Cumulative Glucocorticoid Dose Research Articles

SP0090 Steroid myopathy - do molecular mechanisms bring us closer to novel treatment strategies?

Introduction of glucocorticoids in the treatment of inflammatory myopathies and other inflammatory conditions in the 1950s had a major impact on survival and morbidity. However, it was already early recognized...

FRI0210 Poor immunization with hepatitis B vaccination in patients with granulomatosis with poliangiitis (wegener’s) and more favorable antibody response in females

BackgroundHepatitis B (HepB) is an endemic infection in Turkey, with an intermediate risk rate (2-7%). HepB vaccination has long been advised in high risk population, especially in endemic areas. Granulomatosis...

AB0371 State of the art for treating-to-target in sle: a systematic literature review

BackgroundIn order to develop “treat-to-target” recommendations for SLE, a panel of experts identified topics related to the treatment of the disease and commissioned a systematic literature search.ObjectivesTo provide the literature-based...

AB0683 Parameters of arterial stiffness in a population of SLE patients with long disease duration: Something new to be examined?

BackgroundPatients with Systemic Lupus Erythematosus (SLE) are at increased risk to develop cardiovascular (CV) events. Arterial stiffness (AS) expresses structural changes in the arterial wall. The presence of AS can...

THU0331 Management of osteoporosis in children: Experience from a pediatric rheumatology center

BackgroundOsteoporosis (OP) is being increasingly recognized in pediatric practice as a consequence of several factors. The diagnosis of OP in children and adolescents should not be made on the basis...

Analysis of the prevalence of cataracts and glaucoma in systemic lupus erythematosus and evaluation of the rheumatologists' practice for the monitoring of glucocorticoid eye toxicity

Chronic glucocorticoid (GC) therapy is associated with an increased risk of developing cataracts and glaucoma, and recommendations have been developed for monitoring these side effects in patients with rheumatic diseases. The aim of this study was to assess the prevalence of cataracts and glaucoma and the adherence to the existing recommendations for monitoring eye toxicity of chronic GC therapy among systemic lupus erythematosus (SLE) patients in routine clinical practice. Clinical charts of 170 patients were examined, and 34 (20%) of them never underwent an eye assessment. The remaining 136 underwent an eye assessment with an interval of 75 ± 61.7 months. Only 45 (33%) had received an evaluation during the previous 12 months. All these 170 patients were taking chronic CG therapy at a mean daily dose of 5.4 ± 2.4 mg prednisone and a mean cumulative dose of 27.6 ± 20.5 g. Out of the 136 patients with at least one eye assessment, cataracts were observed in 39 patients (29%) and glaucoma in 4 patients (3%). Cataracts were diagnosed at a mean age of 46.5 ± 10 years; the development of cataracts was associated with age, disease duration, and cumulative GC dose. Glaucoma was diagnosed at a mean age of 40.5 ± 16 years; due to the small number of patients, no correlations were made. The prevalence of cataracts and glaucoma is higher than in the general population, and these conditions occur early in the life of SLE patients. An association between GC and cataracts is confirmed. The adherence to recommendations is suboptimal as only 33% of patients underwent an eye assessment over the previous 12 months. These data reinforce the need to improve adherence to recommendations for eye monitoring among SLE patients under chronic therapy with GC.

A Search for Variables Predicting Cortisol Response to Low-Dose Corticotropin Stimulation Following Supraphysiological Doses of Glucocorticoids

