The Relationship Between IgE and Allergic Disease

The relationship between IgE and allergic disease
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http://www.uptodate.com/contents/the-relationship-between-ige-and-all...
Official reprint from UpToDate

www.uptodate.com 2014 UpToDate
Authors
Jeff Stokes, MD, FAAAAI, FACAAI
Thomas B Casale, MD
Section Editor
Bruce S Bochner, MD
Deputy Editor
Anna M Feldweg, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2014. | This topic last updated: Jul 16, 2013.
INTRODUCTION Allergen-specific IgE is integral to the pathogenesis of allergic disorders. However, the utility
of measuring total serum IgE or allergen-specific IgE for purposes of diagnosis and management is variable. It is
important to recognize that levels of total IgE rarely provide information about IgE to specific allergens, and that
the presence of IgE to a specific allergen does not necessarily equate to a clinically meaningful allergic response to
that substance. It is also necessary to demonstrate that the individual develops appropriate signs and symptoms
upon exposure to the allergen in question.
This topic will review basic concepts concerning the generation of the allergic response and provide an overview of
the roles of total and allergen-specific IgE in various allergic diseases. The biology of IgE and the diagnosis of
specific allergic diseases are discussed separately. (See "The biology of IgE" and "Diagnosis of asthma in
adolescents and adults" and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis" and
"Epidemiology, clinical manifestations, and diagnosis of atopic dermatitis (eczema)".)
TERMINOLOGY The terms atopy, sensitization, and allergy are often used loosely in the medical literature,
although each has a distinct definition.
Atopy Atopy is the genetic predilection to produce specific IgE following exposure to allergens. At a cellular
level, atopy appears to result, in part, from a predisposition toward a certain response on the part of CD4+ T
helper cells, called a Th type 2 (Th2) response [1]. Th2 cells secrete large quantities of IL-4 and IL-13, which
promote the production of allergen-specific IgE by plasma cells. (See "T helper subsets: Differentiation and role in
disease" and "The biology of IgE", section on 'Regulation of synthesis'.)
Sensitization Sensitization refers to the production of allergen-specific IgE. Sensitization to an allergen is not
synonymous with being allergic to that allergen, because individuals may produce IgE to allergens in a given
substance, but not develop symptoms upon exposure to that substance. It is unclear why some individuals
demonstrate only sensitization while others have active allergic disease.
Sensitization is usually demonstrated by skin testing or in vitro immunoassays for IgE to specific allergens
(sometimes referred to as RAST testing, although this term describes an antiquated form of the test). Thus,
sensitization is necessary but not sufficient for the development of allergic disease. Because a person can be
sensitized to an allergen but not react to it upon exposure, it is prudent to limit allergy testing to those allergens
which are implicated by the clinical history.
The production of allergen-specific IgE is summarized briefly here in simplified form and reviewed in greater detail
elsewhere. (See "The biology of IgE", section on 'Synthesis' and "Immunoglobulin genetics" and "Normal B and T
lymphocyte development".)
Once a substance enters the body (through ingestion, inhalation, or injection), it is degraded, and allergens (usually
proteins but occasionally carbohydrates) are taken up by antigen presenting cells, including macrophages, CD1+
dendritic cells, B cells, and possibly epithelial cells. Antigen presenting cells further degrade the allergen and
present peptide fragments of it on the cell surface, in the setting of class II (MHC) molecules. The peptide/MHC II
complexes are recognized by Th2 cells. (See "Antigen presenting cells".)
Th2 cells then interact with B cells and, in the presence of various costimulatory signals, stimulate the B cell to
mature into a plasma cell that produces IgE specific to the component of the allergen in question. B cell maturation
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primarily occurs within mucosal lymphoid tissue.

After IgE antibodies specific for a certain allergen are synthesized and secreted, they diffuse throughout the body,
binding to high-affinity receptors (FcRI) on mast cells in the tissues and basophils in the circulating blood (figure
1).
