Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Nomenclature of allergy Diagnosis of IgE Sensitization Allergic hypersensitivity (immunological mechanism defined or strongly suspected) Non-allergic hypersensitivity (immunological mechanism excluded) IgE-mediated Not IgE-mediated Johansson SGO et al. Allergy 2001 and JACI 2004 Atopy Allergic disease progression with age Atopy is a personal and/or familial tendency, usually expressed anytime in life from childhood and adolescence, into maturity, to become sensitized and produce IgE antibodies in response to ordinary exposures to allergens, usually proteins. As a consequence, atopic persons can develop IgE-mediated allergic diseases including asthma, rhinoconjunctivitis, or eczema. WAO Nomenclature Review Committee Johansson et al. J Allergy Clin Immunol 2004;113:832-6 Saarinen UM et al. Lancet 1995 The essential components of allergy diagnosis Clinical History and Physical Examination Symptoms versus Exposure Diagnostic Confirmatory Test Skin Test (Puncture, Intradermal) Allergen-specific IgE antibody serology Provocation Test Oral, Nasal, Bronchial Challenge Key concepts in allergy diagnosis • A proper allergy history involves determining the symptom complex, any relationship to allergen exposure and a careful physical examination, looking for the specific signs of allergy. • Once allergic disease is suspected, a confirmatory test (skin test or IgE antibody serology) is performed to verify sensitization by the presence of allergen specific IgE antibody.1-3 • Where it can be performed and interpreted, skin prick testing (SPT) remains the primary confirmatory test because it is fast, safe, sensitive, minimally invasive and results correlate with nasal and bronchial challenges. • Quantitative IgE antibody serology is an accepted alternative. • SPT and/or IgE serology are essential adjuncts to history and physical exam when making the diagnosis of allergy. • Provocation tests are sometimes needed to confirm sensitization. 1. Oppenheimer Ann Allergy 2006;S1:6-12, 2. 2. Bousquet Clin Allergy 17:529-36, 1987 3. Cockroft Am Rev Respir Dis 135:264-7., 1987 Allergy History • • • • Demographics (age) Symptoms: frequency and severity Pattern: intermittent, persistent or seasonal Response to environmental factors: – Temperature changes, odors, humidity, alcohol • Occupation and hobbies • Identification of allergens/irritants in the home, office or environment • Treatment, past and present: efficacy, compliance, side effects Allergy Symptoms Clinical History Drives the Diagnosis • Hypersensitivity to an injected, ingested, or inhaled antigen in response to a first exposure. – – – – Skin: itch, rash, swelling, redness Eyes: itchy, tears, watery, redness, crusting Nose: runny, itchy, congestion, sneezing Lung: wheezing, cough, tightness, shortness of breath – Stomach-Intestines: nausea, vomiting, bloating, diarrhea – Heart-Blood Vessels: anaphylaxis, syncope, faintness, death Allergy Physical Examination: The Everted Eyelid Allergy Physical Examination: The Swollen Nasal Mucosa Allergen extracts • An allergen extract used for diagnosis or treatment is prepared by incubating the allergenic material in a physiological buffer followed by lipid extraction. Selection of aeroallergens • An evidence-based approach that minimizes irrelevant test antigens can reduce patient discomfort and costs. • An understanding of pollen aerobiology and knowledge of allergenic cross-reactivity between regional pollinating plant families is necessary in selecting appropriate aeroallergen test panels. Practice Parameters for Allergy Diagnostic Testing Ann Allergy 1995; 75:543-625 Skin testing and IgE antibody serology Powerful adjuncts for confirming allergy in: • • • • • • Rhinitis and sinusitis Asthma, cough, dyspnea Eczema Food allergy Insect sting allergy Drug allergy (some i.e. beta-lactams and local anesthetics) • Occupational (some) • Anaphylaxis Confirmatory Skin Testing Use of skin prick tests (SPT) • Diagnosis of allergy • Confirmatory evidence (positive, negative) of IgE sensitization in support of the clinical history • Identifies the allergen against which IgE is specifically directed, which is essential for allergen avoidance measures • Educational value: visual reinforcement strengthens compliance of verbal advice Skin prick testing • SPT is easy to perform and rarely causes generalized reactions. • Patients may have positive SPT but no clinical disease. A positive SPT indicates the presence of IgE antibodies against that allergen but does not indicate clinical sensitivity. A correlation between the history and SPT is essential. • The results can be unreliable if the patient takes certain drugs, such as anti-histamines and tricyclic anti-depressants. General rules for successful SPT • It is imperative that the technician performing the skin tests as well as the clinician ordering/interpreting these tests understands the characteristics of the specific tests they are administering. • This includes: – type of skin testing – device used – placement of tests (location and adjacent