dr. T.Mamfaluti, Mkes,. Sp.

PD

Sub. Alergi Imunologi
Bagian Ilmu Penyakit Dalam FK Unsyiah/RSUD Dr Zainoel Abidin
Banda Aceh
Reaksi hipersensitivitas tipe 1
Sistemik
Mengancam hidup
Timbul beberapa menit
Gejala :
Saluran nafas
Kardiovaskuler
Kulit
Saluran cerna
Lawan kata : PROPHYLAXIS
ANAPHYLACTOID IgE
Sifat alergen
Atopik
Jalur pemberian obat
Genetik


PREDISPOSISI :
Indonesia ?
USA : 150 oleh makanan
1 tahun 400 800 oleh antibiotik
250 1000 oleh media kontras
Protein : Hormon, enzym, Pollen,
Non Pollen, Makanan,
Antiserum
Polisakarida : Bahan pengawet vaksin
(thyomerosal)
Obat : Antibiotik, Anestesi lokal
MEDICATIONS
Nonsteroidal antiinflammatory drugs, aspirin,
antibiotics, opioid analgesics, insulin, protamine,
general anesthetics, streptokinase, blood
products, progesterone, radiocontrast media,
biologic agents, immunotherapy
FOODS
Peanuts, tree nuts, fish, shellfish, milk, eggs,
bisulfites
HYMENOPTERA VENOM
Honeybees, fire ants etc
MISCELLANEOUS
Latex, exercise, gelatin, menstruation, seminal fluid,
dialysis membranes
Adapted from Rusznak and Peebles.
A. Miyamoto: Clinical allergology 2
nd
edition, Nankoudou, 1998, pp94 (modified)
Type
(Alternative names)
Antibody
(Ab)
Antigen
(Ag)
Related cells Mediators Representative diseases
Type
(Immediate type,
Anaphylactic type)
IgE Foreign antigen
(Mite, pollen,
Fungi, etc.)
Mast cell
Basophil
Eosinophil
Histamine
Leukotriene
PAF, etc.
Asthma
Allergic rhinitis
Urticaria
Atopic dermatitis
Type
(Cytotoxic type,
IgG
IgM
Fereign antigen
(drugs)
Self antigen
Killer cell Complement Drug allergy
Autoimmune hemolytic anemia
Type
(Immune complex type,
Arthus type)
IgG
IgM
Foreign antigen
(Bacteria, drugs)
Self antigen
Mast cell
Basophil
Eosinophil
Complement
Ag-Ab complex
Systemic lupus erythematosus
Rheumatoid arthritis
Glomerular nephritis
Type
(Delayed type,
Cell-mediated immune type,
Tuberculin type)
Foreign antigen
(Bacteria, fungi)
Self antigen
T cell Cytokine Contact dermatitis
Tuberculin reaction
Coombs & Gell classification of hypersensitivity
Ab-dependent type)
Type Type of
immun
respon
Pathophy
siology
Clinical
symptoms
Chrononology of
the reaction
IVa Th1 (IFNy) Monocytic
inflamation
Eczeme 5-21 hari
IVb TH2 (IL-5 dan
IL-4)
Eosinophilic
inflamation
Maculo-
papular
exanthema,
bullous
exanthema
2- 6 minggu
IVc Cytotoxic T
cells
Keratinocyte
death
mediated by
CD4 or CD8
Maculo-
papular
exanthema,
bullous
exanthema
2 hari setelah
pengobatan fixed
drug eruption, 7-
21 hari setelah
pengobatan SJS
atau TEN
IVd T cells (IL-8 ) Neutrophilic
inflammation
Acute
generalized
exanthemato
us pustulosis
Kurang dari 2 hari
ALERGEN
Diproses
di monocytic lineage cell
Stimulasi T cell (Th
2
)
Sitokin
IL 4
Stimulasi sel plasma
IgE spesik
Mast cell
basofil
terikat
Alergen
Reexposure
Mediator
Bioaktif
Histamin, dll
Respons Biologi
al. Kulit Sal. Nafas - Vaskuler
Activation of
Eosinophil
Promotion of Eosinophil
differentiation and proliferation
Histamine release
and PAF, LTC
4
, LTD
4

