Anaphylaxis reactions mechanism

Three different mechanisms have been proposed to explain the reaction to sulfites in asthmatic patients. The first is explained by the inhalation of sulfur dioxide, which produces bronchoconstriction in aU asthmatics through direct stimulation of afferent parasympathetic irritant receptors. Furthermore, inhalation of atropine or the ingestion of doxepin protects sulfite-sensitive patients from reacting to the ingestion of sulfites. The second theory, IgE-mediated reaction, is supported by reported cases of sulfite-sensitive anaphylaxis reaction in patients with positive sulfite skin test. Finally, a reduced concentration of sulfite oxidase enzyme (the enzyme that catalyzes oxidation of sulfites to sulfates) compared with normal individuals has been demonstrated in a group of sulfite-sensitive asthmatics. 

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

Studies have now started to clarify the role of histamine Hi and H2 receptors in the cardiovascular manifestations of anaphylaxis. However, histamine can activate H3 and H4 receptors [56, 57]. Levi and coworkers [58-60] identified H3 receptors as inhibitory heteroreceptors in cardiac adrenergic nerve endings. This suggests a mechanism by which endogenous histamine can activate norepinephrine release in normal and ischemic conditions [61,62]. The functional identification ofH3 receptors in the human heart [59] means that these receptors might be directly and/or indirectly involved in the cardiovascular manifestations of anaphylactic reactions. 

The mechanisms of the allergy-like reactions to RCM are still a matter of speculation (table 2). Anaphylaxis to RCM has been discussed to be due to a direct membrane effect possibly related to the osmolality of the RCM solution or the chemical structure of the RCM molecule (pseudo-allergy) [2], an activation of the complement system [27], a direct bradykinin formation [28], or an IgE-mediated mechanism [3]. 

Immunological reactions to human serum albumin tend to be non-IgE-mediated anaphylactic reactions (0.011% of cases treated), about a third of which are life-threatening (9). A case in which the mechanism seemed to be IgE-mediated anaphylaxis against native albumin has been reported (10). 

Dejarnatt AC, Grant JA. Basic mechanisms of anaphylaxis and anaphylactoid reactions. Immunol Allergy Clin North Am 1992 12 33-46. 

Among the anaphylactic reactions to NSAIDs that result in different types of reaction (urticaria, angioedema, asthma, or hypotension), there have been very few reports of anaphylactic shock. However, anaphylaxis has been described in patients taking celecoxib (135,136) or rofecoxib (137). Rofecoxib caused anaphylaxis in a patient who had had a similar reaction to diclofenac, suggesting that COX-2 inhibitors may be not safe in all individuals who have adverse reactions to non-selective COX inhibitors. It also suggests that different mechanisms may be involved in patients with asthma and in those with anaphylactoid reactions to NSAIDs. 

In addition to injection-site reactions, other mild to moderate reactions include fever, dizziness, sweating, and nausea. Low incidences of severe infusion reactions (e.g., hypotension, cardiac dysfunction, anaphylaxis, and bron-chospasms) have also been reported with Rituximab, Cetuximab, and even with humanized mAb Trastuzumab.46 Once again, the underlying mechanisms are poorly understood, limiting the application of mechanistic mathematical modeling for predicting infusion site reactions. 

Anaphylactoid—Anaphylaxis-like reactions that do not involve IgE-medicated mechanisms. 

---