Case and research letter
Nystatin-Induced Acute Generalized Exanthematous Pustulosis
Pustulosis exantemática aguda generalizada inducida por nistatina
I. Ocerin-Guerra, C. Gomez-Bringas, L. Aspe-Unanue, J.A. Ratón-Nieto
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Servicio de Dermatología, Hospital Universitario de Cruces, Barakaldo, Bizkaia, Spain
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Ocerin-Guerra, C. Gomez-Bringas, L. Aspe-Unanue, J.A. Ratón-Nieto" "autores" => array:4 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Ocerin-Guerra" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Gomez-Bringas" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Aspe-Unanue" ] 3 => array:4 [ "nombre" => "J.A." "apellidos" => "Ratón-Nieto" "email" => array:1 [ 0 => "jaraton@aedv.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital Universitario de Cruces, Barakaldo, Bizkaia, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pustulosis exantemática aguda generalizada inducida por nistatina" ] ] "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" => 1125 "Ancho" => 1500 "Tamanyo" => 143866 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Positive patch test to nystatin, 2%, in petroleum jelly at 96<span class="elsevierStyleHsp" style=""></span>h.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption (estimated incidence, 1 to 5 cases per million population per year<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>) that is usually induced by drugs. It was recently reviewed in this journal.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> AGEP consists of the rapid appearance of numerous sterile nonfollicular pustules on a background of erythematous-edematous skin and is associated with fever and leukocytosis. The eruption is self-limiting after withdrawal of the offending drug. Few cases of nystatin-induced AGEP have been published. Nystatin is an antifungal agent that is widely used throughout the world and that is usually well tolerated because of its minimal systemic absorption. In all published cases, patch testing was useful to confirm the diagnosis of this toxic dermatitis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient was an 83-year-old woman with a history of systemic hypertension, diabetes mellitus, and allergy to sulfamides. She was admitted to our hospital for a 1-week history of fever, malaise, and skin rash. The skin lesions had developed 48<span class="elsevierStyleHsp" style=""></span>hours after starting treatment with nystatin mouthwashes for oral candidiasis; this had been the only change to her usual treatment. On admission the patient was febrile (38.3<span class="elsevierStyleHsp" style=""></span>°C). She presented erythroderma and the skin was covered by numerous pustules of 1 to 3<span class="elsevierStyleHsp" style=""></span>mm in diameter; the pustules were not centered on follicles and were more evident on the trunk and roots of the limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The mucosas were not affected and the Nikolsky sign was negative. Blood tests revealed a white cell count of 18 400/μL with neutrophilia (88.9%) but without eosinophilia, and elevation of the acute-phase reactants (erythrocyte sedimentation rate, 63<span class="elsevierStyleHsp" style=""></span>mm; C-reactive protein, 127<span class="elsevierStyleHsp" style=""></span>mg/dL). Blood cultures, the cultures of 2 pustules, and viral serology for rubella virus, cytomegalovirus, Epstein-Barr virus, parvovirus B19, enterovirus, varicella-zoster virus, and human immunodeficiency virus were negative. Biopsy of 1 of the pustules showed a spongiform dermatitis with the formation of subcorneal pustules and a dermal infiltrate rich in polymorphonuclear cells and eosinophils (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>); the infiltrate was negative to staining with periodic acid-Schiff. The nystatin mouthwashes were discontinued and the patient was administered a short course of oral corticosteroids. She was discharged after 13 days with a good general state of health and presenting only erythema and minimal residual desquamation.