DOI: 10.1111/jdv.16309 JEADV ORIGINAL ARTICLE Chronic nodular prurigo: clinical profile and burden. A European cross-sectional study M.P. Pereira,1,* V. Hoffmann,1 E. Weisshaar,2 J. Wallengren,3 J.A. Halvorsen,4 S. Garcovich,5 L. Misery, E. Brenaut,6 E. Savk,7 N. Potekaev,8 A. Lvov,8 S. Bobko,8 J.C. Szepietowski,9 A. Reich,10 6 A. Bozek,11 F.J. Legat,12 M. Metz,13 M. Streit,14 E. Serra-Baldrich,15 M. Goncß alo,16 M. Storck,17 I. Greiwe,1 €nder,1 C. Zeidler1 on behalf of the EPP Consensus Conference Par- T. Nau,1 S. Steinke,1 M. Dugas,17 S. Sta † ticipants 2017 1 Department of Dermatology and Center for Chronic Pruritus, University Hospital Mu €nster, Mu €nster, Germany 2 Occupational Medicine, Department of Dermatology, University of Heidelberg, Heidelberg, Germany 3 Department of Clinical Sciences Lund, Dermatology and Venereology and Skane University Hospital, Lund, Sweden 4 Department of Dermatology, Oslo University Hospital, University of Oslo, Oslo, Norway 5  Cattolica del Sacro Cuore, Rome, Italy Institute of Dermatology, F. Policlinico A. Gemelli IRCCS, Universita 6 Department of Dermatology, University Hospital of Brest, Brest, France 7 Department of Dermatology, Aydin Adnan Menderes University, Aydın, Turkey 8 Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology, Moscow, Russia 9 Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland 10 Department of Dermatology, University of Rzeszow, Rzeszo w, Poland 11 Department of Dermatology, School of Medicine, University of Information Technology and Management, Rzeszow, Poland 12 Department of Dermatology, Medical University of Graz, Graz, Austria 13 Department of Dermatology and Allergy, Charite  – Universita €tsmedizin Berlin, Berlin, Germany 14 Department of Dermatology, Kantonsspital Aarau, Aarau, Switzerland 15 Department Dermatology, Sant Pau Hospital, Barcelona, Spain 16 Department of Dermatology, University Hospital and Faculty of Medicine, University of Coimbra, Coimbra, Portugal 17 €nster, Mu Institute of Medical Informatics, University of Mu €nster, Germany *Correspondence: M.P. Pereira. E-mail: manuelpedro.pereira@ukmuenster.de Abstract Background Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this condition, especially regard- ing its clinical characteristics and impact on quality of life is still lacking. Objectives Aim of this pan-European multicentre cross-sectional study was to establish the clinical profile of CNPG, including its associated burden. Methods Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres’ own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co-morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed. Results A total of 509 patients (210 male, median age: 64 years [52; 72]) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to sev- ere worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the dis- ease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%). Conclusions This multicentre cross-sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe. Received: 30 September 2019; Accepted: 27 January 2020 † See Appendix 1. JEADV 2020, 34, 2373–2383 © 2020 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-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. 14683083, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 2374 Pereira et al. Conflicts of interest MPP, VH, EW, JW, JAH, SG, LM, EB, ES, NP, AL, SB, FJL, MM, MS, ESB, MG, MS, IG, TN, SS, MD, CZ, FD, JE, CF, CR, GS and HS declare no conflicts of interest. MPP is an investigator in a clinical trial sponsored by Trevi and has received speaker honoraria from Galderma and Trevi. JCS is advisor for AbbVie, Almirall, Celgene, Dignity Sciences, LEO Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, Sienna Biopharmaceuticals and Trevi, Toray Corporation, and has received speaker honoraria from AbbVie, Janssen-Cilag, LEO Pharma, Novartis, SunFarm, Sandoz and Eli Lilly; and clinical trial funding from AbbVie, Almirall, Amgen, Janssen-Cilag, Menlo Therapeutica, Merck, Novartis, Pfizer, Regeneron, Trevi and UCB. AR is a consultant or speaker for AbbVie, Bioderma, Celgene, Chema Elektromet, Eli Lilly, Galderma, Janssen, Leo Pharma, Medac, Menlo Therapeutics, Novartis, Pierre-Fabre, Sandoz and Trevi and a principal investigator or subin- vestigator in clinical trials sponsored by AbbVie, Drug Delivery Solutions Ltd, Galderma, Genentech, Janssen, Kymab Limited, Leo Pharma, Menlo Therapeutics, MetrioPharm, MSD, Novartis, Pfizer and Trevi. AB is a subinvestigator in clini- cal trials sponsored by Drug Delivery Solutions Ltd, Genentech, Leo Pharma, Menlo Therapeutics and Trevi. SST is a consultant for Almirall, Bayer, Beiersdorf, Bionorica, Cara Therapeutics, Celgene, DS Biopharma, Galderma, Kneipp, Menlo Therapeutics, NeRRe Therapeutics, Novartis, Perrigo, Sienna Therapeutics, ACO HUD Nordic, Toray, Sanofi, Trevi Therapeutics, Bellus Health and an investigator for Dermasence, Galderma, Kiniksa, Menlo Therapeutics, Trevi Thera- peutics, Novartis. TB is an advisor for Menlo Therapeutics (products may be related) and Novartis (unrelated). Funding source European Academy of Dermatology and Venereology (EADV, No. 2016-012 to MP). Introduction centres from Germany (M€ unster, Heidelberg and Berlin), Chronic nodular prurigo (CNPG; synonym: prurigo nodularis) is Northern Europe (Sweden and Norway), Central Europe a subtype of chronic prurigo, which is considered a disease char- (Switzerland, France and Austria), Eastern Europe (Poland- acterized by chronic itch (i.e. itch lasting for 6 weeks or longer), a Wroclaw, Poland-Rzeszow and Russia) and Southern Europe prolonged scratching behaviour and the presence of localized or (Italy, Turkey, Spain and Portugal). Distribution of countries disseminated pruriginous