How to Read an Allergy Skin Test?
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Measurement and interpretation of skin prick exam results
Clinical and Translational Allergy volume vi, Article number:8 (2015) Cite this commodity
Abstract
Background
There are several methods to read skin prick test results in blazon-I allergy testing. A commonly used method is to characterize the wheal size by its 'average diameter'. A more accurate method is to scan the area of the wheal to calculate the actual size. In both methods, peel prick examination (SPT) results can be corrected for histamine-sensitivity of the skin by dividing the results of the allergic reaction by the histamine command. The objectives of this written report are to compare different techniques of quantifying SPT results, to determine a cut-off value for a positive SPT for histamine equivalent prick -index (HEP) area, and to study the accuracy of predicting cashew nut reactions in double-blind placebo-controlled nutrient claiming (DBPCFC) tests with the unlike SPT methods.
Methods
Information of 172 children with cashew nut sensitisation were used for the analysis. All patients underwent a DBPCFC with cashew nut. Per patient, the average diameter and scanned surface area of the wheal size were recorded. In addition, the same data for the histamine-induced wheal were collected for each patient. The accuracy in predicting the consequence of the DBPCFC using four different SPT readings (i.e. average bore, surface area, HEP-index bore, HEP-alphabetize surface area) were compared in a Receiver-Operating Characteristic (ROC) plot.
Results
Characterizing the wheal size by the average diameter method is inaccurate compared to scanning method. A wheal average diameter of 3 mm is generally considered as a positive SPT cut-off value and an equivalent HEP-alphabetize area cut-off value of 0.iv was calculated. The four SPT methods yielded a comparable area under the bend (AUC) of 0.84, 0.85, 0.83 and 0.83, respectively. The four methods showed comparable accuracy in predicting cashew nut reactions in a DBPCFC.
Conclusions
The 'scanned area method' is theoretically more than accurate in determining the wheal area than the 'average bore method' and is recommended in academic research. A HEP-index expanse of 0.4 is determined equally cut-off value for a positive SPT. However, in clinical practice, the 'average diameter method' is likewise useful, considering this method provides like accuracy in predicting cashew nut allergic reactions in the DBPCFC.
Trial registration: Trial number NTR3572
Background
Standard diagnostics for Blazon-I acute allergic reactions to foods are based on the patient's history combined with sensitisation tests and, optionally, a nutrient challenge exam [ane]. Tests to measure out sensitisation comprise in vitro specific IgE (sIgE) decision and skin prick testing (SPT). The issue of the SPT can effect in a diversity of wheal shapes, and there are several methods to mensurate these outcomes. In clinical practice and in almost academic research, information technology is common to narrate the wheal shape by the 'boilerplate diameter' [ii]. However, with this method, it is implicitly causeless that the wheal may exist described reasonably well by an ellipse or circle, which is not e'er the case in practice and this method is prone to errors [3]. For this reason, a more advanced scanning method for SPT measurement has been practical for more than a decade in the Erasmus Medical Middle in Rotterdam. To even further increase the accuracy of SPT results, the histamine-induced wheal size of the positive control might be considered also to correct for skin histamine sensitivity. Furthermore, differences in technique of performing SPTs (inter-observer variability) contribute to the variation in wheal size [4]. We divided the area (or diameter) of the allergen-induced wheal by the area (or diameter) of the positive histamine-induced wheal controls to right for these factors. This ratio is defined every bit the histamine equivalent prick (HEP)-alphabetize expanse (or diameter) or histamine-equivalent wheal sizes (HEWS) [5]. The first objective of this study is to compare different techniques of quantifying SPT results. The second objective is to determine a cut-off value for area, HEP-bore and HEP-alphabetize expanse equivalent to the standard used average bore cutting-off value of 3 mm, whereby the HEP-alphabetize surface area is considered as the most important, because of the accurateness of this method (area measurement) and the correction for skin sensitivity (HEP-index measurement). The last objective is to study the accuracy of diagnosing cashew nut allergic reactions in the double-blind placebo-controlled (DBPCFC) tests with the 4 SPT methods.
