Download 106 - Allergic Disorders

SECTION X IMMUNE SYSTEM DISORDERS
Allergic Disorders
Aaron N. Barksdale and T. Paul Tran
KEY POINTS
• Allergy refers to inappropriate responses
(hypersensitivity) by the host’s immune system.
• Anaphylaxis is an acute, potentially fatal, systemic
allergic reaction. Deaths in patients with anaphylaxis
are caused by acute respiratory failure.
• Foods, medications, and insect stings are the most
common agents causing anaphylaxis.
• Epinephrine is the first-choice medication in the
treatment of anaphylaxis, with H1 and H2 antihistamines
and steroids being helpful adjuncts.
• Most cases of angioedema are mediated by IgE and
respond to allergic therapy. Certain forms of
angioedema, however, are mediated by bradykinin and
may respond to new classes of medications, the
kallikrein inhibitor (ecallantide) and C1 esterase inhibitor
concentrates (Cinryze, Berinert).
ALLERGIC DISEASE: ALLERGIC RHINITS,
INSECT STINGS, DRUG ALLERGY
EPIDEMIOLOGY
The prevalence of allergic disorders, including the incidence
of anaphylaxis, has been increasing worldwide in the last few
decades and is a topic of intensive study.1,2 Features of Western
lifestyles, such as changes in infant diets, widespread use of
antibiotics, smaller family size, and cleaner child care, are
believed to reduce stimulatory antigenic exposure in an individual’s early years. This has led to an environment in which
the immune system is dominated by a persistent allergy-prone
system.3
ALLERGIC RHINITIS
It is estimated that up to 42% of Americans suffer from some
form of allergic rhinitis at any one time,4 and it has been
shown to have a strong correlation with asthma. In recent
studies, nearly 40% of adults with allergic rhinitis were also
found to have asthma, and 80% of asthmatics demonstrated
signs of rhinitis.
106 INSECT STINGS
Serious systemic reactions to insect stings are rare and occur
in 1% of children and 3% of adults. Anaphylactic reactions
account for approximately 50 deaths annually in the United
States. There is a 2 : 1 male-to-female distribution, and adult
male agricultural workers are considered the most vulnerable
population. Individuals who experience large local reactions
are less likely to have a systemic reaction (5% to 10%).5
DRUG ALLERGY
A drug allergy is defined as an immune-mediated adverse
response to a drug. An adverse drug reaction is defined as a
noxious, unintended, or undesired response to a drug taken at
a normal dose for the prevention, diagnosis, or treatment of a
disease,6 and a drug side effect is an expected and known
(adverse) effect of taking the drug that is not the intended
therapeutic outcome. Although the true frequency is unknown,
drug allergy is thought to account for approximately one third
of adverse drug reactions.7 Adverse drug reactions affect 10%
to 20% of hospitalized patients and more than 7% of the
general population.
PATHOPHYSIOLOGY
The immune system protects the host by distinguishing self
from nonself; it tolerates the former but attacks the latter.8,9
Allergy, allergic diseases, and hypersensitivity reactions arise
when our immune system reacts inappropriately to allergens
with resultant harm to the host.1,2,10,11 For allergic diseases to
occur, predisposed individuals need to first be exposed to an
allergen through a process called sensitization.
The term atopy is used to describe the propensity in affected
patients to produce IgE in response to otherwise innocuous
environmental allergens. Atopic patients have higher serum
levels of IgE antibody and a propensity for the development
of one or more atopic diseases (e.g., allergic asthma,
allergic rhinoconjunctivitis, atopic dermatitis, urticaria,
angioedema).
Hypersensitivity reactions are mechanistically divided into
four types of reactions according to the Gell and Combs classification system (Box 106.1). The immediate hypersensitivity
reaction (type I), which is mediated by IgE, serves as the
classic model of the immune response to allergen. On initial
exposure to allergen, T helper 2 (TH2) cells are activated,
which results in the production of an array of cytokines that
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IMMUNE SYSTEM DISORDERS
exert their effects on the T cells themselves, B cells, and
antigen-presenting cells. IgE is elaborated and attached to the
high-affinity Fc receptor on the surface of mast cells and
basophils. Fixation of allergen-specific IgE leads to a series
of cellular and molecular changes that prime these cells for
future exposure. On reexposure, allergen cross-links the cellbound IgE on the surface of mast cells and basophils, thereby
setting in motion a complex cascade of events that lead to the
release of preformed mediators such as histamine, lipid mediators, and cytokines and subsequent activation of various
inflammatory pathways. These mediators and products of secondary inflammatory pathways cause adherence and chemotaxis of inflammatory cells, increased capillary permeability,
vasodilation, smooth muscle contraction, and sensory nerve
stimulation. A few allergen molecules can thus cause the
release of a large number of mediator molecules in a designed
amplification response. Examples of type I hypersensitivity
reactions include allergic rhinitis, allergic asthma, urticaria,
angioedema, and anaphylaxis.
See Box 106.1, Types of Hypersensitivity, online at
www.expertconsult.com.
and discharge (clear or can resemble strings of cheese); nasal
congestion; itching of the nose; sneezing; rhinorrhea; and
mild cough. Patients may report a temporal association with
exposure to certain environment allergens (seasonal allergy,
pollen, mold, animal dander). On physical examination, the
nasal membranes are swollen with enlarged, pale turbinates
and a clear nasal discharge. The maxillary sinuses may feel
full and tender on palpation.
INSECT STINGS (HYMENOPTERA VENOM
ALLERGY)
Patients with systemic allergic reactions from stings may
exhibit generalized urticaria, angioedema, wheezing, stridor,
anxiety, or other signs of respiratory and circulatory insufficiency. Most stings, however, cause self-limited local reactions consisting of redness, pain, and itching at the site of the
sting. These reactions typically develop within minutes and
usually last for a few hours. Local reactions rarely put patients
at risk for future systemic reactions.5 Fire ant stings tend to
produce pustulelike lesions. Local stings that result in subsequent swelling near the oropharynx (either cutaneous or deep)
can cause airway compromise, and affected patients should
be observed in the emergency department (ED) until the
symptoms have resolved.
Allergens are typically carbohydrate or protein molecules
(or parts of a larger molecule) that elicit an immune
response.10
The inflammation that occurs in allergy is divided into three
temporal phases.10 Early-phase reactions occur within minutes
of exposure and are considered immediate type I hypersensitivity reactions. Late-phase reactions typically occur within
2 to 6 hours and peak 6 to 9 hours after exposure. This
response is thought to be due to newly synthesized cytokines,
growth factors, and chemokines, which were released more
slowly than the preformed mediators primarily responsible
for the early-phase reaction. This reaction often involves
airway narrowing and hypersecretion of mucus in the lungs,
in addition to the erythema, warmth, and pain experienced
in the skin. In some individuals there is no clinical distinction
between the early and late phases. Chronic allergic
inflammation is the final phase in the inflammatory process.
It occurs after persistent or repetitive exposure to specific
allergens and results in tissue remodeling and structural
changes in affected cells. Chronic allergic inflammation can
further increase epithelial injury, mucus production, and
thickening of airway walls.
