Research letter
Stevens-Johnson syndrome: a case report
a Department of Pediatric Allergy, Trakya University, Faculty of Medicine, Edirne, Turkey
b Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey
c Department of Internal Medicine, Trakya University, Faculty of Medicine, Edirne, Turkey
d Department of Pathology, Trakya University, Faculty of Medicine, Edirne, Turkey
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Bisaccioni, E. Cajuela, R. Câmara Agondi, J. Kalil, P. Giavina-Bianchi" "autores" => array:5 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Bisaccioni" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Cajuela" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Câmara Agondi" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Kalil" ] 4 => array:2 [ "nombre" => "P." "apellidos" => "Giavina-Bianchi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030105460900024X?idApp=UINPBA00004N" "url" => "/03010546/0000003700000004/v1_201304101017/S030105460900024X/v1_201304101017/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research letter</span>" "titulo" => "Stevens-Johnson syndrome: a case report" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "219" "paginaFinal" => "221" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Yazicioglu, B. Iscan, B. Turgut, O. Yalcin" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Yazicioglu" "email" => array:1 [ 0 => "yazicioglu@superonline.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "B." "apellidos" => "Iscan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "B." "apellidos" => "Turgut" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] ] ] 3 => array:3 [ "nombre" => "O." "apellidos" => "Yalcin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff4" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Pediatric Allergy, Trakya University, Faculty of Medicine, Edirne, Turkey" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Department of Internal Medicine, Trakya University, Faculty of Medicine, Edirne, Turkey" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Department of Pathology, Trakya University, Faculty of Medicine, Edirne, Turkey" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff4" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 734 "Ancho" => 980 "Tamanyo" => 330262 ] ] "descripcion" => array:1 [ "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Squamous epithelium on skin surface is hyperkeratotic. Note full-thickness epithelial necrosis and dermo-epidermal separation on the left corner as well as sparse lymphocyte exocytosis into the epithelium and sparse perivascular leukocyte infiltration of the upper dermis. H&E, X50.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p class="elsevierStylePara elsevierViewall">Stevens-Johnson syndrome (SJS) is a life-threatening vesiculobullous disease characterized by an acute eruption that involves the skin and mucous membranes. Various etiologic factors have been implicated as a cause of SJS, including infection, vaccination, drugs, systemic diseases, physical agents, and food. Drugs are the most commonly blamed.</p><p class="elsevierStylePara elsevierViewall">The incidence of SJS is estimated to be between 1.1 and 7.1 cases per million person-years.<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a> SJS is currently considered to be a part of bullous disease syndromes [SJS, SJS- toxic epidermal necrolysis (TEN) overlap syndrome, and TEN] in which keratinocyte cell death results in subepidermal separation. In SJS, skin detachment is limited to less than 10% of the body surface area (BSA). TEN requires skin detachment of more than 30% of the BSA. An overlap group of SJS/TEN has been defined with erosions between 10% and 30% of the BSA.<a class="elsevierStyleCrossRefs" href="#bib1"><span class="elsevierStyleSup">1–3</span></a> The pathogenesis of SJS has yet to be clarified.