Update Rinitis Alergi Bengkulu PDF

Update Rinitis Alergi
PGPKT Bengkulu, 24 Agustus 2019, Bengkulu

dr. Yanuar Iman Santosa Sp. THTKL, Msi.Med - FK UNDIP SEMARANG
http://lanungga.com/
DAFTAR RIWAYAT HIDUP
Nama : dr. Yanuar Iman Santosa Sp. THT-KL

NIP : 198201302009121008
Pendidikan
 Dokter umum 2000 - 2006 : FK UNDIP Semarang
 Dokter Spesialis 2008 - 2012 : PPDS IK THTKL FK UNPAD Bandung
 S2 Kedokteran 2014-2017 : Magister Biomedis FK UNDIP Semarang
Riwayat Pekerjaan
2009 – sekarang : Dosen IK THTKL FK UNDIP
2018 – Sekarang : Ketua Bagian IK THTKL FK UNDIP
Tempat Praktek :
1. RS Hermina Pandanaran, Jl. Pandanaran no 24 Semarang

2. RS Columbia Asia Semarang, Jl. Siliwangi no 143, Semarang
3. RS Nasional Diponegoro, JL Prof Soedarta, Semarang.

Speaker Disclaimer
dr. Yanuar Iman Santosa Sp. THT-KL, Msi.Med- Divisi Alergi Imunologi - Departemen THT-KL FK UNDIP - Semarang
+ OMSK
+ OME
The Allergy Epidemic
Pendahuluan • Rinitis Alergi ( RA )  gangguan fungsi hidung setelah pajanan
alergen  inflamasi mukosa hidung  IgE
• Gejala: hidung tersumbat, bersin-bersin, beringus, gatal

palatum, kulit, mata, lelah, sakit kepala
 ↓ Kwalitas Hidup
The Role of microbiome
Rinitis Alergi
Sewaktu ringan
Sewaktu sedang-berat
Menetap ringan
Menetap sedang-berat
Rinitis Alergi (Lv 4)
• rinitis alergi hipersensitifitas tipe I, diperantai oleh Ig E 
target utama: mukosa hidung gejala :
hidung gatal, hidung tersumbat, beringus dan bersin
http://health- http://www.sinomarin.com/nose_3_1.htm http://www.shiply.com/blog/2009/10/sneezing-while-driving-how-dangerous.html

7.com/Atlas%20of%20Pediatric%20Physical%20Dia
gnosis/Systemic%20Anaphylaxis/3
• Faktor penyebab utama adanya kontak dengan alergen hirup

KLASIFIKASI RINITIS ALERGI
MENURUT ARIA-WHO 2008
SEWAKTU-WAKTU MENETAP
Gejala Gejala
• < 4 hari per minggu • > 4 hari per minggu
• atau < 4 minggu • dan > 4 minggu
SEDANG-BERAT
RINGAN SATU ATAU LEBIH GEJALA
• Tidur normal • Tidur terganggu
• Aktifitas sehari-hari saat olahraga • Aktifitas sehari-hari saat olahraga
dan saat santai normal dan saat santai terganggu
• Saat bekerja dan sekolah normal • Saat bekerja dan sekolah terganggu
• Tidak ada keluhan yang • Ada keluhan yang mengganggu
mengganggu
(ARIA WHO Consensus 2001)

dr. Yanuar Iman Santosa Sp. THT-KL, Msi.Med- Divisi Alergi Imunologi - Departemen THT-KL FK UNDIP
6 - Semarang
ALERGEN DAN SUMBER ALERGEN
Alergen  antigen yang menginduksi
dan bereaksi dgn antibodi IgE
Alergen hirup (Aeroallergens)
Mites : house dust mites
Dermatophagoides pteronyssinus (Dpt)
Alergen binatang: anjing, kucing, kuda, kecoa

Spora jamur, serbuksari bunga
Polutan: asap rokok, gas buang knalpot.

