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1.
Eosinophilic Esophagitis: Etiology and Therapy.
Patel, RV, Hirano, I, Gonsalves, N
Annual review of medicine. 2021;:183-197
Abstract
Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.
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2.
Atopic dermatitis and its relation to food allergy.
Graham, F, Eigenmann, PA
Current opinion in allergy and clinical immunology. 2020;(3):305-310
Abstract
PURPOSE OF REVIEW To present the most recent evidence on atopic dermatitis and its relation to food allergy. RECENT FINDINGS Atopic dermatitis is a chronic inflammatory disorder of the skin characterized by impaired skin barrier because of multifactorial causes including genetic factors, immune dysregulation, and skin microbiome dysbiosis. Infants with temporary skin barrier disruption and/or persistent atopic dermatitis are particularly at risk of developing food allergy (during the so-called atopic march), with up to half of patients demonstrating positive food-specific IgE and one-third of severe cases of atopic dermatitis having positive symptoms on oral food challenge. A high proportion of children with atopic dermatitis exhibit asymptomatic sensitization to foods, and skin testing to identify potential food triggers is not recommended unless the patient has a history suggestive of food allergy and/or moderate-to-severe atopic dermatitis unresponsive to optimal topical care. Indeed, indiscriminate testing can lead to a high proportion of false-positive tests and harmful dietary evictions. Promising strategies to prevent food allergy in children with atopic dermatitis include early skincare with emollients and treatment with topical steroid, and early introduction of highly allergenic foods. SUMMARY Further studies are required to identify risk factors for atopic dermatitis to help prevent the development of food allergy in this high-risk population.
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3.
[Osteoporosis-frequent comorbidity in patients with rheumatism].
Gaubitz, M
Zeitschrift fur Rheumatologie. 2019;(3):249-254
Abstract
Osteoporosis is one of the most frequent comorbidities in inflammatory rheumatic diseases. The immune system is substantially involved in the regulation of bone homeostasis and chronic inflammatory diseases influence this equilibrium at several levels. Besides the immunologically mediated inflammatory activity, immobility and glucocorticoid treatment are further risk factors for osteoporosis. Diagnostic and therapeutic recommendations are based on the current guidelines for osteoporosis of the Governing Body on Osteoporosis (DVO). Monitoring of the risk factors and bone mineral density testing is meaningful in each patient with a newly diagnosed rheumatic disease. In the case of a T-score ≤-1.5 a specific drug treatment with bisphosphonates, teriparatide or denosumab should be started together with optimizing preventive measures, such as reduction of glucocorticoid dosage, calcium and vitamin D intake and life style modifications. The risk of osteonecrosis of the jaw (ONJ) in patients with osteoporosis is small; however, there appears to be a significant increase in multiple vertebral fractures after discontinuation of denosumab.
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4.
Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis.
Ciardulli, A, D'Antonio, F, Magro-Malosso, ER, Manzoli, L, Anisman, P, Saccone, G, Berghella, V
Acta obstetricia et gynecologica Scandinavica. 2018;(7):787-794
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Abstract
INTRODUCTION The aim of this study was to explore the effect of maternal fluorinated steroid therapy on fetuses affected by second-degree immune-mediated congenital atrioventricular block. MATERIAL AND METHODS Studies reporting the outcome of fetuses with second-degree immune-mediated congenital atrioventricular block diagnosed on prenatal ultrasound and treated with fluorinated steroids compared with those not treated were included. The primary outcome was the overall progression of congenital atrioventricular block to either continuous or intermittent third-degree congenital atrioventricular block at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used. RESULTS Five studies (71 fetuses) were included. The progression rate to congenital atrioventricular block at birth in fetuses treated with steroids was 52% (95% confidence interval 23-79) and in fetuses not receiving steroid therapy 73% (95% confidence interval 39-94). The overall rate of regression to either first-degree, intermittent first-/second-degree or sinus rhythm in fetuses treated with steroids was 25% (95% confidence interval 12-41) compared with 23% (95% confidence interval 8-44) in those not treated. Stable (constant) second-degree congenital atrioventricular block at birth was present in 11% (95% confidence interval 2-27) of cases in the treated group and in none of the newborns in the untreated group, whereas complete regression to sinus rhythm occurred in 21% (95% confidence interval 6-42) of fetuses receiving steroids vs. 9% (95% confidence interval 0-41) of those untreated. CONCLUSIONS There is still limited evidence as to the benefit of administered fluorinated steroids in terms of affecting outcome of fetuses with second-degree immune-mediated congenital atrioventricular block.
