Raveinal

Division of Allergy and Clinical Immunology

Department of Internal Medicine
FKUA/RS M Jamil Padang
Reaksi Anaphylaxis
Case 1
Mr. W 65 years old, came to E.R at 2.00 PM. With loss of consciousness
since 20 minute before admission.

PH: twenty minutes before admission, due to his tooth ache he took
amoxilline 500 mg, mephenemic acid 500 mg and dexametasone 0,5 mg
tablets. One or two minute after ingestion those medicine, he felt itchy
almost the whole bodies, followed by nausea vomiting, diaphoresis and
felt down due to unconscious. His family took him right away to the
nearest hospital. No history of drug allergy, or asthma, except history of
wheezing but very rare

On admission he was found soporous, perspiration the whole body.
Pulse not palpable, blood pressure could not be measured. Respiration
rate 28 per minute, heart rate 132/minute. gallop -, wheezing +/+, no
rales, liver/spleen not palpable. Extremities: warm
Case 1
ECG: normal, except sinus tachycardia. He was treated with:
Oksigen 6 liter/minute
Normal saline: free fall (1 liter)
Epinephrine 0,3 ml i.m lateral thigh
Dexamethasone 1 amp i.v
02.10 blood pressure : 50/palp. Pulse 120/minute very weak
Epinephrine 0,3 ml i.m
Ranitidine 1 amp i.v
Diphenhydramine 1 cc i.v
02.20 BP: 70/50 pulse 108/minutes.
Somnolence, contact ,
Dopamine drip was given 5-10 g/kg BW/mnt
BP: 90/70 pulse: 96/minute, apathy, contact
The patient was discharged the next morning with BP 130/80 pulse
80/minute, fully alert, normal activities and advised to visit Allergy Clinic
he was given methylprednisolone tab 16 mg/day, cetirizine 10 mg/day
for 3 days.
Case 2
Mr I 32 years old, come to E.R at 12.00, with general flushing, and itchy
almost the whole bodies 1 hour after he took griseovulvin.

PH: one hour after taking griseovulvin 125 mg, he felt very itchy and
redness the whole body, he also had nausea, vomiting 5 times and felt
sleepy. He slept for almost 1or 2 hours, when he woke up. he still had
itchy, redness of the skin and swollen of his face. No history of drug
allergy before. On arrival at ER, he was fully alert. Pulse: 120/minutes
weak. BP: 85/60, RR 16/minute his skin redness and warm, no wheezing,
abdomen: normal, extremities warm

Th : NaCL 0,9% free fall 1l, 0
2
4 - 6 l/minute, ephineprine 0,3 cc i.m,
Diphenhydramine 1 cc, dexametasone 1 cc 1 amp, ramtidine 1 amp.

12.20 BP: 100/70 HR: 96/minute, fully alert, felt better.
He was observed in E.R for 2 hours and BP 110/80 he was transferred to
the ward and discharged the following day with BP 130/80 and no more
rush or itchy. He was given mprednisolone 16 mg/day and cetrizine 5
mg/day for 3 days

Anafilaksis merupakan reaksi
alergi sistemik yang berat,
dapat menyebabkan kematian,
terjadi secara tiba-tiba
sesudah terpapar oleh alergen
atau pencetus lainnya
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
What is anaphylaxis?
Mechanisms underlying human
anaphylaxis
Human anaphylaxis
Immunologic
Idiopathic
Non-Immunologic
IgE, FcRI
foods, venoms,
latex, drugs
Other
blood products,
immune aggregates,
drugs
Physical
exercise, cold
Other
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
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
I 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
submukosa)*
Eritema luas,edema periorbita,atau
angioedema
Sedang (keterlibatan
pernapasan,
kardiovaskuler,atau
gastrointestinal
Sesak, stridor, mengi, mual, muntah,
pusing, presinkop diaforesis, rasa
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 SpO
2
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
0
5
10
15
20
25
30
35
P
e
r
c
e
n
t

o
f

C
a
s
e
s

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
Interval from exposure to first arrest. Drug reaction
were fastest, mostly taking less than 5 minutes
0
5
10
15
20
25
30
<1 1-2 2.1-4.5 4.6-9.9 10-20 21-45 46-99 100-
214
>215
minutes from exposure to first arrest
Food Stings Drug
Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:121
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 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
intravascular coagulation
5 1 1 2 4
Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:120
DIAGNOSIS
Kriteria klinik diagnosis anafilaksis
1
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 anafilaksis
2
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 anafilaksis
3
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:





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.
Mulai dengan infuse adrenalin sesuai dengan panduan/protocol rumah sakit

ATAU

Ulang adrenalin i.m setiap 3-5 menit

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
2
-receptor

1
-adrenergic
receptor

2
-adrenergic
receptor
vasoconstriction
peripheral vascular resistance
mucosal edema
insulin release
neropinephrine release
inotropy
chronotropy
bronchodilation
vasodilation
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
Estelle FER. J Allergy Clin Immunol 2004;113:837-44
34 14 (5-120) minutes
p < 0.05
5 10 15 20 25 30 35
8 2 minutes
Time to C
max
after infection (minutes)
Intramuscular
epinephrine
(Epipen)
Subcutaneous
epinephrine
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