High-dose Prednisolone Research Articles

Salvage Therapies for Autoimmune Hepatitis: A Critical Review.

Several salvage therapies have been identified for autoimmune hepatitis refractory or recalcitrant to conventional therapy; however, the optimal salvage strategy remains unclear. High-dose prednisolone is currently recommended as the front-line salvage therapy, with alternative immunosuppressive therapies reserved for continuing treatment failure. Of the second-line therapies, the calcineurin inhibitors, cyclosporine and tacrolimus, and mycophenolate mofetil are preferred and have the most accrued clinical data. However, none of these have undergone rigorous clinical evaluation via randomized clinical trials. Tacrolimus is generally preferred over cyclosporine because of its higher potency and increased utility in organ transplantation. Mycophenolate is particularly useful for azathioprine intolerance but also for nonresponse to standard treatment. Subjects with progressive liver failure should undergo liver transplantation evaluation. The appropriate timing, dosing, and monitoring of salvage therapies require determination. Several promising immunosuppressive therapies have been developed for autoimmune diseases including molecular agents that may enhance regulatory T cell activity and function.

The possible protective effects of vitamin E and selenium administration in oxidative stress caused by high doses of glucocorticoid administration in the brain of rats

Acute exposure to high doses of glucocorticoids (GCs) may potentially increase the basal levels of reactive oxygen species (ROS) by altering the defence capacity against oxidative damage. Also, antioxidants may affect the oxidative breakdown of tissues. Therefore, the aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation (LPO) as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defence mechanisms in the brain of rats treated with high doses of prednisolone. Two hundred and fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20mg vitamin E, 0.3mg Se, and a combination of vitamin E and Se, respectively, for 30days. For 3days subsequently, the control (group 1) was treated with a placebo, and the remaining 4 groups were injected intramuscularly with 100mg/kg body weight (bw) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48h and the activities of enzymes selenium-glutathione peroxidase (Se-GSH-Px) and catalase (CAT), and the levels of reduced glutathione (reduced GSH) and TBARS in their brains were measured. Se-GSH-Px and CAT enzyme activities, and reduced GSH levels in the prednisolone treatment group (group 2) began to decrease gradually at 4h (p<0.01, p<0.05, respectively), falling respectively to 60, 50, and 40% of the control levels by 24h (p<0.001, p<0.01), and recovering to the control levels at 48h. In contrast, prednisolone administration caused an increase in the brain TBARS, reaching up to six times the level of the control at 24h (p<0.001). However, supplementation with vitamin E and Se had a preventive effect on the elevation of the brain TBARS and improved the diminished activities of antioxidative enzymes and the levels of reduced GSH. Therefore, the present study attempts to determine the sequence of cellular membrane damage in the brain of the rats after high doses GC administration and the possible roles in vivo of vitamin E and Se, and their combination.

Scleromyxedema associated with ankylosing spondylitis treated successfully with cyclosporine and high dose corticosteroids

Scleromyxedema (SM) is a rare disorder which initially presents with waxy skin stiffness and maculopapular lesions. It also has non-dermatologic manifestations, such as serum paraproteinemia and myopathies, and is sometimes associated with other autoimmune disorders. A 52-year-old man was referred for treatment because of torso-dominant skin stiffness. He also had a neglected history of bilateral inflammatory back pain and chronic Helicobacter pylori-negative gastritis. Skin histopathology confirmed a diagnosis of SM. A grade 4 bilateral sacroilitis and a positive human leukocyte antigen B27 led to the patient also being diagnosed with ankylosing spondylitis (AS). Upon further analysis, monoclonal gammopathy of immunoglobulin (Ig) G/kappa (lower than 3 g/dl) and a normal percentage of plasma cells in his bone marrow aspiration sample were discovered. Due to the patient’s IgA deficiency, intravenous immunoglobulin (IVIG) could not be used to treat his SM; due to his positive tuberculin skin test (25 mm) and history of gastritis, anti-tumor necrosis factor alpha and non-steroid anti-inflammatory drugs were also withheld. The patient received a drug regimen of cyclosporine (3mg/kg/day) and high-dose prednisolone (0.5mg/kg/day) which successfully controlled both his SM and AS disorders. In this paper, we report a previously unreported case of SM-associated gammopathy and AS. We also show the efficacy of cyclosporine and high-dose prednisolone in the treatment of both of these conditions.

