Topical Calcineurin Inhibitors Research Articles

Understanding Vitiligo: Causes, Diagnosis, Promising Advances in Treatment and Management and the Impact on Mental Health

Vitiligo is a chronic skin disorder characterized by the loss of pigmentation, resulting in white patches on the skin. The condition arises from the destruction of melanocytes, the cells responsible for producing melanin, the pigment that gives colour to the skin, hair, and eyes. Although the exact etiology of vitiligo remains elusive, it is believed to involve a complex interplay of genetic, autoimmune, and environmental factors.
 This overview provides the key aspects of vitiligo, including its epidemiology, pathogenesis, clinical manifestations, and current treatment approaches. The prevalence of vitiligo varies globally, affecting individuals of all ethnic backgrounds and age groups.
 The autoimmune hypothesis proposes that the immune system mistakenly targets and attacks melanocytes, leading to their destruction. Triggering factors, such as oxidative stress, viral infections, and neural factors, may contribute to the initiation and progression of vitiligo.
 Clinically, vitiligo can significantly impact the quality of life for affected individuals, both psychologically and socially. The distribution and extent of involvement vary, and the condition can affect any part of the body.
 Various treatment modalities are available for vitiligo, ranging from topical corticosteroids and calcineurin inhibitors to phototherapy and surgical interventions. While these approaches may help to re-pigment the skin to some extent, there is no definitive cure, and the outcomes can be unpredictable. Ongoing research is focused on understanding the molecular mechanisms underlying vitiligo and developing targeted therapies to address the root causes of the disease.
 Keywords: Vitiligo, Autoimmune, Melanocytes, Pigmentation, Corticosteroids, quality of life.

Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Burden of Disease and Treatment Patterns Amongst Patients With Vitiligo: Findings From a National, Longitudinal Retrospective Study in the United Kingdom.

This retrospective study, using UK Clinical Practice Research Datalink and Hospital Episode Statistics databases, analysed 17,239 incident patients with vitiligo. Mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years (range: 0.10 [2010-COVID] to 0.19 [2013/2018]); prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%), and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time were most commonly depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%), and sleep disturbance (12.7%); recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5%, and 3.9%, respectively. Mental health comorbidities were more common among White patients (eg, depression and/or anxiety, 29.0%) than Black (18.8%), Asian (16.1%), and other ethnicities (21.4%). In adolescents, depression and/or anxiety was most commonly diagnosed after vitiligo diagnosis (7.4% vs before, 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 person-years) and general practitioner consultations (97.9/100 person-years). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatments (ie, topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids, phototherapy), increasing to 82.0% the next year; median (95% CI) time from diagnosis to first treatment was 34.0 (31.6-36.4) months. Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments; 16.6% had a record of antidepressant and/or anxiolytic treatments. Most patients were not on vitiligo-related treatments within a year of diagnosis, with time to first treatment >2 years, suggesting that vitiligo may be dismissed as unimportant and not treated early, in part due to limited effectiveness of available treatments. New effective treatments, early initiation, and psychological intervention and support are needed to reduce vitiligo burden on patients.

Characteristics and Management of Patients with Alopecia Areata and Selected Comorbid Conditions: Results from a Survey in Five European Countries.

Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss and can impose a high psychosocial burden on patients. The presence of comorbid conditions may impact the management of AA in clinical practice. This analysis aims to describe disease characteristics and management of AA in patients with concomitant atopic, autoimmune, and psychiatric comorbid conditions. Data were collected from the Adelphi Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with AA conducted in France, Germany, Italy, Spain, and the UK between October 2021 and June 2022. Patients' disease severity was based on physician's definition. Physician-reported data on demographics, AA clinical characteristics, comorbid conditions, and information related to AA therapies were analyzed. Analyses were descriptive. Overall, 239 dermatologists provided data for 2083 patients, of which 558 patients (27%) had at least one atopic, autoimmune, or psychiatric comorbid conditions. The most common comorbid conditions were atopic dermatitis, autoimmune thyroid disease, and anxiety. The mean (standard deviation) patient age for the three comorbidity groups was 37.6years (12.1) and 56% of the patients were women (n = 313). In the three comorbidity groups, 51%, 50%, and 55% of patients with atopic, autoimmune, and psychiatric comorbidities had severe AA with disease progression reported as worsening in 30%, 28%, and 30%, respectively, whereas in the group with no comorbidities, 37% were described as having severe AA and 21% getting worse. Scalp hair loss was the primary sign reported across the three groups of comorbid conditions (atopic, 91%; autoimmune, 91%; psychiatric, 88%). Patients with preselected comorbidities presented more frequently AA-related signs and symptoms beyond scalp hair loss than patients without comorbid conditions. These patients were also more likely to receive topical calcineurin inhibitors, topical immunotherapy, conventional systemic immunosuppressants, and oral Janus kinase inhibitors for the treatment of their AA. This analysis provided insights into the burden and management of AA in patients presenting with atopic, autoimmune, and psychiatric comorbid conditions in five European countries.