Methods
Report pattern and patients' characteristics
This study included a total of 172 children (trial number NTR3572). All patients underwent a SPT with cashew nut extract and a DBPCFC test with cashew nut. The hateful age of the children was 8.viii years (range 2–17 years), with 102 boys (59 %) and seventy girls (41 %). Symptoms consistent with eczema were reported by 65 children (38 %), with asthma by 52 children (thirty %) and with hay fever by 89 children (52 %). Medical ethical approval was obtained and all patients signed informed consent.
Peel prick tests
The children underwent a SPT with homemade cashew nut extracts, a positive control (histamine ten mg/ml ALK-Abello, Nieuwegein, The Netherlands) in duplicate and a negative command. Cashew nuts (roasted, unsalted) were homogenised mechanically, ground with a mortar, defatted by ether extraction, and later the extracts were air-dried. A ten % due west/five extract in phosphate-buffered saline (PBS) with the pre-treated material was fabricated and stored at −20 °C in small aliquots. Before testing the aliquots were defrosted and mixed. The SPT was performed by applying a drop of the allergen extract on the skin of the volar attribute of the forearm. 20 minutes subsequently the skin tests, the contours of the wheal were encircled with a fine-tip pen and transferred to a tape sheet by translucent record [6].
Different techniques quantifying skin prick examination results
The outcome of the SPT can consequence in a variety of wheal shapes, as shown in Fig. ane. To determine the boilerplate diameter, the mean value of the longest and the midpoint orthogonal diameter (mm) of the wheal were measured (Fig. ii). The area of the wheal was determined past using a flatbed scanner (Hewlett Packard) in combination with software earlier developed by Erasmus MC: Precise Automated Area Measurement of Skin Examination (PAAMOST) [6, 7]. Mean values of two histamine-induced wheal sizes of the positive control were collected likewise. Based on the measured information the HEP-indices were calculated for both the average diameter and area.
Typical observed wheal forms in SPT'south
Definition of D1 and D2
Consequently the four readings were defined as:
- 1.
Average bore (allergen-induced average wheal bore).
- two.
Area (allergen-induced area measured by scanning device).
- 3.
HEP-index bore (allergen-induced average bore divided by histamine-induced average diameter).
- 4.
HEP-index area (allergen-induced area divided past the histamine-induced average area).
Nutrient claiming test
The children underwent a DBPCFC cashew nut test with an 8-stride incremental dose regime. The children consumed 3180 mg cashew nut poly peptide (22 cashew nuts) when the child consumed all 8 dose steps. The validated and standardised food challenge material used in the DBPCFC was prepared co-ordinate to the recipe developed by Berber-Vlieg et al. [8]. The DBPCFC was considered as positive when (1) objective symptoms occurred, (ii) when subjective symptoms occurred twice on three successive administration of the challenge fabric, or (iii) when subjective symptoms persisted for more than 1 h [ix]. In total, 137 children had a positive challenge examination.
Analysis
Receiver operating characteristics (ROC) curves and Expanse under the Curve (AUC) were calculated to evaluate the unlike SPT methods. An area under the bend of 0.9–one is considered as excellent, 0.8–0.9 as good and 0.7–0.8 as fair [x]. All analyses were done with SPSS software, 20th edition.
Results
SPT
In full 172 SPT results with cashew, positive (in duplicate) -and negative command were evaluated. Median histamine wheal diameter was v.38 mm (range ii.75–10.75 mm). All negative controls were negative. Hateful variability between the duplicate measurements of histamine was 14 % (range 0–100 %). Median average bore, area, HEP-diameter and HEP-index surface area of the SPT with cashew were ten.50 mm (range 0–26 mm), 71.eight mm2 (range 0–324.ane mm2), 1.83 (range 0–v.13) and 2.97 (range 0–fifteen.16), respectively.
Different techniques of interpreting peel prick examination results
Equally a first step of assessing the unlike techniques of interpreting the SPT results, a comparison is made betwixt the common-used average diameter method (1) and the scanned area method (PAAMOST) (2). These two methods are compared in a scatterplot in Fig. 3. Every dot represents one patient. The dotted line shows the trend line of the data.
