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Serum IgE reduction and paradoxical eosinophilia associated with allergic conjunctivitis after dupilumab therapy
Journal of Ophthalmic Inflammation and Infection Pub Date : 2021-02-15 , DOI: 10.1186/s12348-020-00234-y
Ayaka Kimura , Ayaka Takeda , Toyo Ikebukuro , Junko Hori

Introduction

Dupilumab is a fully human monoclonal antibody against the α subunit of the interleukin (IL)-4 receptor (IL-4Rα), and inhibits IL-4 and IL-13 signalling pathways. These pathways are involved in B-cell differentiation, immunoglobulin (Ig) E production, and a Th-2-dominant immune response [1]. IL-4 and IL-13 are important drivers of various atopic or allergic diseases, such as atopic dermatitis (AD) [2, 3]. Dupilumab has demonstrated efficacy and safety against multiple Th-2-type inflammatory diseases including AD [1,2,3], asthma [4], chronic rhinosinusitis with nasal polyps [5] and eosinophilic oesophagitis [6] in clinical trials, and has recently been used for AD, asthma, and chronic rhinosinusitis with nasal polyposis when existing treatments fail [7].

Adverse effects of dupilumab have been noted to include pathologies of the ocular surface, including conjunctivitis, blepharitis, keratitis, eye pruritus, dry eye, nasopharyngitis, upper respiratory tract infection, herpes simplex virus, exacerbation of AD, injection-site infection, facial redness, alopecia, and arthralgia [8, 9]. Biologic therapies such as dupilumab inhibit certain cytokines and suppress inflammation of the target organs, but often paradoxically induce or enhance inflammation in other organs. These phenomena are called “paradoxical reactions” [10].

Head and neck erythema have been reported as paradoxical reactions after dupilumab therapy for AD [11]. Histological examination of skin biopsies of such erythema have revealed a psoriasiform reaction pattern suggestive of a drug-induced skin reaction [11]. The frequency of conjunctivitis in clinical trials of dupilumab and in real-world data from a systematic review and meta-analysis have been reported as 8.6–22.1% and 26.1%, respectively [8, 9]. This report presents a case of allergic conjunctivitis associated with eosinophilia as paradoxical reactions induced by dupilumab therapy for AD.

Case report

A 46-year-old woman was referred to the ocular inflammation service at Nippon Medical School Tama-Nagayama Hospital, for bilateral red eyes and itchiness. She was undergoing a sixth cycle of dupilumab in 10 weeks for AD. Slit lamp examination revealed bilateral conjunctive hyperemia, papillary hyperplasia, and bilateral blepharitis (Fig. 1a). No intraocular inflammation was evident in either eye. She had no past ocular history.

Fig. 1
figure1

Clinical findings of bilateral blepharitis and conjunctivitis after dupilumab. Bilateral blepharitis, bilateral conjunctival hyperemia, and papillary hyperplasia were observed at 10 weeks after dupilumab administration for AD (a). These findings disappeared at 30 weeks by treatment with 0.1% cyclosporine eye drops and 0.1% methylprednisolone ointment (b)

Full size image

Blood tests revealed a high eosinophil count (1400 cells/μL) and a high concentration of IgE (8520 IU/mL) at her first visit to our ocular inflammation service. Atopic dermatitis was improved after dupilumab administration, with the Investigator Global Assessment scale for Atopic Dermatitis (IGA) score improved from 4 before dupilumab administration to 2 at 10 weeks after starting dupilumab therapy. However, at the same time as improvement of dermatitis, allergic conjunctivitis paradoxically occurred. When the conjunctivitis appeared (i.e., after 10 weeks of dupilumab administration), serum IgE levels were lower than before dupilumab administration (Fig. 2a). If the allergic conjunctivitis had been a response to pollen or other antigens, serum IgE levels should have been increased, as serum IgE levels in patients with allergic conjunctivitis have been reported as high [12]. In addition, the patient had no nasal symptoms suggestive of allergic rhinitis, such as runny nose or nasal congestion. We therefore ruled out allergic conjunctivitis due to pollen or other antigens.

