Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

BACKGROUND: Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. METHODS: Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03-34.65 kg/m2), aged 18-30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. RESULTS: VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: - 31.46 ± 9.53, p < 0.001) and the DLQI score (Δ%: - 45.44 ± 24.02, p < 0.001) after the intervention. These improvements coincided with significant decreases in TMAO (p < 0.001) and dROMs (p < 0.001) levels and a significant increase in PhA (Δ%: + 8.60 ± 7.40, p < 0.001). Changes in the GAGS score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjusting for Δ% FM. Changes in the DLQI score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjustment for Δ% FM. CONCLUSION: Given the side effects of drugs used for acne, there is an increasing need for safe, tolerable, and low-cost treatments that can be used for acne disease. The 45-day active phase of VLCKD demonstrated notable improvements in acne severity, and these improvements seemed to be attributable to the known antioxidant and anti-inflammatory effects of VLCKD.

Efficacy and Safety of bimekizumab in psoriasis management in real-life: bio-naïve vs bio-experienced.

Bimekizumab is the latest monoclonal antibody approved for the management of moderate-to-severe plaque psoriasis. Currently, data investigating its use in real-life setting are limited. Therefore, we performed a short term [(16 weeks (W)] real-life, monocentric, prospective study aiming to assess the efficacy and safety of bimekizumab, also comparing bio-naïve vs bio-experienced patients. Globally, 56 patients were included. At baseline, mean PASI and DLQI were 16.9±7.8 and 22.6±5.9, respectively. PASI75/90/100 were reached by 76.8%/50.0%/42.9% of patients at W4 and by 92.9%/82.1%/69.6% of subjects at W16. In our cohort, 29 (51.8%) patients were bio-naïve whereas 27 (48.2%) bio-experienced. At baseline, both PASI and DLQI were significantly higher in bio-naïve cohort as compared with bio-experienced group (PASI: 19.4±7.7 vs 14.2±7.0, p<0.05; DLQI: 25.3±4.5 vs 19.7±6.0, p<0.001). Despite not significant, a higher percentage of patients in bio-naïve cohort as compared with bio-experienced group reached PASI75 (79.3% vs 63.0%, p=0.176), PASI90 (62.1% vs 44.4%, p=0.186) and PASI100 (48.3% vs 37.0%, p=0.396) at W4. However, the percentage of PASI75/90/100 response were similar between the two cohorts at W16. Regarding safety, 3 candidiasis (5.4%) and 1 (1.8%) eczematous reaction were reported, without differences between the two groups. Finally, 2 (3.6%) bimekizumab discontinuation for treatment failure and 3 (5.4%) for AEs were collected.

Viral reactivation following COVID-19 vaccination: a review of the current literature.

Currently, four vaccines for COVID-19 have been licensed by the European Medicines Agency: two viral vector-based vaccines and two mRNA-based vaccines. Since their approval, several cutaneous reactions related to vaccination have been reported in the literature. Among these, viral reactivations are one of the most frequent. The aim of this article was to investigate the current literature regarding viral reactivations following COVID-19 vaccination, focusing attention on pityriasis rosea (PR), herpes zoster and herpes simplex. A comprehensive literature search using various databases was performed and we included metanalyses, reviews, letters to the editor, real-life studies, case series and reports. A total of 48 articles involving 2067 patients were selected. Of these, 32, 6 and 17 articles reported varicella zoster virus (VZV) reactivation (1758 patients), herpes simplex virus (HSV) (238 patients) onset and PR (71 patients), respectively (some articles discussed more than one of these three reactivations). Possible pathogenetic mechanisms underlying viral reactivation are still not understood. Also, the possible correlations between vaccination and viral reactivation should be clarified. Certainly, vaccination should not be discouraged.

Unaddressed Challenges in the Treatment of Cutaneous Melanoma?

