Case Letter
Acute generalized exanthematous pustulosis with features mimicking toxic epidermal necrolysis secondary to amiodarone
Cheryl Distel
, María Luz Bollea Garlatti, Ana Clara Torre, Julia Riganti
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Department of Dermatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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"nombre" => "Julia" "apellidos" => "Riganti" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Dermatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "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" => 941 "Ancho" => 755 "Tamanyo" => 126336 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Bullous lesions that led to small erosions on flanks.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute generalized exanthematous pustulosis (AGEP) is an infrequent cutaneous drug eruption, with a short latency of 24–48<span class="elsevierStyleHsp" style=""></span>h between the exposure and the onset of lesions.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> The symptoms consist of fever and small, sterile, non-follicular pustules on a background of erythema.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> Mucous membrane and internal organ involvement are unusual.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> The most common laboratory abnormality is leukocytosis and neutrophilia<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>7000/mL.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> A score, developed by the EuroSCAR group, that takes into account clinical and histopathological criteria is useful for diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> AGEP is usually a self-limited disease, which typically resolves with cutaneous desquamation in less than 15<span class="elsevierStyleHsp" style=""></span>days after suspending the causative drug, and it has an excellent prognosis.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> However, although infrequent, patients can develop purpuric, targetoid, and bullous lesions, areas of denuded skin, a positive Nikolsky sign, and mucosal and multi-organ involvements, which denotes a more serious outcome.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> The present report describes a patient with AGEP induced by an atypical drug, who presented with this serious clinical picture.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 69-year-old female patient, with a history of supraventricular extrasystoles, presented with fever, malaise, and small, non-follicular pustules on a background of erythema in the axillae and groin. Twenty-four hours earlier she had switched her antiarrhythmic treatment from bisoprolol to amiodarone. Upon admission, she was dyspneic and presented tachycardia, tachypnea, and suboptimal oxygen saturation. Her mucous membranes were not involved and the Nikolsky sign was negative. Her laboratory studies revealed leukocytosis (26,689<span class="elsevierStyleHsp" style=""></span>cell/mm<span class="elsevierStyleSup">3</span>) with neutrophilia (88.25%). Blood cultures showed no growth and the chest X-ray did not reveal any abnormalities. AGEP was suspected, amiodarone was suspended, skin biopsies were obtained, and oral meprednisone 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day was started because of her pulmonary symptoms. Histopathology revealed subcorneal pustules with no necrotic keratinocytes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The EuroSCAR score was 11, compatible with definite AGEP. In spite of the initial treatment, 24<span class="elsevierStyleHsp" style=""></span>h later the patient's lesions evolved and extended. She experienced diarrhea and developed purpuric and targetoid lesions in the thighs and the gluteal area (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>); and bullous lesions that led to small erosions on her flanks (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Nikolsky sign was again negative. Taking into account this torpid progression, it was hypothesized that intestinal absorption of corticosteroid could not have been sufficient, the prolonged half-life of amiodarone was playing a role, and the patient could have been undergoing a different drug reaction such as toxic epidermal necrolysis (TEN) or that she could have been suffering from an overlapping of two adverse drug reactions. At this point new skin biopsies were obtained. The histopathology was again compatible with AGEP. Meprednisone dose was raised to 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day and was administered intravenously. Finally, the skin lesions and systemic symptoms resolved with skin desquamation 11 days after the onset. However, after five months from the onset of symptoms, she continued to developed new recurrences every time corticosteroid was intended to be suspended.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The relationship between the beginning of the new antiarrhythmic and the development of systemic and cutaneous symptoms, together with the clinical and histopathological findings, resulted in the diagnosis of AGEP induced by amiodarone. After extended research of the English and Spanish literature, to the best of the authors’ knowledge, this is the first report of AGEP triggered by this medication. Amiodarone is a fat soluble drug with a prolonged half-life of 15–142<span class="elsevierStyleHsp" style=""></span>days (mean of 58) even after the administration of a single dose.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> This could explain why the patient kept presenting new lesions after the discontinuation of the drug even though the medication had been suspended.</p><p id="par0020" class="elsevierStylePara elsevierViewall">This case exhibited unusual features for classical AGEP: targetoid and bullous lesions together with torpid evolution and internal organ involvement. A diagnosis of TEN was considered, but in the absence of necrotic keratinocytes in the biopsy, it was concluded that this was actually TEN-like AGEP presentation.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Although internal organ involvement is present in less than 17–20% of patients, when it occurs, hepatic and renal failure are the most common manifestations.