Case and Research Letters
Primary Cutaneous Aspergillosis Complicating Tumor Necrosis Factor-α Blockade Therapy in a Patient With Psoriasis
Aspergilosis cutánea primaria que complica el tratamiento con inhibidores del factor de necrosis tumoral α en un paciente con psoriasis
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Osório, S. Magina, F. Azevedo" "autores" => array:3 [ 0 => array:4 [ "nombre" => "F." "apellidos" => "Osório" "email" => array:1 [ 0 => "filipaosorio@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Magina" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "F." "apellidos" => "Azevedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Dermatology and Venereology, Centro Hospitalar de São João EPE, Porto, Portugal" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Institute of Pharmacology and Therapeutics, Faculdade de Medicina da Universidade do Porto, Portugal" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Aspergilosis cutánea primaria que complica el tratamiento con inhibidores del factor de necrosis tumoral α en un paciente con psoriasis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1637 "Ancho" => 1583 "Tamanyo" => 189709 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Two colonies of <span class="elsevierStyleItalic">Aspergillus fumigatus</span> growing on solid Sabouraud medium with gentamicin and chloramphenicol (25<span class="elsevierStyleHsp" style=""></span>°C).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 52-year-old male farmer with a history of generalized plaque psoriasis and psoriatic arthritis was being treated with etanercept 50<span class="elsevierStyleHsp" style=""></span>mg once weekly for 3 years with a good response. He presented to our department with painful erythematous nodular lesions on the right forearm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) and in the left periorbital region (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The lesions had appeared 10 days earlier, following a rabbit bite on the forearm. There were no associated systemic symptoms or fever.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">A cutaneous biopsy was performed, and as we suspected a fungal infection, the patient was started on itraconazole 100<span class="elsevierStyleHsp" style=""></span>mg twice daily and etanercept was withdrawn. The biopsy showed an inflammatory infiltrate consisting primarily of polymorphonuclear cells forming abscess-like areas (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Periodic acid-Schiff (PAS) and Grocott-Gomori methenamine-silver staining did not reveal any fungi, but skin culture on solid Sabouraud medium with gentamicin and chloramphenicol (25<span class="elsevierStyleHsp" style=""></span>°C) revealed <span class="elsevierStyleItalic">Aspergillus fumigatus</span> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The potassium hydroxide (KOH 10%) test did not show hyphae in the microbiological sample and the polymerase chain reaction (PCR) for fungal DNA in the skin was negative. Blood tests and the chest X-ray were normal.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The lesions resolved completely with 4 weeks of treatment with itraconazole. One week after the end of treatment, the patient restarted etanercept and developed no further lesions.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Aspergillus</span> species are ubiquitous and infection occurs most commonly in immunosuppressed individuals,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> like our patient; indeed, after <span class="elsevierStyleItalic">Candida</span> species, these fungi are the most frequent opportunistic pathogens in this group of patients.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Cutaneous aspergillosis is normally a manifestation of disseminated disease, which typically begins as a pulmonary infection.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Primary cutaneous aspergillosis is rare but it can occur, especially in the case of skin injury,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> such as that caused by a rabbit bite.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The skin manifestations of cutaneous aspergillosis are non-specific but are usually characterized by erythematous to violaceous indurated nodules progressing to ulcers with a central eschar.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In our case, an early diagnosis prevented this progression.