High-dose Prednisolone Research Articles

Long-term outcomes after early treatment with rituximab for Japanese children with cyclosporine- and steroid-resistant nephrotic syndrome.

Although rituximab (RTX) may be effective treatment in children with nephrotic syndrome who are resistant to cyclosporine A and steroid (CsA-SRNS), long-term outcomes after B cell depleting therapy remain unclear. We retrospectively reviewed the clinical courses (median follow-up, 5.1years) of six CsA-SRNS children (three boys; median age at RTX, 4.2years) unresponsive to oral cyclosporine combined with ≥ 2 courses of intravenous methylprednisolone pulses, who received RTX within 6months after disease onset (median 11weeks). After initial RTX treatment (median two doses of 375mg/m2) followed by retreatment with intravenous methylprednisolone pulses and/or high-dose prednisolone, all patients achieved complete remission at a median of 158days. Although 17 relapses occurred in five patients during follow-up, all but one patient became steroid sensitive. Severe neutropenia and hypogammaglobulinemia developed in two and four patients, respectively. However, no life-threatening infections were identified in the cohort. At last visit (median age, 11.3years), all patients maintained complete remission without renal insufficiency. Although late-onset adverse events should be considered, particularly for young patients, early RTX treatment may have positive outcomes in children with CsA-SRNS in the long term.

Challenges in managing graft-versus-host disease in developing countries: a perspective.

Hematopoietic cell transplant (HCT) activity is increasing worldwide due to safer techniques, widening indications, and more availability of donors. New HCT centers have recently been established in many developing countries including Asian and African countries. Due to limited resources, logistic, political, and social issues in developing countries, the treatment of orphan diseases like graft-versus-host disease (GVHD) can be challenging. We intended to delineate the current issues that institutions and clinicians face in managing GVHD. We conducted a comprehensive systematic electronic review of peer-reviewed published articles on GVHD management in developing countries. We used PubMed, Cochrane, and Embase databases as our primary source of data. Studies that were included described the treatments for both acute and chronic GVHD. Consensus on the use of high-dose methyl-prednisone and prednisolone as the initial therapy was widely accepted and used in practice. Socio-economic factors were found to be the major factor involved in GVHD management in lower income patients. Delayed diagnosis and treatment, lack of availability of healthcare professionals, lack of knowledge among cancer patients, and poverty are major concerns in the developing world. For optimal management, HCT programs should develop systems in place for long-term follow-up of HCT survivors and have a low threshold to initiate treatments for GVHD early. Awareness and health policy programs must be initiated at the grass-root level for long-term management of these survivors in developing countries.

THUR 213 An unusual case of cluster acetylcholine receptor antibody positive myasthenia gravis

A 73-year-old builder presented with fatigable ptosis and ophthalmoplegia. He was started on pyridostigmine for presumed ocular myasthenia gravis (MG). Despite making an initial improvement he subsequently developed dysarthia, dysphonia and a head drop within 3 weeks. At this time, he also had mild proximal weakness and marked asymmetrical distal weakness of the upper limbs and mild distal lower limb weakness.Conventional serological screening for acetylcholine receptor (AChR) and muscle specific kinase antibodies were negative. However, extended testing using a cell-based cluster assays demonstrated AChR antibody positivity. Repetitive nerve stimulation demonstrated significant decrement more prominent in distal muscles.Despite high dose prednisolone, azathioprine, several courses of IV Immunoglobulins and plasma exchange the patient has had frequent admissions to the high dependency and intensive care setting with respiratory failure.Cluster AChR antibody positive MG has been described only within the last decade and is usually mild and treatment responsive. This is the first case reported to have required intubation and ventilation due to respiratory failure. This case highlights the importance of extending the routine panels for antibody testing in patients with ‘seronegative’ MG and the need to remain vigilant in patients with cluster-AChR positive disease.

