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Michaels L, Noor M, Aslam T. Clinical and imaging strategies for the assessment of the ocular side effects of systemic targeted anti-cancer therapies. Eur J Cancer 2025; 222:115452. [PMID: 40306116 DOI: 10.1016/j.ejca.2025.115452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/14/2025] [Accepted: 04/17/2025] [Indexed: 05/02/2025]
Abstract
Systemic targeted anti-cancer therapies selectively target cancerous cells whilst limiting systemic side effects. The eye however, is a particularly sensitive organ and the expanding use of the newer targeted chemotherapy agents has been associated with multiple ocular side effects. In this review we provide an update of the ocular side effects of the newer targeted chemotherapy agents along with suggested minimum, pragmatic, evidence-based strategies for effective screening or monitoring for potential ocular side effects. This framework is designed to guide oncologists, trial managers, protocol developers and regulatory authorities so that appropriate ophthalmic clinical examinations and non-invasive modern imaging can be requested and commissioned according to a patient's specific treatment.
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Affiliation(s)
- Luke Michaels
- St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, United Kingdom
| | - Maha Noor
- Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WL, United Kingdom
| | - Tariq Aslam
- Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WL, United Kingdom; School of Health Sciences, University of Manchester, Oxford Road, Manchester M139PL, United Kingdom.
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2
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Gershon R, Vishnevskia-Dai V. Assessing clinical and morphological features of megalotrichosis induced by Tyrosine kinase inhibitors versus Prostaglandins analogues. PLoS One 2024; 19:e0313326. [PMID: 39739702 PMCID: PMC11687796 DOI: 10.1371/journal.pone.0313326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 10/17/2024] [Indexed: 01/02/2025] Open
Abstract
PURPOSE Describing the features of Megalotrichosis (MT) induced by Tyrosine kinase inhibitors (TKI) and differentiate it from Prostaglandins (PGs)-induced MT. METHODS Medical data of patients with MT referred to our center between 2012-2021 were retrieved for: demographic parameters, medical, surgical and oncologic background, and ophthalmologic background along with diagnoses and treatment. Time from PGs/TKI introduction to MT presentation, MT clinical characteristics, associated complaints, and prescribed therapies in relevant cases were also documented. Ophthalmologic exam, ocular photography and data retrieved from medical records were used to assess MT features among the two groups. Morphological evaluation included number of upper (UL) and lower lid (LL) eyelash rows, poliosis, individual elongated eyelash and eyelash curvature. Masked evaluation of all the patients was performed. RESULTS We found 11 patients, of which 6 treated with PGs for glaucoma and 5 treated with TKIs for non-ocular cancer suspected of dissemination. TKIs-induced MT was characterized by more individual elongated eyelashes (p = .047), UL eyelash rows (p = .03) and eyelash curvature (p = .076); poliosis characterized PGs-induced MT (p = .076). MT-associated complaints were more frequent in TKIs-induced MT (p = .06). time from drug administration to MT onset was shorter with TKI compared to PGs (median 176 Vs. 440 days, p = .257). CONCLUSIONS The study suggests that TKI-induced MT presents faster than PGs-induced MT and might be more bothering to patients. Knowledge of the morphological and clinical features that characterize each form of MT might be beneficial for patients and guide clinicians for intervention when needed. Larger cohorts are needed to reproduce and clarify our findings.
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Affiliation(s)
- Rotem Gershon
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Vicktoria Vishnevskia-Dai
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- The Goldschleger Eye Institute, Ocular Oncology Service, Sheba Medical Center, Ramat-Gan, Israel
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3
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Maity P, Chatterjee J, Patil KT, Arora S, Katiyar MK, Kumar M, Samarbakhsh A, Joshi G, Bhutani P, Chugh M, Gavande NS, Kumar R. Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities. J Med Chem 2023; 66:3135-3172. [PMID: 36812395 DOI: 10.1021/acs.jmedchem.2c01242] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
Epidermal growth factor receptor (EGFR) is an oncogenic drug target and plays a critical role in several cellular functions including cancer cell growth, survival, proliferation, differentiation, and motility. Several small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) have been approved for targeting intracellular and extracellular domains of EGFR, respectively. However, cancer heterogeneity, mutations in the catalytic domain of EGFR, and persistent drug resistance limited their use. Different novel modalities are gaining a position in the limelight of anti-EGFR therapeutics to overcome such limitations. The current perspective reflects upon newer modalities, importantly the molecular degraders such as PROTACs, LYTACs, AUTECs, and ATTECs, etc., beginning with a snapshot of traditional and existing anti-EGFR therapies including small molecule inhibitors, mAbs, and antibody drug conjugates (ADCs). Further, a special emphasis has been made on the design, synthesis, successful applications, state-of-the-art, and emerging future opportunities of each discussed modality.
