Inflammatory rheumatic diseases frequently affect women of childbearing age.Biologic therapy during pregnancy is an important topic that is yet unresolved.The majority of documented experiences are in case series,case...Inflammatory rheumatic diseases frequently affect women of childbearing age.Biologic therapy during pregnancy is an important topic that is yet unresolved.The majority of documented experiences are in case series,case reports,or registries.Tumor necrosis factor(TNF) inhibitors are now better known.Some evidence suggests that it is possible that differences between drugs regarding safety are associated with the structure and capacity to cross the placenta,but we are not aware of any study that supports unequivocally this statement.Most of the monoclonal antibodies are actively transferred to fetal circulation using the neonatal Fc receptor.Although this transfer does not appear to be associated with the risk of miscarriage,stillbirth,or congenital abnormality,the rate of premature births and lower birth weight may be increased.During fetal development,the neonatal period,and childhood,the immune system is constantly maturing.The ability to produce cytokines in response to infectious stimulus remains low for years,but is similar to that of an adult around the age of 3 years owing to the adaptive nature of the newborn's immune system as a result of exposure to microbes.Therefore,exposure to TNF inhibitors may have serious consequences on the newborn,such as severe infections or allergic reactions.Regarding the former,an anecdotal case report described a fatal case of disseminated bacillus Calmette-Guérin(BCG) infection in an infant born to a mother taking infliximab for Crohn's disease.Although the baby was born and progressed well initially,he died at 4.5 mo after he was vaccinated with BCG.Fortunately,serious infections do not appear to be frequent in newborns exposed to in utero biologic therapy.However,very limited short-term experiences are available regarding complications in an exposed fetus,and no data are available about long-term implications on the child's developing immune system.Therefore,we must be aware of potential complications in later years.Although the clinical data to date are promising,no firm展开更多
Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but als...Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem celltherapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.展开更多
文摘Inflammatory rheumatic diseases frequently affect women of childbearing age.Biologic therapy during pregnancy is an important topic that is yet unresolved.The majority of documented experiences are in case series,case reports,or registries.Tumor necrosis factor(TNF) inhibitors are now better known.Some evidence suggests that it is possible that differences between drugs regarding safety are associated with the structure and capacity to cross the placenta,but we are not aware of any study that supports unequivocally this statement.Most of the monoclonal antibodies are actively transferred to fetal circulation using the neonatal Fc receptor.Although this transfer does not appear to be associated with the risk of miscarriage,stillbirth,or congenital abnormality,the rate of premature births and lower birth weight may be increased.During fetal development,the neonatal period,and childhood,the immune system is constantly maturing.The ability to produce cytokines in response to infectious stimulus remains low for years,but is similar to that of an adult around the age of 3 years owing to the adaptive nature of the newborn's immune system as a result of exposure to microbes.Therefore,exposure to TNF inhibitors may have serious consequences on the newborn,such as severe infections or allergic reactions.Regarding the former,an anecdotal case report described a fatal case of disseminated bacillus Calmette-Guérin(BCG) infection in an infant born to a mother taking infliximab for Crohn's disease.Although the baby was born and progressed well initially,he died at 4.5 mo after he was vaccinated with BCG.Fortunately,serious infections do not appear to be frequent in newborns exposed to in utero biologic therapy.However,very limited short-term experiences are available regarding complications in an exposed fetus,and no data are available about long-term implications on the child's developing immune system.Therefore,we must be aware of potential complications in later years.Although the clinical data to date are promising,no firm
文摘Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem celltherapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.