To determine which biological or clinical variables may predict cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation following supraphysiological doses of glucocorticoids in children. This retrospective study included all patients who underwent ACTH testing (1 μg) between October 2008 and June 2010 at the Sainte-Justine University Hospital Center, Montreal, after supraphysiological doses of glucocorticoids. Data from 103 patients (median age, 8.0 years; range, 0.6-18.5 years; 57 girls) were analyzed, revealing growth deceleration in 37% and excessive weight gain in 33%. Reasons for glucocorticoid treatment included asthma (n = 30) and hematologic (n = 22), dermatologic (n = 19), rheumatologic (n = 16), and miscellaneous (n = 16) disorders. The following information was recorded: duration of glucocorticoid treatment (median, 374 days; range, 5-4226 days); duration of physiological hydrocortisone replacement (median, 118 days; range, 0-1089 days); maximum daily (median, 200 mg/m(2)/day; range, 12-3750 mg/m(2)/day) and cumulative (median, 16 728 mg/m(2); range, 82-178 209 mg/m(2)) doses, in hydrocortisone equivalents; and interval since the last dose (median, 43 days; range, 1-1584 days). Sixty-two patients (58%) exhibited a normal response (ie, peak cortisol >500 nmol/L) to ACTH stimulation. Peak cortisol level was not related to sex, prior morning cortisol level, duration of treatment, or cumulative glucocorticoid dose; 28% of the patients with normal baseline cortisol levels nevertheless demonstrated a subnormal response to ACTH. Given the absence of clinical or biological predictors of the cortisol response to ACTH after suppressive doses of glucocorticoids, physicians have only 2 options: (1) empirically advocate glucocorticoid stress coverage during 18 months after cessation of high-dose glucocorticoid treatment; or (2) perform serial ACTH testing in all such patients until a normal peak cortisol level is attained.

Risk Factors in Cardiovascular Disease in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disorder which predominantly affecting women. The most common cause of death in SLE patients affected by disease for more than 5 years is cardiovascular disease (CVD). Epidemiological observations suggest that, together with classical conventional risk factors, other mechanisms (non-conventional/disease-specific factors) promote accelerated atherosclerosis in inflammatory diseases like SLE. Traditional CVD risk factors included age, hypertension, diabetes mellitus, dyslipidemia, previous vascular event defined as previous history of cerebrovascular accidents or ischemic heart disease, menopause and smoking. The non-traditional factors presents in SLE are disease-specific like renal disease manifestation as Lupus nephritis (LN), presence of pro-inflammatory cytokines, some of inflammatory mediators, antiphospholipid antibodies, anti-oxLDL antibodies, corticosteroid uses and cumulative dose of glucocorticoids. We will review traditional and non-traditional risk factors associated with CVD in SLE patients.

Risk Factors in Cardiovascular Disease in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disorder which predominantly affecting women. The most common cause of death in SLE patients affected by disease for more than 5 years is cardiovascular disease (CVD). Epidemiological observations suggest that, together with classical conventional risk factors, other mechanisms (non-conventional/disease-specific factors) promote accelerated atherosclerosis in inflammatory diseases like SLE. Traditional CVD risk factors included age, hypertension, diabetes mellitus, dyslipidemia, previous vascular event defined as previous history of cerebrovascular accidents or ischemic heart disease, menopause and smoking. The nontraditional factors presents in SLE are disease-specific like renal disease manifestation as Lupus nephritis (LN), presence of pro-inflammatory cytokines, some of inflammatory mediators, antiphospholipid antibodies, anti-oxLDL antibodies, corticosteroid uses and cumulative dose of glucocorticoids. We will review traditional and non-traditional risk factors associated with CVD in SLE patients. Keywords: Nontraditional risk factors, cardiovascular disease, systemic lupus erythematosus

The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

OBJECTIVE:To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosusMETHODS:This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay.RESULTS:A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection.CONCLUSIONS:The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.

Glucocorticoid-Induced Avascular Bone Necrosis: Diagnosis and Management

Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty.

Charcot Neuroarthropathy After Simultaneous Pancreas-Kidney Transplant

Immunosuppressive regimen is associated with several metabolic adverse effects. Bone loss and fractures are frequent after transplantation and involve multifactorial mechanisms. A retrospective analysis of 130 patients submitted to simultaneous pancreas-kidney transplantation (SPKT) and an identification of risk factors involved in de novo Charcot neuroarthropathy by multivariate analysis were used; P<0.05 was considered significant. Charcot neuroarthropathy was diagnosed in 4.6% of SPKT recipients during the first year. Cumulative glucocorticoid doses (daily dose plus methylprednisolone pulse) during the first 6 months both adjusted to body weight (>78 mg/kg) and not adjusted to body weight were associated with Charcot neuroarthropathy (P=0.001 and P<0.0001, respectively). Age, gender, race, time on dialysis, time of diabetes history, and posttransplantation hyperparathyroidism were not related to Charcot neuroarthropathy after SPKT. Glucocorticoids are the main risk factors for de novo Charcot neuroarthropathy after SPKT. Protocols including glucocorticoid avoidance or minimization should be considered.

