PRESENTER – DR. ASHRAY .

V
 DEFINITION
 In simple terms, "anaphylaxis is a serious allergic
reaction that is rapid in onset and may cause death.“

 anaphylaxis is the term now used to refer to both IgE and

non-IgE reactions (e.g., IgE-independent, IgG- and immune
complex complement–mediated).
 CLINICAL CRITERIA FOR ANAPHYLAXIS:
 1) Acute onset of an illness (minutes to several hours) with involvement
of the skin and/or mucosal tissue (e.g., hives/urticaria, pruritus,
flushing, swollen lips, tongue, or uvula) associated with at least one of
the following:
i) Respiratory compromise (e.g., dyspnea, wheeze, stridor, etc.)
or
ii) Reduced blood pressure
or
iii) Associated symptoms of organ dysfunction (e.g., hypotonia,
syncope, incontinence, etc.)

2) Two or more of the following that occur rapidly after exposure to a

likely allergen for that patient (minutes to several hours):
 Involvement of the skin and/or mucosal tissue
 Respiratory compromise.
 Reduced blood pressure or associated symptoms
 Persistent GI symptoms (e.g., cramps, vomiting).

3) Anaphylaxis should be suspected when patients are

exposed
to a known allergen and develop hypotension
  CAUSES OF ANAPHYLAXIS

1) DRUGS : Beta Lactam antibiotics , Acetylsalicylic acid ,

Trimethoprim-sulfamethoxazole , Vancomycin, NSAIDs , any other
drugs.

2) FOODS AND ADDITIVES : Soybeans, peanuts , Wheat , Milk , eggs ,

Mango’s, Food containing Sulfites.

3) BITES : Hymenoptera stings (Bees , wasp’s) ,

4) RADIOGRAPHIC CONTRAST MATERIAL

5) LATEX ALLERGY : Surgical gloves .

6) VACCINES : D.P.T , MMR , Hepatitis – B .

 The lifetime individual risk of anaphylaxis is presumed to be 1% to
3%, with a mortality rate of 1%.

 In India, antibiotics, radiocontrast agents and anesthetic agents

are considered major causes of anaphylaxis, and blood products,
insulin and growth hormones are also mentioned (Ref – WORLD
ALLERGY ORGANISATION website
http://www.worldallergy.org/wao_societies/aboutwao.php).
 PATHOPHYSIOLOGY AND MECHANISM
 Anaphylaxis is believed to arise from the activation of mast cells and
basophils generally involving crosslinking of IgE and aggregation of the
high-affinity receptors for IgE.

 Upon activation, mast cells and/or basophils quickly release preformed

mediators from secretory granules like histamine, tryptase,
carboxypeptidase A, and proteoglycans.

 Downstream activation of phospholipase A2, followed by

cyclooxygenases and lipo-oxygenases, produces arachidonic acid
metabolites, including prostaglandins, leukotrienes, and platelet-
activating factor.

 The inflammatory cytokine, tumor necrosis factor- is released as a

preformed mediator, and also as a late-phase mediator with other
cytokines and chemokines.

 Many of these mediators are believed responsible for the

pathophysiology of anaphylaxis.
MEDIATORS OF ANAPHYLAXIS
 Histamine : stimulates vasodilation and increases vascular
permeability, heart rate, cardiac contraction, and glandular
secretion.

 Prostaglandin D2 : is a bronchoconstrictor, pulmonary and

coronary vasoconstrictor, and peripheral vasodilator.

 Leukotrienes : produce bronchoconstriction, increase

vascular permeability, and promote airway remodeling.

 Platelet-activating factor : is also a potent

bronchoconstrictor and increases vascular permeability.

 Tumor necrosis factor: activates neutrophils, recruits other

effector cells, and enhances chemokine synthesis.
 CLINICAL FEATURES
 Early Symptoms - pruritus, cutaneous flushing, and urticaria
, sense of fullness in the throat, anxiety, a sensation of chest
tightness, shortness of breath, and light-headedness.

 As the cascade progresses, decreased level of consciousness,

respiratory distress, and circulatory collapse may occur. In its
severest form, loss of consciousness and cardiorespiratory
arrest may occur. A complaint of a "lump in the throat" and
hoarseness indicates life-threatening laryngeal edema in a
patient with symptoms of anaphylaxis.

 In the vast majority of patients, signs and symptoms begin

suddenly, often within 60 minutes of exposure.

 In general, the faster the onset of symptoms, the more severe

the reaction, as evidenced by the fact that one half of
anaphylactic fatalities occur within the first hour.
 There is a risk of recurrence of symptoms and the exact
incidence is not known but it has been reported in 3% to 20%
of patients.

 The Recurrence is caused by a second phase of mediator

release, peaking 4 to 8 hours after the initial exposure and
exhibiting itself clinically 3 to 4 hours after the initial clinical
manifestations have cleared.

The late-phase allergic reaction is primarily mediated by the

release of newly generated cysteinyl leukotrienes, the former
slow-reacting substance of anaphylaxis.
 DIAGNOSIS

 The diagnosis is easily made if there is a clear history of exposure,

such as a bee sting, shortly followed by the multisystem signs and
symptoms .

