Case and Research Letters
Halo Nevi Associated With Interferon Beta-1a Therapy
Halo nevi asociados al tratamiento con interferón beta-1a
E. Vera-Iglesias
, M. García-Arpa, P. Sánchez-Caminero
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F.E.A. Servicio de Dermatología, Hospital General de Ciudad Real, Ciudad Real, Spain
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Vera-Iglesias, M. García-Arpa, P. Sánchez-Caminero" "autores" => array:3 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Vera-Iglesias" "email" => array:1 [ 0 => "everaigl@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "García-Arpa" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Sánchez-Caminero" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "F.E.A. Servicio de Dermatología, Hospital General de Ciudad Real, Ciudad Real, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Halo nevi asociados al tratamiento con interferón beta-1a" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 709 "Ancho" => 948 "Tamanyo" => 59467 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Halo nevi on the back.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The interferons are a group of more than 20 glycoproteins produced by numerous body cells in response to the presence of viruses, double-stranded RNA, polypeptides, or bacterial products. All of them share the ability to inhibit viral replication and cell proliferation, and to regulate and modulate immune cells.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> From an immunologic point of view, interferons increase the expression of class I or II molecules of the major histocompatibility complex and stimulate natural killer (NK) lymphocytes.</p><p id="par0010" class="elsevierStylePara elsevierViewall">There are 2 types of interferon: type 1, which is divided into alpha, beta, omega, and tao, and type 2 which comprises gamma interferon. The principal interferons of medical interest are alpha interferons, produced mainly by leukocytes, beta interferons, produced by fibroblasts, and gamma interferons, produced by T lymphocytes and NK cells. Interferons are primarily used in medicine to treat malignant neoplasms, viral diseases, and autoimmune diseases. Type 1 is more effective as an antiviral agent and type 2 has a more specific effect on regulation of the immune response.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We describe a 22-year-old woman with an 8-month history of multiple sclerosis. She had been receiving interferon beta-1a subcutaneously at doses of 22<span class="elsevierStyleHsp" style=""></span>mcg 3 times weekly for the previous 3 months. The patient reported depigmentation around nevi on her skin, with onset of the depigmentation only a few weeks after interferon therapy was started. She had no personal or family history of vitiligo and presented no previous halo nevi.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Physical examination revealed an achromic hypopigmented halo around almost all the nevi on the patient's skin, a total of 15, most of them on the back (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) as well as around several intradermal nevi on the face (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The nevi were stable and had been present for some time; none presented clinical or dermoscopic atypia.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The interferon was well tolerated, with no liver or thyroid abnormalities and with satisfactory control of multiple sclerosis, which was in remission at the time.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Halo nevi express an autoimmunity phenomenon that manifests as an achromic hypopigmented halo around the nevus, which often disappears. Histology shows a lymphohistiocytic infiltrate directed against the melanocytes. Immune involvement in the genesis of this phenomenon is supported by the presence or increased numbers of T lymphocytes, mainly CD8+ cells, and antigen-presenting cells at the site of depigmentation.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Additionally, the local endogenous production and activation of type 1 interferon have been seen to be involved in the regression of melanomas and other melanocytic lesions.