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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Interferons &#40;IFN&#41; are a family of pleiotropic cytokines that exert antiviral and antitumor effects through several different mechanisms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> These cytokines are of interest to dermatologists mainly because of their effectiveness in the treatment of basal cell carcinoma &#40;BCC&#41;&#44; squamous cell carcinoma&#44; Kaposi sarcoma&#44; and melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Intralesional IFN was first demonstrated to effectively treat BCC in 1986&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and it produced complete responses in between 67&#37; and 80&#37; of patients in published series&#46; IFN can be administered as monotherapy or as an adjuvant after surgery&#46; Here&#44; we describe the use of IFN administered topically in ophthalmic eyedrops in the management of a BCC on the free margin of the eyelid&#46; This formulation is used in ophthalmology to treat squamous conjunctival papillomata&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> squamous neoplasms of the ocular surface&#44; Kaposi sarcomas&#44; and conjunctival melanomas&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of an 88 year-old woman with a histologically-confirmed&#44; solid papular BCC of 5<span class="elsevierStyleHsp" style=""></span>mm in diameter on the margin of the lower left eyelid &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The patient refused surgical treatment&#46; Other treatment options&#44; such as photodynamic therapy and imiquimod cream&#44; were considered&#44; but were ruled out due to the characteristics and location of the lesion&#46; The patient also refused treatment with intralesional IFN due to a fear of injections&#46; It was decided to treat the BCC with IFN alfa-2b in ophthalmic eyedrops at a concentration of 1 million IU&#47;mL&#44; administered 4 times per day&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> This treatment was continued for 4 months&#44; resulting in a decrease in the size of the lesion &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; No adverse effects were observed during treatment&#44; and there was no change in the clinical appearance of the lesion on follow-up at 39 months&#46; The patient still refuses to undergo either surgery or a control biopsy&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The efficacy of IFN alfa-2b eyedrops in various tumors of the conjunctiva&#44; eyelid&#44; and ocular surface is described in the ophthalmic literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5&#44;7&#44;8</span></a> The recommended dose is 1 drop of IFN alfa-2b at 1 million IU&#47;mL 4 times per day for 3 to 4 months&#46; Some authors recommend a maintenance regimen of 1 drop every 12<span class="elsevierStyleHsp" style=""></span>hours&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Several studies have compared ophthalmic with intralesional IFN alfa-2b administration<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> in the treatment of both non-invasive and invasive ocular surface squamous neoplasia&#44; reporting better patient compliance and lower rates of local and systemic side effects in patients treated with eyedrops&#46; The only local side effects reported are mild and resolve upon discontinuation of treatment&#46; They include punctate keratitis&#44; follicular conjunctivitis&#44; and conjunctival hyperemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;8&#44;9</span></a> Development of the flu syndrome characteristic of systemic or intralesional IFN therapy is rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> Comparison of IFN alfa-2b eyedrops with surgical treatment of non-invasive squamous neoplasia has revealed a comparable cure rate &#40;total resolution in 96&#46;4&#37; of patients&#41;&#44; with eyedrops producing better cosmetic results and less destruction of limbal stem cells&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">While we found no mention of this treatment in the dermatological literature&#44; several ophthalmologic publications describe the effectiveness of topical IFN alfa-2b in cases of viral warts&#44; intraepidermal carcinomas&#44; and even melanomas on the eyelids and ocular surface&#44; although these results are described in small series or isolated cases and should thus be interpreted with caution&#46; We found no other cases in which IFN alfa-2b eyedrops have been used in the management of BCC of the eyelid&#46; BCC is an accepted indication for IFN alfa-2b&#44; and our findings point to a new potential route of administration&#46; In our case the volume of the tumor decreased considerably&#44; and the patient remains clinically stable after 3 years&#46; However&#44; we have no objective evidence of resolution&#44; which requires close monitoring in a clinical setting&#46; Our isolated experience should in no way change the standard accepted approaches used for the management of nonmelanoma skin cancer&#46; Controlled clinical trials will be necessary to definitively determine the effectiveness of this treatment&#46; However&#44; given its ease of administration and its few&#44; 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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Suppression of cell proliferation</span>&nbsp;\t\t\t\t\t\t\n
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Journal Information
Vol. 105. Issue 2.
Pages 207-208 (March 2014)
Vol. 105. Issue 2.
Pages 207-208 (March 2014)
Case and Research Letter
Full text access
Interferon Eyedrops in the Treatment of Basal Cell Carcinoma of the Eyelid
Colirio de interferón y carcinoma basocelular palpebral
Visits
10751
V.M. Leis-Dosil
Corresponding author
vmanuel.leis@salud.madrid.org