Sudden sensorineural hearing loss in children and adolescents: Clinical characteristics and age-related prognosis

ObjectiveAlthough many studies have investigated sudden sensorineural hearing loss (SSNHL) in adults, there were few studies on SSNHL in the pediatric population; especially research on treatment and prognosis of pediatric SSNHL was limited. The aim of this study was to evaluate clinical characteristics, treatment outcomes and prognostic factors in children and adolescents with SSNHL. MethodsA retrospective review of medical records of 67 pediatric patients (67 ears) who had diagnosed with SSNHL at our hospitals was performed to analyze patients’ clinical manifestations and audiograms. All patients were treated with high-dose systemic prednisolone (1mg/kg), and 17 of them underwent intratympanic steroid injection therapy. Audiological evaluation was carried out before and after treatment, and hearing recovery was defined as complete recovery and partial recovery according to Siegel’s criteria. Patients were divided into two groups: childhood group (ages between 4 and 12 years old) and adolescence group (age>12years), and clinical characteristics and treatment outcomes were investigated. In addition, patients were divided into two groups according to degree of hearing recovery, and evaluation was made regarding possible prognostic factors. ResultsThe recovery rate in total 67 patients was 55.2%. The recovery rate of the childhood group was significantly lower than that of the adolescence group (p=0.038). While the presence of vertigo did not significantly correlate with prognosis (p=0.219), the presence of tinnitus was significantly associated with hearing recovery (p=0.005). Audiological assessment revealed that a low initial hearing threshold, high speech discrimination score, and descending type of audiogram were positively associated with hearing recovery (p=0.002, p=0.003, and p=0.029, respectively). ConclusionThe childhood group had worse treatment outcomes than the adolescence group. High initial hearing threshold and absence of tinnitus were poor prognostic factors of hearing recovery. Active treatment is required for patients with these poor prognostic factors and childhood patients with SSNHL.

Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin: A 12-Month Assessment of Spasm Control in West Syndrome

ObjectiveWe earlier completed a single-blind, parallel-group, randomized clinical trial to test the null hypothesis that adrenocorticotropic hormone (ACTH) is not superior to high-dose prednisolone for short-term control of West syndrome. We now present long-term follow-up data for spasm control for individuals who completed this earlier trial. MethodsInfants with untreated West syndrome were randomized to receive 14 days of prednisolone (40 to 60 mg/day) or intramuscular long-acting ACTH (40 to 60 IU every other day). They were evaluated at three, six, and 12 months to evaluate long-term spasm control. ResultsThe total number of infants treated was 97 (48 prednisolone; 49 ACTH). All completed the treatment course. Eighty-five, 82, and 76 children were available for follow-up at three, six, and 12 months. The number lost to follow-up at each interval was not statistically different. Likelihood of spasm freedom at three months was significantly higher for prednisolone (64.6%) than for ACTH (38.8%) (P = 0.01; odds ratio = 2.9; 95% confidence interval = 1.3 to 6.6). At six months (P = 0.19) and twelve months (P = 0.13), the control of spasms was not statistically different, although a trend in favor of prednisolone was documented at both of these time points (58.3% versus 44.9% for ACTH at six months and 56.2% versus 40.8% with ACTH at 12 months). After initial remission by day 14 (n = 46), the likelihood of a relapse within the next 12 months was not statistically different between the two treatment groups (P = 0.1). ConclusionsControl of spasms at three months was significantly better if initially treated with prednisolone. Control of spasms at six and 12 months was not significantly different despite a trend favoring prednisolone. Risk of relapse following initial remission was similar in the two groups.