The majority of serious sting-related reactions are caused
by insects belonging to the order Hymenoptera (yellow
jackets, hornets, honeybees, wasps, and fire ants).5 Their
venom contains histamine, dopamine, various peptides, and
protein enzymes that are either vasoactive or can elicit significant allergic reactions (IgE mediated).
DRUG ALLERGY
Most allergic reactions occur within 1 hour of taking the
medication, and symptoms typically include urticaria, morbilliform rash, itching (lips, tongue, face), or sensitivity to light.
Symptoms of anaphylaxis may also occur (see later in chapter).
Late symptoms (1 to 2 weeks) include fever, muscle and joint
aches, and swollen lymph nodes.
PRESENTING SIGNS AND SYMPTOMS
INSECT STINGS (HYMENOPTERA VENOM
ALLERGY)
Considerations include secondary bacterial infection, cellulitis, abscess, urticaria, angioedema, and anaphylactic reaction.
Screening laboratory examinations for infection (complete
blood count, wound culture) should be done if signs of infection are noted on physical examination.
ALLERGIC RHINITIS
A detailed history is important in making the diagnosis of
allergic rhinitis. Patients often acknowledge a history of seasonal allergies (hay fever). Patients with allergic rhinitis frequently suffer from symptoms such as eye itching, swelling,
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DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
ALLERGIC RHINITIS
Box 106.2 lists other diagnostic considerations in patients
with symptoms that may mimic allergic rhinitis.12 Patients
older than 20 years should be investigated for nonallergic
causes (e.g., polyps). Atopic patients with severely inflamed
conjunctivae, lids, and periorbital structures should raise the
possibility of atopic keratoconjunctivitis (Fig. 106.1) and
vernal keratoconjunctivitis (Fig. 106.2). These two types of
chronic allergic conjunctivitis have the potential to cause
corneal erosions and ulcers leading to vision loss and should
be managed in consultation with an ophthalmologist.
Typically, no diagnostic tests need to be performed in the
ED. Specific IgE serum assays such as the radioallergosorbent
test (RAST), enzyme-linked immunosorbent assay (ELISA),
skin prick test, and nasal smears are usually performed by
allergists.
CHAPTER 106
Allergic Disorders
BOX 106.1 Types of Hypersensitivity
Type I Hypersensitivity
Immediate or immunoglobulin E (IgE)-mediated reaction:
Binding of antigens to IgE on the surface of mast cells and
basophils leads to the release of inflammatory mediators
(maximal reaction in 20 minutes). This type of hypersensitivity
reaction is seen with allergic diseases, drug reactions, urticaria or angioedema, and anaphylaxis.
Type II Hypersensitivity
Cytotoxic antibody reaction: Binding of antigens to their own
cells (or foreign cells with foreign antigens) attracts binding
by IgM/IgG antibodies, which subsequently causes injury and
lysis of cells via the complement or mononuclear cell system.
Type III Hypersensitivity
Immune complex (IC)-mediated reaction: Binding of antigens
to IgE forms soluble ICs, which are deposited on vessel walls
and cause a local inflammatory reaction (Arthus reaction) by
attaching to FγRIII receptors on inflammatory cells (maximum
reaction, 4 to 8 hours).
Type IV Hypersensitivity
Cell-mediated delayed hypersensitivity reaction: Sensitized
lymphocytes (TH1 cells) recognize the antigen and recruit
additional lymphocytes and mononuclear cells to the site,
thereby starting the inflammatory reaction. This type of
hypersensitivity reaction is seen with contact dermatitis, erythema multiforme, Stevens-Johnson syndrome, and toxic
epidermal necrolysis (maximum reaction, 48 to 72 hours).
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Allergic Disorders
BOX 106.2 Causes of Rhinorrhea and Nasal
Obstruction
Nonallergic Rhinitis with Eosinophilia Syndrome
Nasal smears negative for allergens but with an abundance
of eosinophils
Mechanical Obstruction
Foreign body
Previous trauma involving the septum
Polyps
Adenoid disease
Infectious Rhinosinusitis
Primary or secondary bacterial, viral, or fungal infections
Vasomotor Rhinitis
Profuse, clear rhinorrhea and nasal congestion—may be triggered by environmental conditions such as cold air,
odors, or changes in atmospheric pressure or by the
ingestion of hot or spicy foods
Drug Induced
Includes entities such as rhinitis medicamentosa (rebound
from prolonged use of topical decongestants)
May be triggered by aspirin, nonsteroidal antiinflammatory
drugs, or oral contraceptive use
Systemic Disease
Wegener disease, sarcoidosis
Head trauma
Modified from Greiner AN. Allergic rhinitis: impact of the disease and
considerations for management. Med Clin North Am 2006;90:17-38.
Fig. 106.1 Atopic keratoconjunctivitis. (From Baba I. Red
eye—first aid at the primary level. Community Eye Health
2005;18:70-72.)
DRUG ALLERGY
Understanding the involvement of an immunologic mechanism in drug allergy may help physicians in determining
whether a reaction represents an adverse drug reaction or a
true drug allergy. For example, the stomach discomfort that
may result from taking nonsteroidal antiinflammatory drugs
(NSAIDs) is an adverse drug event and not a drug allergy.
Factors that favor a drug allergy include a history of previous
Fig. 106.2 Vernal keratoconjunctivitis. Notice the lumpy
appearance on the conjunctivae. (From Yorston D, Zondervan M.
Red eye picture quiz. Community Eye Health 2005;18:72-78.)
sensitization (the drug was taken before) and typical allergic
symptoms (urticaria, angioedema, wheezing).
Common entities to consider are infection (viral exanthem,
mononucleosis, Rocky Mountain spotted fever, syphilis, cellulitis, sepsis), insect bite, pityriasis rosea, serum sickness,
vasculitides, contact dermatitis, fixed drug eruption, and drug
hypersensitivity syndrome.
Diagnosis of an adverse drug reaction relies on a careful
history and thorough skin examination. A complete blood
count, chemistry panel, and erythrocyte sedimentation rate
may be ordered to evaluate possible infections or vasculitis.
Skin testing is of limited value. RAST and ELISA for serum
IgE require known immunogenic epitopes for the drugs, information that is usually unavailable. In cases of hemolytic
anemia, the indirect Coombs test can be used to diagnose
immune-mediated destruction of red blood cells.
Studies show that 4.4% of patients whose penicillin allergy
history was confirmed by a positive skin test experienced an
allergic reaction to cephalosporins.13 Only 10% to 20% of
patients who report a history of penicillin allergy are truly
allergic when assessed by skin testing.14 Although the overall
risk for a cross-allergic reaction to cephalosporins in patients
with a history of a penicillin allergy is low, the use of cephalosporins requires weighing the risks versus benefits based on
an informed discussion between the patient and treating physician. Table 106.1 shows the incidence of allergic reactions
to penicillin.15 Some factors can transiently cause T cells to
falsely identify the penicillin epitope as being allergic. For
example, in up to half (50%) of patients with mononucleosis,
a maculopapular rash develops after taking amoxicillin. These
same patients often have no adverse drug reaction on subsequent challenge with amoxicillin at a later time. Penicillin
allergy should not be diagnosed in such patients.
