Effectiveness and safety of risankizumab in HIV patients with psoriasis: A case series.

Biological therapies represent the gold-standard treatment of severe forms of plaque psoriasis. However, people living with HIV are often under-treated for psoriasis because very limited data are available on the use of biologics in this population. We report four cases of patients affected by HIV and moderate-to-severe plaque psoriasis, all treated with risankizumab, a monoclonal antibody that selectively targets interleukin-23. After 16 weeks, all patients experienced complete or almost complete skin clearance without any adverse events. Data on the effectiveness and safety of biological therapies in people living with HIV are limited to case reports or small case series, especially for the most recently approved inhibitors of interleukin-23. Our experienced, although limited, supports the role of risankizumab as a safe and effective therapy for psoriasis amongst patients living with HIV.

Rapidly and successful improvement of nail psoriasis with risankizumab.

This clinical case demonstrates quick resolution of nail psoriasis in a patient treated with risankizumab, highlighting the role of IL-23 in the pathogenesis of nail psoriasis.

Circadian Oscillations of Minimal Erythema Dose (MED) are Also Influenced by Diet in Patients with Psoriasis: A Chronomedical Study.

INTRODUCTION: Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations. METHODS: In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched. RESULTS: In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p < 0.001). The time effect was statistically significant in both groups before and after phototherapy. In the second phase, we enrolled 144 PsO patients (vegan, vegetarian, paleo, ketogenic, intermittent circadian fasting, and omnivore). MED circadian oscillations preserved a significant difference also after clearance and were influenced by diet type and time of day (p < 0.001). In particular, vegans displayed the lowest MED values, whilst Ramadan fasting showed the highest values in morning, afternoon, and evening. CONCLUSIONS: Diet, like other ongoing therapies, should be reported in the medical records of patients with psoriasis undergoing NB-UVB and patients with lower MEDs should be preferentially treated in the morning when the MED is higher.

The Relevant Oral Burden of Patients with Hidradenitis Suppurativa.

INTRODUCTION: Interleukin-17 plays a pivotal role in both hidradenitis suppurativa (HS) and in maintaining oral homeostasis, but their potential link remains unknown. Thus, we aimed to evaluate and quantify the oral burden of patients with HS. METHODS: In this real-life, multicenter, cross-sectional study, patients with HS were clinically evaluated by two board-certified dermatologists and two board-certified dentists. Oral comorbidities were carefully collected with medical history and therapeutic information. RESULTS: A total of 102 patients (44.0 ± 0.9 years, body mass index 27.0 ± 2.2 kg/m2) were enrolled. Remarkably, 48% and 43% did not undergo at least an oral hygiene or a dental visit each year, respectively. Oral disorders were found in 55.9% of patients with HS, in particular 39.2% had caries and 46.7% reported at least one missing tooth. The main oral manifestations in patients with HS were recurrent aphthous stomatitis (N = 19, 19.2%), amalgam tattoo (N = 14, 14.1%), leukoplakia (N = 11, 11.1%), nicotinic stomatitis (N = 9, 9.1%), papilloma (N = 8, 8.1%), and geographic tongue (N = 8, 8.1%). Whilst the main predictor of oral pathological conditions was Hurley staging (P = 0.0276), multivariate regression analysis indicated that gender and International Hidradenitis Suppurativa Severity Score System (IHS4) were the main predictors for the presence of caries and number of missing teeth. CONCLUSION: As a result of the relevant oral burden in patients with HS, dentists should be part of the multidisciplinary team and oral education should be promoted among patients with HS.

Effectiveness of risankizumab in plaque psoriasis with involvement of difficult-to-treat areas: a real-world experience from two referral centers.

