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A letter to the editor is presented in response to the article about the use of ultraviolet (UV) B phototherapy to improve the therapeutic response to biologics in patients with psoriasis by F. J. Legat, A. Hofer, A. Wackernagel and colleagues in the previous issue.

The article focuses on adoption of daylight photodynamic therapy (dPDT) for treatment of sun damage among patients with field cancerization of actinic keratoses (AKs). Topics discussed include usage of methyl aminolevolinate (MAL) as prodrug for photosensitzer protoporphyrin IX (PpIX); analysis of different in pain sensation with the therapy in comparison to conventional methods that leads to reactive oxygen species (ROS) damage; and consideration of dosimetry usage for dPDT.

Photochemotherapy is very effective for the treatment of skin diseases such as psoriasis, as well as for the prophylactic ‘hardening’ therapy of patients suffering from polymorphic light eruption. The photosensitizers most widely used for oral photochemotherapy are the furocoumarins 8-methoxypsoralen and 5-methoxypsoralen. Beside light-induced phototoxic reactions due to the photosensitizing activity of psoralens, side-effects after the oral intake of psoralens are nausea and vomiting, headaches, anxiety and sleeplessness. We report a rare case of anaphylaxis to 5-methoxypsoralen that developed during prophylactic ‘hardening’ therapy in a 36-year-old woman suffering from polymorphic light eruption. Anaphylaxis to 5-methoxypsoralen was established by placebo-controlled oral provocation tests. [ABSTRACT FROM AUTHOR]

Background: Patients with prurigo nodularis (PN) have multiple itchy nodules, impaired quality of life and sleep deprivation. Prurigo nodularis patients have a high burden of disease, primarily due to the intensity of the itch. It is reasonable to expect that rapid relief of itch – and associated improvement of sleep – are highly valued clinical outcomes for patients. Nemolizumab is an IL‐31A‐receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN. Objectives: To evaluate the onset of action of nemolizumab on itch and sleep disturbances. Methods: Post hoc analysis of a phase 2 trial of nemolizumab 0.5 mg/kg SC vs. placebo in patients (n = 70) with moderate‐to‐severe PN (≥20 nodules) and severe pruritus (NRS ≥ 7). Time to significant reduction was assessed for peak pruritus (PP) and sleep disturbance (SD) using numerical rating scales (NRS), also assessed was scratching time during sleep. Results: Nemolizumab significantly reduced itch vs. placebo within 48 h (PP NRS −19.5% vs. −5.8%, respectively, P = 0.014). Significant difference between nemolizumab and placebo in reducing itch by ≥4 on PP NRS was achieved at Day 3 (23.5% vs. 0%, P < 0.001). A significant difference in SD NRS was reported by Day 4 (−24.0% vs. −4.3% placebo, P = 0.012). In addition, there was a separation between groups in SD responders (decrease of ≥4 points) in favour of nemolizumab by Day 2 (8.8% vs. 0%, P = 0.037). Sleep continued improving through Week 4, when there was a −56.0% reduction in SD NRS vs. −22.9% placebo (P < 0.001). Actigraphy data showed improvement in scratch/sleep duration for nemolizumab vs. placebo, respectively, by Week 1 (−32.15 vs. +28.15 min/h, P = 0.001). Conclusion: Nemolizumab has a rapid and robust onset of action in PN with itch reduction and improvement of sleep within 48 h. [ABSTRACT FROM AUTHOR]