Average bore (method ane) versus scanned area (method two). A comparison is made between the common-used boilerplate bore method and the scanned area method. Every dot represents 1 patient. The dotted line shows the trend line of the data. The lower bound value for α is 1 is shown by the red line. The upper spring value for α is 6.67 is shown past the grey line
The average diameter on the horizontal axis in Fig. 3 is defined equally the mean value of the longest (D 1 ) and the midpoint orthogonal bore (D 2 ) of the wheal, as shown in Fig. ii:
$$D = \left( {\frac{{D_{one} + D_{ii} }}{2}} \correct)$$
(1)
In most studies, the average diameter is presented, while the originally measured values of D1 and D2 are non shown. This results in loss of crucial information. Without the parameters D1 and D2, there is no indication about the original shape of the wheal. To avert this, nosotros introduce, side by side to the parameter D, the parameter α as the ratio between D 1 and D 2 :
$$\alpha = \frac{{D_{1} }}{{D_{ii} }}$$
(ii)
The combination of parameters D and α contains exactly the aforementioned information as the measured parameters D1 and D2. A value for α close to 1.0 indicates a circular shaped wheal, college values indicate an elliptical shaped wheal.
In our study population of 172 patients, the parameter α varies between 1.0 and 6.67. Assuming that nosotros can reasonably well estimate the wheal size past an ellipse, the area of the wheal (A) is defined every bit:
$$A = \frac{\pi }{4}D_{1} D_{two}$$
(three)
In Eq.( 3) the wheal area is defined as a function of D 1 and D 2 , while the wheal size is ordinarily characterized past the average diameter, in detail in method 1. Combining Eqs. (1) to (three), the wheal area tin be rewritten as a function of the average diameter D and the ratio α:
$$A = \frac{\alpha }{{\left( {ane + \blastoff } \right)^{2} }}\pi D^{2}$$
(4)
The lower jump value of α is one.0 (D 1 =D 2). In this case, the wheal shape is round and Eq. (four) simplifies to the well-known formula describing the area of circle, A =Ï€/4·D ii . In Fig. three, this lower bound instance (surface area equally a circle) is shown by the red line. Based on our set of 172 patients, the upper spring value of α is vi.67. Substituting α = 6.67 into Eq. four, the upper bound (expanse equally an ellipse) is obtained. This is shown past the grey line in Fig. 3. Nearly all 172 dots are lying in betwixt these two lines, with merely a few exceptions. The reason for these outliers is that an ellipse could not sufficiently well represent the shape of these wheals. From Fig. 3 information technology can exist ended that characterizing the wheal size past the average diameter method could be rather inaccurate. For a given average wheal diameter, the actual wheal expanse could vary between 50 % under and 50 % higher up the trend line, visually in between the blood-red and greyness line. For example, if the mean wheal diameter is 15 mm, the real wheal surface area could lie between 80 mm2 (α = 6.67) and 176 mmtwo (α = 1.0), which is a rather big variation. Effigy 3 shows also that the accented error grows with wheal size. This inaccuracy, of up to fifty %, is completely eliminated if one applies the scanning method, i.e. method 2.
If for applied reasons, one would like to apply the average diameter method, the 'all-time' human relationship between the average diameter D and the wheal surface area A may exist obtained from the dotted tendency line in Fig. 3. This line can be estimated by the following equation:
$$A = \frac{\pi }{half dozen}D^{ii}$$
(5)
It is interesting to notation that this expression is rather different than the unremarkably used expression A =Ï€/4·D 2 , which implicitly assumes a round wheal shape.
To make up one's mind the cut-off value for HEP-alphabetize area equivalent to the standard used 3 mm average bore cut-off value [xi], comparison is made between the average diameter method (1) and the scanned HEP- expanse method (4). These two methods are compared in a scatterplot in Fig. four. The dotted line shows the trend line of the information. This tendency line can be estimated past the following equation:
$$HEP - alphabetize \;expanse = 0.0096 D^{2} + 0.2674 D - 0.5033$$
(6)
Boilerplate diameter (method 1) versus HEP-alphabetize area (method iv)
Substituting D = 3 mm into Eq. (6), the HEP-index area is obtained and results in 0.iv. Therefore, a HEP-alphabetize area value of 0.four is considered as the cut-off value for a positive SPT.
The cutting-off values for expanse and HEP-index diameter were measured on the aforementioned method. This results in an area and HEP-index diameter cutting-off values of iv.71 mmtwo and 0.6, respectively.