The management of plaque psoriasis that affects difficult-to-treat areas can be challenging. Biologics have become the treatment of choice for moderate-to-severe plaque psoriasis. However, there are limited data on their efficacy in difficult-to-treat sites (including scalp, palms/soles, nails and genitalia). We conducted a 52-week retrospective study to evaluate the effectiveness of risankizumab in 202 patients with moderate-to-severe involvement of at least one difficult-to-treat area. One hundred and sixty-five patients had scalp psoriasis, 21 had involvement of palms or soles, 72 were affected by genital psoriasis, and 50 patients reported the involvement of the fingernails. After one year of treatment, 97.58% of patients with scalp involvement, 95.28% of patients with palmoplantar psoriasis, 100% of patients with genital psoriasis and 82% of patients with nail involvement achieved a site-specific Physician's Global Assessment of 0 or 1 (clear or almost clear). No serious adverse events were observed during the study. Our study supports the effectiveness of risankizumab in plaque psoriasis involving difficult-to-treat sites.

Long-term management of pediatric psoriasis with ixekizumab: a case report.

Psoriasis in pediatric patients is uncommon and the management of moderate-to-severe cases can be challenging. We report the case of a 17-year-old girl who presented with severe plaque psoriasis unresponsive to UVB phototherapy. The Psoriasis Area Severity Index (PASI) was 18 and the Dermatology Life Quality Index was 24. We decided to prescribe ixekizumab, observing complete skin clearance after only 8 weeks. The patient is still on treatment with no reported adverse events after two years.

A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist.

Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies.

Do Sleep Disorders and Western Diet Influence Psoriasis? A Scoping Review.

Western diet may trigger sleep disorders and vice versa, but their single and mutual effects on systemic inflammatory diseases (i.e., psoriasis) are far from being fully elucidated. At the same time, psoriatic patients display a great burden of sleep disorders and dysmetabolisms related to an unhealthy lifestyle (i.e., diet). These patients are also affected by a chronic disorder deeply modulated by environmental factors (i.e., sleep and diet) capable to influence drug-response and disease progression. Thus, we aimed to summarize the evidence in the literature that may highlight a potential link among psoriasis-diet-sleep in order to further promote a multidisciplinary approach to psoriatic patients in the scientific community.

Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle.

Vitiligo is an acquired skin depigmentation disease involving multiple pathogenetic mechanisms, which ultimately direct cytotoxic CD8+ cells to destroy melanocytes. Abnormalities have been described in several cells even in pigmented skin as an expression of a functional inherited defect. Keratinocytes regulate skin homeostasis by the assembly of a proper skin barrier and releasing and responding to cytokines and growth factors. Alterations in epidermal proliferation, differentiation, and lipid composition as triggers for immune response activation in vitiligo have not yet been investigated. By applying cellular and lipidomic approaches, we revealed a deregulated keratinocyte differentiation with altered lipid composition, associated with impaired energy metabolism and increased glycolytic enzyme expression. Vitiligo keratinocytes secreted inflammatory mediators, which further increased following mild mechanical stress, thus evidencing immune activation. These findings identify intrinsic alterations of the nonlesional epidermis, which can be the prime instigator of the local inflammatory milieu that stimulates immune responses targeting melanocytes.

Facial atopic dermatitis may be exacerbated by masks: insights from a multicenter, teledermatology, prospective study during COVID-19 pandemic.

BACKGROUND: Patients with atopic dermatitis (AD) display a defective skin barrier, consequently they may experience inflammatory flares with different exposures, including masks. Actually, beside scattering case reports, no study focused on the possible AD flaring due to masks. METHODS: In this multicenter prospective study AD patients with facial manifestation were followed with teledermatology and evaluated by two board-certified dermatologists at the baseline (T0) and after 1 month (T1) in which patients started to wear masks >6 hours per day. Demographics and clinical parameters, included and not limited to Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI), were carefully collected and analyzed. RESULTS: We enrolled 57 AD patients (M/F 28/29, 33.91±12.26 years old) that wore surgical masks (38 [66.7%]), community masks (11 [19.3%] and N95 (8 [14.0%]). Both DLQI and EASI increase during the time period (P<0.0001). DLQI variation was not influenced by age, BMI, and gender, mask type used and AD therapy (P=0.99), whilst EASI variation was significantly influenced by BMI, gender, and therapy (P=0.004). CONCLUSIONS: Mask wearing may prove detrimental to patients with atopic eczema and the same may not necessarily be the case for asthma patients.

