"Quality of Life in Epidermolysis Bullosa" and "Epidermolysis Bullosa Burden of Disease": Italian translation, cultural adaptation, and pilot testing of two disease-specific questionnaires.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of skin fragility disorders characterized by blister formation following minor trauma. Four major types are distinguished based on the level of cleavage within the skin. Most EB forms present severely disabling cutaneous and systemic signs and symptoms. Management relies on daily time-consuming and distressing topical medications, and symptomatic treatment of systemic findings. Disease manifestations, symptoms, and daily care strongly affect patient and caregiver quality of life (QoL). To date, there are two validated EB-specific questionnaires, the "Quality of Life in Epidermolysis Bullosa" (QOLEB) and the "Epidermolysis Bullosa Burden of Disease" (EB-BoD) for the evaluation of patient and family disease burden, respectively. The aim of our study was to develop an Italian translation of the two questionnaires and to pilot-test them. METHODS: The guidelines for translation and cross-cultural adaptation of health-related QoL measures were followed. Initially, two separate translations were generated for each questionnaire, and subsequently reconciled by an expert committee. This was followed by a back-translation process. The original texts and all translations underwent revision by the expert committee, resulting in definitive versions. The final versions were then tested in a pilot study involving cognitive debriefing in a group of 17 families, representative of all EB major types. RESULTS: The translation and reconciliation process led to minor changes to obtain semantic/idiomatic/cultural equivalence of the Italian versions with the original ones and to reconcile the questions with the answer options. The cognitive debriefing process showed a good understanding and did not require text modifications. CONCLUSIONS: The Italian versions of the QOLEB and EB-BoD provide valuable tools in everyday clinical practice of reference centers, and they allow the participation in multicenter international real-life observational studies as well as in controlled clinical trials. They enable the identification of disease-specific psychological and socioeconomic challenges for EB patients and their families, guiding targeted interventions to ensure appropriate and timely care.

Gender equity in academic dermatology: Problems aplenty, yet paths ahead.

Efforts to achieve gender equity of health professionals should be a priority in all fields of medicine, including academic dermatology. This review aimed, first, to summarize available evidence about the status of gender equity in various domains of academic dermatology-headship positions, salary, editor and editorial board appointments, publications, conference presentations, receipt of research grants and academic prizes-second, to identify challenges to achieving gender equity and, third, to articulate the components of a multifaceted strategy for gender parity. A variety of databases were searched. Manual searching of reference lists and searching of grey literature were also undertaken. It was found that, despite improvements in some domains, the gender inequity persists in all of the above-mentioned areas of academic dermatology. Challenges to achieve gender parity include time in pregnancy, disproportionate participation in childrearing and domestic tasks compared with men, suboptimal legislation in many jurisdictions for parenting and childcare leave, and unconscious biases about women. Elements of a multipronged approach include strengthening women's dermatology societies that advocate for women in academia; celebrating the careers of distinguished female academic dermatologists; mentoring; promoting leadership courses; striving for a greater representation of women among editors-in-chief, authors, and conference presenters, among others; seeking better pay, leave conditions and other work entitlements; conducting high-quality research about gender inequity in academic dermatology; imposing sanctions for violations of gender equity; supporting dermatologists' health; and learning from the experience of other fields of academic medicine.

Keratosis Pilaris Treatment Paradigms: Assessing Effectiveness Across Modalities.

This review aims to present a comprehensive synthesis of the existing treatment modalities for keratosis pilaris (KP) and evaluate their therapeutic efficacy. Keratosis pilaris (KP) is a prevalent chronic dermatological condition typified by its unique 'chicken skin appearance', with the cheeks being the most commonly involved sites. Numerous therapeutic interventions have emerged, given its substantial prevalence and impact on skin aesthetics and psychological well-being. Nonetheless, a consistent therapeutic response has been challenging to achieve. This review endeavors to collate and critically appraise the current treatment landscape for KP. An exhaustive literature search was performed using databases such as Ovid, PubMed and Scopus. From an initial count of 459 articles identified post-deduplication, 52 were selected for inclusion after a thorough full-text examination for articles with concrete outcome data highlighting the efficacies of different therapeutic modalities while excluding articles that lacked data or were tangential to the core focus on KP treatment. These articles were then cataloged based on the nature of treatment strategies and their respective outcomes. Among the various therapeutic interventions, laser and light modalities appear to be supported by the most substantial evidence base. Notably, the Nd: YAG laser, attributed to its longer wavelength, emerges as a preferred option. While other therapeutic avenues have also exhibited notable improvements in skin texture and discoloration relative to baseline, the inconsistency in outcome measures underscores the imperative need for a standardized, KP-specific scoring system to foster a more coherent comparison across treatments. Based on the current evidence, Nd: YAG laser therapy demonstrates promising effectiveness with a relatively favorable side effect profile. However, the landscape of KP treatment is multifaceted, and further studies are essential to solidify recommendations.

Efficacy and Safety of Rilzabrutinib in Pemphigus: PEGASUS Phase 3 Randomized Study.