Roflumilast Cream 0.3% for the Treatment of Recalcitrant Lichen Nitidus

Introduction:
 Lichen nitidus is a rare chronic inflammatory condition that presents as shiny, flat-topped papules. The pathophysiology of lichen nitidus is not well understood but has been theorized to stem from allergens that cause antigen presenting cells to activate, thus causing a cell-mediated response that ultimately creates the distinct inflammatory papules1. Cytokines produced by this cell-mediated response may cause an increase in T-helper 2 cells which have the potential to produce the superficial dermal granulomas seen in lichen nitidus2.  Currently, no FDA approved treatments for lichen nitidus exist. Due to the inflammatory nature of the disease, off-label therapies may include topical corticosteroids, topical calcineurin inhibitors and UV light1. Lichen nitidus can be a chronic condition and in cases where long term topical corticosteroid use is required, has been associated with hypopigmentation in African Americans. Roflumilast cream 0.3% is a highly selective, non-steroidal and potent topical phosphodiesterase 4 (PDE4) inhibitor approved in 2022 by the FDA for the treatment of psoriasis, including intertriginous disease. Here, we report the case of a 51-year-old African American patient with lichen nitidus that is pruritic and refractory to typical off-label treatments including emollients, triamcinolone and clobetasol. The patient was started on roflumilast cream 0.3% daily with complete resolution of lesions and pruritus in 4 weeks.
  
 Case Report:
 We report the case of a 51-year-old African American patient presenting to the clinic with a history of firm, pruritic, white colored papules on both of his hands that made it hard for him to drive. These lesions had been present for 2 years and did not respond to previous treatment with emollients and topical corticosteroids including triamcinolone cream 0.1% and clobetasol ointment 0.05% both twice daily. A biopsy was performed and demonstrated lymphocytic infiltrate in the upper dermis and the classic “claw and ball” configuration consistent with lichen nitidus. The patient was subsequently started on topical roflumilast 0.3% daily which resulted in complete resolution of lesions and pruritus within 4 weeks.
  
 Conclusion:
 We reported a case of a 51-year-old African American papules on both hands that were consistent with lichen nitidus. In this case, the patient’s lichen nitidus was refractory to topical corticosteroids and emollients. Long term corticosteroid use is also associated with hypopigmentation in this population. After starting topical roflumilast 0.3% daily, the patient reported complete resolution of the lesions and puritus. This report suggests reduction of inflammation with roflumilast cream 0.3%, can offer a treatment option for patients with lichen nitidus.

Advancing Treatment in Atopic Dermatitis: A Comprehensive Review of Clinical Efficacy, Safety, and Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, and Phosphodiesterase-4 Inhibitors as Topical Therapies.

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation features the emergence of crisaborole, a phosphodiesterase four inhibitor. Its innovative mode of action, benign safety profile, and applicability to mild and moderate AD are thoroughly evaluated. The review also includes challenges, particularly cost considerations, which constrain accessibility and necessitate nuanced implementation in therapeutic regimens. This study underscores the need for persistent investigation, teamwork, and innovations in managing AD. In this regard, AD requires a united approach between clinicians, researchers, affected individuals, and policymakers to refine patient-focused treatment and develop precise, economical strategies to address this chronic and frequently life-altering health condition.

