Skin Side Effects Research Articles

Blistering skin side-effects associated with checkpoint inhibitor treatment for cancer

Abstract Linked Article: Kawsar et al. Br J Dermatol 2022; 187:981–987.

INNV-22. A CASE REPORT OF MULTIPLE LESIONS DISAPPEARING AFTER TMZ+TTFIELDS+ DARAFENIB AND TRAMETINIB IN A PATIENT WITH GBM

Abstract A 44-year-old female patient developed the disease with left visual field defect in both eyes. Brain MRI on September 13, 2021, showed irregular masses in the right basal ganglia, thalamus, and hippocampus of temporal lobe, with the lesion extending to the right midbrain and right optic tract. On September 28, 2021, intraoperative total resection of lesions in right gyrus, hippocampus, thalamus and cingulate herniawas performed under nuclear magnetic navigation and electrophysiological detection. The pathological integration diagnosis result was glioblastoma, IDH wild type with TERT C228T mutation, chromosome 7 amplification and BRAF V600E mutation, WHO grade 4, MGMT non-methylation, postoperative visual acuity same as before. Based on the protocols and data of the clinical trials that have been conducted, and the safety of simultaneous use of TTFields during radiotherapy is controllable and patients can benefit, we started the follow-up treatment: standard TMZ (75mg/m2/d), combined with TTFields and retaining the transducer arrays placed on the shaved scalp. The dose of 60/54Gy, 30 times was selected. The application time of TTFields was relatively long throughout the radiotherapy period, and patient compliance was good, with treatment duration of about 20 hours per day. One month after conventional radiotherapy, reexamination indicated that local T1 enhanced hypersignal and PWI showed hyperperfusion. The methionine PET suggested that tumor activity might still exist. We found that the BRAF V600E mutation may provide therapeutic benefit, so this patient was treated with TMZ (standard 5/28 regimen) +TTFields+ Darafenib and Trametinib. Nearly two months after the follow-up treatment, a re-examination found a remarkable phenomenon, the multiple lesions disappeared. At present, the patient continues to be treated with TTFields for a relatively long time, and the skin side effects are only grade ONE. The combination of TTFields with targeted agents and chemotherapy brought clinical benefit to the patient with manageable adverse reactions.

Importance of education on infection control and on the hand skin health of dental personnel.

Hand hygiene plays a significant role in infection control, yet it is performed correctly only 40% of the time. The daily use of soap, disinfectants and gloves can also affect hand skin health. Periodical educational interventions regarding hand hygiene can improve infection control. The current study aimed to identify the existing hand hygiene practices applied by dental personnel, to evaluate knowledge about infection control, to determine the adverse effects of hand hygiene on the skin, and to assess the effectiveness of the educational interventions concerning these topics. This study was carried out at the Vilnius University Hospital Žalgiris Clinic, Lithuania. At the 1st stage, data was collected by using a self-administered questionnaire. At the 2nd stage, dental personnel underwent an educational intervention and the surveys were redistributed to determine any changes in the level of knowledge. In most cases, dental workers performed hand hygiene when it was needed. The proper method was selected by 53.4% on average. The main mistakes were the excessive use of soap and only occasional use of a disinfectant. The reported hand skin side effects included dryness (68.8%) and fissures (37.5%). Only half (50.5%) of the staff regularly used emollients. After the educational intervention, there was a 24.9% improvement in hand hygiene compliance. The correct procedure for hand hygiene was reported by half of the participants. Washing hands with soap was the preferable choice, while alcohol-based hand rub (ABHR) was avoided. Skin problems were reported by more than 70% of the respondents. Training had a positive impact on the hand hygiene knowledge of the dental personnel.

