14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License DOI: 10.1111/jdv.17111 JEADV ORIGINAL ARTICLE Pruritus Intensity Scales across Europe: a prospective validation study M. Storck,1,* S. Sandmann,1 P. Bruland,1,2 M.P. Pereira,3 S. Steinke,3 C. Riepe,3 I. Soto-Rey,1,4 5 6 S. Garcovich, M. Augustin, C. Blome, S. Bobko, F.J. Legat,8,9 N. Potekaev,7 A. Lvov,7 6 7 L. Misery, 10 ß avk,12 M. Streit,13 E. Serra-Baldrich,14 J.C. Szepietowski,15 W. Weger, A. Reich,11 E. S 8 €nder,3 C. Zeidler3 M. Dugas,1 S. Sta 1 Institute of Medical Informatics, University of Mu€nster, Mu€nster, Germany 2 inIT – Institute Industrial IT, Ostwestfalen-Lippe University of Applied Sciences, Lemgo, Germany 3 Department of Dermatology and Center for Chronic Pruritus, University Hospital Mu €nster, Mu €nster, Germany 4 IT-Infrastructure for Translational Medical Research, Faculty of Applied Computer Science, Faculty of Medicine, University of Augsburg, Augsburg, Germany 5 Dermatology, F. Policlinico Universitario A. Gemelli IRCCS, Universit a Cattolica del Sacro Cuore, Rome, Italy 6 Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf, Hamburg, Germany 7 Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology, Moscow, Russia 8 Department of Dermatology, Medical University of Graz, Graz, Austria 9 Das Kurhaus, Bad Gleichenberg, Austria 10 Department of Dermatology, University Hospital of Brest, Brest, France 11 Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, Rzeszo w, Poland 12 Department of Dermatology, Aydin Adnan Menderes University, Aydin, Turkey 13 Department of Dermatology, Kantonsspital Aarau, Aarau, Switzerland 14 Cutaneous Allergy Unit, Department of Dermatology, Hospital Sant Pau, Universitat Auto noma, Barcelona, Barcelona, Spain 15 Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland *Correspondence: M. Storck. E-mail: michael.storck@uni-muenster.de Abstract Background Chronic pruritus (CP) is a subjective symptom, and it is necessary to assess its intensity with validated patient-reported outcome tools in order to allow determination of the treatment course. Objectives So far, the itch intensity scales were validated in small cohorts and in single languages. Here, we report the validation of the numerical rating scale, the verbal rating scale and the visual analogue scale for the worst and average pruritus intensity in the last 24h in several languages across Europe and across different pruritic dermatoses. Methods After professional translation, the intensity scales were digitized for use as a tablet computer application. Validation was performed in clinics for Dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. Results A total of 547 patients with contact dermatitis, chronic nodular prurigo, psoriasis vulgaris, lichen planus or cutaneous T-cell lymphoma were included. The intensity scales showed a high level of reproducibility and inter-correlations with each other. The correlation with the Dermatology Life Quality Index was weak to strong in nearly all countries and dermatoses with the exception of France and patients with chronic nodular prurigo, for which no statis- tically significant correlations were found. Conclusions The numerical rating scale, the verbal rating scale und the visual analogue scales are valid instruments with good reproducibility and internal consistency in German (Germany, Austria, Switzerland), French, Italian, Polish, Russian, Spanish and Turkish for different pruritic dermatoses. VAS worst was the best reproducible and consistent measuring instrument in all countries. Received: 15 October 2020; Accepted: 1 December 2020 Conflicts of interest None. Funding sources €nder). This article was supported by the European Academy of Dermatology and Venereology (EADV, No. 2014-022 to Sonja Sta JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pruritus intensity scales across Europe 1177 Introduction the course of pruritus and to evaluate the efficacy of the treat- Chronic pruritus (CP; lasting for six weeks or longer) is a com- ment. The most frequently used instruments to assess itch inten- mon symptom in dermatology. Estimates are that more than sity are