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There is an incessant interest in transfer of common chemical processes from organic solvents to water, which is vital for the development of bioinspired and green chemical technologies. Diarylethenes feature a rich photochemistry, including both irreversible and reversible reactions that are in demand in organic synthesis, materials chemistry, and photopharmacology. Herein, we introduce the first versatile class of diarylethenes, namely, potassium 2,3-diarylmaleates (DAMs), that show excellent solubility in water. DAMs obtained from highly available precursors feature a full spectrum of photoactivity in water and undergo irreversible reactions (oxidative cyclization to phenanthrenes or rearrangement) or reversible photocyclization (switching), depending on their structure. This finding paves a way towards wider application of DAEs in photopharmacology and bioinspired technologies that require aqueous media for photochemical reactions.

Altres ajuts: European Academy of Dermatology and Venereology (EADV, No. 2016-012 to MP). 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.

Gardner-Diamond syndrome is an extremely rare autoimmune disorder characterized by sensitization to phosphatidylserine of erythrocyte stroma leading to ecchymoses triggered by stressful events. Diagnostic criteria include typical history, typical skin lesions, normal parameters of blood count and blood coagulation and a positive test with intracutaneous injections of 1 ml of autoerythrocytes. Most patients with Gardner-Diamond syndrome have co-morbid mental disorders. Psychotherapy and psychopharmacotherapy (selective serotonin reuptake inhibitors, tricyclic antidepressants) seem to be most pathogenetically supported treatment modalities.

Altres ajuts: European Academy of Dermatology and Venereology (EADV, No. 2014-022). 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.

Trichotillomania (TTM) or hair pulling disorder (HPD) is defined as a recurrent pulling of one’s own hair leading to significant hair loss, i.e. self-inflicted alopecia, traction alopecia or mechanical alopecia, accompanied by repeated unsuccessful attempts to decrease or stop the behaviour. TTM often onsets following a stressful event or when one is in persistent distress. It is important to identify an acute stress (death of a partner/significant other, parental divorce, employment termination, etc.) or chronic stress (ongoing domestic violence, poor scholarly or job performance, long-lasting overwork, etc.). It is essential to overlook the general situation of an individual’s life circumstances, as there could be important signs of positive or negative reinforcement for hair pulling. Optimal or gold standard treatment is still lacking. Psychiatric referral is recommended, however, there could be other organisation forms like multidisciplinary psychodermatological clinics or consultation-liaison services. There is evidence for pharmacological treatment, as for psychotherapy. A combination of both may be more effective than either approach independently. In this chapter, the evidence for psychodermatopharmacology, psychotherapy and other therapies will be discussed.

Altres ajuts: European Academy of Dermatology and Venereology (EADV, 2016-012); Galderma S.A; Kiniksa Pharmaceuticals; Menlo Therapeutics. Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

Manipulating the equilibrium between a ketone and an enol by exposure to light opens up ample opportunities in material chemistry and photopharmacology since it allows one to reversibly control the content of the enol tautomer, which acts as a hydrogen atom donor, with high spatio-temporal and energy resolution. Although tautomerization of β-ketoesters or their analogs was studied in numerous papers, their light-induced reversible tautomerization to give thermally stable enols (photoenolization) is an unexplored area. To shed light on this “blind spot”, we report an unprecedented property of diarylethene 2A assembled from fragments of photoactive dithienylethene and a β-ketoester as part of the cyclohexenone bridge. In a pristine state, the tautomeric equilibrium of 2 is almost completely shifted towards the ketone. Photocyclization of the hexatriene system results in a new equilibrium system containing a significant fraction of the enol tautomer, both in polar and non-polar solvents. Due to the considerable spectral separation (35 nm), the keto-enol tautomerization process could be observed visually. The tendency of 2A to undergo light-induced enolization was proved by isolating a related byproduct of photochemical 1,2-dyotropic rearrangement stabilized in the enolic form. Our results provide a novel tool for controlling the keto-enol tautomerism that might find use in the development of novel photocontrollable processes.

