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1. Managing AntiTuberculosis Drug
Hypersensitivity
Heru Sundaru
Divisi Alergi Imunologi Klinik
Departemen Ilmu Penyakit Dalam FKUI/RSCM
Dibawakan di JACIN 2023

2. Gambaran Kasus TBC di Dunia
+ Estimasi jumlah kasus TBC di dunia tahun 2021 mencapai 10,6 juta kasus per tahun dan menjadikan TBC
sebagai salah satu penyakit infeksi penyebab kematian terbesar di seluruh dunia
+ Sekitar 4 dari 10 juta orang pengidap TBC belum diidentifikasi dan dilaporkan sebagai kasus sehingga belum
mendapat perawatan. Hal ini menyebabkan penyebaran penyakit terus berlanjut.

3. Tuberculosis di Indonesia
Indonesia menjadi peringkat negara kedua dengan kasus TB terbanyak di dunia (WHO, 2022).

4. Beban Penyakit TBC di Indonesia
+ Insidens TB di Indonesia mengalami peningkatan pada tahun 2020 ke
2021, yang awalnya 301 menjadi 354 kasus per 100.000 populasi.
+ Kematian karena TB mengalami peningkatan, dari 34 kasus di tahun
2020 menjadi 52 kasus di tahun 2021.
+ Sebanyak 187.000 orang mengalami kematian karena TBC dan HIV.

5. Panduan Pengobatan TB di Indonesia
Alur Diagnosis TB & Dosis Rekomendasi OAT lini pertama
Sumber: Pedoman Nasional Layanan Kedokteran, Tatalaksana Tuberculosis, 2020.

6. Adverse drug reaction
(WHO definition 1972):
A response to a drug which is noxious, unintended, and undesired and which
occurs at doses normally used in human for the prophylaxis, diagnosis, or therapy
of disease, or for the modification of physiological function.
Classification of adverse drug reactions
A. Predictable (70-80%) – generally dose dependent, related to the
pharmacologic action of the drug, occurs in otherwise normal individuals.
B. Unpredictable (20-30%) – dose independent, unrelated to the
pharmacologic action of the drug, tends to occur in susceptible individuals.
Beneficence

7. Reactions
Example
Drug Result
Predictablea
Overdosage
Sided effect
Secondary effect
Drug-drug interaction
Unpredictableb
Intolerance
Idiosyncratic
Allergic
Pseudoallergic
Acetaminophen
Albuterol
Clindamycin
Terfenadine/erythromycin
Aspirin
Chloroquine
Penicillin
Radio contrast material
Hepatic necrosis
Tremor
Clostridiun difficile
pseudomembranous colitis
Torsade de pointes arrhytmia
Tinnitus (at usual doses)
Hemolytic anemia in
G6PD-deficient patient
Anaphylaxis
Anaphylactiod reaction
Classification of adverse drug reaction
a Predictable, or type A, reactions occur in otherwise normal patients, are generally dose-independent, and related to the known
pharmacologic actions of the drug.
b Unpredictable, or type B, reactions occur only in susceptible individuals, are dose-independent and not related to the
pharmacologic actions of the drug.
Solensky Roland, MD*; Med Clin N Am 90 ; 233-260 ; 2006
Beneficence

9. Klasifikasi reaksi hipersensitivitas imun/alergik
Front. Pharmacol. 7:396. doi: 10.3389/fphar.2016.00396

10. Anaphylactic

11. Immune Pathomechanism and Classification of Drug
Hypersensitivity
Allergy. 2019 Mar 6. doi: 10.1111/all.13765

13. Gejala-gejala klinik

14. Gejala-gejala klinik
Beneficence

15. Major mucocutaneous manifestations of drug allergy
Maculopapular rash
Urticaria or angioedema
Fixed drug eruption
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Vasculitis
Beneficence

16. Diagnosis Drug-Hypersensitivity
1
2
3
1. Systematic history taking:
European Network for Drug
Allergy (ENDA) form
2. Skin testing (if available)
3. Drug provocation test
(if other tests-
inconclusive results)
In vitro test (esp. severe reaction)
Bousquet PJ et al. Current Pharmaceutical
Design 2008;14: 2792-2802
Beneficence

17. A through history is very important in the
evaluation of suspected drug allergy.
❑ History of prior ingestion of same drug or drugs belonging to the same class
❑ History of prior drug reactions
❑ Documentation of all medications ingested including OTC drugs, alternative medicines
and health supplements
❑ Family history of drug allergy
History may be the only way to reach a diagnosis
History should include:
Deciding which drug is the most likely culprit:
❑ Consistency of timing
❑ Knowledge of propensity of drug to cause the reaction
Beneficence

