Early azathioprine in acute Vogt-Koyanagi-Harada disease: a prospective 24-month follow-up study with multimodal imaging and electroretinogram

Background: First-line immunosuppressive therapy (IMT) associated with high-dose corticosteroid (CS) has been proposed for the treatment of acute Vogt-Koyanagi-Harada disease (VKHD) to prevent chronicity and to prevent long-term CS side effects. However, there are very few studies that systematically evaluated visual and inflammatory outcomes in acute VKHD with early IMT. This study aimed to evaluate the outcome of high-dose corticosteroids with early addition of azathioprine (AZA) in patients with acute Vogt-Koyanagi-Harada disease (VKHD) followed for 24-month with systematic multimodal and electroretinogram exams.Methods: Prospective interventional study. Fifteen consecutive patients (30 eyes) with acute VKHD at a tertiary uveitis referral centre were followed for 24 months with systematic multimodal and full-field electroretinogram (ffERG) exams. Patients were treated with intravenous methylprednisolone followed by oral prednisone 1mg/kg/daily (CS) with slow taper and AZA introduction within 4 months. Anterior uveitis relapse, subclinical inflammation, best-corrected visual acuity (BCVA) and ffERG parameters were analyzed.Results: Fifteen patients (14 female) with a median age of 32 years were included. In the first month, 27 eyes (90%) had BCVA ≥20/40; at M24, all eyes (100%) had BCVA ≥20/25. Uveitis resolved in 28 eyes (93.3%) and became chronic recurrent in 2 eyes (6.7%); subclinical inflammation was still present in all eyes during the 24-month follow-up. ffERG parameters initially improved in all eyes; at M24, 23 eyes (76.7%) had subnormal results and 20 eyes (66.7%) had stable parameters. Eyes with very early treatment (n=12) had lower indocyanine green angiography score than eyes with early treatment (n=18) at M1 (p=0.012), but they had similar rates of recurrence, complications and ffERG parameters. Conclusion: Early AZA associated with high-dose corticosteroid was effective in improving BCVA and in controlling clinical inflammation. Isolate subclinical inflammation persisted in all eyes with no impact on ffERG in, at least, two thirds of these eyes, indicating that isolate subclinical inflammation may not be enough to indicate treatment increment.

Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial

Background Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. Method/design This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 μg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. Discussion This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. Trial registration ClinicalTrials.gov, NCT03773822. Registered on 12 December 2018

Date of Admission during COVID-19 Pandemic Impacted Patient Outcomes in Addition to the Higher Efficacy of Tocilizumab Plus High-Dose Corticosteroid Therapy Compared to Tocilizumab Alone

Background: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. Methods: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400–600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. Results: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. Conclusions: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.

Concurrent Paraneoplastic Dermatomyositis and Acquired C1 Esterase Inhibitor Deficiency in Primary Laryngeal Small Cell Carcinoma

Small cell carcinoma is associated with a number of paraneoplastic syndromes. We report a case of a 42-year-old female who presented with primary laryngeal small cell carcinoma associated with concurrent paraneoplastic dermatomyositis and paraneoplastic angioedema secondary to acquired C1 esterase inhibitor deficiency. The patient required extensive treatment for her dermatomyositis including high-dose corticosteroid therapy and intravenous immunoglobulin followed by steroid-sparing disease-modifying immunosuppression. Her angioedema also required multiple lines of therapy including bradykinin inhibitors and human recombinant C1 esterase. We believe this is the first reported case of either of these paraneoplastic syndromes arising from an extrapulmonary small cell carcinoma and highlights the difficulty of its initial diagnosis as well as concurrent management.

Prednisone combined with antiviral agents for the treatment of early idiopathic brachial plexus neuritis: report of five cases

<p><strong>Background and Objective: </strong>The aim of this study was to report the short-term outcomes of early idiopathic brachial plexus neuritis after low-dose corticosteroid combined with antiviral agent.</p> <p><strong>Methods:</strong> Five patients with early brachial plexus neuritis presenting from April to June 2019 were included in this study. According to individual patient conditions, electromyography (EMG), nerve B-ultrasound and/or brachial plexus magnetic resonance imaging (MRI) were performed. After the diagnosis was confirmed, modified conservative treatments were initiated, including low-dose corticosteroid therapy and antiviral therapy for 2 weeks each while neurotrophic therapy for 4 weeks.</p> <p><strong>Results: </strong>Of the five patients, only two patients had symptoms of pain at onset, and three patients had sensory disturbances. Two patients reported a common cold before onset. The lesion involved the upper trunk of the brachial plexus in two patients. MRI showed slightly intense signals, of which one patient also had supraclavicular lymph node augmentation. The other three patients suffered ipsilateral radial nerve (RN) palsy. At 1 month of modified treatment, four patients recovered well with almost complete shoulder and hand movements; however, their muscle strength was still weaker comparing with the contralateral side. One patient restored full range of motion after surgery in 2 months.</p> <p><strong>Conclusion:</strong> Early treatment is the key to good prognosis in patients with brachial plexus neuritis. Antiviral therapy combined with lowdose corticosteroid therapy may be superior to traditional treatment alone. In terms of early diagnosis, the clinical value of imaging examinations such as ultrasound and MRI is more specific as compared to that of EMG.</p>

