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Dermatology Research and Practice 2024Papulopustular rash (PPR) is the most frequent cutaneous adverse event during treatment with epidermal growth factor receptor inhibitors (EGFRis). Although often mild in...
Papulopustular rash (PPR) is the most frequent cutaneous adverse event during treatment with epidermal growth factor receptor inhibitors (EGFRis). Although often mild in severity, it can impair patients' quality of life and may also be a reason for discontinuing or changing the dose of the antineoplastic treatment. During COVID-19 pandemics, the use of surgical masks drastically increased and it had an impact on the face skin microenvironment, favoring the worsening of dermatological pathologies. We reported the relapse of PPR in patients treated with EGFR inhibitors who consistently wore face masks (>6 hours/day). All the patients developed the PPR within 6 months of starting mask use. Compared to the PPR occurred previously, after mask use, the skin eruption was more severe and affected mainly those regions of the face which came into contact with the mask. Patients received topical or systemic treatment, obtaining complete response in 65.7% of the cases. The establishment of an early treatment for the PPR allows continuing the oncologic treatment, without any suspension which could result in a decreased oncologic outcome. In conclusion, when using these devices, it is recommended to use special precautions, particularly in oncologic patients, by using a daily prophylactic skincare and replacing masks regularly with regular and frequent breaks.
PubMed: 38249546
DOI: 10.1155/2024/8859032 -
The Oncologist Aug 2009Rash has been reported in up to 76% of patients with lung cancer who have received the epidermal growth factor receptor inhibitor (EGFRI) erlotinib. It has also been...
Rash has been reported in up to 76% of patients with lung cancer who have received the epidermal growth factor receptor inhibitor (EGFRI) erlotinib. It has also been observed in patients treated with other agents that have a similar mode of action. Erlotinib-associated skin toxicity typically presents as a papulopustular, follicular, acneiform rash. In most cases, it is mild, transient, and well tolerated, but in 8%-12% of patients, it may be sufficiently severe and persistent to necessitate intervention. Increasingly strong data suggest that the incidence and severity of skin toxicity may be predictive of response and survival in patients treated with erlotinib. This has prompted some clinicians to consider "treatment to rash" (i.e., increasing the dosage until a rash appears) as a rational management strategy. In 2007, an international consensus was developed for the management of EGFRI-associated skin toxicity. Subsequently, a multidisciplinary group (the U.K. Erlotinib Skin Toxicity Management Consensus Group) met to validate and modify the international recommendations for U.K. use, with specific reference to erlotinib. Although many aspects of the international consensus were approved by the group as being relevant for the U.K., certain parts were modified. The resulting expert opinion is a practical and workable version of the international proposal that considers all applicable national issues regarding the management of erlotinib-associated skin toxicity.
Topics: Drug Eruptions; Erlotinib Hydrochloride; Humans; Protein Kinase Inhibitors; Quinazolines; Survival Rate; United Kingdom
PubMed: 19679688
DOI: 10.1634/theoncologist.2009-0055 -
Journal of Dermatological Science Apr 2016
Inhibition of epidermal growth factor receptor induces tumor necrosis factor-α via activation of peroxisome proliferator-activated receptor-γ and nuclear factor-κB in sebocytes: A possible pathogenesis of papulopustular rash.
Topics: Cell Line; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; NF-kappa B; PPAR gamma; Protein Kinase Inhibitors; Quinazolines; Sebaceous Glands; Signal Transduction; Skin Diseases, Papulosquamous; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation
PubMed: 26742624
DOI: 10.1016/j.jdermsci.2015.12.004 -
Oncotarget May 2017Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib,...
Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash. With a predictive value for the rash these biomarkers may also have a prognostic value for survival and disease outcome.The concentrations of amphiregulin, hepatocyte growth factor (HGF) and calcidiol were determined by specific enzyme-linked immunosorbent assays in plasma samples from 211 patients.We observed a significant inverse correlation between the plasma concentration of HGF and overall survival in patients with an inhibitor-induced rash (p-value = 0.0075; mean overall survival low HGF: 299 days, high HGF: 240 days) but not in patients without rash. The concentration of HGF was also significantly inversely correlated with severity of rash (p-value = 0.00124).High levels of HGF lead to increased signaling via its receptor MET, which can activate numerous pathways which are normally also activated by epidermal growth factor receptor. Increased HGF/MET signaling might compensate the inhibitory effect of epidermal growth factor receptor inhibitors in skin as well as tumor cells, leading to less severe skin rash and decreased efficacy of the anti-tumor therapy, rendering the plasma concentration of HGF a candidate for predictive biomarkers.