111 A LUPUS NEPHRITIS PATIENT WITH BREATHLESSNESS FOLLOWING PLASMA EXCHANGE

Category: Other Presenter: Dr WAN HASNUL HALIMI WAN HASSAN Keywords: SLE, lupus nephritis, plasma exchange, fluid overload A 17 years old girl, diagnosed with Lupus nephritis since 2014. She had Lupus Nephritis class III , in partial remission following treatment with t.mycophenolate mofetil (MMF). She was transferred to high dependency ward requiring non invasive ventilation after 4th cycle of plasmapharesis. This is due to fluid overload and her condition improves after hemodialysis and ultrafiltration. She initially presented with symptoms of facial puffiness and leg swelling for 2 weeks. She was admitted was started on high dose prednisolone (60mg OD) and t.MMF 1g BD. Progressive worsening renal function was noted (urea 29/creat 190; baseline renal function was normal urea/creat) Renal biopsy results shows Crescentric Lupus Nephritis, ISN/RPS class IV-G (A/C). activity index 15/24, chronicity index 4/12. (57% cellular crescent, 15% global sclerosis). IV cyclophosphamide induction and plasma exchange was initiated. She completed total of 10 plasmapheresis cycle and is currently still ongoing 3rd cyclophosphamide induction. Her renal profile shows improvement (urea 15.7/creatinine 116). Plasma Exchange is a recognized modality of treatment in more severe and/or resistant lupus nephritis, moreover for crescentic glomerulonephritis. The complication rate of is not high. The Swedish registry reported no fatalities during 20,485 procedures, and an overall adverse incidence rate of only 4.3% of all exchanges (0.9% for severe adverse events) of which 27% were paresthesias, 19% transient hypotension, 13% urticaria, and 8% nausea. An overall complication rate of 1.4% has been reported in more than 15,000 treatments in patients receiving albumin, and 20% in patients receiving FFP. There's increases the risk of bleeding as a result of depletion of coagulation factors in patients receiving albumin as sole replacement colloid. A study in Japan looking at 53 kidney transplant recipients receiving plasma exchange for desensitization, recorded the were no severe adverse event, milder events were pruritus 53%, numbness 40% and mild dyspnea 5%. The incidence of numbness during plasma exchange was less in patients receiving combined hemodialysis. In our case, fluid overload was noted as a major complication requiring non invasive ventilation and hemodialysis. This is due to the large volume exchange and associated renal impairment. Although uncommon, fluid overload and other complication related to large volume plasma exchange is needed to be taken under account in a renal impaired patient.

Takayasu\u2019s arteritis: a case with relapse after urgent coronary revascularization

BackgroundVasculitides are commonly unrecognized causes of coronary stenosis and myocardial ischemia. We report on a 24-year old patient with Takayasu’s arteritis who underwent urgent percutaneous coronary intervention, suffered from symptomatic restenosis of the left main coronary artery during standard immunosuppressive therapy.Case presentationA 24-year old woman was referred for coronary angiography because of typical progressive angina pectoris. On bicycle ergometry, there were both reproducible symptoms and deep ST segment depressions on precordial leads. Semi-selective angiography of the left coronary artery revealed high-grade ostial stenosis. Because of persistent angina pectoris and electrocardiographic signs of acute myocardial ischemia, immediate percutaneous coronary angioplasty with subsequent implantation of an everolimus-eluting stent was performed. This intervention was performed with excellent angiographic results. Because of several concomitant criteria including hypoechogenicity on postprocedural intravascular ultrasonography, the diagnosis of Takayasu’s disease was made. The patient was treated with prednisolone and cyclophosphamide for 5 months. Because of recurrent angina pectoris, another coronary angiography was performed, which revealed high-grade in-stent-restenosis. Immunomodulatory therapy was switched to high-dose prednisolone and the anti-IL-6 receptor antagonist tocilizumab. The high-grade in-stent-restenosis persisted, and aortocoronary bypass graft surgery was performed with two saphenous vein grafts to the left anterior descending and circumflex artery. Since then, the patient has been doing well for 2 years.ConclusionIn cases of treatment refractoriness during standard immunosuppressive therapy, more recently developed biological compounds may offer an alternative strategy.

Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone

Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (≥5 mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. The primary outcome was incident hip fracture. Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

High-dose prednisolone after intravenous methylprednisolone improves prognosis of acute exacerbation in idiopathic interstitial pneumonias.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) (AE-IPF) is a poor prognostic disorder. AE is also reported to occur in other idiopathic interstitial pneumonias (IIPs). There are limited data available regarding the effectiveness of treatment for AE-IIPs. The objective of this study was to clarify the prognostic impact of the initial dose of prednisolone (PSL) for treating AE-IIPs. Eighty-five patients with AE-IIPs, diagnosed according to the criteria of the Japanese Respiratory Society, were enrolled in this study (IPF/non-IPF: 63/22 patients) from 2004 to 2013. We performed multivariate Cox proportional hazard regression analysis to identify poor prognostic factors. HRCT patterns at the onset of AE-IIPs were classified as diffuse or non-diffuse. We evaluated the prognostic significance of the initial dose of PSL by adjusting for other prognostic factors. Median survival time (MST) after AE-IIPs diagnosis was 49 days. MST of AE-IPF and AE-non-IPF was 39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher serum surfactant protein-D at AE diagnosis, long-term oxygen therapy (LTOT) before AE and positive pressure ventilation (PPV) use for AE were significant poor prognostic factors for all patients, as were LTOT before AE and lower serum IgG for no-PPV patients. High-dose PSL ≥ 0.6 mg/kg was a significant prognostic factor for no-PPV patients after adjusting for other prognostic factors. We concluded that a dose of PSL ≥ 0.6 mg/kg after i.v. high-dose methylprednisolone therapy should be recommended for the treatment of AE-IIPs.