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Affiliation(s)
- Pritam Maity
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
| | - Joydeep Chatterjee
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
| | - Kiran T Patil
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
| | - Sahil Arora
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
| | - Madhurendra K Katiyar
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
| | - Manvendra Kumar
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
| | - Amirreza Samarbakhsh
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, United States
| | - Gaurav Joshi
- Department of Pharmaceutical Science, Hemvati Nandan Bahuguna Garhwal (A Central) University, Srinagar 246174, Dist. Garhwal (Uttarakhand), India
| | | | - Manoj Chugh
- In Vitro Diagnostics, Transasia BioMedical Pvt. Ltd. 400072 Mumbai, India
| | - Navnath S Gavande
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, United States.,Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, United States
| | - Raj Kumar
- Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India
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Abstract
The proliferation of targeted anticancer agents over the last two decades has revolutionized cancer treatment and improved survival in many previously refractory malignancies. However, many agents are associated with characteristic ophthalmic adverse effects. It is important that ophthalmologists recognize and maintain a high index of suspicion for these side effects in patients on targeted therapy. Most ophthalmic adverse effects can be treated with specific ocular therapy without discontinuation of cancer treatment, although it is important to be aware of the life-threatening and vision-threatening circumstances that would require therapy cessation in conjunction with the patient's oncologist. This review aims to summarize the ophthalmic adverse effects of targeted and hormonal anticancer agents and briefly describe their management.
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5
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Jin HD, Blessing NW. Cicatricial ectropion and madarosis associated with panitumumab treatment of metastatic colorectal cancer. Am J Ophthalmol Case Rep 2020; 19:100810. [PMID: 32642599 PMCID: PMC7334291 DOI: 10.1016/j.ajoc.2020.100810] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 05/11/2020] [Accepted: 06/28/2020] [Indexed: 12/26/2022] Open
Abstract
Purpose To report a case of cicatricial ectropion and madarosis with the use of anti-epidermal growth factor receptor medication panitumumab. Observations An 82-year-old man with metastatic colorectal cancer presented with cicatricial ectropion and madarosis after starting panitumumab, an anti-epidermal growth factor receptor medication used to treat metastatic colorectal cancer. His findings resolved several weeks after discontinuation of panitumumab and treatment with lubrication and antibiotic/steroid ointment. Conclusion This case demonstrates the importance to consider potential medication side effects when treating periocular conditions in patients taking anti-epidermal growth factor receptor (anti-EGFR) agents.
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Affiliation(s)
- Haoxing D Jin
- Dean McGee Eye Institute, Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Nathan W Blessing
- Dean McGee Eye Institute, Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Chiang JCB, Zahari I, Markoulli M, Krishnan AV, Park SB, Semmler A, Goldstein D, Edwards K. The impact of anticancer drugs on the ocular surface. Ocul Surf 2020; 18:403-417. [PMID: 32344148 DOI: 10.1016/j.jtos.2020.03.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 03/01/2020] [Accepted: 03/27/2020] [Indexed: 02/07/2023]
Abstract
Cancer is a global health problem and is one of the leading causes of death worldwide. Pleasingly, the rate of survival has improved and continues in an upward trend mainly due to better diagnosis and treatment modalities. In particular, the development of anticancer drugs including cytotoxic chemotherapy, hormonal agents and targeted therapies have provided the most effective treatment options in combatting cancerous cells. However, the antineoplastic mechanisms of these drugs can also lead to undesirable systemic and ocular side effects resulting from cytotoxicity, inflammation and neurotoxicity. While survival rates are projected to increase with time, the number of patients presenting with these side effects that can substantially impact quality of life will also rise. The current paper reviews the ocular surface and adnexal side effects of anticancer drugs, the appropriate management and possible interactions between drugs for ocular surface pathology treatment and the anticancer drugs.
