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Alergi Makanan

Wisnu Barlianto
Divisi Alergi-Imunologi
Lab. Ilmu Kesehatan Anak
FK Universitas Brawijaya/RS dr. Saiful Anwar
Malang
Pokok bahasan

Klasifikasi reaksi simpang makanan


Patogenesis alergi makanan
Manifestasi klinis dan diagnosis
alergi makanan
Tata laksana alergi makanan
Prognosis alergi makanan
Klasifikasi reaksi simpang makanan

Adverse
Food
Reaction

Immune
Non-Immune
Mediated
Mediated
(food allergy
(primarily food
and celiac
intolerances)
disease)

IgE Mediated Non-IgE Mediated Mixed IgE and non


(eg. Food protein- Cell mediated
(e.g acute IgE mediated
induced (eg. Allergic
urticaria, oral enteropathy, celiac (eg. Eosinophilic
contact dermatitis)
allergy syndrome) gastroenteritis)
disease)

Boyce JA et al. J Allergy Clin Immunol 2010;126:S1-S58


Klasifikasi reaksi simpang makanan

Adverse
Food
Reaction

Non-Immune
Mediated
(primarily food
intolerances)

Metabolic Toxic Other/Idiopathic


Pharmacologic
(eg.lactose (eg. Scambroid Undefined
intolerance) (eg. caffeine) (eg.sulfites)
fish toxin)

Boyce JA et al. J Allergy Clin Immunol 2010;126:S1-S58


Apakah alergi makanan?
Reaksi simpang makanan yang disebabkan
oleh respon imun spesifik terhadap makanan

Apakah food allergen?


Komponen spesifik di dalam makanan yang
merangsang respon imun spesifik

Apakah intoleransi makanan?


Reaksi simpang makanan yang disebabkan
oleh mekanisme non imunologis
Eggs Milk
Peanuts

Tree nuts

Almonds Food Allergens Shellfish


Cashews 8 top allergens cause
Walnuts 90% of food allergens Crab
Lobster
Shrimp

Wheat
Fish
Soy
Bass
Cod
flounder
67.8
70

60.2 59.3 59.3


60 56.8

50 46.6
Hasil SPT positif dalam %

40

30

20

10

0
coklat udang telur susu kepiting tongkol

Data Poli Alergi Anak RSSA tahun 2008


Makanan yang sering menyebabkan
alergi makanan
Bayi Anak Anak lebih tua / dewasa
Susu sapi Susu sapi Kacang-kacangan
Telur Telur Tree nut
Kacang-kacangan Kacang-kacangan Ikan
Susu soya Susu soya Kerang
Gandum
Tree nut (walnut, kacang
mente, dll)
Ikan
Kerang
Usia saat munculnya alergi makanan terhadap
makanan berbeda

Usia (tahun) Makanan


01 Susu, telur
12 Kacang, ikan di negara
Scandinavian
>2 Buah, legumes, sayur-
sayuran
>3 Serbuk bunga terkait
reaksi silang (Oral Allergy
Syndrome)
Prevalensi alergi makanan pada satu tahun pertama
(Cantana A, 2008. Pediatric Allergy Asthma & Immunology 1st ed)
Patogenesis alergi makanan
Protein digestion
Antigen processing
Some Ag enters blood

IgE-Mediated
IgE-receptor
APC
Mast cell
Non-IgE-
Mediated
Histamine
B cell T cell TNF-
IL-5
The immunologic spectrum

IgE-Mediated Non-IgE-Mediated

Rhinitis alergica Eosinophilic esophagitis Protein-induced enterocolitis


Asthma bronchiale Eosinophilic gastritis Protein-induced enteropathy
Urtikaria Eosinophilic gastroenteritis Eosinophilic proctitis
Anaphylaxis Atopic dermatitis Dermatitis herpetiformis
Celiac disease

Clinical manifestation
Dermatitis atopi
Asma bronkhial
Rhinitis alergi
Pendekatan diagnosis alergi makanan

- Anamnesis
- Gejala klinis
- Uji tusuk kulit (Skin Prick Test)
- IgE spesifik alergen
- Eliminasi dan provokasi
- Endoskopi dan biopsi
APA TANDA DAN GEJALA
ALERGI MAKANAN?
Organ system Immediate symptoms Delayed symptoms
Cardiovascular Dizziness
Fainting
Hypotension
Loss of consciousness
Tachycardia
(occasionally
bradycardia
in anaphylaxis
Cutaneous Angioedema Angioedema
Erythema Eczematous rash
Morbilliform eruption Erythema
Pruritus Flushing
Urticaria Morbilliform eruption
Pruritus
Gastrointestinal Colicky abdominal Abdominal pain
(lower) pain Diarrhea
Diarrhea Hematochezia
Nausea Irritability and
Reflux food refusal with
Vomiting weight loss (young
children)
Nausea or vomiting
Reflux
Yawn BP. Am Fam Physician. 2012;86(1):43-50.
Organ system Immediate symptoms Delayed symptoms