TREATMENT
ALLERGIC RHINITIS
Oral second-generation H1 blockers (loratadine, fexofenadine), oral decongestants (pseudoephedrine), and nasal
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Table 106.1 Estimated Incidence of Allergic Reactions to Penicillin
TYPE OF
REACTION
MANIFESTATION
Late
Rash
Accelerated
Immediate
TIME OF OCCURRENCE
AFTER FIRST DOSE
PERCENTAGE OF PATIENTS
SHOWING REACTION
≥72 hr
1.4
Urticaria
1-72 hr
0.3
Generalized urticaria
2-30 min
0.3
Anaphylaxis
2-30 min
0.04
Death from anaphylaxis
0.001
From Asthma and the other allergic diseases. NIAID Task Force Report, NIH Publ No. 79-387. Bethesda, MD: National Institutes of Health; 1979.
decongestants (oxymetazoline, phenylephrine) can be used
for mild, intermittent symptoms.16 Moderate to severe and
persistent nasal symptoms may require the addition of intranasal steroid (fluticasone, triamcinolone, budesonide), or
chromone derivative such as cromoglycate and nedocromil.
An intraocular antihistamine (olopatadine), intraocular chromone, or intraocular ketorolac can be used for ocular allergies,
including conjunctivitis.17
INSECT STINGS (HYMENOPTERA VENOM
ALLERGY)
The stinger should be removed if present. For minor local
reactions, antihistamines and NSAIDs such as ibuprofen
should be sufficient. Ice can be used to decrease the inflammation, and elevation will decrease the swelling. The pseudopustules caused by fire ant stings contain mostly necrotic
material and should not be unroofed. These lesions should be
managed similar to second-degree burns, with the therapeutic
goal being pain control and minimization of the risk for secondary bacterial infection.
Treatment of large local reactions includes cold compresses, NSAIDs, H1 antihistamines, and high-potency topical
steroids. Prednisone (1 mg/kg or 60 mg orally) as a single
dose or for 5 days might decrease local swelling. The swelling
typically resolves in 7 to 10 days. Antibiotics should be prescribed only if signs of secondary bacterial infection are
present. Coverage for methicillin-resistant Staphylococcus
aureus should be considered. Management of systemic reactions to stings is similar to that for anaphylaxis.
DRUG ALLERGY
The most prudent approach in managing possible drug
allergy–related complaints in the ED is to discontinue use of
the suspect medication or medications, treat the allergic
symptoms, and prescribe a suitable alternative drug or drugs.
Severe symptoms should be treated in the same way as
anaphylaxis (see Box 106.8). Patients with Stevens-Johnson
syndrome and toxic epidermal necrolysis require a multidisciplinary approach that includes an intensivist, burn surgeon,
and endocrinologist or allergist. For minor allergic drug reactions, H1 antihistamines can be prescribed for itching, flushing, and rash. Steroids are reserved for serious or extensive
drug reactions.
920
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
ALLERGIC RHINITIS
Patients are advised to avoid allergens when practically feasible. Those who are sensitive to pollen should minimize time
spent outdoors during periods of high pollen counts and lessen
the allergen load indoors by keeping windows closed. Use of
HEPA (high-efficiency particulate air) filters, infestation
control (cockroach), and impermeable covers for mattresses
and pillows may also decrease the severity of symptoms.
INSECT STINGS (HYMENOPTERA VENOM ALLERGY)
Patients with systemic reactions to stings warrant overnight
observation in the hospital. Patients with limited or large local
reactions can be managed as outpatients.
Patients with urticaria or angioedema reactions should
be referred to an allergist for possible skin testing and v
enom immunotherapy. These patients should wear a MedAlert bracelet. Before discharge it is important that patients
be educated about prevention of stings (always wearing
shoes when outdoors and not wearing brightly colored
clothes or fragrances in high-risk areas), the early signs of a
systemic reaction, and how to self-administer an Epi-Pen. At
least two Epi-Pens should be prescribed for emergency
self-injection.
DRUG ALLERGY
The majority of patients with late (>1 hour to days) reactions
to medications who have a mild to moderate rash can be
safely discharged home. Those with immediate drug reactions
(<1 hour) need to be observed in the ED. Patients with a
systemic reaction whose symptoms resolve after a 4- to 6-hour
observation period in the ED can be discharged home in the
company of a family member. They should be prescribed two
Epi-Pens, H1 antihistamines, a short course of steroids, and a
Med-Alert bracelet. Patients at risk for a recurrent systemic
drug reaction who have poor social support, comorbid conditions, and moderate to severe allergic syndromes warrant a
hospital stay. At the end of the ED visit, patients should be
educated about the nature of a drug allergy versus an adverse
drug reaction.
CHAPTER 106
URTICARIA
EPIDEMIOLOGY
Urticaria (hives) is a fairly common reaction that affects
approximately 20% of the population at some point in their
lifetime.18 It has numerous different underlying causes and
consists of several different types and subtypes. Spontaneous
urticaria is broadly divided into acute (<6 weeks) and chronic
(≥6 weeks) forms, with the latter representing approximately
10% to 20% of cases.
PATHOPHYSIOLOGY
The classic wheal lesions associated with urticaria are the
result of edema within the mid and upper dermal layers of the
skin. Dilation of lymphatic vessels and capillary venules
allows extravasation of protein-rich fluid into the surrounding
tissue. This complex inflammatory process involves a variable
mixture of macrophages, T cells, neutrophils, eosinophils, and
mast cells.19
PRESENTING SIGNS AND SYMPTOMS
Patients with urticaria usually have hives of variable duration
and location.20,21 Urticarial lesions are pruritic, erythematous,
raised rashes that blanch on palpation. The lesions are typically round or oval with serpiginous borders, but they may
vary in color, size, and shape (Fig. 106.3). They may be localized or appear throughout the body, but there is a slight predilection for the trunk, hands, feet, lips, tongue, and ears.
Urticaria usually starts with erythema (flare) as a result of
capillary vasodilation in the superficial layer of the dermis.
As the protein-rich fluid extravasates into surrounding tissue,
it evolves into raised wheals and may change from red to
white. A history of pruritic red rash that changes in size and
Allergic Disorders
shape, with extension and regression over a period of hours
or days, favors the diagnosis of urticaria.
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
The first step in narrowing the differential diagnosis of urticaria is to determine whether the urticaria is acute (<6 weeks
of symptoms) or chronic (≥6 weeks of symptoms).20,21 The
differential diagnosis of urticaria is outlined in Box 106.3 and
illustrated in Figure 106.4.
See Box 106.3, Differential Diagnosis of Urticaria, online at www.expertconsult.com
Evaluation of acute urticaria and angioedema is based on a
careful history and skin examination; little additional laboratory testing should be needed. The work-up for chronic urticaria is usually performed by an allergist in the office.