testing) – the particular extracts (source, concentration) being used – the potential confounder of medications that may suppress skin test response. Skin Prick Testing Solutions Skin prick testing Prick-prick test reactions Not all allergens are available as a skin test extract: fruit prick-prick test Puncture skin testing devices • There are several different devices available for skin prick testing. QTS GTK • These devices result in varying degrees of trauma to the skin with differing levels of skin test reaction. • Thus, the physician should be familiar with the characteristics of the device used in his/her practice, as each require different criteria for what constitutes a positive reaction. M T 2 AS QT ST GP QNT Suppression of skin tests by medication • Most antihistamines and anti-depressants suppress skin tests for 3-7 days. • H2 antagonists have no, or a very minor, effect. • Bronchodilators do not affect skin tests. • Short-term and low dose oral corticosteroids have no effect. – Reports vary on long-term high-dose use. Cook J Allergy Clin Immunol 1973;51:71-7 Rao KS J Allergy Clin Immunol 1988;82:752-7 Miller J J Allergy Clin Immunol 1989;84:895-99 Slott RIJ Allergy Clin Immunol 1974;554:229-34 Skin test safety Review of surveys of fatal reactions to skin testing between 1959-2001 • 9 deaths associated with skin testing • 1 death associated with SPT – History of unstable asthma with FEV-1 36% 1 week prior – Tested to 90 foods Lockey JACI 1987;79:66077 Reid JACI 1993;92:6-15 Bernstein JACI 2004;113:1129-36 In-Vivo provocation tests • Provocation tests involve the challenge of the affected organ by serial dilutions of an allergen extract or by the actual, suspected allergen source material, e.g. food or drug. • A provocation test is time-consuming. It can result in dangerous clinical reactions and should only be performed by experienced persons with access to lifesaving equipment. Due to space limitations, details of nasal, lung and insect sting challenge tests will not be discussed further in this presentation. Confirmatory Total and Allergen-Specific IgE Antibody Serological Testing Serological testing for allergen-IgE antibody is recommended when InVivo tests cannot be used Skin testing • When the patient is taking anti-histamines or other confounding medications for skin tests • When the patient has eczema or dermographism • Immediately (up to 6 weeks) following an anaphylactic event • If the patient is morbidly afraid of skin testing Interpretation of allergenspecific IgE antibody results • Presence of allergen-specific IgE antibodies in serum indicates sensitization. It does not equal clinical symptoms. • Serum IgE antibody is an absolute prerequisite for the development of IgEmediated symptoms. • With precise, quantitative assays, IgE antibody production can be detected at an early stage, even before clinical symptoms have fully developed. In Vitro testing • Allergen • IgE that is specific IgE free floating that is bound in patient’s to patient’s serum mast cells Clinical Utility of Diagnostic (Skin and Serology) Confirmatory Tests Prick skin tests correlate with nasal challenge Nasal Challenge (Pollen Grains) 1215 Relationship between nasal challenges with pollen grains and skin prick test Endpoints in patients allergic to Dactylis glomerata 405 135 45 15 0 0 1 2 3 4 5 6 Even SPT may result in “false positives” in respiratory allergy • SPT results need to be interpreted carefully. There MUST be a correlation with the history • Skin tests are a diagnostic tool, an adjunct to the history, and do not make the diagnosis 7 8 Prick Test Endpoint (Log3 Allergen Dose) Rs= 0.54 p< 0.005 Bousquet Clin Allergy 1987;17:529-38 IgE antibody determination allows evaluation of disease prognosis Early sensitization can be predictive of future allergies: • IgE antibodies to food early in life may be associated with a high risk of developing IgE antibodies to inhalants later in life. • IgE antibodies to inhalants prior to symptoms also predict evolving allergic disease. • Even low levels of IgE antibodies to an allergen are of importance, since they can predict a later development of symptoms caused by this allergen. Adinoff & Nelson. JACI 1990;86:766 Utility of In-vivo and I-vitro diagnostic methods for cat allergy: conclusions • Both the SPT and IgE antibody serology (Immuno-CAP System) exhibited an equivalent excellent efficiency (83.1%, 83.4%) in the diagnosis of cat allergy. RA Wood, et al. JACI 1999;103:773 Tests for diagnosis of food allergy skin tests vs challenge test • PPV of positive SPT - <50% vs DBPCFC • NPV of negative SPT - >95% vs DBPCFC Diagnosis of allergic diseases summary • The decision that the patient’s symptoms and clinical signs represent an allergic disease is made by an experienced clinician on the basis of the case history, physical examination, and symptoms following allergen exposure. • Measurement of IgE antibodies by SPT or serological assays confirm the presence of specific IgE antibodies and are an essential adjunct in making a definitive diagnosis of allergic disease.