What is the pathophysiological mechanism of anaphylaxis?

From the Guidelines

Anaphylaxis is a severe, potentially life-threatening allergic reaction that occurs when the immune system overreacts to an allergen, triggering a systemic release of inflammatory mediators, primarily through IgE binding and cross-linking of the high affinity IgE receptor (FcεRI) on the surface of mast cells and basophils, as noted in the 2020 practice parameter update 1. The pathophysiological mechanism of anaphylaxis involves the binding of an allergen to IgE antibodies attached to mast cells and basophils, causing these cells to rapidly degranulate and release preformed mediators such as histamine, tryptase, and proteoglycans.

• Key steps in the pathophysiological mechanism include:
  • The binding of the allergen to IgE antibodies on mast cells and basophils
  • The rapid degranulation of these cells, releasing preformed mediators
  • The production of newly synthesized mediators, including leukotrienes, prostaglandins, and platelet-activating factor
  • The activation of the complement system and coagulation cascades, further amplifying the inflammatory response
• The resulting physiological effects of anaphylaxis include:
  • Hypotension due to peripheral vasodilation and fluid extravasation
  • Respiratory distress from bronchospasm and laryngeal edema
  • Tissue edema throughout the body
  • Activation of the complement system and coagulation cascades, which may further amplify the inflammatory response, as discussed in the guidelines for the diagnosis and management of food allergy in the United States 1. The prompt administration of epinephrine is crucial in the treatment of anaphylaxis, as it addresses the pathophysiologic changes that occur in anaphylaxis, including increased vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema, as well as bronchodilation and decreased release of mediators of inflammation from mast cells and basophils 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action Epinephrine acts on both alpha and beta-adrenergic receptors. 12. 2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis

The pathophysiological mechanism of anaphylaxis involves vasodilation and increased vascular permeability, leading to loss of intravascular fluid volume and hypotension, as well as bronchospasm, wheezing, and dyspnea. Key features of anaphylaxis include:

• Vasodilation: widening of blood vessels
• Increased vascular permeability: increased leakage of fluid from blood vessels
• Bronchospasm: constriction of airways
• Hypotension: low blood pressure The drug label does not provide a comprehensive description of the pathophysiological mechanism of anaphylaxis, but rather describes the effects of epinephrine on this mechanism 2.

From the Research

Pathophysiological Mechanism of Anaphylaxis

The pathophysiological mechanism of anaphylaxis involves a complex interplay of immune activation and release of immunomodulators, leading to a rapid, systemic, and potentially life-threatening reaction 3.

Key Features of Anaphylaxis

• Anaphylaxis is an acute and potentially lethal multi-system allergic reaction 4
• It is characterized by symptoms such as urticaria, difficulty breathing, and mucosal swelling 5
• The most common triggers are medications, stinging insect venoms, and foods, although unidentified triggers can occur in up to one-fifth of cases 5

Role of Epinephrine in Anaphylaxis

• Epinephrine is the first-line treatment for anaphylaxis and is universally recommended as the drug of choice 4, 5, 3
• Early administration of epinephrine is critical to prevent a potentially fatal outcome 5, 3
• Epinephrine acts rapidly, with maximal plasma concentrations reached in less than 10 minutes, making it more effective than antihistamines in relieving symptoms of anaphylaxis 3

Comparison with Antihistamines

• Antihistamines are often used to treat anaphylaxis, but they do not relieve or prevent all of the pathophysiological symptoms of anaphylaxis, including airway obstruction, hypotension, and shock 3
• Antihistamines do not act as rapidly as epinephrine, with maximal plasma concentrations reached between 1 and 3 hours 3
• Some studies suggest a beneficial effect of antihistamines in anaphylaxis, but their use should be considered after epinephrine administration 6

Other Treatment Options

• Corticosteroids are sometimes used in anaphylaxis, but their effectiveness is unclear, and some studies suggest they may be associated with adverse outcomes 6
• Other treatment options, such as beta2 agonists and glucagon, may be considered in specific cases, but epinephrine remains the primary treatment for anaphylaxis 5