Fig. 2
figure2

Decreased levels of IgE and paradoxical transient eosinophilia in peripheral blood after dupilumab therapy. IgE level decreased markedly from 23,100 IU/mL at 3 weeks before to 8520 IU/mL at 10 weeks after dupilumab administration (a). The number of eosinophils paradoxically increased from 365 cells/μL at 3 weeks before to 1400 cells/μL at 10 weeks after dupilumab administration (b)

Full size image

Allergic conjunctivitis as a paradoxical reaction induced by dupilumab was diagnosed, and she was treated with topical 0.1% cyclosporine eye drops 4 times/day and 0.1% methylprednisolone ointment twice/day for eyelids. Conjunctivitis and blepharitis gradually improved after starting these treatments, and disappeared at 30 weeks (Fig. 1b). She continued to receive dupilumab therapy, which led to decreased levels of serum Th2-type chemokines such as thymus and activation-regulated chemokine (TARC) from 470 to 241 pg/mL by 34 weeks after dupilumab therapy, indicating reduced severity of AD.

It is worth noting that laboratory data showed inverse changes in eosinophils and IgE before and after starting dupilumab (Fig. 2). IgE levels decreased markedly from 23,100 IU/mL at 3 weeks before to 8520 IU/mL at 10 weeks after dupilumab administration (Fig. 2a). On the other hand, eosinophil count paradoxically increased from 365 cells/μL to 1400 cells/μL (Fig. 2b). Conjunctivitis occurred concomitant with eosinophilia.

Discussion

Dupilumab has been reported to induce eosinophilia with a peak at around 4 weeks after administration [13]. In clinical trials of dupilumab for AD patients, 155 of 465 patients showed eosinophilia at 4 weeks and 3 of 465 patients showed Grade 3 eosinophilia (> 5 × 109 cells/L) [13]. Inhibition of eosinophil recruitment from peripheral blood to inflamed skin tissues by dupilumab has been reported as a mechanism underlying increased eosinophils in peripheral blood [13].

Eosinophils are major pathogenic immune cells in allergic conjunctivitis [14]. Dupilumab-mediated eosinophilia as a paradoxical reaction may be one of the potential mechanisms behind allergic conjunctivitis induced by dupilumab [14]. Further studies are needed to evaluate whether dupilumab-mediated eosinophilia led to eosinophil infiltration into the conjunctiva. Risk factors for the development of dupilumab-associated conjunctivitis have been reported to include AD severity, history of conjunctivitis and elevated levels of biomarkers such as TARC, IgE, and eosinophil counts in peripheral bood [8]. The patient in this report was obviously a high-risk patient, showing high AD severity with an Investigator Global Assessment scale for Atopic Dermatitis score of 4 and elevated levels of both IgE and eosinophils.

Conclusion

We examined serum IgE, eosinophil counts, and clinical findings of conjunctivitis after dupilumab therapy for more than 6 months in a single patient. This is the first report to describe serum IgE reduction and eosinophilia occurred simultaneously in a patient with allergic conjunctivitis associated with paradoxical eosinophilia after dupilumab therapy. Topical cyclosporine eye drops and steroid ointment offered significant efficacy against dupilumab-associated conjunctivitis, and enabled the AD patient to continue dupilumab therapy.

Not applicable.

IL:

Interleukin

IL-4Rα:

Interleukin-4 receptor alpha

Ig:

Immunoglobulin

AD:

Atopic dermatitis

TARC:

Thymus and activation-regulated chemokine

  1. 1.

    Simpson EL, Bieber T, Guttman-Yassky E et al (2016) Two phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 375:2335–2348

    CAS Article Google Scholar

  2. 2.

    Beck LA, Thaçi D, Hamilton JD et al (2014) Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 371:130–139

    Article Google Scholar

  3. 3.

    Thaçi D, Simpson EL, Beck LA et al (2016) Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet 387:40–52

    Article Google Scholar

  4. 4.

    Castro M, Corren J, Pavord I et al (2018) Dupilumab efficacy and safety in moderate to severe uncontrolled asthma. N Engl J Med 378:2486–2496

    CAS Article Google Scholar

  5. 5.