Allergy Individuals are considered to have clinically significant allergy or allergic disease when they have both
allergen-specific IgE and develop symptoms upon exposure to substances containing that allergen. Therefore,
greater numbers of people are sensitized to an allergen then are clinically allergic to it. This was illustrated in the
National Health and Nutrition Examination Survey (NHANES) 2005-6, in which over 8000 people from the general
population of the United States were interviewed and tested (using in vitro blood tests) for sensitization to 19
common inhalant allergens [2]. Specific IgE antibodies to at least one allergen were present in 44 percent,
whereas only 34 percent had symptoms suggestive of allergic disease. Similar findings have been documented for
food allergy. In a population-based birth cohort study in the United Kingdom, 12 percent of children were sensitized
to peanut at eight years of age, but only 2 percent were allergic [3].
A sensitized person may develop symptoms when re-exposed to the relevant allergen, if the allergen is able to bind
to IgE antibodies on the surface of mast cells and basophils in sufficient numbers to cause clustering (called crosslinking) of the IgE molecules. Cross-linking of enough IgE receptors results in the generation of activating signals.
Upon activation, mast cells and basophils release preformed and newly-formed chemical and protein mediators,
which directly and indirectly lead to the signs and symptoms of allergic reactions. These mediators include
histamine, prostaglandins, leukotrienes, platelet activating factor, cytokines, and others. (See "Mast cell derived
mediators".)
Common allergic diseases include allergic asthma, allergic rhinitis, atopic dermatitis, food allergy, stinging-insect
venom allergy, and drug allergy.
The atopic march Atopic dermatitis (AD), allergic rhinitis, and asthma often affect the same patients and
develop in temporal succession. This progression from atopic dermatitis in infancy to allergic rhinitis and asthma in
childhood and young adulthood is referred to as the allergic march or atopic march [4-7]. Nearly 80 percent of
children with AD will subsequently develop allergic rhinitis or asthma [8].
RELATIONSHIPS BETWEEN TOTAL IgE LEVELS AND ALLERGIC DISEASE A total serum IgE level of 100
int. unit/mL is typically cited as the upper limit of normal in older adolescents and adults. Elevations in total serum
IgE are seen in several types of disorders, including allergic diseases, some primary immunodeficiencies, parasitic
and viral infections, certain inflammatory diseases, some malignancies, and a handful of other diseases (table 1).
Thus, elevated total serum IgE is not specific to allergic disease. Studies concerning allergic diseases are
reviewed here, while studies of IgE in other diseases are reviewed separately. (See "The biology of IgE", section
on 'Increased total IgE'.)
Elevated total serum IgE Many patients with allergic disorders have elevated levels of total IgE; however,
there is no specific cutoff value that discriminates patients with allergic disease from those without, and there is
considerable overlap [9,10]. Thus, total IgE by itself is rarely adequate to diagnose allergic disease. The following
studies are illustrative:
Adults with IgE >66 int. unit/mL have a 37-fold greater risk of having allergen-specific IgE antibodies to
aeroallergens compared to those patients with the lowest levels of total IgE [11].
In one study, school-aged children had a mean IgE level of 51 int. unit/mL. Children with both atopic
dermatitis and asthma had mean IgE levels of 985 int. unit/mL, asthma alone 305 int. unit/mL, eczema alone
273 int. unit/mL, and allergic rhinitis 171 int. unit/mL [12].
Among atopic patients of all ages, those with atopic dermatitis tend to have the highest IgE levels followed
by atopic asthma, perennial allergic rhinitis, and seasonal allergic rhinitis [9].
Using a total serum IgE level of 100 int. unit/mL to discriminate allergic from nonallergic patients, the
sensitivity was 78 percent for patients with asthma and 60 percent for rhinitis, but 20 percent of patients
were misclassified [13].
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Low or normal levels of total serum IgE The authors and editors of UpToDate know of no studies to suggest
that low levels of total serum IgE can be used to exclude the presence of atopic disease, because of the wide
overlap in total serum IgE among atopic and nonatopic populations. Patients with low or normal serum IgE levels
could still have local production of allergen-specific IgE in the tissues. (See "The biology of IgE", section on
'Localized IgE production'.)
Utility in predicting the development of allergic disease Because elevations in total serum IgE are
associated with established allergic disease, researchers have questioned whether IgE levels predict its
development. Studies suggest that elevated total IgE is associated with an increased risk of allergic disease,
although there is significant overlap between affected individuals and normals, such that the measurement is most
useful in the context of population studies, rather than in the diagnosis or management of an individual.
