Case and Research Letters
Pembrolizumab: a New Drug That Can Induce Exacerbations of Psoriasis
Pembrolizumab, un nuevo fármaco capaz de inducir un brote psoriasis
A. Sahuquillo-Torralba
, R. Ballester-Sánchez, C. Pujol-Marco, R. Botella-Estrada
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Servicio de Dermatología, Hospital Universitari i Politécnic La Fe, Universidad de Valencia, Valencia, Spian
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Sahuquillo-Torralba, R. Ballester-Sánchez, C. Pujol-Marco, R. Botella-Estrada" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Sahuquillo-Torralba" "email" => array:1 [ 0 => "saucodos@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Ballester-Sánchez" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Pujol-Marco" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Botella-Estrada" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Universitari i Politécnic La Fe, Universidad de Valencia, Valencia, Spian" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pembrolizumab, un nuevo fármaco capaz de inducir un brote psoriasis" ] ] "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" => 1375 "Ancho" => 1501 "Tamanyo" => 266809 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Detail of the generalization of the psoriasis lesions after the second cycle of pembrolizumab.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pembrolizumab is a monoclonal antibody that belongs to a group of new antitumor drugs that stimulate the immune system. These drugs act by blocking key steps in the immune cascade. Specifically, pembrolizumab blocks the programmed cell death receptor (PD-1) whose function is to induce T-cell apoptosis, preventing excessive proliferation and function; this inhibition therefore leads to stimulation of the immune response.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> A number of cancers, including melanoma and lung, kidney, and breast cancer, can present overexpression of PD-1 ligand (PD-L1) by the tumor cells as a mechanism of immune evasion. Blockade of the PD-1 receptor would help to end this evasion.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 67-year-old man with a history of myocardial infarction and cerebellar stroke, diagnosed 3 months earlier with metastatic adenocarcinoma of the lung with PD-L1 expression in more than 5% of tumor cells, measured immunohistochemically. The patient was referred to dermatology for evaluation and treatment of his psoriasis before entering a clinical trial investigating pembrolizumab for his lung neoplasm. The patient had psoriasis affecting the elbows, knees, and buttocks; the disease was stable on topical treatments, with a psoriasis area severity index (PASI) score of 3 and body surface area (BSA) involvement of 5%. The psoriasis deteriorated progressively after the first cycle of pembrolizumab, with a PASI score of 22 and BSA of 60%; after the second infusion, the severity became almost compatible with erythrodermic psoriasis, with a BSA of 81% and a PASI score of 33 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Treatment was started with acitretin at a dose of 25<span class="elsevierStyleHsp" style=""></span>mg/d. This had to be increased to 35<span class="elsevierStyleHsp" style=""></span>mg/d after the deterioration seen during the second cycle. The tumor response to pembrolizumab was excellent after the second infusion of the drug, as was the improvement of his psoriasis with acitretin after 6 weeks of treatment. It was therefore decided to continue treatment with both drugs. There have been no further outbreaks of psoriasis during the following 3 infusion cycles. Three months after the initial outbreak, the patient had a PASI score of 4 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), which allowed us to reduce the dose of acitretin to 20<span class="elsevierStyleHsp" style=""></span>mg/d.