Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with Gefitinib

Alopecia associated with epidermal growth factor receptor (EGFR) inhibitor therapy is a rare cutaneous side effect with the potential to progress to scarring alopecia. Thus, dermatologists should make an early diagnosis. We present the case of a 57-year-old Japanese female with scarring alopecia associated with gefitinib, which is an EGFR inhibitor, including trichoscopic findings. The patient treated with gefitinib for non-small cell lung cancer experienced skin rash and hair loss of the scalp. The scalp lesions appeared similar to erosive pustular dermatosis of the scalp. Trichoscopic examination showed follicular keratotic plugging, milky red areas, white patches, hair shaft disorder, tapering hair, and absence of follicular opening. Histological examination showed ruptured hair follicles with a perifollicular infiltration of plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid treatment produced no improvement. With a reduction in the gefitinib dosage, alopecia gradually improved, although scarring remained. We consider these trichoscopic findings and suspect that follicular keratotic plugging might be a finding associated with scarring alopecia due to EGFR inhibitor therapy.

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Ibrutinib-Induced Vasculitis in a Patient with Metastatic Colon Cancer Treated in Combination with Cetuximab

Case Reports in Oncological Medicine ◽

10.1155/2020/6154213 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Jeffrey Chi ◽

Jennifer Park ◽

Muhammad Wasif Saif

Keyword(s):

Colon Cancer ◽

Growth Factor ◽

Combination Therapy ◽

Growth Factor Receptor ◽

Hematologic Malignancies ◽

Hair Follicles ◽

Metastatic Colon Cancer ◽

Egfr Inhibitor ◽

Gastrointestinal Malignancies ◽

Btk Inhibitor

Combination therapy with ibrutinib and cetuximab is being studied in a phase 1b/2 trial in patients with advanced gastrointestinal and genitourinary malignancies. Rash is a common cutaneous adverse effect for both medications. Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment of several hematologic malignancies. The rash can be asymptomatic, nonpalpable, mild skin eruption, or palpable purpuric rash. A rarer panniculitis form has also been reported. Cetuximab, an epidermal growth factor (EGFR) inhibitor, approved for treatment in head and neck and advanced gastrointestinal malignancies is also known to cause acneiform rash in majority of patients. The rash is due to inhibition of EGFR in the basal keratinocytes and hair follicles. In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash. The combination therapy with the BTK inhibitor and a direct EGFR inhibitor may potentiate the rash inducing effects of the drugs. Here, we describe a case of vasculitis in a patient with metastatic colon cancer who received both ibrutinib and cetuximab on a phase Ib/II clinical trial.

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Epidermal growth factor receptor inhibitor therapy for recurrent respiratory papillomatosis

F1000Research ◽

10.12688/f1000research.2-202.v1 ◽

2013 ◽

Vol 2 ◽

pp. 202 ◽

Cited By ~ 2

Author(s):

Matthew M. Moldan ◽

Bruce C Bostrom ◽

Robert J Tibesar ◽

Timothy A. Lander ◽

James D. Sidman

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Adjuvant Therapy ◽

Growth Factor Receptor ◽

Recurrent Respiratory Papillomatosis ◽

Inhibitor Therapy ◽

Egfr Inhibitors ◽

Egfr Inhibitor ◽

Epidermal Growth

The epidermal growth factor pathway has been implicated in various tumors, including human papillomavirus (HPV) lesions such as recurrent respiratory papillomatosis (RRP). Due to the presence of epidermal growth factor receptors in RRP, epidermal growth factor receptor (EGFR) inhibitors have been utilized as adjuvant therapy. This case series examines the response to EGFR inhibitors in RRP. Four patients with life-threatening RRP were treated with EGFR inhibitors. Operative frequency and anatomical Derkay scores were calculated prior to, and following EGFR inhibitor treatment via retrospective chart review. The anatomical Derkay score decreased for all four patients after initiation of EGFR inhibitor therapy. In one patient, the operative frequency increased after switching to an intravenous inhibitor after loss of control with an oral inhibitor. In the other patients there was a greater than 20% decrease in operative frequency in one and a more than doubling in the time between procedures in two. This study suggests that EGFR inhibitors are a potential adjuvant therapy in RRP and deserve further study in a larger number of patients.

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DRES-13. DUAL KINASE INHIBITION TO COMBAT EGFR-INHIBITOR RESISTANCE IN GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.300 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi74-vi74

Author(s):

Erin Smithberger ◽

Abigail Shelton ◽

Madison Butler ◽

Alex Flores ◽

Ryan Bash ◽

...

