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1.
Arch. argent. pediatr ; 119(5): e550-e553, oct. 2021. ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1292810

ABSTRACT

Las leucemias son las neoplasias malignas más frecuentes en la infancia; la leucemia linfoblástica aguda (LLA) es la más frecuente. Desde principios de los 80, la adición de metotrexato intratecal a los esquemas de quimioterapia ha sido beneficiosa para prevenir la recidiva en el sistema nervioso central y evitar el uso de radioterapia. Su mecanismo de acción es la inhibición de la enzima dihidrofolato reductasa, por lo que posee múltiples efectos adversos (neurotoxicidad aguda, subaguda o crónica) después de la infusión intratecal o de dosis altas por vía intravenosa.Se presenta un paciente de 11 años con diagnóstico de LLA de línea T (LLA-T), que presenta hemiparesia faciobraquial y afasia de expresión de instauración aguda 8 días después de la administración intratecal de metotrexato. Luego de excluir otras patologías más frecuentes de origen vascular y la evolución típica del cuadro, con resolución espontánea ad integrum de los síntomas, se arribó al diagnóstico de encefalopatía subaguda reversible por metotrexato.


Leukemias are the most frequent malignant neoplasms in childhood; acute lymphoblastic leukemia (ALL) is the most frequent. The addition of intrathecal methotrexate to chemotherapy regimens has been beneficial in preventing relapse to the central nervous system and avoiding the use of radiation therapy. Due to its mechanism of action, by inhibiting the enzyme dihydrofolate reductase, when it is used systemically, it has multiple expected adverse effects such as mucositis, myelosuppression and it has also been observed after intrathecal administration or high intravenous doses, acute, subacute neurotoxicity where stroke like syndrome is found. We present an 11-year-old patient diagnosed with T-ALL, who manifested after 8 days of intrathecal administration of methotrexate, faciobrachial hemiparesis and acute onset expression aphasia. The diagnosis of subacute encephalopathy reversible by methotrexate was reached by excluding other more frequent pathologies and the typical evolution, with spontaneously ad integrum resolution of the symptoms


Subject(s)
Humans , Child , Stroke/chemically induced , Neurotoxicity Syndromes , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/adverse effects
2.
Article in Chinese | WPRIM | ID: wpr-878932

ABSTRACT

To systemically evaluate the efficacy and safety of sinomenine combined with methotrexate(SIN+MTX) in the treatment of rheumatoid arthritis(RA). Literature databases of Wanfang, CNKI, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were retrieved comprehensively for relevant clinical trials. The literature retrieval time was from database establishment to February 4, 2020. The quality of literatures was assessed by the Cochrane Evaluation Handbook 5.1.0, and qualified literature was reviewed and analyzed by using the RevMan 5.3 statistical software. Twenty randomized controlled trials met the inclusion criteria, and were enrolled in the Meta-analysis. The results showed that SIN+MTX remarkably reduced DAS28(MD=-0.85, 95%CI[-1.03,-0.67], P<0.000 01), and improved total efficiency(P<0.000 01). SIN+MTX could inhibit swollen joint count(MD=-1.19, 95%CI[-1.75,-0.63], P<0.000 1), tender joint count(MD=-1.58, 95%CI[-2.89,-0.28], P=0.02) and reduce morning stiffness time(MD=-8.44, 95%CI[-11.82,-5.07], P<0.000 01) compared with control group. The results showed that SIN+MTX was equal to control group in grip strength(SMD=0.20,95%CI[-1.11,1.51],P=0.77). SIN+MTX remarkably alleviated the erythrocyte sedimentation rate(MD=-9.87, 95%CI[-14.52,-5.22], P<0.000 1), C-reactive protein(SMD=-0.30, 95%CI[-0.51,-0.09], P=0.005), and rheumatoid factor(MD=-11.23,95%CI[-13.81,-8.65],P<0.000 01). The frequency of adverse reactions were reduced compared with that in the control group(P<0.000 01). Current clinical studies demonstrate that the efficacy and safety of SIN+MTX in the treatment of RA were superior to control group. However, due to the low quality and quantity of the included studies, high-quality randomized controlled trials are necessary to support the clinical evidences.


Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Drugs, Chinese Herbal/adverse effects , Humans , Methotrexate/adverse effects , Morphinans
3.
Article in Chinese | WPRIM | ID: wpr-887884

ABSTRACT

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoproliferative Disorders , Methotrexate/adverse effects
4.
Article in Portuguese | LILACS | ID: biblio-1146948

