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.

Real-World Clinical, Psychosocial, and Economic Burden of Atopic Dermatitis: Results From the ESSENTIAL AD Multicountry Study.

INTRODUCTION: Limited real-world evidence exists about the burden of atopic dermatitis (AD) in patients receiving systemic or non-systemic therapies in clinical practices. ESSENTIAL AD was an observational study that aimed to fill this information gap. METHODS: ESSENTIAL AD enrolled (September 2021-June 2022) adult patients with physician-confirmed AD that was routinely managed with systemic and non-systemic treatment in a real-world setting from 15 countries in Eastern Europe, the Middle East, and Africa. Primary outcome variables were Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI) assessed during one office visit. RESULTS: A total of 799 enrolled patients fulfilled selection criteria and were included in the study. Patients mean (standard deviation [SD]) age was 36.3 (14.4) years, 457 (57.2%) were female, and the majority of patients were white (647 [81.0%]). Mean (SD) time since AD diagnosis was 17.6 (15.2) years (median 16.5; interquartile range [IQR] 3.3-26.8). The mean (SD) EASI, SCORAD, and DLQI total scores were 11.3 (11.3 [median 8.1; IQR 3.6-15.8]), 37.8 (17.9 [median 35.5; IQR 24.2-49.0]), and 10.6 (7.2 [median 10.0; IQR 5.0-15.0]), respectively. Patients receiving systemic treatment had significantly higher disease burden (mean [SD] EASI 13.3 [13.0]; median [IQR] 9.6 [3.9-17.9]) versus non-systemic treatment (mean [SD] 9.3 [8.7]; median [IQR] 6.8 [3.0-13.2]; P < 0.0001). Results were similar for SCORAD (39.9 [19.6] vs 35.6 [15.7]; median [IQR] 38.6 [24.7-53.1] vs 32.6 [23.9-44.6]; P = 0.0017), and DLQI total scores (11.4 [7.4] vs 9.9 [6.9]; median [IQR] 11.0 [5.0-16.0] vs 9.0 [5.0-14.0]; P = 0.0033, respectively). CONCLUSION: Patients with AD continue to have substantial disease burden despite treatment with systemic therapy, suggesting that a need for effective disease management remains, including effective therapies that improve psychological outcomes and reduce economic burden of AD, in Eastern Europe, the Middle East, and Africa.

Patients with atopic dermatitis often suffer from debilitating symptoms that impact their everyday lives. Although several treatment options are available, many patients continue to experience symptoms of disease. The ESSENTIAL AD study assessed burden of atopic dermatitis in patients receiving systemic and/or non-systemic therapies in real-life clinical practices across 15 countries in Eastern Europe, the Middle East, and Africa. The results of the study demonstrated that adult patients with atopic dermatitis continue to have substantial disease burden regardless of treatment with systemic therapy or non-systemic therapy. The findings suggest that optimal management of atopic dermatitis needs to be reassessed in Eastern Europe, the Middle East, and Africa, especially as new, more effective treatment options become available to patients.

Does the effectiveness of biological medications in the treatment for psoriasis depend on the moment of starting therapy? A preliminary study.

Introduction: It is well known that biological medications acting on selected elements of the immune response are highly effective in psoriasis treatment. It is a common perception that psoriasis is a seasonal disorder with improvement in warmer months, however it has not been unequivocally confirmed. It is not known whether the time of year of starting systematic therapy for psoriasis influences treatment outcomes. Material and methods: Changes in psoriasis severity scores during treatment with biologics were investigated. The scores were recorded for 62 patients with moderate to severe psoriasis at the beginning, after 1, 4 and 7 months of the therapy. Patients were divided into two groups: those beginning the treatment in the cold period of the year (November-March) and in the warm period (May-September). The seasonal groups were also divided into subgroups according to the type of biologics used: interleukin inhibitors and tumor necrosis factor α (TNF-α) inhibitors. Results of the treatment were analysed using standard statistical tests of differences between samples. Results: After 1 and 4 months of the therapy, better efficacy of interleukin inhibitors was found in patients starting treatment in summer. The course of psoriasis improvement in patients taking TNF-α inhibitors resulted in consistent improvement regardless of the season. The outcome of the treatment after 7 months was similar for both seasonal groups and types of biologics used. Conclusions: Our understanding of the effectiveness of the treatments depending on the time of the year combined with the type of biologics used, may further improve results of the therapy.

Case report: Successful treatment with biologics in a pediatric patient with a severe inflammatory skin disease and novel CARD14 mutation.