</p><p class="elsevierStylePara elsevierViewall">We report a 10-year-old male patient who was admitted to our department with a widespread bullous, erythematous pruritic eruption, bilateral conjunctivitis, oedema of lips and eyelids, haemorrhagic crusts of the lips, superficial erosions of the hard palate, an ulceration on the penile meatus (<a class="elsevierStyleCrossRef" href="#fig1">Fig. 1</a>), and high fever (38.2<span class="elsevierStyleHsp" style=""></span>°C). The symptoms first started 2 days before, approximately 7<span class="elsevierStyleHsp" style=""></span>h after intramuscular administration of the 2nd dose of cefazolin (2×500<span class="elsevierStyleHsp" style=""></span>mg, i.m) which had been prescribed with the diagnosis of acute pharyngitis. He did not take any other drug apart from the antibiotics. He had no history of adverse drug reactions and had not been treated with cefazolin before. Other personal and family history was unremarkable. The clinical diagnosis of drug induced SJS was made with epidermal detachment of 7–8% of total body surface area.<a class="elsevierStyleCrossRefs" href="#bib1"><span class="elsevierStyleSup">1–3</span></a></p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">Laboratory results on admission revealed WBC count, 2330/mm<span class="elsevierStyleSup">3</span>; lymphocytes, 25%; platelets, 160000/mm<span class="elsevierStyleSup">3</span>; erythrocyte sedimentation rate (ESR), 36/h; C-reactive protein, 5.08<span class="elsevierStyleHsp" style=""></span>mg/dl (0-1); aspartate aminotransferase (AST), 54<span class="elsevierStyleHsp" style=""></span>U/l (15-41); alanine aminotransferase (ALT), 16U/l (14-54). Blood urea nitrogen (BUN), 41<span class="elsevierStyleHsp" style=""></span>mg/dl; creatinin and urine analysis were normal. Serum Na, 131<span class="elsevierStyleHsp" style=""></span>mEq/l; K, 4.6<span class="elsevierStyleHsp" style=""></span>mEq/l; total protein, 5.7<span class="elsevierStyleHsp" style=""></span>gr/dl; albumin, 2.6<span class="elsevierStyleHsp" style=""></span>gr/dl.</p><p class="elsevierStylePara elsevierViewall">Haemoculture and swab culture from skin lesions were negative. Serum cold haemagglutinin titers and viral serology were negative.</p><p class="elsevierStylePara elsevierViewall">With immunophenotypic analysis (Coulter Epics XL), absolute numbers of peripheral blood lymphocytes were calculated as: CD19<span class="elsevierStyleSup">+</span>, 136; CD4<span class="elsevierStyleSup">+</span>, 156; CD8<span class="elsevierStyleSup">+</span>, 236 (CD4<span class="elsevierStyleSup">+</span>/CD8<span class="elsevierStyleSup">+</span> ratio, 0.66), and CD3<span class="elsevierStyleSup">−</span>CD16<span class="elsevierStyleSup">+</span> CD56<span class="elsevierStyleSup">+</span> (NK cells), 29<span class="elsevierStyleHsp" style=""></span>cells/μl. The predominant phenotype of the gated lymphocytes among blister fluid mononuclear cells was CD8+ (48.7%). Other cell subsets were CD19<span class="elsevierStyleSup">+</span> (0.2%), CD4+ (25.2%), and NK cells (3.4%).</p><p class="elsevierStylePara elsevierViewall">Microscopically, the surface epithelium of the skin biopsy was hyperkeratotic. There was full-thickness epithelial necrosis, dermo-epidermal separation, as well as sparse lymphocyte exocytosis into the epithelium, and sparse perivascular leukocyte infiltration of the upper dermis (<a class="elsevierStyleCrossRef" href="#fig2">Fig. 2</a>). The epidermal lymphocytes showed labelling with anti-CD8 by immunohistochemical staining. These changes were considered to be consistent with SJS (<a class="elsevierStyleCrossRef" href="#fig3">Fig. 3</a>).</p><elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="fig3"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">The patient's symptoms began to improve after initiation of intravenous methylprednisolone and hydroxizine in conjunction with supportive therapy. Corticosteroid dose was gradually tapered after the 4th day of treatment. He had gastrointestinal bleeding during his hospitalisation. This is attributed to the gastrointestinal system involvement in SJS. The patient was discharged with markedly clinical improvement 12 days after admission. Follow-up visits were conducted by our Ophthalmology Clinic for his dry eye syndrome as a long term effect of SJS. The patient was patch tested with cefazolin 2 months after the reaction. However, he removed the test tape after 24<span class="elsevierStyleHsp" style=""></span>h because of itching and did not return for evaluation.