Assuntos
Imunossupressores/uso terapêutico , Líquen Plano/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Idoso , Avaliação de Medicamentos , Substituição de Medicamentos , Redução da Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Esteroides Fluorados/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: To explore the effect of maternal fluorinated steroid therapy on fetuses affected by immune-mediated complete atrio-ventricular block (CAVB) in utero. MATERIAL AND METHODS: Pubmed, Embase, Cinahl, and ClinicalTrials.gov databases were searched. Only studies reporting the outcome of fetuses with immune CAVB diagnosed on prenatal ultrasound without any cardiac malformations and treated with fluorinated steroids compared to those not treated were included. The primary outcome observed was the regression of CAVB; secondary outcomes were need for pacemaker insertion, overall mortality, defined as the occurrence of either intrauterine (IUD) or neonatal (NND) death, IUD, NND, termination of pregnancy (TOP). Furthermore, we assessed the occurrence of all these outcomes in hydropic fetuses compared to those without hydrops at diagnosis. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used to combine data. RESULTS: Eight studies (162 fetuses) were included. The rate of regression was 3.0% (95%CI 0.2-9.1) in fetuses treated and 4.3% (95%CI 0.4-11.8) in those not treated, with no difference between the two groups (odds ratio (OR): 0.9, 95%CI 0.1-15.1). Pacemaker at birth was required in 71.5% (95%CI 56.0-84.7) of fetuses-treated and 57.8% (95%CI 40.3-74.3) of those not treated (OR: 9, 95%CI 0.4-3.4). There was no difference in the overall mortality rate (OR: 0.5, 95%CI 0.9-2.7) between the two groups; in hydropic fetuses, mortality occurred in 76.2% (95%CI 48.0-95.5) of the treated and in 23.8% (95%CI 1.2-62.3) of the untreated group, while in those without hydrops the corresponding figures were 8.9% (95%CI 2.0-20.3) and 12% (95%CI 8.7-42.2), respectively. Improvement or resolution of hydrops during pregnancy occurred in 76.2% (95%CI 48.0-95.5) of cases treated and in 23.3% (95%CI 1.2-62.3) of those nontreated with fluorinated steroids. CONCLUSIONS: The findings from this systematic review do not suggest a potential positive contribution of antenatal steroid therapy in improving the outcome of fetuses with immune CAVB.
Assuntos
Bloqueio Atrioventricular/tratamento farmacológico , Hidropisia Fetal/tratamento farmacológico , Esteroides Fluorados/uso terapêutico , Bloqueio Atrioventricular/complicações , Bloqueio Atrioventricular/imunologia , Bloqueio Atrioventricular/mortalidade , Feminino , Humanos , Hidropisia Fetal/imunologia , GravidezRESUMO
OBJECTIVES: Extension of disease beyond the atrioventricular (AV) node is associated with increased mortality in cardiac neonatal lupus (NL). Treatment of isolated heart block with fluorinated steroids to prevent disease progression has been considered but published data are limited and discordant regarding efficacy. This study evaluated whether fluorinated steroids given to manage isolated advanced block prevented development of disease beyond the AV node and conferred a survival benefit. METHODS: In this retrospective study of cases enrolled in the Research Registry for NL, inclusion was restricted to anti-SSA/Ro-exposed cases presenting with isolated advanced heart block in utero who either received fluorinated steroids within 1â week of detection (N=71) or no treatment (N=85). Outcomes evaluated were: development of endocardial fibroelastosis, dilated cardiomyopathy and/or hydrops fetalis; mortality and pacemaker implantation. RESULTS: In Cox proportional hazards regression analyses, fluorinated steroids did not significantly prevent development of disease beyond the AV node (adjusted HR=0.90; 95% CI 0.43 to 1.85; p=0.77), reduce mortality (HR=1.63; 95% CI 0.43 to 6.14; p=0.47) or forestall/prevent pacemaker implantation (HR=0.87; 95% CI 0.57 to 1.33; p=0.53). No risk factors for development of disease beyond the AV node were identified. CONCLUSIONS: These data do not provide evidence to support the use of fluorinated steroids to prevent disease progression or death in cases presenting with isolated heart block.