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Interferon beta-1b and 1a are approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis. They have proven to be disease-modifying drugs that can prevent exacerbations or lengthen the time between them.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The drugs acts as immunomodulators, activating cytotoxic CD8+ T cells, and may modify the immune response. The most common side effects are inflammatory reactions at the injection site and flu-like symptoms. Asymptomatic elevation of liver enzymes and cytopenias are also observed. Rarely, they can cause various autoimmune phenomena such as thyroiditis, myasthenia gravis, rheumatoid arthritis, lupus erythematosus, and Raynaud phenomenon.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">.</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The appearance of autoimmune hepatitis has also been described in a few reports.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Autoantibodies, such as thyroglobulin and microsomal autoantibodies, have been detected occasionally with administration of the drug, but their significance is uncertain.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Our report is the first to relate the appearance of multiple halo nevi with the use of interferon beta-1a. Another report describes a patient on treatment with interferon beta-1a who developed vitiligo that improved when the drug was discontinued.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The authors postulated that interferon beta-1a could stimulate CD8+ lymphocytes to recognize melanocyte-derived proteins; these cells are known to play a key role in vitiligo. Several cases of vitiligo with the use of interferon alpha-2a have also been described.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although the exact pathophysiology of halo nevi and vitiligo is unknown, the 2 manifestations appear to have a common pathophysiology and often present together. Several theories suggest that these manifestations are the result of an immune response against melanocytes, probably mediated by CD8+ cell activation, as might occur with the use of interferon.</p><p id="par0050" class="elsevierStylePara elsevierViewall">A literature review found 2 reports of drug-induced multiple halo nevi of sudden onset with the use of infliximab and imatinib.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> In the first case, the condition was associated with worsening of previous alopecia areata, and the authors proposed that anti-TNF drugs induce autoimmune phenomena that include alopecia areata and halo nevi. In the second case, there was a relationship with c-Kit tyrosine kinase inhibition.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, our patient developed multiple halo nevi a few weeks after the start of interferon therapy. We believe that in our patient there was a relationship between the use of interferon and the development of multiple halo nevi, due to the temporal association and the immune system modifications that this therapy induces through CD8+ cell activation, favoring autoimmune phenomena; this is an important event in the pathophysiology of the development of halo nevi. The use of systemic or intralesional interferon has been shown to shrink or eliminate some melanoma metastases, probably by the same mechanism that induces the formation of halo nevi and vitiligo. This highlights the importance of immunity in the biology of melanocytic lesions and opens the door to possible therapeutic approaches to melanoma treatment.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Vera-Iglesias E, et al. Halo nevi asociados al tratamiento con interferón beta-1a. Actas Dermosifiliogr. 2012;103:75–6.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 709 "Ancho" => 948 "Tamanyo" => 59467 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Halo nevi on the back.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 706 "Ancho" => 948 "Tamanyo" => 84575 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Halo nevi on the face.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interferon in oncological practice: review of interferon biology, clinical applications and toxicities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 2 | 8 | 10 |
| 2024 Octubre | 63 | 50 | 113 |
| 2024 Septiembre | 89 | 38 | 127 |
| 2024 Agosto | 109 | 69 | 178 |
