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.

Scleroderma-like Syndrome in the Setting of Pembrolizumab Therapy for Non-Small Cell Lung Cancer: Diagnosis and Dermatologic Management.

Immune checkpoint inhibitors play an important role in the treatment of malignancies. ICIs consist of monoclonal antibodies directed against inhibitory immune receptors cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death-ligand 1 (PD-L1). PD-1 is a receptor expressed by T lymphocytes and has the role of inhibiting their activation. Pembrolizumab is a humanized anti-PD-1 monoclonal antibody. It can improve the immune function of T-cells, which results in significant clinical benefit in the treatment of cancer. Despite its wide use, immunotherapy is associated with a spectrum of side effects known as immune-related adverse events. We present a case of an 82-year-old patient with widespread fibroatrophic skin areas that occurred during a treatment with pembrolizumab for non-small cell lung cancer. Clinical, serological, and histopathological examinations led to the diagnosis of generalized morphea. The patient discontinued pembrolizumab and switched to chemotherapy with pemetrexed and carboplatin. A good therapeutic response was obtained with phototherapy, corticosteroids, and topical calcineurin inhibitors. A focus on the therapeutic management of this skin toxicity in oncological patients is provided.

Clinical associations and classification of immune checkpoint inhibitor-induced cutaneous toxicities: a multicentre study from the European Academy of Dermatology and Venereology Task Force of Dermatology for Cancer Patients.

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.

Vitiligo-like lesions in patients with advanced breast cancer treated with cycline-dependent kinases 4 and 6 inhibitors.

PURPOSE: Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2- metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. METHODS: We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018-December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients' quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: Sixteen women (median age: 62.5 years; range 40-79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). CONCLUSIONS: We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients' quality of life and their treatment is challenging.

Immune checkpoint-mediated psoriasis: A multicenter European study of 115 patients from the European Network for Cutaneous Adverse Event to Oncologic Drugs (ENCADO) group.

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.

Skin Toxicities During Colorectal Cancer Chemotherapy: Incidence and Pearls of Treatment in Our Experience.

INTRODUCTION: Medical treatment of advanced colorectal cancer is effective in prolonging the survival of patients. The aim of this study was to describe the most common skin toxicities that occur in those patients, analyzing the association between the type of reaction and the different chemotherapeutic drugs; and to evaluate the importance of an outpatient dermatologic service to improve quality of life. PATIENTS AND METHODS: Seventy-two patients with skin reactions from advanced colorectal cancer chemotherapy were included. Each patient underwent physical examination and digital photographic imaging, and completed a quality-of-life questionnaire (Dermatology Life Quality Index [DLQI]). RESULTS: Papulopustular rash was the most common side effect observed. It was statistically associated with EGFRi + irinotecan, EGFRi + FOLFOX, and EGFRi. Xerosis occurred in 50% of patients during EGFRi therapy. Periungual pyogenic granuloma-like lesions occurred in 30% of patients during EGFRi therapy. Our data underline a statistically significant association between capecitabine, FOLFOX + EGFRi, FOLFIFI + EGFRi, and hand-foot syndrome (P < .001). Because none of patients treated with EGFRi alone developed this kind of reaction, we suppose that it is associated with the use of 5-fluorouracil. Fifty percent of patients receiving anti-epidermal growth factor receptor (EGFR) therapy developed trichomegaly. These data underline a statistically significant association between these reactions and this specific drug. CONCLUSION: A dermatologic visit is useful, both for the correct diagnosis of and for the adequate therapy of chemotherapy side effects. The prevention and treatment of these toxicities are important, not only to improve quality of life but also to avoid unnecessary dose reduction or interruption, which can have a negative effect on treatment outcome.

Safe distance, safe patients! Therapeutic management of oncological patients affected by cutaneous and mucosal adverse events during the COVID-19 pandemic: an Italian experience.

Stringent measures have been taken to contain COVID-19 spread, limiting access only for urgent visits, surgery procedures, or hospitalizations and using teledermatology services for non-urgent cases. Management of oncological patients affected by chemo-, immune-, and radiotherapy-related cutaneous and mucosal adverse events is a challenge. Firstly because of the differential diagnosis of cutaneous rash (e.g., drug-related rash or paraviral exanthema). Secondly, oncological patients can suffer from xerosis, pruritus, and mucositis that contribute to cutaneous and mucosal barrier lesions, thus becoming vulnerable site for viral or bacterial colonization. These lesions can also be aggravated by the use of protective mask and gloves. Here, we report also our results of a teledermatological survey on 87 oncological patients, where the health status of oncological patients referred to our dedicated clinic was assessed during the COVID-19 pandemic. Therefore, it is fundamental that oncological patients are followed up by their dermatologists even if the clinics are closed. Teledermatology represents a crucial means of communication. Patients can contact the dermatological staff by emails and telephone, 24 h a day, 7 days a week, for video calls and dermatological consultations.

Current Recommendations and Novel Strategies for the Management of Skin Toxicities Related to Anti-EGFR Therapies in Patients with Metastatic Colorectal Cancer.

