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Overview of Allergic and Atopic Disorders

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Medically Reviewed Oct 2022
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Topic Resources

Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are misdirected against intrinsic body components (self), leading to autoimmune disorders Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following types of hypersensitivity reactions may be involved: Type II: Antibody-coated... read more This topic focuses on type I hypersensitivity reactions.

Classification of Hypersensitivity Reactions

Hypersensitivity reactions are divided into 4 types (I through IV) by the Gell and Coombs classification. Hypersensitivity disorders often involve more than 1 type.

Type I

Type I reactions (immediate hypersensitivity) are IgE-mediated. Antigen binds to IgE that is bound to tissue mast cells and blood basophils, triggering release of preformed mediators (eg, histamine, proteases, chemotactic factors) and synthesis of other mediators (eg, prostaglandins, leukotrienes, platelet-activating factor, cytokines). These mediators cause vasodilation, increased capillary permeability, mucus hypersecretion, smooth muscle spasm, and tissue infiltration with eosinophils, type 2 helper T (TH2) cells, and other inflammatory cells.

Overview of Type I Hypersensitivity
VIDEO

Type I hypersensitivity reactions develop < 1 hour after exposure to antigen.

Type I reactions underlie all atopic disorders (eg, atopic dermatitis Atopic Dermatitis (Eczema) Atopic dermatitis is a chronic relapsing inflammatory skin disorder with a complex pathogenesis involving genetic susceptibility, immunologic and epidermal barrier dysfunction, and environmental... read more Atopic Dermatitis (Eczema) , allergic asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , rhinitis Allergic Rhinitis Allergic rhinitis is seasonal or perennial itching, sneezing, rhinorrhea, nasal congestion, and sometimes conjunctivitis, caused by exposure to pollens or other allergens. Diagnosis is by history... read more , conjunctivitis Allergic Conjunctivitis Allergic conjunctivitis is an acute, intermittent, or chronic conjunctival inflammation usually caused by airborne allergens. Symptoms include itching, lacrimation, discharge, and conjunctival... read more Allergic Conjunctivitis ) and many allergic disorders (eg, anaphylaxis Anaphylaxis Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more , some cases of angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute but sometimes a chronic mast cell–mediated reaction caused by exposure to a drug (eg, angiotensin-converting... read more Angioedema , urticaria Urticaria Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin. Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation... read more Urticaria , latex and some food allergies Food Allergy Food allergy is an exaggerated immune response to dietary components, usually proteins. Manifestations vary widely and can include atopic dermatitis, gastrointestinal or respiratory symptoms... read more ). The terms atopy and allergy are often used interchangeably but are different:

  • Atopy is an exaggerated IgE-mediated immune response; all atopic disorders are type I hypersensitivity disorders.

  • Allergy is any exaggerated immune response to a foreign antigen regardless of mechanism.

Atopic disorders most commonly affect the nose, eyes, skin, and lungs. These disorders include conjunctivitis Allergic Conjunctivitis Allergic conjunctivitis is an acute, intermittent, or chronic conjunctival inflammation usually caused by airborne allergens. Symptoms include itching, lacrimation, discharge, and conjunctival... read more Allergic Conjunctivitis , extrinsic atopic dermatitis Atopic Dermatitis (Eczema) Atopic dermatitis is a chronic relapsing inflammatory skin disorder with a complex pathogenesis involving genetic susceptibility, immunologic and epidermal barrier dysfunction, and environmental... read more Atopic Dermatitis (Eczema) (the most common type of eczema), immune-mediated urticaria Urticaria Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin. Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation... read more Urticaria , some forms of angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute but sometimes a chronic mast cell–mediated reaction caused by exposure to a drug (eg, angiotensin-converting... read more Angioedema , acute latex allergy, some allergic lung disorders (eg, allergic asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , IgE-mediated components of allergic bronchopulmonary aspergillosis Allergic Bronchopulmonary Aspergillosis (ABPA) Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species (generally A. fumigatus) that occurs almost exclusively in patients with asthma... read more Allergic Bronchopulmonary Aspergillosis (ABPA) ), allergic rhinitis Allergic Rhinitis Allergic rhinitis is seasonal or perennial itching, sneezing, rhinorrhea, nasal congestion, and sometimes conjunctivitis, caused by exposure to pollens or other allergens. Diagnosis is by history... read more , and allergic reactions to venomous stings Insect Stings Stinging insects are members of the order Hymenoptera of the class Insecta. Hymenoptera venoms cause local toxic reactions in all people and allergic reactions only in those previously sensitized... read more Insect Stings .