PENATALAKSANAAN RA
Allergen
avoidance
indicated when
possible
Immunotherapy
Pharmacotherapy effectiveness
safety specialist prescription
effectiveness may alter the natural
easy administration course of the disease
Patient
education
always indicated
dr. Yanuar Iman Santosa Sp. THT-KL, Msi.Med- Divisi Alergi Imunologi - Departemen THT-KL FK UNDIP
18 - Semarang
Diagnosis of allergic rinitis Check for asthma
espescially in patients
with moderate-severe
Intermittent symptoms and/or persistent
Persistent symptoms
rinitis
Mild Moderate-severe Mild Moderate-severe
Not in preferred order

Antihistamin oral +
Not in preferred order Evaluasi
In preferredulang
order diagnosis +
• Oral H-1 antihistamine • Antihistamin oral +
Oral H-1 antihistamine •Intranasal CS
decongestan sistemik
• Intranasal- H-1 antihistamine • decongestan sistemik
Intranasal- H-1 antihistamine penambahan
•Oral obator: LTRA
H-1 antihistamine
• and/or decongestant or • and/or decongestant or - Antileukotrien : Montelukast
•LTRA • Intranasal CS review the patient after 2-4 weeks
• LTRA or - Anti PAF : Rupatadine
• Intranasal
(Chromone) steroid
Improved Failure
2 In
minggu s/d2-4 2 bulan
persistent rinitis review the Step-down and Review diagnosis
patient after weeks
Jika perlu:
continue treatment
for 1 month
Review compliance
Query infections
If failure: step-up Operasi or other causes
If improved: continue for 1 month
- reduksi konka
Increase Itch sneeze:
- septoplasty
Rhinorrhea: Blockage: add
intranasal add H-1 - minifessadd ipratropium decongestant, or oral
CS dose antihistamine CS (short term)
Failure:
Surgical refferal
Hindari allergen + cuci hidung
Allergen and irritant avoidance may be appropriate
Imunoterapi
If + Conjunctivitis add:
• Oral H-1-blocker or Intraocular H1-blocker or Intraocular Chromone (or saline)
Consider Specific Immunotherapy

Efek Mediator pada Gejala Alergi
RINGKASAN TERAPI RINITIS ALERGI
RA persist. Mod. Severe
Antihistamin oral
RA Inter. Mod. severe + Decongestan oral
RA persist. Mild Intranasal steroid
Cuci hidung
RA inter. Mild Antihistamin oral
Decongestan oral Imunoterapi
Hindari alergen Intranasal steroid Operasi
Antihistamin oral Cuci hidung Reduksi konka
Px. Penunjang
Decongestan oral Septoplasti
Skin Prick Test No Antibiotic FESS
Ig E Atopy / Ig E Spesifik
1. Antihistamin non sedatif dengan afinitas
dan selektifitas tinggi terhadap reseptor
H1
2. Onset cepat, durasi kerja panjang
3. BIOEKUIVALEN dengan ORIGINATOR
A Positive family history for allergy Genetic Factors
Risk of Allergy
Both parent no One sibling One parent

allergies with allergy with allergy Both parent
with allergies
5-15% 25-30% 20-40% 40-60%

risk of allergy risk of allergy risk of allergy risk of allergy
50-80%
The same
manifestation
Koning,1996; Bousquet,2002
“ The Allergic March “
Thank You
dr. YANUAR Iman Santosa
+628122544052
yanuar.tht@gmail.com
Lanungga.com
DESLOTINE BIOEKUIVALEN vs ORIGINATOR
Artinya
ARIA Guidelines: Congestion Efficacy
“
Corticosteroids are the most effective pharmacological treatment
for allergic rhinitis.”
The effect of topical corticosteroids on nasal blockage and their
anti-inflammatory properties favor them above other treatments.
Itching/
Congestion Rhinorrhea Sneezing Duration
Intranasal steroids +++ +++ ++/+++ 12-48h
Oral antihistamines +/++ ++ +++/++ 12-24h
Intranasal decongestants ++++ - -/- 3-6h
Intranasal cromones + + +/+ 2-6h
Anticholinergics - ++ -/- 4-12h
Antileukotrienes ++ + -/- Not
reported
Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi

Imunologi - Departemen THT FKUI/RSCM Jakarta
Adapted from Bousquet et al. Allergy. 2002;57:841.
Effect of Glucocorticoids (GC) on nasal mucosa mucosa. Okano M. Mechanism and clinical implications of GC in the treatment of AR.Clin .Exp. Immunol
2009;158:164-73
Mechanism action of corticosteroid
• Intranasal corticosteroids downregulate the recruitment and

influx of inflammatory cells
• Inhibit the secretion of pro-inflammatory mediators during the
late phase of the inflammatory response

INS Have Multiple Anti-Inflammatory Activities
X
Histamine (H1) Vascular permeability, stimulates SMCs
Early-Phase Response
Ag X
Enzymes (eg. Tryptase,
Chymase, etc.)
Tissue damage/remodeling
X
PGD2 Vasodilation, neutrophil chemotaxis
X
LTC 4 (LTD4, LTE4) Mucus secretion, vascular permeability
PAF Chemotaxis/activation of leukocytes,
vascular permeability
X X
TNF-α, MIP-1α Promote inflammation
Mast cells (and
Basophils)
X IL-5
IL-3, X Mast cell proliferation, eosinophil
production/activation
X
IL-4, IL-13 TH2 differentiation
X
Major basic protein, ECP X Cell damage
Late-Phase Response
Enzymes (eg. Tissue damage/remodeling

