High-dose Prednisolone Research Articles

Membranoproliferative Glomerulonephritis and X-Linked Agammaglobulinemia: An Uncommon Association

Introduction. X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by agammaglobulinemia requiring replacement treatment with immunoglobulin. The association of XLA and membranoproliferative glomerulonephritis (MPGN) is unexpected and, to our knowledge, only one case was previously published. Case Report. The authors report the case of a 10-year-old boy with family history and prenatal diagnosis of XLA, treated from birth with intravenous immunoglobulin replacement therapy. He presented with pneumonia, macroscopic hematuria, nephrotic proteinuria, hypoalbuminemia, and hypercholesterolemia with normal renal function and serum complement levels. Renal histology showed immune complex mediated MPGN. He was started on high dose prednisolone and ramipril and switched to weekly subcutaneous immunoglobulin. After a 4-month treatment, hematuria and proteinuria significantly improved and prednisolone was gradually tapered without relapse. Conclusion. The pathogenic process underlying MPGN development in this patient is unknown but residual humoral immunity might play an important role. Thus, this case highlights the risk of autoimmune disorders among patients with XLA.

Nedeni Bilinmeyen Ateş Şeklinde Sunulan Poliarteritis Nodosa: Nadir Bir Olgu Raporu

Classical polyartheritis nodosa (PAN) is a systemic vasculitis which affects small and medium sized arteries, and characterized by necrotizing inflammatory lesions. The disease may also manifest as fever of unknown origin. In this case, a 44-year-old male patient who was followed up due to high fever, and diagnosed with PAN according to the American College of Rheumatology (ACR) 1990 criteria after exclusion of all infectious causes which could be tested was presented. The patient achieved remission with high-dose prednisolone, and monthly pulse cyclophosphamide treatment. Systemic vasculitis syndromes should be definitely considered in the etiology of fever of unknown origin, though they are seen rarely.

A case of lupus mesenteric vasculitis

A 35-year-old man presented to our emergency department with a 4-day history of intermittent abdominal pain, watery diarrhea and fever. Physical examination revealed a flat and soft abdomen with marked tenderness of the umbilical region, but no abdominal rebound tenderness or guarding. Abdominal computed tomography showed ascites and edematous thickening of the wall of the ascending colon and part of the small intestine. Colonoscopy revealed mucosal edema, diffuse reddening, multiple ulcerations, and erosions in the terminal ileum. These findings and the pathological examination results strongly suggested the diagnosis of lupus mesenteric vasculitis. Treatment was commenced with high-dose prednisolone (40 mg/day, intravenous) , cyclophosphamide (1000 mg/day, intravenous) , and dalteparin sodium (5000 IU/day, intravenous) . The patient achieved gradual and complete control of the illness, which allowed tapering of the prednisolone dose and warfarin therapy. Post-treatment, colonoscopy revealed normal mucosa and normalization of most of the serological parameters.

The Paradoxical Beneficial Effect on Thrombocytopenia in Refractory Immune Thrombocytopaenic Purpura by Leishmaniasis

The phenomenon of platelet recovery in untreated patients with severe chronic refractory immune thrombocytopenic purpura (ITP) has never been described. A 44 year old lady presented with pyrexia. The blood count was Hb 9.8 g/l WBC 6.5 × 109/l Platelets 125 × 109/l. A bone marrow aspirate revealed macrophage hyperplasia with heavy infiltration by Leishman Donovani. The patient had a twenty year history of severe ITP responsive only to high doses of prednisolone. She had undergone two splenectomies and failed to respond to the sequential administration of dapsone, azathiaprine and cyclosporine. The minimum daily dose of prednisolone required to maintain the platelet count was 30 mg and she was on this maintenance dose for most of the duration of the disease. Intensive treatment with liposomal amphotericin and sodium stibogluconate failed to clear the parasites and for the rest of her life (14 months) she remained a carrier of leishmania requiring maintainance monthly doses of Leishmaniacides. During this period the platelet count remained normal even though the steroids were tapered to zero. The normalisation of the platelet count without steroids was unexpected and had never been observed before in her case. It was noted that she maintained a normal platelet count spontaneously even though she had developed transfusion dependent anaemia. Moreover, by then she had developed severe neutropenia partially corrected with granulocyte colony stimulating factor. Both cytopenic effects were a consequence of the ongoing sepsis. The patient eventually succumbed to renal failure secondary to a diabetic nephropathy. Kala-azar in normal subjects characteristically causes thrombocytopenia partly because of hypersplenism and partly because of consumption by the diffuse macrophage hyperplasia within the reticuloendothelial system. Also, in HIV infection where ITP is common, visceral leishmaniasis has been shown to worsen the thrombocytopenia. The main reason for thrombocytopenia in ITP is macrophage mediated phagocytosis of the antibody coated platelets. Two highly effective therapeutic agents are directed against this macrophage activity. Intravenous immunoglobulin saturates the macrophage receptor sites, thereby sparing the sensitised platelets by competitive inhibition [1]. Anti–D transiently diverts macrophages from destruction of platelets by focusing their activity against the sensitised erythrocytes [2]. Using the similar paradigm of these immunemodulatory agents, I postulate that the continual saturation of macrophages with the Leishmania parasites likewise had a platelet sparing effect. This observation may be of interest for pharmaceutical companies in their drug development research.

