Management of cutaneous adverse events caused by antineoplastic therapies: a single-center experience.

INTRODUCTION: Cutaneous adverse events can occur in patients treated with antineoplastic treatments, albeit their incidence has not been defined yet. The clinical presentation of CAEs related to anticancer treatments can vary. The purpose of our study is to characterize skin toxicities during oncological treatments, manage such adverse events to improve patients' quality of life, and ensure therapeutic adherence. METHODS: We conducted a single-center prospective study which provided the enrollment of all patients referred to the Skin Toxicity Outpatient Clinic for the occurrence of cutaneous adverse events secondary to an ongoing antineoplastic treatment, between July 2021 and June 2023. We analyzed clinical features, and we described our therapeutic approach. RESULTS: Based on the type of drug assumed, chemotherapy-induced skin toxicity in 24 (38.7%) of the 62 evaluated patients, target therapies in 18 (29.0%), CDK4/6 cyclin inhibitors in 12 (19.4%), and immunotherapy in 6 (9.7%), while skin adverse events secondary to hormone therapy were seen in two patients. The most common cutaneous adverse event in our experience was rosaceiform rash of the face, followed by eczematous rash, hand-foot syndrome, and folliculitis. CONCLUSION: The present study is aimed at describing the variability and heterogeneity of clinical manifestations of different pharmacological classes used in oncological patients, as well as the different pathogenesis of skin damage. Chemotherapy very frequently causes skin toxicities that are often underestimated by clinicians. Their adequate recognition and optimal treatment lead to total recovery and allow better adhesion to chemotherapy.

Successful treatment of PD1-inhibitor induced psoriasiform dermatitis using IL-17 blockade without compromising immunotherapy efficacy.

INTRODUCTION: Pembrolizumab is a monoclonal PD-1 inhibitor used in the treatment of lung cancer in addition to several other malignancies. Psoriasiform dermatitis is a well-documented adverse effect. CASE REPORT: We present a 68 year-old-male with a 50-year smoking history and a 30-year remote history of plaque psoriasis, limited to the knees and elbows, who presented with metastatic non-small cell lung cancer. He was started on a chemotherapy regimen of carboplatin, paclitaxel, and pembrolizumab. One month later, he presented to dermatology with diffuse erythematous scaly papules coalescing into plaques on 80% of body surface area (BSA). MANAGEMENT & OUTCOME: Pembrolizumab treatment was paused. The patient was prescribed triamcinolone 0.1% twice daily, but still had significant BSA at one-month and was started on an Il-17 inhibitor, ixekizumab, clearing the psoriasiform dermatitis. He was rechallenged with pembrolizumab every 3 weeks and repeat PET/CT demonstrated excellent tumor response. DISCUSSION: This case prompted a literature review to further characterize the use of IL-17 inhibitors for psoriasiform dermatitis in the setting of ICI therapy. All six cases demonstrated improvement of psoriasiform dermatitis, with two cases showing partial response and four cases showing complete resolution. In three of the six cases, the patients exhibited clinical response to the primary malignancy after rechallenging with ICI, while remaining on an IL-17 inhibitor. Our case, in conjunction with the other reported cases, seems to suggest that IL-17 blockade can maintain a fine balance in this challenging clinical scenario by treating psoriasiform dermatitis without compromising the efficacy of immunotherapy.

The diverse landscape of dermatologic toxicities of non-immune checkpoint inhibitor monoclonal antibody-based cancer therapy.

BACKGROUND: Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non-immune checkpoint inhibitor (non-ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited. METHODS: A comprehensive review was conducted on dermatologic toxicities associated with different classes of non-ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta-analyses; and case series/reports. RESULTS: Dermatologic toxicities were associated with several types of non-ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non-ICI mAbs. Immunobullous reactions were rare and a subset of non-ICI mAbs were associated with the development of vitiligo cAEs. CONCLUSION: Dermatologic toxicities of non-ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non-ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Cutaneous adverse events associated with PD-1 inhibitor-based therapy in patients with non-small-cell lung cancer.

Aim: To analyze the incidence and characteristics of cutaneous adverse events (CAEs) in non-small-cell lung cancer patients treated with PD-1 inhibitor-based therapy. Methods: A total of 150 non-small-cell lung cancer patients under PD-1 inhibitor-based therapy from February 2018 to September 2021 were included and were followed up with regularly. Results: Over one-half of patients (88/150; 58.7%) had CAEs. Reactive cutaneous capillary endothelial proliferation, maculopapular rash and pruritus were the most common CAEs. The incidences of CAEs were 50.0 (18/36), 67.0 (50/75) and 51.3% (20/39) with PD-1 inhibitor monotherapy, PD-1 inhibitor in combination with chemotherapy and PD-1 inhibitor in combination with antivascular/targeted therapy, respectively. Conclusion: CAEs occur frequently in PD-1 inhibitor-based therapy but are generally tolerable.