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The erythematous nodules on the forearm of our patient were distributed in a sporotrichoid (lymphocutaneous) pattern, which is seen more often in sporotrichosis and atypical mycobacterial infections (particularly due to <span class="elsevierStyleItalic">Mycobacterium marinum</span>) than in aspergillosis. Other unusual agents associated with the sporotrichoid pattern are <span class="elsevierStyleItalic">Nocardia</span> species, pyogenic bacteria (<span class="elsevierStyleItalic">Staphylococcus aureus</span>, <span class="elsevierStyleItalic">Streptococcus pyogenes</span>), and <span class="elsevierStyleItalic">Pseudallescheria boydii</span>. Noninfectious causes of this pattern include lymphoma, Langerhans cell histiocytosis, and in-transit metastases. Additionally, perineural spread of leprosy can mimic a lymphocutaneous pattern.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The patient also had periorbital lesions, which probably resulted from self-inoculation, with the forearm being the most likely portal of entry.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A diagnosis of aspergillosis is supported by the presence of septated hyphae with acute-angle branching under microscopic examination with special fungal stains (PAS, Grocott),<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4</span></a> but it must be confirmed by culture.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In disseminated disease, which was not the case in our patient, the serum galactomannan antigen detection test is useful to establish an early diagnosis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> PCR-based testing, which was negative in our case, has yet to be standardized and validated for this purpose.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">There are no treatment guidelines for primary cutaneous aspergillosis as there are for disseminated disease,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> but reported cases have been successfully treated with amphotericin B, itraconazole, or voriconazole, with or without surgical ressection.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4,7</span></a> Cutaneous aspergillosis may respond better to treatment than other forms of aspergillosis because it is recognized early, hence allowing rapid institution of treatment,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> as occurred in our case.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Our patient was immunosuppressed due to treatment with etanercept. There are no published data about primary cutaneous aspergillosis in patients treated with tumor necrosis factor-α (TNF-α) blockers but disseminated aspergillosis accounts for 23% of invasive fungal infections in these patients.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> TNF-α appears to have an important role in host defenses against <span class="elsevierStyleItalic">A. fumigatus</span>, enhancing leukocyte recruitment<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and phagocytosis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Furthermore, TNF-α blockade has been seen to increase mortality in animal models infected with <span class="elsevierStyleItalic">Aspergillus</span>.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> TNF-α blockade appears to increase susceptibility to fungal infections via the following mechanisms: decreased production of interferon-γ with decreased cellular immune response, decreased toll-like receptor 4 expression with diminished fungal recognition ability, and decreased granuloma formation and phagocytosis.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">To the best of our knowledge, this is the first report of primary cutaneous aspergillosis in a patient with psoriasis treated with a TNF-α blocker. Our case shows the need to monitor patients treated with these blockers and to retain a high index of suspicion of infections, in particular those caused by fungi. Finally, it demonstrates how a patient recently treated with etanercept responded well to anti-fungal therapy.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">The work should be attributed to: Department of Dermatology and Venereology, Centro Hospitalar de São João EPE, Porto, Portugal.</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" => 1615 "Ancho" => 2500 "Tamanyo" => 525155 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Multiple painful erythematous nodules on the right forearm. (B) Multiple painful erythematous nodules in the left periorbital region.</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" => 1290 "Ancho" => 2667 "Tamanyo" => 644948 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histological image showing abscess-like areas.</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" => 1637 "Ancho" => 1583 "Tamanyo" => 189709 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Two colonies of <span class="elsevierStyleItalic">Aspergillus fumigatus</span> growing on solid Sabouraud medium with gentamicin and chloramphenicol (25<span class="elsevierStyleHsp" style=""></span>°C).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous aspergillosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 14 | 12 | 26 |