High-dose intravenous immunoglobulin therapy for eosinophilic granulomatosis with polyangiitis.

BackgroundRegulatory T (Treg) cells are implicated in the development and progression of eosinophilic granulomatosis with polyangiitis (EGPA). We previously showed beneficial effects of intravenous immunoglobulin (IVIG) therapy combined with corticosteroid and immunosuppressant treatment on clinical symptoms, including mononeuritis multiplex and cardiac dysfunction, and Treg cell frequency, during EGPA. Whether the timing of administration (during initial treatment or at relapse after remission) or previous treatment affects the clinical and immunologic efficacy of IVIG is unknown. We evaluated whether the frequency of Treg cells varied depending on when IVIG was provided relative to the start of conventional therapy for EGPA.MethodsThe patient population for this retrospective analysis comprised 17 patients with severe mononeuritis multiplex or heart failure whose EGPA did not respond to corticosteroids combined with immunosuppressant therapy. Ten patients first received IVIG during initial treatment, whereas the remaining 7 patients first received IVIG on relapse after remission. We measured the percentage of Treg cells, defined as FOXP3+CD4+ T cells, present before the first round of IVIG and at 1 month after the last IVIG treatment.ResultsFOXP3+CD4+ T cells were increased in patients who required only a single course of IVIG to achieve remission compared with those who needed two or more courses. The dosage of prednisolone at initial IVIG was inversely correlated with the ratio of the number of FOXP3+CD4+ T cells before IVIG and that at 1 month thereafter.ConclusionPatients with severe EGPA who receive IVIG after nonresponse to high-dose prednisolone during initial treatment may need multiple courses of IVIG to achieve remission. An increase in the frequency of Treg cells after IVIG may predict the need for additional IVIG in EGPA.

Corticosteroids for Dengue – Why Don't They Work?

BackgroundDysregulated immune responses may contribute to the clinical complications that occur in some patients with dengue.FindingsIn Vietnamese pediatric dengue cases randomized to early prednisolone therapy, 81 gene-transcripts (0.2% of the 47,231 evaluated) were differentially abundant in whole-blood between high-dose (2 mg/kg) prednisolone and placebo-treated patients two days after commencing therapy. Prominent among the 81 transcripts were those associated with T and NK cell cytolytic functions. Additionally, prednisolone therapy was not associated with changes in plasma cytokine levels.ConclusionThe inability of prednisolone treatment to markedly attenuate the host immune response is instructive for planning future therapeutic strategies for dengue.

Does dipeptidyl peptidase-4 inhibition prevent the diabetogenic effects of glucocorticoids in men with the metabolic syndrome? A randomized controlled trial

