MRSA and Skin Infections in Psoriatic Patients: Therapeutic Options and New Perspectives.

Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective.

The pharmacological treatment and management of hyperhidrosis.

INTRODUCTION: Idiopathic hyperhidrosis is a dysfunctional disorder involving eccrine sweat glands, and its impact on patients' daily quality of life is well known. Unlike some years ago, when only poor effective and safe therapeutic alternatives were available, nowadays, several emerging pharmacological active substances have gained significant space as treatment options. AREAS COVERED: The authors report on, in this narrative review, the emerging data from the literature focusing on the pharmacological treatments to draw up a drug treatment flow chart for patients with idiopathic hyperhidrosis, taking into consideration specific differences among axillary, palmoplantar, and craniofacial hyperhidrosis. EXPERT OPINION: Idiopathic hyperhidrosis, regardless of the site of involvement, remains a functional disorder that places a significant burden on patients. After balancing efficacy against adverse events, systemic therapy, although off-label for all forms of hyperhidrosis, can be an added therapeutic option for patients with insufficient response to topical treatment. Until the pathophysiological mechanisms underlying hyperhidrosis are clear and the etiological therapeutic approach becomes realistic, the greatest challenge in the therapeutic management of hyperhidrotic patients seems to be the search for the most convenient combination between different therapeutic modalities (topical and systemic agents, and botulinum toxins) to achieve long-term control of the disease symptoms.

Deferred time of delivery of biologic therapies in patients with stabilized psoriasis leads to a 'perceived satisfaction': a multicentric study.

OBJECTIVE: Thanks to their specificity of action, biologic drugs often lead to complete clearance of psoriatic lesions. In order to maintain its effectiveness, biological therapies cannot be discontinued. The aim of the study was to investigate the effect of widening the administration window of four biologic drugs, thus improving the quality of life of psoriatic patients and satisfying their desire to feel free from the disease, without loss of effectiveness. METHODS: We performed a multicentric cohort study considering patients with moderate-severe plaque psoriasis and/or arthropathic psoriasis treated with infliximab, adalimumab, etanercept or ustekinumab. The study group included patients with stabilized psoriasis in which the administration regimen of the biologic drug was deferred. The control group included psoriatic patients treated according the product monograph. RESULTS: The percentage of relapses in case of deferred administration intervals was comparable to that of standard administration intervals. The delayed administration modality got a good psychological consensus from the patients themselves, that reported a greater 'perceived satisfaction'. A consistent economic advantage was reported in case of prolonged administration intervals. CONCLUSIONS: The administration of biologic drugs with prolonged intervals maintains the same effectiveness as standard administration and produces a 'perceived satisfaction' in psoriatic patients.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. METHODS: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. RESULTS: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. CONCLUSIONS: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Effects of in vivo application of an overnight patch containing Allium cepa, allantoin, and pentaglycan on hypertrophic scars and keloids: Clinical, videocapillaroscopic, and ultrasonographic study.

Several therapeutic approaches have been described for their treatment of hypertrophic scars and keloids, but to date, the optimal treatment has not been established yet. Our in vivo study was conducted to evaluate the effect of a medical device consisting in an adhesive patch containing onion extract (Allium cepa) 10%, allantoin 1%, and pentaglycan 4% (Kaloidon patch) on hypertrophic scars and keloids. Thirty-nine patients with hypertrophic scars and seven patients with keloids were asked to apply an adhesive patch containing Allium cepa, allantoin, and pentaglycan once/day for at least 8 h consecutively, for 24 weeks. Patients were reevaluated 6 weeks (T6), 12 weeks (T12), and 24 weeks (T24) after starting the treatment through POSAS scale v 2.0, ultrasonographic, and videocapillaroscopic assessment. The investigated medical device was able to induce a significant improvement of POSAS starting from T12, with a positive amelioration trend until T24. However the patient-assessed POSAS sub-items showed improvement already after 6 weeks, whereas a significant improvement of the observer-assessed POSAS sub-items was observed only after 12 weeks (P < .001). Ultrasonography and intravital videocapillaroscopy confirmed a significant improvement of skin scars thickness (P < .001) and vascularization (P < .001) after 12 weeks of medical device application at least, with increasing improvement until T24. Applying an adhesive patch containing Allium cepa, allantoin, and pentaglycan once a day for at least 8 consecutive hours seems to be able to improve the clinical and morphological characteristics of the scars of the skin in 24 weeks.