Gastrointestinal Angioedema of the


(oral) lips, tongue, or
palate
Oral pruritus
Tongue swelling
Ocular Conjunctival Conjunctival
erythema erythema
Periorbital edema Periorbital edema
Pruritus Pruritus
Tearing Tearing
Respiratory Accessory muscle use Cough
(lower) Chest tightness Dyspnea
Cough Wheezing
Dyspnea
Intercostal retractions
Wheezing
Respiratory Dry staccato cough
(upper) Hoarseness
Laryngeal edema
Nasal congestion
Rhinorrhea
Sneezing
BAGAIMANA MENDIAGNOSIS
ALERGI MAKANAN?
Allen KJ et al. MJA
2006; 185: 394
400
Anamnesis

Description of symptoms and signs


Timing from ingestion to onset of symptoms
Frequency with which reactions have
occurred
Time of most recent occurrence
Quantity of food required to evoke the
reaction
Associated factor (activity, medication,
alcohol)
Metode diagnostik
Pemeriksaan SPT atau IgE spesifik saja
tidak dapat menegakkan diagnosis alergi
makanan
SPT dan IgE spesifik dapat membantu
diagnosis alergi makanan yang diperantarai
IgE
SPT memiliki nilai prediksi positif yang
rendah
IgE spesifik memiliki nilai prediksi yang
tidak konsisten
Boyce JA et al. J Allergy Clin Immunol 2010;126:S1-S58
Tata laksana
ASI eksklusif selama 6 bulan
Menghindari segala bentuk alergen
Anti histamin
Adrenalin
Lini pertama adalah
menghindari alergen
penyebab

Obat tidak
direkomendasikan

Anti histamin
adrenalin

Boyce JA et al. J Allergy Clin Immunol 2010;126:S1-S58


ALERGI PROTEIN SUSU
SAPI
Alergi susu sapi (ASS) adalah suatu
reaksi yang tidak diinginkan yang
diperantarai secara imunologis
terhadap protein susu sapi
ASS biasanya dikaitkan dengan
reaksi hipersensitifitas tipe 1 yang
diperantarai IgE
ASS dapat diakibatkan oleh reaksi
imunologis yang tidak diperantarai
oleh IgE atau kombinasi keduanya
Komposisi protein susu sapi

Protein Berat molekul %


(Dalton)
Casein
-s1-casein 23.000 32
-s2-casein 25.000 8
-casein 24.000 32
Kappa-casein 19.000 8
80
Whey protein
-Lactoglobulin 18.000 12
-Lactalbumin 14.000 4
Immunoglobulin 3
Serum albumin 1
20
The proteins in cows milk [1]

Alessandro F, et al. Cows Milk Allergy in Children and Adults.


1Alessandro F, et al. Cows Milk Allergy in Children and Adults.
Gejala klinis
Gastrointestinal 50-60%
Kulit 50-60%
Sistem pernapasan 20-30%
Biasanya timbul sebelum usia 1
bulan
Vandenplas et al. 2007. Arc Dis Child:92:902-8
Host A. 2002. Ann Allergy Asthma Immunol;89 (Suppl 1):33-7
Klasifikasi

IgE Non-IgE
mediated mediated

Gejala klinis Gejala klinis


timbul 30 menit timbul lebih
sampai 1 jam lambat (1 3 jam)

Urtikaria, angioedema, ruam Eosinophilic


kulit, dermatitis atopi, muntah, gastroenteropathy, kolik,
diare, rinokonjungtivitis, enterokolitis, proktokolitis,
bronkospasme, anafilaksis anemia, gagal tumbuh
ASS ringan/sedang
Regurgitasi berulang, muntah, diare,
konstipasi, darah pada tinja
Anemia defisiensi besi
Dermatitis atopik, angioedema,
urtikaria
Pilek, batuk kronik, mengi
Kolik persisten (> 3 jam perhari, 3
hari/minggu selama lebih dari 3
minggu)
ASS berat
Gagal tumbuh karena diare atau
regurgitasi
Anemia defisiensi besi karena
kehilangan
darah melalui tinja, protein-losing
enteropathy
Dermatitis atopik berat
Laringoedema akut atau obstruksi
bronkhus dengan kesulitan bernapas
Syok anafilaksis
Pendekatan diagnosis alergi
susu sapi
- Riwayat alergi terhadap susu sapi
- Gejala klinis
- Uji tusuk kulit (Skin Prick Test)
- Uji RAST
- Eliminasi dan provokasi
- Endoskopi dan biopsi
Vandenplas et al. 2007. Arc Dis Child;92:902-8
Nowak-Wegrzyn and Sampson. 2006. Med Clin N Am;90:97-127
Scurlock, et al. 2005. Immunol Allergy Clin N Am;25:369-88
Burks and Weber. 2000. J Pediatr Gastroenterol Nutr;30:1-26
In vivo In vitro
IgE
Uji kulit
spesifik