Topics: Adult; Aged; Aged, 80 and over; Amphiregulin; Biomarkers, Tumor; Calcifediol; Cetuximab; ErbB Receptors; Erlotinib Hydrochloride; Exanthema; Female; Gefitinib; Hepatocyte Growth Factor; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Quinazolines; Signal Transduction; Survival Analysis
PubMed: 28456787
DOI: 10.18632/oncotarget.17060 -
Journal of Clinical Medicine Jul 2021Colorectal cancer (CRC) is an important public health issue, in terms of incidence and mortality, with approximately 1.8 million new cases reported worldwide in 2018.... (Review)
Review
Colorectal cancer (CRC) is an important public health issue, in terms of incidence and mortality, with approximately 1.8 million new cases reported worldwide in 2018. Advancements in understanding pathophysiological key steps in CRC tumorigenesis have led to the development of new targeted therapies such as those based on epidermal growth factor receptor inhibitors (EGFR inhibitors). The cutaneous adverse reactions induced by EGFR inhibitors, particularly papulopustular rash, often require long-term antibiotic treatment with tetracycline agents (mostly minocycline and doxycycline). However, this raises several issues of concern: possible occurrence of gut dysbiosis in already vulnerable CRC patients, selection of highly antibiotic resistant and/or virulent clones, development of adverse reactions related to tetracyclines, interference of antibiotics with the response to oncologic therapy, with a negative impact on disease prognosis etc. In the context of scarce information regarding these issues and controversial opinions regarding the role of tetracyclines in patients under EGFR inhibitors, our aim was to perform a thorough literature review and discuss the main challenges raised by long-term use of tetracyclines in advanced CRC patients receiving this targeted therapy.
PubMed: 34362003
DOI: 10.3390/jcm10153219 -
Targeted Oncology Apr 2009The use of epidermal growth factor receptor (EGFR) inhibitors in several epithelial tumors has increased considerably in recent years. Currently, they are approved in... (Review)
Review
The use of epidermal growth factor receptor (EGFR) inhibitors in several epithelial tumors has increased considerably in recent years. Currently, they are approved in non-small cell lung cancer (NSCLC), pancreatic cancer, colorectal cancer and head and neck cancer. Skin toxicity is a class-specific side effect that is typically manifested as a papulopustular rash in the majority (45-100%) of patients receiving EGFR inhibitors. The skin toxicity is related to the inhibition of EGFR in the skin, which is crucial for the normal development and physiology of the epidermis. Although rarely life-threatening, skin toxicity may cause significant physical and psycho-social discomfort. Nevertheless, the presence and severity of skin rash is associated with improved clinical efficacy in patients receiving EGFR inhibitors. The goal of managing EGFR inhibitor-associated skin toxicity is to minimize the detrimental effects of the rash on patients' quality of life and treatment course without antagonizing the clinical efficacy of EGFR inhibitors. There is currently no evidence-based treatment guideline to prevent or treat the EGFR inhibitor-associated skin toxicities. Expert panels recommend a proactive, multidisciplinary approach that includes patient education and the use of a grade-based treatment algorithm. Elucidation of the mechanisms of EGFR inhibitor-associated skin toxicity and development of mechanism-based novel therapies are urgently needed. Preclinical data suggest topical application of a potent phosphatase inhibitor menadione (Vitamin K3) can rescue the inhibition of EGFR and downstream signaling molecules in the skin of mice receiving systemic EGFR inhibitor erlotinib or cetuximab. A randomized, double-blinded, placebo-controlled study has been initiated to evaluate the clinical efficacy of menadione topical cream, in the treatment or prevention of EGFR inhibitor-induced skin toxicity.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Cetuximab; Clinical Trials as Topic; ErbB Receptors; Erlotinib Hydrochloride; Exanthema; Head and Neck Neoplasms; Humans; Mice; Pancreatic Neoplasms; Patient Education as Topic; Prognosis; Protein Kinase Inhibitors; Quality of Life; Quinazolines; Vitamin K 3
PubMed: 19452131
DOI: 10.1007/s11523-009-0114-0 -
Postepy Dermatologii I Alergologii Oct 2017Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and... (Review)
Review
Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them. The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors. The most common side effects are pruritus, xerosis, papulopustular rash, hand-foot skin reaction, alopecia and dystrophy of the hair, and paronychia. This work presents options for prevention and suggestions for managing these adverse events, which are of importance in the care of patients undergoing oncological treatment.
