Restoration of Skin Barrier Abnormalities with IL4/13 Inhibitors and Jak Inhibitors in Atopic Dermatitis: A Systematic Review.

Background and Objectives: Atopic dermatitis is a chronic inflammatory skin disorder with a significant burden on patients' quality of life. This systematic review aims to evaluate the restoration of skin barrier abnormalities with interleukin-4/interleukin-13 (IL-4/IL-13) inhibitors and Janus kinase (JAK) inhibitors in atopic dermatitis. Materials and Methods: A comprehensive review of the literature was conducted, focusing on studies that assess the use of IL-4/IL-13 inhibitors and JAK inhibitors for atopic dermatitis. We identified eligible studies by searching Medline via PubMed with a special focus on their effect on the restoration of the epidermal barrier. Included studies evaluated the transepidermal water loss (TEWL), the reduction in epidermal thickness (ET), the improvement in ceramide synthesis, and the increase in stratum corneum hydration (SCH) with IL-4/IL-13 inhibitors and JAK inhibitors. The quality of included studies was assessed using the ROBINS-I and the RoB 2.0 tool for assessing the risk of bias. Results: Ten of the included studies concern dupilumab, while two concern JAK inhibitors. Ten were observational studies and two were randomized controlled trials (RCTs). The total number of included participants was 378 concerning dupilumab and 38 concerning JAK inhibitors. Five studies did not include any comparison group, three included healthy volunteers, two were conducted versus placebo, and two compared dupilumab with other treatments. The follow-up period ranged between 29 days and 32 weeks. The results demonstrated a significant decrease in transepidermal water loss (TEWL) and an increase in SCH on eczematous lesions for patients with sustained response to dupilumab treatment and observed improvements in ET and filaggrin (FLG) staining, which further support the efficacy of JAK inhibitors in enhancing skin barrier function. Conclusions: This review underscores the efficacy of IL-4/IL-13 inhibitors in improving skin barrier function. However, the limited number of studies focusing on JAK inhibitors and the overall lack of RCTs highlight the need for further research to establish the definitive role of IL-4/IL-13 inhibitors and JAK inhibitors in the restoration of the skin barrier.

Real-Life Data on the Management of Incompletely Excised Basal Cell Carcinoma.

BACKGROUND: The histopathologic presence of basal cell carcinoma (BCC) cells at one or more margins of the specimen after surgical excision is considered suggestive of incomplete tumor clearance. The management of incompletely excised BCC might vary in different clinical scenarios from re-excision to application of other treatments or even watchful waiting. OBJECTIVE: The aims of the study were to report the real-life management of incompletely excised BCC in a tertiary referral center and compare the recurrence rates according to the selected management modality. METHODS: A retrospective study was conducted at a tertiary Dermatology Center in Northern Greece. Our electronic database was scanned over a 5-year period to retrieve all BCCs with available histopathologic assay reporting at least one involved margin (lateral or deep). The included patients were divided into 3 groups according to the selected management after incomplete excision: group 1 included those who underwent immediate re-excision (n = 26), group 2 those who were followed up without any additional therapy (n = 40), and group 3 those who were treated with adjuvant/complementary non-surgical treatment (n = 18). Finally, we recorded the presence or absence of residual tumor in the new histopathologic report of those tumors that were selected to be re-excised (group 1). The primary outcome was the appearance of clinical tumor recurrence. RESULTS: Of 1,689 BCCs recorded in our database, 84 met the inclusion criteria and were included in the analysis. Re-excision had been selected in 26 of 84 patients (group 1), watchful waiting in 40 (group 2), and non-surgical treatments in 18 (group 3). The histopathologic reports of the 26 tumors of group 1 that were re-excised revealed residual tumor in 14 (53.8%) cases. Overall, a clinical recurrence occurred in 14 of 84 patients (16.7%) after a mean follow-up of 17 months. The median time to recurrence was 14 months. Of 40 patients without any treatment, recurrence developed in 10 (25%), while only 2 of 18 patients treated with non-surgical treatments recurred (11.1%). CONCLUSIONS: Our study suggests that positive histopathologic margins after BCC excision result in a clinical recurrence only in a proportion of patients. This percentage is higher when no further treatment is applied and lower when the area is re-excised or treated with imiquimod alone or combined with cryotherapy.

Accuracy of dermoscopic criteria for the differential diagnosis between irritated seborrheic keratosis and squamous cell carcinoma.

