Clinical case
Ana is a 25-year-old girl who lives in Amsterdam. She has been previously diagnosed with a dairy allergy so she ensures she avoids items containing milk protein. On December 25th, 2020, Ana was having dinner with her friends at a restaurant when she suddenly started to wheeze and asked her friends to call for an ambulance as she started gasping for air. Her friend Nagori who is a nurse saw severe urticaria on Ana's arms. She suspected that Ana was having an anaphylactic attack and made her lay flat down till help arrived. Nagori asked Ana if she was carrying an EpiPen with her but she said she had forgotten to carry it with her. Ana was rushed to the hospital where she was injected with 0.3 mg of epinephrine injections and given intravenous corticosteroids to stabilise her.
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*Please note that the names used in this clinical presentation are fictional.
Disease Name: Anaphylaxis
Allergy is a reaction that arises when an individual's immune system gets dysregulated and starts to overreact to innocuous substances thus raising a false alarm. This leads to an over-exaggerated immune response against that substance or antigen [1, 2]. Anaphylaxis is a systemic allergic reaction that often involves manifestations in multiple organs, making it a life-threatening condition [1]. It can either be IgE mediated or non-IgE mediated [2] and usually occurs in an individual after they have been re-exposed to an allergen [3] that their immune system has previously been sensitised to.
Clinical Manifestations
Skin and gastrointestinal symptoms are observed in more than 90% of anaphylaxis cases [4]. Ana (our patient in this case) suffers from many of the symptoms in the diagram above including difficulty in breathing, wheezing and urticaria on her arms which indicated towards her having an anaphylactic reaction.
Common Triggers
Some of the common triggers of an anaphylactic reaction include (but not restricted to):
Food items including milk, nuts and fish. Food is one of the most common elicitors responsible for emergency anaphylaxis cases presenting to hospitals [2, 5]
Certain medications including antibiotics like penicillin, non-steroidal anti-inflammatory drugs (NSAIDs) and anaesthetics [6].
Insect stings [7]
Sometimes, a trigger cannot be identified and that condition is known as idiopathic anaphylaxis [8].
Differential Diagnosis
Patients presenting with anaphylactic-like symptoms or anaphylaxis respond to a similar line of treatment. There are however several conditions which mimic many of the symptoms that one observes during an anaphylactic reaction including [9]:
Severe asthma
myocardial infarction
Systemic mastocytosis
scombroid fish ingestion,
hereditary angioedema
Hyperventilation syndrome
panic attacks, vocal cord
Immunological mechanisms
People who have been previously predisposed to an allergen (in this case milk protein), develop IgE antibodies specific to the allergen.
How? Antigen-presenting cells (APCs) take up the allergen and present them (milk proteins here) to naïve CD4 T cells.
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When this allergen bound to MHC Class II molecules on APC interacts with T cell receptors in presence of co-stimulatory signals and cytokines like IL-4, it leads to differentiation into CD4+ Th2 cells [10].
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Th2 cells, secrete IL-4 and IL-13, which stimulate the production of allergen-specific IgE by B cells [10].
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These antibodies bind to the Fc receptors on the basophils, macrophages, mast cells, and dendritic cells and cause sensitisation to food allergens [7, 10].
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Now, when the person is exposed to the allergen once again, the allergen reaches the bound and cross-link the bound IgE antibodies on immune cells [10].
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This activates Lyn tyrosine kinase, which phosphorylates the receptor's immunoreceptor tyrosine-based activation motif (ITAM). This initiates a cascade of downstream intracellular signalling [11].
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Then the events lead to an intracellular Ca2+ increase that results in mast cell degranulation with the release of chemical mediators [11].
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The mediators result in vasodilation, smooth muscle spasms, increased vascular permeability, eosinophil activation, recruitment of cytokines, etc [12]. All of the released mediators are responsible for clinical manifestations like prolonged inflammation observed during anaphylaxis.
Management and treatment
Identify triggers by assessing the detailed history of events preceding the reaction.
After identification of the trigger, steps to avoid it is crucial.