ABSTRACT

Introdução: A quimioterapia, uma das formas de tratamento de neoplasias malignas, tem sua administração associada a inúmeras drogas, sendo uma delas o metotrexato (MTX), de alta toxicidade, responsável por inúmeros fatores agravantes para a saúde e bem-estar do paciente. Uma das principais complicações é a mucosite oral, manifestação clínica resultante do tratamento oncológico que pode interferir no tratamento e na cura. Objetivo: Avaliar, comparativamente, por meio de um estudo retrospectivo, o efeito do laser preventivo na ocorrência da mucosite oral quimioinduzida em pacientes com osteossarcoma não metastático submetidos a altas doses de MTX, bem como a intensidade da mucosite oral, utilizando o laser preventivo após os ciclos quimioterápicos contendo o medicamento MTX nos pacientes atendidos no Hospital de Câncer infantojuvenil de Barretos/SP. Método: Estudo de coorte com coleta retrospectiva em prontuários. Os pacientes foram divididos em dois grupos, um submetido à terapia profilática com laser de baixa intensidade após infusão do MTX e outro grupo não submetido a essa terapia. Resultados: Os dados obtidos mostraram que houve redução da gravidade da mucosite oral com o uso da laserterapia preventiva, com resultados estatisticamente significativos (p<0,001), corroborando os resultados encontrados na literatura. Conclusão: O uso da laserterapia é uma terapêutica auxiliar importante na prevenção e na redução da severidade da mucosite oral em pacientes submetidos a altas doses de MTX, diminuindo o número de internações por mucosite e os atrasos no protocolo terapêutico, o que reduz gastos e melhora o prognóstico para o paciente.


Introduction: Chemotherapy, one of the treatments for malignant neoplasms, is associated to innumerous drugs, one of them methotrexate (MTX), of high toxicity, responsible for several health damages and impact on the patient's well-being. One of the main complications is oral mucositis, a clinical manifestation resulting from the oncologic treatment that can interfere in the treatment and cure. Objective: To evaluate comparatively through a retrospective study, the effect of preventive laser in the occurrence of chemo-induced oral mucositis in patients with non-metastatic osteosarcoma submitted to high doses of methotrexate (MTX), and the intensity of oral mucositis, using the preventive laser after the chemotherapy cycles containing the drug methotrexate (MTX) in the patients treated at the Child and Adolescent Cancer Hospital of Barretos/SP. Method:Retrospective cohort study with charts review. The patients were divided in two groups, one submitted to low-intensity laser prophylaxis therapy after infusion of MTX and another group not submitted to prophylactic therapy. Results: The data obtained showed that preventive laser-therapy reduced the severity of oral mucositis with statistically significant results (p<0.001), corroborating the results found in the literature. Conclusion: The use of laser therapy is an important auxiliary therapy in the prevention and reduction of severity of oral mucositis in patients submitted to high doses of MTX, reducing the number of hospitalizations and delays in therapeutic protocol, which reduces costs and improves the patient prognosis.


Introducción: La quimioterapia, es uma de las formas de tratamiento de las neoplasias malignas, tiene su administración asociada a numerosas drogas siendo una de ellas el metotrexato (MTX), de alta toxicidad, responsable de numerosos factores agravantes para la salud y bienestar del paciente. Una de las principales complicaciones es la mucositis oral, manifestación clínica resultante del tratamiento oncológico que puede interferir en el tratamiento y cura. Objetivo: Evaluar, comparativamente, a través de um estudio retrospectivo, el efecto del láser preventivo em la aparición de la mucositis oral quimio inducida em pacientes com osteosarcoma no mestastásico sometido a altas dosis de MTX, bien como la intensidade de la mucositis oral, utilizando el láser preventivo después de los ciclos quimioterápicos que contiene el medicamento MTX en los pacientes antendidos en el Hospital del Cáncer Infantojuvenil de Barretos/SP. Método: Estudio de coorte con colección retrospectiva en prontuários. Los pacientes fueron divididos em dos grupos, uno sometido a terapia profiláctica con láser de baja intensidade después de la infusión de MTX y otro grupo no sometido a terapia profiláctica. Resultados: Los dados obtenidos mostraron que hubo una reducción en la severidad de la mucositis oral con el uso de la terapia láser preventiva, con resultados estáticamente significativos (p<0,001), corroborando los resultados encontrados em la literatura. Conclusión: El uso de la terapia con láser es una terapia auxiliar importante en la prevención y reducción de la severidad de la mucositis oral em pacientes sometidos a altas dosis de MTX, diminuendo el número de internaciones por mucositis y retrasos en el protocolo terapéutico, lo que reduce los gastos y mejora el pronóstico para el paciente.