Type II

Type II reactions (antibody-dependent cytotoxic hypersensitivity) result when antibody binds to cell surface antigens or to a molecule coupled to a cell surface. The surface-bound antigen-antibody structure (as opposed to the circulating antigen-antibody complex in type III hypersensitivity) activates cells that participate in antibody-dependent cell-mediated cytotoxicity (eg, natural killer cells, eosinophils, macrophages), complement, or both. The result is cell and tissue damage.

Overview of Type II Hypersensitivity
VIDEO

Type III

Type III reactions (immune complex disease) cause inflammation in response to circulating antigen-antibody immune complexes deposited in vessels or tissue. These complexes can activate the complement system or bind to and activate certain immune cells, resulting in release of inflammatory mediators.

Consequences of immune complex formation depend in part on the relative proportions of antigen and antibody in the immune complex. Early in the immune response, there is excess antigen with small antigen-antibody complexes, which do not activate complement. Later, when antigen and antibody are more balanced, immune complexes are larger and tend to be deposited in various tissues (eg, glomeruli, blood vessels), causing systemic reactions. The isotype of induced antibodies changes during an immune response, and the isotype, glycosylation, size, and charge of the complex’s components contribute to the clinical response.

Overview of Type III Hypersensitivity
VIDEO

Type III disorders include serum sickness, systemic lupus erythematosus (SLE) Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) , rheumatoid arthritis (RA) Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more Rheumatoid Arthritis (RA) , leukocytoclastic vasculitis Cutaneous Vasculitis Cutaneous vasculitis refers to vasculitis affecting small- or medium-sized vessels in the skin and subcutaneous tissue but not the internal organs. Cutaneous vasculitis may be limited to the... read more Cutaneous Vasculitis , cryoglobulinemia Cryoglobulinemia Conditions that cause an abnormal protein content in the blood, typically in the form of immunoglobulins, can affect vascular fragility and lead to purpura. (See also Overview of Vascular Bleeding... read more Cryoglobulinemia , acute hypersensitivity pneumonitis Hypersensitivity Pneumonitis Hypersensitivity pneumonitis is a syndrome of cough, dyspnea, and fatigue caused by sensitization and subsequent hypersensitivity to environmental (frequently occupational or domestic) antigens... read more Hypersensitivity Pneumonitis , and several types of glomerulonephritis Overview of Glomerular Disorders The hallmark of glomerular disorders is proteinuria, which is often in the nephrotic range (≥ 3 g/day). Glomerular disorders are classified based on urine changes as those that manifest predominantly... read more .

Type III reactions develop 4 to 10 days after exposure to antigen and, if exposure to the antigen continues, can become chronic.

Type IV

Type IV reactions (delayed hypersensitivity) do not involve antibodies but are mediated by T cells.

Overview of Type IV Hypersensitivity
VIDEO

T cells, sensitized after contact with a specific antigen, are activated by continued exposure or reexposure to the antigen; they damage tissue by direct toxic effects or through release of cytokines, which activate eosinophils, monocytes and macrophages, neutrophils, or natural killer cells.

Disorders involving type IV reactions include Stevens-Johnson syndrome Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous hypersensitivity reactions. Drugs, especially sulfa drugs, antiseizure drugs, and antibiotics, are the most common... read more Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) , toxic epidermal necrolysis (SJS/TEN) Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous hypersensitivity reactions. Drugs, especially sulfa drugs, antiseizure drugs, and antibiotics, are the most common... read more Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) , drug rash with eosinophilia and systemic symptoms (DRESS) Symptoms and Signs , contact dermatitis Contact Dermatitis Contact dermatitis is inflammation of the skin caused by direct contact with irritants (irritant contact dermatitis) or allergens (allergic contact dermatitis). Symptoms include pruritus and... read more Contact Dermatitis (eg, poison ivy), subacute and chronic hypersensitivity pneumonitis Hypersensitivity Pneumonitis Hypersensitivity pneumonitis is a syndrome of cough, dyspnea, and fatigue caused by sensitization and subsequent hypersensitivity to environmental (frequently occupational or domestic) antigens... read more Hypersensitivity Pneumonitis , acute and chronic allograft rejection Rejection Transplants may be The patient’s own tissue (autografts; eg, bone, bone marrow, and skin grafts) Genetically identical (syngeneic [between monozygotic twins]) donor tissue (isografts) Genetically... read more , the immune response to tuberculosis, and many forms of drug hypersensitivity Drug Hypersensitivity Drug hypersensitivity is an immune-mediated reaction to a drug. Symptoms range from mild to severe and include rash, anaphylaxis, and serum sickness. Diagnosis is clinical; skin testing is occasionally... read more .