the numerical rating scale (NRS, range: 0–10), visual one-third of dermatological patients suffer from CP.1 CP can analogue scale (VAS, range: 0–10/0–100) and the verbal rating arise from various dermatoses, as well as from internal, neuro- scale (VRS, range: 0–4). These scales were originally developed logical and mental diseases.2 It has a high humanistic burden3 to assess the intensity of pain and have been validated success- and affects the quality of life negatively.4 Due to its subjectivity, fully in chronic pain in several studies.5,6 Analogous to pain it is necessary to use a valid patient-reported measuring instru- these scales proved to be a valid instrument for the assessment of ment for recording the intensity of pruritus in order to assess CP intensity in various pruritic conditions in German- and Pol- ish-speaking patients7,8 and in a cohort of CP patients in the Republic of Korea,9 Japan10 and Sweden. Using the VAS and NRS, the Special Interest Group of the International Forum for the Study of Itch categorized the severity of pruritus according to the following cut-offs: 0: no pruritus, 1–<3: mild pruritus, 3– <7: moderate pruritus, 7–<9: severe pruritus and 9–10: very sev- ere pruritus.11 In previous validation studies, the assessment of the pruritus intensity via NRS was validated further for atopic dermatitis12 and psoriasis vulgaris13,14 in the USA and for chronic nodular prurigo in Germany.15 Data on the validity of the intensity scales in other pruritic diseases and in different lan- guages are still lacking. In order to validate and harmonize pruritus assessment tools for both routine care and randomized clinical trials (RCTs) across Europe, the European Network on Assessment of Severity Figure 1 Visual analogue scale (worst) (a), verbal rating scale and Burden of Pruritus (PruNet) was founded in 2014.16 As a (worst) (b) and numerical rating scale (worst) (c) within the mobile patient questionnaire application MoPat. result of PruNet’s efforts, three pruritus intensity scales (VAS, NRS and VRS) were validated European-wide and in several Table 1 Description of the study population (AD: atopic dermatitis; CD: contact dermatitis; CNPG: chronic nodular prurigo; Pso: psoria- sis; LP: lichen planus; CTCL: cutaneous T-cell lymphoma) Austria France Germany Italy Poland Russia Switzerland Spain Turkey All Total, n 60 54 68 71 68 51 53 55 67 547 Gender, n Female 35 24 40 42 29 34 28 41 40 313 Male 25 30 28 29 39 17 25 14 27 234 Age in years Min 18 18 22 25 20 18 18 20 18 18 Max 83 98 81 80 91 87 90 90 81 98 Mean 46.65 51.26 54.49 53.04 50.49 50.45 58.28 53.64 46.61 51.56 SD (+/) 15.86 21.93 15.25 15.53 17.64 18.96 19.93 20.18 16.91 18.14 Median 47 50.5 56 54 52 50 60 55 48 52 Diagnosis, n (%) AD 23 (38) 10 (19) 20 (29) 25 (35) 12 (18) 18 (35) 25 (47) 27 (49) 2 (3) 162 (30) CD 1 (2) 14 (26) 1 (1) 11 (15) 6 (9) 18 (35) 7 (13) 17 (31) 19 (28) 94 (17) CNPG 7 (12) 5 (9) 12 (18) 8 (11) 8 (12) 3 (6) 8 (15) 7 (13) 11 (16) 69 (13) Pso 28 (47) 20 (37) 28 (41) 21 (30) 34 (50) 8 (16) 10 (19) 1 (2) 30 (45) 180 (33) LP 1 (2) 3 (6) 3 (4) 5 (7) 2 (3) 3 (6) 2 (4) 3 (5) 5 (7) 27 (5) CTCL 0 (0) 2 (4) 4 (6) 1 (1) 6 (9) 1 (2) 1 (2) 0 (0) 0 (0) 15 (3) Duration (n) <6 weeks 0 4 1 5 7 9 4 3 9 42 6 weeks to 6 months 0 6 6 14 10 11 6 6 8 67 6 to 12 months 5 7 2 12 6 4 6 7 7 56 1 to 10 years 12 19 25 32 23 14 22 24 32 203 >10 years 43 18 34 8 22 13 15 15 11 179 JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1178 Storck et al. Table 2 Descriptive statistics for the intensity scales overall and segregated for the participating sites Austria France Germany Italy Poland Russia Switzerland Spain Turkey All VAS average Mean 5 5.74 4.29 5.44 5.9 4.24 4.77 5.18 6.6 5.27 Median 5 6 4 5 6 4 5 5 6 5 Range 1–10 1–10 0–10 1–10 2–10 1–9 1–9 0–10 2–10 0 1. Quartile 3.75 4 3 4 4 2 3 3 4.5 3 3. Quartile 7 7 6 7 8 6,5 7 6 10 7 VAS worst Mean 5.58 6.43 5.29 6.7 6.96 4.96 6.51 5.87 7.46 6.24 Median 6 7 5 7 7 5 7 7 8 7 Range 0–10 0–10 0–10 0–10 2–10 1–9 0–10 0–10 1–10 0 1. Quartile 3.75 5 3 4.25 5.75 2.5 3.5 5 5 4 3. Quartile 8 8 7 8,75 9 7 8 9 10 8 NRS average Mean 5.42 5.54 4.81 6.01 6.37 5.37 5.04 5.73 7 5.73 Median 