ANAPHYLAXIS

INTRODUCTION

 Anaphylaxis is defined as a serious allergic reaction that is

rapid in onset and may cause death.

 Anaphylaxis in children, particularly infants, is

underdiagnosed.

 Anaphylaxis occurs when there is a sudden release of potent

biologically active mediators from mast cells and basophils,
leading to cutaneous , respiratory, cardiovascular and
gastrointestinal (nausea, colicky) symptoms
 EPIDEMIOLOGY
 The overall annual incidence of anaphylaxis in the
United States is estimated at 50 cases/100,000
persons/yr, totaling >150,000 cases/yr, with the
highest rate for the pediatric age group (0-19 yr)
at 70/100,000 persons/yr.
 An Australian parental survey found that 0.59% of
children 3-17 yr of age had experienced at least 1
anaphylactic event.
 Having asthma and the severity of asthma are
important anaphylaxis risk factors
 ETIOLOGY
 The most common causes of anaphylaxis in children are
different for hospital and community settings.

HOSPITAL COMMUNITY SETTINGS

 Anaphylaxis occurring in the hospital
results primarily from allergic
reactions to medications and latex.
 In the hospital, latex is a particular
problem for children undergoing
multiple operations.
 Patients with latex allergy may also
experience food-allergic reactions
from homologous proteins in foods
such as bananas, kiwi, avocado,
chestnut, and passion fruit.
 Food allergy is the most common cause
of anaphylaxis occurring outside the
hospital, accounting for about half of
the anaphylactic reactions reported in
pediatric surveys from the United
States, Italy, and South Australia.
 Peanut allergy is an important cause of
food-induced anaphylaxis, accounting
for the majority of fatal and near-fatal
reactions.
SIGN AND SYMPTOM
RISK FACTOR
OF
ANAPHYLAXIS
 PATHOGENESIS
 Acute bronchial obstruction
with pulmonary
hyperinflation
FATAL  Pulmonary edema
ANAPHYLAXIS  Intraalveolar hemorrhaging
 Visceral congestion
 Latyngeal edema
 Urticaria and angioedema
 Acute hypotension
It is commonly, but not always, mediated by

an allergic mechanism, usually by IgE

ROLE MAST CELL
Acutely released mediators of anaphylaxis

Degranulation of mast cells and basophils causes the release

of:
- Preformed granule-associated substances, eg histamine,
tryptase, chymase, carboxypeptidase, and cytokines
- Newly-generated lipid-derived mediators, eg prostaglandin D2,
leukotriene (LT) B4, LTC4, LTD4, LTE4, and platelet activating
factor.
OTHER IgE MEDIATED REACTION OF
CLINICAL ANAPHYLAXIS
 Direct release of mediators from mast cells by medications and
physical factors (morphine, exercise, cold)

 Disturbances of leukotriene metabolism (aspirin and nonsteroidal

antiinflammatory drugs)

 Immune aggregates and complement activation (blood products),

probable complement activation

 (radiocontrast dyes, dialysis membranes)

 IgG-mediated reactions (high-molecular-weight dextran, chimeric or

humanized monoclonal antibodies)
 Onset Of Symptoms
 The onset of symptoms may vary depending on the
cause of the reaction.

 Reactions from ingested allergens (foods,

medications) are delayed in onset (minutes to 2 hr)
compared with those from injected allergens (insect
sting, medications) and tend to have more
gastrointestinal symptoms.
 Pruritus about the mouth and face
 A sensation of warmth, weakness, and
apprehension (sense of doom)
 Flushing
 urticaria and angioedema,
 oral or cutaneous pruritus
 tightness in the throat, dry staccato cough
and hoarseness
INITIAL
 periocular pruritus
 Nasal congestion, sneezing, dyspnea,
SYMPTOMS
deep cough and wheezing
 nausea, abdominal cramping, and
vomiting, especially with ingested
allergens
 uterine contractions (manifesting as lower
back pain)
 Faintness
 Loss of consciousness in severe cases
 …CLINICAL SYMPTOMS

