Page 618 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 42 Urticaria, Angioedema, and Anaphylaxis 595

least 500 units pd-C1-INH 1 hour before the procedure, with a of coronary and peripheral arteries, and vasodilation of venules,
further dose available in case a swelling develops. Other strate- thereby producing clinical symptoms of anaphylaxis. IgE-
gies include increasing the dose of prophylactic treatment with mediated reactions occur in presensitized patients (e.g., those
anabolic steroids (danazol or stanozolol) or plasmin inhibitors experiencing penicillin-, insulin-, latex-, or peanut-induced
(tranexamic acid or ε-aminocaproic acid) for at least 48 hours anaphylaxis). IgG- or IgM-related transfusion reactions should
before and after the procedure. Specific guidance on dosing for be classified as immunological, non–IgE-mediated anaphylaxis. In
adults and children can be found elsewhere. contrast, some substances, such as opioids, radiocontrast media,
vancomycin, and some muscle relaxants, are capable of direct
Long-Term Prophylaxis release of mediator (histamine) from basophils and mast cells
Anabolic steroids are the mainstay of long-term prophylaxis in without involvement of IgE. Although reactions to NSAIDs are
countries where they are licensed for use in the treatment of considered pharmacological rather than immunological (because
HAE. They increase the production of C1-INH by the liver in of the downstream effects of COX inhibition), an IgE-mediated
heterozygotes with a functioning allele. The dose should be titrated mechanism has been suspected in a few patients but is difficult
against the clinical response rather than blood levels of C1-INH to prove. Apart from IgE, other antibodies may be involved: In
to the lowest level that prevents or ameliorates the condition. murine models IgG-mediated FcγRIII-dependent anaphylaxis
Virilizing side effects can be problematic for women, and anabolic elicited by a high dose of allergen has been described. The key
steroids are avoided in children because of concerns about growth participating cells in this type of anaphylaxis are macrophages,
retardation. Monitoring of liver function and lipid profiles should with platelet-activating factor being the main mediator. 37
be undertaken periodically. Performing a liver ultrasound
examination every 3 years to screen for development of hepatoma Etiology of Anaphylaxis
is usually recommended in patients on long-term prophylaxis. Anaphylaxis is most commonly caused by foods, drugs, general
Plasmin inhibitors are generally less effective for prophylaxis anesthetic agents, insect stings, and latex. Rare causes include
compared with anabolic steroids but are preferred in children. vaccines, semen, and aeroallergen inhalation. Exercise can
pd-C1-INH infusions twice a week may be given as prophylaxis occasionally cause anaphylaxis either on its own (exercise-induced
during pregnancy and in rare situations when alternative therapies anaphylaxis) or after ingestion of a food to which the individual
are not appropriate. is presensitized (food- and exercise-induced anaphylaxis). Up
to 20% of patients with systemic mastocytosis present with
Anaphylaxis anaphylaxis during their lifetime. Anaphylaxis mostly occurs
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Anaphylaxis is a severe, life-threatening, systemic reaction of in reaction to hymenoptera stings, NSAIDs, and opioids and in
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sudden onset and involves respiratory compromise, cardiovascular the perioperative setting. Idiopathic anaphylaxis accounts for
collapse, or both. Its clinical features and management have been up to 60% of anaphylaxis cases in ambulatory adults and for
40
summarized in international guidelines. 25-28 10% of cases in children. It is increasingly recognized that some
anaphylactic cases are multifactorial. Cofactors are thought to
Epidemiology of Anaphylaxis lower the threshold for the induction of anaphylaxis and are
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Estimates of the incidence of anaphylaxis in the general population implicated in about 30% of anaphylaxis cases in adults. The
in Europe and the United States vary from 50 to 103 cases per risk of severe anaphylaxis is increased in patients taking beta-
29
100 000 per annum. Lifetime personal risk estimate for ana- blockers or ACEIs, or both. 28
30
phylaxis in the general population is believed to be 0.05–2%. The most common routes of allergen exposure are oral and
The mortality rate in anaphylaxis is estimated to be below parenteral, although inhalation of allergens (e.g., fish or legume
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0.001%. In the United Kingdom, anaphylaxis accounts for 20 allergens after cooking, latex particles in health care settings) or
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deaths per year, which represents 1 death in 3 million people. percutaneous penetration after skin contact can induce anaphy-
According to the European Anaphylaxis Registry, a life-threatening laxis in highly sensitized patients.
or fatal anaphylaxis occurs in about 1 in 100 children experiencing
severe anaphylaxis. 33 Food-Induced Anaphylaxis
There was a sevenfold increase in anaphylaxis admissions in According to a meta-analysis of 34 studies, food-induced ana-
34
England and Wales in 1992–2002. Severe anaphylaxis was phylaxis was reported to occur with an incidence of 0.14 cases
diagnosed in 1–9 per 10 000 people attending emergency depart- per 100 000 person-years at all ages and up to 7 per 100 person-
35
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ments in the United Kingdom, Australia, and the United States. years in children aged 0–4 years. According to the European
It is estimated that in a 12-month period, 1 in 12 patients with Anaphylaxis Registry, foods are a predominant cause of anaphy-
previous anaphylaxis will have a recurrence, and 1 in 50 will laxis in the first decade of life. Teenagers and young adults in
require hospitalization or treatment with epinephrine. 36 their second and third decades of life are known to be at the
highest risk of fatal food-induced anaphylaxis. 34
Pathophysiology of Anaphylaxis Peanuts, tree nuts, fish, and shellfish are the most frequent
Although anaphylaxis is often subdivided into immunological culprits in food-induced anaphylaxis, but almost any food can
and nonimmunological types, the clinical presentation is similar be implicated. Many cases of severe anaphylaxis are caused by
in both, and most authorities no longer make a distinction. unintended exposure to hidden food allergens. In addition,
Immunological anaphylaxis is further classified as IgE-mediated cofactors, such as alcohol, NSAIDs, and exercise, may increase
and non-IgE-mediated anaphylaxis. In IgE-mediated anaphylaxis, the severity of a food-induced allergic reaction. 27
allergen cross-links allergen-specific IgE on the surface of mast cells
and basophils, leading to their degranulation. Release of mediators Drug-Induced Anaphylaxis
causes bronchoconstriction, mucus secretion, diminished cardiac Drug-induced anaphylaxis is more common in hospitalized
contractility, increased vascular permeability, vasoconstriction patients than in the community. Any drug can cause anaphylaxis,