Accuracy of diagnosing cashew allergy
To study the accuracy of diagnosing cashew nut allergy with the four SPT methods, a ROC plot was generated. The four SPT methods, i.e. the boilerplate bore, expanse, HEP-index diameter and HEP-index area, yielded a comparable area under the curve of 0.84, 0.85, 0.83 and 0.83, respectively. All four SPT methods were considered as adept and equally accurate in diagnosing cashew nut allergy (Fig. 5).
Receiver-operating characteristic curves for the 4 SPT methods
Discussion
To make up one's mind the outcome of the SPT, it is common to characterize the wheal shape by the 'average bore'. However, this method is prone to errors, because information technology is assumed that the wheal size varies between a circle and an ellipse. In fact, the wheals have pseudopodia and interpretation based on ii orthogonal diameters is not authentic. This report showed that for a given average wheal diameter, the actual wheal expanse could vary quite significantly and this inaccuracy grows with wheal size. This inaccuracy is completely eliminated if one applies the scanning method. This more precise method for measuring the wheal size surface area is previously described by Pijnenborg et al. [12]. The scanning method is also fast, easy in use, has a loftier reproducibility and is very useful in scientific research [ii, half dozen, 12, 13].
To even further increment the accuracy of SPT results, the HEP-index tin can be calculated, to dominion out differences in skin reactivity. At that place are several factors that contribute to this departure, e.chiliad., poly-sensitised patients and patients with mould sensitisation have significantly higher skin reactions [14] and the pare response varies in unlike ethnicities [15]. Furthermore, differences in technique of performing SPTs (inter-observer variability) contribute to the variation in wheal size [four]. To correct for these factors, the calculation of the HEP-alphabetize is useful and too easy to determine with the scanning method.
Notwithstanding all advances of the scanning method inclusive the HEP-index calculation, the 'average bore' method is as accurate in diagnosing cashew nut allergy as the 'HEP-index area' method. Therefore, the 'average diameter' method can be used if at that place is no scanning device available. However, the 'all-time' relationship between the average diameter and the wheal expanse can exist better estimated past the equation \(A = \frac{\pi }{6}D^{2}\) instead of the equation \(A = \frac{\pi }{4}{\text{D}}^{2}\). Therefore, if one wishes to calculate the area out of the average diameter for due east.thousand. research purposes, the equation \(A = \frac{\pi }{6}D^{two}\) should be used to guess the area most accurate.
Conclusions
This written report demonstrates that the scanning method for SPT measurement is more authentic to measure out the wheal surface area in a Type-I allergy than the average diameter. The average wheal diameter gives an overestimation or underestimation of the actual surface area upwards to fifty %. It is possible to correct for skin sensitivity and inter-observer variability by using the 'HEP-index area' method. The HEP-alphabetize surface area value 0.4 can be considered as an equal cut-off value of 3 mm wheal average diameter. However, in clinical exercise, the 'average diameter method' is also useful, because this method is equally accurate in predicting cashew nut allergic reactions in the DBPCFC tests.
Abbreviations
- AUC:
-
Expanse under the curve
- DBPCFC:
-
Double-blind, placebo-controlled food claiming
- HEP:
-
Histamine equivalent prick
- sIgE:
-
Specific IgE
- ROC:
-
Receiver-operating characteristic
- SPT:
-
Pare prick test
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Authors' contributions
JPMV main author, RGW main reviewer, EH Development of the technical programme used in this article, LG assistant for all measurements in the report, reviewer, IMG assistant for all measurements in the study, reviewer, NWJ initiator of this commodity, main reviewer. All authors read and approved the final manuscript.
Acknowledgements
We would like to give thanks Dr. Ir. G. L. Kuiper for the mathematical back up in our report.
Competing interests
The authors declare that they have no competing interests.
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van der Valk, J.P.M., Gerth van Wijk, R., Hoorn, E. et al. Measurement and interpretation of peel prick test results. Clin Transl Allergy 6, 8 (2015). https://doi.org/10.1186/s13601-016-0092-0
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DOI : https://doi.org/10.1186/s13601-016-0092-0
Keywords
- Allergy
- Cut-off value
- Histamine equivalent index
- Mean wheal diameter
- Skin prick test
Source: https://ctajournal.biomedcentral.com/articles/10.1186/s13601-016-0092-0
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