    Bachert C, Mannent L, Naclerio RM et al (2016) Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA 315:469–479

    CAS Article Google Scholar

  6. 6.

    Hirano I, Dellon ES, Hamilton JD et al (2017) Dupilumab efficacy and safety in adult patients with active eosinophilic oesophagitis: a randomised double-blind placebo controlled phase 2 trial. United Eur Gastroenterol J 5:1138–1150

    Article Google Scholar

  7. 7.

    Sanofi and Regeneron Pharmaceuticals, Inc. (2020) Take Action With DUPIXENT® (dupilumab). https://www.dupixent.com/ Accessed 8 Aug 2020

  8. 8.

    Akinlade B, Guttman-Yassky E, Bruin-Weller DM et al (2019) Conjunctivitis in dupilumab clinical trials. Br J Dermatol 181:459–473

  9. 9.

    Halling AS, Dyrberg LN, Silverberg JI et al (2020) Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am Acad Dermatol S0190–9622(20):32442–32447

    Google Scholar

  10. 10.

    Ramos-Casals M, Roberto PA, Diaz-Lagares C et al (2010) Autoimmune diseases induced by biological agents. A double-edged sword? Autoimmun Rev 9:188–193

    CAS Article Google Scholar

  11. 11.

    Wijs de LEM, Nguyen NT, Kunkeler ACM, Nijsten T et al (2019) Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series. In: Br J Dermatol

    Google Scholar

  12. 12.

    Mimura T, Usui T, Mori M et al (2011) Relationship between total tear and serum IgE in allergic conjunctivitis. Int Arch Allergy Immunol 154(4):349–352

    CAS Article Google Scholar

  13. 13.

    Wollenberg A, Beck LA, Blauvelt A et al (2020) Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials. (LIBERTY AD SOLO1, LIBERTY AD SOLO2, LIBERTY AD CHRONOS). Br J Dermatol 182:1120–1135

    CAS Article Google Scholar

  14. 14.

    Thyssen JP, Toft PB, Halling-Overgaard AS, Gislason GH, Skov L, Egeberg A (2017) Incidence, prevalence, and risk of selected ocular disease in adults with atopic dermatitis. J Am Acad Dermatol 77:280–286

    Article Google Scholar

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The authors would especially like to acknowledge Dr. Naoyuki Azuma, at Department of Dermatology, Nippon Medical School Tama-Nagayama Hospital for his support.

This work was supported from the Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science 20 K09813(J.H.). The role of the funding is writing and English proofreading.

Affiliations

  1. Department of Ophthalmology, Nippon Medical School Tama-Nagayama Hospital, 1-7-1, Nagayama, Tama, Tokyo, 206-8512, Japan

    Ayaka Kimura, Ayaka Takeda, Toyo Ikebukuro & Junko Hori

  2. Department of Ophthalmology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo, Tokyo, 113-8603, Japan

    Toyo Ikebukuro

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Contributions

AK contributed to the data collection, review of literature, and writing the manuscript. AT and TI curated the patient data. JH interpreted the patient data, and contributed in supervision, writing, and editing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Junko Hori.

Ethics approval

The ‘Nippon Medical School Tama Nagayama Hospital’ ‘Ethics Committee of Tama Nagayama Hospital’ confirmed that ethics approval was not required.

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Written informed consent was obtained from the patient for publication of her details and accompanying images in this manuscript.

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The authors declare that they have no competing interests.

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Kimura, A., Takeda, A., Ikebukuro, T. et al. Serum IgE reduction and paradoxical eosinophilia associated with allergic conjunctivitis after dupilumab therapy. J Ophthal Inflamm Infect 11, 3 (2021). https://doi.org/10.1186/s12348-020-00234-y

