Drug-induced ectropion following the chronic use of topical Natamycin,Journal of Ophthalmic Inflammation and Infection

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Drug-induced ectropion following the chronic use of topical Natamycin
Journal of Ophthalmic Inflammation and Infection Pub Date : 2020-12-21 , DOI: 10.1186/s12348-020-00230-2
Mohammad Soleimani , Farzad Pakdel , Mohammad Mehrpour

To the Editor.

Drug-induced ectropion is a rare condition secondary to drug hypersensitivity. It was reported following administration of topical and systemic medications [1,2,3,4,5,6,7]. Among topical drugs, anti-glaucoma medications were the most reported drugs causing periorbital dermatitis and ectropion; however, other topical agents such as topical 5% fluorouracil cream and topical Tretinoin were described in the literature [4, 5]. Early cessation of offending medication was mentioned as the most important prognostic factor to reverse this complication without surgical intervention in previous studies [8].

Topical 5% Natamycin is the empirical topical medication for the treatment of fungal keratitis [9]. We reported drug-induced ectropion following chronic use of Natamycin in this study. To the best of our knowledge, there was no study in the literature reporting ectropion as a complication of Natamycin.

A 15-year-old lady presented with symptoms of allergic conjunctivitis such as epiphora, pain, and redness of the lid margin of the right eye. On her eye examination, she had visual acuity of counting finger from 1 m, diffuse vascularized corneal opacity, ectropion and injected conjunctiva with papillary reaction. Additionally, she had physical signs of allergy such as periorbital edema, erythema and scaling of adjacent skin (Fig. 1a, b). However, there were not any signs of cicatricial component such as lamellar shortening or lid retraction. She had a history of admission in our ward for the same eye fungal keratitis 9 months ago (Fig. 1c). She had been treated with topical Natamycin (Natacyn, Alcon, Fort Worth, TX). After partial improvement of the corneal ulcer, she had been discharged with topical 5% Natamycin four times a day. She hadn’t come for follow up visits and continued using Natamycin for a total of 9 months until her recent visit. She did not use any other topical or systemic medication during that time. We stopped Natamycin and administered lubrication and a topical steroid (0.1% Fluorometholone (FML, Allergan, Inc., Irvine, CA) every 6 h. One month later, the ectropion resolved completely (Fig. 1d, e).

To the best of our knowledge, we reported the first case of ectropion induced by topical Natamycin.

Natamycin is a fungicidal tetraene polyene antibiotic; it has been reported as the most effective medication against Fusarium and Aspergillus [9]. Allergic reactions such as eyelid edema, conjunctival hyperemia and irritation were reported as common side effects of Natamycin [10].

The pathophysiology of drug-induced ectropion was described as a two-phase process. First, the allergic reaction results in tissue edema which can exacerbate lid laxity and cause mechanical ectropion; however, lid laxity was not detected in our patient. Second, chronic hypersensitivity leads to cicatrization causing anterior lamellar shortening and cicatricial ectropion [8]. Delay in stopping responsible medication and establishment of cicatrization decrease the rate of spontaneous resolution of ectropion [1, 8]. However, in our case, in spite of 9 months use of natamycin, the cessation of drug administration improved ectropion entirely.

Hegde et al. investigated 13 patients with drug-induced ectropion. Dorzolamide followed with brimonidine were the most offending medications in their study. They concluded that all patients who had been managed with stopping responsible drug and a short course of steroid therapy did not need corrective surgery which was consistent with our experience [8]. In other studies, topical dipivefrin, apraclonidine, fluorouracil, and Tretinoin were reported as causative agents of ectropion [2,3,4,5]. In addition, the systemic use of epidermal growth factor receptor (EGFR) inhibitors such as cetuximab and erlotinib was reported as a cause of reversible cicatricial ectropion [11]. In contradiction to these studies whose cases were elderly patients considered to have some degree of involutional ectropion, our case was young. It should be noted that the above-mentioned side effect could be related to benzalkonium chloride 0.02% (the preservative in Natacyn); however, the concentration is not significant and despite wide-spread use in different ophthalmic drops, there is not any report regarding this complication.

This is an interesting case report illustrating natamycin causing reversible ectropion. Usually the most difficult part is isolating the offending allergy, but given the patient’s history of only using natamycin, authors are able to pinpoint natamycin as the culprit.

Our data are available in medical records of Farabi Eye Hospital.

EGFR:: Epidermal growth factor receptor

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Ocular Trauma and Emergency Department, Farabi Eye Hospital, Tehran, Iran
Mohammad Soleimani, Farzad Pakdel & Mohammad Mehrpour

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Mohammad SoleimaniView author publications
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Contributions

MS visited the patient at first presentation, performed treatment and collated the patient data and also revised the manuscript. MM wrote the manuscript. FP revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammad Mehrpour.