Discovery of potent and selective HER2 PROTAC degrader based Tucatinib with improved efficacy against HER2 positive cancers

HER2 is a validated therapeutic target for HER2 positive breast cancer and gastric cancer. TKIs have significantly improved the prognosis of patients with HER2 positive cancer. However, the pan-HER TKIs always caused gastrointestinal and skin side effects, and acquired drug resistance inevitable compromised their therapeutic efficacy. Herein, we describe the discovery of the first potent and selective HER2 PROTAC degrader based Tucatinib with improved antitumor activity in vitro and in vivo. The preferred selective HER2 PROTAC, CH7C4, efficiently degraded HER2 with DC50 of 69 nM and Dmax of 96%, and inhibited the proliferation of BT-474 cells with IC50 of 0.047 ± 0.006 nM via long lasting HER2 degradation and strong repression of downstream pathway. Moreover, CH7C4 had acceptable pharmacokinetic profiles with a half-life of 5.31 h, and significantly inhibited the growth of BT-474 xenografts in vivo with TGI of 73%. As the first selective HER2 PROTAC degrader with better activity in vitro and in vivo than Tucatinib, CH7C4 provides new insights into the development of new therapeutic strategy for HER2 positive cancer.

3D-printed bolus ensures the precise postmastectomy chest wall radiation therapy for breast cancer.

PurposeTo investigate the values of a 3D-printed bolus ensuring the precise postmastectomy chest wall radiation therapy for breast cancer.Methods and materialsIn the preclinical study on the anthropomorphic phantom, the 3D-printed bolus was used for dosimetry and fitness evaluation. The dosimetric parameters of planning target volume (PTV) were assessed, including Dmin, Dmax, Dmean, D95%, homogeneity index (HI), conformity index (CI), and organs at risk (OARs). The absolute percentage differences (|%diff|) between the theory and fact skin dose were also estimated, and the follow-up was conducted for potential skin side effects.ResultsIn preclinical studies, a 3D-printed bolus can better ensure the radiation coverage of PTV (HI 0.05, CI 99.91%), the dose accuracy (|%diff| 0.99%), and skin fitness (mean air gap 1.01 mm). Of the 27 eligible patients, we evaluated the radiation dose parameter (median(min–max): Dmin 4967(4789–5099) cGy, Dmax 5447(5369–5589) cGy, Dmean 5236(5171–5323) cGy, D95% 5053(4936–5156) cGy, HI 0.07 (0.06–0.17), and CI 99.94% (97.41%–100%)) and assessed the dose of OARs (ipsilateral lung: Dmean 1341(1208–1385) cGy, V5 48.06%(39.75%–48.97%), V20 24.55%(21.58%–26.93%), V30 18.40%(15.96%–19.16%); heart: Dmean 339(138–640) cGy, V30 1.10%(0%–6.14%), V40 0.38%(0%–4.39%); spinal cord PRV: Dmax 639(389–898) cGy). The skin doses in vivo were Dtheory 208.85(203.16–212.53) cGy, Dfact 209.53(204.14–214.42) cGy, and |%diff| 1.77% (0.89–2.94%). Of the 360 patients enrolled in the skin side effect follow-up study (including the above 27 patients), grade 1 was the most common toxicity (321, 89.2%), some of which progressing to grade 2 or grade 3 (32, 8.9% or 7, 1.9%); the radiotherapy interruption rate was 1.1%.ConclusionA 3D-printed bolus can guarantee the precise radiation dose on skin surface, good fitness to skin, and controllable acute skin toxicity, which possesses a great clinical application value in postmastectomy chest call radiation therapy for breast cancer.

35341 The application of an emollient helps to reduce the skin side effects of anticancer treatments

Skin-related side effects of cancer treatment, a recurring complaint from patients, lead to further deterioration in patient’s quality of life (QOL). Patients also develop skin sores or cracks, causing discomfort or pain and increasing infection risks. The study objective was to assess skin acceptability in patients undergoing cancer treatment and receiving an emollient containing shea butter, Thermal Spring Water, niacinamide, microresyl and Aqua Posae Filiformis as actives. 47 patients were included, 42 were eligible for analysis.