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中文翻译:

dupilumab治疗后与过敏性结膜炎相关的血清IgE降低和反常嗜酸性粒细胞增多

介绍

Dupilumab是针对白介素(IL)-4受体(IL-4Rα)的α亚基的完全人类单克隆抗体,可抑制IL-4和IL-13信号通路。这些途径与B细胞分化,免疫球蛋白(Ig)E的产生和Th-2-优势免疫反应有关[1]。IL-4和IL-13是各种特应性或过敏性疾病(如特应性皮炎(AD))的重要驱动力[2,3]。在临床试验中,Dupilumab已证明对多种Th-2-型炎性疾病(包括AD [1,2,3],哮喘[4],伴鼻息肉的慢性鼻鼻窦炎[5]和嗜酸性食管炎[6])具有疗效和安全性,并且具有当现有的治疗方法无效时,最近已被用于AD,哮喘和鼻息肉的慢性鼻-鼻窦炎[7]。

已知dupilumab的不良反应包括眼表病理,包括结膜炎,睑缘炎,角膜炎,眼瘙痒,干眼症,鼻咽炎,上呼吸道感染,单纯疱疹病毒,AD恶化,注射部位感染,面部发红,脱发和关节痛[8,9]。诸如dupilumab之类的生物疗法可抑制某些细胞因子并抑制靶器官的炎症,但常常自相矛盾地诱发或增强其他器官的炎症。这些现象称为“自相矛盾的反应” [10]。

有报道称dupilumab治疗AD后头颈部红斑为反常反应[11]。对这种红斑的皮肤活检组织学检查发现,牛皮癣样反应模式提示药物诱导的皮肤反应[11]。据报道,在dupilumab的临床试验中结膜炎的发生率以及在系统综述和荟萃分析中的真实数据中,结膜炎的发生率分别为8.6–22.1%和26.1%[8,9]。该报告介绍了一种与嗜酸性粒细胞增多有关的变应性结膜炎的病例,这是由dupilumab治疗AD引起的自相矛盾的反应。

案例报告

一名46岁的女性因双眼红肿和瘙痒而被转诊至日本医学院多摩长山医院眼部炎症科。她在10周内接受了dupilumab的第六次周期性AD治疗。裂隙灯检查发现双侧结膜充血,乳头状增生和双侧睑缘炎(图1a)。两只眼睛都没有明显的眼内炎症。她没有过去的眼病史。

图。1
图1

dupilumab术后双侧睑缘炎和结膜炎的临床发现。dupilumab给予AD后第10周观察到双侧睑缘炎,双侧结膜充血和乳头状增生(a)。通过使用0.1%环孢素滴眼液和0.1%甲基强的松龙软膏治疗,这些发现在30周时消失了(b

全尺寸图片

血液测试显示,她首次去我们的眼部炎症服务中心时,嗜酸性粒细胞计数很高(1400个细胞/微升),IgE浓度很高(8520 IU / mL)。给予dupilumab后特应性皮炎得到改善,研究者全球异位性皮炎评估量表(IGA)评分从给予dupilumab前的4分提高到开始给予dupilumab治疗后10周的2分。然而,在改善皮炎的同时,变态反应性结膜炎反常发生。当结膜炎出现时(即在给予dupilumab 10周后),血清IgE水平低于dupilumab给予之前(图2a)。如果过敏性结膜炎是对花粉或其他抗原的反应,则应提高血清IgE水平,因为据报道过敏性结膜炎患者的血清IgE水平较高[12]。另外,该患者没有提示变态反应性鼻炎的鼻症状,例如流鼻涕或鼻充血。因此,我们排除了由于花粉或其他抗原引起的过敏性结膜炎。

图2
图2

dupilumab治疗后外周血中IgE水平降低和矛盾的短暂嗜酸性粒细胞增多。IgE水平从dupilumab给药后第3周的23,100 IU / mL显着降低至10周后的8520 IU / mL(a)。嗜酸性粒细胞的数量反常增加,从给予dupilumab后的3周时的365细胞/μL增加到给予dupilumab后的10周的1400细胞/μL(b

全尺寸图片

诊断为变应性结膜炎为dupilumab引起的自相矛盾的反应,并用0.1%环孢素局部滴眼液每天4次和0.1%甲基泼尼松龙软膏眼霜两次每天进行治疗。开始这些治疗后,结膜炎和睑缘炎逐渐好转,并在30周时消失(图1b)。她继续接受dupilumab治疗,导致dupilumab治疗后34周血清Th2型趋化因子(如胸腺和活化调节趋化因子(TARC))的水平从470 pg / mL降至241 pg / mL,表明AD的严重程度降低。

