tubuh dan menyebar ke seluruh tubuh dalam waktu 1-2 hari. (2)
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Gambar 1.2. Erupsi obat morbiliformis (eksantema) akibat antibiotic.(sumber gambar: James, James, William D, timothy G Berger, dan Dirk M Elston. Andrew’s Elston. Andrew’s Disease of the Skin, Clinical Dermatology. Ed 8. Canada: Saunders Elsevier; chapter 6. page
108-120
1.8 Diagnosis
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10
Sebuah algoritma telah dilaporkan bahwa informasi yang detail dapat memprediksi apakah obat yang diberikan yang menyebabkan gejala ADR. Informasi tersebut meliputi
(2)
:
1. Obat yang dikonsumsi 2. Riwayat penyakit dahulu (gejala yang serupa sebelumnya) 3. Etiologi alternative lainnya yang memungkinkan 4. Durasi mulai dari awal konsumsi obat hingga muncul gejala. 5. Dosis dan kekuatan obat 6. Outcome bila obat di hentikan pemakaiannya B. Pemeriksaan fisik Pengamatan efloresensi sesuai dengan gejala klinis di atas. C. Skin testing dan patch test. Drug skin test dapat dilakukan 6 minggu hingga 6 buat setelah resolusi komplit dari reaksi. Drug prick test dilakukann di
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dermatitis medikamentosa yang positife terhadap pemeriksaan patch test dan intradermal test, sehingga prosedur ini di anggap tidak efektif untuk menegakkan diagnosis.
(2,6)
D. Laboratorium Eosinophilia perifer, perivascular limfosit dan eosinophil. (1) 1.9 Diagnosis banding
Exanthema viral, syphilis sekunder, dermatitis kontak alergi (3), pitriasis rosea atipikal. (3,8) 1. Exanthema viral
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ed. 7 vol. 2008. United States of America: Mc Graw-Hill Companies; Chapter 192. Page 1852)
b. Ebstain Barr Virus Juga diebut dengan Human Herpesvirus 4 (HHV-4) Gejala dan tanda klinis: terdapat trias demam, limfadenopati (sering didapatkan di leher) dan faringitis. Erupsi obat biasa muncul ketika penderita mengkonsumsi obat antibiotic. Lesi pada kulit muncul muncul setelah 7-10 hari setelah minum obat antibiotic. Macula papula eritematosa gatal(3)
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hingga hari kedua setelah demam hilang, dan lesi kulit ini menetap selama 3-5 hari. Predileksi terutama pada leher dan batang tubuh, terkadang pada wajah dan ekstrimitas proksimal.
(3)
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Gambar 1.6 Erupsi papuloskuamosa disseminate pada syphilis sekunder (Sumber Gambar: Klaus W, Lowell A, Goldsmith Stephen I, editors. Fitzpatrick’s: Color Atlas and Synopsis
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1.10 Penatalaksanaan
Pada kasus dermatitis medikamentosa diberikan te rapi supportif. Erupsi akan hilang dengan sendirinya setelah 2 minggu pasca penghentian penggunaan obat penyebab.(2) terapi suportif meliputi steroid topical (2,4) Maupun oral (2) seperti glukokortikoid
(3,4,8)
dan antihistamin sistemik.
(3,4,8,9)
Pada Kelainan urtikaria,
eritema, dermatitis medikamentosa, purpura, eritema nodusum, eksantema fikstum karena alergi obat, dosis standar untuk orang dewasa ialah 3 x 10 mg prednisone sehari.(10) 1.12 Prognosis
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DAFTAR PUSTAKA
1. Burns, Tony, Stephen Breathnach, Neil Cox, dan Christoper Griffiths. Rook’s Griffiths. Rook’s Textbook of Dermatology ed. 8, vol 1. 2010. John Wiley & Sons, Ltd
publication, UK; chapter 75.1-75.177 75.1-75.177
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7. Kakande, B, R J Leyloenya. Leyloenya. Drug Reactions Associated with Antituberculosis Drugs. 2015. Division of Dermatology, Department of Medicine, University
of Cape Town Vol 28, No 4 8. Sterry, Wolfram, at all. Thiene Clinical Companions Dermatology. 2006. Germany: Götz, Ludwigsbur publisher . chapter 11. page 179-189
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BAB II TINJAUAN KASUS
2.1 Identitas Pasien
Nama
: Ny. N
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bermacam-macam di seluruh tubuh. Di awali di lengan bawah lalu menjalar ke seluruh tubuh.. gatal juga disertai dengan rasa yang sedikit panas, dan pasien tidak mengeluhkan perih atau nyeri pada kulitnya. . Selama ini pasien mengobati gatalnya dengan mengoleskan caladine, namun gatal tidak reda. Tidak ada keluhan demam, tidak ada keluhan di daerah genital dan tidak nyeri
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Status higenitas
: Cukup
Vital sign
: Stabil
Kepala
: Dalam batas normal (tidak ada kelainan mukosa mata, mulut)
Leher
: Lihat status dermatologi
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