CA Naranjo

DP Steensma

FW Fraunfelder

I Beiran

LA Anderson

P Fietta

RS Moorthy

Journal of Ophthalmic Inflammation and Infection

Jonathan Li

Stephen E. Orlin

Karen E. Revere

John H. Kempen

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LETTER TO THE EDITOR Open AccessAcute onset anterior uveitis afterdarbepoetin alfa infusionJonathan Li1, Stephen E. Orlin1, Karen E. Revere1 and John H. Kempen1,2,3*AbstractA 79-year-old female with a 2-month history of newly diagnosed myelodysplastic syndrome for which she receivedblood transfusion with darbepoetin alfa presented with bilateral anterior uveitis 1 day after her fourth transfusion.On exam, visual acuity was 20/20 in both eyes with biomicroscopy notable for conjunctival injection and anteriorchamber cell and flare consistent with anterior uveitis. She had no systemic symptoms, no history of eye trauma,and no known infections. This case, along with prior reports in the literature, suggests that anterior uveitis may bean idiosyncratic complication of darbepoetin alfa therapy.Keywords: Anterior uveitis; Iritis; Erythropoietin; DarbepoetinFindingsIntroductionThe proportion of uveitis cases attributed to drug-induceduveitis is reportedly less than 0.5 % [1]. Drug-induced uve-itis more typically is caused by intraocular or topical ratherthan systemic medications [2]. However, systemic medica-tions have become increasingly recognized as potentialcauses of uveitis. Several drugs are now more definitivelyassociated with anterior uveitis, such as cidofovir, rifabutin,sulfonamides, bisphosphonates, fluoroquinolones, and di-ethylcarbamazine [3, 4]. Recognizing potential causes ofmedication-related intraocular inflammation is importantbecause it can avoid unnecessary workups and may allowfor clinical improvement by stopping the causative agent.Although not well established, an association betweenepoetin alfa, a human recombinant erythropoietin, andanterior uveitis has been reported previously in the lit-erature, with 13 patients across three medical centersdeveloping anterior uveitis after receiving epoetin alfaduring hemodialysis [2]. All of these patients wereundergoing hemodialysis for end stage renal failure andreceiving epoetin alfa for chronic anemia [2].Case reportA 79-year-old Caucasian female presented with acuteonset, 1-day history of bilateral blurry vision, eyeredness, photophobia, and tearing. Past medical historyincluded a new diagnosis of myelodysplastic syndrome2 months prior, for which she had received four bloodtransfusions with darbepoetin alfa, a longer-actinghuman recombinant erythropoietin. Her last transfusionwith darbepoetin alfa was 1 day before presentation. Shereported no other systemic symptoms, eye trauma, orunderlying infections. She had no history of ocularinflammation or infection prior to beginning bloodtransfusions with darbepoetin alfa, which includes a1-month period in which she had myelodysplasticsyndrome but had not yet received any darbepoetin. Shenoted bloodshot eyes and ocular tenderness to palpa-tion after two of her prior blood transfusions withdarbepoetin alfa (to a degree that was less severe andwhich had spontaneously resolved).On exam, her visual acuity was 20/20-2 in each eye.Her intraocular pressures were 15 mmHg in the righteye and 16 mmHg in the left eye. Anterior segmentbiomicroscopy revealed marked conjunctival injection,grade 2+ cell and flare in the anterior chamber, and 2+nuclear sclerosis in each eye. There was no vitreousinflammation, and dilated fundus exam was normalwithout inflammatory signs.She was diagnosed with bilateral, acute anterior uveitisand treated with prednisolone acetate 1 % hourly and* Correspondence: john.kempen@uphs.upenn.edu1Department of Ophthalmology, Scheie Eye Institute, 51 N 39th St,Philadelphia, PA 19104, USA2Department of Biostatistics and Epidemiology, Philadelphia, PA, USAFull list of author information is available at the end of the article© 2015 Li et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 InternationalLicense (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in anymedium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commonslicense, and indicate if changes were made.Li et al. Journal of Ophthalmic Inflammation and Infection  (2015) 5:31 DOI 10.1186/s12348-015-0061-0homatropine 5 % three times a day. Two weeks later,she reported that all her symptoms had rapidly resolved;the visual acuity continued to be 20/20-2 in each eyeand biomicroscopy demonstrated complete resolution ofanterior uveitis.Due to the temporal association of the patient’s darbe-poetin alfa infusion with her acute onset anterior uveitis,and history of previous suggestive similar episodes justafter infusions, a consensus decision was made with herhematologist to discontinue the use of