值得注意的是,实验室数据显示,在开始使用dupilumab前后,嗜酸性粒细胞和IgE呈负相关(图2)。IgE水平从dupilumab给药后的3周前的23,100 IU / mL显着降低至10周后的8520 IU / mL(图2a)。另一方面,嗜酸性粒细胞计数从365个细胞/微升反常增加到1400个细胞/微升(图2b)。结膜炎伴有嗜酸性粒细胞增多。

讨论

据报道,Dupilumab诱导嗜酸性粒细胞增多,给药后约4周达到峰值[13]。在dupilumab对AD患者的临床试验中,465名患者中有155名在4周时出现嗜酸性粒细胞增多,465名患者中有3名表现为3级嗜酸性粒细胞增多(> 5×10 9细胞/ L)[13]。据报道,dupilumab抑制嗜酸性粒细胞从外周血募集到发炎的皮肤组织,是导致外周血嗜酸性粒细胞增加的一种机制[13]。

嗜酸性粒细胞是过敏性结膜炎的主要致病性免疫细胞[14]。Dupilumab介导的嗜酸性粒细胞增多是一种悖论性反应,可能是dupilumab诱发过敏性结膜炎的潜在机制之一[14]。需要进一步的研究来评估dupilumab介导的嗜酸性粒细胞增多是否导致嗜酸性粒细胞浸润到结膜中。据报道,与dupilumab相关性结膜炎发展的危险因素包括AD严重程度,结膜炎病史以及外周血中诸如TARC,IgE和嗜酸性粒细胞计数等生物标志物水平升高[8]。该报告中的患者显然是高危患者,表现出较高的AD严重程度,特应性皮炎炎评分的研究者全球评估量表为4,而IgE和嗜酸性粒细胞水平均升高。

结论

我们在单例患者中检查了dupilumab治疗超过6个月后的血清IgE,嗜酸性粒细胞计数以及结膜炎的临床表现。这是第一个描述在dupilumab治疗后伴有反常性嗜酸性粒细胞增多的变应性结膜炎患者同时发生血清IgE降低和嗜酸性粒细胞减少的报道。局部用环孢素滴眼液和类固醇软膏可有效预防dupilumab相关性结膜炎,并使AD患者可以继续dupilumab治疗。

不适用。

IL:

白介素

IL-4Rα:

白介素4受体α

Ig:

免疫球蛋白

广告:

特应性皮炎

TARC:

胸腺和激活调节趋化因子

  1. 1。

    辛普森(Simpson EL),比伯(Bieber T),古特曼·雅斯基(Guttman-Yassky E)等人(2016年)在特应性皮炎中进行了Dupilumab与安慰剂的两项3期试验。英格兰医学杂志375:2335–2348

    CAS文章Google学术搜索

  2. 2。

    Beck LA,ThaçiD,Hamilton JD et al(2014)成人中度至重度特应性皮炎的Dupilumab治疗。英格兰医学杂志371:130–139

    文章Google学术搜索

  3. 3。

    ThaçiD,Simpson EL,Beck LA等人(2016)在局部治疗不足以控制中重度特应性皮炎的成人中,dupilumab的疗效和安全性:一项随机,安慰剂对照,剂量范围为2b的试验。柳叶刀387:40–52

    文章Google学术搜索

  4. 4。

    Castro M,Corren J,Pavord I等人(2018)Dupilumab在中度至重度无法控制的哮喘中的疗效和安全性。英格兰医学杂志378:2486–2496

    CAS文章Google学术搜索

  5. 5,

    Bachert C,Mannent L,Naclerio RM等人(2016)皮下注射dupilumab对慢性鼻窦炎和鼻息肉病患者鼻息肉负担的影响:一项随机临床试验。牙买加315:469–479

    CAS文章Google学术搜索

  6. 6。

    Hirano I,Dellon ES,Hamilton JD等人(2017)Dupilumab在活动性嗜酸性食管炎成年患者中的有效性和安全性:一项随机双盲安慰剂对照2期试验。联合欧洲胃肠病杂志5:1138–1150

