Immunotherapy Safety for the Primary Care ... - U.S. Coast Guard

4) Hymenoptera stings
Although almost 25% of the population may be at risk, fewer than 100 deaths
occur each year
5) Immunotherapy
Despite its widespread use, fatalities from allergen immunotherapy are extremely
rare. (45 fatalities since 1945)
Complement mediated anaphylaxis. This type of anaphylaxis doesn’t depend on IgE, but
rather the other antibodies: IgG, IgM, and IgA antibodies. Both the classic complement
pathway and the alternate pathway are implicated in the generation of anaphylatoxins,
C3a and C5a. These products are then capable of causing mast cell (and basophil)
degranulation.
The most classic examples of complement mediated anaphylaxis are reactions to blood and its
products:
• Example 1: IgG aggregates (Gamma globulin)
Administration of gamma globulin has been associated with anaphylactoid
reactions because it contains IgG dimers and polymers capable of activating
complement spontaneously.
• Cl combines with the aggregated immunoglobulins and eventually leads
to the production of C3 convertase and CS convertase which, in turn, result in the
release of the anaphylatoxins C3a and C5a
• Both C3a and C5a then act on the mast cell to promote mediator release.
• Example 2: IgG or 1gM anti-IgA
Probably the best defined example is the anaphylaxis which can result when an
IgA deficient patient receives blood products containing IgA. These patients
frequently will produce IgG or 1gM anti-IgA antibodies, which will combine with
the infused IgA in the administered blood products, and release anaphylatoxins.
(IgA anaphylaxis can also occur through the more typical most cell
sensitization with IgE anti -IgA)
Mast Cell Activated Anaphylaxis. Numerous agents have been reported to be capable of
causing direct degranulation of mast cells with histamine release. The most clinically relevant
are:
1. Opiates (generally limited to the skin)
2. Muscle relaxants (curare, d-tubocurarine)
3. Highly charged polyanionic antibiotics (polymyxin B)
4. Radiocontrast media (Some sources suggest it might be complement mediated)
• Initial exposure: 1-10% risk of anaphylaxis (with conventional RCM)
• Reexposure, in those with previous reaction: 17-35% risk of anaphylaxis
• No in-vitro or in-vivo testing available (Not IgE mediated)
• Rx -- prevent recurrence:
• Pretreatment (Prednisone, Benadryl, and ephedrine)
• Low osmolality RCM