An overview of the efficacy of phototherapy in oncodermatology.

BACKGROUND: Cutaneous adverse events (AEs) following cancer immunotherapy, targeted therapy, and chemotherapy have been well-documented in the literature. A number of case reports have identified phototherapy, a form of light therapy that mimics sunlight exposure, as a noninvasive treatment modality for these cutaneous toxicities. By inducing local suppression of the immune system, phototherapy is a skin-directed treatment with minimal effect on tumor response. Phototherapy may therefore be a viable treatment option for cutaneous AEs from cancer therapies. METHODS: We reviewed the literature for patients treated with phototherapy for cutaneous AEs following cancer immunotherapy, targeted therapy, or chemotherapy. We also included three previously unpublished cases from our own institution. RESULTS: We identified 24 patients (80% male, mean age 67 years, range 49-75 years). Patients received the following phototherapy types: NB-UVB (n = 17), PUVA (n = 6), or PDT (n = 1). A topical steroid was used in conjunction with phototherapy in seven patients. At phototherapy onset, cancer treatment was either continued, temporarily discontinued, or discontinued (n = 9, 6, 7, respectively; in two cases, the cancer treatment course was unknown). Improvement of cutaneous AEs was observed in 96% of patients. CONCLUSIONS: Phototherapy resulted in full or partial improvement in all but one patient. A topical steroid was used in nearly a third of patients, suggesting some oncodermatologists co-administer topicals to further boost response. Continuation of cancer therapy in the majority of patients highlights an additional advantage of phototherapy. We believe phototherapy may be an effective adjunctive treatment to topical steroids when treating these cutaneous toxicities.

Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors.

PURPOSE: To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). PATIENTS AND METHODS: Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. RESULTS: Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. CONCLUSION: Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

Dermatological Aspects of Nursing Oncology: Meaningful Observations Ensuring Better Quality of Life.

Modern cancer management has changed over the period of time and now shifted to multidisciplinary care approach to ensure a better quality of life (QOL) of the surfing patients. Every form of cancer treatment has side effects and affects the QOL. Many of the side effects have been discussed in detail because of the need for timely interventions to prevent the consequences of the side effects. Dermatological adverse events due to cancer treatment are important but most commonly ignored in our clinical practice. Nursing staffs have a critical role in the early identification of such events and by briefing and training of the nursing staff in the identification of adverse events which can aid in the prevention of complications. As dermatologists may not be available round the clock, nursing staff are looking after the patients round the clock can prove very vital in screening cutaneous AE and adequately setting up referrals to aid early recognition and treatment of not only mild but also potentially life-threatening complications. The nursing staff, which is a cadre of health caregivers that are intimately involved in cancer care, can be trained to identify timely, skin-related adverse events. A literature search of scientific publications was done using the electronic databases PubMed, Science Direct, Cochrane Library, and Google Scholar. The search included terms 'Adverse events (AEs) post-chemotherapy,' 'AE post-radiotherapy,' 'AE post-immunotherapy,' 'AE post-hormonal therapy for cancer' and 'AE post-cancer surgery.' Data obtained from these studies and case reports were compiled and interpreted to prepare this review. This review focuses on various ways in which skin can be involved adversely as a part of cancer management and their classic and tell-tale signs to help the nurses in their better and quicker identification so that dermatologists are timely intimated and the treatment can be instituted to improve the patient's QOL.

Evaluating health related quality of life in outpatients receiving anti-cancer treatment: results from an observational, cross-sectional study.

BACKGROUND: The aim of the study was to assess health-related quality of life (HRQOL) in outpatients receiving anti-cancer treatment. METHODS: Observational, cross-sectional, single-center study that assessed HRQOL in cancer patients receiving antineoplastic treatment. RESULTS: A total of 184 patients were included in the study; the median total FACT-G score was 66 ± 12.9; the scores for the physical well-being, social/family well-being, emotional well-being and functional well-being domains were 17.8 + 4.8, 19.1 ± 4.4, 14.8 ± 3.8 and 14.3 ± 4.7 respectively. Patients with adverse events had poorer HRQOL compared to those without them (FACT-G score 62.2 vs. 67.3; p < 0.05). In the multivariate analysis the variables associated with poorer HRQOL in the form of a gradient were tumor stage and performance status (ECOG); female sex was also associated with poorer HRQOL. CONCLUSION: In our study, the neoplastic disease and anti-cancer treatment toxicities had an impact on HRQOL. Patients had poorer scores in the functional well-being domain and higher ones in the social/family well-being domain. Variables associated with worse HRQOL were tumor stage, performance status (ECOG) and female sex.