TRIAL DESIGN: Pemphigus is a rare, but life-threatening autoimmune disease requiring long-term treatment that minimizes corticosteroid (CS) exposure while providing consistent disease control. The phase 2 pemphigus study of oral, reversible, covalent Bruton tyrosine kinase (BTK) inhibitor rilzabrutinib demonstrated rapid and sustained efficacy with well-tolerated safety. METHODS: Adults (18-80 y) were randomized 1:1 to rilzabrutinib 400 mg (n=65) or placebo (n=66) twice daily (with CS ≤0.5 mg/kg/d) for 37 weeks in the phase 3 PEGASUS study in moderate-to-severe pemphigus vulgaris/foliaceus (PV/PF). RESULTS: The primary endpoint of complete remission (CR) from week 29-37 with the amended endpoint CS dose ≤10 mg/d was not significant for 13/54 (24%) rilzabrutinib vs. 10/55 (18%) placebo patients with PV (P=0.45). Secondary endpoints showed numerical, but non-significant, improvements with rilzabrutinib (vs. placebo) in reduced CS use, prolonged CR duration, and faster time to first CR. CONCLUSIONS: Overall, rilzabrutinib was well-tolerated with similar adverse events reported in both groups. Using minimal CS dose ≤10 mg/d and excluding remote observations, the primary efficacy endpoint was not met. However, results from a prespecified sensitivity analysis using CS dose ≤5 mg/d, considering all observations, and including all patients support BTK inhibition as a viable therapeutic approach for pemphigus.

Study Design of a Phase 2/3 Randomized Controlled Trial of Dupilumab in Adults with Bullous Pemphigoid: LIBERTY-BP ADEPT.

BACKGROUND: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial. OBJECTIVES: We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP. METHODS: LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18-90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS). PLANNED OUTCOMES: The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36. CONCLUSION: The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04206553.

Translation, cultural adaptation and validation of the German Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire.

Epidermolysis bullosa (EB) is a rare disease characterised by skin fragility and a wide variety of symptoms. The Quality of Life in Epidermolysis Bullosa (QOLEB) score is an English 17-item EB-specific validated measurement tool with two dimensions: functioning and emotions. The aim of this cross-sectional study was to develop and validate a culturally adapted German QOLEB. The following steps were carried out: translation, expert evaluation, back translation, linguistic and cultural adaptation, sample-based psychometric testing and evaluation. Data analysis was performed with n = 46 patients across all EB types. The reliability and internal consistency of the translated German QOLEB were excellent (α = 0.901). Regarding convergent validity, the QOLEB correlated highly with the iscorEB (r = 0.879; p < 0.001). Structural similarity with the English original version was confirmed through exploratory factor analysis. In conclusion, the German QOLEB demonstrates internal reliability and construct validity and is suitable to assess the quality of life in German-speaking EB patients.

S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

Precision in treatment evaluation: importance of minimal clinically important differences (MCIDs) of outcome measures for autoimmune blistering diseases.

Autoimmune blistering diseases (AIBDs) comprise a group of rare conditions marked by autoantibodies that specifically target intercellular adhesion molecules. Despite the progress made in comprehending the disease and the increasing number of treatment options available, there is still no definitive cure for AIBDs such as pemphigus, and it continues to have a devastating impact on those affected. The challenges in achieving new approved therapies for AIBDs are complex and multifaceted. One significant obstacle was the prior lack of validated and standardized outcome measures, which are crucial for ensuring precise comparisons between new and traditional therapies. This gap in knowledge has prompted the development of minimal clinically important differences (MCIDs), which enable efficient and reliable comparison of therapeutic outcomes between trials. MCID is defined as the minimum difference in an outcome measure that indicates a clinically significant improvement/deterioration in disease severity. Additionally, MCIDs provide a patient-centered approach to evaluating treatment efficacy, by considering whether patients experience a subjective improvement in their symptoms. Therefore, this literature review will examine the derivation and significance of MCIDs for various scoring systems in AIBDs.

A Review of the Scoring and Assessment of Keratosis Pilaris.

Disease severity assessment tools play a large part in evaluating skin conditions in dermatology. Currently, there is no existing validated assessment tool for keratosis pilaris (KP), a benign yet highly prevalent follicular disorder. A range of proposed scoring tools have been used in different clinical trials for the assessment of potential treatments for KP. A literature review of the current scoring systems used for KP shows that there is a lack of consistency with most studies using varying versions of unvalidated investigator global assessment (IGA) scores and quartile grading systems. A review of these studies shows that current methods of evaluating KP in clinical trials are subjective, unreliable, and inconsistent. A standardised and validated scoring system would be significant as it could be used in clinical trials to advance the current knowledge of KP.

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH METHODS: We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality. MAIN RESULTS: We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group. AUTHORS' CONCLUSIONS: Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.

Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study.

BACKGROUND: Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. OBJECTIVES: To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. METHODS: In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. RESULTS: Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. CONCLUSIONS: The results support the further development of roflumilast foam for treating scalp and body psoriasis.