BACKGROUND: Even with the addition of dermoscopy, a significant morphologic overlap exists between irritated seborrheic keratosis (ISK) and squamous cell carcinoma (SCC). OBJECTIVE: The aim of this study was to investigate the dermoscopic criteria that could serve as potent predictors for the differential diagnosis between ISK and SCC. METHODS: Dermoscopic images of histopathologically diagnosed ISKs and SCCs were evaluated by 3 independent investigators for the presence of predefined criteria. RESULTS: A total of 104 SCCs and 61 ISKs were included. The main dermoscopic predictors of SCC were dotted vessels (odds ratio [OR], 10.4), branched linear vessels (OR, 5.30), white structureless areas (OR, 6.78), white circles surrounding follicles (OR, 23.45), a diffuse irregular (OR, 2.55) or peripheral (OR, 2.8) vessel arrangement, and a central scale arrangement (OR, 3.35). Dermoscopic predictors of ISK were hairpin vessels (OR, 0.38), a diffuse regular vessel arrangement (OR, 0.39 and OR, 0.36), and white halos surrounding vessels covering more than 10% of the lesion (OR, 0.29 and OR, 0.12). LIMITATIONS: First, the retrospective design of the study; second, the differential diagnosis included in the study was restricted to ISK and SCC. CONCLUSIONS: We confirmed the significant morphologic overlap between ISK and SCC, but we also identified potent predictors for the differential diagnosis between these 2 entities.

The dermatoscopic spectrum of cutaneous lupus erythematosus: A retrospective analysis by clinical subtype with clinicopathological correlation.

The skin is the most common organ of involvement during the course of lupus erythematosus (LE). The literature data concerning the dermatoscopic patterns of the different clinical variants of cutaneous LE (CLE), namely chronic (CCLE), subacute (SCLE), and acute (ACLE), are scarce. To determine the dermatoscopic spectrum of CLE and to correlate the dermatoscopic features with the histological findings. This was a retrospective, observational, multicenter, cohort study. We evaluated the dermatoscopic features in a cohort of patients diagnosed with CLE. Furthermore, we investigated their frequency per clinical subtype and correlated them with the anatomic alterations. We included 79 patients. The most prevalent dermatoscopic features of CCLE included follicular plugs (86.4%, P < .01), patchy distribution (75%, P = .1) of mostly linear curved vessels (56.8%, P = .8), white scales (68.2%, P < .01), and structureless white color (68.2%, P < .01). The most common criteria of SCLE were patchy distribution (90%, P = .1) of mostly linear curved vessels (53.3%, P = .8) and fine white scales (60%, P < .01), while ACLE was characterized by erythema (100%, P < .05) and patchy distribution (100%, P = .1) of mostly dotted vessels (60%, P = .4). Follicular plugs/rosettes in dermatoscopy strongly correlated with follicular plugs in histology (rho = 0.919). Hyperkeratosis significantly correlated with white (rho = 0.644) and yellow/brown scales (rho = 0.225), telangiectasia with linear curved vessels (rho = 0.321) and white color with dermal fibrosis (rho = 0.623). Depending on CLE subtype, distinct dermatoscopic patterns are recognized. In CLE there is a high correlation between certain dermatoscopic criteria and the underneath anatomic alteration.

Real-life data on basal cell carcinoma treatment: Insights on clinicians' therapeutic choices from an institutional hospital registry.

Basal cell carcinoma (BCC) is the most common skin cancer in white skin individuals. The treatment of choice is surgical excision, but several other therapeutic choices are available and might also be efficient and cost-effective in selected cases of low-risk BCC or when surgery is complicate or contraindicated. The aim of the current study was to analyze the applied treatments for BCC in the real-life practice of a tertiary hospital, and investigate factors associated to the tumor and the patients that might influence the treatment selection of clinicians. Data on all BCCs treated from 1st January 2018 to 31st December 2019 were extracted. A total of 751 BCCs from 585 patients were included. The baseline characteristics of patients and tumors, the type of applied treatment and the histopathologic report when available were analyzed. Most tumors were located on the head/neck (64.2%). The most frequently applied treatment was surgical excision (580/751, 77.2%). In 22.8% of tumors a nonsurgical treatment was selected. The most frequently selected alternative treatments were, imiquimod, cryosurgery, their combination (immunocryosurgery), and vismodegib. A pretreatment diagnosis of superficial BCC was associated with a 12-fold increased probability of selecting a nonsurgical treatment except of vismodegib. Every added year of age increased the probability of selecting a nonsurgical treatment by 3-fold. Every added mm of diameter increased the possibility of vismodegib use by 4%. Surgery is the most frequently applied BCC treatment, but nonsurgical modalities do also have an essential role in real settings.

Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the "atopic march" and disrupting the "itch-scratch" cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care.

Psychiatric manifestations, personality traits and health-related quality of life in cancer of unknown primary site.

OBJECTIVE: Psychiatric manifestations and personality traits are known to influence cancer patients. We aimed to assess psychological distress symptoms, psychosocial factors and health-related quality of life (HRQoL) in cancer of unknown primary site (CUP) and to test whether these parameters differ between CUP and Metastatic (MKPC) or Non-Metastatic Known Primary Cancers (N-MKPC) after controlling for demographics and clinical variables. METHODS: In this cross-sectional study, we recruited 50 CUP, 264 N-MKPC and 52 MKPC participants. We assessed depressive symptoms (Center for Epidemiologic Studies-Depression [CES-D]), psychological distress symptoms (Symptom Distress Checklist-90 Revised), sense of coherence (SOC), ego defense mechanisms (Life Style Index) and HRQoL (World Health Organization Quality of Life Instrument, Short Form). RESULTS: The prevalence of clinically significant depressive symptoms (CES-D ≥ 23) was 40.0% in CUP, 28.8% in MKPC and 23.5% N-MKPC (p=0.037). Multivariate logistic regression analysis showed that N-MKPC patients were 5 times less likely (p=0.028) and MKPC patients 3.3 times less likely (p=0.05) to be assessed with probable depression compared with CUP patients after controlling for the major demographic and clinical variables studied. CUP patients presented also higher levels of somatization, anxiety and depressive symptoms; they also had more impaired Physical (p=0.005), Mental (p=0.041) and Social Relations (p=0.044) HRQoL, along with lower scores on SOC and intellectualization defense and higher scores on repression defense, compared with MKPC and N-MKPC patients. CONCLUSIONS: These findings suggest that psychiatric manifestations are frequent in CUP, and the patients' resources to cope with the burden of their illness are limited. Attention to CUP patients' psychological distress and coping resources and capacities may enable oncologists to identify and manage modifiable aspects of HRQoL.

Metformin in Hidradenitis Suppurativa: Is It Worth Pursuing Further?

Hidradenitis suppurativa (HS) often coexists with obesity, metabolic syndrome, diabetes mellitus, or impaired glucose tolerance and insulin resistance and polycystic ovarian syndrome. Metformin is a medication used for the treatment of diabetes, acting in multiple ways. There is evidence that it decreases inflammatory cytokines, some of which are implicated in the pathogenesis of HS (TNF-α, IL-17). We performed a systematic review of data regarding the efficacy and safety of metformin for the treatment of HS. Four electronic databases (MEDLINE, ScienceDirect, Cochrane Library, and ClinicalTrials.gov), as well as the abstracts compendia of major dermatologic congresses, were searched. A total of 133 patients received metformin for HS across 6 studies, 117 of whom received it as monotherapy. The great majority of participants were female, in their thirties and overweight or obese, with one study including only children. The efficacy tools employed varied widely. Four studies (106 patients) documented improvement, 1 documented treatment failure, and 1 had mixed results. Only mild and transient side effects were noted. Metformin has been tried in few HS patients with acceptable efficacy in a fair number of them. As it is generally well tolerated and reasonably priced, carefully designed clinical trials comparing it with placebo are worth performing.

Photodynamic Therapy for Field Cancerization in the Skin: Where Do We Stand?

INTRODUCTION: Photodynamic therapy (PDT) with a photosensitizer is available for the treatment of multiple actinic keratoses (AKs) in a restricted skin area or, as it is established, for the field-cancerized skin. OBJECTIVES: Our review aims to present the up-to-date literature on skin field cancerization using PDT employing different topical photosensitizers, modified light delivery protocols and combination treatments to obtain excellent efficacy and safety in everyday clinical practice. METHODS: We sought PubMed, MEDLINE, Scopus, OVID, Embase, Science Direct, Cochrane Library, Research Gate and Google Scholar for [(aminolevulinic acid OR aminolevulinate) AND photodynamic therapy] with (field-directed OR field cancerization, (actinic keratosis), and (efficacy OR effectiveness OR pain OR tolerability) for studies published until February 2023. RESULTS: Advantages of PDT compared to the other field treatments, including imiquimod, 5-fluorouracil, ingenol mebutate gel and diclofenac, reported better cosmetic outcomes and greater patient satisfaction. On the other hand, some drawbacks of field PDT include pain and treatment duration. Alternate illumination methods have also been investigated, including daylight as a light source. Pretreating the affected area may enhance photosensitizer absorption leading to better therapeutic results, while combinational treatments have also been tested. Patients prefer daylight PDT to traditional light sources since it is more well-tolerated and equally effective. Even as a preventive treatment, field PDT yields promising outcomes, especially for high-risk individuals, including organ transplant recipients. CONCLUSIONS: This review provides a thorough display of the field of PDT on cancerized skin, which will facilitate physicians in applying PDT more efficiently and intuitively.

