Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases

Saint-Jean, Alejandro; Maza, Maite Sainz de la; Morral, Mercè; Torras, Josep; Quintana, Ramon; Molina, Juan José Caballero; Molina-Prat, Nicolás

doi:10.1016/j.ophtha.2012.03.002

Cited by 66 publications

(63 citation statements)

References 39 publications

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“…3 These ocular side effects may be associated with inhibition of EGFR which is expressed on corneal, limbal and conjunctival epithelium, however, the exact mechanism still remains elusive. In the previously reported cases of erlotinib-related ectropion, time onset of ectropion ranged between the first and sixth week of erlotinib treatment, [4][5][6] while it was approximately the fourth week of treatment in the present case. Preceding papulopustular rash associated with erlotinib treatment in our case may have been producing cicatricial traction leading to ectropion development and age related lid laxity may have been contributing to it.…”

Section: Discussionmentioning

confidence: 45%

“…2 Ocular toxicity may also occur with erlotinib treatment. [3][4][5][6] In a recent review of 69 cases with EGFR inhibitors related ocular toxicity, the most common ocular side effects were dysfunctional tear syndrome, blepharitis, trichomegaly and trichiasis. Other less common toxicities included conjunctivitis, keratitis, corneal ulceration, chalazion and ectropion.…”

Section: Discussionmentioning

confidence: 99%

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Erlotinib induced ectropion following papulopustular rash

Salman

Çerman

Seçkin

et al. 2015

J Dermatol Case Rep

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Background: Erlotinib is a targeted anti-cancer drug which acts through the inhibition of epidermal growth factor receptor (EGFR). Main observations:A 79-year-old developed bilateral ectropion after he received erlotinib treatment for lung adenocarcinoma. The ectropion completely resolved with symptomatic treatment without any modification in erlotinib therapy.Conclusions: EGFR inhibitors are frequently associated with a variety of mucocutaneous adverse events. Ocular toxicity associated with these agents has been reported rarely. We present this case to underline the importance of recognition of newly reported cutaneous and ocular adverse events of targeted therapies. (J Dermatol Case Rep. 2015; 9(2) IntroductionChemotherapeutic agents may be the cause of a wide spectrum of dermatological adverse events affecting the skin, skin appendages and mucous membranes. These adverse events are largely dependent on these agents' mechanism of action in cancer treatment. Recently developed targeted agents in cancer therapy are effective by acting on specific pathways and molecules and are therefore less frequently associated with systemic side effects compared with standard chemotherapy. Basal keratinocytes of the epidermis, hair follicles, sebaceous and eccrine epithelium, corneal, limbal and conjunctival epithelium are among the EGFR expressing cells and tissues. [1][2][3] The major functions of the EGFR in the skin are regulation of proliferation, differentiation, migration, apoptosis of cells and stimulation of keratinocyte migration and epidermal growth. 1 Therefore, despite their relative safety in terms of systemic toxicity, mucocutaneous side effects are seen rather frequently with EGFR inhibitors. Case reportA 79-year-old man presented with one-week-history of rash involving his face. He was on his second week of erlotinib treatment for lung adenocarcinoma. His past medical history was insignificant except for hypertension, vertigo and his medications included amlodipine and betahistine. Dermatological examination revealed monomorphic, erythematous papules and pustules over the centrofacial region. Based on the clinical findings, a diagnosis of erlotinib DOI: http://dx.doi.org/10.3315/jdcr.2015.1203 46 induced papulopustular rash was made. Treatment with hydrocortisone acetate cream twice daily for three days and sodium sulfacetamide lotion twice daily was commenced. After 3 weeks of treatment, his skin lesions completely resolved but he complained of recently developed burning sensation and dryness in his eyes. Bilateral ectropion of the lower eyelids were noted on physical examination and the patient was referred to ophthalmology department with a presumptive diagnosis of erlotinib induced ectropion (Fig. 1). Ophthalmological examination showed blepharitis, tear film dysfunction leading to dry eye and bilateral ectropion of the lower eyelids. As these findings were mild, no modification in erlotinib treatment was required and the ectropion ameliorated with symptomatic treatment in three weeks. The pati...

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Section: Discussionmentioning

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Erlotinib induced ectropion following papulopustular rash

Salman

Çerman

Seçkin

et al. 2015

J Dermatol Case Rep

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“…For instance, the most significant model contained EGF and EGFR, which are known to have a biological interaction as the gene product of EGFR is a receptor for the gene product of EGF. Epidermal growth factor is found in human tears [23], and ocular effects have been found after the administration of EGFR inhibitors administered to patients [24]. Interestingly, three of the models that passed our significance cutoff contained two of the same genes, FYN, a member of the protein-tyrosine kinase oncogene family implicated in cell growth, and DOCK1, dedicator of cytokinesis 1.These models as a whole implicate genes related to cell growth, the cell cycle, and epidermal growth.…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Analysis of Cataracts: Determining Knowledge Driven Gene-Gene Interactions Using Biofilter, and Gene-Environment Interactions Using the Phenx Toolkit

