Implementing well-being in the management of psoriasis: An expert recommendation.

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well-being are essential to a comprehensive approach to the disease. With the inclusion of more people-centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well-being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well-being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well-being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well-being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence.

Effectiveness and Safety of Deucravacitinib for the Management of Psoriasis: A Review of the Current Literature.

Psoriasis management may be challenging, particularly for moderate-to-severe forms of the disease. Indeed, conventional systemic treatments are often avoided for contraindications or the risk of adverse events as well as phototherapy is often limited by logistic concerns. Despite the development of biological drugs and small molecules revolutionized the treatment options showing promising results in terms of safety and effectiveness, some limitations remain. Thus, there is still a need for new therapies that are always welcome in order to tailor the treatment to the patient and to have a higher level of performance, especially in order to maintain long-term effectiveness. In this scenario, deucravacitinib, an oral small molecule which selectively inhibits Tyrosine Kinase 2, may represent a promising weapon in psoriasis management. The aim of our manuscript is to review the current knowledge on the efficacy and safety of deucravacitinib for the management of psoriasis.

The holistic approach to psoriasis patients with comorbidities: the role of investigational drugs.

INTRODUCTION: Psoriasis is a high-burden syndrome characterized by cutaneous and extracutaneous manifestations that profoundly reduce patients' quality of life. The presence of concomitant comorbidities often represents a limit to the most appropriate psoriasis treatment that will be overcome by the development of drugs effective for diseases with common pathogenetic pathways. AREAS COVERED: The current review summarizes the latest findings on investigational drugs for psoriasis and their role on potentially concomitant diseases that share similar pathogenetic pathways. EXPERT OPINION: The development of novel drugs that target key-molecules in the pathogenesis of several diseases, including psoriasis, will impact on the reduction of polypharmacy and drug interaction with increased patients' compliance to treatment, wellbeing, and quality of life. Certainly, the efficacy and safety profile of each novel agent must be defined and evaluated in real-life since the performance may vary according to comorbidities and their severity. Anyway, future is now, and research must continue in this direction.

Anti-IL23 biologic therapies in the treatment of psoriasis: real-world experience versus clinical trials data.

Nowadays, the biological equipment available for the treatment of moderate-to-severe psoriasis is plenty. Anti-interleukin-23 represents the latest class of biologic approved for the management of moderate-to-severe psoriasis. Their efficacy and safety have been assessed through two major sources: clinical trials (CTs) and real-world experiences data (RWE). Notably, the two sources differ from one another, but together, they complement information and current knowledge on both efficacy and safety of biological therapy. We carry out a review on CTs and RWE reports on the latest group of biological approved for moderate-to-severe psoriasis: anti-IL23 (guselkumab, risankizumab, and tildrakizumab).

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.

Scleroderma-like Syndrome in the Setting of Pembrolizumab Therapy for Non-Small Cell Lung Cancer: Diagnosis and Dermatologic Management.

Immune checkpoint inhibitors play an important role in the treatment of malignancies. ICIs consist of monoclonal antibodies directed against inhibitory immune receptors cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death-ligand 1 (PD-L1). PD-1 is a receptor expressed by T lymphocytes and has the role of inhibiting their activation. Pembrolizumab is a humanized anti-PD-1 monoclonal antibody. It can improve the immune function of T-cells, which results in significant clinical benefit in the treatment of cancer. Despite its wide use, immunotherapy is associated with a spectrum of side effects known as immune-related adverse events. We present a case of an 82-year-old patient with widespread fibroatrophic skin areas that occurred during a treatment with pembrolizumab for non-small cell lung cancer. Clinical, serological, and histopathological examinations led to the diagnosis of generalized morphea. The patient discontinued pembrolizumab and switched to chemotherapy with pemetrexed and carboplatin. A good therapeutic response was obtained with phototherapy, corticosteroids, and topical calcineurin inhibitors. A focus on the therapeutic management of this skin toxicity in oncological patients is provided.

Towards Personalized Medicine in Psoriasis: Current Progress.