Assuntos
Anticorpos Antinucleares/sangue , Doenças Fetais/tratamento farmacológico , Bloqueio Cardíaco/tratamento farmacológico , Esteroides Fluorados/uso terapêutico , Adulto , Progressão da Doença , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/mortalidade , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/diagnóstico por imagem , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/mortalidade , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/congênito , Masculino , Marca-Passo Artificial , Cuidado Pré-Natal/métodos , Sistema de Registros , Estudos Retrospectivos , Ultrassonografia Pré-Natal , Estados Unidos/epidemiologiaRESUMO
Transplacental transfer of maternal anti-Ro and/or anti-La autoantibodies can result in fetal cardiac disease, including congenital heart block and cardiomyopathy, called cardiac neonatal lupus (NL). Thousands of women are faced with the risk of cardiac NL in their offspring, which is associated with significant morbidity and mortality. There are no known therapies to permanently reverse third-degree heart block in NL, although several treatments have shown some effectiveness in incomplete heart block and disease beyond the atrioventricular node. Fluorinated steroids taken during pregnancy have shown benefit in these situations, although adverse effects may be concerning. Published data are discordant on the efficacy of fluorinated steroids in the prevention of mortality in cardiac NL. ß-agonists have been used to increase fetal heart rates in utero. The endurance of ß-agonist effect and its impact on mortality are in question, but when used in combination with other therapies, they may provide benefit. No controlled experiments regarding the use of plasmapheresis in cardiac NL have been performed, despite its theoretical benefits. Intravenous immunoglobulin was not shown to prevent cardiac NL at a dose of 400 mg/kg, although it has shown effectiveness in the treatment of associated cardiomyopathy both in utero and after birth. Retrospective studies have shown that hydroxychloroquine may prevent the recurrence of cardiac NL in families with a previously affected child, and a prospective open-label trial is currently recruiting patients in order to fully evaluate this relationship.
Assuntos
Bloqueio Cardíaco/congênito , Lúpus Eritematoso Sistêmico/congênito , Agonistas Adrenérgicos beta/uso terapêutico , Feminino , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/prevenção & controle , Bloqueio Cardíaco/terapia , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/prevenção & controle , Lúpus Eritematoso Sistêmico/terapia , Plasmaferese/métodos , Gravidez , Cuidado Pré-Natal/métodos , Diagnóstico Pré-Natal/métodos , Prevenção Secundária , Esteroides Fluorados/uso terapêuticoRESUMO
Complete congenital atrio-ventricular (AV) heart block develops in 2-5% of fetuses of Ro/SSA and La/SSB autoantibody-positive pregnant women. During pregnancy, the Ro/SSA and La/SSB antibodies are transported across the placenta and affect the fetus. Emerging data suggest that this happens by a two-stage process. In the first step, maternal autoantibodies bind fetal cardiomyocytes, dysregulate calcium homestasis and induce apoptosis in affected cells. This step might clinically correspond to a first-degree heart block, and be reversible. La/SSB antibodies can bind apoptotic cardiomyocytes and thus increase Ig deposition in the heart. The tissue damage could, as a second step, lead to spread of inflammation in genetically pre-disposed fetuses, progressing to fibrosis and calcification of the AV-node and subsequent complete congenital heart block. Early intrauterine treatment of an incomplete AV-block with fluorinated steroids has been shown to prevent progression of the heart block, making it clinically important to find specific markers to identify the high-risk pregnancies.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Fetais/imunologia , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/imunologia , Animais , Feminino , Terapias Fetais , Bloqueio Cardíaco/prevenção & controle , Humanos , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/patologia , Gravidez , Esteroides Fluorados/uso terapêuticoAssuntos