Cord blood Cord blood IgE levels have been studied in an attempt to identify newborns who are at
increased risk for the development of allergic disease. Maternal IgE does not normally cross the placenta, although
fetal cord blood can be contaminated by maternal blood during late pregnancy and delivery and must be carefully
collected [14]. The majority of studies suggest that elevated total IgE in cord blood is an indicator of higher risk. As
examples, studies have shown that newborns with elevated cord IgE levels had an increased risk of developing
urticarial food reactions at one year of age [15], atopic dermatitis by age two [16], allergen sensitization and
wheezing at seven years [17], or allergic rhinitis by 11 and 20 years of age [18]. However, no relationship was
found between cord blood IgE levels and the development of asthma, allergic rhinitis or atopic dermatitis by the
time the child was 18 to 21 years of age despite a modest association with total IgE levels at those ages in
another study [19]. (See "The biology of IgE", section on 'Childhood levels'.)
Childhood IgE levels Elevated IgE in young children appears to be an early predictor of the subsequent
development of allergen-specific IgE and of allergic disease [20]. However, the clinical utility of this is limited by the
extensive overlap between normals and atopic individuals, and the fact that patients with asthma have higher total
IgE compared with nonasthmatics, regardless of atopic status. (See 'Relationships between total IgE levels and
allergic disease' above and 'Asthma' below.)
Timeline of sensitization In most cases, the presence of allergen-specific IgE precedes the onset of
symptoms by several years. In a study of nearly 1000 college students, subjects were evaluated initially and again
7 and 16 years later using questionnaires and skin testing [21]. At the seven-year follow-up, subjects with prior
positive skin tests demonstrated an increased risk of developing allergic rhinitis and asthma. When these same
patients were reassessed 16 years later, a 2.3-fold greater risk of developing allergic rhinitis was found in those
subjects with positive allergen skin tests [22]. Positive allergy skin tests and allergic rhinitis increased the likelihood
of developing asthma threefold.
In a small minority of patients, sensitization occurs only in the affected tissues, presumably due to low levels of
allergen-specific IgE being produced by local mucosal plasma cells. This phenomenon of local IgE production is
termed entopy. In such patients, allergen-specific IgE is not demonstrable by either allergy skin testing or blood
work, which presents diagnostic challenges. This is best described for some patients with rhinitis who have
negative skin and in vitro tests for allergen-specific IgE, yet react to challenge with inhaled allergen. (See "Chronic
nonallergic rhinitis", section on 'Diagnosis'.)
THE ROLE OF IgE IN SPECIFIC DISORDERS The role of total and allergen-specific IgE levels in pathogenesis
and diagnosis differs among the leading allergic disorders.
Asthma Children and adults with asthma tend to have higher IgE levels than individuals without asthma, although
there is no absolute cutoff that distinguishes between the two groups [23]. Conversely, nonatopic patients with high
levels of IgE are more likely to have asthma than those with normal IgE levels [24]. In one study, nonallergic
patients with a total serum IgE level greater than 150 int. unit/mL were at a fivefold higher risk of having asthma
[25]. Still, the increase in elevated total IgE in asthmatics compared to nonasthmatics is generally driven by atopic
individuals [26].
Increased expression of the high affinity IgE receptor (FcRI) has been demonstrated on cells in the airways of
both atopic and nonatopic asthma patients compared to nonatopic control patients [27-29]. IgE positively regulates
FcRI levels, so both IgE and FcRI tend to increase or decrease in parallel. Patients with atopic dermatitis and
asthma are more likely than controls to have mutations in the alpha subunit of FcR1 (the subunit that directly binds
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to IgE) associated with increased serum IgE levels [30].

In allergic patients with asthma, anti-IgE therapy (omalizumab) improves symptoms, reduces exacerbations and
medication requirements, and decreases multiple inflammatory markers, demonstrating the role of IgE in allergic
asthma. Total IgE levels are required for appropriate dosing of omalizumab in persistent asthma patients.
(See "Anti-IgE therapy", section on 'Efficacy'.)
Lung function correlates with IgE IgE levels correlate with asthma severity; serum IgE levels are
proportionately higher in asthmatic patients with lower lung function (FEV1) [31]. This may also be true for allergenspecific IgE; in patients with lower respiratory symptoms to specific aeroallergens (eg, cat), levels of allergenspecific IgE correlated well with asthma symptoms and lung function [32].
