Análisis de las notificaciones de úlceras cutáneas inducidas por medicamentos en España / Analysis of notifications of drug-induced skin ulcers in Spain

Las úlceras cutáneas son un serio problema de salud, el cual tiene repercusiones socioeconómicas y laborales muy importantes con una elevada tendencia a la cronicidad y recidiva, estimándose que hasta el 50% de ellas permanecerán activas entre 6 meses y un año. Objetivo: Estudio del papel de los medicamentos en la etiología de las úlceras cutáneas. Material y método: Estudio de todas las notificaciones espontáneas relativas a úlceras cutáneas que constan en la base de datos del Sistema Español de Farmacovigilancia de medicamentos de uso humano.Resultados: Se identificaron 292 notificaciones en las que constaban sospechas de reacción adversa a medicamentos (RAM) del tipo lesión ulcerosa relacionadas con el consumo de medicamentos. Estaban implicados 369 medicamentos que suponen 427 principios activos. Las úlceras fundamentalmente aparecían en mujeres con una media de edad de 56,6 años. Los medicamentos sospechosos más frecuentemente notificados fueron los iSGLT-2, vacunas frente al COVID-19, metotrexato, hidroxicarbamida, trimetropim-sulfametoxazol, foscarnet trisódico hexahidrato, ribavirina, docetaxel, acenocumarol e imiquimod y asociación de lidocaína Hcl-pentosano polisulfato sodio-triamcinolona acetónido. Discusión: Numerosos medicamentos tienen como reacción adversa la aparición de úlceras. No debería descartarse esta posibilidad ante la aparición de una lesión cutánea nueva tras la administración de un nuevo medicamento dado que el 25% de las RAM eran desconocidas en el momento de su notificación, como eran los casos de úlceras asociadas a los i-SGLT2 y a las vacunas contra el COVID al inicio de su comercialización; sin embargo, gracias al hecho de seguir notificando las sospechas de RAM, se crearon alertas sanitarias advirtiendo de este hecho y es por ello que aconsejamos seguir notificando cualquier sospecha de RAM a los sistemas regionales de farmacovigilancia.(AU)

Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year. Aim: To study the role of drugs in the aetiology of skin ulcers. Material and method: A comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database. Results: A total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide. Discussion: Numerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.(AU)

[Analysis of notifications of drug-induced skin ulcers in Spain]. / Análisis de las notificaciones de úlceras cutáneas inducidas por medicamentos en España.

Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year. AIM: To study the role of drugs in the aetiology of skin ulcers. MATERIAL AND METHOD: A comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database. RESULTS: A total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide. DISCUSSION: Numerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.

Seguridad de los iSGLT-2. Revisión de las reacciones adversas notificadas a nivel nacional / Safety of SGLT2 inhibitors. A review of the adverse drug reactions registered in a national database

Objetivo. Conocer las reacciones adversas medicamentosas (RAM) producidas por los inhibidores del co-transportador sodio-glucosa tipo 2 (iSGLT-2) notificadas en España desde su comercialización. Material y métodos. Estudio de todas las notificaciones existentes en la base de datos del Sistema Español de Farmacovigilancia de medicamentos de uso humano derivadas del uso de iSGLT-2. Resultados. Se recopilaron 311 notificaciones: 169 relacionadas con dapagliflozina (54,34%), 81 con empagliflozina (26,05%) y 61 con canagliflozina (19,61%). El 52,1% de los pacientes fueron mujeres y el 47,6%, hombres. La edad media fue de 62,07±12,176años. Un total de 167 notificaciones (53,7%) fueron clasificadas como no-graves y 144 (46,3%), como graves. Se notificaron 534 RAM, siendo las más frecuentes las infecciones del tracto urinario (37 casos; 6,9%), cetoacidosis diabética (30; 5,6%), balanopostitis (24; 4,5%), cetoacidosis (16; 3%), candidiasis vulvovaginal (16; 3%), mareo (11; 2,1%) y disuria, balanitis candidiásica y prurito vulvovaginal (10; 1,9%). El desenlace de las 534 RAM fue: recuperado sin secuelas, 55,6%; todavía no recuperado, 14%; no recuperado, 4,9%; mortal, 1,1%, y desconocido, 24,3%. Conclusiones. La mayoría de las RAM notificadas son infecciones del tracto urogenital, cetoacidosis y daño renal, y aunque las primeras en su mayoría no fueron graves, la cetoacidosis y el daño renal sí lo fueron, generando ingresos y haciendo peligrar la vida de los pacientes, por lo que creemos que ello nos obliga a hacer una prescripción cuidadosa, a consultar las advertencias publicadas por las autoridades sanitarias y notificar cualquier RAM que se sospeche de esta familia terapéutica para su mejor y más completo conocimiento (AU)

