Case and Research Letters
Adalimumab-Induced Neutropenia in a Man With Hidradenitis Suppurativa
Neutropenia inducida por adalimumab en un paciente con hidradenitis supurativa
J.M. Rueda Carnero
, D. Nieto Rodríguez, R. de Lucas Laguna, M. Feito Rodríguez
Corresponding author
Servicio de Dermatología, Hospital Universitario La Paz, Madrid, Spain
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Rueda Carnero, D. Nieto Rodríguez, R. de Lucas Laguna, M. Feito Rodríguez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J.M." "apellidos" => "Rueda Carnero" "email" => array:1 [ 0 => "joserc88@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Nieto Rodríguez" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "de Lucas Laguna" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Feito Rodríguez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Universitario La Paz, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neutropenia inducida por adalimumab en un paciente con hidradenitis supurativa" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Anti-tumor necrosis factor (TNF) agents are among the drugs used to treat hidradenitis suppurativa. These treatments are generally well tolerated, but patients must be monitored closely when taking them. Hematologic complications are an uncommon adverse effect of anti-TNF therapy and have only rarely been described in the literature. We report a case of severe neutropenia (< 500/mm<span class="elsevierStyleSup">3</span>) in a man with hidradenitis suppurativa. The complication developed within 3 months of his starting anti-TNF therapy.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case Description</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 21-year-old man who had been diagnosed with hidradenitis suppurativa (Hurley stage 3) in adolescence. He had been treated with acitretin (50 mg/d), rifampicin (600 mg/d) combined with clindamycin (300 mg/d) and adjuvant intralesional corticosteroids (triamcinolone) in succession, without experiencing improvement. There were no other relevant aspects of his medical history; nor was he on other medications. Treatment with adalimumab began at an initial dose of 160 mg the first week, followed by 80 mg the second week and 40 mg every 2 weeks after that. The previous treatments with rifampicin and clindamycin were suspended 3 weeks before adalimumab was started, and the patient was taking no analgesics or other medications. Before treatment his white blood cell count was 5450/mm<span class="elsevierStyleSup">3</span> (neutrophils, 1980/mm<span class="elsevierStyleSup">3</span>). Later blood tests showed gradually decreasing neutrophil counts, to 1540/mm<span class="elsevierStyleSup">3</span> at 1 month and 480/mm<span class="elsevierStyleSup">3</span> at 2 months after the first injection of adalimumab. Hemoglobin, red blood cell, lymphocyte, and platelet counts were normal, and no infections could be demonstrated during this period. The patient had no signs or symptoms of infection at any time, and serology for syphilis and human immunodeficiency virus, Epstein-Barr virus, parvovirus, and enterovirus infection were all negative, as they had been at the start of treatment.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Adalimumab was suspended 8 weeks after it was started, due to the neutropenia and because the skin lesions had only partially improved at that point. The neutrophil count quickly became normal and had reached 2760/mm<span class="elsevierStyleSup">3</span> a month after the last injection of adalimumab.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">A finding of fewer than 1500 neutrophils per cubic millimeter of blood defines neutropenia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Mild neutropenia is defined by a neutrophil count of 1000–1500/mm<span class="elsevierStyleSup">3</span>, moderate neutropenia by a count of 500–1000/mm<span class="elsevierStyleSup">3</span>, and severe neutropenia by a count under 500/mm<span class="elsevierStyleSup">3</span>.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Neutropenia is sometimes an adverse effect of medication and confers high risk of infection. An adverse drug effect can be established when there are no other concomitant medications being taken or other symptoms that could explain the event. The diagnosis is clear if the effect appears when a drug is introduced and resolves when it is withdrawn, as occurred in the case we report.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Neutropenia is a rare adverse effect of anti-TNF therapy. The agents most often implicated are infliximab and etanercept.