35349 The use of photoprotection reduces skin side effects of patients undergoing anti-cancer treatments

The use of photoprotection reduces skin side effects of patients undergoing anti-cancer treatments. As some cancer treatments are photosensitizing, even indirect sunlight exposure requires protection. Using anti-UVB and anti-UVA sunscreens is an easily accessible way to prevent skin reactions. The study objective was to assess skin acceptability in patients undergoing cancer treatment who received a daily sun protector SPF100 UVA-PF36. 59 patients were included, 56 were eligible for analysis. Patients (mean age 60.2 years ± 12.8) were predominantly women (71%).

Pinnae and facial hypertrichosis induced by cetuximab.

Anti-EGFR targeted anti-cancer treatment is associated with various skin adverse events. Cetuximab is often associated with acneiform papules and skin disorders. Hypertrichosis cited in face pinnae and eyelash trichomegaly are seldom described. A 72-year-old female cancer patient presented deteriorating facial-pinnae hypertrichosis and eyelash prolongation post cetuximab infusion. Consecutive cetuximab administration led to exaggerating hairy skin side effects, fully alleviated when the drug was discontinued. To the best of our knowledge, this is the first reported case of an anti-EGFR-associated diffuse pinnae hypertrichosis presentation in a female patient in literature. This distinct entity can be easily diagnosed and manipulated with early drug withdrawal. An extensive review of relevant basic molecular research is provided to increase physicians' awareness.

Two doses of the Pfizer-BioNTech vaccine, two different side effects: Skin and eye

A 47-year-old male patient presented to our clinic with the complaints of eye pain, reduced vision and redness in the right eye three days after administration of the second dose of the Pfizer-BioNTech vaccine. The patient was diagnosed with uveitis associated with the Pfizer-BioNTech vaccine and inflammatory glaucoma due to the uveitis. In addition, an erythematous, morbilliform rash had developed three days after the first dose of the vaccine. This is the first case report in the literature to show both skin and eye side effects after the Pfizer-BioNTech vaccine.

Gut Microbiota Imbalance in Metastatic Colorectal Patients Treated With EGFRI and Long-Term Antibiotic Therapy for Cutaneous Toxicity: A Pilot Study

Patients with metastatic colorectal cancer (mCRC) frequently experience epidermal growth factor inhibitors (EGFRI)-induced skin side effects. Antibiotic treatment with doxycycline is often required in order to manage the skin and mucosal toxicity. Since these patients already have significant gut dysbiosis, the long-term antibiotic treatment may destabilize their gut microbiome.ObjectivesThe assessment of intestinal dysbiosis in patients undergoing treatment with EGFRI, who require antibiotic treatment with doxycycline in order to manage adverse skin effects.MethodsWe conducted a prospective pilot study between 2020 and 2021 involving 10 patients with mCRC. These patients were undergoing treatment with EGFRI and required either short-term or long-term treatment with doxycycline in order to manage skin toxicity.ResultsThe patients with mCRC who were treated with doxycycline for 8 weeks showed overexpression of Escherichia coli, Candida, and Geotrichum species compared to the patients who only received doxycycline treatment for two weeks.ConclusionsThe elevated levels of Escherichia coli and Candida species in the patients who received doxycycline for eight weeks compared to the patients who received the treatment for two weeks could provide a starting point for the development of a standardized guideline regarding the use of pre-active or reactive antibiotic treatment. We also highlight the importance of analyzing the intestinal microbiome of these patients. The identification of overexpressed species, as well as the deficiency of certain protective species, could guide the administration of probiotics to cover and repair the affected intestinal flora.

Pityriasis Rosea After Pfizer-BioNTech Covid-19 Vaccine: A Case Report

After the pandemic started, vaccines against SARS-CoV-2 were developed and applied in a short time. Later, various side effects were reported during the use of these vaccines. Among the skin side effects, besides local skin reactions at the injection site, urticaria, maculopapular rash and pityriasis rosea-like reactions were observed. We presented a female case who developed pityriasis rosea after administering the 3rd dose of the Pfizer-BioNTech COVID-19 vaccine.

