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
Corresponding author
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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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 13 | 10 | 23 |
| 2024 October | 83 | 53 | 136 |
| 2024 September | 68 | 31 | 99 |
| 2024 August | 111 | 56 | 167 |
| 2024 July | 91 | 39 | 130 |
| 2024 June | 99 | 44 | 143 |
| 2024 May | 101 | 38 | 139 |
| 2024 April | 67 | 21 | 88 |
| 2024 March | 66 | 36 | 102 |
| 2024 February | 54 | 39 | 93 |
| 2024 January | 63 | 33 | 96 |
| 2023 December | 50 | 16 | 66 |
| 2023 November | 41 | 33 | 74 |
| 2023 October | 41 | 13 | 54 |
| 2023 September | 44 | 26 | 70 |
| 2023 August | 35 | 17 | 52 |
| 2023 July | 51 | 45 | 96 |
| 2023 June | 47 | 25 | 72 |
| 2023 May | 55 | 26 | 81 |
| 2023 April | 29 | 24 | 53 |
| 2023 March | 44 | 28 | 72 |
| 2023 February | 59 | 21 | 80 |
| 2023 January | 46 | 20 | 66 |
| 2022 December | 40 | 38 | 78 |
| 2022 November | 25 | 23 | 48 |
| 2022 October | 33 | 29 | 62 |
| 2022 September | 23 | 46 | 69 |
| 2022 August | 27 | 35 | 62 |
| 2022 July | 31 | 38 | 69 |
| 2022 June | 20 | 21 | 41 |
| 2022 May | 58 | 45 | 103 |
| 2022 April | 38 | 37 | 75 |
| 2022 March | 52 | 48 | 100 |
| 2022 February | 28 | 24 | 52 |
| 2022 January | 23 | 38 | 61 |
| 2021 December | 44 | 35 | 79 |
| 2021 November | 41 | 50 | 91 |
| 2021 October | 33 | 50 | 83 |
| 2021 September | 40 | 44 | 84 |
| 2021 August | 29 | 25 | 54 |
| 2021 July | 25 | 21 | 46 |
| 2021 June | 31 | 41 | 72 |
| 2021 May | 26 | 33 | 59 |
| 2021 April | 56 | 49 | 105 |
| 2021 March | 34 | 32 | 66 |
| 2021 February | 43 | 18 | 61 |
| 2021 January | 28 | 25 | 53 |
| 2020 December | 27 | 15 | 42 |
| 2020 November | 22 | 14 | 36 |
| 2020 October | 17 | 3 | 20 |
| 2020 September | 30 | 10 | 40 |
| 2020 August | 22 | 22 | 44 |
| 2020 July | 35 | 14 | 49 |
| 2020 June | 23 | 16 | 39 |
| 2020 May | 22 | 15 | 37 |
| 2020 April | 41 | 15 | 56 |
| 2020 March | 33 | 16 | 49 |
| 2020 February | 4 | 2 | 6 |
| 2020 January | 4 | 0 | 4 |
| 2019 December | 8 | 6 | 14 |
| 2019 November | 4 | 9 | 13 |
| 2019 October | 0 | 3 | 3 |
| 2019 September | 4 | 7 | 11 |
| 2019 August | 4 | 10 | 14 |
| 2019 July | 4 | 17 | 21 |
| 2019 June | 6 | 35 | 41 |
| 2019 May | 5 | 47 | 52 |
| 2019 April | 3 | 17 | 20 |
| 2019 March | 4 | 12 | 16 |
| 2019 February | 2 | 1 | 3 |
| 2019 January | 3 | 5 | 8 |
| 2018 December | 2 | 7 | 9 |
| 2018 November | 2 | 0 | 2 |
| 2018 October | 6 | 0 | 6 |
| 2018 September | 5 | 1 | 6 |
| 2018 August | 0 | 3 | 3 |
| 2018 July | 0 | 1 | 1 |
| 2018 June | 0 | 2 | 2 |
| 2018 May | 0 | 3 | 3 |
| 2018 February | 50 | 4 | 54 |
| 2018 January | 44 | 6 | 50 |
| 2017 December | 31 | 10 | 41 |
| 2017 November | 36 | 12 | 48 |
| 2017 October | 29 | 6 | 35 |
| 2017 September | 24 | 4 | 28 |
| 2017 August | 38 | 7 | 45 |
| 2017 July | 24 | 11 | 35 |
| 2017 June | 44 | 19 | 63 |
| 2017 May | 26 | 7 | 33 |
| 2017 April | 30 | 11 | 41 |
| 2017 March | 29 | 36 | 65 |
| 2017 February | 51 | 14 | 65 |
| 2017 January | 25 | 11 | 36 |
| 2016 December | 46 | 15 | 61 |
| 2016 November | 61 | 9 | 70 |
| 2016 October | 60 | 17 | 77 |
| 2016 September | 61 | 10 | 71 |
| 2016 August | 45 | 8 | 53 |
| 2016 July | 37 | 11 | 48 |
| 2016 June | 14 | 9 | 23 |
| 2016 May | 11 | 9 | 20 |
| 2016 April | 7 | 1 | 8 |
| 2016 March | 14 | 11 | 25 |
| 2016 February | 10 | 12 | 22 |
| 2016 January | 7 | 1 | 8 |
| 2015 December | 9 | 2 | 11 |
| 2015 November | 8 | 1 | 9 |
| 2015 October | 6 | 1 | 7 |
| 2015 September | 6 | 2 | 8 |
| 2015 August | 6 | 6 | 12 |
| 2015 July | 33 | 2 | 35 |
| 2015 June | 33 | 6 | 39 |
| 2015 May | 38 | 7 | 45 |
| 2015 April | 25 | 3 | 28 |
| 2015 March | 19 | 6 | 25 |
| 2015 February | 25 | 3 | 28 |
| 2015 January | 26 | 15 | 41 |
| 2014 December | 20 | 5 | 25 |
| 2014 November | 16 | 18 | 34 |
| 2014 October | 23 | 13 | 36 |
| 2014 September | 15 | 4 | 19 |
| 2014 August | 20 | 7 | 27 |
| 2014 July | 13 | 7 | 20 |
| 2014 June | 24 | 7 | 31 |
| 2014 May | 22 | 12 | 34 |
| 2014 April | 11 | 4 | 15 |
| 2014 March | 17 | 8 | 25 |
| 2014 February | 25 | 6 | 31 |
| 2014 January | 13 | 10 | 23 |
| 2013 December | 14 | 3 | 17 |
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