Surgical management of raised intra-ocular tension in the hostile ocular surface - recurrent tube erosion in a patient with systemic sclerosis: a case report

BackgroundThe surgical management of patients with uncontrolled glaucoma and scleroderma is challenging, as the hostile ocular surface poses a challenge to surgery. A serious complication is tube erosion, with the risk of subsequent endophthalmitis. Here, we present a novel technique of harvesting autologous tissue to successfully manage recurrent tube extrusion.Case presentationMG is a 60-year-old Arabic lady diagnosed with scleroderma, that was previously managed with systemic corticosteroids. She has chronic open angle glaucoma, with a failed left eye trabeculectomy, which was then managed by a Baerveldt tube (BVT) insertion. Eight months after this primary surgery, she developed an anterior uveitis. This was further complicated by conjunctival erosion, tube exposure, leak around the sclerostomy site and hypotony. The erosion was likely secondary to her tight eyelids as a result of her scleroderma. She was taken back to theatre for tube revision, with single layer amniotic membrane transplant (AMT) over the exposed area, but the tube was eroding again after 2 months. She eventually underwent tube extraction, pars plana tube plate stabilisation, pars plana vitrectomy (PPV), pars plana tube insertion, phacoemulsification and intra-ocular lens insertion, jointly with the vitreo-retinal surgeons and with high dose prednisolone cover both pre- and post-operatively. We harvested the capsule which had grown over the end plate of the original tube. We sutured this over the new tube, specifically over a single layer of tutoplast prior to conjunctival closure. Almost a year on, the pars plana tube remains in place with no complications.ConclusionsThis case highlights the role of a pars plana tube in cases of cicatricial disease, with the use autologous tissue instead of grafts wherever possible. In patients with systemic disease such as scleroderma, pre-operative immunosuppression helps to reduce the of erosion in difficult cases.

Treating Infantile Spasms with High-Dose Oral Corticosteroids: A Retrospective Review of 87 Children

BackgroundHormonal therapy is the treatment of choice in most patients with infantile spasms, but the optimal way to provide this therapy is unclear. Intramuscular adrenocorticotropic hormone (ACTH) has historically used first-line; however, there are significant logistical and financial issues. Our institution has used high-dose prednisolone as the first-line hormonal treatment of infantile spasms since 2006 and published our early experience with 15 infants in 2009. This study updates our institutional experience over more than 10 years of continuous use. MethodsCharts of infants who presented to the Johns Hopkins Hospital with infantile spasms and were treated with high-dose oral prednisolone (40-60 mg/day) from January, 2006 through December, 2016 were reviewed. Electroclinical response was defined as clinical spasm-freedom and resolution of hypsarrhythmia within two weeks of initiation of therapy. Presence of infantile spasms at three months and adverse effects throughout treatment were evaluated. ResultsOver the 10-year period, 87 infants with new-onset infantile spasms were treated. Electroclinical response occurred in 64% infants within two weeks; 62% were spasm-free at three months. Fifty-two percent had side effects, primarily irritability, weight gain, and gastroesophageal reflux. Five percent had major adverse events, including gastrointestinal bleeding (n = 2), herpes simplex virus reactivation (n = 1), and necrotizing enterocolitis (n = 1). ConclusionsOur results continue to demonstrate that high-dose oral prednisolone is very effective for the treatment of new-onset infantile spasms, with few major adverse effects. Oral prednisolone represents a less expensive, readily available alternative to adrenocorticotropic hormone injections.

Spontaneous pregnancy after full recovery from hypopituitarism caused by lymphocytic hypophysitis.

SummaryLymphocytic hypophysitis (LyH) has been known to be associated with pregnancy. We herein report the case of a 33-year-old woman who underwent vaginal delivery without massive bleeding at 40 weeks of gestation. Because of the presence of headache and terrible fatigue after childbirth, she visited our hospital. Severe hyponatremia (Na, 118 mEq/L) and visual field abnormality was noted upon examination. MRI revealed pituitary enlargement with a swollen pituitary stalk, albeit at low signal intensity. Basal pituitary hormone levels were all reduced and remained low after exogenous administration of hypothalamic-releasing hormones. She was diagnosed with LyH and was started on prednisolone 60 mg/day. A month later, her pituitary function had gradually improved together with a decrease in pituitary enlargement and recovery of her visual field. The dose of prednisolone was gradually reduced and finally withdrawn 27 months later. After prednisolone withdrawal, her pituitary function remained normal despite the absence of any hormonal replacement. A year later, she became pregnant without medication and delivered a second baby without LyH recurrence. Thereafter, her pituitary function has been normal for more than 5 years. Two valuable observations can be highlighted from the case. First, the patient completely recovered from LyH through prompt prednisolone therapy during its initial phase and had almost normal pituitary function. Second, after recovery from LyH, she was able to undergo spontaneous pregnancy and deliver a baby. We believe that reporting incidences of spontaneous pregnancy after complete normalization of pituitary function in patients with LyH is of great significance.Learning points:Females are more affected by LyH than males given its strong association with pregnancy.LyH possesses characteristic findings on pituitary MRI.Glucocorticoid therapy for LyH has been recommended as an effective treatment.A history of previous pregnancies does not increase the risk of developing AH in subsequent pregnancies.Early induction of high-dose prednisolone was therapeutically effective in treating LyH.