Latex Sensitivity

Latex sensitivity is an exaggerated immune response to water-soluble proteins in latex products (eg, rubber gloves, dental dams, condoms, tubing for respiratory equipment, catheters, enema tips with inflatable latex cuffs).

Beginning in the late 1980s, incidence increased among health care workers when emphasis on universal precautions resulted in routine use of latex gloves.

Reactions to latex may be

  • Acute (IgE-mediated)

  • Delayed (cell-mediated)

Acute reactions cause urticaria and anaphylaxis; delayed reactions cause dermatitis.

After health care workers wear latex gloves, the skin often becomes irritated and crusted, but this reaction is usually chemical irritation, not latex allergy.

Diagnosis of latex sensitivity is based primarily on history. Skin testing and assays for detecting IgE antilatex antibodies are available.

Treatment is avoidance of latex. For the most part, health care institutions are now latex-free, and the incidence of latex allergy has dramatically decreased.*

*See Raulf M: Current state of occupational latex allergy. Curr Opin Allergy Clin Immunol 20 (2):112–116, 2020.

Etiology of Allergic and Atopic Disorders

Complex genetic, environmental, and site-specific factors contribute to development of IgE-mediated allergies.

Genetic factors may be involved, as suggested by familial inheritance of disease, association between atopy and specific human leukocyte antigen (HLA) loci, and polymorphisms of several genes, including those for the high-affinity IgE receptor beta-chain, IL-4 receptor alpha-chain, interleukin (IL)-4, IL-13, CD14, dipeptidyl-peptidase 10 (DPP10), and a disintegrin and metalloprotease domain 33 (ADAM33).

Environmental factors interact with genetic factors to maintain type 2 helper T (TH2) cell–directed immune responses. TH2 cells activate eosinophils, promote IgE production, and are proallergic. Early childhood exposure to bacterial and viral infections and endotoxins (eg, lipopolysaccharide) may normally shift native TH2-cell responses to type 1 helper T (TH1)–cell responses, which suppress TH2 cells and therefore discourage allergic responses. Regulatory T (Treg) cells (eg, CD4+CD25+Foxp3+), which are capable of suppressing TH2-cell responses, and IL-12–secreting dendritic cells, which drive TH1-cell responses, are perhaps also involved. Trends in developed countries toward smaller families with fewer children, cleaner indoor environments, and early use of antibiotics may limit children's exposure to the infectious agents that drive a predominantly TH1-cell response; such trends may explain the increased prevalence of some allergic disorders.

Other factors thought to contribute to allergy development include chronic allergen exposure and sensitization, diet, and environmental pollutants.

Site-specific factors include adhesion molecules in bronchial epithelium and skin and molecules in the gastrointestinal (GI) tract that direct TH2 cells to target tissues. The composition of the GI tract, respiratory tract, and skin microbiota appears to strongly influence the development of allergy. These microbiota may provide new targets for allergy therapy.

Allergens

By definition, an allergen induces type I IgE-mediated or type IV T-cell–mediated immune responses. Allergic triggers are almost always low molecular weight proteins; many of them can become attached to airborne particles.

Allergens that are the most common causes of acute and chronic allergic reactions (type I and type IV) include

For type IV hypersensitivity reactions, drugs are the most common cause.

Pathophysiology of Allergic and Atopic Disorders

When allergen binds to IgE-sensitized mast cells and basophils, histamine is released from their intracellular granules. Mast cells are widely distributed but are most concentrated in skin, lungs, and gastrointestinal (GI) mucosa; histamine facilitates inflammation and is the primary mediator of clinical atopy. Physical disruption of tissue and various substances (eg, tissue irritants, opiates, surface-active agents, complement components C3a and C5a) can trigger histamine release directly, independent of IgE.

