Lineamientos para la prevención y el tratamiento de la osteoporosis inducida por glucocorticoides en pediatría / Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in pediatrics

Objetivo. Proporcionar un marco para profesionales de la salud que tratan a pacientes pediátricos bajo terapia con glucocorticoides (GC) y desarrollar recomendaciones para la prevención y el tratamiento de la osteoporosis inducida por GC en la población pediátrica. Métodos. Un panel de expertos en enfermedades óseas y pediátricas generó una serie de preguntas PICO que abordan aspectos relacionados con la prevención y el tratamiento de osteoporosis en pacientes bajo tratamiento con GC. Siguiendo la metodología GRADE, se realizó una revisión sistemática de la literatura, se resumieron las estimaciones del efecto y se calificó la calidad de la evidencia. Luego se procedió a la votación y a la formulación de las recomendaciones. Resultados. Se desarrollaron 7 recomendaciones y 6 principios generales para osteoporosis inducida por GC en población pediátrica. Conclusión. Estas recomendaciones proporcionan orientación para los médicos que deben tomar decisiones en pacientes pediátricos bajo tratamiento con GC.

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC.

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Guidelines for diagnosis and treatment of glucocorticoid-induced osteoporosis / 中华内科杂志

Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.

Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics / 中国骨伤

OBJECTIVE@#To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics.@*METHODS@#Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis.@*RESULTS@#Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway.@*CONCLUSION@#Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Hipo persistente: una rara complicación de una inyección epidural transforaminal de corticoides / Persistent hiccup: a rare complication of a transforaminal epidural corticoid injection / Soluços persistentes: uma complicação rara da injeção peridural transforaminal de corticosteroide

Se describe el caso de un paciente que instaló un hipo persistente luego de recibir una inyección epidural transforaminal lumbar de corticoides. Se destaca que es una complicación raramente reportada y por ende poco conocida por quienes practican intervencionismo en dolor. Se discuten los posibles mecanismos por los que puede presentarse, se reseña la evolución observada, y se describe el tratamiento instituido. Se señala el impacto que el hipo puede tener sobre la calidad de vida.

The case of a patient who installed a persistent hiccup after receiving a lumbar transforaminal epidural injection of corticosteroids is described. It is highlighted that it is a rarely reported complication and little known by those who practice interventional pain medicine. Possible mechanisms by which it may occur are discussed, the evolution observed and the treatment instituted are reviewed. The impact that hiccups can have on quality of life is pointed out.

Descrevemos o caso de um paciente que desenvolveu soluços persistentes após receber uma injeção peridural transforaminal lombar de corticosteróides. Ressalta-se que é uma complicação pouco relatada e, portanto, pouco conhecida por quem pratica o intervencionismo na dor. Discutem-se os possíveis mecanismos pelos quais pode ocorrer, revisa-se a evolução observada e descreve-se o tratamento instituído. O impacto que os soluços podem ter na qualidade de vida é apontado.

Hiperglicemia y diabetes inducidas por esteroides / Hyperglycemia and steroid-induced diabetes

La hiperglicemia y/o diabetes inducida por esteroides, se define como la elevación de la glicemia, causada por la acción de los fármacos glucocorticoideos, sobre el metabolismo de los carbohidratos, y presenta una prevalencia entre un 20% al 50%, en pacientes sin diabetes previa, existiendo mayor riesgo para esta patología en pacientes con diabetes pre-existente, obesidad, uso crónico de esteroides o en dosis altas, entre otros. El diagnóstico se rige por los criterios para diabetes en la mayoría de los casos. No obstante, existen casos en donde la hiperglicemia por esteroides es sub-diagnosticada. Su manejo se basa en el tratamiento farmacológico (antidiabéticos orales, subcutáneos e insulina) y no farmacológico (dieta y ejercicio), tomando en cuenta, el patrón glicémico, peso, edad, co-morbilidades, dosis, tipo y tiempo de uso de los esteroides. La relevancia de conocer como diagnosticar y tratar dicha patología, se debe al riesgo de ingreso hospitalario, de infección, de mala cicatrización y de mortalidad en casos no tratados. En vista del aumento del uso de glucocorticoides en la actualidad, se hace una revisión del abordaje terapéutico de la hiperglicemia y diabetes inducida por esteroides.