Anti-inflammatory glucocorticoid (GC) therapy often induces hyperglycemia due to insulin resistance and islet-cell dysfunction. Incretin-based therapies may preserve glucose tolerance and pancreatic islet-cell function. In this study, we hypothesized that concomitant administration of the dipeptidyl peptidase-4 inhibitor sitagliptin and prednisolone in men at high risk to develop type 2 diabetes could protect against the GC-induced diabetogenic effects. Men with the metabolic syndrome but without diabetes received prednisolone 30 mg once daily plus sitagliptin 100 mg once daily (n=14), prednisolone (n=12) or sitagliptin alone (n=14) or placebo (n=12) for 14 days in a double-blind 2 × 2 randomized-controlled study. Glucose, insulin, C-peptide, and glucagon were measured in the fasted state and following a standardized mixed-meal test. β-cell function parameters were assessed both from a hyperglycemic-arginine clamp procedure and from the meal test. Insulin sensitivity (M-value) was measured by euglycemic clamp. Prednisolone increased postprandial area under the curve (AUC)-glucose by 17% (P<0.001 vs placebo) and postprandial AUC-glucagon by 50% (P<0.001). Prednisolone reduced 1st and 2nd phase glucose-stimulated- and combined hyperglycemia-arginine-stimulated C-peptide secretion (all P ≤ 0.001). When sitagliptin was added, both clamp-measured β-cell function (P=NS for 1st and 2nd phase vs placebo) and postprandial hyperglucagonemia (P=NS vs placebo) remained unaffected. However, administration of sitagliptin could not prevent prednisolone-induced increment in postprandial glucose concentrations (P<0.001 vs placebo). M-value was not altered by any treatment. Fourteen-day treatment with high-dose prednisolone impaired postprandial glucose metabolism in subjects with the metabolic syndrome. Concomitant treatment with sitagliptin improved various aspects of pancreatic islet-cell function, but did not prevent deterioration of glucose tolerance by GC treatment.

Efficacy of perioperative high-dose prednisolone therapy during thymectomy in myasthenia gravis patients

BackgroundThis study aimed to investigate the benefits of administering perioperative high-dose prednisolone in conjunction with thymectomy in patients with myasthenia gravis.MethodsWe retrospectively reviewed data from patients with Myasthenia Gravis Foundation of America Clinical Class I to IIIB who had undergone an extended thymectomy between 1992 and 2009. Perioperative high-dose prednisolone was administered at starting doses of 10 to 20 mg and escalated up to 100 mg on alternate days. The treatment group comprised 70 patients receiving perioperative high-dose prednisolone, whereas the control group included 61 patients not treated with preoperative steroids. The two groups were compared with respect to baseline clinical characteristics, incidence of postoperative complications, and follow-up disease status.ResultsPrednisolone-treated patients presented with more advanced disease compared to controls (Class IIB or greater, 42 [60.0%] versus 7 [11.3%], respectively; P < 0.001). Mean preoperative%FVC was lower and FEV1.0% was higher in treated patients than in controls (%FVC: 92.4 ± 2.3% versus 99.5 ± 2.4%, respectively; P = 0.037, FEV1.0%: 85.2 ± 1.3% versus 81.4 ± 0.9%, respectively; P = 0.017). The groups were similar in other variables including presence of thymoma, and operative procedure. In the treatment group, disease status was significantly improved only by the induction of high-dose prednisolone before the surgery (P < 0.001), and these patients discontinued anti-cholinesterase therapy more frequently than controls (P < 0.001). Moreover, the treatment group demonstrated markedly lower rates of postoperative crisis (12.2% versus 2.9%, respectively; P = 0.045). The incidence of infection, wound dehiscence, and diabetes mellitus were comparable between groups. Survival analysis demonstrated higher rates of treated patients with improved disease status at three and five years (92% and 96%, respectively) compared to controls (57% and 76%, respectively; P < 0.001). Likewise, significantly greater proportions of treated patients achieved complete stable remission or pharmacologic remission at three, five, and ten years (23%, 42%, and 72%, respectively) compared to controls (10%, 20%, and 44%, respectively; P = 0.002).ConclusionsPerioperative high-dose prednisolone therapy is a safe, promising strategy for managing patients with myasthenia gravis and may reduce the incidence of postoperative crisis while improving disease status.

Rapidly progressive dementia due to neurosarcoidosis.

Rapidly progressive dementia (RPD) is typically defined as a cognitive decline progressing to severe impairment in less than 1-2 years, typically within weeks or months. Accurate and prompt diagnosis is important because many conditions causing RPD are treatable. Neurosarcoidosis is often cited as an unusual reversible cause of RPD.METHODSWe report two cases of neurosarcoidosis presenting as RPD.RESULTSCase 1: A 61-year-old woman developed a RPD associated with visual loss. In seven months she was dependent for self-care. Magnetic resonance imaging (MRI) revealed temporal and suprasellar brain lesions. Treatment with high-dose intravenous prednisolone was associated with partial improvement. Case 2: A 43-year-old woman who was being treated for diabetes insipidus developed a severe episodic amnesia one year after onset of cognitive symptoms. Previous MRI had shown a hypothalamic lesion and she had been treated with oral prednisone and cyclophosphamide. There was reduction of the MRI findings but no improvement in the cognitive deficits. Brain biopsy disclosed noncaseous granulomas and granulomatous angiitis; treatment was changed to high-dose intravenous methylprednisolone, with poor symptomatic response.CONCLUSIONThe diagnosis of RPD due to neurosarcoidosis can be challenging when the disease is restricted to the nervous system. In these cases, clinical presentation of RPD associated with neuroendocrine and visual dysfunction, imaging findings showing hypothalamic lesions and, in some cases, brain biopsy, are the key to a correct diagnosis. It is possible that earlier diagnoses and treatment could have led to a better outcome in these patients.

