Case and Research Letters
Toxic epidermal necrolysis vs. acute cutaneous graft versus host disease after hematopoietic stem cell transplantation: A diagnostic and therapeutic challenge
Necrólisis epidérmica tóxica versus enfermedad injerto contra huésped cutánea aguda después de un trasplante de células madre hematopoyéticas: un desafío diagnóstico y terapéutico
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Rodríguez Tejero, J. Badiola González, L. Roldán Mateo, A. Molina Leyva" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Rodríguez Tejero" "email" => array:1 [ 0 => "andrea_13_3217@hotmail.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" => "J." "apellidos" => "Badiola González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "L." "apellidos" => "Roldán Mateo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Molina Leyva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "UGC Dermatología Hospital Virgen de las Nieves de Granada. Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "UGC Hematologías Hospital Virgen de las Nieves de Granada. Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "UGC Anatomía Patológica Hospital Virgen de las Nieves de Granada. Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Necrólisis epidérmica tóxica versus enfermedad injerto contra huésped cutánea aguda después de un trasplante de células madre hematopoyéticas: un desafío diagnóstico y terapéutico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1078 "Ancho" => 1255 "Tamanyo" => 176710 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A.</span> Clinical image of patient two. <span class="elsevierStyleBold">B.</span> Hematoxylin-Eosin on a biopsy of patient two (20x). <span class="elsevierStyleBold">C</span>. CD4+ lymphocytes on a skin biopsy of patient two (40x)<span class="elsevierStyleBold">. D.</span> CD8+ lymphocytes on a skin biopsy of patient two (40x). Note that in the dermal lymphocytic infiltrate, a CD8 / CD4 ratio of 2.5, less than 4 and more suggestive in this case of GHVD.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Toxic epidermal necrolysis (TEN) is a life-threatening blistering skin disease induced by a medication. The incidence and main features of TEN in patients with hematopoietic stem cell transplantation (HSCT) have been poorly evaluated and there are only a few documented cases in the literature.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The extensive blistering and desquamation presentation of the cutaneous acute graft versus host disease (GVHD) is the most severe variant of this condition and it mimics a TEN.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Both skin diseases have exhibit clinical and histological similarities which makes it virtually impossible to differentiate between them in the context of HSCT.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Clinical cases</span><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Patient one:</span> A 47-year-old man with myelodysplastic syndrome undergoing allogeneic HSCT. On day +84, the patient referred the development of a pruritic generalized acute erythema, associating fever and lichenoid erosions in the oral mucosa. A severe GVHD was suspected and intensification of treatment with sirolimus, ruxolitinib and extracorporeal photopheresis was decided. However, the eruption progressed with blistering and epidermolysis. Given the lack of response, TEN was suspected and all not strictly necessary drugs were withdrawn, while immunosuppressive treatment is reduced. From this moment on, the patient improved and epithelization of all the detached surface was achieved in some weeks. After numerous complications, on the day +229, the patient was released from the hospital with cutaneous, hepatic and ocular chronic GVHD, that was treated with immunosuppressive therapy until day +322, when he died from respiratory infection.</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Patient two</span>: An allogeneic HSCT was performed in a 61-year-old woman with chronic lymphatic leukemia. The day +16 she developed a gastric GVHD treated with corticosteroid and cyclosporine. On day +38, the patient reported a worsening of her digestive symptoms, associating fever and mild skin rash. Sirolimus was initiated and it coincided with the appearance of a more significant, painful and confluent rash, with serous blisters, epidermal denudation and fibrinoid exulcerations in oral mucosa. Sirolimus was interrupted, along with most of the prophylactic treatments of HSCT, but the rest of the immunosuppressive therapy, with high doses of corticosteroids, cyclosporine, ruxolitinib and photoapheresis, was prolonged. Progressive re-epithelialization and correct clinical-analytical stability are achieved. The patient was discharged from hospital on day +80, and later she showed typical lesions of chronic cutaneous GVHD (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">In the common scenario of an allogenic HSCT, it is very difficult to clearly separate a TEN from a severe acute cutaneous GVHD.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Acute cutaneous GVHD usually debuts in the first 4–6 weeks after allogeneic hematopoietic stem cell transplantation (HSCT), with common association with digestive and hepatic symptoms. The severe forms involve more than 50% of the body surface area (stage III) with even blistering and epidermolysis (stage IV). It corresponds to interface dermatitis with keratinocyte necrosis and dermal lymphocytic infiltrate predominantly T CD8, adding formation of a subepidermal cleavage in grade III and dermo-epidermal separation in grade IV.