One of the key features of asthma is airway hyperresponsiveness, typically measured by bronchoprovocation
challenges. In patients with asthma, elevated total IgE levels are associated with positive responses to
methacholine challenges [33]. Airway hyperresponsiveness in children correlates closely with total IgE level even
after exclusion of children with asthma [34]. However, airway hyperresponsiveness was more closely correlated to
positive allergen skin test reactions than total IgE levels in children [35].
Smoking is associated with increased IgE levels in a dose-dependent fashion, possibly due to the lack of expected
decreases in IgE levels with aging [36]. The inverse relationship between IgE levels and lung function was stronger
in asthmatic patients in both current and never smokers, compared with nonasthmatic subjects [37].
Allergic bronchopulmonary aspergillosis Allergic bronchopulmonary aspergillosis (ABPA) is one of the few
disorders in which total IgE values are used directly in diagnosis and treatment. ABPA typically occurs in patients
with asthma or cystic fibrosis. The ubiquitous mold Aspergillus fumigatus causes localized immunologic-mediated
damage in the lung. Diagnostic features include increased total IgE (>417 kU/L for patients with asthma and >1000
kU/L for those with cystic fibrosis) and evidence of increased specific IgE and IgG to A fumigatus [38]. Levels of
total IgE increase during exacerbations of ABPA, and fall with successful therapy. (See "Allergic bronchopulmonary
aspergillosis", section on 'Diagnosis'.)
Allergic rhinitis Allergic rhinitis is associated with positive skin-test reactions (or allergen-specific IgE
antibodies), but is independent of total IgE levels [39]. Measurement of total IgE has low sensitivity (44 percent)
for identification of patients with current allergic rhinitis [40]. In patients with perennial allergic rhinitis, total IgE
levels did not correlate with either skin test reactivity or in vitro specific IgE testing [41]. In addition, a normal IgE
level does not rule out allergic rhinitis [42]. The diagnosis of allergic rhinitis, seasonal or perennial, requires a
suggestive history and physical exam and the demonstration of specific IgE to clinically-relevant aeroallergens [43].
(See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis".)
Atopic dermatitis Even though it is called atopic dermatitis (AD), about 30 percent of patients are nonatopic,
as determined by the absence of other allergic diseases, negative skin tests for common inhalant and food
allergens, and normal total serum IgE levels [44]. The importance of allergic triggers remains controversial. (See
"Role of allergy in atopic dermatitis (eczema)".)
Elevated total IgE levels can be demonstrated in 80 to 85 percent of patients with AD, although the precise
relationship between the elevated IgE levels and disease pathogenesis is unclear [45]. Some individuals have
extremely high total IgE levels. Children with very high IgE (ie, >10,000 kU/L) are at greater risk for severe AD,
sensitization to food and inhaled allergens, and anaphylaxis, compared to children with lesser elevations (ie, 1000
to 4000 kU/L) [46].
In patients with AD, the rate of sensitization to foods ranges from 30 to 80 percent, depending upon the population
studied, although the actual rate of confirmed food allergy is much lower. The diagnosis of food allergy in patients
with atopic dermatitis is reviewed in detail separately. (See "Role of allergy in atopic dermatitis (eczema)", section
on 'Allergen sensitization'.)
Food allergy Assessment of food-specific IgE is predominantly useful for the evaluation of immediate
allergic reactions, such as those that cause hives, wheezing, or anaphylaxis. Foods are also associated with other
types of adverse reactions including celiac sprue (gluten sensitivity) and lactose intolerance, neither of which are
IgE-mediated. (See "Clinical manifestations of food allergy: An overview", section on 'Non IgE-mediated
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reactions'.)
The gold standard testing for food allergy is the double blind placebo-controlled oral challenge. This can be a labor
intensive procedure with potential severe allergic reactions resulting from testing. Therefore, alternatives such as
prick skin testing and in vitro food-specific IgE testing have been used as a substitute. Total IgE levels should not
be used to make a diagnosis of food allergy [47]. (See "Oral food challenges for diagnosis and management of
food allergies" and "Diagnostic evaluation of food allergy".)