6 5 5 6 6 5 5 6 7 6 Range 1–10 0–9 1–10 3–10 2–10 1–10 0–10 0–10 2–10 0 1. Quartile 3.75 4 3 4 5 3 4 4 5 4 3. Quartile 7 7 6 8 8 7 8 6 10 7 NRS worst Mean 6.15 6.59 5.88 7.06 7.3 6.29 6.81 6.76 7.76 6.75 Median 6 7.5 6 7 8 7 7.5 7 8.5 7 Range 1–10 0–10 1–10 1–10 3–10 2–10 0–10 0–10 3–10 0 1. Quartile 4 5 4.75 6 6 4 5 5 5.25 5 3. Quartile 8 8 8 9 9 8 9 9 10 9 VRS average Mean 1.95 2.24 1.82 2.28 2.56 2.06 2.18 1.92 2.65 2.20 Median 2 2 2 2 2.5 2 2 2 2 2 Range 1–4 0–4 0–4 0–4 1–4 1–4 0–4 0–4 1–4 0 1. Quartile 1 2 1 2 2 2 2 1 2 2 3. Quartile 2.25 3 2 3 3 2 3 2 4 3 VRS worst Mean 2.23 2.59 2.18 2.62 2.83 2.25 2.56 2.31 2.71 2.49 Median 2 3 2 3 3 2 3 2 3 2 Range 1–4 0–4 0–4 0–4 1–4 1–4 0–4 0–4 0–4 0 1. Quartile 1.75 2 2 2 2 2 2 2 2 2 3. Quartile 3 3 3 3 3 3 3 3 4 3 pruritic dermatoses. We present and discuss the results of these scientists, 2 psychologists) took place to identify the most com- validation studies in this article. mon itch assessment tools. In a Delphi process, the instruments VAS, NRS und VRS were chosen to be validated European Material and methods wide.16 The recall period of these three intensity scales was deter- mined to be 24 h; both the worst pruritus intensity and the aver- Patients in PruNet age pruritus intensity were recorded with each of the three The data collection was part of the non-interventional prospec- scales. All pruritus intensity scales were validly translated (for- tive cohort study performed in the PruNet project. Data were ward/backward translation)17 into the respective languages by a collected in dermatological centres in Austria, France, Germany, professional translation office. Data collection was performed Italy, Poland, Russia, Spain, Switzerland and Turkey. using the mobile patient survey application MoPat18 on an iPad, Adult CP patients with atopic dermatitis (AD), contact der- and entered data were transferred into the electronic study data- matitis (CD), chronic nodular prurigo (CNPG), psoriasis vul- base (x4T-EDC) located in M€ unster, Germany. MoPat is a vali- garis (Pso), lichen planus (LP) or cutaneous T-cell lymphoma dated system for the collection of electronic patient-reported (CTCL) were included in this study. Patients without sufficient outcome.19 Fig. 1 depicts the pruritus intensity scales within understanding of the local language were excluded. MoPat. Subjects were recruited by the local principal investigators Study design and associated physicians. A trained medical student supported In February 2015, a consensus meeting with 28 pruritus experts data collection and administrative processes of each site for a from 15 EU countries (21 dermatologists, 5 medical computer period of three to four weeks. After signing an informed consent, JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pruritus intensity scales across Europe 1179 Table 3 Descriptive statistics for the intensity scales overall and segregated for the dermatoses (AD: atopic dermatitis; CD: contact der- matitis; CNPG: chronic nodular prurigo; Pso: psoriasis; LP: lichen planus; CTCL: cutaneous T-cell lymphoma) AD CD CNPG Pso LP CTCL All VAS average Mean 4.93 5.59 6.22 5.14 4.96 4.87 5.27 Median 5 5 6 5 5 5 5 Range 0–10 0–10 1–10 0–10 1–10 2–9 0 1. Quartile 3 3 5 3 3,5 3 3 3. Quartile 7 8 8 7 6 6 7 VAS worst Mean 6.05 6.46 7.25 5.89 6.26 6.4 6.24 Median 7 7 7 6 6 6 7 Range 0–10 0–10 1–10 0–10 1–10 1–10 0 1. Quartile 4 4 5.75 4 5 5 4 3. Quartile 8 9.75 10 8 8 9 8 NRS average Mean 5.41 6.09 6.54 5.53 5.93 5.33 5.73 Median 5 6 6 5 6 5 6 Range 0–10 0–10 3–10 0–10 3–10 2–10 0 1. Quartile 4 4.25 5 4 4 3,5 4 3. Quartile 7 8 8 7 7,5 6,5 7 NRS worst Mean 6.69 7.13 7.65 6.32 6.48 6.47 6.75 Median 7 7.5 8 7 7 7 7 Range 0–10 0–10 3–10 0–10 3–10 2–10 0 1. Quartile 5 5 6 4 5 5 5 3. Quartile 9 9.75 9 8 8 9,5 9 VRS average Mean 2.12 2.31 2.43 2.1 2.19 2.47 2.2 Median 2 2 2 2 2 3 2 Range 0–4 0–4 1–4 0–4 0–4 1–4 0 1. Quartile 2 2 2 2 2 2 2 3. Quartile 3 3 3 3 3 3 3 VRS worst Mean 2.52 2.5 2.7 2.36 2.56 2.53 2.49 Median 2 2 3 2 2 3 2 Range 0–4 0–4 1–4 0–4 1–4 1–4 0 1. Quartile 2 2 2 2 2 2 2 3. Quartile 3 3 3 3 3 3 3 subjects were registered to the study database and basic demo- Spain, Switzerland