We examined the association between the duration of untreated psychosis and outcome for patients with delusional infestation. This multi-centre international study included 211 consecutive patients. Illness severity was evaluated at first presentation and outcome was measured with the Clinical Global Impression scale (CGI) at baseline and follow-up. A regression analysis showed a clear clinical and statistically significant association between shorter duration of untreated psychosis and better outcome at follow-up. Patients with a duration of untreated psychosis of less than one year showed a CGI-S change from 5.37 to 2.07; those with a duration of untreated psychosis of 1–5 years a change from 5.48 to 2.59, and those with a duration of untreated psychosis of >5 years a change from 5.59 to 3.37. This difference of 1.1 CGI points between the groups resembles a clinically relevant difference in patient outcome. Our results suggest that longer duration of untreated psychosis in patients with delusional infestation is associated with significantly less favour­able clinical outcomes.

The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new psychotherapies and psychotropic drugs without forgetting the most important relational characteristics required for dealing with people with these disorders. The management of self-inflicted skin lesions necessitates empathy and a doctor–patient relationship based on trust and confidence. Cognitive behavioural therapy and/or psychodynamic and psychoanalytic psychotherapy (alone, or combined with the careful use of psychotropic drugs) seem to achieve the best results in the most difficult cases. Relatively new therapeutic techniques, such as habit reversal and mentalization-based psychotherapy, may be beneficial in the treatment of skin picking syndromes., SCOPUS: ar.j, info:eu-repo/semantics/published

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/Sezary syndrome and with CP >= 3 on the numerical rating scale were included. ItchyQoL showed a high level of consistency (Cronbach's-alpha, 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.

Itch is a highly prevalent and multidimensional symptom. We aimed to analyze the association between itch and mental health in dermatological patients. This multicenter study is observational and cross-sectional and was conducted in dermatological clinics across 13 European countries. A total of 3,530 patients and 1,094 healthy controls were included. Patients were examined clinically. Outcome measures were itch (presence, chronicity, and intensity), the Hospital Anxiety and Depression Scale, EQ-5D visual analogue scale, sociodemographics, suicidal ideation, and stress (negative life events and economic difficulties). Ethical approval was obtained. Results showed significant association between the presence of itch in patients and clinical depression (odds ratio, 1.53; 95% confidence interval, 1.15–2.02), suicidal ideation (odds ratio, 1.27; 95% confidence interval, 1.01–1.60), and economic difficulties (odds ratio, 1.24; 95% confidence interval, 1.10–1.50). The mean score of reported generic health status assessed by the EQ-5D visual analogue scale was 65.9 (standard deviation = 20.1) in patients with itch, compared with 74.7 (standard deviation = 18.0) in patients without itch (P < 0.001) and 74.9 (standard deviation = 15.7) in controls with itch compared with 82.9 (standard deviation = 15.6) in controls without itch (P < 0.001). Itch contributes substantially to the psychological disease burden in dermatological patients, and the management of patients should include access to multidisciplinary care., SCOPUS: ar.j, info:eu-repo/semantics/published

