Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal ...homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25–85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients’ quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.
The therapeutic use of anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab) is rapidly increasing. Given their mechanism of action that triggers T-cell activation, these immune checkpoint inhibitors ...induce specific adverse events that are mostly of immunologic origin. In this way, cutaneous toxicities represent the most frequent immune-related adverse events (irAEs). The purpose of this review is to summarize the most prevalent dermatologic complications induced by PD-1/PD-L1 immune checkpoint-blocking antibodies and to compare their dermatologic safety profile with anti-CTLA-4 ipilimumab.
More than 40% of melanoma patients treated with anti-PD-1 therapy are faced with dermatologic irAEs. However, these cutaneous complications usually remain self-limiting and readily manageable. Nonspecific macular papular rash and pruritus represent the most common manifestations. More characteristic lichenoid dermatitis or psoriasis may also develop. Vitiligo is also frequent in patients with melanoma but has not been reported in other types of solid cancers. Mucosal involvement may also occur, including xerostomia and lichenoid reactions. Although available data remain scarce, anti-PD-L1 antibodies present a similar dermatologic safety profile.
Dermatologic irAEs induced by PD-1 or PD-L1 blockade therapy rarely result in significant morbidity or permanent discontinuation of treatment. However, early recognition and appropriate management are crucial for restricting dose-limiting toxicities.
Adjuvant systemic treatments in breast cancer are indicated to reduce the risk of relapse. Their systemic side effects have been well documented and include menopausal symptoms such as impaired ...libido and vaginal dryness, increased risk of endometrial cancer, stroke, musculoskeletal symptoms including arthralgia and myalgia, osteopenia and fractures, skin rashes, and hypercholesterolemia. However, few articles have focused on the oral mucosal reactions related to adjuvant endocrine therapies (AETs) which clearly differ from those reported with chemotherapies or other targeted therapies used for breast cancer. AETs primarily expose patient to a higher risk of worsened periodontal health, salivary flow modifications, taste disturbance, and global deterioration of oral health-related quality of life. Although the rate of permanent discontinuation of AETs because of oral mucosal changes remains low, an interdisciplinary approach to evaluate oral health and to optimize oral supportive care appears essential to ensure an appropriate management and limit dose adjustment in treated patients. In this respect and based on our clinical experience, we propose recommendations to allow oncologists, nurses, and attending practitioners to implement appropriate measures rapidly and/or refer patients to dentists.
Summary Patients treated with systemic anticancer drugs often show changes to their nails, which are usually well tolerated and disappear on cessation of treatment. However, some nail toxicities can ...cause pain and functional impairment and thus substantially affect a patient's quality of life, especially if they are given taxanes or EGFR inhibitors. These nail toxicities can affect both the nail plate and bed, and might present as melanonychia, leukonychia, onycholysis, onychomadesis, Beau's lines, or onychorrhexis, as frequently noted with conventional chemotherapies. Additionally, the periungual area (perionychium) of the nail might be affected by paronychia or pyogenic granuloma, especially in patients treated with drugs targeting EGFR or MEK. We review the nail changes induced by conventional chemotherapies and those associated with the use of targeted anticancer drugs and discuss preventive or curative options.
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.
Sensitive skin syndrome was first described in 1977; however, no robust study has been carried out to evaluate its prevalence in Japan. A national representative sample of the Japanese population ...over the age of 18 years was taken. Individuals were questioned by telephone and selected according to the quota method. When asked “Do you have a sensitive skin?”, 52.84% of men and 55.98% of women answered “rather sensitive” or “very sensitive”. There was no significant difference (P = 0.22) between the two sexes. The non‐response rate among respondents was zero, suggesting that the term “sensitive skin” held a meaning for the majority of the population. Concerning questions about the onset of a rash, tingling or irritation in the presence of various factors, such as emotional issues, cold, heat, sun, dry air, air‐conditioning, water, air pollution and temperature variations, respondents with rather sensitive or very sensitive skin responded “yes” more often than others: approximately three‐times more often for water (18.97%/6.15%), air pollution (39.29%/12.45%) and warm climatic conditions (29.74%/9.8%). To our knowledge, this epidemiological study is the first to focus on sensitive skin among Japanese people of this century. It is of particular interest for two reasons: (i) it was conducted on a representative sample of the Japanese population; and (ii) the methodology used was identical to that used for sensitive skin assessment studies conducted in Europe and the USA, making it possible to draw certain comparisons.
Immune checkpoint inhibitors are a new class of oncologic drugs that act via the inhibition of checkpoints, thereby unlocking the immune system to attack cancer cells. Their emergence has radically ...changed the concept of therapy in oncologic patients. However, despite their overall favorable profile, their use has been associated with specific toxicities that may potentially affect treatment. The so-called immune-related adverse events (irAEs) mostly correspond to dysimmune reactions that can affect nearly every organ system, in theory, notably with the development of colitis, hepatitis, pneumonitis, or thyroiditis. Dermatologic irAEs are also among the most common, reaching a rate of approximately 40%. They are characterized by a wide phenotypic range, including mainly eczematous or lichenoid rashes, psoriasis, or autoimmune bullous disorders. Pruritus may accompany the aforementioned rashes or develop as an isolated symptom without the presence of skin changes. Depigmentation and hair/nail changes can be also observed in association with immune checkpoint inhibitor treatment. In the current article, we present an overview of the clinical spectrum of irAEs and provide tips for early recognition and management of dermatologic irAEs. We highlight the role that dermatologists can play in relieving patients and allowing for oncologic treatment to be maintained and administered more safely.
Introduction Sensitive skin is a complex dermatological condition, defined by abnormal sensory symptoms. The aim of this epidemiological survey was to assess the prevalence of sensitive skin and ...collect data on sensitive skin in the US population.
Methods A phone survey was conducted in the USA by a poll institute in 2007. A sample was drawn from a representative national cohort of the American population at least 18 years of age through the quota method. Data on demographic characteristics, environmental and climatic factors, skin characteristics, dermatological disorders, cosmetics use, and visits to the dermatologist were collected.
Results Of 994 subjects who answered (495 men and 499 women), 44.6% declared having “sensitive” or “very sensitive” skin. Women were more concerned than men (50.9% vs. 38.2%, P < 0.0001). There was no significant difference related to geographic localization, age, or ethnic distribution. Subjects with sensitive skin had mainly dry (34.5%) or mixed skin (35.7%), fair phototypes, dermatological disorders, higher skin reactivity to cosmetics and various environmental factors in comparison with subjects who stated having only a “slightly” sensitive or not sensitive skin. The dermatologist had a strong influence on subjects with “sensitive” or “very sensitive” skin through the prescription of skin care products.
Conclusion This study, based on a representative sample of the American population, reveals a high prevalence of sensitive skin in the USA. Sensitive skin is mainly associated with dry skin, fair phototype, reactivity to climatic and environmental factors, and cosmetics. American dermatologists seem largely involved in the care of this condition.
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