Sebaceous Neoplasms.

Sebaceous neoplasms describe a group of tumors with sebaceous differentiation commonly seen in lesions located primarily in the face and neck. The majority of these lesions are benign, while malignant neoplasms with sebaceous differentiation are uncommon. Sebaceous tumors present a strong association with the Muir-Torre Syndrome. Patients suspected with this syndrome should undergo neoplasm excision, followed by histopathologic and additional immunohistochemistry and genetics examinations. Clinical and dermoscopic features of the sebaceous neoplasms, as well as management procedures collected from the literature analysis regarding sebaceous carcinoma, sebaceoma/sebaceous adenoma, and sebaceous hyperplasia are described in the current review. A special note is made for describing the Muir-Torre Syndrome in patients presenting multiple sebaceous tumors.

Quality-of-Life Endpoints in Women of Childbearing Age with Hidradenitis Suppurativa: A Tertiary-Care-Centre-Based Study.

Background: Hidradenitis suppurativa (HS) principally affects women of childbearing age, who face gender-specific challenges and have lower life-quality than men. HS also seems to impact desire for procreation. Objective: To investigate various quality-of-life endpoints in women of childbearing age with HS. Study design: A cross-sectional questionnaire-based study was performed at a university dermatology department. Eighteen yes/no and one open-ended questions explored impact of HS on social life, sexual life, family planning, working life and healthcare-backed support. A sensitivity analysis was performed for women under 25, who are significantly less likely to be married/in a permanent relationship in Greece, as this could act as a confounding factor regarding family planning. Results: Ninety-six women were included. Most women (80.8%) carry a stigma because of HS, which also affects their choice of clothes and social relationships. Sexual impairment affects 73.1% of women. One third of women wants less or no children because of HS, 67.7% worry about its impact on pregnancy, birth, and the postpartum, and 84.6% worry about the impact of HS treatment on fertility and their babies' health. Almost 43% fear losing their job because of HS, 34.4% are discriminated against at work and 33.3% state HS has hindered their career. Most women are not adequately informed about their disease or available support groups/material and 41.7% have not received good enough care through pregnancy/postpartum. Conclusions: Life-quality endpoints should be meticulously screened in women. Multidisciplinary-led treatment should be offered during pregnancy and the postpartum.

Elderly patients with psoriasis: long-term efficacy and safety of modern treatments.

OBJECTIVE: The increasing number of elderly psoriatic patients presents a challenge for dermatologists. Biologicals and small-molecule inhibitors in the general population have demonstrated a sufficient efficacy and safety profile; yet, studies about their use in the geriatric population are lacking. In this study, we evaluated the efficacy and safety of biological and apremilast among psoriatic patients ≥65 years old. MATERIALS AND METHODS: Clinical records of patients over 65 years old receiving biological drugs or apremilast were retrospectively reviewed. Efficacy was evaluated using Psoriasis Area and Severity Index (PASI) score at treatment onset and weeks 12, 24, 52 and 3 years. Adverse events were also recorded. RESULTS: A total of 154 patients with a mean age of 70.7 ± 6.3 years-old were included in our study. Secukinumab, ustekinumab and brodalumab showed fast-acting results, while the sustained efficacy of secukinumab, ustekinumab, infliximab, adalimumab and brodalumab was also notable. Overall, 30 out of 154 (19.5%) patients reported side effects. Lower respiratory system infections (n = 6; 3.9%) and hepatic enzyme elevation (n = 6; 3.9%) were the most frequently observed events. CONCLUSIONS: Biologicals and apremilast demonstrate adequate efficacy in elderly psoriatic patients. Incidence and severity of reported adverse events were similar to those reported among patients of younger age in relevant clinical studies.