TREATMENT
Therapy for acute urticaria includes avoidance of the suspected causative agent and administration of H1 antihistamines (see Fig. 106.4). The second-generation H1 antihistamines
(cetirizine, loratadine, fexofenadine, desloratadine) are currently recommended as the first-line drugs.18,20
For urticaria judged difficult to control with antihistamines
alone, prednisone can be added.20 If the urticarial rash is
extensive and pruritus is severe, epinephrine can be administered (0.3 to 0.5 mL of a 1 : 1000 dilution intramuscularly). It
may be repeated every 1 to 2 hours as needed. Caution is
advised when administering epinephrine to patients at risk for
coronary heart disease (>35 years of age, other risk factors
for coronary artery disease). Patients with chronic urticaria
can be prescribed a nonsedating H1 antihistamine (in higher
dosages) as a temporizing measure and be referred to an allergist for further care.
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Most patients with urticaria (acute and chronic) can be
managed as outpatients. Usually, a 7-day course of a secondgeneration H1 antihistamine is sufficient, although a corticosteroid (prednisone) in a tapering course is sometimes added
for moderate to severe cases.
ANGIOEDEMA
EPIDEMIOLOGY
Fig. 106.3 Acute urticaria. (Copyright 2001–03, Johns Hopkins
University School of Medicine. Shahbaz Janjua: Dermatlas.
Available at http://www.dermatlas.org. With permission.)
Angioedema (not including hereditary angioedema [HAE])
may affect 10% to 20% of the population at some time in
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CHAPTER 106
Allergic Disorders
BOX 106.3 Differential Diagnosis of Urticaria
Foods, Additives
Seafood (fish, shellfish, scombroid), tree nuts, eggs, seeds
Foods containing allergens that are cross-reactive with latex,
including bananas, avocados, kiwi fruit, chestnuts
Food preservatives such as tartrazine, benzoates, and sulfites
Other: cow’s milk, pork, strawberries, wheat, chocolate,
tomatoes
Medications
IgE mediated: penicillins, sulfonamides, cephalosporins
Nonimmunologic release of histamine: acetylsalicylic acid, nonsteroidal antiinflammatory drugs, indomethacin, angiotensinconverting enzyme inhibitors, morphine, codeine,
acetylcholine, iodinated contrast dye, beta-blockers,
vancomycin
Infections
Viral infections: Epstein-Barr virus, hepatitis, coxsackievirus
Bacterial (occult) infections: sinusitis, dental infections or
abscesses, chronic cholecystitis
Fungal infections: candidiasis, dermatophytosis
Parasitic infections
Systemic Disease
Rheumatologic or immunologic: vasculitis, serum sickness,
systemic lupus erythematosus, juvenile rheumatoid
arthritis
Endocrinologic: thyroid (both hyperthyroid and hypothyroid)
disease, progesterone dermatitis, pruritic urticarial papules
and plaques of pregnancy, premenstrual flare-up
Skin disease: mastocytosis, dermatitis herpetiformis, amyloidosis, pemphigoid
Neoplastic: paraneoplastic syndrome, Hodgkin disease,
leukemia
Inhalants
Pollen
Animal dander
House mite dust
Mold spores
Household chemicals, aerosols
Hymenoptera
Yellow jackets, honeybees, hornets, wasps most commonly
reported; fire ants
Types of Urticaria
Dermatographism: may begin suddenly after a viral illness or
drug therapy
Pressure or vibratory urticaria: caused by tight clothing around
the waist (may be misdiagnosed as scabies)
Heat urticaria: may be caused by a rise in core temperature
after a hot bath, fever, vigorous exercise (also known as
cholinergic urticaria because it can be induced by injection
of a cholinergic agent)
Cold urticaria: caused by exposure to cold temperatures
Solar urticaria: occurs after exposure to intense sunlight or
artificial light (antigens produced in the skin may interact
with immunoglobulin E)
Water urticaria: prickling skin sensation without skin lesions
within 15 minutes of contact with water
Exercise urticaria: may progress to anaphylaxis
Household chemicals, aerosols
Contact urticaria: urticarial wheals or hives develop within 30
to 60 minutes after cutaneous exposure to certain agents,
including plants (nettles), animals (caterpillars, jellyfish),
latex, cosmetics, and various chemicals
Modified from Dibbern Jr DA. Urticaria: selected highlights and recent advances. Med Clin North Am 2006;90:187-209.
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IMMUNE SYSTEM DISORDERS
History and skin examination consistent with urticaria
<6 weeks
≥6 weeks
Chronic urticaria
Acute urticaria
1. Review history
• Food and drink
• New medications
• Environmental allergens (e.g., plants, animals,
cosmetics, history of travel)
• Insect bite
• Serum sickness causes
• Physical urticaria (exercise, heat, cold, solar)
• Constitutional symptoms c/w a viral/bacterial/
fungal infection
2. Physical examination
• Wheals and flares (evanescent)
• Signs of infection
3. Management
• 2nd-generation antihistamine
• H2 blocker
• Epinephrine in selected cases (see text)
• Steroids in selected cases (see text)
• Primary care physician referral
1. Review history
• Food and drink (food additives, dyes)
• Medication (ASA, NSAIDs)
• Physical urticaria (exercise, heat, cold, solar)
• Constitutional symptoms (e.g., weight gain,
fever, fatigue)
2. Physical examination
• Fixed wheals and flares
• Signs of occult infection
3. Management
• Allergist referral
• 2nd-generation antihistamine
• Doxepin, 25 mg qid
• Steroids—indicated for angioedema-urticariaeosinophilia syndrome
• Other screening examinations for
consultants (see text)
Fig. 106.4 Algorithm for the diagnosis and treatment of urticaria. ASA, Acetylsalicylic acid; c/w, consistent with; NSAIDs, nonsteroidal
antiinflammatory drugs.
their lives; most chronic angioedema is idiopathic. HAE is an
autosomal dominant genetic disorder with an estimated prevalence of 1 per 10,000 to 150,000 persons. The incidence of
angiotensin-converting enzyme inhibitor (ACEI)-associated
angioedema is approximately 0.2% to 0.7% and slightly
higher in the African American population. Episodes have
been reported to occur within days of initiating ACEI therapy
and up to 8 years later, with an average onset of approximately
10 months. Ten percent to 25% of cases of angioedema
encountered in the ED are considered to be life-threatening.
African Americans are more susceptible to angioedema
induced by ACEIs. Other forms of angioedema have no clear
association between race and the frequency or severity of the
disease. In HAE, affected women tend to have more frequent
attacks and a more severe clinical course. Chronic idiopathic
angioedema is more common in females than in males.
Angioedema can affect patient of all ages. For patients with
HAE, the onset of symptoms is often around puberty. Idiopathic angioedema is more common in those aged 30 to 50
years than in other age groups. Patients typically experience
minor swelling in childhood that may go unnoticed, with
increased severity noted around puberty. However, type III
HAE is found in the second decade of life or later and occurs
only rarely before puberty. Five percent of adult HAE carriers
are asymptomatic and identified only after their children are
found to be symptomatic.