lesions.1,2 CNPG develops in predis- by regions was performed according to a historic widely posed patients regardless of the aetiology of the underlying itch, accepted classification. which can be of dermatological, systemic, neurological, psychi- The study was approved by the local ethics committees corre- atric/psychosomatic, multifactorial or unknown nature.3 The sponding to the study centres (main ethics committee: Medical pathophysiology of CNPG remains largely unknown, but neu- Faculty of the University of M€ unster, nb.: 2017-168-f-S). Addi- ronal sensitization mechanisms and a continuous itch-scratch tionally, we registered the study at the German registry of clinical cycle are thought to contribute to the chronicity of the disease.4 trials (DRKS00012876, registration date: 09.08.2017). A comprehensive understanding of CNPG is still lacking. Establishing the clinical profile of the disease (demographic Subjects characteristics of the affected patient population, co-morbidities, Local investigators informed and invited adult CNPG patients, as itch intensity, concomitant sensory symptoms and secondary defined by the European Academy of Dermatology and Venereol- burden of the disease) is a major need for attending physicians. ogy Task Force Pruritus1, to participate in the study. Patients were Even though no epidemiology studies have assessed the preva- either recruited at the centre when presenting to a routine appoint- lence of CNPG, this condition is considered to be relatively rare. ment or were contacted via the centres’ own databases. Patients Therefore, multicentre studies are needed in order to explore with CNPG presenting to the centre in the previous 10 years were this disease. We performed a prospective cross-sectional patient- contacted. After signing the informed consent, patients received reported questionnaire study, in which 15 centres across 12 the questionnaire (Appendix S1) consisting of 37 questions either European countries participated, with the aim of establishing the in paper or electronic format. Access to the mobile patient survey clinical profile and burdens of CNPG. This is an important step system (MoPat@Home) developed by the Institute of Medical in order to gain a better understanding of the disease and conse- Informatics at the University of M€ unster, Germany5 was provided quently to provide a better care for affected patients. via a link sent by email. The patients’ answers were automatically pseudonymized and sent SSL-encrypted to a central database in Methods M€ unster, Germany. Data from paper questionnaires were entered In the frame of the European Prurigo Project (EPP),1 we in the database by the investigators. The database identified the conducted a prospective, cross-sectional, cohort study in country of origin and date of release by the patient. JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 Chronic prurigo: clinical profile 2375 Preparation of the questionnaire performed using the Kolmogorov–Smirnov test. The chi- In order to address the aims of the study, a steering committee squared test, Mann–Whitney U test and the Kruskal–Wallis test (M. Augustin, C. Forner, F. Legat, M. Pereira, C. Riepe, S. were used for group comparisons, as appropriate. Spear- St€ander, J. Sziepietowski, J. Wallengren, E.Weisshaar, C. Zeidler) mans’rho was applied for correlation analyses. Data are shown prepared the scientific background and discussion on relevant as number of cases/total number of assessments (percentage) or aspects needed to be unveiled in respect to the clinical profile of as median [interquartile range]. Not all patients answered all CNPG, as well as a set of questions. This set of questions was dis- items of the questionnaire. The total number of patients, who cussed and refined and finally approved via voting using the Del- answered the question, is shown for each item. All statistical tests phi method6 in a consensus conference held on 3 February 2017 were two sided, and the significance level was set at P < 0.05. in M€ unster (Germany). The consensus conference was attended by 25 participants (24 dermatologists and one specialist for psy- Results chosomatics and psychotherapy) from 12 different countries and was moderated by an external neutral physician. Consensus was Demographics obtained when 75% or more of the participants agreed on the Between March 2017 and June 2019, 509 patients (59% female, question being voted. Questions, for which no agreement could 41% male), aged 18–100 years (median 64 years [52; 72], be reached during the consensus meeting, were further discussed n = 498), were enrolled in the various centres. Males (67 [54; 73], and agreed upon using a postmeeting paper-based Delphi n = 203) were older than females (62 [50; 70], n = 295; method (March 8–15th, 2017). P < 0.001). Demographics and co-morbidities for the whole pop- The questionnaire was translated and backtranslated by a pro- ulation and by region are given in Table 1. Females reported more fessional translation agency involving also for quality checks the often suffering from rhinitis/conjunctivitis compared to men native investigators of all participating centres. The preliminary [n = 97 (34%) vs. n = 46 (22%), P = 0.005], while no sex differ- translated version was reviewed by each centres’ principal investi- ences were observed for atopic eczema or asthma. Patients gator, and eventual corrections or adjustments were sent back to reported a median duration of CNPG of 6 [3; 13] years (n = 437, the professional translation office until a final version was agreed. only patients reporting disease begin in adulthood were consid- A first translator performed the translation; a second and indepen- ered, Table 1). The skin type