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How Much Is Allergy Skin Prick Test

  • Journal List
  • Clin Transl Allergy
  • v.iii; 2013
  • PMC3565910

Clin Transl Allergy. 2013; 3: 3.

The skin prick test – European standards

Lucie Heinzerling, corresponding author 1 Adriano Mari,ii Karl-Christian Bergmann,3 Megon Bresciani,iv Guido Burbach,3 Ulf Darsow,v Stephen Durham,6 Wytske Fokkens,vii Mark Gjomarkaj,eight Tari Haahtela,ix Ana Todo Bom,10 Stefan Wöhrl,11 Howard Maibach,12 and Richard Lockey13

Lucie Heinzerling

oneSection of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany

Adriano Mari

2Board Member of the EAACI Allergy Diagnosis Interest Grouping, IDI-IRCCS, Center for Molecular Allergology, Rome, Italian republic

Karl-Christian Bergmann

threeDepartment of Dermatology and Allergy, Charité Universitätsmedizin-Berlin, Berlin, Frg

Megon Bresciani

fourConsiglio Nazionale delle Ricerche, Rome, Italy

Guido Burbach

3Department of Dermatology and Allergy, Charité Universitätsmedizin-Berlin, Berlin, Germany

Ulf Darsow

fiveDepartment of Dermatology and Allergy Biederstein and Division of Environmental Dermatology and Heart of Allergy and Surroundings (ZAUM), Technical University, Munich, Frg

Stephen Durham

6Section of Respiratory Medicine, Purple Brompton Hospital, London, U.k.

Wytske Fokkens

viiDepartment of Otorhinolaryngology, Bookish Medical Centre, Amsterdam, Netherlands

Mark Gjomarkaj

eightConsiglio Nazionale delle Ricerche, Palermo, Italy

Tari Haahtela

9Skin and Allergy Hospital, University Central Hospital, Helsinki, Republic of finland

Ana Todo Bom

10ImunoAlergologia, Coimbra University, Coimbra, Portugal

Stefan Wöhrl

elevenDepartment of Dermatology, Medical Academy of Vienna, Vienna, Republic of austria & Floridsdorf Allergy Center (FAZ), Vienna, Republic of austria

Howard Maibach

12Department of Dermatology, Academy of California, San Francisco, California, U.s.

Richard Lockey

13Division of Allergy & Immunology, Academy of Southward Florida College of Medicine, Tampa, Florida, United states of america

Received 2012 Sep 20; Accustomed 2013 January 18.

Supplementary Materials

Additional file i: Tabular array S3 Peel prick test panel – inhalant allergens.

GUID: 424BD37F-BFC2-4B41-AE1C-83F2E5D26CA9

Abstract

Skin prick testing is an essential test process to confirm sensitization in IgE-mediated allergic disease in subjects with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and food and drug allergy. This manuscript reviews the available evidence including Medline and Embase searches, abstracts of international allergy meetings and position papers from the world allergy literature. The recommended method of prick testing includes the appropriate use of specific allergen extracts, positive and negative controls, estimation of the tests after fifteen – xx minutes of awarding, with a positive upshot defined every bit a wheal ≥three mm diameter. A standard prick test panel for Europe for inhalants is proposed and includes hazel (Corylus avellana), alder (Alnus incana), birch (Betula alba), plane (Platanus vulgaris), cypress (Cupressus sempervirens), grass mix (Poa pratensis, Dactilis glomerata, Lolium perenne, Phleum pratense, Festuca pratensis, Helictotrichon pretense), Olive (Olea europaea), mugwort (Artemisia vulgaris), ragweed (Ambrosia artemisiifolia), Alternaria alternata (tenuis), Cladosporium herbarum, Aspergillus fumigatus, Parietaria, cat, dog, Dermatophagoides pteronyssinus, Dermatophagoides farinae, and cockroach (Blatella germanica). Standardization of the skin examination procedures and standard panels for different geographic locations are encouraged worldwide to allow better comparisons for diagnostic, clinical and research purposes.

