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Type I hypersensitivity reactions underlie all atopic and many allergic disorders. The terms atopy and allergy are often used interchangeably but are different:
Thus, all atopic disorders are considered allergic, but many allergic disorders (eg, hypersensitivity pneumonitis) are not atopic. Allergic disorders are the most common disorders among people.
Atopic disorders most commonly affect the nose, eyes, skin, and lungs. These disorders include atopic dermatitis, contact dermatitis, urticaria (see Approach to the Dermatologic Patient: Urticaria), angioedema (which may be primary skin disorders or symptoms of systemic disorders), latex allergy (see Sidebar 1: Allergic and Other Hypersensitivity Disorders: Latex Sensitivity ), allergic lung disorders (eg, asthma, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis), and allergic reactions to venomous stings.
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Sidebar 1
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Etiology
Complex genetic, environmental, and site-specific factors contribute to development of allergies.
Genetic factors may be involved, as suggested by familial inheritance of disease, association between atopy and specific HLA loci, and polymorphisms of several genes, including those for the high-affinity IgE receptor β-chain, IL-4 receptor α-chain, 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 immune responses, which activate eosinophils and 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 (CD4+CD25+Foxp3+) cells (which are capable of suppressing TH2-cell responses) and IL-12–secreting dendritic cells (which drive TH1-cell responses) are perhaps also involved. But trends in developed countries toward smaller families with fewer children, cleaner indoor environments, and early use of vaccinations and antibiotics may deprive children of exposure to 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 in skin and molecules in the GI tract that direct TH2 cells to target tissues.
Allergens:
By definition, an allergen induces IgE-mediated and TH2-cell immune responses. Allergic triggers are almost always low molecular weight proteins; many of them can be constituted as airborne particles.
Allergens that most commonly cause acute and chronic allergic reactions include
Pathophysiology
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 GI mucosa; histamine facilitates inflammation and is the primary mediator of clinical atopy. Physical disruption of tissue and various substances (eg, tissue irritants, opioids, surface-active agents, complement components C3a and C5a) can trigger histamine release directly, independent of IgE.
Histamine causes the following:
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
Common symptoms include rhinorrhea, sneezing, and nasal congestion (upper respiratory tract); wheezing and dyspnea (lower respiratory tract); and itching (eyes and skin).
Signs may include nasal turbinate edema, sinus pain during palpation, wheezing, conjunctival hyperemia and edema, and skin lichenification. Stridor, wheezing, and sometimes hypotension are life-threatening signs of anaphylaxis (see Allergic and Other Hypersensitivity Disorders: Anaphylaxis). In some children, a narrow and high-arched palate, narrow chin, and elongated maxilla with overbite (allergic facies) are thought to be associated with chronic allergy.
Diagnosis
A thorough history is generally more reliable than testing or screening. History should include
Age at onset may be important in asthma because childhood asthma is likely to be atopic and asthma beginning after age 30 is not.
Nonspecific tests:
Certain tests can suggest but not confirm an allergic origin of symptoms.
CBC should be ordered to detect eosinophilia in all patients except those taking corticosteroids, which reduce the eosinophil count. An eosinophil differential of 5 to 15% of total WBCs suggests atopy but is nonspecific; 16 to 40% may reflect atopy or other conditions (eg, drug hypersensitivity, cancer, autoimmune disorders, parasitic infection); a differential of 50 to 90% almost never occurs in atopic disorders and is more characteristic of hypereosinophilic syndrome or visceral larva migrans. Total WBC is usually normal.
Conjunctival or nasal secretions or sputum can be examined for leukocytes; finding any eosinophils indicates that TH2-mediated allergic 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, infectious mononucleosis, autoimmune disorders, drug reactions, immunodeficiency disorders (hyper-IgE syndrome—see Immunodeficiency Disorders: Hyper-IgE Syndrome—and Wiskott-Aldrich syndrome—see Immunodeficiency Disorders: Wiskott-Aldrich Syndrome), and in some forms of multiple myeloma. IgE levels are probably most helpful for following response to therapy in allergic bronchopulmonary aspergillosis (see Asthma and Related Disorders: 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 symptoms. Skin testing has higher positive predictive values for diagnosing allergic rhinosinusitis 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 mites, animal danders and sera, insect venom, foods, and β-lactam antibiotics. Choice of antigens to include is based on patient history and geographic prevalence.
Two skin test techniques can be used
The prick test can detect most allergies. The intradermal test is more sensitive but less specific; it can be used to evaluate sensitivity to allergens with negative or equivocal prick test results.