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Six months later, patch testing was performed under normal conditions with the standard series of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) plus nystatin, 2%, in petroleum jelly (AllergEAZE, Brial Allergen GmbH). Positive results were obtained only with the nystatin patch at 48 and 96<span class="elsevierStyleHsp" style=""></span>hours (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>); the subsequent study with nystatin, 2%, in petroleum jelly in 11 controls was negative. The reaction caused by the patch in our patient produced the same clinical and histological changes as had been observed initially with the toxic dermatitis, confirming the diagnosis of nystatin-induced AGEP.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Nystatin is a fungistatic drug of the polyenic group, isolated from <span class="elsevierStyleItalic">Streptomyces noursei</span>. It is widely used throughout the world for its efficacy against <span class="elsevierStyleItalic">Candida</span> and for its good tolerance; the main indication for treatment with nystatin as a mouthwash is oropharyngeal candidiasis. Toxic dermatitis due to this drug is rare as it undergoes minimal intestinal absorption after ingestion and is therefore very unlikely to cause systemic reactions. In our patient the clinical presentation (including the temporal relationship with the administration of the drug and clinical course of the lesions) and the histopathological findings were characteristic of AGEP according to current criteria.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In a review of the literature we found 5 cases of nystatin-induced AGEP.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–6</span></a> They were all clinically identical to our case and were also confirmed using various tests, including patch tests and intradermal tests. Our case is the first to be reported in Spain. Other forms of toxic dermatitis caused by oral nystatin, namely generalized dermatitis,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> maculopapular eruption,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> generalized eruption with angioedema,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and generalized maculopapular rash,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> have been described in case reports. In all the cases, patch testing performed at different concentrations (always >10%) yielded positive results. In our patient we showed that patch testing with a 2% concentration of nystatin is sufficient to make the diagnosis. In general, it is known that the sensitivity of patch testing in the study of AGEP is around 50% (80% for some antibiotics), which is higher than that found in other types of toxic dermatitis, including Stevens-Johnson syndrome.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Collation of the evidence confirms the participation of drug-specific T lymphocytes in the pathophysiological mechanisms of AGEP, which is a specific form of delayed hypersensitivity.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, AGEP should be included in the differential diagnosis of pustular skin eruptions in patients on treatment with oral nystatin, despite its minimal gastrointestinal absorption. Patch testing has high diagnostic value in drug-induced AGEP and other drug-induced forms of toxic dermatitis. In our patient we observed positive results with the drug diluted to lower concentrations than those previously reported in the literature.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara"><span class="elsevierStyleBold">Please cite this article as:</span> Ocerin-Guerra I, et al. Pustulosis exantemática aguda generalizada inducida por nistatina. Actas Dermosifiliogr. 2012;103:927–8.</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" => 1125 "Ancho" => 1500 "Tamanyo" => 267742 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image of the nonfollicular pustules on erythematous skin on the back.</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" => 1123 "Ancho" => 1500 "Tamanyo" => 313428 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Subcorneal pustule with edema of the papillary dermis and a neutrophil-rich inflammatory infiltrate. (Hematoxylin-eosin, original magnification ×10).</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" => 1125 "Ancho" => 1500 "Tamanyo" => 143866 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Positive patch test to nystatin, 2%, in petroleum jelly at 96<span class="elsevierStyleHsp" style=""></span>h.</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" => "Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.M. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 22 | 21 | 43 |