Subject(s)
Humans , Male , Female , Stomatitis/radiotherapy , Methotrexate/adverse effects , Low-Level Light Therapy , Stomatitis/chemically induced , Stomatitis/prevention & control , Bone Neoplasms/drug therapy , Osteosarcoma/drug therapy , Retrospective Studies , Cohort Studies , Antimetabolites, Antineoplastic/adverse effects
5.
Int. j. odontostomatol. (Print) ; 14(4): 572-574, dic. 2020. graf
Article in Spanish | LILACS | ID: biblio-1134540

ABSTRACT

RESUMEN: Las úlceras orales (UO) son uno de los signos de toxicidad por metotrexato (Mtx) aún en pacientes con esquemas de dosis bajas para el control de artritis reumatoide (AR). En estos casos establecer un diagnóstico correlacionando UO con el medicamento puede ser un reto. Presentamos 2 casos clínicos de pacientes con AR en tratamiento con Mtx, las cuales desarrollaron UO. En los dos casos, interesantemente los pacientes fueron evaluados tanto por especialistas del área médica y oral sin tener un resultado satisfactorio después de múltiples tratamientos. Las UO resolvieron posterior a la suspensión del medicamento. Se estableció el diagnóstico de Estomatitis por Metotrexato (EMtx) por un especialista en medicina oral. El manejo multidisciplinario en estos casos es clave para el establecimiento de un diagnóstico y tratamiento oportuno.


ABSTRACT: Oral ulcers (OU) are a sign of methotrexate (Mtx) toxicity, even in patients with rheumatoid arthritis (RA) that are under a low-dose regime. In those cases, establishing a diagnosis correlating OU with the medication can be quite a challenge. Here we present 2 clinical cases of RA patients under Mtx treatment that developed OU. Interestingly, in both cases the patients were evaluated by two specialists in the medical and dentistry area, and following multiple treatments there was no satisfactory result. However, oral ulcers resolved after stopping the treatment. A diagnosis of Metotrexato stomatitis was established (SMtx) by a specialist in oral medicine. Multidisciplinary management in these cases is key for the establishment of an opportune diagnosis and treatment.


Subject(s)
Humans , Female , Aged , Stomatitis, Aphthous/diagnosis , Methotrexate/adverse effects , Oral Ulcer/diagnosis , Oral Ulcer/therapy , Arthritis, Rheumatoid , Oral Ulcer/complications , Oral Ulcer/chemically induced , Toxicity
6.
An. bras. dermatol ; 95(2): 150-157, Mar.-Apr. 2020. tab
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1130840

ABSTRACT

Abstract Background: Psoriasis is associated with atherosclerosis and increased cardiovascular risk. Currently, an automated ultrasound, called quantitative intima media thickness, has proven to be a useful method to evaluate subclinical atherosclerosis. Objectives: To compare increased cardiovascular risk in psoriasis patients receiving two types of treatments: Methotrexate and tumor necrosis factor inhibitor and to evaluate the correlation between the Framingham score and quantitative intima media thickness. Methods: Fifty patients with plaque psoriasis were selected from June 2017 to July 2018, divided into two groups, receiving methotrexate and tumor necrosis factor inhibitor. Measurement of abdominal circumference, blood pressure, body mass index and presence of metabolic syndrome were performed. Afterwards, the patients were evaluated for increased cardiovascular risk with the Framingham score and for the quantitative intima media thickness of the carotid arteries. Results: The mean age was 54.8 (±12.5) with a slight male predominance (58%). Overall, 84% of the patients had elevated waist circumference, 82% had a body mass index above ideal, and 50% had a metabolic syndrome. For the correlation between quantitative intima media thickness and Framingham Score, Pearson's linear correlation coefficient was 0.617 (p < 0.001), indicating a moderate to strong positive association. Study limitations: The protective effect of the therapies cited in relation to the increased cardiovascular risk was not evaluated. Conclusions: A moderate to strong positive association was found correlating the Framingham Score values with the quantitative intima media thickness measurement and it is not possible to state which drug has the highest increased cardiovascular risk.


Subject(s)
Humans , Male , Female , Adult , Aged , Psoriasis/complications , Psoriasis/drug therapy , Cardiovascular Diseases/chemically induced , Methotrexate/adverse effects , Dermatologic Agents/adverse effects , Carotid Intima-Media Thickness , Tumor Necrosis Factor Inhibitors/adverse effects , Psoriasis/epidemiology , Reference Values , Severity of Illness Index , Brazil/epidemiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/diagnostic imaging , Body Mass Index , Comorbidity , Cross-Sectional Studies , Risk Factors , Risk Assessment , Waist Circumference , Middle Aged
8.
Adv Rheumatol ; 60: 43, 2020. tab
Article in English | LILACS | ID: biblio-1130790

