Therapeutic Impact and Management of Persistent Head and Neck Atopic Dermatitis in Dupilumab-Treated Patients.

BACKGROUND: Localization of atopic dermatitis (AD) in exposed areas such as the hands, head, and neck has been considered as a negative factor impacting on dupilumab response, although a comparison of exposed versus unexposed areas is not currently available. OBJECTIVES: The aim of this study is to evaluate the clinical response to dupilumab depending on the presence or persistency of AD skin manifestations in specific body areas. METHODS: The study retrospectively collected clinical and demographic data of adult patients affected by moderate to severe AD. Based on the anatomical sites involved, 5 subcohorts of patients were identified. RESULTS: A total of 41 patients were included in the study. Disease amelioration was detected during the study period, although baseline head/neck and hand localization was associated with a significantly lower likelihood of achieving an Eczema Area Severity Index (EASI) ≤1. In addition, patients with head/neck persistency showed a significantly lower response when compared to patients without persistency of head/neck AD in terms of both mean EASI and Dermatology Life Quality Index (DLQI) reduction. CONCLUSION: AD localization in exposed areas at the baseline and AD persistency at the head/neck may have a negative impact on certain treatment response parameters to dupilumab therapy.

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the "outside-inside" theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.

Efficacy and safety of a combined pharmacological and surgical approach in patients affected by hidradenitis suppurativa: data from a retrospective real-world clinical study.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating chronic skin disease; its therapeutic approach often requires combined medical and surgical treatment. METHODS: The aim of this study was to assess the efficacy and safety of the surgical approach combined with different pharmacological treatments, evaluating the proportion of patients achieving the hidradenitis suppurativa clinical response (HiSCR), along with the incidence of postoperative complications, and local recurrence. A retrospective study of HS patients (Hurley I-III) presenting at least one skin lesion requiring surgery was performed. Demographic and clinical data were collected (kind and anatomical location of lesion excised, type of surgical procedure). Further data included: Hurley stage and IHS4 at baseline and week 16, HiSCR at week 16 after surgery, ongoing therapy at the time of surgery (topical, systemic antibiotic, biologics), postoperative complications and local recurrence at week 16. RESULTS: Forty-two patients with female predominance (66.7%, 28/42), with a mean age of 30.3 (SD±10.5) years, were enrolled. At week 16, 53% of patients achieved HiSCR, with baseline Hurley III inversely related to HiSCR achievement (P<0.05). No increased incidence of postoperative complications was detected. Three cases of local recurrence were reported at week 16. CONCLUSIONS: The results support the efficacy and safety of the combined therapy in the management of HS; no increased risk of complications emerged among patients concomitantly treated with biologics, compared to those on conventional systemic therapy or exclusively treated with surgery.

Evidence on Hidradenitis Suppurativa as an Autoinflammatory Skin Disease.

Hidradenitis suppurativa (HS) is a chronic and debilitating inflammatory skin disease that often exhibits heterogeneity in its clinical presentation, especially in the context of its rare syndromic forms. The pathogenesis of HS results from a complex interplay of genetic predisposition, innate and adaptive immunity dysregulation, smoking, obesity and environmental factors. In the early phase of the disease, the innate immune system is hyperactivated, contributing to tissue damage and triggering the activation and amplification of the adaptive immune response, which plays a pivotal role in the chronic stages of the disease. Recent studies focused on elucidating the importance of innate immunity impairment and autoinflammation in HS and increasing evidence has emerged on the occurrence of the disease in the context of well-known monogenic and polygenic autoinflammatory syndromes (AIDs). This review provides a comprehensive examination of the current scientific background supporting the contribution of autoinflammation to HS etiology, including genetic data, molecular studies and clinical evidence, as well as the association between HS and AIDs. However, further research is needed to shed light on the pathogenic mechanism of this challenging condition and to identify potential perspectives for future therapeutic approaches.

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa.

