Quality of life measurement in urticaria: Position statement of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient-Oriented Outcomes and Urticaria and Angioedema.

The European Academy of Dermatology and Venereology (EADV) Task Forces on quality of life (QoL) and patient-oriented outcomes and on urticaria and angioedema recommendations for the assessment of Health-related (HR) QoL in all patients with urticaria in research and practice are as follows: to use the DLQI for adults and the CDLQI for children as dermatology-specific and the CU-Q2oL as a disease-specific HRQoL instruments in urticaria; to use generic instruments to provide comparison of data on urticaria with non-dermatologic diseases, or to compare with healthy volunteers or the general population; to select validated HRQoL instruments with appropriate age limits; to present exact numeric data for HRQoL results; correct title of any HRQoL instrument should be used, along with its correct abbreviation and the reference to its original publication, where possible. The EADV TFs discourage the use of non-validated HRQoL instruments and modified HRQoL instruments that have not undergone standard validation.

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.

Orismilast for the treatment of mild to severe hidradenitis suppurativa: Week 16 data from OSIRIS, a Phase 2a, open-label, single-centre, single-arm, dose-finding clinical trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a disease with an unmet need for treatment. OBJECTIVE: To examine tolerability, safety and efficacy of oral phosphodiesterase-4 (PDE4) inhibitior orismilast 10-40 mg twice daily (BID) in HS. METHODS: A Phase 2a, single-arm, single-centre, open-label, 16-week trial in HS patients. Adjustments in maximal dose and titration were allowed, to improve tolerability, dividing the study population in two groups who completed and discontinued 16 weeks of treatment. Descriptive statistics were applied to efficacy data from patients who completed treatment and patients who discontinued treatment prematurely. A last-observation-carried-forward (LOCF) approach was used for patients who discontinued treatment. The primary endpoint was percent change in the total number of abscesses and nodules (AN-count) at Week 16, with the HS Clinical Response with a 50% reduction in the AN-count (HiSCR50) as key secondary endpoint. RESULTS: Of the 20 patients included, 9 completed 16 weeks of treatment and 11 discontinued treatment prematurely. The mean AN-count was reduced with 33.1% in patients who completed treatment and with 12.0% in patients who discontinued. HiSCR50 was achieved by 67.0% and 27.0% of patients who completed and discontinued treatment, respectively. Most adverse events were mild to moderate. CONCLUSIONS: Oral orismilast demonstrated a dose-dependent tolerability, with mild to moderate adverse effects. Further, the results of this exploratory trial indicate that orismilast may lead to clinical improvements in HS. However, larger trials with tolerable dose ranges are warranted. The Trial is registered at Clinicaltrials.gov (UNI50007201) and EudraCT.ema.europa.eu (2021-000049-42).

The differentiating effect of COVID-19-associated stress on the morbidity of blood donors with symptoms of hidradenitis suppurativa, hyperhidrosis, or psoriasis.

PURPOSE: The burden of different skin diseases may vary leading individuals to have different sensitivity to stress. Therefore, we compared the health-related quality of life (HRQoL) and stress before and during the universal stress from the severe acute respiratory syndrome coronavirus-2-pandemic in individuals with and without hyperhidrosis, hidradenitis suppurativa, or psoriasis. METHODS: The study cohort was the Danish Blood Donor Study. Overall, 12,798 participants completed a baseline questionnaire before the pandemic, in 2018-2019, and a follow-up questionnaire during the pandemic, in 2020. Regression determined the association between the skin diseases and outcomes. Outcomes were the physical and mental component summary (MCS, PCS, respectively), which assess the mental and physical HRQoL, and the perceived stress scale, which assesses stress in the past four weeks. RESULTS: Overall, 1168 (9.1%) participants had hyperhidrosis, 363 (2.8%) had hidradenitis suppurativa, and 402 (3.1%) had psoriasis. At follow-up, the participants with hyperhidrosis had worse MCS (coefficient -0.59 [95% confidence interval (CI) -1.05, -0.13]) and higher odds of moderate-to-severe stress (odds ratio 1.37 [95% CI 1.13, 1.65]) and the participants with hidradenitis suppurativa worse PCS (coefficient -0.74 [95% CI -1.21, -0.27]) than the control groups. The associations were independent of baseline HRQoL, stress, the Connor-Davidson Resilience scale, and other covariables. Psoriasis was not associated with the outcomes. CONCLUSION: Individuals with hyperhidrosis or hidradenitis suppurativa experienced worse mental or physical well-being and individuals with hyperhidrosis also had higher stress during the pandemic compared to healthy individuals. This suggests that individuals with these skin diseases are particularly susceptible to external stress.

Hidradenitis suppurativa in Black and White patients - a clinical study.

