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It is important to note that anaphylactoid reactions can happen upon the initial exposure to an allergen or substance whereas an anaphylactic reaction comes after someone has already experienced an initial exposure and becomes re-exposed to the same allergen.

https://www.merckmanuals.com/home/immune-disorders/allergic-reactions-and-other-hypersensitivity-disorders/anaphylactic-reactions

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"Anaphylactoid" reactions involve direct stimulation of mast cells that undergo degranulation in the same way as an IgE mediated reaction. This causes the release of histamine, tryptase, prostaglandin, and leukotrienes resulting in mild to severe anaphylaxis-like symptoms (Dewachter & Savic, 2019).

Medications like propofol, vancomycin, and even NSAIDS can activate the abnormal immune response by way of non-specific mechanisms, calcium- and phospholipase-dependent mechanisms, and selective inhibition of cyclooxygenase 1, respectively (Dewachter & Savic, 2019).

Source:

Dewachter, P., & Savic, L. (2019). Perioperative anaphylaxis: Pathophysiology, clinical presentation and management. BJA Education, 19(10), 313–320. https://doi.org/10.1016/j.bjae.2019.06.002

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When is anaphylaxis NOT a type 1 hypersensitivity reaction?

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When is anaphylaxis NOT a type 1 hypersensitivity reaction?

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Anaphylactoid Reaction
When anaphylactic reactions are not mediated by IgE antibodies, these are called anaphylactoid reactions. The clinical manifestations of anaphylaxis and anaphylactoid reactions are deemed indistinguishable in the health care setting. However, performing additional tests can assist in determining the cause. According to Pattanaik et al. (2014), in some institutions, the use of the term "anaphylactoid" is to be phased out because signs, symptoms, and intervention are so similar to true IgE mediated reactions.

Sources:

Lieberman, P. L. (2014). Recognition and first-line treatment of anaphylaxis. The American Journal of Medicine, 127(1). https://doi.org/10.1016/j.amjmed.2013.09.008

Pattanaik D, & Yataco J.C., & Lieberman P (2014). Anaphylactic and anaphylactoid reactions. Hall J.B., & Schmidt G.A., & Kress J.P.(Eds.), Principles of Critical Care, 4e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=1340&sectionid=80028592

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Is anaphylaxis a true type 1 hypersensitivity reaction? The answer: Yes and No

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Is anaphylaxis a true type 1 hypersensitivity reaction? The answer: Yes and No

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Though anaphylaxis is a severe inappropriate reaction to an allergen, it is still typically IgE mediated and fast-acting.

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Hypersensitivity Type I reaction (Immediate or allergic reaction) - pathophysiology

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Symptoms of anaphylaxis include:

skin reactions such as hives, flushed skin, or paleness

suddenly feeling too warm

feeling like you have a lump in your throat or difficulty swallowing

nausea, vomiting, or diarrhea

abdominal pain

a weak and rapid pulse

runny nose and sneezing

swollen tongue or lips

wheezing or difficulty breathing

a sense that something is wrong with your body

tingling hands, feet, mouth, or scalp

If you think you’re experiencing anaphylaxis, seek medical attention immediately. If anaphylaxis has progressed to anaphylactic shock, the symptoms can include:

struggling to breathe

dizziness

confusion

sudden feeling of weakness

loss of consciousness

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Certain individuals are more prone to episodes of anaphylaxis than others, and evidence of risk factors should be elicited during history taking or retrieved from existing documentation (Figure 2). These risk factors include patients with atopic illness such as hay fever, eczema and, in particular, asthma, which is most typically the case in children and young adults with food-related anaphylaxis (Brown 2006). Approximately 12% of those with anaphylaxis also have a family history of allergy or anaphylaxis, making this a significant risk factor (NICE 2011, American Academy of Allergy, Asthma & Immunology 2013).

http://apeartd.blogspot.com/2019/05/risk-factors-in-anaphylaxis.html

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https://youtu.be/Cr3eidODuDE

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Immediate response: Type I Hypersensitivity Reaction

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An EpiPen auto-injects epinephrine into an individual when there is a Type 1- IgE Mediated Reaction or anaphylaxis. After an epinephrine injection has been administered, it is important to seek medical attention right away.

Source: https://www.epipen.com/en

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Prevention/Treatment for Type 1 IgE- Mediated Reaction

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Prevention/Treatment for Type 1 IgE- Mediated Reaction

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-  Avoid allergen
-  Injected low-dose allergens to desensitize response
- Antihistamines (H1 receptor antagonists)

-  Corticosteroids

-  Bronchodilators

-  Leukotriene receptor antagonists (e.g. montelukast)

-  Epinephrine (adrenaline), injected

Source: https://www.ncbi.nlm.nih.gov/books/NBK560561/

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- Hypotension
- Tachycardia
- Dysrhythmias

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Normal Nasal Pathway vs Nasal Pathway With Rhinitis 

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- Rhinitis
- Bronchospasm
- Laryngeal edema
- Asthma

Image from: https://www.ent-phys.com/ent-services/nose/chronic-rhinitis/

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- Urticaria (hives)
- Itching
- Atopic eczema
- Angioedema
- Conjunctivitis

Image from: https://www.doc4kids.com/all-about-hives-urticiaria/

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- Nausea
- Vomiting
- Diarrhea
- Abdominal pain

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- Confusion
- Headache
- Lightheadedness

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Clinical Manifestations of Different Body Systems

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Type 1 IgE-Mediated Reactions effect multiple systems in the body. The symptoms varies depending on which organ system is affected.