Short-Term Outcome of Intravenous Methylprednisolone Pulse Therapy in Patients With Infantile Spasms

BackgroundMany studies advocate hormonal treatments including high-dose oral prednisolone as an effective treatment for epileptic spasms. However, little is known about the effects of intravenous methylprednisolone pulse therapy on infantile spasms. We investigated the short-term response to intravenous methylprednisolone pulse therapy for the treatment of infantile spasms. MethodsPatients with newly diagnosed infantile spasms and hypsarrhythmia on electroencephalography (EEG) at two tertiary centers in Korea were included. Patients received intravenous infusions of 30 mg/kg/day methylprednisolone for three days with tapering doses of oral prednisolone for two to four weeks for the treatment of infantile spasms. Response to methylprednisolone pulse therapy was evaluated by seizure frequency and follow-up EEG within three weeks. ResultsFourteen patients were sudied. The mean age at the onset of spasms was 7.0 months (range, 2.0 to 11.0 months). Etiological factors included structural abnormalities (N = 11), chromosomal anomaly (N = 1), and unknown (N = 2). Nine of 14 participants (64.3%) demonstrated complete freedom from spasm and resolution of hypsarrhythmia on EEG within 3 weeks; however, only five of nine responders (55.5%) remained free of spasms after the discontinuation of oral steroids. Adverse effects, including irritability or infection, were observed in four patients but were tolerable in all. ConclusionsShort-term methylprednisolone pulse therapy for the treatment of infantile spasms or hypsarrhythmia demonstrated rapid improvement in EEG and cessation of spasms without serious adverse effects. Further studies are needed to determine the long-term effects of spasm control.

The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study.

Atypical femoral fractures (AFFs) have been reported to occur with minimal or spontaneous subtrochanteric and femoral shaft fractures with a characteristic transverse pattern, compared with typical femoral fractures in young patients with high-energy trauma. AFFs are related to long-term use of bisphosphonates (BPs), glucocorticoids and rheumatic diseases. We have estimated a blind analysis of AFFs in rheumatic patients receiving BPs and glucocorticoids ordinary over a long time in all Yamagata prefectural area through radiographic examination. The 123 AFFs including suspected cases over six years were collected and reviewed by two independent orthopedic surgeons. We found 86 patients with a total of 99 AFFs between 2009 and 2014 (1.43 cases/100,000 person/year). Of these 99 AFFs, 11 were in 8 rheumatic patients including three patients with bilateral AFFs. The incidence of AFFs in rheumatic patients had trend to increase from 2012. The mean age of all 8 patients was 54.9 years. All 8 patients received BPs and 7/8 received prednisolone (PSL). The mean dose of PSL was 14 mg/day. Compared to patients with unilateral AFFs, those with bilateral AFFs in rheumatic patients were on a higher dose of PSL (20 mg/day vs. 7 mg/day) and had less femoral neck-shaft angle (129° vs. 136°, p < 0.05). In conclusion, the incidence of AFFs in rheumatic patients showed a trend to increase from 2012 to 2014 in Yamagata prefecture. Careful management of AFFs is of particular importance in rheumatic patients who have taken high doses of PSL and have small femoral neck-shaft angle.

Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal nail fold capillaries, interstitial lung disease, Raynaud's phenomenon, esophageal dysmotility, and positivity for rheumatoid factor and anti-SSA antibodies. She developed massive inflammatory changes of the cutis, the subcutis, and the muscle fasciae of the right leg, that after several failed attempts of immunosuppressive treatments were found to be caused by Mycobacterium intracellulare. While she was receiving high-dose prednisolone, as worsening of her connective tissue disease was suspected to be the cause of the inflammatory changes, she had Listeria monocytogenes meningitis and was hospitalized for several weeks, but she recovered from this without sequelae. After Mycobacterium intracellulare infection was diagnosed, she was treated with clarithromycin and rifampicin. Her skin manifestations, arthralgias, and fatigue improved considerably, and the wounds of the right leg healed, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma.