 Some degree of obstructive laryngeal edema is typically

encountered with severe reactions.
 Cutaneous symptoms may be absent in up to 20% of cases,
and the acute onset of severe bronchospasm in a previously
well asthmatic person should suggest the diagnosis of
anaphylaxis.
 Sudden collapse in the absence of cutaneous symptoms
should also raise suspicion of vasovagal collapse,
myocardial infarction, aspiration, pulmonary embolism, or
seizure disorder.
 Laryngeal edema, especially with abdominal pain, may also
be a result of hereditary angioedema
Comments about anaphylaxis signs
and symptoms

 skin symptoms occur most commonly ( > 90% of patients)

 skin, oral, and throat symptoms are often the first ones noted
 respiratory symptoms occur in 40% to 70% of patients
 gastrointestinal symptoms occur in about 30% of patients
 shock occurs in about 10% of patients
 signs and symptoms are usually seen within 5 to 30 minutes
 the more rapid the onset, the more serious the reaction
LABORATORY FINDINGS
 IgE antibodies specific to a suspected causative
agent
 Plasma histamine is elevated for a brief period but
is unstable and difficult to measure in a clinical
setting
 Plasma tryptase is more stable and remais
elevated for several hours but often is not elevated,
especially in food – induced anaphylactic reactions
Laboratory tests in the diagnosis of anaphylaxis

Plasma histamine
Serum tryptase
24-hr Urinary histamine
metabolite

0 30 60 90 120 150 180 210 240 270 300 330

DIAGNOSIS OF
ANAPHYLAXIS
DIFFERENTIAL DIAGNOSIS
 Other forms of shock (hemorrhagic, cardiogenic, septic)
 Vasopressor reactions including flush syndromes such as carcinoid
syndrome
 Excess histamine syndromes (systemic mastocytosis),
 Ingestion of monosodium glutamate
 scombroidosis,
 Hereditary angioedema.
 Panic attack
 Vocal cord dysfunction,
 Pheochromocytoma
 Red man syndrome (caused by vancomycin)
 TREATMENT
INITIAL ASSESSMENT  Intramuscular (First Line)
or intravenous epinephrine
 Adequate airways with  H1 and H2 antihistamine
antagonists
effective respiration  Oxygen
 Intravenous fluids
 Circulation
 Inhaled  agonists
 Corticosteroid
 Perfusion
EPINEPHRINE THERAPY
Intramuscular route to the lateral thigh (1 : 1000
dilution) doses: 0.01 mg/kg; max 0.5 mg).

For children ≥12 yr, many recommend the 0.5 mg

intramuscular dose.

The intramuscular dose can be repeated 2 or 3 times at intervals

of 5-15 min if an intravenous continuous epinephrine infusion has
not yet been started and symptoms persist
 …Epinephrine Therapy

 The 1 : 10,000 dilution of epinephrine should be

used for intravenous administration.

 If IV access is not readily available, then

epinephrine can be administered via the
endotracheal or intraosseous routes
 Special Considerations

 The patient should be placed in a supine position and lower

extremities elevated when there is concern for hemodynamic
compromise.

 Fluids are also important in patients with shock.

 Other drugs (antihistamines, glucocorticosteroids) have a

secondary role in the management of anaphylaxis.
BIPHASIC ANAPHYLAXIS
 Patients may experience biphasic anaphylaxis, which occurs
when anaphylactic symptoms recur after apparent resolution.

 without subsequent allergen exposure

 More than 90% of biphasic responses occur within 4 hr, so
patients should be observed for at least 4 hr before being
discharged from the emergency department.

 Referrals should be made to appropriate specialists for further

evaluation and follow-up.
 up to 20% of anaphylactic reactions are biphasic
 patients with biphasic anaphylaxis may require more
epinephrine to control initial symptoms
 in protracted anaphylaxis, symptoms may be continuous for
5-32 hrs
 Biphasic/late-phase reaction
Cellular infiltrates: 3 to 6 hours (LPR)
Eosinophil
CysLTs, GM-CSF,
Histamine IL-4, IL-6 TNF-, IL-1, IL-3, PAF,
ECP, MBP

Allergen
3 to 6 hours Basophil
Histamine,
(CysLTs, PAF, CysLTs, Return
IL-5) TNF-, IL-4, IL-5, IL-6
of
Monocyte Symptoms
PGs CysLTs CysLTs, TNF-, PAF,
IL-1
Proteases

Mast cell Lymphocyte

IL-4, IL-13, IL-5,
IL-3, GM-CSF
EPR 15 min
(Early-Phase Reaction)
Algorithm Anaphylaxis Treatment In Outpatient Setting
 PREVENTION
 Avoiding the triggering agent

 Education regarding early recognition of anaphylactic symptoms and

administration of emergency medications

 Patients with food allergies must be educated in allergen avoidance,

including active reading of food ingredient labels and knowledge of
potential contamination and high-risk situations.

