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
Corresponding author
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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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 17 | 24 |
| 2024 October | 63 | 50 | 113 |
| 2024 September | 89 | 38 | 127 |
| 2024 August | 109 | 69 | 178 |
| 2024 July | 76 | 50 | 126 |
| 2024 June | 83 | 50 | 133 |
| 2024 May | 65 | 43 | 108 |
| 2024 April | 60 | 30 | 90 |
| 2024 March | 78 | 32 | 110 |
| 2024 February | 64 | 38 | 102 |
| 2024 January | 51 | 44 | 95 |
| 2023 December | 59 | 35 | 94 |
| 2023 November | 71 | 37 | 108 |
| 2023 October | 69 | 23 | 92 |
| 2023 September | 79 | 45 | 124 |
| 2023 August | 49 | 28 | 77 |
| 2023 July | 58 | 57 | 115 |
| 2023 June | 69 | 35 | 104 |
| 2023 May | 116 | 47 | 163 |
| 2023 April | 85 | 24 | 109 |
| 2023 March | 59 | 23 | 82 |
| 2023 February | 54 | 23 | 77 |
| 2023 January | 45 | 50 | 95 |
| 2022 December | 54 | 43 | 97 |
| 2022 November | 29 | 22 | 51 |
| 2022 October | 50 | 29 | 79 |
| 2022 September | 72 | 23 | 95 |
| 2022 August | 44 | 49 | 93 |
| 2022 July | 28 | 39 | 67 |
| 2022 June | 31 | 39 | 70 |
| 2022 May | 91 | 34 | 125 |
| 2022 April | 69 | 33 | 102 |
| 2022 March | 70 | 48 | 118 |
| 2022 February | 67 | 30 | 97 |
| 2022 January | 119 | 42 | 161 |
| 2021 December | 65 | 34 | 99 |
| 2021 November | 65 | 45 | 110 |
| 2021 October | 71 | 56 | 127 |
| 2021 September | 75 | 49 | 124 |
| 2021 August | 95 | 41 | 136 |
| 2021 July | 68 | 30 | 98 |
| 2021 June | 58 | 35 | 93 |
| 2021 May | 65 | 53 | 118 |
| 2021 April | 131 | 47 | 178 |
| 2021 March | 87 | 28 | 115 |
| 2021 February | 77 | 23 | 100 |
| 2021 January | 38 | 27 | 65 |
| 2020 December | 47 | 19 | 66 |
| 2020 November | 25 | 9 | 34 |
| 2020 October | 14 | 13 | 27 |
| 2020 September | 29 | 14 | 43 |
| 2020 August | 21 | 16 | 37 |
| 2020 July | 26 | 21 | 47 |
| 2020 June | 39 | 37 | 76 |
| 2020 May | 21 | 18 | 39 |
| 2020 April | 24 | 16 | 40 |
| 2020 March | 31 | 20 | 51 |
| 2020 February | 2 | 5 | 7 |
| 2020 January | 4 | 5 | 9 |
| 2019 December | 4 | 2 | 6 |
| 2019 November | 4 | 5 | 9 |
| 2019 October | 0 | 2 | 2 |
| 2019 September | 0 | 1 | 1 |
| 2019 August | 6 | 0 | 6 |
| 2019 July | 4 | 7 | 11 |
| 2019 June | 4 | 6 | 10 |
| 2019 May | 4 | 19 | 23 |
| 2019 April | 2 | 16 | 18 |
| 2019 March | 2 | 5 | 7 |
| 2019 February | 0 | 6 | 6 |
| 2019 January | 2 | 0 | 2 |
| 2018 December | 2 | 0 | 2 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 2 | 0 | 2 |
| 2018 September | 2 | 0 | 2 |
| 2018 August | 0 | 1 | 1 |
| 2018 June | 0 | 1 | 1 |
| 2018 May | 0 | 6 | 6 |
| 2018 April | 0 | 1 | 1 |
| 2018 March | 1 | 1 | 2 |
| 2018 February | 49 | 10 | 59 |
| 2018 January | 71 | 9 | 80 |
| 2017 December | 52 | 9 | 61 |
| 2017 November | 53 | 8 | 61 |
| 2017 October | 53 | 8 | 61 |
| 2017 September | 54 | 6 | 60 |
| 2017 August | 104 | 22 | 126 |
| 2017 July | 79 | 4 | 83 |
| 2017 June | 77 | 24 | 101 |
| 2017 May | 75 | 17 | 92 |
| 2017 April | 66 | 7 | 73 |
| 2017 March | 54 | 44 | 98 |
| 2017 February | 44 | 8 | 52 |
| 2017 January | 50 | 14 | 64 |
| 2016 December | 51 | 14 | 65 |
| 2016 November | 84 | 5 | 89 |
| 2016 October | 121 | 10 | 131 |
| 2016 September | 192 | 4 | 196 |
| 2016 August | 164 | 7 | 171 |
| 2016 July | 66 | 16 | 82 |
| 2016 June | 13 | 18 | 31 |
| 2016 May | 6 | 20 | 26 |
| 2016 April | 4 | 1 | 5 |
| 2016 March | 7 | 1 | 8 |
| 2016 February | 7 | 1 | 8 |
| 2016 January | 6 | 2 | 8 |
| 2015 December | 8 | 6 | 14 |
| 2015 November | 21 | 2 | 23 |
| 2015 October | 26 | 7 | 33 |
| 2015 September | 28 | 5 | 33 |
| 2015 August | 19 | 8 | 27 |
| 2015 July | 71 | 10 | 81 |
| 2015 June | 51 | 9 | 60 |
| 2015 May | 90 | 20 | 110 |
| 2015 April | 58 | 5 | 63 |
| 2015 March | 69 | 7 | 76 |
| 2015 February | 39 | 13 | 52 |
| 2015 January | 53 | 10 | 63 |
| 2014 December | 57 | 10 | 67 |
| 2014 November | 37 | 9 | 46 |
| 2014 October | 53 | 21 | 74 |
| 2014 September | 42 | 15 | 57 |
| 2014 August | 55 | 25 | 80 |
| 2014 July | 54 | 20 | 74 |
| 2014 June | 73 | 16 | 89 |
| 2014 May | 81 | 13 | 94 |
| 2014 April | 72 | 12 | 84 |
| 2014 March | 76 | 18 | 94 |
| 2014 February | 54 | 12 | 66 |
| 2014 January | 61 | 21 | 82 |
| 2013 December | 23 | 4 | 27 |
| 2013 November | 25 | 10 | 35 |
| 2013 October | 16 | 7 | 23 |
| 2013 September | 19 | 9 | 28 |
| 2013 August | 13 | 9 | 22 |
| 2013 July | 13 | 15 | 28 |
| 2013 June | 11 | 14 | 25 |
| 2013 May | 21 | 5 | 26 |
| 2013 April | 14 | 8 | 22 |
| 2013 March | 12 | 4 | 16 |
| 2013 February | 32 | 4 | 36 |
| 2013 January | 51 | 5 | 56 |
| 2012 December | 32 | 17 | 49 |
| 2012 November | 1 | 2 | 3 |
| 2012 October | 1 | 2 | 3 |
| 2012 September | 0 | 3 | 3 |
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