Metabolic, pharmacokinetic, and toxicological issues of biologic therapies currently used in the treatment of hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa is a chronic, relapsing, debilitating inflammatory dermatologic disease of the terminal hair follicles at intertriginous sites clinically characterized by painful inflammatory nodules, abscesses, draining sinus tracts, and dermal fibrosis. The management of hidradenitis suppurativa is a challenge and usually consists of both medical and surgical approaches, which must often be combined for best outcome. The introduction of biological therapies, specifically TNFα-inhibitors such as adalimumab, has profoundly changed the therapeutic armamentarium of the disease. AREAS COVERED: The PubMed database was searched using combinations of the following keywords: hidradentis suppurativa, biologic therapy, TNF-α inhibitors, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions of on-label and off-label use of TNF-α inhibitors in HS. EXPERT OPINION: Biologic agents, particularly adalimumab, exhibit clinical efficacy in patients with hidradenitis suppurativa. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of the TNF-α inhibitor. Familiarity with biologic agents is crucial because these agents could become a consolidated treatment option in the clinician's therapeutic approaches.

Ixekizumab for treatment of moderate to severe plaque psoriasis: real world clinical experience.

BACKGROUND: Data concerning clinical experience in real world setting with ixekizumab for psoriasis are still exiguous. So, the aim of this report was to provide our experience in the use of ixekizumab in outpatient setting. METHODS: Fifteen Caucasian individuals (10 male, 5 females; mean age: 58.1; range: 30-75 years) affected by moderate to severe plaque psoriasis (PASI≥10 and/or DLQI≥10 and/or BSA≥10) were treated with ixekizumab, following dosing regimen of technical data sheet and clinically evaluated after 4 weeks (T4) and 12 weeks (T12) after. At baseline median PASI was 16.3 (range: 10-30, SD=6.0). The median BSA was 21.3 (10-35, SD=7.0), the median PGA was 3.4 (2-6, SD=1.2), the median DLQI was 18.6 (14-25, SD=3.6), the median m-NAPSI was 42.0 (30-56, SD=13.11). The median absolute value of PASI, BSA, PGA, DLQI and m-NAPSI showed a statistically significant decrease (P<0.05) already after 4 weeks of treatment, in order to testify treatment effectiveness. RESULTS: At T4, 93.3% of the patients reached PASI50, 6.9% reached PASI75; at T12, 100% of the patients reached PASI50, 80% reached PASI75, 13% reached PASI90 and 6.9% reached PASI100. One-third of observed patients reached MDA after 12 weeks of treatment. Injection site reactions were the only side effects occurring during the first 12 weeks of treatment. CONCLUSIONS: Our preliminary results seem to confirm the efficacy and safety profile provided through the UNCOVER pivotal trials (UNCOVER 1-3) although further larger observational studies are needed.

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

BACKGROUND: Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. METHODS: Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). RESULTS: Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. CONCLUSIONS: The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant Staphylococcus aureus Infection Model.

Prolonged hospitalization and antibiotic therapy are risk factors for the development of methicillin-resistant Staphylococcus aureus (MRSA) infections in thermal burn patients. We used a rat model to study the in vivo efficacy of daptomycin in the treatment of burn wound infections by S. aureus, and we evaluated the wound healing process through morphological and immunohistochemical analysis. A copper bar heated in boiling water was applied on a paraspinal site of each rat, resulting in two full-thickness burns. A small gauze was placed over each burn and inoculated with 5 × 107 CFU of S. aureus ATCC 43300. The study included two uninfected control groups with and without daptomycin treatment, an infected control group that did not receive any treatment, and two infected groups treated, respectively, with intraperitoneal daptomycin and teicoplanin. The main outcome measures were quantitative culture, histological evaluation of tissue repair, and immunohistochemical expression of wound healing markers: epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF-2). The highest inhibition of infection was achieved in the group that received daptomycin, which reduced the bacterial load from 107 CFU/ml to about 103 CFU/g (P < 0.01). The groups treated with daptomycin showed better overall healing with epithelialization and significantly higher collagen scores than the other groups, and these findings were also confirmed by immunohistochemical data. In conclusion, our results support the hypothesis that daptomycin is an important modulator of wound repair by possibly reducing hypertrophic burn scar formation.

Biologic Therapy in Psoriasis (Part II): Efficacy and Safety of New Treatment Targeting IL23/IL-17 Pathways.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disorder that is estimated to affect 2-3% of the general population. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. METHODS: Biologics licensed for psoriasis include the TNFα inhibitors (infliximab, adalimumab, etanercept), the interleukin (IL)-12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). RESULTS: In this section, we analyse the role of IL-12, IL-23, and IL-17 in psoriasis and evaluated the efficacy and safety of biologic therapies targeting this cytokine. CONCLUSION: Dosing regimens, administration modality, and pharmacodynamics profiles of currently available anti-IL-12/IL-23 and IL-17 inhibitors are also examined.

