Case and Research Letters
Coma Blisters After an Overdose of Central Nervous System Depressants
Ampollas del coma tras sobredosis de fármacos depresores del sistema nervioso central
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Vázquez-Osorio, P. Gonzalvo-Rodríguez, E. Rodríguez-Díaz" "autores" => array:3 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "Vázquez-Osorio" "email" => array:1 [ 0 => "rogivaos@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "P." "apellidos" => "Gonzalvo-Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Rodríguez-Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ampollas del coma tras sobredosis de fármacos depresores del sistema nervioso central" ] ] "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" => 1248 "Ancho" => 850 "Tamanyo" => 296729 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Focal epithelial necrosis in the eccrine coils with neutrophilic periglandular infiltration (hematoxylin-eosin, original magnification ×20). B, Predominantly neutrophilic perivascular and periadnexal infiltrates and foci of fibrinoid necrosis in the walls of dermal capillaries, with neutrophilic infiltration of the walls (hematoxylin-eosin, original magnification ×20).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The term <span class="elsevierStyleItalic">coma blisters</span> refers to a condition that occurs in patients who lose consciousness. It was first described in 1812 by Larrey<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> in soldiers with carbon monoxide poisoning. Since then, it has been mainly associated with overdose of drugs and nervous system depressants, such as barbiturates, tricyclic antidepressants, opiates and alcohol; neurological disorders, such as meningoencephalitis, cerebrovascular disease, and cranioencephalic trauma; and metabolic disorders, such as hyperkalemia, hypoglycemia, and diabetic ketoacidosis.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–4</span></a> Coma blisters, however, have also been described in patients without an altered state of conscience, in particular in cases of long immobilization or Wegener granulomatosis.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 24-year-old woman with a history of a personality disorder and occasional consumption of cocaine and amphetamines who was found unconscious in her home. She had taken multiple pills from her regular medication supply (topiramate, duloxetine, quetiapine, and clorazepate).</p><p id="par0015" class="elsevierStylePara elsevierViewall">On arrival at the emergency department, she had a low level of consciousness (score 6 on the Glasgow Coma Scale), pale skin, and reactive mydriatic pupils. Partial improvement (Glasgow Coma Scale 10) was observed following physical stimulation, and the patient was treated with oxygen, fluid therapy, gastric lavage, and activated charcoal.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There was no evidence of acute intracranial lesions on the computed tomography scan. The laboratory workup showed a serum creatine kinase level of 5590<span class="elsevierStyleHsp" style=""></span>U/L and normal kidney function. The urine drug screening test showed high levels of benzodiazepines.</p><p id="par0025" class="elsevierStylePara elsevierViewall">During her first 24<span class="elsevierStyleHsp" style=""></span>hours in hospital, the patient developed asymptomatic skin lesions located mainly on bony prominences. The physical examination showed tense clear fluid-filled blisters on well-delimited erythematous plaques (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A,B). The lesions had an artifactual morphology and were characteristically located on pressure points (metacarpophalangeal joints on the right hand, right hip, and left knee).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The histopathologic examination showed a subepidermal blister with foci of reepithelialization (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) and focal epithelial necrosis of eccrine coils, with periglandular infiltration of neutrophils (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A). Additional findings included dermal, perivascular, and periadnexal infiltrates, which were predominantly neutrophilic, together with foci of fibrinoid necrosis in the walls of the small dermal capillaries and neutrophilic infiltration of the walls (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>B).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Administration of topical antibiotics led to resolution of the lesions within 3 weeks, and there were no signs of scarring or recurrence.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The clinical presentation and histopathologic findings were consistent with a diagnosis of coma blisters.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Clinically, coma blisters are characterized by tense clear or hemorrhagic blisters that develop on erythematous-violaceous macules or plaques of varying size. The lesions typically appear within 24<span class="elsevierStyleHsp" style=""></span>hours of the intake of drugs and within 48 to 72<span class="elsevierStyleHsp" style=""></span>hours of the loss of consciousness. They primarily develop on pressure points, such as fingers and toes, elbows, knees, ankles, and heels. They are self-limiting and heal within days or weeks, without causing scarring or atrophy. The only treatment indicated thus is topical treatment to prevent secondary infections.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Multiple factors have been implicated in the etiology and pathogenesis of coma blisters, including local pressure or friction, generalized hypoxia and tissue ischemia, direct toxicity due to drugs excreted in sweat, immune mechanisms, and vasomotor changes in comatose states.