EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo: Current challenges and future solutions.

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

Relationship between sensitive skin and sleep disorders, fatigue, dust, sweating, food, tobacco consumption or female hormonal changes: Results from a worldwide survey of 10 743 individuals.

BACKGROUND: Sensitive skin is related to environmental factors. OBJECTIVES: We aimed to investigate the roles of poorly known associated and triggering factors on sensitive skin in a large global population. METHODS: A survey was administrated to a representative sample of the adult population aged 18-75 years in five different countries (Brazil, China, France Russia, and the United States). All participants answered a web-based questionnaire on sociodemographic characteristics, sensitive skin and environmental factors. RESULTS: Among the 10 743 included individuals (5285 men and 5458 women), 48.2% declared that they had sensitive skin. The group with sensitive skin reported significant increases in fatigue, dust or sweating and to a lesser extent food or tobacco consumption. The members of this group also declared that they experienced more sleep disorders than individuals without sensitive skin. Sensitive skin was very frequent in pregnant women, women with painful menstruations or women using contraceptive pills. CONCLUSIONS: This large cohort study identified new factors, including female hormonal status, fatigue, sleep disorders and food, associated with sensitive skin. These associations suggest that sensitive skin is not restricted to an epidermal disorder but may be included in a larger context. The identified factors are potential upstream drivers of neurogenic inflammation in sensitive skin.

Google search trends for itch in Europe: a retrospective longitudinal study.

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.

Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau.

BACKGROUND: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. OBJECTIVES: To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. METHODS: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. CONCLUSIONS: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

Chronic nodular prurigo: clinical profile and burden. A European cross-sectional study.

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.

Pathophysiology and management of sensitive skin: position paper from the special interest group on sensitive skin of the International Forum for the Study of Itch (IFSI).

The special interest group on sensitive skin of the International Forum for the Study of Itch previously defined sensitive skin as a syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus and tingling sensations) in response to stimuli that normally should not provoke such sensations. This additional paper focuses on the pathophysiology and the management of sensitive skin. Sensitive skin is not an immunological disorder but is related to alterations of the skin nervous system. Skin barrier abnormalities are frequently associated, but there is no cause and direct relationship. Further studies are needed to better understand the pathophysiology of sensitive skin - as well as the inducing factors. Avoidance of possible triggering factors and the use of well-tolerated cosmetics, especially those containing inhibitors of unpleasant sensations, might be suggested for patients with sensitive skin. The role of psychosocial factors, such as stress or negative expectations, might be relevant for subgroups of patients. To date, there is no clinical trial supporting the use of topical or systemic drugs in sensitive skin. The published data are not sufficient to reach a consensus on sensitive skin management. In general, patients with sensitive skin require a personalized approach, taking into account various biomedical, neural and psychosocial factors affecting sensitive skin.

Triggering factors in sensitive skin from the worldwide patients' point of view: a systematic literature review and meta-analysis.

Sensitive skin (SS) is a syndrome defined by the occurrence of unpleasant sensations in response to stimuli that normally should not provoke such sensations. In most patients, symptoms occur within 1 h following exposure to trigger factors and may persist for minutes or even hours. Numerous triggering factors (physical, chemical or psychological) are suspected and described in articles. The aim of this article was to perform a systematic literature review to collect data on the triggering factors involved in SS and to then perform a meta-analysis. Thirteen studies were included in the systematic literature review. Subjects were classified into groups, SS or no sensitive skin (NSS), and triggering factors were researched through responses to different questions. SS could be triggered by numerous factors. The most important triggering factor was cosmetics, with an odds ratio (OR) equal to 7.12 [3.98-12.72]. Other triggering factors were physical (variations in temperature, cold, heat, wind, sun, air conditioning, wet air and dry air), chemical (water and pollution) or psychological (emotional) factors. After cosmetics, the most important factors were wet air, OR 3.83 [2.48-5.91]; air conditioning, OR 3.60 [2.11-6.14]; heat, OR 3.5 [2.69-4.63]; and water, OR 3.46 [2.56-4.77].