ABSTRACT

Abstract Background: Methotrexate (MTX) intolerance is frequent, and its early identification may impact treatment, leading to timely changes in medication that may promote patient compliance and better control of rheumatoid arthritis (RA). The objective of this study was to identify the frequency of, and risk factors for, MTX intolerance using the Brazilian Portuguese version of the Methotrexate Intolerance Severity Score (MISS) questionnaire in patients with RA. Methods: This cross-sectional study was performed between April 2018 and April 2019 and enrolled patients with RA in regular use of oral or subcutaneous MTX for at least 3 months. Patients were invited to answer the Brazilian Portuguese version of the MISS questionnaire, and MTX intolerance was defined by a score ≥ 6 points. Age, sex, disease duration, time of MTX use, dose, route of administration, concomitant medications, comorbidities, smoking, and Disease Activity Score for 28joint (DAS28) data were collected from institutional medical records. Results: Among 120 patients, 103 (85.8%) were female, the mean age was 61 (±12.5) years, the mean duration of disease was 16 (±10.3) years, and the average duration of MTX use was 7 (±5.5) years. The frequency of MTX intolerance was 21.6%. The most frequent symptoms reported after the use of MTX were nausea (92.3%), abdominal pain (46.1%), and vomiting (30.7%). Behavioral symptoms occurred in 96.1% of patients with MTX intolerance, the most frequent being restlessness and irritability. Patients who used corticosteroids were more likely to develop MTX intolerance than those not using corticosteroids (odds ratio = 2.73; 95% confidence interval, 1.06 to 7.06; p = 0.038). Conversely, increasing age showed marginally significant association with decreased risk of MTX intolerance (p = 0.059). Conclusions: The use of the MISS questionnaire disclosed high frequencies of anticipatory, associative, and behavioral symptoms in MTX-intolerant patients, and the use of corticosteroid increases the risk of MTX intolerance. We suggest that the MISS questionnaire be used routinely in clinical practice.(AU)


Subject(s)
Humans , Arthritis, Rheumatoid/drug therapy , Methotrexate/adverse effects , Drug Tolerance , Cross-Sectional Studies/instrumentation , Surveys and Questionnaires
9.
Adv Rheumatol ; 60: 53, 2020. tab, graf
Article in English | LILACS | ID: biblio-1130783

ABSTRACT

Abstract Background: Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs. Methods: A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug. Results: We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying antirheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs. Conclusions: Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.(AU)


Subject(s)
Humans , Arthritis, Juvenile/drug therapy , Methotrexate/adverse effects , Glucocorticoids/adverse effects , Epidemiology, Descriptive , Retrospective Studies , Pharmacovigilance
10.
J. bras. nefrol ; 41(3): 427-432, July-Sept. 2019. tab
Article in English | LILACS | ID: biblio-1040255

ABSTRACT

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.


Resumo Apesar de sua toxicidade, o metotrexato é um medicamento eficaz no controle de várias doenças. A mielossupressão, um de seus principais efeitos adversos, aumenta em gravidade e frequência nos pacientes com insuficiência renal. Apresentamos o caso de um homem de 68 anos de idade com doença renal terminal relacionada à vasculite associada ao ANCA em diálise peritoneal, que recebeu a medicação em dose baixa em função da atividade da doença e que teve como complicação pancitopenia grave com mucosite, tratada com medidas de suporte e diálise peritoneal com múltiplas trocas. Revisamos 20 casos publicados até o presente momento sobre pancitopenia associada a metotrexato em pacientes em diálise. Foi identificada alta morbidade e mortalidade, razão pela qual seu uso nesse tipo de paciente não é recomendado. No entanto, quando esta complicação ocorre, uma opção terapêutica pode ser o uso de diálise peritoneal com múltiplas trocas, além da terapia de suporte para toxicidade medicamentosa. Maiores estudos são necessários para demonstrar o papel da diálise peritoneal com múltiplas trocas na remoção desse medicamento.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Vasculitis/drug therapy , Methotrexate/adverse effects , Methotrexate/therapeutic use , Peritoneal Dialysis/methods , Folic Acid Antagonists/adverse effects , Folic Acid Antagonists/therapeutic use , Kidney Failure, Chronic/therapy , Pancytopenia/etiology , Pancytopenia/therapy , Shock, Septic/etiology , Shock, Septic/drug therapy , Methotrexate/blood , Treatment Outcome , Mucositis/etiology , Mucositis/drug therapy , Folic Acid Antagonists/blood , Anti-Bacterial Agents/therapeutic use
11.
Rev. Assoc. Med. Bras. (1992) ; 65(4): 530-534, Apr. 2019.
Article in English | LILACS | ID: biblio-1003055

ABSTRACT

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


Subject(s)
Humans , Psoriasis/drug therapy , Dermatologic Agents/administration & dosage , Immunosuppressive Agents/administration & dosage , Antibodies, Monoclonal/administration & dosage , Psoriasis/pathology , Time Factors , Severity of Illness Index , Brazil , Methotrexate/administration & dosage , Methotrexate/adverse effects , Treatment Outcome , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Acitretin/administration & dosage , Acitretin/adverse effects , Dermatologic Agents/adverse effects , Clinical Decision-Making , Immunosuppressive Agents/adverse effects , Antibodies, Monoclonal/adverse effects
12.
Prensa méd. argent ; 104(5): 240-243, jul2018.
Article in Spanish | LILACS, BINACIS | ID: biblio-1049296