Effects of cyclosporine on bone mineral density in patients with glucocorticoid-dependent nephrotic syndrome in remission

Cyclosporine (CsA) is often prescribed to patients with glucocorticoid (GC)-dependent nephrotic syndrome. Although it is well known that long-term administration of GC causes osteoporosis, the effects of CsA on bone metabolism are not fully established. Therefore, we examined the effects of CsA on bone metabolism in patients with GC-dependent nephrotic syndrome in remission. We followed 23 patients treated with prednisolone alone (GC alone group) and 17 patients treated with CsA in combination with prednisolone (GC + CsA group). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and biochemical markers of bone metabolism were simultaneously measured in serum and urine samples. BMD decreased significantly in the GC group from 752 to 623 mg/cm(2) but non-significantly in the GC + CsA group from 751 to 684 mg/cm(2). Although the cumulative dose of GC increased in both groups, there were no significant differences in biochemical markers at either the start or the end of the study. Vertebrate bone fracture and other side effects associated with CsA treatment did not occur in our study. Our results indicate that CsA does not accelerate GC-induced osteoporosis in patients with nephrotic syndrome. We conclude that CsA is appropriate for the treatment of GC-dependent nephrotic syndrome, because it does not adversely affect bone metabolism and has favorable glomerular effects.

Bone Mineral Density and Body Composition in Men With Multiple Sclerosis Chronically Treated With Low-Dose Glucocorticoids

The aim of the study was to compare the bone mineral density (BMD) and body composition between ambulatory male MS patients and control subjects and to evaluate the relationships among body composition, motor disability, glucocorticoids (GC) use, and bone health. Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age: 45.2 years) chronically treated with low-dose GC and in 54 healthy age-matched men. Compared to age-matched controls, MS patients had a significantly lower total body bone mineral content (TBBMC) and BMD at all measured sites except for the radius. Sixty five male MS patients (62.5 %) met the criteria for osteopenia and twenty six of them (25 %) for osteoporosis. The multivariate analysis showed a consistent dependence of bone measures (except whole body BMD) on BMI. The total leg lean mass % was as an independent predictor of TBBMC. The Expanded Disability Status Scale (EDSS), cumulative GC dose and age were independent determinants for BMD of the proximal femur. We conclude that decreasing mobility in male MS patients is associated with an increasing degree of osteoporosis and muscle wasting in the lower extremities. The chronic low-dose GC treatment further contributes to bone loss.

Beneficial Cardiovascular Effects of Low-dose Glucocorticoid Therapy in Inflammatory Rheumatic Diseases

To the Editor: We read with great interest the report by Mazzantini, et al 1. That retrospective analysis of a large cohort of patients with polymyalgia rheumatica (PMR) demonstrated that duration or cumulative dose of longterm low-dose glucocorticoid (GC) therapy was significantly associated with higher risk of arterial hypertension and acute myocardial infarction. However, in a multivariate analysis adjusted for traditional cardiovascular (CV) risk factors, arterial hypertension was confirmed as the only adverse effect significantly associated with treatment duration. It is thought that longterm GC treatment, especially at high dose, may indirectly increase the risk of CV disease through its well-recognized effect on traditional CV risk factors, including arterial hypertension, dyslipidemia, hyperglycemia, and obesity2. As summarized in Table 1, GC have been associated with higher incidence of subclinical atherosclerosis, and their detrimental effects on the CV system seem to occur at a preclinical phase. Although results are not uniform, duration of treatment exposure and higher cumulative … Address correspondence to Dr. Gerli; E-mail: gerlir{at}unipg.it

Significantly higher estimated 10-year probability of fracture in lupus patients with bone mineral density comparable to that of healthy individuals