Corresponding author.
, I. Prats-Caelles, C. Rubio-Flores
Sección de Dermatología, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain
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Table 1. Interferons: Indications and Mechanisms of Action.
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To the Editor:

Interferons (IFN) are a family of pleiotropic cytokines that exert antiviral and antitumor effects through several different mechanisms (Table 1).1 These cytokines are of interest to dermatologists mainly because of their effectiveness in the treatment of basal cell carcinoma (BCC), squamous cell carcinoma, Kaposi sarcoma, and melanoma.2

Table 1.

Interferons: Indications and Mechanisms of Action.

Indications 
Antiviral 
Hepatitis Ba,b 
Hepatitis Ca,b 
Human papilloma virusa,c 
Antitumor 
Hepatocarcinomab 
Chronic myeloid leukemia,a,b hairy cell leukemia,a,b multiple myelomab 
Kaposi sarcomaa,b 
Renal carcinomaa 
Basal cell carcinomab 
Squamous cell carcinomab 
Melanomaa,b 
 
Mechanisms of action 
Suppression of cell proliferation 
Increased macrophage-mediated phagocytosis 
Inhibition of viral replication 
Inhibition of angiogenesis 
Increase in cellular immune response of T lymphocytes 

Interferon subtype: a, alfa-2a; b, alfa-2b; c, alfa-n3.

Intralesional IFN was first demonstrated to effectively treat BCC in 1986,3 and it produced complete responses in between 67% and 80% of patients in published series. IFN can be administered as monotherapy or as an adjuvant after surgery. Here, we describe the use of IFN administered topically in ophthalmic eyedrops in the management of a BCC on the free margin of the eyelid. This formulation is used in ophthalmology to treat squamous conjunctival papillomata,4 squamous neoplasms of the ocular surface, Kaposi sarcomas, and conjunctival melanomas.5

We report the case of an 88 year-old woman with a histologically-confirmed, solid papular BCC of 5mm in diameter on the margin of the lower left eyelid (Fig. 1). The patient refused surgical treatment. Other treatment options, such as photodynamic therapy and imiquimod cream, were considered, but were ruled out due to the characteristics and location of the lesion. The patient also refused treatment with intralesional IFN due to a fear of injections. It was decided to treat the BCC with IFN alfa-2b in ophthalmic eyedrops at a concentration of 1 million IU/mL, administered 4 times per day.6,7 This treatment was continued for 4 months, resulting in a decrease in the size of the lesion (Fig. 2). No adverse effects were observed during treatment, and there was no change in the clinical appearance of the lesion on follow-up at 39 months. The patient still refuses to undergo either surgery or a control biopsy.

Figure 1.

Basal cell carcinoma on the lower margin of the left eyelid: appearance before starting treatment.

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Figure 2.

Decrease in lesion size after 4 months of treatment.

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The efficacy of IFN alfa-2b eyedrops in various tumors of the conjunctiva, eyelid, and ocular surface is described in the ophthalmic literature.2,5,7,8 The recommended dose is 1 drop of IFN alfa-2b at 1 million IU/mL 4 times per day for 3 to 4 months. Some authors recommend a maintenance regimen of 1 drop every 12hours.6 Several studies have compared ophthalmic with intralesional IFN alfa-2b administration8 in the treatment of both non-invasive and invasive ocular surface squamous neoplasia, reporting better patient compliance and lower rates of local and systemic side effects in patients treated with eyedrops. The only local side effects reported are mild and resolve upon discontinuation of treatment. They include punctate keratitis, follicular conjunctivitis, and conjunctival hyperemia.5,8,9 Development of the flu syndrome characteristic of systemic or intralesional IFN therapy is rare.6,7 Comparison of IFN alfa-2b eyedrops with surgical treatment of non-invasive squamous neoplasia has revealed a comparable cure rate (total resolution in 96.4% of patients), with eyedrops producing better cosmetic results and less destruction of limbal stem cells.10