distribution is displayed in Fig. 1. dent translator performed the back-translation of the questionnaire Concerning the educational level, 21.1% (104/494) of all patients in order to compare it to the original version. If needed, additional finished school without further education, 32.2% (159/494) did adjustments were performed at this stage. The questionnaire was an apprenticeship, 32.8% (162/494) had a graduate degree, 11.1% available both in electronic and paper format for every language. (55/494) had another education and 2.8% (14/494) abstained from answering. More than half of the patients (51.5%, 258/501) Assessments were retired, while 34.3% (172/501) were employed and 14.2% In this present paper, data from the first 26 questions of the (71/501) unemployed at the time of questioning. questionnaire including demography (age, sex, height, weight, Of the 509 enrolled patients, 79.8% (n = 406) answered ques- skin type, highest education, employment status and age of tions 13 and 14 both positively and completed the whole ques- CNPG onset; questions 1–9), current co-morbidities (atopic tionnaire (Germany: 137/185, 74.1%; Northern Europe: 69/92, eczema, asthma and rhinitis/conjunctivitis; questions 10–12), 75.0%; Central Europe: 57/70, 81.4%; Eastern Europe: 76/84, worst itch intensity in the past 24 h assessed by the verbal rating 90.5%; and Southern Europe: 67/78, 85.9%). The data presented scale 0–47 (VRS 24 h; question 15) and by the numerical rating in the next sections refer to the 406 patients who answered posi- scale 0–107 (NRS 24 h; question 16), sensory symptoms (ques- tively to both qualification questions (questions 13/14). tions 17), quality of life (questions 18–22 corresponding to the 5-PLQ (pruritus life quality) questionnaire8), highest burden Itch, sensory symptoms and underlying diseases (question 23), emotional experience of itch (question 24) and The median worst itch intensity in the previous 24 h assessed by underlying diseases (questions 25–26) are reported. Data from the NRS was 7 [4; 8] (moderate intensity; n = 393), while the the remaining questions will be presented in a second paper. VRS self-categorization scale showed moderate to severe itch Questions 13 (have you had itch within the last 7 days?) and scores (Fig. 2). We recorded lower itch intensity scores in Ger- 14 (have you had prurigo lesions within the last 7 days?) quali- many compared to Eastern Europe (NRS: P = 0.003; VRS: fied the patients to continue completing the questionnaire, if P < 0.001) and Southern Europe (NRS: P = 0.02; VRS: both were positively answered. P = 0.003), in Northern Europe compared to Eastern Europe (NRS: P = 0.03; VRS: P = 0.002) and Southern Europe (VRS: Statistics P = 0.02) and in Central Europe compared to Eastern Europe Data analysis was performed with IBM SPSS Statistics for Win- (NRS: P = 0.04). There were no sex differences in itch intensity dows, v. 25.0 (Armonk, NY, USA). Analysis of normality was assessed by the NRS (male: 7 [4; 8], female: 7 [4; 8]; P = 0.62, JEADV 2020, 34, 2373–2383 © 2020 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 2376 Table 1 Demographics and co-morbidities of the enrolled patients in total (All) and by region i.e. Germany (Mu €nster, Heidelberg and Berlin), Northern Europe (Sweden and Nor- way), Central Europe (Switzerland, France and Austria), Eastern Europe (Poland-Wroclaw, Poland-Rzeszow and Russia) and Southern Europe (Italy, Turkey, Spain and Portugal) JEADV 2020, 34, 2373–2383 Characteristic All Germany Northern Europe Central Europe Eastern Europe Southern Europe N (%) 509 (100) 185 (36.3) 92 (18.1) 70 (13.8) 84 (16.5) 78 (15.3) Age, years 64 [52; 72], n = 498 63 [52; 70], n = 182 69 [60; 75], n = 88 63 [50; 72], n = 66 65 [50; 70], n = 84 56 [42; 70], n = 78 Male, n (%) 210 (41.3), 79 (42.7) 42 (45.7) 26 (37.1) 43 (51.2) 20 (25.6) Height, cm 168 [162; 175], n = 502 170 [164; 176], n = 183 171 [165; 178], n = 90 168 [163; 175], n = 68 167 [162; 173], n = 84 163 [158; 168], n = 77 Weight, kg 77 [65; 93], n = 500 79 [67; 95], n = 183 78 [68; 97], n = 88 75 [63; 88], n = 69 77 [65, 89], n = 82 73 [60, 88], n = 78 BMI (kg/m2) 27.0 [23.7; 31.3], n = 496 27.0 [24.2; 31.1], n = 182 25.8 [23.3; 33.0], n = 87 25.7 [23.2; 30.0], n = 68 27.2 [23.8; 32.0], n = 82 27.5 [22.8; 32.7], n = 77 Disease duration (years) 6 [3; 13], n = 437 6.5 [3.3;13], n = 156 6 [11; 20.5], n = 77 6 [3; 13], n = 62 6 [3; 13], n = 70 3.5 [1; 9.8], n = 72 Co-morbidities, n (%) High blood pressure 217 (42.6) 82 (44.3) 34 (37.0) 32 (45.7) 39 (46.4) 30 (38.5) Back pain 148 (29.1) 73 (39.5) 25 (27.2) 24 (34.3) 13 (15.5) 13 (16.7) Heart disease 96 (18.9) 27 (14.6) 13 (14.1) 13 (18.6) 27 (32.1) 16 (20.5) Depression 92 (18.1) 45 (24.3) 14 (15.2) 8 (11.4) 4 (4.8) 21 (26.9) Diabetes 89 (17.5) 34 (18.4) 12 (13.0) 8 (11.4) 17 (20.2) 18 (23.1) Lung disease 49 (9.6) 22 (11.9) 7 (7.6) 6 (8.6) 9 (10.7) 5 (6.4) Arthritis 48 (9.4) 23 (12.4) 7 (7.6) 3 (4.3) 12 (14.3) 3 (3.8) Ulcer/stomach disease 37 (7.3) 10 (5.4) 9 (9.8) 1 (1.4) 11 (13.1) 6 (7.7) Kidney disease 33 (6.5) 16 (8.6) 3 (3.3) 2 (2.9) 6 (7.1) 6 (7.7) Anaemia/blood disease 30 (5.9) 10 (5.4) 2 (2.2) 6 (8.6) 4 (4.8) 8 (10.3) Liver disease 29 (5.7) 13 (7.0) 2 (2.2) 1 (1.4) 10 (11.9) 3 (3.8) Rheumatoid arthritis 28 (5.5) 12 (6.5) 6 (6.5) 4 (5.7) 3 (3.6) 3 (3.8) Cancer 20 (3.9) 5 (2.7) 4 (4.3) 6 (8.6) 1 (1.2) 4 (5.1) Other 166 (32.6) 63 (34.1) 23 (25.0) 12 (17.1) 36 (42.9) 32 (41) None 76 (14.9) 21 (11.4) 19 (20.7) 14 (20.0) 10 (11.9) 12 (15.4) Atopy, n (%) Atopic eczema 163/492 (33.1) 76/180 (42.2) 45/90 (50.0) 15/68 (22.1) 11/78 (14.1) 16/76 (21.1) Rhinitis/conjunctivitis 143/492 (29.1) 48/174 (27.6) 29/90 (32.2) 28/69 (40.6) 22/83 (26.5) 16/76 (21.1) Asthma 103/594 (20.4) 47/185 (25.4) 20/91 (22.0) 17/69 (24.6) 7/82 (8.5) 12/77 (15.6) Data are presented number of cases (percentage) or median [interquartile range]. BMI, Body Mass Index. Pereira et al. © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 14683083, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 Chronic prurigo: clinical profile 2377 Type 1 Type 2 Quality of life and Burden Type 3 Type 4 Type 5 Type 6 Skin types per region The highest burden reported by patients was itch (49.3%), fol- lowed by visibility of skin lesions (21.4%), bleeding of skin 60 53.9% lesions (14.1%), impact on everyday life activities (4.9%), sleep 51.2% 45.3% 50 disturbance (4.3%), psychological consequences (3.3%) and Percentage of patients (%) 43.6% 40.7% 39.5% pain (2.3%; n = 304; Fig. 3, Table 3). As for the emotional expe- 37.7% 37.7% 36.6% 34.8% 40 34.8% rience of itch, patients (n = 406) described their itch in various 26.9% 30 ways, with disturbing (55.2%), burdensome (50.7%), agonizing 23.1% (46.6%) and intractable (35.0%) mentioned most often (Fig. 4, 20 13.0% Table 3). 11.4% 9.9% 71.1% of patients reported experiencing itch often or always 6.1% 10 4.5% 4.3% 3.9% 3.8% 3.4% 3.0% 2.9% 2.4% 1.4% (n = 402). Their everyday life was negatively affected in 53.1% 1.2% 1.1% 0.6% 0.4% 0 of the cases (very or rather affected, n = 405). The itch affected l y e e e e Al an op op op op the interaction of the patients with others in 37.6% of the cases m r ur r r Eu Eu Eu er lE G (very or rather affected, n = 404). Sleep was impaired in 42.5% n n rn tra er er he en th st ut Ea or of patients (very or rather affected, n = 405), while the joy and C So N mood were negatively affected in 44.4% of patients (very or Figure 1 Proportion of patients per skin type (according to the rather affected, n = 403). Figure 5 shows the results for all the Fitzpatrick classification) in the whole study population (All, patients and by region. n = 499; abstain: 3.6%) and by region i.e. Germany (Mu € nster, Hei- Quality of life as assessed by the 5PLQ scale was moderately delberg and Berlin) n = 181; Northern Europe (Sweden and Nor- way) n = 89; Central Europe (Switzerland, France and Austria) impaired due to CNPG (2.4 [1.6; 3.0], n = 405; Fig. 6). The n = 69; Eastern Europe (Poland-Wroclaw, Poland-Rzeszow and 5PLQ score correlated positively with the NRS score [r = 0.62 Russia) n = 82; and Southern Europe (Italy, Turkey, Spain and Por- (moderate correlation strength), P < 0.001]. We recorded lower tugal) n = 78. 5PLQ scores in Germany compared to Eastern Europe (P = 0.01) and Southern Europe (P = 0.04) and in Northern n = 393), and age did not correlate with NRS scores (r = 0.02, Europe compared to Central Europe (P = 0.007), Eastern Eur- P = 0.67, n = 386). We observed a negative correlation between ope (P < 0.001) and Southern Europe (P = 0.03). NRS scores and height [r = 0.101 (low correlation strength), P = 0.047, n = 390], but not between NRS and weight Discussion (r = 0.097, P = 0.057, n = 387) or body mass index This large European cross-sectional questionnaire study con- (r = 0.070, P = 0.173, n = 385). There were no differences in tributes to a better understanding of CNPG, providing compre- NRS scores from patients reporting having atopic eczema hensive data on the clinical profile of the disease including (P = 0.79, n = 386) or asthma (P = 0.75, n = 392) compared to associated dimensions of burden. those not suffering from these conditions, while a negative cor- Itch was considered the highest burden of the disease by relation between NRS scores and disease duration was recorded CNPG patients (49%). Using the NRS, we recorded a severe [r = 0.116 (low correlation strength), P = 0.032]. NRS scores median worst itch intensity (7 [4; 8]), with 51.2% of patients did not differ across skin types (P = 0.14, n = 388) or according rating the itch 7/10 or higher in the NRS scale (severe or very to employment status (P = 0.21, n = 390). As for educational severe itch). The intensity showed only minor variations degree, patients with lower educational level (regular school throughout Europe. It cannot be ruled out that seasonal varia- only) showed higher NRS scores (NRS: 8 [5; 9], n = 84) com- tions or current treatments influenced itch assessments as we did pared to those with an additional apprenticeship (NRS: 6 [4; 8], not control for these factors. Interestingly, the assessment on the n = 110; P = 0.001) or a graduate degree (NRS: 6 [4; 8], NRS correlated well with the self-categorization on the VRS. n = 136; P < 0.001). Only a small proportion of patients underrated the severity in In addition to itch, the most frequently reported sensory relation to the intensity (Fig. 2). So, when asked to verbalize symptoms were burning (39.9%), stinging (35.7%) and pain their itch intensity, almost half of the patients (48.2%) rated (32.5%). The distribution of the reported sensory symptoms by their itch as severe or very severe. The itch intensity recorded in regions is presented in Table 2. our study is in line with previous reports. In a large multicentre Over 30% of patients (141/395) indicated being told that their European study analysing itch in patients with different skin dis- CNPG was related to an underlying disease (question 25). This eases, itch intensity scores of CNPG patients were comparable to disease was in most of the cases a psychiatric/psychosomatic dis- those from our study, however, only 17 prurigo patients were ease (19.3%, 21/109), followed by diabetes (15.6%, 17/109) and assessed (mean itch intensity 6.15  2.98).9 Lower itch intensi- allergy (9.2%, 10/109; Table 2). ties were recorded for other skin conditions such as atopic JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 2378 Pereira et al. (a1) Itch intensity