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

ANAPHYLAXIS
• First reported case was in 2640 BC – pharoh died from sting of wasp
• Occurs in 1 of every 3,000 hospitalized patients
• Annual deaths: at least 500
• No known epidemiologic characteristics that reliably identify those at risk
• Most studies suggest that an atopic person is at no greater risk
Mast Cell Mediators:
Once stimulated, the mast cells secrete two groups of mediators:
1) preformed mediators and
2) newly formed mediators.
• The preformed mediators have been synthesized in advance and stored in granules, to
be released immediately upon stimulation of the mast cell. This group of mediators
include histamine, proteolytic enzymes (tryptase), heparin, and chemotactic factors.
• The newly formed mediators consists of lipids that are synthesized after the mast cell is
stimulated. The stimulus activates phospholipase A2, which acts to break down
phospholipids in the cell membrane to arachidonic acid. Arachidonic acid can then either
enter the cyclo-oxygenase pathway to produce prostaglandins and thromboxanes or the
lipoxygenase pathway, to produce the leukotrienes.
Mediator actions: These mediators rapidly act
• on the smooth muscle
• in the lung to cause bronchospasm and
• in the gastrointestinal tract to cause abdominal cramping and diarrhea.
• on the bronchial airways to produce
• increased mucus production and
• an inflammatory infiltrate
• on the circulatory system to produce
• vasodilation and
• increased vasculature permeability, leading to bronchial edema, urticaria, and
hypotension.
Tryptase. The biologic action of tryptase in anaphylactic reactions remains uncertain; however,
it can serve as an important marker of anaphylaxis.
• Whereas histamine is very transient and difficult to measure, tryptase doesn’t peak until
1-2 hours after the stimulus and remains in the circulation up to 6-8 hours. The detection
of tryptase in the serum can serve to confirm your suspicions when a patient presents
with symptoms of anaphylaxis.
Mast Cell Activation: Three main triggers of mast cell activation:
1) IgE hypersensitivity. Antigen crosslinks IgE antibodies attached to mast cells through
Fc epsilon receptors. When it crosslinks two IgE molecules, it draws the attached
IgE receptors close to one another. Such aggregation of receptors activates the
cell.