</p><p class="elsevierStylePara elsevierViewall">SJS is an uncommon and potentially serious mucocutaneous disease. More than 100 drugs have been associated with the development of SJS and TEN.<a class="elsevierStyleCrossRef" href="#bib4"><span class="elsevierStyleSup">4</span></a> Cefazolin would be responsible for inducing SJS in our patient. The role of corticosteroid therapy in SJS is still controversial.<a class="elsevierStyleCrossRefs" href="#bib1"><span class="elsevierStyleSup">1,2,5</span></a> Our patient's symptoms improved after initiation of intravenous methylprednisolone and hydroxizine in conjunction with supportive therapy.</p><p class="elsevierStylePara elsevierViewall">The pathogenesis of SJS has yet to be clarified. The scenario suggested by today's literature points towards drug-specific CD8+cytotoxic T cells utilising perforin/granzyme B trigger keratinocyte apoptosis.<a class="elsevierStyleCrossRef" href="#bib6"><span class="elsevierStyleSup">6</span></a> In TEN, several studies stated a predominance of CD8+ T lymphocytes along dermoepidermal junction, in the epidermis, or in the blister fluid of early blisters.<a class="elsevierStyleCrossRefs" href="#bib7"><span class="elsevierStyleSup">7–11</span></a> In keeping with these findings, Behrendt et al.<a class="elsevierStyleCrossRef" href="#bib12"><span class="elsevierStyleSup">12</span></a> reported a higher percentage of perforin positive CD8+ T lymphocytes in PBMC of patients with SJS on the day of their admission than in healthy donors. Similarly, Psodas et al.<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a> showed increased mRNA expression of perforin and granzyme B in PBMC of SJS and TEN patients compared to controls and suggested that there may even be association between disease severity and perforin and granzyme B levels. The expression levels were markedly higher in mononuclear cells obtained from blister fluid compared to PBMC, suggesting local production of both of these transcripts.<a class="elsevierStyleCrossRef" href="#bib6"><span class="elsevierStyleSup">6</span></a> These findings lend further support to the theory that keratinocyte apoptosis is triggered by drug-specific cytotoxic T lymphocytes (CTL) using the perforin/granzyme B pathway. Subsequently, there may be an expansion of apoptosis involving the interaction of either membrane-bound or soluble Fas ligand (sFasL) with its receptor Fas. However, the cellular source of sFasL remains controversial, with both peripheral lymphocytes and keratinocytes themselves as potential candidates.<a class="elsevierStyleCrossRefs" href="#bib2"><span class="elsevierStyleSup">2,6</span></a></p><p class="elsevierStylePara elsevierViewall">Our data are in agreement with previous reports of the presence of CD8<span class="elsevierStyleSup">+</span> T cells at the site of skin lesions in patients with SJS,<a class="elsevierStyleCrossRefs" href="#bib7"><span class="elsevierStyleSup">7–12</span></a> and further support the involvement of cytotoxic CD8<span class="elsevierStyleSup">+</span>T cells in eliciting tissue damage in SJS. We concluded that the cells contained in the blister fluid during SJS would provide an interesting way to investigate the immune mechanisms in bullous drug reactions.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1474 "Ancho" => 980 "Tamanyo" => 258855 ] ] "descripcion" => array:1 [ "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Vesiculo-bullous skin and mucous membrane lesions with detachment of epidermis.</p>" ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 734 "Ancho" => 980 "Tamanyo" => 330262 ] ] "descripcion" => array:1 [ "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Squamous epithelium on skin surface is hyperkeratotic. Note full-thickness epithelial necrosis and dermo-epidermal separation on the left corner as well as sparse lymphocyte exocytosis into the epithelium and sparse perivascular leukocyte infiltration of the upper dermis. H&E, X50.</p>" ] ] 2 => array:7 [ "identificador" => "fig3" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 735 "Ancho" => 980 "Tamanyo" => 330980 ] ] "descripcion" => array:1 [ "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Note spare anti-CD8 immunoreactive lymphocytes in the epithelium. CD8, x100.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Letko" 1 => "D.N. Papaliodis" 2 => "G.N. Papaliodis" 3 => "Y.J. Daoud" 4 => "A.R. Ahmed" 5 => "C.S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 113 | 13 | 126 |
