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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

IgE-mediated anaphylaxis

Non-allergic 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, FcRI

Other

Physical

Other

foods, venoms,
latex, drugs

blood products,
immune aggregates,
drugs

exercise, cold

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.
2.
3.
4.

1 : 2300 attendees at ED in UK (Stewart & Ewan, 1996)


Anaphylaxis hospital discharge 5.6/100.000 (1991 2)
10.2/100.000 (1994 - 5) (Sheik & Alves, 2000)
13.230 admission for anaphylaxis 1990 - 2000 (Gupta,
et al. 2003)
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
Urticaria & angiodema
Flushing
Pruritus without rash
Respiratory
Dyspnea, wheeze
Upper airway angioedema
Rhinitis
Dizziness, syncope, hypotension
Abdominal
Nausea, vomiting, diarrhea, cramping pain
Miscellaneous
Headache
Substernal pain
Seizure

90%
85-90%
45-55%
2-5%
40-60%
45-50%
50-60%
15-20%
30-35%
25-30%
5-8%
4-6%
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

Pruritus
Flush
Urticaria
Angiodema

II

Pruritus
Flush
Urticaria
Angiodema (not
mandatory)

Nausea
Cramping

Rhinorrhoea
Hoarseness
Dyspnoea

Tachycardia (> 20 bpm)


Blood pressure change (>
20 mmHg systolic)
Arrhytmia

III

Pruritus
Flush
Urticaria
Angiodema (not
mandatory)

Vomiting
Defecation
Diarroea

Laryngeal oedema
Bronchospasm
Cyanosis

Shock

IV

Pruritus
Flush
Urticaria
Angiodema (not
mandatory)

Vomiting
Defecation
Diarrhoea

Respiratory arrest

Cardiac arrest

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

Gambaran klinik

Ringan (hanya kulit dan jaringan Eritema luas,edema periorbita,atau


submukosa)*
angioedema
Sedang (keterlibatan
Sesak, stridor, mengi, mual, muntah,
pernapasan, kardiovaskuler,atau pusing, presinkop diaforesis, rasa
gastrointestinal
tertekan di dada atau tenggorok atau
sakit perut
Berat (hipoksia,hipotensi,atau
defisit neurologik)

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

Defined by

Mild (skin and subcutaneous


tissue only)*

Generalized erythema, urticaria,


periorbital oedema or angiodema

Moderate (features suggesting


respiratory, cardiovascular or
gastrointestinal involvement)

Dyspnoea, stridor, wheeze, nausea,


vomiting, dizziness (presyncope)

Severe (Hypoxia, hypotension


or neurological compromised

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

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
media

11

9 iodinated, 1 technetium, 1 fluorescein

Other

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

24

11

21

26

Upper + lower airways

13

19

Upper airways

16

12

Shock + asphyxia

21

12

15

Shock

32

18

23

29

Disseminated
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

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, mengibronkospasme, 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 bibirlidah-uvula)
b.Gangguan pernapasan (sesak, mengibronkospasme, 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-receptor

vasoconstriction
peripheral vascular resistance
mucosal edema

2-receptor

insulin release
neropinephrine release

1-adrenergic
receptor

inotropy
chronotropy

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

2-adrenergic
receptor

bronchodilation
vasodilation
glycogenolysis
mucosal edema

Absorption of epinephrine is faster


after intramuscular injection than
after subcutaneous injection

Intramuscular
epinephrine
(Epipen)

8 2 minutes

Subcutaneous
epinephrine

34 14 (5-120) minutes
p < 0.05

10

15

20

25

30

Time to Cmax after infection (minutes)

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

35

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