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.

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.

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).

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.

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.

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.

Frontal Fibrosing Alopecia: Is There a Link in Relatives?

Frontal fibrosing alopecia (FFA) is an acquired primary lymphocytic cicatricial alopecia characterized by frontotemporal hairline recession, leading to scarring alopecia with a band-like distribution. Prevalence is increasing worldwide, being the most frequent cause of primary scarring alopecia. The natural history of this condition is variable; however, slow progression with spontaneous remission is the most frequent reported outcome. The etiopathogenesis of FFA remains to be elucidated; numerous hypotheses concerning hormonal effects, environmental factors, and genetic predisposition have been proposed. Special interest on genetic basis has emerged since the first familial case was reported. Only a few more familial cases have been published. We report 6 additional cases of female patients with familial FFA (F-FFA) from 3 different families. Sixty-six percent had a family history of autoimmune disease in first-degree relatives; these same patients had a personal history of autoimmune disease. The families described in this cohort study plus the personal and family history of autoimmune disease, as well as the recently described involved genomic loci; reinforced the hypothesis of this disease being genetic. It is important to consider studying this entity since there are scarce data regarding familial cases and this might give us a better insight toward understanding its pathogenesis.