Initiation Of Glucocorticoid Therapy Research Articles

A case of de novo glomerulonephritis following COVID-19 in a patient with preexistent IgA vasculitis.

During the unprecedented COVID-19 outbreak, new-onset or relapsing glomerulonephritis, such as ANCA-associated glomerulonephritis and Immunoglobulin A (IgA) nephropathy, following COVID-19 has been reported. However, to date, the association of COVID-19 with preexistent IgA vasculitis (IgAV) remains unclear. Here, we present the case of a 20-something old Japanese woman with preexistent IgAV who newly developed glomerulonephritis following COVID-19. At the diagnosis of IgAV, she had cutaneous purpura, joint pains, and gastrointestinal symptoms, but no signs of kidney involvement. Three months ago, she was tested positive for COVID-19 and subsequently developed hematuria and proteinuria. She was then admitted to our hospital and renal biopsy showed glomerular mesangial expansion and hypercellularity and cellular and fibrocellular crescents, accompanied by diffuse IgA and C3 deposits. With the diagnosis of de novo IgAV nephritis, the patient was treated with intravenous methylprednisolone followed by oral prednisolone. She had favorable responses to this treatment and has achieved and maintained the remission of hematuria and proteinuria after initiation of glucocorticoid therapy. Our case highlights that immune response to SARS-CoV-2 infection could trigger the onset of glomerulonephritis in the IgAV patients who have no renal involvement.

Диагностическое значение определения IgG4 сыворотки в дифференциальной диагностике склерозирующих холангитов

The aim: to determine the cut-off levels of serum IgG. IgG4 and IgG4/IgG ratio for the differential diagnosis of IgG4-sclerosing cholangitis and primary sclerosing cholangitis. Material and methods. We conducted a single-center study of 32 and 67 patients with IgG4-sclerosing cholangitis and primary sclerosing cholangitis. which were verified according to HISORt and EASL criteria. respectively. Patients underwent determination of total IgG and IgG4 in serum by enzyme immunoassay. and the IgG4/IgG ratio was calculated before the initiation of glucocorticoid therapy. The reference values for IgG were 7–16 g/L and for IgG4 ≤ 1.35 g/L. ROC-analysis was used to determine the cut-off values of serum IgG. IgG4. IgG4/IgG ratio for differential diagnosis between primary sclerosing cholangitis and IgG4-sclerosing cholangitis. Results. The mean age at diagnosis of IgG4-sclerosing cholangitis was 59 ± 13 years and primary sclerosing cholangitis was 41 ± 20 years (p < 0.001). IgG4-sclerosing cholangitis was initially misdiagnosed as primary sclerosing cholangitis in 41.2% of patients (95% CI 24.6–59.3). The median time before diagnosis of IgG4-sclerosing cholangitis was 10.5 months. The median serum IgG4 level was 2.7 g/L [1.92; 6.48] in patients with IgG4-sclerosing cholangitis and 0.6 g/L [0.60; 1.45] in patients with primary sclerosing cholangitis. 33% of patients with primary sclerosing cholangitis had blood IgG4 levels exceeded 1.35 g/L. Whereas among patients with IgG4-sclerosing cholangitis. 19.4% had normal values of this parameter. The cut-off values of serum IgG and IgG4 and IgG4/IgG ratios for distinguishing primary sclerosing cholangitis from IgG4-sclerosing cholangitis were 17.1 g/L (sensitivity 75.0% and specificity 72.4%). 1.99 g/L (sensitivity 92.3% and specificity 74.2%). and 0.11 (sensitivity 84.2% and specificity 64.3%). respectively. Conclusions. The cut-off values of IgG. IgG4 concentration and IgG4/IgG ratio in serum can be used for differential diagnosis of primary sclerosing cholangitis and IgG4-sclerosing cholangitis.

Extensive Expertise in Endocrinology: Advances in the Management of Glucocorticoid-Induced Osteoporosis.

Osteoporosis is a common consequence of long-term oral glucocorticoid therapy and the resulting fractures cause significant morbidity. Bone loss occurs rapidly after initiation of glucocorticoid therapy; the accompanying increase in risk of fracture is dose-dependent and occurs within a few months of starting therapy. The adverse effects of glucocorticoids on bone are mediated by inhibition of bone formation accompanied by an early but transient increase in bone resorption, due both to direct and indirect effects on bone remodelling. Fracture risk assessment should be performed as soon as possible after long-term glucocorticoid therapy (≥3 months) is initiated. FRAX can be adjusted for the dose of prednisolone but does not currently take fracture site, recency or number into account and therefore may underestimate fracture risk, particularly in individuals with morphometric vertebral fractures. Vertebral fracture assessment should therefore be regarded as a routine part of fracture risk estimation in individuals receiving long-term glucocorticoid therapy. Bone protective therapy should be started promptly in individuals at high-risk, together with calcium and vitamin D supplements. Bisphosphonates are generally regarded as first line options on the grounds of their low cost, but anabolic therapy should be considered as an alternative first line option in very high-risk individuals.

Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica.

Neutrophils are important in host defence. However, neutrophils are also linked to inflammation and organ damage. The purpose of this study was to assess whether markers of neutrophil activation are increased in PMR. Levels of immune complexes (IC), calprotectin and neutrophil extracellular traps (NETs) were measured in plasma of healthy individuals (n = 30) and patients with PMR (n = 60), at flare and upon treatment with glucocorticoids using ELISA. Plasma-mediated neutrophil activation was assessed in presence of an FcγRIIA inhibitory antibody (IV.3). Plasma levels of calprotectin and NETs were elevated in PMR (P < 0.001). Mechanistically, neutrophil activation was driven by ICs, present in plasma, able to up-regulate neutrophil activation markers CD66b and CD11b (P < 0.0001) in an FcγRIIA-dependent manner (P < 0.01). Of note, circulating levels of IC correlated with plasma induced CD66b and CD11b (r = 0.51, P = 0.004, and r = 0.46, P = 0.01, respectively) and decreased after glucocorticoid therapy. In contrast to NETs, calprotectin significantly decreased after glucocorticoid therapy (P < 0.001) and was higher in PMR without overlapping GCA compared with patients with overlapping disease (P = 0.014). Interestingly, musculoskeletal involvement was associated with elevated levels of calprotectin before initiation of glucocorticoid therapy (P = 0.036). Neutrophil activation, including NET formation, is increased in PMR, through IC-mediated engagement of FcγRIIA. Clinically, neutrophil activation is associated with musculoskeletal involvement, with calprotectin, but not NETs, being a biomarker of treatment response in PMR patients. In all, IC-mediated neutrophil activation is a central process in PMR pathogenesis identifying potential novel therapeutic targets (FcγRIIA), as well as soluble markers for disease monitoring (calprotectin).

ODP110 Parathyroid Hormone Independent Hypercalcaemia Secondary to Granulomatous Inflammation: Could This Be Melioidosis?

Abstract Background Hypercalcemia has been described in patients with most granulomatous disorders, most commonly in sarcoidosis and tuberculosis, but never in melioidosis. Clinical Case A 45-year-old woman presented with two-day history of abdominal pain, nausea, lethargy and intermittent fevers during Darwin's wet season. Medications included daily methadone, diazepam and mirtazapine. On examination she was febrile with stable hemodynamics and left upper quadrant tenderness. Investigations revealed pancytopenia, deranged liver function tests with a cholestatic pattern, raised CRP of 53 (&amp;lt;5mg/L) and normal serum calcium. Blood cultures were negative but melioidosis serology was positive (indirect hemagglutination antibody (IHA) titer 1: 1280). Abdominal computed tomography demonstrated hepatosplenomegaly with peripheral splenic infarcts and a 7mm intrasplenic aneurysm, but no abscesses. PET showed no hypermetabolic lesions. After extensive investigation, she was treated for presumptive culture-negative melioidosis with intravenous meropenem. Clinically she improved despite gradual elevation in serum calcium which peaked at 3.31 (2.1-2.6mmol/L) five weeks after presentation. Initial biochemical investigations revealed suppressed PTH at 0.5 (1.4-9.1pmol/L), low 25-hydroxy-Vitamin D of 26 (50-150nmol/L), elevated phosphate at 2.43 (0.75-1.5mmol/L) and moderate renal impairment (eGFR 34mL/min/1.73m 2). Hypercalciuria was present with urine calcium to creatinine ratio of 812 (100-580mmol/mol). Her 1,25-dihydroxy-Vitamin D (calcitriol) was elevated at 219 (48-190pmol/L) suggestive of PTH-independent hypercalcemia. The patient remained asymptomatic of hypercalcemia and aggressive intravenous hydration produced minimal biochemical improvement. Renal impairment precluded bisphosphonate use. She was commenced on prednisolone 50mg while continuing intravenous meropenem. Serum calcium normalized in 10 days and prednisolone dose was gradually tapered. A liver biopsy was performed due to persistent liver derangement and histology showed granulomatous inflammation. She completed six weeks of antibiotics for melioidosis and was discharged on day 50, with a planned six months of eradication therapy. Outpatient follow-up demonstrated normal serum calcium after cessation of prednisolone with decreasing IHA titer (1: 320). We hypothesize that this case reflects PTH-independent hypercalcemia secondary to granulomatous inflammation, presumptively caused by melioidosis. The rise in calcium after commencement of antibiotics and normalization following initiation of glucocorticoid therapy, with no rebound post cessation, is consistent with successful therapy of an infection with granulomatous inflammation. Activated macrophages within granulomas have unregulated 1-alpha-hydroxylase expression which is thought to increase conversion of 25-hydroxy-Vitamin D to calcitriol and therefore increase intestinal calcium absorption. Treatment with glucocorticoids inhibits calcitriol synthesis leading to quick resolution of hypercalcemia. While use of glucocorticoids are commonplace in the management of granulomatous disease due to sarcoidosis, they have been increasingly recognized as an important risk factor for melioidosis, considered to result from suppression of innate immunity. However, use of glucocorticoids if required is not contraindicated once antibiotic therapy for melioidosis has commenced. Conclusion In areas where melioidosis is endemic, clinicians should be aware of hypercalcemia and the potential risks associated with its treatment. Presentation: No date and time listed