| 2024 Octubre | 78 | 47 | 125 |
| 2024 Septiembre | 97 | 35 | 132 |
| 2024 Agosto | 142 | 63 | 205 |
| 2024 Julio | 112 | 58 | 170 |
| 2024 Junio | 121 | 76 | 197 |
| 2024 Mayo | 82 | 45 | 127 |
| 2024 Abril | 69 | 28 | 97 |
| 2024 Marzo | 93 | 45 | 138 |
| 2024 Febrero | 71 | 30 | 101 |
| 2024 Enero | 69 | 29 | 98 |
| 2023 Diciembre | 84 | 29 | 113 |
| 2023 Noviembre | 63 | 34 | 97 |
| 2023 Octubre | 50 | 20 | 70 |
| 2023 Septiembre | 77 | 26 | 103 |
| 2023 Agosto | 84 | 26 | 110 |
| 2023 Julio | 81 | 37 | 118 |
| 2023 Junio | 66 | 31 | 97 |
| 2023 Mayo | 107 | 25 | 132 |
| 2023 Abril | 54 | 30 | 84 |
| 2023 Marzo | 65 | 24 | 89 |
| 2023 Febrero | 87 | 32 | 119 |
| 2023 Enero | 66 | 32 | 98 |
| 2022 Diciembre | 57 | 56 | 113 |
| 2022 Noviembre | 26 | 22 | 48 |
| 2022 Octubre | 36 | 22 | 58 |
| 2022 Septiembre | 27 | 49 | 76 |
| 2022 Agosto | 44 | 37 | 81 |
| 2022 Julio | 47 | 29 | 76 |
| 2022 Junio | 24 | 22 | 46 |
| 2022 Mayo | 38 | 37 | 75 |
| 2022 Abril | 55 | 38 | 93 |
| 2022 Marzo | 60 | 61 | 121 |
| 2022 Febrero | 48 | 47 | 95 |
| 2022 Enero | 35 | 29 | 64 |
| 2021 Diciembre | 42 | 51 | 93 |
| 2021 Noviembre | 49 | 47 | 96 |
| 2021 Octubre | 44 | 54 | 98 |
| 2021 Septiembre | 54 | 49 | 103 |
| 2021 Agosto | 48 | 37 | 85 |
| 2021 Julio | 47 | 30 | 77 |
| 2021 Junio | 60 | 30 | 90 |
| 2021 Mayo | 84 | 49 | 133 |
| 2021 Abril | 89 | 60 | 149 |
| 2021 Marzo | 85 | 43 | 128 |
| 2021 Febrero | 86 | 28 | 114 |
| 2021 Enero | 39 | 23 | 62 |
| 2020 Diciembre | 36 | 14 | 50 |
| 2020 Noviembre | 16 | 15 | 31 |
| 2020 Octubre | 26 | 9 | 35 |
| 2020 Septiembre | 36 | 22 | 58 |
| 2020 Agosto | 38 | 15 | 53 |
| 2020 Julio | 21 | 10 | 31 |
| 2020 Junio | 25 | 25 | 50 |
| 2020 Mayo | 12 | 17 | 29 |
| 2020 Abril | 27 | 21 | 48 |
| 2020 Marzo | 23 | 23 | 46 |
| 2020 Febrero | 4 | 6 | 10 |
| 2020 Enero | 4 | 8 | 12 |
| 2019 Diciembre | 8 | 7 | 15 |
| 2019 Noviembre | 4 | 5 | 9 |
| 2019 Octubre | 0 | 2 | 2 |
| 2019 Septiembre | 10 | 10 | 20 |
| 2019 Agosto | 4 | 3 | 7 |
| 2019 Julio | 4 | 4 | 8 |
| 2019 Junio | 6 | 24 | 30 |
| 2019 Mayo | 6 | 27 | 33 |
| 2019 Abril | 2 | 13 | 15 |
| 2019 Marzo | 2 | 7 | 9 |
| 2019 Febrero | 3 | 5 | 8 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 4 | 6 | 10 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Marzo | 1 | 0 | 1 |
| 2018 Febrero | 25 | 2 | 27 |
| 2018 Enero | 35 | 5 | 40 |
| 2017 Diciembre | 40 | 10 | 50 |
| 2017 Noviembre | 37 | 3 | 40 |
| 2017 Octubre | 32 | 5 | 37 |
| 2017 Septiembre | 45 | 5 | 50 |
| 2017 Agosto | 55 | 14 | 69 |
| 2017 Julio | 54 | 14 | 68 |
| 2017 Junio | 69 | 10 | 79 |
| 2017 Mayo | 49 | 6 | 55 |
| 2017 Abril | 39 | 11 | 50 |
| 2017 Marzo | 55 | 27 | 82 |
| 2017 Febrero | 36 | 8 | 44 |
| 2017 Enero | 19 | 5 | 24 |
| 2016 Diciembre | 46 | 12 | 58 |
| 2016 Noviembre | 51 | 10 | 61 |
| 2016 Octubre | 56 | 15 | 71 |
| 2016 Septiembre | 59 | 18 | 77 |
| 2016 Agosto | 58 | 24 | 82 |
| 2016 Julio | 34 | 7 | 41 |
| 2016 Junio | 9 | 13 | 22 |
| 2016 Mayo | 9 | 7 | 16 |
| 2016 Abril | 13 | 1 | 14 |
| 2016 Marzo | 12 | 0 | 12 |
| 2016 Febrero | 8 | 4 | 12 |
| 2016 Enero | 10 | 1 | 11 |
| 2015 Diciembre | 10 | 3 | 13 |
| 2015 Noviembre | 10 | 5 | 15 |
| 2015 Octubre | 20 | 3 | 23 |
| 2015 Septiembre | 19 | 3 | 22 |
| 2015 Agosto | 33 | 2 | 35 |
| 2015 Julio | 58 | 11 | 69 |
| 2015 Junio | 69 | 13 | 82 |
| 2015 Mayo | 64 | 17 | 81 |
| 2015 Abril | 75 | 12 | 87 |
| 2015 Marzo | 63 | 10 | 73 |
| 2015 Febrero | 36 | 11 | 47 |
| 2015 Enero | 34 | 13 | 47 |
| 2014 Diciembre | 40 | 14 | 54 |
| 2014 Noviembre | 16 | 6 | 22 |
| 2014 Octubre | 36 | 6 | 42 |
| 2014 Septiembre | 21 | 7 | 28 |
| 2014 Agosto | 30 | 10 | 40 |
| 2014 Julio | 16 | 9 | 25 |
| 2014 Junio | 50 | 2 | 52 |
| 2014 Mayo | 43 | 11 | 54 |
| 2014 Abril | 32 | 6 | 38 |
| 2014 Marzo | 27 | 6 | 33 |
| 2014 Febrero | 16 | 5 | 21 |
| 2014 Enero | 12 | 7 | 19 |
| 2013 Diciembre | 22 | 8 | 30 |
| 2013 Noviembre | 18 | 4 | 22 |
| 2013 Octubre | 10 | 8 | 18 |
| 2013 Septiembre | 8 | 5 | 13 |
| 2013 Agosto | 7 | 16 | 23 |
| 2013 Julio | 8 | 10 | 18 |
| 2013 Junio | 4 | 11 | 15 |
| 2013 Mayo | 14 | 7 | 21 |
| 2013 Abril | 16 | 11 | 27 |
| 2013 Marzo | 15 | 4 | 19 |
| 2013 Febrero | 37 | 8 | 45 |
| 2013 Enero | 47 | 8 | 55 |
| 2012 Diciembre | 33 | 8 | 41 |
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