by NRS (a2) 10 25 8 20.1 20 NRS score 6 Percentage (%) 14.8 4 15 12.0 11.7 2 10 9.2 8.4 7.6 6.1 6.4 0 5 3.1 l y e pe e pe Al an p op 0.8 ro ro ro m r Eu Eu Eu Eu 0 er G rn l n rn tra 0 1 2 3 4 5 6 7 8 9 10 er e he en th st ut Ea or C So Weak Moderate Severe Very severe N 9.2% 40.0% 32.1% 18.1% NRS All Germany Northern Central Eastern Southern Europe Europe Europe Europe Median 7 6 6 7 7.5 7 [IQR] [4;8] [4;8] [5;8] [4;8] [5;9.8] [5;8] n= 393 136 60 56 76 65 Severe Moderate Moderate Severe Severe Severe (b1) (b2) Itch intensity by VRS 4 45 39.9 40 3 35.3 35 31.8 32.1 VRS score Percentage (%) 30 2 25 20 18.1 1 15.7 16.4 15 9.2 0 10 5 l y pe e pe pe Al an op ro ro ro 0.7 0.8 m ur Eu Eu Eu 0 er lE G n n rn tra None Weak Moderate Severe Very severe er er he en th st ut Ea or C So N NRS All Germany Northern Central Eastern Southern Europe Europe Europe Europe Median 2 2 2 3 3 3 [IQR] [2;3] [2;3] [2;3] [2;3] [2;4] [2;4] n= 402 135 68 56 76 67 Moderate Moderate Moderate Severe Severe Severe Figure 2 Worst itch intensity of the previous 24 h assessed by the NRS (scale 0–10, n = 393) and VRS (scale 0–4, n = 402). (a1) Median NRS worst itch intensity scores by region. (a2) Distribution of NRS scores for the whole study population. (b1). Median VRS worst itch intensity scores by region. (b2) Distribution of VRS (dark blue) and NRS (light blue) scores for the whole study population. NRS, numerical rating scale; VRS, verbal rating scale. Median [interquartile range] are shown in a1 (NRS) and b1 (VRS), while the distribution of scores is presented in percentage in a2 (NRS) and b2 (VRS, NRS) for all patients. dermatitis, hand eczema, urticaria, psoriasis or bullous diseases.9 patients with chronic pruritus, in which socioeconomic status Interestingly, itch intensity did not differ between patients with does not seem to be an important factor.10 CNPG patients with atopic conditions such as atopic eczema or asthma and those lower educational levels may have a lower level of health literacy without them. Thus, atopic diathesis does not seem to be a rele- and detrimental coping strategies for CNPG. vant factor for the itch intensity in CNPG, as non-atopic patients In addition to itch, CNPG patients also experience other sen- are equally affected. Patients with lower educational levels sory symptoms such as burning, stinging and pain. These sensa- reported suffering from higher itch intensities. This differs from tions are typically found in neuropathic itch conditions,11 which JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 Chronic prurigo: clinical profile 2379 Table 2 Chronic nodular prurigo related sensations and other contributing diseases for all patients (n = 406) and by region i.e. Germany (Mu €nster, Heidelberg and Berlin) n = 137; Northern Europe (Sweden and Norway) n = 69; Central Europe (Switzerland, France and Aus- tria) n = 57; Eastern Europe (Poland-Wroclaw, Poland-Rzeszow and Russia) n = 76; and Southern Europe (Italy, Turkey, Spain and Portu- gal) n = 67 Characteristic All Germany Northern Europe Central Europe Eastern Europe Southern Europe Sensory symptoms Burning 162 (39.9) 53 (38.7) 20 (29.0) 23 (40.4) 31 (40.8) 35 (52.2) Superficially localized 149 (36.7) 53 (38.7) 39 (56.5) 26 (45.6) 18 (23.7) 13 (19.4) Stinging 145 (35.7) 59 (43.1) 19 (27.5) 17 (29.8) 28 (36.8) 22 (32.8) Localized deep inside 136 (33.5) 54 (39.4) 30 (43.5) 17 (29.8) 12 (15.8) 23 (34.3) Painful 132 (32.5) 59 (43.1) 23 (33.3) 21 (36.8) 17 (22.4) 12 (17.9) Prickling 71 (17.5) 24 (17.5) 9 (13.0) 8 (14) 15 (19.7) 15 (22.4) Spiky 70 (17.2) 16 (11.7) 16 (23.2) 10 (17.5) 6 (7.9) 22 (32.8) Sharp 52 (12.8) 12 (8.8) 10 (14.5) 13 (22.8) 7 (9.2) 10 (14.9) Stroking 34 (8.4) 10 (7.3) 15 (21.7) 1 (1.8) 4 (5.3) 4 (6) Other 21 (5.2) 9 (6.6) 5 (7.2) 3 (5.3) 4 (5.3) 0 (0.0) Suspected contributing disease 141/395 (35.7) 53/135 (39.3) 11/65 (16.9) 16/56 (28.6) 22/73 (30.1) 39/66 (59.1) Psychiatric/Psychosomatic disease 21 (5.3) 4 (3.0) 2 (3.1) 5 (8.9) 0 (0) 10 (15.1) Diabetes 17 (4.3) 4 (3.0) 0 (0) 2 (3.6) 2 (2.7) 9 (13.6) Atopic eczema 10 (2.5) 6 (4.4) 0 (0) 0 (0) 1 (1.4) 3 (4.5) Allergy 10 (2.5) 5 (3.7) 3 (4.6) 0 (0) 0 (0) 2 (3.0) Liver disease 7 (1.8) 2 (1.5) 0 (0) 0 (0) 4 (5.5) 1 (1.5) Iron deficiency 4 (1.0) 0 (0) 0 (0) 0 (0) 0 (0) 4 (6.1) Kidney disease 4 (1.0) 0 (0) 0 (0) 0 (0) 0 (0) 4 (6.1) Neurologic disease 4 (1.0) 1 (0.7) 1 (1.5) 1 (1.8) 0 (0) 1 (1.5) Thyroid disease 4 (1.0) 2 (1.5) 0 (0) 0 (0) 1 (1.4) 1 (1.5) Malignant neoplasm 3 (0.8) 1 (0.7) 0 (0) 2 (3.6) 0 (0) 0 (0) Eczema (not atopic) 2 (0.5) 1 (0.7) 0 (0) 1 (1.8) 0 (0) 0 (0) Atopic disposition 1 (0.3) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.5) Drug intake 1 (0.3) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.5) HIV 1 (0.3) 0 (0) 0 (0) 0 (0) 1 (1.4) 0 (0) Skin infection 1 (0.3) 1 (0.7) 0 (0) 0 (0) 0 (0) 0 (0) Skin lymphoma 1 (0.3) 0 (0) 0 (0) 0 (0) 1 (1.4) 0 (0) Unknown 2 (0.5) 0 (0) 0 (0) 0 (0) 2 (2.7) 0 (0) Other 16 (4.1) 6 (4.4) 1 (1.5) 4 (7.1) 3 (4.1) 2 (3.0) Data presented as n (%). support recent findings of altered epidermal neuroanatomy in while 5.2% saw it as a contributing factor for CNPG. According patients with CNPG12 and confirm previous reports.13 to the 5PLQ, quality of life was moderately to severely impaired The humanistic burden of CNPG seems to be high according due to CNPG (5PLQ: 2.4 [1.6; 3.0], n = 405). This is in line with to available literature. Previous studies reported similar or even a previous study, in which a high Dermatological Life Quality higher rates of clinical anxiety and depression (as assessed by the Index20 score was recorded in CNPG patients (12.4  7.3), Hospital Anxiety and Depression Scale14) compared to patients reflecting a severe impairment of the quality of life.15 More than