Urticaria-associated angioedema occurs in nearly 50% of
children with urticaria. Because urticaria occurs in 2% to 3%
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of children, urticaria-associated angioedema is estimated to
occur in 1% to 2% of the general population.
PATHOPHYSIOLOGY
Angioedema (swelling) refers to vasodilation and edema in
the lower dermis and subcutaneous layers of the skin.22 In the
majority of cases angioedema shares a similar allergic mechanism, but in selected cases it is the result of a reaction mediated by bradykinin. Both forms of angioedema can appear
similar clinically, with bradykinin-mediated angioedema typically being manifested as angioedema without urticaria. They
both commonly affect the eyelids, face, lips, and tongue and
can potentially cause life-threatening respiratory compromise.
It is important to distinguish the two forms because bradykininmediated angioedema may respond better to the new classes
of medications, including recombinant C1 factor, kallikrein
inhibitor, or a bradykinin receptor antagonist.
Bradykinin-mediated angioedema typically falls into one
of two groups, HAE or acquired angioedema (AAE). HAE
was first described by William Osler in 1888. It is a rare
autosomal dominant disorder with an overall incidence of 1
in 50,000.23 Approximately 25% of cases are the result of a
spontaneous mutation. HAE has three subtypes. Type I (85%)
is characterized by low levels of C1 esterase inhibitor (C1
INH), type II (<15%) consists of normal but poor functioning
levels of C1 INH, and type III (rare) has normal C1 INH levels
CHAPTER 106
and activity but probably involves another unidentified defect
or gene mutation at the receptor level. Currently, bradykinin
is thought to be the primary molecule responsible for angioedema in patients with HAE. Documented triggers include
infection, stress, trauma, oral contraceptives, pregnancy, and
menstruation.23
AAE comprises a heterogeneous group that includes druginduced, idiopathic, and environmental agent–related angioedema and acquired C1 INH deficiency (ACID). ACID is
characterized by a lack of inheritance and low-level or nonfunctional C1 INH. Drug-induced angioedema is most commonly caused by ACEIs.24 Up to 50% of those who still take
an ACEI after an episode of angioedema will experience
recurrent episodes. Discontinuation of the medication results
in resolution of the symptoms in the majority of patients
(within 24 to 48 hours). ACEIs block the degradation of kinins
and thereby lead to elevated levels of bradykinin and other
peptides. This results in vasodilation and tissue edema of the
deeper layers of the skin, which is clinically manifested as
angioedema.24
PRESENTING SIGNS AND SYMPTOMS
Angioedema has a brawny appearance and occurs when
extravasation of fluid occurs at the subcutaneous and deep
dermal layers of the skin. Patients with angioedema experience less pruritus than urticaria and often complain of a pain
or burning sensation at affected sites. Angioedema also tends
to involve the face, tongue, lips, and larynx but can occur in
the mucosal layer of the gastrointestinal tract and genitalia in
men. Involvement of the gastrointestinal tract can cause
nausea, vomiting, diarrhea, and abdominal pain.
HAE is usually manifested in the second decade of life and
appears either alone or with urticaria. Recurrent angioedema
without urticaria later in life (e.g., middle age) may suggest
some form of AAE, including ACID- and ACEI-induced
angioedema (if undergoing ACEI therapy). Both HAE and
ACEI-induced angioedema tend to have a predilection for the
face, tongue, lips, oropharynx, and larynx. Patients with HAE
may complain of a lump or tightness in the throat and progressive dyspnea. Physical examination may reveal hoarseness,
inspiratory stridor, and rarely, urticaria. Prompt attention to
airway management can be lifesaving. After stabilization,
these patients need to be identified and referred to an allergist
for further work-up and treatment.
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
When angioedema is suggested by the history and physical
examination, it is important to determine whether it is associated with other allergic findings, urticaria, a family history, or
other medications (ACEIs). The differential diagnosis of
angioedema is outlined in Box 106.4.
Patients suspected of having HAE should first have their
complement 4 (C4) and complement 2 (C2) levels checked.
As recommended by the consulting allergist or internist, other
tests can include a CH50 (total complement activity) test, C1
INH test, or C1 functional assay. Additional screening tests
may be considered to help rule out occult infection,
Allergic Disorders
BOX 106.4 Differential Diagnosis
of Angioedema
Cellulitis, erysipelas
Acute contact dermatitis
Crohn disease (of the mouth and lips)
Dermatomyositis
Venous obstructive disease (superior vena cava syndrome)
Heart failure
Photodermatitis
Tumid discoid lupus erythematosus
Melkersson-Rosenthal syndrome
Ascher syndrome
Facial lymphedema
Renal disease
From Kaplan AP, Greaves MW. Angioedema. J Am Acad Dermatol
2005;53:373-88.
hematologic or oncologic pathology, and rheumatologic or
inflammatory disorders, which may aid the consultant in subsequent evaluation of these patients.
TREATMENT
The first priority in the management of patients with acute
angioedema is to secure a patent airway if needed.22,23 Endotracheal intubation should be considered early in patients with
progressive laryngeal edema. As soon as the patient is situated, intravenous access should be established, oxygen administered, and the patient placed on a monitor.
The majority of cases of angioedema are type I hypersensitivity reactions. If signs of airway compromise or hypoxia
are present, epinephrine should be administered (0.3 to 0.5 mL
of a 1 : 1000 dilution intramuscularly) and repeated every 5
minutes as needed. Nebulized racemic (or regular) epinephrine (0.5 mL of a 2.25% racepinephrine solution; multiple
doses are acceptable in patients without intravenous access)
can be a temporizing measure for pharyngeal and laryngeal
edema before or in addition to parenteral administration of
epinephrine. In patients with mild symptoms and no airway
involvement, H1 and H2 antihistamines should be used
first. Parenteral steroids (methylprednisolone, 125 mg intravenously) should be administered for moderate to severe
attacks.
Epinephrine, antihistamines, and corticosteroids are generally ineffective in the treatment of HAE and ACEI-induced
angioedema, although they are commonly given in the acute
setting. The use of new drugs for acute HAE attacks and
ACEI-induced angioedema is still in the formative stage.
Plasma-derived C1 INH concentrate (Berinert, 20 U/kg intravenously, Cinryze, 1000 units intravenously) is currently
available in the United States.15 Ecallantide, a kallikrein inhibitor (30 mg subcutaneously in adults), is another recent agent
approved by the Food and Drug Administration for the treatment of acute HAE. Aminocaproic acid, tranexamic acid, and
anabolic androgens (danazol, stanozolol) are often prescribed
for HAE prophylaxis but may be considered for the treatment
923
SECTION X
IMMUNE SYSTEM DISORDERS
of acute episodes. Additional treatment alternatives include
solvent detergent–treated plasma or fresh frozen plasma,
although these therapies are considered less safe.23
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Patients with mild symptoms who improved clinically after
treatment and were observed for 4 to 6 hours in the ED can
be discharged home with H1 antihistamines and a short course
of steroids. If the patient was taking an ACEI, its use should
be stopped. Replacement candidates include calcium channel
blockers and thiazides. Angiotensin receptor blockers are
deemed acceptable by some authorities because the risk for
angioedema from these agents is considered acceptably
low.24,25 Beta-blockers are not advised in the initial setting
because of the theoretic risk of exacerbating the angioedema
and potential antagonistic effects with epinephrine.