Hyperglycemia and Steroid-induced Diabetes is defined as the elevation of glycemia caused by the action of glucocorticoid drugs on carbohydrate metabolism, with a prevalence between 20% and 50% in patients without Diabetes. Though, there is a greater risk of this pathology in patients with pre-existing Diabetes, Obesity, chronic use of steroids or in high doses, among others. In most cases, the diagnosis is governed by the criteria of Diabetes; however, there are cases where hyperglycemia Steroid-induced is under-diagnosed. Its management is based on pharmacological treatment (oral and subcutaneous hypoglycemic agents and insulin) and non-pharmacological treatment (diet and exercise), in accordance with the glycemic pattern, weight, age, co-morbidities, dose, type and the duration of the use of steroid. The relevance of knowing how to diagnose and treat this pathology is the risk of hospital admission, infection, poor healing and mortality in untreated cases. In view of the increased use of glucocorticoids nowadays, a review is made about the therapeutic approach to hyperglycemia and steroid-induced Diabetes.

Effect of glucocorticoid therapy on long-term growth and development of children with bronchiolitis / 中国当代儿科杂志

OBJECTIVES@#To explore the effect of glucocorticoid therapy on the growth and development of children with bronchiolitis.@*METHODS@#A total of 143 children with bronchiolitis who were treated with glucocorticoids from February 2017 to March 2018 were enrolled. The medical data were retrospectively collected, including height, weight, course of the disease, and diagnosis and treatment plan at initial admission. After three years of treatment, physical development indices were measured, growth and development were evaluated by Z-score, and related hematological parameters were measured, including osteocalcin, serum phosphorus, and insulin-like growth factor-1.@*RESULTS@#As for the children with bronchiolitis, the incidence rates of growth retardation and obesity increased significantly after three years of glucocorticoid therapy (P<0.05). The children treated with glucocorticoids for ≥29 days showed a significantly higher incidence rate of obesity than those treated with glucocorticoids for <29 days (P<0.05), while nebulized glucocorticoid treatment had no effect on the growth and development (P>0.05). Compared with the children with growth retardation, the children with normal development had significantly higher levels of serum phosphorus and insulin-like growth factor-1 (P<0.05).@*CONCLUSIONS@#Glucocorticoid therapy can adversely affect long-term growth and development in children with bronchiolitis.

Crisis adrenal asociada al uso de modafinilo / Adrenal crisis associated with modafinil use

Resumen La crisis adrenal es la forma más extrema de presentación de la insuficiencia adrenal y representa una urgencia endocrinológica que llega a poner en riesgo la vida. Esta situación puede ser des encadenada por diferentes causas, entre las cuales se incluye el uso de fármacos inductores del CYP3A4, que aceleran la depuración de la hidrocortisona. Describimos el caso de una mujer de 85 años, con antecedentes de insuficiencia adrenal secundaria y enfermedad renal crónica, que presentó síntomas compatibles con crisis adrenal (astenia, adinamia, hiponatremia grave con síntomas neurológicos e hipotensión arterial) luego de nueve días del inicio de tratamiento con modafinilo. El cuadro clínico mejoró rápidamente con la suspensión del modafinilo y la administración de hidrocortisona endovenosa. Luego de descartar las posibles causas desencadenantes (infecciosas, isquémicas, tromboembolismo pulmonar y omisión en la toma de hidrocortisona), se interpretó que el modafinilo precipitó los síntomas de insuficiencia adrenal al aumentar la depuración del corticoide. El modafinilo tiene la capacidad de inducir la actividad del CYP3A4 y, en consecuencia, disminuir la biodisponibilidad de la hidrocortisona. Recalcamos la necesidad de ajustar la dosis de reemplazo de corticoides en sujetos que reciben fármacos inductores del metabolismo.

