Gastrointestinal symptoms in patients using methotrexate: A cross-sectional study in a sample with rheumatoid arthritis.

BACKGROUND: Gastrointestinal intolerance is common in rheumatoid arthritis (RA) patients using methotrexate and may lead to treatment discontinuation. AIM: To study the prevalence of gastrointestinal symptoms in a sample of RA methotrexate users as well as its possible association with clinical and epidemiological variables. METHODS: Cross-sectional study of 192 patients with gastrointestinal symptoms using the MISS (methotrexate intolerance severity score). Clinical and epidemiological variables were collected through chart review and direct questioning. Patients' adherence to methotrexate was evaluated through Moriski-Green-Levin questionnaire. RESULTS: The prevalence of gastrointestinal complaints was high with 55.7% of the sample classified as intolerant. Nausea and pain after drug ingestion were the most common reported complaints. This intolerance was associated with afro-descendant background (p=0.02); presence of associated fibromyalgia (p=0.04), concomitant use of glucocorticoids (p=0.03) and Jak inhibitors (0.03). A tendency towards association with leflunomide use was observed (p=0.06). Logistic regression was used to test drug associations with methotrexate intolerance, and showed that glucocorticoid use was independently associated with methotrexate intolerance OR=1.85; 95% CI=1.01-3.44; p=0.04. Route of administration, presence of previous gastric complaints, age and methotrexate dose did not interfere with MISS. MISS results were associated with moderate adherence to the drug. CONCLUSIONS: There is a high rate of methotrexate intolerance that is more common in afro-descendants, those with associated fibromyalgia, glucocorticoid and Jak inhibitors users.

Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study.

INTRODUCTION: High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment. METHODS: This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t½ (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model. RESULTS: Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t½ calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56-0.69) and DME at 0.86 (IQR 0.73-1.00). After adjusting for age, sex, dose (mg/m2), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03-1.65. CONCLUSION: Early MTX elimination t½ measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.

Chemotherapy-induced oral mucositis: hierarchical analysis of recurrence factors.

PURPOSE: This study aimed to analyze, through a hierarchical model, the risk factors associated with the recurrence of chemo-induced oral mucositis (OM) in children and adolescents. METHODS: A retrospective cohort with 31 individuals of both sexes, aged 1-18 years, who were undergoing chemotherapy, and presented OM lesions was conducted. Data collection included analysis of medical records, interviews, and intraoral examination. Information regarding patients' socioeconomic and demographic profile, underlying disease, antineoplastic regimen, hematological condition, and oral health status were collected. To assess the association of independent variables with the outcome, the Chi-square, Fisher's Exact, and Mann-Whitney tests were used, in addition to a binary logistic regression model, with a maximum error of 5% and a 95% confidence interval. RESULTS: Significant associations were observed between the history of OM and the diagnosis of the child/adolescent, neutrophil count, previous cancer treatments and the chemotherapy scheme in use (p < 0.05). Binary logistic regression revealed a 13.69 higher risk of developing OM recurrence in individuals who received high-dose methotrexate (MTX) therapy. CONCLUSION: Socioeconomic and demographic factors did not influence OM recurrence. However, clinical variables, such as neutropenia, diagnosis of leukemia, and high-dose MTX protocols increase the chance of OM new cases.

Autochtonal case of chronic, unifocal, pulmonary paracoccidioidomycosis with methotrexate use, in Salvador ‒ Brazil.

We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible environmental exposures in endemic rural areas, supposedly resulting from reactivation of a latent pulmonary focus secondary to the use of methotrexate for the control of Chikungunya arthropathy. Laboratory investigation ruled out other immunosuppression. Her only symptoms were a dry cough and chest pain. Diagnosis confirmed by needle lung biopsy. There were no abnormalities on physical examination nor evidence of central nervous system involvement. MRI of the total abdomen showed no involvement of other organs. Computed chest tomography showed a favorable evolution under the use of itraconazole (200 mg/day). Different tomographic presentations findings are highlighted when performed before and after treatment. CONCLUSIONS: PCM should be considered even in a woman without a history of consistent environmental exposure and in a non-endemic geographic area.