and Turkey). For each pruritus intensity graphic data and disease-related parameters were entered.20 scales (VAS, NRS and VRS), we evaluated (1) re-test relia- Afterwards, the subject filled in following patient-reported out- bility, (2) correlation among the intensity scales and (3) cor- come tools: for testing test–retest reliability, all subjects recorded relation with the impairment of quality of life measured by their average and worst pruritus intensity in the previous 24 h the DLQI. by completing the NRS, VAS and VRS twice after 30–60 min. For ordinal variables, we used the weighted Kappa statistic Additionally, subjects filled in the Dermatology Life Quality jw, as a meaningful measure of agreement. The statistic mea- Index (DLQI).21 sures the proportion of weighted agreement corrected for chance The study was approved by the leading ethic committee in agreement.23 We evaluated re-test reliability using (equal-spac- M€ unster (2015-171-f-S) and by each ethic committee of the par- ing) weighted Cohen’s Kappa jw and confusion-matrix plots ticipating sites. The study was registered at the German Clinical with weights according to the fraction of column and row popu- Trial Register (DRKS00007958). lation size for ordinal data.23 Cohen’s Kappa jw coefficients above 0.8 are considered as almost perfect, and between 0.61 Statistical analysis and 0.8 are considered as substantial.24 Correlation analyses The statistical analysis was performed using R (version across pruritus intensity scales and between these scales and 3.6.0).22 Subgroup analysis was performed for each pruritic DLQI were performed using Spearman’s rank correlation coeffi- condition (AD, CD, CNPG, Pso, LP and CTCL) and recruit- cient.25 All reported p values were corrected for multiple testing ing centre (Austria, France, Germany, Italy, Poland, Russia, applying Bonferroni correction. JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1180 Storck et al. Figure 2 Correlation between the repeatedly stated intensity Figure 4 Correlation between the different intensity scales segre- scales at two points of time t0 and t1 segregated for the participat- gated for the participating sites using the Spearman correlation ing sites using the weighted Kappa jW (<0 Less than chance coefficient (0.00–0.30 negligible correlation, 0.30–0.50 Low corre- agreement, 0.01–0.20 Slight agreement, 0.21–0.40 Fair agreement, lation, 0.50–0.70 Moderate correlation, 0.70–0.90 High correlation, 0.41–0.60 Moderate agreement, 0.61–0.80 Substantial agreement, 0.90–1.00 Very high correlation). The number of cases is shown in 0.81–0.99 Almost perfect agreement). The number of cases is the upper right corner, and the adjusted p-value is shown in the shown in the upper right corner, and the adjusted p-value is shown lower right corner for the particular correlation. in the lower right corner for the particular correlation. Figure 3 Correlation between the repeatedly stated intensity scales at two points of time t0 and t1 segregated for the (AD: ato- Figure 5 Correlation between the different intensity scales segre- pic dermatitis; CD: contact dermatitis; CNPG: chronic nodular gated for the dermatoses (AD: atopic dermatitis; CD: contact der- prurigo; Pso: psoriasis; LP: lichen planus; CTCL: cutaneous T-cell matitis; CNPG: chronic nodular prurigo; Pso: psoriasis; LP: Lichen lymphoma) using the weighted Kappa jW (<0 Less than chance planus; CTCL: cutaneous T-cell lymphoma) using the Spearman agreement, 0.01–0.20 Slight agreement, 0.21–0.40 Fair agreement, correlation coefficient (0.00–0.30 negligible correlation, 0.30–0.50 0.41–0.60 Moderate agreement, 0.61–0.80 Substantial agreement, Low correlation, 0.50–0.70 Moderate correlation, 0.70–0.90 High 0.81–0.99 Almost perfect agreement). The number of cases is correlation, 0.90–1.00 Very high correlation). The number of cases shown in the upper right corner, and the adjusted p-value is shown is shown in the upper right corner and the adjusted P-value is in the lower right corner for the particular correlation. shown in the lower right corner for the particular correlation. Results Study population The two