Cutaneous Adverse Events to Targeted Therapies and Immuno-therapies in Children: A Retrospective Study of 103 Patients from Two Tertiary Haemato-Oncology Referral Centres.

Targeted medications and immunotherapies are being developed to specifically target the pathways involved in tumours. There is limited experience with these new medications and their cutaneous side-effects in the paediatric population. A retrospective study of all paediatric oncological patients treated with targeted therapies and immunotherapies between 1 January 2013 and 1 August 2020 was carried out in 2 haemato-oncological referral centres. A total of 103 children were included in the study. The median (interquartile range) age was 13 years (8.4-16.9), male:female ratio 1.5:1, median (interquartile range) follow-up was 7 months (2-18). Fifty (48%) of the children developed cutaneous adverse events. Treatment was discontinued in only 3 (6%) cases and was altered in only (2%) 1 case due to a cutaneous adverse event. When targeted therapies and immunotherapies for tumours in children are used, there is an increased incidence of cutaneous adverse events. Nevertheless, treatment modification or discontinuation due to cutaneous side-effects is rarely needed.

Cutaneous adverse events in a randomized controlled trial of flash glucose monitoring among youth with type 1 diabetes mellitus.

BACKGROUND: The literature regarding flash glucose monitoring (FGM)-associated cutaneous adverse events (AE) is limited. OBJECTIVES: This study among youth participating in a 6 month randomized controlled trial aimed to compare cutaneous AE between FGM and self-monitored blood glucose (SMBG) use and evaluate premature FGM sensor loss. METHODS: Patients aged 13 to 20 years with type 1 diabetes were randomized to intervention (FGM and usual care) or control (SMBG and usual care). Participants self-reported cutaneous AEs electronically every 14 days. Reports were analyzed to determine frequency, type, and severity of cutaneous AEs, and evaluate premature sensor loss. RESULTS: Sixty-four participants were recruited; 33 randomized to FGM and 31 to control. In total, 80 cutaneous AEs were reported (40 in each group); however, the proportion of participants experiencing cutaneous AEs was greater in the FGM group compared to control (58% and 23% respectively, P = .004). FGM participants most frequently reported erythema (50% of AEs), while controls most commonly reported skin hardening (60% of AEs). For FGM users, 80.0% of cutaneous AEs were mild, 17.5% moderate, and 2.5% severe. Among controls, 82.5% of cutaneous AEs were mild and 17.5% moderate. One participant ceased using FGM due to recurring cutaneous AEs. Additionally, over 6 months, 82% of FGM participants experienced at least one premature sensor loss, largely unrelated to a cutaneous AE. CONCLUSIONS: Cutaneous FGM-associated AEs are common, and mostly rated as mild. However, the majority of users continued FGM despite cutaneous AEs. Awareness of cutaneous complications and mitigation measures may reduce cutaneous AEs and improve the overall experience of FGM.

Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management.

BACKGROUND: There is increasing recognition of distinct inflammatory eruptions associated with checkpoint inhibitors. A better understanding of their severity, therapeutic response, and impact on cancer treatment is needed. OBJECTIVE: To analyze the different rashes associated with immunotherapy referred to our institution's oncodermatology clinic and inpatient consultative service and to evaluate their therapeutic response and impact on immunotherapy. METHODS: We retrospectively reviewed the medical records of patients referred to the oncodermatology clinic or inpatient dermatology service during 2016-2018 at Yale-New Haven Hospital for eruptions that developed during immunotherapy. RESULTS: In total, 98 patients (51 men, 47 women) treated with checkpoint inhibitors developed 103 inflammatory eruptions, with a range of mean latency of 0.2-17.7 months. A minority of patients (25/103; 24.3%) required immunotherapy interruption; most of these cases involved immunobullous (7/8; 87.5%), lichenoid (8/26; 30.8%), maculopapular (6/18; 33.3%), and Stevens-Johnson syndrome-like (2/2, 100%) reactions. Only 3 of 16 (18.8%) patients who had their immunotherapy interrupted had a grade 2 or 3 flare on rechallenge. Most reactions (93/103; 90.3%) responded to dermatologic therapy or immunotherapy interruption. LIMITATIONS: This was a retrospective study from a single tertiary care center. CONCLUSION: A variety of inflammatory reactions might occur from immunotherapy with differing degrees of severity. While most rashes responded to topical treatment, immunobullous and exfoliative presentations frequently interrupted immunotherapy. Increased awareness and early recognition could reduce the need for unnecessary immunotherapy interruption.