Dermatite de Contato/diagnóstico , Dermatite de Contato/terapia , Administração Oral , Administração Tópica , Adulto , Algoritmos , Antialérgicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Criança , Pré-Escolar , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/terapia , Dermatite de Contato/fisiopatologia , Diagnóstico Diferencial , Suscetibilidade a Doenças , Feminino , Glucocorticoides/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Masculino , Testes do Emplastro , Plantas/efeitos adversos , Plantas/química , Prognóstico , Próteses e Implantes/efeitos adversos , Esteroides Fluorados/administração & dosagem , Esteroides Fluorados/uso terapêuticoRESUMO
BACKGROUND: Mothers with anti-SSA/Ro antibodies who have had a previous fetus with congenital heart block (CHB) have a risk of recurrence estimated to be up to 16%. OBJECTIVE: To improve the management of these "high risk patients" by determining (a) whether or not prophylactic treatment is efficient; (b) whether or not fluorinated steroids (betametasone and dexamethasone) that do cross the placenta in an active form are safe for the fetus; and (c) which prophylactic treatment should be used. METHODS: Retrospective study performed on seven mothers sent to a university hospital owing to a past history of one (six mothers) or two children (one mother) with CHB. RESULTS: 13 subsequent pregnancies occurred. No CHB was observed. All four pregnancies in women treated with 10 mg/day prednisone were uneventful. Three pregnancies in women receiving no steroids resulted in two early spontaneous abortions and one live birth. The six pregnancies in women treated with dexamethasone (4-5 mg/day) ended in one early and one late spontaneous abortion, two stillbirths, and two live births with intrauterine growth restriction and mild adrenal insufficiency. A histological study of one stillbirth disclosed intrauterine growth restriction and marked adrenal hypoplasia. CONCLUSION: Adverse obstetric outcomes were often seen here and major concerns have been raised by paediatricians about the safety of fluorinated steroids, owing to the results of animals studies, retrospective data, and randomised trials. Because fluorinated steroids have not been shown to improve prophylactic treatment of CHB in pregnant women at high risk, their use is questionable.
Assuntos
Anticorpos Antinucleares/sangue , Dexametasona/efeitos adversos , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/prevenção & controle , Gravidez de Alto Risco/imunologia , Esteroides Fluorados/efeitos adversos , Insuficiência Adrenal/etiologia , Dexametasona/uso terapêutico , Feminino , Retardo do Crescimento Fetal/etiologia , Bloqueio Cardíaco/imunologia , Humanos , Recém-Nascido , Prednisolona/uso terapêutico , Gravidez , Estudos Retrospectivos , Esteroides Fluorados/uso terapêutico , Falha de TratamentoRESUMO
Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7-14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.
Assuntos
Asma/metabolismo , Testes Respiratórios , Cisteína/metabolismo , Leucotrieno B4/metabolismo , Leucotrienos/metabolismo , Respiração , Adolescente , Asma/tratamento farmacológico , Biomarcadores , Criança , Proteção da Criança , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Óxido Nítrico/metabolismo , Respiração/efeitos dos fármacos , Índice de Gravidade de Doença , Estatística como Assunto , Esteroides Fluorados/uso terapêutico , Resultado do Tratamento , Reino UnidoRESUMO
Our studies of mononuclear leukocyte peripheral blood homogenates demonstrate significantly increased cyclic adenosine monophosphate-specific phosphodiesterase activity in patients with atopic dermatitis who were untreated for 1 week, compared with normal adult nonatopic control subjects. Phosphodiesterase activity is not related to the extent or activity of the patient's disease or the presence or absence of allergic respiratory disease. Enzyme kinetic studies showed a triphasic plot in normal mononuclear leukocytes but a biphasic plot in atopic dermatitis. This may be interpreted as an absence of an enzyme with a low (0.080) Michaelis Menton constant (Km) in atopic dermatitis samples. One week of therapy with a topical fluorinated steroid ointment caused a significant reduction in disease activity. Although a slight reduction in mean total phosphodiesterase activity occurred, it did not reach statistical significance. One week's treatment, however, caused the abnormal biphasic kinetic plot to revert to a triphasic plot with return of the low Km enzyme form in those patients who showed a fall in phosphodiesterase activity. This finding suggests that the elevated phosphodiesterase activity in atopic dermatitis may be responsive in a limited degree to topical steroid therapy.