The Occurrence and Management of Adverse Skin Events due to Continuous Glucose Monitoring

The use of continuous glucose monitoring (CGM) for blood glucose control is increasing and is effective in changing treatment methods and improving lifestyle by identifying problems in blood sugar patterns. However, adverse skin events are increasing due to the insertion of invasive tools or attachment of sensors to the skin for 14 days for intermittent CGM. These adverse events can be the reason for the discontinuation of CGM. Therefore, this paper aims to determine methods to identify and manage skin irritation and side effects caused by CGM accessories.

Nanostructured lipid carrier-embedded polyacrylic acid transdermal patches for improved transdermal delivery of capsaicin

Capsaicin has been used as a topical treatment for skeletomuscular and neuropathic pain. However, it has some side effects when it is applied to the skin such as burning, erythema, and skin irritation resulting in poor patient compliance. These adverse effects are caused by the rapid penetration of capsaicin into the outer layer of the epidermis and low permeation to the dermis layer. This study aimed to develop nanostructured lipid carriers (NLCs) embedded transdermal patches for improved transdermal delivery of capsaicin. An optimum formulation of NLCs (0.3% capsaicin) with a particulate size smaller than 200 nm, narrow size distribution, and acceptable colloidal stability was used for preparing transdermal patches. Polyacrylic acid (7%) was employed as the polymer base of the transdermal patches as it provided high adhesive performance and a sustained release of capsaicin. Moreover, the patches containing capsaicin-loaded NLCs could offer a higher deposition of capsaicin in the deeper layer of the skin compared to the conventional capsaicin patches. In vivo skin irritation studies indicated that the conventional capsaicin patches can cause skin irritation and redness, whereas capsaicin NLCs-loaded patches exhibited lower skin side effects. Therefore, the capsaicin NLCs-loaded patches could be a potential delivery system of capsaicin through the skin with possibly reduced skin irritation.

Exploration of the Potential Mechanism of Qi Yin San Liang San Decoction in the Treatment of EGFRI-Related Adverse Skin Reactions Using Network Pharmacology and In Vitro Experiments.

BackgroundAdverse skin reactions are the most common side effects of epidermal growth factor receptor inhibitors (EGFRIs) in the treatment of cancer, significantly affecting the survival rate and quality of life of patients. Qi Yin San Liang San Decoction (QYSLS) comes from folk prescription and is currently used in the clinical treatment of adverse skin reactions caused by EGFRIs. However, its therapeutic mechanism remains unclear.ObjectivesTo explore the potential mechanism of QYSLS in the treatment of adverse skin reactions caused by EGFR inhibition using network pharmacology and experimental research.MethodsFirst, we verified the effectiveness of QYSLS in vivo using model mice. Second, the related targets of adverse skin reactions associated with EGFR inhibition were predicted by the Gene Expression Omnibus (GEO) database, and effective components and predictive targets of QYSLS were analyzed by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Batman-TCM databases. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed via the Bioconductor (R) V3.8 bioinformatics software. Molecular docking studies verified the selected key ingredients and targets. Finally, the results of network pharmacology were verified by in vitro experiments.ResultsIn the in vivo mouse model, QYSLS effectively reduced the occurrence of skin side effects. Network pharmacological results showed that the active ingredient luteolin, quercetin, licochalcone a, and kaempferol and the effective targets prostaglandin-endoperoxide synthase 2 (PTGS2), matrix metallopeptidase 9 (MMP9), and C–C motif chemokine ligand 2 (CCL2) were related to the interleukin-17 (IL-17) and tumor necrosis factor (TNF) pathway. Subsequently, the related active compounds and targets were verified using HaCaT cells as an in vitro adverse reaction model. The results showed that luteolin and quercetin increased the expression of PTGS2 and MMP9 and reduced the expression of CCL2 in HaCaT cells treated with gefitinib.ConclusionsThe results revealed that QYSLS effectively treats EGFRI-related adverse skin reactions through multi-target and multi-pathway mechanisms. Luteolin and quercetin may be the core active ingredients of QYSLS in the treatment of EGFRI-related adverse skin reactions, and their therapeutic effects are potentially mediated through PTGS2, CCL2, and MMP9 in the IL-17 and TNF signaling pathway.

