Definition of Anaphylaxis
Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction that is rapid in onset and results from the sudden systemic release of mediators from mast cells and basophils. 1
Core Defining Features
Anaphylaxis is an acute, life-threatening systemic reaction with varied mechanisms, clinical presentations, and severity that can cause death within minutes to hours of onset. 1
There is no universally accepted clinical definition of anaphylaxis, which has made diagnosis challenging in clinical practice. 1
Minor, localized, or non-systemic reactions are explicitly excluded from the definition of anaphylaxis—only generalized or systemic reactions qualify. 1
Mechanistic Classification
The European Academy of Allergy and Clinical Immunology (EAACI) divides anaphylaxis into two categories based on mechanism:
Allergic anaphylaxis occurs when the reaction is mediated by an immunological mechanism, including IgE antibodies, IgG antibodies, or complement activation by immune complexes. 1
Non-allergic anaphylaxis produces identical clinical features but is not mediated by immunological mechanisms. 1
Important Terminology Note
The term "anaphylactoid" was previously used for non-IgE-mediated reactions, but the EAACI recommends this term should no longer be used. 1
However, this recommendation has not been universally accepted—American guidelines still distinguish between anaphylactic (IgE-mediated) and anaphylactoid (non-IgE-mediated) reactions, though acknowledging they are clinically identical. 1
Clinical Presentation Characteristics
Respiratory compromise and cardiovascular collapse are the most concerning manifestations because they are the most frequent causes of anaphylactic fatalities. 1
Urticaria and angioedema are the most common manifestations and often occur as initial signs, but cutaneous findings may be delayed or absent in 10-20% of rapidly progressive anaphylaxis cases. 1
The more rapidly anaphylaxis develops, the more likely the reaction is to be severe and potentially life-threatening—this temporal relationship is a critical prognostic indicator. 1
Pathophysiological Complexity
Anaphylaxis is not a homogeneous process—the pathways, mediators, time course, and response to treatment depend on multiple factors including the trigger agent, route and rate of administration, the patient's hypersensitivity mechanism, and underlying health conditions. 1
Clinical presentations vary widely: while anaphylaxis commonly involves respiratory, cutaneous, and circulatory changes, variations such as shock with gastrointestinal disturbance alone, or isolated cardiovascular collapse are possible. 1
Fatal reactions may occur without significant shock except as a terminal event following respiratory arrest. 1
Cardiovascular and Respiratory Mechanisms
Intravascular volume redistribution is an important component of anaphylactic shock, with cardiac output decreased due to reduced coronary perfusion pressure and impaired venous return. 1
Coronary artery spasm may occur from local mediator release, and features of acute left or right ventricular failure can develop, with myocardial ischemia and ECG changes expected within minutes of severe anaphylactic shock. 1
Asphyxia may result from upper airway occlusion caused by angioedema, or bronchospasm with mucus plugging of lower airways—both processes can occur simultaneously, particularly in reactions to foods, latex, beta-lactam antibiotics, or aspirin. 1
Time Course and Resolution
Anaphylaxis usually resolves in 2-8 hours, but secondary pathology from the reaction or its treatment may prolong this duration. 1
Resolution is typically complete except when cerebral hypoxia at the peak of the reaction has caused significant brain damage, or when disordered clotting leads to bleeding. 1
Critical Diagnostic Pitfall
Hypotension is NOT required for the diagnosis of anaphylaxis—this is a common misconception that can delay recognition and treatment. 2
Symptoms not immediately life-threatening might progress rapidly unless treated promptly and appropriately, emphasizing the need for early intervention even with seemingly mild presentations. 1