Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

Objectives: This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. Methods: A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. Results: The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. Conclusion: The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years. METHODS: In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed. RESULTS: In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported. CONCLUSION: Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.

Algorithm to attenuate atopic dermatitis and for promoting a healthy skin barrier using skincare in newborns and infants.

The human skin barrier is structurally and functionally immature at birth, with elevated skin surface pH, lower lipid content, and lower resistance to chemicals and pathogens. Infants at risk for atopic dermatitis (AD) may present with xerosis almost immediately after birth. The current algorithm on skincare for newborns and infants aims to promote a healthy skin barrier and potential mitigation of AD. The project used a modified Delphi hybrid process comprising face-to-face discussions followed by an online follow-up replacing a questionnaire. During the meeting, a panel of eight clinicians who treat newborns and infants discussed the systematic literature review results and a draft algorithm addressing non-prescription skincare for neonates and infants. Online the panel reviewed and adopted the algorithm using evidence coupled with the panel's expert opinion and clinical experience. The algorithm provides clinical information for pediatric dermatologists, dermatologists, and pediatric healthcare providers treating neonates and infants. The advisors adopted a scale based on clinical signs for the algorithm: 1) scaling/xerosis; 2) erythema; and 3) erosion/oozing. Skincare for newborns and infants includes: aim for a cool environment and soft cotton clothing, give lukewarm baths (~5 min, 2-3 x week) with consideration of a gentle cleanser (pH 4-6) and the application of a full-body moisturizing after bath, while avoiding products with toxic and irritating ingredients. A growing body of evidence recognizes the benefits of ongoing daily use of non-alkaline cleansers and moisturizers. Gentle cleansers and moisturizers containing barrier lipids help maintain the protective skin barrier when applied from birth onwards.

Observational study of pimecrolimus 1% cream for prevention of transcutaneous sensitization in children with atopic dermatitis during their first year of life.

Introduction: Epidermal barrier dysfunction in children with atopic dermatitis can cause transcutaneous sensitization to allergens and allergic diseases. We evaluated the effectiveness of an early-intervention algorithm for atopic dermatitis treatment, utilizing pimecrolimus for long-term maintenance therapy, in reducing transcutaneous sensitization in infants. Method: This was a single-center cohort observational study that enrolled children aged 1-4 months with family history of allergic diseases, moderate-to-severe atopic dermatitis, and sensitization to ≥ 1 of the investigated allergens. Patients who sought medical attention at atopic dermatitis onset (within 10 days) were group 1 "baseline therapy with topical glucocorticoids with subsequent transition to pimecrolimus as maintenance therapy"; patients who sought medical attention later were group 2 "baseline and maintenance therapy with topical glucocorticoids, without subsequent use of pimecrolimus". Sensitization class and level of allergen-specific immunoglobulin E were determined at baseline, and 6 and 12 months of age. Atopic dermatitis severity was evaluated using the Eczema Area and Severity Index score at baseline and 6, 9 and 12 months of age. Results: Fifty-six and 52 patients were enrolled in groups 1 and 2, respectively. Compared with group 2, group 1 demonstrated a lower level of sensitization to cow's milk protein, egg white and house dust mite allergen at 6 and 12 months of age, and a more pronounced decrease in atopic dermatitis severity at 6, 9 and 12 months of age. No adverse events occurred. Discussion: The pimecrolimus-containing algorithm was effective in treating atopic dermatitis and prophylaxis of early forms of allergic diseases in infants. Trial registration: https://clinicaltrials.gov/ NCT04900948, retrospectively registered, 25 May 2021.

Our experience of using Losartan for esophageal stenosis in children with dystrophic form of congenital epidermolysis bullosa.

