Reaksi Anaphylaxis

Raveinal

Division of Allergy and Clinical Immunology

Department of Internal Medicine
FKUA/RS M Jamil Padang
 What is anaphylaxis?
Anaphylaxis is a severe, life-threatening,
generalized or systemic hypersensitivity reaction

Anaphylaxis

Allergic anaphylaxis Non-allergic anaphylaxis

IgE-mediated anaphylaxis Non-IgE-mediated allergic anaphylaxis

Johansson SGO, et al. Allergy 2001;56:813-824

Anafilaksis merupakan reaksi
alergi sistemik yang berat,
dapat menyebabkan kematian,
terjadi secara tiba-tiba
sesudah terpapar oleh alergen
atau pencetus lainnya
 Mechanisms underlying human
anaphylaxis

Human anaphylaxis

Immunologic Non-Immunologic
Idiopathic

IgE, FcεRI Other Physical Other

foods, venoms, blood products, exercise, cold drugs
latex, drugs immune aggregates,
drugs

Simon FER. J Allergy Clin Immunol 2006;117:367-77

 Why we should know?
 Anaphylaxis can be fatal
 Unpredictable and suddenly
 Can happen anywhere
 Its prevalence increased
 Medico legal ?
 Epidemiology :
 Prevalence of anaphylaxis
1. 1 : 2300 attendees at ED in UK (Stewart & Ewan, 1996)
2. Anaphylaxis hospital discharge 5.6/100.000 (1991 – 2)
 10.2/100.000 (1994 - 5) (Sheik & Alves, 2000)
3. 13.230 admission for anaphylaxis 1990 - 2000 (Gupta,
et al. 2003)
4. 214 death attributed to anaphylaxis in UK 1992 – 2001
(Pumphrey, 2004)
Anaphylaxis: population study in 5 years
 Incidence (annual): 21 per 100.000 person – year
 133 residents who experienced 154 anaphylactic
episode : - 116 residents 1 episode
- 13 resident 2 episode
- 4 residents 3 episode
 53% atopy
 68% allergen identified: food, medication and insect
sting
 52% allergy consultation
 7% hospitalization
 1 patient died
Yocum, et al. JACI 1999;104:452-6
 Anaphylaxis can be fatal
 Be able to recognize the symptoms
 Know and avoid the triggers
 Have an emergency action plan
 Treat it promptly and appropriately
CLINICAL FEATURES
 Anaphylaxis symptoms
 MOUTH itching swelling of lips and/or tongue
 THROAT itching, tightness, closure, hoarseness
 SKIN itching, hives, redness, swelling
 GUT vomiting, diarrhea, cramps
 LUNG shortness of breath, cough, wheeze
 HEART weak pulse, dizziness, passing out
 NEURO headache, visual loss, loss of
consciousness, incontinence, confusion
 Frequency of occurrence of signs &
symptoms of anaphylaxis*+
Signs & symptoms
Cutaneous 90%
Urticaria & angiodema 85-90%
Flushing 45-55%
Pruritus without rash 2-5%
Respiratory 40-60%
Dyspnea, wheeze 45-50%
Upper airway angioedema 50-60%
Rhinitis 15-20%
Dizziness, syncope, hypotension 30-35%
Abdominal
Nausea, vomiting, diarrhea, cramping pain 25-30%
Miscellaneous
Headache 5-8%
Substernal pain 4-6%
Seizure 1-2%
* On the basis of a compilation of 1865 patients reported in references 1 through 14
+ Percentages are approximations
 Grading of anaphylactic reactions according to severity of clinical symptoms
Symptoms
Grade Dermal Abdominal Respiratory Cardiovascular
I Pruritus
Flush
Urticaria
Angiodema
II Pruritus Nausea Rhinorrhoea Tachycardia (> 20 bpm)
Flush Cramping Hoarseness Blood pressure change (>
Urticaria Dyspnoea 20 mmHg systolic)
Angiodema (not Arrhytmia
mandatory)
III Pruritus Vomiting Laryngeal oedema Shock
Flush Defecation Bronchospasm
Urticaria Diarroea Cyanosis
Angiodema (not
mandatory)
IV Pruritus Vomiting Respiratory arrest Cardiac arrest
Flush Defecation
Urticaria Diarrhoea
Angiodema (not
mandatory)
Bpm = beats perminute
Ring J, Brockow K & Behrendt. History and classification of anaphylaxis. In Anaphylaxis. Novartis Foundation 2004:12
 Derajat berat reaksi hipersensitivitas
yang luas
Derajat
Ringan (hanya kulit dan jaringan
submukosa)*
Sedang (keterlibatan
pernapasan,
kardiovaskuler,atau
gastrointestinal
Berat (hipoksia,hipotensi,atau
defisit neurologik)
Gambaran klinik
Eritema luas,edema periorbita,atau
angioedema
Sesak, stridor, mengi, mual, muntah,
pusing, presinkop diaforesis, rasa
tertekan di dada atau tenggorok atau
sakit perut
Sianosis, atau SpO2 < 92% pada tiap
tingkat, hipotensi (tek sistolik < 90 mm
Hg pd dewasa), bingung kolaps, hilang
kesadaran atau inkontinens