Venom allergy Patients who have experienced a systemic allergic reaction to a stinging insect (ie, bee, wasp,
etc) or fire ants, or select patients with severe large local reactions to insect stings, should be evaluated for venom
allergy [48]. Skin testing is the preferred method of diagnosing venom allergy. If initial testing is negative, in vitro
testing for venom-specific IgE can be performed, or skin testing can be repeated [49].
Measurement of total IgE has no role in the diagnosis of venom allergy. Patients with confirmed venom allergy
should be offered venom immunotherapy, which is highly effective at reducing the risk of reactions to subsequent
stings. (See "Diagnosis of Hymenoptera venom allergy".)
Drug allergy In patients with a history suggestive of an immediate hypersensitivity allergic reaction, skin testing
can be helpful to confirm the diagnosis [50]. Penicillin is the only drug with validated testing available, although skin
testing is performed with other medications as well. (See "An approach to the patient with drug allergy", section on
'Testing for immediate reactions'.)
In vitro testing for drug-specific IgE is not generally useful, because its sensitivity is inferior to skin testing [51].
Total serum IgE is of no value in the evaluation of drug allergy.
Chronic urticaria Chronic idiopathic urticaria is defined as spontaneous wheals and/or angioedema daily or
near daily for more than six weeks without any identifiable cause. About 40 percent of these patients produce IgG
autoantibodies to either IgE or its high affinity receptor, FcRI. Despite IgE levels not being associated with this
disease, the use of anti-IgE (omalizumab) therapy has been effective in reducing signs (number of hives) and
symptoms (itch severity) in patients who remain symptomatic despite standard treatments [52,53]. (See "Chronic
urticaria: Treatment of refractory symptoms", section on 'Omalizumab'.)
RATIO OF ALLERGEN-SPECIFIC IgE TO TOTAL IgE The ratio of allergen-specific IgE to total IgE has been
termed the specific activity [54]. Its utility has been examined in the diagnosis of several allergic disorders, and in
predicting individuals responses to omalizumab therapy. One study found that, in the diagnosis of food allergy, the
specific activity was no more useful than allergen-specific IgE alone [55]. However, in the treatment of asthma with
omalizumab, a specific activity greater than 3 to 4 percent was predictive of a reduced response to omalizumab
therapy [56]. At present, the ratio of allergen-specific IgE to total IgE remains largely a research tool and overall
clinical usefulness has not been established.
SUMMARY
Allergen-specific IgE production is a fundamental component of the pathogenesis of allergic disease.
However, the measurement of total IgE and allergen-specific IgE has variable utility in the diagnosis and
management of allergic disorders. (See 'Introduction' above.)
Atopy refers to the genetic predilection to produce allergen-specific IgE. Sensitization refers to the presence
of allergen-specific IgE, in the absence of clinical disease. Individuals are considered to have clinically
significant allergy or allergic disease when they have both allergen-specific IgE and develop symptoms upon
exposure to that allergen. (See 'Terminology' above.)
Elevated total IgE is seen with some allergic disorders, as well as several nonallergic diseases (table 1).
Many patients (although not all) with allergic disorders have elevated levels of total IgE; however, there is no
specific cutoff value that discriminates patients with allergic disease from those without, and there is
considerable overlap. (See 'Relationships between total IgE levels and allergic disease' above.)
Elevated total IgE is associated with an increased risk of allergic disease, although there is significant
overlap between affected individuals and normals, such that the measurement is most useful in the context
of population studies, rather than in the diagnosis or management of an individual. Allergen-specific IgE is
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usually detectable several years before a person becomes reactive to that allergen, although only a subset
of sensitized people will ever develop symptoms. (See 'Utility in predicting the development of allergic
disease' above.)
The role of total and allergen-specific IgE levels in pathogenesis and diagnosis differs among the leading
allergic disorders. Asthma correlates with increased total IgE levels, regardless of atopic status. Allergic
rhinitis is associated with allergen-specific IgE antibodies, although not with total IgE levels. Patients with
atopic dermatitis may have very elevated levels of total IgE, although only a minority of patients (mostly
children with severe AD) has clinically-apparent allergic reactions to food. Thus the usefulness of measuring
total IgE in allergic rhinitis and atopic dermatitis is very limited. (See 'The role of IgE in specific disorders'
above.)