most frequent dermatoses were psoriasis vulgaris From August 2015 until June 2016, a total of 547 (57.2% female) (33.0%) and atopic dermatitis (30.0%). Most of the participants subjects were enrolled (Table 1). The participants were aged had been suffering from CP for one to ten years (37.1%) or even between 18 and 98 (mean 51.6, SD  18.1, median 52.0) years. more than ten years (32.7%). There were no significant JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pruritus intensity scales across Europe 1181 (Tables 2 and 3). The average and worst intensity measured by VAS were highest in Turkey with a mean of 6.6 and 7.46 and a median of 6 and 8, respectively. Accordingly, the NRS was rated in Turkey with a mean and median of 7 for average and with 7.76 and 8.50 for the worst intensity. While in Poland the VAS and NRS were slightly lower, the NRS was similar to Turkey. The lowest intensities were found in Germany and Russia. While the reported VAS and VRS were quite similar in Germany and Russia, the NRS was slightly lower in Germany (average mean: 4.81 to 5.37 and worst mean: 5.88 to 6.29). Regarding the con- sidered diagnoses, the highest intensities of pruritus were found in the CNPG group. The mean of the VAS average and VAS worst was 6.22 and 7.25 and for the NRS 6.54 and 7.65. In con- trast, the lowest average intensities were measured for the atopic Figure 6 Correlation between the different intensity scales and dermatitis and cutaneous T-cell lymphoma, while the lowest the DLQI segregated for the participating sites using the Spearman worst intensities were found in psoriasis vulgaris. correlation coefficient (0.00–0.30 negligible correlation, 0.30–0.50 Low correlation, 0.50–0.70 Moderate correlation, 0.70–0.90 High correlation, 0.90–1.00 Very high correlation). The number of cases Reproducibility is shown in the upper right corner, and the adjusted P-value is Testing for re-test reliability, mostly substantial agreement was shown in the lower right corner for the particular correlation. found (0.61 ≤ jw ≤ 0.8), while 8 correlation coefficients hat only moderate agreement (0.41 ≤ jw ≤ 0.6) (Figs 2 and 3). The best agreement was observed in Russia with consistently almost perfect agreement (0.81 ≤ jw ≤ 0.99). For some intensity scales, only moderate agreement (0.41 ≤ jw ≤ 0.6) was obtained, for example for the VAS average in France. The correlation segre- gated by dermatosis was even more consistent. Only two correla- tions were slightly below (VAS average for cutaneous T-cell lymphoma) or above (VAS worst for atopic dermatitis) the sub- stantial agreement, while all other correlations had substantial agreement. Intraclass Correlation between the Intensity Scales The intraclass correlation was high for most scales and sites (Fig. 4). One exception was recorded in France, in which the correlation between the VAS and the NRS and VRS was low. Figure 7 Correlation between the different intensity scales and Considering the pruritus intensity scales for each dermatosis the DLQI segregated for the dermatoses (AD: atopic dermatitis; (Fig. 5), the intraclass correlation coefficient was also high, while CD: contact dermatitis; CNPG: chronic nodular prurigo; Pso: psori- in 13.89% of the cases a moderate correlation was shown. asis; LP: lichen planus; CTCL: cutaneous T-cell lymphoma) using the Spearman correlation coefficient (0.00–0.30 negligible correla- tion, 0.30–0.50 Low correlation, 0.50–0.70 Moderate correlation, Convergent validity 0.70–0.90 High correlation, 0.90–1.00 Very high correlation). The The correlation of the pruritus intensity scales with the DLQI number of cases is shown in the upper right corner, and the was low. The lowest correlation was measured at the French adjusted p-value is shown in the lower right corner for the particu- study site (0.04–0.30), while the highest correlation was attained lar correlation. in Russia (0.49–0.62) (Fig. 6). With regard to the dermatoses (Fig. 7), the correlations were very similar. Mostly, the analysis differences in itch intensity between males and females in any of resulted in a low correlation, but the lowest correlation was the six