PubMed: 29507555
DOI: 10.5114/ada.2017.71106 -
International Journal of Dermatology Mar 2014Dermatologic toxicities (DT) to targeted cancer therapy may present as inflammatory dermatoses, keratoses, and as benign and malignant squamous proliferations. (Review)
Review
BACKGROUND
Dermatologic toxicities (DT) to targeted cancer therapy may present as inflammatory dermatoses, keratoses, and as benign and malignant squamous proliferations.
METHODS
Published reports of DT with cancer therapy with epidermal growth factor receptor (EGFR), tyrosine kinase (TK), MEK, PI3K, AKT, and BRAF inhibitors were reviewed.
RESULTS
DT associated with targeted cancer therapy demonstrated similar reactions and may be grouped as (i) DT as cutaneous inflammation, and (ii) DT as cutaneous epithelial proliferation. EGFR inhibitor, cetuximab, and MEK inhibitors, selumetinib and trametinib, demonstrated papulopustular rash with a suppurative folliculitis in 83%, 93%, and 80% of the patients on therapy, respectively. Common DT with EGFR inhibitors erlotinib and tyrosine kinase inhibitor sorafenib were hand-foot skin reactions in 30-60% of patients on therapy. PI3K inhibitor BKM-120 and AKT inhibitor MK2206 produced maculopapular eruptions seen as dermal hypersensitivity reaction on the skin biopsy. RAF inhibitors vemurafenib and sorafenib were associated with a variety of cutaneous epithelial proliferations (keratosis pilaris, seborrheic keratosis, verruca vulgaris, actinic keratosis, keratoacanthoma, and squamous cell carcinoma.
CONCLUSION
Various anticancer agents may target similar cellular compounds and/or cell signaling pathways thus share similar clinical and histologic features of DT. The knowledge of the overlap of DT with different types of targeted cancer therapy will assist in evaluation of cutaneous reactions.
Topics: Antineoplastic Agents; Databases, Factual; Drug Eruptions; Humans; Neoplasms; Precision Medicine; Signal Transduction
PubMed: 23879247
DOI: 10.1111/ijd.12205 -
ELife Mar 2022Anti-epidermal growth factor receptor (EGFR) therapy-associated cutaneous toxicity is a syndrome characterized by papulopustular rash, local inflammation, folliculitis,...
Anti-epidermal growth factor receptor (EGFR) therapy-associated cutaneous toxicity is a syndrome characterized by papulopustular rash, local inflammation, folliculitis, and microbial infection, resulting in a decrease in quality of life and dose interruption. However, no effective clinical intervention is available for this adverse effect. Here, we report the atrophy of dermal white adipose tissue (dWAT), a highly plastic adipose tissue with various skin-specific functions, correlates with rash occurrence and exacerbation in a murine model of EGFR inhibitor-induced rash. The reduction in dWAT is due to the inhibition of adipogenic differentiation by defects in peroxisome proliferator-activated receptor γ (PPARγ) signaling, and increased lipolysis by the induced expression of the lipolytic cytokine IL6. The activation of PPARγ by rosiglitazone maintains adipogenic differentiation and represses the transcription of IL6, eventually improving skin functions and ameliorating the severity of rash without altering the antitumor effects. Thus, activation of PPARγ represents a promising approach to ameliorate cutaneous toxicity in patients with cancer who receive anti-EGFR therapy.
Topics: Adipose Tissue; Animals; ErbB Receptors; Exanthema; Humans; Interleukin-6; Mice; PPAR gamma; Quality of Life
PubMed: 35324426
DOI: 10.7554/eLife.72443 -
Journal of Cutaneous Medicine and... Jul 2016Hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder that affects multiple systems. One of the early findings is a papulopustular rash,...
BACKGROUND
Hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder that affects multiple systems. One of the early findings is a papulopustular rash, which has a wide differential diagnosis.
METHOD
The authors report the case of a male newborn diagnosed with HIES. He presented with papulopustular dermatitis on the scalp. The authors also present a review of current theory on the pathophysiology, clinical presentation, and management of HIES.
CONCLUSION
Although HIES is a multisystem disorder, many of the manifestations of HIES may present after the neonatal period. The cutaneous manifestations of HIES are usually present shortly after birth, and the presentation of pustules in a newborn may be one of the reasons a dermatologist would be asked to assess a patient in the neonatal period.
Topics: Humans; Infant, Newborn; Job Syndrome; Male
PubMed: 26801049
DOI: 10.1177/1203475416629593