Although innovative targeted therapies have positively revolutionized psoriasis treatment shifting treatment goals to complete or almost complete skin clearance, primary or secondary lack of efficacy is still possible. Hence, identifying robust biomarkers that reflect the various clinical psoriasis phenotypes would allow stratify patients in subgroups or endotypes, and tailor treatments according to the characteristics of each individual (precision medicine). To sum up the current progress in personalized medicine for psoriasis, we performed a review on the available evidence on biomarkers predictive of response to psoriasis treatments, with focus on phototherapy and systemic agents. Relevant literature published in English was searched for using the following databases from the last five years up to March 20, 2022: PubMed, Embase, Google Scholar, EBSCO, MEDLINE, and the Cochrane library. Currently, more evidence exists towards biologicals, as justified by the huge health care costs as compared to phototherapy or conventional systemic drugs. Among them, most of the studies focused on anti-TNF and IL12/23, with still few on IL17 (mainly secukinumab). The most discussed biomarker gene is the HLA-C*02:06 status that has been shown to be associated with psoriasis, and also differential response to biologicals. Although its positivity is associated with great response to MTX, debatable results were retrieved concerning both anti-TNF and IL12/23 while it seems not to affect secukinumab response. Personalized treatment in psoriasis would provide excellent outcome minimizing the risk of side effects. To date, although several candidates were proposed and assessed, the scarcity and heterogeneity of the results do not allow the identification of the gold-standard biomarker per each treatment. Anyway, the creation of a more comprehensive panel would be more reliable for the treatment decision process.

Probiotic supplement combined with topical therapy in the treatment of mild to moderate acne: results from an Italian single centre interventional study.

BACKGROUND: Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from different cofactors. The alteration of the skin microbiome has recently been revealed to play a role in acne pathogenesis. Concerns with side effects of available systemic treatment for acne resulted in a greater focus on topical therapies, such as topical azelaic acid which showed to be an effective and safe treatment option for acne. The aim of our study was to evaluate the efficacy of a new treatment protocol for acne based on an oral supplement composed of biotin and 3 strains of lactic ferments combined with a topical gel composed of azelaic acid, hydroxypinacolone retinoate, and α-hydroxy acids. METHODS: An Italian single-center interventional study was performed enrolling patients suffering from mild-to-moderate-acne. Patients were treated with a supplement based on biotin and 3 strains of lactic ferments, combined with a topical gel product (azelaic-acid, hydroxypinacolone retinoate, and α-hydroxy acids). All enrolled patients were scheduled for a total of 2 visits, a baseline visit (V0) and a follow-up visit after 60 days of treatment (V1). RESULTS: A total of 30 patients were enrolled in the study. Between V0 (baseline) and V1 (60 days), there was a reduction of 37.4% in the GAGS Score, 40.7% in the SEBUTAPEtm Score, and 18% in the TEWL Score, and an increment of 44% in the T-Blue Test Score. No cases of serious AEs were reported in our experience. CONCLUSIONS: Our results confirmed the promising therapeutic role of a probiotic supplement associated with topical therapy in the treatment of mild to moderate acne.

Update on the Management of Pediatric Psoriasis: An Italian Consensus.

INTRODUCTION: Psoriasis affects children with a considerable burden in early life. Treating pediatric psoriasis is challenging also because of the lack of updated specific guidelines. With the recent approval of several biologics for pediatric psoriasis and the ongoing COVID-19 pandemic, the management of young psoriatic patients is facing major changes. A revision of treatment recommendations is therefore needed. METHODS: In September 2021, a board of six Italian dermatologists convened to update treatment recommendations. The board issued evidence- and consensus-based statements covering relevant areas of pediatric psoriasis, namely: assessment of psoriasis severity, management of children with psoriasis, and treatment of pediatric psoriasis. To reach consensus, the statements were submitted to a panel of 24 experts in a Delphi process performed entirely via videoconference. A treatment algorithm was produced. RESULTS: There was full consensus that psoriasis severity is determined by the extension/severity of skin lesions, site of lesions, and impact on patient quality of life. Agreement was reached on the need for a multidisciplinary approach to pediatric psoriasis and the importance of patient/parents education. The relevance of vaccinations, including COVID-19 vaccination, for psoriatic children was acknowledged by all participants. Management issues that initially failed to reach consensus included the screening for psoriasis comorbidities and early treatment with biologics to prevent them and the use of telemedicine to facilitate patient follow-up. There was full consensus that topical corticosteroids are the first choice for the treatment of mild pediatric psoriasis, while phototherapy and systemic therapy are used in children with moderate-severe psoriasis. According to the proposed treatment algorithm, biologics are the first line of systemic therapy. CONCLUSIONS: Targeted systemic therapies are changing the treatment of moderate-severe pediatric psoriasis, while topical corticosteroids continue to be the first choice for mild disease. Children-centered research is needed to further improve the treatment of pediatric psoriasis.