To study clinical characteristics of burning mouth syndrome or glossalgia is a functional disorder with painful sensations in the oral cavity with verification of the psychopathological structure, typology and nosology of the syndrome within the continuum of neurotic/psychotic disorders and dermatological pathology, i.e. lichen planus (LP).The study sample (The psychopathological picture of glossalgia syndrome has a binary structure. Basic coenesthesiopathies, ranging in severity from homonomous sensations (isteralgias) to heteronomic sensopathies (senestopathies, senesthesia), are associated with secondary hypochondriacal phenomena: from health anxiety and monopatophobia to mastery of ideas and somatopsychic confusion, respectively. According to the psychopathological register (neurotic/psychotic) and the fact of objective verification of a dermatological disease (hypochondria sine materia/cum materia), there are three types of glossalgic syndrome: 1) organo-neurotic; 2) somatopsychotic; 3) dermatological (stress-induced somatic reactions).BMS is a local syndrome limited to the oral cavity, however, in fact, it covers the entire clinical spectrum of psychosomatic pathology from mental diseases to psychodermatological ones.Описать клинические проявления глоссалгии (синдром «горящего рта»), расстройства, выражающегося патологическими телесными сенсациями в полости рта, с верификацией психопатологической структуры, типологии и нозологии синдрома в пределах континуума расстройств невротического/психотического регистров и дерматологической патологии (красный плоский лишай (КПЛ)).Выборку составили 30 пациентов (27 женщин, средний возраст 59,3±15,6 года), прошедших комплексное психопатологическое, психометрическое, дерматологическое, неврологическое обследования. Пациенты соответствовали диагностическим критериям глоссалгии согласно классификации IASP и МКБ-10 для глоссодинии (код К14.6). В 8 наблюдениях коморбидным заболеванием являлся КПЛ слизистой оболочки полости рта.Психопатологическая картина синдрома глоссалгии имеет бинарную структуру. Базисные коэнестезиопатии, ранжируемые по тяжести от гомономных сенсаций (истералгий) до гетерономных сенстопатий (сенестопатии, сенестезии), ассоциированы с вторичными ипохондрическими феноменами: от тревоги о здоровье и монопатофобий до овладевающих представлений и соматопсихической растерянности соответственно. Согласно психопатологическому регистру (невротический/психотический) и факту объективной верификации дерматологического заболевания (ипохондрия sine materia/cum materia), выделено три типа глоссалгического синдрома: 1) органоневротический; 2) соматопсихотический; 3) дерматологический (стресс-индуцированные соматические реакции).Глоссалгия — локальный, ограниченный полостью рта синдром, фактически охватывающий все условное клиническое пространство психосоматической патологии, на одном из полюсов которого доминируют психические заболевания, а на другом — дерматологические.

Chronic prurigo (CPG) is a highly burdensome pruritic disease characterized by chronic itch, a prolonged scratching behavior and the development of localized or generalized hyperkeratotic pruriginous lesions. Neuronal sensitization and the development of an itch-scratch cycle contribute to the augmentation of pruritus and the chronicity of the disease. We provide here the first international guideline for a rational diagnostic and therapeutic approach for CPG. Recommendations are based on available evidence and expert opinion. The diagnosis of CPG is made clinically. A detailed medical history together with laboratory and radiological examinations are advised in order to determine the severity of CPG, identify the underlying origin of the itch and assist in the elaboration of a treatment plan. Therapeutically, it is advised to adopt a multimodal approach, including general strategies to control itch, treatment of the underlying pruritic conditions, and of the pruriginous lesions. Topical (corticosteroids, calcineurin inhibitors, capsaicin) and systemic antipruritic agents (eg, gabapentinoids, immunosuppressants, and opioid modulators) as well as physical treatment modalities (phototherapy, cryotherapy) should be employed in a step-wise approach. Psychosomatic or psychological interventions may be recommended in CPG patients with signs of psychiatric/psychological comorbidities. (Less)

Background: Chronic pruritus is a multifactorial, challenging symptom of global relevance. Objective: The European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) investigation aimed to analyze the severity and humanistic burden of chronic pruritus in patients suffering from inflammatory dermatoses across Europe. Methods: Prospectively collected routine data on 552 patients (with atopic dermatitis, contact dermatitis, prurigo nodularis, psoriasis vulgaris, lichen planus, or mycosis fungoides [pruritus numeric rating scale score >= 3]) from 9 European centers (in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland, and Turkey) were analyzed by univariate and multivariate variance analyses of various itch characteristics and quality of life (as measured by the Dermatology Life Quality Index and the ItchyQoL). Results: Duration, frequency, and intensity of pruritus (according to a numeric rating scale and visual analog scale) and related impairment of quality of life differed between European centers and dermatologic diagnoses (P < .05). The country in which the center was located had a greater impact on how patients evaluated pruritus intensity and quality of life than diagnosis did (P < .001). Limitations: One center per country was included. Conclusion: The humanistic burden of chronic pruritus in patients with inflammatory dermatoses is high. European cross-cultural factors may have a stronger influence than a specific dermatologic diagnosis on how patients rate intensity of pruritus and quality of life.

