Treatment of locally advanced and metastatic basosquamous carcinoma, navigating among sonic hedgehog pathway inhibitors, immune checkpoint inhibitors, chemotherapy, and radiotherapy: A case series and literature review.

Locally advanced (laBSCs) and metastatic basosquamous carcinomas (mBSCs) represent a therapeutic challenge. By definition, these forms are not amenable to surgery or radiotherapy, but according to literature reports, sonic hedgehog pathway inhibitors (HHIs), anti-programmed death 1 receptor antibodies (anti-PD-1), and other treatment approaches involving chemotherapy, surgery, and radiotherapy have been used. This work features 5 real-life cases of advanced BSCs, treated at the Dermato-Oncology Unit of Trieste (Maggiore Hospital, University of Trieste). In addition, a review of the current treatment options reported in the literature for laBSC and mBSC is provided, collecting a total of 17 patients. According to these preliminary data, HHIs such as sonidegib and vismodegib could represent a safe and effective first line of treatment, while the anti-PD-1 cemiplimab may be useful as a second-line option. Chemotherapy and combined approaches involving surgery and radiotherapy have been also reported to be suitable in some patients.

Development and Implementation of a Web-Based International Registry Dedicated to Atypical Pigmented Skin Lesions of the Face: Teledermatologic Investigation on Epidemiology and Risk Factors.

Background: Atypical pigmented facial lesions (aPFLs) often display clinical and dermoscopic equivocal and/or overlapping features, thus causing a challenging and delayed diagnosis and/or inappropriate excisions. No specific registry dedicated to aPFL paired with clinical data is available to date. Methods: The dataset is hosted on a specifically designed web platform. Each complete case was composed of the following data: (1) one dermoscopic picture; (2) one clinical picture; (3) two lesion data, that is, maximum diameter and facial location (e.g., orbital area/forehead/nose/cheek/chin/mouth); (4) patient's demographics: family history of melanoma, history of sunburns in childhood, phototype, pheomelanine, eyes/hair color, multiple nevi/dysplastic nevi on the body; and (5) acquisition device (videodermatoscope/camera-based/smartphone-based system). Results: A total of 11 dermatologic centers contributed to a final teledermoscopy database of 1,197 aPFL with a distribution of 353 lentigo maligna (LM), 146 lentigo maligna melanoma (LMM), 231 pigmented actinic keratoses, 266 solar lentigo, 125 atypical nevi, 48 seborrheic keratosis, and 28 seborrheic-lichenoid keratoses. The cheek site was involved in half of aPFL cases (50%). Compared with those with the other aPFL cases, patients with LM/LMM were predominantly men, older (69.32 ± 12.9 years on average vs. 62.69 ± 14.51), exhibited larger lesions (11.88 ± 7.74 mm average maximum diameter vs. 9.33 ± 6.46 mm), and reported a positive history of sunburn in childhood. Conclusions: The iDScore facial dataset currently represents a precious source of data suitable for the design of diagnostic support tools based on risk scoring classifiers to help dermatologists in recognizing LM/LMM among challenging aPFL in clinical practice.

Kaposi's sarcoma, biologics and small molecules: Navigating the complex interplay between host immunity and viral biology. A case series with focused review of the literature.

The consequences of cytokine-specific immune modulation in the development and course of Kaposi's sarcoma (KS) are poorly understood. A retrospective chart review of patients treated with biologic/small molecule drugs and followed at the dedicated KS outpatient service of our Dermatology Unit was performed. The literature on biologic and small molecule drug use in KS patients was also reviewed. Data concerning 12 KS patients treated with biologic/small molecule drugs were collected. After a median delay of 6 months following biologic or small molecule drug introduction, nine patients experienced either KS onset or reactivation. Drugs associated with KS onset or flaring were: rituximab, infliximab, ruxolitinib apremilast (1), mirikizumab, abatacept (1). After a median follow-up of 25 months, all cases achieved persistent complete response through culprit drug discontinuation or drug withdrawal plus treatment. No effect on KS course was recorded with tocilizumab and vedolizumab. Based on our experience with the largest case series reported to date as well as the available literature, tocilizumab and ustekinumab seem to exert an overall neutral effect on KS. On the other hand, rituximab, infliximab, and ruxolitinib have been associated with the development or worsening of pre-existing KS and should be carefully pondered before use. Due to limited and partly controversial evidence, no definitive conclusions can be drawn on vedolizumab, apremilast, mirikizumab, abatacept.

Locally advanced basal cell carcinoma: Real-life data with sonidegib.

In recent years, the category of hedgehog pathway inhibitor (HHI) has shown great results in patients with advanced basal cell carcinoma (aBCC), but few real-life data on efficacy and safety profile of sonidegib are available. We report our management of locally advanced BCCs (laBCCs) with sonidegib, also describing the favorable response of locally advanced basosquamous carcinomas (laBSCs) treated with this hedgehog signaling inhibitor. Sonidegib was generally well tolerated and it achieved high response rates, improving quality of life. Our single-center experience could be useful to better delineate long-term efficacy and tolerability profile demonstrated in the trials described in literature. Moreover, our cases provide preliminary evidence that sonidegib might be effective for laBSC.