ABSTRACT

El tratamiento de pacientes con artritis reumatoide (AR) debe ser temprano y agresivo para prevenir el daño articular y la discapacidad. Los fármacos no biológicos modificadoes de enfermedad, como el metotrexato, han sido utilizados par controlar la actividad de la enfermedad y para prevenir el daño de las articulaciones. Existen pacientes con AR resistentes al tratamiento con fármacos modificadores de la enfermedad y otros que no responden adecuadamente a la terapia con inhibidores de factores de necrosis tumoral. Nosotros describimos el caso de una paciente de sexo femenino de 77 años que se presentó al servicio de emergencias con fiebre, mucositis y mal estado general luego de recibir una dosis de abatacept. A su ingreso el laboratorio demostró: glóbulos blancos 500 cel/mm3, neutrófilos 150 cel/mm3, plaquetas 21000 cel/mm3, hematocrito 29%, VCM 81, LDH 314 UI/L, función renal y hepatograma normales. En el examen clínico se objetivaron ulceras y lesiones ampollares en mucosa yugal. El medulograma evidenció hipocelularidad, con disminución de las tres series. El informe anatomopatológico fue de médula ósea hipoplásica. Recibió tratamiento con factor estimulante de colonias de neutrófilos, ácido fólico y metilprednisona, con resolución del cuadro a los 3 días de instituido el tratamiento. Hasta nuestro conocimiento esta es la primera comunicación de pancitopenia asociada a abatacept es una paciente con artritis AR intolerante a metotrexato


Treatment of patient with rheumatoid arthritis (RA) should be early and aggressive to prevent joint injury and disability. Disease-modifying antirheumatic drugs (DMARDs) like methotrexate has been used as initial treatment toward the disease activity and to prevento joint damage. Some patients with RA are resistant to initial therapy with nonbiiologic DMARDs or TNF inhibitiors. We described a 77 years old women who presented to the emergency room with fever andoral lesions after been treated with abatacept. On examination patient appeared ill. She had oral ulcers. laboratory testing showed white cells count 500 cells per mm3, hematocrit 29 %, platelets count 21000 cells per mm3, LDH 314 U/l. Renal and liver functions were normal. Bone marrow showed decreased in the three cells lineages. Patient was treated with granulocyte colony-stimulating factor, folic acid, and prednisone. Patient improved her physical and laboratory features three days after admission. This case showed the rare association between pancytopenia and abatacept in a patient with RA


Subject(s)
Humans , Female , Aged , Pancytopenia/diagnosis , Arthritis, Rheumatoid/therapy , Methotrexate/adverse effects , Methotrexate/therapeutic use , Abatacept/therapeutic use
13.
Int. j. morphol ; 36(2): 737-742, jun. 2018. tab, graf
Article in English | LILACS | ID: biblio-954179

ABSTRACT

Methotrexate (MTX) is commonly used as a chemotherapy agent and immune system suppressant but its adverse effect on male reproductive system is still limited. This study aimed to investigate the effect of MTX on structure and functional proteins of testis and seminal vesicle. Adult male rats were divided into control and MTX groups (n =12). In 30 experimental days, the treated animals were injected with MTX (tail i.v., 75 mg/KgBW) at days 8 and 15. Then, the reproductive parameters and histology of both groups were examined. Thickness of seminal seminal vesicle epithelia was analyzed. Also, the expressions of testicular tyrosine phosphorylated proteins and steroidogenic acute regulatory (StAR) protein were investigated. The results showed that MTX could significantly decrease epididymal sperm concentration. In addition, the germ cell degeneration, increased spaces of interstitial tissues, and low epididymal sperm mass density were observed in MTX group. The thickness of seminal vesicle epithelia in MTX group was significantly lower than that of control group. Moreover, the intensity of testicular phosphorylated proteins of 31, 32, 72, and 85 kDas was significantly increased while of 42 and 47 kDas in MTX group was decreased as compared to control. The expression of testicular StAR protein in MTX group was also significantly decreased as compared to the control. In conclusion, MTX affects testicular and seminal tissues and changes testicular functional proteins in adult rats.


El metotrexato (MTX) se usa comúnmente como agente de quimioterapia y supresor del sistema inmunitario, pero su efecto adverso en el sistema reproductor masculino sigue siendo limitado. Este estudio tuvo como objetivo investigar el efecto del MTX sobre la estructura y las proteínas funcionales del testículo y la vesícula seminal. Ratas macho adultas se dividieron en grupos control y grupo con MTX (n = 12). En 30 días experimentales, a los animales tratados se les inyectó MTX (cola i.v., 75 mg / KgBW) los días 8 y 15. Luego, se examinaron los parámetros reproductivos y la histología de ambos grupos. Se analizó el espesor del epitelio de la vesícula seminal. Además, se investigaron las expresiones de la proteína tirosina testicular fosforilada y de la proteína reguladora aguda esteroidogénica (StAR). Los resultados mostraron que el MTX podría disminuir significativamente la concentración de espermatozoides epididimarios. Además, se observó la degeneración de las células germinales, el aumento de los espacios de los tejidos intersticiales y la baja densidad de masa del espermatozoide epididimal en el grupo de MTX. El grosor del epitelio de la vesícula seminal en el grupo MTX fue significativamente menor que el del grupo control. Además, la intensidad de las proteínas testiculares fosforiladas de 31, 32, 72 y 85 kDas aumentó significativamente, mientras que la de 42 y 47 kDas en el grupo MTX disminuyó en comparación con el control. La expresión de la proteína StAR testicular en el grupo MTX también se redujo significativamente en comparación con el control. En conclusión, el MTX afecta los tejidos testiculares y seminales y cambia las proteínas funcionales testiculares en ratas adultas.


