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Penatalaksanaan Alergi Makanan Pada Anak

Prof DR Dr ARIYANTO HARSONO SpA(K)

Lab/SMF Ilmu Kesehatan AnakFK Unair/RSUD Dr. Soetomo

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Pendahuluan

• The American Academy of Allergy and Immunology– Alergi Makanan : Reaksi imunologi yang

menyimpang terhadap makanan, sebagian besar reaksi ini melalui reaksi hipersensitifitas tipe I

Food Hypersensitivity: reaksi terhadap makanan dengan dasar reaksi tipe II, III, IV

Food Intolerance: reaksi terhadap makanan dengan dasar reaksi non imunologi

Contoh: Toksik Metabolik Idiosinkrasi

3Prof DR Dr Ariyanto Harsono SpA(K)

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Patofisiologi

• Alergen Makanan– Protein, glikoprotein, polipeptida– BM > 18.000 dalton– tahan panas– tahan enzim proteolitik

Prof DR Dr Ariyanto Harsono SpA(K)

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patofisiologi

• Pada ikan : alergen M• Pada telur : ovomucoid• Pada susu : betalaktoglobulin (BLG)

alfalaktalbumin (ALA) bovin serum

albumin (BSA) bovin gama globulin (BGG)

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Cow's milk -caseins Whey

-Casein,-Casein-Casein-Casein -Lactoglobulin-Lactalbumin

Exposure of allergen

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patofisiologi

• Pada kacang tanah : Arachin Conarachin

• Pada permunian : Peanut I Glicoprotein

180.000 dalton

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patofisiologi

• Pada udang : – alergen I (21.000 dalton)– alergen II (200.000 dalton)

• Pada gandum :– albumin– pseudoglobulin– euglobulin

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1. Genetic: Atopy2. Exposure

3. Mucosal Barrier

Immunology Paradigm

Factors Of Allergy Development

Prof DR Dr Ariyanto Harsono SpA(K)

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a, b, c, d : HLA DRe : HLA DMf : HLA DM CIITA

Genetic

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patofisiologi

• Paparan awal– sel yang berperan

• sel penyaji antigen• sel T• sel B

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Macrophage are abundant in the lamina propria of the villi.Function:1.Phagocytosis2.Immune regulation by cytokines release3.APC

Goblet Cells

Aktivasi sel-selImuno-kompeten•Sel T•Sel B•Sel Mast•Sel Langer- hans

Aktivasi sel-selstruk-tural

•Sel endotel•Sel epitel

Aktivasi dan Rekruitmen

•Sel Mast•Eosinofil•Neutrofil

•Basofil

Pelepasan mediator

Kerusakan epitel

Stimulasi neural

Dilatasi & peningkatan

permeabilitas vaskulerl

Bronkokonstriksi

Perbaikan epitel

•Proliferasi fibroblast

•Deposisi kolagen•Hipertropi/

hiperplasia otot polos

•Ekspansi vaskuler

Penyempitan saluran nafas

bawah

Symptom alergi

Bronkus hiper-reaktif

ALERGEN

A B C D EImunopatologi alergi

Airway remodelling

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SpA(K)

Trigger

Macam Reaksi

• Reaksi tipe cepat (Rapid onset reaction)• Reaksi tipe lambat (Delayed onset Reaction)• Target organ:

– Mengenai 1 atau lebih organ tertentu– Contoh :

• Paru : asma bronkial• Hidung : rinitis alergika• Kulit : urtikaria, dermatitis atopik• Kardiovaskuler : renjatan anafilaktik

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VACCINATION

ACTIVATIONANTIGEN SPECIFIC B

CELL

GENERATION OF MEMORY

ACTIVATED CD4

+ Th-2 CELL IL-4

DIFFERENTIATION& AFFINITY

MATURATION

ANTIBODY SECRETING PLASMA CELLS

ANTIGEN PROCESSING &PRESENTATION

MHC Class II B CELL IMMUNOGLOBULINE

T CELL RECEPTOR ANTIGEN

B CELL

IL-5,IL-13

Cow’s Milk Protein

Cow’s Milk epitope

Granule contents:Histamine,TNF-

Proteases, Heparin Lipid mediators:Prostaglandins

Leukotrienes

Cytokine production:Specifically IL-4, IL-13

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IgGIgG mediated: Kolik, Protein loosing enteropathy, Gastro-intestinal haemorrhageProf DR Dr Ariyanto Harsono SpA(K)

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Unsoluble allergen

IgMIgM mediated: Kolik, Protein loosing enteropathy, Gastro-intestinal haemorrhage

Prof DR Dr Ariyanto Harsono SpA(K)

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Unsoluble allergen

Prof DR Dr Ariyanto Harsono SpA(K)

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paparan awal...