Keywords: Sensitization, Inhalant allergens, Skin prick test panel, Aallergies, Type I allergy, Diagnostic test, Asthma

Skin prick testing (SPT) is a reliable method to diagnose IgE-mediated allergic affliction in patients with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and suspected food and drug allergy. It provides evidence for sensitization and can help to confirm the diagnosis of a suspected type I allergy. It is minimally invasive, inexpensive, results are immediately available and when carried out past trained health professionals, reproducible. Since the outset publication about SPT past Helmtraud Ebruster in 1959 [one], who extensively researched this diagnostic test, it has been used as a primary diagnostic tool to detect type I hypersensitivity reactions. Although the principle of SPT notwithstanding largely resembles the original methods described, a wide array of interpretations and modifications has led to macerated comparability when SPT results are reported. In addition, the different kind of extracts used in diverse countries makes comparison of data difficult.

The Global Allergy and Asthma European Network (GAiiLEN) is a network of research investigators formed to broaden the cooperation of allergy and asthma inquiry throughout Europe. The purpose of the GAtwoLEN quality direction is to standardize procedures used to diagnose and treat allergic diseases. A survey was conducted to assess SPT practices at the different participating centres at the debut of the program. Although there were similarities in technique for SPT, e.g., the utilize of positive and negative controls and requesting information from the patient about medications that could interfere with test results, there were likewise hitting differences [2]. These investigators realized that standardization of SPT procedures is desirable so that findings from clinical exercise and research become more comparable. Therefore, a GA2LEN protocol was developed using a mutual console of inhalant allergens (Table1) and a standard operating procedure to perform and appropriately interpret SPT results based on published practice guidelines, the European Academy of Allergy and Clinical Immunology (EAACI) Position Paper, the Nordic standards and the International Study of Asthma and Allergies in Childhood (ISAAC) stage Ii protocol. The large multicenter GAiiLEN study was carried out in 17 centers in 14 countries and showed that a proposed standard protocol and allergen panel for SPT are feasible [three,4].

Table 1

Standard prick examination console for inhalant allergens

Allergen/command
Histamindihydrochloride 0,1 % (positive command)

NaCl 0.9% (negative command)

Hazel
Corylus avellana
Alder
Alnus incana
Birch
Betula alba
Plane
Platanus vulgaris
Cypress
Cupressus sempervirens
Grass mix
smooth meadow grass/Poa pratensis, erect's pes grass/Dactilis glomerata, perennial rye grass/Lolium perenne, timothy grass/Phleum pratense, meadow fescue/Festuca pratensis, meadow oat grass/Helictotrichon pretense
Olive
Olea europaea
Mugwort
Artemisia vulgaris
Ragweed
Ambrosia artemisiifolia
Alternaria
Alternaria alternata (tenuis)
Cladosporium
Cladosporium herbarum
Aspergillus
Aspergillus fumigatus
Parietaria
Parietaria
Cat

Dog

Dermatophagoides pteronyssinus

Dermatophagoides farinae

Blatella Blatella germanica

Indication for SPT

SPT is indicated if a type I (immediate type) allergy is suspected, based on the medical history and clinical symptoms; they can identify sensitivity to inhalant, food, drug or occupational allergens. SPTs thus provide objective confirmation of sensitivity, whereas the relevance of such sensitivity to allergens should always exist carefully interpreted in the light of the clinical history so that appropriate advice concerning avoidance measures tin exist given and, as necessary, the correct allergen(s) prescribed for specific immunotherapy (SIT). SPT results correlate with those of nasal challenge which may also exist used as a surrogate to test clinically relevant sensitization [five].

Another indication of SPT is to screen for a predisposition to develop atopic diseases, which tin be done with a limited number of allergens, or to identify all sensitized subjects in a given population. SPT also tin be used in epidemiologic studies to determine trends in sensitization rates or regional differences and to aid standardize allergen extracts.