measures, and there was no significant correlation found for CNPG (0.12 up to 0.22) and the highest for CTCL between itch intensity and age and gender (Figure S2). (0.58–0.83). Pruritus intensity scales Concurrent validity For all pruritus intensity scales, observed scores ranged from An overview of the correlation analyses between the VAS and their minimum, 0 to their maximum, 4 (VRS) or 10 (VAS, NRS) NRS categories (no pruritus, mild, moderate, severe, very severe JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1182 Storck et al. Figure 8 Visualization of the correlation between the different grouped (0 ≙ No pruritus; 1 ≙ Mild pruritus; 2 ≙ Moderate pruritus; 3 ≙ Severe pruritus; 4 ≙ Very severe pruritus) intensity scales ((a) VAS average; (b) VAS worst; (c) NRS average; (d) NRS worst) and the DLQI segregated for the dermatoses (AD: atopic dermatitis; CD: contact dermatitis; CNPG: chronic nodular prurigo; Pso: psoriasis; LP: lichen planus; CTCL: cutaneous T-cell lymphoma). pruritus) and the DLQI can be seen in Fig. 8 (segregated by different languages and in different dermatoses.26 With a few country) and Fig. 9 (segregated by dermatosis). Generally, analy- exceptions, the reproducibility showed a substantial agreement sis in patients with no, mild, moderate, severe and very severe in all countries. A moderate agreement between the scores of the pruritus for VAS and NRS showed increasing DLQI scores with two measurement time points were found in France VAS average stronger pruritus intensity. and VRS worst, in Poland VAS average, in Switzerland NRS average and VRS average, and in Turkey VAS average and NRS Discussion worst. VAS worst showed a good result for the reproducibility in In this study, the most commonly used patient-reported instru- all countries. The intracorrelation coefficients indicated with at ments for measuring pruritus intensity were validated in least moderate correlation between the measures – with two JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pruritus intensity scales across Europe 1183 Figure 9 Visualization of the correlation between the different grouped (0 ≙ No pruritus; 1 ≙ Mild pruritus; 2 ≙ Moderate pruritus; 3 ≙ Severe pruritus; 4 ≙ Very severe pruritus) intensity scales ((a) VAS average; (b) VAS worst; (c) NRS average; (d) NRS worst) and the DLQI segregated for the dermatoses (AD: atopic dermatitis; CD: contact dermatitis; CNPG: chronic nodular prurigo; Pso: psoriasis; LP: lichen planus; CTCL: cutaneous T-cell lymphoma). exceptions: in France, VAS average correlated only weakly with Germany and Russia and also in pruritic dermatosis like atopic both NRS and VRS. dermatitis, contact dermatitis, psoriasis vulgaris and cutaneous As a second objective, the validity of the intensity scales was T-cell lymphoma. The low-to-moderate correlation between the tested in various pruritic dermatoses. Here, test–retest showed a intensity scales and the DLQI might be a sign of a low validity; substantial agreement and an at least moderate correlation otherwise, it can be assumed that the impairment of QoL with between the scales showing a good temporal stability and inter- subdimensions of function, emotion and symptoms is more item correlation. independent of intensity of pruritus. The highest (moderate) Intensity of pruritus correlated significantly with QoL in Italy, correlation to the DLQI was found in Germany, Italy, Poland Poland, Switzerland, Turkey, Spain and with one exception in and Russia. In France, there was only a significant correlation JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1184 Storck et al. with NRS average und VRS average. An explanation for the planus and cutaneous T-cell lymphoma. Country-specific, the small proportion of statistically significant correlations between VAS worst was the best reproducible and consistent measuring the intensity scales and the DLQI could be that in France more instrument in all countries. The NRS worst also showed a good patients were male and the population was the third youngest in correlation to the other intensity scales, but only a moderate this investigation. It could be assumed that younger