Oral isotretinoin for acne: a complete overview.

INTRODUCTION: Acne is one of the most common and widespread skin conditions, affecting the health as much as patients' quality of life. A wide variety of treatments for acne, topical and systemics, could be prescribed, depending on its degree of severity. Isotretinoin, a derivative of retinol, has been widely used for the treatment of severe forms of acne and those forms not responding to conventional treatments. In literature, there are several studies describing its efficacy, also reporting side-effects related to the drug; therefore, this has led the scientific community to request further studies qualifying its characteristics and comparing its efficacy and safety with other classic acne treatments, as well as with different treatment regimes, in order to find the dose with the best efficacy/safety ratio. AREAS COVERED: The aim of this article is to provide a complete overview on the use of oral isotretinoin for the treatment of acne describing the efficacy, safety, and tolerability of the drug. EXPERT OPINION: Oral isotretinoin represents a valid therapeutic alternative in treating severe and mild-to-moderate acne lesions, also reducing scarring damage. There are no standardized protocols regarding the use of oral isotretinoin and its association with other therapies; however, the correct patient selection and a tailored treatment protocol according to acne lesions severity and type should be considered in order to obtain optimal results.

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach.

BACKGROUND: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. METHODS: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. RESULTS: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. CONCLUSIONS: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach.

Assessment of the efficacy, skin acceptability and cosmetic quality of an adjuvant cream based on 40% urea and amino-inositol in the treatment of mild psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease with a multifactorial genesis. Structural changes are encountered in psoriasis and skin barrier function is impaired. Tight junctions (TJs) play a key role in skin barrier dysfunction. Loss of profilaggrin or filaggrin leads to changes in the stratum corneum and consequent loss of water and the development of xerosis. METHODS: We carried out an observational study to evaluate the efficacy, skin acceptability and cosmetic qualities of a cream formulation, based on 40% urea and amino-inositol, in the treatment of mild psoriasis in the absence of other associated cosmetic/pharmacological treatments. All parameters were evaluated before (T0) and after 4 weeks (T4). Efficacy assessment was based on both clinical evaluation and photographic documentation. RESULTS: The results showed significant clinical improvement (-64.18% PASI, -57.11% BSA, -61.84% Plaque Score, -41.86% PGA and -76.34% VAS -77.5 DLQI) in 4 weeks of treatment. No significant side effects were reported. Similarly, the degree of satisfaction with the product and adherence to its use were particularly satisfactory among patients. CONCLUSIONS: The tested product was found to be a promising, effective adjuvant treatment in patients with mild psoriasis, and was also useful in reducing itchy symptoms, the impact on quality of life, as well as significantly reducing the clinical signs of psoriasis.

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.

Topical oil formulation of plant extracts and vitamins as effective treatment for stretch marks and xerosis-An observational longitudinal study.