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Psoriasis is a chronic inflammatory disease. Evidence points ever more to an autoinflammatory disorder in which hyperreactive T cells produce large amounts of interleukins and tumor necrosis factor, leading to increased epidermal turnover. To date there are no reports of a deterioration or induction of psoriasis in patients treated with pembrolizumab or other immune checkpoint blockers, though, given the drug's mechanism of action and the pathophysiology of psoriasis, it would appear logical that such adverse reactions could occur. Recent studies have shown decreased expression of the PD-1 receptor in peripheral blood lymphocytes in patients with psoriatic arthritis and rheumatoid arthritis; this appears to show an inverse correlation with severity of the joint disease, as it would reduce the lymphocyte population susceptible to inhibition by the PD-1 pathway, although it does not seem to affect the PASI of patients with psoriasis.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4,5</span></a> Based on this evidence, it may be surmised that certain quantitative changes take place in the PD-1<span class="elsevierStyleSup">+</span> T cells in patients with psoriasis, leading to T-cell hyperactivity that would increase exponentially with the use of PD-1–receptor blockers, explaining the notable deterioration in our patient's psoriasis. Confirmation of this hypothesis would require larger series of patients with psoriasis, and would need to include measurement of PD-1<span class="elsevierStyleSup">+</span> lymphocyte count by flow cytometry and immunohistochemistry techniques and of the PD-L1 levels by immunohistochemistry. In the way, we could define more accurately the pathophysiology of psoriasis and even open the door to new therapeutic targets.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There are still no publications on the treatment of psoriasis induced or exacerbated by immune checkpoint blockers. Based on our experience, acitretin could be a good option to achieve optimal control of a patient's psoriasis and would be compatible with continuation of the anticancer treatment. Studies of patient series are needed to confirm our clinical experience.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In general, the main side effects associated with the new immune checkpoint blockers are derived from their pharmaceutical action, provoking an autoimmune response against different body tissues. The most commonly described alterations have been hypo- and hyperthyroidism, hepatitis, diarrhea, enterocolitis, and hypophysitis. Skin manifestations include pruritus and a maculopapular rash, and there have even been reports of erythroderma, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Patients at highest risk of developing these side effects are those with a history of autoimmune disease, which is a relative contraindication to the use of such drugs.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6–8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The immune checkpoint blockers are achieving a good response in certain types of cancer.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> This would suggest that their use will increase in cancer patients. We must be alert to their adverse effects and perform more thorough follow-up and therapeutic management in patients with underlying autoimmune or autoinflammatory diseases.</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: Sahuquillo-Torralba A, Ballester-Sánchez R, Pujol-Marco C, Botella-Estrada R. Pembrolizumab, un nuevo fármaco capaz de inducir un brote psoriasis. Actas Dermosifiliogr. 2016;107:264–266.</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" => 1375 "Ancho" => 1501 "Tamanyo" => 266809 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Detail of the generalization of the psoriasis lesions after the second cycle of pembrolizumab.</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" => 662 "Ancho" => 1501 "Tamanyo" => 132082 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical improvement after 3 months of treatment with acitretin, despite further infusions of pembrolizumab.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The blockade of immune checkpoints in cancer immunotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.M. 