SPT is used to test adults and children from nativity onwards. Repeated testing may be necessary in order to detect new sensitizations, especially in children, when symptoms change, or if new environmental allergens are suspected.

General principle in SPT

SPT interpretation utilizes the presence and caste of cutaneous reactivity as a surrogate marking for sensitization within target organs, i.e., eyes, nose, lung, gut and pare. When relevant allergens are introduced into the skin, specific IgE bound to the surface receptors on mast cells are cantankerous-linked, mast cells degranulate, and histamine and other mediators are released. This produces a wheal and flare response which tin can be quantitated. Many unlike allergens tin can be tested simultaneously because the resultant reaction to a specific allergen is localized to the immediate area of the SPT.

Comparison with other methods

The primary reward of SPT equally compared to an in vitro measurement of specific IgE antibodies is that the test can exist interpreted within 15 to xx minutes after the reagent is applied to the skin. Moreover, the test gives a visual indication of the sensitivity which can be used in order to bear upon the patient'south behavior. SPT can also be utilized to test less common allergens, such as certain medications, and fresh fruits and vegetables where no specific IgE antibiotic measurements are available.

The skin scratch test, kickoff described by Blackley in 1873 [6], is not recommended every bit a test modality for inhalant or food allergens since results are more than difficult to translate and standardize. Scratch testing may event in varying quantities of allergen absorbed, mechanical irritation of the skin [7] , bleeding at the exam site, and carries a higher hazard of inducing a systemic allergic reaction.

The in vitro measurement of specific IgE antibodies [8-10] is an important complementary tool to diagnose type I allergy, especially in subjects who cannot undergo SPT. For example, SPT is not practical in patients who accept extensive eczema, dermographism, urticaria, or who are taking antihistamines or other medications which interfere with the proper interpretation of the examination results (Tabular array2). In vitro test methods may exist less sensitive [11,12] and/or less specific [13,14] than SPT depending on the method utilized and the allergens employed. Furthermore, in subjects with very high full serum IgE antibodies, depression levels of specific IgE antibodies of doubtful clinical relevance are ofttimes detected. Concordance between in vitro specific IgE antibody assays and SPT results is between 85% and 95%, depending on the allergen existence tested [15-18] and the method used to notice specific IgE [xix-21]. In a report of over 8000 subjects, SPT versus quantitation of specific IgE antibodies, for example, with the CAP FEIA engineering science (Phadiatop®, Pharmacia, Uppsala, Sweden), had the best positive predictive value to decide clinical allergy for respiratory allergic diseases [22]. Moreover, SPT provides firsthand data versus in vitro exam results which may not be bachelor for days or weeks. Thus, SPT has greater flexibility and is usually less plush.

Tabular array ii

Potential interference of medications with the pare test reaction (adapted from Demoly (2003) [23]; Rueff (2010) [24]and Position Newspaper: Allergen standardization and skin tests: The European University of Allergy (1993))

Drug
Suppression
Abstinence before testing
Reference
0: no evidence; (+): possible, +: slight; ++: medium, +++: potent
Antihistamines



1st generation H1-blocker
+++
> 2 days
Dreborg (1989) [25]
Hydroxyzine
2nd generation H1-blocker
+++
7 days
Devillier (2008) [26]
Cetirizine, Loratadine, etc.
Ketotifen
+++
> five days

H2-blocker
0 - +
Ø





Glucocorticosteroids



  Topical (in test area)
+
> 1 week 1
Hammarlund (1990) [27], Pipkorn (1989) [28], Gradman (2008) [29]
  Nasal
0
Ø

  Inhaled
0
Ø

  Systemic/short term (up to x days)
0 / (+)


  < 50 mg/d Prednisolone-equivalent
0 / (+)
> 3 days
Hammarlund (1990) [30]
  > 50 mg/d Prednisolone-equivalent
(+)
> 1 calendar week 2
Des Roches (1996) [31]
  Systemic/long term (more than than 10 days)