with psoriasis or atopic dermatitis, while suicidal ideation was half of the patients reported their daily life being rather or very also more frequently reported in CNPG.15,16 In a large retrospec- affected by CNPG. Particular aspects of daily life such as the tive study, significant associations between CNPG and anxiety interaction with others, sleep quality, mood and joy of life were and depression, as well as with the use of anxiolytics and antide- substantially affected in a considerable number of patients (38– pressants, were found.17 The prevalence of current or past psy- 44%). The fact that symptoms are always or often present adds chiatric co-morbidities was 48% in a small study including 50 to the burden in the majority of the patients (71%). The highest patients with CNPG18 and 65.9% in a sample of 44 inpatients burden associated with the disease was the itch, which was with CNPG from a dermatological university ward.19 Our study described as disturbing (55.2%), burdensome (50.7%) or ago- confirms previous reports pointing out a high burden in CNPG nizing (46.6%) by a substantial number of patients and has been patients. Clinical depression was found in 18.1% of the patients, shown to contribute substantially to psychological disease JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 2380 Pereira et al. Presence of pain 2% Other Psychological Emotional experience of itch 0% consequences 3% Disturbing 55.2% Sleep Burdensome 50.7% disturbance 4% Impact on Agonizing 46.6% everyday life 5% Intractable 35.0% Itching 22.4% I'm becoming aggessive 21.7% Bleeding of Cruel 18.2% skin lesions Presence Beastly 17.0% 14% of itch 50% Horrendous 15.0% Other 3.2% Visibility of skin lesions None 3.0% 22% 0 10 20 30 40 50 60 Percentage (%) Figure 3 Highest burden of chronic nodular prurigo reported by Figure 4 Emotional experience of itch and CNPG as reported by patients (n = 304). patients (n = 406). burden.21 Accordingly, the impairment of the quality of life cor- Atopic eczema (33%), rhinoconjunctivitis (29%) and asthma related with itch intensity, as observed for other pruritic dis- (20%) were reported by a substantial number of patients, which eases.22 Other aspects of the disease such as the visibility of the is lower (possibly due to lack of self-reporting) compared to pre- skin lesions and bleeding from the lesions were also mentioned vious reports stating that an atopic predisposition is present in as the highest burden, but only by a minority of the patients up to half of the patients with CNPG.13 Moreover, patients from (14–21%) and thus seem to play a secondary role for patients. our cohort suffered from systemic conditions, which may lead to €nster, Table 3 Highest burden and emotional experience of chronic nodular prurigo for all the patients and by region i.e. Germany (Mu Heidelberg and Berlin); Northern Europe (Sweden and Norway); Central Europe (Switzerland, France and Austria); Eastern Europe (Poland-Wroclaw, Poland-Rzeszow and Russia); and Southern Europe (Italy, Turkey, Spain and Portugal) Characteristic All Germany Northern Europe Central Europe Eastern Europe Southern Europe Highest burden n = 304 n = 91 n = 42 n = 54 n = 51 n = 66 Presence of itch 150 (49.3) 33 (36.3) 14 (33.3) 32 (59.3) 35 (68.6) 36 (54.5) Visibility of skin lesions 65 (21.4) 19 (20.9) 16 (38.1) 9 (16.7) 11 (21.6) 10 (15.2) Bleeding of lesions 43 (14.1) 15 (16.5) 6 (14.3) 5 (9.3) 4 (7.8) 13 (19.7) Impact on daily activities 15 (4.9) 9 (9.9) 0 (0) 4 (7.4) 1 (2) 1 (1.5) Sleep disturbance 13 (4.3) 9 (9.9) 2 (4.8) 1 (1.9) 0 (0) 1 (1.5) Psychological consequences 10 (3.3) 4 (4.4) 2 (4.8) 1 (1.9) 0 (0) 3 (4.5) Presence of pain 7 (2.3) 1 (1.1) 2 (4.8) 2 (3.7) 0 (0) 2 (3) Other 1 (0.3) 1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) Experiencing itch as: n = 406 n = 137 n = 69 n = 57 n = 76 n = 67 Disturbing 224 (55.2) 91 (66.4) 37 (53.6) 30 (52.6) 23 (30.3) 43 (64.2) Burdensome 206 (50.7) 97 (70.8) 28 (40.6) 34 (59.6) 31 (40.8) 16 (23.9) Agonizing 189 (46.6) 88 (64.2) 42 (60.9) 22 (38.6) 24 (31.6) 13 (19.4) Intractable 142 (35.0) 61 (44.5) 30 (43.5) 17 (29.8) 7 (9.2) 27 (40.3) Only itching 91 (22.4) 35 (25.5) 7 (10.1) 10 (17.5) 21 (27.6) 18 (26.9) I’m aggressive due to itch 88 (21.7) 33 (24.1) 6 (8.7) 17 (29.8) 9 (11.8) 23 (34.3) Cruel 74 (18.2) 34 (24.8) 10 (14.5) 6 (10.5) 14 (18.4) 10 (14.9) Beastly 69 (17.0) 33 (24.1) 8 (11.6) 6 (10.5) 9 (11.8) 13 (19.4) Horrendous 61 (15.0) 26 (19) 3 (4.3) 7 (12.3) 17 (22.4) 8 (11.9) Other 13 (3.2) 2 (1.5) 7 (10.1) 2 (3.5) 1 (1.3) 1 (1.5) None 12 (3.0) 1 (0.7) 0 (0) 1 (1.8) 9 (11.8) 1 (1.5) Data presented as n (%). JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 Chronic prurigo: clinical profile 2381 How often did you have symptoms? To what extent has the itching affected your everyday life? Percentage of affected patients Percentage of affected patients 60.3% 70 70 57.1% 60 60 48.9% 47.0% 50 50 38.2% 37.3% 38.0% 34.3% 32.9% 33.3% 31.3% 31.6% 31.4% 40 40 30.3% 29.4% 26.9% 26.3% 24.1% 23.7% 23.9% 23.7% 23.0% 22.2% 21.7% 20.9% 20.6% 20.0% 20.6% 20.6% 19.6% 30 30 19.4% 18.2% 17.6% 17.5% 16.8% 16.1% 15.3% 14.3% 13.2% 12.3% 11.7% 11.8% 10.5% 10.5% 20 20 9.4% 8.9% 7.5% 7.1% 7.5% 6.2% 6.0% 3.9% 2.9% 2.9% 3.0% 2.6% 2.6% 10 10 1.5% 0.0% 0.0% 0 0 n= 402 135 68 56 76 67 n= 405 137 68 57 76 67 l y e e e e l y e e e e Al Al an an p p p p p p p p ro ro ro ro ro ro ro ro m m Eu Eu Eu Eu Eu Eu Eu Eu er er G G rn l n rn rn l n rn tra tra er er e he e he en en th st th st ut ut Ea Ea or or C C So So N N To what extent has the itching affected To what extent is the itching your interaction with others? affecting your sleep? Percentage of affected patients Percentage of affected patients 70 70 60 60 50 50 35.8% 35.3% 32.9% 40 40 29.9% 29.8% 28.9% 