CASE AND RESEARCH LETTER
Skin Toxicity Due to Telaprevir: A New Drug We Should Be Familiar With
Toxicidad cutánea por telaprevir: un nuevo fármaco que es necesario conocer
M.T. López-Villaescusa
, L.J. Pérez-García, M. Rodríguez-Vázquez, M.L. Martínez-Martínez
Corresponding author
Servicio de Dermatología, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
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López-Villaescusa, L.J. Pérez-García, M. Rodríguez-Vázquez, M.L. Martínez-Martínez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.T." "apellidos" => "López-Villaescusa" "email" => array:1 [ 0 => "lopezvillaescusa@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L.J." "apellidos" => "Pérez-García" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Rodríguez-Vázquez" ] 3 => array:2 [ "nombre" => "M.L." "apellidos" => "Martínez-Martínez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Complejo Hospitalario Universitario de Albacete, Albacete, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Toxicidad cutánea por telaprevir: un nuevo fármaco que es necesario conocer" ] ] "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" => 1353 "Ancho" => 901 "Tamanyo" => 158178 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Urticarial rash with an annular morphology that affected around 30% of the body surface area and was most prominent on the proximal third of the lower limbs.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis C virus (HCV) infection is common, with an incidence of 3% in the general population. It can present as acute hepatitis or, more frequently, as chronic asymptomatic hepatitis, which, over years, can progress to more severe disease, such as cirrhosis of the liver or hepatocellular carcinoma. Until recently, the treatment of chronic hepatitis C infection has been based on the combined use of pegylated interferon alfa-2a or 2b plus ribavirin, achieving a persistent virological response in less than 50% of patients with genotype-1 infection. This has made it necessary to develop new treatments, one of which is telaprevir (Incivo), a novel drug whose main dose-limiting side effect is skin toxicity. In order to make dermatologists aware of the existence of this new drug, we present the case of a 58-year-old woman treated with telaprevir.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient had been diagnosed with chronic HCV genotype 1 infection, but had no other past medical history of interest. She had previously been treated with peginterferon and ribavirin, achieving a transitory response with subsequent relapse. It was decided to start triple therapy by adding telaprevir to the aforementioned drugs, achieving an undetectable viral load in week 3 of treatment. She was seen in dermatology outpatients in week 4 of treatment for the appearance of persistent, pruritic skin lesions that had started to appear 4 days earlier. Physical examination revealed an urticarial rash (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) with an annular morphology that affected around 30% of the body surface area. The rash was located on the proximal third of the lower limbs and on the back (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The lesions blanched under pressure and the mucosas were not affected. Topical therapy with betamethasone 17-valerate was prescribed and weekly follow-up was performed until the end of treatment. During this period the lesions showed no progression and they resolved 2 weeks after completing the course of telaprevir.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Knowledge of the replication cycle of HCV and characterization of the viral enzymes has led to the identification of new therapeutic targets that inhibit these enzymes. Telaprevir is an NS3/4A protease inhibitor approved by the Food and Drug Administration and the European Medicines Agency for the treatment of chronic HCV infection in naïve patients and in those previously treated with interferon and ribavirin for genotype 1 infection. The introduction of this drug has led to an increase in the rate of persistent viral response, and treatment time can occasionally be shortened.