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Byline: L. Panariello, D. Fattore, E. Cinelli, M. Campanino, G. Mansueto, G. Fabbrocini To the Editor, Foreign body granuloma and migration of the implanted material are possible delayed side effects [...]

Background Objective Methods Results Conclusion There is a need for unified guidance in the management of acneiform rash induced by epidermal growth factor receptor inhibitors (EGFRi) among dermatologists.To establish unified international guidelines for the management of acneiform rash caused by EGFR inhibitors, based on an experts' Delphi consensus.The initiative was led by five members of the European Academy of Dermatology and Venereology Task Force ‘Dermatology for Cancer Patients’ who developed a questionnaire that was circulated to a group of 32 supportive oncodermatology experts in Europe, Canada, Argentina, the US States and Asia. The questionnaire consisted of 84 statements in total, regarding diagnosis and treatment of EGFRi‐induced acneiform rash. Experts responded to an anonymous 5‐point Likert scale survey. The coordinators collected the first‐round responses that were checked for consensus (≥75% agreement in positive [agree or strongly agree] or in negative [disagree or strongly disagree] vote). The statements that did not reach strong consensus in the first round were revised, according to experts' feedback, for a second‐round survey.Strong consensus was reached in 75/84 (89.3%) of the statements, whilst moderate consensus was achieved in 6/84 elements. Key points include consideration of low‐dose isotretinoin for refractory grade II/III acneiform rash, use of topical steroid‐sparing agents like topical pimecrolimus in the maintenance phase and use of doxycycline in either 100 or 200 mg per day as prophylactic treatment. Interestingly, experts did not recommend topical antibiotics, neither for prevention, nor for treatment. Consensus failure in 3/84 objects is mostly related to the lack of robust data on these topics.This consensus offers crucial insights often overlooked by radiotherapists, general practitioners, dermatologists and oncologists, and it is expected to improve the management of oncologic patients treated with EGFRi in different settings and continents. [ABSTRACT FROM AUTHOR]

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.

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.

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., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Introduction: Radiation-induced alopecia (RIA) is a side effect resulting from cranial radiation therapy (RT) and it can be temporary or permanent. In cancer patients, RIA is a less frequent event than chemotherapy-induced alopecia, although the former is more likely to cause permanent hair loss. It is characterized initially by intense anagen effluvium caused by acute dose-dependent damage to the matrix cells of anagen follicles. Proton therapy (PT) is a specific type of RT used in the treatment of brain tumors, which sometimes can cause proton-induced alopecia (PIA), a rare subtype of RIA. Below, we report a case of a patient who presented PIA following PT treatment of a meningioma of the frontal region., Case Presentation: A 38-year-old female patient presented to our trichology outpatient clinic for widespread hair loss in the frontal region. Following a diagnosis of meningioma of the frontal region 3 years ago, adjuvant radiotherapy treatment of the frontal region with scanning beam PT (mean dose of 45 Gy) was performed. Two weeks after the end of treatment, the patient came to our attention with diffuse hair loss at the level of the PT-treated area. Trichoscopy showed flame hairs, broken hairs, black dots, and pigtail hairs. A diagnosis of PIA was established, and topical treatment with minoxidil 5% solution twice a day was initiated. At the follow-up visit after 4 months, the patient had total hair regrowth., Conclusion: PIA is a subtype of RIA still poorly studied in the literature. Hair loss is caused by aggression by radiations of the hair follicle in the anagen phase, leading to an interruption of the mitotic activity of the matrix cells. The cells of the follicular bulb are characterized by marked mitotic activity at this stage and are consequently more susceptible to cytotoxic damage. All this causes tightening of the proximal portion of the hair shaft, increasing its fragility and susceptibility to breakage., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Merli, Accorinti, Romagnuolo, Marzano, Di Zenzo, Moro, Antiga, Maglie, Cozzani, Parodi, Gasparini, Sollena, De Simone, Caproni, Pisano, Fattore, Balestri, Sena, Vezzoli, Teoli, Ardigò, Vassallo, Michelerio, Satta, Dika, Melotti, Ribero and Quaglino.)

Background: The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes., Methods: We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score., Results: Seventy-nine patients (median age: 62.3 years; range 39-83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments., Conclusions: To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes.

Competing Interests: Conflicts of interest VN, KL, CC, PS, ZA, MS, DF, GF, SS, and JR, have nothing to disclose. AF-M, consultant of ISDIN, L'Oreal, Galderma, and Shook, Hardy, Bacon LLP who represent Sanofi Aventis US LLC, and VS, speaker, or advisory role for Incyte, Bristol Myers Squibb, Novartis, Pierre Fabre, Bayer, Astellas, Amgen, Synox, MSD.