The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted therapies do not have the systemic adverse reactions of chemotherapy, they are associated with toxicities that can be severe and impair patient quality of life and adherence to anti-cancer treatment. Panitumumab and cetuximab, two monoclonal antibodies against epidermal growth factor receptor (EGFR), are recommended for the treatment of metastatic colorectal cancer (mCRC). The majority of patients with mCRC who are treated with anti-EGFR therapy develop skin toxicities, including papulopustular rash (the most common), xerosis, painful cracks and fissures on the palms and soles of the feet, paronychia, pruritus, and abnormal hair and eyelash growth; they are also more prone to skin infections. Given the involvement of EGFR in normal epidermis physiology, development and function, skin toxicities caused by anti-EGFR therapy are not unexpected. In recent years, recommendations have been formulated for the prevention and treatment of anti-EGFR therapy-related skin toxicities. Indeed, proper and timely management of these toxicities is important for ensuring uninterrupted anti-cancer treatment and optimal outcomes. Here, we review the current knowledge of anti-EGFR therapy-related skin toxicities and the latest recommendations for their management. We also present a treatment approach for papulopustular rash based on the combination of fusidic acid plus betamethasone in a lipid-enriched topical formulation. The effectiveness of this approach is documented by the presentation of five cases successfully treated in clinical practice for anti-EGFR therapy-related rash.

Treatment Outcomes of Immune-Related Cutaneous Adverse Events.

PURPOSE: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Retrospective Analysis of Skin Toxicity in Patients under Anti-EGFR Tyrosine Kinase Inhibitors: Our Experience in Lung Cancer.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of life. However, TKIs can lead to cutaneous toxicities, including papulopustular rash, xerosis, paronychia with/without pyogenic granulomas, scalp disorders, facial hair and/or eyelash growth. AIM: In this study, we describe retrospectively all cases of mucocutaneous side effects in patients with lung cancer under TKIs referring to our outpatient for the skin care of oncological patients. METHODS: We included patients referring from January 2016 to January 2018 affected by lung cancer and under TKIs. We collected data about the clinical exam, clinical photography, dermoscopy, histology and direct microscopic examination for each patient and we performed retrospectively descriptive analyses to assess whether a specific TKIs is linked significantly to particular cutaneous toxicity. RESULTS: The majority of skin toxicities were due to afatinib, and the most common skin reaction was rash. We selected 60 patients with skin reactions, treated by TKIs for lung cancer. The majority of skin toxicities were due to afatinib (47/102 adverse reactions) and erlotinib (39/102). The most common skin reaction was rash (63% of patients), followed by xerosis (30%) and granulomas (30%). There was no significant relationship between a specific type of cutaneous reaction and specific EGFRi except for granulomas, developed more frequently in patients under afatinib (p < 0.05). CONCLUSION: Most of our patients (63%) developed a cutaneous rash under TKIs. Most commonly afatinib was the drug involved, although it wasn't the most used EGFRi. Moreover, we noticed a significant correlation between afatinib therapy and appearance of granulomas.

Confocal microscopy can assess the efficacy of combined microneedling and skinbooster for striae rubrae.

Striae distensae or stretch marks are dermal scars characterized by flattening and atrophy of the epidermis. They develop particularly during adolescence but they can also appear in other situations such as pregnancy, the use of prolonged therapies with topical or systemic corticosteroids, Cushing's syndrome, Marfan's syndrome, prolonged use of lightening creams, cachexia, rapid weight loss or the use of androgenic and anabolic substances. Treatment options often take a long time, and the results are often disappointing, causing significant psychological distress in patients. We propose a completely innovative approach, combining the skinbooster technique with the microneedling technique. These minivasive methods work by inducing tissue remodeling and stimulating the synthesis of new collagen. Confocal microscopy can show and follow the skin changes made by these therapies, thus becoming an important and valid therapeutic monitoring tool for aesthetic dermatology.

Unconventional therapies for hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating skin disease, which usually occurs after puberty with painful, deep-seated, inflammatory lesions in the apocrine gland-bearing areas of the body. Several pharmacologic agents have been described to reduce lesion activity and inflammation in HS. However, conventional treatment may not always get the desired results. Therefore, unconventional therapies must be taken into account. Areas covered: Recently, the better understanding of HS pathogenesis has been used to improve treatment strategies with many emerging conventional and unconventional therapeutics options. Adalimumab is the only FDA-approved biologic available for therapy of moderate-to-severe HS. Nevertheless, novel therapeutic approach, including both topical and systemic as well as novel laser device, showed good clinical outcome. Several molecules, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-17, IL-12, IL-23, phosphodiesterase 4 (PDE4), lymphocyte function-associated antigen 1 (LFA-1), and complement component 5a (C5a), are modulated by such new biologic agents in HS. Expert commentary: In the next years, many therapeutic options for HS will be available. Clinical trials showed the efficacy of several biologic drugs, antibiotics, laser light device. Novel therapeutic options seem to be promising, but dermatologists will have to evaluate their effectiveness and safety in daily clinical practice.

Dermoscopy of scalp melanoma: report of three cases.

Scalp melanoma is rare and often late-discovered because of its unusual position. As a consequence, its prognosis is poorer than melanoma on other body sites and only few clinical reports about its dermoscopic pattern have been published. In this paper, we report three clinical cases of scalp melanoma with photographic documentation and dermoscopic images, in order to improve the early detection of scalp melanoma.

Epidemiology of skin cancer: role of some environmental factors.

The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases in biologically damaging solar UVB radiation reaching the earth's surface. In humans, arsenic is known to cause cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney. Exposure to high levels of arsenic in drinking water has been recognized in some regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been reported to be associated with ingestion of arsenic alone or in combination with other risk factors. The impact of changes in ambient temperature will influence people's behavior and the time they spend outdoors. Higher temperatures accompanying climate change may lead, among many other effects, to increasing incidence of skin cancer.