TNF-α promoter hypomethylation is frequent in oncopediatric patients who recovered from mucositis.

The aim of this study was to investigate the DNA methylation profile in genes encoding catalase (CAT) and superoxide dismutase (SOD3) enzymes, which are involved in oxidative stress mechanisms, and in genes encoding pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-α) in the oral mucosa of oncopediatric patients treated with methotrexate (MTX®). This was a cross-sectional observational study and the population comprised healthy dental patients (n = 21) and those with hematological malignancies (n = 64) aged between 5 and 19 years. Oral conditions were evaluated using the Oral Assessment Guide and participants were divided into 4 groups: 1- healthy individuals; 2- oncopediatric patients without mucositis; 3- oncopediatric patients with mucositis; 4- oncopediatric patients who had recovered from mucositis. Methylation of DNA from oral mucosal cells was evaluated using the Methylation-Specific PCR technique (MSP). For CAT, the partially methylated profile was the most frequent and for SOD3 and IL6, the hypermethylated profile was the most frequent, with no differences between groups. For TNF-α, the hypomethylated profile was more frequent in the group of patients who had recovered from mucositis. It was concluded that the methylation profiles of CAT, SOD3, and IL6 are common profiles for oral cells of children and adolescents and have no association with oral mucositis or exposure to chemotherapy with MTX®. Hypomethylation of TNF-α is associated with oral mucosal recovery in oncopediatric patients who developed oral mucositis during chemotherapy.

The protective effect of Ozone on the mice testicular damage induced by methotrexate.

OBJECTIVE: Methotrexate (MTX) is widely administered for the treatment of various cancers. However, MTX induces male reproductive toxicity. In the current study, the effect of ozone therapy (OT) on reducing the toxic effects of MTX in the mouse testicles has been investigated. METHODS: Twenty-four mice were divided into four groups: control, OT (4 mg/kg ozone), MTX (20 mg/kg), and MTX + OT. Testosterone levels, histological changes, and oxidative stress biomarkers were assessed to evaluate the protective effects of OT. RESULTS: The results demonstrated that MTX disrupted germinal epithelium, reduced serum testosterone levels, and enhanced oxidative stress in testicular tissue. However, treatment with OT attenuated these adverse effects. OT effectively restored the levels of antioxidant enzymes, such as catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD). OT reduced lipid peroxidation, as indicated by decreased malondialdehyde (MDA) levels. OT preserved normal spermatogenesis, improved morphometric parameters, and reduced histological changes by MTX. Moreover, OT effectively restored testosterone levels. CONCLUSIONS: OT protects against MTX-induced testicular damage by suppressing oxidative stress.

Mucositis oral como efecto adverso al uso del metotrexato en el tratamiento de la artritis reumatoide: una revisión sistematizada de casos / Oral mucositis as an adverse effect of the use of methotrexate in the treatment of rheumatoid arthritis: a systematized review of cases

Introducción: el metotrexato se usa ampliamente para el tratamiento de una variedad de enfermedades neoplásicas y autoinmunes. Sin embargo, como todo fármaco, su eficacia viene marcada por cierto grado de toxicidad debido a la farmacocinética del medicamento. El metotrexato se creó como un fármaco anticancerígeno; sin embargo, se ha convertido en el tratamiento de elección contra la artritis reumatoide. Principalmente, el metotrexato causa inflamación de las mucosas epiteliales. La mayoría de los efectos secundarios del metotrexato se pueden detectar de forma temprana y son reversibles. La mucositis del tracto alimentario es el principal efecto secundario de la quimioterapia contra el cáncer. Se le conoce colectivamente como lesión de la mucosa inducida por quimioterapia, afecta todo el canal alimentario desde la boca hasta el ano, ocasionando la mucositis oral y la mucositis intestinal. Material y métodos: se buscaron casos clínicos en los que se reporte mucositis causada por metotrexato en tratamiento de artritis reumatoide. Se empleó un diagrama de flujo, PRISMA modificado para la búsqueda de artículos. Finalmente, se cotejó que los casos clínicos cumplieran con los fundamentos de la CARE guide, para manejar una correcta estructura y bajo riesgo a sesgo. Conclusiones: una correcta anamnesis y exploración clínica oral es lo más importante de la medicina oral. Es relevante indagar sobre las enfermedades que presentan los pacientes, así como la historia de medicamentos que se administren, especialmente en pacientes mayores, con mayores padecimientos de enfermedades sistémicas (AU)