Chronic Relapsing Remitting Sweet's Syndrome- a Harbinger Of Myelodysplastic Syndrome (MDS), Single Centre Analysis Of 31 Patients

BackgroundSweet's syndrome (SS) is an acute febrile neutrophilic dermatosis. It has been associated with malignant disease, especially acute myeloid leukaemia (AML) and drugs, particularly granulocyte colony stimulating factor (GCSF). No cause is found in the rest and is labeled idiopathic. We describe 31 patients with a readily diagnosed form of SS, which we believe represent an autoimmune phenomenon secondary to the myelodysplastic syndrome (MDS). MethodsA retrospective study was conducted to identify patients with SS with underlying diagnosed or occult haematological disorders over a 7 year period. The skin histology was reviewed independently by histopathologist and additionally frequency of CD4+ and CD8+ T cells, B cells and NK cells were investigated in 6 patients with chronic relapsing SS in comparison with 4 healthy age matched donors. ResultsWe identified 31 patients with SS in a cohort of 744 patients with MDS and 215 with AML seen between 2004-2011. The median age was 58 yrs (37-82 yrs), with male female ratio of 1.2;1 (male 17, female 14). Of these, 74% (N=23) were associated with myelodysplastic syndrome, 13 %( N=4) with AML, 6% (n=2) with chronic myeloid leukemia, 3% (n=1) with acute lymphoblastic leukaemia and 3% (n=1) with polycythaemia rubra vera.We grouped the patients into those with a chronic relapsing/remitting type of skin eruption (n=15) and the second group consisting of patients with a single episode of classical SS (n=16).Patients presenting with this chronic relapsing remitting form of SS (n=15) were not generally known to have MDS at the time of their initial skin eruption. The median time from diagnosis of SS to diagnosis of MDS was 17 months (1.4 years) (range 0-157 months). The WHO subtypes of MDS were RCMD (N= 13), RAEB-1 (N=1) and MDS/MPN-U (N=2).All except two patients (trisomy 8 and del 11q) had normal bone marrow karyotype. The IPSS risk groups were; Low (N=10), Int-1 (n=5).Transfusion dependency was subsequently seen in 6 of 15 patients. Progression to high-risk occurred in two patients (RAEB 1), whilst none had leukaemic transformation.The clinical features of the chronic form were identical to those described by Sweet ; raised, tender plaques which were red and urticated. Some of the lesions had mamillated (“nipple like”) elevation on the surface of these plaques. They were found to be scattered on the torso and limbs, neck and face. Larger more nodular plum coloured lesions may also be found.All 15 patients had constitutional symptoms including fever and sweats at the time of skin eruptions. Arthralgia was seen in a majority of patients (n=12).Additionally, other associated autoimmune conditions or dermatological conditions seen included seronegative rheumatoid arthritis (n=1), relapsing polychondritis (n=1), pyoderma gangrenosum (n=1) and Behcets disease (n-1).Compared to MDS without SS (n=711), patients with SS and MDS were on an average 8 years younger, low/int-1 risk, less likely to receive MDS therapy and had lower propensity to leukaemic transformation (all p<0.001).The frequency of γδ Tcells (3.6% ± 1.66% v 2.2% ± 0.6%, p=0.51), effector CD4+ T cells (12.6% ± 5.7 v 4.5% ± 1.8%, p=0.2) and resting Tregs (11.1 ±2.5 v 5.5% ± 0.6%, p=0.4) in patients were higher compared to healthy aged match donors.The chronic relapsing remitting of SS was recalcitrant to treatment. Most patients had to be maintained on a higher doses of prednisolone (>15-20mg) to prevent recurrent episodes. The response to immunosuppressive therapy (IST) was variable with median of 4 ISTs (range 0-12) per patient. The treatment associated with complete resolution of the skin eruptions with no relapses were 5-azacitidine in four patients, infliximab in one patient and one with methotrexate but other agents were disappointing. Corticosteroids were effective in all patients; however doses of prednisolone below 15mgs resulted invariably in relapse of SS.The cause in 16 patients could be attributed either to administration of GCSF or after chemotherapy. The eruption was brief and disappeared spontaneously or following withdrawal of GCSF ConclusionsWe describe a chronic debilitating episodic clinically distinctive skin eruption with features of Sweet's syndrome but not always definitive histopathology often associated with immunological abnormalities affecting other systems (especially rheumatological) universally related to underlying occult ‘lower risk' MDS. Disclosures:No relevant conflicts of interest to declare.

Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii

An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. P. jirovecii isolates from 22 transplant cases, 2 colonized RTRs, and 19 Pneumocystis control samples were genotyped by restriction fragment length polymorphism and multilocus sequence typing analysis. Contact tracing was used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs, and a colonized RTR in three distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only cytomegalovirus viremia was consistently associated with PCP (P=0.03; P=0.009). Mycophenolate mofetil was associated with PCP risk only in the RTR population (P=0.04). We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by interhuman transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months after transplantation. Because patients at risk cannot be identified clinically and outbreaks cannot be predicted, 6 months of PCP chemoprophylaxis should be considered for all RTRs and LTRs.

Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone

This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms. Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy. Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response. Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.

Azathioprine-induced Sweet syndrome in ANCA-associated vasculitis.

A 38-year-old man with a history of myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented after 4 days of fever >38°C, red eye, arthralgias and skin lesions. The patient's vasculitis was initially treated with a 7-month course of intravenous cyclophosphamide and oral corticosteroids, reaching complete remission. The patient had been transferred, 2 weeks before, to oral azathioprine (200 mg/day) as maintenance therapy. The physical examination found fever, conjunctivitis and painful erythematous edematous papules, with occasional pustules, involving the neck, upper back and extremities (Figure 1). In the lower legs, there were also erythematous, tender deep nodules (Figure 2). Laboratory findings revealed 12.2 × 109/L leukocytes with 85% neutrophils, elevation of both erythrocyte sedimentation rate and C-reactive protein, acute kidney injury, haematoproteinuria and leukocyturia. Infectious disease was ruled out. A skin biopsy, from an erythematous papule, showed a dense neutrophilic infiltrate in the upper dermis, junctional oedema and focal karyorrhexis. There was no vasculitis in the biopsy specimen and testing for ANCAs was negative. Fig. 1. Erythematous papules, involving the neck and upper back, typical of Sweet syndrome, with occasional pustules. Fig. 2. Erythematous deep nodules in the lower legs (mimic erythema nodosum) typical of the subcutaneous presentation of Sweet syndrome. The diagnosis of Sweet syndrome was established, and the temporal relationship between azathioprine administration and clinical presentation raised the suspicion for drug-induced Sweet syndrome. Azathioprine was withdrawn and high-dose prednisolone was initiated with a rapid and dramatic response of both cutaneous and extracutaneous manifestations. The diagnosis of azathioprine-induced Sweet syndrome was confirmed. Methotrexate was selected as maintenance therapy. Azathioprine treats a variety of autoimmune conditions, and, in nephrology, its main indication is maintenance therapy of ANCA-associated vasculitis. Sweet syndrome is one of the several recognized clinical patterns of azathioprine hypersensitivity syndrome. Sweet syndrome is characterized by fever, constitutional symptoms, peripheral neutrophilia and abrupt onset of erythematous papules, plaques or nodules [1]. Sweet syndrome presents in three clinical settings: classical, malignancy-associated and drug-induced. The criteria for drug-induced Sweet syndrome include: (i) abrupt onset of painful erythematous plaques or nodules, (ii) histopathological evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (iii) fever >38°C, (iv) temporal relationship between drug ingestion and clinical presentation and (v) temporal resolution of lesions after drug withdrawal or treatment with systemic corticosteroids [2]. The first case of azathioprine-induced Sweet syndrome was reported in 2003 [3] and since then only 18 [4] cases have been described. We emphasize the importance of considering azathioprine-induced Sweet syndrome, within weeks of azathioprine initiation, in the differential diagnosis of infection and disease flare in patients with ANCA-associated vasculitis. Subsequent azathioprine avoidance is crucial as rechallenge can lead to anaphylaxis [5].

JUST A GRAZE?