The immunopathogenesis of HS is partially understood and exhibits features of an autoinflammatory disease; it is associated with the potential involvement of B cells and the contribution of Th1 or Th17 cell subsets. Recently, the pathogenic role of both innate immunity and IL-1 family cytokines in HS has been deeply investigated. Several agents targeting the IL-1 family pathway at different levels are currently available and under investigation for the treatment of HS. HS is still characterized by unmet clinical needs and represents an expanding field in the current scientific research. The aim of this narrative review is to describe the pathological dysregulation of IL-1 family members in HS and to provide an update on therapeutic strategies targeting IL-1 family cytokine signaling. Further clinical and preclinical data may likely lead to the enrichment of the therapeutic armamentarium of HS with IL-1 family cytokine antagonists.

Investigational systemic drugs for moderate to severe plaque psoriasis: What's new?

INTRODUCTION: The therapeutic armamentarium for the treatment of psoriasis, a chronic inflammatory skin disease, is now reasonably broad and structured, with several therapeutic agents that demonstrated a successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of the existing ones. AREAS COVERED: The aim of this review is to thoroughly explore new therapeutic strategies and novel drugs that are currently in the pipeline for the treatment of psoriasis, focusing primarily on agents that are currently in phase I/II of clinical development. Some of which retrace already existing therapeutic approaches, such as the IL23/Th17 pathway inhibition, while others unveil new and yet unexplored ones. EXPERT OPINION: Since the therapeutic landscape of psoriasis is wide, it is not yet clear whether novel agents will fill the remaining gaps in the context of a broader and more diversified set of oral and biologic therapies. Nevertheless, with the development of precision medicine approaches, the development of innovative targeted drugs will still have a therapeutic rationale in psoriasis.

Infectious adverse events in patients with atopic dermatitis treated with baricitinib.

Baricitinib is a JAK1-2 inhibitor recently approved in Europe and Japan for the treatment of moderate-to-severe atopic dermatitis in adult patients at doses of 2 and 4 mg daily. The aim of this article is to discuss the safety profile of baricitinib in atopic dermatitis using data from clinical trials and the supporting literature, with a focus on infectious adverse events. An integrated analysis of safety data from eight clinical trials described infections as the most frequent treatment-emergent adverse events, mainly of mild-to-moderate severity, notably upper respiratory tract infections and herpes simplex exacerbations. Real-world data are still limited and will contribute to precisely profile the patients that might benefit from this treatment.

Baricitinib is a drug taken by mouth, currently approved for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy, a medication that is designed to be absorbed into the bloodstream and work throughout the body. Baricitinib is available as 2- and 4-mg tablets and has been shown to improve the cutaneous manifestations, such as dry and cracked skin, redness and symptoms of atopic dermatitis, especially itchiness. Baricitinib is generally well tolerated. The most common adverse events that have emerged from clinical trials include headache, nausea and high cholesterol. Another reported side effect is an increased risk of infections, mainly of mild-to-moderate severity, especially upper respiratory tract infections such as nasopharyngitis (inflammation of the nose and throat) and reactivation of herpes zoster, a virus that causes a painful rash on one side of the body, and herpes simplex, which causes clustered blisters usually on the lips or genitals. There is still a lack of data from real-world experience, which will be important for the development of a more precise profile of patients who may benefit from this treatment.

IL-17 Inhibition: A Valid Therapeutic Strategy in the Management of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant negative impact on the quality of life of patients. To date, the therapeutic landscape for the management of the disease has been extremely limited, resulting in a profound unmet need. Indeed, adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the only approved biologic agent for HS, obtaining a therapeutic response in only 50% of HS patients. Numerous clinical trials are currently ongoing to test novel therapeutic targets in HS. The IL-17-mediated cascade is the target of several biologic agents that have shown efficacy and safety in treating moderate-to-severe HS. Both bimekizumab and secukinumab, targeting IL-17 in different manners, have successfully completed phase III trials with promising results; the latter has recently been approved by EMA for the treatment of HS. The aim of this review is to summarize the current state of knowledge concerning the relevant role of IL-17 in HS pathogenesis, highlighting the key clinical evidence of anti-IL-17 agents in the treatment of this disease.

Clinical Features and Response to Treatment in Elderly Subjects Affected by Hidradenitis Suppurativa: A Cohort Study.

Hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. Geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. This study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (≥65 years old). We designed a multicentric observational study, gathering data from seven Italian university hospitals. Demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. Overall, 57 elderly subjects suffering from HS were enrolled. At baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as Hurley III. The gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. Gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, Hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to Hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging.

