Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study.

BACKGROUND: Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. METHODS: Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. RESULTS: VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: - 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). CONCLUSION: The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity.

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.

Guselkumab in Patients with Scalp Psoriasis: A post hoc Analysis of the VOYAGE 2 Phase III Randomized Clinical Trial.

Scalp psoriasis affects approximately 80% of patients with psoriasis and can negatively impact their quality of life. This post hoc analysis of the VOYAGE 2 Phase III randomized clinical trial evaluated scalp response to guselkumab treatment and its association with skin response and patient-reported outcomes. The study included patients with moderate-to-severe plaque psoriasis and baseline scalp psoriasis who were initially randomized to receive guselkumab. Patients were divided into 3 groups based on their achievement of a Psoriasis Area and Severity Index 90 response at week 28: responder continuation, non-responder continuation and responder withdrawal. In all 3 groups, mean Psoriasis Area and Severity Index head and scalp-specific Investigator's Global Assessment scores improved through week 28. In the responder withdrawal group, these scores worsened after treatment withdrawal at week 28, but remained stable through week 48 in both continuation groups. Trends in Dermatology Life Quality Index and Psoriasis Symptoms and Signs Diary itch scores mirrored those of mean scalp-specific Investigator's Global Assessment scores through week 48. Within-subject correlations were 0.83 between scalp-specific Investigator's Global Assessment and Psoriasis Area and Severity Index head scores and 0.78 between scalp-specific Investigator's Global Assessment and Psoriasis Symptoms and Signs Diary itch scores. Through week 252, Psoriasis Area and Severity Index head scores remained stable in the responder continuation group, improved in the non-responder continuation group and rapidly improved by week 84 in the responder withdrawal group after retreatment.

Efficacy of JAK inhibitors in the treatment of psoriasiform atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease with multiple clinical manifestations. Among AD phenotypes, psoriasiform AD shows the coexisting of eczematous itching lesions in flexural areas with psoriasiform plaques. The use of anti-IL-4 and anti-IL-13 in psoriasiform AD may lead to therapeutic failure or worsening of manifestations. A recent Delphi consensus proposed JAK inhibitors (JAKi) as a viable alternative, even in the first line, in patients with different clinical phenotypes of AD, including psoriasiform AD. A retrospective analysis of patients in our dermatology clinic with moderate-severe AD and treated with JAKi was performed. Among the 192 overall patients, 21 had psoriasiform AD. EASI, p-NRS and DLQI were the severity scores considered and their reduction was observed in all 21 patients at weeks 4, 16 and 24 of treatment. At week 16 the percentage of patients achieving EASI-75 and EASI-90 was 80.95% and 66.67%, respectively. While at week 24 95.23% of patients achieved EASI-75 and 85.71% obtained EASI-90. No adverse event lead to treatment interruption. This study confirmed the clinical effectiveness of JAKi treatment in adult patients with moderate-to-severe psoriasiform AD, with a good safety profile. These drugs are proposed as the first choice for the treatment of this form of AD, although further studies with larger cohorts are required.

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.

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.

The effect of the ketogenic diet on Acne: Could it be a therapeutic tool?

Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation, and bacterial colonization of the hair follicles of the face, neck, chest and back by Propionibacterium acnes. Overall, inflammation and immune responses are strongly implicated in the pathogenesis of acne. Although early colonization with Propionibacterium acnes and family history may play an important role in the disease, it remains unclear exactly what triggers acne and how treatment affects disease progression. The influence of diet on acne disease is a growing research topic, yet few studies have examined the effects of diet on the development and clinical severity of acne disease, and the results have often been contradictory. Interestingly, very low-calorie ketogenic diet (VLCKD) has been associated with both significant reductions in body weight and inflammatory status through the production of ketone bodies and thus it has been expected to reduce the exacerbation of clinical manifestations or even block the trigger of acne disease. Given the paucity of studies regarding the implementation of VLCKD in the management of acne, this review aims to provide evidence from the available scientific literature to support the speculative use of VLCKD in the treatment of acne.

Real-life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104-week multicenter retrospective study - IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28-02-2023], after first online publication: 'humanized monoclonal antibody' has been changed to 'fully human monoclonal antibody' in the preceding sentence.] OBJECTIVES: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. METHODS: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. RESULTS: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. CONCLUSION: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

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.

Very low-calorie ketogenic diet (VLCKD) in patients with psoriasis and obesity: an update for dermatologists and nutritionists.

Psoriasis is a chronic skin immune-mediated disease with systemic pro-inflammatory activation; both genetic and lifestyles factors contribute to its pathogenesis and severity. In this context, nutrition plays a significant role, per se, in psoriasis' pathogenesis. Obesity is another important risk factor for psoriasis, and weight reduction may improve psoriasis' clinical severity. The excess body weight, particularly visceral fat mass, can affect both drug's pharmacokinetics and pharmacodynamics. Therefore, psoriasis and obesity share a certain degree of synergy, and the chronic inflammatory state represents the basis of this vicious cycle. Evidence reported that nutrition has different impact on the clinical severity of psoriasis, though some specific diets have been more investigated in clinical studies compared to others. Diets with systemic anti-inflammatory properties seem to have a higher effect on improving the clinical severity of psoriasis. Of interest, very-low-calorie ketogenic diet (VLCKD), through the production of ketone bodies, has been associated with both a significant reduction of body weight and inflammatory state. VLCKD leading to both weight loss and reduction of systemic inflammation may decrease the exacerbation of the clinical manifestations or even it may block the trigger of psoriatic disease. This dietary pattern could represent a potential first-line treatment in psoriatic patients with obesity. The review aims to summarize the current evidence regarding VLCKD and psoriasis with specific reference to antioxidant and anti-inflammatory effects of this dietary pattern.