Background: Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs)., Objectives: To investigate clinical associations of cutaneous toxicities induced by different ICI therapies., Methods: This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models., Results: In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01-0·76] and vitiligo (OR 0·07, 95% CI 0·006-0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02-0·31), lichenoid reactions (OR 0·15, 95% CI 0·03-0·77) and eczematous reactions (OR 0·24, 95% CI 0·07-0·78), all compared with pruritic rash., Conclusions: Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy. Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer. The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus. Clinical awareness and specialized dermatological consultation should be advocated., (© 2022 British Association of Dermatologists.)

The introduction of immune checkpoint inhibitors (ICIs) opened a new era in oncologic therapy. The favourable profile of ICIs in terms of efficacy and safety can be overshadowed by the development of immune-related adverse events (irAEs). Dermatologic irAEs (dirAEs) appear in about 40% of patients undergoing immunotherapy and mainly include maculopapular, psoriasiform, lichenoid and eczematous rashes, auto-immune bullous disorders, pigmentary disorders, pruritus, oral mucosal lesions, hair and nail changes, as well as a few rare and potentially life-threatening toxicities. The EADV task force Dermatology for Cancer Patients merged the clinical experience of the so-far published data, incorporated the quantitative and qualitative characteristics of each specific dirAEs, and released dermatology-derived, phenotype-specific treatment recommendations for cutaneous toxicities (including levels of evidence and grades of recommendation). The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients' relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment., (© 2021 European Academy of Dermatology and Venereology.)

Immune system escape is one of the major strategies required for cancer growths. In this scenario, the advent of immune checkpoint inhibitors (ICIs) revolutionized the landscape of treatment options for tumors. Despite their wide use, these agents are associated with a unique spectrum of toxicities known as immune-related adverse events (irAEs). IrAEs are cause of treatment suspension (up to 60% of all causes of treatment interruption) and potentially impact on patients' quality of life. These toxicities are the main limitations on the use of these innovative drugs. IrAEs are peculiar, due to the mechanism of actions of ICIs, and any body organs may be involved (skin, thyroid, colon, lungs, in particular). Thus, the management often requires a multidisciplinary approach. The aim of this manuscript is to review current literature on autoimmune skin diseases described in association with ICIs (i.e., vitiligo, lupus erythematosus, vasculitis, morphea/scleroderma, alopecia areata, bullous pemphigoid, dermatomyositis), in order to provide a comprehensive overview for the physician.

Background: Atopic dermatitis management is challenging and usually requires intermittent or continuous, long-term treatment with topical and/or systemic anti-inflammatory agents and appropriate skin care. Most patients affected by atopic dermatitis improve during sun exposure. It has been reported that the change from a subartic/temperate to a subtropical climate for 4 weeks improved significantly skin symptoms and quality of life in children, even for 3 months after return. However, until now the effect of sun exposure on adult patients with atopic dermatitis has never been investigated., Methods: We conducted a retrospective study to assess the short-term effect of sun exposure during summer holidays on skin symptoms of adults affected by AD., Results: One hundred and fourteen patients were enrolled in the study (62 males; aged 18-72 years, mean age 35.3±12.6). Seventy-three out of 114 patients (64%) spent their holidays at the seaside, and 41/114 (36%) in the mountains; 38/41 (92.7%) subjects from the latter group reported that during their holidays they frequented outdoor swimming pools or solariums almost every day of their vacation. The sunlight effect was considered beneficial by 68/114 (59.6%) of patients. In particular, 38/114 patients (33.3%%) reported the improvement of AD and 30/114 (26.3%) the complete resolution of the disease during summer holiday., Conclusions: Our data seem to suggest that sun exposure is beneficial in most patients, but not in all patients. In fact, sun exposure does not appear to improve skin symptoms or even aggravate them in about 4 out of 10 patients. This could be particularly important also considering ongoing climate changes that may affect the clinical history of several skin diseases, among which AD.

Background: Immune checkpoint inhibitor (ICI)-mediated psoriasis poses significant diagnostic and therapeutic challenges., Objective: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm., Methods: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions., Results: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P = .03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P < .001). Guttate psoriasis and grade 2 or 3 disease were significant positive predictors for antitumor response of ICI, whereas pruritus was a negative predictor., Limitations: Retrospective design., Conclusion: Acitretin, apremilast, and methotrexate are safe and effective modalities for ICI-mediated psoriasis. In most cases, ICI can be completed unhindered. A therapeutic algorithm is proposed., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020. Published by Elsevier Inc.)