Case and Research Letters
Topical 0.2% Rapamycin to Treat Facial Angiofibromas and Hypomelanotic Macules in Tuberous Sclerosis
Rapamicina tópica al 0,2% para el tratamiento de angiofibromas faciales y máculas hipomelanóticas en la esclerosis tuberosa
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"apellidos" => "Hervás" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Son Espases, Palma de Mallorca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Universitario de Ciencias de la Salud-IUNICS, Universidad de las Islas Baleares, Palma de Mallorca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rapamicina tópica al 0,2% para el tratamiento de angiofibromas faciales y máculas hipomelanóticas en la esclerosis tuberosa" ] ] "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" => 621 "Ancho" => 1000 "Tamanyo" => 129507 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Facial angiofibromas and hypomelanotic macules. A, Before treatment. B, After 20 weeks of 0.2% topical rapamycin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberous sclerosis is an autosomal dominant neurocutaneous disorder caused by mutations in tumor suppressor genes <span class="elsevierStyleItalic">TSC1</span> (in chromosome 9q34), which encodes hamartin, and <span class="elsevierStyleItalic">TSC2</span> (in chromosome 16p13.3), which encodes tuberin. Hamartin and tuberin, under normal circumstances, form a complex that inhibits the mammalian target of rapamycin (mTOR), which plays a crucial role in cell-cycle regulation. Mutations in the <span class="elsevierStyleItalic">TSC1</span> and <span class="elsevierStyleItalic">TSC2</span> genes lead to defective functioning of these proteins and result in uncontrolled cell proliferation that is characterized by the formation of hamartomas in multiple organs, including the skin and kidneys, and in the central nervous system.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Rapamycin (sirolimus) is an immunosuppressant that inhibits the mTOR pathway. Its only approved indication is prophylaxis of renal transplant rejection. Thanks to its antineoplastic properties, sirolimus inhibits angiogenesis and tumor cell proliferation, and has also been shown to be effective in reducing the number and size of tumors in patients with tuberous sclerosis. Recent publications suggest that topical rapamycin is effective for treating facial angiofibromas<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–7</span></a> and reducing hypomelanotic macules<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> in patients with tuberous sclerosis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report a case of a 13-year-old boy who had been clinically diagnosed with tuberous sclerosis at age 4 months based on the presence of typical manifestations of this condition, namely epilepsy, multiple hypomelanotic macules, and facial angiofibromas. Genetic analysis confirmed sporadic tuberous sclerosis caused by a c5043C>G mutation in exon 38 of the <span class="elsevierStyleItalic">TSC2</span> gene, changing the sequence to the N1681K variant. Magnetic resonance imaging of the brain showed multiple cortical and subcortical tubers, multiple intraventricular and subependymal hamartomas, and bilateral retinal astrocytomas. Abdominal ultrasound revealed the presence in the liver and kidneys of multiple angiomyolipomas, which were asymptomatic at the time of evaluation. Skin manifestations included facial angiofibromas that appeared gradually, multiple hypomelanotic macules, a periungual fibroma, and a shagreen patch on the back.