Case and Research Letters
Erythema Multiforme Associated With Phenytoin and Cranial Radiation Therapy (EMPACT Syndrome) in a Patient With Lung Cancer
Síndrome Erythema Multiforme associated with Phenytoin And Cranial radiation Therapy (EMPACT) en paciente con neoplasia pulmonar
A. Vilas-Sueiroa,
, I. Vázquez-Osoriob, J.M. Suárez-Peñarandac, D. Sánchez-Aguilarb
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a Servicio de Dermatología, Complejo Hospitalario Universitario de Ferrol, Ferrol, La Coruña, Spain
b Servicio de Dermatología, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, La Coruña, Spain
c Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, La Coruña, Spain
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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute bullous dermatoses caused mainly by the use of drugs such as phenytoin.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 54-year-old man diagnosed with pulmonary adenocarcinoma (T3-4N2M1) with a single intracranial metastasis underwent cranial radiation therapy with a total dose of 30<span class="elsevierStyleHsp" style=""></span>Gy (fractional dose<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>cGy). The radiation therapy was completed 1 week before the onset of the skin condition. The patient had been receiving phenytoin as a prophylactic anticonvulsant and oral dexamethasone for 5 weeks. Physical examination revealed small, atypical, target-shaped, erythematous-edematous lesions with a tendency to coalesce on the face, neck, trunk, and root of the upper limbs, occupying 35% of the body, with skin detachment in the affected areas. Marked conjunctival injection and intense involvement of the oral mucosa, with labial edema and erosive lesions, were also present (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Biopsy of a lesion in the supraclavicular region revealed an intense interface lesion in both the epidermis and the follicular epithelium, with abundant necrotic keratinocytes (isolated or in groups), a moderate lymphocytic inflammatory response, and areas of epidermal detachment with partial necrosis of the detached epidermis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). As therapeutic management, treatment with phenytoin was suspended and substituted by levetiracetam, and adjuvant therapy was also started. The lesions responded well, remaining stable in relation to the neoplastic disease.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Prophylactic use of anticonvulsants is routine in patients who undergo cranial radiation therapy. As in the case of our patient, phenytoin is usually the drug of choice, although other drugs, such as carbamazepine, levetiracetam, and lamotrigine are occasionally used.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Although skin reactions occur after ingestion of phenytoin in 19% of cases, severe cutaneous manifestations such as SJS and TEN are rare.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a> Although these conditions are unusual, it is very important that they be taken into account in order to avoid potentially life-threatening complications.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In recent years, the association of cranial radiation therapy and phenytoin has been shown to increase the risk of skin lesions known as the EMPACT syndrome.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> However, severe SJS-type or TEN-type cutaneous-mucosal manifestations, such as those seen in our patient, only occur in a small percentage of cases and can be life-threatening.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> This complication presents as erythematous-edematous macules and papules that are initially limited to the irradiated area, later progressing to epidermal detachment in larger areas (Nikolsky sign) with considerable involvement of the oral and ocular mucosas.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> In our patient, oral mucosal involvement was the first manifestation—an indication of the variability of the first manifestations.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The pathogenesis is unknown, although it has been suggested that radiation therapy could induce a deficit of epoxide hydroxylase, an enzyme responsible for eliminating toxic metabolites of phenytoin.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> More controversial is the possibility of a type <span class="elsevierStyleSmallCaps">IV</span> hypersensitivity reaction to phenytoin and its metabolites, exacerbated by the action of the radiation therapy and the deficient metabolization of the toxic products of the drug.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5,7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The use of levetiracetam or gabapentin as alternative drugs—either initially or as a substitute for phenytoin—should therefore be considered because the degradation of these drugs does not take place via the same metabolic pathway.