C-Reactive Protein Level can be a Better Indicator than Erythrocyte Sedimentation Rate in Assessing the Severity of Inflammation and Guiding Glucocorticoid Therapy in Subacute Thyroiditis.

Background:Despite the widespread use of several diagnostic tests in subacute thyroiditis (SAT), their usage remains largely subjective. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are useful indicators of inflammation in patients with SAT. The purpose of this study was to compare the scope for utilising CRP and ESR objectively in deciding the requirement of glucocorticoid therapy.Methods:A total of 28 patients with SAT were included in this study. Serum CRP and ESR were measured in all the patients. The characteristics of these tests were assessed firstly by using previously accepted positivity criterion for the particular diagnostic test. The area under the receiver operating characteristics (ROC) curve was obtained to provide an index of the overall discriminative ability of both tests.Results:Fifteen out of 28 patients were found to have features of significant thyroid inflammation eventually requiring glucocorticoid based on the current recommendations. The mean CRP value was significantly higher in patients requiring glucocorticoids. The ROC curves indicated that the optimal positivity criterion was 19.3 mg/L for the CRP level and 46 mm at the 1st hour for ESR. CRP with a sensitivity of 0.67, a specificity of 0.92, a positive likelihood ratio of 8.67, and an accuracy of 0.64 appeared better than ESR, which showed a sensitivity of 0.93, a specificity of 0.53, a positive likelihood ratio of 2.02, and an accuracy of 0.60.Conclusions:The serum CRP level provided a clear advantage over ESR in the assessment of the severity of inflammation before initiation of glucocorticoid therapy in SAT. However, a well-powered study is needed to examine the clinical relevance of such a role for CRP in thyroidology.

Lupus associated acute pancreatitis following initiation of glucocorticoid therapy: should corticosteroids be discontinued or kept? (case report)

Lupus associated acute pancreatitis following initiation of glucocorticoid therapy: should corticosteroids be discontinued or kept? (case report)

Interstitial Lung Disease in Giant Cell Arteritis: Review of 23 Patients.

Giant cell arteritis (GCA) is a large-vessel vasculitis with systemic manifestations. A few case reports have described a possible association of GCA with interstitial lung disease (ILD). The primary aim of the present study was to describe the pattern, severity, and course of ILD in patients with GCA. This medical records review study evaluated adult patients presenting to Mayo Clinic in Rochester, MN, from January 1, 1997, through December 31, 2018, who had the diagnoses of GCA and ILD. Clinical, laboratory, and radiologic data were analyzed. In total, 23 patients were in the study. Median (range) age was 78 (58-93) years, and 14 (61%) were women. Six patients (26%) had a cough at GCA diagnosis. At ILD diagnosis, 15 patients had respiratory symptoms, including dyspnea (n = 12, 52%), dry cough (n = 6, 26%), wheezing (n = 1, 4%), and chest pain (n = 1, 4%). On initial chest computed tomography, the most common pattern of ILD was probable usual interstitial pneumonia (n = 7, 30%), indeterminate for usual interstitial pneumonia (n = 5, 22%), and combined pulmonary fibrosis and emphysema (n = 3, 13%). Airway abnormalities were present in 10 patients: 6 with bronchial wall thickening, 2 with bronchiectasis, and 2 with both. At follow-up computed tomography, 8 patients had ILD progression. Three patients with cough improved after initiation of glucocorticoid therapy. Interstitial lung disease and airway abnormalities may be associated with GCA. Although cough may improve, ILD in some patients with GCA may progress despite immunosuppressive therapy.