Histamine causes the following:

  • Local vasodilation (causing erythema)

  • Increased capillary permeability and edema (producing a wheal)

  • Vasodilation of surrounding arterioles mediated by neuronal reflex mechanisms (causing flare—the redness around a wheal)

  • Stimulation of sensory nerves (causing itching)

  • Smooth muscle contraction in the airways (bronchoconstriction) and in the GI tract (increasing GI motility)

  • Increased nasal, salivary, and bronchial gland secretions

When released systemically, histamine is a potent arteriolar dilator and can cause extensive peripheral pooling of blood and hypotension; cerebral vasodilation may be a factor in vascular headache. Histamine increases capillary permeability; the resulting loss of plasma and plasma proteins from the vascular space can worsen circulatory shock. This loss triggers a compensatory catecholamine surge from adrenal chromaffin cells.

Symptoms and Signs of Allergic and Atopic Disorders

Common symptoms of type I hypersensitivity allergic disorders include

  • Rhinorrhea, sneezing, and nasal congestion (upper respiratory tract)

  • Wheezing and dyspnea (lower respiratory tract)

  • Itching (eyes, nose, skin)

Signs may include nasal turbinate edema, sinus pain during palpation, wheezing, conjunctival hyperemia and edema, urticaria, angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute but sometimes a chronic mast cell–mediated reaction caused by exposure to a drug (eg, angiotensin-converting... read more Angioedema , dermatitis, and skin lichenification.

Diagnosis of Allergic and Atopic Disorders

  • Clinical evaluation

  • Sometimes complete blood count (to check for eosinophilia) and occasionally serum IgE levels (nonspecific tests)

  • Often skin testing and allergen-specific serum IgE testing (specific tests)

  • Rarely provocative testing

A thorough history is generally more reliable than testing or screening. History should include

  • Questions about frequency and duration of attacks and changes over time

  • Triggering factors if identifiable

  • Relation to seasonal or situational settings (eg, predictably occurring during pollen seasons; after exposure to animals, hay, or dust; during exercise; or in particular places)

  • Family history of similar symptoms or of atopic disorders

  • Responses to attempted treatments

Nonspecific tests

Certain tests can suggest but not confirm an allergic origin of symptoms.

Complete blood count (CBC) may be done to detect eosinophilia if patients are not taking corticosteroids, which reduce the eosinophil count. However, CBC is of limited value because although eosinophils may be increased in atopy or other conditions (eg, drug hypersensitivity, cancer, inflammatory bowel disease, parasitic infection), a normal eosinophil count does not exclude allergy. Total white blood cell count is usually normal. Anemia and thrombocytosis are not typical of allergic responses and should prompt consideration of a systemic inflammatory disorder.

Conjunctival or nasal secretions or sputum can be examined for leukocytes; finding any eosinophils suggests that TH2-mediated inflammation is likely.

Serum IgE levels are elevated in atopic disorders but are of little help in diagnosis because they may also be elevated in parasitic infections Approach to Parasitic Infections Human parasites are organisms that live on or in a person and derive nutrients from that person (its host). There are 3 types of parasites: Single-cell organisms (protozoa, microsporidia) Multicellular... read more , infectious mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more Infectious Mononucleosis , some autoimmune disorders Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following types of hypersensitivity reactions may be involved: Type II: Antibody-coated... read more , drug reactions, immunodeficiency disorders (hyper-IgE syndrome Hyper-IgE Syndrome Hyper-IgE syndrome is a hereditary combined B- and T-cell immunodeficiency characterized by recurrent staphylococcal abscesses of the skin, sinopulmonary infections, and severe pruritic eosinophilic... read more and Wiskott-Aldrich syndrome Wiskott-Aldrich Syndrome Wiskott-Aldrich syndrome results from a combined B- and T-cell defect and is characterized by recurrent infection, eczema, and thrombocytopenia. (See also Overview of Immunodeficiency Disorders... read more ), IgG4-related disease, and in some forms of multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more Multiple Myeloma . IgE levels are probably most helpful for following response to therapy in allergic bronchopulmonary aspergillosis Allergic Bronchopulmonary Aspergillosis (ABPA) Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species (generally A. fumigatus) that occurs almost exclusively in patients with asthma... read more Allergic Bronchopulmonary Aspergillosis (ABPA) .

Specific tests

Skin testing uses standardized concentrations of antigen introduced directly into skin and is indicated when a detailed history and physical examination do not identify the cause and triggers for persistent or severe symptoms. Skin testing has higher positive predictive values for diagnosing allergic rhinitis and conjunctivitis than for diagnosing allergic asthma or food allergy; negative predictive value for food allergy is high.

The most commonly used antigens are pollens (tree, grass, weed), molds, house dust mite feces, animal danders and sera, insect venom, foods, and beta-lactam antibiotics. Choice of antigens to include is based on patient history and geographic prevalence.