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> It can also present with respiratory symptoms<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> as in the present patient, in whom after ruling out infectious causes and TEN, pulmonary involvement was attributed to AGEP. Moreover, though in classical AGEP the cessation of the causative drug is the only necessary intervention, systemic corticosteroids are mandatory when organ involvement or severe cutaneous lesions are present, as in the present case.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">We believe that this case supports the decision of some authors to consider AGEP a severe cutaneous drug reaction and why it is important to closely follow these patients, in order to identify critical cases and intensify treatment to reduce mortality rate.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Financial support</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors’ contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Cheryl Distel: Drafting and editing of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0040" class="elsevierStylePara elsevierViewall">María Luz Bollea Garlatti: Approval of the final version of the manuscript; drafting and editing of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Ana Clara Torre: Approval of the final version of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Julia Riganti: Approval of the final version of the manuscript; intellectual participation in the 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="par0060" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:2 [ "identificador" => "xack475739" "titulo" => "Acknowledgment" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-06-28" "fechaAceptado" => "2019-11-30" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">How to cite this article: Distel C, Bollea Garlatti ML, Torre AC, Riganti J. Acute generalized exanthematous pustulosis with features mimicking toxic epidermal necrolysis secondary to amiodarone. An Bras Dermatol. 2020;95:540–2.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.</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" => 1007 "Ancho" => 755 "Tamanyo" => 239441 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Subcorneal pustules and spongiosis (Hematoxylin & eosin, x100).</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" => 579 "Ancho" => 755 "Tamanyo" => 58707 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Purpuric and targetoid lesions in the thighs and the gluteal area.</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" => 941 "Ancho" => 755 "Tamanyo" => 126336 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Bullous lesions that led to small erosions on flanks.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute generalized exanthematous pustulosis: pathogenesis, genetic background, clinical variants and therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. 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Available from: <a target="_blank" href="https://www.uptodate.com/contents/amiodarone-drug-information">https://www.uptodate.com/contents/amiodarone-drug-information</a> [accessed 12.11.18]." ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute generalized exanthematous pustulosis: atypical presentations and outcomes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T.C. Kostopoulos" 1 => "S.M. Krishna" 2 => "N.K. Brinster" 3 => "A.G. Ortega-Loayza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.12721" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2015" "volumen" => "29" "paginaInicial" => "209" "paginaFinal" => "214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25201706" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack475739" "titulo" => "Acknowledgment" "texto" => "<p id="par0065" class="elsevierStylePara elsevierViewall">The authors are very thankful to Dr. Luis Mazzuoccolo, head of the Department of Dermatology, Hospital Italiano de Buenos Aires, for critical review and approval of the final version of the manuscript.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03650596/0000009500000004/v3_202008041755/S0365059620301276/v3_202008041755/en/main.assets" "Apartado" => array:4 [ "identificador" => "82769" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case Letter" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03650596/0000009500000004/v3_202008041755/S0365059620301276/v3_202008041755/en/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059620301276?idApp=UINPBA00008Z" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 24 | 11 | 35 |
| 2024 Outubro | 119 | 68 | 187 |
| 2024 Setembro | 163 | 74 | 237 |
| 2024 Agosto | 139 | 99 | 238 |
| 2024 Julho | 138 | 110 | 248 |
| 2024 Junho | 100 | 72 | 172 |
| 2024 Maio | 90 | 68 | 158 |
| 2024 Abril | 110 | 88 | 198 |
| 2024 Março | 120 | 58 | 178 |
| 2024 Fevereiro | 118 | 75 | 193 |
| 2024 Janeiro | 94 | 56 | 150 |
| 2023 Dezembro | 77 | 65 | 142 |
| 2023 Novembro | 76 | 74 | 150 |
| 2023 Outubro | 73 | 77 | 150 |
| 2023 Setembro | 84 | 70 | 154 |
| 2023 Agosto | 68 | 35 | 103 |
| 2023 Julho | 73 | 31 | 104 |
| 2023 Junho | 69 | 40 | 109 |
| 2023 Maio | 52 | 18 | 70 |
| 2023 Abril | 51 | 18 | 69 |
| 2023 Março | 66 | 49 | 115 |
| 2023 Fevereiro | 53 | 28 | 81 |
| 2023 Janeiro | 36 | 23 | 59 |
| 2022 Dezembro | 54 | 24 | 78 |
| 2022 Novembro | 73 | 64 | 137 |
| 2022 Outubro | 62 | 55 | 117 |
| 2022 Setembro | 49 | 65 | 114 |
| 2022 Agosto | 64 | 44 | 108 |
| 2022 Julho | 47 | 56 | 103 |
| 2022 Junho | 44 | 55 | 99 |
| 2022 Maio | 36 | 48 | 84 |
| 2022 Abril | 36 | 44 | 80 |
| 2022 Março | 36 | 66 | 102 |
| 2022 Fevereiro | 46 | 29 | 75 |
| 2022 Janeiro | 76 | 71 | 147 |
| 2021 Dezembro | 39 | 55 | 94 |
| 2021 Novembro | 51 | 63 | 114 |
| 2021 Outubro | 67 | 82 | 149 |
| 2021 Setembro | 42 | 50 | 92 |
| 2021 Agosto | 46 | 63 | 109 |
| 2021 Julho | 31 | 57 | 88 |
| 2021 Junho | 35 | 68 | 103 |
| 2021 Maio | 39 | 67 | 106 |
| 2021 Abril | 78 | 222 | 300 |
| 2021 Março | 65 | 62 | 127 |
| 2021 Fevereiro | 21 | 20 | 41 |
| 2021 Janeiro | 31 | 18 | 49 |
| 2020 Dezembro | 25 | 18 | 43 |
| 2020 Novembro | 34 | 16 | 50 |
| 2020 Outubro | 68 | 8 | 76 |
| 2020 Setembro | 94 | 20 | 114 |
| 2020 Agosto | 21 | 12 | 33 |
| 2020 Julho | 28 | 14 | 42 |
| 2020 Junho | 20 | 16 | 36 |
| 2020 Maio | 8 | 10 | 18 |
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