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Affiliation(s)
| | - Ilyanoon Zahari
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Department of Optometry & Visual Science, International Islamic University Malaysia, Kuantan, Malaysia
| | - Maria Markoulli
- School of Optometry & Vision Science, University of New South Wales, Sydney, Australia
| | - Arun V Krishnan
- Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
| | - Susanna B Park
- Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Annalese Semmler
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
| | - David Goldstein
- Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia
| | - Katie Edwards
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
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Scofield-Kaplan S, Todaro J, Winn BJ. Reversible cicatricial ectropion associated with EGFR inhibitors. Orbit 2018; 37:364-367. [PMID: 29336655 DOI: 10.1080/01676830.2017.1423342] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The management of cicatricial ectropion resulting from epidermal growth factor receptor (EGFR) inhibitors is unclear. We describe two cases of bilateral cicatricial ectropion following the use of an EGFR inhibitor who were treated with oral doxycycline, topical ophthalmic steroid and antibiotic ointment to the eyelids, and topical facial steroid cream with lubrication. The first case resolved with discontinuation of panitumumab infusions along with institution of the aforementioned regimen. However, it is unclear whether the resolution was from discontinuation of the infusions or from the instituted regimen. The second case resolved without a dose adjustment of cituximab. This case may provide support for the use of this regimen prior to discontinuation of the offending agent, as there was a successful outcome without alteration of the infusions. Additional cases are necessary to determine if this is a successful means of treating bilateral lower-lid cicatricial ectropion from EGFR inhibitors.
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Affiliation(s)
- Stacy Scofield-Kaplan
- a Department of Ophthalmology , Columbia University Medical Center , New York , New York , USA
| | - James Todaro
- b Department of Ophthalmology , Kresge Eye Institute , Detroit , Michigan , USA
| | - Bryan J Winn
- a Department of Ophthalmology , Columbia University Medical Center , New York , New York , USA
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Yang QC, Bao J, Li C, Tan G, Wu AH, Ye L, Ye LH, Zhou Q, Shao Y. A murine model of dry eye induced by topical administration of erlotinib eye drops. Int J Mol Med 2017; 41:1427-1436. [PMID: 29286080 PMCID: PMC5819933 DOI: 10.3892/ijmm.2017.3353] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Accepted: 12/19/2017] [Indexed: 12/22/2022] Open
Abstract
In the present study, the effects of erlotinib on mouse tear function and corneal epithelial tissue structure were investigated. Throughout the 3 weeks of treatment, no notable differences were observed in the body, eye or lacrimal gland weights of the control and experimental mice. However, in the experimental group, the tear volume and break‑up times of tear film were significantly lower following treatment with erlotinib compared with the control group. Corneal fluorescein staining in the experimental group revealed patchy staining, and the Lissamine green staining and inflammatory index were significantly higher in the experimental group at 3 weeks than in the control group. In the experimental group, the number of corneal epithelium layers increased significantly following treatment with erlotinib for 3 weeks and a significant increase in the number of vacuoles was observed compared with the control group. Treatment with erlotinib significantly increased the corneal epithelial cell apoptosis, and led to a significantly increased number of epithelial cell layers and increased keratin 10 expression. It also significantly reduced the number of conjunctival goblet cells. Transmission electron microscopy and scanning electron microscopy revealed that the corneal epithelial surface was irregular and there was a substantial reduction and partial loss of the microvilli in the experimental group. Mice treated with erlotinib also exhibited an increased protein expression of tumor necrosis factor‑α and decreased protein expression of phosphorylated‑epidermal growth factor receptor in the corneal epithelial cells. The topical application of erlotinib eye drops was revealed to induce dry eyes in mice. This is a novel method of developing a model of dry eyes in mice.
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Affiliation(s)
- Qi-Chen Yang
- Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jing Bao
- Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Cheng Li
- Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian 361102, P.R. China
| | - Gang Tan
- Department of Ophthalmology, The First Affiliated Hospital of the University of South China, Hengyan, Hunan 421001, P.R. China
| | - An-Hua Wu
- Department of Ophthalmology, The First Affiliated Hospital of the University of South China, Hengyan, Hunan 421001, P.R. China
| | - Lei Ye
- Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Lin-Hong Ye
- Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qiong Zhou
- Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Yi Shao
- Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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9
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Zheng H, Zhang H, Zhang T, Wang Q, Hu F, Li B. Trichomegaly and scalp hair changes following treatment with erlotinib in pulmonary adenocarcinoma patients: A case report and literature review. Exp Ther Med 2016; 12:1287-1292. [PMID: 27588051 PMCID: PMC4998076 DOI: 10.3892/etm.2016.3460] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 04/01/2016] [Indexed: 12/11/2022] Open
Abstract
Erlotinib is among the oral EGFR-tyrosine kinase inhibitors used to treat non-small cell lung cancer. The common side effects of erlotinib include acne form rash and diarrhea. Eyelash trichomegaly and alterations of scalp hair are rarely observed symptoms. In the present study, we report changes in eyelash trichomegaly and scalp hair in six cases of pulmonary adenocarcinoma patients that had been administered erlotinib. The symptoms of eyelash trichomegaly include curly, irregular, excessively long and brittle eyelashes, and alterations of scalp hair include curly or straight, brittle, fine or rigid, reduced growth rate and volume. Since these side effects does not substantially impact patient quality of life, no treatments were administered. These changes in eyelashes and scalp hair gradually disappeared after withdrawal of erlotinib.