production from mast cell
LTC
4
, PAF production
and EPO, ECP, MBP
release from grunulocyte
Immediate phase
reaction
Late phase
reaction
IgE production
Promotion of B cell
differentiation and proliferation
Eosinophil
Thymus
Differentiation
IL-5
IL-4
IL-5
IL-4
Promotion of
differentiation
IL-5
Eosinophil
LT
Immediate and Late phase reaction of type I hypersensitivity
Mast cell
Th0
Th2
Th1
B cell
Several min 10 min
6-12 hours
Hematopoietic
stem cell
Bone marrow
Antigen
Differentiation
Leukocyte responses
Adherence
Chemotaxis
IgE production
Mast Cell proliferation
Eosinofil activation

Fibroblast responses
Proliferation
Vacuolation
Globopentaosylceramide
production
Collagen production

Substrate responses
Activation of matrix
metalloproteases
Activation of coagulation
cascade

Microvascular responses
Augmented venular permeability
Leukocyte adherence
Constriction
dilatation
Lipid mediators
LTB
4
LTC
4
PAF
PGD
2

Secretory granule
preformed mediators
Histamine
Proteoglycans
Tryptase and chymase
Carboxypeptidase A

Cytokines
IL-3
IL-4
IL-5
IL-6
GM-CSF
IL-13
IL-1
INF-
TNF-
Activited Mast Cell
Lipid mediators (PGD2, PAF, Leukotriene, dll)
Cytokine (IL-3, IL-4, IL-5, IL-6, TNF, INF, dll)
Secretory granule preformed mediators (Histamin,
typtase, dll)

Respons Biologi
Lekosit (aderen, kemotaksis, aktivasi eosinofil)
Aktivasi sistim koagulasi ( DIC)
Mikrovaskuler (permeabilitas , dilatasi)
Cysteinil leukotrienes konstruksi bronhus
Histamin urtikaria, angioedema, hipotensi
Sistim kinin, PGD2 HIPOTENSI


ONSET : - ~ INDIVIDU
- Detik Menit
Riwayat Allergen Parenteral, Peroral
20% : 6 12 jam Rekurens, bifasik
Rochester Epidemiologic study (1983 1987) :
150 kasus Kulit 100%, Sal. Nafas 69%,
K. Vaskuler 41%, Sal. Cerna 24%

Edema Laring (mengganjal, serak, stridor insp.)
Bronchospasme (tertekan dada, wheezing)
Batuk
Rhinorrhea
Tanda khas DD
Jarang sebagai gejala pertama
Urtikaria (lokal, general : < 48 jam)
Flushing
Angioedema
Rasa terbakar, pedih, tidak terasa
Hipotensi
Syok
Gejala pertama
Aritmia
Gangguan konduksi
Iskemi miokard
Sal. Cerna
Mual, Muntah, Kolik, Diare
Patients (N=133)
Symptom or Sign N %
Cutaneous
Urticaria
Angioedema
Pruritus
Flushing
Conjunctivitis or chemosis
Respiratory
Dyspnea
Throat tightness
wheezing
Rhinitis
Laryngeal edema
Hoarseness

73
74
73
48
30

67
37
34
22
9
9

56
56
55
36
23

43
28
26
17
7
7
Reproduced with permission from Yocum et al.
Source : Semin Respir Crit Care Mes @ 2004 Thieme Medical Publisher
Patients (N=133)
Symptom or Sign N %
Oral and gastrointestinal
Intraoral angioedema
Emesis
Nausea
Abdominal cramps
Dysphagia
Oral prurius
Diarrhea
Cardiovascular
Tachycardia
Presyncope
Hypotension
Syncope
Shock
Chest pain
Bradycardia
Orthostatis