For the prick test, a drop of antigen extract is placed on the skin, which is then pricked or punctured through the extract by tenting up the skin with the tip of a 27-gauge needle held at a 20° angle or with a commercially available prick device.
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 yr) 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 min. 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 OTC and prescription antihistamines, tricyclic antidepressants, and monoamine oxidase inhibitors. Patients taking β-blockers should not be tested.
Radioallergosorbent testing (RAST) detects the presence of allergen-specific serum IgE and is indicated when skin testing is contraindicated because of generalized dermatitis, dermatographism, history of anaphylaxis to the allergen, or need to continue antihistamines. A known allergen in the form of an insoluble polymer-allergen conjugate is mixed with the serum to be tested and with 125I-labeled anti-IgE antibody. Any allergen-specific IgE in the serum binds the conjugate and can be quantified by measuring the 125I-labeled antibody.
Provocative testing involves direct exposure of the mucosae to allergen and is indicated for patients who must document their reaction (eg, for occupational or disability claims) and sometimes for diagnosis of food allergy.
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).
Treatment
Environmental control:
Removal or avoidance of allergic triggers is the primary treatment for allergy, as well as the primary preventive strategy (see see Allergic and Other Hypersensitivity Disorders: Prevention)
Antihistamines:
Antihistamines block receptors; they do not affect histamine production or metabolism. H1 blockers are a mainstay of treatment for allergic disorders. H2 blockers are used primarily for gastric acid suppression and have limited usefulness for allergic reactions; they may be indicated for certain atopic disorders, especially chronic urticaria.
Oral H1 blockers relieve symptoms in various atopic and allergic disorders (eg, seasonal hay fever, allergic rhinitis, conjunctivitis, urticaria, other dermatoses, minor reactions to blood transfusion incompatibilities and to x-ray radiopaque dyes); they are less effective for allergic bronchoconstriction and vasodilation. Onset of action is usually 15 to 30 min, with peak effects in 1 h; duration of action is usually 3 to 6 h.
Oral H1 blockers are classified as sedating or nonsedating (better thought of as less sedating). Sedating antihistamines are widely available without prescription. All have significant sedative and anticholinergic properties; they pose particular problems for the elderly and for patients with glaucoma, benign prostatic hyperplasia, constipation, or dementia. Nonsedating (nonanticholinergic) antihistamines are preferred except when sedative effects may be therapeutic (eg, for nighttime relief of allergy, for short-term treatment of insomnia in adults or nausea in younger patients). Anticholinergic effects may also partially justify use of sedating antihistamines to relieve rhinorrhea in URIs.
Antihistamine solutions may be intranasal (azelastine to treat rhinitis) or ocular (azelastine, emedastine, ketotifen, levocabastine, or olopatadine to treat conjunctivitis). Topical diphenhydramine is available but should not be used; its efficacy is unproved, drug sensitization (ie, allergy) may occur, and anticholinergic toxicity can develop in young children who are simultaneously taking oral H1 blockers.
Mast cell stabilizers:
These drugs (eg, cromolyn) block the release of mediators from mast cells; they are used when other drugs (eg, antihistamines, topical corticosteroids) are ineffective or not well tolerated. Ocular forms (eg, lodoxamide, olopatadine, pemirolast) are also available.
Anti-inflammatory drugs:
Corticosteroids can be given intranasally (see Table 3: Allergic and Other Hypersensitivity Disorders: Inhaled Nasal Corticosteroids and Mast Cell Stabilizers ) or orally. Oral corticosteroids are indicated for systemic allergic disorders that are severe but self-limited (eg, seasonal asthma flares, severe widespread contact dermatitis) and for disorders refractory to other measures. NSAIDs are typically not useful, with the exception of topical ketorolac for allergic conjunctivitis.
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Table 3
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| Inhaled Nasal Corticosteroids and Mast Cell Stabilizers |
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Drug
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Dose per Spray
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Initial Dose (Sprays per Nostril)
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Sprays or Actuations per Canister
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Inhaled nasal corticosteroids
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Beclomethasone
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42 μg
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> 12 yr: 1 spray bid to qid
6–12 yr: 1 spray bid
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200
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Budesonide
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32 μg
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≥ 6 yr: 1 spray once/day
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200
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Flunisolide
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29 μg
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6–14 yr: 1 spray tid or 2 sprays bid
Adults: 2 sprays bid
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125
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Fluticasone
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50 μg
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4–12 yr: 1 spray once/day
> 12 yr: 2 sprays once/day
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120
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Triamcinolone acetonide
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55 μg
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> 6–12 yr: 1 spray once/day
> 12 yr: 2 sprays once/day
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100
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Mast cell stabilizers
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Cromolyn
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5.2 mg
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≥ 6 yr: 1 spray tid or qid
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200
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Leukotriene modifiers are indicated for treatment of mild persistent asthma (see Asthma and Related Disorders: Drug therapy) and seasonal allergic rhinitis.