X
Peroxidases, etc.)
X
LTC4 (LTD4, LTE4) Mucus secretion, vascular permeability
Eosinophil X X X
IL-3, IL-5, GM-GSF Mast cell proliferation, eosinophil
production/activation
X IL-10,
IL-8, X Slide Presentasi
RANTES, Inflammation, chemotaxis of leukocytes
dr. Nina Irawati Sp. THT-KL - Divisi Alergi
X X
MIP-1α, eotaxin 52
Intranasal Corticosteroid
• Binding glucocorticoid receptor localized to the
cytoplasma of target cells.
• Inhibit gene transcription
• Antiinflammation effect :
• Inhibit uptake & processing APC
• reduced eosinophil & its chemical mediator
• Reduced the influx inflammation cells & T cells
• Reduced the release of pro-inflam.chemical
mediator & mucosal hyperesponsiveness
• Inhibit release & synthesis chemical mediator :
histamin, cytokine,leucotriene, chemokine
•Control AR comorbidity
Treatment Implications of INS in UAD
▷ Meta analysis study by Soler et al. (2013)*
○ 18 studies, 2162 patients (1659 completed the study, 503
withdrew or dropped out).
○ In patients with both AR and asthma, INCS significantly
improved morning and peak expiratory flow.
▷ Systematic review by Passali et al. (2016)**
○ 40 studies
○ In Acute Rhinosinusitis (ARS), mometasone furoate (MF) as
monotherapy or adjuvant to antibiotics: recurrence rate,
usage of related prescriptions and medical consultations.
○ In Chronic Rhinosinusitis (CRS) with nasal polyposis, MF polyps
size, nasal congestion, improves quality of life and sense of
smell, daytime cough.
○ MF has great efficacy in management of adenoidal hypertrophy
and otitis media of atopic children
*Lohia S, Schlosser RJ, Soler ZM. Impact of intranasal corticosteroids on asthma outcomes in allergic rhinitis: a meta-analysis. Allergy. 2013; 68: 569-79
**Passali D, Spinosi MC, Crisanti A, Bellussi LM. Mometasone furoate nasal spray: a systematic review. Multidisciplinary Respiratory Medicine. 2016; 11(18).

A Pharmacological Study of INS
• Rank orders of potency  mometasone furoate,
fluticasone propionate, & fluticasone furoate
• MF has the highest relative receptor affinity (RAA)
• MF occupy the same number of receptors at a lower
drug concentration
• Furoate & propionate ester  highly lipophilic: facilitate
their absorption through nasal mucosa & uptake across
phospholipid cell membranes
• Increased in lipophilicity  drug particles dissolve more
slowly in nasal mucosa  longer intranasal residency
Derendorf H, Meltzer EO.Molecular & clinical pharmacology of INS corticosteroids: clinical & therapeutic
implications. Allergy. 2008 Oct;63(10):1292-300
Mometasone Furoate Provides Effective Nasal Congestion
Relief in SAR: Pooled Analysis of 4 Trials
Baseline congestion score

All patients >2.5 >2.75 3
(LS mean symptom score)

0
2-week average change
-0.2
from baseline
-0.4 n=492
-0.6 n=72
n=173 n=113
*
-0.8 n=490
-1.0 *
n=163 * *
n=103 n=64
-1.2
Mometasone Furoate 200 μg qd
Placebo
*P<0.001 vs placebo. Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi
Berger et al. Ann Pharmacother. 2005;39:1984. Imunologi - Departemen THT FKUI/RSCM Jakarta
Mometasone Furoate rapid onset of action 5-7 hours :
significant total symptom relief within hours of
a single dose in patients with SAR
0
Mean change from baseline Change in Total Symptoms
in total symptom score -2
Mometasone Furoate 200 μg
(n=119)
Placebo (n=116)
-4
-6
-8 * *8 * * * * * *
0 1 2 3 4 5 6 7 9 10 11 12
Hours after dosing
*P<0.05 vs placebo. Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi
Berkowitz et al. Allergy Asthma Proc. 1999;20:167. Imunologi - Departemen THT FKUI/RSCM Jakarta
Mometasone Furoate Safety
Profile
▷ Low (<0.1%) bioavailability due to low rate of
absorption from GI tract and high rate of
hepatic metabolism1
▷ Systemic bioavailability also depends on
systemic absorption through the nasal mucosa.
▷ Mucociliary clearance removes solid drug
particles from nasal mucosa  minimal fraction
enters the nasal tissues and bloodstream
1. Brannan et al. J Allergy Clin Immunol. 1996;97(pt 3):198.
2. Hochhaus G. Pharmacokinetic/Pharmacodynamic profile of mometasone furoate nasal spray: potential effects on clinical safety and efficacy. Clin Ther. 2008; 30: 1-13
3. Daley et al. Bioavailability of fluticasone propionate and mometasone furoate aqueous nasal spray. Eur J Clin Pharmacol. 2004; 60:265-8.
Mometasone : Kortikosteroid dengan Bioavailability paling rendah sehingga
Efek samping minimal
Derendorf & Meltzer. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications. Allergy 2008; 63: 1292-1300.

