Case Letter
Safety and efficacy of an interleukin 12/23 inhibitor in a patient with constitutional neutropenia and psoriasis vulgaris
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Mariana Reis e Rocha Dultra, Juliana de Morais Fernandes Krakheche" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Jéssica Vianna" "apellidos" => "Starek" "email" => array:1 [ 0 => "jessicastarek@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Cristina Santos Ribeiro" "apellidos" => "Bechara" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Mariana Reis e Rocha" "apellidos" => "Dultra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Juliana de Morais Fernandes" "apellidos" => "Krakheche" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Complexo Hospitalar Padre Bento de Guarulhos, Guarulhos, SP, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "General Dermatology and Severe Psoriasis Outpatient Clinic, Complexo Hospitalar Padre Bento de Guarulhos, Guarulhos, SP, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1473 "Ancho" => 1674 "Tamanyo" => 121455 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PASI 0, discrete residual macules after 3 years of treatment.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Psoriasis is a chronic, immune-mediated and complex inflammatory disease. The immunopathogenesis of the disease involves interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and specific interleukins (ILs) that coordinate the interaction between inflammatory cells and keratinocytes.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">IL inhibitors represent a new group of biological agents with greater specificity for the treatment of psoriasis, as they selectively target inflammatory pathways.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Ustekinumab is a fully human monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit, shared by cytokines IL-12 and IL-23.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Its action prevents the binding of IL-12 and IL-23 to their receptor, blocking the Th1 and Th17-mediated inflammatory pathways.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Benign constitutional neutropenia is an asymptomatic condition characterized by mild chronic neutropenia (neutrophil count < 1500/mm<span class="elsevierStyleSup">3</span>) in patients with no history of recurrent infections and no secondary causes.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> As these patients are susceptible to infections, the use of immunobiological agents in this population may require special care regarding their safety. There are no reports in the literature on the use and safety of IL-12 and IL-23 inhibitors in these patients.</p><p id="par0025" class="elsevierStylePara elsevierViewall">A 44-year-old dark-skinned male patient started follow-up at a dermatology referral service 10 years ago due to severe psoriasis, without joint involvement. He had a previous diagnosis of familial constitutional leukopenia 17 years ago, with a mean leukocyte count of 2600 mm<span class="elsevierStyleSup">3</span> and neutrophil count of 770 mm<span class="elsevierStyleSup">3</span>. He had been previously treated with acitretin, topical medications and undergone around 400 phototherapy sessions, but persisted with erythematous-desquamative plaques on the lower limbs, upper limbs, trunk, and scalp, with progressive worsening. In 2017, due to treatment refractoriness, with a Dermatological Life Quality Index (DLQI) of 13, Psoriasis Area and Severity Index (PASI) of 12.9 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and, considering the constitutional neutropenia, the use of ustekinumab was proposed with the caveat of undergoing monthly monitoring and withdrawing the treatment if the patient had a neutrophil count < 500/mm<span class="elsevierStyleSup">3</span>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">After undergoing the initial tests before starting the immunobiological treatment, which were all within the normal range, treatment with ustekinumab 45 mg was introduced, with the induction phase taking place in weeks 0 and 4 and then every 12 weeks, associated with calcipotriol, twice a day. The patient showed significant lesion improvement after12 weeks, with residual macules only and currently with PASI 0 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The patient continues to use the medication up to the present date, without any adverse effects or infections during the entire period (3 years of use). He maintained stable absolute neutrophil values, demonstrating the safety of the medication.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Evidence indicates that neutropenia during therapy with ustekinumab is rare, and when it occurs it is mild; therefore, periodic monitoring is recommended.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> As our patient already had a diagnosis of constitutional neutropenia, this adverse effect was the most feared one and the laboratory follow-up was performed monthly, and no relevant alterations were noted after 3 years of drug use.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0040" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0045" class="elsevierStylePara elsevierViewall">Jessica Vianna Starek: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis and interpretation of data; critical review of the literature; critical review of the manuscript.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Mariana Reis and Rocha Dultra: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Cristina Santos Ribeiro Bechara: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Juliana de Morais Fernandes Krakheche: Approval of the final version of the manuscript; design and planning of the study; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 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:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-10-18" "fechaAceptado" => "2020-11-09" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">How to cite this article: Starek JV, Bechara CSR, Dultra MRR, Krakheche JM. Safety and efficacy of an interleukin 12/23 inhibitor in a patient with constitutional neutropenia and psoriasis vulgaris. An Bras Dermatol. 2021;96:795–7.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Complexo Hospitalar Padre Bento de Guarulhos, Guarulhos, SP, Brazil.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1321 "Ancho" => 1674 "Tamanyo" => 164563 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">PASI 12.9, erythematous-scaling plaques.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1473 "Ancho" => 1674 "Tamanyo" => 121455 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PASI 0, discrete residual macules after 3 years of treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 1 | 5 |
| 2024 October | 95 | 66 | 161 |
| 2024 September | 158 | 72 | 230 |
| 2024 August | 154 | 103 | 257 |
| 2024 July | 139 | 98 | 237 |
| 2024 June | 104 | 69 | 173 |
| 2024 May | 82 | 61 | 143 |
| 2024 April | 107 | 90 | 197 |
| 2024 March | 102 | 57 | 159 |
| 2024 February | 137 | 75 | 212 |
| 2024 January | 76 | 51 | 127 |
| 2023 December | 73 | 55 | 128 |
| 2023 November | 84 | 86 | 170 |
| 2023 October | 52 | 72 | 124 |
| 2023 September | 76 | 71 | 147 |
| 2023 August | 64 | 37 | 101 |
| 2023 July | 56 | 22 | 78 |
| 2023 June | 57 | 44 | 101 |
| 2023 May | 41 | 13 | 54 |
| 2023 April | 30 | 12 | 42 |
| 2023 March | 64 | 38 | 102 |
| 2023 February | 39 | 37 | 76 |
| 2023 January | 47 | 40 | 87 |
| 2022 December | 43 | 42 | 85 |
| 2022 November | 74 | 58 | 132 |
| 2022 October | 112 | 57 | 169 |
| 2022 September | 56 | 71 | 127 |
| 2022 August | 46 | 56 | 102 |
| 2022 July | 47 | 57 | 104 |
| 2022 June | 42 | 59 | 101 |
| 2022 May | 51 | 58 | 109 |
| 2022 April | 54 | 64 | 118 |
| 2022 March | 67 | 80 | 147 |
| 2022 February | 45 | 37 | 82 |
| 2022 January | 101 | 109 | 210 |
| 2021 December | 154 | 98 | 252 |
| 2021 November | 108 | 71 | 179 |
| 2021 October | 42 | 63 | 105 |
| 2021 September | 22 | 32 | 54 |
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