Introduction: methotrexate is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, like all drugs its efficacy is marked by a certain degree of toxicity due to the pharmacokinetics of the drug. Methotrexate was developed as an anticancer drug, however, it has become the treatment of choice for rheumatoid arthritis. Methotrexate primarily causes inflammation of the epithelial mucous membranes. Most of the side effects of methotrexate can be detected early and are reversible. Mucositis of the alimentary tract is the main side effect of cancer chemotherapy. It is collectively known as chemotherapy-induced mucosal injury, affecting the entire alimentary canal from the mouth to the anus, where oral mucositis and intestinal mucositis are both common. Material and methods: we searched for clinical cases reporting mucositis caused by methotrexate in the treatment of rheumatoid arthritis, using a modified PRISMA flowchart to search for articles. Finally, the clinical cases were checked for compliance with the fundamentals of the CARE guide, in order to manage a correct approach to oral medicine. It is important to inquire about the diseases the patients present, as well as the history of medications administered, especially in older patients, with more systemic disease conditions, structure, and low risk of bias. Conclusion: a correct anamnesis and oral clinical examination is the most important aspect of oral medicine. It is important to inquire about the diseases that the patients present, as well as the history of medications that are administered, especially in older patients with major systemic diseases (AU)

Role of intrathecal chemotherapy in the management of meningeal carcinomatosis in patients with breast cancer.

OBJECTIVE: To evaluate whether intrathecal chemotherapy improves clinical outcomes in patients with meningeal carcinomatosis. METHODS: This retrospective cohort study included consecutive patients with breast cancer diagnosed with meningeal carcinomatosis. Clinical and treatment data were collected from the patients' medical charts. The primary outcome was overall survival, and the secondary outcomes were time to neurological deterioration and reporting of clinical benefit. Logistic regression and Cox proportional hazard models adjusted for potential confounders were used to evaluate the clinical response and overall survival, respectively. RESULTS: Overall, 109 female patients were included, 50 (45.9%) of whom received intrathecal chemotherapy with methotrexate and dexamethasone. The median treatment duration was 3 weeks (range, 1-13 weeks). Patients treated with intrathecal chemotherapy were more likely to report clinical benefit (74% versus 57.7%, adjusted odds ratio [OR] = 9.0, 95%CI=2.6-30.9, p<0.001). However, there was no difference in the time to neurologic deterioration (hazard ratio [HR] = 0.96, 95%CI= 0.57-1.59, p=0.86). Patients who received intrathecal chemotherapy did not show an increase in overall survival compared with that of patients who did not receive intrathecal chemotherapy (median overall survival = 1.8 months, 95%CI= 1.27-3.0 versus 2.5, 95%CI= 1.9-3.9, adjusted HR = 0.71, 95%CI= 0.41-1.22, p=0.21). There was a significant interaction between intrathecal chemotherapy and systemic treatment, and patients who received systemic therapy without intrathecal chemotherapy had better overall survival than that of the no-treatment group (adjusted HR = 0.38, 95%CI= 0.20-0.70, p=0.002). CONCLUSION: Intrathecal chemotherapy did not increase overall survival or time to neurological deterioration and should not preclude or postpone systemic treatments.

Prediction of Rupture by Complete Blood Count in Tubal Ectopic Pregnancies Treated with a Single-Dose Methotrexate Protocol.