We describe a case of a diagnostically difficult stroke mimic, cephalic tetanus.1 Currently there are 12–15 cases of tetanus reported annually in the United Kingdom,2 but worldwide it accounts for...

Hypothalamic-Pituitary-Adrenal Axis Recovery Following Prolonged Prednisolone Therapy in Infants

The duration of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid treatment is uncertain. We aimed to determine the duration of HPA axis suppression in prednisolone-treated infants and the age at which circadian variation in salivary cortisol is established in healthy infants. Before the adoption of propranolol treatment by the Vascular Birthmarks Clinic, 12 infants with infantile hemangioma received high-dose prednisolone for 12 to 25 weeks' duration, weaned over 4 to 6 weeks, and ceased at age 21 to 31 weeks. Parents collected serial salivary samples at two time points per day (before first and last feed) until circadian variation in salivary cortisol (measured by radioimmunoassay) was observed, when a confirmatory 1 μg Synacthen test was performed. Ten healthy control infants had serial salivary cortisol measurements to determine the age at which circadian variation is established. We defined circadian variation as evening salivary cortisol <50% of the early morning level on two consecutive sampling weeks. Circadian variation appeared within 6 weeks (median 2.7, range 1.4-5.4) of prednisolone cessation. All confirmatory Synacthen tests were normal (peak serum cortisol >600 nmol/L) and were performed within 12 weeks of prednisolone cessation. Healthy controls developed circadian variation at median 16 weeks of age (range 8-24). HPA recovery occurred within 6 to 12 weeks, shorter than empirical recommendations, to give stress cover for 6 to 12 months. Reduced duration of stress-cover precautions may reduce parental anxiety and side effects from unnecessary glucocorticoid use. Healthy control infants established circadian variation in salivary cortisol between 2 and 6 months of age.

Four Cases of Multiple Cranial Nerve Involvement with Varicella‐Zoster Virus

Objectives: We report 4 cases of unilateral paralysis of the 7th, 8th, 9th, and 10th cranial nerves caused by varicella-zoster virus. Methods: Retrospective study with 4 cases from May 2008 to May 2012.The patients were 58, 69, 72, and78 years old. There were 2 male patients and 2 female patients. Results: Every case confirmed 9th or 10th cranial nerve paralysis preceding 7th or 8th cranial nerve paralysis. Every case was treated by antiviral medicine and high-dose prednisolone. Conclusions: There are various theories of the mechanisms involved in the spread of cranial nerve palsy. Our cases confirmed only 7th, 8th, 9th, or 10th cranial nerve paralysis. If cranial neuropathy spread via cerebrospinal fluid, lymph nodes, or by blood, other cranial nerves may be paralyzed. If cranial neuropathy spread by revitalization of every nerve ganglion, we cannot explain these systematic conditions. We discussed the spreading mechanisms of cranial neuropathy via intervention nerve ( for example, tympanic nerve, less petrosal nerve).

Glucocorticoid treatment impairs microvascular function in healthy men in association with its adverse effects on glucose metabolism and blood pressure: a randomised controlled trial

Glucocorticoids (GCs) are widely used anti-inflammatory agents that frequently induce side effects, including insulin resistance, diabetes and hypertension. Here, we investigated the contribution of microvascular dysfunction to the development of these adverse effects in healthy men. In a randomised, placebo-controlled, dose-response intervention study, 32 healthy normoglycaemic men (age: 21 ± 2 years; BMI: 21.9 ± 1.7 kg/m(2)) were allocated to receive prednisolone 30 mg once daily (n = 12), prednisolone 7.5 mg once daily (n = 12) or placebo (n = 8) for 2 weeks using block randomisation. A central office performed the treatment allocation, and medication was dispersed by the hospital pharmacy that was also blinded. Treatment allocation was kept in concealed envelopes. Participants, study personnel conducting the measures and assessing the outcome were blinded to group assignment. The study was conducted at a university hospital. Primary endpoint was prednisolone-induced changes in microvascular function, which was assessed by capillary microscopy. Insulin sensitivity was determined by hyperinsulinaemic-euglycaemic clamp and postprandial glycaemic excursions by standardised meal tests. Compared with placebo, prednisolone 7.5 mg and 30 mg decreased insulin-stimulated capillary recruitment by 9 ± 4% and 17 ± 3%, respectively (p < 0.01). In addition, prednisolone 7.5 mg and 30 mg reduced insulin sensitivity (M value) by -11.4 ± 4.5 μmol kg(-1) min(-1) and -25.1 ± 4.1 μmol kg(-1) min(-1) (p < 0.001) and increased postprandial glucose levels by 11 ± 5% and 27 ± 9% (p < 0.001), respectively. Only high-dose prednisolone increased systolic blood pressure (6 ± 1.2 mmHg, p = 0.006). Prednisolone-induced changes in insulin-stimulated capillary recruitment were associated with insulin sensitivity (r = +0.76; p < 0.001), postprandial glucose concentrations (r = -0.52; p < 0.03) and systolic blood pressure (r = -0.62; p < 0.001). Prednisolone increased resistin concentrations, which were negatively related to insulin-stimulated capillary recruitment (r = -0.40; p = 0.03). No effects were noted on adiponectin and leptin concentrations. Prednisolone treatment was well tolerated; none of the participants left the study. Prednisolone-induced impairment of insulin-stimulated capillary recruitment was paralleled by insulin resistance, increased postprandial glucose levels, hypertension and increased circulating resistin concentrations in healthy men. We propose that GC-induced impairments of microvascular function may contribute to the adverse effects of GC treatment on glucose metabolism and blood pressure. isrctn.org ISRTCN 78149983. The study was funded by the Dutch Top Institute Pharma T1-106.