</p><p id="par0015" class="elsevierStylePara elsevierViewall">With the aim of improving the patient's facial appearance by reducing the number of angiofibromas, we obtained informed consent to start treatment with a 0.2% rapamycin ointment formulated by the hospital pharmacy and provided at no cost to the patient. We prescribed once-daily application 5 days a week, for 12 months.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The ointment was applied only to the face; because of the high cost of the drug preparation we did not consider treating the macules on the trunk and limbs.</p><p id="par0025" class="elsevierStylePara elsevierViewall">After 2 weeks of treatment we began to observe a reduction in the number of facial angiofibromas, with maximum effect observed at 12 weeks. We also noted considerable improvement in the hypomelanotic macules on the patient's face, with similar responses in the glabella and left cheek (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment was well tolerated with no local or systemic adverse effects, and plasma rapamycin levels remained below 0.3 ng/mL. We decided to maintain this treatment for a year to prevent the development of new angiofibromas.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Facial angiofibromas are a characteristic feature of tuberous sclerosis. Although benign, they have a considerable psychological impact on patients.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our case shows that 0.2% topical rapamycin is a safe and effective therapy for both facial angiofibromas and hypomelanotic macules. The high cost of treatment and the lack of an approved indication for topical rapamycin limit the use of this therapeutic agent in daily practice. This is the third case published in the literature describing a marked improvement in hypomelanotic macules, with almost complete remission. The effectiveness of rapamycin against hypomelanotic macules might be explained by the fact that it increases transcription of microphthalmia transcription factor (MITF), which is involved in melanogenic gene expression and in the induction of melanogenesis in melanoma cells.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion, the present case further supports the usefulness of topical rapamycin to treat hypomelanotic macules in patients with tuberous sclerosis. However, more patients treated with topical rapamycin are needed in order to establish its safety and long-term effectiveness and to determine the most appropriate treatment regimen.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Knöpfel N, Martín-Santiago A, Bauza A, Hervás JA. Rapamicina tópica al 0,2% para el tratamiento de angiofibromas faciales y máculas hipomelanóticas en la esclerosis tuberosa. Actas Dermosifiliogr. 2014;105:802–803.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 621 "Ancho" => 1000 "Tamanyo" => 129507 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Facial angiofibromas and hypomelanotic macules. A, Before treatment. B, After 20 weeks of 0.2% topical rapamycin.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The tuberous sclerosis complex" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Octubre | 96 | 45 | 141 |
| 2024 Septiembre | 110 | 33 | 143 |
| 2024 Agosto | 156 | 64 | 220 |
| 2024 Julio | 111 | 32 | 143 |
| 2024 Junio | 77 | 25 | 102 |
| 2024 Mayo | 85 | 31 | 116 |