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Effects of Glucocorticoids in the Immune System.
Oppong, E, Cato, AC
Advances in experimental medicine and biology. 2015;:217-33
Abstract
Glucocorticoids (GCs) are steroid hormones with widespread effects. They control intermediate metabolism by stimulating gluconeogenesis in the liver, mobilize amino acids from extra hepatic tissues, inhibit glucose uptake in muscle and adipose tissue, and stimulate fat breakdown in adipose tissue. They also mediate stress response. They exert potent immune-suppressive and anti-inflammatory effects particularly when administered pharmacologically. Understanding these diverse effects of glucocorticoids requires a detailed knowledge of their mode of action. Research over the years has uncovered several details on the molecular action of this hormone, especially in immune cells. In this chapter, we have summarized the latest findings on the action of glucocorticoids in immune cells with a view of identifying important control points that may be relevant in glucocorticoid therapy.
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Steroid-sensitive nephrotic syndrome in children: triggers of relapse and evolving hypotheses on pathogenesis.
Uwaezuoke, SN
Italian journal of pediatrics. 2015;:19
Abstract
Nephrotic syndrome remains the most common manifestation of glomerular disease in childhood. Minimal change nephropathy is the most common cause of the syndrome in children. Despite its initial high response rate to corticosteroids and its favorable prognosis, relapses are common leading to increased morbidity and cost of treatment.This review seeks to appraise the common triggers of relapse and to highlight the evolving hypotheses about the pathogenesis of the syndrome. Literature search was conducted through PubMed, Google web search and Cochrane Database of Systematic reviews using relevant search terms.Acute respiratory infections and urinary tract infections are the most frequent infectious triggers of relapse. Targeted interventions like initiating corticosteroid or its dose-adjustment during episodes of acute respiratory infection and zinc supplementation are reportedly effective in reducing relapse rates. Hypotheses on pathogenesis of the syndrome have evolved from the concepts of 'immune dysregulation', 'increased glomerular permeability' to 'podocytopathy'.Although development of drugs which can regulate the pathways for podocyte injury offers future hope for effective and targeted treatment, the relapse-specific interventions currently contribute to significant reduction in disease morbidity.
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7.
The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis.
Danby, SG, Chittock, J, Brown, K, Albenali, LH, Cork, MJ
The British journal of dermatology. 2014;(4):914-21
Abstract
BACKGROUND Atopic dermatitis (AD) is an inflammatory skin disease arising as a result of immune system and skin barrier defects. Topical corticosteroids are safe and effective treatments for AD, when used in short courses. Prolonged use is associated with skin barrier damage. Topical calcineurin inhibitors are alternative immune-modulating treatments for AD purported to have no negative effects on the skin barrier. OBJECTIVES To compare the effects of betamethasone valerate 0·1% cream (BMVc) and tacrolimus 0·1% ointment (TACo) on the skin barrier. METHODS Twenty volunteers with quiescent AD (no active signs for 6 months) participated in a randomized observer-blind study, wherein BMVc was applied to one forearm and TACo to the other, twice daily for 4 weeks. The biophysical/biological properties of the stratum corneum were assessed before and after treatment. Nine volunteers with active disease and 10 with healthy skin were assessed at untreated sites. RESULTS BMVc significantly reduced skin barrier function, integrity and cohesion, and the levels of pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) towards the subclinical barrier defect observed in patients with AD (nonlesional sites). TACo preserved skin barrier function, integrity, cohesion and PCA and UCA levels, while significantly increasing skin hydration to levels comparable with healthy skin. Both treatments reduced skin surface pH and trypsin-like protease activity, with TACo doing so to a significantly greater degree. CONCLUSION In quiescent AD, 4 weeks of BMVc treatment adversely affected the biophysical properties of the skin and reduced the levels of natural moisturizing factor, whereas TACo improved the condition of the skin barrier.