Background: Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed. Objective: To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu opioid antagonist nalbuphine extended release (NAL‐ER) tablets in a phase 2, multicentre, randomized, double‐blind, placebo‐controlled trial with an open‐label, 50‐week extension phase. Methods: Subjects with moderate‐to‐severe PN were randomized to NAL‐ER 81 mg (NAL‐ER81) or 162 mg (NAL‐ER162) tablets twice‐daily or placebo for 8 weeks of stable dosing following a 2‐week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI‐NRS) score ≥5 at the time of rollover (or during the observation period) were eligible for open‐label treatment. Results: Of 63 randomized subjects, 62 were treated and comprised the modified intent‐to‐treat population (MITT), 50 completed 10 weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL‐ER162 (P = 0.32) and 6 (27.3%) treated with NAL‐ER81 (P = 0.78) achieved ≥30% reduction from baseline in 7‐day WI‐NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8/12 (66.7%) subjects completing Week 10 treated with NAL‐ER162 vs. placebo (8/20, 40.0%; P = 0.03). Additionally, 6 subjects (33.3%) treated with NAL‐ER162 and 3 (13.6%) treated with NAL‐ER81 achieved ≥50% reduction from baseline in 7‐day WI‐NRS at Week 10 (coprimary endpoint). Extended open‐label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild‐to‐moderate severity. The safety profile did not change with extended open‐label treatment. Conclusion: In adult subjects with PN, oral treatment with NAL‐ER 162 mg twice daily provided measurable anti‐pruritic efficacy in subjects completing ≥10 weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419). [ABSTRACT FROM AUTHOR]

Summary Background Treatment with the interleukin-12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque-type psoriasis. Objectives To determine whether concomitant 311-nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab. Methods Ten patients (five women and five men; mean age 58 years, range 48-66) with moderate to severe plaque-type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90 mg subcutaneously depending on body weight (below or above 100 kg) at weeks 0 and 4. Within 2 days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311-nm UVB-based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6 weeks. Treatment response was monitored weekly in terms of half-body PASI. Results Nine patients completed the study. Analysis of their data showed that 311-nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311-nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3-5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV-irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P = 0·007). At week 12, this synergistic effect of 311-nm UVB was still apparent although not significantly so. Conclusions Treatment with 311-nm UVB accelerates the clearance of psoriatic lesions in ustekinumab-treated patients. [ABSTRACT FROM AUTHOR]

Background: Itch is a common symptom in the general population. Affected individuals often do not seek medical consultation and rely on Internet searches to obtain information regarding their itch. Objectives: The aim of this study was to attain insights into common concerns of the general population regarding itch can by analysing itch‐related Internet search behaviour. Methods: Google AdWords Keyword Planner was used to assess search volumes for itch‐related terms in 15 European countries between September 2014 and August 2018. All identified keywords were qualitatively categorized. Itch‐related terms were descriptively analysed and are shown as number of searches/100 000 inhabitants. Results: The search volume for the keyword 'itch' per 100 000 inhabitants was highest in Northern Europe, followed by Eastern, Central and Southern Europe. In 4/15 countries, itch was searched for more often in the autumn/winter months compared to in the spring/summer months. Most itch‐related terms were related to dermatological conditions such as inflammatory skin diseases (e.g. psoriasis, atopic dermatitis), allergic or immunologic conditions (e.g. urticaria), and infectious diseases or infestations (e.g. scabies). In terms of body location, genitoanal itch dominated the searches. Symptoms and signs related to itch, possible non‐dermatological aetiologies, and treatment options were also among the most searched terms. Conclusions: These analyses provided for the first time insights into the search behaviour patterns related to itch across Europe. People from Northern and Eastern Europe are more likely to seek online information regarding itch. Causes for the itch, especially dermatological conditions, and genitoanal itch are the most important concerns for Internet users. This unconventional and inexpensive method identifies medical needs of people beyond the medical setting, including people who do not seek medical consultation. Accordingly, the data could be used to guide public health interventions and manage respective inhabitants' medical needs. [ABSTRACT FROM AUTHOR]

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 statistically 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. [ABSTRACT FROM AUTHOR]

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 regarding 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 severe 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 disease 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. [ABSTRACT FROM AUTHOR]