Keyword(s):

Kinase Inhibitors ◽

Alternative Pathway ◽

Growth Factor Receptor ◽

Cell Types ◽

Genetically Engineered ◽

Differentially Expressed ◽

Egfr Inhibitor ◽

Tumor Resistance ◽

Pten Deletion ◽

In Cells

Abstract Glioblastoma (GBM) is an aggressive primary brain tumor with a poor survival rate. One of the most common molecular alterations seen in GBM is amplification and/or mutation of the Epidermal Growth Factor Receptor (EGFR), which has made it an attractive therapeutic target. However, several EGFR tyrosine kinase inhibitors have been tested clinically in GBM with minimal success. One reason for this lack of efficacy could be due to acute, adaptive resistance via alternative pathway activation. To investigate this mechanism of tumor resistance, we used RNA-seq and multiplex inhibitor bead/mass spectrometry (MIB-MS) to analyze the transcriptomes and kinomes of genetically engineered murine astrocytes with common GBM genotypes. We have previously shown that 38% of the expressed kinome varied among a panel of diverse nGEM astrocytes harboring Cdkn2a deletion (C) plus Pten deletion (CP), wild-type human EGFR (CE) or EGFRvIII (CEv3) overexpression or both EGFRvIII overexpression and Pten deletion (CEv3P). Although CE have a similar transcriptional profile to C cells at baseline, when treated with the EGFR inhibitor afatinib, CE respond more similarly to CEv3 cells. When cells containing endogenous murine EGFR (C and CP) are treated with afatinib, fewer than 0.5% of kinases showed differential expression. In cells with EGFR overexpression alone, more than 6% of kinases were differentially expressed upon afatinib treatment, including Ntrk3, Fgfr2 and 3, Lyn, Bmx, Epha2 and 5, Fn3k, a kinase involved in fructosamine processing, and Nrbp2, a kinase involved in regulation of apoptosis. This effect was blunted in cells lacking Pten in addition to having EGFRvIII (CEv3P), resulting in less than 2% of kinases being differentially expressed. The only kinase upregulated in all three EGFR-overexpressing cell types was Coq8a, which is involved in electron transport and response to DNA damage. Given this overlap in response, Coq8a could be a potential dual treatment target for GBM.

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Incidence of Adverse Cutaneous Reactions to Epidermal Growth Factor Receptor Inhibitors in Patients with Non-Small-Cell Lung Cancer

Dermatology ◽

10.1159/000513233 ◽

2021 ◽

pp. 1-5

Author(s):

Paolo Gisondi ◽

Davide Geat ◽

Alessandra Mattiucci ◽

Fiorella Lombardo ◽

Antonio Santo ◽

...

Keyword(s):

Lung Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor Receptor ◽

Small Cell ◽

Egfr Inhibitor ◽

Small Cell Lung ◽

Nail Changes ◽

Cutaneous Reactions ◽

Epidermal Growth ◽

Oncologic Treatment

Background: Epidermal growth factor receptor (EGFR) inhibitors are routinely used in advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, their use is associated with gastrointestinal and cutaneous toxicities, including acneiform eruptions, pruritus, xerosis, nail and hair changes. Aside from reducing patients’ quality of life, such cutaneous reactions have a considerable impact on the oncologic treatment given that dose reduction or even drug discontinuation may be necessary, especially for the severe forms. Objectives: To assess the incidence, impact on treatment and management of EGFR inhibitor-related cutaneous reactions in patients with NSCLC. Methods: We conducted a prospective observational study on 87 consecutive patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors from January to December 2019. Patients who developed mucocutaneous reactions were evaluated and treated by both oncologists and dermatologists, and underwent dermatologic follow-up until resolution of the cutaneous reaction. Demographic and clinical data were collected for each patient, and the severity of the cutaneous reaction was graded using the Common Terminology Criteria for Adverse Events. Results: Seventy-one patients (81.6%) developed cutaneous reactions. The number of cutaneous reactions per patient was 1 in 37%, 2 in 41% and 3 or more in 22%. The most common cutaneous reactions included acneiform eruptions (56.3%), xerosis ± asteatotic eczema (48.3%), nail changes (39.1%), mucositis (29.9%), pruritus (24.1%) and hair changes (12.6%). Afatinib was associated with a higher rate of nail changes and mucositis (p < 0.01 and p < 0.005, respectively) compared to other agents, while no patient-related predictive factors were identified. Dose reduction was performed in 18% of patients. Multidisciplinary management involving dermatologists allowed to resume the drug in all patients who had discontinued it due to the cutaneous reactions. Conclusions: A multidisciplinary approach to EGFR inhibitor-related cutaneous reactions is advantageous and can reduce the need to discontinue oncologic treatment.