| 2024 Julio | 76 | 50 | 126 |
| 2024 Junio | 83 | 50 | 133 |
| 2024 Mayo | 65 | 43 | 108 |
| 2024 Abril | 60 | 30 | 90 |
| 2024 Marzo | 78 | 32 | 110 |
| 2024 Febrero | 64 | 38 | 102 |
| 2024 Enero | 51 | 44 | 95 |
| 2023 Diciembre | 59 | 35 | 94 |
| 2023 Noviembre | 71 | 37 | 108 |
| 2023 Octubre | 69 | 23 | 92 |
| 2023 Septiembre | 79 | 45 | 124 |
| 2023 Agosto | 49 | 28 | 77 |
| 2023 Julio | 58 | 57 | 115 |
| 2023 Junio | 69 | 35 | 104 |
| 2023 Mayo | 116 | 47 | 163 |
| 2023 Abril | 85 | 24 | 109 |
| 2023 Marzo | 59 | 23 | 82 |
| 2023 Febrero | 54 | 23 | 77 |
| 2023 Enero | 45 | 50 | 95 |
| 2022 Diciembre | 54 | 43 | 97 |
| 2022 Noviembre | 29 | 22 | 51 |
| 2022 Octubre | 50 | 29 | 79 |
| 2022 Septiembre | 72 | 23 | 95 |
| 2022 Agosto | 44 | 49 | 93 |
| 2022 Julio | 28 | 39 | 67 |
| 2022 Junio | 31 | 39 | 70 |
| 2022 Mayo | 91 | 34 | 125 |
| 2022 Abril | 69 | 33 | 102 |
| 2022 Marzo | 70 | 48 | 118 |
| 2022 Febrero | 67 | 30 | 97 |
| 2022 Enero | 119 | 42 | 161 |
| 2021 Diciembre | 65 | 34 | 99 |
| 2021 Noviembre | 65 | 45 | 110 |
| 2021 Octubre | 71 | 56 | 127 |
| 2021 Septiembre | 75 | 49 | 124 |
| 2021 Agosto | 95 | 41 | 136 |
| 2021 Julio | 68 | 30 | 98 |
| 2021 Junio | 58 | 35 | 93 |
| 2021 Mayo | 65 | 53 | 118 |
| 2021 Abril | 131 | 47 | 178 |
| 2021 Marzo | 87 | 28 | 115 |
| 2021 Febrero | 77 | 23 | 100 |
| 2021 Enero | 38 | 27 | 65 |
| 2020 Diciembre | 47 | 19 | 66 |
| 2020 Noviembre | 25 | 9 | 34 |
| 2020 Octubre | 14 | 13 | 27 |
| 2020 Septiembre | 29 | 14 | 43 |
| 2020 Agosto | 21 | 16 | 37 |
| 2020 Julio | 26 | 21 | 47 |
| 2020 Junio | 39 | 37 | 76 |
| 2020 Mayo | 21 | 18 | 39 |
| 2020 Abril | 24 | 16 | 40 |
| 2020 Marzo | 31 | 20 | 51 |
| 2020 Febrero | 2 | 5 | 7 |
| 2020 Enero | 4 | 5 | 9 |
| 2019 Diciembre | 4 | 2 | 6 |
| 2019 Noviembre | 4 | 5 | 9 |
| 2019 Octubre | 0 | 2 | 2 |
| 2019 Septiembre | 0 | 1 | 1 |
| 2019 Agosto | 6 | 0 | 6 |
| 2019 Julio | 4 | 7 | 11 |
| 2019 Junio | 4 | 6 | 10 |
| 2019 Mayo | 4 | 19 | 23 |
| 2019 Abril | 2 | 16 | 18 |
| 2019 Marzo | 2 | 5 | 7 |
| 2019 Febrero | 0 | 6 | 6 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Agosto | 0 | 1 | 1 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Mayo | 0 | 6 | 6 |
| 2018 Abril | 0 | 1 | 1 |
| 2018 Marzo | 1 | 1 | 2 |
| 2018 Febrero | 49 | 10 | 59 |
| 2018 Enero | 71 | 9 | 80 |
| 2017 Diciembre | 52 | 9 | 61 |
| 2017 Noviembre | 53 | 8 | 61 |
| 2017 Octubre | 53 | 8 | 61 |
| 2017 Septiembre | 54 | 6 | 60 |
| 2017 Agosto | 104 | 22 | 126 |
| 2017 Julio | 79 | 4 | 83 |
| 2017 Junio | 77 | 24 | 101 |
| 2017 Mayo | 75 | 17 | 92 |
| 2017 Abril | 66 | 7 | 73 |
| 2017 Marzo | 54 | 44 | 98 |
| 2017 Febrero | 44 | 8 | 52 |
| 2017 Enero | 50 | 14 | 64 |
| 2016 Diciembre | 51 | 14 | 65 |
| 2016 Noviembre | 84 | 5 | 89 |
| 2016 Octubre | 121 | 10 | 131 |
| 2016 Septiembre | 192 | 4 | 196 |
| 2016 Agosto | 164 | 7 | 171 |
| 2016 Julio | 66 | 16 | 82 |
| 2016 Junio | 13 | 18 | 31 |
| 2016 Mayo | 6 | 20 | 26 |
| 2016 Abril | 4 | 1 | 5 |
| 2016 Marzo | 7 | 1 | 8 |
| 2016 Febrero | 7 | 1 | 8 |
| 2016 Enero | 6 | 2 | 8 |
| 2015 Diciembre | 8 | 6 | 14 |
| 2015 Noviembre | 21 | 2 | 23 |
| 2015 Octubre | 26 | 7 | 33 |
| 2015 Septiembre | 28 | 5 | 33 |
| 2015 Agosto | 19 | 8 | 27 |
| 2015 Julio | 71 | 10 | 81 |
| 2015 Junio | 51 | 9 | 60 |
| 2015 Mayo | 90 | 20 | 110 |
| 2015 Abril | 58 | 5 | 63 |
| 2015 Marzo | 69 | 7 | 76 |
| 2015 Febrero | 39 | 13 | 52 |
| 2015 Enero | 53 | 10 | 63 |
| 2014 Diciembre | 57 | 10 | 67 |
| 2014 Noviembre | 37 | 9 | 46 |
| 2014 Octubre | 53 | 21 | 74 |
| 2014 Septiembre | 42 | 15 | 57 |
| 2014 Agosto | 55 | 25 | 80 |
| 2014 Julio | 54 | 20 | 74 |
| 2014 Junio | 73 | 16 | 89 |
| 2014 Mayo | 81 | 13 | 94 |
| 2014 Abril | 72 | 12 | 84 |
| 2014 Marzo | 76 | 18 | 94 |
| 2014 Febrero | 54 | 12 | 66 |
| 2014 Enero | 61 | 21 | 82 |
| 2013 Diciembre | 23 | 4 | 27 |
| 2013 Noviembre | 25 | 10 | 35 |
| 2013 Octubre | 16 | 7 | 23 |
| 2013 Septiembre | 19 | 9 | 28 |
| 2013 Agosto | 13 | 9 | 22 |
| 2013 Julio | 13 | 15 | 28 |
| 2013 Junio | 11 | 14 | 25 |
| 2013 Mayo | 21 | 5 | 26 |
| 2013 Abril | 14 | 8 | 22 |
| 2013 Marzo | 12 | 4 | 16 |
| 2013 Febrero | 32 | 4 | 36 |
| 2013 Enero | 51 | 5 | 56 |
| 2012 Diciembre | 32 | 17 | 49 |
| 2012 Noviembre | 1 | 2 | 3 |
| 2012 Octubre | 1 | 2 | 3 |
| 2012 Septiembre | 0 | 3 | 3 |
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