Differences in clinical Pneumocystis pneumonia in rheumatoid arthritis and other connective tissue diseases suggesting a rheumatoid-specific interstitial lung injury spectrum.

To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for "clinical PCP": (1) positive plasma β-D-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone "pulse" therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer's exact probability test to compare the two groups and Jonckheere-Terpstra's test and Ryan's procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.

Experience with very high dose (8mg/kg/day, maximum 60mg/day) prednisolone for West syndrome in a resource limited setting

Objectives: To assess efficacy of very high dose (8mg/kg/day, maximum 60mg/day) prednisolone in patients with West syndrome. Method: This was an observational study conducted at a tertiary level hospital from August 2014 to August 2015. Children, aged 2 to 23 months, presenting with infantile spasms with hypsarrhythmia or its EEG variants, were enrolled. Study participants were started on very high dose prednisolone (8 mg/kg/day, maximum 60mg/day). The primary outcome measure was complete cessation of spasms and clearance of hypsarrhythmia on EEG after 2 weeks of prednisolone treatment. The study was approved by the institutional ethical committee. Results: Forty children were started on very high dose prednisolone (8 mg/kg/day, maximum 60mg/day) of whom four did not come for the 2 week follow up and were excluded. Response rate in the remaining 36 patients was 55.6% after 2 weeks of steroid therapy Side effects seen during hormone therapy included increased appetite in 29 (80.6%) patients, irritability in 27 (75.0%) patients and weight gain in 26 (72.2%) patients. Conclusions: Use of a very high dose prednisolone regime (8mg/kg/day, maximum 60mg/day) resulted in a complete cessation of spasms and clearance of hypsarrhythmia on EEG after 2 weeks in 55.6% of children with West syndrome in this study. Sri Lanka Journal of Child Health , 2018; 47 (2): 137-140

Preliminary Study of Bone Marrow-Derived Mesenchymal Stem Cells Pretreatment With Erythropoietin in Preventing Acute Rejection After Rat Renal Transplantation

Renal transplantation is currently the most effective treatment for end-stage kidney diseases, and acute allograft rejection is well treated with high dose prednisolone and immunosuppressive agents, but long-term use of immunosuppressants will be detrimental to the long-term survival of the transplanted kidney and will have many side effects on the human body. Thus, a local and alloantigen-specific immunological tolerance may be a promising approach to improving kidney transplantation. The aim of this study is to examine the therapeutic potential of transforming bone marrow-derived mesenchymal stem cells (BMSCs) pretreated with erythropoietin (EPO) in inducing immunosuppression in renal grafts after transplantation. The immunity suppression effects were tested, focusing on the decrease of serum creatinine and the cells' ability to regulate the expression of the cytokines associated with acute rejection. Our findings demonstrate that a transfusion of BMSCs pretreated with EPO (EPO-BMSCs) can produce an immunosuppressive effect and reduce the occurrence of acute rejection. Their reciprocal effects on the induction and function of regulatory T cells (Tregs) resulted in the balance of IFN-γ/IL-4 and improved immunosuppressive effects in local kidney grafts. Our data also suggest that the acute rejection microenvironment had a directional chemotactic effect on BMSCs, which is related to the upregulation of CXCR4, and could be further enhanced by EPO treatment. Thus, transfusion of EPO-BMSCs can induce a greater local immunosuppressive effect in renal grafts after transplantation compared with untreated BMSCs. Therefore, transplantation with EPO-BMSCs can be a novel and effective approach to lower the acute rejection ratio following transplantation.