CARD14 (caspase activation and recruitment domain) mutations have been associated with psoriasis vulgaris, psoriatic arthritis, generalized and palmoplantar pustular psoriasis, pityriasis rubra pilaris, and atopic dermatitis. We present a pediatric patient with a novel CARD14: c.394A > T/- (Ile123Phe) mutation, diagnosed with CARD14-associated papulosquamous eruption (CAPE), who was successfully treated with biological treatment.

Vaccinations in Selected Immune-Related Diseases Treated with Biological Drugs and JAK Inhibitors-Literature Review and Statement of Experts from Polish Dermatological Society.

The growing use of biological drugs in immune-mediated chronic diseases has undoubtedly revolutionized their treatment. Yet, the topic of vaccinations in this group of patients still raises many concerns and implies many therapeutic problems that require discussion and standardization of management. The aim of this literature review is to present current knowledge regarding safety and efficacy of vaccinations in dermatological and rheumatological patients treated with biological drugs and JAK inhibitors. Additionally, this article provides recommendation from experts of the Polish Dermatological Society about proper use of vaccinations during therapy with biologics. Generally, all live attenuated vaccines are contraindicated during immunosuppressive/immunomodulatory therapy. If there is need, they should be administered long enough prior to the therapy or after cessation. Yet, inactivated vaccines mostly can be safely used, but the problem in this case is the effectiveness of the vaccination. Most studies report that the immune response in patients on biologics after administration of different inactivated vaccines is similar to or even better than in the control group. Thus, the importance of vaccination among patients on biologics must be emphasized to reduce omissions and the fear of possible side effects or insufficient post-vaccination response.

Shift in skin microbiota of children with atopic dermatitis after topical gentian violet application.

Introduction: Increasing usage of antimicrobial agents may contribute to bacterial resistance in atopic dermatitis (AD). In this case an alternative topical treatment might be gentian violet (GV), suggested for its antibacterial and antifungal properties. Aim: To assess the microbial composition of lesional skin in children with AD and a control group aged 2-12 years, before and after 3 days of 2% aqueous GV application. Material and methods: Skin samples were taken from 30 AD patients and 30 healthy controls aged 2-12 years. The procedure was done two times - before and after 3 days of 2% aqueous GV application. The material was collected from skin lesions in the cubital fossa using 25 cm2 impression plates, containing CHROMagar Staph aureus and CHROMagar Malassezia. After the incubation period, the grown colonies were counted and identified by the Phoenix BD testing system. Results: The results revealed a statistically significant reduction in total counts of bacteria in both groups of children after GV application (p < 0.05). The significant decrease in the number was seen in Staphylococcus spp. (S. aureus, S. capitis, S. haemolyticus, S. cohnii) in AD patients. The number of Staphylococcus spp. was comparable in patients with AD after GV treatment and healthy patients before GV exposure (p = 1.000). Conclusions: Our study results show that GV does not damage the skin surface ecosystem and allows the reduction of excessive bacterial counts on eczematous lesions to a 'safe' level, similar to that of healthy children.

The relationship between atopic dermatitis and atopic itch in children and the psychosocial functioning of their mothers: A cross-sectional study.

Atopic dermatitis is a chronic inflammatory skin disease significantly affecting patients' and their parents' lives. Mothers are mostly responsible for the long-term treatment and their wellbeing is essential. The major objective of this cross-sectional study was to investigate the relationship between atopic dermatitis in children, especially concomitant itch, and the quality of life, stress, sleep quality, anxiety, and depression of their mothers. The study included 88 mothers of children with atopic dermatitis and 52 mothers of children without atopic dermatitis. All mothers completed sociodemographic questionnaire, the Perceived Stress Scale, the Athens Insomnia Scale and the Hospital Anxiety and Depression Scale. Additionally, mothers of children with atopic dermatitis filled in the Family Dermatology Life Quality Index. The severity of atopic dermatitis and pruritus intensity were evaluated by the Scoring Atopic Dermatitis Index and the Numerical Rating Scale, respectively. The severity of atopic dermatitis and itch significantly correlated with the quality of life, insomnia, and perceived stress of the mothers. Mothers whose children had had atopic dermatitis for more than 6 months had significantly higher scores of anxiety and depression. The results highlight the importance of screening mothers for functional impairment to provide adequate support. More attention should be directed to the standardization of stepped care interventions addressing factors resulting in the impaired functioning of mothers.

Off-label medications in the treatment of hospitalized children with atopic dermatitis.