Subject(s)
Animals , Male , Rats , Seminal Vesicles/drug effects , Testis/drug effects , Methotrexate/pharmacology , Organ Size , Phosphorylation , Spermatozoa/drug effects , Methotrexate/adverse effects , Blotting, Western , Rats, Sprague-Dawley , Phosphotyrosine/drug effects
14.
Rev. méd. Chile ; 146(6): 802-807, jun. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-961462

ABSTRACT

Intrathecal chemotherapy may be complicated with the development of myelopathies or toxic radiculopathies. This myeloradicular involvement, of toxic character, is unpredictable, since these patients have repeatedly received Intrathecal chemotherapy with the same drugs without apparent injury. The toxic effect should be mainly attributed to Cytarabine and not to methotrexate, since the central nervous system lacks Cytidine deaminase, the enzyme that degrades Cytarabine. We report two patients, an 18-year-old woman and a 16 years old male, who received systemic and intrathecal chemotherapy (methotrexate, cytarabine) for the treatment of an acute lymphoblastic leukemia and developed, in relation to this procedure, a spinal subacute combined degeneration. They had a proprioceptive and motor alteration of the lower extremities and neuroimaging showed selective rear and side spinal cord hyper intensity produced by central axonopathy. Two weeks later the woman developed a quadriplegia and the young man a flaccid paraplegia due to added root involvement.


Subject(s)
Humans , Female , Adolescent , Methotrexate/adverse effects , Cytarabine/adverse effects , Subacute Combined Degeneration/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antimetabolites, Antineoplastic/adverse effects , Injections, Spinal , Magnetic Resonance Imaging , Methotrexate/administration & dosage , Fatal Outcome , Cytarabine/administration & dosage , Subacute Combined Degeneration/diagnostic imaging , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Antimetabolites, Antineoplastic/administration & dosage
15.
Arch. argent. pediatr ; 116(3): 459-462, jun. 2018. tab, ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-950027

ABSTRACT

La necrólisis epidérmica tóxica y el síndrome de StevensJohnson son enfermedades mucocutáneas raras que están asociadas a una evolución prolongada y a un desenlace potencialmente mortal. Principalmente están inducidas por fármacos y las tasas de mortalidad son muy elevadas. Aunque la piel es la más comprometida, también pueden estar afectados múltiples aparatos o sistemas como el cardiovascular, pulmonar, gastrointestinal y urinario. En este artículo, describimos el caso de un paciente con síndrome de Stevens-Johnson asociado al tratamiento con metotrexato, quien desarrolló insuficiencia cardíaca aguda y hemorragia gastrointestinal además de las manifestaciones en la piel. El paciente recibió un tratamiento satisfactorio con metilprednisolona e inmunoglobulina por vía intravenosa y continuó la quimioterapia con metotrexato.


Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of StevensJohnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again.


Subject(s)
Humans , Male , Child , Methotrexate/adverse effects , Stevens-Johnson Syndrome/etiology , Antimetabolites, Antineoplastic/adverse effects , Methylprednisolone/administration & dosage , Methotrexate/administration & dosage , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/drug therapy , Immunoglobulins, Intravenous/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Heart Failure/chemically induced , Gastrointestinal Hemorrhage/chemically induced , Antimetabolites, Antineoplastic/administration & dosage
16.
Medicina (B.Aires) ; 78(1): 50-53, feb. 2018. ilus, tab
Article in Spanish | LILACS | ID: biblio-894549

ABSTRACT

El metotrexato es un antimetabolito análogo al ácido fólico que inhibe competitivamente la enzima dihidrofolato reductasa y timidilato sintetasa, indispensables para la síntesis de ADN y ARN. Se utiliza ampliamente en dermatología y sus efectos adversos en la piel y mucosas son variados, incluyendo reacciones leves y graves. Las erosiones y úlceras cutáneas como manifestación de citotoxicidad por metotrexato son infrecuentes y representarían un signo cutáneo temprano de pancitopenia por toxicidad medular secundaria a dicha droga. En la mayoría de los casos existen enfermedades cutáneas previas a la ulceración, principalmente psoriasis. En ausencia de dermatitis subyacente, la presencia de ulceraciones es excepcional. Se presentan ocho casos de pacientes con signos cutáneos de intoxicación por metotrexato, con y sin dermatosis previas. En la mayoría hubo asociación de mucositis y compromiso medular. Se recomiendan pautas de tratamiento.