Prednisolone treatment reduces the osteogenic effects of loading in mice.

Glucocorticoid treatment, a major cause of drug-induced osteoporosis and fractures, is widely used to treat inflammatory conditions and diseases. By contrast, mechanical loading increases bone mass and decreases fracture risk. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone. Three-month-old female C57BL/6 mice were treated with high-dose prednisolone (15 mg/60 day pellets/mouse) or vehicle for two weeks. During the treatment, right tibiae were subjected to short periods of cyclic compressive loading three times weekly, while left tibiae were used as physiologically loaded controls. The bones were analyzed using peripheral quantitative computed tomography, histomorphometry, real-time PCR, three-point bending and Fourier transform infrared micro-spectroscopy. Loading alone increased trabecular volumetric bone mineral density (vBMD), cortical thickness, cortical area, osteoblast-associated gene expression, osteocyte- and osteoclast number, and bone strength. Prednisolone alone decreased cortical area and thickness and osteoblast-associated gene expression. Importantly, prednisolone treatment decreased the load-induced increase in trabecular vBMD by 57% (p < 0.001) and expression of osteoblast-associated genes, while completely abolishing the load-induced increase in cortical area, cortical thickness, number of osteocytes and osteoclasts, and bone strength. When combined, loading and prednisolone decreased the collagen content. In conclusion, high-dose prednisolone treatment strongly inhibits the loading-induced increase in trabecular BMD, and abolishes the loading-induced increase in cortical bone mass. This phenomenon could be due to prednisolone inhibition of osteoblast differentiation and function.

002 Biopsy proven giant cell arteritis in a patient with psoriatic arthritis on TNF-alpha inhibitor treated with high dose prednisolone and a switch to secukinumab (anti IL-17)

002 Biopsy proven giant cell arteritis in a patient with psoriatic arthritis on TNF-alpha inhibitor treated with high dose prednisolone and a switch to secukinumab (anti IL-17)

Initial treatment with pulse methylprednisolone followed by short-term prednisolone and tonsillectomy for childhood IgA nephropathy.

Although a combination therapy, comprising 2-year high-dose oral prednisolone (PSL), is effective for treating childhood immunoglobulin A nephropathy (IgAN), severe adverse effects and residual proteinuria occur in some patients after the therapy. To clarify the efficacy of intravenous pulse methylprednisolone (IVMP; 15-20mg/kg; maximum 600mg/day; for 3 consecutive days/week for 3weeks) followed by short-term reduced-dose PSL (initially 1mg/kg; maximum 30mg on alternate days; tapered off within approximately 12months) and tonsillectomy as an initial treatment, we retrospectively reviewed the clinical courses of 54 consecutive children with IgAN (32 boys; mean age at onset, 12.2years; follow-up period of > 2years) after initiating the treatment. According to the Japanese pediatric IgAN guidelines, we divided the 54 patients into the following two groups: group 1, comprising 24 patients with severe IgAN, and group 2, comprising 30 patients with mild IgAN. After the treatment, proteinuria disappeared in all patients at a median of 1.6months (group 1, 2.8 months; group 2, 0.4months) and hematuria disappeared in 47 patients (87%) at a median of 13.2months (group 1, 15.9 months; group 2, 13.2months). During the follow-up period (median 5years), no severe adverse effects were observed in any patient. At the last visit, although two patients (4%) had mild proteinuria, none developed hypertension or renal insufficiency. As an initial treatment, IVMP followed by short-term PSL and tonsillectomy appears to be effective for treating childhood IgAN.

Head to head comparison of adverse effects and efficacy between high dose deflazacort and high dose prednisolone in systemic lupus erythematosus: a prospective cohort study.

