Case Letter
Cyclosporine-induced childhood generalized hypertrichosis
Karilena Fernandes Souza
, Paulo Fernando Barbosa de Camargo Andrade, Flávia de Freire Cassia, Maria Cristina Ribeiro de Castro
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Department of Dermatology, Hospital Federal da Lagoa, Rio de Janeiro, RJ, Brazil
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Among the causes of acquired generalized hypertrichosis is the use of certain drugs, and the most frequently involved agents are phenytoin, cyclosporin, and minoxidil. Unlike hirsutism, hypertrichosis in prepubertal children is not related to underlying endocrinopathies, with the main triggering factor being adverse effects of medications.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This case report highlights this association, illustrating an exuberant clinical presentation related to the use of Cyclosporin A (CsA).</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 6-year-old white female patient with a history of nephrotic syndrome for five years was using CsA because she had shown no improvement to corticosteroid therapy alone. There was a recent worsening of proteinuria, so pediatric nephrology decided to increase the dosage of CsA to 5<span class="elsevierStyleHsp" style=""></span>mg/kg/day. Three months later, the child developed a diffuse increase of terminal hairs on the face, trunk, limbs (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>) and trichomegaly (excessive growth of eyelashes) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>), and was referred to the dermatology department.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The hormonal profile did not show abnormalities. Abdomen ultrasonography exam was also normal and the hirsutism hypothesis was discarded clinically and by laboratorial analysis. There were no ocular or oral cavity changes and the child's neuropsychomotor development was normal. However, the serum level of CsA was increased (467<span class="elsevierStyleHsp" style=""></span>ng/mL; Reference value: 150–300<span class="elsevierStyleHsp" style=""></span>ng/mL). These findings allowed the diagnosis for acquired generalized hypertrichosis related to Cyclosporin A. The proposed therapeutic measures included a reduction in daily medication dosage and temporary chemical epilation.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Cyclosporin is an immunosuppressive, calcineurin inhibitor whose mechanism of action is to selectively inhibit the function of the helper T lymphocytes (CD4+), consequently blocking the production of interleukins, especially IL-2.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> It is widely used in dermatology, including the treatment of psoriasis and atopic dermatitis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> and in other specialties, such as steroid-resistant nephrotic syndrome. Among the main adverse effects of dermatological interest are hypertrichosis, gingival hyperplasia, increased incidence of cutaneous neoplasia and infections.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The pathogenesis of cyclosporin-induced hypertrichosis is not well established, but the literature describes that it is a dose-dependent side effect most commonly observed in children within the first six months of medication.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Our patient had used CsA for a long time but developed generalized hypertrichosis specifically when a significant increase in cyclosporinemia was identified.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Xu et al. defend that CsA induces the anagen phase and inhibits the catagenic phase of the hair follicle and have demonstrated in animal models that the drug stimulates hair growth by promoting matrix cells proliferation, in addition to increasing the expression of growth factors such as Vascular Endothelial Growth Factor (VEGF).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> On the other hand, Ponticelli et al. attribute this adverse reaction to a possible induction in the alpha-reductase enzyme activity increase, responsible for the conversion of androgens to dihydrotestosterone in tissues.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Other changes in the pilosebaceous unit such as sebaceous hyperplasia, keratosis pilaris, and acne are described and probably result from the elimination of the drug by the sebaceous glands because it is a lipophilic medication.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> However, the patient did not present cutaneous manifestations besides the exuberant hypertrichosis.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Drug-induced hypertrichosis is reversible with the suspension of the drug and may take from months to years to complete resolution, depending on the hair cycle of the affected area (face: about three months, arms about one year).