Anti-IgE antibody (omalizumab) is indicated for moderately persistent or severe asthma refractory to standard treatment (see Asthma and Related Disorders: Drug therapy).
Immunotherapy:
Exposure to allergen in gradually increasing doses (hyposensitization or desensitization) via injection or in high doses sublingually can induce tolerance and is indicated when allergen exposure cannot be avoided and drug treatment is inadequate. Mechanism is unknown but may involve induction of IgG antibodies, which compete with IgE for allergen or block IgE from binding with mast cell IgE receptors; induction of interferon-γ, IL-12, and cytokines secreted by TH1 cells; or induction of regulatory T cells.
For full effect, injections must be given monthly. Dose typically starts at 0.1 to 1.0 biologically active units (BAU), depending on initial sensitivity, and is increased weekly or biweekly by ≤ 2 times with each injection until a maximum tolerated concentration is reached; patients should be observed for about 30 min postinjection during dose escalation because anaphylaxis may occur after injection. Maximum dose should be given q 4 to 6 wk 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 mites, molds, and venom of stinging insects. Insect venoms are standardized by weight; a typical starting dose is 0.01 μg, and usual maintenance dose is 100 to 200 μg. 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. Food desensitization is not indicated. Desensitization for penicillin and certain other antibiotics and for foreign (xenogeneic) serum can be done (see Allergic and Other Hypersensitivity Disorders: Anaphylaxis).
Adverse effects are most commonly related to overdose, occasionally via an inadvertent IM or IV injection, and range from mild cough or sneezing to generalized urticaria, severe asthma, anaphylactic shock, and, rarely, death. They can be prevented by the following:
Reducing the dose of pollen extract during pollen season is recommended. Epinephrine, O2, and resuscitation equipment should be immediately available for prompt treatment of anaphylaxis.
Prevention
Allergic triggers should be removed or avoided. Strategies include the following:
Adjunctive nonallergenic triggers (eg, cigarette smoke, strong odors, irritating fumes, air pollution, cold temperatures, high humidity) should also be avoided or controlled when possible.
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 and skin testing. Treatment is with a combination of antihistamines, decongestants, nasal corticosteroids, and, for severe, refractory cases, desensitization.
Allergic rhinitis may occur seasonally (hay fever) or throughout the year (perennial rhinitis). At least 25% of perennial rhinitis is nonallergic.
Seasonal rhinitis is caused by
Causes also differ by region, and seasonal rhinitis is occasionally caused by airborne fungal spores. Perennial rhinitis is caused by year-round exposure to indoor inhaled allergens (eg, dust mites, cockroaches, animal dander, mold) or by strong reactivity to plant pollens in sequential seasons.
Allergic rhinitis and asthma frequently coexist; whether rhinitis and asthma result from the same allergic process (one-airway hypothesis) or rhinitis is a discrete asthma trigger is unclear.
Nonallergic forms of perennial rhinitis include infectious, vasomotor, atrophic, hormonal, drug-induced, and gustatory rhinitis (see Nose and Paranasal Sinus Disorders: Rhinitis).
Symptoms and Signs
Patients have itching (in the nose, eyes, or mouth), sneezing, rhinorrhea, and nasal and sinus obstruction. Sinus obstruction may cause frontal headaches; sinusitis is a frequent complication. Coughing and wheezing may also occur, especially if asthma is also present.
The most prominent feature of perennial rhinitis is chronic nasal obstruction, which, in children, can lead to chronic otitis media; symptoms vary in severity throughout the year. Itching is less prominent than in seasonal rhinitis.
Signs include edematous, bluish-red nasal turbinates, and, in some cases of seasonal rhinitis, conjunctival injection and eyelid edema.
Diagnosis
Allergic rhinitis can almost always be diagnosed based on history alone. Diagnostic testing is not routinely needed unless patients do not improve when treated empirically; for such patients, skin tests are done to identify a reaction to pollens (seasonal) or to dust mite, cockroach, animal dander, mold, or other antigens (perennial), which can be used to guide additional treatment. Occasionally, skin test results are ambivalent, or testing cannot be done (eg, because patients are taking drugs that interfere with results); then, RAST is done. Eosinophilia detected on nasal smear plus negative skin tests suggests aspirin sensitivity or nonallergic rhinitis with eosinophilia (NARES).