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Affiliation(s)
- Hua Zheng
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China
| | - Hongmei Zhang
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China
| | - Tongmei Zhang
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China
| | - Qunhui Wang
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China
| | - Fanbin Hu
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China
| | - Baolan Li
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China
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10
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Kau HC, Tsai CC. Erlotinib-related keratopathy in a patient underwent laserin situkeratomileusis. Cutan Ocul Toxicol 2015; 35:257-9. [DOI: 10.3109/15569527.2015.1072546] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Wang SB, Lei KJ, Liu JP, Jia YM. Eyelash trichomegaly following treatment with erlotinib in a non-small cell lung cancer patient: A case report and literature review. Oncol Lett 2015; 10:954-956. [PMID: 26622603 DOI: 10.3892/ol.2015.3265] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Accepted: 04/04/2015] [Indexed: 02/04/2023] Open
Abstract
Inhibitors of epidermal growth factor receptor (EGFR), including tyrosine kinase inhibitors (TKIs), present significant clinical benefits in the treatment of non-small cell lung cancer (NSCLC), particularly in patients with an EGFR mutation. However, TKI treatment also results in unwanted cutaneous toxic side effects, such as a skin rash. Eyelash trichomegaly is rarely reported as a side effect; however, it causes cosmetic issues or eyeball irritation in patients, which may result in the early termination of TKI treatment. Therefore, although TKI-induced eyelash trichomegaly is rare, it should be considered carefully by lung cancer physicians. The present study reported a case of erlotinib-induced eyelash trichomegaly in a 65-year-old Chinese female patient suffering from NSCLC with an EGFR mutation. To the best of our knowledge, this is the first reported case of erlotinib-induced trichomegaly in a Chinese patient.
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Affiliation(s)
- Shan-Bing Wang
- Department of Oncology, The Second People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China
| | - Kai-Jian Lei
- Department of Oncology, The Second People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China
| | - Jia-Pei Liu
- Department of Laboratory Medicine, The Second People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China
| | - Yu-Ming Jia
- Department of Oncology, The Second People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China
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Celik T, Kosker M. Ocular side effects and trichomegaly of eyelashes induced by erlotinib: A case report and review of the literature. Cont Lens Anterior Eye 2015; 38:59-60. [DOI: 10.1016/j.clae.2014.08.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Revised: 08/19/2014] [Accepted: 08/28/2014] [Indexed: 10/24/2022]
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13
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Yin VT, Merritt H, Esmaeli B. Targeting EGFR and sonic hedgehog pathways for locally advanced eyelid and periocular carcinomas. World J Clin Cases 2014; 2:432-8. [PMID: 25232546 PMCID: PMC4163765 DOI: 10.12998/wjcc.v2.i9.432] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Revised: 07/24/2014] [Accepted: 08/27/2014] [Indexed: 02/05/2023] Open
Abstract
For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations.
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Goel V, Raina S, Chandragouda D, Singh S, Talwar V, Patnaik N. Trichomegaly of eyelashes after treatment with erlotinib in carcinoma pancreas. Int J Trichology 2014; 6:23-4. [PMID: 25114450 PMCID: PMC4124690 DOI: 10.4103/0974-7753.136755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Epidermal growth factor receptor (EGFR) inhibitors have been widely used for the treatment of epithelial malignancies. A wide spectrum of skin toxicities have been described in patients receiving EGFR inhibitors. Trichomegaly, especially of the eyelashes is a rare side effect of this therapy. We report a case of trichomegaly of eyelashes in a 39-year-old male, a case of carcinoma pancreas. This side-effect of these medications gives prospects as a therapy to stimulate the growth of hair.