Apremilast in Psoriasis Patients With Serious Comorbidities: a Case Series and Systematic Review of Literature.

Introduction: Patients with serious comorbidities are traditionally excluded from clinical trials. Apremilast is not contraindicated in active infections, malignancy and serious hepatic or renal impairment, but real-life data is needed to support this recommendation. Objectives: The aim of this paper is to present our personal as well as literature-sourced real-world evidenced on apremilast use in psoriasis patients with serious baseline comorbidities. Methods: A case-series and systematic literature review were performed. The psoriasis archives of a tertiary-care hospital, four electronic databases (MEDLINE, ScienceDirect, Cochrane Library, Google scholar) and other sources were searched (January 2014 - July 2021). Identified records were considered eligible, if they reported on the use of apremilast monotherapy in psoriasis patients with chronic infections, history of malignancy, serious liver, renal, psychiatric, or other disease(s). Results: At least 841 psoriasis patients with serious baseline diseases received apremilast. Only 3 cases of cancer progression and no infection reactivations or worsening of other diseases were documented. No increased frequency/severity of adverse events or reduced drug efficacy were noted. Main limitations of this study are the exclusion of a few reports due to inappropriately documented data and the fact that at least some patients might have been counted more than once. Conclusions: Apremilast is a safe and adequately efficacious option for psoriasis that cannot be treated/is challenging to treat with classic systemic agents and/or biologics.

New and Upcoming Topical Treatments for Atopic Dermatitis: A Review of the Literature.

Atopic dermatitis (AD) is a chronic inflammatory dermatosis with periods of exacerbation and remissions. AD is characterized by intense, persistent pruritus and heterogeneity in clinical symptomatology and severity. Therapeutic goals include the amelioration of cutaneous eruptions, diminishing relapses and eventually the disease burden. To date, topical corticosteroids (TCS) and calcineurin inhibitors (TCI) have yet been deemed the mainstay of topical treatments in AD management. Nevertheless, despite their indisputable efficiency, TCS and TCI are not indicated for continuous long-term use given their safety profile. While research in AD has concentrated predominantly on systemic therapies, more than 30 novel topical compounds are under development. The existing data appear encouraging, with some regimens that are already FDA-approved (ruxolitinib was the most recent in September 2021) and several pharmaceutical pipeline products for mild-to-moderate AD that are in an advanced stage of development, such as tapinarof, difamilast and roflumilast. Larger, long-term studies are still required to evaluate the efficacy and safety of these novel compounds in the long run and weigh their advantages over present treatments. In this review, we aim to provide an overview of the latest knowledge about AD topical treatments, echoing upcoming research trends.

Scalp Psoriasis and Biologic Agents: A Review.

Scalp-localized psoriasis is common among patients affected with plaque psoriasis, rendering its treatment exceedingly difficult. Furthermore, the symptoms caused by the disease like scaling, erythema, and pruritus, among others, pose a major psychological impact and a significant regression in the quality of life of the affected patients. Biologics have proved their efficacy in assuaging the symptoms, in terms of Psoriasis Area and Severity Index (PASI) reduction, and offering optimum quality of life, by decreasing the Dermatology Life Quality Index (DLQI) in the patients suffering from plaque psoriasis. Herein, we sought to evaluate the efficacy of biologics and small molecules in controlling the symptoms and their ability to offer long-term maintenance in the disease activity.

Treatment Options and Post-Treatment Malignant Transformation Rate of Actinic Cheilitis: A Systematic Review.

Actinic cheilitis is a premalignant condition that may evolve to squamous cell carcinoma. A consensus on its management has not been established, and large clinical trials are lacking. We aimed to review the existing data regarding the treatment of actinic cheilitis with various modalities regarding safety, efficacy, recursions, and post-treatment malignant transformation. A systematic review was conducted through Pubmed, Ovid and the Cochrane library for studies in English language and the references of included papers from inception to January 2021. Case series were considered if ≥6 patients were included. Of the 698 articles, 36 studies and, overall, 699 patients were eventually reviewed. Laser ablation and vermilionectomy provided the best clinical and aesthetic outcomes with few recurrences, while photodynamic therapy was linked to more relapses. Generally, the adverse events were minor and there was no risk of post-treatment malignant transformation. The limitations of our review include the heterogeneity and the small number of patients across studies. Conclusively, invasive treatments demonstrated superior therapeutic and safety profile. Nevertheless, high-quality head-to-head studies that assess different modalities for actinic cheilitis and report patient preferences are lacking.