Magnetic Resonance Imaging as a Noninvasive Method for Longitudinal Monitoring of Infusion Site Reactions Following Administration of a Novel Apomorphine Formulation.

Infusion site reactions are common following subcutaneous infusion of drugs. Such reactions can lead to discontinuation of the treatment. Therefore, assessment of such reactions is essential during preclinical safety studies, and magnetic resonance imaging (MRI) can assist in evaluation. Here, in vivo and ex vivo MRI evaluations were used in addition to classical histopathology to assess the infusion site reaction to ND0701, a novel formulation of apomorphine base developed for the treatment of Parkinson's disease, in comparison to the commercial apomorphine hydrochloride (HCl) formulation. Both formulations, each at two concentrations, were continuously administered subcutaneously for 20 hr to each of 3 male and 3 female domestic pigs. Based on MRI evaluations, there was a gradual decrease in the volume of the subcutaneous lesions over 4 weeks, with smaller lesions and quicker resolution with ND0701 at concentrations 2.5- to 5-fold higher when compared to the commercial apomorphine HCl formulation. Histopathological evaluation of ND0701 revealed only minimal inflammation at the sites of infusion, whereas the commercial apomorphine HCl caused persistent inflammatory reactions and necrosis. This study provides support to the use of MRI in preclinical testing of subcutaneous drugs when evaluating local site reactions.

Cutaneous Adverse Events Associated with Interferon-ß Treatment of Multiple Sclerosis.

Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-ß who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

The spectrum of cutaneous toxicities related to novel genitourinary cancer therapies.

CONTEXT: Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities. OBJECTIVE: To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors. EVIDENCE ACQUISITION: A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs). EVIDENCE SYNTHESIS: Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender. CONCLUSIONS: Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.

Facial Hyperpigmentation: A Rare Side Effect of Adalimumab.

This report describes a case of facial hyperpigmentation in a patient with Crohn's disease receiving adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. The onset of hyperpigmentation coincided with adalimumab administration, and its discontinuation resulted in significant improvement. Histopathological findings suggest a postinflammatory process at the dermo-epidermal junction. However, the precise mechanism remains unclear.

Cutaneous adverse events following COVID-19 vaccination: A case series of 30 Japanese patients and a review of 93 Japanese studies.

In Japan, cutaneous adverse events (AEs) following the coronavirus disease 2019 (COVID-19) vaccination have been frequently described; however, a larger case series and literature review are lacking. There is an urgent need for an extensive investigation of new cases and previous reports to provide a thorough body of information about post-COVID-19 immunization cutaneous AEs. We aimed to analyze patients with cutaneous AEs after COVID-19 vaccination in our hospital and review previous studies of cutaneous AEs. We analyzed post-COVID-19 vaccination cutaneous AEs in our department, the Japanese Registry, and previous literature. We enrolled 30 patients with cutaneous post-vaccination AEs in our department over 2 years (April 1, 2021, to March 31, 2023). We also confirmed cases registered in the Ministry of Health, Labor, and Welfare COVID-19 vaccine side effect reporting system (February 17, 2021-March 12, 2023). A total of 587 records were retrieved and 93 articles were included for data extraction. A total of 28 non-injection-site cutaneous AEs and two injection-site AEs were identified. Six (20.0%) patients developed new-onset erythematous eruptions, and five (16.7%) patients developed urticaria. Pruritic eruption, eczema, shingles, and sweating symptoms have also been reported. In previous studies on non-injection-site cutaneous AEs, individuals who received the BNT162b2 vaccine were older than those who received mRNA-1273 (P < 0.01). Cutaneous AEs were mostly nonsignificant and self-limiting reactions; however, rare, severe, or life-threatening AEs were also reported. Physicians should be aware of the various possible cutaneous AEs associated with the COVID-19 vaccination.

Cutaneous Hypersensitivity Reactions to Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread application of ICIs has unveiled a spectrum of immune-related adverse events (irAEs), most often affecting the skin. Cutaneous irAEs (cirAEs) encompass a range from common morbilliform and lichenoid rashes to more severe conditions such as bullous dermatoses and psoriasiform eruptions, each presenting distinct clinical challenges. Moreover, less common but clinically severe cutaneous reactions like toxic epidermal necrolysis have also been observed. cirAEs are frequently observed, with an incidence ranging from 37% to 70% for anti-cytotoxic T lymphocyte-associated antigen-4 antibodies and 17% to 40% for anti- programmed death-1/anti-programmed death ligand-1 antibodies. Recognizing the critical need for effective therapeutic strategies, this review carefully examines current approaches and guidelines for managing cirAEs.