Anaphylaxis is a systemic allergic reaction involving the respiratory and/or the cardiovascular system; it has a rapid onset with the possibility of causing death. However, less severe reaction may be also defined as “anaphylaxis” if there is a high index of suspicion for allergic reaction in the setting of previously diagnosed allergy (Sanchez et al. 1999; Simons et al. 2007; Tang and Liew, 2008). It was observed by Simons (2006) that anaphylaxis is a disease of modern times; sporadic cases report of anaphylaxis were only published in 17th, 18th and 19th centuries and within the past four decades, the rates of allergic diseases have been increasing dramatically. The most common identifiable triggers of anaphylaxis would be food, insect venom or medication while less commonly by allergen such as natural rubber latex or physical factor such as exercise (Simons, 2006). It is usually mediated by immunological mechanism which could result in the sudden systemic release of mast cells and basophils mediator. It will consist of some or all of the following signs and symptoms with the onset within 5 – 30 minutes; diffuse erythema, pruritus, urticaria and/or angioedema; brochospasm; laryngeal edema; hyperperistalsis; hypotension and/or cardiac arrhythmias. Other symptoms that might occur would be nausea, vomiting, lightheadedness, headache, feeling of impending doom and unconscious. However, it must be noted that reaction sometimes might not develop for several hours (Kemp and Lockey, 2002). In many individual, anaphylaxis is mediated by the expansion of T helper 2 cell (TH2-cell), a subset of T cells, together with isotype switching of B cells to generate IgE antibodies specific for common environment allergens (Holgate and Polosa, 2008). Thus, IgE is seen as having a crucial role in anaphylaxis where it would be synthesized in response to an allergen exposure and becoming fixed to FcεRI on the surface of mast cells and basophils. Then, during the re-exposure to the same allergen, it will result in cellular activation, mediator release and immediate hypersensitivity response (Gould and Sutton, 2008; Simons, 2008). Either than the IgE, there are also other potential immunological mechanisms in anaphylaxis which includes the involvement of immune aggregates, IgM, IgG, platelets and T cells; shift in eicosanoid metabolism toward leukotriene formation; and activation of the complement systems. There are also non-immunological factor which could activate mast cell by mechanism not fully understood yet; it includes exercise, cold air, radiation and many more. Regardless of which mechanism the anaphylaxis follows, mast cells and basophils are the one initiating and amplifying the acute allergic response (Simons, 2008).
Anaphylaxis is first initiated by the uptake of allergen by professional antigen presenting cells (APCs) which will present selected peptides on MHC class II molecule to naive T cells. This will then direct them in favour of a TH¬2- cell phenotype where the transcription factor GATA3 mediates cytokine secretion. This process is known as the “sensitization” stage where the dendritic cells play a crucial role as the professional APCs. Then in the presence of co-stimulation, T-cells coordinately upregulate expression of the genes encoded on human chromosome 5q31-33 where the cytokines will be synthesized. There are involved in the class-switching of B cells to IgE synthesis (Interleukin-3 [IL-3] and IL-4), maturation of eosinophils and basophils (IL-3 and IL-4) and the recruitment of mast cells (IL-4, IL-9 and IL13) which are the main mediator-secreting effector cells of the allergic response (Holgate and Polosa, 2008). Once an individual is sensitized to a particular allergen, subsequent encounter to the allergen will cause the crosslinking of IgE-FcεRI complex on the mast-cell surface. This will lead to the “early stage of the allergic reaction” involving the mast-cell degranulation and the synthesis of lipid mediators; histamine, tryptase, chymase, heparin, histamine-releasing factor, PGD2 leukotriene (LT) B4, platelet-activating factor (PAF), LTC4, LTD4 and LTE4 (Kemp and Lockey, 2002; Gould and Sutton, 2008; Holgate and Polosa, 2008). Then the cytokines and chemokines liberated in the early phase will initiate the ‘late phase’, which peaks hours later and involving the recruitment and activation of inflammatory cells at sites sensitive to the allergen. There is also another pathway in the anaphylaxis that is called the “alternative pathway” which is still not fully understood; through the study of the IgE and FcεRI deficient mice, it was found that anaphylaxis is mediated by the IgG antibodies, IgG receptor FcγRIII and the release of mediators, predominantly PAF (Finkelman et al. 2004; Finkelman, 2007). The sign and symptoms of the anaphylaxis will start to occur when the mediators that were secreted activates its complement receptors. The histamine will activate the H1 ¬and H2 receptors; Prutius, rhinorrhea, tachycardia and brochospasm is caused by the activation of H1 receptors while headache, flushing and hypotension are caused by the activation of both H2 and H1 receptors. Tryptase is a protein which has been linked to the clinical severity of anaphylaxis; postmortem measurements have established that high concentration of tryptase as one of the causing death in anaphylaxis. Lastly are the metabolites of arachidonic acids, products of the lipoxygenase, cycloxygenase pathways and other inflammatory pathways has been shown that there are probably important in the prolongation and amplification of anaphylaxis (Kemp and Lockey, 2002; Simons, 2008).