Background and Objectives: While the management of noninvasive cutaneous melanoma (CM) is typically limited to a secondary excision to reduce recurrence risk and periodic follow-up, treating patients with advanced melanoma presents ongoing challenges. Materials and Methods: This review provides a comprehensive examination of both established and emerging pharmacologic strategies for advanced CM management, offering an up-to-date insight into the current therapeutic milieu. The dynamic landscape of advanced CM treatment is explored, highlighting the efficacy of immune checkpoint inhibitors and targeted therapies, either in monotherapy or combination regimens. Additionally, ongoing investigations into novel treatment modalities are thoroughly discussed, reflecting the evolving nature of melanoma management. Results: The therapeutic landscape for melanoma management is undergoing significant transformation. Although various treatment modalities exist, there remains a critical need for novel therapies, particularly for certain stages of melanoma or cases resistant to current options. Conclusions: Consequently, further studies are warranted to identify new treatment avenues and optimize the utilization of existing drugs.

Autoimmune Skin Diseases and Immune Checkpoint Inhibitors.

Immune system escape is one of the major strategies required for cancer growths. In this scenario, the advent of immune checkpoint inhibitors (ICIs) revolutionized the landscape of treatment options for tumors. Despite their wide use, these agents are associated with a unique spectrum of toxicities known as immune-related adverse events (irAEs). IrAEs are cause of treatment suspension (up to 60% of all causes of treatment interruption) and potentially impact on patients' quality of life. These toxicities are the main limitations on the use of these innovative drugs. IrAEs are peculiar, due to the mechanism of actions of ICIs, and any body organs may be involved (skin, thyroid, colon, lungs, in particular). Thus, the management often requires a multidisciplinary approach. The aim of this manuscript is to review current literature on autoimmune skin diseases described in association with ICIs (i.e., vitiligo, lupus erythematosus, vasculitis, morphea/scleroderma, alopecia areata, bullous pemphigoid, dermatomyositis), in order to provide a comprehensive overview for the physician.

Hidradenitis Suppurativa and JAK Inhibitors: A Review of the Published Literature.

Background: Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil's disease, is a chronic, inflammatory, recurrent, and debilitating skin disease of the hair follicles characterized by inflammatory, painful, deep-rooted lesions in the areas of the body characterized by the presence of the apocrine glands. Unfortunately, huge unmet needs still remain for its treatment. Objective: The purpose of our review was collecting all cases, case series, trials, and ongoing studies available in the literature on the use of this class of drugs for HS. Materials and Methods: The investigated manuscripts included trials, reviews, letters to the editor, real-life studies, case series, and reports. Manuscripts were identified, screened, and extracted for the relevant data following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Results: We selected 56 articles of which 25 met the selection criteria for our review. Among the JAK inhibitors to date, there is only one published clinical trial in the literature (Janus kinase 1 inhibitor INCB054707), a real-life study with 15 patients up to week 24 in which upadacitinib was used and a case series where tofacitinib was successfully used. Conversely, there are several ongoing clinical trials. Conclusions: Results to date in the literature show promising levels of efficacy and the safety of JAK inhibitors in HS. Several clinical trials are underway from which it will be very important to compare the available data. There are still too few studies conducted with a low sample size, so it remains critical to investigate this issue further in the future with a real-life study involving a large sample of patients in order to provide safe and viable therapeutic alternatives for HS.

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis.

Strategies on long-term management of patients affected by atopic dermatitis (AD) undergoing treatment with dupilumab achieving good clinical response (GCR) or experiencing dupilumab-related adverse events (AEs) are scant. Data of patients who implemented longer than scheduled dupilumab dosing interval due to GCR (at least 52 weeks of treatment and controlled AD activity [Eczema Area Severity Index ≤7 and Dermatology Life Quality Index ≤5 for at least 6 months]) or AEs (dupilumab-related and treatment-resistant conjunctivitis) were retrospectively collected. Dupilumab was tapered to Q3W or Q4W based on physician-patient shared decision. At baseline (T0) and each follow-up (week 16 [T1] and week 32 [T2]) disease severity was assessed. A total of 59 patients implemented longer than scheduled dosing interval (44 GCR, 15 AEs). Among these, 50 (35 GCR and 15 conjunctivitis) patients switched to 300 mg Q3W, while nine GCR subjects to Q4W. In the GCR group Q3W, 34 and 31 patients maintained clinical response at T1 and T2, whereas eight and seven Q4W subjects maintained clinical response at the same timepoints, respectively. No significant differences in AD severity were observed between T1 and T2 in both groups. Contrariwise, one Q3W and one Q4W patients at T1, and three Q3W and one Q4W subjects at T2, returned to dupilumab labeled dosage due to AD worsening. In conjunctivitis group, dupilumab Q3W was maintained in eight and four patients at T1 and T2, respectively. Three patients at T1 and three at T2 subjects returned to the labeled interval due to conjunctivitis remission. Four patients at T1 and four subjects at T2 interrupted dupilumab due to the persistence of conjunctivitis. A longer dupilumab dosing interval may be a valuable option in patients with a GCR and may be a useful strategy to reduce treatment-related conjunctivitis, also with pharmacoeconomic benefit.