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–5</span></a> The development of moderate neutropenia after exposure to etanercept, and successive recurrences after reexposure to the same agent and later exposure to infliximab have been described,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> suggesting that the adverse effect is related to anti-TNF agents as a group. Also described are cases of neutropenia induced by adalimumab in patients with rheumatoid arthritis.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> A systematic review of the literature describing hematologic complications of anti-TNF therapy found that the incidence of neutropenia was greater in patients treated with etanercept (72.8%), followed by infliximab (18.5%) and adalimumab (9%). Rajakulendran et al<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> reported that neutropenia developed in 14.3% of their patients on anti-TNF therapy and Hastings et al<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> reported an incidence of 18.8% in theirs; the agents implicated were adalimumab, infliximab, and etanercept.</p><p id="par0035" class="elsevierStylePara elsevierViewall">When seriously low neutrophil counts (<500/mm<span class="elsevierStyleSup">3</span>) are detected, treatment must be suspended and other secondary causes of neutropenia investigated. Possible causes include exposure to other drugs; infections (especially viral); nutritional deficiencies (folic acid or vitamin B<span class="elsevierStyleInf">12</span>); hematologic, congenital, or chronic diseases; systemic lupus erythematosus or other autoimmune diseases; and Felty syndrome. Serology for antineutrophil antibodies should be ordered.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Evidence suggests that the frequency of this adverse effect might be underestimated, so regular monitoring of leukocyte counts is recommended for patients on anti-TNF agents, whether alone or in combination with methotrexate or other drugs used routinely to treat rheumatoid arthritis and inflammatory bowel disease.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">As far as we know, this is the first case report of severe neutropenia due to the use of adalimumab to treat hidradenitis suppurativa. Dermatologists and other physicians who use adalimumab to manage this or other diseases should be aware of the possibility of the adverse event we report and the need for differential diagnosis.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case Description" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of Interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-04-12" "fechaAceptado" => "2018-08-15" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rueda Carnero JM, Nieto Rodríguez D, de Lucas Laguna R, Feito Rodríguez M. Neutropenia inducida por adalimumab en un paciente con hidradenitis supurativa. Actas Dermosifiliogr. 2020;111:273–274.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary and secondary autoinmune neutropenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F. Capsoni" 1 => "P. Sarzi-Puttini" 2 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 6 | 16 |
| 2024 October | 107 | 41 | 148 |
| 2024 September | 101 | 26 | 127 |
| 2024 August | 124 | 48 | 172 |
| 2024 July | 99 | 34 | 133 |
| 2024 June | 121 | 46 | 167 |
| 2024 May | 119 | 29 | 148 |
| 2024 April | 96 | 21 | 117 |
| 2024 March | 98 | 32 | 130 |
| 2024 February | 84 | 38 | 122 |
| 2024 January | 91 | 32 | 123 |
| 2023 December | 83 | 14 | 97 |
| 2023 November | 131 | 31 | 162 |
| 2023 October | 95 | 25 | 120 |
| 2023 September | 87 | 31 | 118 |
| 2023 August | 84 | 13 | 97 |
| 2023 July | 77 | 27 | 104 |
| 2023 June | 67 | 22 | 89 |
| 2023 May | 61 | 20 | 81 |
| 2023 April | 61 | 19 | 80 |
| 2023 March | 88 | 33 | 121 |
| 2023 February | 58 | 29 | 87 |
| 2023 January | 34 | 37 | 71 |
| 2022 December | 57 | 49 | 106 |
| 2022 November | 30 | 32 | 62 |
| 2022 October | 33 | 19 | 52 |
| 2022 September | 22 | 40 | 62 |
| 2022 August | 25 | 35 | 60 |
| 2022 July | 39 | 38 | 77 |
| 2022 June | 27 | 20 | 47 |
| 2022 May | 49 | 36 | 85 |
| 2022 April | 64 | 37 | 101 |
| 2022 March | 64 | 59 | 123 |
| 2022 February | 77 | 35 | 112 |
| 2022 January | 73 | 54 | 127 |
| 2021 December | 60 | 39 | 99 |
| 2021 November | 46 | 41 | 87 |
| 2021 October | 58 | 45 | 103 |
| 2021 September | 45 | 40 | 85 |
| 2021 August | 46 | 37 | 83 |
| 2021 July | 53 | 32 | 85 |
| 2021 June | 57 | 24 | 81 |
| 2021 May | 45 | 37 | 82 |
| 2021 April | 88 | 41 | 129 |
| 2021 March | 59 | 28 | 87 |
| 2021 February | 52 | 20 | 72 |
| 2021 January | 55 | 17 | 72 |
| 2020 December | 44 | 19 | 63 |
| 2020 November | 34 | 19 | 53 |
| 2020 October | 20 | 7 | 27 |
| 2020 September | 41 | 16 | 57 |
| 2020 August | 34 | 14 | 48 |
| 2020 July | 16 | 10 | 26 |
| 2020 June | 34 | 37 | 71 |
| 2020 May | 53 | 41 | 94 |
| 2020 April | 19 | 15 | 34 |
| 2020 March | 14 | 4 | 18 |
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