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.

Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

BACKGROUND: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. RESULTS: 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch-related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. CONCLUSION: This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment.

[To the problem of somatic-hypochondriac paranoia]. / K probleme somaticheskoi-ipokhondricheskoi paranoii.

OBJECTIVE: To unite within the framework of a single clinical entity (based on the model of hypochondriacal paranoia) phenomena of the somatopsychotic and hypochondriacal range, which, in accordance with modern systematics, are classified as various categories of psychosomatic, affective disorders and personality disorders. MATERIAL AND METHODS: The sample for analysis consisted of 29 patients (with the diagnosis of delusional disorder (ICD-10; F22.0 in ICD-10), 10 men (34.5%) and 19 women (64.5%), the average age was 42.9±19.9 years; men - 10 nab. (34.5%), women - 19 nab. (64.5%). The average duration of the disease iswas 9.4±8.5 years. The psychopathological method was used as the main one. RESULTS: The article forms an alternative concept of somatic paranoia based on the model of hypochondriacal paranoia. The fundamental difference between the construct of somatic paranoia is an obligate connection between somatopsychic and ideational disorders. Somatopsychic (coenesthesiopathic) symptoms do not exist as an independent (equivalent to the structure of somatic clinical syndromes) dimensions and are formed exclusively with the participation of ideational phenomena. CONCLUSION: In accordance with the presented concept, coenesthesiopathic symptoms within the framework of somatic paranoia act as a somatic equivalent of delusional disorders.

[Pain syndromes and insomnia: the role of association with comorbid mental disorders (on the model of glossalgia)]. / Bolevye sindromy i insomniya: rol' assotsiatsii s komorbidnymi psikhicheskimi rasstroistvami (na modeli glossalgii).

OBJECTIVE: To test the association between pain severity and anxiety, depression, and somatoform symptoms in burning sleep syndrome (BMS). MATERIAL AND METHODS: The study included 36 patients (33 women, 3 men), mean age 58.0±14.8 years. Psychopathological, clinical-dermatological, parametric, statistical methods were used. Psychometric examination included the Visual Analogue Scale (VAS) for assessment of pain (severity of glossalgia), PHQ-4 for self-assessment of severity of anxiety (GAD-2) and depression (PHQ-2), the Hospital Anxiety and Depression Scale (HADS), the Screening for Somatoform Symptoms-2 (SOMS-2), the Pittsburgh Sleep Quality Index (PSQI), the EQ-5D-5L quality of life assessment scale. RESULTS AND CONCLUSION: Insomnia in chronic pain is very common. On the one hand, studies show that sleep deprivation can enhance pain perception. On the other hand, chronic pain can trigger a variety of sleep disorders. One of the localizations of chronic pain syndrome is the oral mucosa. Somatoform pain disorder related to oral mucosa called «glossalgia¼ or «burning mouth syndrome¼ (BMS). The prevalence of insomnia in the study sample was 61.1%. The statistically significant positive correlation was found between the severity of insomnia (PSQI) and the severity of anxiety on both GAD-2 and HADS, while insomnia showed no correlation with depression and pain severity. At the same time, the severity of anxiety showed statistically significant positive correlation with the severity of pain assessed by VAS.

[Glossalgia as a psychodermatological syndrome]. / Glossalgiya kak sindrom psikhodermatologicheskoi patologii.

OBJECTIVE: 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). MATERIAL AND METHODS: The study sample (n=30, 27 female, mean age 59.3±15.6 years) was examined by dermatologist, neurologist and psychiatrist both clinically and psychometrically. The patients met the diagnostic criteria for glossalgia according to the IASP classification and ICD-10 for glossodynia (code K14.6). In 7 subjects, there was comorbidity with LP of the oral mucosa. RESULTS: 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). CONCLUSION: 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.

Pruritus Intensity Scales across Europe: a prospective validation study.

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.

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.

Photochemical rearrangement of diarylethenes: synthesis of functionalized phenanthrenes.

A novel protocol for the synthesis of functionalized phenanthrenes through photocyclization of diarylethenes (DAE) under UV irradiation is proposed. The reaction proceeds through 6π-electrocyclization with the formation of a cyclic (closed) intermediate that undergoes a rearrangement affording unsymmetrical phenanthrenes in good yields. However, in contrast to benzene derivatives, the photocyclization of naphthalene diarylethenes proceeds more slowly, which is confirmed by DFT calculations. The transformation was performed on a 1 mmol scale. The scalability showed that the diarylethenes bearing oxazole, thiazole, pyrazole and imidazole as aryl moieties are more prone to photorearrangement and can be used in preparative organic synthesis.