  <10 mg/d Prednisolone-equivalent
0
Ø
Olson (1990) [32]
  >10 mg/d Prednisolone-equivalent
0
> 3 weeks two
Des Roches (1996) [31]
  Topical calcineurin inhibitors
+
> 1 calendar week
Gradman (2008) [29]
Other systemic drugs



Omalizumab
++
> 4 weeks
Noga (2003) [33]
Leukotriene receptor adversary
0
Ø
Cuhadaroglu (2001) [34], Hill (2003) [35]
Cyclosporin A
0
Ø
Munro (1991) [36]
Theophylline
0
Ø
Spector (1979) [37]
Antidepressants



  Doxepin
++
seven days
Rao (1988) [38]
  Desipramine
++
3 days
Rao (1988) [38]
  SSRI: Citalopram, Fluoxetin, Sertralin
0
Ø
Isik (2011) [39]
β-adrenergic agonists
0
Ø
Abramowitz (1980) [40], Spector (1979) [39]
  Salbutamol, Salmeterol, Bambuterol,       Terbutalin 0 Petersen (2003) [41]

Intradermal skin tests are more than sensitive only less specific than SPT [42]. They are more labor-intensive and require more precise techniques. These tests have occasionally been associated with serious systemic allergic reactions and even death from anaphylaxis [43,44]. In clinical practice, SPT tests should always be performed offset since a positive test circumvents the necessity for intradermal peel testing. Extracts utilized for intradermal skin testing are less concentrated (1:10–1:1000; 0.00001 μg/ml upwardly to ane μg/ml [42,45]) than those utilized for SPT and should exist free of glycerine, in order to avert false-positive reactions. In the diagnosis of pollen allergy, several studies indicate that positive intradermal skin tests practice not necessarily correlate with clinical symptoms [22,42] whereas there is a very good correlation between SPT results and clinical allergy symptoms [25]. Thus, for the most part, SPT is preferable to intradermal testing, the latter beingness primarily used for Hymenoptera venom sensitivity, sensitization to medications, and where an allergen is considered historically relevant and in the circumstance that the SPT is negative [46]. Titration tests for Hymenoptera venoms are unremarkably begun at concentrations of i:1000 or afterwards prior negative SPT using 1:100.

Performance of the skin prick test

Training, precautions and contraindications

SPT is safe with no reported fatalities in a 5-yr USA study [47]. Because systemic allergic reactions and rare deaths accept occurred associated with SPT [44,48], a physician or other health care professional person and emergency equipment should be immediately bachelor when such tests are performed. This is especially truthful when testing for a nutrient or medication associated with the onset of anaphylaxis [49]. Systemic side effects are very unlikely for commercially available respiratory allergens [50]. Symptomatic asthma may be a risk cistron for exacerbation of asthma associated with testing [44]. When reactions occur, they commonly do and so within 30 minutes of testing [50]. Measurement of specific IgE antibodies or titrated SPT are sometimes desirable for patients with astringent anaphylaxis suspected from a specific allergen to which they are being tested, i.east., peanuts, tree basics and shellfish. SPT should exist performed with extra caution during the respective allergy season when the patient has allergic symptoms, or when baseline tryptase levels are elevated. The latter is a take chances factor for anaphylaxis [51]. Too, patients, especially those taking a beta blocker, or less oftentimes, angiotensin converting enzyme (ACE)-inhibitor, may be at a higher run a risk because of less response to epinephrine that might be needed to care for a systemic allergic reaction. Relative contraindications for SPT include pregnancy, in view of a remote possibility of inducing a systemic allergic reaction that could induce uterine contractions or necessitate the apply of epinephrine (idea to cause constriction of the umbilical artery [52]). SPTs are hard to perform in patients with severe eczema, dermographism, or who are taking antihistamines or other medications such every bit sure antidepressants or calcineurin inhibitors (see Tabular array2) which can interfere with the proper interpretation of the examination results. In vitro testing is recommended in these cases. The degree of pare test reactivity tin can be decreased in subjects with chronic illnesses such as renal failure, or cancer. Furthermore, chronic or acute UV-B radiation of the skin in the test area may reduce the wheal size from SPT [53].