OBJECTIVE: The availability of reliable and inexpensive markers that can be used to determine the risk of rupture during methotrexate (MTX) treatment in ectopic pregnancies (EPs) is considerable. The aim of the present study is to investigate the role of systemic inflammatory markers such as leukocytes (or white blood cells, WBCs), the neutrophil-to-lymphocyte ratio (NLR), and platelet distribution width (PDW), which are among the parameters of the complete blood count (CBC), in the prediction of rupture of EPs under MTX treatment. MATERIALS AND METHODS: A total of 161 patients with tubal EP who underwent a single-dose methotrexate (MTX) protocol were retrospectively analyzed, and the control group (n = 83) included patients cured by MTX, while the ruptured group (n = 78) included patients who were operated on for tubal rupture during the MTX treatment. The features of EP, beta-human chorionic gonadotropin (ß-hCG) levels, sonographic findings, and CBC-derived markers such as WBC, NLR, and PDW, were investigated by comparing both groups. RESULTS: The NLR was found to be higher in the ruptured group, of 2.92 ± 0.86%, and significantly lower in the control group, of 2.09 ± 0.6%. Similarly, the PDW was higher (51 ± 9%) in the ruptured group, and it was significantly lower a (47 ± 13%) in the control group (p < 0.05). Other CBC parameters were similar in both groups (p > 0.05). CONCLUSION: Systemic inflammation markers derived from CBC can be easily applied to predict the risk of tubal rupture in Eps, since the CBC is an inexpensive and easy-to-apply test, which is first requested from each patient during hospitalization.

OBJETIVO: A disponibilidade de marcadores confiáveis e baratos que podem ser usados para determinar o risco de ruptura durante o tratamento com metotrexato (MTX) em gestações ectópicas (GEs) é considerável. O objetivo do presente estudo é investigar o papel de marcadores inflamatórios sistêmicos, como leucócitos (ou glóbulos brancos, glóbulos brancos), a relação neutrófilo-linfócito (NLR) e largura de distribuição de plaquetas (PDW), que estão entre os parâmetros do hemograma completo (hemograma), na predição de ruptura de PEs sob tratamento com MTX. MATERIAIS E MéTODOS: Foram analisados retrospectivamente 161 pacientes com EP tubária submetidas a protocolo de dose única de metotrexato (MTX), sendo que o grupo controle (n = 83) incluiu pacientes curadas com MTX, enquanto o grupo roto (n = 78) incluíram pacientes operadas por ruptura tubária durante o tratamento com MTX. As características de EP, beta-gonadotrofina coriônica humana (ß-hCG), achados ultrassonográficos e marcadores derivados de CBC, como WBC, NLR e PDW, foram investigados comparando os dois grupos. RESULTADOS: A RNL foi maior no grupo roto, de 2,92 ± 0,86%, e significativamente menor no grupo controle, de 2,09 ± 0,6%. Da mesma forma, o PDW foi maior (51 ± 9%) no grupo roto, e foi significativamente menor a (47 ± 13%) no grupo controle (p < 0,05). Outros parâmetros do hemograma foram semelhantes em ambos os grupos (p > 0,05). CONCLUSãO: Marcadores inflamatórios sistêmicos derivados do hemograma podem ser facilmente aplicados para predizer o risco de ruptura tubária na Eps, uma vez que o hemograma é um exame de baixo custo e fácil aplicação, solicitado primeiramente a cada paciente durante a internação.

Neurotoxicidad subaguda por metotrexato en pacientes con enfermedad oncohematológica. Reporte de tres casos / Subacute methotrexate neurotoxicity in patients with oncohematological disease. A report of 3 cases

El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.

Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.

Paternal methotrexate exposure affects sperm small RNA content and causes craniofacial defects in the offspring.

Folate is an essential vitamin for vertebrate embryo development. Methotrexate (MTX) is a folate antagonist that is widely prescribed for autoimmune diseases, blood and solid organ malignancies, and dermatologic diseases. Although it is highly contraindicated for pregnant women, because it is associated with an increased risk of multiple birth defects, the effect of paternal MTX exposure on their offspring has been largely unexplored. Here, we found MTX treatment of adult medaka male fish (Oryzias latipes) causes cranial cartilage defects in their offspring. Small non-coding RNA (sncRNAs) sequencing in the sperm of MTX treated males identify differential expression of a subset of tRNAs, with higher abundance for specific 5' tRNA halves. Sperm RNA methylation analysis on MTX treated males shows that m5C is the most abundant and differential modification found in RNAs ranging in size from 50 to 90 nucleotides, predominantly tRNAs, and that it correlates with greater testicular Dnmt2 methyltransferase expression. Injection of sperm small RNA fractions from MTX-treated males into normal fertilized eggs generated cranial cartilage defects in the offspring. Overall, our data suggest that paternal MTX exposure alters sperm sncRNAs expression and modifications that may contribute to developmental defects in their offspring.