| 2024 Octubre | 67 | 40 | 107 |
| 2024 Septiembre | 77 | 26 | 103 |
| 2024 Agosto | 104 | 53 | 157 |
| 2024 Julio | 100 | 21 | 121 |
| 2024 Junio | 103 | 29 | 132 |
| 2024 Mayo | 68 | 38 | 106 |
| 2024 Abril | 59 | 25 | 84 |
| 2024 Marzo | 79 | 33 | 112 |
| 2024 Febrero | 89 | 34 | 123 |
| 2024 Enero | 60 | 34 | 94 |
| 2023 Diciembre | 83 | 25 | 108 |
| 2023 Noviembre | 53 | 36 | 89 |
| 2023 Octubre | 53 | 14 | 67 |
| 2023 Septiembre | 64 | 30 | 94 |
| 2023 Agosto | 49 | 9 | 58 |
| 2023 Julio | 40 | 25 | 65 |
| 2023 Junio | 61 | 16 | 77 |
| 2023 Mayo | 74 | 26 | 100 |
| 2023 Abril | 84 | 31 | 115 |
| 2023 Marzo | 122 | 31 | 153 |
| 2023 Febrero | 73 | 24 | 97 |
| 2023 Enero | 54 | 33 | 87 |
| 2022 Diciembre | 69 | 35 | 104 |
| 2022 Noviembre | 28 | 36 | 64 |
| 2022 Octubre | 24 | 23 | 47 |
| 2022 Septiembre | 54 | 33 | 87 |
| 2022 Agosto | 42 | 37 | 79 |
| 2022 Julio | 24 | 22 | 46 |
| 2022 Junio | 40 | 40 | 80 |
| 2022 Mayo | 73 | 26 | 99 |
| 2022 Abril | 78 | 40 | 118 |
| 2022 Marzo | 73 | 60 | 133 |
| 2022 Febrero | 93 | 23 | 116 |
| 2022 Enero | 86 | 48 | 134 |
| 2021 Diciembre | 53 | 37 | 90 |
| 2021 Noviembre | 51 | 42 | 93 |
| 2021 Octubre | 61 | 53 | 114 |
| 2021 Septiembre | 43 | 44 | 87 |
| 2021 Agosto | 95 | 31 | 126 |
| 2021 Julio | 69 | 33 | 102 |
| 2021 Junio | 50 | 35 | 85 |
| 2021 Mayo | 29 | 49 | 78 |
| 2021 Abril | 56 | 70 | 126 |
| 2021 Marzo | 40 | 22 | 62 |
| 2021 Febrero | 45 | 15 | 60 |
| 2021 Enero | 35 | 22 | 57 |
| 2020 Diciembre | 24 | 9 | 33 |
| 2020 Noviembre | 23 | 9 | 32 |
| 2020 Octubre | 31 | 11 | 42 |
| 2020 Septiembre | 23 | 7 | 30 |
| 2020 Agosto | 22 | 18 | 40 |
| 2020 Julio | 19 | 15 | 34 |
| 2020 Junio | 27 | 26 | 53 |
| 2020 Mayo | 19 | 14 | 33 |
| 2020 Abril | 18 | 18 | 36 |
| 2020 Marzo | 28 | 16 | 44 |
| 2020 Febrero | 5 | 0 | 5 |
| 2020 Enero | 0 | 1 | 1 |
| 2019 Diciembre | 4 | 3 | 7 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 3 | 0 | 3 |
| 2019 Agosto | 0 | 2 | 2 |
| 2019 Julio | 0 | 2 | 2 |
| 2019 Junio | 2 | 0 | 2 |
| 2019 Mayo | 0 | 8 | 8 |
| 2019 Abril | 0 | 2 | 2 |
| 2019 Marzo | 2 | 9 | 11 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 3 | 0 | 3 |
| 2018 Marzo | 1 | 0 | 1 |
| 2018 Febrero | 31 | 4 | 35 |
| 2018 Enero | 32 | 7 | 39 |
| 2017 Diciembre | 37 | 9 | 46 |
| 2017 Noviembre | 24 | 5 | 29 |
| 2017 Octubre | 30 | 5 | 35 |
| 2017 Septiembre | 38 | 14 | 52 |
| 2017 Agosto | 44 | 9 | 53 |
| 2017 Julio | 35 | 4 | 39 |
| 2017 Junio | 62 | 26 | 88 |
| 2017 Mayo | 47 | 11 | 58 |
| 2017 Abril | 49 | 22 | 71 |
| 2017 Marzo | 41 | 14 | 55 |
| 2017 Febrero | 26 | 9 | 35 |
| 2017 Enero | 23 | 12 | 35 |
| 2016 Diciembre | 28 | 7 | 35 |
| 2016 Noviembre | 44 | 11 | 55 |
| 2016 Octubre | 77 | 9 | 86 |
| 2016 Septiembre | 114 | 11 | 125 |
| 2016 Agosto | 35 | 17 | 52 |
| 2016 Julio | 22 | 8 | 30 |
| 2016 Junio | 8 | 8 | 16 |
| 2016 Mayo | 7 | 14 | 21 |
| 2016 Abril | 5 | 2 | 7 |
| 2016 Marzo | 8 | 1 | 9 |
| 2016 Febrero | 10 | 1 | 11 |
| 2016 Enero | 10 | 10 | 20 |
| 2015 Diciembre | 11 | 1 | 12 |
| 2015 Noviembre | 18 | 1 | 19 |
| 2015 Octubre | 15 | 1 | 16 |
| 2015 Septiembre | 13 | 3 | 16 |
| 2015 Agosto | 15 | 3 | 18 |
| 2015 Julio | 37 | 16 | 53 |
| 2015 Junio | 25 | 7 | 32 |
| 2015 Mayo | 43 | 12 | 55 |
| 2015 Abril | 35 | 18 | 53 |
| 2015 Marzo | 35 | 8 | 43 |
| 2015 Febrero | 28 | 9 | 37 |
| 2015 Enero | 24 | 10 | 34 |
| 2014 Diciembre | 22 | 17 | 39 |
| 2014 Noviembre | 7 | 6 | 13 |
| 2014 Octubre | 17 | 8 | 25 |
| 2014 Septiembre | 9 | 6 | 15 |
| 2014 Agosto | 13 | 9 | 22 |
| 2014 Julio | 11 | 5 | 16 |
| 2014 Junio | 15 | 3 | 18 |
| 2014 Mayo | 18 | 7 | 25 |
| 2014 Abril | 6 | 4 | 10 |
| 2014 Marzo | 7 | 1 | 8 |
| 2014 Febrero | 7 | 3 | 10 |
| 2014 Enero | 12 | 5 | 17 |
| 2013 Diciembre | 11 | 4 | 15 |
| 2013 Noviembre | 9 | 5 | 14 |
| 2013 Octubre | 3 | 1 | 4 |
| 2013 Septiembre | 4 | 4 | 8 |
| 2013 Agosto | 3 | 4 | 7 |
| 2013 Julio | 7 | 2 | 9 |
| 2013 Junio | 2 | 3 | 5 |
| 2013 Mayo | 6 | 8 | 14 |
| 2013 Abril | 10 | 12 | 22 |
| 2013 Marzo | 12 | 5 | 17 |
| 2013 Febrero | 36 | 3 | 39 |
| 2013 Enero | 30 | 5 | 35 |
| 2012 Diciembre | 23 | 8 | 31 |
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