INTRODUCTION: Dystrophic epidermolysis bullosa (DEB) is one of the most severe forms of congenital epidermolysis bullosa and characterized by the formation of many surgical complications. Esophageal stenosis is a common complication of DEB and occurs in almost 76% of cases. Balloon dilatation (BD) under X-ray control is the main therapeutic technique, however conservative treatment is necessary to prevent restenosis. The use of the drug losartan is promising due to its antifibrotic effect through the suppression of transforming growth factor-ß1 (TGF-ß1). PURPOSE: To evaluate the efficacy of losartan in the prevention of restenosis after BD of esophageal stenosis in children with DEB. MATERIALS AND METHODS: The study included 19 children from 2 to 16 years old (mean age 9.2 ± 3.58 years) with DEB and X-ray confirmed esophageal stenosis. All children underwent BD. In the main group 9 children after BD have received losartan, in the control group of 10 children - only standard therapy. The observation period was 12 months. RESULTS: In the main group, 1 child (11.1%) required repeated dilatation, in the control group - 4 children (40%). Indicators of nutritional deficiency (THINC scale) and the disease severity index (EBDASI) were significantly lower in the group of children treated with losartan. No undesirable actions of the drug were recorded. CONCLUSIONS: In this study losartan showed its safety, contributed to a decrease in the restenosis frequency and an improvement in the nutritional status of children with DEB after BD. However, further studies are required to confirm its effectiveness. LEVEL OF EVIDENCE: IV.

Pimecrolimus 1% cream for mild-to-moderate atopic dermatitis: a systematic review and meta-analysis with a focus on children and sensitive skin areas.

This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate atopic dermatitis (AD), focusing on children and sensitive skin areas. An SLR was conducted in MEDLINE, Embase and Cochrane Library databases on January 15th, 2020, to identify randomized controlled trials (RCTs) with pimecrolimus as a study arm. Another SLR performed on October 5th, 2020 identified RCTs with a crisaborole study arm. Direct pair-wise meta-analysis was used to compare pimecrolimus with vehicle, tacrolimus or topical corticosteroids (TCS; n = 27 studies). Outcomes included Investigator's Global Assessment (IGA) score 0/1 up to week 6 and adverse events. Pimecrolimus was more efficacious than vehicle in achieving IGA 0/1 up to week 6 in children, and similar safety profiles were observed with pimecrolimus and vehicle in children and the mixed population, including on sensitive skin. No significant differences in efficacy and safety were observed between pimecrolimus and tacrolimus 0.03%. Efficacy and safety were similar for pimecrolimus and mild medium potency TCS; mildly potent steroids caused transient epidermal thinning in sensitive skin areas (not seen with pimecrolimus). Pimecrolimus can be considered as a first-line option for mild-to-moderate AD, particularly in children and sensitive skin areas.

Targeted NGS in Diagnostics of Genodermatosis Characterized by the Epidermolysis Bullosa Symptom Complex in 268 Russian Children.

The pathogenic variants of genes encoding proteins, participating in the formation and functioning of epidermis and dermo-epidermal junctions, create a large variety of clinical phenotypes from: small localized to severe generalized dermatitis, as well as early, or even, prenatal death due to extensive epidermis loss. The diagnostic panel in this study was developed for the purposes of identifying these pathogenic genetic variants in 268 Russian children, who possessed the epidermolysis bullosa symptom complex in a selection of 247 families. This panel included the targeted areas of 33 genes, which are genetic variants that can lead to the development of the phenotype mentioned above. The usage of next generation sequencing allowed the revelation of 192 various altered alleles (of which 109 alleles were novel, i.e., had not been described previously). In addition, it allowed the definition of the genetic variants that are both typical for most of the examined children and for the separate ethnic groups inhabiting modern Russia. We found that the most characteristic mutations for the Dargin and Chechen ethnic groups are the c.3577del deletion in the COL7A1 gene and the c.2488G>A missense mutation in the COL17A1 gene, respectively. In addition, the study of haplotypes of microsatellite markers, which we managed to conduct in the Dargin population, confirmed the presence of the founder effect.

Expert consensus on ceramides containing skincare in newborns and infants and potential mitigation of atopic dermatitis.