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, the most important limitation to treatment comes from the drug's adverse skin effects. The recommended treatment regimen includes 12 weeks of triple therapy (telaprevir, peginterferon, and ribavirin) followed by a further 12 to 36 weeks of treatment with peginterferon plus ribavirin.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In the phase II and phase III placebo-controlled studies, the incidence of skin reactions during the 12-week treatment period with telaprevir was 56%, in comparison with 34% observed in patients treated with placebo and peginterferon alfa/ribavirin.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The skin reactions included local reactions at the site of injection and pruritic maculopapular rashes on the trunk and limbs; the reactions were usually well tolerated and showed a low probability of progression to more severe disorders.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The management and treatment of the skin reaction are based on the severity of the lesions and on the presence of systemic symptoms and abnormalities in the blood tests. Grade I, or mild, is defined as a localized or limited skin rash with no systemic signs and with no mucosal involvement. Grade II, or moderate, is a reaction that affects a maximum of 50% of the body surface area and that causes no epidermal detachment. Mucosal inflammation may be present but there are no ulcers or systemic symptoms such as fever and joint pain, and no eosinophilia. Grade III, or severe, is a reaction in which the skin lesions affect more than 50% of the body surface area, or a lower percentage if any of the following characteristics are observed: presence of vesicles or bullae, mucosal ulcers, epidermal detachment, target lesions, palpable purpura, or erythema that does not blanch under pressure. Finally, grade IV, or life-threatening, is defined as the presence of acute generalized exanthematous pustulosis, a delayed drug hypersensitivity syndrome (DRESS), toxic epidermal necrolysis, or Stevens-Johnson syndrome.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In patients, 90% of these reactions were grade I or II, characterized by pruritic eczematous lesions that affected less than 30% of the body surface area. Most reactions occurred during the first 4 weeks of treatment. Only a small percentage of patients treated with telaprevir developed serious skin reactions of grade III or IV.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Treatment interruption is not required for grade I or grade II reactions; in these patients, periodic follow-up should be performed until complete resolution of the reaction because of its possible progression to a severe skin reaction.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Treatment with telaprevir should only be interrupted for reactions of grade III or IV, with the subsequent sequential interruption of ribavirin and interferon if no improvement is observed over the following 7 days. Telaprevir should never be reintroduced.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The skin lesions can be treated with topical corticosteroids, but an association with systemic corticosteroids can produced a loss of efficacy of telaprevir and can modify its serum levels due to an interaction through both the CYP3A4 and the glycoprotein-P pathways.<span class="elsevierStyleSup">20</span> For the same reason, the simultaneous use of telaprevir with other drugs, such as astemizole and terfenadine, is also contraindicated.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The fecal excretion of telaprevir after it undergoes hepatic metabolism is probably the cause of anorectal symptoms such as pruritus.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, we have presented a skin reaction to a new drug for the treatment of HCV infection. Management of this reaction requires dermatologic follow-up in order to optimize treatment.</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: López-Villaescusa M, Pérez-García L, Rodríguez-Vázquez M, Martínez-Martínez M. Toxicidad cutánea por telaprevir: un nuevo fármaco que es necesario conocer. Actas Dermosifiliogr. 2014. 105:315–317.</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" => 1353 "Ancho" => 901 "Tamanyo" => 158178 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Urticarial rash with an annular morphology that affected around 30% of the body surface area and was most prominent on the proximal third of the lower 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" => 755 "Ancho" => 1000 "Tamanyo" => 126506 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Detail of the lesions on the back.</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" => "Triple therapy with telaprevir: Results in hepatitis C virus-genotype 1 infected relapsers and non-responders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 13 | 12 | 25 |