In atopic individuals, allergen sensitization is the basis to development of any allergic disease. Thus, avoidance of allergens before and after sensitization would be beneficial as primary or secondary prophylaxis (Simons et al. 2007). Trials done on the effect of decreased exposure to house dust mites in early childhood produced mixed results, with most trials either showing no effect or increase in IgE sensitization. This shows that only complete avoidance of allergen is only capable of preventing IgE sensitization though extremely low allergen exposure would lead to sensitization. Thus, single and combination of intervention to decrease exposure to both dietary and aeroallergens would only result in a meaningful and sustained improvement in the prevention of anaphylaxis episodes. However, in adults, the data are far less convincing as there are many allergenic and non-allergenic factors that can contribute to ongoing disease. It would be best that an individual undergo confirmation of sensitization to an allergen after the anaphylaxis episode. Optimally, the test should be conducted at 3-4 weeks after the anaphylaxis episode; skin prick/ puncture test with appropriate positive and negative controls and quantitative measurement of allergen-specific IgE would be performed (Simons et al. 2007; Holgate and Polosa, 2008).
Finkelman, F.D., Rothenberg, M.E., Brandt, E.B., Morris, S.C. and Strait, R.T. (2004) Molecular Mechanism of Anaphylaxis: Lessons from Studies with Murine Models. Journal of Allergy and Clinical Immunology, Vol. 115, No.3, p. 449 – 458.
Finkelman, F.D. (2007) Anaphylaxis: Lesson from Mouse Models. Journal of Allergy and Clinical Immunology, Vol. 120, No.3, p.506 – 516.
Gould, H.J. and Sutton, B.J. (2008) IgE in Allergy and Asthma Today. Nature Review: Immunology, Vol. 8, p. 205 – 218
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Simons, F.E.R., Frew, A.J., Ansotegui, I.J., Bochner, B.S., Golden, D.B.K., Finkelman, F.D., Leung, D.Y.M., Lotvall, J., Marone, G., Metacalfe, D.D., Müller, U., Rosenwasser, L.J., Sampson, H.A., Schwartz, L.B., Hage, M.V. and Walls, A.F. (2007) Risk Assessment in Anaphylaxis: Current and Future Approaches. Journal of Allergy and Clinical Immunology, Vol. 120, No. 1, p. S2 – S 24.
Simons, F.E.R., (2008) Anaphylaxis. Journal of Allergy and Clinical Immunology, Vol. 121, No. 2, p. S402- S408
Tang, M.L.K and Liew, W.K (2008) Prevention and Treatment of Anaphylaxis. Paediatrics and Child Health, Vol. 18, No.7, p. 309 – 317.
Corticosteroids, β2-adrenoreceptor agonist, mediator antagonist and synthesis inhibitors are the mainstay of anaphylaxis treatment as advocated by disease management guidelines. The corticosteroids will diffuse across the cell membrane, where they interact with cytoplasmic glucocorticoid receptor, where the activation of these receptors will modulate the transcriptional activity. This will suppress the TH2-cell-mediated inflammation through the inhibition of expression of cytokines, chemokines and adhesion molecules, whose encoding genes are regulated by transcription factors such as nuclear factor – κB and activator protein 1. Β2-adrenoreceptor agonists are usually used for asthma related allergic disease where it will be inhaled (Holgate and Polosa, 2008). These agonists (e.g. epinephrine) bind to the Β2-adrenoreceptors and stimulate the adenylate cyclase through signal-transducing G protein, increasing cyclic adenosine 3’5’-monophosphate (cAMP), activating protein kinase A. This will mediate smooth-muscle relaxation through phosphorylation of myosin light chain kinase and by opening Ca2+- dependent K+¬ (KCa) channels which relieve bronchoconstriction in asthma. Lastly, mediator antagonists such as H1- antihistamines are used to treat allergic reaction by binding to the H1 receptor, thus preventing histamine from binding (Simons, 2004; Holgate and Polosa, 2008).