Diagnosis of infectious, vasomotor, atrophic, hormonal, drug-induced, and gustatory rhinitis is usually based on history or therapeutic trials.
Treatment
Treatment of seasonal and perennial allergic rhinitis is generally the same, although attempts at environmental control (eg, eliminating dust mites and cockroaches) are recommended for perennial rhinitis.
The most effective first-line drug treatments are
Less effective alternatives include nasal mast cell stabilizers (eg, cromolyn) given bid to qid, the nasal H1 blocker azelastine 2 puffs once/day, and nasal ipratropium 0.03% 2 puffs q 4 to 6 h, which relieves rhinorrhea. Intranasal saline, often forgotten, helps mobilize thick nasal secretions and hydrate nasal mucous membranes.
Immunotherapy may be more effective for seasonal than for allergic perennial rhinitis; it is indicated when symptoms are severe, allergen cannot be avoided, and drug treatment is inadequate.
Desensitization may be needed for severe, refractory rhinitis. First attempts at desensitization should begin soon after the pollen season ends to prepare for the next season; adverse reactions increase when desensitization is started during the pollen season because the person's allergic immunity is already maximally stimulated.
Montelukast relieves allergic rhinitis symptoms, but its role relative to other treatments is uncertain. Anti-IgE antibody is under study for treatment of allergic rhinitis but will probably have a limited role because less expensive, effective alternatives are available.
Treatment of NARES is nasal corticosteroids. Treatment of aspirin sensitivity is aspirin avoidance, with desensitization and leukotriene blockers as needed. Nasal polyps may respond to nasal corticosteroids.
Food Allergy
Food allergy is an exaggerated immune response to dietary proteins.
Food allergy should be distinguished from nonimmune reactions to food (eg, lactose intolerance, irritable bowel syndrome, infectious gastroenteritis) and reactions to additives (eg, monosodium glutamate, metabisulfite, tartrazine) or food contaminants (eg, latex dust in food handled by workers wearing latex gloves), which cause most food reactions. Prevalence of true food allergy ranges from < 1 to 3% and varies by geography and method of ascertainment; patients tend to confuse intolerance with allergy.
Etiology
Almost any food or food additive can cause an allergic reaction, but the most common triggers include
Cross-reactivity between food and nonfood allergens exists, and sensitization may occur nonenterally. For example, patients with oral allergies (typically, pruritus, erythema, and edema of the mouth when fruits and vegetables are eaten) may have been sensitized by pollen exposure; children with peanut allergy may have been sensitized by topical creams containing peanut oil used to treat rashes. Many patients who are allergic to latex are also allergic to bananas, kiwis, avocadoes, or a combination.
In general, food allergy is mediated by IgE, T cells, or both. IgE-mediated allergy (eg, urticaria, asthma, anaphylaxis) is acute in onset, usually develops during infancy, and occurs most often in people with a strong family history of atopy. T cell–mediated allergy (eg, dietary protein gastroenteropathies, celiac disease) manifests gradually and is chronic. Allergies mediated by both IgE and T cells (eg, atopic dermatitis, eosinophilic gastroenteropathy) tend to be delayed in onset or chronic.
Eosinophilic gastroenteropathy:
This unusual disorder causes pain, cramps, and diarrhea with blood eosinophilia, eosinophilic infiltrates in the gut, protein-losing enteropathy, and a history of atopic disorders. Eosinophilic esophagitis sometimes accompanies eosinophilic gastroenteropathy. Initially, it may cause dysphagia and dysmotility or, in children, feeding intolerance and abdominal pain.
Symptoms and Signs
Symptoms and signs vary by allergen, mechanism, and patient age. The most common manifestation in infants is atopic dermatitis alone or with GI symptoms (nausea, vomiting, diarrhea). Children usually outgrow these manifestations and react increasingly to inhaled allergens, with symptoms of asthma and rhinitis; this progression is called atopic march. By age 10 yr, patients rarely have respiratory symptoms after the allergenic food is eaten, even though skin tests remain positive. If atopic dermatitis persists or appears in older children or adults, its activity seems largely independent of IgE-mediated allergy, even though atopic patients with extensive dermatitis have much higher serum IgE levels than those who are free of dermatitis.