20
12
12
11
7
5
1

36
20
15
4
7
4
2
2

15
9
9
8
5
4
1

27
15
11
3
5
3
2
2
Reproduced with permission from Yocum et al.
Source : Semin Respir Crit Care Mes @ 2004 Thieme Medical Publisher
Secara klinis !!
Riwayat (Alergen, Onset)
Pemeriksaan Fisik : Gambaran Klinik
Lab
IgE Test
Tryptase Test
DD
Penyebab lain dari Syok, Hipotensi dan
Respiratory Distress
Evaluasi Tanda Vital
Medikamentosa
1. Epinephrine
Vasokontriksi, bronchodilator, permeabilitas
vaskuler, sintesa mediator
Sedini mungkin
Tidak dapat diganti yang lain !
SC/1m iv
2. Oksigen
3. Infus replacement cairan
4. Vasopressor (Dopamine) ditambahkan ?
Lainnya
5. Nebulizer tambahan untuk Bronchospasme
6. Intubasi/Trakheotomi lihat hipoksia progresif ?
7. Antihistamin kel. Kulit, sal. Cerna
8. Aminofilin tambahan untuk Bronchospasme
9. Kartikosteroid >< Rekuren/prolong Reaction
10. Terapi Aritmia
11. CVP ?
Source : Curr Opin Allergy Clin Immunol @ 2005 Lippincott Williams & Wilkins
1. Epinephrine Infusion
1 mg in 100 ml (1:100 000, 10 g/ml) intravenously by infusion pump
commence at 30 100 ml/h (5-17 g/min)according to reaction severity
titrate up or down according to response and side effects, aiming for
lowest effective infusion rate
tachycardia, tremor and pallor in the setting of a normal or raised blood
pressure are signs of epinephrine toxicity; consider a reduction in infusion
rate
stop infusion 30 min after resolution of all symptomps and signs
continue observation for at least 2 h after ceasing infussion (longer for
severe or complicated reactions); discharge only if remains symptom-free
2. Normal saline rapid infusion
1000 ml (pressurized) infused over 1-3 min and repeat as necessary
give if hypotension is severe or does not respond promptly to epinephrine
Reprinted with permission from the BMU.
Table 2.
Source : Curr Opin Allergy Clin Immunol @ 2005 Lippincott Williams & Wilkins
1. Lie flat, elevate legs/Trendelenburg position, high-flow oxygen, support
airway and assist ventilation as required
2. Administer IM epinephrine 0.01 mg/kg (max 0.5 mg) into the anterolateral
thigh and proceed to obtain wide-bore intravenous access.
(if IV access is present and patient is in an appropriate environment, may omit
IM epinephrine and proceed directly to intravenous infusion of epinephrine)
3. Once IV access is available, commence rapid volume resuscitation with
Normal Saline or Hartmanns Solution (20 ml/kg start under pressure,
repeated as necessary).
4. If remains hypotensive despite above steps, consider in the following
sequence :
a) Intravenous infusion of epinephrine using an infusion pump (Table 2)
b) Intravenous bolus of atropine, if there is significant bradycardia
c) Intravenous bolus of vasoconstrictor (e.g. Mataraminol, Methoxamine,
Vasopressin)
d) Further investigation/monitoring (central/pulmonary artery cannulation,
echocardiography) to monitor intravascular volume and cardiac function
e) Intravenous glucagon, milrinone/amrinone and/or mechanical support (intra
aortic ballon pump) if remain hypotensive with a suspicion of cardiac failure
rather than volume depletion/vasodilation. Cardiac support may be more
likely to be required if there is coexisting beta-blockade or underlying
cardiac disease.
Table 3. Suggested Management of Anaphylactic Shock
Anamnesa :
Skin Test :
Penting !
Riwayat alergi/anafilaksis
(walau tidak menjamin !!)
Cari alergennya
Awas reaksi silang
Harus dilakukan pada zat
yang bisa alergen
Ideal :



Tidak menjamin
Prick Skin Test/
Scratch Test
Tersedia Kit
Siaga
Monitor post exposure
Desensitisasi ?
Edukasi untuk yang resiko !
Epinephrine Autoinjector Kit
Berat reaksi
Lamanya onset
Edema Laring
Syok
Waktu antara onset Klinik
dan dimulai terapi