Strong Association of Celiac Disease Serology with Idiopathic Autoimmune Hemolytic Anemia from Western India

▪Idiopathic autoimmune hemolytic anemia (AIHA) may be associated with positive autoimmune serology and some of the patients develop autoimmune disorder, malignancy on long follow up.There are no cohort studies on AIHA from India with long follow up. As AIHA has no known etiology and different populations of the world differ in their genetic makeup, environment background, it is likely that underlying conditions associated with AIHA will also vary in different countries with different population characteristics.Present study evaluates association of autoimmune markers along with follow up of a cohort of 21 well characterized AIHA patients from Gujarat, a western state of India.The cohort comprises of 2 men and 19 women aged between 20-72 years (Mean 36 years), followed up for a varying period of 6 month to 25 years (Mean 41/2years) after the diagnosis. AIHA was diagnosed by classical criteria of clinical presentation with severe weakness with feeling of being unwell, pallor and yellow discoloration coupled with laboratory parameters showing low hemoglobin (3.7-7.2 g/dL), high serum bilirubin level ( 2.1-3.8 mg/dl) , high reticulocyte count (5-69%) and strong direct anti human globulin(AHG) test coupled with absence of any other disease on detailed biochemical, flow cytometry (PNH, clonal disorders excluded) and other relevant imaging studies. Bone marrow examination was done in all patients. Splenomegaly of varying degree was present in 16/21 (78%) of the patients.All patients except 3/21 (14%) received red cell transfusions following the diagnosis as the Hb levels were very low. Best cross matched red cells were provided along with high dose prednisolone (1 mg/kg body weight). One of the patients, a 32 year old lady presented with intense hemolysis, hepatosplenomegaly, lymphadenopathy and hemophagocytosis in peripheral blood and in the marrow. After their stabilization the patients were tested for several autoimmune markers e.g. ANA, Anti ds-DNA, Antiparietal Cell, Antithyroid, AntiCardiolipin, Anti-β2glycoprotein, anti-tissue transglutaminase antibody IgA and lupus anticoagulants. 11/21 patients became AHG negative within one year, however they continued to show positive reaction by western blot test.7/21 (34%) positive for LA screening test (3 confirmed by platelet neutralization (14%), 2/21 positive for anti-β2 glycoprotein antibody. Anticardiolipin antibody and antiparietal cell antibody was negative in all. 4/21 were positive for antithyroid antibody and one of them needed thyroxine. 7/21 (34%) were ANA positive (6/7 anti dsDNA positive), one of them went on to develop SLE. One patient with LA positivity developed DVT in left leg and portal vein thrombosis.Most striking association in our cohort was seen with anti-transglutaminase antibody IgA, 8/21 (38%) were strongly positive for the antibody and 6/21 (28%) were in the borderline range. Hence 66% of our cohort had abnormal serology for celiac disease. AIHA in all our patients were well controlled 16/21 (78%) with steroid and azathioprine only, 4/21 underwent (18%) splenectomy. Single patient presenting with extensive hemophagocytosis and immune hemolytic anemia received weekly courses of Rituximab (375mg/m2), 4 cycles and her Hb was stabilized.Association of Celiac disease marker with AIHA in a large majority of patients needs further exploration. Western blot can be used when AHG tests become negative during follow up. DisclosuresNo relevant conflicts of interest to declare.

Investigations of Glucocorticoid Action in GN.

For several decades, glucocorticoids have been used empirically to treat rapid progressive GN. It is commonly assumed that glucocorticoids act primarily by dampening the immune response, but the mechanisms remain incompletely understood. In this study, we inactivated the glucocorticoid receptor (GR) specifically in kidney epithelial cells using Pax8-Cre/GRfl/fl mice. Pax8-Cre/GRfl/fl mice did not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic serum to induce crescentic nephritis (rapidly progressive GN), this genetic inactivation of the GR in kidney epithelial cells exerted renal benefits, including inhibition of albuminuria and cellular crescent formation, similar to the renal benefits observed with high-dose prednisolone in control mice. However, genetic inactivation of the GR in kidney epithelial cells did not induce the immunosuppressive effects observed with prednisolone. In vitro, prednisolone and the pharmacologic GR antagonist mifepristone each acted directly on primary cultures of parietal epithelial cells, inhibiting cellular outgrowth and proliferation. In wild-type mice, pharmacologic treatment with the GR antagonist mifepristone also attenuated disease as effectively as high-dose prednisolone without the systemic immunosuppressive effects. Collectively, these data show that glucocorticoids act directly on activated glomerular parietal epithelial cells in crescentic nephritis. Furthermore, we identified a novel therapeutic approach in crescentic nephritis, that of glucocorticoid antagonism, which was at least as effective as high-dose prednisolone with potentially fewer adverse effects.