18. TES
KULIT
TES
PROVOKASI
TES
INVITRO
•Tes tusuk (prick test)
•Tes intradermal
•Tes tempel (patch test)
• Tes IgE spesifik
(RAST, ELISA, FEIA)
• Tes basofil
( Basophil activation test ,
basophil mediator release)
•Tes mediator inflamasi
•Tes lab lain
( Coombs test, komplemen,
lymphocyte transformation
test)
PEMERIKSAAN PENUNJANG
Beneficence
& Non-maleficence

19. Uji Provokasi Obat
+ Drug challenge, graded challenge, atau test dosing
+ Standar emas untuk diagnosis reaksi hipersensitivitas obat dan
identifikasi obat penyebab
+ EAACI 2003: mungkin lebih berguna untuk mencari alternatif yang
aman daripada menguji dengan obat yang merupakan penyebab dari
masalah tersebut
+ AAAAI & ACAAI 2010: hanya merekomendasikan uji provokasi obat
pada pasien yang berisiko rendah mengalami reaksi berat
Demoly P, et al. Allergy. 2014;69(4):420–37.

20. Graded Challenge
Graded challenge
+ Diagnostic or therapeutic
+ At the time when patient
require immediate Rx with the
drug
+ No intention to induce
tolerance
+ Start 1/100 of daily dose
+ Interval: 30 min, bid, od, …
+ When negative: EXCLUDE
+ Graded challenges are a medical
procedure used to assess and
manage drug allergies,
particularly when there is
uncertainty about the patient’s
sensitivity to a medication.
+ The process involves
administering gradually
increasing doses of the
suspected allergen under close
medical supervision to determine
if the patient can tolerate the
medication safely
Rerkpattanapipat T, et al. Curr Opin Allergy Clin Immunol 2011; 11:299–304
Beneficence

23. Sim DW, et al. World Allergy Organ J. 2021;14(7):100562.

24. Manajemen
1. Hentikan obat OAT
2. Berikan terapi sesuai dengan beratnya gejala reaksi hipersensitivitas
obat
3. Mencari obat alternatif
4. Lakukan uji provokasi
5. Berikan obat OAT yang sesuai (re-challenge)
6. Lakukan desentisisasi bila diperlukan
7. Edukasi kepada pasien tentang penyakit dan rencana pengobatan

25. Nugroho NP, Kusmiati T, Jurnal Respirasi, Mei 2021, VOL 07 (02); 79-85

26. Desensitization
+ Desensitization in drug allergy is a
medical procedure used to safety
reintroduce a medication to a
patient who has previously
experienced an allergic reaction to
that drug.
+ It is typically reserved for situations
where the medication is essential
for the patient’s treatment, and
there are no suitable alternatives.
Desensitization
+ Therapeutic
+ At the time when patient
require immediate Rx with
the drug
+ Intend to induce temporary
tolerance
+ Start 1/100,000-1/1,000
+ Interval: 15 min (45 min)
+ When negative: don’t know
Rerkpattanapipat T, et al. Curr Opin Allergy Clin Immunol 2011; 11:299–304
Beneficence

27. Katran et al. Allergy Asthma Clin Immunol. 2022 Nov 21;18(1):97

28. Katran et al. Allergy Asthma Clin Immunol. 2022 Nov 21;18(1):97

29. G.-Y. Ban et al. Respiratory Medicine 147 (2019) 44–50

30. G.-Y. Ban et al. Respiratory Medicine 147 (2019) 44–50

31. G.-Y. Ban et al. Respiratory Medicine 147 (2019) 44–50

32. Thong et al. Asia Pac Allergy. 2014 Jul;4(3):156-63.

33. Thong et al. Asia Pac Allergy. 2014 Jul;4(3):156-63.

34. Cernadas et al, Allergy 2010; 65: 1357–1366.

35. Kesimpulan
1. Tuberkulosis masih menjadi masalah kesehatan masyarakat yang harus
diperhatikan, baik oleh masyarakat maupun pemerintah
2. Kejadian reaksi hipersensitivitas terhadap obat anti TB (OAT) berkisar
antara 4-5%
3. Kewaspadaan dini terhadap reaksi hipersensitivitas OAT perlu diketahui
oleh setiap dokter yang memberi pelayanan kepada pasien tuberculosis
4. Uji provokasi dilakukan pasien yang diduga hipersensitif terhadap obat TB
5. Praktek desentisisasi dilakukan bila tidak ada alternatif lain dan untungnya
lebih besar daripada risikonya
6. Baik uji provokasi maupun desensitisasi harus dilakukan di fasilitas
kesehatan yang mempunyai fasilitas untuk menangani kejadian reaksi
hipersensitivitas obat yang berat dan dilakukan oleh dokter ahli alergi

36. Terima Kasih