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48. Golden DB, Moffitt J, Nicklas RA, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J
Allergy Clin Immunol 2011; 127:852.
49. Golden DB, Kagey-Sobotka A, Norman PS, et al. Insect sting allergy with negative venom skin test
responses. J Allergy Clin Immunol 2001; 107:897.
50. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American
College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. Drug allergy:
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51. Macy E, Goldberg B, Poon KY. Use of commercial anti-penicillin IgE fluorometric enzyme immunoassays to
diagnose penicillin allergy. Ann Allergy Asthma Immunol 2010; 105:136.
52. Maurer M, Rosn K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous
urticaria. N Engl J Med 2013; 368:924.
53. Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic
idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol 2013; 132:101.
54. Hamilton RG, MacGlashan DW Jr, Saini SS. IgE antibody-specific activity in human allergic disease. Immunol
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55. Mehl A, Verstege A, Staden U, et al. Utility of the ratio of food-specific IgE/total IgE in predicting
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56. Johansson SG, Nopp A, Oman H, et al. The size of the disease relevant IgE antibody fraction in relation to
'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment. Allergy 2009; 64:1472.
Topic 83038 Version 2.0
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GRAPHICS
Allergen-specific IgE production and dissemination
Allergens (in this figure, aeroallergens) enter the tonsils within which they
are taken up and degraded by antigen presenting cells (APC). APCs
then interact with T helper cells type 2 (Th2) cells and B cells in the lymph
nodes, leading to allergen-specific IgE production. The IgE enters the blood
stream, and then diffuses through tissues (especially the skin and mucosal
tissues of the respiratory and gastrointestinal tracts). The IgE binds to
high-affinity Fc receptors (FcepsilonRI) on the surface of the tissue mast cells
and circulating basophils. When these IgE-coated cells encounter that specific
aeroallergen subsequently, they become activated, leading to the release of
inflammatory mediators, which results in the signs and symptoms of
IgE-mediated allergic reactions.
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IgE: immunoglobulin E.
Graphic 55328 Version 6.0
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Conditions associated with elevated serum IgE

Infectious diseases
Parasitic
Ascariasis
Schistosomiasis
Strongyloidiasis
HIV infection
Mycobaterium tuberculosis
Cytomegalovirus
Epstein-Barr virus (EBV)
Candidiasis
Atopic diseases
Allergic bronchopulmonary aspergillosis (ABPA)

Allergic fungal sinusitis
Atopic dermatitis
Allergic asthma
Allergic rhinitis
Immunodeficiencies
Hyperimmunoglobulin E syndrome
Wiskott-Aldrich syndrome
Netherton's disease
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked
syndrome (IPEX)
Omenn syndrome
Atypical complete DiGeorge syndrome
Inflammatory
diseases
Churg-Strauss vasculitis
Neoplasms
Hodgkin's lymphoma
Kimura disease
Immunoglobulin E (IgE) myeloma

Others
Tobacco smokers
Cystic fibrosis
Nephrotic syndrome
Bone marrow transplantation
Bullous pemphigoid
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Disclosures
Disclosures: Jeff Stokes, MD, FAAAAI, FACAAI Nothing to disclose. Thomas B Casale, MD Grant/Research Support: Novartis [chronic
urticaria (omalizumab)]; Genentech [asthma (omalizumab)]. Consultant/Advisory Boards: Novartis [chronic urticaria (omalizumab)];
Genentech [asthma (omalizumab)]. Bruce S Bochner, MD Grant/Research/Clinical Trial Support: NIAID; NHLBI; GSK [Siglec-8, Siglec-9,
asthma, COPD, anaphylaxis, imaging; eosinophilic granulomatosis with polyangiitis (Mepolizumab)]. Consultant/Advisory Boards: TEVA;
Sanofi; Merck; Glycomimetics; Allakos; Biogen Idec; Svelte Medical Systems. Patent Holder: Siglec-8 and its ligand; anti-Siglec-8
antibodies [held by Johns Hopkins University]. Employment: Northwestern University Feinberg School of Medicine. Equity
Ownership/Stock Options: Glycomimetics; Allakos. Other Financial Interest: Elsevier [royalties]. Anna M Feldweg, MD Employee of
UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a
multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced
content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
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