An Emollient PLUS Balm Is Useful for the Management of Xerosis in Patients Treated for Cancer: A Real-World, Prospective, Observational, Multicenter Study.

IntroductionXerosis is a common skin side effect of current anticancer therapies, including chemotherapy, targeted therapy, radiotherapy, and hormonotherapy. We evaluated the effectiveness of an emollient PLUS containing an Aquaphilus dolomiae extract (ADE-G1) for the management of xerosis in adult patients treated for cancer.MethodsThis real-world, prospective, observational, multicenter study involved 319 xerotic cancer patients, who were prescribed the study product according to the usual practice of their physician. The practitioner assessed xerosis severity and objective clinical signs, and the patients assessed subjective clinical signs and the impact of their skin condition on their quality of life, at inclusion and after around 4 weeks of use. Overall effectiveness and tolerance were assessed at the end of the study. Clinical success was defined by the combination of several of these effectiveness outcomes.ResultsDaily application of the emollient PLUS reduced xerosis severity in 62.7% of patients (p < 0.0001). The mean total severity scores for objective and subjective clinical signs were reduced by 67.7% and 57.4% (p < 0.0001), respectively, compared with baseline. The mean Dermatology Life Quality Index (DLQI) score also significantly improved at the end of follow-up (−56.6%, p < 0.0001). The product was rated as “effective” or “very effective” by the physician for over 80% of patients, regardless of the initial severity grade of xerosis. Overall clinical success was achieved in 73.7% of patients. A trend toward higher effectiveness and clinical success was observed in patients under hormonotherapy. The study product was well tolerated, regardless of the anticancer therapy being received.ConclusionThis study shows that the emollient PLUS containing ADE-G1 is an effective treatment for xerosis in cancer patients, regardless of the initial grade of xerosis and the anticancer treatment received.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00685-2.

P558 Should we introduce early a new biological agent in patients with Inflammatory Bowel Disease after anti-TNF discontinuation due to severe anti-TNF-induced skin lesions? A multicenter cohort study

Abstract Background Data to manage patients with Inflammatory Bowel Disease (IBD) after anti-TNF discontinuation due to severe induced skin lesions are scarce. Our study aimed to assess dermatological and IBD outcomes after discontinuation of an anti-TNF agent related to skin side effects. Methods We conducted a multicenter retrospective study including consecutive IBD patients who discontinued anti-TNF due to induced skin lesions. Objectives were to determine factors associated with remission of induced skin lesions and with IBD relapse in patients with inactive disease at inclusion, particularly the impact of early introduction of a new biological agent within three months of anti-TNF discontinuation. Results Among the 181 patients (134 women, 160 Crohn’s disease) included in the 13 participating centers, 99 (55%) started a new biological agent within the first three months that was mainly ustekinumab in 75% of them. Remission of induced skin lesions occurred in 110 (62%) patients with a median [interquartile range (IQR)] interval of 8.0 (6.8–11.0) months since anti-TNF discontinuation. Scalp location was independently associated with a reduced risk of remission of induced skin lesions [HR 0.64 (95%CI 0.43- 0.94), p=0.02] while early biological therapy was independently associated with a higher probability of remission of skin lesions [HR 1.64 (95%CI 1.1–2.5), p=0.02]. Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 (51%) patients with a median (IQR) interval of 26.0(23.0–39.1) months. Survival rates without IBD relapse at 1 year were 85.8% (95%CI 77.5–94.9) in the early introduction group and 59.3% (95%CI 48.9–71.9) in the other group (p&amp;lt;0.01). Conclusion Early introduction of a new biological is associated with higher probability of healing of anti-TNF-induced skin lesions and significantly reduces risk of IBD relapse.