Objective. To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. Material and methods. An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. Results. A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26.05%) to empagliflozin, and 61 (19.61%) to canagliflozin. There was a ratio of 52.1% women to 47.9% men. The mean age was 62.07±12.17years. There were 167 (53.7%) notifications were classified as non-serious and 144 (46.3%) as serious. A total of 534 ADRs were notified, with the most common being urinary tract infections in 37 (6.9%) cases, diabetic ketoacidosis in 30 (5.6%), balanoposthitis in 24 (4.5%), ketoacidosis in 16 (3%), vulvovaginal candidiasis in 16 (3%), dizzy spells in 11 (2.1%), and 10 (1.9%) with dysuria, Candida balanitis, and vulvovaginal pruritus. As regards the outcomes of the 534 ADRs, 55.6% recovered with no sequelae, with 14% still recovering, 4.9% not recovered, fatal in 1.1%, and unknown in 24.3%. Conclusions. The majority of the ADRs notified are infections of the urogenital tract, ketoacidosis, and kidney damage. Although the majority of the former were not serious, the ketoacidosis and kidney damage were, leading to hospital admission and being life threatening in some patients. For these reasons, it is recommended that they are, prescribed with caution, the warnings published by the health authorities consulted, as well as notify any ADR that is suspected in this therapeutic group, in order to improve and provide us with further knowledge (AU)

[Safety of SGLT2 inhibitors. A review of the adverse drug reactions registered in a national database]. / Seguridad de los iSGLT-2. Revisión de las reacciones adversas notificadas a nivel nacional.

OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26.05%) to empagliflozin, and 61 (19.61%) to canagliflozin. There was a ratio of 52.1% women to 47.9% men. The mean age was 62.07±12.17years. There were 167 (53.7%) notifications were classified as non-serious and 144 (46.3%) as serious. A total of 534 ADRs were notified, with the most common being urinary tract infections in 37 (6.9%) cases, diabetic ketoacidosis in 30 (5.6%), balanoposthitis in 24 (4.5%), ketoacidosis in 16 (3%), vulvovaginal candidiasis in 16 (3%), dizzy spells in 11 (2.1%), and 10 (1.9%) with dysuria, Candida balanitis, and vulvovaginal pruritus. As regards the outcomes of the 534 ADRs, 55.6% recovered with no sequelae, with 14% still recovering, 4.9% not recovered, fatal in 1.1%, and unknown in 24.3%. CONCLUSIONS: The majority of the ADRs notified are infections of the urogenital tract, ketoacidosis, and kidney damage. Although the majority of the former were not serious, the ketoacidosis and kidney damage were, leading to hospital admission and being life threatening in some patients. For these reasons, it is recommended that they are, prescribed with caution, the warnings published by the health authorities consulted, as well as notify any ADR that is suspected in this therapeutic group, in order to improve and provide us with further knowledge.

Anemia ferropénica resistente al tratamiento / Refractory iron deficiency anaemia

No disponible

Síndrome de Otelo / Othello síndrome

No disponible

Urgencia en Atención Primaria: cuadros distónicos secundarios a la toma de neurolépticos / No disponible

La distonía se define como un trastorno caracterizado por la existencia de contracciones musculares mantenidas que frecuentemente determinan movimientos repetitivos y detorsión o posturas anómalas. La dificultad inherente al manejo del paciente psiquiátrico provoca, en algunas ocasiones, que la anamnesis no sea todo lo completa que debiera, por lo que cuadros como las distonías pueden pasar desapercibidos o bien ser diagnosticados como cuadros musculares banales. Presentamos dos casos en los que el tratamiento antipsicótico, con risperidona o con olanzapina, ha causado cuadros distónicos etiquetados inicialmente como contracturas musculares. Aunque la causa más frecuente de afectación muscular en Atención Primaria son las contracturas por sobrecarga y la incidencia de distonías, en los pacientes tratados con antipsicóticos atípicos es menor que en los que reciben haloperidol, ante cuadros como los descritos debería incluirse siempre en el diagnóstico diferencial la posibilidad de estar ante una reacción adversa (AU)

Dystonia is defined as a disorder characterized by the existence of sustained muscle contractions that frequently cause repetitive movements and twisting or abnormal postures. Because of the difficulty inherent to the management of the psychiatric patient, the anamnesis sometimes is not as complete as it should be. Thus, pictures such as dystonias may be overlooked or diagnosed as common muscle pictures. We present two cases in which the antipsychotic treatment with risperidone or with olanzapine have caused dystonic pictures that were initially labeled as muscle contractures. Although the most frequent cause of muscle problems in Primary Care are overload contractures and the incidence of dystonias in patients treated with atypical antipsychotics is less than in those who receive haloperidol, when there are pictures such as those described herein, the possibility that there may be an adverse reaction should also be included in the differential diagnosis (AU)

[Ischaemic stroke in a patient with giant aneurysms in the internal carotid]. / Ictus isquémico en un paciente conaneurismas gigantes de carótida interna.