Real world practice indirect comparison between guselkumab and risankizumab: Results from an Italian retrospective study.

IL-23-inhibitors, such as guselkumab and risankizumab, represent the newest class of biologics approved for psoriasis. Phase III trials have shown their efficacy and safety. However, real life data are still scant. to indirectly compare the effectiveness, safety and tolerability of guselkumab and risankizumab in real world practice. An Italian single-center retrospective cohort study enrolling moderate-to-severe psoriasis patients from September 1, 2018 and December 31, 2020 was performed to indirectly compare guselkumab and risankizumab efficacy and safety. Sixty eight patients were included (36 received guselkumab and 32 risankizumab). The groups were comparable for all analyzed characteristics, except for mean psoriasis duration (p < 0.01) which was higher for guselkumab. In guselkumab group, mean PASI reduced from 16.1 ± 6.4 (baseline) 2.1 ± 0.9 (week-28) (p < 0.001) up to 0.9 ± 0.8 (week-44) (p < 0.001). In risankizumab group mean PASI decreased from 13.5 ± 4.9 (baseline) 1.9 ± 0.8 (p < 0.001), (week-28) (p < 0.001) up to 0.9 ± 0.4 (week-40) (p < 0.001). No significant difference in mean PASI and BSA were observed between the treatments. No cases of serious AEs, injection site reaction, candida, malignancy, cardiovascular events were reported in both groups. Guselkumab and risankizumab showed favorable efficacy and safety profile, being comparable in terms of PASI90 and PASI100 responses as well as in AEs frequency and discontinuation rates.

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.

Risankizumab shows high efficacy and maintenance in improvement of response until week 52.

Risankizumab has been recently approved for moderate-to-severe plaque psoriasis; however, real-life studies are scarce. Analysis of possible predictor factors of treatment response are limited to body mass index (BMI) and previous biologic experience. Our objectives were to evaluate the effectiveness and safety of Risankizumab and to investigate on possible predictor factors response. We retrospectively analyzed 166 patients from two centers in Italy who undergone Risankizumab for psoriasis. The proportion of patients achieving a 100%, 90%, 75% of improvement in Psoriasis Area Severity Index (PASI) and PASI <3 were collected at weeks 16, 28, 40, and 52. Study population was analyzed in subgroups to investigate possible predictors of response to Risankizumab since week 40. At the time of analysis 165, 103, 30, and 11 patients had completed 16, 28, 40, and 52 weeks of treatment, respectively. The mean PASI score decreased from 12.5 ± 5.1 at baseline to 1.9 ± 2.4 at week 16. Similar reductions were observed when considering PASI <3, PASI 75, PASI 90, and PASI 100. Previous biologics failure, different smoking habits, obesity, and joint involvement resulted in a lower response to risankizumab. In particular, significant differences in mean PASI at any time-points was observed between psoriatic arthritis (PSA) and non-PSA patients: 2.7 versus 1.7 (p = 0.036), 1.9 versus 0.4 (p = 0.006), and 4.1 versus 0.5 (p = 0.016) at 16, 28, and 40 weeks, respectively. No difference in response to risankizumab occurred in the case of involvement of difficult-to-treat areas. In this population, Risankizumab was effective and safe. Smoking habits, joint involvement, obese status, and previous biologic experience may negatively affect treatment response, while difficult body sites involvement have minor impact.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Eczematous drug eruption in patients with psoriasis under anti-interleukin-17A: does interleukin-22 play a key role?

BACKGROUND: Eczematous drug eruption (EDE) is a spongiotic skin reaction in response to systemic medications. To date, EDE has been described in patients treated with anti-interleukin (IL)-17A monoclonal antibodies with a prevalence of 2.2%-12.1%. AIM: To describe the clinical and histological features and the skin cytokine milieu in patients with EDE induced by anti-IL-17A biologics. METHODS: This was a prospective study, enrolling patients with psoriasis who developed EDE during treatment with two anti-IL-17 biologics, ixekizumab and secukinumab, from June 2019 to April 2021. Skin biopsies were taken from all patients: a 5-mm lesional biopsy (LB) and a 3-mm nonlesional biopsy (NLB). The LB sample was split into two parts, one for histological examination and the other for cytokine profile evaluation. RESULTS: During the study period, treatment with an anti-IL-17A drug was given to 289 patients of whom 8 (2.8%) developed EDE during the treatment. Histopathological evaluation suggested a diagnosis of spongiotic dermatitis in all eight patients. Cytokine gene expression showed a predominance of T helper (Th)2/Th22 cytokines in EDE lesions with a large increase in IL-4, IL-22 and S100A7 levels in both LB and NLB samples compared with healthy skin. IL-4, IL-22 and S100A7 were significantly higher in LB compared with NLB samples. IL-26 levels were also significantly increased in both LB and NLB compared with healthy skin, whereas low levels of IL-23A were found in both LB and NLB. CONCLUSION: Eczematous drug eruption skin lesions have mainly Th2/Th22 features, with IL-22 playing a major role in their pathogenesis. EDE seems to be the result of an imbalance towards a Th2/Th22 response, secondary to the blockade of IL-17A activity.