INTRODUCTION: The vulnerable skin of neonates and infants is still developing anatomically and functionally and more susceptible to skin barrier disruption. The current consensus paper explores challenges in caring for neonates and infants' skin, skincare use and evaluates the role of ceramides (CERs) containing cleansers and moisturizers. EVIDENCE AQUISITION: A panel of eight clinicians who treat neonates and infants developed a consensus paper on new-born and infant skin barrier integrity and CERs-containing skincare importance. The consensus process consisted of a modified Delphi technique. The selected information from the literature searches, coupled with the panel's opinion and experience, was used to adopt statements to provide clinical data for pediatric dermatologists, dermatologists, and pediatric healthcare providers who treat neonates and infants. EVIDENCE SYNTHESIS: Increasingly, evidence supports skincare starting early in life, recognizing the benefits of ongoing daily use of non-alkaline cleansers and moisturizers to maintain skin barrier function. Skincare for neonates and infants should be safe, effective, and fragrance as well as sensitizing agent-free. Skincare with CERs may benefit the stratum corneum's lipid and water content. CONCLUSIONS: When applied from birth onwards, gentle cleansers and moisturizers containing barrier lipids help maintain the protective skin barrier and soothe the skin with long-term moisturizing benefits.

Practical algorithm to inform clinical decision-making in the topical treatment of atopic dermatitis.

Atopic dermatitis is a chronic relapsing, inflammatory skin disorder associated with skin barrier dysfunction, the prevalence of which has increased dramatically in developing countries. In this article, we propose a treatment algorithm for patients with mild-to-moderate and severe atopic dermatitis flares in daily clinical practice. An international panel of 15 dermatology and allergy experts from eight countries was formed to develop a practical algorithm for the treatment of patients with atopic dermatitis, with a particular focus on topical therapies. In cases of mild-to-moderate atopic dermatitis involving sensitive skin areas, the topical calcineurin inhibitor pimecrolimus should be applied twice daily at the first signs of atopic dermatitis. For other body locations, patients should apply a topical calcineurin inhibitor, either pimecrolimus or tacrolimus, twice daily at the first signs of atopic dermatitis, such as pruritus, or twice weekly in previously affected skin areas. Emollients should be used regularly. Patients experiencing acute atopic dermatitis flares in sensitive skin areas should apply a topical corticosteroid twice daily or alternate once-daily topical corticosteroid/topical calcineurin inhibitor until symptoms improve. Following improvement, topical corticosteroid therapy should be discontinued and patients switched to a topical calcineurin inhibitor. Maintenance therapy should include the use of pimecrolimus once daily for sensitive areas and tacrolimus for other body locations. This treatment algorithm can help guide clinical decision-making in the treatment of atopic dermatitis.

Signatures of Dermal Fibroblasts from RDEB Pediatric Patients.

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.

Epidemiology of fragile skin: Internet-based surveys in Mexico and Russia.

BACKGROUND: Fragile skin is a poorly understood skin condition, particularly in the general adult population. There are currently limited epidemiological data on the prevalence of fragile skin in adults. The objectives of this study were to assess the prevalence of perceived fragile skin across different skin types in representative samples of the general adult populations in Mexico and Russia, and to identify skin characteristics associated with perceived fragile skin. METHODS: Two identical cross-sectional surveys, using a short online self-administered questionnaire, were conducted on samples of recruited individuals that were representative of the general Mexican and Russian populations. Participants responded to questions about fragile skin, with the main question being "In your opinion, do you have fragile skin (ie, skin less resistant and reacting quickly to external aggressions)?". The survey also covered questions relating to skin appearance, skin symptoms, skin disease, dermatological procedures, and living environment and climate. RESULTS: Overall, 1,210 individuals in Mexico (N=606) and Russia (N=604) completed the online survey. Fragile skin was perceived in 50.0% and 45.9% of participants in Mexico and Russia, respectively. The principal skin appearance characteristics reported by individuals with perceived fragile skin were thin, easily wrinkled, and transparent; the main skin symptoms were dryness, redness, and/or itching (≥50% of individuals in Mexico), and dryness, tightness, and/or redness (>60% of individuals in Russia). Individuals with perceived fragile skin had experienced skin disease and/or undergone a dermatological procedure in the past 12 months, and they reported being exposed to stress (>80% of individuals in both surveys). CONCLUSION: A substantial proportion of the general adult population of Mexico and Russia perceived that they had fragile skin, regardless of their skin type; fragile skin was perceived more frequently in women. These findings should assist dermatologists to extend their understanding and management of individuals with perceived fragile skin.