Comparison of Mometasone Furoate Monohydrate and Fluticasone Propionate
Nasal Sprays in the treatment of Dust Mite – sensitive Children with
Perennial Allergic Rhinitis
Result

Mometasone Furoate Safety
Profile
▷ No HPAA suppression detected in clinical studies1
○ Minimal effect on diurnal HPAA rhythm.2
○ Administration of MF in the morning does not changes daytime
cortisol level and the normal circadian rhythm of HPAA2
▷ No evidence of nasal atrophy3
▷ Low incidence of local adverse events3
▷ One - year studies INS in children : mometasone furoate, fluticasone
furoate & budesonide  no adverse effects on HPAA function or
growth4
HPAA = hypothalamic-pituitary-adrenal axis

1. Allen DB. Systemic effects of intranasal steroids: an endocrinologist’s perspective. J Allerg Clin Immunol.2000;106:179-90.
2. Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648
3. Schenkel EJ et al. Absence of growth retardation in chldren with perennial allergic rhinitis after one year of treatment with mometasone 4. Mometasone furoate aqueous nasal
spray. Pediatrics. 2000; 105:E22
Result
Gbr 1. Rata-rata perubahan tinggi badan selama 1 tahun Gbr 2. Respon plasma kortisol terhadap stimulasi cosyntropin
terapi dengan MFNS 100 mcg QD atau placebo selama 1 tahun terapi dengan MFNS 100 mcg QD atau placebo
Pemberian terapi Mometasone Furoate Nasal Spray 100 mcg selama 1 tahun dapat
ditoleransi dengan baik, tanpa memberikan efek gangguan pertumbuhan atau penekanan
fungsi HPA-Axis pada pasien riinitis alergi perenial
Long-Term Treatment With
Mometasone Furoate: No Evidence of Nasal Atrophy
Nasal Biopsies After 12 Months of MF

Before MF Treatment
200 µg/d Treatment
Disruption of epithelium Epithelium intact
Eosinophil infiltration No eosinophil infiltration
Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648.


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Update Rinitis Alergi

PGPKT Bengkulu, 24 Agustus 2019, Bengkulu

Nama : dr. Yanuar Iman Santosa Sp. THT-KL

2018 – Sekarang : Ketua Bagian IK THTKL FK UNDIP

1. RS Hermina Pandanaran, Jl. Pandanaran no 24 Semarang

3. RS Nasional Diponegoro, JL Prof Soedarta, Semarang.

• Gejala: hidung tersumbat, bersin-bersin, beringus, gatal

http://health- http://www.sinomarin.com/nose_3_1.htm http://www.shiply.com/blog/2009/10/sneezing-while-driving-how-dangerous.html

• Faktor penyebab utama adanya kontak dengan alergen hirup

(ARIA WHO Consensus 2001)

Alergen binatang: anjing, kucing, kuda, kecoa

Polutan: asap rokok, gas buang knalpot.

Mild Moderate-severe Mild Moderate-severe

Not in preferred order

Consider Specific Immunotherapy

RA persist. Mod. Severe

Both parent no One sibling One parent

5-15% 25-30% 20-40% 40-60%

Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi

• Intranasal corticosteroids downregulate the recruitment and

Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi

Enzymes (eg. Tissue damage/remodeling

Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi

Baseline congestion score

(LS mean symptom score)

Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi

Slide Presentasi dr. Nina Irawati Sp. THT-KL - Divisi Alergi

HPAA = hypothalamic-pituitary-adrenal axis

Nasal Biopsies After 12 Months of MF

Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648.

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