Abstract Adrenal crisis is the most extreme presentation form of adrenal insufficiency and represents a life-threatening endocrinological emergency. This situation can be triggered by different causes including the use of CYP3A4-inducing drugs, which accelerate hydrocortisone clearance. We describe the case of an 85-year-old woman with secondary adrenal insufficiency and chronic renal disease, who presented symptoms compatible with adrenal crisis (asthenia, adynamia, severe hyponatremia associated with neurological symptoms and hypotension) nine days after the start of modafinil treat ment. The clinical picture improved rapidly with the suspension of modafinil and the administration of intravenous hydrocortisone. After ruling out the possible triggering causes (infectious, ischemic, pulmonary thromboembo lism and failure to take hydrocortisone), it was interpreted that modafinil precipitated the symptoms of adrenal insufficiency by increasing the steroid clearance. Modafinil has the ability to induce the activity of CYP3A4 and consequently decrease the bioavailability of hydrocortisone. We emphasize the need to adjust steroid dose re placement in subjects receiving metabolism-inducing drugs.

Relationship between corticotherapy and increased cardiac risk in patients with rheumatoid arthritis

Rheumatoid arthritis is an autoimmune inflammatory joint disease with global prevalence of 0.4% to 1.0%. Extra-articular manifestations increase its morbidity and severity, and cardiovascular diseases present the greatest risk. Therapeutic approaches have been used to treat rheumatoid arthritis, often involving the use of multiple classes of drugs with different mechanisms and forms of action. Corticosteroid therapy is widely used in this therapeutic combination; however, its use has been widely questioned because of its high toxicity and some negative effects, including the possibility of increased cardiovascular risk, depending on the dosage. Some studies have provided important insights into how glucocorticoids have an impact on cardiac complications in patients with rheumatoid arthritis. Most of these studies have concluded that exposure to these drugs at high or cumulative doses is associated with increased risk of death, as well as possibly being associated with the presence of a positive rheumatoid factor.

Hepatopatia esteroidal em gatas após terapia com prednisolona: aspectos laboratoriais, tomográficos e histopatológicos / [Steroid hepatopathy in cats after prednisolone use: laboratory, tomographic, and histopathologic aspects]

Glicocorticoides são amplamente utilizados na clínica de pequenos animais, entretanto seu uso contínuo pode causar efeitos colaterais. Os gatos são considerados menos susceptíveis a esses efeitos do que outras espécies, mas existem poucos trabalhos abordando os efeitos adversos em felinos. O objetivo deste estudo foi avaliar possíveis alterações laboratoriais, histopatológicas e do grau de atenuação radiográfica do parênquima hepático de gatas submetidas à terapia com prednisolona. Um ensaio clínico foi realizado em quatro gatas hígidas, as quais receberam prednisolona, por via oral, na dose de 3mg/kg, durante 60 dias consecutivos. Nos achados histopatológicos após 60 dias de tratamento, observou-se desorganização dos cordões de hepatócitos e degeneração vacuolar, além de necrose de hepatócitos, porém não foram observados sinais de fibrose no parênquima hepático. Os dados da tomografia computadorizada demonstram aumento do grau de atenuação do parênquima hepático a partir do 30º dia da administração de prednisolona, que persistiu até o final do experimento. No presente estudo, foi possível caracterizar a existência de hepatopatia esteroidal em gatos em estágios precoces da terapia com prednisolona.(AU)

Glucocorticoids are widely used medications in small animal practice; however, its continuous use can have side effects. Cats are considered less susceptible than other species, however, the literature does not usually address adverse effects in felines. The objective of this study was to evaluate possible laboratory and histopathologic changes, as well as changes to the degree of radiographic attenuation of the hepatic parenchyma in cats treated with prednisolone. A clinical trial was done in four healthy cats, who received prednisolone orally at 3mg/kg during 60 consecutive days. In the histopathologic findings at 60 days of treatment, there were disorganized hepatocyte chords and vacuolar degeneration, as well as hepatocyte necrosis, however, there were no signs of fibrosis in the hepatic parenchyma. Data obtained via computed tomography showed increase of the degree of attenuation in the hepatic parenchyma from day 30 of prednisolone therapy, which persisted until the end of the experiment. In the present study, it was possible to characterize the existence of steroidal hepathopathy in cats in the early stages of prednisolone therapy.(AU)

Adverse drug reactions associated with treatment in patients with chronic rheumatic diseases in childhood: a retrospective real life review of a single center cohort

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)

Insuficiencia suprarenal secundaria al uso de corticoides inhalados: reporte de caso / Adrenal insufficiency secondary to use of inhaled corticosteroids: case report

