Long-term Systemic Glucocorticoid Research Articles

Performance of ultra-high-frequency ultrasound in the evaluation of skin atrophy in patients with long-term oral glucocorticoid therapy in a tertiary rheumatology center.

Ultra-high-frequency ultrasound (UHF-US) allows visualization of the epidermis, dermis, and subcutis and precise measurement of skin thickness. The aim of this study was to assess the performance and interobserver reliability of UHF-US for measuring skin thickness in patients with long-term systemic glucocorticoid (GC) therapy compared to patients without GC therapy or treated for a shorter period.156 patients with known or suspected inflammatory rheumatic diseases underwent US evaluation for skin thickness by 3 experts in 3 anatomical sites (hand, distal, and proximal forearm). 87 patients were classified as "frequent users" who had received continuous oral GCs for at least one year or at least 3 years with various interruptions. 69 patients without any oral GC therapy in the past or treated for a shorter period were classified as "non-frequent users".UHF-US allowed a precise measurement of skin thickness. Skin thickness at all 3 anatomical sites was significantly decreased in "frequent users" of GCs compared to "non-frequent users" (distal and proximal forearm: p < 0.001; hand: p < 0.05). At all 3 anatomical sites, skin thickness was decreased in patients with clinically assessed parchment-like skin compared to patients without parchment-like skin (distal and proximal forearm: p < 0.001; hand: p < 0.05). Interobserver variability was excellent [hand intraclass correlation coefficient (ICC) = 0.99; proximal forearm ICC = 0.85; distal forearm ICC = 0.84].These data support the idea of UHF-US as an objective and reliable imaging tool for monitoring skin atrophy as adverse effects of GC therapy.

Long-term systemic glucocorticoid therapy and weight gain: a population-based cohort study.

To describe the variation in weight gain in people chronically exposed to systemic glucocorticoids in primary care and to identify the risk factors for weight gain. Data were analysed from the British database, The Health Improvement Network. Body weight variations of individuals prescribed systemic glucocorticoids for at least 3 months at a mean dose ≥10 mg/day were described. The risk factors associated with weight gain ≥10% of the usual weight were assessed. A total of 31516 adults prescribed glucocorticoids and 26967 controls were included in the study. During glucocorticoid exposure, only 12475 (39.6%) individuals gained >2 kg compared with their usual weight. Younger women were more likely to gain weight (mean weight gain in 18-39-year-old glucocorticoid-exposed women: 3.6 kg (s.d. 8.6) compared with 2 kg (s.d. 7.3) in the control group; the absolute mean difference was 1.6 kg (95% CI 0.9, 2.2; P < 0.001). Weight gain ≥10% of the usual weight was observed in 10.2% (n = 3208) of those chronically exposed to glucocorticoids. Women, younger people, those living in areas of higher deprivation, smokers, those on higher doses of the drug and those previously exposed to glucocorticoids were at higher risk. The risk was lower in people prescribed glucocorticoids for an inflammatory condition when compared with asthma or chronic obstructive pulmonary disease. After taking into account usual weight rather than weight just before glucocorticoid initiation and the natural history of weight variation, the amount of weight gain induced by systemic glucocorticoids as prescribed in primary care is less than usually thought. 18THIN081.

Management of Adrenal Insufficiency Risk After Long-term Systemic Glucocorticoid Therapy in Duchenne Muscular Dystrophy: Clinical Practice Recommendations.

Long-term glucocorticoid therapy has improved outcomes in patients with Duchenne muscular dystrophy. However, the recommended glucocorticoid dosage suppresses the hypothalamic-pituitary-adrenal axis, leading to adrenal insufficiency that may develop during severe illness, trauma or surgery, and after discontinuation of glucocorticoid therapy. The purpose of this review is to highlight the risk of adrenal insufficiency in this patient population, and provide practical recommendations for management of adrenal insufficiency, glucocorticoid withdrawal, and adrenal function testing. Strategies to increase awareness among patients, families, and health care providers are also discussed.