OBJECTIVE: It is suggested that hidradenitis suppurativa (HS) is more prevalent and causes greater morbidity in Black patients than in White. Clinical data are however lacking. PATIENTS AND METHODS: We therefore describe HS risk factors, disease severity and clinical phenotypes in the Blacks and Whites. Patients referred for HS between 1984 and 2019 at the Johns Hopkins Hospital were identified using the Pathology Data System (PDS). Clinical and sociodemographic characteristics were extracted and the van der Zee & Jemec HS clinical phenotypes were recovered. RESULTS: A total of 278 patients were identified. Ethnically, 108 (38.8%) were White, and 170 (61.2%) Black. The following HS phenotypes were found: Regular (n=193, 69.4%), scarring folliculitis (n=40, 1.4%) frictional furuncle (11.2%), conglobata (n=9, 3.2%), syndromic (n=3, 1.1%) and ectopic (n=2, 0.7%). No statistically significant ethnic differences in clinical presentation were found. Blacks however had more severe diseases than Whites (p= 0.024 for trend). With multivariate logistic regression analysis, we found that male sex, disease duration, and smoking were independent predictors of regular HS phenotype. Major limitations are the limited number of cases studied and the lack of data regarding response to therapies. CONCLUSIONS: Demographics and phenotypical presentation of HS patients do not seem to be associated with Black ethnicity. However, there is a significant trend for Blacks to present with more Hurley stage 2 and 3 disease compared to White patients. It is speculated that ethnic differences are epiphenomena to social factors, highlighting the broader importance of ethnicity.

Optical coherence tomography for presurgical delineation of basal cell carcinomas on the face-A comparison with histopathology.

BACKGROUND: To minimize the risk of incomplete excision of basal cell carcinomas (BCC) the macroscopic tumor margins should be adequately defined. Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide structural and vascular information about skin cancer lesions. The study objective was to compare the presurgical delineation of facial BCC by clinical examination, histopathology, and OCT imaging in tumors undergoing full excision. METHODS: Ten patients with BCC lesions on the face were examined clinically, with OCT and histopathology at 3-mm intervals, from the clinical lesion border and beyond the resection line. The OCT scans were evaluated blinded and a delineation estimate of each BCC lesion was made. The results were compared to the clinical and histopathologic results. RESULTS: OCT evaluations and histopathology were in agreement in 86.6% of the collected data points. In three cases the OCT scans estimated a reduction of the tumor size compared to the clinical tumor border set by the surgeon. CONCLUSION: The results of this study support the notion that OCT can have a role in the clinical daily practice by aiding clinicians in delineating BCC lesions before surgery.

Human leukocyte antigen system associations in Malassezia-related skin diseases.

BACKGROUND: The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD. MATERIALS AND METHODS: Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests. RESULTS: A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94). CONCLUSION: Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles.

Methylated miRNAs may serve as potential biomarkers and therapeutic targets for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non-genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility. OBJECTIVES: Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs. RESULTS: We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR-29, miR-200, miR-205, miR-548 and miR-132. The miR-192 is implicated in non-alcoholic fatty liver disease. The miR-200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age-associated alterations in wound repair. miR-132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation. CONCLUSIONS: Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.

The temporal association of hyperhidrosis and its comorbidities - a nationwide hospital-based cohort study.

BACKGROUND: Research on hyperhidrosis comorbidities has documented the co-occurrence of diseases but has not provided information about temporal disease associations. OBJECTIVE: To investigate the temporal disease trajectories of individuals with hospital-diagnosed hyperhidrosis. METHODS: This is a hospital-based nationwide cohort study including all patients with a hospital contact in Denmark between 1994 and 2018. International Classification of Diseases version-10 diagnoses assigned to inpatients, outpatients and emergency department patients were collected from the Danish National Patient Register. The main outcome was the temporal disease associations occurring in individuals with hyperhidrosis, which was assessed by identifying morbidities significantly associated with hyperhidrosis and then examining whether there was a significant order of these diagnoses using binomial tests. RESULTS: Overall, 7 191 519 patients were included. Of these, 8758 (0.12%) patients had localized hyperhidrosis (5674 female sex [64.8%]; median age at first diagnosis 26.9 [interquartile range 21.3-36.1]) and 1102 (0.015%) generalized hyperhidrosis (606 female sex [59.9%]; median age at first diagnosis 40.9 [interquartile range 26.4-60.7]). The disease trajectories comprised pain complaints, stress, epilepsy, respiratory and psychiatric diseases. The most diagnosed morbidities for localized hyperhidrosis were abdominal pain (relative risk [RR] = 121.75; 95% Confidence Interval [CI] 121.14-122.35; P < 0.001), soft tissue disorders (RR = 151.19; 95% CI 149.58-152.80; P < 0.001) and dorsalgia (RR = 160.15; 95% CI 158.92-161.38; P < 0.001). The most diagnosed morbidities for generalized hyperhidrosis were dorsalgia (RR = 306.59; 95% CI 302.17-311.02; P < 0.001), angina pectoris (RR = 411.69; 95% CI 402.23-421.16; P < 0.001) and depression (RR = 207.92; 95% CI 202.21-213.62; P < 0.001). All these morbidities were diagnosed before hyperhidrosis. CONCLUSIONS: This paper ascertains which hospital-diagnosed morbidities precede hospital-diagnosed hyperhidrosis. As hyperhidrosis mainly is treated in the primary health care sector, the trajectories suggests that these morbidities may lead to a worse disease course of hyperhidrosis that necessitates treatment in hospitals. Treating these morbidities may improve the disease course of hyperhidrosis.