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.

[Pretibial myxedema: pathogenetic features and clinical aspects].

Pretibial myxedema (PTM) or thyroid dermopathy is a rare extrathyroidal manifestation of Graves' disease. The condition is accompanied by mucinous skin changes, mainly in the anterior tibial surface. Severe forms may lead to lymphatic congestion and disability. Prolonged and intense autoimmune aggression is supposed to be necessary for PTM manifestation. However, data on the role of TSHR antibodies in the development of thyroid dermopathy are very ambiguous; evidence of IGF-1 receptor involvement in the pathogenesis was reported recently. Typically, PTM is localized on the anterior and lateral surfaces of both tibias and can be represented by diffuse, tumorous, plaque-like, or elephantiasic forms. Currently, early diagnostics involves regular preventive examination of the pretibial area. A diagnostic biopsy is indicated only in complex cases. Maintaining euthyroidism, smoking cessation, preventing injuries, and avoiding tight shoes that disturb lymphatic drainage are measures reducing the risk of PTM in GD patients. Currently, there are no accepted clinical guidelines for the diagnosis and treatment of thyroid dermopathy. This review provides the recent scientific data on etiopathogenesis and management of patients with PTM.

Determination of Micro-Quantities of DNA Using DNAse and Fluorescence of Hoechst 33258 and Light-Scattering.

The DNA hydrolysis by deoxyribonuclease (DNAse I) in aqueous solution was studied, using fluorescence spectroscopy and high-sensitive light-scattering detection. Specific hydrolysis of high-polymer DNA or fragmented DNA by the enzyme led to a strong decrease in the fluorescence of the Hoechst dye. The hydrolysis of mitochondrial DNA was accompanied by a decrease in the fluorescence of the dye only in 1.6 times. Hydrolysis within minutes and even hours led to appearance of large polynucleotide fragments, but not to short oligonucleotides, that was confirmed using polarized fluorescence and highly sensitive measurement of light-scattering. At the moment of the time of formation of a complex between DNA and DNAse I, a strong light-scattering occurred, which then dropped sharply during hydrolysis of high-molecular DNA, and slowly decreased during hydrolysis of fragmented DNA. The proposed methods can be applied for selective detection of trace amounts of various types of DNA, as well as for studying their physic-chemical properties.

Photocyclization of diarylethenes: the effect of imidazole on the oxidative photodegradation process.

We have studied the photoreaction of 1,2-diarylethenes under aerobic conditions in the presence of various amines to prevent side processes promoted by singlet oxygen. It has been found that the most amines quite effectively deactivate processes associated with singlet oxygen, but primary and secondary amines unlike tertiary ones, react with substrates resulting in various side products. Among the studied amines, the most effective additive for preventing side processes, including those associated with singlet oxygen is imidazole, which is practically not consumed in photoreaction. It was shown that imidazole can also prevents the photodegradation of organic photochromes in solutions. The results obtained can be used in various branches of science, technology and medicine to improve the photostability of photosensitive organics (dyes).

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.

Cross-European validation of the ItchyQoL in pruritic dermatoses.

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.

Dermatologists across Europe underestimate depression and anxiety: results from 3635 dermatological consultations.

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. RESULTS: Analysis 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. CONCLUSIONS: Dermatologists 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.

The burden of common skin diseases assessed with the EQ5D™: a European multicentre study in 13 countries.

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 ß = -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.

Autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome): review of the literature.

A review of the literature concerning psychogenic purpura is presented. The diagnosis is usually based on typical anamnestic data, clinical presentation (painful inflammatory skin lesions, which progressed to ecchymoses during the next 24 h) and positive diagnostic tests with intracutaneous injections of 80% solution of washed autologous erythrocytes. No pathological findings of blood coagulation parameters are usually detected. Histopathological evaluations of lesional biopsies revealed non-specific changes. Taking into account the high frequency of psychic disorders and stress dependence of skin symptoms, therapy with psychotropic drugs (according to indications) and psychotherapy are pathogenetically grounded methods of treatment in psychogenic purpura, and should be provided together with symptomatic therapy.