* Reaksi ringan dapat dibagi lagi, disertai atau tidak ada angiodema
 Grading system for generalized
reactions (from Brown 2004)
Grade
Mild (skin and subcutaneous
tissue only)*
Moderate (features suggesting
respiratory, cardiovascular or
gastrointestinal involvement)
Severe (Hypoxia, hypotension
or neurological compromised
Defined by
Generalized erythema, urticaria,
periorbital oedema or angiodema
Dyspnoea, stridor, wheeze, nausea,
vomiting, dizziness (presyncope)
Cyanosis or SpO2 ≤ 92%, hypotension
(SBP < 90 mm Hg in adults), confusion,
collapse, LOC or incontinence

* The mild grade does not represent anaphylaxis according to the National Institute of Allergy and
Infections Disease-food Allergy and Anaphylaxis Network (NIAID-FAAN) definition (Box 2), loss of
consciousness; SBP, systolic blood pressure.
Brown SGA. JACI, 2004:114:371-6
 Elicitors of anaphylaxis (including anaphylactoid reactions)
Drugs
Foods
Drug and food additives
Occupational substances (e.g. latex)
Animal venoms
Aeroallergens
Seminal fluid
Contact urticariogens
Physical agents (colt, heat, ultraviolet radiation)
Exercise
Echinococcal cyst
Summation anaphylaxis
Underlying disease
Complement factor 1-inactivator deficiency
Systemic mastocytosis
Idiopathic (?)
Ring J, Brockow K & Behrendt. History and classification of anaphylaxis. In Anaphylaxis. Novartis Foundation 2004:12
 The causes of anaphylaxis
35

30

25
Percent of Cases

20

15

10

0
Food Drug/Bio Sting Allergen Exercise Idiopathic
Golden DBK, Patterns of anaphylaxis: Acute & late phase features of allergic reactions. In Anaphylaxis. Novartis
foundation 2004: 103
 Suspected cause of death 212 reactions
Sting 47 29 wasp, 4 bee, 14 unidentified

Nuts 32 2 almond, 2 brazil, 1 hazel, 10 peanut, 6 walnut, 11 mixed or

unidentified
Food 13 1 banana, 2 chickpea, 2 fish, 5 milk, 2 crustacean, 1 snail

Food? 18 1 ?fish, 5 during meal, 1 ?grape, 3 ?milk, 3 ?nut, 1 ?sherbet, 1

?strawberry, 1 ?yeast, 1 ?nectarine
Antibiotic 27 1 benzypenicillin, 10 aminopenicillin, 12 cephalosporin, 1
ciprofloxacin, 1 vancomycin, 2 amphotericin
Anesthetic 35 19 suxamethonium, 7 vecuronium, 6 attracurium, 7 at induction