The stability and expiration engagement of the allergen extracts utilized should always be checked. Test extracts should be stored at +2°C - +8°C when not utilized to maintain stability. Histamine dihydrochloride (10 mg/ml or 0.i%) can be used as a positive command and diluent, every bit used in the test extracts, equally a negative control. For oral allergy syndrome induced by sure foods, raw foods, i.eastward., fresh fruits and vegetables are preferably used. The pare of the fruit or vegetable is pricked and and then the skin of the allergic patient, in order to determine skin examination reactivity.

SPT procedure

Patients should exist accordingly screened for asthma, and, where possible, discontinued on medications that interfere with test results, accentuate systemic allergic reactions or render patients less responsive to treatment with epinephrine. In patients with a history of astringent systemic allergic reactions to food or drugs, an intravenous line for immediate circulatory access tin be recommended. A meridian flow of less than 70% in patients with asthma is a relative contraindication. Asthma should exist controlled or testing deferred until control is achieved. When testing patients with a history of a astringent systemic allergic reactions, skin test titration, first utilizing diluted extracts, is recommended. SPT should ideally be performed at least 4–half-dozen weeks following a systemic allergic reaction, in item, for Hymenoptera hypersensitivity, since exam reactivity may be falsely negative for weeks post-obit such a reaction [24,54].

The location of each allergen can be marked with a pen or by using a test filigree on the forearm to properly identify test results (Figureonea). Tests should be applied to the volar aspect of the forearm, at least 2 – 3 cm from the wrist and the antecubital fossae [52]. The back tin can too be used for SPT, especially in infants. The skin on the back is more sensitive than the forearm which may result in larger wheals and thus possibly a greater number of positive test results [55]. The distance between 2 pare prick tests (≥ 2 cm) is disquisitional to avoid false-positive reactions due to straight contamination of a nearby examination or secondary to an axon reflex [55]. A drop of each test solution should exist placed on the skin in identical gild for each subject tested and immediately pricked.

An external file that holds a picture, illustration, etc.  Object name is 2045-7022-3-3-1.jpg

SPT procedures. (a) Preparation for skin prick exam on forearm. (b) Prick testing with lancet through a drop of allergen extract.

A single-head metal lancet exhibits fantabulous reproducibility with few faux-negative results and is thus the preferred testing instrument for SPT [56-58]. It is pressed through the drib of allergen extract and held against the skin for at least ane 2d (Figureaneb), with equal pressure practical for each examination. The epithelial layer of the pare should exist penetrated without inducing bleeding, which can lead to false-positive results. A new lancet should be utilized for each allergen since wiping a previously used one between tests could result in cross-contamination from the previous allergen tested [59]. Wiping lancets also represents a potential chance factor for the healthcare professional performing the exam. Excess solution from drops on the peel tin be blotted using a clean tissue. It is of import to assure that there is no cross-contamination between drops of dissimilar allergen extracts, i.e., that the drops exercise non run together. A timer, with an warning, should exist utilized and so that all tests, including the histamine and negative control examination results are read 15–twenty minutes post-obit awarding. Such timing for test results is recommended even though the histamine control can acme earlier at approximately 8–10 minutes [60].

It is hard or impossible to develop stable exam extracts for sure allergens, in particular, sure foods, e.thousand., for pare testing to uncooked fruits and vegetables. A prick-to-prick technique is utilized, i.e., kickoff pricking the fresh food with the lancet and so pricking the skin, to test for sensitization to such allergens when clinical allergy is suspected, in particular, oral allergy syndrome. Dry foods, due east.g., nuts or cereal, can be pestled in saline and as well utilized using the prick-to-prick technique. There tin can exist differences in the degree of skin test reactivity depending on the variety of a fruit or vegetable, how ripe it is, and how it has been stored prior to its apply [61].