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Soleimani, M., Pakdel, F. & Mehrpour, M. Drug-induced ectropion following the chronic use of topical Natamycin. J Ophthal Inflamm Infect 10, 38 (2020). https://doi.org/10.1186/s12348-020-00230-2

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Received: 23 September 2020
Accepted: 04 December 2020
Published: 21 December 2020
DOI: https://doi.org/10.1186/s12348-020-00230-2

中文翻译：

长期使用纳他霉素后药物引起的外翻

致编辑。

药物引起的外翻是继药物超敏反应之后的罕见病。据报道，在局部和全身药物治疗后[1,2,3,4,5,6,7]。在局部用药中，抗青光眼药物是引起眶周皮炎和外翻的最报道的药物。但是，其他局部用药，如局部用5％氟尿嘧啶霜和局部维甲酸在文献中有描述[4，5]。在先前的研究中，提早停止违规药物是逆转这种并发症的最重要的预后因素，无需手术干预[8]。

5％局部纳他霉素是治疗真菌性角膜炎的经验性局部用药[9]。在这项研究中，我们报道了纳他霉素长期使用后药物引起的外翻。据我们所知，在文献中还没有研究报道外翻是纳他霉素的并发症。

一位15岁的女士表现出过敏性结膜炎的症状，例如泪溢，疼痛和右眼睑缘发红。通过眼部检查，她的视力从1 m开始算起手指，弥漫性血管化角膜混浊，外翻并注射了结膜伴乳头状反应。此外，她还有过敏的体征，如眶周水肿，红斑和邻近皮肤的鳞屑（图1a，b）。但是，没有任何瘢痕形成的迹象，例如片状缩短或眼睑缩回。她有9个月前在我们病房接受过同一眼真菌性角膜炎的病史（图1c）。她曾接受局部用纳他霉素治疗（那他汀，爱尔康，德克萨斯州沃思堡）。角膜溃疡部分改善后，她一天四次局部用5％纳他霉素治疗。她没有来进行随访，直到最近一次随访为止，他一直使用纳他霉素共9个月。在此期间，她没有使用任何其他局部或全身药物。我们每隔6小时停止纳他霉素的使用并给予润滑和局部类固醇（0.1％氟甲龙（FML，Allergan，Inc.，Irvine，CA））。一个月后，外植体完全消退（图1d，e）。

据我们所知，我们报道了第一例由纳他霉素引起的外翻。

纳他霉素是一种杀真菌的四烯多烯抗生素。据报道，它是对抗镰刀菌和曲霉菌最有效的药物[9]。据报道，那他霉素的常见副作用是眼睑浮肿，结膜充血和刺激等过敏反应[10]。

药物诱发的外翻的病理生理学被描述为两个阶段的过程。首先，过敏反应导致组织水肿，从而加剧眼睑松弛并引起机械性外翻；但是，在我们的患者中未检测到眼睑松弛。其次，慢性超敏反应导致瘢痕形成，导致前板层缩短和瘢痕性外翻[8]。延迟停止使用负责任的药物和建立瘢痕化会降低自发消退的比率[1，8]。然而，就我们而言，尽管纳他霉素使用了9个月，但停药却完全改善了外翻。

Hegde等。调查了13例药物诱发的外翻。在他们的研究中，多佐胺和溴莫尼定是最令人讨厌的药物。他们得出的结论是，所有接受过停药和短期激素治疗的患者都不需要进行矫正手术，这与我们的经验是一致的[8]。在其他研究中，局部使用didivivefrin，阿普拉克隆定，氟尿嘧啶和维甲酸是导致外翻的病因[2,3,4,5]。此外，据报道全身使用表皮生长因子受体（EGFR）抑制剂如西妥昔单抗和厄洛替尼是可逆的瘢痕性外翻的原因[11]。与这些研究的病例是老年患者相比，这些研究被认为具有一定程度的内卷性外翻，与此相反，我们的病例是年轻的。应当指出的是，上述副作用可能与苯扎氯铵0.02％（那他汀中的防腐剂）有关。然而，该浓度并不显着，尽管在不同的眼药水中广泛使用，但尚无有关这种并发症的报道。

这是一个有趣的病例报告，说明那他霉素引起可逆性外植。通常，最困难的部分是分离令人讨厌的过敏，但鉴于患者仅使用纳他霉素的病史，作者能够确定纳他霉素为罪魁祸首。

我们的数据可在Farabi眼科医院的医疗记录中获得。

EGFR：: 表皮生长因子受体

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Brodell LP，Asselin D，Brodell RT（1992）在光损伤的皮肤上长期使用局部维甲酸后可逆性外植。J Am Acad Dermatol 27（4）：621–622
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Frankfort BJ，Garibaldi DC（2007）眼周皮肤毒性和瘢痕性外翻：抑制EGFR信号传导的抗肿瘤药的潜在作用。眼科整形外科手术23（6）：496–497
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会费

MS在第一次就诊时就拜访了患者，进行了治疗并核对了患者数据，还修改了手稿。MM写了手稿。FP修改了手稿。所有作者阅读并认可的终稿。

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