Other drug 15 3 ACE inhibitor, 6 NSAID, 5 gelatines, 2 protamine, 2 vitamin K,

1 Diamox (acetazolamide), 1 etoposide, 1 pethidine, 1 heroin, 1
kabikinase, 1 local anaesthetic
Contrast 11 9 iodinated, 1 technetium, 1 fluorescein
media
Other 3 1 latex, 1 hair dye, 1 hydatid, 1 idiophatic
Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:118
 Mode of death

Drug Sting Food Food? Male Female

Lower airways 11 3 24 11 21 26

Upper + lower airways 6 4 13 3 5 19

Upper airways 7 8 5 3 16 12

Shock + asphyxia 21 4 2 12 15

Shock 32 18 2 23 29

Disseminated 5 1 1 2 4
intravascular coagulation

Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:120
Interval from exposure to first arrest. Drug reaction
were fastest, mostly taking less than 5 minutes
Food Stings Drug
30

25

20

15

10

0
<1 1-2 2.1-4.5 4.6-9.9 10-20 21-45 46-99 100- >215
214
minutes from exposure to first arrest

Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:121
DIAGNOSIS
 Kriteria klinik diagnosis anafilaksis1

1. Terjadinya gejala penyakit segera (beberapa menit

sampai jam), yang melibatkan kulit, jaringan mukosa,
atau keduanya (urtikaria yang merata, pruritus,atau
kemerahan, edema bibir-lidah-uvula) DAN PALING
SEDIKIT SATU DARI BERIKUT INI :
a. Gangguan pernapasan (sesak, mengi-
bronkospasme, stridor, penurunan Arus Puncak
Ekspirasi (APE), hipoksemia.
b. Penurunan tekanan darah atau berhubungan
dengan disfungsi organ (hipotonia atau kolaps,
pingsan, inkontinens)
Kriteria klinik diagnosis anafilaksis2
2. Dua atau lebih dari petanda berikut ini yang terjadi
segera setelah terpapar serupa alergen pada penderita
(beberapa menit sampai jam):
a.Keterlibatan kulit-jaringan mukosa (urtikaria yang
merata, pruritus-kemerahan, edema pada bibir-
lidah-uvula)
b.Gangguan pernapasan (sesak, mengi-
bronkospasme, stidor, penurunan APE, hipoksemia)
c.Penurunan tekanan darah atau gejala yang
berhubungan (hipotonia-kolaps, pingsan,
inkontinens)
d.Gejala gastrointestinal yang menetap(kram perut,
sakit, muntah)
Kriteria klinik diagnosis anafilaksis3

3. Penurunan tekanan darah segera setelah terpapar

alergen (beberapa menit sampai jam)
a. Bayi dan anak : tekanan darah sistolik rendah
(tgt umur), atau penurunan lebih dari 30%
tekanan darah sistolik.
b. Dewasa : tekanan darah sistolik kurang dari 90
mm Hg atau penurunan lebih dari 30% nilai basal
pasi
* Tekanan darah sistolik rendah untuk anak didifinisikan bila < 70 mm
Hg antara 1 bulan sampai 1 tahun, kurang dari (70 mm Hg [2x
umur]) untuk 1 sampai 10 tahun, dan kurang dari 90 mm Hg dari 11
sampai 17 tahun.
TREATMENT
 Penatalaksanaan anafilaksis
1. Hentikan pencetus, nilai beratnya dan berikan terapi yang sesuai

Minta bantuan

Adrenalin i.m (paha lateral) 0.01mg/kg boleh sampai 0.5mg

Pasang infuse

Berbaring rata/ tinggikan posisi kaki bila bias

Berikan oksigen aliran tinggi,alat bantu napas/ventilasi bila diperlukan

BILA HIPOTENSI

Akses i.v.tambahan (jarum 14G atau 16G pada orang dewasa) utk
infus NaCl fisiologis. NaCl fisiologis bolus atau infus 20 mL/kg
diberikan secepatnya bila perlu dengan tekanan
 Penatalaksanaan anafilaksis
2. Bila respons tidak adekuat, keadaan mengancam kehidupan, atau memburuk:

