immunology allergic disorders
Overview of Allergic and Atopic Disorders
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 Age at onset may be important in Asthma because childhood asthma is likely to be atopic and asthma beginning after age 30 is not. 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. are elevated in atopic disorders but are of little help in diagnosis because they may also be elevated in Approach to Parasitic Infections , Skin testinguses 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 theprick 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 theintradermal 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 asepinephrine. Allergen-specific serum IgE testsuse 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 testingincludes 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 testinghas no advantage over skin testing and is rarely used. 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 Work-Related Asthma ). 