Treating juvenile idiopathic arthritis to target: recommendations of an international task force

Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations...

The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis

ABSTRACTObjective: Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. Methods: Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6–12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004–2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. Results: Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0–≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0–2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. Conclusions: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.

Vital to monitor, prevent and treat metabolic and cardiovascular adverse events induced by long-term systemic glucocorticoid therapy

Given the potentially severe consequences of the metabolic and cardiovascular adverse events often induced by the long-term use of systemic glucocorticoids, it is essential that patients receive adequate screening, preventative care and treatment. However, as data are currently limited and largely inconclusive, medical consensus and optimal management strategies have yet to be established; further study is needed.

The prediction and monitoring of toxicity associated with long-term systemic glucocorticoid therapy.

Glucocorticoids are often required for adequate control of inflammation in many serious inflammatory diseases; common indications for long-term treatment include polymyalgia rheumatica, giant cell arteritis, asthma and chronic obstructive pulmonary disease. Long-term glucocorticoid therapy is, however, associated with many adverse effects involving skin, gastro-intestinal, eye, skeletal muscle, bone, adrenal, cardio-metabolic and neuropsychiatric systems. This balance between benefits and risks of glucocorticoids is important for clinical practice and glucocorticoid-related adverse effects can significantly impair health-related quality of life. Understanding the nature and mechanisms of glucocorticoid-related adverse effects may inform how patients are monitored for toxicity and identify those groups, such as older people, that may need closer monitoring. For clinical trials in diseases commonly treated with glucocorticoids, standardised measurement of glucocorticoid-related adverse effects would facilitate future evidence synthesis and meta-analysis.

Systemic glucocorticoid therapy: a review of its metabolic and cardiovascular adverse events.

The prevalence of use of long-term systemic glucocorticoid therapy in the general adult population is 1%. This figure increases to up to 3% in elderly women. Metabolic (i.e. diabetes mellitus, dyslipidemia, weight gain, lipodystrophy) and cardiovascular (i.e. hypertension, cardiovascular events) adverse events are commonly observed in these patients and can be life threatening. Paradoxically, there is very few data on some of these adverse events and many of the available studies remain inconclusive. Incidence of and risk factors for dyslipidemia, weight gain and lipodystrophy are poorly defined. The optimal treatment plan for patients diagnosed with glucocorticoid-induced diabetes or hypertension is undetermined. Finally, there is no medical consensus on the best strategies for the prevention and detection of these complications. However, certain of these questions can be answered by looking at available data on patients with endogenous hypercortisolism (i.e. Cushing's syndrome). This article reviews the pathophysiology, incidence, risk factors, screening, and treatment of glucocorticoid-induced weight gain, lipodystrophy, diabetes, dyslipidemia, hypertension, and cardiovascular events. It also focuses on the possible prevention of these adverse events by targeting the glucocorticoid receptor using selective glucocorticoid receptor modulators.

Long-term systemic glucocorticoid therapy: Patients’ representations, prescribers’ perceptions, and treatment adherence

IntroductionGlucocorticoids have been used since 1948 for their anti-inflammatory and structural effects in various inflammatory diseases. The optimal use of glucocorticoids remains controversial. Patients may have a number of concerns about the effects of glucocorticoids. Many factors can adversely affect treatment adherence. ObjectivesTo evaluate the main adverse effects reported by patients and physicians, and to assess representations associated with glucocorticoid therapy and the underlying disease, via measurements of treatment adherence, with the goal of optimizing treatment strategies and improving patient information. MethodsFrom December 2011 to May 2012, we conducted two surveys in 125 patients receiving long-term glucocorticoid therapy and followed-up at the rheumatology department of the teaching hospital in Casablanca, Morocco, and in 85 hospital physicians in various specialties, respectively. ResultsMean glucocorticoid therapy duration was 6years, mean maximal prescribed dosage was 44.87mg/d, and 50.4% of the patients had inflammatory joint disease. Adverse neuropsychiatric effects were reported by 70 out of 125 (56%) patients. Weight gain was the adverse effect deemed most bothersome by the physicians, who significantly underestimated the occurrence of neuropsychiatric adverse effects (27% vs 56%, P=0.034). Adherence was poor in 80 out of 125 (64%) patients, and 22 out of 125 (18%) patients reported episodes of treatment discontinuation. ConclusionPrescribers underestimate the frequency of neuropsychiatric adverse effects of long-term systemic glucocorticoid therapy. Regular follow-up visits during treatment, with collection of systemic adverse effects might improve treatment adherence.