Clinical efficacy and safety of full-dose versus half-dose corticosteroids plus leflunomide for IgA nephropathy

Background The results of leflunomide (LEF) in patients with IgA nephropathy (IgAN) were inconsistent. Methods A total of 149 kidney biopsy-confirmed IgAN patients with an estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 and protein excretion levels ≥0.75 g/d were enrolled, with 65 subjects receiving half-dose CS plus LEF (LEF group), and the 84 counterpart patients accepting full-dose corticosteroid (Full CS group). The primary outcomes included the complete remission (CR) rates and incidence of adverse events (AEs). The secondary outcomes were the overall remission (OR) rates and a combined event (eGFR reduced ≥30%, end-stage renal disease [ESRD], hemodialysis, peritoneal dialysis or kidney transplantation). Results During the 18 months of follow-up, the CR rates were 72 and 64% in the LEF and Full CS groups (P = 0.299), respectively. The proportion of patients with OR rates in the LEF group and Full CS group was 89% versus 75%, respectively (P = 0.027). Serious AEs were observed only in the Full CS group (P = 0.017). The incidences of total AEs (P = 0.036) and infections (P = 0.024) were lower in the LEF group than in the Full CS group. Conclusions LEF combined with half-dose CS is superior to full-dose CS in the treatment of IgAN.

Low disease activity state in juvenile-onset systemic lupus erythematosus

Objectives To determine the rate of achieving The Lupus Low Disease Activity State (LLDAS) in children with systemic lupus erythematosus (SLE) for tracing pertinent treatment modalities. Methods A total of 122 juvenile-onset SLE (jSLE) patients from six pediatric rheumatology centers in Turkey were enrolled in the study. LLDAS-50 was defined as encountering LLDAS for at least 50% of the observation time. According to the achievement of LLDAS-50, clinical features, immunological profiles, and treatments of patients with jSLE have been revealed. Results LLDAS of any duration was achieved by 82% of the cohort. Although only 10.8% of the patients achieved remission, 68.9% reached LLDAS-50. A significant difference was found between patients who reached LLDAS-50 and those who did not, in terms of the time to reach low-dose corticosteroid treatment ( p = 0.002), the presence of subacute cutaneous findings ( p = 0.007), and the presence of proteinuria ( p = 0.002). Both of the groups were under similar treatment approaches. However, the number of patients being treated with corticosteroids at the last visit was found to be significantly higher in patients who achieved LLDAS-50 ( p<0.001). Conclusion Targeting LLDAS in jSLE, even with long-term, low-dose corticosteroid use, seems to be an achievable goal in clinical practice.

Paediatric anti-GABAB receptor encephalitis associated with SARS-CoV-2 (COVID-19) infection

Though we are approaching the end of second wave of COVID pandemic, we are still unrevealing the various presentation this viral infection can result in. There are few cases reported to have anti NMDA autoimmune encephalitis associated with COVID-19 infection or MIS-C. Here we are reporting one of its variants that was anti-GABAB receptor encephalitis associated with COVID-19 infection. We are reporting a 9 years old female child who was a known case of seizure disorder and on regular medications presented on 4th day of RT-PCR positive status for COVID-19 with complains of convulsions which was managed with antiepileptics. On day 6 of hospitalization she had autonomic instability in the form of tachyarrhythmia, repitation of speech, sudden outburst of laughter and on day 7 child landed in status epilepticus. Autoimmune encephalitis suspected secondary to COVID-19 infection and the child was started on IVIG but not much of improvement seen with this. CSF analysis showed weakly positive anti GABAB antibodies and child had persistently elevated inflammatory markers hence started on high dose corticosteroid. MIS-C ruled out. Child showed drastic improvement both clinical and biochemical after high dose corticosteroids. Prompt treatment with IVIG/corticosteroids have shown a drastic improvement in our child just like in any other autoimmune encephalitis. Though further detailed study is required to prove its exact mechanism in COVID-19 infection, it should be thought of when appropriate and prompt early initiation of therapy will help us reduce morbidity and mortality associated with it.