Biologic Therapy in Psoriasis (Part I): Efficacy and Safety of Tumor Necrosis Factor- α Inhibitors.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disorder, with an estimated global prevalence of 2-3%. Psoriasis is associated with an impaired health-related quality of life and a substantial economic burden. Biologics, which target the pathways involved in the pathogenesis of psoriasis, represent an established therapeutic approach for moderate-to-severe plaque psoriasis, with remarkable efficacy and safety profile extensively examined and monitored. METHODS: Biological therapies currently available can be divided into three main categories: the TNFα antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol), the interleukin (IL)- 12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). RESULTS: In this section, we explore the complex role of TNFα in psoriasis as well as the efficacy and safety of TNFα inhibitors largely used in the management of the cutaneous disease. CONCLUSION: Dosing regimens, administration, pharmacodynamics profiles, efficacy, and safety of licensed anti-TNFα are here discussed in detail.

Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine model of multiresistant Acinetobacter baumannii sepsis.

We investigated the efficacy of colistin combined with teicoplanin or daptomycin in an experimental mouse model of multiresistant Acinetobacter baumannii infection. Animal received intraperitoneally 1ml saline containing 2×1010CFU of A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or teicoplanin were given by intraperitoneal administration 2h after bacterial challenge. A control group received sodium chloride solution. In the in vitro study A. baumannii showed to be susceptible only to colistin with MIC of 2mg/l. In the in vivo study, colistin alone showed a good antimicrobial efficacy. When combined with teicoplanin or daptomycin, colistin produced the lowest bacterial and the best survival rates. In immunological studies, when colistin was associated to daptomycin or teicoplanin, both the number and the cytotoxic activity of NK cells increased. In conclusion, colistin combined with teicoplanin or daptomycin may improve the therapy of multiresistant A. baumannii infection.

Efficacy and Safety of Topical Pidobenzone 4% as Adjuvant Treatment for Solar Lentigines: Result of a Randomized, Controlled, Clinical Trial.

BACKGROUND/OBJECTIVE: This study aims at the evaluation of the efficacy and safety of a combination therapy based on pidobenzone 4% and fractional CO2 laser or cryotherapy in the treatment of solar lentigines and the prevention of eventual posttreatment hyperchromia. METHODS: Efficacy was clinically evaluated by grading the pigmentation level with the Skin Tone Color Scale (STCS), and by grading patients' impression through a Visual Analog Scale (VAS). RESULTS: Our study shows that the associated treatment was safe and that it improves the therapeutic results on solar lentigines and prevents postiatrogenic hyperpigmentation compared with physical therapy alone. CONCLUSION: The combination of cryotherapy and pidobenzone 4% has been found to be the most useful treatment.

The transitioning from conventional therapy to biological treatment in psoriatic patients: STRATOS, a project of Marche Region.

BACKGROUND: STRATOS is the acronym of the "STRuctured Approach to the Treatment of psOriatic patientS". The optimization of the psoriasis's therapeutic management is one of the most important goals for dermatologists. According to Mrowietz's consensus report, the transitioning from conventional therapy to biological therapy is mainly due to the lack/loss of efficacy and/or for safety reasons. The aim of the manuscript was to describe the principal results obtained by the Dermatologic Clinic of Polytechnic University of Marche Region and the Units of Dermatology of the Marche Region applying, in our regional reality, Mrowietz's protocol for the daily management of patients with moderate-to-severe plaque. METHODS: Forty-seven patients with moderate to severe chronic plaque psoriasis have been monitored during the six-months study period. RESULTS: Psoriatic patients with diabetes showed further concomitant comorbidities compared to non-diabetics, as hypertension and hypercholesterolemia. Moreover, based on WHO classification, overweight was diagnosed in female patients, whereas obesity was prevalent in male patients. This aspect confirms the strict link between the multifaceted aspects of psoriatic patient which is primarily related to the persistent low-grade inflammation. In our psoriatic group, 10% of monitored patients were affected by Crohn disease or ulcerative colitis. CONCLUSIONS: The Mrowietz's transitioning protocol is a useful, reliable and feasible tool to manage the therapeutic iter of psoriatic patients in an Italian clinical setting also at regional level.