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patofisiologi

• Patologi yang timbul disebabkan :– intereksi antar sel– mediator – sitokin

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patofisiologi

• Paparan selanjutnya mulai berperan

– limfosit T– netrofil– eosinofil

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Paparan selanjutnya

Mast Cells and basophiles involve in allergic reaction in the context of antigen-IgE complex

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Physiologic barriers Block penetration of ingested antigens: Epithelial cells Glycocalyx Intestinal microvillus membrane structure Tight junctions joining adjacent enterocytes Intestinal peristalsisBreak down ingested antigens: Salivary amylases and mastication Gastric acid and pepsins Pancreatic enzymes Intestinal enzymes Intestinal epithelial cell lysozyme activity

Immunologic barriers Block penetration of ingested antigens: Antigen-specific s-IgA in gut lumen Clear antigens penetrating gastrointestinal barrier: Serum antigen-specific IgA and IgG Reticuloendothelial system

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Intestinal Epithelial Cells (IECs)

Central regulatory role in *Determining allergen absorption*Pattern of uptake of ingested Ag*Function as APC

Mucosal immunoglobulins

S-IgA: Non inflammatoryMucosal protection

S-IgM similar to PlasmaIgM, activates complement and phagocytes

IgG: Neutralization, potentially inflammatory, Activates Complement and phagocytesIgE: Adverse hypersensitivity states, parasite expulsion

IgA

Immunological BarrierThe role of B Cells

Component (SC)

Dimeric

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mAb-IgA

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mAb-SC

Development of Cow’s Milk AllergyEarly introduction of food antigens • stimulate production of IgE • IgE-mediated response to an allergen

– result of a series of molecular & cellular interactions

– Involving APC, T cells and B cells.

APCs present epitope• MHC class II molecules to T cells; peptide-MHC complex. • "first signal" leads to:

– T-cell proliferation, differentiation– initiation of "second"signal

These cells and their products

• interact with B-cells bearing appropriate antigen-specific receptors

• isotype switching • generation of antigen-

specific IgE.

IgE in Relation to Cow’s Milk Allergy

• In atopic children– early antigenic exposure ->

IgE production – sensitisation of mast cells

• gastro-intestinal • respiratory tracts.

• IgE production starts early – primary immune response to food – continue even when the allergen is

avoided by an elimination diet.

• Food IgE-antibody concentrations:– increase to individual peak levels and

thereafter decline– sensitised through breast-milk to foods their

mother have eaten

This explains • infants already react to their first intake of

cow's milk formula• Infants with onset of allergic to one food,

also at high risk of developing allergy to other foods.

once IgE response to cow’s milk protein is initiated

Prevention of food allergy using hypoallergenic milk formula in the first

trimester of life is very important, because:

it progresses throughout the infant life sensitisation to other food allergen may

develop

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Immunoglobulin Other Than IgE

IgG, IgM1. Anaphylactoid

2. Malabsorption.

3. Protein Losing Enteropathy

Induction of Oral ToleranceT-cells regulation: 1.Intra Epithelial Lymphocytes: extrathymically derived, have limited TCR repertoir, capable of recognizing common microbiologic Ags, and demonstrate predominantly cytolytic functions

2.Lamina Propria Lymphocytes: thymicaly derived, contributes to limiting TCR/CD3-mediated signals in the mucosa.

M Cell

Epithelial Cell

Intra EpithelialLymphocyte

Lamina PropriaLymphocyte

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IEL

LPL

CD3

Anergy/Tolerance

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Infiltrasi eosinofil...