Assessing the SPT

Positive and negative controls should be measured first. The negative control excludes the presence of dermographism which, when present, makes the tests difficult to translate. The histamine control should exist positive to make sure that the test materials are applied correctly and to exclude negative SPT results due to potentially interfering medications taken by the test subject field (Tabular arrayii). The largest diameter of the wheal of each particular test is measured, a positive beingness a wheal of ≥ 3 mm [62] since the longest diameter is a better approximate of wheal surface area than the mean perpendicular diameters of a skin prick test to a higher place a certain value (17 mm2). The negative control is no longer used to deduct its size from the positive tests. Including the longest diameter of pseudopods does not increment sensitivity for determining the degree of sensitisation.

Since histamine reactivity in the peel varies among individuals, independent of skin test reactivity to allergens [52], the peel examination results to allergens should not be related to the size of the histamine reaction [63]. The size of the wheal is not solely due to histamine as some subjects with positive SPT reaction show no pregnant histamine release to these allergens equally assessed past microdialysis technique [64]. Reproducibility is greater when but the diameter of the wheal, and non the associated erythema, is measured [65,66]. In order to achieve a permanent record, the size of the wheal may be outlined with a pen, blotted onto a cellophane record, and transcribed onto paper and/or stored electronically.

Clinical relevance

The SPT confirms sensitization to a specific allergen, however, its clinical relevance must be interpreted based on the medical history and clinical symptoms (see Boosted file 1: Table S3). Sometimes, conjunctival, intranasal, oral or even bronchial challenge provocation tests are performed to support clinically relevant sensitivity. The clinical relevance of SPT results varies, depending on the allergen utilized and the population tested. For example, sensitization to house dust mite occurs in some subjects in the absence of clinical relevance [iv].

Extracts

Allergen extracts ideally should be standardized based on the content of the major and minor allergenic determinants since not all patients are allergic to each antigen within an individual extract. They should have batch-to-batch consistency and the pare test results should be comparable when the same extracts from different manufacturers are utilized. Since allergen extracts are biological mixtures containing a diversity of different proteins, glycoproteins and polysaccharides, this is difficult to reach. In fact, SPT results obtained with the same allergen with extracts from different manufacturers vary [67-72]. Thus, when SPT results are compared, the allergen extract utilized should be obtained from the same manufacturer. Likewise, effective allergen immunotherapy requires specified quantities of allergenic components in the extracts used for immunotherapy.

The fact that authentic standardization of extracts is of great importance for their quality has led manufacturers to implement extensive protocols for standardization. Each company uses its own in-house reference cloth and unique units to express potencies. Such variability among different manufacturers leads to an inability to compare dissimilar products and test results. However, since nearly major allergens of relevant allergens have been identified during the last several decades, the concept introduced is to quantitate the major allergens in each of the private extracts. Such quantification will allow comparing between products by different manufacturers. In 2001, an EU funded project, the CREATE project, was introduced to encourage standardisation of allergen extracts based on their content of major allergen(s). The projection evaluated the use of recombinant allergens as reference materials for major allergen measurements [73]. Another try to standardize extracts involved the development of recombinant allergen extracts. Even though some of these recombinant allergens show comparability to allergen extracts derived from source material [74-76], they only cover a limited number of allergens and are still under investigation.

Extracts should non contain preservatives which can cause false positive reactions, east.m., sodium merthiolate. Nor should they be mixed with other allergens, due east.thousand. house grit mite with dog dander extract. When testing with not-commercial allergens, there is a real need to employ control tests in non-allergic subjects to compare the results with subjects who are allergic. For certain plant allergens, especially for fresh foods and vegetables, the prick-to-prick method is more than reliable than using manufactured extracts [61].

The tight regulation of skin exam extracts has made their production and registration problematic and plush for the pharmaceutical industry. This has led to gaps in the registration of specific extracts in certain European countries.