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Affiliation(s)
- Varun Goel
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Shubhra Raina
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - D Chandragouda
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Sajjan Singh
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Vineet Talwar
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Nivedita Patnaik
- Department of Pathology, University College of Medical Sciences, Guru Teg Bahadur Hospital, New Delhi, India
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Retrospective review of eyelash number in patients who have undergone full-thickness eyelid resection. Ophthalmic Plast Reconstr Surg 2014; 30:1-6. [PMID: 24398479 DOI: 10.1097/iop.0b013e3182a650bb] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
PURPOSE The purpose of this study was to determine whether a localized full-thickness eyelid excision results in a proportional decrease in the total number of eyelashes or whether a full complement of visible lashes persists, thus suggesting a compensatory increase in the anagen/telogen ratio among the remaining follicles. METHODS A retrospective chart review was performed on 38 patients who underwent full-thickness eyelid resections repaired with primary eyelid closure for either benign or malignant eyelid lesions. Demographic and surgical data were collected, postoperative eyelid photographs were reviewed, and eyelashes were counted. RESULTS There were 10 upper eyelids and 28 lower eyelids in 10 men and 28 women, with an average age of 57.9 years (range, 14-86 years). The lesion pathology was benign in 21 cases (55%) and malignant in 17 cases (45%). The full-thickness defect involved <25% of the eyelid in 16 cases (42%) and >25% of the eyelid in 22 cases (58%). The follow-up period ranged from 50 to 319 days, with an average of 94 days. In contralateral controls, upper eyelids had an average of 72.1 lashes and lower eyelids had an average of 38.2 lashes, and there was no statistical significance between men and women. In lower lids that underwent <25% resection, control lids had an average of 37.3 lashes and operative lids had 37.1 lashes. In lower lids that underwent >25% resection, control lids had an average of 38.7 lashes and operative lids had 34.2 lashes. This represents an 11.6% decrease and was statistically significant. In upper eyelids that underwent <25% resection and >25% resection, control eyelids had an average of 74.9 lashes and 69.3 lashes and operative eyelids had 77.6 lashes and 69.1 lashes, respectively. Finally, lash count was compared by benign versus malignant pathologic diagnosis. In upper eyelids with benign lesions and malignant lesions, control eyelids had an average of 73.8 lashes and 65.3 lashes and operative eyelids had 74.6 lashes and 68.3 lashes, respectively. In lower eyelids with benign pathology and malignant lesions, control eyelids had an average of 34.5 lashes and 41.4 lashes and operative eyelids had 33.8 lashes and 36.8 lashes. This represents an 11.1% decrease and was statistically significant. CONCLUSIONS Full-thickness excision of eyelid margin tissue including lashes does not usually affect postoperative lash numbers. Because the total number of follicles is reduced, the percentage of lashes in the anagen versus the resting or telogen phase apparently increases compared with the preoperative state. This eyelash study contributes to the growing body of literature on the poorly understood topic of hair follicle cycle regulation.
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Ho WL, Wong H, Yau T. The ophthalmological complications of targeted agents in cancer therapy: what do we need to know as ophthalmologists? Acta Ophthalmol 2013; 91:604-9. [PMID: 22970709 DOI: 10.1111/j.1755-3768.2012.02518.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Recently, there has been an increase in the use of targeted therapies for cancer treatments. Nevertheless, the ocular side-effects of the commonly used targeted agents are generally under-reported and not well studied in the literature. We conducted multiple searches in databases, including Medline, EMBASE, Cochrane Library and conference proceedings, using the following strings: 'name of targeted therapeutic agent (both generic and commercial names)' AND 'eye OR ocular OR vision OR ophthalmological'. Various targeted agents have been found to be associated with ocular side-effects due to their specific targeting of activities in the eye. Imatinib commonly causes periorbital oedema, epiphora and occasionally conjunctival haemorrhage. Cetuximab causes corneal lesions, meibomian gland dysfunction, periorbital and lid dermatitis, blepharitis and conjunctivitis. Erlotinib is related to various ocular toxicities, mainly on the ocular surface, and perifosine has been reported to be associated with severe keratitis. Bevacizumab could potentially disrupt intrinsic ocular circulation and lead to the development of thromboembolic events; there are rare reported cases of optic neuritis or optic neuropathy. Other targeted agents, such as trastuzumab, sunitinib and crizotinib, also have specific ocular toxicities. In conclusion, ocular effects of targeted agents are not uncommon in cancer patients receiving targeted therapy. Ophthalmologists should have high indexes of suspicion to diagnose and treat these complications promptly.
