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.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

[My tongue is burning!-Glossodynia/orofacial pain disorder]. / Meine Zunge brennt! ­ Glossodynie/orofaziales Schmerzsyndrom.

Glossodynia or orofacial pain disorder is known as burning mouth syndrome. It is a therapeutic challenge. Its etiology is not well defined. Recent studies show not only a correlation with neuropathic changes, but there are also indications of comorbidities such as depression, anxiety, and carcinophobia. These can also manifest as a reaction to the disease and are not necessarily considered causative. Burning mouth syndrome poses a diagnostic challenge since its differential diagnosis is broad. With regard to dermatological aspects, lichen planus mucosae, oral leucoplakia, pemphigus vulgaris, and aphthous mouth ulcers should be considered. Diabetes, anemia, vitamin deficiency, and endocrinological influences should be considered regarding the predominance of elderly and female patients. Meta-analyses of treatment studies usually show a low level of evidence of the randomized, controlled trials. According to the literature mainly psychotherapy and antidepressants are proposed for therapy. Alpha lipoic acid as a dietary supplement shows short-term improvement and low-level laser therapy might have some benefit.

Recalcitrant erythrodermic ichthyosis with atopic dermatitis successfully treated with Dupilumab in combination with Guselkumab.

Background: Autosomal recessive congenital ichthyosis refers to a group of rare inherited disorders of keratinization and defective epidermal barrier resulting in varying clinical presentations and severities ranging from harlequin ichthyosis to congenital ichthyosiform erythroderma (CIE). Secondary atopic dermatitis (AD) can aggravate the disease state for CIE patients leading to recalcitrant CIE/AD with potentially unfavourable side effects and low tolerability. Aims: Here, we report about a 38-year-old male patient with severe CIE as well as AD over the last 30 years. Materials and Methods: The patients suffered from severe inflammation, pruritus and recurrent infections for decades without disease control and intolerable adverse events of previous therapies. Results: Dupilumab (targeting IL-4Ra, 300 mg q2w) partially controlled pruritus, but only the combination of Dupilumab with Guselkumab (anti-IL23p19) controlled both CIE and AD with markedly reduced inflammation, itch and recurrent infections. Guselkumab alone was not sufficient to treat the severe CIE/AD. Discussion: Further studies are required to assess the efficacy and safety of targeted therapies like Dupilumab/Guselkumab combination therapy in severe CIE/AD.

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children.

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Evidence supporting the enhanced efficacy of pentavalent antimonials with adjuvant therapy for cutaneous leishmaniasis: a systematic review and meta-analysis.

Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the first-line choice despite their toxicity and limited efficacy. The combination of two drugs has risen as a potential alternative to increase the cure rate while lowering the side-effects caused by pentavalent antimonials (PA). The objective of this study was to critically review and appraise the potential synergism of the adjuvant therapies of PA with other drugs/interventions previously used in the literature. We carried out a search of literature from PubMed, MEDLINE, Embase, Cochrane and clinicaltrials.gov. Articles that described a two-arm or three-arm design in which one of the arms consisted in a combination of a drug/intervention with intralesional or systemic PA were selected. The primary outcome was proportion of complete clearance of the lesions defined as complete re-epithelization and/or negative direct smear. Our literature search identified 554 references. Thirty-one records with a total sample size of 2668 participants met the eligibility criteria. The studies investigated the association of PA with the following: cryotherapy (five studies), allopurinol, imiquimod, pentoxifylline (four studies each), trichloroacetic acid 50% (three studies) and other additional interventions (eleven studies). Overall, the combined therapy of PA with a supplementary intervention was superior to PA monotherapy (RR: 1.23 95% CI: 1.11-1.35, I2  = 64%). In association with PA, the comparator-specific stratified analysis showed that cryotherapy (RR: 1.50 95% CI: 1.25-1.81, I2  = 57%) and allopurinol (RR: 1.70 95% CI: 1.37-2.12, I2  = 28%) were superior to PA in monotherapy. On the contrary, the combined therapy with imiquimod (RR: 1.08 95% CI: 0.88-1.32, I2  = 40%) and pentoxifylline (RR: 1.14 95% CI: 0.94-1.40, I2  = 41%) revealed a non-significant result. The application of TCA along with PA did not show significant differences in the clearance rate, although it was close to it (RR: 1.31 95% CI: 0.99-1.73, I2  = 84%). The present work represents an attempt to find new and reliable treatment modalities to enhance the efficacy based on the adjuvant therapy of pre-existing drugs/interventions with PA. According to our results, the combination of allopurinol-PA is the most effective adjuvant therapy. The application of cryotherapy and TCA stand as useful and encouraging supplementary interventions. The combination of imiquimod-PA and pentoxifylline adds no additional benefit. The results of this work may be helpful in devising and modifying the current guidelines for CL which face major remaining evidence gaps. Triple therapies consisting in cryotherapy-PA-TCA or allopurinol-PA-cryotherapy or allopurinol-PA-TCA can represent promising treatments yet to be confirmed in future trials.