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Regarding the treatment, the use of glucocorticoids, usually topical and systemic, is accepted as the first line. The second line is not clearly defined, being valid different combinations of immunosuppressants as well as extracorporeal photopheresis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Given that clinically and histologically TEN and severe acute cutaneous GVHD can be identical, dual moderate management is usually chosen. However, it is important to promote studies that define criteria for differential diagnosis, since optimal management of each entity runs in some differences.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The following points may be useful for the differential diagnosis:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Appearance of NET in the 4 weeks following the incorporation of a new medication, with discontinuity of denudation once the suspect drug has been removed. On the contrary, in GVHD it is possible that skin reactions progress or recur, even in a changing manner.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">The coexistence of gastrointestinal or hepatic GVHD, supports the diagnosis of severe acute cutaneous GVHD.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Although the histology may be similar, and immunofluorescence lacks of value because it is negative or non-specific, the immunohistochemistry in both reflects a clear predominance of T CD8 lymphocytes in the dermal infiltrate. Recent studies advocate for a CD8 / CD4 ratio higher in the NET, where at least it will be > 4.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">The determination, during the first hours of the suspicious eruption, of certain elevated serum biomarkers like elafin, regenerating islet-derived 3-α (REG3α) or soluble interleukin-2 receptor-α (sIL-2Rα), is a non-invasive procedure that can guide both for the diagnosis of the onset of GVHD, as to predict the evolution towards severe GVHD. In particular, the three biomarkers mentioned, measured jointly just when the symptomatology appears, constitute a composite panel that has shown with statistical significance, to be able to differentiate non-GVHD versus any degree GVHD. The analysis in recent literature of the ROC curve of this panel to diagnose GVHD at the time of onset of symptoms, describes a specificity of 100% and a sensitivity of 55.6%.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, we present two clinical cases in which the diagnostic difficulty between these two entities and the importance of looking for clinical, analytical and anatomopathological data that allow to focus therapeutic management, is reflected.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Clinical cases" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rodríguez Tejero A, Badiola González J, Roldán Mateo L, Molina Leyva A. Necrólisis epidérmica tóxica versus enfermedad injerto contra huésped cutánea aguda después de un trasplante de células madre hematopoyéticas: un desafío diagnóstico y terapéutico. Actas Dermosifiliogr. 2021;112:81–82.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1078 "Ancho" => 1255 "Tamanyo" => 176710 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A.</span> Clinical image of patient two. <span class="elsevierStyleBold">B.</span> Hematoxylin-Eosin on a biopsy of patient two (20x). <span class="elsevierStyleBold">C</span>. CD4+ lymphocytes on a skin biopsy of patient two (40x)<span class="elsevierStyleBold">. D.</span> CD8+ lymphocytes on a skin biopsy of patient two (40x). Note that in the dermal lymphocytic infiltrate, a CD8 / CD4 ratio of 2.5, less than 4 and more suggestive in this case of GHVD.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review of Cutaneous Graft-vs-Host Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Ballester-Sanchez" 1 => "M. Navarro-Mira" 2 => "J. Sanz-Caballer" 3 => "R. Botella-Estrada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ad.2015.10.003" "Revista" => array:7 [ "tituloSerie" => "Actas dermo-sifiliograficas." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 7 | 13 |
| 2024 October | 75 | 48 | 123 |
| 2024 September | 71 | 21 | 92 |
| 2024 August | 99 | 63 | 162 |
| 2024 July | 81 | 32 | 113 |
| 2024 June | 84 | 26 | 110 |
| 2024 May | 69 | 45 | 114 |
| 2024 April | 81 | 41 | 122 |
| 2024 March | 89 | 24 | 113 |
| 2024 February | 72 | 43 | 115 |
| 2024 January | 67 | 37 | 104 |
| 2023 December | 63 | 25 | 88 |
| 2023 November | 56 | 27 | 83 |
| 2023 October | 59 | 19 | 78 |
| 2023 September | 45 | 25 | 70 |
| 2023 August | 45 | 17 | 62 |
| 2023 July | 43 | 27 | 70 |
| 2023 June | 59 | 23 | 82 |
| 2023 May | 59 | 23 | 82 |
| 2023 April | 44 | 26 | 70 |
| 2023 March | 58 | 29 | 87 |
| 2023 February | 49 | 23 | 72 |
| 2023 January | 39 | 32 | 71 |
| 2022 December | 59 | 46 | 105 |
| 2022 November | 30 | 25 | 55 |
| 2022 October | 30 | 24 | 54 |
| 2022 September | 27 | 36 | 63 |
| 2022 August | 35 | 35 | 70 |
| 2022 July | 24 | 43 | 67 |
| 2022 June | 33 | 38 | 71 |
| 2022 May | 55 | 43 | 98 |
| 2022 April | 77 | 48 | 125 |
| 2022 March | 69 | 70 | 139 |
| 2022 February | 53 | 41 | 94 |
| 2022 January | 67 | 51 | 118 |
| 2021 December | 68 | 52 | 120 |
| 2021 November | 58 | 58 | 116 |
| 2021 October | 66 | 85 | 151 |
| 2021 September | 67 | 59 | 126 |
| 2021 August | 61 | 57 | 118 |
| 2021 July | 47 | 45 | 92 |
| 2021 June | 41 | 48 | 89 |
| 2021 May | 52 | 59 | 111 |
| 2021 April | 169 | 110 | 279 |
| 2021 March | 89 | 62 | 151 |
| 2021 February | 77 | 53 | 130 |
| 2021 January | 55 | 38 | 93 |
| 2020 December | 46 | 28 | 74 |
| 2020 November | 13 | 6 | 19 |
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