Inpatient admission is warranted for those with moderate
to severe symptoms who fail to display signs of resolution
after 4 to 6 hours in the ED. In particular, patients with HAE
should be managed in consultation with their primary physician or allergist. Most of these patients, especially those with
face and laryngeal involvement, warrant observation overnight in the hospital.
ANAPHYLAXIS
EPIDEMIOLOGY
Anaphylaxis is a life-threatening systemic hypersensitivity
reaction that is rapid in onset and usually precipitated within
minutes of exposure to an allergen. Because of lack of data
the true incidence of anaphylaxis is unknown, but recent evidence suggests that it is increasing and its incidence may be
as high as 2%.26,27 Risk factors for anaphylaxis include atopy,
higher socioeconomic status, northern locations, female sex
(adults), and route of allergen exposure. An individual with a
history of asthma is more likely to experience a severe or fatal
reaction.27
TRIGGERS
Foods, predominantly peanuts, tree nuts, shellfish, fish, eggs,
soy, and cow milk, are the most common cause of anaphylaxis
and are responsible for up to 30% of all fatal cases. Insect
stings, primarily by those belonging to the order Hymenoptera, are the second most common cause of anaphylaxis. They
account for approximately 18.5% of anaphylactic cases. Medications are the third most common cause of anaphylaxis
(13.7%). Although the β-lactams (penicillin) are commonly
involved, several other drugs are known to cause anaphylaxis,
including NSAIDs, aspirin, protamine, vancomycin, neuromuscular blocking agents, and newer biologic modifiers such
as omalizumab, infliximab, and cetuximab.27,28
Although the three groups just mentioned (foods, stings,
and drugs) are responsible for the majority of anaphylactic
reactions, other prominent triggers of anaphylaxis include
latex, seminal fluid, transfusion products, allergen immunotherapy, contrast dye, methylmethacrylate (bone cement), and
924
physical activity (exercise). Exercise-induced anaphylaxis is
noteworthy because its pathophysiology is unknown. Some
authorities suspect co-triggers, such as a specific food, drug,
or recent high pollen exposure as the actual culprit.29 In
approximately 20% of anaphylactic cases, no identifiable triggers are found, and the reaction is termed idiopathic
anaphylaxis.30
PATHOPHYSIOLOGY
Anaphylaxis is commonly an IgE-mediated type I hypersensitivity reaction, but it can also occur through other immunologic mechanisms or direct mast cell activation (formerly
known as an anaphylactoid reaction). The resultant degranulation of mast cells and basophils causes the release of
preformed mediators such as histamine, tryptase, carboxypeptidase A3, chymase, and tumor necrosis factor-α, as well as
newly generated mediators such as leukotrienes, prostaglandins, cytokines, and platelet-activating factor. These vasoactive molecules together are believed to be responsible for the
pathophysiology of anaphylaxis. Of these mediators, histamine is probably the most important. It mediates systemic
vasodilation and increases vascular permeability, cardiac contractility, and glandular secretion. The leukotrienes, together
with platelet-activating factor, contribute to vascular permeability and, in combination with prostaglandins (D2), cause
bronchoconstriction.
PRESENTING SIGNS AND SYMPTOMS
Anaphylaxis is a systemic reaction of rapid onset that involves
multiple organ systems, principally the cutaneous, respiratory,
cardiovascular, gastrointestinal, and central nervous systems
(Box 106.5).31 Patients may initially experience warmth and
tingling of the face, mouth, and chest, followed by nasal congestion, sneezing, and ocular itching and tearing. Urticaria,
pruritus, and angioedema occur roughly 90% of the time.
The majority of anaphylactic reactions become clinically
evident within minutes after parenteral exposure (average of
5 to 30 minutes), with a longer latent time (2 hours) after the
ingestion of a triggering agent. In general, the sooner the
clinical syndrome is manifested after exposure to the allergen,
the more severe the reaction. Most fatalities occur within the
first 30 minutes after exposure. In the setting of shock, cutaneous symptoms may be absent as a result of compensatory
vasoconstriction. Anaphylaxis may precipitate an acute coronary syndrome in what is known as cardiac anaphylaxis.32
More commonly in the elderly, the initial complaint may be
abdominal pain and cramping.
In approximately 20% of patients, anaphylaxis may recur
1 to 72 hours after apparent clinical resolution of all signs
and symptoms in what is called a biphasic reaction.33
There is currently no evidence or expert consensus on clinical
predictors of the occurrence of a biphasic anaphylactic reaction, although it has been suggested that a biphasic reaction
is rare in patients without hypotension and airway obstruction
during the initial evaluation.34 Most authorities recommend an
observation period (8 to 24 hours) after the initial mani­
festation to minimize the untoward effects of the biphasic
reaction.33
CHAPTER 106
BOX 106.5 Common Clinical Findings in
Patients with Anaphylaxis
Cutaneous, Subcutaneous, Mucosal Tissue
Urticaria (hives), angioedema, flushing, pruritus, morbilliform
rash, pilar erection
Conjunctival erythema, tearing
Pruritus and swelling of the lips, tongue, uvula/palate
Pruritus of the genitalia, palms, soles
Respiratory
Nasal congestion, rhinorrhea, sneezing
Throat tightness and soreness, dysphonia and hoarseness,
dry staccato cough, stridor, dysphagia
Dyspnea, chest tightness, deep cough, wheezing,
bronchospasm
Gastrointestinal
Nausea, vomiting (stringy mucus), dysphagia, cramping
abdominal pain, diarrhea
Cardiovascular
Chest pain, palpitations, tachycardia, bradycardia, or other
dysrhythmia
Dizziness, altered mental status, hypotension, shock
Central Nervous System
Aura of impending doom, uneasiness, throbbing headache,
dizziness, confusion, tunnel vision
Infants and children: sudden behavioral changes, such as
irritability, cessation of play, and clinging to parent
Other
Metallic taste in the mouth
Uterine contractions in postpubertal female patients
Modified from Simons FE. Anaphylaxis. J Allergy Clin Immunol 2010;
125(Suppl 2):S161-81 (with permission).
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
The clinical spectrum of anaphylaxis overlaps that of several
other syndromes, especially those involving the skin and cardiorespiratory system (Box 106.6). Vasovagal reactions may
mimic early anaphylaxis, although these patients usually have
bradycardia, hypotension, diaphoresis, and pallor, as opposed
to the tachycardia, hypotension, diaphoresis, and urticaria
usually associated with anaphylaxis. Anaphylactic shock may
also appear clinically indistinguishable from other forms of
shock (distributive, septic, or cardiogenic). The acute onset and
characteristic angioedematous urticarial rash favor the diagnosis of anaphylactic shock. Flushing syndromes also frequently
mimic anaphylactic reactions. They may be associated with dry
skin or diaphoresis and are the result of numerous different
drugs, ingestants, and other physiologic syndromes.
