Case and Research Letter
Acute Generalized Exanthematous Pustulosis Induced by Galantamine
Pustulosis exantemática aguda generalizada inducida por galantamina
M.P. Pérez-García
, J.M. Sánchez Motillas, A. Mateu-Puchades, T. Díaz-Corpas
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Servicio de Dermatología del Hospital Dr. Peset, Valencia, Spain
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Pérez-García, J.M. Sánchez Motillas, A. Mateu-Puchades, T. Díaz-Corpas" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.P." "apellidos" => "Pérez-García" "email" => array:1 [ 0 => "glupipg@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Sánchez Motillas" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Mateu-Puchades" ] 3 => array:2 [ "nombre" => "T." "apellidos" => "Díaz-Corpas" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología del Hospital Dr. Peset, Valencia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pustulosis exantemática aguda generalizada inducida por galantamina" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 750 "Ancho" => 1000 "Tamanyo" => 227994 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Subcorneal pustule and perivascular infiltrate of lymphocytes and eosinophils. Hematoxylin-eosin, original magnification ×40.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">At present, Alzheimer disease has no effective treatment due to its complex pathophysiology, which is not yet completely understood. However, abnormal cholinergic function has been shown to play an important role in the many types of brain neurotransmitter dysfunction found in Alzheimer patients. Accordingly, cholinesterase inhibitors that strengthen cholinergic neurotransmission, including galantamine, donepezil, and rivastigmine, are considered first-line drugs for the treatment of mild to moderate Alzheimer disease.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the first reported case of acute generalized exanthematous pustulosis (AGEP) following the administration of galantamine.</p><p id="par0015" class="elsevierStylePara elsevierViewall">An 81-year-old woman with a history of hypertension, dyslipidemia, spondyloarthropathy, and recently diagnosed Alzheimer-type degenerative dementia was brought to our department for emergency examination. She presented with a generalized itchy skin rash that had developed 5 days earlier, associated with a sensation of poor temperature regulation and no measurable fever.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The physical examination showed large erythematous, edematous plaques on the trunk and limbs with multiple nonfollicular monomorphic pustules. The lesions on the limbs were more isolated and had a target morphology (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Small isolated areas of superficial epidermal detachment were also observed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">No involvement of the oral or genital mucosa or ocular discomfort was observed. Palpation did not reveal visceromegaly or enlarged lymph nodes.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The only relevant recent change in medication was the addition of galantamine, which had been prescribed by the neurologist in the preceding month to treat the patient's dementia. Galantamine was being administered in increasing doses and the dosage of all other drugs had not changed.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Based on the suspected diagnosis of AGEP induced by galantamine, the patient was admitted to hospital for monitoring and treatment with the drug was discontinued. Her symptoms were treated with fluid therapy, oral antihistamines, and local dressings.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Histology revealed subcorneal pustules filled with neutrophils, edema in the papillary dermis, and a slight perivascular infiltrate of lymphocytes and eosinophils (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Blood tests showed intense leukocytosis (38 × 10<span class="elsevierStyleSup">9</span>/L) with neutrophilia (34.6 × 10<span class="elsevierStyleSup">9</span>/L), normal blood cell morphology, and increased levels of acute phase reactants, including fibrinogen and C-reactive protein.