Unaddressed Challenges in the Treatment of Cutaneous Melanoma?

Background and Objectives: While the management of noninvasive cutaneous melanoma (CM) is typically limited to a secondary excision to reduce recurrence risk and periodic follow-up, treating patients with advanced melanoma presents ongoing challenges. Materials and Methods: This review provides a comprehensive examination of both established and emerging pharmacologic strategies for advanced CM management, offering an up-to-date insight into the current therapeutic milieu. The dynamic landscape of advanced CM treatment is explored, highlighting the efficacy of immune checkpoint inhibitors and targeted therapies, either in monotherapy or combination regimens. Additionally, ongoing investigations into novel treatment modalities are thoroughly discussed, reflecting the evolving nature of melanoma management. Results: The therapeutic landscape for melanoma management is undergoing significant transformation. Although various treatment modalities exist, there remains a critical need for novel therapies, particularly for certain stages of melanoma or cases resistant to current options. Conclusions: Consequently, further studies are warranted to identify new treatment avenues and optimize the utilization of existing drugs.

Drug-induced photosensitivity associated with anticancer therapies.

INTRODUCTION: Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event. EVIDENCE ACQUISITION: A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. EVIDENCE SYNTHESIS: A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies. CONCLUSIONS: Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.

Risk Factors for Psoriasis Flares: A Narrative Review.

Psoriasis is a chronic inflammatory cutaneous disease with multifactorial pathogenesis involving both genetic and environmental factors as well as the innate and acquired immune response. Several triggering factors may exacerbate or worsen the disease. In this context, we performed a review manuscript with the aim of investigating current literature on psoriasis risk factors, also showing possible mechanisms by which they act on psoriasis. Globally, risk factors can be divided in classic risk factors (eg, mechanical stress, infections and dysbiosis of the skin, common drugs, environment and pollution, lifestyle, psychological stress, hormonal and metabolic alterations) which have long been known to be responsible for worsening and/or reoccurrence of psoriatic manifestations, and emerging risk factors (eg, biological drugs, immunotherapy for oncologic disease, Covid-19, and vaccines) defined as those newly identified risk factors. Accurate patient information and monitoring of risk factors as well as planned follow-ups may help to prevent and treat the worsening of psoriasis and consequently improve the quality of life of psoriatic patients.

Management of Psoriasis Patients with Serious Infectious Diseases.

The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.

Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation.

Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients' comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer.

Biological Therapy for Psoriasis in Cancer Patients: An 8-Year Retrospective Real-Life Study.

Background: It is now recognized that psoriasis plays a key role in the development of several comorbidities, such as cardiovascular disease, and metabolic syndrome. Some authors have hypothesized that patients with psoriasis may have an increased risk of developing certain types of cancer. The efficacy and safety of biologic drugs are well-documented in clinical trials and in real-life studies. However, there is limited evidence on the safety of the use of biologic treatments in cancer patients with psoriasis, and the use of this therapeutic class in patients with a pre-existing or concomitant malignancy is still debated. Methods: We have conducted a retrospective observational study of a group of oncology patients with moderate-to-severe psoriasis treated with biologic therapy at the Dermatology Clinic of the University of Naples Federico II, during the period from 2016 to 2024. We included 20 adult patients; in 15 of them the diagnosis of neoplasm preceded the start of treatment biologic, while four of these patients had been diagnosed with cancer during the course of therapy biologics. Results: The most represented neoplasms in our population were breast carcinoma, prostate carcinoma, thyroid carcinoma, and chronic lymphatic leukemia. Anti-IL17 drugs were the most frequently prescribed (47.7%), followed by anti-IL23p19 (36.8%), anti-IL-12/23 (10.5%) and anti-TNF alpha (5.26%). All patients showed improvement of psoriasis after starting the therapy. Conclusions: Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.

Psoriasis and Molecular Target Therapies: Evidence of Efficacy in Preventing Cardiovascular Comorbidities.

Psoriasis is now considered a systemic disease, and several comorbidities have been described such as cardiovascular diseases, neurologic and psychiatric disorders, chronic inflammatory bowel disease, psoriatic arthritis, etc. Regarding cardiovascular comorbidities, major adverse cardiovascular events have been reported in psoriasis patients by multiple epidemiologic studies. Moreover, smoking, obesity, metabolic syndrome, hypertension, dyslipidemia, diabetes and reduced physical activity are associated with psoriasis, increasing cardiovascular risk. Consequently, several aspects should be considered when making the treatment decision. The aim of this review manuscript was to investigate the effectiveness and safety of biologic drugs acting on molecular mechanisms involved in the pathogenesis of psoriasis in preventing cardiovascular complications.