Mulai dengan infuse adrenalin sesuai dengan panduan/protocol rumah sakit

ATAU
Ulang adrenalin i.m setiap 3-5 menit

Pertimbangkan hal-hal berikut

 Hipotensi
o Ulangi infuse NaCl fisiologis 10-20 ml/kg dapat mencapai 50 ml/kg dalam 30 menit.
o i.v. atropine 0.02 mg/kg bila bradikardi berat dosis minimum 0.1 mg
o i.v vasopresor untuk mengatasi vasodilatasi. Pada henti jantung adrenalin dapat
ditingkatkan menjadi 3-5 mg setiap 2-3 menit mungkin efektif.
o i.v. glucagons pada pasien yang memakai obat penyekat beta. Dosis orang dewasa
1-5 mg diikuti 5-15 ug/mnt
 Bronkospasme
o Inhalasi salbutamol secara kontinyu
o i.v. hidrokortison 5mg/kg diikuti prednisone 1mg/kg maksimal (50 mg) selama 4 hari
 Obstruksi saluran napas bagian atas
o Adrenalin inhalasi (5 mg atau 5 ml sediaan adrenalin 1;1000) mungkin membantu.
o Persiapkan tindakan bedah.
 Penatalaksanaan anafilaksis
3 . Lama observasi dan tindak lanjut
1 Observasi paling tidak 4 jam setelah semua gejala dan tanda
menghilang.
 Bila memungkinkan periksa kadar triptase serum saat dating, 1 jam
stelahnya, dan sebelum dipulangkan.
 Pada kasus yang berat pasien dirawat semalam, terutama pasien
yang mempunyai riwayat reaksi yang berat atau asma yang tidak
terkontrol dan pasien yang datang pada malam hari.
2 Sebelum dipulangkan pasien diberikan penjelasan mengenai alergen
tersangka dan upaya penghindarannya
Setelah dipulangkan pasien dirujuk ke ahli alergi terutama pada kasus
yang sedang – berat, dan yang ringan karena alergi makanan yang
disertai asma.
3 Di negara maju setelah dibekali penjelasan dan pelatihan sebagian
pasien di berikan EpiPen yaitu adrenalin 0.3 atau 0.15 mg yang siap
pakai
 Pharmacology of epinephrine

Epinephrine

1-adrenergic 2-adrenergic
1-receptor 2-receptor
receptor receptor

 vasoconstriction  insulin release  inotropy  bronchodilation

 peripheral vascular resistance  neropinephrine release  chronotropy  vasodilation
 mucosal edema  glycogenolysis
 mucosal edema

Estelle FER. J Allergy Clin Immunol 2004;113:837-44

 Absorption of epinephrine is faster after
intramuscular injection than after
subcutaneous injection

Intramuscular
epinephrine 8  2 minutes
(Epipen®)

Subcutaneous 34  14 (5-120) minutes

epinephrine p < 0.05

5 10 15 20 25 30 35

Time to Cmax after infection (minutes)

Estelle FER. J Allergy Clin Immunol 2004;113:837-44

PREVENTION
 Education of anaphylaxis
 Individuals and their families
 Caregivers
 Health case professional (doctors, nurses)
 First responden
 Emergency medical services
 Teachers coaches, child care providers
 Food industries, restaurant, law makers
 Why is follow up is needed ?

 Anaphylaxis can occur repeatedly

 The trigger need to be confirmed
 Long-term preventive strategies need to be
implemented
 Sample Chef Card
To the Chef:
WARNING! I am allergic to peanuts. In order to avoid a life-threatening
reaction, I must avoid the following ingredients:
Artificial nuts
Beer nuts
Cold pressed, expelled, or extruded peanut oil
Ground nuts
Mandelonas
Mixed nuts
Monkey nuts
Nut pieces
Peanut
Peanut butter
Peanut flour
Please ensure any utensils & equipment used to prepare my meal, as
well as prep surfaces, are thoroughly cleaned prior to use. Thanks for
your cooperation
Munoz. Anaphylaxis 2004. Wiley, Chichester. P. 265-75
THANK YOU