 Any child with food allergy and a history of asthma, peanut, tree nut, fish
or shellfish allergy, or a previous anaphylactic reaction should be given
an epinephrine autoinjector (Adrenaclick, Auvi-Q, EpiPen), (liquid
cetirizine and a written emergency plan in case of accidental ingestion.
 …Prevention

 In cases of food-associated exercise-induced anaphylaxis,

children must not exercise within 2-3 hr of ingesting the

triggering food and, like children with exercise-induced

anaphylaxis, should exercise with a friend, learn to recognize

the early signs of anaphylaxis (sensation of warmth and facial

pruritus), stop exercising, and seek help immediately if

symptoms develop.
 …Prevention

 Children experiencing a systemic anaphylactic reaction including

respiratory symptoms to an insect sting should be evaluated and
treated with immunotherapy, which is more than 90% protective.

 Reactions to medications can be reduced and minimized by using

oral medications in preference to injected forms and avoidance
of cross-reacting medications.

 The use of nonlatex gloves and materials should be used in

children undergoing multiple operations
 …Prevention

Any child who is at risk for anaphylaxis should receive

emergency medications (including epinephrine
autoinjector), education on identification of signs
and symptoms of anaphylaxis and proper
administration of medications, and a written
emergency plan in case of accidental exposure, and
encouraged to wear medical identification jewelry.
Office management of anaphylaxis:
checklist of equipment and drugs required
 stethoscope and sphygmomanometer
 tourniquets, syringes, needles (including large bore 14-gauge)
 injectable epinephrine (adrenaline) 1:1000
 oral airway and endotracheal tubes
 oxygen, and equipment to administer it
 diphenhydramine (or similar) injectable antihistamine
 corticosteroids for IV injection
 vasopressor (eg dopamine, noradrenaline)
 glucagon
 automatic defibrillator
 STEVENS-JOHNSON
SYNDROME AND TOXIC
EPIDERMAL NECROLYSIS
 DEFINITION

 Epidermal detachment of <10% is suggestive of SJS,

30% detachment suggests TEN, and 10-30%
detachment suggests overlap of the 2 syndromes.
 STEVENS-
TOXIC EPIDERMAL
JOHNSONS
NECROLYSIS
SYNDROME

SJS TEN

THE RISK OF INFECTION AND

MORTALITY ARE HIGH
 STEVENS-JOHNSON SYNDROME

 The features of SJS include confluent purpuric macules on face

and trunk and severe, explosive mucosal erosions, usually at
more than 1 mucosal surface, accompanied by fever and
constitutional symptoms.

Stevens-Johnson syndrome is an immune-complex–mediated hypersensitivity

disorder that may be caused by medications, viral infections, and malignancies.

Pathologically, cell death results causing separation of the epidermis from the dermis
Sindroma Stevens-Johnson ( SSJ ) :
kumpulan gejala klinis yang ditandai oleh trias :
1. kelainan pada kulit
2. kelainan pada mukosa orifisium
3. kelainan pada mata
 Insidens : 1 – 10 per 1.000.000 setiap tahun.
 Sinonim :
 Sindrom de Friessinger-Rendu,

 Sindroma Muko-kutaneo-okular

 Eritema poliform bulosa, dll.