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8.
Novel treatments for NEC: keeping IBD in mind.
Harpavat, S, Pammi, M, Gilger, M
Current gastroenterology reports. 2012;(5):373-9
Abstract
Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease of premature newborns, thought to result in part from overactivity of the innate immune system. NEC has been well-studied from the perspective of prevention; however, after the disease onset, there are limited treatment options to control its progression. This review discusses four potential therapies that target the overactive immune response in NEC: pentoxifylline, platelet activating factor modulators, glucocorticoids, and vasoactive substances. In addition, given the similar pathogenesis of NEC and inflammatory bowel disease (IBD), we propose that IBD therapies could provide promising leads for novel strategies with which to treat NEC.
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9.
Calcipotriene/betamethasone in the treatment of psoriasis: a review article.
Saraceno, R, Gramiccia, T, Frascione, P, Chimenti, S
Expert opinion on pharmacotherapy. 2009;(14):2357-65
Abstract
Plaque-type psoriasis is a chronic and immune-mediated skin disease affecting approximately 1-3% of the Caucasian population. Most cases are of mild or moderate severity and benefit from local treatment that represents the mainstay therapy. Topical corticosteroids and vitamin D(3) analogues remain the option of choice. Optimization of these treatments is made by the combination of calcipotriene and betamethasone dipropionate. This formulation combines the keratinocyte differentiation and antiproliferative action of the vitamin D(3) analogues with the anti-inflammatory effect of steroids enhancing effectiveness while reducing the side-effect profile of the single topical agent. In this article, we highlight the advantages of the association of calcipotriene and betamethasone in the treatment of localized plaque-type, scalp and nail psoriasis.
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10.
Clinical features associated with glucocorticoid receptor polymorphisms. An overview.
Manenschijn, L, van den Akker, EL, Lamberts, SW, van Rossum, EF
Annals of the New York Academy of Sciences. 2009;:179-98
Abstract
The glucocorticoid receptor (GR) is crucial for the effects of glucocorticoids (GCs). Several polymorphisms of the GR are associated with altered sensitivity to GCs. For the ER22/23EK polymorphism, a relative GC resistance has been demonstrated. In vivo, this was suggested by a smaller response to a dexamethasone suppression test (DST), whereas in vitro experiments showed a diminished transactivational activity. The associated features of ER22/23EK carriers consist of favorable metabolic and body compositional conditions. In elderly subjects this polymorphism was associated with longevity and decreased risk of dementia. Interestingly, recent studies also showed an increased risk of major depression. In contrast, the N363S polymorphism was reported to be associated with an enhanced sensitivity to GCs, as was demonstrated by a DST. This polymorphism has also been associated with increased body mass index (BMI) and LDL-cholesterol levels, as well as increased risk of cardiovascular disease. However, additional studies yielded conflicting results, showing no associations with being overweight. The BclI polymorphism is also associated with increased GC sensitivity. In addition, associations with increased abdominal fat mass, Crohn's disease and, remarkably, major depression have been reported. Another GR polymorphism, located in exon 9beta, is associated with increased expression and stabilization of the dominant negative splice variant GR-beta. Carriers of this polymorphism displayed a relative GC resistance in vitro as evidenced by diminished transrepressional activity, which is important for the immune system and inflammation. Associations have been found with increased inflammatory parameters, cardiovascular disease, and rheumatoid arthritis. In this article, studies concerning these clinically relevant GR variants are discussed.