Page 621 - Clinical Immunology_ Principles and Practice ( PDFDrive )

598 ParT fivE Allergic Diseases

treatment because of a risk of potentially fatal cardiac arrhythmias Patients should be instructed how to avoid culprit allergens and
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and myocardial infarction. The recommended dose is a 1 : 100 cross-reactive agents and should be advised on safe alternatives.
000 solution (i.e., 1 mg in 100 mL saline at initial infusion rate The education of patients, their families, and, in the case of
of 2–10 µg/min, titrated up or down, depending on the clinical children, caregivers and school staff about anaphylaxis, and
response or epinephrine side effects). availability of first-aid measures is of primary importance. Written
Common pharmacological adverse effects of epinephrine personalized emergency action plans should be provided to
include anxiety, fear, headache, pallor, tremor, dizziness, and patients at special risk, such as school children. Emergency
palpitation. In the event of an overdose, unwanted effects may medications, such as epinephrine autoinjectors, should be dis-
include increased Q–T interval on electrocardiography, ven- pensed, and patients should receive training on their correct
tricular arrhythmias, angina, myocardial infarction, increased use. Patients should be advised to carry an epinephrine autoinjec-
blood pressure, pulmonary edema, and intracranial hemorrhage. tor with them at all times. Immunotherapy is very effective for
Patients with cardiovascular diseases and thyrotoxicosis and prophylaxis of bee- and wasp venom–induced anaphylaxis in
cocaine users are particularly susceptible to the adverse effects of sensitized patients and can be lifesaving. Drug-induced anaphy-
epinephrine. laxis can be prevented by avoidance of culprit drugs and cross-
The efficacy of epinephrine can be decreased by concomitant reacting agents, by premedication (for radiocontrast media), and,
therapy with beta-blockers, which is associated with unopposed in some cases, by drug desensitization for antibiotics, chemo-
stimulation of α adrenoreceptors and reflex vagotonic effects, therapeutic agents, insulin, vaccines, biological agents, and so
leading to bradycardia, hypertension, coronary artery constriction, on. For food-induced anaphylaxis, avoidance of the culprit food
bronchoconstriction, and augmented mediator release. Anaphy- is essential; oral immunotherapy is available in some allergy
laxis in patients on beta-blockers can be severe, protracted, and centers. In idiopathic anaphylaxis, patients with frequent episodes
unresponsive to treatment. Patients treated with beta-blockers (>6 episodes per year or ≥2 episodes within 2 months) can be
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may require fluid replacement and treatment with glucagon, treated with steroids to prevent further episodes. Omalizumab
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which increases intracellular cAMP independently of β adrenergic and rituximab have been reported to be effective in preventing
receptors. Glucagon can be administered intravenously 1–5 mg idiopathic anaphylaxis. Prevention strategies for anaphylaxis
(20–30 mg/kg in children, maximum 1 mg) over 5 minutes, should also involve promoting public awareness and public health
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followed by infusion at 5–15 mg/min titrated to clinical response. measures, such as appropriate food labeling, disclosure of food
Glucagon may improve hypotension in 1–5 minutes with maximal ingredients in restaurants, withdrawal of peanuts from in-flight
effect at 5–15 minutes. Side effects of glucagon include nausea refreshments, first-aid training in anaphylaxis for school staff,
and vomiting. and establishment of national anaphylaxis registries.
Corticosteroids are often administered in anaphylaxis to
minimize the risk of recurrent or protracted anaphylaxis. The TRANSLATIONAL RESEARCH OPPORTUNITIES
beneficial effects of corticosteroids develop 6–12 hours after
administration. Therefore their main role in anaphylaxis is likely
to be the prevention of relapse, but it is still unclear how they ON THE HOriZON
work. • Defining the role of functional autoantibodies and understanding the
If there is no response to epinephrine, life support measures mast-cell activation signals in chronic spontaneous urticaria should
should be instituted. The treatment choice depends on the clinical improve clinical assessment and management of patient subgroups.
presentation. In hypotension, large volumes of fluids should be • Development of new bradykinin and kallikrein inhibitors for patients
given rapidly using 1–2 L of 0.9% normal saline, infused rapidly with hereditary angioedema should further improve the acute manage-
(5–10 mL/kg within the first 5 minutes for an adult and up to ment of this rare but very important condition.
30 mL/kg in the first hour for children), to compensate for • Understanding the full clinical spectrum of patients with cryopyrin-
peripheral vasodilatation and for fluid loss into the extravascular associated periodic syndrome with NLRP-3 mutations should allow
earlier identification and treatment of these individuals with interleukin-1
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space. According to a Cochrane review, crystalloid normal saline blockers to improve quality of life and prevent later complications.
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should be preferred to colloids for intravenous fluid resuscitation.
Other vasopressors (dopamine, glucagon) may be needed to
reverse severe hypotension. Oxygen should also be administered Ongoing research into the importance of functional autoantibod-
in circulatory or respiratory failure. Bronchospasm should be ies in chronic urticaria and the cause or causes of mast-cell
treated with nebulized or inhaled β 2 agonists. If there is severe activation in patients with “idiopathic” disease should help to
laryngeal edema, endotracheal intubation and even emergency refine clinical assessment and management pathways.
tracheostomy may be needed to maintain the airway. Methylene The effectiveness of a bradykinin receptor antagonist and
blue, a selective nitric oxide cyclic guanosine monophosphate a kallikrein inhibitor for emergency treatment of HAE has
(cGMP) inhibitor, can prevent vasodilatation and has been illuminated the key role of the kallikrein–kininogen–kinin
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reported to be effective in refractory anaphylaxis. Patients pathway in disease pathogenesis. Development of new inhibi-
presented with respiratory compromise should be observed in tors of this pathway may offer additional benefits to patients in
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a hospital setting for at least 6–8 hours. In severe cases of the future.
hypotension, an observation period of 12–24 hours is Clarification of the phenotypic spectrum of patients with
advisable. 27 cryopyrin-associated periodic syndrome with NLRP-3 mutations
will facilitate early detection of affected individuals who present
Prevention of Anaphylaxis in childhood with persistent urticaria and would benefit from
The first step in prevention is to identify those at risk of ana- treatment with IL-1 blockers. Early treatment should improve
phylaxis. Therefore all patients with a history of anaphylaxis quality of life and may prevent the development of systemic
should be referred for assessment and undergo allergy evaluation. amyloidosis, nephropathy, and deafness in adulthood.