Effectiveness of a music intervention on pruritus: an open randomized prospective study.

BACKGROUND: Pruritus is a common symptom in many skin diseases. Music interventions have demonstrated their efficacy in different symptoms or diseases such as pain, depression and anxiety. OBJECTIVE: To evaluate the effects of a music intervention on pruritus. PATIENTS AND METHODS: A randomized controlled trial was conducted from November 2018 to April 2019. Fifty inpatients with pruritus intensity ≥3/10 in various chronic skin diseases were randomized in a music group or an emollient group. The primary endpoint was the evolution of pruritus as measured by the Numerical Rating Scale before and one hour after the procedure. The secondary judgement criteria were the effects on patient anxiety, the impact of pruritus on the quality of life and patient satisfaction (NCT03701971). RESULTS: Fifty patients with chronic pruritus were included, 62% were male, and the average age was 60.7 years. The most common diseases were psoriasis (N = 10), atopic dermatitis (N = 8) and contact eczema (N = 6). The average ItchyQol score was 64.8/110, showing a significant impact on quality of life. The intensity of pruritus decreased more significantly in the music intervention group than in the emollient group: 2.3 (SD 2.1) and 1.2 (SD 1.7), respectively (P < 0.05). There was a decrease in anxiety in both groups, with no statistical significant difference between groups. Among patients who received the music intervention, 64% reported feeling an improvement, 91% would recommend the music intervention, and 64% would like to continue this practice. DISCUSSION: Pruritus management is complex and requires first-line aetiological treatment. Aetiological or symptomatic treatments do not always provide enough relief; it is useful to find other therapeutic options. The music intervention has shown interest in our study. Its repeated use over the long term will be interesting to evaluate. As in pain, music may work by activating inhibitory neural circuits. The use of music is a simple method to manage chronic pruritus.

Association of sensitive skin with sensitive corneas and sensitive eyelids.

BACKGROUND: Sensitive scalp or irritable bowel syndrome has been previously shown to be associated with sensitive skin. We wondered whether sensitive eyelids and sensitive eyes could also be associated with sensitive skin. METHODS: A cross-sectional epidemiological study was carried out on a representative sample of French people, according to the quota method, using a questionnaire. RESULTS: A total of 2048 subjects were included in the present study. Notably, 52.2% declared sensitive eyes, which was more frequent in women than in men. The subjects who reported sensitive eyes were more numerous according to the severity of skin sensitivity, the severity of sleep disorders and the presence of bright eyes. More than half of the subjects with sensitive eyes thought that they were sensitive to sun exposure, dust, computer or touch pads or dry air. The presence of sensitive eyelids was reported by 18.65% (more frequent in women) and was associated with sensitive skin and sensitive eyes, sun exposure and exposure to dust. CONCLUSION: This study is the first to investigate sensitive eyelids or sensitive eyes. Sensitive eyelids can be considered a localization of sensitive skin. The concept of sensitive eyes is not commonly used by ophthalmologists and remains to be more precisely defined.

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis.

BACKGROUND: Three biotherapies - etanercept, adalimumab and ustekinumab - are licensed in childhood psoriasis. The few data available on their efficacy and tolerance are mainly derived from industry trials. However, biological drug survival impacts long-term performance in real-life settings. OBJECTIVE: The objective of this study was to evaluate the survival rates of biological therapies in children with psoriasis in real-life conditions. Secondary objectives were to evaluate the factors associated with the choice of the biological therapy and to report severe adverse events. MATERIALS AND METHODS: This study was an observational retrospective study. Data were extracted from the clinical records of 134 children. Kaplan-Meier estimates were used to analyse drug survival overall and in subgroups of plaque psoriasis, bio-naïve and non-naïve patients. RESULTS: We analysed 184 treatment courses: 70 with etanercept, 68 with adalimumab and 46 with ustekinumab. Factors associated with the choice of first-line biological agent were age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03) and baseline Psoriasis Assessment Severity Index and Physician global assessment (both higher for adalimumab, P < 0.001). Drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P < 0.0001) for all treatment and all psoriasis types, plaque-type psoriasis (P = 0.0003), patients naïve for biological agents (P = 0.0007) and non-naïve patients (P = 0.007). We reported eight serious adverse events (SAEs): severe infections (n = 3), significant weight gain (n = 2), psoriasis flare (n = 1) and malaise (n = 1). Biological therapy was discontinued in three children (one with psoriasis flare and two with weight gain). Only the two cases of weight gain resulted in an unfavourable outcome. CONCLUSIONS: Our real-life comparative study found that ustekinumab had the best drug survival outcome. The profile of SAEs in children was comparable to that in adults. These results will assist dermatologists in the decision-making process when choosing treatment options for children with psoriasis in daily practice.

