Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Hipo-Hidrose/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pele/patologiaRESUMO
Background: Immune checkpoint blockade therapies including cytotoxic-T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) inhibitors have become indispensable tools for treating melanoma and other cancers. An increasing number of diverse cutaneous adverse reactions to immunotherapy have been documented in the literature and have been reported to affect up to 40% of patients treated with targeted therapies. Method & results: Herein, we report a case of a patient with metastatic melanoma treated with checkpoint inhibitor therapy who developed vitiligo, gastritis and hepatitis, all identified as adverse immune events and attributable to his immunotherapy regimen. He subsequently developed acquired idiopathic generalized hypohidrosis with biopsy of lesional skin demonstrating a peri-eccrine lymphocytic infiltrate. Conclusion: These findings suggest this acquired generalized hypohidrosis represents a lymphocyte-mediated adverse immune event related to this patient's checkpoint inhibitor therapy.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Hipo-Hidrose/induzido quimicamente , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Hipo-Hidrose/imunologia , Ipilimumab/uso terapêutico , Masculino , Melanoma/imunologia , Nivolumabe/uso terapêuticoRESUMO
Based on epidemiological data it was believed that botulinumtoxin type D (BT-D) may not block human cholinergic synapses. We wanted to investigate BT-D's effect on the autonomic cholinergic synapse in humans. For this, we compared in four volunteers intraindividually the hypohidrotic effect of intradermal BT-D and BT-A in Minor's iodine starch sweat test. Altogether, we studied BT-D in doses of 4, 8, 16 and 32MU and BT-A in doses of 2, 4, 8 and 16MU at weekly intervals throughout a period of 13 weeks. All BT doses were diluted in 0.2 ml 0.9% NaCl/H2O. Overall 704 data points were collected. Combined over all four subjects and all four doses BT-D's hypohidrotic effect intensity was half of BT-A's. BT-D's effect peaked around 5 weeks, BT-A's around 7 weeks. BT-D's effect duration was around 12 weeks, of BT-A's was around 14 weeks. For both BT types the hypohidrotic effect was dose dependent. BT-D, when injected intradermally, can block autonomic cholinergic synapses in humans. Compared to BT-A, BT-D's effect intensity was half and its effect duration was some 2 weeks shorter. With its weaker and shorter effect BT-D does not seem to promise therapeutic effects superior to BT-A.
Assuntos
Inibidores da Liberação da Acetilcolina/administração & dosagem , Toxinas Botulínicas/administração & dosagem , Neurônios Colinérgicos/efeitos dos fármacos , Hipo-Hidrose/induzido quimicamente , Sinapses/efeitos dos fármacos , Inibidores da Liberação da Acetilcolina/toxicidade , Adulto , Toxinas Botulínicas/toxicidade , Neurônios Colinérgicos/fisiologia , Relação Dose-Resposta a Droga , Humanos , Hipo-Hidrose/diagnóstico , Masculino , Pessoa de Meia-Idade , Sinapses/fisiologiaRESUMO
BACKGROUND: Different diffusion of different botulinum toxin type A (BoNTA) preparations may account for differences in outcomes in cosmetic clinical practice. OBJECTIVES: A double-blind, randomized, self-controlled study was performed to evaluate the diffusion characteristics of onabotulinumtoxinA and a Chinese type A botulinum toxin (CBTX-A). MATERIALS AND METHODS: Healthy volunteers (N = 20) were recruited to receive a 0.05-mL (2 U) injection of BoTNA at four forehead sites (medial forehead (subcutaneous (SC)) and temporal forehead (intradermal (ID))). On day 14, the Minor's iodine starch test was performed and photographs were taken for calculating the area and dimensions of anhydrotic area. RESULTS: When BoNTAs were different, the anhidrosis ID area was significantly greater with CBTX-A than onabotulinumtoxinA, the vertical dimension was significantly longer with CBTX-A ID than onabotulinumtoxinA ID and the horizontal dimension was significantly greater with CBTX-A ID than onabotulinumtoxinA ID. The area of anhidrosis SC was significantly greater with CBTX-A than onabotulinumtoxinA. When injection depths were different, the mean horizontal dimension was significantly greater with onabotulinumtoxinA SC than ID. Comparing the dimension of the same BoNTA and injection method, the vertical dimension was significantly greater than the horizontal dimension. CONCLUSION: OnabotulinumtoxinA diffuses less than CBTX-A. ID injection technique may result in less diffusion than SC.
Assuntos
Toxinas Botulínicas Tipo A/farmacocinética , Testa , Fármacos Neuromusculares/farmacocinética , Adulto , Toxinas Botulínicas Tipo A/química , Método Duplo-Cego , Feminino , Humanos , Hipo-Hidrose/induzido quimicamente , Pessoa de Meia-Idade , Fármacos Neuromusculares/químicaAssuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hipo-Hidrose/induzido quimicamente , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Carboplatina/efeitos adversos , Toxidermias/etiologia , Feminino , Transtornos de Estresse por Calor/induzido quimicamente , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Paclitaxel/efeitos adversosAssuntos
Anestésicos Locais/efeitos adversos , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Bupivacaína/efeitos adversos , Rubor/induzido quimicamente , Hipo-Hidrose/induzido quimicamente , Adenocarcinoma/cirurgia , Idoso , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Complicações Pós-Operatórias/induzido quimicamenteRESUMO
A 2-year-old mentally retarded boy with frontal lobe epilepsy presented with an episode that resembled heat stroke during the administration of zonisamide. He developed hyperpyrexia with oligohidrosis and central neurological symptoms, including, chorea-like involuntary movements, resting tremor, and cogwheel rigidity. A sweat test using pilocarpine iontophoresis revealed a marked reduction in the sweat response, which suggested a postganglionic sweating dysfunction. A skin biopsy examined by light and electron microscopy showed no morphological abnormality in the sweat glands. The oligohidrosis caused by zonisamide was reversible in that the patient regained the ability to sweat within 2 weeks of the cessation of drug administration. Children receiving zonisamide should be monitored for oligohidrosis and the development of neurological symptoms associated with an elevation of body temperature.