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The pathophysiological process of anaphylaxis 

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The pathophysiological process of anaphylaxis 

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Histamine
Histamine is a chemical created in the body that is released by white blood cells into the bloodstream when the immune system is defending against a potential allergen. Mast cells and basophils likely represent the main sources of histamine in anaphylaxis.

Platelet-activating factor (PAF)
Platelet activating factor (PAF) is an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses. PAF is also implicated in platelet aggregation.

*In study, combined inhibition of histamine and PAF almost entirely blocked anaphylaxis, suggesting additive or synergistic effects of histamine and PAF

Leukotrienes
Leukotrienes are inflammatory chemicals the body releases after coming in contact with an allergen or allergy trigger. Leukotrienes cause tightening of airway muscles and the production of excess mucus and fluid.

Sources:

Bruce, Debra Fulghum. “Leukotriene Modifiers and Allergies.” WebMD, WebMD, https://www.webmd.com/allergies/leukotriene.

Reber, Laurent L, et al. “The Pathophysiology of Anaphylaxis.” The Journal of Allergy and Clinical Immunology, U.S. National Library of Medicine, Aug. 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657389/.

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Sensitization Phase
*Occurs during first exposure
1. After allergen particles enter the body, antigen-presenting cells (APCs) bind and take in the particles via receptors and travel to the lymph nodes.
2. APCs then present the antigen, along with a co-stimulatory molecule, to CD4 T helper cells, which bind to the antigen and co-stimulatory molecule, resulting in "priming" and conversion of the TH cell to a TH2 cell. This occurs in response to various small proteins, or interleukins, that promote the conversion of TH cells to TH2 cells, such as IL-4, IL-5, or IL-10 (cytokines).
3. TH2 cells release IL-4, which causes B cells to undergo antibody class switching and begin producing IgE antibodies specific to the allergen, instead of IgM antibodies. TH2 cells also release IL-5, which stimulates production and activation of eosinophils.
4. IgE antibodies begin to attach to Fc receptors on the surface of mast cells.

Early Phase Reaction from Subsequent Exposure
*Immediate, occurs within minutes
1. When allergen particles enter the body again, mast cells bind to a molecule of the antigen. The antigen may bind simultaneously to two molecules of IgE-Fc receptor complexes on the mast cell's surface (cross-link), resulting in the activation of intracellular pathways and mast cell degranulation.
2. Mast cells release pro-inflammatory molecules called mediators during degranulation, which ultimately cause the effects seen in an allergic reaction. One the major mediators released is histamine, which binds to H1 receptors and causes the smooth muscles around the bronchi to contract and the blood vessels to dilate and become more permeable. Bronchial smooth muscle contraction causes the patient to experience dyspnea, and increased vasodilation and vessel permeability leads to edema and urticaria. In addition to histamine, mast cells also release proteases and eosinophils.

Late Phase Reaction from Subsequent Exposure
*Delayed, occurs within 8-12 hours
1. TH2 cells, eosinophils, and basophils are recruited to the site of the allergen because of the cytokines and pro-inflammatory molecules produced during the early phase of the reaction. These include IL-4, IL-5, IL-10, and leukotrienes, which are smaller molecules composed of fatty-acids that facilitate communication between local cells. The leukotrienes that are involved include LTB4 and LTC4, which cause smooth muscle contraction and attract more immune cells, such as neutrophils, mast cells, and eosinophils, to their location even if the allergen is no longer present.

Sources:

Felver, Linda, et al. Study Guide for: Pathophysiology: The Biologic Basis for Disease in Adults and Children, Eighth Edition. Mosby, 2019.

“Type I Hypersensitivity (IGE-Mediated Hypersensitivity) - Causes, Symptoms, Pathology.” YouTube, Osmosis, 20 June 2016, https://www.youtube.com/watch?v=2tmw9x2Ot_Q.

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IgE has a relatively short life span in the blood due to its rapid binding to high-affinity Fc receptors on the plasma membranes of mast cells.

Atopic individuals tend to produce higher quantities of IgE and have more Fc receptors for IgE on their mast cells.

Source:

Felver, Linda, et al. Study Guide for: Pathophysiology: The Biologic Basis for Disease in Adults and Children, Eighth Edition. Mosby, 2019.

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Basophils and mast cells are the principal effector cells involved in type I hypersensitivity reactions

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Basophils
Basophils are a type of white blood cell known as granulocytes. The granules in basophils are composed of different chemicals, including histamine and heparin. When needed, basophils will break open (degranulate) to release these chemicals as part of the body's immune defense.

Mast cells
Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. Mast cells generate and release multi-potent molecules, such as histamine, proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors, allowing them to play a key role in regulating the functions of many organs and tissues.

Sources:

Krystel-Whittemore, Melissa, et al. “Mast Cell: A Multi-Functional Master Cell.” Frontiers, Frontiers, 1 Jan. 1AD, https://www.frontiersin.org/articles/10.3389/fimmu.2015.00620/full.

Suzanne Dixon, MPH. “Basophils Are Your Body's Natural Tick Fighter.” Verywell Health, https://www.verywellhealth.com/what-are-basophils-797206.

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NHS. (2019, November 29). Anaphylaxis. NHS choices. Retrieved March 17, 2022, from https://www.nhs.uk/conditions/anaphylaxis/ 

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Anaphylaxis is the result of the immune system overreacting to a trigger. This is often something you're allergic to, but not always. Common anaphylaxis triggers include foods (nuts, milk, fish, shellfish, eggs) me