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Regarding this case, neuropediatrics chose to reduce the dosage of the drug until normalization of the serum level of cyclosporine was achieved, resulting in improvement of the skin changes, but we preferred to associate temporary chemical epilation until complete resolution of the dermatological changes since the child was suffering from bullying because of her appearance.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In renal transplant or nephropathic patients tacrolimus can be substituted for CsA, since both act similarly and tacrolimus causes fewer cutaneous abnormalities and does not trigger gingival hyperplasia.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The reported case illustrates exuberant cyclosporin-induced hypertrichosis that, despite being a well-documented adverse effect, is poorly observed by dermatologists.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors' contributions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Karilena Fernandes Souza: Statistic analysis; approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Paulo Fernando Barbosa de Camargo Andrade: Statistic analysis; approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Flávia de Freire Cassia: Approval of the final version of the manuscript; elaboration and writing of the manuscript; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Maria Cristina Ribeiro de Castro: Approval of the final version of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors' contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:2 [ "identificador" => "xack473885" "titulo" => "Acknowledgment" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-05-22" "fechaAceptado" => "2019-08-20" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">How to cite this article: Souza KF, Andrade PFBC, Cassia FF, Castro MCR. Cyclosporine-induced childhood generalized hypertrichosis. An Bras Dermatol. 2020;95:403–5.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Hospital Federal da Lagoa, Rio de Janeiro, RJ, Brazil.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1052 "Ancho" => 905 "Tamanyo" => 101192 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hypertrichosis on the back and upper limbs.</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" => 981 "Ancho" => 905 "Tamanyo" => 90139 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diffuse growth of thick terminal hairs on upper limb and abdomen.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 483 "Ancho" => 905 "Tamanyo" => 58939 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Ciliary hypertrichosis (trichomegaly).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Causes and manegement of hypertrichosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.M. 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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 25 | 10 | 35 |
| 2024 Outubro | 117 | 52 | 169 |
| 2024 Setembro | 168 | 101 | 269 |
| 2024 Agosto | 192 | 99 | 291 |
| 2024 Julho | 154 | 112 | 266 |
| 2024 Junho | 137 | 90 | 227 |
| 2024 Maio | 135 | 72 | 207 |
| 2024 Abril | 116 | 89 | 205 |
| 2024 Março | 121 | 68 | 189 |
| 2024 Fevereiro | 116 | 68 | 184 |
| 2024 Janeiro | 92 | 53 | 145 |
| 2023 Dezembro | 104 | 47 | 151 |
| 2023 Novembro | 116 | 72 | 188 |
| 2023 Outubro | 136 | 100 | 236 |
| 2023 Setembro | 119 | 80 | 199 |
| 2023 Agosto | 81 | 35 | 116 |
| 2023 Julho | 95 | 58 | 153 |
| 2023 Junho | 112 | 70 | 182 |
| 2023 Maio | 71 | 31 | 102 |
| 2023 Abril | 115 | 30 | 145 |
| 2023 Março | 110 | 51 | 161 |
| 2023 Fevereiro | 105 | 43 | 148 |
| 2023 Janeiro | 79 | 48 | 127 |
| 2022 Dezembro | 101 | 24 | 125 |
| 2022 Novembro | 111 | 60 | 171 |
| 2022 Outubro | 154 | 56 | 210 |
| 2022 Setembro | 103 | 65 | 168 |
| 2022 Agosto | 96 | 58 | 154 |
| 2022 Julho | 79 | 51 | 130 |
| 2022 Junho | 103 | 53 | 156 |
| 2022 Maio | 82 | 51 | 133 |
| 2022 Abril | 83 | 46 | 129 |
| 2022 Março | 109 | 72 | 181 |
| 2022 Fevereiro | 89 | 31 | 120 |
| 2022 Janeiro | 91 | 76 | 167 |
| 2021 Dezembro | 56 | 57 | 113 |
| 2021 Novembro | 80 | 51 | 131 |
| 2021 Outubro | 96 | 77 | 173 |
| 2021 Setembro | 63 | 47 | 110 |
| 2021 Agosto | 122 | 64 | 186 |
| 2021 Julho | 74 | 45 | 119 |
| 2021 Junho | 45 | 47 | 92 |
| 2021 Maio | 56 | 76 | 132 |
| 2021 Abril | 97 | 176 | 273 |
| 2021 Março | 64 | 67 | 131 |
| 2021 Fevereiro | 47 | 16 | 63 |
| 2021 Janeiro | 44 | 17 | 61 |
| 2020 Dezembro | 49 | 14 | 63 |
| 2020 Novembro | 50 | 15 | 65 |
| 2020 Outubro | 16 | 14 | 30 |
| 2020 Setembro | 32 | 12 | 44 |
| 2020 Agosto | 11 | 5 | 16 |
| 2020 Julho | 54 | 6 | 60 |
| 2020 Junho | 16 | 19 | 35 |
| 2020 Maio | 16 | 9 | 25 |
| 2020 Abril | 0 | 5 | 5 |
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