Reduction of permanent hearingloss by local glucocorticoid application : Guinea pigs with acute acoustic trauma.

High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as along-term consequence. Here, atreatment regime was developed to limit permanent damage based on apreclinical animal model of acute noise trauma. To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. Aseries of experiments with different impulse noise exposures were performed. Permanent hearing loss and hair cell density were assessed 14days after exposure. Hearing and hair cell preservation were investigated as afunction of the glucocorticoid dose. After impulse noise exposure, local application to the round window of the cochlea of high-dose prednisolone (25mg/ml) or methylprednisolone (12.5mg/ml) resulted in astatistically significant reduction in hearing loss compared with the control group. The local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.

Very high frequency of fragility fractures associated with high-dose glucocorticoids in postmenopausal women: A retrospective study

PurposeTo evaluate the incidence of fragility fractures associated with high-dose glucocorticoid therapy in patients with systemic rheumatic disease.Methods: A retrospective study of patients who were treated with high-dose prednisolone (>0.8mg/kg) for systemic rheumatic disease at Kobe University Hospital from April 1988 to March 2012. The primary outcome was a major osteoporotic fracture (defined as a clinical vertebral, hip, forearm, or proximal humerus fracture) after high-dose glucocorticoid therapy. For postmenopausal women and men over 40 of age, the patient's fracture risk at the beginning of high-dose glucocorticoid therapy was assessed by the World Health Organization's Fracture Risk Assessment Tool (FRAX®).ResultsOf 229 patients (median age: 49years), 57 suffered a fragility fracture during the observation period (median observation period: 1558days). Of 84 premenopausal patients, 5 suffered a fracture. In contrast, of 86 postmenopausal female, 36 suffered a fracture. Fragility fractures were far more frequent than predicted by the FRAX® score. Patients with FRAX® scores over 8.3% had a particularly high risk of fracture.ConclusionsFragility fractures associated with high-dose glucocorticoid therapy are common among postmenopausal women. Extreme care should be taken especially for postmenopausal women when high-dose glucocorticoid therapy is required.

Long-term Prednisolone in Post-stroke Complex Regional Pain Syndrome

Background: There is no study on the long-term use of prednisolone in post-stroke complex regional pain syndrome-1 (CRPS1). Objective: To evaluate the efficacy and safety of long-term low dose prednisolone in post-stroke CRPS-I. Study Design: Open-labeled randomized controlled trial. Setting: Tertiary care teaching institute. Methods: Seventy-seven out of 396 (19.4%) patients with stroke had CRPS-1 and 58 met the inclusion criteria. Their clinical details and CRPS, Visual Analogue Scale (VAS), modified Rankin Scale (mRS), and Barthel Index (BI) scores were noted. The patients were prescribed 40 mg prednisolone for 2 weeks followed by tapering in the next 2 weeks. Patients who responded were randomly assigned prednisolone 10 mg daily (group I) or no prednisolone (group II). They were followed up for the first and second month of randomization and their CRPS, VAS, mRS, and BI scores were noted. The primary outcome was improvement in CRPS score and secondary outcomes were VAS, mRS, BI scores, and severe adverse events (SAE). Results: Fifty-six of fifty-eight (96.5%) patients responded to the initial high dose prednisolone and 26 each were assigned group I and group II treatment. Group I patients had further improvement in CRPS score. Fifty percent of patients in group II had deterioration at one month and needed reinstitution of prednisolone; following which 77% of them improved in the next month. The improvement in CRPS score paralleled the VAS score but not mRS and BI scores in the first and second months in group I compared to group II. There was no SAE necessitating withdrawal of prednisolone. Limitation: The design of the study is not double blind. Conclusion: In post-stroke CRPS-I, continuation of low dose prednisolone for 2 months is safe and effective. Key words: Shoulder hand syndrome, CRPS, corticosteroid, prednisolone, stroke, Visual Analogue Scale