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti-interleukin-17 treatment: A real-life 52-week retrospective study.

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)-23 inhibitor approved for the treatment of moderate-to-severe-psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti-IL-12/23 and/or anti-IL-17 treatment. A 52-week single-center retrospective study was performed enrolling moderate-to-severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti-IL-17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti-IL-12/23 compared to anti-IL-17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real-life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate-to-severe psoriasis even in those who previously failed ustekinumab and/or anti-IL-17 treatment.

Onset of vitiligo in a psoriasis patient on ixekizumab.

INTRODUCTION: Vitiligo is an acquired skin disorder clinically characterized by hypopigmentated macules and patches. Psoriasis is a chronic-inflammatory-skin-condition characterized by erythematous-plaques covered with scales particularly over the extensor-surfaces, scalp, and lumbosacral region. Recent major-researches-advancements have significantly expanded our understanding of psoriasis-pathophysiology, resulting in the development of highly effective targeted-therapies, such as anti TNFα, IL-12/23-inhibitors, IL-17-inhibitors, or IL-23-inhibitors. Particularly, ixekizumab, a humanized-monoclonal immunoglobulin-G 4 antibody, specifically binding IL-17A, demonstrated strong efficacy in threating recalcitrant psoriasis. Nevertheless, paradoxical reactions due to IL-17 inhibitors have been described. CASE REPORT: Herein, we report the case of a 53-year-old Caucasian man who obtained complete skin clearance of psoriasis plaques after 16 weeks of ixekizumab treatment together with the appearance of vitiligo patches localized on the facial area. He had never suffered of vitiligo and his family history excluded vitiligo diagnosis. We also could exclude post inflammatory psoriasis hypopigmentation because of absence of facial involvement at baseline. Our experience suggests that vitiligo might be considered a rare adverse effects of anti-IL-17 therapy.

Therapeutic update of biologics and small molecules for scalp psoriasis: a systematic review.

Scalp psoriasis represents the most common difficult-to-treat area in psoriasis patients. Its presence is linked to severe discomfort and impairment of quality of life given the associated symptoms (most of all, scaling and pruritus) and the location in a highly visible area, thus a prompt treatment is required. Its management may be challenging as the scalp is quite sensitive to long-term treatment with topical corticosteroids and usually resistant to topical and systemic agents. Likely, the currently available therapeutic armamentarium has been enriched with biologicals and small molecules that revolutionized psoriasis treatment and that of scalp psoriasis. Nevertheless, the lack of international dedicated guidelines pushed us to perform a comprehensive review on the efficacy and safety of biologics and small molecules on scalp psoriasis with the aim to put the basis for a therapeutic algorithm. After reviewing all the available evidence on the short-term and long-term efficacy of biologics and small molecules on scalp psoriasis the use of the newest biologics (anti-IL-17 and anti-IL-23) seems to be linked to the highest clinical performances in controlling scalp psoriasis. However, head-to-head comparisons between different biologics or biologics and small molecules are lacking. Hence, treatment selection should always be individualized.

A Critical Reappraisal of Off-Label Use of Photodynamic Therapy for the Treatment of Non-Neoplastic Skin Conditions.

BACKGROUND: In the past 30 years, topical photodynamic therapy (PDT) has been investigated for the treatment of a broad spectrum of cosmetic, inflammatory, and infectious skin conditions with variable, and often contrasting, results. However, the non-expert clinician may be in difficulty evaluating these results because different sensitizers, concentrations, formulations, light sources, and irradiation protocols have been used. In addition, many of these studies have poor quality design being case reports and uncontrolled studies of few cases. SUMMARY: With the aim to clarify the potential usefulness of PDT for the treatment of infectious and inflammatory skin diseases as well as selected cosmetic indications, we searched for randomized controlled clinical trials, non-randomized comparative studies, retrospective studies, and case series studies with a number of at least 10 patients, published since 1990. Later, we reappraised the results in order to give a simple critical overview. Key Messages: Evidence from the literature seems to strongly support the use of ALA- and MAL-PDT for the treatment of common skin diseases such as acne, warts, condylomata, and Leishmania skin infection and for photorejuvenation, i.e., the correction of selected cosmetic changes of aging and photoaging. For other disorders, the level of evidence and strength of recommendation are lower, and controlled randomized studies with prolonged follow-ups are necessary in order to assess the clinical usefulness and other potential advantages over current treatment options.