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.

Commentary on Dermoscopy as a complementary tool for positive margin demarcation on the Mohs' map.

Mohs micrographic surgery (MMS) is a technique that allows removal of complex or ill-defined skin cancer, combining tissue preservation and complete microscopic margin control. One of the main challenges of Mohs surgery is to illustrate the exact location of the tumour detected by light microscope. Using a dermoscope allows a fast, easy, reproducible way to accurately illustrate the location of a positive tumour on the Mohs map and ultimately transpose it to the surgical defect of the patient in a more precise way.

Micro needling: A novel therapeutic approach for androgenetic alopecia, A Review of Literature.

Androgenetic alopecia (AGA) is an androgen-dependent hereditary trait resulting in hair miniaturization. It is the most common type of alopecia in men and women. During the last years, multiple treatment modalities have been studied, but only topical minoxidil and finasteride have been approved by the US Food and Drug Administration. Microneedling (MN) is a minimally invasive technique that induces collagen formation, as well as growth factors production and neovascularization. Even though not many studies of MN in alopecia have been performed, it remains a favorable treatment modality; however, no standardized protocol for MN in hair loss has been proposed yet. Current evidence is not sufficient to allow a direct comparison with other therapies, but it shows promises to increase hair density, thickness, and quality of hair, especially when combined with other treatments or when used as a drug delivery system. This article aims to summarize the available literature regarding the use of MN alone or associated with other therapies for the treatment of androgenetic alopecia.

[DRESS syndrome: Report of nine cases]. / Reacción por drogas con eosinofilia y síntomas sistémicos (síndrome de DRESS): Estudio retrospectivo de nueve casos.

BACKGROUND: DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is an uncommon disease caused by drugs. It is characterized by a polymorphic disseminated eruption with fever and multiple organ dysfunction. AIM: To report the etiology, characteristics, treatment, prognosis, and follow up of patients with DRESS Syndrome admitted to a clinical hospital. MATERIAL AND METHODS: Review of medical records of patients admitted for drug reactions, selecting those patients complying with clinical criteria for DRESS Syndrome. Drugs used during three months prior to the onset of symptoms were evaluated as possible causes of the disease. RESULTS: Nine patients aged 16 to 68 years (six males) complied with the clinical criteria for the disease. The causative medications were carbamazepine in three patients, phenytoin in three, antituberculous drugs in two and amoxicillin in one. All were treated with systemic steroids with a complete clinical resolution. CONCLUSIONS: DRESS syndrome is usually underdiagnosed and has a good response to systemic steroids.

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).

Psoriatic Alopecia and Paradoxical Psoriasis Induced by Adalimumab Successfully Treated with Certolizumab: Clinical, Trichoscopic, and in vivo Reflectance Confocal Microscopy Features.

Introduction: Psoriatic alopecia is considered a type of hair loss occurring in patients with psoriasis. Adalimumab is a fully humanized recombinant anti-TNF-alpha monoclonal antibody approved for treatment of psoriasis and psoriatic arthritis (PsA), rarely related to the occurrence of dermatological disorders. Case Presentation: We report the case of a 56-year-old female with PsA developing psoriatic alopecia and paradoxical psoriasis induced by adalimumab and successfully treated switching to certolizumab, evaluating response at both thrichoscopy and in vivo reflectance confocal microscopy. Discussion: Among anti-TNF-α agents, certolizumab is the least involved in the development of paradoxical reactions such as psoriatic alopecia and showed to be an effective and safe alternative therapeutic options to manage psoriasis and PsA minimizing the risk of paradoxical reactions.

Development of a Patient-Reported Outcome Measure (PROM) for Dysgeusia During Treatment With Smoothened (SMO) Inhibitors for Basal Cell Carcinomas: The SMO-iD Questionnaire.

INTRODUCTION: Dysgeusia may occur during conventional or target-therapies and affect patients adherence-to-treatment. Therefore, it should be monitored to improve clinical outcome. To date, available questionnaires on dysgeusia relate to traditional antineoplastics and do not apply to target-therapies as the pathogenetic mechanism and clinical expression differ. OBJECTIVES: To develop a patient-reported outcome measure (PROM) to screen for and monitor the occurrence and severity of dysgeusia in patients under Smoothened (SMO) inhibitors: the SMO-iD questionnaire. METHODS: Patients with locally advanced basal cell carcinomas referring dysgeusia under SMO inhibitors at the University Hospital of Naples Federico II, were enrolled between January-December 2020. The PROM was elaborated based on chemotherapy-induced dysgeusia (CiTas) scale (development phase) and then validated by measuring internal consistency and reliability (validation phase). RESULTS: Thirty-nine patients were enrolled and interviewed every 8 weeks. In the first phase, 160 CiTas questionnaires were collected, and the SMO-iD questionnaire was developed. In the second phase, 195 SMO-iD questionnaires were recorded, and reliability and validity assessed. Cronbach alpha was 0.89. CONCLUSIONS: The SMO-iD questionnaire is a validated questionnaire that shows high face and content validity as well as high internal consistency and reliability. Hence, it may be introduced in daily clinical setting to monitor dysgeusia in patients under SMO-inhibitors.

Hair Aging and Hair Disorders in Elderly Patients.