Introduction: Off-label prescribing is defined as using medications outside conditions of the marketing authorisation including their licensed indications, dosage, age and route. Atopic dermatitis (AD) is the most common chronic skin condition in children which can be related to a high level of off-label prescribing. Aim: To investigate the frequency of off-label prescribing and the medications involved in relation to indications and age in paediatric patients hospitalized for atopic dermatitis in a paediatric dermatology ward in 2019. Material and methods: One hundred and seventy-five consecutive discharge letters of patients were analysed regarding gender, age and medications used during hospital stay and prescribed on discharge. Each medication was checked against the licensed age and indications. Results: Altogether 564 medications were prescribed, including 289 topical and 275 systemic ones with 278 prescribed off-label (49.1%). Out of 289 topical medications, 113 (39.1%) were prescribed off-label regarding indications and 34 (11.76%) regarding the age of the patients. In the systemic medications group, 96 (34.53%) were prescribed off-label as AD was not a registered indication and 35 (12.73%) as the age of the patients was outside the marketing authorization. The most frequent medications prescribed off-label were antihistamines, antibiotics and corticosteroids. Conclusions: Prescribing off-label in paediatric population is a common practice. Both topical and systemic medications are frequently used in AD patients off-label, therefore doctors should be familiar with the pitfalls of prescribing beyond the licensed indications and age.

Risankizumab Therapy for Moderate-to-Severe Psoriasis-A Multi-Center, Long-Term, Real-Life Study from Poland.

The present multi-center, long-term, real-life study made an attempt to assess the efficacy of risankizumab in the treatment of moderate-to-severe plaque psoriasis. The study comprised 185 patients from 10 Polish dermatologic departments undergoing risankizumab treatment. The disease severity was measured using the Psoriasis Area and Severity Index (PASI) before the start of the risankizumab treatment and next at the defined timepoints, i.e., 4, 16, 28, 40, 52 and 96 weeks of treatment. The percentage of patients achieving PASI90 and PASI100 responses as well as the PASI percentage decrease at the defined timepoints were calculated, and correlations with clinical characteristics and therapeutic effect were analyzed. The number of patients evaluated at the defined timepoints was: 136, 145, 100, 93, 62, and 22 at 4, 16, 28, 40, 52 and 96 weeks of treatment, respectively. At 4, 16, 28, 40, 52 and 96 weeks, the PASI90 response was achieved in 13.2%, 81.4%, 87.0%, 86.0%, 88.7% and 81.8% of patients, whereas the PASI100 response was achieved in 2.9%, 53.1%, 67.0%, 68.8%, 71.0% and 68.2% of patients, respectively. Our study revealed a significant negative correlation between a decrease in the PASI and the presence of psoriatic arthritis as well as the patient's age and duration of psoriasis at several timepoints throughout the observation period.

Secukinumab for the Treatment of Psoriasis in Pediatrics: Patient Selection and Acceptability.

Psoriasis (PsO) is a chronic, systemic, immune-mediated inflammatory skin disease affecting 1% to 5% population worldwide. In one-third of patients, the first symptoms of PsO manifest in childhood, with a mean age of nine years. Psoriasis in children under 16 years of age constitutes 4% of dermatological problems in this age group. Chronic inflammation of the skin observed in PsO is associated with a development of potentially serious comorbidities, including psoriatic arthritis, hypertension, metabolic syndrome, cardiovascular diseases, inflammatory bowel disease, depression and anxiety. It is reported that among children with psoriasis between 5 and 16 years of age health-related quality of life is reduced by 30.5%. Early diagnosis and effective treatment are crucial in pediatric psoriatic patients to avoid future complications and stigmatization. Treatment for psoriasis consists of a range of topical medications, phototherapy and non-biologic and biologic systemic therapies. Approved biologics for PsO in pediatric patients include etanercept, adalimumab, ustekinumab, ixekizumab and secukinumab. Secukinumab, a recombinant, fully human monoclonal antibody targeting IL-17A, was approved by the EMA (2020) and FDA (2021) in pediatric patients above 6 years of age for the treatment of moderate to severe plaque psoriasis who are candidates for systemic therapy. This review discusses the selection and acceptability of secukinumab in children with psoriasis.