Long-Term Efficacy of Guselkumab in an Adolescent Hidradenitis Suppurativa Patients: A Case Report.

Managing HS has long posed a significant challenge for dermatologists. Adalimumab stands as the sole biologic drug sanctioned for HS, receiving approval in 2015 as an anti-tumor necrosis factor (TNF)-α drug. Real-life evidence over the years has debated its efficacy, suggesting a success rate hovering around 70%. However, the variability in existing treatments and the chronic-recurrent nature of the condition make its treatment and management exceedingly challenging. Hence, identifying new therapeutic targets for HS in the future becomes imperative. Recently, on October 31, 2023, the FDA approved secukinumab for moderate-severe HS, marking a significant development. There has been substantial discourse on the potential of anti-interleukin-23 drugs as new therapeutic avenues for treating HS in recent years. Here, we report a case of 17-year-old man successfully treated with Guselkumab. The results were confirmed at week 52.

Secukinumab in Hidradenitis Suppurativa Patients Who Failed Adalimumab: A 52-Week Real-Life Study.

Background: The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, adalimumab the only biologic drug approved for HS is adalimumab, an anti-tumor necrosis factor (TNF)-α drug, the approval of this drug dates to 2015, data provided by real life show an effectiveness rate of about 60% percent. Recently (31 October 2023) FDA approves secukinumab for moderate-severe HS. The treatment and management of HS is very challenging as available treatments are very limited and show very variable outcomes. Methods: We conducted a prospective monocentric study designed to evaluate the efficacy and safety of secukinumab treatment in HS patients in a real-life setting. Results: The initial cohort of patients recruited included 21 HS patients including 12 females and 9 males. About 57.1% of patients achieved the primary endpoint and recorded significant decrease in all the severity assessment scales (IHS4, DLQI and VAS pain scale) at week 16 and 52, when HiSCR reached 71.4%. Conclusion: The results of our study highlight that treatment with secukinumab in patients with severe HS who failed adalimumab may be a safe and effective therapeutic weapon.

JAK Inhibitors in Psoriatic Disease.

Psoriasis is now considered to be the cutaneous phenotype of a systemic inflammatory condition, recognized under the term Psoriatic Disease (PsD). PsD has several extracutaneous manifestations, such as inflammatory articular and entheseal involvement, leading to psoriatic arthritis (PsA), and the less frequent intestinal and ocular manifestations with colitis/inflammatory bowel disease and uveitis, respectively. There have also been several reports of an increased frequency of comorbidities such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular manifestations during the course of PsD. The link between psoriasis and related comorbidities is considered a long-term disease sequela, often characterized by an unhealthy lifestyle and a consequence of systemic inflammation; hence, psoriasis requires adequate and prompt treatment, with the aim of controlling not only cutaneous manifestations but also extracutaneous manifestations and systemic inflammation. Pharmacological strategies for PsD have significantly increased over recent years. Recently, the targeted synthetic DMARDs, Janus kinase (JAK) inhibitors, tofacitinib and upadacitinib, were added to the therapeutic armamentarium for treating PsA, and deucravacitinib for psoriasis. These oral agents act directly on inflammatory mechanisms underlining the disease, as antagonists of the intracellular JAK signal pathway and, by STAT phosphorylation, inhibit gene proinflammatory cytokine transcription. JAK inhibitors represent a recent additional treatment strategy for PsD management and, among these, tofacitinib and upadacitinib have recently been approved for PsA, and deucravacitinib for psoriasis. In this review we describe ongoing and recent phase II and III randomized controlled trials (RCTs) evaluating the efficacy and safety of investigational JAK inhibitors in psoriasis and PsA.

An update on the current and emerging pharmacotherapies for basal cell carcinomas.