Belimumabe intravenoso para o tratamento adjuvante de pacientes adultos com lúpus eritematoso sistêmico com alto grau de atividade apesar da terapia padrão e que apresentem falha terapêutica a dois imunossupressores prévios / Intravenous belimumab for the adjuvant treatment of adult patients with systemic lupus erythematosus with a high degree of activity despite standard therapy and who experience treatment failure in two cases previous immunosuppressants

INTRODUÇÃO: O lúpus eritematoso sistêmico (LES) é uma doença autoimune multissistêmica crônica, que apresenta características polimórficas, com destaque para sintomas constitucionais, erupção cutânea e artrite. Também pode levar a complicações graves, como nefrite lúpica, citopenias autoimunes e doenças do sistema nervoso. Além da atividade de doença, o uso contínuo de corticoide em altas doses é associado a maiores danos acumulados e óbitos. O objetivo do tratamento é controlar a atividade da doença e evitar o surgimento de fatores de risco para complicações,sendo utilizados medicamentos como antimaláricos, corticoides e imunossupressores. Após a remissão clínica, recomenda-se a redução gradual das doses dos medicamentos, mantendo o uso da hidroxicloroquina. RECOMENDAÇÕES ANTERIORES DA CONITEC: Em 2018, o Plenário da Conitec deliberou por unanimidade pela não incorporação do belimumabe para o tratamento de LES no âmbito do Sistema Único de Saúde (SUS), conforme Relatório de Recomendação nº 344. Na ocasião, a pergunta de pesquisa se diferiu em relação aos desfechos e tipo de estudo, considerando-se apenas a melhora no Systemic Lupus Erythemathosus Response Index (SRI) e meta-análises de ensaios clínicos randomizados (ECRs), respectivamente. A

Subacute methotrexate neurotoxicity in patients with oncohematological disease. A report of 3 cases. / Neurotoxicidad subaguda por metotrexato en pacientes con enfermedad oncohematológica. Reporte de tres casos.

Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occursbetween 2 and 14 days after administration and may present as a wide range of neurological symptoms.In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.

El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.

In-Vitro and Ex-Vivo Evaluation of Transfersomal Gel of Methotrexate

Abstract Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.

Systemic treatment for severe atopic dermatitis in children: a case series.

BACKGROUND: Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications. METHODS: We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months. RESULTS: We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil. CONCLUSIONS: Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.

INTRODUCCIÓN: La dermatitis atópica (DA) es la enfermedad inflamatoria crónica de la piel más común en niños. En la mayoría de los pacientes la enfermedad se controla con tratamientos tópicos; sin embargo, algunos pacientes con DA grave no responden a estos tratamientos, por lo que requieren de terapia sistémica. Existe poca información acerca de la dosis ideal, tiempo de uso, respuesta clínica y seguridad del tratamiento sistémico en niños con DA grave. Se realizó este estudio para describir las características clínicas de pacientes con DA grave que requirieron un tratamiento sistémico, los medicamentos utilizados, la evolución clínica, los efectos secundarios y las complicaciones asociadas. MÉTODOS: Se llevó a cabo una revisión retrospectiva de los expedientes de pacientes pediátricos con DA grave atendidos en el Servicio de Dermatología, Instituto Nacional de Pediatría (2000 a 2018), que hayan requerido tratamiento sistémico por más de 3 meses. RESULTADOS: Se incluyeron 21 pacientes. La media de edad de inicio de la enfermedad fue de 3.31 años. Los fármacos utilizados fueron metotrexato (57.1%), talidomida (38%), prednisona (42.8%), azatioprina (19%), mofetil micofenolato (9.5%), ciclosporina (4.7%) y esteroides sistémicos como terapia puente (42.8%). Se observaron efectos secundarios leves en dos pacientes (9.5%) tratados con metotrexato y mofetil micofenolato. CONCLUSIONES: El metotrexato fue el medicamento utilizado en más del 50% de los pacientes con remisión en la mayoría de ellos. La ciclosporina, azatioprina y mofetil micofenolato también fueron efectivos. Los efectos secundarios fueron leves y poco frecuentes. Es necesario realizar estudios comparativos de tratamientos sistémicos para DA grave en la población pediátrica.