| 2024 Abril | 90 | 22 | 112 |
| 2024 Marzo | 69 | 18 | 87 |
| 2024 Febrero | 52 | 33 | 85 |
| 2024 Enero | 60 | 39 | 99 |
| 2023 Diciembre | 76 | 32 | 108 |
| 2023 Noviembre | 91 | 33 | 124 |
| 2023 Octubre | 60 | 43 | 103 |
| 2023 Septiembre | 78 | 39 | 117 |
| 2023 Agosto | 70 | 10 | 80 |
| 2023 Julio | 87 | 31 | 118 |
| 2023 Junio | 72 | 27 | 99 |
| 2023 Mayo | 113 | 23 | 136 |
| 2023 Abril | 91 | 27 | 118 |
| 2023 Marzo | 57 | 24 | 81 |
| 2023 Febrero | 68 | 21 | 89 |
| 2023 Enero | 62 | 19 | 81 |
| 2022 Diciembre | 90 | 31 | 121 |
| 2022 Noviembre | 39 | 27 | 66 |
| 2022 Octubre | 48 | 28 | 76 |
| 2022 Septiembre | 61 | 28 | 89 |
| 2022 Agosto | 38 | 36 | 74 |
| 2022 Julio | 25 | 38 | 63 |
| 2022 Junio | 30 | 27 | 57 |
| 2022 Mayo | 94 | 39 | 133 |
| 2022 Abril | 98 | 30 | 128 |
| 2022 Marzo | 89 | 36 | 125 |
| 2022 Febrero | 80 | 25 | 105 |
| 2022 Enero | 60 | 36 | 96 |
| 2021 Diciembre | 50 | 27 | 77 |
| 2021 Noviembre | 59 | 41 | 100 |
| 2021 Octubre | 78 | 48 | 126 |
| 2021 Septiembre | 80 | 34 | 114 |
| 2021 Agosto | 77 | 28 | 105 |
| 2021 Julio | 67 | 30 | 97 |
| 2021 Junio | 51 | 33 | 84 |
| 2021 Mayo | 74 | 26 | 100 |
| 2021 Abril | 210 | 67 | 277 |
| 2021 Marzo | 102 | 28 | 130 |
| 2021 Febrero | 102 | 35 | 137 |
| 2021 Enero | 71 | 18 | 89 |
| 2020 Diciembre | 33 | 19 | 52 |
| 2020 Noviembre | 24 | 18 | 42 |
| 2020 Octubre | 32 | 18 | 50 |
| 2020 Septiembre | 42 | 15 | 57 |
| 2020 Agosto | 37 | 20 | 57 |
| 2020 Julio | 37 | 22 | 59 |
| 2020 Junio | 44 | 27 | 71 |
| 2020 Mayo | 36 | 23 | 59 |
| 2020 Abril | 24 | 20 | 44 |
| 2020 Marzo | 38 | 17 | 55 |
| 2020 Febrero | 5 | 4 | 9 |
| 2020 Enero | 4 | 6 | 10 |
| 2019 Diciembre | 8 | 3 | 11 |
| 2019 Noviembre | 4 | 2 | 6 |
| 2019 Octubre | 3 | 6 | 9 |
| 2019 Septiembre | 9 | 8 | 17 |
| 2019 Agosto | 4 | 2 | 6 |
| 2019 Julio | 2 | 5 | 7 |
| 2019 Junio | 6 | 7 | 13 |
| 2019 Mayo | 2 | 13 | 15 |
| 2019 Abril | 0 | 1 | 1 |
| 2019 Marzo | 2 | 5 | 7 |
| 2019 Enero | 1 | 2 | 3 |
| 2018 Diciembre | 0 | 1 | 1 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 1 | 0 | 1 |
| 2018 Junio | 0 | 4 | 4 |
| 2018 Mayo | 0 | 5 | 5 |
| 2018 Abril | 0 | 5 | 5 |
| 2018 Marzo | 1 | 6 | 7 |
| 2018 Febrero | 42 | 10 | 52 |
| 2018 Enero | 78 | 10 | 88 |
| 2017 Diciembre | 40 | 11 | 51 |
| 2017 Noviembre | 40 | 8 | 48 |
| 2017 Octubre | 50 | 15 | 65 |
| 2017 Septiembre | 34 | 12 | 46 |
| 2017 Agosto | 39 | 16 | 55 |
| 2017 Julio | 28 | 9 | 37 |
| 2017 Junio | 38 | 20 | 58 |
| 2017 Mayo | 26 | 22 | 48 |
| 2017 Abril | 25 | 9 | 34 |
| 2017 Marzo | 23 | 30 | 53 |
| 2017 Febrero | 19 | 11 | 30 |
| 2017 Enero | 18 | 13 | 31 |
| 2016 Diciembre | 35 | 28 | 63 |
| 2016 Noviembre | 43 | 18 | 61 |
| 2016 Octubre | 35 | 17 | 52 |
| 2016 Septiembre | 1 | 13 | 14 |
| 2016 Agosto | 0 | 2 | 2 |
| 2016 Julio | 8 | 1 | 9 |
| 2016 Junio | 5 | 1 | 6 |
| 2016 Mayo | 10 | 3 | 13 |
| 2016 Abril | 17 | 32 | 49 |
| 2016 Marzo | 12 | 2 | 14 |
| 2016 Febrero | 15 | 16 | 31 |
| 2016 Enero | 9 | 1 | 10 |
| 2015 Diciembre | 21 | 1 | 22 |
| 2015 Noviembre | 16 | 2 | 18 |
| 2015 Octubre | 13 | 3 | 16 |
| 2015 Septiembre | 8 | 5 | 13 |
| 2015 Agosto | 17 | 1 | 18 |
| 2015 Julio | 28 | 3 | 31 |
| 2015 Junio | 21 | 4 | 25 |
| 2015 Mayo | 22 | 11 | 33 |
| 2015 Abril | 11 | 7 | 18 |
| 2015 Marzo | 13 | 4 | 17 |
| 2015 Febrero | 9 | 7 | 16 |
| 2015 Enero | 11 | 5 | 16 |
| 2014 Diciembre | 9 | 4 | 13 |
| 2014 Noviembre | 8 | 4 | 12 |
| 2014 Octubre | 13 | 2 | 15 |
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