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, we present a case of the EMPACT syndrome with unusually severe cutaneous and mucosal involvement. Prophylactic use of anticonvulsants should be considered on a case-by-case basis. If anticonvulsant use is essential, the appearance of cutaneous-mucosal lesions should be monitored closely and the drug should be suspended when the first suspicious symptom appears.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vilas-Sueiro A, Vázquez-Osorio I, Suárez-Peñaranda JM, Sánchez-Aguilar D. Síndrome Erythema Multiforme associated with Phenytoin And Cranial radiation Therapy (EMPACT) en paciente con neoplasia pulmonar. Actas Dermosifiliogr. 2016;107:169–170.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 800 "Ancho" => 800 "Tamanyo" => 156855 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous-edematous plaques with areas of skin detachment and erosive semimucosal lesions on the lips.</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" => 746 "Ancho" => 990 "Tamanyo" => 217503 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Skin detachment and epidermal necrosis with dyskeratotic keratinocytes and lymphocytic inflammatory infiltrate (hematoxylin-eosin, original magnification ×10).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Erythema multiforme associated with phenytoin and cranial radiation therapy: A report of three patients and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "I. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 10 | 8 | 18 |
| 2024 Octubre | 89 | 43 | 132 |
| 2024 Septiembre | 87 | 31 | 118 |
| 2024 Agosto | 92 | 56 | 148 |
| 2024 Julio | 77 | 38 | 115 |
| 2024 Junio | 102 | 39 | 141 |
| 2024 Mayo | 81 | 35 | 116 |
| 2024 Abril | 75 | 18 | 93 |
| 2024 Marzo | 91 | 44 | 135 |
| 2024 Febrero | 77 | 39 | 116 |
| 2024 Enero | 69 | 35 | 104 |
| 2023 Diciembre | 81 | 21 | 102 |
| 2023 Noviembre | 85 | 28 | 113 |
| 2023 Octubre | 80 | 39 | 119 |
| 2023 Septiembre | 79 | 33 | 112 |
| 2023 Agosto | 54 | 25 | 79 |
| 2023 Julio | 84 | 30 | 114 |
| 2023 Junio | 69 | 25 | 94 |
| 2023 Mayo | 93 | 26 | 119 |
| 2023 Abril | 69 | 34 | 103 |
| 2023 Marzo | 67 | 30 | 97 |
| 2023 Febrero | 71 | 19 | 90 |
| 2023 Enero | 49 | 29 | 78 |
| 2022 Diciembre | 66 | 28 | 94 |
| 2022 Noviembre | 29 | 18 | 47 |
| 2022 Octubre | 26 | 17 | 43 |
| 2022 Septiembre | 21 | 35 | 56 |
| 2022 Agosto | 27 | 32 | 59 |
| 2022 Julio | 21 | 29 | 50 |
| 2022 Junio | 23 | 24 | 47 |
| 2022 Mayo | 38 | 26 | 64 |
| 2022 Abril | 35 | 22 | 57 |
| 2022 Marzo | 27 | 34 | 61 |
| 2022 Febrero | 31 | 24 | 55 |
| 2022 Enero | 39 | 32 | 71 |
| 2021 Diciembre | 29 | 35 | 64 |
| 2021 Noviembre | 47 | 32 | 79 |
| 2021 Octubre | 37 | 44 | 81 |
| 2021 Septiembre | 41 | 42 | 83 |
| 2021 Agosto | 31 | 16 | 47 |
| 2021 Julio | 38 | 28 | 66 |
| 2021 Junio | 47 | 30 | 77 |
| 2021 Mayo | 27 | 34 | 61 |
| 2021 Abril | 76 | 50 | 126 |
| 2021 Marzo | 59 | 23 | 82 |
| 2021 Febrero | 69 | 24 | 93 |
| 2021 Enero | 48 | 22 | 70 |
| 2020 Diciembre | 42 | 14 | 56 |
| 2020 Noviembre | 47 | 25 | 72 |
| 2020 Octubre | 38 | 10 | 48 |
| 2020 Septiembre | 31 | 7 | 38 |
| 2020 Agosto | 45 | 14 | 59 |
| 2020 Julio | 26 | 20 | 46 |
| 2020 Junio | 47 | 31 | 78 |
| 2020 Mayo | 35 | 16 | 51 |
| 2020 Abril | 43 | 19 | 62 |
| 2020 Marzo | 33 | 10 | 43 |
| 2020 Febrero | 8 | 0 | 8 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 9 | 0 | 9 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 1 | 0 | 1 |
| 2019 Septiembre | 10 | 0 | 10 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 6 | 1 | 7 |
| 2019 Abril | 2 | 3 | 5 |
| 2019 Marzo | 2 | 5 | 7 |
| 2019 Febrero | 2 | 0 | 2 |
| 2018 Diciembre | 4 | 0 | 4 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 5 | 0 | 5 |
| 2018 Septiembre | 4 | 0 | 4 |
| 2018 Agosto | 0 | 9 | 9 |
| 2018 Julio | 0 | 6 | 6 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Mayo | 0 | 6 | 6 |
| 2018 Abril | 0 | 2 | 2 |
| 2018 Marzo | 2 | 3 | 5 |
| 2018 Febrero | 21 | 2 | 23 |
| 2018 Enero | 28 | 6 | 34 |
| 2017 Diciembre | 37 | 12 | 49 |
| 2017 Noviembre | 26 | 5 | 31 |
| 2017 Octubre | 30 | 8 | 38 |
| 2017 Septiembre | 23 | 12 | 35 |
| 2017 Agosto | 33 | 11 | 44 |
| 2017 Julio | 19 | 9 | 28 |
| 2017 Junio | 26 | 25 | 51 |
| 2017 Mayo | 28 | 11 | 39 |
| 2017 Abril | 20 | 7 | 27 |
| 2017 Marzo | 26 | 42 | 68 |
| 2017 Febrero | 21 | 10 | 31 |
| 2017 Enero | 17 | 13 | 30 |
| 2016 Diciembre | 20 | 19 | 39 |
| 2016 Noviembre | 22 | 28 | 50 |
| 2016 Octubre | 19 | 30 | 49 |
| 2016 Septiembre | 0 | 3 | 3 |
| 2016 Agosto | 0 | 5 | 5 |
| 2016 Julio | 1 | 5 | 6 |
| 2016 Junio | 0 | 1 | 1 |
| 2016 Mayo | 0 | 5 | 5 |
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