La insuficiencia suprarrenal es un síndrome que se produce por la disminución de niveles séricos de glucocorticoides, la cual se clasifica en primaria o secundaria, según la etiología. El uso prolongado de corticoides exógenos a altas dosis puede producir una inhibición en el eje hipotálamo-hipofisiario-adrenal, y la supresión aguda de éstos produce insuficiencia suprarrenal secundaria. Los glucocorticoides inhalados, usados ampliamente como tratamiento del asma bronquial, pudiesen tener un impacto a nivel del eje adrenal, principalmente en la población pediátrica. Por el momento, si bien hay reportes de casos que evidencian insuficiencia suprarrenal secundaria al uso de corticoides tanto tópicos como inhalatorios, aún es materia de discusión esta interacción a nivel sistémico, con artículos que se contraponen en sus resultados. Se presenta un caso clínico de una paciente usuaria de glucocorticoides inhalatorios por el antecedente de asma bronquial, que desarrolla una clínica de insuficiencia suprarrenal en el periodo de lactancia.

Adrenal insufficiency is a syndrome that is produced by the decrease in serum glucocorticoid levels, which is classified as primary or secondary, according to the etiology. Prolonged use of exogenous corticosteroids at high doses may cause inhibition in the hypothalamic-pituitary-adrenal axis, and acute suppression of these results in secondary adrenal insufficiency. Inhaled glucocorticoids, widely used as a treatment for bronchial asthma, could have an impact at the level of the adrenal axis, mainly in the pediatric population. At the moment, although there are reports of cases that show adrenal insufficiency secondary to the use of both topical and inhalation corticosteroids, this interaction at systemic level is still a matter of discussion, with articles that contrast in their results. We present a clinical case of a patient using inhaled glucocorticoids due to a history of bronchial asthma, which develops a clinical of adrenal insufficiency in the period of breastfeeding.

Intercellular mediators in bone remodeling regulation in the experimental renal pathology / Mediadores intercelulares de la regulación de la remodelación ósea en un modelo experimental de patología renal

Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappa b receptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG). The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids. Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzymelinked immunoassay was used to measure intercellular mediator levels in the serum. The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals' blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group. In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future. (AU)

Las enfermedades metabólicas óseas se caracterizan por un desequilibrio en el proceso de remodelación ósea en los que participan mediadores tales como receptor del activador del factor nuclear- kappa- b (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, recuentemente empleados en el tratamiento de la enfermedad renal crónica, exacerban este desequilibrio. En la enfermedad esclerótica renal, las moléculas de adhesión celular P-selectina and galectina-3 tienen un rol fundamental. El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelación ósea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crónica con tratamiento glucocorticoideo. Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crónica con afección de la remodelación ósea (ERC); animales con afección de la remodelación ósea expuestos a glucocorticoides (GC); enfermedad renal crónica con afección de la remodelación ósea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioquímicamente, histológicamente y por medición de la densidad ósea. RANKL, OPG, Pselectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno análisis. En los 3 grupos experimentales la densidad ósea se evidenció reducida y los niveles séricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmática en GC y ERC+GC se encontró reducida y aumentada en los animales ERC, en comparación con los animales controles. La concentración sérica de P-selectina sérica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmáticos de los animales intactos. El avance del conocimiento sobre la regulación de la remodelación ósea a través de la interacción de mediadores sistémicos, en un futuro, puede conducir al desarrollo de nuevas estrategias terapéuticas para la prevención de la osteoporosis en pacientes con enfermedad renal crónica. (AU)

Paracoccidioidomycosis in a child: exuberant presentation due to the inadvertent use of systemic corticosteroids

Abstract: Paracoccidioidomycosis is a fungal infection that occurs in immunocompetent patients and are classified into two forms: the acute-subacute form, predominantly in young patients, and the chronic adult form that may present classic ulcerated lesions to rare sarcoid ones. We present the case of a boy whose infection began with sarcoid lesions but, after being mistakenly diagnosed with cutaneous sarcoidosis and treated (for three years) with prednisone, developed painful ulcerations throughout the body. After the correct diagnosis, with evidence of the fungus in histopathological and mycological examinations, the patient was properly treated with itraconazole for eight months and evolved with total remission of the disease.