Pan-European skin prick exam panel for respiratory allergens

The authors suggest that a standard SPT console for inhalant allergens, based on the GAtwoLEN written report [3], be utilized throughout Europe. This panel includes the following eighteen allergens: hazel (Corylus avellana), alder (Alnus incana), birch (Betula alba), plane (Platanus vulgaris), cypress (Cupressus sempervirens), grass mix (smooth meadow grass/Poa pratensis, cock's pes grass/Dactilis glomerata, perennial rye grass/Lolium perenne, timothy grass/Phleum pratense, meadow fescue/Festuca pratensis, meadow oat grass/Helictotrichon pretense), Olive (Olea europaea), mugwort (Artemisia vulgaris), ragweed (Ambrosia artemisiifolia), Alternaria alternata (tenuis), Cladosporium herbarum, Aspergillus fumigatus, Parietaria, true cat, dog, Dermatophagoides pteronyssinus, Dermatophagoides farinae, and cockroach (Blatella germanica). Allergens tin can be supplemented as necessary for regional or for item patient needs.

Interpretation of SPT results

SPT results should be appropriately interpreted based on clinical symptoms, medical history, and, where necessary, other test results (specific IgE antibody measurements) in order to assess possible allergy to a specific allergen. The probability of a given sensitization to be clinically relevant depends on the type of allergen and country where the patient lives [4]. The clinical relevance of any detected sensitization should exist determined by an allergologist after taking a complete history and performing a physical examination. When SPT results and the history are inconclusive, provocation tests may help to determine the clinical relevance of the SPT sensitization, e.1000., before initiation of a specific immunotherapy.

SPT is highly specific and sensitive, seventy-95% and 80-97%, respectively, to diagnose inhalant allergies [76]. The positive predictive value to diagnose allergic rhinitis based only on the clinical history is 77% for persistent allergy and 82-85% for intermittent seasonal allergy [17]. This increases to 97-99% if SPT is utilized [17].

The negative predictive value of a negative SPT and in vitro IgE antibody test for cat allergen are identical at 72-75% for cat allergy [42]. A negative SPT for Dermatophagoides pteronyssinus has a negative predictive value in older adults of 90%-95%. However, the positive predictive value ranges from 29% to 43% in older subjects and 77% to 100% for younger subjects [23].

Sensitivity and specificity are lower for food allergens, ranging from thirty-ninety% and xx-threescore%, depending on the type of allergen and methods utilized, i.eastward. pricking with extracts vs. prick-to-prick techniques described earlier [77]. Double-bullheaded placebo-controlled challenge studies in children demonstrate that SPT possesses a positive predictive value of 76% and 89% for clinical reactions to cow'southward milk and hen'south egg, respectively [78].

The objective value of SPT for drug allergy depends on the tested drug. In nearly cases, a positive SPT makes drug allergy very likely; whereas a negative event does not necessarily indicate that the patient volition non react on claiming to the drug [79]. Withal, for penicillin, the negative predictive value is high. In 98.5% of patients with a negative SPT, no type I allergy was observed upon claiming while the remaining 1.five% of patients had mild and self-limiting reactions, due east.g., urticaria [lxxx]. In many cases, intradermal testing is advisable after negative SPT. Some drugs, e.grand., muscle relaxants or opioids may cause SPT imitation-positive results. When evaluating patients for IgE-mediated drug allergy to antibiotics other than penicillin, SPT should exist performed with the unadulterated pharmaceutical agent. Belatedly readings (> 24h) of SPTs and especially intradermal skin tests are very valuable in the description of adverse drug reactions.

For suspected insect venom allergy, intradermal tests are the primary mode for detecting sensitization. SPT is performed prior to intradermal testing.

Sensitizations to aeroallergens, as measured by SPT, may precede symptomatic allergy. Prospective studies show that xxx-threescore% of such subjects become allergic depending on the blazon of allergen tested and the time to follow-up [81,82]. Furthermore, sensitization can exist to an allergen that is no longer clinically relevant.