| 2024 October | 74 | 46 | 120 |
| 2024 September | 86 | 18 | 104 |
| 2024 August | 116 | 74 | 190 |
| 2024 July | 78 | 31 | 109 |
| 2024 June | 104 | 44 | 148 |
| 2024 May | 70 | 33 | 103 |
| 2024 April | 109 | 22 | 131 |
| 2024 March | 146 | 29 | 175 |
| 2024 February | 93 | 23 | 116 |
| 2024 January | 88 | 25 | 113 |
| 2023 December | 49 | 17 | 66 |
| 2023 November | 93 | 22 | 115 |
| 2023 October | 111 | 20 | 131 |
| 2023 September | 67 | 34 | 101 |
| 2023 August | 51 | 18 | 69 |
| 2023 July | 84 | 31 | 115 |
| 2023 June | 50 | 19 | 69 |
| 2023 May | 67 | 25 | 92 |
| 2023 April | 49 | 20 | 69 |
| 2023 March | 83 | 17 | 100 |
| 2023 February | 77 | 28 | 105 |
| 2023 January | 53 | 23 | 76 |
| 2022 December | 62 | 24 | 86 |
| 2022 November | 53 | 33 | 86 |
| 2022 October | 37 | 15 | 52 |
| 2022 September | 32 | 46 | 78 |
| 2022 August | 43 | 42 | 85 |
| 2022 July | 38 | 30 | 68 |
| 2022 June | 36 | 25 | 61 |
| 2022 May | 35 | 51 | 86 |
| 2022 April | 38 | 25 | 63 |
| 2022 March | 54 | 55 | 109 |
| 2022 February | 57 | 26 | 83 |
| 2022 January | 45 | 46 | 91 |
| 2021 December | 35 | 33 | 68 |
| 2021 November | 50 | 41 | 91 |
| 2021 October | 40 | 52 | 92 |
| 2021 September | 28 | 31 | 59 |
| 2021 August | 25 | 40 | 65 |
| 2021 July | 22 | 27 | 49 |
| 2021 June | 32 | 36 | 68 |
| 2021 May | 41 | 28 | 69 |
| 2021 April | 70 | 51 | 121 |
| 2021 March | 78 | 12 | 90 |
| 2021 February | 37 | 18 | 55 |
| 2021 January | 31 | 14 | 45 |
| 2020 December | 31 | 10 | 41 |
| 2020 November | 20 | 5 | 25 |
| 2020 October | 30 | 7 | 37 |
| 2020 September | 19 | 15 | 34 |
| 2020 August | 26 | 10 | 36 |
| 2020 July | 27 | 6 | 33 |
| 2020 June | 22 | 16 | 38 |
| 2020 May | 23 | 9 | 32 |
| 2020 April | 33 | 7 | 40 |
| 2020 March | 24 | 9 | 33 |
| 2020 February | 7 | 0 | 7 |
| 2020 January | 0 | 3 | 3 |
| 2019 December | 4 | 4 | 8 |
| 2019 November | 0 | 1 | 1 |
| 2019 September | 4 | 2 | 6 |
| 2019 July | 0 | 1 | 1 |
| 2019 June | 2 | 0 | 2 |
| 2019 May | 1 | 8 | 9 |
| 2019 April | 0 | 14 | 14 |
| 2019 March | 2 | 8 | 10 |
| 2019 January | 2 | 5 | 7 |
| 2018 December | 1 | 0 | 1 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 3 | 0 | 3 |
| 2018 September | 4 | 0 | 4 |
| 2018 March | 1 | 0 | 1 |
| 2018 February | 57 | 5 | 62 |
| 2018 January | 47 | 2 | 49 |
| 2017 December | 65 | 6 | 71 |
| 2017 November | 50 | 5 | 55 |
| 2017 October | 27 | 2 | 29 |
| 2017 September | 19 | 4 | 23 |
| 2017 August | 24 | 6 | 30 |
| 2017 July | 24 | 7 | 31 |
| 2017 June | 37 | 9 | 46 |
| 2017 May | 32 | 4 | 36 |
| 2017 April | 30 | 11 | 41 |
| 2017 March | 25 | 7 | 32 |
| 2017 February | 21 | 10 | 31 |
| 2017 January | 26 | 5 | 31 |
| 2016 December | 37 | 11 | 48 |
| 2016 November | 48 | 8 | 56 |
| 2016 October | 54 | 9 | 63 |
| 2016 September | 69 | 6 | 75 |
| 2016 August | 35 | 3 | 38 |
| 2016 July | 41 | 3 | 44 |
| 2016 June | 10 | 0 | 10 |
| 2016 May | 9 | 5 | 14 |
| 2016 April | 4 | 0 | 4 |
| 2016 March | 5 | 0 | 5 |
| 2016 February | 6 | 3 | 9 |
| 2016 January | 10 | 1 | 11 |
| 2015 December | 3 | 0 | 3 |
| 2015 November | 5 | 0 | 5 |
| 2015 October | 2 | 3 | 5 |
| 2015 September | 1 | 2 | 3 |
| 2015 August | 11 | 2 | 13 |
| 2015 July | 29 | 8 | 37 |
| 2015 June | 38 | 6 | 44 |
| 2015 May | 52 | 2 | 54 |
| 2015 April | 27 | 4 | 31 |
| 2015 March | 21 | 5 | 26 |
| 2015 February | 16 | 1 | 17 |
| 2015 January | 25 | 1 | 26 |
| 2014 December | 36 | 5 | 41 |
| 2014 November | 16 | 5 | 21 |
| 2014 October | 17 | 6 | 23 |
| 2014 September | 16 | 4 | 20 |
| 2014 August | 10 | 3 | 13 |
| 2014 July | 10 | 5 | 15 |
| 2014 June | 20 | 5 | 25 |
| 2014 May | 20 | 156 | 176 |
| 2014 April | 26 | 35 | 61 |
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