Single-centre experience of the macrophage activation marker soluble (s)CD163 - associations with disease activity and treatment response in patients with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is characterised by liver inflammation with reversibility upon anti-inflammatory treatment. Soluble (s)CD163, a specific macrophage activation marker, is associated with inflammation in other liver diseases, but never investigated in AIH. To investigate sCD163 in patients with acute AIH and in complete and incomplete responders to standard anti-inflammatory pharmacotherapy, and during follow-up in treatment naive patients. In a cross-sectional design, we studied 121 AIH patients (female/male 89/32, median age 49 years); of these, we prospectively studied 10 treatment naïve AIH patients during prednisolone treatment and tapering. Twenty patients had variant syndromes of AIH and primary biliary cholangitis or primary sclerosing cholangitis. sCD163 was compared with markers of disease activity, severity and treatment response. In the patients with acute AIH (n = 21), sCD163 was sixfold increased compared with the normalised levels in patients (n = 32) with complete response to standard treatment [9.5 (3.3-28.8) vs. 1.6 (0.8-3.2) mg/L, P < 0.01)], while the patients (n = 27) with incomplete response had higher sCD163 [2.2 (1.3-7.9), P < 0.05] than the complete responders. sCD163 was positively associated with ALAT, IgG and bilirubin (rho: 0.45-0.59, P < 0.001, all), and negatively to external coagulation factors (rho:-0.34, P < 0.001). In the treatment naïve patients, sCD163 fell during high-dose prednisolone treatment and tapering. Immunohistochemical staining confirmed increased CD163 expression in liver biopsies from patients with acute AIH. sCD163 was markedly elevated in AIH in the acute phase, normalised by successful treatment in complete responders, but remained higher in the incompletely responding cases. Our results demonstrate macrophage activation in AIH paralleling disease activity, severity and treatment response, suggesting a role for macrophage activation in AIH.

Cerebral Venous Thrombosis in Behçet's Disease Patients Compared to Other Causes of Cerebral Venous Thrombosis: a Retrospective Study.

This study aims to report the outcomes of patients with Behçet's disease (BD) with cerebral venous thrombosis (CVT) due to BD compared to patients with CVT due to other causes and to discuss the treatment options. Files of 47 patients admitted to our outpatient clinic for CVT between January 2007 and November 2014 were retrospectively reviewed. Patients were divided into two groups; group 1 included 21 CVT patients with BD (9 males, 12 females; mean age 47±12 years; range 27 to 69 years) and group 2 included 26 CVT patients without BD (11 males, 15 females; mean age 45±16 years; range 25 to 79 years). We collected data for diagnosis for BD and CVT, duration of all medications, functional system involvement, baseline Expanded Disability Status Scale scores, modified Rankin Scale scores at follow-up, and localizations of lesions in brain magnetic resonance imaging and magnetic resonance venography. Mean follow-up duration was four years in group 1 and two years in group 2. There was no significant difference between the groups regarding age, sex, neurological symptoms/findings and baseline Expanded Disability Status Scale scores. Localizations of occluded sinus in group 1 and group 2 were similar. For acute CVT, patients were treated with intravenous high dose prednisolone in group 1 and with anticoagulant in group 2. Follow-up modified Rankin Scale score was 0 in both groups. Our study revealed similar clinical and radiological findings in CVT patients with or without BD. Although medications used for treatment were different between the groups, treatment responses were good in both groups. Treatment with prednisolone may be sufficient and anticoagulation therapy may not be necessary for acute CVT attacks in BD.

Pseudotumor Cerebri as the First Manifestation of Juvenile Systemic Lupus Erythematosus

IntroductionHeadache is a common neuropsychiatric manifestation of juvenile systemic lupus erythematous (JSLE). Pseudotumor cerebri (PTC) is an uncommon cause of headache, presenting especially in active JSLE. In this paper, we report a case of missed intractable headache that was eventually diagnosed as PTC and presented as the first manifestation of JSLE.Case PresentationA 9-year-old girl with a history of progressive headache for four months, fever, fatigue, myalgia, arthralgia, small-joint arthritis of the hands, and recent diplopia was referred to our clinic. The diagnosis of PTC in the background of JSLE was made based on her history, physical examination, positive laboratory findings, and increased intracranial pressure, with normal neuroimaging. Treatment with high-dose prednisolone led to dramatic resolution of the headache.ConclusionsIt seems that a complete neurologic examination in newly diagnosed SLE patients is mandatory, especially in the presence of any neuropsychiatric manifestations, such as headache.