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Anti-cancer Drugs Sep 2023Epidermal growth factor receptor (EGFR) is one of therapeutic targets in oncology for solid tumors originating from epithelial tissue, such as non-small-cell lung... (Review)
Review
Epidermal growth factor receptor (EGFR) is one of therapeutic targets in oncology for solid tumors originating from epithelial tissue, such as non-small-cell lung carcinoma (NSCLC) and breast cancer. EGFR inhibitors used in cancer treatment may cause a broad spectrum of dose-dependent cutaneous adverse events, including acneiform papulopustular rash, nail and hair disturbances, xerosis, and mucositis. The pathogenesis of the EGFR inhibitor-induced adverse reactions originates from disturbances in keratinocyte differentiation, cytokine secretion, and neutrophil chemotaxis. One of the rare, yet distressing adverse events may be folliculitis decalvans, a progressive neutrophil-driven scarring alopecia with hair tufts formation resembling doll's hair. Early diagnosis and introduction of treatment are crucial for disease prognosis since a long course of the disease leads to decreased quality of life. Here, we review the literature cases of EGFR inhibitor-induced folliculitis decalvans and provide guidance on management and prevention of this condition in oncologic patients. Furthermore, we report the first afatinib-associated folliculitis decalvans in three female patients with NSCLC.
Topics: Humans; Female; Folliculitis; Carcinoma, Non-Small-Cell Lung; Quality of Life; Lung Neoplasms; ErbB Receptors; Alopecia
PubMed: 36708507
DOI: 10.1097/CAD.0000000000001494 -
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 -
Internal Medicine (Tokyo, Japan) Dec 2019
PubMed: 31462590
DOI: 10.2169/internalmedicine.3214-19 -
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 -
Frontiers in Pharmacology 2022Epidermal growth factor receptor inhibitors (EGFRIs), including cetuximab, erlotinib, gefitinib and icotinib, have been proven to be effective in treating colorectal...
Epidermal growth factor receptor inhibitors (EGFRIs), including cetuximab, erlotinib, gefitinib and icotinib, have been proven to be effective in treating colorectal cancer or lung cancer. However, most of patients who receive EGFRIs treatment experience cutaneous toxicities, such as acneiform or papulopustular rashes, which affects quality of life and leads to discontinuation of cancer therapies. Honeysuckle is a traditional herb historically used to treat skin rash for thousands of years in Eastern Asia and showed proven safety in human. To investigate whether honeysuckle therapy could control EGFRIs induced acneiform rashes, a total of 139 colorectal and lung cancer patients with EGFRIs treatments were recruited in a prospective study. Patients were randomized to 3 arms (Arm A: prophylactic treatment with honeysuckle before rash occurred; Arm B: symptomatic treatment with honeysuckle when rash occurred; Arm C: conventional treatment with minocycline and a topical solution when rash occurred). The incidences, severities and recovery time of acneiform rash were observed in each arm. Honeysuckle treatment reduced incidences of EGFRIs induced acneiform rash, which were 56.5, 68.1 and 71.7% in Arm A, B and C, respectively ( = 0.280). Severities of rash (CTCAE grade 2 and 3) were significantly lower in prophylactic honeysuckle treatment (Arm A) compared to conventional treatment (Arm C) ( = 0.027), which was 10-21%, respectively. Patients with honeysuckle treatment recovered more quickly from pruritus, the median time was 22, 36 and 58 days in Arm A, B and C, respectively ( = 0.016). Honeysuckle was effective in reducing incidences and severities of EGFRIs induced acneiform rash, especially for prophylactic treatment.
PubMed: 35250582
DOI: 10.3389/fphar.2022.835166 -
Journal of Clinical Medicine Jan 2021Epidermal Growth Factor Receptor inhibitors (EGFRi) are approved as therapeutic options in several solid tumors. Cutaneous papulopustular eruption is the most frequent...
Epidermal Growth Factor Receptor inhibitors (EGFRi) are approved as therapeutic options in several solid tumors. Cutaneous papulopustular eruption is the most frequent cutaneous adverse-event (AE), usually treated with emollient or corticosteroids according to toxicity grade. Our study evaluated the efficacy and safety of a topical product containing polydatin, a glycosylated polyphenol, natural precursor of resveratrol showing anti-inflammatory and anti-oxidative activities, for the prevention and treatment of skin papulopustular rash in EGFRi-treated patients. Forty oncologic patients treated with EGFRi were enrolled in two groups: group-A, 20 patients with papulopustular AE, and group-B, 20 patients without cutaneous manifestations. The study consisted of twice-daily application of polydatin cream 1.5% (group-A) and 0.8% (group-B) for 6 months. In group-A patients, we observed at week 4 a remarkable improvement of skin manifestation and quality of life evaluated with National-Cancer-Institute-Common-Terminology-Criteria for Adverse-Events (NCI-CTCAE), Dermatology-Life-Quality-Index (DLQI) score and Visual-Analogue-Scale (VAS) pruritus, with a statistical significance of < 0.05. None of the patients of group-B developed skin AEs to EGFRi. No cutaneous AEs related to the polydatin product were reported in both groups. Polydatin can be a good topical aid for the prevention and management of papulopustular rash in cancer patients receiving EGFRi, also capable of improving cancer patients' quality of life.
