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 Idiopathic IgE, FcRI

foods, venoms, latex, drugs

Non-Immunologic

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.
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 THROAT SKIN GUT LUNG HEART NEURO

itching swelling of lips and/or tongue itching, tightness, closure, hoarseness itching, hives, redness, swelling vomiting, diarrhea, cramps shortness of breath, cough, wheeze weak pulse, dizziness, passing out 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 I Dermal Pruritus Flush Urticaria Angiodema Pruritus Flush Urticaria Angiodema (not mandatory) Pruritus Flush Urticaria Angiodema (not mandatory) Pruritus Flush Urticaria Angiodema (not mandatory) Abdominal Respiratory Cardiovascular

II

Nausea Cramping

Rhinorrhoea Hoarseness Dyspnoea Laryngeal oedema Bronchospasm Cyanosis Respiratory arrest

Tachycardia (> 20 bpm) Blood pressure change (> 20 mmHg systolic) Arrhytmia Shock

III

Vomiting Defecation Diarroea Vomiting Defecation Diarrhoea

IV

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
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 5 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 Nuts Food Food? Antibiotic Anesthetic Other drug 47 32 13 18 27 35 15 29 wasp, 4 bee, 14 unidentified 2 almond, 2 brazil, 1 hazel, 10 peanut, 6 walnut, 11 mixed or unidentified 1 banana, 2 chickpea, 2 fish, 5 milk, 2 crustacean, 1 snail 1 ?fish, 5 during meal, 1 ?grape, 3 ?milk, 3 ?nut, 1 ?sherbet, 1 ?strawberry, 1 ?yeast, 1 ?nectarine 1 benzypenicillin, 10 aminopenicillin, 12 cephalosporin, 1 ciprofloxacin, 1 vancomycin, 2 amphotericin 19 suxamethonium, 7 vecuronium, 6 attracurium, 7 at induction 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 9 iodinated, 1 technetium, 1 fluorescein 1 latex, 1 hair dye, 1 hydatid, 1 idiophatic

Contrast media Other

11
3

Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:118

Mode of death
Drug Lower airways 11 Sting Food Food? Male Female 3 24 11 21 26

Upper + lower airways

Upper airways Shock + asphyxia Shock Disseminated intravascular coagulation

6
7 21 32 5

4
8 4 18 1

13
5 2 2 1

3
3

5
16 12 23 2

19
12 15 29 4

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
30 25 20 15 10 5 0 <1 1-2 2.1-4.5 4.6-9.9 10-20 21-45 46-99 100214 >215

Stings

Drug

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, 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

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

Intramuscular epinephrine (Epipen) Subcutaneous epinephrine

8 2 minutes

34 14 (5-120) minutes p < 0.05

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