Treatment and referral patterns of patients with atopic dermatitis from the Danish primary care system to the tertiary care system

AbstractBackgroundPatients with atopic dermatitis (AD) are mostly managed by general practitioners (GPs) and practicing dermatologists (PDs) in Denmark. In cases of severe and refractory AD, the primary physician can refer the patient to a specialised dermatology department.ObjectivesAim of the study was to investigate treatment at the time of referral to a specialised dermatology department and the cause stated by the GP in a Danish cohort of AD patients referred to the Department of Dermatology, Aarhus University Hospital from 2019 to 2021.MethodsOne hundred and thirty cases were randomly selected via diagnosis codes for AD. Information regarding the cause for referral and treatment given at time of referral was obtained from medical records. 18 cases were excluded due to missing referral in the patients' medical records, other diagnosis than AD or treatment initiation before 2019. The final cohort consisted of 112 cases. Differences between patients referred from GP and PD were analysed with Fisher's exact test.ResultsMost cases were referred by PDs (45.5%) and GPs (24.1%). GPs primarily referred due to acute flare‐ups in need of treatment (40.7%), and PDs due to lacking disease control (64.7%), (p‐values < 0.0018). GPs generally included more descriptive information in their referrals than PDs, however, only the difference in mentioning sleep disturbance was significant (p‐value = 0.0144). Topical corticosteroids were the preferred treatments before referral regardless of the referring doctor, with no statistical differences. Topical calcineurin inhibitors were significantly more used among PD‐referred patients compared to GP‐referred patients (p‐value = 0.0018). Systemic therapy was initiated in 45 patients (40.2%) at the tertiary hospital with no differences between referral from either GPs or PDs.ConclusionsThe study identified few differences in the referral pattern of AD to a tertiary treatment center from GPs and PDs. No major deviations from Danish guidelines were found.

[Localized scleroderma].

Localized scleroderma (LS), also called circumscribed scleroderma or morphea, comprises aheterogeneous group of diseases that can be classified into four subtypes: limited, linear, generalized, and mixed LS. All manifestations are primarily due to chronic progressive fibrosis of the skin or structures close to the skin. Involvement of internal organs or the transition to systemic sclerosis is excluded by definition. Adistinction is made between forms that primarily affect the skin (up to the dermis) or that severely involve subcutaneous fat tissue, muscle fascia or muscles. Adetailed examination is required for clinical diagnosis. In order to improve comparability of findings, photo documentation and the use of clinical scores should be carried out. For superficial subtypes the use of topical glucocorticosteroids, calcineurin inhibitors or phototherapy is initially recommended, whereas for severe forms with deep involvement or overall therapy refractoriness, the diagnosis should first be expanded and systemic therapy initiated at an early stage. Especially, in cross joint or extremity-dominant forms of linear LS or in cases with head and neck involvement, such as en coup de sabre, Parry-Romberg syndrome and other subtypes with aprominent musculoskeletal affection, an MRI examination should be arranged. Depending on location, an ophthalmological, neurological, orthodontic, rheumatological or orthopedic consultation may be necessary. For systemic therapy, methotrexate alone or in combination with systemic glucocorticosteroids as pulse therapy is recommended as first-line treatment.

Assessing effectiveness of adding niosomal atorvastatin 1% ointment to topical calcineurin inhibitor treatment in non-segmental vitiligo.

Treatment of vitiligo is still a big challenge for dermatologists. The efficacy of statins in the treatment of vitiligo is controversial. We studied possible therapeutic effect of topical 1% niosomal atorvastatin ointment combined with topical 0.1% tacrolimus in treatment of non-segmental vitiligo. This is a triple blind, pilot, randomized placebo-controlled trial (RCT) that was performed in dermatology clinic. All the patients used topical 0.1% tacrolimus cream twice daily (BD). Moreover, the intervention group participants used topical 1% niosomal atorvastatin ointment, and control group participants were prescribed placebo ointment, BD. Patients were evaluated using vitiligo area surface index (VASI) score and patients' satisfaction at baseline and after 3 months treatment. The mean patient satisfaction in the intervention and control groups were 5 ± 1.4 and 3.5 ± 1.9; the difference between groups was not statistically significant (p = 0.9). We found statistically significant difference in VASI score before and after treatment in both intervention and control groups (p = 0.01 and p = 0.03, respectively). However, comparison of the VASI score between groups was not statistically significant (p = 0.62). We also found no significant correlation between VASI score and other variables. The result of this study indicates that adding of niosomal atorvastatin 1% ointment to topical calcineurin inhibitor has no additional effect on non-segmental type of vitiligo. Further large studies with different combinations are recommended before any conclusive result can be concluded on efficacy of statins in vitiligo.