Risankizumab treatment in psoriasis patients who failed anti-IL17: A 52-week real-life study.

Recent knowledge on the key role of interleukin (IL) 23/17 axis in psoriasis pathogenesis, led to development of new biologic drugs. Risankizumab is a humanized immunoglobulin G1 monoclonal antibody specifically targeting IL23. Its efficacy and safety were showed by both clinical trials and real-life experiences. However, real-life data on effectiveness and safety of risankizumab in patients who previously failed anti-IL17 are scant. To assess the efficacy and safety of risankizumab in patients who previously failed anti-IL17. A 52-week real-life retrospective study was performed to assess the long-term efficacy and safety of risankizumab in patients who previously failed anti-IL17. A total of 39 patients (26 male, 66.7%; mean age 50.5 ± 13.7 years) were enrolled. A statistically significant reduction of psoriasis area severity index (PASI) and body surface area (BSA) was assessed at each follow-up (PASI at baseline vs. week 52: 13.7 ± 5.8 vs. 0.9 ± 0.8, p < 0.0001; BSA 21.9 ± 14.6 vs. 1.9 ± 1.7, p < 0.0001). Nail psoriasis severity index improved as well, being statistically significative only at week 16 and thereafter [9.3 ± 4.7 at baseline, 4.1 ± 2.4 (p < 0.01) at week 16, 1.4 ± 0.8 (p < 0.0001) at week 52]. Treatment was discontinued for primary and secondary inefficacy in 1(2.6%) and 3(7.7%) patients, respectively. No cases of serious adverse events were assessed. Our real-life study confirmed the efficacy and safety of risankizumab, suggesting it as a valuable therapeutic weapon among the armamentarium of biologics, also in psoriasis patients who previously failed anti-IL17 treatments.

Ixekizumab and brodalumab indirect comparison in the treatment of moderate to severe psoriasis: Results from an Italian single-center retrospective study in a real-life setting.

Eleven biologic drugs are currently approved for psoriasis management. Real-life studies are needed to guide clinicians in choosing a tailored-tail therapy. The aim of our retrospective study is to indirectly compare the efficacy and safety of ixekizumab and brodalumab in psoriasis patients. A single-centre real-life retrospective study was performed enrolling moderate-to-severe psoriatic patients under biologic treatment with ixekizumab or brodalumab. For each patient, clinical and demographic data were collected and the effectiveness and safety of brodalumab and ixekizumab treatment were evaluated at weeks 4, 12, and 24. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) were used for psoriasis severity. A total of 139 patients were included in the study: 98(70.5%) and 41(29.5%) patients received ixekizumab and brodalumab, respectively. Mean PASI and BSA significantly reduced at each follow up for both ixekizumab and brodalumab groups. Even if ixekizumab reached higher rates of PASI90 and PASI100 than brodalumab (PASI90: 43.8% vs. 39.0% PASI100: 20.4% vs. 17.1% at week4 and PASI90: 83.6% vs. 75.6% PASI100: 71.5% vs. 60.9% at week24), these results were not statistically significant. Adverse events, mainly mild, were registered in 25.5% of ixekizumab and 26.8% of brodalumab group, respectively. Discontinuation rate was higher for brodalumab (17.1% vs. 9.1%), without statistical significance. Our study showed comparable efficacy and safety for ixekizumab and brodalumab.

A 24-weeks real-world experience of dupilumab in adolescents with moderate-to-severe atopic dermatitis.