Localized basal left ventricular dyssynchrony induced by manifest accessory pathway: Successful differentiation from cardiac involvement of sarcoidosis with administration of flecainide acetate

We present a patient with non-cardiac sarcoidosis complicated with manifest ventricular preexcitation. Initially, cardiac involvement of sarcoidosis was suspected from the echocardiographic findings showing localized hypokinesia at the left ventricular basal inferior wall. We, however, considered that the hypokinesia was a preexcitation-induced mechanical dyssynchrony rather than cardiac sarcoidosis, because polarities of the delta-waves indicated a left ventricular inferior accessory pathway. Temporal administration of oral flecainide acetate eliminated the basal left ventricular motion abnormality. Accordingly, we could successfully differentiate the mechanism of hypokinesia. In this context, we could rule out cardiac sarcoidosis, and initiation of glucocorticoid therapy was reasonably withheld.

Time-dependent haemoperfusion after acute paraquat poisoning

Early haemoperfusion (HP) therapy has been found to be very effective in acute paraquat (PQ) poisoning, but the effective rescue window is still uncertain. Demographic data and the type of therapies administered of 621 patients were included as confounding factors in this retrospective study. After receiver operating characteristic curve analysis and intra-group/subgroup analysis, the initiation of glucocorticoid therapy within 3 hrs of exposure with a second treatment given <21 hrs after exposure, HP initiated within 4 hrs of exposure with a second treatment given <20 hrs after exposure, the appearance of pulmonary lesions ≤8 days after exposure and six other variables were used in a multiple analysis. The strength of positivity of the PQ urine test on admission, HP initiated within 4 hrs of exposure with a second treatment given <20 hrs after exposure, the appearance of pulmonary lesions ≤8 days after exposure, and stage III AKI on admission were independent factors of survival probability. HP therapy for acute PQ poisoning was the main therapeutic intervention investigated in this study. Outcomes were time dependent, and the crucial factor was the initiation of therapy within 4 hrs of PQ poisoning followed by a second treatment within 20 hrs.

Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI) were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5%) had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT) increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI) at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

Analysis of bone metabolism during early stage and clinical benefits of early intervention with alendronate in patients with systemic rheumatic diseases treated with high-dose glucocorticoid: Early DIagnosis and Treatment of OsteopoRosis in Japan (EDITOR-J) study.

We conducted a prospective multicenter study to assess early changes in the dynamics of bone metabolism in patients with systemic connective tissue diseases following commencement of high-dose glucocorticoid therapy and the benefits of early treatment with bisphosphonate and vitamin D analogue. The subjects of this randomized controlled trial were 106 female patients with systemic connective tissue diseases treated for the first time with glucocorticoids at doses equivalent to prednisolone ≥20mg/day (age≥18years). One week after initiation of glucocorticoid therapy, patients were randomly assigned to treatment with alfacalcidol at 1μg/day (n=33), alendronate 35mg/week (n=37), and alfacalcidol plus alendronate (n=36). The primary endpoints were changes in lumbar spine bone density at 6months of treatment and the frequency of bone fracture at 12months. Commencement of glucocorticoid therapy was associated with a rapid and marked bone resorption within 1week. The combination of alfacalcidol and alendronate administered after the first week of glucocorticoid therapy halted the pathological processes affecting bone metabolism, increased bone density, and reduced the incidence of bone fracture over a period of 12months. Taken together, the use of the combination of alfacalcidol and alendronate improved bone metabolism, increased bone density, and significantly reduced the incidence of bone fracture during 1-year high-dose glucocorticoid therapy.

Serum C-reactive protein level is a better indicator than erythrocyte sedimentation rate in assessing the severity of inflammation before initiation of glucocorticoid therapy in the sub acute thyroiditis patients

Serum C-reactive protein level is a better indicator than erythrocyte sedimentation rate in assessing the severity of inflammation before initiation of glucocorticoid therapy in the sub acute thyroiditis patients

THU0390 Effect of Glucocorticoid Treatment on Wnt Signalling Antagonists (Sclerostin and Dkk-1) and their Relationship to Bone Turnover and Bone Mass

BackgroundWnt-ß-catenin signalling and its antagonists (sclerostin and Dkk-1) play an important role in the regulation of bone mass and osteoblastogenesis. Glucocorticoid therapy (GCCT) is a well known factor related to...