Two skin test techniques can be used:

  • Percutaneous (prick)

  • Intradermal

The prick test can detect most common allergies; it is usually done first. The intradermal test is more sensitive but less specific; it can be used to evaluate sensitivity to allergens when prick test results are negative or equivocal.

For the prick test, a drop of antigen extract is placed on the skin, which is then tented up and pricked or punctured through the extract with the tip of a 27-gauge needle held at a 20° angle or with a commercially available prick device.

If no allergen is identified in the prick test, an intradermal test is done.

For the intradermal test, just enough extract to produce a 1- or 2-mm bleb (typically 0.02 mL) is injected intradermally with a 0.5- or 1-mL syringe and a 27-gauge short-bevel needle.

Prick and intradermal skin testing should include the diluent alone as a negative control and histamine (10 mg/mL for prick tests, 0.01 mL of a 1:1000 solution for intradermal tests) as a positive control. For patients who have had a recent (< 1 year) generalized reaction to the test antigen, testing begins with the standard reagent diluted 100-fold, then 10-fold, and then the standard concentration.

A test is considered positive if a wheal and flare reaction occurs and wheal diameter is 3 to 5 mm greater than that of the negative control after 15 to 20 minutes.

False positives occur in dermatographism (a wheal and flare reaction provoked by stroking or scraping the skin). False negatives occur when allergen extracts have been stored incorrectly or are outdated.

Certain drugs can also interfere with results and should be stopped a few days to a week before testing. These drugs include over-the-counter (OTC) and prescription antihistamines, tricyclic antidepressants, omalizumab, and monoamine oxidase inhibitors. Some clinicians suggest that testing should be avoided in patients taking beta-blockers because these patients are more likely to have risk factors for severe reactions. These risk factors tend to predict limited cardiopulmonary reserve and include coronary artery disease, arrhythmias, and older age. Also, beta-blockers can interfere with treatment of severe reactions by blocking response to beta-adrenergic agonists such as epinephrine.

Allergen-specific serum IgE tests use an enzyme-labeled anti-IgE antibody to detect binding of serum IgE to a known allergen. These tests are done when skin testing might be ineffective or risky—for example, when drugs that interfere with test results cannot be temporarily stopped before testing or when a skin disorder such as eczema or psoriasis would make skin testing difficult. For allergen-specific serum IgE tests, the allergen is immobilized on a synthetic surface. After incubation with patient serum and enzyme-labeled anti-IgE antibody, a substrate for the enzyme is added; the substrate provides colorimetric, fluorescent, or chemiluminescent detection of binding. Allergen-specific IgE tests have replaced radioallergosorbent testing (RAST), which used 125-I-labeled anti-IgE antibody. Although the allergen-specific serum IgE tests are not radioactive, they are still sometimes referred to as RAST.

Provocative testing includes an oral challenge, which involves direct exposure of the mucosae to allergen; it is indicated for patients who must document their reaction (eg, for occupational or disability claims) and for excluding an IgE-mediated allergy in patients thought to be at low risk of allergy. This test is frequently done to exclude food and drug allergy. Other types of provocative testing include asking patients to exercise to diagnose exercise-induced asthma. Various provocative tests for physical urticaria can be done in the office; they include placing an ice cube on the skin for 4 minutes to diagnose cold-induced urticaria, asking patients to exercise to increase body temperature and thus confirm cholinergic urticaria, and placing a vortex (laboratory vibratory device) on a patient's arm or hand to identify mast-cell mediated vibratory urticaria.

Ophthalmic testing has no advantage over skin testing and is rarely used.

Nasal and bronchial challenge are primarily research tools, but bronchial challenge is sometimes used when the clinical significance of a positive skin test is unclear or when no antigen extracts are available (eg, for occupation-related asthma Occupational Asthma Occupational asthma is reversible airway obstruction that develops after months to years of sensitization to an allergen encountered in the workplace. Symptoms are dyspnea, wheezing, cough,... read more ).

Treatment of Allergic and Atopic Disorders

  • Emergency treatment

  • Removal or avoidance of allergic triggers

  • H1 blockers

  • Mast cell stabilizers

  • Anti-inflammatory corticosteroids and leukotriene inhibitors

  • Immunotherapy (desensitization)

Emergency treatment

Patients who have severe allergic reactions should be advised to always carry a prefilled, self-injecting syringe of epinephrine and oral antihistamines and, if a severe reaction occurs, to use these treatments as quickly as possible and then go to the emergency department. There, patients can be closely monitored and treatment can be repeated or adjusted as needed.