Usefulness of heparin loading 18F-fluoro-2-deoxyglucose positron emission tomography for the diagnosis of cardiac sarcoidosis and evaluation of the response to therapy

Purpose: Heparin loading 18F-fluoro-2-deoxyglucose positron emission tomography (HL 18F-FDG PET) has advantages for the assessment of myocardial inflammation because heparin administration increases free-fatty acids (FFA), followed by shift of myocardial substrate utilization from glucose to FFA under normal conditions. Our goal was to evaluate the usefulness of HL 18F-FDG PET for the diagnosis of cardiac sarcoidosis and evaluation of the response to therapy. Methods: We screened 49 consecutive patients, who underwent HL 18F-FDG PET based on a suspicion of cardiac sarcoidosis. Five patients were diagnosed by the Japanese Ministry of Health and Welfare guidelines and showed 18F-FDG uptake on PET-CT (G(+) group). Twelve patients did not fulfill the diagnostic criteria but showed 18F-FDG uptake on PET-CT, so they were treated as cardiac sarcoidosis (G(-) group). 18F-FDG uptake was expressed as the maximum standardized uptake value (SUVmax). We compared reductions of SUVmax in response to therapy in both groups. Furthermore, the relationship between the 18F-FDG uptake pattern and prognosis was examined. Results: After steroid therapy, SUVmax was significantly reduced in both the G(+) group (from 8.0±0.9 to 4.0±0.4, p=0.04) and the G(-) group (from 8.3±3.4 to 6.2±3.2, p<0.01). Neither the absolute value of SUVmax nor the ΔSUVmax after steroid therapy were significantly correlated with event-free survival. After steroid therapy, ten patients showed diffuse uptake on 18F-FDG PET and five patients showed focal uptake. Major cardiac events (sudden cardiac death, ventricular arrhythmia, heart failure and complete AV block) occurred in 60% of patients with diffuse and 20% of those with focal uptake. Ten patients relapsed after reducing the dose of prednisolone. 18F-FDG uptake was significantly increased with low-dose prednisolone (mean 9.3±4.8 mg) compared with high-dose prednisolone. Conclusions: This study suggests that some cases of cardiac sarcoidosis cannot be diagnosed by current guidelines, and HL 18F-FDG PET might be useful for diagnosis of cardiac sarcoidosis and evaluation of the response to therapy.

AB0748 Carbimazole induced ANCA associated renal vasculitis

BackgroundWe present a case of renal antineutrophil cytoplasmic antibody (ANCA)-associated-vasculitis (AAV) precipitated following introduction of carbimazole while treating hyperthyroidism.MethodsA 22 yr old female was newly diagnosed with thyrotoxicosis with raised...

THU0274 Combination of Mycophenolate Mofetil and Tacrolimus for Refractory Lupus Nephritis: A 12-Month Open-Labeled Trial

ObjectivesTo evaluate the efficacy and tolerability of combined low-dose mycophenolate mofetil (MMF) and tacrolimus (Tac) for refractory lupus nephritisMethodsPatients with refractory lupus nephritis were recruited. Inclusion criteria: (1) Active nephritis...