Background It was recently demonstrated that a significant number of patients with common skin diseases across Europe are clinically depressed and anxious. Studies have shown that physicians not trained as psychiatrists underdiagnose depression. This has not been explored among dermatologists. Objectives To estimate the concordance between clinical assessment of depression and anxiety by a dermatologist and assessment with the Hospital Anxiety and Depression Scale (HADS). Methods The study was an observational cross‐sectional multicentre study of prevalent cases of skin diseases in 13 countries in Europe. Consecutive patients were recruited in outpatient clinics and filled in questionnaires prior to clinical examination by a dermatologist who reported any diagnosis of skin disease and signs of mood disorders.ResultsAnalysis of the 3635 consultations showed that the agreement between dermatologist and HADS was poor to fair (lower than 0·4) for all diagnosis categories. The true‐positive rate (represented by the percentage of dermatologists recognizing signs of depression or anxiety in patients with depression or anxiety as defined by a HADS value ≥ 11) was 44·0% for depression and 35·6% for anxiety. The true negative rate (represented by the percentage of dermatologists not detecting signs of depression or anxiety in non‐depressed or non‐anxious patients defined by HADS‐value < 11) was 88.8% for depression and 85.7% for anxiety.ConclusionsDermatologists in Europe tend to underestimate mood disorders. The results suggest that further training for dermatologists to improve their skills in diagnosing depression and anxiety might be appropriate. When present, the psychological suffering of patients with dermatological conditions needs to be addressed.

An observational, exploratory, cross-sectional study was performed to assess whether the presence of atypical naevi (AN) in adolescents is associated with psychological and psychovegetative stress parameters. Fifty-one students of a secondary school in Graz, Austria, completed a defined test procedure consisting of an initial period of rest, a standardised mental stress task, another period rest and a questionnaire, the change-sensitive symptom list (ASS-SYM). Electrocardiogram and blood pressure were recorded continuously. The study population was divided in two groups: probands without AN (NAN, n = 33), and probands with at least one AN (n = 18). We found higher values for the AN group in all scales of ASS-SYM, reaching statistical significance in the dimensions "nervousness and mental tension" (p = 0.025), "psychophysiological dysregulation" (p = 0.020), burden of pain" (p = 0.023) and "general symptoms and problems" (p = 0.031). Regarding physiological parameters, the AN group showed higher vegetative strain reflected in heart rate and heart rate varibility during the periods of rest as well as a reduced baroreceptor sensitivity. On the basis of our results, the presence of AN in adolescents seems to be associated with a higher vegetative arousal. Additionally, participants with AN complained significantly more often about stress-associated general psychological symptoms and problems.

There are limited data on the differences in the impact of psoriasis between various countries with respect to quality of life (QoL). The aim of this study was to explore the psychosocial health of patients with psoriasis in different European countries. A total of 682 patients were recruited in 13 European countries. All patients completed a questionnaire regarding sociodemographic information, negative life events, suicidal ideation and satisfaction with their dermatologist. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and QoL with the Dermatology Life Quality Index (DLQI) and EuroQoL (EQ-5D). The lowest anxiety and depression scoring was noted in patients from Denmark, the lowest level of impairment in QoL in subjects from Spain, and the highest level of impairment in QoL in patients from Italy. The most relevant parameters influencing patients’ well-being were severity of pruritus and satisfaction with their dermatologist. The level of anxiety and depression symptoms correlated significantly with suicidal ideation., SCOPUS: ar.j, info:eu-repo/semantics/published