 Case report :

Steven Johnson Syndrome due

to “unknown” drug

Improvement during
hospitalization  discharge
 Case report :
A 9 years old girl admitted with
Steven Johnson Syndrome due
to antibiotic ( DD : NET)

Steroid as part of treatment

Discharge from hospital with

clinical improvement
 ETIOLOGY
 Various etiologic factors have been implicated as causes of
Stevens-Johnson syndrome. Drugs most commonly are blamed.
The 4 etiologic categories are as follows:

a. Infectious

b. Drug-induced

c. Malignancy-related

d. Idiopathic
 MANIFESTASI KLINIS

• Gejala prodromal : 1 - 14 hari

demam, malaize, batuk, koriza, sakit
menelan, nyeri dada, muntah, dll
timbul lesi di kulit, mukosa dan mata
dapat diikuti kelainan viseral .
• Gejala klinis SSJ  biasanya cepat &
menakutkan dengan KU yang berat .
• Perjalanan penyakit  berlangsung
beberapa hari – 6 minggu .
 MANIFESTASI KLINIS ( 2 )

Kulit :
 Eritem, papula, vesikel, atau bula
 Predilepsi : ektensor tangan, kaki + muka,
yang meluas ke seluruh tubuh sampai ke
kulit kepala .
 Keadaan lanjut : erosi, ulserasi, kulit
mengelupas .
 MANIFESTASI KLINIS ( 3 )
• Mukosa :
 Mulut, tenggorokan dan genital
 Vesikel, bula, erosi, ekskoreasi, pedarahan,
krusta warna merah .
 Pada faring bisa terbentuk
pseudomembrane  sulit menelan .
• Mata :
Konjungtivitis kataralis, blefrokonjungtivitis,
iritis, iridosiklitis, palpebra edema dan sulit
dibuka
Pada kasus berat : erosi dan perforasi kornea .
 KOMPLIKASI

1. Ulcus kornea 5. Bronkopneumoni

2. Simblefaron 6. Nefritis
3. Miositis 7. Poliartrithis
4. Mielitis 8. Septikemia
 DIAGNOSIS

• Anamnesis“trias”kelainan kulit,mukosa,mata,
dan mencari penyebab .

• Pemeriksaan fisik  “trias” kelainan

kulit,mukosa,mata, dan hubungannya dengan
penyebab

• Laboratorium :
 mencari hubungan dengan penyebab
 untuk tatalaksana secara umum.
Laboratorium : ( lanjutan )
1. Rutin : darah tepi  Hb, Ht, Lekosit, Trombosit,
Diff Count,hitung Eosinofil total, LED
2. Pem Imunologik : kadar Ig, komplemen C3 & C4 ,
komplek imun .
3. Kultur + sensitivitas ( darah & lesi )
4. Histopatologik : biopsi kulit .
5. Pem. Imunofloresen melihat endapan IgM,
IgA,C3 dan fibrin .

• Diagnosis Banding Utama :

 N E T ( Nekrosis Epidermal Toksik )

 Staphylococcal scalded skin syndrome
 Irradiation



Trauma
Progressive systemic sclerosis
DIFFERENTIAL

(scleroderma)
Erythroderma ichthyosiform congenita
DIAGNOSES
 Porphyria cutanea tarda
 Epidermolysis bullosa acquisita
 Linear immunoglobulin A bullous disease  Atopic Keratoconjunctivitis
 Chemical Burns
 Paraneoplastic pemphigus
 Emergent Management of
 Bullous systemic lupus erythematosus Thermal Burns
 Corynebacterium diphtheriae conjunctivitis  Exfoliative Dermatitis
 Sebaceous cell carcinoma  Ocular Burns
 Sjogren Syndrome
 Adenoviral conjunctivitis
 Toxic Shock Syndrome
 Intraepithelial epithelioma  Trachoma
 Acute generalized exanthematic
pustulosis
 THERAPY
Patients should be treated with special attention to airway and
hemodynamic stability, fluid status, wound/burn care, and pain
control.
Therapy for Stevens-Johnson syndrome proceeds as follows:
 Withdrawal of any agent suspected of causing the condition is

critically important
 Oral lesions are managed with mouthwashes; topical
anesthetics are useful in reducing pain and allowing the patient
to take in fluids
 Areas of denuded skin must be covered with compresses of
saline or Burow solution
 Tetanus prophylaxis must be addressed
 TERAPI
1. Tx Cairan dan elektrolit, serta kebutuhan
kalori dan protein.
2. Antibiotika spektrum luas atasi infeksi
3. Kortikosteroid parentral
4. Perawatan kulit dan mata serta terapi
antibiotika topikal
5. Faktor Penyebab : segera ditasi .
 OCULAR THERAPY

 The treatment of acute ocular manifestations usually

begins with aggressive lubrication of the ocular
surface.