Incidence and remission rates of self-reported hidradenitis suppurativa - A prospective cohort study conducted in Danish blood donors.

BACKGROUND: A large discrepancy between physician-diagnosed and self-reported Hidradenitis suppurativa (HS) exists. Knowledge regarding incidence and remission rates of self-reported HS is missing, but may help bridge the gap in understanding between these two phenotypes. OBJECTIVES: To determine the incidence and remission rates of self-reported HS, and to what degree these are affected by sex, smoking and BMI. METHODS: A prospective cohort of 23 930 Danish blood donors. Information on self-reported HS, symptom-localisation, sex, age, BMI and smoking status was collected at baseline and study termination. Self-reported HS fulfilled clinical obligatory diagnostic criteria. Cox proportional hazards regression analyses were conducted for both incidence and remission rates providing a hazard ratio (HR) of risk for each variable in the regression. RESULTS: Incidence rate of self-reported HS was 10.8/1000 person-years (95% confidence interval (CI): 9.9-11.7), decreasing as a function of numbers of areas affected. Female BMI points above 25 (HR = 1.11, 95% CI: 1.09-1.13), male BMI points above 25 (HR = 1.07, 95% CI: 1.04-1.11), active smoking (HR = 1.72, 95% CI: 1.15-2.57), male sex (HR = 0.55, 95% CI: 0.45-0.67) and years of age above 25 (HR = 0.97, 95% CI: 0.96-0.97) were all statistically associated with the development of self-reported HS. Remission rate of self-reported HS was 256.7/1000 person-years (95% CI: 223.9-292.6), decreasing as a function of numbers of affected areas. Symptoms in ≥3 areas (HR = 0.54, 95% CI: 0.34-0.85), active smoking (HR = 0.49, 95% CI: 0.32-0.76) and female weight loss (every percentage drop in BMI: HR = 1.07, 95% CI: 1.05-1.11) all significantly affected the remission rate. CONCLUSIONS: Both incidence and remission rates of self-reported HS are high, indicating that many with self-reported HS are unlikely to be diagnosed, as they to a higher degree experience mild transient HS symptoms.

Evidence of gene-gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins.

BACKGROUND: Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology. OBJECTIVES: To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS. METHODS: Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)-8 (705·91) and ICD-10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene-gene interaction via the multilocus modelling approach. RESULTS: Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case-wise concordance rate of 28% [95% confidence interval (CI) 7-49], corresponding to a familial risk of 73 (95% CI 13-133) times that of the background population. The biometrical modelling suggested a heritability of 0·80 (95% CI 0·67-0·93), and the multilocus index estimate was 230 (95% CI 60-400). This is highly indicative of gene-gene interactions, with the possibility of up to six interacting loci. CONCLUSIONS: This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of HS susceptibility, and HS is most likely caused by gene-gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a single-nucleotide polymorphism (SNP)-SNP level should be implemented in future HS genome-wide association studies.

Electrochemotherapy with bleomycin for basal cell carcinomas: a systematic review.

Basal cell carcinoma (BCC) is the most common type of cancer and an increasing incidence stimulates the interest in new treatments such as electrochemotherapy (ECT) with bleomycin. This systematic review focuses on literature from the MEDLINE, Embase, Web of Science, and Cochrane databases. Bleomycin-ECT studies (n = 32) were sorted by the level of evidence adjusted for their BCC data only. The studies included a single randomised controlled trial (RCT), 15 uncontrolled clinical trials, three registry studies, six prospective case series and seven retrospective case series. A Cochrane risk-of-bias assessment of the RCT identified some minor concerns but no predicted risk of bias. The studies were also grouped by bleomycin administration routes: intravenous (n = 14), intralesional (n = 9) and mixed reporting/usage (n = 9). A meta-analysis was not conducted due to the lack of RCTs and the heterogeneity of the included studies. The results of the RCT generally reflected the findings of the other included studies and showed a 92% complete response in 65 bleomycin-ECT-treated BCCs after 2 months, improving to 100% after re-treatment, with a low risk of recurrence. Based on the RCT results and overall data, future studies on BCC treatment with bleomycin-ECT should include large RCTs that compare bleomycin-ECT with standard of care, cost analyses, and clinical feasibility.