</p><p id="par0050" class="elsevierStylePara elsevierViewall">During her stay in hospital, the patient's condition improved rapidly with a reduction in rash severity, no progression of the de-epidermized areas, and a return to normal blood test results. On examination 2 weeks after withdrawal of galantamine the lesions had completely disappeared and only slight superficial scaling was observed.</p><p id="par0055" class="elsevierStylePara elsevierViewall">AGEP is a rare condition characterized by an initially acute nonbacterial pustular rash that is frequently febrile and resolves quickly and spontaneously.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Over 90% of AGEP cases are induced by medication, mainly antibiotics such as macrolides and β-lactams.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Other drugs associated with AGEP include nonsteroidal anti-inflammatory drugs, antimycotics, calcium channel blockers, paracetamol, carbamazepine, and hydroxychloroquine.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Based on the frequently positive patch test results reported in these patients, the presence of neutrophilia in peripheral blood, and the accumulation of neutrophils in the lesions, it is currently believed that AGEP is mediated by T cells. However, the specific underlying mechanism of this condition is still unknown.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Clinically, AGEP presents as a febrile pustular rash that appears suddenly and is preceded by an itching or burning sensation that starts on the face and intertriginous areas and spreads to the trunk and limbs.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Typically, hundreds of sterile nonfollicular pustules (<5<span class="elsevierStyleHsp" style=""></span>mm) develop on large erythematous, edematous areas. The lesions sometimes develop an erythema multiforme-like target morphology, as was the case in our patient.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Following withdrawal of the drug, generalized superficial scaling develops and the lesions completely resolve, usually after a period of 2 weeks.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The most frequent laboratory findings are intense leukocytosis with neutrophilia and, occasionally, eosinophilia.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Characteristic histologic findings include subcorneal spongiform pustules associated with foci of necrotic keratinocytes, edema in the papillary dermis, and perivascular infiltrate containing lymphocytes, neutrophils, and a few eosinophils.</p><p id="par0090" class="elsevierStylePara elsevierViewall">A diagnosis of AGEP is based on a combination of medication history, clinical course, and pathologic findings. Patch tests are a useful way to confirm the diagnosis, although it should be noted that the results are positive in only 50% of cases.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Treatment consists of withdrawing the causative agent and symptomatic treatment with antihistamines, antipyretics, or topical corticosteroids.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In our review of the literature we found no reported cases of AGEP induced by galantamine, although there are reports involving other cholinergic drugs, including varenicline, a partial agonist of the receptor acetylcholine that was approved by the FDA in 2006 for the treatment of tobacco addiction.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In our patient the diagnosis was based on clinical, histologic, and laboratory criteria. We identified galantamine as the probable cause because of its recent introduction, the absence of any other triggering agents, and the rapid resolution of the symptoms upon withdrawal of the drug.</p><p id="par0110" class="elsevierStylePara elsevierViewall">We present this case because it involves an emergent drug being used to treat Alzheimer disease, a condition that has recently been reported to affect 5% to 10% of the Spanish population over 65 years of age.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-06-05" "fechaAceptado" => "2012-10-14" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pérez-García MP, Sánchez Motillas JM, Mateu-Puchades A, Díaz-Corpas T. Pustulosis exantemática aguda generalizada inducida por galantamina. Actas Dermosifiliogr. 2013;104:930–931.</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" => 1176 "Ancho" => 999 "Tamanyo" => 148856 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous, edematous plaques with multiple nonfollicular pustules.</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" => 750 "Ancho" => 1000 "Tamanyo" => 227994 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Subcorneal pustule and perivascular infiltrate of lymphocytes and eosinophils. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 11 | 10 | 21 |