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Affiliation(s)
- Wing L Ho
- Department of Ophthalmology, Caritas Medical Centre, Hong KongDivision of Haematology and Medical Oncology, Department of Medicine, Queen Mary Hospital, Hong Kong
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Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma. Ophthalmic Plast Reconstr Surg 2013; 29:87-92. [PMID: 23446297 DOI: 10.1097/iop.0b013e3182831bf3] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE To review the literature on targeted therapy for orbital and periocular basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) and provide examples of patients recently treated with such therapy. METHODS The authors reviewed the literature on clinical results of targeted therapy and the molecular basis for targeted therapy in orbital and periocular BCC and cutaneous SCC. The authors also present representative cases from their practice. RESULTS Mutation in the patched 1 gene (PTCH1) has been implicated in BCC, and overexpression of epidermal growth factor receptor (EGFR) has been shown in SCC. Vismodegib, an inhibitor of smoothened, which is activated upon binding of hedgehog to Ptc, has been shown to significantly decrease BCC tumor size or even produce complete resolution, especially in cases of basal cell nevus syndrome. Similarly, EGFR inhibitors have been shown to significantly decrease SCC tumor size in cases of locally advanced and metastatic disease. The authors describe successful outcomes after vismodegib treatment in a patient with basal cell nevus syndrome with numerous bulky lesions of the eyelid and periocular region and erlotinib (EGFR inhibitor) treatment in a patient with SCC who was deemed not to be a good surgical candidate because of advanced SCC of the orbit with metastasis to the regional lymph nodes, advanced age, and multiple medical comorbidities. CONCLUSIONS Targeted therapy using hedgehog pathway and EGFR inhibitors shows significant promise in treatment of orbital and periocular BCC and cutaneous SCC, respectively. Such targeted therapy may be appropriate for patients who are not good candidates for surgery.
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18
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Jeon SH, Ryu JS, Choi GS, Kim JS, Kwon HY, Kim MS, Nam HS, Cho JH, Kwak SM, Lee HL, Kim HJ, Hong GJ. Erlotinib induced trichomegaly of the eyelashes. Tuberc Respir Dis (Seoul) 2013; 74:37-40. [PMID: 23390452 PMCID: PMC3563702 DOI: 10.4046/trd.2013.74.1.37] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Revised: 07/15/2012] [Accepted: 07/16/2012] [Indexed: 11/24/2022] Open
Abstract
Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for non-small-cell lung cancer patients. Its untoward cutaneous effects are largely well known and developed in many patients treated with EGFR TKIs. However trichomegaly of eyelash is rarely reported. Although trichomegaly is not a drug-limiting side effect, it could be troublesome of continuing the treatment because of cosmetic issue or eyeball irritation by long eyelashes. Therefore clinicians are needed to pay attention to this uncommon effect. We herein describe erlotinib induced trichomegaly of eyelashes in a woman with adenocarcinoma of the lung.
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Affiliation(s)
- Sang-Hoon Jeon
- Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
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Borkar DS, Lacouture ME, Basti S. Spectrum of ocular toxicities from epidermal growth factor receptor inhibitors and their intermediate-term follow-up: a five-year review. Support Care Cancer 2012; 21:1167-74. [PMID: 23151647 DOI: 10.1007/s00520-012-1645-y] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2012] [Accepted: 10/29/2012] [Indexed: 11/27/2022]
Abstract
PURPOSE Epidermal growth factor receptor (EGFR) inhibitors and kinases are commonly used in the treatment regimen of various solid tumors including non-small cell lung, colorectal, head and neck, breast, and pancreatic cancers. The aim of this study is to describe common ocular adverse effects associated with EGFR inhibitor treatment, outline successful management options, and provide data on intermediate-term follow-up of these patients. METHODS A retrospective chart review was performed of all patients presenting to the ophthalmology clinic with an adverse ocular effect while on an EGFR inhibitor. Duration of EGFR inhibitor treatment, symptoms, diagnosis, and treatment information were collected. Statistical analyses were done to ascertain differences in adverse effects based on duration and type of EGFR inhibitor treatment using the Fisher exact test. RESULTS The two most common EGFR inhibitors in this group of patients were erlotinib and cetuximab. The most common adverse ocular effects for patients on EGFR inhibitors were dysfunctional tear syndrome (DTS), followed by blepharitis and eyelash changes (trichomegaly and trichiasis). Two patients had epithelial defects (corneal abrasions). There was no significant difference in adverse effects based on specific EGFR inhibitor medication or duration of treatment. Almost all patients were successfully managed with treatment regimens that we have outlined in this paper. Intermediate-term follow-up (range 6-17 months) showed a persistence of DTS and eyelash changes. CONCLUSION We present what is, to our knowledge, the largest reported cohort of patients with ocular toxicities from EGFR inhibitors--the spectrum of eye toxicities, their management, and the intermediate-term follow-up of patients with eye toxicities. Awareness of this information is important for oncologists and oncology nurses to facilitate proper counseling and management/referral of patients developing eye toxicity while on EGFR inhibitors.