INTRODUCTION: Presentation of signs and symptoms of haemorrhage and/or ischaemia associated to an intracranial dissecting aneurysm is quite frequent. CASE REPORT: A 77-year-old male with a history of a stroke probably due to a cardioembolic causation, and consequently anticoagulation therapy was established. Ten years later, a tomography scan performed because of persistent headaches revealed the presence of fusiform mirror aneurysms in both supraclinoid carotids and early stages of development in the two middle cerebral arteries with predominance of the left-hand side. The anticoagulation therapy was withdrawn. Said aneurysmal alterations did not exist in the previous study, and so they are thought to have originated due to spontaneous dissection. A month later the patient suffered a stroke in the territory of the right middle cerebral artery, caused by partial occlusion of the aneurysm by a thrombus that gave rise to turbulent flow; distal micro-embolisms were also detected in the right middle cerebral artery. Our aetiological hypothesis, in view of the way events progressed, is an arterio-arterial embolism from the aneurysmal thrombus. Supported by data from the specialised literature available on the matter, we decided to implement surgical treatment, although this possibility was rejected by the family; the decision was thus taken to establish an antiaggregating treatment regimen and follow-up. CONCLUSIONS: Giant aneurysms are a potential source of haemorrhagic events, but we must not forget that secondary ischaemic events may also appear; more especially, the aneurysmal lumen can become partially occluded by thrombi and these then become the focus point for embolic events. A complete neuro-ultrasonographic study would be a very appropriate option with which to tailor the therapeutic decision to each patient.

Ictus isquémico en un paciente con aneurismas gigantes de carótida interna / Ischaemic stroke in a patient with giant aneurysms in the internal carotid

La presentación de cuadros hemorrágicos y/o isquémicos asociados a un aneurisma disecante intracranealno es un hecho infrecuente. Caso clínico. Varón de 77 años, con antecedente de accidente cerebrovascular de probable origen cardioembólico, por lo que fue anticoagulado. Diez años después, tras realizarle una tomografía por cefalea persistente,se objetivaron aneurismas fusiformes en espejo en ambas carótidas supraclinoideas e inicio en ambas arterias cerebrales medias con predominio de la izquierda, por lo que se suspendió el tratamiento anticoagulante. Dichas alteraciones aneurismáticas no existían en el estudio previo, por lo que se presupone que se originaron por disección espontánea. Al mes, el paciente sufre un ictus agudo en el territorio de la arteria cerebral media derecha, debido a la oclusión parcial del aneurismapor un trombo que provoca un flujo turbulento, y además se detectan microembolias distales en la arteria cerebral media derecha. Nuestra hipótesis etiológica, según el desarrollo de los acontecimientos, es un embolismo arterioarterial desde eltrombo aneurismático. Apoyados por la bibliografía disponible, decidimos plantear un tratamiento quirúrgico, si bien éste fue rechazado por la familia, por lo que se decidió pautar tratamiento antiagregante y seguimiento. Conclusiones. Los aneurismasgigantes constituyen una fuente potencial de eventos hemorrágicos, pero no debemos olvidar que también pueden aparecer eventos isquémicos secundarios, en especial si puede ocluirse parcialmente la luz aneurismática mediante trombos y ser éstos un foco de eventos embólicos. El estudio neuroecográfico completo sería una opción muy adecuada con la que individualizarla decisión terapéutica de cada paciente

Presentation of signs and symptoms of haemorrhage and/or ischaemia associated to an intracranialdissecting aneurysm is quite frequent. Case report. A 77-year-old male with a history of a stroke probably due to a cardioembolic causation, and consequently anticoagulation therapy was established. Ten years later, a tomography scan performed because of persistent headaches revealed the presence of fusiform mirror aneurysms in both supraclinoid carotids and early stages of development in the two middle cerebral arteries with predominance of the left-hand side. The anticoagulation therapy was withdrawn. Said aneurysmal alterations did not exist in the previous study, and so they are thought to have originated due to spontaneous dissection. A month later the patient suffered a stroke in the territory of the right middle cerebral artery, caused by partial occlusion of the aneurysm by a thrombus that gave rise to turbulent flow; distal microembolisms were also detected in the right middle cerebral artery. Our aetiological hypothesis, in view of the way events progressed, is an arterio-arterial embolism from the aneurysmal thrombus. Supported by data from the specialised literature available on the matter, we decided to implement surgical treatment, although this possibility was rejected by the family; the decision was thus taken to establish an antiaggregating treatment regimen and follow-up. Conclusions. Giant aneurysms are a potential source of haemorrhagic events, but we must not forget that secondary ischaemic events may also appear; more especially, the aneurysmal lumen can become partially occluded by thrombi and these then become the focus point for embolic events. A complete neuro-ultrasonographic study would be a very appropriate option with which to tailor the therapeutic decision to each patient