28.4% 26.9% 24.6% 24.8% 25.0% 24.8% 25.0% 25.0% 24.6% 23.9% 24.0% 23.7% 23.3% 23.2% 23.4% 23.0% 22.8% 22.4% 22.4% 21.9% 21.9% 21.2% 21.1% 20.9% 20.4% 20.0% 30 30 19.3% 19.4% 19.3% 19.3% 17.5% 16.8% 16.8% 15.8% 16.1% 16.2% 16.2% 15.8% 15.8% 14.4% 14.5% 13.9% 13.4% 13.2% 11.7% 11.9% 11.9% 11.8% 11.9% 10.4% 10.4% 20 20 9.2% 8.8% 7.4% 10 10 0 0 n= 404 137 67 57 76 67 n= 405 137 68 57 76 67 e pe pe pe pe e y pe l y pe l Al Al an an op op ro ro ro ro ro ro m m ur ur Eu Eu Eu Eu Eu Eu er er lE lE G G n rn n rn n n tra tra er er er er he he en en st st th th ut ut Ea Ea or or C C So So N N To what extend is itching depressing you? Percentage of affected patients 70 60 50 38.2% 32.8% Never/Not at all 31.3% 30.9% 29.9% 40 27.5% 27.6% 26.3% 24.3% 23.9% Rarely/A little bit 22.8% 21.8% 20.1% 19.7% 30 19.3% 19.3% 19.1% 16.9% Sometimes/Somewhat 16.4% 16.4% 16.4% 15.4% 13.6% 11.9% 12.3% 11.9% 10.3% 10.5% 20 Often/Rather 9.0% 3.9% Always/Very 10 0 n= 403 136 67 57 76 67 pe pe y pe e l Al an op ro ro ro m ur Eu Eu Eu er lE G n n n ra er er er t en st h th ut Ea or C So N Figure 5 Percentage of patients affected in their quality of life by chronic nodular prurigo. Data presented for all patients and stratified by region i.e. Germany (Mu €nster, Heidelberg and Berlin; DE); Northern Europe (Sweden and Norway; NRN EUR); Central Europe (Switzer- land, France and Austria; CNTRL EUR); Eastern Europe (Poland-Wroclaw, Poland-Rzeszow and Russia; ERN EUR); and Southern Europe (Italy, Turkey, Spain and Portugal; SRN EUR). itch and ultimately to CNPG, including diabetes (17.5%), kidney congestive heart failure, HIV infection23 as well as solid tumours disease (6.5%), liver disease (5.7%) or cancer (3.9%). CNPG has and malignancies of the hematopoietic system.24 been associated with systemic diseases such as chronic kidney Chronic nodular prurigo is considered a disease in its own disease, hepatitis C, chronic obstructive pulmonary disease, right independent of the origin of the underlying itch.1 The JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 2382 Pereira et al. Germany, the highest recruiting centres, suggesting that the 5PLQ observed regional differences are not centre dependent. 4.00 Academia has gained interest for CNPG in recent years. How- 3.50 3.00 ever, only limited data were available on the profile of the dis- 2.50 ease. This large multicentre European study addressed this issue 2.00 by gathering data from a very large sample, contributing to a 1.50 comprehensive understanding of the clinical profile and associ- 1.00 ated burdens of the disease. Our findings raise awareness for 0.50 CNPG and highlight the urgency of developing standardized 0.00 diagnostic and therapeutic guidelines in order to provide a bet- l y e e e e Al an p p p p ter care for these patients. ro ro ro ro m Eu Eu Eu Eu er G rn l n rn tra er e he en th st ut Ea or C So N Acknowledgements NRS All Germany Northern Central Eastern Southern Europe Europe Europe Europe We thank B. Pfleiderer M.D. for assistance in the study prepara- Median 2.4 2.2 2.0 2.6 2.6 2.8 tion and Galderma S.A., Kiniska Pharmaceuticals and Menlo [IQR] [1.6;3.0] [1.2;3.0] [1.4;2.6] [1.6;3.2] [1.8;3.2] [1.8;3.4] Therapetics Inc. for the support of the study. This study was supported by the European Academy of Dermatology and Figure 6 Impairment of the quality of life assessed by 5-Pruritus Venereology (EADV, No. 2016-012 to MP). Life Quality (5PLQ) for all patients (n = 405) and by region i.e. Ger- many (Mu € nster, Heidelberg and Berlin) n = 137; Northern Europe (Sweden and Norway) n = 68; Central Europe (Switzerland, France References and Austria) n = 57; Eastern Europe (Poland-Wroclaw, Poland- 1 Pereira MP, Steinke S, Zeidler C et al. European academy of dermatology Rzeszow and Russia) n = 76; and Southern Europe (Italy, Turkey, and venereology European prurigo project: expert consensus on the defi- Spain and Portugal) n = 67. nition, classification and terminology of chronic prurigo. J Eur Acad Der- matol Venereol 2018; 32: 1059–1065. 2 Pereira MP, Zeidler C, Nau T et al. Position statement: linear prurigo is a majority of patients in our study (254/395, 64%) were not aware subtype of chronic prurigo. J Eur Acad Dermatol Venereol 2019; 33: 263–266. 3 Stander S, Weisshaar E, Mettang T et al. Clinical classification of itch: a of any condition contributing to the CNPG. More diagnostic position paper of the international forum for the study of itch. Acta Derm efforts may be needed in order to find the underlying cause for Venereol 2007; 87: 291–294. the itch in these patients. Interestingly, of those reporting having 4 Zeidler C, Stander S. The pathogenesis of Prurigo nodularis - ’Super-Itch’ a condition associated with their CNPG, psychiatric conditions in exploration. Eur J Pain 2016; 20: 37–40. 5 Storck M, Zeidler C, Rehr M et al. Validation of pruritus measures gath- were the most often mentioned (19%). This is in line with the ered with the electronic patient-reported outcome system MoPat. Acta studies cited above, which reported high levels of anxiety and Derm Venereol 2018; 98: 38–43. depression or other psychiatric co-morbidities in patients with 6 Jones J, Hunter D. Consensus methods for medical and health services CNPG.15,17–19 From our data, we cannot conclude, however, research. BMJ 1995; 311: 376–380. 7 Phan NQ, Blome C, Fritz F et al. Assessment of pruritus intensity: whether psychiatric co-morbidity is a consequence of CNPG or prospective study on validity and reliability of the visual analogue scale, rather an etiological factor for the disease. numerical rating scale and verbal rating scale in 471 patients with chronic There were some small regional differences regarding the per- pruritus. Acta Derm Venereol 2012; 92: 502–507. 