The self-assessed psychological comorbidities of prurigo in European patients: a multicentre study in 13 countries.

BACKGROUND: Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. OBJECTIVE: The aim of this study was to assess the psychological burden of prurigo in patients of European countries. METHODS: In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. RESULTS: There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10 of 27 (37%) suffered from anxiety and 8 of 27 (29%) from depression. Suicidal ideation was reported in 5 of 27 (19%) patients, and for four of these five patients, suicidal ideation was related to their skin disease. These frequencies were higher in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers). The impact on quality of life was severe, with a mean Dermatologic Life Quality Index (DLQI) of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. CONCLUSION: The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments.

Sensitive skin can be small fibre neuropathy: results from a case-control quantitative sensory testing study.

BACKGROUND: Sensitive skin syndrome (SSS) is defined as the occurrence of unpleasant sensations (itch, pain, burning, prickling) in response to stimuli that should not normally cause such sensations. Previous studies show that SSS could be a small fibre neuropathy, but quantitative sensory testing (QST) is lacking. OBJECTIVES: Using QST, to determine the presence or absence of tactile sensitivity disorder, mainly heat pain threshold (HPT), in patients with SSS. METHODS: This monocentric case-control study included 21 patients with SSS and 21 controls. The patients underwent QST. Neuropathic pain was assessed by two questionnaires: the Douleur Neuropathique 4 (DN4) and the Neuropathic Pain Symptom Inventory (NPSI). RESULTS: Forty-two patients were included in the study. The HPT was significantly lower in the cases (14·5 ± 2·8) than in the controls (17·8 ± 2·5) (P < 0·001). Intermediate pain (HPT 5·0) was also significantly decreased in patients with SSS. The DN4 and NPSI scores were significantly higher in the cases than in the controls. CONCLUSIONS: The decrease in HPT in patients with SSS compared with controls suggests the presence of hyperalgesia, probably due to the damage of C-fibres. These findings, as well as the increased DN4 and NPSI scores, strengthen the neuronal hypothesis of SSS and are new arguments for consideration of SSS as small fibre neuropathy.

Development and validation of a new tool to assess the Burden of Sensitive Skin (BoSS).

BACKGROUND: Sensitive skin usually manifests itself as unpleasant sensations and sometimes erythema. There are various triggering factors for this condition. Although sensitive skin may alter quality of life, its burden has not yet been explored. OBJECTIVE: The aim of this study was to develop and validate a specific sensitive skin burden questionnaire called the BoSS (Burden of Sensitive Skin). METHODS: A conceptual phase was developed, followed by a development phase, external validation, psychometric analysis, test-retest analysis and, finally, a translation, cross-cultural adaptation and cognitive debriefing. RESULTS: A total of 6471 individuals participated in the study (4614 people in the validation study). The dimensionality of items was evaluated using factor analyses, suggesting three dimensions (self-care, daily life and appearance). Unidimensionality was confirmed by higher order factor analysis. The overall Cronbach's α coefficient was high, and intradimensional coherences all demonstrated good reliability. The final instrument consisted of 14 items. The test-retest reliability demonstrated very good reproducibility. The intraclass correlation of each dimension was high. External validity was confirmed by the correlation coefficients of the BoSS vs. those of the SF-12 and the DLQI assessment tools. CONCLUSION: BoSS is the first reliable tool to assess the burden of sensitive skin.