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Chow" 3 => "W.J. Hwu" 4 => "S.L. Topalian" 5 => "P. Hwu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1200694" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "2455" "paginaFinal" => "2465" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22658128" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack276189" "titulo" => "Acknowledgments" "texto" => "<p id="par0035" class="elsevierStylePara elsevierViewall">We would like to thank Dr. Óscar Juan Vidal of the Oncology Department of Hospital Universitari i Politécnic La Fe in Valencia, Spain, for his help.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010700000003/v2_201704010117/S1578219016000202/v2_201704010117/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010700000003/v2_201704010117/S1578219016000202/v2_201704010117/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016000202?idApp=UINPBA000044" ]
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| 2024 Septiembre | 106 | 30 | 136 |
| 2024 Agosto | 150 | 69 | 219 |
| 2024 Julio | 132 | 30 | 162 |
| 2024 Junio | 114 | 36 | 150 |
| 2024 Mayo | 127 | 34 | 161 |
| 2024 Abril | 106 | 31 | 137 |
| 2024 Marzo | 131 | 33 | 164 |
| 2024 Febrero | 95 | 34 | 129 |
| 2024 Enero | 89 | 37 | 126 |
| 2023 Diciembre | 94 | 15 | 109 |
| 2023 Noviembre | 116 | 31 | 147 |
| 2023 Octubre | 99 | 39 | 138 |
| 2023 Septiembre | 83 | 35 | 118 |
| 2023 Agosto | 98 | 27 | 125 |
| 2023 Julio | 132 | 41 | 173 |
| 2023 Junio | 119 | 33 | 152 |
| 2023 Mayo | 125 | 30 | 155 |
| 2023 Abril | 92 | 26 | 118 |
| 2023 Marzo | 115 | 21 | 136 |
| 2023 Febrero | 101 | 22 | 123 |
| 2023 Enero | 87 | 30 | 117 |
| 2022 Diciembre | 104 | 32 | 136 |
| 2022 Noviembre | 78 | 29 | 107 |
| 2022 Octubre | 62 | 24 | 86 |
| 2022 Septiembre | 52 | 31 | 83 |
| 2022 Agosto | 50 | 30 | 80 |
| 2022 Julio | 39 | 28 | 67 |
| 2022 Junio | 41 | 26 | 67 |
| 2022 Mayo | 76 | 20 | 96 |
| 2022 Abril | 124 | 35 | 159 |
| 2022 Marzo | 98 | 39 | 137 |
| 2022 Febrero | 112 | 37 | 149 |
| 2022 Enero | 76 | 33 | 109 |
| 2021 Diciembre | 48 | 45 | 93 |
| 2021 Noviembre | 62 | 45 | 107 |
| 2021 Octubre | 61 | 55 | 116 |
| 2021 Septiembre | 51 | 43 | 94 |
| 2021 Agosto | 65 | 36 | 101 |
| 2021 Julio | 97 | 36 | 133 |
| 2021 Junio | 58 | 38 | 96 |
| 2021 Mayo | 78 | 35 | 113 |
| 2021 Abril | 203 | 78 | 281 |
| 2021 Marzo | 100 | 37 | 137 |
| 2021 Febrero | 79 | 44 | 123 |
| 2021 Enero | 61 | 34 | 95 |
| 2020 Diciembre | 55 | 19 | 74 |
| 2020 Noviembre | 55 | 33 | 88 |
| 2020 Octubre | 34 | 23 | 57 |
| 2020 Septiembre | 45 | 24 | 69 |
| 2020 Agosto | 24 | 20 | 44 |
| 2020 Julio | 26 | 21 | 47 |
| 2020 Junio | 45 | 41 | 86 |
| 2020 Mayo | 28 | 41 | 69 |
| 2020 Abril | 34 | 30 | 64 |
| 2020 Marzo | 32 | 31 | 63 |
| 2020 Febrero | 5 | 17 | 22 |
| 2020 Enero | 0 | 12 | 12 |
| 2019 Diciembre | 4 | 6 | 10 |
| 2019 Noviembre | 0 | 2 | 2 |
| 2019 Septiembre | 4 | 1 | 5 |
| 2019 Agosto | 0 | 8 | 8 |
| 2019 Julio | 0 | 13 | 13 |
| 2019 Junio | 2 | 28 | 30 |
| 2019 Mayo | 0 | 20 | 20 |
| 2019 Abril | 0 | 6 | 6 |
| 2019 Marzo | 2 | 14 | 16 |
| 2019 Febrero | 0 | 3 | 3 |
| 2019 Enero | 3 | 0 | 3 |
| 2018 Diciembre | 15 | 0 | 15 |
| 2018 Noviembre | 8 | 0 | 8 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 4 | 5 | 9 |
| 2018 Agosto | 0 | 10 | 10 |
| 2018 Julio | 0 | 18 | 18 |
| 2018 Junio | 0 | 2 | 2 |
| 2018 Mayo | 0 | 7 | 7 |
| 2018 Abril | 0 | 7 | 7 |
| 2018 Marzo | 0 | 3 | 3 |
| 2018 Febrero | 31 | 9 | 40 |
| 2018 Enero | 59 | 19 | 78 |
| 2017 Diciembre | 54 | 14 | 68 |
| 2017 Noviembre | 39 | 11 | 50 |
| 2017 Octubre | 43 | 17 | 60 |
| 2017 Septiembre | 34 | 9 | 43 |
| 2017 Agosto | 37 | 33 | 70 |
| 2017 Julio | 40 | 17 | 57 |
| 2017 Junio | 39 | 36 | 75 |
| 2017 Mayo | 35 | 41 | 76 |
| 2017 Abril | 42 | 24 | 66 |
| 2017 Marzo | 18 | 23 | 41 |
| 2017 Febrero | 28 | 19 | 47 |
| 2017 Enero | 29 | 22 | 51 |
| 2016 Diciembre | 37 | 25 | 62 |
| 2016 Noviembre | 44 | 23 | 67 |
| 2016 Octubre | 29 | 30 | 59 |
| 2016 Agosto | 1 | 1 | 2 |
| 2016 Julio | 1 | 1 | 2 |
| 2016 Mayo | 0 | 5 | 5 |
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