Masks trigger facial seborrheic dermatitis and psoriasis: evidence from a multicenter, case-control study during COVID-19 pandemic.

BACKGROUND: Wearing masks is an optimal preventive strategy during COVID-19 pandemic, but it may increase facial sebum production. However, few case reports have described seborrheic dermatitis (SeBD) and psoriasis (PsO) flares due to masks. Hence, we conducted a multicenter study to clarify the possibility of increased SeBD and PsO flares in association with mask wearing during the COVID-19 pandemic. METHODS: This multicenter study enrolled patients with a diagnosis of facial SeBD and PsO. All dermatological consultations were conducted in teledermatology at baseline (T0) and after 1 month (T1) Of >6 hours/day wearing mask. PsO patients were assessed using PsO Area and Severity Index (PASI) and self-administered PASI (SAPASI), whilst SeBD patients with symptom scale of seborrheic dermatitis' (SSSD) and seborrheic dermatitis area and severity index (SEDASI). RESULTS: A total of 33 (20 males, 13 females, average age 43.61±9.86) patients with PsO and 33 (20 males, 13 females, average age 44.00±8.58) with SeBD were enrolled. After 1 month, PsO patients displayed higher values of both PASI and SAPASI (P<0.0001), while SeBD patients experienced a flare, as testified by the increment of both SSSD and SEDASI (P<0.0001). Mask type did not seem to influence the flare severity. CONCLUSIONS: Masks remain an optimal preventive strategy during COVID-19 pandemic, but patients with PsO and SeBD may experience facial flares. Thus, therapeutic approach should be more aggressive in these groups of patients to counteract the triggering effect of masks.

Secukinumab Loss of Efficacy Is Perfectly Counteracted by the Introduction of Combination Therapy (Rescue Therapy): Data from a Multicenter Real-Life Study in a Cohort of Italian Psoriatic Patients That Avoided Secukinumab Switching.

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0-9.0] and 13 [12.0-15.0], to 3 [2.8-4.0] and 3 [2.0-3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.

Antihistamines-refractory chronic pruritus in psoriatic patients undergoing biologics: aprepitant vs antihistamine double dosage, a real-world data.

BACKGROUND: Psoriasis-related pruritus (PRP) in patients under systemic treatment is challenging. The risk to switch anti-psoriatic drugs and to lose response to previous therapy is high, thus dermatologists prefer to add an anti-pruritic agent. OBJECTIVES: To evaluate the effect of anti-histamines and aprepitant in treating PPR of psoriatic patients undergoing systemic anti-psoriatic therapies. METHODS: A pilot observational open-label study was performed on responsive psoriatic patients with PPR under treatment. Initial therapy included oral rupatadine (10 mg/day for 30 days). In case of the Epworth Sleepiness Scale (ESS) was above 14, patients were switched to aprepitant (80 mg/day for 7 days), otherwise, rupatadine dosage was increased (20 mg/day for 7 days). Clinical evaluation was performed at the baseline (T0) and after 7 days (T7). RESULTS: We enrolled 40 patients with PPR, 20 in each group. Age, gender, Psoriatic arthritis (PsA) and the itch - VAS, were matched. At T7, aprepitant displayed higher improvements than rupatadine (itch - VAS = 4 [3-5] vs 8.5 [8-9], p < .01, DLQI = 14 [13-16] vs. 18 [16-21], p < .01 and ESS = 5 [4-7] vs 15 [14-16], p < .01). Doubling the rupatadine dosage from 10 mg to 20 mg/day only slightly improve itch (itch - VAS = 9 [8-10] vs 9 [8-9], p = .03), conversely no modifications in the quality of life (DLQI = 18 [17-20] vs 18 [17-21], p = .73) and increased sleepiness (ESS = 10 [9-11] vs 15 [14-16], p < .01). CONCLUSIONS: Aprepitant may be a valid alternative in PPR patients with ESS >14 under antihistamines.