Neoadjuvant Therapy for Non-melanoma Skin Cancer: Updated Therapeutic Approaches for Basal, Squamous, and Merkel Cell Carcinoma.

OPINION STATEMENT: Recently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.

Trichophyton indotineae, an Emerging Drug-Resistant Dermatophyte: A Review of the Treatment Options.

Background: Dermatophytosis is a prevalent superficial infection caused by filamentous fungi, primarily affecting the skin and/or its appendages. In recent years, there has been a notable increase in mycotic strains resistant to standard antifungal therapies, including Trichophyton indotineae, a dermatophyte of the Trichophyton mentagrophytes complex. This review aims to provide a comprehensive overview of the treatment options for T. indotineae, elucidating their effectiveness in managing this challenging mycotic infection. Methods: For this review, a search was conducted in the PubMed, Scopus, Web of Science, Embase, and Google Scholar databases, encompassing all published data until March 2024. English-language articles detailing therapy outcomes for patients confirmed to be affected by T. indotineae, identified through molecular analysis, were included. Results: Itraconazole was shown to be a good therapeutic choice, particularly when administered at a dosage of 200 mg/day for 1-12 weeks. Voriconazole was also demonstrated to be effective, while terbinafine exhibited a reduced response rate. Griseofulvin and fluconazole, on the other hand, were found to be ineffective. Although topical treatments were mostly ineffective when used alone, they showed promising results when used in combination with systemic therapy. Mutational status was associated with different profiles of treatment response, suggesting the need for a more tailored approach. Conclusions: When managing T. indotineae infections, it is necessary to optimize therapy to mitigate resistances and relapse. Combining in vitro antifungal susceptibility testing with mutational analysis could be a promising strategy in refining treatment selection.

Bullous pemphigoid triggered by dulaglutide: a case report and a review of the literature.

Bullous pemphigoid (BP) is an autoimmune disease with a chronic relapsing course, predominantly affecting elderly people. Drugs are one of the possible triggers. A class of antidiabetic drugs often associated with the development of BP are inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors or gliptins), while less known is the association with glucagon-like-peptide-1 receptor agonists. We describe a case of BP caused by dulaglutide and summarize the other few cases described in the literature. As a class of drugs widely used in clinical practice, it is important to know about this possible adverse event.

Pilomatrix Carcinoma: Report of Two Cases of the Head and Review of the Literature.

BACKGROUND: Pilomatrix carcinoma (PC) is a rare skin tumor arising from hair follicle matrix cells. It is locally aggressive with a high rate of local recurrence after surgical excision. Few cases in the literature have been described and the management is not well defined. OBJECTIVES: The aim of this study was to present two cases of PC located on the head and review the relevant literature about epidemiology, clinical and dermoscopic evaluation, characteristics of local and distant metastases, local recurrence rate and management of this rare skin tumor. METHODS: We consulted databases from PubMed, Research Gate and Google Scholar, from January 2012 to November 2022. We reviewed the literature and reported two additional cases. RESULTS: We selected 52 tumors in middle-aged to older patients located mostly on the head. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. The most definitive treatment was wide local excision, but local recurrences were common. In total, we observed 11 cases of recurrences and 9 patients with locoregional or distant metastases. Four patients received adjuvant radiotherapy, two patients needed chemotherapy and local cancer therapy and one patient received radiochemotherapy. CONCLUSION: Our reports and the review of the literature can provide a better awareness and management of this rare tumor.

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response.

BACKGROUND: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs). SUMMARY: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions. KEY MESSAGES: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts.

Dupilumab as promising treatment for prurigo nodularis: current evidences.

Prurigo nodularis (PN) is a debilitating chronic disease characterized by intense itching and excoriated hyperkeratotic nodules distributed on the trunk and extremities, especially the extensor surfaces. The pathophysiology includes complex and not yet well-understood mechanisms involving inflammation and dysregulation of the nervous system. Currently, there are no approved therapies by the Food and Drug Administration (FDA) and the few treatment approaches for this condition are often ineffective and related to severe side effects. An emerging therapeutic option is dupilumab, a monoclonal antibody for adults and adolescents with moderate-to-severe atopic dermatitis, that inhibits interleukin-4 receptor alpha subunit (IL4-Rα) and the signaling pathways activated by interleukin (IL)-4 and IL-13. These cytokines seem to be involved in the development and perpetuation of PN and other type-2 inflammation diseases. Data on this topic are limited, but the emergent positive effects of this drug, reported in the literature and summarized in this review, suggest that it can be a safe and efficient therapy in PN.