Tinea capitis asymptomatic carriers: what is the evidence behind treatment?

Tinea capitis is a fungal infection mostly affecting children. Epidemiology is changing over time due to migration, and it has been estimated that up to 40% of children from certain developing countries are affected. The mechanism of transmission is still unclear although asymptomatic carriage seems to have an influence in establishing persistent reservoirs that can cause or fuel epidemics. Screening and prophylactic treatment of close contacts of tinea capitis patients are therefore recommended by several international guidelines, but vaguely and not consistent. The treatments involved can be expensive, hard to integrate in everyday life, have well-known side effects and some are not approved for the treatment of children. The aim of this review was to clarify the evidence behind treatment of human asymptomatic carriers of tinea capitis. Databases were searched for the 'tinea capitis', 'carriers' and 'treatment'. Inclusion criteria were clinical trials, observational and interventional studies including case series (10+ cases) and case reports in English, Danish, Swedish, Norwegian and French. Reviews, guidelines, unclear reports and in vitro trials were excluded. A systematic review identified 10 studies with low to moderate evidence levels. The topical treatments ketoconazole, povidone-iodine, miconazole and the systemic antifungals terbinafine and itraconazole have all shown significant effects in the mycological eradication of fungal conidia. General prophylactic hygienic measures may have a benefit. The scientific evidence behind the treatment of asymptomatic carriage of scalp dermatophytes is sparse and not of high quality. Yet, both topical and systemic antifungal agents show treatment efficacy. Considering the possible adverse effects, topical agents are preferable, but with necessary attention to the compliance of asymptomatic contacts with treatment.

Quality of life measurement in alopecia areata. Position statement of the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes.

New treatment options may lead to an increased interest in using reliable and sensitive instruments to assess health-related quality of life in people with alopecia areata (AA). The purpose of this paper is to present current knowledge about quality of life assessment in AA. The dermatology-specific Dermatology Life Quality Index (DLQI) was the most widely reported health-related quality of life instrument used in AA. Three AA-specific (Alopecia Areata Symptom Impact Scale, Alopecia Areata Quality of Life Index and Alopecia Areata Patients' Quality of Life) and three hair disease-specific instruments (Hairdex, Scalpdex and 'hair-specific Skindex-29') were identified with a range of content and validation characteristics: there is little evidence yet of the actual use of these measures in AA. Scalpdex is the best-validated hair disease-specific instrument. Further extensive validation is needed for all of the AA-specific instruments. The European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes recommends the use of the dermatology-specific DLQI questionnaire, hair disease-specific Scalpdex and the alopecia areata-specific instruments the Alopecia Areata Symptom Impact Scale or Alopecia Areata Quality of Life Index, despite the limited experience of their use. We hope that new treatment methods will be able to improve both clinical signs and health-related quality of life in patients with AA. In order to assess the outcomes of trials on these new treatment methods, it would be helpful when further development and validation of AA-specific instruments is being encouraged and also conducted.

Convergent Validity of Suffering and Quality of Life as Measured by The Hidradenitis Suppurativa Quality of Life.

BACKGROUND: Hidradenitis suppurativa (HS) is a painful chronic, recurrent inflammatory skin disease with great impact on health-related quality of life (HRQOL). Recently, Hidradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) established HRQOL as a core domain set for HS clinical trials and developed the Hidradenitis Suppurativa Quality of Life (HiSQOL) as a validated outcome measurement instrument. OBJECTIVES: To provide further convergent validity of HiSQOL by comparing it to Dermatology Life Quality Index (DLQI) and Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2). METHODS: In this cross-sectional study, 103 participants completed HiSQOL, PRISM-R2 and DLQI. PRISM-R2 is an instrument designed to measure suffering and reports the two measures, Illness Perception Measure (IPM) and Self-Illness Separation (SIS). Correlation analyses were performed including a sub-analysis for a subgroup of patients with high scores in the HS-specific domains of HiSQOL. RESULTS: A very strong correlation was found between HiSQOL and DLQI (ρ = 0.93, P < 2.2 × 10-16 , (95% CI: 0.89;0.95)), and moderately strong correlations were found between HiSQOL and SIS (ρ = -0.73, P < 2.2 × 10-16 , (95% CI: -0.81; -0.62)) and DLQI and SIS (ρ = -0.70, P < 2.2 × 10-16 , (95% CI: -0.79; -0.59)). IPM was positively associated with HiSQOL and DLQI and negatively with SIS. CONCLUSIONS: HiSQOL is a valid measure of quality of life for HS patients, and we suggest that HiSQOL can be used as a measure of suffering as well.