Environmental control

Removal or avoidance of allergic triggers is the primary treatment and preventive strategy Prevention Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are... read more for allergy. However, when patients are sensitized to multiple allergens, complete avoidance is essentially impossible.

Antihistamines

Antihistamines block histamine receptors; they do not affect histamine production or metabolism. There are 4 different histamine receptors: H1, H2, H3, and H4.

Antihistamines that block the H1 receptor (H1 blockers) are a mainstay of treatment for allergic disorders. H2 blockers are used primarily for gastric acid suppression and but are useful for certain allergic reactions; they may be indicated as adjunctive therapy for treatment of anaphylaxis Treatment Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more , mastocytosis Mastocytosis and Mast Cell Activation Syndrome Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more Mastocytosis and Mast Cell Activation Syndrome , and certain atopic disorders, especially chronic spontaneous urticaria.

Products that contain an oral H1 blocker and a sympathomimetic (eg, pseudoephedrine) are widely available over-the-counter for use in adults and children ≥ 12 years. These products are particularly useful when both an antihistamine and an intranasal decongestant are needed; however, they are sometimes contraindicated (eg, if patients are taking a monoamine oxidase inhibitor [MAOI]).

Oral H1 blockers are classified as

  • First-generation: Sedating

  • Second-generation: Nonsedating (better thought of as less sedating)

First-generation antihistamines are widely available without prescription. They easily cross the blood-brain barrier. All have significant sedative and anticholinergic properties; they pose particular problems for older patients and for patients with glaucoma, benign prostatic hyperplasia, constipation, orthostatic hypotension, delirium, or dementia.

Second-generation antihistamines are also widely available without prescription. They do not cross the blood-brain barrier as easily as first-generation antihistamines. Second-generation antihistamines are usually preferred except when sedative effects may be therapeutic (eg, for nighttime relief of allergic symptoms, for short-term treatment of insomnia in adults or nausea in younger patients).

Antihistamines may be given by various routes, including

  • Oral (multiple—see table Oral H1 Blockers Oral H1 Blockers Oral H1 Blockers )

  • Intranasal (azelastine or olopatadine to treat rhinitis)

  • Ocular (eg, azelastine, emedastine, ketotifen, levocabastine, olopatadine, or pemirolast [not available in the US] to treat conjunctivitis)

  • Cutaneous (eg, diphenhydramine, doxepin)

Table

Mast cell stabilizers

Mast cell stabilizers block the release of mediators from mast cells.

Mast cell stabilizers are used when other drugs (eg, antihistamines, topical corticosteroids) are ineffective or not well-tolerated. They are also frequently used in patients with mast cell disease when mast activation and release of mediators overwhelms conventional antihistamines.

These drugs may be given

  • Orally (cromolyn, ketotifen)

  • Intranasally (eg, azelastine, cromolyn)

  • Ocularly (eg, azelastine, cromolyn, lodoxamide, ketotifen, nedocromil, olopatadine, pemirolast)

Several ocular and intranasal drugs (eg, azelastine, ketotifen, olopatadine, pemirolast) are dual-acting mast cell stabilizers/antihistamines.

Anti-inflammatory drugs

Oral corticosteroids are indicated for the following:

Ocular corticosteroids are used only when an ophthalmologist is involved because infection is a risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically not useful, with the exception of topical forms used to relieve conjunctival injection and itching due to allergic conjunctivitis.

Table
Table

A combination of azelastine/fluticasone (137 mcg/50 mcg) is available. Initial dose is 1 spray in each nostril twice a day.

Other drugs

  • Mild persistent asthma; Montelukast, zafirlukast, or zileuton

  • Seasonal allergic rhinitis: Montelukast

  • Urticaria: Montelukast or zafirlukast

Anti-IgE antibody (omalizumab Immunomodulators ) is indicated for the following:

  • Moderately persistent or severe asthma refractory to standard treatment

  • Chronic idiopathic urticaria refractory to antihistamine therapy

  • Nasal polyps

Immunotherapy

Exposure to allergen in gradually increasing doses (hyposensitization or desensitization) via injection or orally or in high doses sublingually can induce tolerance. This therapy is indicated when allergen exposure cannot be avoided and drug treatment is inadequate.