'The psychosocial burden of alopecia areata and androgenetica': a cross-sectional multicentre study among dermatological out-patients in 13 European countries.

BACKGROUND: Hair diseases play an important burden on patients' lives, causing significant emotional and psychosocial distress. However, the impairment due to different hair conditions, such as alopecia areata (AA) and androgenetic alopecia (AGA), has rarely been compared. OBJECTIVE: The aim of this study was to assess the psychological burden of subgroups of patients with different hair diseases and to compare them to a healthy population. METHODS: In this study, we analysed a subgroup of patients with hair diseases from patients of a large multicentre study including 3635 dermatological patients and 1359 controls from 13 European countries. In the subgroup of patients with hair diseases, we analysed the socio-demographic characteristics, the stress level, and the impact of hair diseases on quality of life (QoL), anxiety, and depression and we compared them among patients with AA, AGA and healthy controls. RESULTS: The study population included 115 patients (77% women, 23% men) with hair diseases, 37 of whom with AA and 20 with AGA. Patients with hair diseases had a lower education level than healthy controls (medium educational level: 43% vs. 28%). Overall, 41% of the patients reported stressful life events during the last 6 months compared with 31% of the controls. Patients with the same age, sex, depression level and comorbidities had a worse QoL when suffering from AA than from AGA (Mean Dermatology Life Quality Index score: 5.8 vs. 2.5). CONCLUSION: Patients with hair diseases are more anxious, depressed and have a lower QoL than controls.

Itch induction by audiovisual stimuli and histamine iontophoresis: a randomized, controlled noninferiority study.

BACKGROUND: Previous research has mainly used skin-manipulating methods to induce itch. In comparison, itch induced by audiovisual stimuli lacks direct skin manipulation. OBJECTIVES: The aim of this double blind, noninferiority study was to test the experimental hypothesis that itch induced by audiovisual stimuli is noninferior to itch induced by histamine iontophoresis in case of priming and without priming. METHODS: In 80 of 160 healthy volunteers itch was induced by histamine iontophoresis, while in the other 80 itch was induced by audiovisual stimulation. Forty people in each group experienced either an initial resting phase or dermal priming. Itch intensity was measured by visual analogue scales, while scratch duration and frequency were video-recorded and evaluated by two independent raters. In addition, itch quality and location were measured by self-report. RESULTS: Itch induced by audiovisual stimuli was inferior to itch induced by histamine iontophoresis in the absence of dermal priming. However, in the case of priming, maximal itch induced by audiovisual stimuli was not inferior to maximal itch induced by histamine iontophoresis. Additionally, differences in itch quality and location were observed. CONCLUSIONS: The finding that maximal audiovisually-induced itch was comparable with maximal histamine itch only after priming emphasizes that attention plays a dominant role in mentally-induced itch. The comparability of maximal histamine and audiovisually-induced itch in the case of priming opens up new research opportunities. What's already known about this topic? Itch is a multidimensional sensation that is altered by, among other things, attention. To induce itch in basic research, different methods are used, which are partially invasive or cause skin manipulation. Noninvasive audiovisual stimuli can be used to induce itch. What does this study add? This study investigated whether itch induced by audiovisual stimuli is noninferior to itch induced by histamine iontophoresis. Itch induced by audiovisual stimuli is noninferior with regard to maximal intensity in the case of priming. Noninferiority was not shown in the case of no priming, emphasizing the role of attention in itch induction. Histamine and audiovisually-induced itch differ in terms of quality and location, but not in affective reaction.

Lichen planus: a comprehensive evidence-based analysis of medical treatment.

Lichen planus (LP) is a chronic-relapsing inflammatory skin disease. Although many drugs have been used for the management of LP, some of them lack the backup by strong therapeutic evidence, while others are not suitable for some patients due to safety profile issues. The aim of this study was to review the recent status of available medical therapies for LP to help physicians make better decisions upon best medical practice while facing patients with this condition. A review of published articles on management of LP was conducted with the MEDLINE and PubMed databases. The quality of the evidence was graded as high, moderate, low or very low. A total of 1366 articles were retrieved, and 219 (16%) were included in the final analysis. Twenty-one different treatment modalities were analysed. The quality of evidence was high for topical steroid and calcineurin inhibitor, while it was moderate for oral steroids. All the other modalities reached low or very low quality of evidence. Topical steroids and calcineurin inhibitors are the current first-line therapies, while for other therapies the strength of recommendation is not so evident. Unfortunately, larger randomized, controlled trials to support the efficacy, safety and tolerability of other therapies in LP are lacking, and many of them are recommended based on studies with small sample sizes, lack of standardized outcome measures or lack of controlled duration or even in anecdotal evidence. Thus, large-scale randomized clinical trials are still warranted to establish the exact benefits of other topical treatments, phototherapy, immunosuppressant and new immunomodulators for an optimized treatment of LP.

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period.

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

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.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.