Keeping a self-injectable adrenaline injection (Epipen) is required.
Once someone suffers from an attack and is taken to the emergency unit, a dose of epinephrine is the cornerstone of therapy. Then patients are kept on preventative care by providing oxygen support. Saline (0.9%) is also given to patients. Other supplementary therapy includes giving saline, H1 and H2 antihistamines, ranitidine and methylprednisolone (glucocorticoid). If the patient undergoes bronchospasm, inhalative β-adreno-receptor agonists like salbutamol can also be administered at the doctor's discretion.
Reasons for using each of the above therapeutic approaches [1]:
- Adrenaline/epinephrine: Adrenaline restores blood pressure and airways (by bronchodilation) and reverses the effects caused to the body by the anaphylactic reaction.
- Oxygen support: Facilitate breathing and maintain oxygen saturation.
- Saline: Given for fluid resuscitation and volume substitution.
- β-adreno-receptor agonists: slowly dilates airways to facilitate breathing.
- Corticosteroids: Functions to inhibit expression of cyclooxygenase-2 and pro-inflammatory cytokines. It stalls neutrophil migration to sites of inflammation thus producing a slow anti-inflammatory effect [13].
- Ranitidine: Relieve predominant abdominal symptoms like cramps or nausea.
- Antihistamines: These are not the first line of therapy due to their slower onset of action. However, it is given as supplemental therapy to block the effects of histamine on the body.
Phago 'Citations'
References List
[1] Ring J, Beyer K, Biedermann T, Bircher A, Duda D, Fischer J, et al. Guideline for acute therapy and management of anaphylaxis: S2 Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Association of German Allergologists (AeDA), the Society of Pediatric Allergy and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Austrian Society for Allergology and Immunology (OGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Society for Psychosomatic Medicine (DGPM), the German Working Group of Anaphylaxis Training and Education (AGATE) and the patient organization German Allergy and Asthma Association (DAAB). Allergo J Int. 2014;23(3):96- 112.
[2] Lopez CM, Yarrarapu SNS, Mendez MD. Food Allergies. StatPearls. Treasure Island (FL)2022.
[3] Packi K, Matysiak J, Matuszewska E, Breborowicz A, Kycler Z, Matysiak J. New Biomarkers of Hymenoptera Venom Allergy in a Group of Inflammation Factors. Int J Environ Res Public Health. 2021;18(8).
[4] Tang R, Xu HY, Cao J, Chen S, Sun JL, Hu H, Li HC, Diao Y, Li Z. Clinical Characteristics of Inpatients with Anaphylaxis in China. Biomed Res Int. 2015;2015:429534.
[5] Brown AF, McKinnon D, Chu K. Emergency department anaphylaxis: A review of 142 patients in a single year. J Allergy Clin Immunol. 2001 Nov;108(5):861-6.
[6] National Clinical Guideline Centre (UK). Drug Allergy: Diagnosis and Management of Drug Allergy in Adults, Children and Young People. London: National Institute for Health and Care Excellence (NICE); 2014 Sep. PMID: 25340226.
[7] Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. 2017;140(2):335-348.
[8] Burrows AG, Ellis AK. Idiopathic anaphylaxis: Diagnosis and management. Allergy Asthma Proc. 2021 Nov 1;42(6):481-488.
[9[ Ellis AK, Day JH. Diagnosis and management of anaphylaxis. CMAJ. 2003 Aug 19;169(4):307-11. PMID: 12925426; PMCID: PMC180656.
[10] Fujita H, Soyka MB, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy. 2012;2(1):2.
[11] Hitomi T, Zhang J, Nicoletti LM, Grodzki AC, Jamur MC, Oliver C, et al. Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation. Blood. 2004;104(13):4122-4128.
[12] Ring J, Behrendt H. Anaphylaxis and anaphylactoid reactions. Classification and pathophysiology. Clin Rev Allergy Immunol. 1999;17(4):387-399.
[13] Williams DM. Clinical Pharmacology of Corticosteroids. Respiratory Care. 2018;63(6):655-670
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