 Unfortunately, diagnosis is not always easy or clear, because:

Symptom onset may be delayed, symptoms mimic other presentations
(e.g., syncope, gastroenteritis, and anxiety), or anaphylaxis may be a
component of other diseases (e.g., asthma).

 And in most cases , like as in food allergy, the inciting substance

may not be known.
 DIFFERENTIAL DIAGNOSIS FOR ANAPHYLAXIS :

 Vasovagal reactions
 myocardial ischemia,
 arrhythmias,
 status asthmaticus,
 Seizure,
 Epiglottitis,
 Hereditary angioedema,
 Foreign body airway obstruction,
 Carcinoid
 Vocal cord dysfunction,
 Non–IgE-mediated drug reactions.

The most common anaphylaxis imitator is a vasovagal reaction,

which is characterized by hypotension, pallor, bradycardia,
diaphoresis, and weakness, and sometimes by syncope.
 MANAGEMENT AND TREATMENT

 FIRST LINE THERAPY

 Emergency management starts with the ABC’s (airway, breathing,
circulation) of resuscitation. Vital signs, IV access, oxygen
administration, cardiac monitoring, and pulse oximetry
measurements should be done immediately.

 AIRWAY MANAGEMENT : Check for signs and symptoms of

angioedema e.g., uvula edema , audible stridor, respiratory
distress, hypoxia. Intubation should be done early when
angioedema is causing respiratory distress to prevent complete
airway obstruction.

 DECONTAMINATION : exposure to the causative agent needs to

be terminated . Sting remnants need to be removed in cases of
insect stings to prevent further envenomation .
 EPINEPHRINE IN ANAPHYLAXIS
 Epinephrine is the drug of choice and the first drug that should be
administered in acute anaphylaxis

 The dose is epinephrine, 0.3 to 0.5 milligram (0.3 to 0.5 mL of the

1:1000 dilution) IM repeated every 5 to 10 minutes according to
response or relapse.

 Most patients do not need more than a single dose.

 IM dosing provides higher, more consistent, and more rapid peak

blood epinephrine levels than SC administration, and should now be
the treatment of choice for adults and children. Injections into the
thigh are more effective at achieving peak blood levels than are
injections into the deltoid area.

Caution is warranted in patients taking -blockers, because

epinephrine use may result in severe hypertension secondary to
unopposed -adrenergic stimulation.
 If the patient is refractory to treatment despite repeated IM
epinephrine, or with signs of cardiovascular compromise or
collapse, then an IV infusion of epinephrine is given. Initially,
epinephrine, 100 micrograms (0.1 milligram) direct IV(
1:100,000 dilution).
 OR
 0.1 milligram (0.1 mL of the 1:1000 dilution), in 10 mL of
normal saline (NS) solution and infusing it over 5 to 10
minutes (a rate of 1 to 2 mL/min).3

 If the patient is refractory to the initial bolus, then

epinephrine infusion -1 milligram (1.0 mL of the 1:1000
dilution), in 500 mL of 5% dextrose or NS and administering
at a rate of 1 to 4 micrograms/min (0.5 to 2 mL/min),
titrating to effect.
 Side effects - tachycardia, arrhythmia, tremor .
The initial adult dose is very dilute & is given over 5 to 10
minutes, and can be stopped immediately if arrhythmias or
chest pain occur.
 CRYSTALLOIDS :
 If hypotension is present, it is generally the result of
distributive shock and responds to fluid resuscitation.

 Patients should receive an NS bolus of 1 to 2 L in adults (10

to 20 mL/kg in children) concurrently with the epinephrine
infusion.

 There is no evidence that albumin or hypertonic saline should

replace NS at this time .
 SECOND LINE THERAPY :

1) Corticosteroids

2) Antihistamines

3)Agents for Allergic Bronchospasm (Asthma medications).

4)Glucagon.
TREATMENT OF BRONCHOSPASM
ADULT DOSE PEDIATRIC DOSE
 URTICARIA :

 Urticaria, or hives, is a cutaneous reaction marked by the

development of pruritic, erythremic wheals of varying size
that generally are described as "fleeting.“
 ANGIOEDEMA :

 Angioedema is believed to be a similar to urticaria but is a

deeper reaction characterized by edema formation in the dermis,
mostly involving the face and neck, and distal extremities.

 Prophylaxis of acute attacks is by attenuated androgens, such as

stanozolol, 2 milligrams/d, or danazol, 200 milligrams/d.

 Acute attacks can be shortened by

C1 esterase inhibitor replacement
by a concentrate or conestat alfa
(trade name Ruconest).

 Successful treatment with fresh

frozen plasma has also been reported
and may be tried if C1 esterase inhibitor is not available.

 Treatment of patients is complex and best done in coordination

with the appropriate specialist
 FOOD ALLERGIES
 Caused by IgE-mediated reactions to food proteins and,
rarely, by additives.

 IgE-coated mast cells lining the GI tract react to allergens in

ingested foods and produce clinical findings associated with
the release of anaphylaxis mediators.

 Dairy products, eggs, nuts, and shellfish , are some of the

most commonly implicated foods.