Uji Plasma
provokasi tryptase
Interpretation of SPT
The peak reactivity of prick/puncture
tests is 15 to 20 minutes at which time
both wheal and erythema diameters (or
areas) should be recorded in
millimeters and compared with positive
and negative controls
(+) = wheal (with equivalent erythema)
of 3 mm or above
Perbandingan uji kulit dan IgE spesifik

Uji kulit IgE spesifik


Prinsip dasar IgE-Mediated
Usia < 2 th dan > 65 th Semua usia
hiporesponsif
Bebas anti histamin 3 hari Tidak perlu
Aeroalergen Sensitivitas 55%-98% Sensitivitas 55%-80%
Spesifisitas 82%-99% Spesifisitas 82%-99%
Alergen makanan Nilai ramal positif Bervariasi, tergantung
<50% cut off point
Tata laksana
ASI eksklusif selama 6 bulan
Menghindari segala bentuk produk
susu sapi
Anti histamin
Epinefrin

Kemp AS et al. 2008. MJA;188:109-12


Brill H. 2008. Can Fam Physician;54: 1258-64
Vandenplas et al. 2007. Arc Dis Child:92:902-8
Osborn DA et al. 2006. Cohrane Database of
Systematic Reviews
Committee on Nutrition AAP. 2000.
Pediatrics;106: 346-9
Proses pembuatan
Formula hidrolisat

Protein in hypoallergenic formula is


hydrolized into peptides and short chain
amino acids
partially extensively synthetic
hydrolyzed hydrolyzed amino acid

ALLERGENICITY

Protein or peptide with shorter peptide chains and


smaller molecule has a lower allergenicity.
Jenis Formula hidrolisat

Formula terhidrolisat sebagian


(berat molekul < 5000 dalton)
Formula terhidrolisat sempurna
(berat molekul < 3000 dalton)
Formula asam amino bebas
Greer FR et al. 2008. Pediatrics;121:183-91
Formula hipoalergenik
Formula terhidrolisat
sempurna

Formula asam amino bebas


Formula
Tidak
penggant
memberikan
Formula i pada
reaksi alergi pada
hipoalergenik anak
90% anak dengan
alergi
alergi susu sapi
susu sapi

Formula
Formula pengganti untuk
terhidrolisat pencegahan
sebagian pada anak yang
belum alergi
Makanan yang mungkin mengandung
protein susu sapi
Batter-fried foods Muffins
Biscuits Other baked goods
Bread Packaged soups
Breakfast cereals Pies
Cakes Puddings
Chocolate Rusks
Cookies Sausages
Cream sauces Sherbet
Cream soups Soy cheese
Custard Soup mixes
Fish in batter Sweets
Gravies and gravy mixes Canned soups
Ice cream (and "non-milk" Vegetarian cheese
fat)
Imitation sour cream
Instant mashed potatoes
Margarine Steinman HA. J Allergy Clin Immunol
Muesli
1996:98:241-50
Label yang menunjukan adanya protein susu
sapi