Background: Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether these lesions belong to the spectrum of CPG. Objective: To achieve a consensus on the classification of pruriginous LSSL and establish criteria to differentiate them from similar appearing conditions of different nature. Methods: Members of the Task Force Pruritus (TFP) of the European Academy of Dermatology and Venereology participated in the consensus conference, discussing representative clinical cases. Using the Delphi method, consensus was reached when ≥75% of members agreed on a statement. Results: Twenty‐one members of the TFP with voting rights participated in the meeting. It was consented that LSSL occurs due to chronic pruritus and prolonged scratching, and share common pathophysiological mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of CPG and the term 'linear prurigo' was chosen to describe this manifestation. Conclusion: Considering linear prurigo as belonging to the spectrum of CPG has important clinical implications, since both the diagnostic and therapeutic approach of these patients should be performed as recommended for CPG. Importantly, linear prurigo should be differentiated from self‐inflicted skin lesions as factitious disorders or skin picking syndromes. In the latter, artificial manipulation rather than pruritus itself leads to the development of cutaneous lesions, which can show clinical similarities to linear prurigo. [ABSTRACT FROM AUTHOR]

Background: Chronic pruritus (CP) is a frequently occurring symptom in inflammatory dermatoses, causing a high burden and limitations to health‐related quality of life (HRQoL). Objective: The ItchyQoL was developed to assess the impairment to HRQoL in patients with CP. However, it has only been validated in English and German. Here, we report the validation in several languages across Europe. Methods: After professional translation, the versions of ItchyQoL were digitized for use as a tablet application. Validation was performed in clinics for dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. Results: Five hundred and thirty‐five patients with either contact dermatitis, chronic prurigo – nodular type, psoriasis vulgaris, lichen planus or mycosis fungoides/Sézary syndrome and with CP ≥ 3 on the numerical rating scale were included. ItchyQoL showed a high level of consistency (Cronbach's‐α, all: 0.95) and test‐retest reliability (intraclass correlation: 0.91). It strongly correlated with the Dermatology Life Quality Index (r = 0.72, P < 0.001) and moderately correlated with itch intensity scales in the study population (visual analogue scale r = 0.46; numerical rating scale r = 0.51; verbal rating scale r = 0.51, for all: P < 0.001). Conclusion: ItchyQoL is now also validated in French, Italian, Polish, Russian, Spanish and Turkish and can be used in clinical trials in countries speaking these languages. [ABSTRACT FROM AUTHOR]

Background Chronic pruritus is a frequently occurring symptom of various dermatoses that causes a high burden and impaired quality of life. An effective anti pruritic therapy is important for the patient, but its effectiveness is difficult to evaluate. Diverse methods and interpretations of pruritic metrics are utilized in clinical trials and the daily clinical practice in different countries, resulting in difficulties comparing collected data. Methods We founded a European Network on Assessment of Severity and Burden of Pruritus (PruNet) that is supported by the EADV. PruNet consists of 28 experts from 15 EU countries (21 dermatologists, 5 medical informaticists, 2 psychologists) and aims to unify the assessment of itch in routine dermatological care. Following a preliminary survey, a consensus conference was held in order to agree upon the prioritization of patient-reported outcome tools. Results Through utilizing the Delphi method, it was agreed that tools for measuring itch intensity (ex. the visual analogue scale) and quality of life (ex. ItchyQoL) are of primary importance and should urgently be foremost validated. Conclusion The validation and harmonization of standards are needed for the improvement of quality care for patients suffering from pruritic dermatoses. This summer, the first validation studies in several EADV member countries already began. [ABSTRACT FROM AUTHOR]

Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid-face) and size of the lesion. Following reports that such difficult-to-treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL-PDT. An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL-PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24-month follow-up is reported here. Ninety-four patients with 123 lesions were enrolled and treated with MAL-PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult-to-treat BCC according to the protocol. The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and 94% at 24 months follow-up. Topical MAL-PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL-PDT preserves the skin and shows favourable cosmetic results. [ABSTRACT FROM AUTHOR]