Aortitis requiring aortic repair associated with glaucoma, thyroiditis, glaucoma, and neuropathy: case report

Aortitis may be due to infectious and non-infectious causes. We observed aortitis, associated with glaucoma, thyroiditis, pericarditis, pleural effusion and neuropathy in a 63-years old woman. Despite antibiotic therapy, inflammatory signs persisted and resolved only after initiation of glucocorticoid therapy. Increasing aortic ectasia necessitated resection of the ascending aorta and implantation of a Vascutek 30 mm prosthesis. Histologically a granulomatous aortitis was diagnosed. Since all other possible causes were excluded, an immunological mechanism of the aortitis is suspected and possible triggering factors are discussed.

Clinical Question: What is the best approach to managing glucocorticoid-induced osteoporosis?

Glucocorticoid-induced osteoporosis is common, and the resulting fractures cause significant morbidity and mortality. Rapid bone loss and increased fracture risk occur soon after the initiation of glucocorticoid therapy and are dose dependent. The increase in fracture risk is partly independent of bone mineral density, probably as a result of changes in bone material properties and increased risk of falling. Fracture risk can be assessed using the FRAX algorithm, although risk may be underestimated in patients taking higher doses of glucocorticoids. Because of the rapidity of bone loss and increase in fracture risk after the start of glucocorticoid therapy, primary prevention should be advised in high-risk individuals, for example older women and men, individuals with a previous fracture history and those with low bone mineral density. Bisphosphonates are the front-line choice for the prevention of fracture in the majority of glucocorticoid-treated patients, with teriparatide as a second-line option. Calcium and vitamin D supplements should be co-prescribed unless there is evidence of an adequate dietary calcium intake and vitamin D status.

Recurrent Interstitial Pneumonitis and Pulmonary Hemorrhage Secondary to Amiodarone Toxicity

Introduction Amiodarone is a commonly used drug for the treatment of cardiac arrhythmias. It has a broad range of toxicity including photosensitivity, blue-gray discoloration of the skin, thyroid dysfunction, corneal deposits, abnormal liver function tests, and bone marrow suppression. 1 Pulmonary toxicity is the most serious adverse effect of amiodarone. Treatment of amiodaroneinduced pulmonary toxicity includes discontinuation of the drug and initiation of glucocorticoid therapy in the majority of symptomatic patients. This case of recurrent amiodarone toxicity was manifested by acute interstitial pneumonitis and diffuse alveolar hemorrhage after a rapid taper of glucocorticoids.

Management of glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis is a common condition that results in significant morbidity and mortality. The skeletal effects of glucocorticoids include both direct and indirect actions on bone that result in an early, transient increase in bone resorption accompanied by a decrease in bone formation, which is maintained for the duration of glucocorticoid therapy. Rapid bone loss and increased fracture risk occur soon after the initiation of glucocorticoid therapy and are dose dependent. The increase in fracture risk is partly independent of bone mineral density, probably as a result of changes in bone material properties and an increased risk of falling. Bisphosphonates are the front-line choice for prevention of fracture in glucocorticoid-treated patients, with teriparatide as the second-line option; calcium and vitamin D supplements should be co-prescribed in the majority of individuals. Future guidelines for the management of glucocorticoid-induced osteoporosis should recognize the limitations of FRAX in assessing fracture risk in glucocorticoid-treated patients, and should include recently approved interventions, such as zoledronate and teriparatide.

Lymphoma‐Associated Polymyositis in Dogs

Lymphoma‐Associated Polymyositis in Dogs

Glucocorticoid Therapy for Hypotension in the Cardiac Intensive Care Unit

In recent years, it has been our practice to treat persistent hypotension in the cardiac intensive care unit with glucocorticoids. We undertook a retrospective review in an attempt to identify predictors of a hemodynamic response to steroids and of survival in these patients. Patients who had received glucocorticoids for hypotension over a 2-year period were identified retrospectively. Summary measures of blood pressure, heart rate, urine output, inotrope score, and volume of infused fluid were calculated for the 12 hours before and the 24 hours following initiation of glucocorticoid therapy. A hemodynamic response was defined as a > or =20% increase in mean blood pressure without an increase in inotrope score following initiation of steroid therapy. Fifty-one patients were included, of whom 6 (11.8%) died. Serum cortisol was measured in 43 patients (84.3%) and was below the lower limit of normal (<5 microg/dl) in 20 of these (46.5%). Following initiation of steroid therapy, blood pressure and urine output increased, whereas heart rate, inotrope score, and infused volume decreased. There were 21 (41.1%) hemodynamic responders, all of whom survived, whereas 6 of 30 (20%) nonresponders died (p = 0.036). No predictors of a hemodynamic response to steroid were identified. Some critically ill children with cardiac disease and inotrope refractory hypotension demonstrated hemodynamic improvement following glucocorticoid administration. An improvement in blood pressure following administration of glucocorticoid was associated with survival, but we were unable to identify predictors of that response.