SPT in epidemiologic studies

Sensitization rates vary depending on the geographic region as measured in population-based and in patient-based studies like the European Community Respiratory Health Survey (ECHRS), the International Study of Asthma and Allergies in Childhood (ISAAC), and the GA2LEN Pan-European skin prick test report. Exposure rates and genetic differences tin explain some of these variations [83,84]. With increased human mobility, differences in exposure to diverse flora or alterations in the allergenicity of pollen, possibly acquired by pollution [85,86], and changes in sensitization occur over time [87]. Longitudinal studies investigating sensitization over time provide data on such trends [88,89].

The aforementioned allergen extracts and ideally fifty-fifty the same batches of extracts should be utilized when comparing a test outcome from one place to another or over time. For epidemiological studies, the standard prick exam panel should be utilized to ensure comparability with the GA2LEN study results (see Tableone; [3]). Distribution of standard operating procedures for both technical aspects and information drove assures the highest degree of comparability. Studies of allergic sensitization should take identify over an extended menstruation of fourth dimension, ideally, a year, since (i) peel test reactivity increases during the pollen season [90] and (ii) allergic individuals tend to seek care when they have symptoms. This can skew detected prevalence of sensitization in such studies. Information technology is also important to notation the seasonal differences of various allergens based on geographic locations which can further distort sensitization rates between countries.

Future directions to use pare tests for allergy diagnosis

More than 1,800 allergenic molecules are identified (http://www.allergome.org/script/statistic.php; [91]). The utilise of recombinant allergen molecules for SPT should meliorate sensitivity and standardization of SPT by reducing not-specific reactivity due to irritant compounds contained in biologically derived extracts, in item, nutrient extracts [92]. New in vitro techniques using recombinant molecules and micro-technology may permit testing of hundreds of compounds simultaneously, thus improving diagnostic possibilities and potentially even eliminating the demand for pare testing [93].

Needs for farther research

Further studies are needed to (1) compare extracts from unlike manufacturers, (2) investigate intra field of study variability, and (3) determine the relevance of SPT for pan-allergens. Since new allergens are being identified in Europe, eastward.g., acerola (Malpighia glabra), and others are becoming more prevalent, e.g., Lepidoglyphus destructor, new studies should also investigate the relevance of these allergens.

Conclusion and outlook

In that location is general understanding that the core diagnostic test for type I firsthand allergy, i.due east. the SPT, should exist farther standardized to include standardized procedures and allergen panels. Additional allergens can be added to this "core", when indicated. Such standards are probable to: (i) improve the quality of patient diagnosis and intendance, and (2) reduce variability of results and thus make test results comparable. Further studies are necessary to define worldwide standards for allergen extracts.

Abbreviations

GAiiLEN: Global Allergy and Asthma European Network; IgE: Immunoglobuline E; Sit down: Specific immunotherapy; SPT: Skin prick test; mm: millimetre; RAST: Radioallergosorbent examination.

Competing interests

No conflicts of interest exist for any of the authors.

Authors' contributions

Conceived and designed the European SPT written report: LMH, MB, GB, UD, SD, WF, MG, Thursday, ATB, SW. Wrote the manuscript: LMH, RL, AM, KCB. Critically reviewed and revised the manuscript: MB, GB, UD, SD, WF, MG, TH, ATB, SW, HM. Final language editing: SD. Agreement with manuscript and conclusions: all. Designed the figures and tables: LMH, RL. All authors read and approved the terminal manuscript.

Authors' information

Lucie Heinzerling, Karl-Christian Bergmann, Megon Bresciani, Guido Burbach, Ulf Darsow, Stephen Durham, Wytske Fokkens, Mark Gjomarkaj, Tari Haahtela, Ana Todo Bom, Stefan Wöhrl: GAiiLEN member.

Supplementary Material

Additional file 1: Table S3:

Skin prick test panel – inhalant allergens.

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