This study aimed at comparing the FRAX 10-year fracture risk between SLE patients and demographically- and anthropometrically matched healthy individuals. Consecutive SLE patients aged ≥ 40 were analyzed for the FRAX 10-year probability of major osteoporotic and hip fractures and their risk was compared with healthy controls matched for age, gender and body mass index. Potential determinants associated with higher 10-year fracture probability in the SLE patients were studied by regression models. Ninety subjects (45 SLE patients and 45 healthy controls) were studied. While the bone mineral density (BMD) of the lumbar spine and dominant hip was comparable between the two groups, the FRAX 10-year probability of major and hip fractures was significantly higher in SLE patients. Significantly more SLE patients had high 10-year fracture risk as defined by the National Osteoporosis Foundation compared with healthy controls (16 vs. 2 %, p = 0.026). After controlling for glucocorticoid use and premature menopause which were significant univariate risk factors, the difference in the 10-year fracture risk became insignificant. Amongst SLE patients, increasing age, lower hip BMD and cumulative glucocorticoid dose independently predicted higher 10-year major fracture risk while higher anti-dsDNA level independently predicted higher hip fracture risk in addition to age and lower hip BMD. Chronic glucocorticoid use and premature menopause led to higher 10-year probability of major osteoporotic and hip fractures in SLE patients compared with their healthy counterparts although their BMD was comparable. Advanced age, lower hip BMD, cumulative glucocorticoid and higher anti-dsDNA level independently predicted higher 10-year fracture risk amongst SLE patients.

Adverse Events During Longterm Low-dose Glucocorticoid Treatment of Polymyalgia Rheumatica: A Retrospective Study

To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC). This was a retrospective study by review of medical records. We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02-1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01-1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03-1.8). Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment.

Frequency of Metabolic Syndrome in Female Patients with Systemic Sclerosis: A Preliminary Report

Objective. A higher prevalence of metabolic syndrome (MetS) has been described in various rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, but no direct studies have investigated the prevalence of MetS in systemic sclerosis (SSc) patients compared with the general population. We compared the frequency of MetS and insulin resistance, as measured by Homeostatic assessment model-insulin resistance (HOMAIR) between female SSc patients and healthy subjects. Methods. In a cross-sectional setting, 35 female SSc patients and 84 age and sex-matched healthy subjects were consecutively recruited at a single center of a tertiary hospital between 2009 and 2010. MetS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel (NCEP-ATP III) 2004 criteria, using the Asian criteria for central obesity. Results. The frequency of MetS was not significantly higher in SSc patients (20.0%) than in healthy subjects (14.3%, p=0.425), but SSc patients had an increased insulin resistance measured by HOMA-IR (p=0.001). Significantly more patients with SSc had increased triglyceride concentrations (p=0.004) and fewer SSc patients tended to meet the waist circumference criterion (p=0.051) according to the individual MetS features. Additionally, there were no significant differences in age, high-sensitivity C-reactive protein, body mass index, HOMA-IR, disease duration, cumulative glucocorticoids dose, modified Rodnan skin score or the proportion of limited SSc cases according to the absence or presence of MetS in SSc patients. Conclusion. Unlike other rheumatic diseases, our preliminary report did not show a significant difference in the prevalence of MetS between female SSc patients and healthy subjects.

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: A national observational study

To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than -2.0 at 12 months compared to 16% of children without IVF (P = 0.011). The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months.

Increased large artery intima media thickness in adolescents with either classical or non-classical congenital adrenal hyperplasia.

Increased artery intima-media thickness (IMT) was found in adults with classical congenital adrenal hyperplasia (CAH). No data are available in patients with non-classical (NC) CAH. To evaluate IMT in adolescents with classical and NC CAH and to compare the results with those recorded in a control population. Eighteen adolescents with either classical (Subgroup A1) or NC CAH (Subgroup A2) were compared with 16 controls (Group B). All subjects underwent IMT ultrasonography measurement at different sites; results were correlated with clinical, metabolic, and insulin resistance (IR) data. When compared with Group B, both subgroups exhibited higher IMT values at all sites. No differences were found between classical and NC CAH. Univariate analysis of factors impacting on IMT of CAH patients demonstrated that: a) abdominal aorta (AA) IMT was positively correlated with cumulative glucocorticoid doses, triglyceride serum levels, and diastolic blood pressure SD score and negatively with androstenendione and ACTH levels; b) common carotid (CC) IMT was positively associated with triglycerides and triglyceride/HDL ratio. At multiple regression analysis, the independent positive predictors of AA and CC IMT were respectively triglyceride levels and triglyceride/HDL ratio. a) Even adolescents with NC CAH and not only those with classical form may be at higher risk of artery alterations; b) this risk is not necessarily associated with either obesity or waist/height ratio or dyslipidemia; c) an important role in the pathogenesis of artery alterations in CAH may be played by intermittent iatrogenic hypercortisolism and secondary IR.