RECOGNITION AND MECHANSIMS OF ANAPHYALXISAnaphylaxis was defined in the 2010 practice parameter as one of three clinical scenarios:
1. Acute onset (minutes-hours) of a reaction involving skin and/or mucosal tissue AND either respiratory compromise, hypotension OR symptoms of end organ dysfunction.
2. Two or more of the following occurring rapidly after exposure to a likely allergen: skin/mucosal tissue, respiratory compromise, reduced blood pressure or associated symptoms, and/or persistent GI symptoms.
3. Reduced blood pressure after exposure to a known allergen.
The definition is inclusive with several key points to be made. The condition may occur without identifiable trigger (scenario 1). Scenarios 1 and 2 also indicate the essential clinical point that anaphylaxis usually involves more than one body system and has very rapid onset and evolution. The only scenario in which the diagnosis is made when only one body system is involved is hypotension after exposure to a known allergen (scenario 3).
The definition from 2004 practice parameter was more succinct and combined all of the above scenarios into one sentence: "An acute multi-system reaction caused by the rapid release of mediators from tissue mast cells and peripheral blood basophils.” The older definition also stresses the rapid multi-system nature of anaphylaxis. Furthermore, it introduces the concept that mediator release from tissue mast cells and circulation basophils is responsible for the signs and symptoms of anaphylaxis.
The earlier document specifies that immunologic mechanism may be IgE-mediated or non-IgE mediated and that non-immunologic mechanisms also cause anaphylaxis. As a result, we no longer use the terms “anaphylactoid” or “pseudo-allergic” (Figure).
Figutre 1 : Mechanisms of anaphylaxis: Anaphylaxis can be triggered by IgE-mediated (Gell and Coombs type 1 hypersensitivity reactions), non-IgE-mediated reactions (Gell and Coombs type 2 and 3 hypersensitivity reactions), or by non-immunologic mechanisms. In idiopathic anaphylaxis, activation of mast cells via immunologic mechanisms can sometimes be demonstrated.
IgE mediated reactions are those with which practitioners and patients are most familiar. Cross linking of IgE bound to the high-affinity IgE receptor (FceR1) on the surface of tissue mast cells and circulating basophils initiates a signaling cascade that results in the rapid release of preformed mediators including histamine and tryptase. Synthesis and release of newly formed mediators follows. Because mast cells also have receptors for complement split products, complement activation has the potential to activate mast cells. IgE mediated episodes of anaphylaxis tend to be more severe and have more rapid onset than other immunologic mechanisms.
The trigger but not the mechanism of physical causes of anaphylaxis is obtained by history. Other triggers to anaphylaxis include non-specific mast cell activators (e.g., opioids, intravenous contrast, vancomycin) and over exposure to mast cell mediators as in systemic mastocytosis and scombroid poisoning.
Idiopathic anaphylaxis has no identifiable preceding trigger. Just as some chronic urticaria are caused by an IgG autoantibody to the a-subunit of FceR1, it is theoretically possible the same could cause anaphylaxis by cross linking the receptor or by activating complement locally.
Signs and symptoms of anaphylaxis
Most mast cells live at surfaces that interface with the outside world (skin, eyes, respiratory tract, gastrointestinal tract, and to a lesser extent bladder and uterus). The signs and symptoms of anaphylaxis reflect mast cell activation at those sites (Table).
Signs and symptoms of mast cell activation.
||Signs and symptoms
||Flushing, urticaria, pruritus, angioedema
|Congestion, discharge, sneezing, pruritus
||Dysphonia, stridor, dyspnea, asphyxiation
||Dyspnea, wheeze, cough, congestion, tightness, asphyxiation
||Nausea, vomiting, bloating, cramping, diarrhea
||Tachycardia, hypotension, shock, bradycardia, cardiovascular collapse
||Urinary urgency, uterine cramping, metallic taste in mouth, sense of “impending doom”
* Can be potentially life threatening
The skin (~90%) and respiratory systems (40-70%) are the two most common body systems affected in anaphylaxis, especially in children. Adults are more likely than children to have cardiovascular involvement. Interestingly, patients who become hypotensive as an early sign of anaphylaxis are less likely to develop cutaneous symptoms (clinical scenario 3).
Temporal patterns of anaphylaxis
There are three recognized patterns of anaphylaxis. The most common is a uniphasic reaction in which the episode is completely resolved once treated.
Biphasic reactions are ones in which symptoms recur 6-12 hours after apparent resolution. Biphasic reactions occur in up to 20% of patients (highest in adults) and typically have a similar presentation as the initial episode. Risk factors for biphasic reactions include ingested allergens, slower onset of severe symptoms, patients who require more than one dose of epinephrine, and a delay in its administration during the initial presentation. Co-factors such as poorly controlled asthma, anxiety, and ß-blocker use may also increase the risk. Many emergency departments have protocols requiring patients with anaphylaxis to be observed for at least 8-12 hours because of the risk of biphasic reactions.
Rarely, patients have protracted anaphylaxis with symptoms persisting for 2 or more days. These unfortunate patients respond incompletely and only briefly to emergency treatments.