Mechanism is unknown but may involve induction of the following:

  • IgG antibodies, which compete with IgE for allergen or block IgE from binding with mast cell IgE receptors

  • Interferon-gamma, IL-12, and cytokines secreted by TH1 cells

  • Regulatory T cells

For full effect, injections are initially given once or twice a week. Dose typically starts at 0.1 to 1.0 biologically active units (BAU), depending on how sensitive the patient appears to be, and is increased weekly or every 2 weeks by 2 times with each injection until the maximum tolerated dose (the dose that begins to elicit moderate adverse effects) is established; patients should be observed for about 30 minutes postinjection during dose escalation because anaphylaxis may occur after injection. Subsequently, injections of the maximum tolerated dose should be given every 2 to 4 weeks year-round; year-round treatment is better than preseasonal or coseasonal treatment, even for seasonal allergies.

Allergens used are those that typically cannot be avoided:

  • Pollens

  • House dust mite feces

  • Molds

  • Venom of stinging insects

Insect venoms are standardized by weight; a typical starting dose is 0.01 mcg, and usual maintenance dose is 100 to 200 mcg. Animal dander desensitization is ordinarily limited to patients who cannot avoid exposure (eg, veterinarians, laboratory workers), but there is little evidence that it is useful. Desensitization for peanut is available, and desensitization for other food allergens is under study. Desensitization Desensitization Drug hypersensitivity is an immune-mediated reaction to a drug. Symptoms range from mild to severe and include rash, anaphylaxis, and serum sickness. Diagnosis is clinical; skin testing is occasionally... read more for penicillin and certain other drugs and for foreign (xenogeneic) serum can be done.

Adverse effects are most commonly related to overdose, occasionally via inadvertent IM or IV injection of a dose that is too high, and range from mild cough or sneezing to generalized urticaria, severe asthma, anaphylactic shock, and, rarely, death. Adverse effects can be prevented by the following:

  • Increasing the dose in small increments

  • Repeating or decreasing the dose if local reaction to the previous injection is large ( 2.5 cm in diameter)

  • Reducing the dose when a fresh extract is used

Reducing the dose of pollen extract during pollen season is recommended. Epinephrine, oxygen, and resuscitation equipment should be immediately available for prompt treatment of anaphylaxis.

Sublingual immunotherapy Treatment Allergic rhinitis is seasonal or perennial itching, sneezing, rhinorrhea, nasal congestion, and sometimes conjunctivitis, caused by exposure to pollens or other allergens. Diagnosis is by history... read more with grass pollen, ragweed, or house dust mite allergen extracts can be used for allergic rhinitis when it is induced by these allergens. The first dose is given in a health care setting; patients should be observed for 30 minutes after administration because anaphylaxis may occur. If the first dose is tolerated, patients take subsequent doses daily at home. In adults, the initial dose is not increased, but in children and adolescents aged 10 to 17 years, the dose is increased over the first 3 days. In patients with grass pollen or ragweed allergy, treatment is initiated 4 months before the onset of each grass pollen or ragweed season and maintained throughout the season.

Oral immunotherapy for peanut allergy Prevention Food allergy is an exaggerated immune response to dietary components, usually proteins. Manifestations vary widely and can include atopic dermatitis, gastrointestinal or respiratory symptoms... read more uses defatted peanut flour. Dose escalation is done using 5 incremental doses from 0.5 mg to 6 mg over one day given in a health care setting. This initial regimen is followed by a daily dose starting at 3 mg and increasing by 50 to 100% every 2 weeks over 22 weeks before reaching the maintenance dose of 300 mg once a day. Each increase in dose is given in a health care setting. If the initial dose is tolerated, subsequent doses are taken daily for 2 weeks; they can be taken at home. After patients successfully tolerate the 300-mg dose in a health care setting, they must take the 300-mg daily dose indefinitely to maintain desensitization.

Allergy treatment during pregnancy and breastfeeding

For pregnant women with allergies, avoidance of the allergen is the best way to control symptoms. If symptoms are severe, an antihistamine intranasal spray is recommended. An oral antihistamine should be used only if antihistamine intranasal sprays are inadequate.

During breastfeeding, nonsedating antihistamines are preferred. Sedating antihistamines can be used, but they may cause drowsiness and irritability in the infant. If a sedating antihistamine is required, the infant should be monitored for these effects.

Antihistamine intranasal sprays are preferred to oral antihistamines. If oral antihistamines are essential for controlling symptoms, they should be taken immediately after breastfeeding. Cyproheptadine is contraindicated during breastfeeding because it lowers prolactin levels and thus may reduce lactation.