et al. 2012

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Investigating the association between biobank derived genomic data and the information of linked electronic health records (EHRs) is an emerging area of research for dissecting the architecture of complex human traits, where cases and controls for study are defined through the use of electronic phenotyping algorithms deployed in large EHR systems. For our study, 2580 cataract cases and 1367 controls were identified within the Marshfield Personalized Medicine Research Project (PMRP) Biobank and linked EHR, which is a member of the NHGRI-funded electronic Medical Records and Genomics (eMERGE) Network. Our goal was to explore potential gene-gene and gene-environment interactions within these data for 529,431 single nucleotide polymorphisms (SNPs) with minor allele frequency > 1%, in order to explore higher level associations with cataract risk beyond investigations of single SNP-phenotype associations. To build our SNP-SNP interaction models we utilized a prior-knowledge driven filtering method called Biofilter to minimize the multiple testing burden of exploring the vast array of interaction models possible from our extensive number of SNPs. Using the Biofilter, we developed 57,376 prior-knowledge directed SNP-SNP models to test for association with cataract status. We selected models that required 6 sources of external domain knowledge. We identified 5 statistically significant models with an interaction term with p-value < 0.05, as well as an overall model with p-value < 0.05 associated with cataract status. We also conducted gene-environment interaction analyses for all GWAS SNPs and a set of environmental factors from the PhenX Toolkit: smoking, UV exposure, and alcohol use; these environmental factors have been previously associated with the formation of cataracts. We found a total of 288 models that exhibit an interaction term with a p-value ≤ 1×10 −4 associated with cataract status. Our results show these approaches enable advanced searches for epistasis and gene-environment interactions beyond GWAS, and that the EHR based approach provides an additional source of data for seeking these advanced explanatory models of the etiology of complex disease/outcome such as cataracts.

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“…[13] This signaling pathway is considered paramount to the healing of corneal epithelial defects and animal tests have shown that the administration of systemic EGFR inhibitors delay corneal healing. [13] There are reported cases of ocular perforations that have required keratoplasty, [9] corneal melting treated with autologous serum, [10] and epithelial defects that have persisted despite topical treatment [8] in patients treated with standard doses of erlotinib. Treatment with autologous PRGF can theoretically decrease the effect of high molecular weight EGFR inhibitors, as they compete for extracellular EGFR binding sites.…”

Section: Resultsmentioning

confidence: 99%

“…[3,4] Although EGFR TK inhibitors show a generally predictable and manageable toxicity, being acneiform rash and diarrhea, the most common adverse events, several ocular side effects have been published, [5–8] from some case reports describing mild discomfort to others showing severe corneal ulcers refractory to medical or surgical treatments. [9] Anti-EGFR treatment discontinuation, [10] or its dose reduction, [11] is considered to be the only option in these cases. Here, we report a case of severe corneal melting successfully treated with plasma rich in growth factors (PRGF-Endoret; BTI Biotechnology Institute, Vitoria-Gasteiz, Spain) without definitive erlotinib discontinuation.…”

Section: Introductionmentioning

confidence: 99%

Plasma rich in growth factors for the treatment of rapidly progressing refractory corneal melting due to erlotinib in nonsmall cell lung cancer

Гуарниери

Alfonso-Bartolozzi²,

Ciufo³

et al. 2017

Medicine

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Rationale:Erlotinib, an antineoplastic agent, is indicated for the treatment of patients with advanced nonsmall cell lung cancer. Most common adverse events are manageable, although more severe ones require dose reduction or discontinuation of erlotinib treatment.Patient concerns:We present a case of severe corneal ulcer treated with autologous plasma rich in growth factors.Diagnoses:A 76-year-old woman with stage IVB (cT2a N0 M1c) lung cancer under erlotinib treatment presented with rapidly progressing corneal ulcer. Evolution was torpid and refractory to conventional treatment.Interventions:Surgical options were dismissed because of the poor performance status of the patient. Despite temporary discontinuation of erlotinib treatment, the corneal ulcer continued to worsen with peripheral corneal neovascularization, stromal thinning, corneal edema, and profuse inflammation of the ocular surface.Outcomes:Treatment with autologous plasma rich in growth factors prevented an imminent corneal perforation and improved the corneal ulcer for over a year of follow-up.Lessons:Considering the poor results of conventional treatment, both medical and surgical, management of the inflammation of the ocular surface together with the stimulation of the healing processes through regenerative therapy such as PRGF, can be an option worth considering in these cases.

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Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases

Cited by 66 publications

References 39 publications

Erlotinib induced ectropion following papulopustular rash

Erlotinib induced ectropion following papulopustular rash

Next-Generation Analysis of Cataracts: Determining Knowledge Driven Gene-Gene Interactions Using Biofilter, and Gene-Environment Interactions Using the Phenx Toolkit

Plasma rich in growth factors for the treatment of rapidly progressing refractory corneal melting due to erlotinib in nonsmall cell lung cancer

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