INTRODUCTION: Despite surgical approach is still the mainstay for basal cell carcinoma (BCC) management, several issues may limit the use of this technique, leading to the need for new treatments to offer patients a personalized approach. AREAS COVERED: A comprehensive review of the available and emerging pharmacologic strategies for BCC management, including mechanisms of action, and potential adverse effects, has been performed to provide with an up-to-date manuscript on the current treatment scenario of BCC. Globally, targeting the Sonic-Hedgehog pathway is one of the main mechanisms of action of currently investigated drugs. Other alternatives are based on the concept of an enhancement of the immune response such as immune checkpoint inhibitors, or intra-tumor treatments. EXPERT OPINION: Although low-risk BCCs are often treated with destructive methods or topical treatments, surgery is the mainstay of treatment for the majority of BCCs. However, several factors may limit the use of surgery in BCC management. Recently, major knowledge on BCCs pathogenesis has led to the development of effective and selective drugs. In our opinion, soon many drugs will be licensed, allowing clinicians to offer patients with BCC the right treatment at the right moment. Certainly, further studies are needed.

Trichoscopic Patterns and Confocal Microscopy Features of Chemotherapy-Induced Alopecia.

Introduction: Chemotherapy-induced alopecia (CIA) can seriously affect the quality of life of cancer patients. Trichoscopic patterns and confocal microscopy (RCM) features of CIA have been scarcely studied. This study aimed to investigate the dermoscopic and RCM features of CIA in 19 females and 5 males, with CIA due to current or recent chemotherapy. Methods: Patients with CIA and current or recent (within 2 months) history of chemotherapy treatment were enrolled. After clinical examination, standard pictures were taken by digital camera (SLR Canon PowerShot G10) and trichoscopic images were captured by the Handyscope device (20x). Images of RCM were acquired by VivaScope 3000 with the VivaStack option. The trichoscopic and confocal images were acquired by three independent observers after central parting on three areas: vertex, middle, and frontal scalp. Results: A total of 24 patients were enrolled. CIA has features of anagen effluvium at trichoscopy but with low frequency of yellow dots and prominence of black dots. The simultaneous presence of pseudo-monilethrix and black dots at trichoscopy confirms the hypothesis that chemotherapy insults the hair follicle intermittently. At RCM, the presence of abnormal hair shaft morphology highlights that the insults affect hair shaft production. Conclusion: These are the first data in this field, so further studies with a higher number of patients analyzed are needed to confirm these findings.

Guselkumab, Risankizumab, and Tildrakizumab in the Management of Hidradenitis Suppurativa: A Review of Existing Trials and Real-Life Data.

The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, the only biologic drugs approved for HS are adalimumab, an anti-tumor necrosis factor (TNF)-α drug, authorized in 2015, and secukinumab, recently licensed. The management of this condition is challenging as the available treatments show variable results, and the course of the condition is often chronic-recurrent; therefore, it will be necessary for the future to identify new therapeutic targets for HS. In recent years, studies have focused on the development towards new therapeutic targets. The purpose of our review was to perform a comprehensive literature review of real-life data on anti-IL23 (guselkumab, tildrakizumab, and risankizumab) in HS to summarize the existing evidence on the efficacy and safety of these drugs. We selected 64 articles, among which 32 had the characteristics that we were looking for in our review. To date, the positive data expressed in real-life experiences contrast with the three existing Phase 2 studies conducted so far, where it seems that these drugs may be useful only for a subgroup of patients with HS whose features need to be elucidated. Data from Phase 3 studies and other real-life experiences, perhaps more detailed and with higher numbers, will certainly be needed to fully understand the efficacy and safety of this class of drugs.

Biologics for the Management of Erythrodermic Psoriasis: An Updated Review.

Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis (less than 3% of cases), characterized by generalized scaling and erythema affecting more than 90% of body surface area. Several systemic symptoms can be present in patients with EP such as lymphadenopathy, arthralgia, fever, fatigue, dehydration, serum electrolyte disturbances, and tachycardia making this condition a possible life-threatening disease, particularly if appropriate treatments are not performed. In this scenario, effective and safe therapies are required. Unfortunately, the rarity of EP makes head-to-head Phase III trials challenging, leading to the lack of established guidelines for its management. Globally, conventional systemic drugs such as cyclosporine, methotrexate, and retinoids often have contraindications linked to patients' comorbidities and have not shown a high profile of efficacy and safety. Recently, the development of biologic drugs including anti-tumor necrosis factor-α and anti-interleukin 12-23, 23, and 17 has revealed favorable results for the management of plaque psoriasis, making them also a possible therapeutic option for EP disease. However, their use in EP is still off-label. The aim of our study was to review current literature on the use of biologic drugs for the treatment of EPs in order to offer a wide perspective on their possible application in EP management.