Can genistein be a potential agent against skin side effects associated with the treatment of breast cancer?

Despite significant medical advances, cancer treatment is still associated with a high risk of side effects. The treatment is usually invasive and devastating and it affects the overall immunity of the whole organism, including the condition of the skin. In recent years there has been a growing interest in isoflavonoids, due to their wide range of biological and pharmacological activity, especially estrogen-like. It gives a broad perspective of their use as active ingredients of preparations, which eliminate skin lesions associated with oncological treatment. This article is an overview describing preclinical and clinical observations on the basis of available literature. It discusses the influence of genistein on skin health in women after breast cancer treatment. The overview focuses on studies conducted with genistein in vitro or in vivo to demonstrate its effect on skin, and anticancer properties. We selected articles from the last 20 years, available in the PubMed and Google Scholar databases.

Efficacy of a tailored moisturizer for reducing chemotherapy-induced skin dryness in breast cancer patients: A randomized controlled clinical trial

To the Editor: Chemotherapy drugs decrease sebum production in the sebaceous glands and cause loss of the skin barrier function.1 This causes loss of moisture and lipids in the stratum corneum of the epidermis with a sensation of skin dryness.1 Although up to 60% of breast cancer patients undergoing chemotherapy experience facial skin side effects reducing the quality of life (QoL),2 it was unclear which individual product was beneficial. Thus, we designed a single-center, randomized controlled trial to test the efficacy of a tailored moisturizer with a high content (1.5%) of pseudo-ceramides that mimics natural ceramides, which comprises more than 50% of skin lipids for managing chemotherapy-induced dryness (Supplementary material 1, available via Mendeley at https://data.mendeley.com//datasets/nmh769k93k/1).

Tre-P-09 - Mogalizumab-induced granulomatous eruption of the scalp: a distinct entity associated with clinical response?

Mogamulizumab is an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, recently approved for the treatment for cutaneous T cell lymphomas (CTCL): mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab has been associated with a variety of cutaneous adverse events. Here we report 6 cases of patients presenting similar eruptions on the scalp, diagnosed as mogamulizumab induced skin side effect. Among 25 patients treated with mogamulizumab for CTCL in two referral centers, we observed 6 patients presenting with similar skin plaques on the scalp and alopecia.

Balneotherapy as a promising method for the correction of dermatologic adverse events of cancer therapy

Cancer treatment with chemotherapy, targeted and immunotherapy is associated with a wide spectrum of dermatologic adverse events. Xerosis (dryness) of the skin is the most prevalent skin side effect in oncologic patients, which occurs both during treatment with "classic" chemotherapy drugs and modern cancer drugs, such as targeted therapy and immunotherapy. Despite the high prevalence of this side effect, current approaches to the correction of skin xerosis in cancer patients are very limited. At the same time, in the absence of adequate supportive treatment of xerosis, the formation of persistent fissures, eczematization and secondary infection is observed, which may lead to antitumor therapy regimen modification. Thus, optimization of prophylactic and treatment strategies for xerosis in patients treated with anticancer drugs remain an important interdisciplinary problem. Balneotherapy is a promising method for the correction of skin xerosis due to a complex positive effect on the level of skin hydration, a decrease in the intensity of inflammatory processes, a beneficial effect on the state of the skin barrier function, as well as an increase in antimicrobial protection. Available data on the use of balneotherapy in the supportive treatment of skin xerosis as a dermatological adverse event of anticancer therapy confirms the high efficacy and safety, as well as good tolerability of this method in cancer patients.