BACKGROUND: Stretch marks are linear scars that result from elastic fiber destruction. They usually occur as the consequence of rapid change in the body mass (weight gain and loss, pregnancy, weightlifting), long-term steroid use, or endocrinopathies. Treatment is challenging and mainly based on topical and procedural therapies, although the standard of care is still under debate. PURPOSE: To evaluate the efficacy and tolerance of a topical oil formulation of plant extracts and vitamins on the aesthetic improvement of stretch marks and xerosis. MATERIALS AND METHODS: Fifty male and female patients, aged between 14 and 45 years, with stretch marks referring at the University Hospital Federico II, Naples, were enrolled between March and November 2019. Topical application of plant extracts and vitamin-rich oil was performed twice daily on affected skin for 4 months. Patients were monitored at baseline (T0), and at two-month (T1) and 4-month (T2) follow-ups, through clinical and dermoscopic assessment, confocal microscopy, cutaneous ultrasound, MoistureMeterEpiD, and X-Rite spectrocolorimeter. Primary endpoints were as follows: 70% clinical improvement of stretch marks and 3-point decrease in clinical score from baseline to T2. Secondary endpoints were as follows: change in the T0 parallel pattern of collagen fibers at confocal microscopy, cutaneous thickness increase at ultrasounds, cutaneous hydration increase at MoistureMeterEpiD, erythema reduction at X-Rite spectrocolorimeter, and safety and adverse events (AEs). RESULTS: At 4-month follow-up, stretch marks improved objectively and subjectively in all patients (p < 0.001). In detail, there was a 29% and 71% improvement in clinical appearance of stretch marks at T1 and T2, respectively, as documented dermoscopically and by the 3-point reduction in the assessor's mean clinical score at each follow-up visits [from 8.1±0.7 at baseline to 5.7±1.0 at T1 and 2.3 ±0.5 at T2 (p < 0.001)]. Erythema decreased by 15% and 30% and in parallel hydration increased by 25% and 71%, at T1 and T2, respectively (p < 0.001). At T2 confocal microscopy of stretch marks, dermal collagenous fibers assumed casual disposition with reticular pattern and refractivity, as signs of collagen remodeling and neocollagenesis, and also the T2 cutaneous ultrasound revealed increased epidermal thickness and decreased dermal hypoechogenicity as for a higher skin hydration. CONCLUSION: Our study showed that a topical oil formulation rich in plant extracts and vitamins appears to be effective and safe in treating stretch marks and xerosis.

Psoriasis awareness among general population: preliminary results of an online survey.

BACKGROUND: Psoriasis represents one of the most common skin diseases in Italy, with a prevalence of 2.9%. It has been defined as a noncommunicable disease, due to its high burden and impact on patients' quality of life. The aim of our observational study was to assess the actual knowledge and perception of psoriasis in Italian population by administering an online 10-question survey to a representative sample general population. METHODS: An online 10-question survey was administered to a representative sample general population from September 2019 to December 2019. A representative sample of general population (age ≥18 years) was enrolled by promoting the online survey through multiple means of communication such as social sites (Facebook, Instagram) or delivering a questionnaire link in public spaces (outpatient clinic, pharmacy). All results were then collected and analyzed in graphs by the Google form platform. RESULTS: One hundred fifty-one individuals participated in the survey. Results showed that 7.3% (N.=11) of general population were not familiar with the term psoriasis; 4.6% (N.=7) thought to psoriasis as an infectious disease and 6% (N.=9) thought that psoriasis was contagious. Interestingly, 39.1% (N.=59) of participants have never heard about targeted/biologic therapy. Our study is limited by the small sample size as well as lack of data regarding sex, age and education level of the study participant. CONCLUSIONS: There is still lack of knowledge of psoriasis among general population, representing an obstacle for patients' everyday activities and quality of life. Future studies to investigate the details of this impaired knowledge and new psoriasis campaign on large scale should fill this gap are required.

Ultraviolet radiation, vitamin D, and COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become pandemic on March 11th, 2020. COVID-19 has a range of symptoms that includes fever, fatigue, dry cough, aches, and labored breathing to acute respiratory distress and possibly death. Health systems and hospitals have been completely rearranged since March 2020 in order to limit the high rate of virus spreading. Hence, a great debate on deferrable visits and treatments including phototherapy for skin diseases is developing. In particular, as regards phototherapy very few data are currently available regarding the chance to continue it, even if it may be a useful resource for treating numerous dermatological patients. However, phototherapy has an immunosuppressive action possibly facilitating virus infection. In the context of COVID-19 infection risk it is important to pointed out whether sunlight, phototherapy and in particular ultraviolet radiation (UV-R) constitute or not a risk for patients. In this review we aimed to focus on the relationship between UV-R, sunlight, phototherapy, and viral infections particularly focusing on COVID-19.