ANAPHYLAXIS

 Definition - Anaphylaxis is an acute, potentially fatal, multi organ system reaction caused by the release of chemical
mediators from mast cells and basophils.
 Type 1 hypersensitivity reactions usually have an early and a late phase. The early phase is generated by mast cell and
basophil mediators that also initiate the later phase events
 Pathophysiology
o SENSITIZATION
 Allergen is either inhaled or ingested and is then processed by an antigen-presenting cell (APC), such as a
dendritic cell, macrophage, or B-cell.
 The antigen-presenting cells then migrate to lymph nodes, where they prime naïve TH cells that bear
receptors for the specific antigen.
 After antigen priming, naïve TH cells differentiate into TH2
 TH2 cells then release IL-4, IL-5, IL-9, and IL-13.
 IL-5 plays a role in eosinophil development, recruitment, and activation.
 IL-9 plays a regulatory role in mast cells activation.
 IL-4 and IL-13 act on B cells to promote production of antigen-specific IgE antibodies.
 For this to occur, B cells must also bind to the allergen via allergen-specific receptors.
 They then internalize and process the antigen and present peptides from it, bound to the major
histocompatibility class II molecules found on B-cell surfaces, to the antigen receptors on TH2 cells.
 The B cell must also bind to the TH2 cell and does so by binding the CD40 expressed on its surface to the
CD40 ligand on the surface of the TH2 cell.
 IL-4 and IL-13 released by the TH2 cells can then act on the B cell to promote class switching from
immunoglobulin M production to antigen-specific IgE production.
 The antigen-specific IgE antibodies can then bind to high-affinity receptors located on the surfaces of
mast cells and basophils.
o REEXPOSURE
 Reexposure to the antigen can then result in the antigen binding to and cross-linking the bound IgE
antibodies on the mast cells and basophils.
 This causes the release and formation of chemical mediators from these cells. These mediators include
preformed mediators, newly synthesized mediators, and cytokines.
 PREFORMED MEDIATORS
 Histamine = acts on histamine 1 (H1) and histamine 2 (H2) receptors
o causes contraction of smooth muscles of the airway and GI tract
o increased vasopermeability and vasodilation
o enhanced mucus production, pruritus, cutaneous vasodilation, and gastric acid secretion.
 Chemotactic factors= An eosinophilic chemotactic factor of anaphylaxis causes eosinophil
chemotaxis.
o Eosinophils release major basic protein and, together with the activity of neutrophils,
can cause significant tissue damage in the later phases of allergic reactions.
 NEWLY FORMED
 Leukotrienes produced via lipoxygenase pathway
o Leukotriene B4 - Neutrophil chemotaxis and activation, augmentation of vascular
permeability
o Leukotrienes C4 and D4 - Potent bronchoconstrictors, increase vascular permeability,
and cause arteriolar constriction
o Leukotriene E4 - Enhances bronchial responsiveness and increases vascular permeability
 Cyclooxygenase products
o Prostaglandin D2 - Produced mainly by mast cells; bronchoconstrictor, peripheral
vasodilator, coronary and pulmonary artery vasoconstrictor, platelet aggregation
inhibitor, neutrophil chemoattractant, and enhancer of histamine release from basophils
o Prostaglandin F2-alpha - Bronchoconstrictor, peripheral vasodilator, coronary
vasoconstrictor, and platelet aggregation inhibitor
o Thromboxane A2 - Causes vasoconstriction, platelet aggregation, and
bronchoconstriction
o
o
 Cytokines
o IL-4 =stimulates and maintains TH2 cell proliferation and switches B cells to IgE synthesis.
o IL-5 = key in the maturation, chemotaxis, activation, and survival of eosinophils. IL-5 primes basophils for histamine
and leukotriene release.
o IL-6 =promotes mucus production.
o IL-13= has many of the same effects as IL-4.
o Tumor necrosis factor-alpha= a pro-inflammatory cytokine which activates neutrophils and eosinophils and increases
monocyte chemotaxis
 Common triggers for pediatric anaphylaxis
 Signs and symptoms
o Foods (most common cause in children) =Milk,
eggs, wheat, soy, fish, shellfish, legumes
(peanuts), tree nuts
o Medicines=
 Antibiotics (penicillins, cephalosporins)
 local anesthetics (lidocaine)
 analgesics (aspirin,NSAIDS,ibuprofen)
 opiates codeine, morphine,
 dextran,
 radiocontrast media
o Biologics = Venoms (bee sting, ant or snake
bite), blood and blood products, vaccines,
allergen extracts
o Other=Latex
o o Unknown=idiopathic causes
DIAGNOSIS CRITERIA
o
ANAPHYLAXIS MANAGEMENT

 Anaphylaxis is a medical emergency that requires immediate recognition and intervention.

 In acute management