Deflazacort (DFZ), an oxazoline derivative of prednisolone (PDN), has a dose equivalence of 1.2:1 (mg) to PDN. No study to date has compared adverse effects and efficacy of high doses of DFZ as against high-dose PDN in systemic lupus erythematosus (SLE). To compare adverse effects of high dose DFZ and PDN in SLE patients, especially in terms of cushingoid features and gain in body weight, 3 and 6 months after initiation of these agents. In both the steroid arms, the following outcome parameters were assessed at 3 and 6 months: (a) cushingoid features by Cushing's Severity Index (CSI) (b) hirsutism by modified Ferriman Gallwey score (c) weight gain by difference (Δ, delta) of weight (in kilograms). Patients on PDN had 1.6 kg (3.2%) and 2 kg (5.1%) higher median weight gain as compared to those on DFZ at 3 and 6 months respectively ( p = 0.012 and 0.001). PDN caused 10% and 22.2% higher increment in median hirsutism scores as compared to DFZ at 3 months and 6 months follow-up, respectively ( p = 0.004 and 0.002). PDN caused 100% higher increase in median CSI scores than DFZ at 6 months ( p = 0.03). There was no significant difference by generalized estimation equation between the groups with respect to changes in SLEDAI, renal SLEDAI, anti-dsDNA titres and C3/C4 levels. There were two serious infections (requiring hospitalization/intravenous antibiotics) in the PDN group, while none in the DFZ group. Comparable intake and tapering of high dose DFZ and PDN in active SLE revealed 2-fold less weight gain, 2.5-fold less hirsutism and 1.5-fold lower cushingoid severity index as well as lower glycaemic elevation in the DFZ group as compared to PDN group. Both had similar efficacy.

Treatment of Immunoglobulin A Nephropathy Recurrence Post–Renal Transplant

Immunoglobulin A nephropathy (IgAN) is the most commonly occurring glomerulonephritis. Recurrence of disease in the transplanted kidney can significantly reduce allograft survival rates. Currently, there is no definitive management plan for IgAN recurrence in a transplant that reduces the rate of decline of allograft function and prolongs time to dialysis or re-transplantation. Herein we present a 48-year-old man who had received a renal transplantation in 2006 following his diagnosis of IgAN. In 2015, the patient was noted to have an elevated blood pressure and proteinuria (urinary protein:creatinine ratio [uPCR] 170 mg/mmol). A transplant biopsy confirmed recurrent IgAN. A year later, he presented with dipstick hematuria, nephrotic-range proteinuria (uPCR 820 mg/mmol), and a serum creatinine of 90 to 140 μmol/L. A second biopsy revealed mesangioproliferative glomerulopathy consistent with crescentic IgAN. An optimal management plan is currently unknown for recurrent crescentic IgAN in the transplanted kidney. We decided to treat this patient with oral cyclophosphamide daily and high-dose prednisolone. The treatment has so far yielded a positive response and managed to preserve allograft function without significant adverse effects for our patient. Our case illustrates the importance of timely biopsies to identify recurrence of disease and highlights an effective therapeutic option for recurrent IgAN with crescent formation in a transplant.

Abstract A101: The MetAction trial: long-lasting responses to molecularly matched therapy in end-stage cancer