Methotrexate is an antimetabolite analog to folic acid that competitively inhibits the enzyme dihydrofolate reductase and thymidylate synthetase, essential for the synthesis of DNA and RNA. It is widely used in dermatology and its adverse effects on the skin and mucous membranes are varied, including mild and severe reactions. The appearance of erosions and skin ulcers as a manifestation of methotrexate cytotoxicity are quite infrequent. These would represent an early cutaneous sign of pancytopenia due to marrow toxicity secondary to this drug. In most of the cases there are cutaneous diseases prior to ulceration, mainly psoriasis. In the absence of underlying dermatitis, the presence of ulcerations is very rare. We present eight cases of patients with cutaneous signs of methotrexate poisoning, with and without previous dermatoses. Most of them associated mucositis and bone marrow involvement. Treatment guidelines are recommended.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Skin Ulcer/chemically induced , Methotrexate/adverse effects , Drug Eruptions/etiology , Immunosuppressive Agents/adverse effects , Skin Ulcer/diagnosis , Retrospective Studies , Drug Eruptions/diagnosis , Diagnosis, Differential
18.
An. bras. dermatol ; 92(3): 401-403, May-June 2017. graf
Article in English | LILACS | ID: biblio-886977

ABSTRACT

Abstract Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.


Subject(s)
Humans , Female , Adult , Pneumonia, Pneumocystis/chemically induced , Methotrexate/adverse effects , Pneumocystis carinii , Dermatologic Agents/adverse effects , Pneumonia, Pneumocystis/diagnostic imaging , Urticaria/drug therapy , Tomography, X-Ray Computed , Methotrexate/administration & dosage , Chronic Disease , Dermatologic Agents/administration & dosage
19.
Brasília; CONITEC; jan. 2017. tab, ilus.
Monography in Portuguese | LILACS, BRISA | ID: biblio-837215

ABSTRACT

Contexto: A AR é uma doença crônica e progressiva, caracterizada pela inflamação da membrana sinovial das articulações. Observa-se um infiltrado linfocítico nas regiões perivasculares e proliferação de células, com consequente angiogênese, hiperplasia sinovial e formação de pannus que levam à destruição articular, cartilagínea e óssea, durante a progressão da AR. O caráter crônico e progressivo da doença pode levar a importante limitação funcional, com perda de capacidade laboral e de qualidade de vida, resultando em significativo impacto pessoal e social, com elevados custos diretos e indiretos. O tratamento precoce de pacientes com AR inicial está associado com uma maior probabilidade de alcance da remissão da doença. Para os pacientes com AR estabelecida, espera-se com o tratamento alcançar a baixa atividade da doença, incluindo a redução da dor e do edema articular, a interrupção do dano ósseo-cartilaginoso, bem como a prevenção de incapacidades e redução da morbimortalidade. Pergunta: O uso de tofacitinibe é eficaz e seguro em pacientes adultos com AR que não obtiveram resposta adequada ao tratamento com metotrexato (MTX) ou outros medicamentos modificadores do curso da doença (MMCD) sintéticos convencionais ou biológicos quando comparado às opções disponíveis atualmente no SUS? Evidências científicas: Em revisões sistemáticas de ensaios clínicos randomizados de fase II e III, tofacitinibe demonstrou melhor eficácia em comparação com MTX e similaridade com os MMCD biológicos para os desfechos ACR 20 e 50, HAQ e redução ou remissão do DAS ou DAS 28. Em relação à segurança não houve diferenças entre tofacitinibe, MTX e MMCD biológico para descontinuação devido a eventos adversos e eventos adversos sérios. No entanto, os pacientes do grupo tofacitinibe apresentaram significativamente menor média de contagem de neutrófilos, aumento da creatinina sérica, aumento de colesterol. LDL (lipoproteína de baixa densidade), maior variação percentual de colesterol LDL e HDL (lipoproteína de alta densidade) e um maior risco de aumento da ALT (alanina aminotranferase) e AST (aspartatoamino transferase) versus placebo ou placebo + MTX. Estudo de comparação indireta realizada pelo demandante mostrou que para ACR20 em 12 semanas, certolizumabe apresentou maior ficácia do que Tofacitinibe. Em 24 semanas e para os demais desfechos observados não foram encontradas diferenças significativas. Para descontinuação por eventos adversos sérios, etanercepte exibiu menor risco de apresentar descontinuação do tratamento do que Tofacitinibe. Também não foram encontradas diferenças com relação a outros eventos adversos. Em estudos observacionais o risco de herpes-zoster foi significativamente maior em usuários de tofacitinibe, sendo aproximadamente o dobro quando comparado ao uso de MMCD biológicos. O risco de perfuração no trato gastrointestinal inferior, foi significantemente superior em usuários de tofacitinibe e tocilizumabe quando comparado aos medicamentos inibidores do fator de necrose tumoral (anti-TNF). As taxas de incidência de câncer observadas permaneceram estáveis ao longo do tempo, não havendo associação entre duração do tratamento com tofacitinibe e risco geral de câncer. Porém, estudos de longo prazo são necessários para avaliar a correlação entre o uso do medicamento e a incidência de câncer. Avaliação econômica: Como o demandante não encontrou diferenças significativas entre Tofacitinibe e os demais biológicos foi feita uma análise de minimização de custos em dois cenários: cenário base ­ que considera apenas os medicamentos; cenário alternativo ­ considera todo o tratamento e inclui custo da medicação, medicamentos concomitantes, administração, acompanhamento e cadeia fria. Para o custo de tofacitinibe 5 mg considerou-se o valor proposto pelo fabricante, de R$ 1.593,18, sem ICMS, para a apresentação de 60 comprimidos (equivalente a um mês de tratamento). A avalição econômica apresenta algumas limitações: 1. O demandante considera que há similaridade com os biológicos em termos de efetividade e segurança, mas há potencial superioridade do certolizumabe em comparação com Tofacitinibe; 2. O demandante considera a necessidade de uso concomitante de MTX em associação com todos os biológicos, mas não com Tofacitinibe. 3. A bula do medicamento sugere o uso concomitante com estatinas e tal custo não foi incluído na análise; 4. Estudos observacionais apontam para uma maior ocorrência de eventos adversos em pacientes em uso de Tofacitinibe em comparação com os demais biológicos, em especial a herpes-zoster. Tal custo não foi incluído na análise. Avaliação de impacto orçamentário: A análise de impacto orçamentário foi dividida entre os cenários base (custo medicamentoso) e cenário alternativo (custo de tratamento), e a população elegível baseou-se em dados do mundo real. O demandante considerou market share progressivo de 2 a 16% em 5 cinco anos. Considerando apenas o custo do medicamento (cenário base), a análise de impacto orçamentário para a inclusão proposta do tofacitinibe no SUS evidencia uma potencial economia de R$64,2 milhões em 5 anos se o produto for incluído na lista de produtos desonerados de PIS e COFINS. Considerando o custo do tratamento (cenário alternativo) a análise de impacto orçamentário feita pelo demandante para a inclusão do tofacitinibe no SUS evidencia uma potencial economia que pode chegar a R$ 73,5 milhões em 5 anos se o produto for incluído na lista de produtos desonerados de PIS e COFINS. Deliberação Final: Aos 30 (trinta) dias do mês de novembro de 2016, os membros da CONITEC recomendaram a incorporação do tofacitinibe para o tratamento de pacientes adultos com artrite reumatoide ativa moderada a grave, conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde e condicionado à negociação de preço. Foi assinado o Registro de Deliberação nº 241/2016. A Portaria Nº 8, de 1º de fevereiro de 2017 - Torna pública a decisão de incorporar o citrato de tofacitinibe para o tratamento de pacientes adultos com artrite reumatoide ativa moderada a grave no âmbito do Sistema Único de Saúde - SUS.