 Symptoms of food allergy : include swelling and itching of the

lips, mouth, and pharynx; nausea; abdominal cramps;
vomiting; and diarrhea.
 Cutaneous manifestations: such as angioedema and urticaria,
as well as anaphylaxis, can occur.
 Treatment for mild reactions is supportive, with the
administration of antihistamines to lessen symptoms.
 INSECT STING ALLERGIC REACTIONS.
 Insect stings can produce significant, and sometimes fatal, reactions,
particularly in sensitized patients.
 True stinging insects belong to the order Hymenoptera, which
includes three families:
1) Apidae (honeybees),
2) Formicidae (fire ants),
3) Vespidae (wasps, yellow jackets, and hornets)

 Diagnosis depends on clinical history, H/o past reactions, and an

examination to locate the site of the sting.

 Mild local reactions can be managed with application of ice and oral
antihistamines.

 More generalized reactions or local reactions of the head and neck

may benefit from a short course of corticosteroids.

 Patients with severe reactions should be advised to carry self-

administered epinephrine and antihistamines.
 ALLERGIC DRUG REACTIONS :

 Penicillin is the drug most common drug causing allergic reactions

and accounts for approximately 90% of all allergic drug reactions.

 When a drug or metabolite becomes protein-bound, either in

serum or on cell surfaces, the drug–protein complex can become
an allergen and stimulate immune system responses. Thus, the
ability of a drug or its metabolites to sensitize the immune system
depends on the ability to bind to tissue proteins.

 A generalized reaction similar to immune-complex or serum

sickness reactions is very common, especially with common agents
like trimethoprim-sulfamethoxazole and certain cephalosporins
(cefaclor being the most frequent).

 Serum sickness usually begins in the first or second week after the
administration of the drug and can take many weeks to subside
after drug withdrawal.
 Generalized malaise, arthralgias, arthritis, pruritus, urticarial
eruptions, fever, adenopathy, and hepatosplenomegaly are
common signs and symptoms of serum sickness.
 Drug fever : may occur without other associated clinical findings
and may also occur without an immunologic basis.

 Circulating immune complexes are responsible for the lupus-

like reactions caused by some drugs.

 Cytotoxic reactions: such as penicillin-induced hemolytic

anemia, can occur. Skin eruptions include erythema, pruritus,
urticaria, angioedema, erythema multiforme, and
photosensitivity.

 Severe reactions, such as those seen in Stevens-Johnson

syndrome and toxic epidermal necrolysis, may also occur.
Pulmonary complications, including bronchospasm and airway
obstruction, can occur.
 Medical procedure that uses controlled exposure to known
allergens to reduce the severity of allergic disease

 Disease accepted to be treated by immunotherapy:

◦ Allergic rhinitis, allergic asthma, allergic conjunctivitis,
insect sting hypersensitivity

 Disease not accepted to be treated by immunotherapy:

◦ Food allergy, urticaria, atopic dermatitis .
 Gradual increase of allergen-specific IgG antibodies --
especially IgG4 subclasses (blocking antibody)
◦ Intercept and neutralize allergen before it bound to cell-
surface IgE.

◦ Form IgG-antigen-IgE complex and bind to the IgG

receptor resulting co-aggregation with the IgE receptor and
inhibition of IgE receptor triggering.

 Decreased allergen-specific IgE antibodies

 Increase IgA and IgM antigen-specific B lymphocytes

◦ May limit antigen penetration into the body from mucosa
 moving immune
system from
CD4+Th2 cell to Th1
cell pathway
 Alter cytokine
production
◦ IL-4, IL-5 as Th2
cytokines
◦ IFN-gamma as Th1
cytokines
 Proven allergy ina patient with skin test positive.

 With allergic symptoms that are significant to the patient

 Attempts to avoid allergens fail or impractical

 Treatment with medicine is not fully successful or when

medication is not well tolerated.

 Young patients without chronic irreversible changes in the

upper airways

 Patient needs to be motivated and compliant with treatment

 Subcutaneous immunotherapy is most commonly used.

 Subcutaneous immunotherapy normally involves a weekly

subcutaneous injection of an extract of the allergen, in
solution, in increasing doses until a standard maintenance
dose is reached.

 This dose is then injected subcutaneously on a regular basis

(at intervals of approximately 20 days) for not less than 3
years for perennial allergens.

 Short term immunotherapy does not affect the cytokine

profile and do not have long-term efficacy after
discontinuation

 It is started at an earlier age, so that adverse changes to the

immune system can be prevented before they become
irreversible
 Widely used and investigated in Europe since late 1980’s

 The extract of the allergen is kept under the tongue for a

couple of minutes and then patient is asked to swallow it

 Dose of allergen is greater than subcutaneous

immunotherapy (about 3-300 times higher).
 Wilson et al.:

◦ systemic review of literature in Cochrane library

◦ 22 clinical studies, a total of 979 patients

◦ They noted a highly significant reduction in symptoms

as well as definite decrease in medicine intake for
symptoms

◦ whether sublingual therapy equals the efficacy of

subcutaneous immunotherapy is not clear