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Affiliation(s)
- Durga S Borkar
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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20
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Paul LJ, Cohen PR, Kurzrock R. Eyelash trichomegaly: review of congenital, acquired, and drug-associated etiologies for elongation of the eyelashes. Int J Dermatol 2012; 51:631-46; quiz 643-4, 646. [PMID: 22607279 DOI: 10.1111/j.1365-4632.2011.05315.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Eyelash trichomegaly is defined as eyelashes which are found to be of increased length, thickness, and pigmentation. This unique finding can be present at birth as part of a variety of congenital syndromes or as a benign familial trait. There are also acquired conditions and drugs that are known to cause these changes. Case reports and clinical studies in the medical literature concerning eyelash trichomegaly were investigated and summarized to compile a comprehensive review of the etiology of eyelash trichomegaly. Previously published reviews and studies that report on the finding of increased generalized hair growth and which do not specifically mention eyelashes were not included. Trichomegaly of the eyelashes may occur as a key feature among rare congenital syndromes, develop in association with certain acquired diseases, or present as an intended or treatment-related adverse drug effect. Eyelash trichomegaly may be present from birth or manifest later in life in association with acquired diseases or drug therapy. The relevance of this finding may be benign, however eyelash trichomegaly in some individuals can be a symptom for immune dysfunction or a clinical measure of response to drug therapy.
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Affiliation(s)
- Laura J Paul
- University of Texas Medical School at Houston, TX, USA
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21
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Saint-Jean A, Sainz de la Maza M, Morral M, Torras J, Quintana R, Molina JJ, Molina-Prat N. Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases. Ophthalmology 2012; 119:1798-802. [DOI: 10.1016/j.ophtha.2012.03.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2011] [Revised: 01/31/2012] [Accepted: 03/01/2012] [Indexed: 01/26/2023] Open
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Abstract
Chemotherapy and its cutaneous side effects are an increasingly common source of iatrogenic injury to the skin, hair, and nails. Cutaneous changes are among the most common side effects from treatment with particular targeted chemotherapeutic agents, especially those that target the epidermal growth factor receptor and small molecule multikinase inhibitors. Less common, but growing in recognition, are the development of secondary cutaneous neoplasms and subacute cutaneous lupus erythematosus as a result of chemotherapy. There is considerable overlap of the multiple entities described as a side effect from conventional chemotherapeutic agents; therefore, the term "toxic erythema of chemotherapy" can be used as an easily understood name.
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23
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Fraunfelder FT, Fraunfelder FW. Trichomegaly and other external eye side effects associated with epidermal growth factor. Cutan Ocul Toxicol 2011; 31:195-7. [DOI: 10.3109/15569527.2011.636118] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Ahn J, Wee WR, Lee JH, Hyon JY. Vortex keratopathy in a patient receiving vandetanib for non-small cell lung cancer. KOREAN JOURNAL OF OPHTHALMOLOGY 2011; 25:355-7. [PMID: 21976946 PMCID: PMC3178773 DOI: 10.3341/kjo.2011.25.5.355] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2009] [Accepted: 04/19/2010] [Indexed: 01/13/2023] Open
Abstract
We report a case of vortex keratopathy in a patient treated with vandetanib for non-small cell lung cancer (NSCLC). A 44-year-old female who underwent two cycles of chemotherapy for NSCLC complained of visual blurring in both eyes after the initiation of vandetanib, an anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor. On ophthalmic examination, visual acuities were 20 / 20 OU and, with the exception of diffuse vortex keratopathy in both eyes, other findings were unremarkable. Vandetanib is believed to have caused vortex keratopathy in this patient. Anti-EGFR properties affecting normal corneal epithelial cell migration and wound healing or drug associated metabolite deposition, which is the case in numerous drug-associated vortex keratopathies, may be possible underlying mechanisms in the formation of this corneal complication.
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Affiliation(s)
- Jeeyun Ahn
- Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Balagula Y, Garbe C, Myskowski PL, Hauschild A, Rapoport BL, Boers-Doets CB, Lacouture ME. Clinical presentation and management of dermatological toxicities of epidermal growth factor receptor inhibitors. Int J Dermatol 2011; 50:129-46. [PMID: 21244375 DOI: 10.1111/j.1365-4632.2010.04791.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The last decade in oncology has been highlighted by the emergence of novel, highly specific anti-cancer agents, targeting a variety of molecular structures and able to inhibit aberrantly activated oncogenic pathways. Epidermal growth factor receptor inhibitors (EGFRIs) represent one type of such "targeted" agents. Their use made treatment more tolerable and resulted in significant reduction of systemic adverse effects. However, EGFRIs are associated with toxicities affecting the skin and adnexal structures, and mucosal surfaces that affect the majority of treated patients. Significant dermatologic toxicities have changed the role and involvement of dermatologists in their care. It is essential to be familiar with these adverse effects, potential complications, long-term sequelae, and available effective treatment strategies in order to appropriately manage these patients. This review will describe the clinical presentation, histopathology, underlying mechanisms, and management options, emphasizing evidence-based approaches.