While we found no mention of this treatment in the dermatological literature, several ophthalmologic publications describe the effectiveness of topical IFN alfa-2b in cases of viral warts, intraepidermal carcinomas, and even melanomas on the eyelids and ocular surface, although these results are described in small series or isolated cases and should thus be interpreted with caution. We found no other cases in which IFN alfa-2b eyedrops have been used in the management of BCC of the eyelid. BCC is an accepted indication for IFN alfa-2b, and our findings point to a new potential route of administration. In our case the volume of the tumor decreased considerably, and the patient remains clinically stable after 3 years. However, we have no objective evidence of resolution, which requires close monitoring in a clinical setting. Our isolated experience should in no way change the standard accepted approaches used for the management of nonmelanoma skin cancer. Controlled clinical trials will be necessary to definitively determine the effectiveness of this treatment. However, given its ease of administration and its few, mild side effects, we propose the use of IFN alfa-2b eyedrops as a neoadjuvant therapy in selected cases to reduce tumor size before microscopically controlled surgical excision.

References
[1]
B.J. Lee, C.C. Nelson.
Intralesional interferon for extensive squamous papilloma of the eyelid margin.
Ophtal Plast Reconstr Surg, 28 (2012), pp. e47-e48
[2]
C.L. Shields, S. Kancherla, C.G. Bianciotto, S.E. Lally, J.E. Shields.
Ocular surface squamous neoplasia (squamous cell carcinoma) of the socket: Management of extensive tumors with interferon.
Ophtal Plast Reconstr Surg, 27 (2011), pp. 247-250
[3]
S. Fenton, S. Kennedy, P. Moriarty.
The role of interferon alpha 2b as an adjunctive treatment in the management of aggressive basal cell carcinoma of the eyelids.
Acta Ophtalmol Scand, 80 (2002), pp. 674-675
[4]
B.A. Schechter, W.J. Rand, G.E. Velazquez, W.D. Williams, L. Starasoler.
Treatment of conjunctival papillomata with topical interferon alfa-2b.
Am J Ophtalmol, 134 (2002), pp. 268-270
[5]
P.T. Finger, R.W. Sedeek, K.J. Chin.
Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex.
Am J Ophtalmol, 145 (2008), pp. 124-129
[6]
A. Galor, C.L. Karp, S. Chhabra, S. Barnes, E.C. Alfonso.
Topical interferon alpha 2b eye-drops for treatment of ocular surface squamous neoplasia: A dose comparison study.
Br J Ophtalmol, 94 (2010), pp. 551-554
[7]
B.A. Schechter, A. Schrier, R.S. Nagler, E.F. Smith, G.E. Velasquez.
Regression of presumed primary conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b.
Cornea, 21 (2002), pp. 6-11
[8]
C.L. Shields, S. Kaliki, H.J. Kim, S. Al-Dahmash, S.U. Shah, S.E. Lally, et al.
Interferon for ocular surface squamous neoplasia in 81 cases: Outcomes based on the American Joint Committee on Cancer Classification.
[9]
P. Verdaguer, M. Fideliz de la Paz, J.P. Álvarez de Toledo, R.I. Barraquer.
Interferón alfa-2b, queratectomía parcial y trasplante de membrana amniótica para el tratamiento de un carcinoma escamoso conjuntival recidivante.
Arch Soc Esp Oftalmol, 86 (2011), pp. 154-157
[10]
V. Huerva.
Interferón alfa-2b tópico o escisión quirúrgica como tratamiento primario de la neoplasia conjuntival intraepitelial.
Arch Soc Esp Oftalmol, 84 (2009), pp. 5-6

Please cite this article as: Leis-Dosil VM, Prats-Caelles I, Rubio-Flores C. Colirio de interferón y carcinoma basocelular palpebral. Actas Dermosifiliogr. 2014;105:207–208.

Copyright © 2012. Elsevier España, S.L. and AEDV
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