Population-Based Trends in Osteoporosis Management after New Initiations of Long-Term Systemic Glucocorticoids (1998–2008)

Our objective was to describe changes in glucocorticoid-induced osteoporosis (GIOP) preventive care from 1998-2008 including rates and correlates of bone mineral density (BMD) testing and osteoporosis treatment in new long-term glucocorticoid initiations. A population-based study of adults aged 20 yr or older in Manitoba, Canada, was conducted using linked healthcare databases. Subjects with new long-term (≥90 d) systemic glucocorticoid initiations were identified within each fiscal year. High-quality GIOP preventive care was defined by the composite of BMD testing or osteoporosis treatment within 6 months of starting glucocorticoids. For each initiation, we identified sociodemographic and clinical characteristics, prednisone dose equivalents, and prescriber specialty. Multivariable Poisson regression models were used to calculate adjusted incidence rate ratios (aIRR). We studied 17,736 new long-term glucocorticoid initiations; one third were at least 10 mg prednisone daily, and most (64%) were prescribed by general practitioners. Overall, 6-month rates of BMD testing were 6%, osteoporosis treatment 22%, and the composite of testing or treatment 25%. From 1998-2008, there were modest increases in BMD testing (from 4 to 6%), osteoporosis treatment (from 15 to 24%), and testing or treatment [from 17 to 27%; aIRR = 1.51; 95% confidence interval (CI) = 1.40-1.63]. High-quality GIOP preventive care varied significantly by age (16% for those <50 yr vs. 27% for those ≥70 yr; aIRR = 0.57; 95% CI = 0.52-0.63), sex (13% for men vs. 34% for women; aIRR = 0.40; 95% CI = 0.37-0.43), and prescriber (23% general practice vs. 44% rheumatology; aIRR = 0.56; 95% CI = 0.52-0.60). Quality of GIOP preventive care has improved but remains suboptimal with only one quarter of those starting long-term glucocorticoids receiving BMD testing or osteoporosis treatment. Interventions to improve GIOP prevention, especially targeting younger patients, men, and nonspecialists, are needed.

Association of polymorphisms of xenobiotic-metabolizing genes with glucocorticoid-induced osteoporosis in patients with bronchial asthma

Investigation of risk factors for glucocorticoid-induced (GI) osteoporosis, which is one of the most frequent and serious complications of long-term systemic glucocorticoid (SGC) therapy for bronchial asthma, is a topical issue of preventative medicine. In the present work, allele-specific hybridization on a biochip was used to determine the allele and genotype frequencies of eight candidate genes for GI osteoporosis in 137 patients with bronchial asthma receiving long-term SGC therapy. The MTHFR polymorphism 677C>T showed a significant association with the proximal femur mineral density (Z-score) in patients treated with SGC (nonparametric Kruskal-Wallis ANOVA, p = 0.0013). On the other hand, carriers of the null genotype by the GSTM1 insertion-deletion polymorphism had lower bone mineral density Z-scores than carriers of at least one functional GSTM1 allele (Mann-Whitney U-test with the Bonferroni correction, p = 0.034). Analysis of gene-gene interactions showed that the MTHFR 677C/C/GSTM1 null genotype combination was associated with significantly lower bone mineral density Z-scores than other genotype variants (Kruskal-Wallis ANOVA, p = 0.0012). Thus, the MTHFR and GSTM1 alleles can modulate the risk of GI osteoporosis in patients with bronchial asthma, which is very important for the identification of patients at a high risk of osteoporosis among individuals receiving SGC, as well as inhaled glucocorticoids.