When food allergy persists in older children and adults, reactions tend to be more severe (eg, explosive urticaria, angioedema, even anaphylaxis). In a few patients, food (especially wheat and celery) triggers anaphylaxis only if they exercise soon afterward; mechanism is unknown. A few patients have food-induced or aggravated migraine, confirmed by blinded oral challenge. Occasionally, cheilitis, aphthae, pylorospasm, spastic constipation, pruritus ani, and perianal eczema are attributed to food allergy.
Diagnosis
Severe food allergy is usually obvious in adults. When it is not and when it occurs in children (usually), diagnosis may be difficult, and the disorder must be differentiated from functional GI problems.
If a food reaction is suspected, the relationship of symptoms to foods is assessed by skin testing or IgE-specific RAST. A positive test does not confirm a clinically relevant allergy, but a negative test excludes it. If a skin test is positive, the tested food is eliminated from the diet; if symptoms are relieved, the patient is reexposed to the food (preferably in a double-blind test) to see whether symptoms recur. (See also the American Gastroenterological Association medical position statement: Guidelines for the evaluation of food allergies.)
Alternatives to skin testing include eliminating foods the patient suspects of causing symptoms and prescribing a diet that consists of relatively nonallergenic foods and that eliminates common food allergens (see Table 4: Allergic and Other Hypersensitivity Disorders: Allowable Foods in Elimination Diets*). No foods or fluids may be consumed other than those specified. Pure products must always be used. Many commercially prepared products and meals contain an undesired food in large amounts (eg, commercial rye bread contains wheat flour) or in traces as flavoring or thickeners, and determining whether an undesired food is present may be difficult.
If no improvement occurs after 1 wk, another diet should be tried. If symptoms are relieved, one new food is added and eaten in large amounts for > 24 h or until symptoms recur. Alternatively, small amounts of the food to be tested are eaten in the clinician's presence, and the patient's reactions observed. Aggravation or recrudescence of symptoms after addition of a new food is the best evidence of allergy.
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Table 4
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| Allowable Foods in Elimination Diets* |
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Food
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Diet No. 1
(No beef, pork, fowl, milk, rye, or corn)
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Diet No. 2
(No beef, lamb, milk, or rice)
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Diet No. 3
(No lamb, fowl, rye, rice, corn, or milk)
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Cereal
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Rice products
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Corn products
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None
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Vegetables
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Artichokes, beets, carrots, lettuce, spinach
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Asparagus, corn, peas, squash, string beans, tomatoes
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Beets, lima beans, potatoes (white and sweet), string beans, tomatoes
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Meats
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Lamb
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Bacon, chicken
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Bacon, beef
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Flour (bread or biscuits)
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Rice
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Corn, 100% rye (ordinary rye bread contains wheat)
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Lima bean, potato, soybean
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Fruits
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Grapefruit, lemons, pears
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Apricots, peaches, pineapple, prunes
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Apricots, grapefruit, lemons, peaches
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Fat
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Cottonseed oil, olive oil
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Corn oil, cottonseed oil
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Cottonseed oil, olive oil
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Beverages
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Coffee (black), lemonade, tea
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Coffee (black), lemonade, tea
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Coffee (black), lemonade, juice from approved fruit, tea
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Miscellaneous
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Cane sugar, gelatin, maple sugar, olives, salt, tapioca pudding
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Cane sugar, corn syrup, gelatin, salt
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Cane sugar, gelatin, maple sugar, olives, salt, tapioca pudding
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*Diet No. 4: If symptoms persist when patients are following any of the above 3 elimination diets and diet is still suspected, daily diet may be restricted to an elemental diet.
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Treatment
Treatment consists of eliminating the food that triggers the allergic reaction. Thus, diagnosis and treatment overlap. When assessing an elimination diet's effect, clinicians must consider that food sensitivities may disappear spontaneously.
Oral desensitization (by first eliminating the allergenic food for a time, then giving small amounts and increasing them daily) is not effective nor is use of sublingual drops of food extracts. Antihistamines are of little value except in acute general reactions with urticaria and angioedema. Oral cromolyn has been used with apparent success. Prolonged corticosteroid treatment is helpful for symptomatic eosinophilic enteropathy.
Anaphylaxis
Anaphylaxis is an acute, life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms include stridor, dyspnea, wheezing, and hypotension. Diagnosis is clinical. Bronchospasm and upper airway edema are treated with inhaled or injected β-agonists and sometimes endotracheal intubation. Hypotension requires IV fluids and vasopressors.