Artificial butter flavor Lactose


Butter Milk
Butter fat Milk derivate
Buttermilk solids Milk protein
Caramel color Milk solids
Caramel flavoring Natural flavoring
Casein Pasteurized milk
Caseinate Rennet casein
Cheese Skim milk powder
Cream Curds Solids
"De-lactosed" whey Sour cream (or solids)
Demineralized whey Sour milk solids
Dried milk Whey
Dry milk solids Whey powder
Fully cream milk powder Whey protein concentrate
High protein flavor Yogurt
Lactalbumin
Lactalbumin phosphate Steinman HA. J Allergy Clin Immunol
1996:98:241-50
Formula kedelai
Apabila susu formula terhidrolisat ekstensif
tidak tersedia atau terdapat kendala biaya,
maka sebagai alternatif bayi dapat
diberikan susu formula yang mengandung
isolat protein kedelai dengan penjelasan
kepada orang tua
Angka kejadian alergi protein kedelai pada
bayi berkisar 10-20% dengan proporsi
25% pada bayi dibawah 6 bulan dan 5%
pada bayi diatas 6 bulan
Studies on soy protein sensitization
and allergy
Study Population Prevalence (%)
Soy sensitization Soy allergy
Western countries
United States6 CMA 59.4 14
Finland8 CMA 20 10
Finland9 CMA 31 0
Asian countries
Japan13 National survey ND 1.4
Food allergy ND 11
Japan11 Food allergy 20 ND
Thailand12 CMA ND 17
Munasir Z et al CMA 17,5% ND
Results
Anthropometric patterns of children fed
SIF were similar
Hb, serum protein, Zn and Ca
concentrations and bone mineral content
were found to be similar
There is no evidence of a negative effect
on reproductive and endocrine functions
Immune measurements and
neurocognitive parameters were similar
Choosing the appropriate substitute
formula in different presentations [1]
Clinical presentation 1st choice 2nd 3rd choice
choice
Anaphylaxis AAF+ eHF#, SF
Immediate gastrointestinal allergy eHF, AAF/SF
Food protein-induced enterocolitis AAF eHF*
syndrome
Asthma and rhinitis eHF, AAF/SF
Acute urticarial or angioedema eHF, AAF/SF
Atopic dermatitis eHF, AAF/SF
Gastroesophageal reflux disease eHF AAF
Alessandro F, et al. Cows Milk Allergy in Children and Adults.
Choosing the appropriate substitute
formula in different presentations
(continued) [1]

Clinical presentation 1st choice 2nd 3rd choice


choice
Allergic eosinophilic esophagitis AAF
Cows milk protein-induced enteropathy eHF, AAF
Constipation eHF AAF Donkey
milk
Severe irritability (colic) eHF AAF
CM protein-induced gastroenteritis and eHF AAF
proctocolitis
Milk-induced chronic pulmonary disease AAF SF eHF
(Heiners syndrome)**

Alessandro F, et al. Cows Milk Allergy in Children and Adults.


Prognosis
45-55% remisi pada tahun pertama
60-75% remisi pada tahun kedua
90% remisi pada tahun ketiga

Vandenplas et al. 2007. Arc Dis Child:92:902-8


Nowak-Wegrzyn and Sampson. 2006. Med Clin N Am;90:97-127
Scurlock, et al. 2005. Immunol Allergy Clin N Am;25:369-88
Host A. 2002. Ann Allergy Asthma Immunol;89 (Suppl 1):33-7
Dapatkah alergi dicegah?
Genetic Environment

Allergy
Diet

Environment
infection

Microbial exposure
in early life

Allergen

Pollution
Primary Prevention of immunological
prevention sensitisation

Secondary Preventing the development


of an allergic disease
prevention following sensitisation

Tertiary Treatment of asthma and


prevention allergic diseases
Perjalanan alamiah alergi susu sapi
Host A, Halken S.1990. Allergy 45:587596
Bagaimana perkembangan alergi pada bayi/anak?
Conclusion: IgE-mediated CMA often persists to school age and is a
risk factor for other atopy; nonIgE-mediated CMA, by contrast, is a
benign infantile condition
(J Allergy Clin Immunol 2005;116:869-75)
Exclusive breastfeeding is recommended for all
infants for the first 4-6 months

Dietary restrictions are not recommended for all


pregnant or lactating mothers

Introduction of complementary foods after the


age of 4 months according to normal standard
weaning practices and nutrition
recommendations

No withholding or encouraging exposure to


highly allergenic foods such as cows milk,
hens egg and peanuts irrespective of atopic
heredity
Muraro A et al,. EAACI Guidelines Food Allergy and Anaphylaxis, 2014
High risk infant
The use of cows milk-based
hydrolysates for the first 4 months,
when breast milk is insufficient, can
reduce the development of eczema
After the age of 4 months a
standard cows milk based formula
is recommended according to
standard nutrition recommendations
No special dietary restrictions after
the age of 4 months for infants with
high risk for development of allergic
disease
Muraro A et al,. EAACI Guidelines Food Allergy and Anaphylaxis, 2014
Ringkasan
Alergi makanan merupakan salah satu
reaksi simpang makanan
Berdasarkan mekanisme terjadinya
dibagi menjadi IgE-mediated dan non-
IgE-mediated
Pendekatan diagnosis dilakukan
dengan anamnesis, gambaran klinis, uji
tusuk kulit, IgE spesifik, eliminasi dan
provokasi
Prinsip utama terapi adalah menghindari
segala bentuk alergen
Ringkasan
ASI eksklusif merupakan salah satu
usaha pencegahan primer terhadap
alergi makanan
Toleransi terhadap alergi makanan tidak
sama pada setiap alergen
Alergi makanan meningkatkan resiko
terjadinya gejala atopi lainnya
Thank you