Impact of glucocorticoid-induced adverse events on adherence in patients receiving long-term systemic glucocorticoid therapy

Factors influencing adherence to long-term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. To evaluate the relationship between glucocorticoid-induced adverse events and therapeutic adherence in patients on long-term glucocorticoid treatment. A cross-sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four-item Morisky-Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34-65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8-72); median daily dose 10 mg (IQR 6-20)]. Among these 255 patients, 199 (78%) reported themselves as 'good adherents' and 56 (22%) as 'poor adherents' to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95-0·99, per increasing year; P < 0·01], presence of glucocorticoid-induced epigastralgia (OR 4·02, 95% CI 2·00-8·09; P < 0·01) and presence of glucocorticoid-induced morphological changes (OR 2·49, 95% CI 1·19-5·21; P = 0·02). Moreover, patients with poor adherence were likely to report concomitantly poor adherence to dietary advice associated with glucocorticoid therapy (OR 2·44, 95% CI 1·12-5·26; P = 0·02). As with other chronic therapies, the presence of glucocorticoid-induced adverse events is associated with an altered self-reported adherence to glucocorticoids. Patients who report epigastric pain or morphological changes that they associate with glucocorticoid therapy are particularly at risk of poor adherence. Adherence to dietary advice associated with glucocorticoid therapy may be an indirect measure of treatment adherence.

Immunologic basis and management of steroid-resistant asthma.

Although the majority of patients with asthma respond favorably to inhaled and systemic glucocorticoids, up to 25% of patients with difficult-to-control asthma have poor clinical responses to high doses of systemic glucocorticoids. Early identification of these patients is required to minimize serious side effects from long-term systemic glucocorticoid therapy in patients who are insensitive to such therapy. Recent studies indicate that these individuals have developed diminished glucocorticoid receptor ligand and DNA binding affinity as the result of poorly controlled immune activation potentially triggered by allergens or infection. The current review will examine the immune mechanisms underlying glucocorticoid resistance and discuss the management of this challenging group of patients.

Steroid-Resistant Asthma: Evaluation and Management

Reading this article will reinforce the reader's knowledge of the definition, pathophysiology, differential diagnosis, and treatment of the steroid-resistant asthmatic patient. Prospective and retrospective data from the authors' experience were evaluated. In addition, a Medline database was searched from 1981, using the key words "asthma," "glucocorticoids," and "glucocorticoid resistance" with the restrictions of English language and human subjects. Relevant articles referenced in retrieved sources and current texts on severe asthma were also utilized. Data source abstracts, pertinent articles, and book chapters meeting the objectives were critically reviewed. Although rare, individuals with steroid-resistant asthma are often the most difficult-to-manage asthmatic patients in that they have severe disease yet fail to respond to glucocorticoids. To make the diagnosis of steroid-resistant asthma, the patient must fail to respond to a 7 to 14-day course of daily prednisone as measured by less than a 15% improvement in morning prebronchodilator FEV1 following the glucocorticoid course. Ongoing inflammation is thought to play a major role in the pathogenesis of steroid-resistant asthma, and recent studies have demonstrated diminished glucocorticoid receptor to glucocorticoid, or diminished glucocorticoid receptor to DNA binding as possible mechanisms for diminished glucocorticoid responsiveness. Alternative asthma therapies such as methotrexate, cyclosporine, and intravenous gammaglobulin are often used in this group of asthmatic patients. The patient with steroid-resistant asthma presents several challenges. These individuals often display many of the sequelae of long-term systemic glucocorticoid use while achieving little therapeutic benefit. Prior to making the diagnosis of steroid-resistant asthma, diseases that can contribute to poor control of asthma must be ruled out, and noncompliance issues addressed. Alternative asthma therapies are often used; however, they also carry the potential for adverse effects, and have not been thoroughly studied in this population of asthmatic patients.