Prevention of Allergic and Atopic Disorders

Allergic triggers should be removed or avoided. Strategies include the following:

  • Using synthetic fiber pillows and impermeable mattress covers

  • Frequently washing bed sheets, pillowcases, and blankets in hot water

  • Frequently cleaning the house, including dusting, vacuuming, and wet-mopping

  • Removing upholstered furniture, soft toys, and carpets or frequently vacuuming upholstered furniture and carpets

  • Exterminating cockroaches to eliminate exposure

  • Using dehumidifiers in basements and other poorly aerated, damp rooms

  • Using high-efficiency particulate air (HEPA) vacuums and filters

  • Avoiding food triggers

  • Limiting pets to certain rooms or keeping them out of the house

  • For people with severe seasonal allergies, possibly moving to an area that does not have the allergen

Adjunctive nonallergenic triggers (eg, cigarette smoke, strong odors, irritating fumes, air pollution, cold temperatures, high humidity) should also be avoided or controlled when possible.

Key Points

  • Atopic reactions (commonly caused by mite feces, animal dander, pollen, or mold) are IgE-mediated allergic reactions that trigger histamine release.

  • Take a thorough history, including a detailed description of the frequency and duration of attacks, relationship of symptoms to seasons or situations, family history, possible triggers, and responses to attempted treatments because history is more reliable than testing.

  • When the history and examination do not identify the cause, skin tests or an allergen-specific serum IgE test may help identify the allergen.

  • Eliminating or avoiding the allergen is key to treatment and prevention; to relieve symptoms, use H1 blockers, topical corticosteroids, and/or mast cell stabilizers.

  • If the allergen cannot be avoided and other treatments are ineffective, immunotherapy may be needed.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Drug Name Select Trade
Xolair, Xolair Prefilled
Adrenaclick, Adrenalin, Auvi-Q, Epifrin, EpiPen, Epipen Jr , Primatene Mist, SYMJEPI, Twinject
Contac Cold 12 Hour, Dimetapp Decongestant, Drixoral, ElixSure Cold, ElixSure Congestion, Entex, Genaphed , KidKare , Myfedrine, NASAL Decongestant, Nasofed, Nexafed, PediaCare Infants' Decongestant, Pseudo-Time, Silfedrine, Sudafed, Sudafed 12 Hour, Sudafed 24 Hour, Sudafed Children's Nasal Decongestant, Sudafed Congestion, Sudafed Sinus Congestion, Sudogest, Sudogest 12 Hour, Sudogest Children's , Tylenol Children's Simply Stuffy, Zephrex-D
Astelin, Astepro, Optivar
Pataday, Patanase, Patanol, Pazeo
Emadine
Livostin
Alamast
Aid to Sleep, Alka-Seltzer Plus Allergy, Aller-G-Time , Altaryl, Banophen , Benadryl, Benadryl Allergy, Benadryl Allergy Children's , Benadryl Allergy Dye Free, Benadryl Allergy Kapgel, Benadryl Allergy Quick Dissolve, Benadryl Allergy Ultratab, Benadryl Children's Allergy, Benadryl Children's Allergy Fastmelt, Benadryl Children's Perfect Measure, Benadryl Itch Stopping, Ben-Tann , Compoz Nighttime Sleep Aid, Diphedryl , DIPHEN, Diphen AF , Diphenhist, DiphenMax , Dytan, ElixSure Allergy, Genahist , Geri-Dryl, Hydramine, Itch Relief , M-Dryl, Nighttime Sleep Aid, Nytol, PediaCare Children's Allergy, PediaCare Nighttime Cough, PediaClear Children's Cough, PHARBEDRYL, Q-Dryl, Quenalin , Siladryl Allergy, Silphen , Simply Sleep , Sleep Tabs, Sleepinal, Sominex, Sominex Maximum Strength, Theraflu Multi-Symptom Strip, Triaminic Allergy Thin Strip, Triaminic Cough and Runny Nose Strip, Tusstat, Unisom, Uni-Tann, Valu-Dryl , Vanamine PD, Vicks Qlearquil Nighttime Allergy Relief, Vicks ZzzQuil Nightime Sleep-Aid
Prudoxin, Silenor, Sinequan, Zonalon
Alaway, Children's Alaway, Claritin Eye, Eye Itch Relief, Itchy Eye, Zaditor, Zyrtec Itchy Eye
Alocril, Tilade
Dymista
Singulair
Accolate
Zyflo, Zyflo CR
Periactin
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