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Gejala klinik

organ sasaran• Kulit• saluran napas• saluran cerna

• Mata• telinga• kardiovaskuler

Target Organ

IgE-mediated disorder Non IgE-mediated disorder

Skin 

Gastro-intestinal    

Respiratory Tract Multi-system

Urticaria and angioedemaAtopic Dermatitis

Oral Allergy SyndromeGastrointestinal anaphylaxisAllergic eosinophilic gastroenteritis   Asthma; Allergic Rhinitis Food-induced anaphylaxisFood associated, exercise-induced anaphylaxis

Atopic DrmatitisDermatitis Herpetiformis

ProctocolitisEnterocolitisAllergic eosinophilic- gastroenteritisEnteropathy syndromeCeliac Disease

Heiner Syndrome

Clinical Manifestation

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Target organ Unusual Clinical manifestation

•Skin

•ENT

•Respiratory

•Gastrointestinal

•Multi system

Vasculitis; Fixed Skin Eruption

Chronic Serous Otitis Media

Chronic Pulmonary disease (Heiner Syndrome)Hypersensitivity pneumonitis

Constipation; Gastroesophageal reflux

Irritability/Sleeplessness in infants; Arthropathy;Nephropathy; Thrombocytopenia

Unusual Clinical Manifestation

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Diagnosis

• Anamnesis• pemeriksaan fisik• laboratorium• uji eliminasi provokasi

diagnosis

• Step 1 : eliminasi– eliminasi diet– minimal diet 1 (modified Rowe’s diet 1)– minimal diet 2 (modified Rowe’s diet 2)– egg & fish free diet– his own’s diet

Diagnosis...

Step 2

• Provokasi :-DBPCFC -Open Challenge

Penatalaksanaan

• “The mainstay of treatment of allergic disease is avoidance of allergen”

• allergen yang ditemukan dg uji eliminasi provokasi harus disingkirkan sebaik mungkin

• desensitisasi tidak dilakukan

Diet Eliminasi 1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free

diet5. His own Diet

Prof DR Dr Ariyanto Harsono SpA(K) 66

Diet Eliminasi

1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free

diet5. His own Diet

Prof DR Dr Ariyanto Harsono SpA(K) 67

Elimination Diet (BSTIK)Alergen utama yang harus dipantang selama 3 mingguBuahSusuTelurIkan Kacang

Diet Eliminasi 1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free

diet5. His own Diet

Makanan hipoalergenik yang diperbolehkan:

Nasi(Beras) Daging sapi Kelapa Kedelai Sayur Wortel Bawang Gula, garam

Prof DR Dr Ariyanto Harsono SpA(K) 68

Diet Eliminasi

1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free

diet5. His own Diet

Makanan hipoalergenik lain yang diperbolehkan:

Kentang Daging kambing Jagung Kacang merah Sayur Wortel Bawang Gula, garam

Prof DR Dr Ariyanto Harsono SpA(K) 69

Diet Eliminasi 1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free

diet5. His own Diet

Diet ini digunakan untuk gejala alergi pada kulit.

Telur Ikan dipantang selama 3

minggu

Prof DR Dr Ariyanto Harsono SpA(K) 70

Diet Eliminasi

1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free

diet5. His own Diet

Diet ini digunakan untuk gejala alergi hirupan pada saluran nafas, pada uji kulit debu rumah dan tungau positif, anamnesa positif. Makanan yang disebutkan oleh pasien sendiri yang dipantang selama 3 minggu

Prof DR Dr Ariyanto Harsono SpA(K) 71

Makanan Pengganti

BuahSusuTelurIkan Kacang

Sayur Kentang Wortel Nasi Teh Susu Formula HA/Soya Kue mangkok, lapis, bikang Daging sapi, hati,paru, otak. Tahu, tempe, kecap

Prof DR Dr Ariyanto Harsono SpA(K) 72

PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)

ImunoterapiDietPharmalogic therapy

Beta-2 agonis Xanthine derivativeCorticosteroidAntagonist H1 generasi II

Prof DR Dr Ariyantoarsono SpA(K) 73

PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)

ImunoterapiDietPharmalogic therapy

Beta-2 agonis Xanthine derivativeCorticosteroidAntagonist H1 generasi II

Prof DR Dr Ariyantoarsono SpA(K) 74

Kehamilan = “Th2-disease”

*Anti-oksidan

*Hindari asap rokok

*Probiotik trimester terakhir kehamilan

Pencegahan Primer: Masa Kehamilan

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• ASI Eksklusif• Diet eliminasi untuk

ibu• Formula HA• Tunda makanan padat

Prof DR Dr Ariyanto Harsono SpA(K) 76

Pencegahan Primer dengan susu Formula

FORMULA H.A.