Assuntos
3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Dermatite Atópica/tratamento farmacológico , Leucócitos Mononucleares/enzimologia , Esteroides Fluorados/uso terapêutico , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , 3',5'-AMP Cíclico Fosfodiesterases/farmacocinética , Administração Tópica , Adulto , Dermatite Atópica/sangue , Feminino , Humanos , Masculino , Pomadas , Proteínas/análise , Esteroides Fluorados/administração & dosagemRESUMO
Sixty-eight patients with histologically diagnosed typical vulvar dystrophies were treated with local administration of steroids. Twenty-three patients with hyperplastic dystrophies received topical fluorinated corticosteroids twice a day for 4 weeks and once a day for another 2 weeks. Thirty-five patients with lichen sclerosus were given local 2% testosterone propionate in vaseline twice a day for 8 weeks, once a day for another 8 weeks and then 3 times a week for another 8 weeks. Ten patients with mixed dystrophy first received topical fluorinated corticosteroids twice a day for 4 weeks and once a day for another 2 weeks, and then local 2% testosterone propionate in vaseline twice a day for 4 weeks and once a day for another 4 weeks. A relief of symptomatology and a regression of gross appearance were obtained in 82.6% and 69.6% of patients respectively with hyperplastic dystrophy, in 82.9% and 65.7% of those with lichen sclerosus and in 80% and 40% of those with mixed dystrophy. A recurrence of symptomatology often occurred at various times after the end of therapy.
Assuntos
Esteroides Fluorados/administração & dosagem , Testosterona/administração & dosagem , Doenças da Vulva/tratamento farmacológico , Administração Tópica , Quimioterapia Combinada , Feminino , Humanos , Recidiva , Esteroides Fluorados/efeitos adversos , Esteroides Fluorados/uso terapêutico , Testosterona/efeitos adversos , Testosterona/uso terapêutico , Doenças da Vulva/etiologia , Doenças da Vulva/patologiaAssuntos
Dermatite das Fraldas/complicações , Granuloma/etiologia , Dermatopatias/etiologia , Nádegas , Dermatite das Fraldas/tratamento farmacológico , Granuloma/tratamento farmacológico , Humanos , Hidrocortisona/uso terapêutico , Lactente , Masculino , Dermatopatias/tratamento farmacológico , Esteroides Fluorados/uso terapêuticoRESUMO
This report deals with a 5-month-old infant who at the age of 2 months was treated with topical fluorinated steroids for dermatitis in the diaper area. The treatment was continued for about 2 months. Some weeks later, multiple oval and round dark brown nodules developed in the inguinogenital areas. Histologic examination of these lesions revealed intense granulomatous infiltration in the upper dermis that consisted of lymphocytes, neutrophilic and eosinophilic granulocytes, and histiocytes. After steroid therapy was discontinued, the nodules slowly disappeared.
Assuntos
Nádegas/efeitos dos fármacos , Dermatite das Fraldas/tratamento farmacológico , Granuloma/induzido quimicamente , Pele/efeitos dos fármacos , Esteroides Fluorados/efeitos adversos , Feminino , Granuloma/patologia , Humanos , Lactente , Pele/patologia , Esteroides Fluorados/uso terapêuticoRESUMO
This study evaluates the benefits of a potent and midstrength topical steroid compared with simple lubricating agents when used in combination with erythemagenic doses of sunlamp fluorescent UV irradiation in psoriasis. Twenty-six patients were studied in a bilateral symmetrical comparison. No significant differences were observed between topical corticosteroids and lubricants in the number of patients achieving a 75% or greater resolution of psoriasis. Topical corticosteroids did not reduce the number of treatments required for clearing. We did not observe faster recurrences in sites treated with topical corticosteroids. More severe burns and slightly less effectiveness were noted in patients irradiated five times weekly compared with three.
Assuntos
Anti-Inflamatórios/uso terapêutico , Fotoquimioterapia , Psoríase/tratamento farmacológico , Esteroides Fluorados/uso terapêutico , Administração Tópica , Queimaduras/etiologia , Glucocorticoides , Humanos , Masculino , Pessoa de Meia-Idade , Bases para Pomadas , Fotoquimioterapia/efeitos adversosRESUMO
Hydrocortisone valerate cream (0.2 percent) was evaluated in three controlled clinical trials involving a total of sixty-eight patients with atopic dermatitis. This new nonfluorinated steroid was found to be as effective as the fluorinated beta-methasone valerate cream (0.1 percent) and significantly more effective than hydrocortisone cream (0.1 percent) and the placebo cream base. All studies were double-blind, paired comparisons, utilizing application of the medications three times a day for up to four weeks or until clearing occurred.