Etiology
Anaphylaxis is typically triggered by
Peanut and latex allergens may be airborne. History of atopy does not increase risk of anaphylaxis but increases risk of death when anaphylaxis occurs.
Pathophysiology
Interaction of antigen with IgE on basophils and mast cells triggers release of histamine, leukotrienes, and other mediators that cause diffuse smooth muscle contraction (bronchoconstriction, vomiting, diarrhea) and vasodilation with plasma leakage.
Anaphylactoid reactions:
These reactions are clinically indistinguishable from anaphylaxis but do not involve IgE and do not require prior sensitization. They occur via direct stimulation of mast cells or via immune complexes that activate complement. The most common triggers are iodinated radiographic radiopaque dye, aspirin, other NSAIDs, opioids, blood transfusions, Ig, and exercise.
Symptoms and Signs
Symptoms typically involve the skin, upper or lower airways, cardiovascular system, or GI tract. One or more areas may be affected, and symptoms do not necessarily progress, although each patient typically manifests the same reaction to subsequent exposure.
Symptoms range from mild to severe and include flushing, pruritus, sneezing, rhinorrhea, nausea, abdominal cramps, diarrhea, sense of choking or dyspnea, palpitations, and dizziness.
Signs include hypotension, tachycardia, urticaria, angioedema, wheezing, cyanosis, and syncope. Shock can develop within minutes, and patients may experience seizures, become unresponsive, and die. Cardiovascular collapse can occur without respiratory or other symptoms.
Diagnosis
Diagnosis is clinical. Risk of rapid progression to shock leaves no time for testing, although mild equivocal cases can be confirmed by measuring 24-h urinary levels of N-methylhistamine or serum levels of tryptase.
Treatment
Epinephrine is the cornerstone of treatment and should be given immediately. It can be given sc or IM (usual dose is 0.3 to 0.5 mL of a 1:1000 solution in adults or 0.01 mL/kg in children, repeated every 10 to 30 min); maximal absorption occurs when the drug is given IM in the lateral thigh. Patients with cardiovascular collapse or severe airway obstruction may be given epinephrine IV in a single dose (3 to 5 mL of a 1:10,000 solution over 5 min) or by continuous drip (1 mg in 250 mL 5% D/W for a concentration of 4 μg/mL, starting at 1 μg/min up to 4 μg/min [15 to 60 mL/h]). Epinephrine may also be given by sublingual injection (0.5 mL of 1:1000 solution) or through an endotracheal tube (3 to 5 mL of a 1:10,000 solution diluted to 10 mL with saline). A 2nd injection of epinephrine sc may be needed. Glucagon 1-mg bolus followed by 1-mg/h infusion should be used in patients taking oral β-blockers, which attenuate the effect of epinephrine.
Patients who have stridor and wheezing unresponsive to epinephrine should be given O2 and be intubated. Early intubation is recommended because waiting for a response to epinephrine may allow upper airway edema to progress sufficiently to prevent endotracheal intubation and require cricothyrotomy.
Hypotension can usually be treated with 1 to 2 L (20 to 40 mL/kg in children) of isotonic IV fluids (eg, 0.9% saline). Hypotension refractory to fluids and IV epinephrine may require vasopressors (eg, dopamine 5 μg/kg/min).
Antihistamines—both H1 blockers (eg, diphenhydramine 50 to 100 mg IV) and H2 blockers (eg, cimetidine 300 mg IV)—should be given q 6 h until symptoms resolve. Inhaled β-agonists are useful for managing bronchoconstriction; albuterol 5 to 10 mg by continuous nebulization can be given.
Corticosteroids have no proven role but may help prevent late-phase reaction in 4 to 8 h; methylprednisolone 125 mg IV initially is adequate.
Prevention
Primary prevention is avoidance of known triggers. Desensitization is used for allergen triggers that cannot reliably be avoided (eg, insect stings). Patients with past reactions to radiopaque dye should not be reexposed; when exposure is absolutely necessary, patients are given 3 doses of prednisone 50 mg po q 6 h, starting 18 h before the procedure, and diphenhydramine 50 mg po 1 h before the procedure; however, no evidence supports the efficacy of this approach (see also Principles of Radiologic Imaging: Allergic-type contrast reactions).
Patients with an anaphylactic reaction to insect stings, foods, or other known substances should wear an alert bracelet and carry a prefilled epinephrine syringe (containing 0.3 mg for adults and 0.15 mg for children) for prompt self-treatment after exposure.
Last full review/revision September 2008 by Peter J. Delves, PhD
Content last modified September 2008
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