Item does not contain fulltext BACKGROUND: Generic instruments measuring health-related quality of life (HRQoL), like EQ5D, enable comparison of skin diseases with healthy populations and nondermatological medical conditions, as well as calculation of utility data. OBJECTIVES: To measure HRQoL in patients with common skin diseases and healthy controls across Europe using the EQ5D. METHODS: This multicentre observational cross-sectional study was conducted in 13 European countries. Each dermatology clinic recruited at least 250 consecutive adult outpatients to complete questionnaires, including the EQ5D. RESULTS: There were 5369 participants (4010 patients and 1359 controls). Mean +/- SD self-rated health state reported by patients was 69.9 +/- 19.7; for controls it was 82.2 +/- 15.5. When adjusted for confounding factors, including comorbidity, mean patient EQ visual analogue scores were 10.5 points lower than for controls (standardized beta = -0.23). Odds ratio with 95% confidence interval for impairment in all five dimensions of EQ5D adjusted for confounders was doubled for patients compared with controls. Patients with hidradenitis suppurativa (HS), blistering conditions, leg ulcers, psoriasis and eczemas had the highest risk for reduction in HRQoL in most dimensions (2-10-fold). Data on differences of impairment by dimensions offer new insights. CONCLUSIONS: This study confirms the large impact skin conditions have on patients' well-being, differentiating between aspects of HRQoL. Patients with HS, blistering diseases, leg ulcers, infections and most chronic skin diseases reported reduced HRQoL compared with patients with chronic obstructive lung disease, diabetes mellitus, cardiovascular disease and cancers. These findings are important in the prioritization of resource allocation between medical fields and within dermatological subspecialities.

The article is devoted to a psychodermatological disorder with self-destructive behavior - hypochondriasis circumscripta. Presented data are based on a clinical analysis of 22 consecutive cases (15 female; mean age - 56.1 ± 12.6 years) observed in the dermatologic department of First Moscow State Medical University and managed in a multidisciplinary approach by dermatologists and a consultation-liaison psychiatrist. Psychopathology, clinical presentations, historical aspects and treatment options are discussed. The self-inflicted skin lesions result from a severe repetitive autodestruction of focal skin loci primarily affected with heterogeneous sensations associated with a hypochondrical over-valued idea. Hypochondriasis сircumscripta is a serious diagnostic and treatment challenge and should be distinguished from dermatitis artefacta, skin picking disorder and delusional infestation.

Rationale In mouse models for atopic dermatitis (AD) hypothalamus pituitary adrenal axis (HPA) dysfunction and neuropeptide-dependent neurogenic inflammation explain stress-aggravated flares to some extent. Lately, cholinergic signaling has emerged as a link between innate and adaptive immunity as well as stress responses in chronic inflammatory diseases. Here we aim to determine in humans the impact of acute stress on neuro-immune interaction as well as on the non-neuronal cholinergic system (NNCS). Methods Skin biopsies were obtained from 22 individuals (AD patients and matched healthy control subjects) before and after the Trier social stress test (TSST). To assess neuro-immune interaction, nerve fiber (NF)-density, NF-mast cell contacts and mast cell activation were determined by immunohistomorphometry. To evaluate NNCS effects, expression of secreted mammal Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP) 1 and 2 (endogenous nicotinic acetylcholine receptor ligands) and their main corresponding receptors were assessed by quantitative RT-PCR. Results With respect to neuro-immune interaction we found higher numbers of NGF+ dermal NF in lesional compared to non-lesional AD but lower numbers of Gap43+ growing NF at baseline. Mast cell-NF contacts correlated with SCORAD and itch in lesional skin. With respect to the NNCS, nicotinic acetylcholine receptor α7 (α7nAChR) mRNA was significantly lower in lesional AD skin at baseline. After TSST, PGP 9.5+ NF numbers dropped in lesional AD as did their contacts with mast cells. NGF+ NF now correlated with SCORAD and mast cell-NF contacts with itch in non-lesional skin. At the same time, SLURP-2 levels increased in lesional AD skin. Conclusions In humans chronic inflammatory and highly acute psycho-emotional stress interact to modulate cutaneous neuro-immune communication and NNCS marker expression. These findings may have consequences for understanding and treatment of chronic inflammatory diseases in the future.