Cognitive impairment and elevated peripheral cytokines in breast cancer patients receiving chemotherapy.

BACKGROUND: Anthracyclines-based regimen (5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); cyclophosphamide, epirubicin, and 5-fluorouracil [CEF]) and non-anthracycline based regimens (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) are widely used as neoadjuvant chemotherapy for breast cancer patients. OBJECTIVE: The present study was conducted to observe the effects of FAC, CEF, and CMF regimen on cognition and circulatory proinflammatory cytokines (interleukin 6 [IL-6] and interleukin 1ß [IL-1ß]) for the duration of three cycles of chemotherapy in breast cancer patients. METHODS: Eighty newly diagnosed HER-2 negative breast cancer patients were enrolled and divided into 3 groups as FAC- (n = 27), CEF- (n = 26), and CMF- (n = 27) receiving patients. Serum IL-6 and IL-1ß levels were measured by using enzyme-linked immunosorbent assay (ELISA), and cognition was assessed using the Mini-Mental State examination (MMSE) questionnaire. RESULTS: Anthracycline-based regimen was found to increase the levels of IL-6, IL-1ß, and decreased MMSE scores compared with CMF regimen (p < 0.05). CONCLUSION: Anthracycline-based regimen caused comparatively higher peripheral inflammation, which could be the reason for more decline in cognition in anthracycline-receiving patients than non-anthracycline group.

ANTECEDENTES: Regime baseado em antraciclinas (5-fluorouracil, doxorrubicina e ciclofosfamida [FAC]; ciclofosfamida, epirrubicina e 5-fluorouracil [CEF]) e regimes não baseados em antraciclina (ciclofosfamida, metotrexato e 5-fluorouracil (CMF]) são amplamente utilizados como quimioterapia neoadjuvante para pacientes com câncer de mama. OBJETIVO: O presente estudo foi realizado para observar os efeitos do regime FAC, CEF e CMF na cognição e citocinas pró-inflamatórias circulatórias (interleucina 6 [IL-6] e interleucina 1ß [IL-1ß]) durante três ciclos de quimioterapia em pacientes com câncer de mama. MéTODOS: Oitenta pacientes recém-diagnosticadas com câncer de mama HER-2 negativo foram recrutadas e divididas em 3 grupos de pacientes que receberam FAC (n = 27), CEF (n = 26) ou CMF (n = 27). Os níveis séricos de IL-6 e IL-1ß foram medidos por enzyme-linked immunosorbent assay (ELISA) e a cognição foi avaliada por meio do questionário Mini-Mental State Examination (MMSE). RESULTADOS: O regime baseado em antraciclinas aumentou os níveis de IL-6, IL-1ß e diminuiu os escores do MMSE em comparação com o regime CMF (p < 0,05). CONCLUSãO: O regime baseado em antraciclinas causou inflamação periférica comparativamente mais alta, o que pode ser a razão para maior declínio na cognição em pacientes que receberam antraciclinas do que no grupo que não recebeu antraciclina.

Case Report: Cutaneous Leishmaniasis in a Rheumatoid Arthritis Patient Receiving Methotrexate.

The immunosuppressive effect of methotrexate has rarely been associated with reactivation of cutaneous leishmaniasis. Here we present a case of a cutaneous leishmaniasis patient with atypical clinical symptoms without splenomegaly but with cutaneous manifestations after treatment of rheumatoid arthritis with methotrexate and blood recovery of the parasite. Next-generation sequencing was used to identify Leishmania infantum chagasi in the patient's blood sample.