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Cohen PR, Escudier SM, Kurzrock R. Cetuximab-associated elongation of the eyelashes: case report and review of eyelash trichomegaly secondary to epidermal growth factor receptor inhibitors. Am J Clin Dermatol 2011; 12:63-7. [PMID: 20726623 DOI: 10.2165/11531920-000000000-00000] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Eyelash trichomegaly is an uncommon drug-associated sequelae experienced during treatment with epidermal growth factor receptor (EGFR) inhibitors. Elongation of the eyelashes induced by these agents has predominantly been observed in oncology patients with either colorectal or lung cancer. It is most frequently associated with cetuximab and erlotinib; however, it has also been described in individuals treated with gefitinib or panitumumab. We describe cetuximab-associated eyelash trichomegaly in a woman with metastatic rectal carcinoma. We review the clinical presentation, adverse effects, and management of EGFR inhibitor-related eyelash trichomegaly. The long eyelashes are not a drug-limiting adverse effect and some patients consider the change to be cosmetically enhancing. Trimming the lashes with scissors can usually ameliorate local symptoms. The eyelashes often return to their original length at variable time periods after EGFR inhibitor therapy is discontinued.
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Affiliation(s)
- Philip R Cohen
- The University of Houston Health Center, University of Houston, Texas, USA.
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27
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Saif MW, Gnanaraj J. Erlotinib-induced trichomegaly in a male patient with pancreatic cancer. Cutan Ocul Toxicol 2009; 29:62-6. [DOI: 10.3109/15569520903440058] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Corneal Verticillata After Dual Anti-Epidermal Growth Factor Receptor and Anti-Vascular Endothelial Growth Factor Receptor 2 Therapy (Vandetanib) for Anaplastic Astrocytoma. Cornea 2009; 28:699-702. [DOI: 10.1097/ico.0b013e3181922146] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
We report here a case of bilateral trichomegaly associated with alopecia areata in a 3-year-old girl, healthy except for mild atopic dermatitis. Trichomegaly is a rare condition and, in many cases, is a side effect of medication such as ophthalmic solution prostaglandin analogs and epidermal growth factor receptor inhibitors. Trichomegaly has also been associated with acquired medical conditions such as HIV, systemic lupus erythematosus, anorexia nervosa, porphyria cutanea tarda, hypothyroidism, and dermatomyositis. In very rare circumstances, trichomegaly has been described as part of congenital conditions such as Oliver-McFarlane syndrome. We believe that the development of bilateral trichomegaly in conjunction with alopecia areata in this patient represents a novel finding as it occurred in the absence of any significant health problems, congenital abnormalities, or medications.
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Affiliation(s)
- Michael R Nazareth
- Department of Dermatology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA
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30
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Braiteh F, Kurzrock R, Johnson FM. Trichomegaly of the eyelashes after lung cancer treatment with the epidermal growth factor receptor inhibitor erlotinib. J Clin Oncol 2008; 26:3460-2. [PMID: 18612164 DOI: 10.1200/jco.2008.16.9391] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Fadi Braiteh
- Department of Investigational Cancer Therapeutics, Phase I Program, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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31
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Heymann WR. Epidermal growth factor receptor inhibitors and hair. J Am Acad Dermatol 2008; 58:642-3. [DOI: 10.1016/j.jaad.2007.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2007] [Revised: 09/04/2007] [Accepted: 09/12/2007] [Indexed: 10/22/2022]
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32
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Periocular cutaneous toxicity and cicatricial ectropion: a potential class effect of antineoplastic agents that inhibit EGFR signaling. Ophthalmic Plast Reconstr Surg 2008; 23:496-7. [PMID: 18030130 DOI: 10.1097/iop.0b013e31815a124b] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Erlotinib (Tarceva, Roche) is a chemotherapeutic agent used in the management of advanced non-small cell lung cancer and other malignancies. We present the case of a patient who developed excessive eyelash growth, called trichomegaly, a rare ocular side effect of this drug.
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34
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2007. [DOI: 10.1002/pds.1370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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