Subject(s)
Humans , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/therapy , Methotrexate/adverse effects , Treatment Failure , Biological Factors , Brazil , Cost-Benefit Analysis/economics , Technology Assessment, Biomedical , Unified Health System
20.
Article in French | AIM, AIM | ID: biblio-1259336

ABSTRACT

Introduction : L'objectif de cette étude est de déterminer l'efficacité et le maintien thérapeutique du méthotrexate utilisé dans le traitement de la polyarthrite rhumatoïde et de déterminer les facteurs prédictifs de sa réponse thérapeutique.Méthodes : nous avons mené une étude rétrospective au service de rhumatologie de l'hôpital Farhat Hached, sur une période de 3 ans (2008-2010), portant sur 100 patients atteints de polyarthrite rhumatoïde, selon les critères ACR 1987, et recevant le méthotrexate comme traitement de fond de 1ère intention en monothérapie. Résultats : l'évaluation du méthotrexate a été faite sur 2 ans reposant sur des paramètres clinico-biologiques et radiologiques. Une réponse EULAR a été obtenue dans 60% et 68,6% des cas respectivement à la 1ère et à la 2ème année et une rémission dans 5% des cas. L'âge jeune, la faible activité de la maladie et l'absence de syndrome inflammatoire biologique initial sont des facteurs prédictifs d'une bonne réponse au méthotrexate.Les effets secondaires ont été observés chez 44% de nos patients mais le méthotrexate n'a été arrêté définitivement que dans 16% des cas. Le maintien thérapeutique du méthotrexate en monothérapie a été de 86% et de 80% des cas respectivement à 1 et à 2 ans. Le principal facteur limitant le maintien du traitement a été la survenue d'effets secondaires:Conclusion Nos résultats indiquent que le méthotrexate reste efficace plus de 24 mois de traitement, avec un profil de toxicité acceptable


Subject(s)
Arthritis, Rheumatoid , Drug Tolerance , Methotrexate , Methotrexate/adverse effects , Retrospective Studies , Tunisia
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