 As inflammation and cicatricial changes ensue, most

ophthalmologists use topical steroids, antibiotics,
and symblepharon lysis.
 PROGNOSIS

• Pada kasus yang tidak berat  baik

• Jika purpura yang luas  prognosis lebih buruk .
• Kematian biasanya oleh karena :
– Gangguan keseimbangan cairan dan elektrolit
– Bronkopneumonia
– Sepsis
 TOXIC EPIDERMAL NECROLYSIS

 Ocular involvement may be particularly severe, and

the liver, kidneys, and lungs may also be involved.
TEN, which appears to be related to keratinocyte
apoptosis, manifests as widespread areas of
confluent erythema followed by epidermal necrosis
and detachment with severe mucosal involvement
TOXIC EPIDERMAL NECROLYSIS
 Presentation TEN
 Fever (often >39) and flu-like illness 1-3 days before
mucocutaneous lesions appear
 Confluent erythema
 Facial edema or central facial involvement
 Lesions are painful
 Palpable purpura
 Skin necrosis, blisters and/or epidermal detachment
 Mucous membrane erosions/crusting, sore throat
 Visual Impairment (secondary to ocular involvement)
 Rash 1-3 weeks after exposure, or days after 2nd
exposure
Differential Diagnosis for Vesicular or Bullous Rash

Bullous
Pemphigoid
Often affects
the elderly

Dermatitis Herpetiformis
Associated with gluten intolerance

Pemphigus
Affects middle-aged or elderly

Cicatricial Pemphigoid
Mucosal involvement, sometimes cutaneous
Differential Diagnosis, cont.

Linear IgA Disease

Itchy, ring-shaped, no internal disease

Herpes Simplex Virus

Varicella/Zoster Virus

Hand-Foot-Mouth
Disease
(Enteroviruses) Contact Dermatitis
 Differential Diagnosis, cont.

 Erythema Multiforme
 Staphylococcal Scalded Skin Syndrome
 Bullous Impetigo
 Toxic Shock Syndrome
 Paraneoplastic Pemphigus
 Cutaneous emboli
 Diabetic Bullae
 Porphyria Cutanea Tarda
 Porphyria Variegata
 Pseudoporphyria
 Bullous dermatosis of Hemodialysis
 Coma Bulloae
 Epidermolysis Bullosa Acquisita
 SKIN BIOPSY

 Skin biopsy differentiates subepidermal cleavage

characteristic of TEN from intraepidermal cleavage
characteristic of the scalded-skin syndrome induced
by staphylococcal toxins.

 TEN must be treated in a burn unit.

 THERAPY
 Corticosteroids are contraindicated because they
can significantly increase the risk of infection.

 High intravenous doses of immunoglobulin have

been shown to be beneficial in patients with TEN,
likely because of inhibition of Fas-mediated
keratinocyte cell death by naturally occurring Fas
blocking antibodies in the intravenous
immunoglobulin preparation.
 Treatment
 Early diagnosis - biopsy
 Immediate discontinuation of offending agent
 Supportive care – pay close attention to ocular
complications
 IV hydration (e.g. Parkland formula)
 Antihistamines
 Analgesics
 Local v. systemic corticosteroids
 Think about nursing requirements!
 Possible treatment in burn unit, wound care
 IVIg?
 PROGNOSIS
 The SCORTEN score (a severity-of-illness score for toxic
epidermal necrolysis) calculates the risk for death in both SJS
and TEN on the basis of the following variables:
 Age >40 years
 Malignancy
 Heart rate >120
 Initial percentage of epidermal detachment >10%
 Blood urea nitrogen (BUN) level >10 mmol/L
 Serum glucose level >14 mmol/L
 Bicarbonate level < 20 mmol/L
Each variable is assigned a value of 1 point.
Mortality rates are as follows:
 0-1 points, ≥3.2%

 2 points, ≥12.1%

 3 points, ≥35.3%

 4 points, ≥58.3%

 5 or more points, ≥90%

TERIMAKASIH