| 2024 Octubre | 83 | 53 | 136 |
| 2024 Septiembre | 68 | 31 | 99 |
| 2024 Agosto | 111 | 56 | 167 |
| 2024 Julio | 91 | 39 | 130 |
| 2024 Junio | 99 | 44 | 143 |
| 2024 Mayo | 101 | 38 | 139 |
| 2024 Abril | 67 | 21 | 88 |
| 2024 Marzo | 66 | 36 | 102 |
| 2024 Febrero | 54 | 39 | 93 |
| 2024 Enero | 63 | 33 | 96 |
| 2023 Diciembre | 50 | 16 | 66 |
| 2023 Noviembre | 41 | 33 | 74 |
| 2023 Octubre | 41 | 13 | 54 |
| 2023 Septiembre | 44 | 26 | 70 |
| 2023 Agosto | 35 | 17 | 52 |
| 2023 Julio | 51 | 45 | 96 |
| 2023 Junio | 47 | 25 | 72 |
| 2023 Mayo | 55 | 26 | 81 |
| 2023 Abril | 29 | 24 | 53 |
| 2023 Marzo | 44 | 28 | 72 |
| 2023 Febrero | 59 | 21 | 80 |
| 2023 Enero | 46 | 20 | 66 |
| 2022 Diciembre | 40 | 38 | 78 |
| 2022 Noviembre | 25 | 23 | 48 |
| 2022 Octubre | 33 | 29 | 62 |
| 2022 Septiembre | 23 | 46 | 69 |
| 2022 Agosto | 27 | 35 | 62 |
| 2022 Julio | 31 | 38 | 69 |
| 2022 Junio | 20 | 21 | 41 |
| 2022 Mayo | 58 | 45 | 103 |
| 2022 Abril | 38 | 37 | 75 |
| 2022 Marzo | 52 | 48 | 100 |
| 2022 Febrero | 28 | 24 | 52 |
| 2022 Enero | 23 | 38 | 61 |
| 2021 Diciembre | 44 | 35 | 79 |
| 2021 Noviembre | 41 | 50 | 91 |
| 2021 Octubre | 33 | 50 | 83 |
| 2021 Septiembre | 40 | 44 | 84 |
| 2021 Agosto | 29 | 25 | 54 |
| 2021 Julio | 25 | 21 | 46 |
| 2021 Junio | 31 | 41 | 72 |
| 2021 Mayo | 26 | 33 | 59 |
| 2021 Abril | 56 | 49 | 105 |
| 2021 Marzo | 34 | 32 | 66 |
| 2021 Febrero | 43 | 18 | 61 |
| 2021 Enero | 28 | 25 | 53 |
| 2020 Diciembre | 27 | 15 | 42 |
| 2020 Noviembre | 22 | 14 | 36 |
| 2020 Octubre | 17 | 3 | 20 |
| 2020 Septiembre | 30 | 10 | 40 |
| 2020 Agosto | 22 | 22 | 44 |
| 2020 Julio | 35 | 14 | 49 |
| 2020 Junio | 23 | 16 | 39 |
| 2020 Mayo | 22 | 15 | 37 |
| 2020 Abril | 41 | 15 | 56 |
| 2020 Marzo | 33 | 16 | 49 |
| 2020 Febrero | 4 | 2 | 6 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 8 | 6 | 14 |
| 2019 Noviembre | 4 | 9 | 13 |
| 2019 Octubre | 0 | 3 | 3 |
| 2019 Septiembre | 4 | 7 | 11 |
| 2019 Agosto | 4 | 10 | 14 |
| 2019 Julio | 4 | 17 | 21 |
| 2019 Junio | 6 | 35 | 41 |
| 2019 Mayo | 5 | 47 | 52 |
| 2019 Abril | 3 | 17 | 20 |
| 2019 Marzo | 4 | 12 | 16 |
| 2019 Febrero | 2 | 1 | 3 |
| 2019 Enero | 3 | 5 | 8 |
| 2018 Diciembre | 2 | 7 | 9 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 6 | 0 | 6 |
| 2018 Septiembre | 5 | 1 | 6 |
| 2018 Agosto | 0 | 3 | 3 |
| 2018 Julio | 0 | 1 | 1 |
| 2018 Junio | 0 | 2 | 2 |
| 2018 Mayo | 0 | 3 | 3 |
| 2018 Febrero | 50 | 4 | 54 |
| 2018 Enero | 44 | 6 | 50 |
| 2017 Diciembre | 31 | 10 | 41 |
| 2017 Noviembre | 36 | 12 | 48 |
| 2017 Octubre | 29 | 6 | 35 |
| 2017 Septiembre | 24 | 4 | 28 |
| 2017 Agosto | 38 | 7 | 45 |
| 2017 Julio | 24 | 11 | 35 |
| 2017 Junio | 44 | 19 | 63 |
| 2017 Mayo | 26 | 7 | 33 |
| 2017 Abril | 30 | 11 | 41 |
| 2017 Marzo | 29 | 36 | 65 |
| 2017 Febrero | 51 | 14 | 65 |
| 2017 Enero | 25 | 11 | 36 |
| 2016 Diciembre | 46 | 15 | 61 |
| 2016 Noviembre | 61 | 9 | 70 |
| 2016 Octubre | 60 | 17 | 77 |
| 2016 Septiembre | 61 | 10 | 71 |
| 2016 Agosto | 45 | 8 | 53 |
| 2016 Julio | 37 | 11 | 48 |
| 2016 Junio | 14 | 9 | 23 |
| 2016 Mayo | 11 | 9 | 20 |
| 2016 Abril | 7 | 1 | 8 |
| 2016 Marzo | 14 | 11 | 25 |
| 2016 Febrero | 10 | 12 | 22 |
| 2016 Enero | 7 | 1 | 8 |
| 2015 Diciembre | 9 | 2 | 11 |
| 2015 Noviembre | 8 | 1 | 9 |
| 2015 Octubre | 6 | 1 | 7 |
| 2015 Septiembre | 6 | 2 | 8 |
| 2015 Agosto | 6 | 6 | 12 |
| 2015 Julio | 33 | 2 | 35 |
| 2015 Junio | 33 | 6 | 39 |
| 2015 Mayo | 38 | 7 | 45 |
| 2015 Abril | 25 | 3 | 28 |
| 2015 Marzo | 19 | 6 | 25 |
| 2015 Febrero | 25 | 3 | 28 |
| 2015 Enero | 26 | 15 | 41 |
| 2014 Diciembre | 20 | 5 | 25 |
| 2014 Noviembre | 16 | 18 | 34 |
| 2014 Octubre | 23 | 13 | 36 |
| 2014 Septiembre | 15 | 4 | 19 |
| 2014 Agosto | 20 | 7 | 27 |
| 2014 Julio | 13 | 7 | 20 |
| 2014 Junio | 24 | 7 | 31 |
| 2014 Mayo | 22 | 12 | 34 |
| 2014 Abril | 11 | 4 | 15 |
| 2014 Marzo | 17 | 8 | 25 |
| 2014 Febrero | 25 | 6 | 31 |
| 2014 Enero | 13 | 10 | 23 |
| 2013 Diciembre | 14 | 3 | 17 |
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