Abstract Background: The first phase of the MetAction trial established the required diagnostic infrastructure, implemented security-approved systems for handling of sensitive information, educated the Trial Team within the context of tumor boards, and estimated costs of the initiative within public health services. The endeavor enabled expedited and safe mutation profiling of metastatic tumors in order to offer molecularly matched medication for end-stage cancer (Ree et al., ESMO Open 2017;2:e000158). The aim of the second trial phase was to investigate the utility of the MetAction pipeline in clinical practice. Procedures: An eligible patient with end-stage metastatic disease from any origin had been on the previous line of systemic therapy for 6 or more weeks with radiologic evaluation intervals of 6-12 weeks and disease progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Biopsy-sampled metastatic tissue was analyzed by DNA sequencing (Ion Oncomine™ Comprehensive Panel), where called variants were filtered prior to assessment and prioritization, supplemented with fluorescence in situ hybridization to cover relevant biomarkers. The Molecular Tumor Board interpreted the findings within the likelihood of signaling pathway activity, for the sequential Clinical Tumor Board to conclude on potential systemic tumor-directed medication. On study therapy, radiologic work-up was performed every 8 weeks. The primary objective was to compare progression-free survival (PFS) on study treatment, termed Period-B, with PFS for the most recent therapy, termed Period-A. If Period-B/Period-A was ≥1.3, the study therapy was deemed to be of benefit. The incidence of diagnostic adverse events and treatment-related grade 3-5 Common Terminology Criteria for Adverse Events (CTCAE) toxicities was secondary end points. Results: 26 patients were enrolled. Biopsy procedures were undertaken at lung or pleural sites (6 cases), liver or peritoneal sites (19 cases), and an inguinal lymph node (1 case), and did not cause adverse events. Histologic entities were 18 adenocarcinomas (AC), 2 undifferentiated carcinomas, 1 case each of cholangiocarcinoma and squamous cell carcinoma, and 4 different sarcoma entities. 13 patients were found eligible for off-label use of molecularly matched therapy (inhibitor of ALK-, BRAF-, EGFR-, FGFR-, mTOR-, PARP-, ROS1-, or PD-1-mediated signaling). Among the 10 individuals who received study treatment until radiologic evaluation, 5 met the primary end point. The patient with cholangiocarcinoma and a patient with rectal AC primaries, both given crizotinib, obtained Period-B/Period-A outcome slightly better than 1.3. Notably, 3 patients with colon AC primaries, receiving either a combination of panitumumab with vemurafenib or chemotherapy or single-agent pembrolizumab, obtained long-lasting responses. In addition, 1 colon AC patient receiving pembrolizumab with RECIST progression (i.e., primary end point failure) before a long-lasting response to off-protocol continuation, reported CTCAE grade 3 toxicity (a colitis event that immediately resolved on high-dose prednisolone). Conclusion: MetAction procedures and treatments were safe. 15% (4/26) of patients with progressing end-stage cancer had the disease course substantially reversed by this biomarker-directed therapy approach. Citation Format: Anne Hansen Ree, Kjersti Flatmark, Vigdis Nygaard, Daniel Heinrich, Kjetil Boye, Svein Dueland, Vegard Nygaard, Eivind Hovig, Klaus Beiske, Marius Lund-Iversen, Vivi A. Flørenes, Christin Johansen, Inger Riise Bergheim, Menaka Sathermugathevan, Sigve Nakken, Gry A. Geitvik, Ole C. Lingjærde, Anne-Lise Børresen-Dale, Hege G. Russnes, Gunhild M. Mælandsmo. The MetAction trial: long-lasting responses to molecularly matched therapy in end-stage cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A101.

Eculizumab as treatment in dense deposit disease in children

Background: Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease that occurs secondary to hyperactivity of the alternative complement pathway. Renal biopsy typically reveals electron-dense deposits in the glomerular basement membrane. However, treatment options are limited. Till date, to the best of our knowledge, no evidence exists for specific treatment influencing the disease course. Eculizumab, a monoclonal antibody, has been reported to prevent membrane attack complex formation by binding to C5 and leads to improvement in clinical findings. However, the number of reported cases in which eculizumab was administered, particularly in children, is limited. Subjects and Methods: In this report, we present our experience with three pediatric cases of DDD receiving eculizumab treatment. All three patients were diagnosed with DDD on kidney biopsy. All patients showed acute kidney injury, high blood pressure, proteinuria >1 g/day, and decreased C3 levels. Immunosuppressive therapy, which included high-dose methylprednisolone, prednisolone, mycophenolate mofetil, or plasma exchange (in the third patient), as well as antihypertensive drugs, was administered to all the patients. Eculizumab treatment was initiated early in two patients but was initiated later in the third patient, who underwent dialysis initially. Results: The two patients with early initiation of eculizumab treatment showed significant improvement of proteinuria and renal function within weeks of treatment. C3 levels were normalized in one patient but remained decreased in the other. The third patient showed no response. She ultimately progressed to end-stage renal disease and eventually needed maintenance dialysis. Conclusions: Early initiation of eculizumab was associated with decreased proteinuria and improved renal function in two patients. These findings were in agreement with previous reports on the beneficial effects of eculizumab in DDD patients.