| 2024 September | 212 | 29 | 241 |
| 2024 August | 170 | 27 | 197 |
| 2024 July | 151 | 31 | 182 |
| 2024 June | 145 | 21 | 166 |
| 2024 May | 127 | 12 | 139 |
| 2024 April | 145 | 17 | 162 |
| 2024 March | 131 | 17 | 148 |
| 2024 February | 149 | 7 | 156 |
| 2024 January | 194 | 20 | 214 |
| 2023 December | 137 | 15 | 152 |
| 2023 November | 271 | 27 | 298 |
| 2023 October | 339 | 28 | 367 |
| 2023 September | 138 | 11 | 149 |
| 2023 August | 199 | 11 | 210 |
| 2023 July | 188 | 23 | 211 |
| 2023 June | 238 | 47 | 285 |
| 2023 May | 194 | 26 | 220 |
| 2023 April | 191 | 10 | 201 |
| 2023 March | 192 | 29 | 221 |
| 2023 February | 146 | 19 | 165 |
| 2023 January | 135 | 16 | 151 |
| 2022 December | 146 | 24 | 170 |
| 2022 November | 164 | 20 | 184 |
| 2022 October | 144 | 29 | 173 |
| 2022 September | 165 | 14 | 179 |
| 2022 August | 185 | 9 | 194 |
| 2022 July | 130 | 18 | 148 |
| 2022 June | 167 | 22 | 189 |
| 2022 May | 222 | 27 | 249 |
| 2022 April | 227 | 35 | 262 |
| 2022 March | 181 | 21 | 202 |
| 2022 February | 167 | 31 | 198 |
| 2022 January | 163 | 19 | 182 |
| 2021 December | 154 | 19 | 173 |
| 2021 November | 160 | 28 | 188 |
| 2021 October | 180 | 26 | 206 |
| 2021 September | 156 | 25 | 181 |
| 2021 August | 149 | 39 | 188 |
| 2021 July | 84 | 26 | 110 |
| 2021 June | 59 | 14 | 73 |
| 2021 May | 63 | 11 | 74 |
| 2021 April | 69 | 16 | 85 |
| 2021 March | 50 | 8 | 58 |
| 2021 February | 13 | 11 | 24 |
| 2021 January | 9 | 4 | 13 |
| 2020 December | 2 | 0 | 2 |
| 2018 February | 9 | 2 | 11 |
| 2018 January | 12 | 0 | 12 |
| 2017 December | 10 | 3 | 13 |
| 2017 November | 22 | 3 | 25 |
| 2017 October | 11 | 1 | 12 |
| 2017 September | 12 | 1 | 13 |
| 2017 August | 7 | 7 | 14 |
| 2017 July | 21 | 4 | 25 |
| 2017 June | 16 | 8 | 24 |
| 2017 May | 28 | 6 | 34 |
| 2017 April | 34 | 4 | 38 |
| 2017 March | 25 | 52 | 77 |
| 2017 February | 29 | 2 | 31 |
| 2017 January | 19 | 1 | 20 |
| 2016 December | 24 | 4 | 28 |
| 2016 November | 29 | 4 | 33 |
| 2016 October | 48 | 5 | 53 |
| 2016 September | 59 | 6 | 65 |
| 2016 August | 30 | 6 | 36 |
| 2016 July | 18 | 3 | 21 |
| 2016 June | 18 | 4 | 22 |
| 2016 May | 24 | 19 | 43 |
| 2016 April | 25 | 10 | 35 |
| 2016 March | 24 | 14 | 38 |
| 2016 February | 32 | 17 | 49 |
| 2016 January | 27 | 21 | 48 |
| 2015 December | 17 | 20 | 37 |
| 2015 November | 25 | 11 | 36 |
| 2015 October | 43 | 8 | 51 |
| 2015 September | 27 | 5 | 32 |
| 2015 August | 41 | 2 | 43 |
| 2015 July | 108 | 3 | 111 |
| 2015 June | 41 | 3 | 44 |
| 2015 May | 43 | 4 | 47 |
| 2015 April | 42 | 8 | 50 |
| 2015 March | 26 | 5 | 31 |
| 2015 February | 13 | 2 | 15 |
| 2015 January | 17 | 0 | 17 |
| 2014 December | 18 | 9 | 27 |
| 2014 November | 18 | 3 | 21 |
| 2014 October | 14 | 3 | 17 |
| 2014 September | 21 | 2 | 23 |
| 2014 August | 11 | 0 | 11 |
| 2014 July | 14 | 2 | 16 |
| 2014 June | 17 | 1 | 18 |
| 2014 May | 9 | 3 | 12 |
| 2014 April | 6 | 2 | 8 |
| 2014 March | 76 | 13 | 89 |
| 2014 February | 81 | 9 | 90 |
| 2014 January | 102 | 9 | 111 |
| 2013 December | 67 | 9 | 76 |
| 2013 November | 78 | 6 | 84 |
| 2013 October | 73 | 10 | 83 |
| 2013 September | 86 | 6 | 92 |
| 2013 August | 85 | 13 | 98 |
| 2013 July | 66 | 11 | 77 |
| 2013 June | 36 | 4 | 40 |
| 2013 May | 45 | 6 | 51 |
| 2013 April | 45 | 10 | 55 |
| 2013 March | 41 | 8 | 49 |
| 2013 February | 13 | 5 | 18 |
| 2013 January | 8 | 2 | 10 |
| 2012 December | 3 | 2 | 5 |
| 2012 November | 1 | 4 | 5 |
| 2012 October | 2 | 1 | 3 |
| 2009 June | 2381 | 0 | 2381 |
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