darbepoetin alfaalong with future blood product infusions. Treatment withdecitabine, a DNA hypomethylating agent that leads tocellular differentiation, was initiated instead to help man-age her myelodysplastic syndrome. The patient has sincereceived two infusions of blood products without furtherepisodes of ocular inflammation.DiscussionOur patient represents the first described case of likelydarbepoetin alfa-induced anterior uveitis. It builds uponthe previous reports of epoetin-induced anterior uveitisreported by Beiran et al. in 1996 [2].The mechanism by which systemic medications induceocular inflammation is largely unknown, with the excep-tion of bisphosphonates, which are associated withincreased intraocular inflammatory cytokines, elevatedC-reactive protein, interleukin-1, and interleukin-6 [5].Beiran et al. postulated a mechanism whereby erythro-poietin could induce an inflammatory effect by alteringprostaglandin E levels, breaking down the tight junctionsthat form the blood-aqueous barrier [2]. Darbepoetinalfa and epoetin alfa both have the same native proteinsequence, differing only in glycosylation patterns [6].Therefore, it is likely that similar mechanisms contrib-uted to the drug-induced anterior uveitis in these previ-ously reported cases as well as our own.Given our patient’s underlying myelodysplastic syndro-me—which can be associated with the development ofautoimmune conditions—it also is possible that an auto-immune process was the cause of her anterior uveitis[7]. However, her reported history of two episodes ofphotophobia and eye redness after previous infusions,coupled with the absence of episodes both before beginningand after discontinuation of darbepoetin alfa infusions,suggests that this was indeed a drug-related anterior uveitis.Further studies are needed to elucidate the mechanism andstrength between the association of darbepoetin alfa andanterior uveitis.Consent to publishConsent to publish this case report has been obtainedfrom the patient.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsAll authors participated in the conception and design of paper, datacollection, and analysis. JL drafted and was involved in critical revision of themanuscript. SO, JK, and KR revised it critically for important intellectualcontent. All authors read and approved the final manuscript and agreed tobe accountable for the work.AcknowledgementsFunding for the project was provided, in part, by the Harold G. ScheieTeaching and Research Fund (Philadelphia, PA, USA); Research to PreventBlindness (New York, NY, USA); the Paul and Evanina Mackall Foundation(New York, NY, USA); and the Lois Pope Life Foundation (New York, NY, USA).None of these contributed to the design of the report; to the collection,analysis, or interpretation of data; to the writing of the manuscript; nor tothe decision to submit for publication.Author details1Department of Ophthalmology, Scheie Eye Institute, 51 N 39th St,Philadelphia, PA 19104, USA. 2Department of Biostatistics and Epidemiology,Philadelphia, PA, USA. 3Center for Clinical Epidemiology and Biostatistics, thePerelman School of Medicine, University of Pennsylvania, Philadelphia, PA,USA.Received: 10 July 2015 Accepted: 13 October 2015References1. Fraunfelder FW, Rosenbaum JT (1997) Drug-induced uveitis: incidence,prevention and treatment. Drug Saf 17(3):197–2072. Beiran I, Krasnitz I, Mezer E, Meyer E, Miller B (1996) Erythropoietin-inducediritis-like reaction. Eur J Ophthalmol 6(1):14–63. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E,Domecq C, Greenblatt DJ (1981) A method for estimating the probability ofadverse drug reactions. Clin Pharmacol Ther 30(2):239–454. Moorthy RS, London NJ, Garg SJ, Cunningham ET Jr (2013) Drug-induceduveitis. Curr Opin Ophthalmol 24(6):589–975. Fietta P, Manganelli P, Lodigiani L (2003) Clodronate induced uveitis. AnnRheum Dis 62:3786. Steensma DP, Loprinzi CL (2006) Epoetin alfa and darbepoetin alfa go headto head. J of Clinical Oncology 24(15):2233–22367. Anderson LA, Pfeiffer RM, Landgren O, Gadalla S, Berndt SI, Engels EA (2009)Risks of myeloid malignancies in patients with autoimmune conditions.Br J Cancer 100(5):822–8Submit your manuscript to a journal and beneﬁ t from:7 Convenient online submission7 Rigorous peer review7 Immediate publication on acceptance7 Open access: articles freely available online7 High visibility within the ﬁ eld7 Retaining the copyright to your article    Submit your next manuscript at 7 springeropen.comLi et al. Journal of Ophthalmic Inflammation and Infection  (2015) 5:31 Page 2 of 2

Acute onset anterior uveitis after darbepoetin alfa infusion

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Acute onset anterior uveitis after darbepoetin alfa infusion

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