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Although a diagnosis can be established on clinical grounds only, a histopathologic study can be of great use. The main histopathologic findings are subepidermal or intraepidermal blisters and eccrine gland necrosis, mainly affecting the secretory portion. The secretory coils and ducts of the eccrine glands show a granular eosinophilic cytoplasm, ghost nuclei, and irregular membranes. However, the absence of necrosis in these glands does not necessarily rule out a diagnosis of coma blisters. Other possible findings are neutrophil exocytosis, necrosis of dermal or subcutaneous tissue or epidermal appendages, predominantly neutrophilic perivascular infiltrates, focal fibrinoid necrosis of the walls of small capillaries and arterioles, and thrombi in the lumen of dermal vascular structures.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The vascular damage observed in drug-induced coma blisters is probably a consequence rather than a cause of the blisters. Furthermore, the absence of an epidermal infiltrate and the presence of thrombi in the dermal vessels are mainly observed in coma blisters not induced by drugs.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Direct immunofluorescence studies performed in certain cases of coma blisters have shown patched intercellular staining for immunoglobulin (Ig) G, IgA, and C3, together with IgG, IgM, and C3 deposits in dermal vessel walls and epidermal keratinocytes. These findings, however, are nonspecific and are not considered to result from an immune-mediated response.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,10</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, coma blisters are a benign, self-limiting condition that should be suspected in patients who develop pressure blisters several hours after an altered state of consciousness. Although the diagnosis is mainly clinical, correlation of clinical and pathologic findings is necessary to rule out other blistering dermatoses.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => 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: Vázquez-Osorio I, Gonzalvo-Rodríguez P, Rodríguez-Díaz E. Ampollas del coma tras sobredosis de fármacos depresores del sistema nervioso central. Actas Dermosifiliogr. 2017;108:81–83.</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" => 508 "Ancho" => 1500 "Tamanyo" => 72601 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Tense clear fluid-filled blisters on well-delimited erythematous plaques on the metacarpophalangeal joints. B, Similar lesions on the left knee with an artifactual morphology.</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" => 675 "Ancho" => 900 "Tamanyo" => 162042 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Subepidermal blister without inflammatory cells and with foci of reepithelialization (hematoxylin-eosin, original magnification ×4).</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" => 1248 "Ancho" => 850 "Tamanyo" => 296729 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Focal epithelial necrosis in the eccrine coils with neutrophilic periglandular infiltration (hematoxylin-eosin, original magnification ×20). B, Predominantly neutrophilic perivascular and periadnexal infiltrates and foci of fibrinoid necrosis in the walls of dermal capillaries, with neutrophilic infiltration of the walls (hematoxylin-eosin, original magnification ×20).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "“The French campaign”, seventh part of “Memoires de chirurgie militaire et campagnes.”(last)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.D. Larrey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Hist Filoz Med." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 24 | 9 | 33 |
| 2024 October | 113 | 46 | 159 |
| 2024 September | 103 | 20 | 123 |
| 2024 August | 139 | 48 | 187 |
| 2024 July | 135 | 31 | 166 |
| 2024 June | 118 | 31 | 149 |
| 2024 May | 107 | 32 | 139 |
| 2024 April | 83 | 25 | 108 |
| 2024 March | 93 | 32 | 125 |
| 2024 February | 81 | 33 | 114 |
| 2024 January | 79 | 39 | 118 |
| 2023 December | 69 | 19 | 88 |
| 2023 November | 85 | 32 | 117 |
| 2023 October | 96 | 35 | 131 |
| 2023 September | 87 | 39 | 126 |
| 2023 August | 58 | 20 | 78 |
| 2023 July | 79 | 32 | 111 |
| 2023 June | 62 | 21 | 83 |
| 2023 May | 104 | 22 | 126 |
| 2023 April | 61 | 29 | 90 |
| 2023 March | 57 | 26 | 83 |
| 2023 February | 77 | 25 | 102 |
| 2023 January | 61 | 35 | 96 |
| 2022 December | 40 | 34 | 74 |
| 2022 November | 34 | 26 | 60 |
| 2022 October | 23 | 33 | 56 |
| 2022 September | 25 | 40 | 65 |
| 2022 August | 19 | 27 | 46 |
| 2022 July | 25 | 31 | 56 |
| 2022 June | 18 | 23 | 41 |
| 2022 May | 47 | 32 | 79 |
| 2022 April | 69 | 37 | 106 |
| 2022 March | 60 | 37 | 97 |
| 2022 February | 83 | 19 | 102 |
| 2022 January | 102 | 32 | 134 |
| 2021 December | 66 | 33 | 99 |
| 2021 November | 67 | 35 | 102 |
| 2021 October | 81 | 42 | 123 |
| 2021 September | 72 | 26 | 98 |
| 2021 August | 99 | 28 | 127 |
| 2021 July | 84 | 30 | 114 |
| 2021 June | 66 | 30 | 96 |
| 2021 May | 94 | 58 | 152 |
| 2021 April | 139 | 75 | 214 |
| 2021 March | 72 | 27 | 99 |
| 2021 February | 73 | 29 | 102 |
| 2021 January | 52 | 20 | 72 |
| 2020 December | 48 | 20 | 68 |
| 2020 November | 28 | 18 | 46 |
| 2020 October | 35 | 25 | 60 |
| 2020 September | 44 | 12 | 56 |
| 2020 August | 50 | 20 | 70 |
| 2020 July | 47 | 17 | 64 |
| 2020 June | 34 | 36 | 70 |
| 2020 May | 30 | 8 | 38 |
| 2020 April | 22 | 15 | 37 |
| 2020 March | 17 | 16 | 33 |
| 2020 February | 6 | 0 | 6 |
| 2019 December | 4 | 0 | 4 |
| 2019 September | 4 | 0 | 4 |
| 2019 May | 3 | 0 | 3 |
| 2019 April | 0 | 5 | 5 |
| 2019 March | 2 | 0 | 2 |
| 2018 December | 5 | 0 | 5 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 1 | 0 | 1 |
| 2018 September | 2 | 0 | 2 |
| 2018 May | 0 | 1 | 1 |
| 2018 March | 0 | 1 | 1 |
| 2018 February | 35 | 6 | 41 |
| 2018 January | 58 | 9 | 67 |
| 2017 December | 94 | 33 | 127 |
| 2017 November | 59 | 6 | 65 |
| 2017 October | 40 | 5 | 45 |
| 2017 September | 35 | 9 | 44 |
| 2017 August | 37 | 7 | 44 |
| 2017 July | 29 | 6 | 35 |
| 2017 June | 61 | 26 | 87 |
| 2017 May | 36 | 45 | 81 |
| 2017 April | 21 | 53 | 74 |
| 2017 March | 30 | 58 | 88 |
| 2017 February | 44 | 56 | 100 |
| 2017 January | 52 | 71 | 123 |
| 2016 December | 3 | 22 | 25 |
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