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.

The Efficacy of Sonidegib in Treating Locally Advanced Basal Cell Carcinoma Involving the Periocular Area.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin malignancy in Caucasians. Globally, about 20% of BCCs involve the periocular region. The treatment of periocular BCC may be very challenging because of its proximity to the intracranial structures. Thus, early diagnosis and early treatment is mandatory. Recently, the introduction of Hedgehog pathway inhibitor therapy revolutionized the management of unresectable BCCs. The aim of our study was to evaluate the outcome of sonidegib treatment in patients affected by periocular locally advanced (la) BCC at our skin cancer center. METHODS: A 3-year retrospective study was carried out enrolling patients with periocular laBCC treated with sonidegib. Therapeutic response was defined as complete remission (CR) in case of complete regression of the tumor, partial remission (PR) in case of tumor regression not achieving complete remission, and stable disease (SD). RESULTS: A total 16 patients (11 men and 5 women; medium age 71.6 ± 11.5 years) with periocular laBCCs undergoing treatment with 200 mg/day of sonidegib were included in our study. Patients included in the study were treated for at least 6 months for a median duration of 9 months. Overall, CR was reported in 9/16 (56.2%) patients, PR was reported in 4/16 patients (25%), and tumor remained stable in 3 patients (18.8%). No cases of disease progression were collected. Fourteen out of 16 patients experienced multiple adverse events (AEs): dysgeusia was reported in 12 (75%) patients, muscle spasms in 13 (81%) patients, and 7 (43.7%) patients presented with alopecia. However, all of the AEs were mild and none required treatment discontinuation. CONCLUSION: To the best of our knowledge, this is the first study investigating the effectiveness and safety of sonidegib in the management of BCC localized at the periocular region. Even if limited, our study suggests this drug as a valuable and safe option in periocular BCC management.

Nail Psoriasis: An Updated Review of Currently Available Systemic Treatments.

Background: Nail psoriasis (NP) has a prevalence that ranges from 10 to 82% among patients with psoriasis (PsO) and is one of the most common difficult to treat site of psoriasis. We performed a thorough review of the literature, exploring evidence regarding all available NP systemic treatments, describing also in detail NP dedicated clinical trials. Methods: A literature search was conducted in PubMed and Embase prior to February 2023 using a combination of the terms "nail" AND "psoriasis" AND "systemic therapy" AND/OR "systemic treatment". A total of 47 original studies and case reports were reviewed in this article. Results: Systemic therapies should be considered when the disorder involves more than 3 nails, has extensive skin and joint involvement, and has a significant impact on QoL, due to their best long-term efficacy. In detail, conventional and biologic systemic drugs demonstrated efficacy in recent trials, including acitretin, methotrexate, cyclosporine, apremilast, adalimumab, infliximab, etanercept, certolizumab, golimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, bimekizumab, guselkumab, risankizumab and tildrakizumab. Conclusion: Several therapies have demonstrated efficacy and safety in the treatment of NP; however, the choice of treatment depends not only on the severity of the nail involvement, but also on whether PsA is present, the patient's comorbidities other than PsA, previous treatment history, and the patient's drug preferences.

Management of Advanced Invasive Melanoma: New Strategies.

The incidence of cutaneous melanoma (CM) is increasing. CM is defined as melanoma in situ when limited within the epidermis and invasive when atypical melanocytes progressively invade the dermis. Treatment of CM is challenging. On one hand, melanoma in situ does not require further treatment except for a limited secondary excision with reduced margins to minimize the risk of local recurrences; on the other, invasive melanoma requires a personalized approach based on tumor staging. Consequently, an association of surgical and medical treatments is often necessary for invasive forms of the disease. In this scenario, new knowledge on melanoma pathogenesis has led to the development of safe and effective treatments, and several drugs are currently under investigation. However, extensive knowledge is required to offer patients a tailored-tail approach. The aim of our article was to review current literature to provide an overview of treatment options for invasive melanoma, highlighting strategical approaches that can be used in patients with these forms of disease.