Hair loss in elderly patients is a common complaint. It can be related to different conditions that affect patients' quality of life and represents a challenge for dermatologists. It affects both men and women during the aging process with an estimated percentage of balding after 65 years of age of 53% and 37%, respectively. Androgenetic alopecia, frontal fibrosing alopecia, senile alopecia, and erosive pustular dermatosis of the scalp are the hair diseases most frequently described in this age group. The objective of this review is to summarize the current knowledge about alopecia affecting elderly patients, differentiating between chronological hair aging signs and pathological changes, to help clinicians, offer an adequate management of these disorders to their patients.

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.

Cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma.

INTRODUCTION: Cutaneous squamous cell carcinoma (CSCC) is the second most frequent malignant skin cancer, with an increasing worldwide incidence. Cemiplimab is a human monoclonal antibody directed against programmed cell death-1 receptor that acts by blocking T-cell inactivation. It is the first drug approved for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation. AREAS COVERED: The aim of this review is to analyze the mechanism of action, including pharmacokinetic and pharmacodynamic properties, clinical efficacy, safety, and tolerability of cemiplimab for squamous cell carcinoma. EXPERT OPINION: The introduction of immune checkpoint inhibitors has revolutionized the therapeutic scenario of advanced skin cancers. Many challenges regarding the use of cemiplimab for locally advanced and metastatic CSCC still exist. The use of combination treatments, including the association of different immune checkpoint inhibitors, could be a strategy to increase treatment response, reducing the possibility of therapeutic failure. Also, different schemes of treatment or dose adjustments should be considered in order to reduce toxicity, avoiding treatment discontinuation and increasing patient´s quality of life.

Looking into a Better Future: Novel Therapies for Metastatic Melanoma.

Even though melanoma represents a small percentage of all cutaneous cancers, it is responsible for most deaths from skin neoplasms. In early stages it can be successfully treated with surgery, but as the disease expands the survival rate drops significantly. For many years the mainstay of treatment for metastatic melanoma was chemotherapeutic agents, even though they failed to prove survival prolongation. After the advent of ipilimumab, a survival benefit and better overall response rate could be offered to the patients. Other new therapies, such as immunotherapies, targeted therapies, vaccines, and small molecules, are currently being studied. Also, combination regimens have demonstrated superiority to some monotherapies. Nowadays, ipilimumab should no longer be considered the first-line therapy given its severe toxicity and lower efficacy, while nivolumab remains efficacious and has a good safety profile. T-VEC as monotherapy has been shown to be an elegant alternative even for the elderly or cases of head and neck melanomas. If the BRAF mutation status is positive, the combination of dabrafenib and trametinib could be an option to consider. Despite the success of the novel treatments, their effectiveness is still limited. New studies have opened up new avenues for future research in melanoma treatment, which is expected to lead to better therapeutic outcomes for our patients. The objective of this review is to discuss the novel therapies for metastatic melanoma that have been tested in humans during the last 3 years to obtain a sharper perspective of the available treatment options for specific patient characteristics.

Expert opinion on sonidegib efficacy, safety and tolerability.

Introduction: Hedgehog inhibitors are an alternative treatment option for patients with advanced BCCs not eligible for standard therapies due to lack of efficacy, high recurrence risk, and high-rate morbidity. Sonidegib, an oral smoothened antagonist, has been approved for the treatment of adult patients with locally advanced basal cell carcinoma. Several studies and randomized controlled trials have been conducted in order to evaluate the efficacy, safety, and tolerability of this new molecule.Areas covered: The aim of this article is to provide a complete overview on the use of sonidegib for the treatment of advanced BCCs describing the efficacy, safety, and drug tolerability of this drug.Expert opinion: Sonidegib, with a different pharmacokinetics profile from that of the other SMO-inhibitor vismodegib, demonstrated to be an efficacious and well-tolerated treatment in patients with locally advanced BCC. Although several drug-related adverse events have already been described, different strategies should be taken into account to better manage this small molecule while avoiding treatment discontinuation. The use of sonidegib as neoadjuvant therapy or combined with other hedgehog pathway inhibitors targeting different sites and to date, only available for pre-clinical studies, should also be considered.

New-Onset Psoriatic Arthritis under Biologics in Psoriasis Patients: An Increasing Challenge?

Psoriasis and psoriatic arthritis (PsA) development is sustained by tumor necrosis factor (TNF)α, interleukin (IL)17, and IL23; hence, biologics targeting those cytokines represent useful therapeutic weapons for both conditions. Nevertheless, biologics strongly reduce PsA risk; several studies reported the possibility of new-onset PsA during biologic therapy for psoriasis. The aim of this 1-year prospective study is to evaluate the prevalence of paradoxical PsA in psoriasis patients under biologic therapy and review the existing literature. For each patient, age, sex, psoriasis duration, psoriasis severity, comorbidities, and previous and current psoriasis treatments were collected, and each subject was screened for PsA using the Early ARthritis for Psoriatic patient (EARP) questionnaire every 3 months for 1 year. New-onset PsA was diagnosed in 10 (8.5%) out of 118 patients (three male, 30.0%; mean age 44.5 years) involving every different biologic class (anti-TNF, anti-IL12/23, anti-IL17, and anti-IL23). No significant risk factor for new-onset PsA was identified; no significant difference was found comparing patients who developed PsA and subjects who did not develop PsA regarding psoriasis severity, past/current therapies, and comorbidities. Clinicians must keep in mind the possibility of PsA onset also in patients undergoing biologics so that PsA screening should be strongly recommended at each follow-up.