    文章Google学术搜索

  7. 7。

    赛诺菲和Regeneron Pharmaceuticals,Inc.(2020)与DUPIXENT®(dupilumab)一起行动。https://www.dupixent.com/ 2020年8月8日访问

  8. 8。

    Akinlade B,Guttman-Yassky E,Bruin-Weller DM等(2019)dupilumab临床试验中的结膜炎。Br J Dermatol 181:459–473

  9. 9。

    Halling AS,Dyrberg LN,Silverberg JI等人(2020)dupilumab疗效和不良事件风险的真实证据:系统评价和荟萃分析。J Am Acad Dermatol S0190–9622(20):32442–32447

    谷歌学术

  10. 10。

    Ramos-Casals M,Roberto PA,Diaz-Lagares C等(2010)由生物制剂诱导的自身免疫性疾病。一把双刃剑?自身免疫Rev 9:188–193

    CAS文章Google学术搜索

  11. 11。

    Wijs de LEM,Nguyen NT,Kunkeler ACM,Nijsten T等人(2019)用dupilumab治疗的特应性皮炎患者头部和颈部红斑自相矛盾的临床和组织病理学特征:一个病例系列。在:Br J Dermatol

    谷歌学术

  12. 12

    Mimura T,Usui T,Mori M等(2011)在过敏性结膜炎中总眼泪与血清IgE之间的关系。国际弓过敏免疫154(4):349–352

    CAS文章Google学术搜索

  13. 13

    Wollenberg A,Beck LA和Blauvelt A等人(2020)在中重度特应性皮炎中使用dupilumab的实验室安全性:三项III期临床试验的结果。(LIBERTY AD SOLO1,LIBERTY AD SOLO2,LIBERTY AD CHRONOS)。Br J Dermatol 182:11​​20–1135

    CAS文章Google学术搜索

  14. 14。

    Thyssen JP,Toft PB,Halling-Overgaard AS,Gislason GH,Skov L,Egeberg A(2017)特应性皮炎成人的发病率,患病率和选择的眼病风险。J Am Acad Dermatol 77:280–286

    文章Google学术搜索

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作者尤其要感谢日本医学院多摩长山医院皮肤科的Naukiuki Azuma博士的支持。

这项工作得到了日本科学促进会20 K09813(JH)的科研补助金的支持。资金的作用是写作和英语校对。

隶属关系

  1. 日本医学院多摩长山医院眼科,东京多摩市长山1-7-1,日本206-8512

    木村y香,武田A香,池袋东洋&ori顺子

  2. 日本东京都文京区千代木1-1-5日本医学院附属医院眼科,日本东京113-8603

    池袋东洋

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  1. 木村y香查看作者的出版物

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  2. 武田彩香查看作者的出版物

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  3. 池袋东洋(Toyo Ikebukuro)查看作者出版物

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  4. Junko Hori查看作者出版物

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会费

AK为数据收集,文献回顾和撰写手稿做出了贡献。AT和TI整理了患者数据。JH解释了患者数据,并为监督,撰写和编辑手稿做出了贡献。所有作者阅读并认可的终稿。

通讯作者

对应于Jun子顺子。

道德认证

“日本医学院多摩长山医院”“多摩长山医院伦理委员会”确认不需要伦理学批准。

同意发表

从患者那里获得了书面知情同意书,以公开其细节和本手稿中的图片。

利益争夺

作者宣称他们没有竞争利益。

发行人须知

对于出版的地图和机构隶属关系中的管辖权主张,Springer Nature保持中立。

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引用本文

Kimura,A.,Takeda,A.,Ikebukuro,T.等。dupilumab治疗后与过敏性结膜炎相关的血清IgE降低和反常的嗜酸性粒细胞增多。ĴOphthal Inflamm传染 11, 3(2021)。https://doi.org/10.1186/s12348-020-00234-y

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  • DOI https //doi.org/10.1186/s12348-020-00234-y

更新日期:2021-02-15
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