Anaphylaxis is diagnosed clinically. The diagnosis is considered highly likely when any of three clinical criteria in Box
106.7 are met.35
Currently, histamine and tryptase are the only measurable
markers of anaphylaxis in clinical laboratories.31 Histamine
plasma levels become elevated approximately 10 minutes
after the onset of symptoms and remain so for up to an hour.
Allergic Disorders
BOX 106.6 Differential Diagnosis of Anaphylaxis
Flush Syndromes
Hereditary angioedema
Urticaria vasculitis
Carcinoid syndrome
Systemic mastocytosis
Urticaria pigmentosa
Vasoactive intestinal polypeptide–secreting tumors
Medullary carcinoma of the thyroid
Pheochromocytoma
Acute alcohol syndrome
Monosodium glutamate toxicity
Sulfites
Scombroidosis
Infections, Respiratory Syndrome
Epiglottitis, supraglottitis
Retropharyngeal, peritonsillar abscess
Laryngeal spasm, foreign body aspiration, tumor
Acute asthma exacerbation, chronic obstructive pulmonary
disease
Shock Syndromes
Hemorrhagic
Cardiogenic
Septic
Spinal shock
Somatoform, Psychogenic
Panic attacks
Munchausen, factitious disorder
Somatoform idiopathic anaphylaxis
Miscellaneous
Idiopathic
Vasodepressor (vasovagal) reactions
Progesterone anaphylaxis
Red man syndrome (vancomycin)
Capillary leak syndrome
Peak levels of serum tryptase occur between 60 and 90
minutes and persist for as long as 6 hours. These markers must
be determined within the time frames mentioned and may be
helpful when it is uncertain whether anaphylaxis has occurred.
It should be noted that food-induced anaphylaxis may not be
accompanied by elevated levels of tryptase. Additional laboratory tests and imaging may be necessary to help rule out other
disease processes.
TREATMENT
Early administration of epinephrine is the mainstay of treatment of anaphylaxis (Box 106.8). It should be administered
quickly and preferably intramuscularly in the lateral aspect of
the thigh (vastus lateralis). Epinephrine should be considered
if anaphylaxis is suspected even when only one system (e.g.,
skin) is involved. Doses can be repeated every 5 to 10 minutes
or more frequently as indicated clinically.27,31 Caution should
be exercised in patients with risk factors for ischemic heart
disease, although there are no absolute contraindications to
epinephrine in those initially seen in anaphylactic shock.
925
SECTION X
IMMUNE SYSTEM DISORDERS
BOX 106.7 Clinical Diagnosis of Anaphylaxis
Anaphylaxis is highly likely when any of the following three
criteria are fulfilled:
1. Acute onset (minutes to hours) of an illness with cutaneous or mucosal involvement AND at least one of the
following:
a. Respiratory compromise (e.g., dyspnea, wheezing/
bronchospasm, stridor, hypoxia)
b. Reduced blood pressure or symptoms of end-organ
dysfunction
2. Two or more of the following occurring rapidly after exposure to a probable allergen (minutes to several hours):
a. Involvement of skin or mucosal tissue
b. Respiratory compromise
c. Persistent gastrointestinal symptoms (e.g., crampy
abdominal pain, vomiting)
3. Reduced blood pressure after exposure to a known allergen for that patient (age specific, less than 90 mm Hg, or
30% decline from baseline)
Reproduced from Sampson HA, Munoz-Furlong A, Campbell RL, et al.
Second symposium on the definition and management of anaphylaxis:
summary report—Second National Institute of Allergy and Infectious
Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg
Med 2006;47:373-80.
Intravenous infusion should be used only in patients who
remain hypotensive and have failed to respond to multiple
intra­muscular injections.27,31 Inhaled epinephrine may be used
as adjunctive therapy for laryngeal edema but should never
replace the intramuscular or intravenous route (Fig. 106.5).
In conjunction with the administration of epinephrine, the
patient should be placed in the supine position with the lower
extremities elevated. Intravenous access should be established,
supplemental oxygen administered, and the patient placed on
a monitor. Patients with rapidly progressive respiratory insufficiency will benefit from early endotracheal intubation. Use
of rapid-sequence intubation should be approached with great
caution because of the potential for rapid deterioration of the
oral and laryngeal edema. Plans for backup airway support
and rescue airway devices, including a surgical airway, may
be prudent.
Hypotension is treated aggressively with crystalloid infusion and colloid as indicated clinically. Caution should be
taken in patients with a history of congestive heart failure.
Patients with persistent hypotension despite appropriate doses
of epinephrine and intravenous fluid resuscitation should be
administered vasopressors drips (see Box 106.8).
H1 antihistamine (diphenhydramine) should be given to
improve the itching and hives in patients with anaphylaxis. H2
antihistamines (ranitidine, cimetidine) have a synergistic
effect with H1 antihistamines and should be given because
BOX 106.8 Treatment Options for Anaphylaxis
General
Two large-bore intravenous lines (intraosseous if unable to
acquire intravenous access)
Placement of the patient on a monitor
Supplement oxygen (nasal canula, non-rebreather mask)
Consideration of a tourniquet—if anaphylaxis is due to an
insect sting at the distal end of an extremity (blood pressure
cuff inflated to approximately 20 mm Hg greater than systolic blood pressure), release every 10 minutes for 1 minute
or when the symptoms resolve
Epinephrine
Intramuscular (subcutaneous acceptable)—1 : 1000; adult: 0.3
to 0.5 mL every 5 minutes as necessary, titrated to effect;
pediatric: 0.01 mL/kg every 5 minutes as necessary, titrated
to effect)
Alternatively, EpiPen (0.3 mL) or EpiPen Jr (0.15 mL) can be
administered into the anterolateral aspect of the thigh;
removal of clothing unnecessary
Intravenous infusion—1 : 100,000; 0.1 mL of a 1 : 1000 dilution
in 10 mL of normal saline (NS), 100 mcg, over a 10-minute
period; equivalent to 10 mcg/min for a 10-min period,
titrated to effect; repeat as necessary; continuous hemodynamic monitoring required
Continuous infusion—1 mL of a 1 : 1000 dilution of epinephrine
in 250 mL of 5% dextrose in water (D5W) results in a concentration of 4 mcg/mL; can be started at 1 mcg/min and
increased to 4 mcg/min if needed
Pediatric continuous infusion—rate of 0.1 mcg/kg/min (up to
30 kg) advised, with increasing increments of 0.1 mcg/kg/
min to a maximum of 1.5 mcg/kg/min
926
Second-Line Medications
Antihistamines
Diphenhydramine (IV or PO)—adult: 50 to 100 mg, up to
400 mg/24 hr, titrated to effect; pediatric: 0.02 mg/kg, up to
300 mg/24 hr, titrated to effect
Ranitidine or other H2 blocker (IV or PO)—adult: 50 mg IV,
300 mg PO (4 mg/kg); pediatric: 1 mg/kg
Aerosolized Beta-Agonists and Others
Albuterol—adult: 2.5 mg; pediatric: 0.02 mL/kg up to 2.5 mg in
3 mL of NS; may be given continuously
Ipratropium—adult: 0.5 mg; pediatric: 0.25 mg in 3 mL of NS;
repeat as necessary
Prednisone
Adult: 40 to 60 mg PO; pediatric: 1 to 2 mg/kg PO
Methylprednisolone
Intravenous infusion—adult: 125 to 250 mg; pediatric: 40 to
80 mg
Glucagon
Intravenous infusion—adult: 1 to 5 mg over a 5-minute period;
pediatric: 0.5 mg, followed by 5 to 15 mcg/min as drops
(gtt); for refractory hypotension or patients receiving
beta-blockers
Dopamine
Intravenous infusion—5 to 20 mcg/kg/min gtt, and/or dobutamine, 5 to 20 mcg/kg/min gtt
Norepinephrine
Intravenous infusion—8 to 12 mcg/min gtt (2 to 3 mL/min;
4 mg added to 1000 mL of D5W provides a concentration
of 4 mcg/mL)
CHAPTER 106
they improve vascular permeability, flushing, gastric secretion, and mucus production in the airway. Antihistamines,
however, should be considered second-line agents after epinephrine. Inhaled β-agonists (albuterol) can be administered
for bronchospasm refractory to appropriate doses of epinephrine. Glucocorticosteroid provides no immediate benefit in the
acute treatment of anaphylaxis, although it may be helpful in
preventing biphasic reactions.