510 - Dupilumab is efficacious in patients with prurigo nodularis regardless of stable use of topical corticosteroids and topical calcineurin inhibitors: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules, which substantially affects quality of life. Although topical treatments are frequently prescribed, these therapies are limited by insufficient demonstrated evidence for efficacy, and/or associated side effects. Objectives This study reports the effect of dupilumab on pruritus, skin lesions, and quality of life in patients with PN, with or without stable use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI), in an analysis of pooled data from two phase 3 trials. Materials & Methods LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two randomized, double-blind, placebo-controlled, 24-week studies. Adults with PN inadequately controlled by topical prescription therapies, or for whom those therapies are inadvisable, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. “Stable use” was defined as maintaining the same medicine (low-to-medium potency TCS and/or TCI) during the study, with the same frequency of treatment (once or twice daily) as from 2 weeks prior to screening. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; scored 0–10; high scores represent a poorer outcome), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; scored 0–4; high scores represent a poorer outcome). Impact on Health-Related Quality of Life (HRQoL) was assessed through the Dermatology Life Quality Index questionnaire (DLQI; 10 questions scored 0–3 with a maximum score of 30; high scores represent poorer HRQoL). Results 311 patients were randomized (dupilumab/placebo n = 153/158), including 182 patients with stable use of TCI/TCS (dupilumab/placebo N = 91/91) and 129 patients without (dupilumab/placebo N = 62/67). Baseline demographics and disease characteristics were well balanced in both subgroups. At Week 24, significantly more patients treated with dupilumab with or without stable use of TCI/TCS achieved a ≥ 4-point improvement in WI-NRS (59.3%/58.1%) vs placebo (13.2%/26.9% [nominal P < 0.0001/P < 0.0001]). The proportion of patients achieving an IGA PN-S score of 0 or 1 at Week 24 was also significantly higher in the dupilumab group for patients with or without stable use of TCI/TCS (48.4%/43.5%), vs placebo (11.0%/25.4% [nominal P < 0.0001/P = 0.0319]). The positive impact of dupilumab treatment on HRQoL was greater, for patients with and without a stable use of TCI/TCS vs placebo, as suggested by the mean change from baseline in DLQI at Week 24 (−12.9/−11.9 vs −5.5/−7.1 [nominal P < 0.0001/P < 0.0001], respectively). Although the placebo response was higher for patients without stable use of TCI/TCS, the effect of dupilumab treatment was comparable in the two subgroups. Treatment-emergent adverse events (TEAEs) occurred with similar rates in dupilumab-treated patients with or without stable use of TCI/TCS (59.3%/60.7%), compared with placebo (53.3%/47.8%). Patients with or without stable use of TCI/TCS had similar rates of severe TEAEs in the dupilumab groups (2.2%/4.9%) and placebo groups (3.3%/4.5%). Conclusion Dupilumab treatment improves itch, skin lesions, and quality of life in patients with PN, with an acceptable safety profile, with little to no influence from concomitant treatment with topical therapies (TCI/TCS).

539 - Baseline patient characteristics, physician-assessed effectiveness, patient-reported outcomes, and safety in adult atopic dermatitis patients in Japan treated with dupilumab: Real-world insights one year into the GLOBOSTAD multinational prospective observational study

Abstract Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study –demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-­inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab ­treatment.

484 - Phase 2 trial in progress - lirentelimab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments

Abstract Background Atopic dermatitis (AD) is a chronic pruritic inflammatory dermatitis that affects approximately 16.5 million (7.3%) adults in the US, of which around 6.6 million (40%) have moderate-to-severe disease. The current standard of care includes topical treatments supplemented with corticosteroids with and without immunosuppressants. Patients with AD inadequately controlled by topical treatments and immunosuppressants are often treated with biologics and/or JAK inhibitors. Some patients do not have an adequate clinical response or are unable to tolerate these treatments prompting the need for novel therapies. Study Rationale Mast cells (MCs) and eosinophils (eos) are implicated in the pathogenesis of AD. Sialic acid-binding Ig-like lectin (Siglec)-8 is expressed selectively on MCs and eos; engagement with an antibody results in broad inhibition of MC activation and eos depletion. Lirentelimab (AK002) is a humanized, nonfucosylated IgG1 monoclonal antibody that binds specifically to Siglec-8. Preclinical data demonstrates that lirentelimab can broadly inhibit multiple modes of mast cell stimulation that drive AD pathogenesis. Lirentelimab, administered every 4 weeks as an infusion (IV), has been tested in over 600 healthy volunteers and patients with inflammatory and allergic diseases; in those with concomitant AD, improvements in AD were observed. Overall, lirentelimab IV has been well-tolerated; the most common AE being infusion related reactions (IRRs) typically associated with the initial infusions. In a phase 1 study, a subcutaneous (SC) formulation of lirentelimab was well-tolerated with no IRRs. The results of these studies provide a strong rationale for conducting this phase 2 proof-of-concept, randomized, double-blind, placebo-controlled study of lirentelimab SC in adults with moderate–severe atopic dermatitis inadequately controlled by topical treatments (NCT05155085, “ATLAS”). Key Inclusion/Criteria Adults (18-80 years) are eligible for screening if they have had chronic AD presented for ≥3 years with moderate-to-severe symptoms defined as: Eczema Area and Severity Index (EASI) score ≥16, involvement of ≥10% of the Body Surface Area (BSA), and Investigator Global Assessment (IGA) score ≥3, documented recent history of inadequate response to treatment with medications such as topical corticosteroids, calcineurin inhibitors, JAK inhibitors, or PDE4 inhibitors (crisaborole), and biologic-naïve or biologic-exposed (secondary loss of response, intolerance, or lack of access). The complete list of inclusion/exclusion criteria will be presented. Study Design 130 patients will be randomized 1:1 to receive either 7 SC injections of 300mg lirentelimab or placebo every two weeks and then followed for 12 weeks after the last dose. The primary endpoint is the proportion of patients who achieve EASI-75 at week 14 (2 weeks after last dose) compared with baseline. All patients who receive study medication will be included in the safety analysis. Secondary endpoints include percent change in EASI at week 14 from baseline and proportion of patients with IGA of 0 or 1 and a 2-point improvement at week 14 compared to baseline. Patients who complete the study (day 99 visit of double-blind period) will be given the option to enroll in an open-label extension (OLE) for 7 doses of 300mg lirentelimab SC for 12 weeks. Qualified participants will receive medication, lab tests and medical care related to the study at no cost. Study Sites This study is currently enrolling in the USA and Germany. Please visit clinicaltrials.gov (NCT05155085) or email atlas.info@allakos.com to learn more about this study.

Moisturizers for the treatment and prophylaxis of atopic dermatitis exacerbations

Atopic dermatitis is a global problem with increasing prevalence. Genetic predisposition to allergies, epidermal barrier dysfunction, and T2 immune response underlie atopic dermatitis. Xerosis, itchy skin, and exacerbation are the main atopic dermatitis symptoms, leading to increased permeability of allergens and microbes through the damaged epidermis and to the development of sensitization. The main purpose of atopic dermatitis therapy is to achieve long-term remission and improve quality of life. Topical treatment includes glucocorticosteroids, topical calcineurin inhibitors, and emollients to reduce inflammation, xerosis, and infection prevention. Daily use of effective emollients as basic skin care can improve epidermal barrier function, provide skin hydration, and reduce the need for topical glucocorticosteroids.

[Radiation-induced morphea-an overview].

Radiation-induced morphea is afibro-inflammatory remodelling process of the subcutaneous connective tissue caused by ionising radiation, most commonly in the context of breast cancer treatment. The underlying pathomechanisms and putative risk factors are unknown. Therefore, misdiagnosis and inappropriate treatment pose asignificant problem in the care of those patients. The aim of the study was to provide an overview as well as guidance for the diagnosis and treatment of radiation-induced morphea based on current case reports and review articles. Radiation-induced morphea is arare condition that represents an interdisciplinary challenge for (gynaecological) oncology, radiotherapy and dermatology. Frequent misdiagnoses include infection (erysipelas), cancer recurrence or radiation dermatitis. Early histological diagnosis and the initiation of anti-inflammatory therapy using topical glucocorticoids or calcineurin inhibitors in combination with phototherapy and/or methotrexate are the most relevant success factors for an adequate clinical response.