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Graham-Little Piccardi Lassueur Syndrome: case report

Anais Brasileiros de Dermatologia ◽

10.1590/s0365-05962012000500019 ◽

2012 ◽

Vol 87 (5) ◽

pp. 775-777 ◽

Cited By ~ 6

Author(s):

Raquel Bissacotti Steglich ◽

Renata Elise Tonoli ◽

Giselle Martins Pinto ◽

Fernanda Melo Müller ◽

Isabelle Maffei Guarenti ◽

...

Keyword(s):

Case Report ◽

Physical Examination ◽

Hair Follicles ◽

Rare Disorder ◽

Rare Syndrome ◽

Scarring Alopecia ◽

History Of

A 33-year-old woman presented with a 3-year history of progressive alopecia of the scalp. Past treatment with hydroxicloroquine did not show improvement. Physical examination revealed multiple areas of alopecia with atrophic aspect of the scalp, and axillary and pubic hypotrichosis. Dermoscopy showed hyperkeratosis and accentuation of follicular ostia. Anatomopathological examination revealed decrease in the number of hair follicles, upper perifollicular infiltrate and areas with fibrosis. The Piccardi-Lassueur-Graham-Little syndrome is a rare disorder, characterized by the triad of multifocal scarring alopecia of the scalp, keratotic follicular eruption and hypotrichosis of axillary and pubic regions. Management is a challenge and many medications tried have controversial results. We report a case of this rare syndrome which improved with corticoids.

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Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: In vitro and in vivo

Cancer Letters ◽

10.1016/j.canlet.2018.02.040 ◽

2018 ◽

Vol 424 ◽

pp. 19-29 ◽

Cited By ~ 25

Author(s):

Guan-Nan Zhang ◽

Yun-Kai Zhang ◽

Yi-Jun Wang ◽

Pranav Gupta ◽

Charles R. Ashby ◽

...

Keyword(s):

Lung Cancer ◽

Epidermal Growth Factor Receptor ◽

Multidrug Resistance ◽

Growth Factor Receptor ◽

Small Cell ◽

Egfr Inhibitor ◽

Small Cell Lung ◽

Epidermal Growth

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The local hypothalamic–pituitary–adrenal axis in cultured human dermal papilla cells

BMC Molecular and Cell Biology ◽

10.1186/s12860-020-00287-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Eun Young Lee ◽

You Jin Nam ◽

Sangjin Kang ◽

Eun Ju Choi ◽

Inbo Han ◽

...

Keyword(s):

Hpa Axis ◽

Hair Loss ◽

Human Hair ◽

Stress Hormones ◽

Dermal Papilla ◽

Hair Shaft ◽

Hair Follicles ◽

Follicle Cells ◽

Dermal Papilla Cells ◽

Underlying Mechanisms

Abstract Background Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs. Results CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone. Conclusion The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.

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When EGFR inhibitor meets autoimmune disease: Severe corneal complications in a patient with Sjögren syndrome after erlotinib treatment

European Journal of Ophthalmology ◽

10.1177/1120672120958300 ◽

2020 ◽

pp. 112067212095830

Author(s):

Mengwei Li ◽

Jun Xiang ◽

Chaoran Zhang

Keyword(s):

Growth Factor Receptor ◽

Sjögren Syndrome ◽

Egfr Inhibitors ◽

Sjogren Syndrome ◽

Egfr Inhibitor ◽

Corneal Surface ◽

Tumor Patients ◽

Corneal Epithelial ◽

First Case ◽

Epidermal Growth

Introduction: To report the first case of severe corneal complications in a patient with Sjögren syndrome after receiving erlotinib treatment. Case description: A 51-year-old woman with Sjögren syndrome presented with persistent corneal epithelial defects, which did not respond to conservative therapies. She had been diagnosed with lung cancer and was being treated with erlotinib, a kind of epidermal growth factor receptor (EGFR) inhibitor, for over 2 years. Cornea stromal melting and perforation were not avoided and a total of four penetrating keratoplasties were performed. Stable corneal surface was achieved after the erlotinib treatment was paused. Conclusion: This report, to the best of our knowledge, is the first description of severe ocular complications present in a patient with Sjögren syndrome after receiving the EGFR inhibitor. The underlying ocular or system diseases that were thought to be irrelevant upon receiving the EGFR inhibitors might negatively influence the tumor patients planning to take these kinds of targeted medication. Therefore, it is important to have eye examinations before and during the EGFR inhibitors treatment and supplement the relative contraindications (such as Sjögren syndrome) to EGFR inhibitor treatments as necessary.

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