Long-term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real-world Setting: An Interim Analysis Through 48 Weeks of Observation.

BACKGROUND: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. METHODS: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. RESULTS: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. CONCLUSION: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change.

Alopecia Areata Occurring after COVID-19 Vaccination: A Single-Center, Cross-Sectional Study.

Limited data concerning the development of autoimmune skin diseases after COVID-19 vaccination are currently available. Recently, a few reports described the development, worsening or recurrence of alopecia areata after the administration of COVID-19 vaccines. High variability in terms of disease onset following vaccination as well as the heterogeneous topical and/or systemic treatment approaches have been described. Methods: All patient-related data and images were obtained as part of clinical routine. Diagnosis of alopecia areata was established according to clinical and trichoscopic findings, along with the exclusion of common differential diagnoses. Results. Twenty-four patients, 20 females (83.3%) and four males (16.7%), with a mean age of 39.1 years (age range: 14-66 years), were examined for the occurrence of alopecia areata within 16 weeks after COVID-19 vaccination. Out of 24, 14 patients (58.3%) experienced a patchy alopecia areata, while an extensive disease occurred in 10/24 patients (41.7%): six patients with whole scalp involvement (alopecia areata totalis) and four patients with the whole body affected (alopecia areata universalis). Twelve patients reported a history of autoimmune disease (50%). Treatment with topical corticosteroid was performed in almost all patients with patchy alopecia areata, whilst it was associated with systemic drugs (corticosteroids, minoxidil, cyclosporin) in the case of generalized alopecia areata and alopecia areata universalis. Mean baseline values of Severity of Alopecia Tool (SALT) score decreased from 43.4 to 36.6 after 12 weeks of treatment, with evidence of hair regrowth in 16/21 patients. Conclusion. This study described the occurrence of alopecia areata after COVID-19 vaccination and its management that implicates the use of both topical and systemic therapies.

Melanoma on tattoos: a case study and review of the literature

Background: Decorative tattooing is a very widespread and constantly increasing practice, especially among young people. Objectives: Here, we report a case study of melanoma occurring on a tattoo on the left arm and provide an overview of all cases reported so far. Materials & Methods: A systematic literature search of publications was conducted from inception to September 2021 via Medline (PubMed), Scopus and Google Scholar, in order to identify all cases of primitive melanomas arising on tattoos. Results: In total, 35 cases (32 males, three females) of melanoma arising on tattoos on skin were identified. Interestingly, most melanomas occurred on dark blue (10/35), black (12/35) or blue tattoos (3/35). Conclusion: Due to the low number of melanoma cases arising on tattoos, it is not possible to confirm whether tattoos play a cancerogenic role. However, tattooing may make it more difficult to detect and monitor pigmented lesions, potentially delaying the diagnosis of cutaneous malignancies. Patients at high risk of melanoma should be warned about the risks associated with such procedures.

Similar Levels of Efficacy of Two Different Maintenance Doses of Adalimumab on Clinical Severity and Quality of Life of Patients with Hidradenitis Suppurativa.

Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4-43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29-39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages.

Factors associated with sunbed use among 3692 outpatients in 18 centers of the Italian Cancer League (LILT).

Indoor tanning is associated with an increased risk of skin cancer. Nonetheless, its use is still widespread. We aimed to investigate the socio-demographic and clinical characteristics of sunbed users in a group of participants in the skin cancer prevention campaign organized by the Italian Cancer League (LILT). During almost 2 years, 4409 individuals were screened in 18 centers. Participants reported having used sunbeds before the age of 15 years in 2.2% of cases, while after age 15 the prevalence of use was 22.2%. Participants with complete information were 3692. Sunbed users aged > 15 years were significantly more frequently females, young, living in Northern Italy, highly educated, and current or former smokers. They had darker phototype, more common nevi, had used sunbeds more frequently before the age of 15, reported a history of sunburns, and use of sunscreens. Indoor tanning is an important public health issue and a relevant target for primary prevention. However, not all countries have adopted the recommendations issued by the World Health Organization (WHO) on health risks associated with artificial tanning. A deeper insight into the topic may contribute to identify the best prevention strategies.