Impact of Crisaborole in Treatment-Experienced Patients With Mild-to-Moderate Atopic Dermatitis.

Background: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of patients with mild-to-moderate atopic dermatitis (AD). Objective: To assess the efficacy and safety of crisaborole in patients with AD who had received prior treatment with (a) corticosteroids (systemic or topical) or topical calcineurin inhibitors (TCIs) or (b) topical corticosteroids (TCSs) or TCIs or (c) who were treatment-naive (TN). Methods: This post hoc analysis comprised patients aged ≥2 years with mild-to-moderate AD. Patients were assigned (2:1) to receive crisaborole or vehicle twice daily for 28 days. Patient response was assessed with the Investigator's Static Global Assessment (ISGA), Dermatology Life Quality Index (DLQI), Children's Dermatology Life Quality Index (CDLQI), and Dermatitis Family Impact (DFI) tools. Safety was also assessed. Results: A significantly higher percentage of patients treated with crisaborole versus vehicle achieved ISGA success regardless of treatment history. Patients treated with crisaborole had significant reductions in DLQI, CDLQI, and DFI scores versus those who received vehicle regardless of treatment history, with the exception of DLQI and DFI scores in the TN group. Crisaborole was well tolerated in all subgroups. Conclusion: Crisaborole demonstrated a favorable efficacy and safety profile in both treatment-experienced and TN patients. ClinicalTrials.gov, NCT02118766 and NCT02118792.

Trends of Diagnosis, Disease Course, and Treatment of Atopic Dermatitis 2012-2021: Real-World Data from a Large Healthcare Provider.

In the last decade, new treatments for atopic dermatitis (AD) have emerged. We aimed to describe trends of the diagnosis, disease course, and treatment of AD over a decade (2012-2021) using data from Maccabi Healthcare Services (a 2.7-million-member healthcare provider in Israel). The AD prevalence was stable (4.0% on 31 December 2021 vs. 4.3% on 31 December 2012). The annual AD incidence was also stable (5.8/1000 in 2012 and 5.7/1000 in 2021). AD-related treatment use was highest in the first year post-diagnosis, and it included, among children (n = 87,414) vs. adults (n = 36,865), low-potency topical corticosteroids (TCS) (41.8% vs. 27.1%), mid-potency TCS (30.1% vs. 28.1%), high-potency TCS (34.9% vs. 60.3%), topical calcineurin inhibitor (10.8% vs. 10.1%), phosphodiesterase-4-inhibitor (0.3% vs. 0.7% overall; approved in 2019), phototherapy (0.1% vs. 2.3%), and systemic/biologic treatments (13.0% vs. 13.3%). Among children diagnosed in 2012 and followed through to 2021 (n = 5248), 21.5% had ≥1 AD diagnosis/treatment 10 years later (among 3223 adults: 38.3%). We conclude that the incidence and prevalence rates of AD were comparable to those in similar database studies and remained relatively stable over the past decade. The results underscore the burden of medication use among children and adults, particularly in the first year after AD diagnosis, and the low rate of AD diagnosis among patients originally diagnosed as children 10 years earlier.

Topical Calcineurin Inhibitors in the Management of Chronic Pruritus in Older Adults: A Research Letter.

In this study, we aimed to analyze the literature to date on the utilization of topical calcineurin inhibitors in the management of pruritus among older adults, ages 65 and older. The 16 studies included in the final analysis demonstrated that topical calcineurin inhibitors are well tolerated across ages and are effective in treating a wide variety of chronic pruritic conditions. Collectively, these findings support that topical calcineurin inhibitors should be considered a safe, plausible option for managing age-associated itch. J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7190e.

The Pediatric Dermatologist's View of Pediatric Vitiligo.

No guidelines exist for pediatric vitiligo. To identify practice patterns of pediatric dermatologists treating vitiligo. A PeDRA survey was completed online by 56 pediatric dermatologists. Practitioners reported feeling most comfortable treating 13- to 17-year-olds and least comfortable treating infants. Quality of life was assessed by interview in 89.3%. Topical calcineurin inhibitors (TCIs), topical corticosteroids (TCSs), narrowband UVB, coverup makeup, topical JAK inhibitors (tJAKis), and 308-nm laser were the leading vitiligo therapeutics chosen. 94.5% of practitioners reported experiencing frustration due to difficulties procuring therapies. Pediatric vitiligo has notable effects on quality of life. Some therapeutic options exist which are preferred by pediatric dermatologists. There is a need for more data on therapeutics in infants and young children, J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7572e.