PubMed: 33530427
DOI: 10.3390/jcm10030466 -
Oncoimmunology Nov 2020Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a...
Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a papulopustular acneiform rash. The aim of the CUTACETUX study was to characterize the skin inflammatory response associated with this rash and its relation to treatment efficacy. This prospective study included patients with mCRC treated with first-line chemotherapy plus cetuximab. Patients underwent skin biopsies before the initiation of cetuximab (D0) and before the third infusion (D28), one in a rash zone and one in an unaffected zone. Expression of Th17-related cytokines (IL-17A, IL-21, IL-22), antimicrobial peptides (S100A7 and BD-2), innate response-related cytokines (IL-1β, IL-6, TNF-α and OSM), T-reg-related cytokines (IL-10 and TGF-β), Th1-related cytokine (IFN-γ), Th2-related cytokine (IL-4), Thymic stromal lymphopoietin and keratinocyte-derived cytokines (IL-8, IL-23 and CCL20) were determined by RT-PCR. Twenty-seven patients were included. Levels of most of the cytokines increased at D28 in the rash zone compared to D0. No significant association was observed between variations of cytokines levels and treatment response in the rash zone and only the increase of IL-4 ( = .04) and IL-23 ( = .02) levels between D0 and D28 in the unaffected zone was significantly associated with treatment response. Increased levels of IL-8 ( = .02), BD-2 ( = .02), IL-1β ( = .004) and OSM ( = .02) in the rash zone were associated with longer progression-free survival. Expression of Th2-related and keratinocyte-derived cytokines in the skin was associated with anti-EGFR efficacy. If this inflammatory signature can explain the rash, the exact mechanism by which these cytokines are involved in anti-EGFR tumor response remains to be studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Colorectal Neoplasms; ErbB Receptors; Humans; Prospective Studies
PubMed: 33299659
DOI: 10.1080/2162402X.2020.1848058 -
Boletin Medico Del Hospital Infantil de... 2022Folliculitis due to Malassezia spp. (MF), caused mainly by Malassezia furfur, is clinically characterized by an acneiform eruption expressing follicular papules and...
BACKGROUND
Folliculitis due to Malassezia spp. (MF), caused mainly by Malassezia furfur, is clinically characterized by an acneiform eruption expressing follicular papules and pustules, predominantly on the trunk. Diagnosis of MF requires confirmation of the presence of yeasts in the hair follicle. The treatment of choice is topical or oral with azoles. We report two cases of folliculitis due to Malassezia spp. of atypical distribution in immunosuppressed patients.
CASE REPORTS
Case 1. We describe a 14-year-old male patient diagnosed with chondroid osteosarcoma who required surgical treatment and chemotherapy. He was hospitalized for fever and neutropenia, presenting a rash of papulopustular lesions on the upper and lower extremities and neck. Direct examination and biopsy were performed to conclude the diagnosis of disseminated atypical Malassezia spp. folliculitis. Case 2. We describe a 16-year-old male patient diagnosed with synovial sarcoma, treated with surgical resection and chemotherapy. During hospitalization due to fever and neutropenia, he presented with disseminated dermatosis of the head, trunk, and upper extremities, showing multiple follicular papules and pustules with erythematous base; on the trunk, there were few lesions. In the supraciliary region, he showed erythema and furfuraceous desquamation. Direct examination of a follicle showed thick-walled round yeasts compatible with MF.
CONCLUSIONS
MF is a frequent entity but of low diagnostic suspicion. Immunosuppressed patients may manifest atypical clinical characteristics in non-seborrheic areas, implying diagnostic difficulty. Biopsy and direct examination are essential to corroborate the etiology in patients with immunosuppression or with a non-classical presentation.
Topics: Adolescent; Biopsy; Dermatomycoses; Folliculitis; Humans; Malassezia; Male; Neutropenia
PubMed: 35086132
DOI: 10.24875/BMHIM.21000055 -
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 -
Frontiers in Oncology 2022Zanubrutinib, a next-generation non-covalent Bruton's tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may...
Zanubrutinib, a next-generation non-covalent Bruton's tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may experience a series of side effects after the treatment of zanubrutinib. Grade 4 dermatological toxicities are rare, which present as severe rash and skin infection. Herein, we retrospectively reported the grade 4 dermatological toxicities of zanubrutinib in three consecutive patients. They were treated with zanubrutinib 160 mg twice daily orally. One patient was diagnosed with Primary Breast Diffuse Large B-cell Lymphoma(PB-DLBCL) and two patients were diagnosed with Chronic Lymphocytic Leukemia(CLL). Within one month after zanubrutinib treatment, all three patients developed grade 4 dermatological toxicities, including bruising, maculopapular rash, petechiae, ecchymosis, hemorrhagic blister, acne-Like rash, papulopustular rash, and skin infections. Zanubrutinib was discontinued in two patients due to unacceptable dermatological toxicities. Safety data from pre-licensing clinical trials showed that zanubrutinib-related side effects were frequent but well tolerated. To date, no severe dermatological toxicities were reported. The majority of patients can be relieved with symptomatic treatment, but a very small percentage of patients may face discontinuation of the drug.
PubMed: 35957865
DOI: 10.3389/fonc.2022.941633