A Rare Case of Infiltrative Cardiomyopathy Secondary to Scleromyxoedema

A 44-year-old woman with a history of treatment-refractory scleromyxoedema presented with clinical heart failure along with dyspnoea and orthopnoea. Her previous transthoracic echo (TTE) 3 months prior showed normal left ventricular (LV) and right ventricular (RV) function with a stable pleural effusion. She had a raised N-terminal pro-B-type natriuretic peptide and creatinine kinase of 773 pmol/L and 4534 U/L, respectively. Her TTE showed new biventricular dysfunction, with diffuse hypokinesis and a LV ejection fraction (EF) of 20–25%. She underwent a coronary angiogram with right heart studies, which ruled out ischaemic cardiomyopathy or pulmonary hypertension. A cardiac magnetic resonance imaging (cMRI) confirmed biventricular failure (LVEF 37%; RVEF 28%) with the known stable pleural effusion (Figure 1A ). Late gadolinium-enhanced images on cMRI showed diffuse patchy enhancement consistent with infiltrative disease. An endomyocardial biopsy showed myocarditis with interstitial fibrosis. There was polymorphous inflammatory infiltrate with accompanying myocyte damage. Interstitial mucin deposition was later confirmed with a colloidal iron stain, a hallmark of scleromyxedema. A thigh MRI and biopsy showed a necrotising myositis, confirming systemic disease. She responded to high-dose prednisolone, thalidomide, and intravenous immunoglobulin. Her follow up TTE showed stable LV function and improved RV function.

Management of Subacute Thyroiditis with Conventional High-Dose Prednisolone; Shooting a Tree Sparrow with a Cannonball

Background: A well-established medical entity, and typically self-limited disorder, the subacute thyroiditis (SAT), has been conventionally treated with a large dose (40-80 mg) of prednisolone per day for decades: a nonevidence- based and utterly large dose of corticosteroid for a disease with clearly predictable self-limiting course. The current study was designed to evaluate the efficacy of prednisolone 15 mg/day instead of routinely prescribed large dose of 40-80 mg, and to investigate the rate of early relapse with low-dose protocol. Subjects and methods: In a prospective study, forty-five cases of SAT were consecutively included. The diagnosis of SAT was made based on defined criteria of persistent sore throat, rapidly developed painful goiter, suppressed TSH, high ESR, and low RAIU. They were treated with 15 mg of prednisolone per day during the first month, 10 mg per day for the second month, and finally 5 mg daily over the third month. All cases were carefully followed for a minimum of one year to track the clinical and biochemical response to therapy and to find out any evidence of early relapse after discontinuation of medication. Results: Of forty-five patients who completed the oneyear- course of follow-up, 38 were female and 7 were male (male/female ratio 5.4). Mean age of affected subjects was 39 ± 10 years, and mean ESR was 70 ± 23 mm/hr (median 75 mm/hr, range 30-117 mm/hr). Among all subjects with full-blown SAT, only one case (2.2%) remained noticeably symptomatic on 15 mg prednisolone daily after two weeks, requiring 30 mg of medicine per day for symptomatic relief and normalization of ESR. After corticosteroid withdrawal, significant relapse occurred in only two patients (4.4%). Conclusion: Our results, not only endorse the efficacy of low-dose prednisolone in management of subacute thyroiditis, but also demonstrate the remarkably less relapse with low dose corticosteroid.

MPO-ANCA associated vasculitis with mononeuritis multiplex following influenza vaccination

BackgroundAlthough influenza vaccines are generally safe and effective, a variety of autoimmune phenomena have been reported after vaccination over the past years, such as Guillain–Barre syndrome, rheumatoid arthritis, pemphigus vulgaris, psoriasis, giant cell arteritis and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV).Case reportWe describe the case of a 67-year old man who presented with a myeloperoxidase-ANCA associated vasculitis with renal involvement and mononeuritis multiplex after seasonal influenza vaccination. He was initially treated with intravenous cyclophosphamide and high-dose prednisolone followed by maintenance treatment consisting of azathioprine and prednisolone.ConclusionWe hypothesize that seasonal influenza vaccination triggered a systemic immune response in a susceptible patient to develop AAV with renal involvement and vasculitic neuropathy. In general, seasonal influenza vaccinations are considered to be safe, however, clinicians should be aware of this rare phenomenon.

Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis (LoVAS): protocol for a multicentre, open-label, randomised controlled trial

IntroductionAntineutrophil cytoplasm antibody-associated vasculitis (AAV) is a form of systemic vasculitis. The current standard induction therapy with the combination of high-dose glucocorticoids and cyclophosphamide or rituximab has high remission rates...