Ocular surface expression of inflammatory cytokines in GvHD and their association with disease development and clinical manifestations

The aim of this study was to investigate the tear cytokine profiles of patients with chronic ocular graft versus host disease (GvHD) and evaluate their association with clinical disease severity. Consecutive patients attending the Haematology clinic with a known or suspected diagnosis of chronic ocular GvHD were invited to participate. To be included, patients had to fulfil either or both of the National Institute of Health (NIH) or the International Chronic Ocular Graft‐vs‐Host‐Disease Consensus Group (ICCGvHD) diagnostic criteria.Clinical parameters recorded included best correct visual acuity (BCVA), Schirmers I test, tear break up time (TBUT), and Oxford surface staining (OSS) along with the overall grading of ocular GvHD severity as defined by the ICCGvHD. Ocular tear samples were collected and levels of cytokine production (IFN‐γ, IL‐1β, IL‐2, Il‐4, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, and TNF‐ α) were assayed using Meso Scale Discovery (MSD) multi‐array technology. The results were compared to those of healthy matched controls using unpaired t test. Results were correlated with clinical parameters using Pearson r correlation.Thirteen patients took part in the study (8 male, 61.5%; 5 female, 38.5%) with an average age of 43.9 years (±13.4). With regards to ocular examinations, patients were found to be heavily dependent on lubricant eye drops (average 8.5 times/day). Patients suffered from both aqueous deficient and evaporative DED with an average Schirmer's measurement of 4.2 mm (±5.7, range of 0–21) and average TBUT of 3.8 s (±1.3, range 1–6). The average Oxford surface staining score was 7.9 (±4.2, range of 0–15). According to the ICCGvHD grading system, and using the average data across both eyes, seven of the patients had ‘Mild/Moderate’ disease (53.8%) and the remainder had ‘Severe’ disease (n = 5, 38.5%).The levels of IFN‐γ, IL‐1β, IL‐2, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, and TNF‐ α were found to be statistically elevated when compared to healthy age and gender matched controls (FDR p value<0.05). In those with early‐stage disease (n = 5), IFN‐γ was found to strongly correlate with lubricant usage (0.98, p = 0.03), and IL‐2 with the severity of ocular surface staining grade (1.00, p = 0.03), implying that these cytokines in particular may play a role in the development of chronic ocular GvHD and represent promising treatment targets for patients in the initial stages of disease.This study demonstrates that ocular tear cytokines are elevated in patients with chronic ocular GvHD, reiterating the role of inflammation in the pathogenesis of disease. Furthermore, the correlation of IFN‐γ and IL‐2 with clinical parameters of disease severity suggest that these cytokines play a role in early disease development. These findings support the implementation of anti‐inflammatory treatment such as topical calcineurin inhibitors, in conjunction with tear replacement and preservation to avoid irreparable damage to the ocular surface, and this may be best utilized in the initial stages of the disease development.

The management of Chronic Hand Eczema: A retrospective patient record review.

Chronic Hand Eczema (CHE) is a heterogeneous fluctuating inflammatory disease that represents a significant burden. Effective treatment options for moderate to severe CHE are limited. To assess how patients with moderate to severe CHE are treated in clinical practice. A retrospective, physician-led patient record review assessed the demographic, clinical and treatment characteristics of patients aged ≥18 years with CHE across seven countries. Each participating physician was requested to review records for their three most recent patients with moderate to severe CHE treated with a topical or systemic therapy. A total of 264 physicians, of whom 88.6% were dermatologists and 70.1% were predominantly or partly hospital-based, reviewed the records of 792 patients. Signs were present on hands only in 56.4% of patients and the mean time on current treatment was 16.7 months. Overall, 62.9% of patients received systemic therapy and almost one-quarter (23.4%) were treated with a biologic; 28.6% of patients were only treated with topical corticosteroids and/or topical calcineurin inhibitors. In patients with moderate to severe CHE, most received systemic therapy with one-quarter on biologic therapy. However, given that many of these treatments have limited evidence of efficacy in CHE, there is a need for studies specifically in patients with CHE as well as new therapeutic options.