8 Zeidler C, Stander S. Kurzfragebogen zur Lebensqualit€at bei chronischem ception of itch intensity and impairment of the quality of life. In Pruritus: ein neues Instrument zur Nutzung in der Praxis. 50 Tagung der general, patients from Southern and Eastern Europe perceived Deutschen Dermatologischen Gesellschaft, Vereinigung Deutschsprachi- itch slightly more intensely and reported a higher impairment of ger Dermatologen e.V. Berlin, 2019: 64–79. their quality of life compared to patients from Germany or 9 Schut C, Dalgard FJ, Halvorsen JA et al. Occurrence, chronicity and intensity of itch in a clinical consecutive sample of patients with skin dis- Northern Europe. However, the magnitude of the recorded dif- eases: a multi-centre study in 13 European Countries. Acta Derm Venereol ferences was small, and these findings were not controlled for 2019; 99: 146–151. possible treatment regimens. In line with our study, previous 10 Carr CW, Veledar E, Chen SC. Factors mediating the impact of chronic reports enrolling patients with pruritic dermatoses revealed pruritus on quality of life. JAMA Dermatol 2014; 150: 613–620. 11 Misery L, Brenaut E, Le Garrec R et al. Neuropathic pruritus. Nat Rev regional differences in itch perception and quality of life across Neurol 2014; 10: 408–416. European countries.25 For example itch intensity of patients with 12 Pogatzki-Zahn EM, Pereira MP, Cremer A et al. Peripheral sensitisation pruritic dermatoses was lower in Germany and higher in Turkey, and loss of descending inhibition is a hallmark of chronic pruritus. while the impairment of the quality of life assessed using the J Invest Dermatol 2020; 140: 203–211. 13 Iking A, Grundmann S, Chatzigeorgakidis E et al. Prurigo as a symp- ItchyQol was higher in Poland (but lower in Russia) compared tom of atopic and non-atopic diseases: aetiological survey in a consec- to the other European centres.25 There were no differences in utive cohort of 108 patients. J Eur Acad Dermatol Venereol 2013; 27: NRS (P = 0.20) or 5PLQ scores (P = 0.16) across centres in 550–557. JEADV 2020, 34, 2373–2383 © 2020 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, 2020, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.16309 by Readcube (Labtiva Inc.), Wiley Online Library on [06/11/2023]. 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 Chronic prurigo: clinical profile 2383 14 Snaith RP. The hospital anxiety and depression scale. Health Qual Life Academy of Dermatology and Venereology Network on Assessment of Outcomes 2003; 1: 29. Severity and Burden of Pruritus (PruNet) cross-sectional trial. J Am Acad 15 Brenaut E, Halvorsen JA, Dalgard FJ et al. The self-assessed psychological Dermatol 2018; 79: 457–463.e5. comorbidities of prurigo in European patients: a multicentre study in 13 countries. J Eur Acad Dermatol Venereol 2019; 33: 157–162. Appendix 1 16 Schneider G, Hockmann J, Stander S et al. Psychological factors in prur- igo nodularis in comparison with psoriasis vulgaris: results of a case- EPP Consensus Conference Participants 2017: F. Dalgard control study. Br J Dermatol 2006; 154: 61–66. (Department of Dermatology and Venereology, Sk ane Univer- 17 Jorgensen KM, Egeberg A, Gislason GH et al. Anxiety, depression and sui- sity Hospital, Lund University, S-20502 Malm€ o, Sweden), cide in patients with prurigo nodularis. J Eur Acad Dermatol Venereol J. Elberling (Department of Dermatology, University Hospital 2017; 31: e106–e107. 18 Dhawan L, Singh SM, Avasthi A et al. The prevalence of psychiatric Gentofte, Copenhagen, Denmark), C. Forner (Department of comorbidity in patients with prurigo nodularis. Indian Dermatol Online J Dermatology and Center for Chronic Pruritus, University 2018; 9: 318–321. Hospital M€ unster, M€ unster, Germany), T. Leslie (St. John’s 19 Schneider G, Driesch G, Heuft G et al. Psychosomatic cofactors and psy- chiatric comorbidity in patients with chronic itch. Clin Exp Dermatol Institute of Dermatology, Guy’s & St Thomas’ Hospital, London, 2006; 31: 762–767. United Kingdom), C. Riepe (Department of Dermatology and 20 Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)–a simple Center for Chronic Pruritus, University Hospital M€ unster, practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: M€ unster, Germany), G. Schneider (Department of Psychosomat- 210–216. 21 Dalgard FJ, Svensson A Halvorsen JA et al. Itch and mental health in der- ics and Psychotherapy, University Hospital M€ unster, M€unster, matological patients across Europe: a cross sectional study in 13 coun- Germany), H. St€ander (Dermatological Practice, Bad Bentheim tries. J Invest Dermatol 2019; 140: 568–573. and Department of Dermatology, Klinikum Dortmund GmbH, 22 Zeidler C, Steinke S, Riepe C et al. Cross-European validation of the Itch- Germany). yQoL in pruritic dermatoses. J Eur Acad Dermatol Venereol 2019; 33: 391–397. 23 Boozalis E, Tang O, Patel S et al. Ethnic differences and comorbidities of Supporting information 909 prurigo nodularis patients. J Am Acad Dermatol 2018; 79: 714– Additional Supporting Information may be found in the online 719.e3. version of this article: 24 Larson VA, Tang O, Stander S et al. Association between itch and cancer in 16,925 patients with pruritus: experience at a tertiary care center. J Am Appendix S1. Questionnaire. Patients with CNPG were asked to Acad Dermatol 2019; 80: 931–937. 25 Steinke S, Zeidler C, Riepe C et al. Humanistic burden of chronic pruritus fill out a questionnaire either in paper or electronic format. Data in patients with inflammatory dermatoses: results of the European obtained from questions 1–26 are analysed in the present article. JEADV 2020, 34, 2373–2383 © 2020 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