SPECIAL CONSIDERATIONS
PATIENTS TAKING BETA-BLOCKERS
Patients currently taking beta-blockers may not respond adequately to epinephrine and intravenous fluids. A glucagon
Possible anaphylaxis
BOX 106.9 Standard Pharmacologic Treatment
Protocol for Patients with a History of
Radiocontrast-Induced Anaphylaxis
Prednisone, 50 mg PO given 13 hours, 7 hours, and 1 hour
before the procedure
Diphenhydramine, 50 mg IM given 1 hour before the
procedure
Consider giving an H2 antagonist, such as ranitidine, 300 mg
PO as drops 3 hours before the procedure
Modified from Lieberman P. Anaphylaxis. Med Clin North Am 2006;
90:77-95.
RED FLAGS
• Remove any triggering agent
• Place patient in Trendelenburg position if hypotensive
• Check airway, breathing, circulation, vital signs
• Racemic epinephrine, 0.5 mL of 2.25% solution in 2.5 mL
of NS via nebulizer while awaiting definitive airway
management; can repeat multiple times
• Establish large-bore IV catheters
• Pulse oxymetry; cardiac monitoring/ECG; portable CXR;
blood draw
• Place a loose tourniquet proximal to the reaction site; if
reaction site on extremity, place extremity in dependent
position
• Administer epinephrine. Inject 0.1-0.2 mL 1 : 1000
epinephrine SQ locally to the reaction site
• Provide O2, nebulized β-agonist; IV access with NS wide
open; put patient on monitor
• Antihistamines, H2-blocker, steroids
Improved
Not improving/
deteriorating
• Observe in ED for 6
hours
• Review medications
• Provide definitive airway
control
• Repeat 0.3 mL 1 : 1000
epinephrine IM every 10-15
minutes, up to 5 doses
• Infuse crystalloid/colloid if
hypotensive (saline, lactated
Ringer solution, hydroxyethyl
starch, 5% albumin); titrate
to blood pressure
• Consider pulmonary artery
catheter, other diagnosis
• Consider IV epinephrine gtt,
glucagon, vasopressors
Discharge
from ED
Allergic Disorders
ICU
Fig. 106.5 Treatment algorithm for possible anaphylaxis (see
Box 106.8 for drug dosages and indications). CXR, Chest
radiograph; ECG, electrocardiogram; ED, emergency department;
gtt, drops; ICU, intensive care unit; IM, intramuscularly; IV,
intravenous; NS, normal saline; SQ, subcutaneously.
Management of Anaphylaxis
Failure to diagnose anaphylaxis early or to recognize the
need to secure the airway early
Delayed administration of epinephrine
Incorrect administration of intravenous epinephrine (e.g., not
diluting it, wrong concentration)
infusion should be strongly considered in these cases (see
Box 106.8).27,31 Conversely, these patients may also demonstrate unopposed α-adrenergic effects after epinephrine
administration and may require an alpha-blocker such as
phentolamine.
PATIENTS WITH ALLERGY TO INTRAVENOUS
CONTRAST MEDIA
Pretreatment with antihistamines and steroids significantly
decreases the frequency and severity of anaphylactoid reactions in patients who have sustained a previous reaction to
intravenous radiocontrast media. Each hospital has its own
pretreatment protocols for clinical procedures; Box 106.9
reproduces one such protocol.36
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Patients who experience complete resolution of symptoms
and were never hypotensive can potentially be discharged
home. Although the time frame for biphasic reactions varies
significantly, limited literature suggests that patients be
observed in the ED for up to 8 hours.33 Oral H1 antihistamines
such as diphenhydramine (50 mg every 6 hours for 72 hours)
and H2 blockers such as ranitidine (150 mg every 12 hours for
72 hours) along with oral prednisone may prevent possible
relapse.37 These patients should be instructed to return to the
ED if they experience any recurrent symptoms consistent with
their previous anaphylactic reaction.
All patients who have experienced an anaphylactic or significant allergic reaction should be prescribed at least two
927
SECTION X
IMMUNE SYSTEM DISORDERS
TIPS AND TRICKS
Prevention of Anaphylaxis and Anaphylactic Death
Obtain a thorough drug allergy and atopic history.
Check all drugs for proper labeling.
Give drugs orally rather than parenterally when possible.
Give drugs in distal end of the extremity if possible when a
parenteral route is necessary.
Always have resuscitation equipment available when administering antigenic compounds.
Ensure that patients remain in the emergency department
for at least 30 minutes after drug administration.
Use unrelated drugs when feasible in susceptible patients.
Encourage patients to carry warning identification (MedicAlert, wallet ID).
Educate patients on the technique of self-injection of
epinephrine and urge them to carry the treatment kit
at all times.
Instruct patients to avoid known antigens (stinging insects,
foods, antibiotics).
Refer patients to an allergist for a skin test and possible
immunotherapy.
928
Epi-Pens, one kept at the common residence and another in
the purse or briefcase. In addition, patients should be taught
how to self-administer it. Predisposed patients should be
encouraged to wear a Medic-Alert bracelet or carry a wallet
card identifying their hypersensitivity. Patients should also be
referred to an allergist for possible skin testing and hyposensitization immunotherapy.
Hospital admission should be considered for patients who
show slow clinical improvement, were hypotensive, and
had upper airway involvement or persistent bronchospasm.
Patients at risk for a biphasic reaction, such as those maintained on chronic beta-blocker therapy, may also be candidates for extended observation in the hospital.
REFERENCES
References can be found
www.expertconsult.com.
on
Expert
Consult
@
CHAPTER 106
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