Promising Immune Treatment of Advanced Cutaneous Squamous Cell Carcinoma with Cemiplimab-Real-World Experience in the Global SARS-CoV-2 Pandemic.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. The standard curative treatment is surgical resection, but the treatment of locally advanced and metastatic disease apart from radiotherapy is currently based on cemiplimab. Cemiplimab has demonstrated efficacy in the treatment of advanced and metastatic cSCC in clinical trials, although real-world data are still limited. We present four cases of cSCC, which showed a tremendous response to cemiplimab-one patient achieved complete response and three of them achieved partial response. Immunotherapy with cemiplimab, a recently approved PD1 inhibitor, is an important addition to the cutaneous oncology therapeutic options that may be considered in patients with advanced disease not amenable to surgery or radiotherapy. In all four cases, the patients postponed visits to the doctor because of the fear of SARS-CoV-2 infection or for administrative and organizational reasons declared difficult access to doctors caused by the pandemic.

Effectiveness of infliximab biosimilars in the treatment of moderate to severe chronic plaque psoriasis: experience of real-world data from the register of the program "Treatment of moderate and severe forms of plaque psoriasis (B.47)" of the National Health Fund in Poland.

Introduction: Infliximab (IFX) is a monoclonal antibody that binds to and neutralizes TNF-α. IFX (Remicade) was approved by the U.S. Food and Drug Administration in 2006 for the treatment of severe plaque psoriasis. In 2013 two infliximab biosimilars: Remsima and Inflectra were also registered. The introduction of biosimilar drugs is associated with a significant reduction in treatment costs. Aim: To evaluate the efficacy of treatment with biosimilar IFX with non-medical switch option in patients with plaque psoriasis under the drug program "Treatment of moderate and severe plaque psoriasis" of the Ministry of Health in Poland. Material and methods: The group of 91 adult patients with moderate to severe plaque psoriasis, unresponsive or with contraindications to the standard treatment were qualified to the drug program (in 2016-2018). Efficacy of treatment with biosimilar IFX was evaluated using the Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index scoring performed at week 0, 14, 46 and 94. Results: The mean change in PASI, DLQI, and BSA scores at week 14 was 89.92%, 93.75% and 90.91%, respectively. By week 14, 83.52% of patients achieved PASI75, 49.45% PASI ≥ 90 and 26.37% PASI100. At week 46, 84.62% of patients achieved PASI75, 54.95% PASI ≥ 90, and 21.98% PASI100. At week 94 of therapy, 80.22% of patients achieved PASI75, 48.35% PASI ≥ 90, and 18.68% PASI100. At week 94 of therapy, PASI100 was maintained by 37.5% of patients who achieved PASI100 at week 14. Conclusions: 94-week therapy with biosimilar infliximab results in high and sustained clinical efficacy in patients with moderate to severe psoriasis.

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Risk Factors and Clinicopathological Features for Developing a Subsequent Primary Cutaneous Squamous and Basal Cell Carcinomas.

BACKGROUND: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. METHODS: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. RESULTS: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. CONCLUSIONS: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.

Comparative effectiveness of adalimumab versus ustekinumab in the treatment of severe chronic plaque psoriasis: The results based on data from the program "treatment of moderate and severe forms of plaque psoriasis (B.47)" of the National Health Fund in Poland.

Biological agents: TNF-α inhibitors, IL-12, and IL-23 blockers, IL-17 inhibitors are used in the treatment of plaque psoriasis. Adalimumab (ADA) is an antibody that binds to TNF-α. Ustekinumab (UST) blocks IL-12 and IL-23. The data obtained from medical records is of exceptional value. The aim of the study was to evaluate the efficacy of ADA and UST during a single 40-week period of biological treatment of patients under the drug program "Treatment of moderate and severe form of plaque psoriasis." The group of 620 adult patients with moderate to severe form of plaque psoriasis, who were unresponsive or had contraindications to the standard treatment were qualified to the drug program. In the evaluated group, 50.64% patients were treated with UST, 49.36% with ADA. The efficacy of treatment was assessed during weeks 0, 4, 16, 28, and 40. At week 16th, PASI75 reached 80.72% patients in ADA treated group, PASI ≥90 54.88%, PASI100 19.6% of patients. In the UST group (week 16th) PASI75 reached 70.38%, PASI90 44.26%, PASI100 15.6% of patients. At week 28th PASI90 and PASI100 were more pronounced in the ADA group than in UST. In addition, the total percentage of PASI improvement was significantly higher in the ADA group (p = 0.0006). The percentage of PASI improvement in week 40 was statistically higher in ADA group compared to UST (p = 0.015). Compared to UST, ADA was clinically more effective during a 40-week observation. Patients receiving ADA achieved PASI75, PASI90, and PASI100 more frequently and faster than those treated with UST. Additionally, ADA improved the quality of life of psoriatic patients more substantially compared to UST.