Dupilumab is a monoclonal antibody approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥12 years. Large, double-blind, randomized, placebo-controlled trials showed its efficacy and safety in adolescents. However, real-life data are few. The aim of this monocentric retrospective observational study (December 2020-November 2021) was to assess the effectiveness and safety of dupilumab in AD adolescents treated for at least 24 weeks. For each patient demographic features, clinical data and adverse events (AEs) were collected. Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS) for pruritus (P-NRS) and for sleep disturbances (S-NRS), and Children Dermatology Life Quality Index (cDLQI) were assessed at baseline, week (W)4, W16, and W24. Twenty-seven patients (18 males; 15.23 ± 3.54 years) were enrolled. Dupilumab was administered subcutaneously at dosage of 600 mg induction dose, followed by 300 mg every 2 weeks in 14 (51.85%) patients with a weight ≥60 kg, while 13 (48.15%) patients with a weight <60 kg were treated with dupilumab 200 mg every 2 weeks after a loading dose of 400 mg. The mean EASI score at baseline was 26.96 ± 4.93 and significantly reduced to 3.74 ± 3.47 at W16 (<0.001), and to 3.4 ± 5.04 at W24 (p < 0.001). P-NRS (9.14 ± 0.94 at baseline vs. 2.33 ± 4.93 at W16 [p < 0.001], and 1.45 ± 2.35 at W24 [p < 0.001]), S-NRS (7.88 ± 1.64 at baseline vs. 0.92 ± 1.35 at W16 [p < 0.001], and 1.66 ± 2.84 at W24 [p < 0.0001]) and cDLQI (26.62 ± 4.45 vs. 2.18 ± 3.51 at baseline vs. 2.18 ± 3.51 at W16 [p < 0.001], and 3.4 ± 5.02 at W24 [p < 0.001]) showed a statistically significative improvement as well. Injection-site reaction (5/27; 18.52%), conjunctivitis (2/27; 7.41%), and asthenia (2/27; 7.41%) were the main AEs collected. This study seems to confirm the efficacy and safety of dupilumab in adolescents with moderate-to-severe AD also in real-life setting.

The Treatment of Advanced Melanoma: Therapeutic Update.

Cutaneous melanoma is the main cause of death for skin cancer. The majority of patients with a diagnosis of melanoma have localized disease, which can be successfully treated with surgical treatment. However, the surgical approach is not curative for advanced melanoma (AM). Indeed, the management of AM is still challenging, since melanoma is the solid tumor with the highest number of mutations and cancer cells have the capacity to evade the immune system. In the past, the treatment of AM relied on chemotherapeutic agents, without showing efficacy data. Recent knowledge on melanoma pathogenesis as well as the introduction of immunotherapies, targeted therapies vaccines, small molecules, and combination therapies has revolutionized AM management, showing promising results in terms of effectiveness and safety. The aim of this review is to assess and to discuss the role of emerging therapies for AM management in order to obtain a complete overview of the currently available treatment options and future perspectives.

Dupilumab effectiveness for the treatment of patients with concomitant atopic dermatitis and chronic rhinosinusitis with nasal polyposis.

Dupilumab is a fully human monoclonal antibody targeting interleukin (IL) 4 and IL13 pathways. We performed a retrospective observational study to evaluate the efficacy of dupilumab for the treatment of adult patients referred to our department, from January 2019 to May 2021, with a diagnosis of moderate to severe atopic dermatitis (AD) and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), with a clinical indication for dupilumab treatment. Skin disease activity was assessed using EASI, Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), and Dermatology Life Quality Index (DLQI). The CRSwNP activity was evaluated using 22-item Sino-Nasal Outcome Test (SNOT-22), endoscopic nasal polyp score (ENPS), nasal congestion or obstruction score (scale 0-3), loss-of-smell score (scale 0-3), and rhinosinusitis disease severity (visual analog scale 0-10 cm). A significant improvement of all the score values was recorded assessing patients at baseline, week (W)16, and W24. In particular, concerning the CRSwNP, a reduction of ENPS score (baseline: 4.9 ± 1.85; W16: 2.49 ± 1.42, p < 0.01; W24: 1.68 ± 1.25, p < 0.01) and SNOT-22 (baseline: 35.9 ± 19.11; W16: 12.85 ± 6.31, p < 0.01; W24: 10.71 ± 7.29, p < 0.01) was observed. Furthermore, dupilumab is a labeled drug for the treatment of both AD and CRSwNP. The use of a single drug to obtain the improvement up to the near remission of AD and CRSwNP increases not only patient's compliance with the treatment, but also the benefits in terms of health cost related to these chronic diseases.