men rate agreement between the test–retest scores in Poland and Turkey. their impairment of QoL lower even though pruritus intensity is According to this analyse, the VAS worst might be superior to high. This is confirmed by the observation that males under the NRS worst. However, in previous work VAS worst showed 65 years of age with CP achieve lower DLQI scores, both as more missing values than the NRS worst.7 Based on this investi- compared to females of the same age and to males over 65 years gation, the sensitivity to change cannot be illustrated. One can of age.27 assume that the VAS worst and the NRS worst do not improve Regarding dermatoses, there was a high correlation of the significantly and very fast under treatment, although it is effec- DLQI Score with the intensity of pruritus in cutaneous T-cell tive. A suitable instrument for detecting an antipruritic effect lymphoma, which suggests that – if present – pruritus has a great would be one that measures the intensity, but also the duration influence on the QoL in this dermatosis,28 whereas there was a and frequency of pruritus in the last 24h, as itch itself is known low correlation in the other diseases. It is particularly striking as a fluctuating symptom. here that the high pruritus intensity of CNPG showed no signifi- cant influence on QoL measured by the DLQI. Previous research Limitations has shown that patients with CNPG have a severe impairment in In this investigation, we tested the validity of pruritus intensity quality of life29; here, in addition to the intensity of pruritus, scales in the mentioned dermatoses and chronic prurigo at one other factors like the frequency of pruritus and the presence of day. The test for responsiveness is missing. Future studies should pruriginous lesions may appear to play also a negative role in also test the validity in chronic pruritus in non-lesional skin like influencing QoL. neuropathic, systemic or psychogenic itch. The concurrent validity showed, with the exception of France and patients with CNPG, a higher impairment of QoL with Acknowledgement increasing severity of CP. In France, there was no further We thank all members in the PruNet group especially Anna increase in the DLQI in the group of very severe pruritus (NRS, Post, Juliane Mozar, Tanja Winter, Friederike Elisabeth Viet- VAS = 9–10). meier and Julia Funke for helping collecting the data. The median pruritus intensity measured by the VAS and NRS values were 5–6. The highest scores were found in Turkey, the References lowest in Russia and Germany. Measuring the itch intensity by 1 Kopyciok MER, St€ander HF, Osada N et al. Prevalence and characteristics of pruritus: a one-week cross-sectional study in a german dermatology the VRS, the median of the VRS was 2; patients in Italy, Poland, practice. Acta Derm Venereol 2016; 96: 50–55. Turkey and Spain scored slightly higher. Neither age, gender, 2 St€ander S. Classification of Itch. Curr Probl Dermatol 2016; 50: 1–4. diagnosis nor duration of pruritus in these countries is particu- 3 Steinke S, Zeidler C, Riepe C et al. Humanistic burden of chronic pruritus larly different from the others. One can assume that this could in patients with inflammatory dermatoses: Results of the European Acad- emy of Dermatology and Venereology Network on Assessment of Severity be a culture effect since the humanistic burden in patients with and Burden of Pruritus (PruNet) cross-sectional trial. J Am Acad Derma- CP in inflammatory dermatoses is also strongly influenced by tol 2018; 79: 457–463.e5. cross-cultural factors.3 However, we did not correct for ongoing 4 Leader B, Carr CW, Chen SC. Pruritus epidemiology and quality of life. Handb Exp Pharmacol 2015; 226: 15–38. therapy, what might be an additional factor. 