Partially hydrolyzed formulas: BUBUR SUSU

BISKUIT SUSU

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BISKUIT/BUBUR SUSU HA V

PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)

ImunoterapiDietPharmalogic therapy

Beta-2 agonis Xanthine derivativeCorticosteroidAntagonist H1 generasi II

Prof DR Dr Ariyantoarsono SpA(K) 78

Pencegahan Sekunder dengan susu Formula

FORMULA E.H.A.

Extensively hydrolyzed formulas:

BUBUR SUSU

BISKUIT SUSU

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BISKUIT SUSU/Bubur susu HA X

Prevensi Sekunder dengan susu Formula

Soy formulas:BUBUR SUSU

BISKUIT SUSU

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BISKUIT SUSU/BUBUR SUSU HA X

Prevensi Sekunder dengan susu Formula

Amino Acids:BUBUR SUSU

BISKUIT SUSU

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BISKUIT SUSU/BUBUR SUSU HA X

PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)

ImunoterapiDietPharmalogic therapy

Prof DR Dr Ariyantoarsono SpA(K) 82

Penatalaksanaan…..

• Eliminasi makanan setelah uji provokasi

• Diberi petunjuk makanan pengganti

– Pengganti Susu Sapi:

• Susu formula hidrolisat kasein

• Susu formula hidrolisat whey

• Susu formula kedelai

– Pengganti Buah: sayur

– Pengganti telur, ikan, ayam: daging sapi/kambing

• Jika diet tidak bisa dilaksanakan harus diberi pengobatan simtomatis

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PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)

ImunoterapiDietPharmacologic therapy

Prof DR Dr Ariyantoarsono SpA(K) 84

penatalaksanaan

• Tujuan penatalaksanaan– frekuensi serangan– intensitas serangan– penggunaan obat– hari bolos sekolah– kualitas hidup

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penatalaksanaan

• Makanan pengganti (substitusi)– susu : formula hidrolisat whey

formula hidrolisat kasein formula kedelai

– buah : sayur– telur/ikan : daging sapi

daging kambing tahu tempe

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penatalaksanaan

• Makan direstoran tidak aman• Dianjurkan melakukan “label reading”• pada bayi, ibu juga harus ikut eliminasi

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penatalaksanaan

• Farmakoterapi– tidak bisa menggantikan eliminasi alergen– mengurangi gejala ringan tapi menutupi gejala

awal kulit

Obat-obatan dan yang digunakan untuk mengobati alergi dapat dibagi menjadi kelompok besar:

1. Obat yang menghambat aktivitas bahan kimia yang dilepaskan dalam tubuh selama reaksi alergi: - antihistamin dan antagonis leukotriene;

2. Obat yang mengendurkan otot di saluran udara dari paru-paru, atau mengecilkan jaringan padat, atau membalikkan efek dari bahan kimia yang dilepaskan selama reaksi alergi: - bronkodilator, dekongestan dan epinefrin; anti acetylchloline

3. Obat-obatan yang mencegah aktivasi sel yang terlibat dalam reaksi alergi: - agen anti-alergi: kromolin, ketotifen

4. Obat yang memiliki efek yang lebih umum dalam mengurangi peradangan: - kortikosteroid;

5. Terapi yang memodifikasi respon imun: - imunoterapi alergen. Prof DR Dr Ariyanto Harsono

SpA(K)89

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penatalaksanaan

• Cromolin, nedocromil– penggunaan pada asma

• asma ringan• asma latihan• gejala GI• dermatitis atopi

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penatalaksanaan

• Glukokortikoid – digunakan pada penderita alergi makanan

dengan gejala• asma• rinitis alergika• anafilaksis

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penatalaksanaan

• Beta adrenergik agonis– beta 2 agonis

• untuk asma– epinefrin

• untuk renjatan anafilaksis

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penatalaksanaan

• Metilxantin– sebagai bronkodilator

• Antagonis kolinergik– untuk pengobatan tambahan pada penderita

dengan gejala asma, rinitis alergika

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penatalaksanaan

• Leukotrien antagonis: Montelukast, Zafirlukast– untuk gejala asma

• kombinasi dengan xantin dan beta 2 agonis

penatalaksanaan

• H1 reseptor antagonis • Generasi II

– efek samping CNS ( - )– dapat digunakan mulai 6 bulan– dapat digunakan dalam jangka lama – efektif untuk

• urtikaria kronik• rinitis alergika• dermatitis atopik• asma ringan