Page 620 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 42 Urticaria, Angioedema, and Anaphylaxis 597

Four clinical patterns of anaphylaxis have been described: parenterally induced. However, a normal tryptase result does
immediate, biphasic, protracted, and delayed. Anaphylaxis can not exclude anaphylaxis. Tryptase within the normal range during
occur within seconds after allergen exposure: The more rapid anaphylaxis is often observed in food-induced anaphylaxis. In
the onset of anaphylaxis after allergen exposure, the more severe infants, tryptase may not be elevated after anaphylaxis, although
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and life-threatening is the reaction. Food-induced anaphylaxis the baseline levels may be increased. The diagnostic value of
takes slightly longer to develop than drug- or insect-induced other mast-cell products, such as histamine, platelet-activating
anaphylaxis. Some patients may have biphasic anaphylaxis, with factor, and proteases (carboxypeptidase A3), in anaphylaxis is
recurrence after 1–72 hours, but usually within 8–10 hours of under investigation.
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the initial attack. According to a meta-analysis of 27 studies, In anaphylaxis, component-resolved diagnosis can be useful
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patients with anaphylaxis presenting with hypotension or having to stratify risk in certain clinical scenarios. For example, patients
an unknown trigger may be at increased risk of biphasic ana- with wheat-dependent exercise-induced anaphylaxis should be
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phylaxis. Some patients may develop protracted anaphylaxis, tested for omega-5-gliadin sensitization, whereas patients with
which sometimes lasts longer than 24 hours, may be extremely anaphylaxis to vegetables, fruits, nuts, and cereals may have IgE
severe, and is often resistant to treatment. Delayed onset of to nonspecific lipid transfer proteins (mostly Pru p 3 and Tri a
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anaphylaxis has been reported anecdotally but is very rarely 14). In delayed anaphylaxis to mammalian meat or anaphylaxis
encountered in clinical practice. to cetuximab, tests for IgE against galactose-α-1,3-galactose
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The diversity and severity of symptoms in anaphylaxis depend (α-gal) should be considered. Certain components are regarded
on the dose of allergen, the route of allergen exposure, the extent as risk factors for anaphylaxis; for example, Mal d 3 sensitivity
of allergen absorption, the degree of sensitization, individual carries a sevenfold greater risk of anaphylaxis to apple compared
allergen threshold for a reaction, target tissue sensitivity, cofac- with Bet v 1. 63
tor involvement, coexisting atopic diseases and their severity,
and concomitant treatment. “Summation anaphylaxis” has Management of Anaphylaxis
been recognized as occurring after simultaneous exposure to Early recognition of anaphylaxis facilitates removal of the cause
various stimuli (physical exercise, infection, stress, or concomitant and prompt institution of treatment. The patient with anaphylaxis
exposure to other allergens or treatment with NSAIDs, ACEIs, should lie down with the legs elevated to increase venous blood
or beta-blockers). return and maintain cardiac output, and intravenous fluids should
Fatal reactions to foods are usually characterized by respiratory be given. In drug-induced or insect-induced anaphylaxis a
symptoms (bronchospasm and hypoxia). In contrast, anaphylaxis tourniquet may be placed proximal to the site of the injection
induced by insect stings is more likely to lead to cardiovascular or insect sting to slow absorption of injected antigens. The
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collapse. Asthma sufferers are at higher risk of fatal anaphylaxis. tourniquet should be released for 3 minutes at 5-minute intervals,
The risk of relapse in anaphylaxis depends on the type of allergen, with the total duration of application not exceeding 30 minutes.
individual allergen threshold, success of allergen avoidance, and Epinephrine should be administered by an intramuscular injection
the availability of immunotherapy. in the mid-outer thigh at the first sign of respiratory failure or
The most dangerous symptoms are laryngeal edema, respira- cardiovascular collapse and repeated after 5–15 minutes if the
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tory failure, and circulatory collapse, which may lead to death. response to the first injection is suboptimal. Epinephrine
Deaths from acute asthma in anaphylaxis occur predominantly autoinjectors for self-administration are available, but a single
in patients with preexisting unstable asthma. Rapid fatal shock pen may be insufficient to reverse severe reactions. Use of these
often occurs without other symptoms, and laryngeal angioedema pens in anaphylaxis outside hospital can be lifesaving. Overall,
is the least common cause of fatality. Fatal anaphylaxis occurs prompt diagnosis of anaphylaxis, early administration of epi-
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mostly within an hour of the onset of anaphylaxis. According nephrine, and fast transport to emergency rooms are crucial
to the UK Fatal Anaphylaxis Registry, the earliest arrest in fatal factors for successful management of anaphylaxis.
food anaphylaxis occurred within 25–35 minutes of exposure, Epinephrine is both an α and β adrenergic agonist with cyclic
slightly slower than with insect stings (10–15 minutes) or adenosine monophosphate (cAMP)–mediated pharmacological
drugs (≤5 minutes in hospital and 10–20 minutes outside effects on target organs. In patients with anaphylaxis, stimulation
hospital). 32 of α 1 adrenergic receptors increases peripheral vascular resistance,
thereby improving blood pressure and coronary perfusion,
Diagnosis of Anaphylaxis reversing peripheral vasodilation, and decreasing angioedema.
Measurement of blood tryptase is now widely used as a marker Activation of β 1 adrenergic receptors increases myocardial
of mast cell degranulation for in vitro confirmation of anaphylaxis. contractility (inotropy, chronotropy) while stimulation of β 2
Beta-tryptase is released from mast cells, but not from basophils, adrenoreceptors causes bronchodilation and decreases the release
and diffuses more slowly compared with histamine. The con- of inflammatory mediators from mast cells and basophils. 27
centration of tryptase peaks 1–2 hours after the onset of reaction, Current guidelines recommend the intramuscular route for
with a half-life of 1.5–2.5 hours. Samples for tryptase testing epinephrine administration because of faster absorption and
should be collected as soon as possible after emergency treatment higher plasma level of epinephrine after intramuscular injection
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of the patients and within 1–2 hours (but not later than 4 hours) compared with subcutaneous injection. The appropriate dosage
of anaphylaxis onset, and again after 24 hours (baseline sample) of epinephrine is 0.01 mg/kg of a 1 : 1000 (1 mg/mL) solution,
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to check that the value has returned to normal. Tryptase may to a maximum of 0.5 mg in adults. Epinephrine has a rapid
also be detected in postmortem specimens after death from but short action, so the dose may need to be repeated every 5–15
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suspected anaphylaxis. 58 minutes until symptoms improve. More than one dose is
Normally, mature tryptase is below detection limits in the required in a third of patients. Intravenous administration of
serum of healthy subjects, whereas it is elevated in most cases epinephrine should be reserved for severe anaphylaxis with
of anaphylaxis with vascular compromise, especially if it is profound life-threatening hypotension that is refractory to other