5 Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain In the dermatoses, the highest pruritus intensity was found intensity rating scales. Pain 2011; 152: 2399–2404. for CNPG in almost all intensity scales. This confirms other 6 Ferraz MB, Quaresma MR, Aquino LR et al. Reliability of pain scales in studies, in which the intensity of CNPG was higher than in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheumatol 1990; 17: 1022–1024. other dermatoses.30 Peripheral sensitization processes have 7 Phan NQ, Blome C, Fritz F et al. Assessment of pruritus intensity: been demonstrated in CPG.31 These can lead to chronicity of prospective study on validity and reliability of the visual analogue scale, the symptom, which results not only in the form of alloknesis numerical rating scale and verbal rating scale in 471 patients with chronic but also in the presence of constant pruritus with a high pruritus. Acta Derm Venereol 2012; 92: 502–507. 8 Reich A, Heisig M, Phan NQ et al. Visual analogue scale: evaluation of intensity.29 the instrument for the assessment of pruritus. Acta Derm Venereol 2012; In summary, the itch intensity scales had good intraclass cor- 92: 497–501. relations, fulfilled the validity criteria ‘reproducibility’ and where 9 Jang YH, Kim SM, Eun DH et al. Validity and reliability of itch assess- independent from age and gender. The ‘convergent’ and ‘con- ment scales for chronic pruritus in adults: A prospective multicenter study. J Am Acad Dermatol 2020; 82: 80–86. current validity’ were good in Italy, Poland, Switzerland, Turkey, 10 Kido-Nakahara M, Katoh N, Saeki H et al. Comparative cut-off value set- Spain and with one exception in Germany and Russia and in ting of pruritus intensity in visual analogue scale and verbal rating scale. atopic dermatitis, contact dermatitis, psoriasis vulgaris, lichen Acta Derm Venereol 2015; 95: 345–346. JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. 14683083, 2021, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.17111 by Readcube (Labtiva Inc.), Wiley Online Library on [08/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pruritus intensity scales across Europe 1185 11 Reich A, Chatzigeorkidis E, Zeidler C et al. Tailoring the cut-off values of 23 Cohen J. A Coefficient of agreement for nominal scales. Educ Psychol the visual analogue scale and numeric rating scale in itch assessment. Acta Measure 1960; 20: 37–46. Derm Venereol 2017; 97: 759–760. 24 Landis JR, Koch GG. The measurement of observer agreement for cate- 12 Yosipovitch G, Reaney M, Mastey V et al. Peak Pruritus Numerical Rat- gorical data. 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Dermatology 2015; 231: 253–259. que psoriasis. Br J Dermatol 2016; 175: 157–162. 28 Holahan HM, Farah RS, Fitz S et al. Health-related quality of life in 15 Kimel M, Zeidler C, Kwon P et al. Validation of psychometric properties patients with cutaneous T-cell lymphoma? Int J Dermatol 2018; 57: of the itch numeric rating scale for pruritus associated with Prurigo 1314–1319. Nodularis: a secondary analysis of a randomized clinical trial. JAMA Der- 29 Pereira MP, Hoffmann V, Weisshaar E et al. Chronic nodular prurigo: matol 2020; 156: 1354. clinical profile and burden. A European cross-sectional study. J Eur Acad 16 St€ander S, Zeidler C, Riepe C et al. European EADV network on assess- Dermatol Venereol 2020; 34: 2373–2383. ment of severity and burden of Pruritus (PruNet): first meeting on out- 30 Schut C, Dalgard FJ, Halvorsen JA et al. Occurrence, chronicity and come tools. 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Validation of pruritus measures gath- ered with the electronic patient-reported outcome system MoPat. Acta Additional Supporting Information may be found in the online Derm Venereol 2018; 98: 38–43. version of this article: 20 Zeidler C, Steinke S, Riepe C et al. Cross-European validation of the Itch- yQoL in pruritic dermatoses. J Eur Acad Dermatol Venereol 2019; 33: 391–397. Figure S1. Distribution of the different intensity scales grouped 21 Basra MKA, Fenech R, Gatt RM et al. The Dermatology Life Quality by gender (F: female; M: male). Index 1994–2007: a comprehensive review of validation data and clinical results. Br J Dermatol 2008; 159: 997–1035. Figure S2. Correlation of the different intensity scales with the 22 R Core Team. R. A Language and Environment for Statistical Computing, age of the participants. 2019: https://www.R-project.org/. JEADV 2021, 35, 1176–1185 © 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.