Frequency of phototherapy for treating psoriasis: a systematic review.

INTRODUCTION: Narrow band ultraviolet B (NB-UVB) and psoralen-ultraviolet A (PUVA) remain inexpensive and effective anti-psoriatic therapies adopted worldwide with different frequency protocols. We aimed to systematically assess the evidence on the effects of different frequency protocols of phototherapy in treating psoriasis. EVIDENCE ACQUISITION: We used the following terms, namely "photochemotherapy," "phototherapy," "psoriasis," "UVB," "UVA" and "ultraviolet therapy," to search the Cochrane Controlled Register of Trials, MEDLINE and Embase databases on August 1, 2019. We organized results using a PRISMA diagram and analyzed bias risks with RoB-2 tool. EVIDENCE SYNTHESIS: We included five randomized controlled trials (RCTs) on oral PUVA and three RCTs on NB-UVB. The five studies on PUVA included a total of 1452 patients with plaque psoriasis and did not find any significant difference in efficacy comparing two- vs. three- vs. four times weekly protocols. The three studies on NB-UVB included a total of 248 patients with plaque psoriasis. No differences in efficacy were reported in comparing different frequencies in delivering NB-UVB, namely twice vs. thrice weekly, twice vs. four times weekly, and thrice- vs. five times weekly protocols. Although protocols with higher treatments frequency per week achieved clearance faster than lower frequency ones, but they did not differ in terms of efficacy. CONCLUSIONS: PUVA and NB-UVB remain effective anti-psoriatic treatments; however further studies are needed to elucidate which protocol may be more effective in different skin phototypes.

Diet-Related Phototoxic Reactions in Psoriatic Patients Undergoing Phototherapy: Results from a Multicenter Prospective Study.

Vegans and vegetarians often consume foods containing photosensitizers capable of triggering phytophotodermatitis. The potential effect of vegan and vegetarian diets on the response of psoriatic patients undergoing phototherapy is not well characterized. We assessed clinical outcomes of vegan, vegetarian and omnivore adult psoriatic patients undergoing band ultraviolet B phototherapy (NB-UVB). In this multicenter prospective observational study, we enrolled 119 adult, psoriatic patients, of whom 40 were omnivores, 41 were vegetarians and 38 were vegans, with phototherapy indication. After determining the minimum erythemal dose (MED), we performed NB-UVB sessions for 8 weeks. The first irradiation dosage was 70.00% of the MED, then increased by 20.00% (no erythema) or by 10.00% (presence of erythema) until a maximum single dose of 3 J/cm2 was reached and constantly maintained. All the enrolled patients completed the 8 weeks of therapy. Severe erythema was present in 16 (42.11%) vegans, 7 (17.07%) vegetarians and 4 (10.00%) omnivores (p < 0.01). MED was lowest among vegans (21.18 ± 4.85 J/m2), followed by vegetarians (28.90 ± 6.66 J/m2) and omnivores (33.63 ± 4.53 J/m2, p < 0.01). Patients with severe erythema were more likely to have a high furocumarin intake (OR 5.67, 95% CI 3.74-8.61, p < 0.01). Vegans consumed the highest amount of furocumarin-rich foods. A model examining erythema, adjusted for gender, age, skin type, MED, phototherapy type, number of phototherapies and furocumarin intake, confirmed that vegans had a lower number of treatments. Vegans had more frequent severe erythema from NB-UVB, even after adjustment of the phototherapy protocol for their lower MED. Assessing diet information and adapting the protocol for vegan patients may be prudent.