Early High-dose Corticosteroids Research Articles

The Acute Optic Neuritis Network (ACON): Study protocol of a non-interventional prospective multicenter study on diagnosis and treatment of acute optic neuritis.

ClinicalTrials.gov, identifier: NCT05605951.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BackgroundCoronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.MethodsThis multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.ResultsAmong 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089).ConclusionOur study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.

Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.

Early high-dose intravenous corticosteroids rapidly arrest Stevens Johnson syndrome and drug reaction with eosinophilia and systemic symptoms recurrence on drug re-exposure

Early high-dose intravenous corticosteroids rapidly arrest Stevens Johnson syndrome and drug reaction with eosinophilia and systemic symptoms recurrence on drug re-exposure

Myelopathy associated with mixed connective tissue disease: clinical manifestation, diagnosis, treatment, and prognosis.

Mixed connective tissue disease (MCTD) is a chronic autoimmune disease, which has a broad range of clinical manifestations shared by systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis. MCTD is featured with high serum titers of anti-ribonucleoprotein antibodies and multiple system involvement. Its spinal cord involvement mainly manifests as transverse myelopathy (TM) and longitudinal extensive transverse myelopathy (LETM). Myelopathy in MCTD is extremely rare, and is usually characterized by serious neurological complications, such as paralysis or muscular paresis, sensory impairment, and smooth muscle dysfunction. Progressive clinical manifestations combined with laboratory examinations and magnetic resonance imaging examinations play important roles in the diagnosis of this disease. In order to prevent permanent neurological damage to the spinal cord, plasmapheresis and intravenous immunoglobulin can be performed in patients at the early disease stage. Early high-dose corticosteroids combined with cyclophosphamide, followed by low doses of immunosuppressors, can improve the long-term prognosis of patients. There are only nine global cases reported on MCTD associated with myelopathy at present. The death rate and disability rate of myelopathy in MCTD are extremely high. In this review, the pathomechanisms, clinical manifestations, auxiliary examination, diagnosis, differential diagnosis, treatment, and prognosis of myelopathy in MCTD were systematically elucidated.

THE ROLE OF TREATMENT WITH HIGH-DOSE CORTICOSTEROIDS IN SEVERE LEPTOSPIROSIS WITH PULMONARY COMPLICATIONS

Objective: To investigate the effectiveness of high-dose corticosteroids in patients with severe leptospirosis, especially in reducing morbidity and mortality rates.
 Methods: Literature searches were conducted using PubMed® and SCOPUS®. One systematic review and one systematic review with meta-analysis were selected from three chosen studies.
 Results: The systematic review from Rodrigo et al. only included qualitative synthesis from four interventional studies. Early administration of methylprednisolone can be beneficial; however, low number and poor methodological quality of the studies question the validity of this review. Duggal et al. stated that there was no significant difference in the therapeutic effects of early high-dose corticosteroids (P ³ 0.05; 95% CI: 0.81–1.37), early low-dose corticosteroids (P ³ 0.05; 95% CI: 0.3–1.03), and late low-dose corticosteroids (P ³ 0.05; 95% CI: 0.11–2.52). Limited number of studies and high statistical heterogeneity, however, are major drawbacks for this review.
 Conclusion: Evidence about the role of high-dose corticosteroids in severe leptospirosis patients with pulmonary complications, especially their benefits, is still limited. Additional randomized, controlled trials with adequate statistical power still need to be conducted.

Full-thickness macular hole: a rare complication of Borrelia burgdorferi neuroretinitis

Borrelia burgdorferi is a known infective cause of neuroretinitis. We present a case of B burgdorferi neuroretinitis complicated by macular hole in a 22-year-old man. The neuroretinitis was managed with...

High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids.

To analyse the rate of clinical recurrences in Brazilian patients with Vogt-Koyanagi-Harada (VKH) disease after early high-dose corticosteroid treatment. Retrospective study including patients treated with early high-dose corticosteroids (prednisone, 1-1.5 mg/kg/day, or 3-day 1 g methylprednisolone pulsetherapy) within 1 month from disease onset followed by slow taper (at least 6 months). Patients with a minimum 12-month follow-up were subdivided based on the presence of disease recurrence or persistence after 6 months from initial presentation into: acute-resolved (AR, no recurrences), chronic-recurrent (CR), and chronic-recurrent with subretinal fibrosis (SRF). Recurrences were defined as the presence of clinical and/or fluorescein angiography findings. Twenty-nine patients (58 eyes) with a median follow-up of 65 months were included. Six (21 %), 11 (38 %) and 12 (41 %) patients were allocated to AR, CR, and SRF groups respectively. Though having received treatment within 1 month of onset, median time to initial treatment differed among groups (11, 15, and 25 days, in AR, CR, and SRF groups respectively). Intensity of immunosuppression, cataract development, and longer time to achieve logMAR visual acuity ≤0.8 differed significantly among the groups, being more severe in SRF group. HLA-DRB1*0405 allele followed the same trend, though not reaching significance (0.5 in AR group, 0.6 in CR, and 0.8 in SRF). VKH disease in Brazilian patients evolved to chronic-recurrent disease in 79 % of cases; 38 % developed subretinal fibrosis, in spite of similar initial treatment regimens. Time to initiate treatment influenced outcomes.

Immunoglobulin G4–related multiple systemic aneurysms and splenic aneurysm rupture during steroid therapy

Immunoglobulin G4 (IgG4)-related disorders in various organs have recently been described, but multiple systemic aneurysms have not yet been reported. Here, we present a 68-year-old Japanese man with multiple systemic aneurysms and tumor-forming pericoronary arteritis who was undergoing low-dose corticosteroid therapy. Elevated serum IgG4 (2390 mg/dL) and IgG4-positive plasmacyte infiltration in the salivary glands led to a diagnosis of IgG4-related disease. High-dose corticosteroid therapy was initiated, whereupon the inflammatory lesions shrank. However, the large, well-developed common hepatic aneurysm and splenic aneurysm did not change. Our patient died of splenic aneurysm rupture in the sixth month of treatment. The autopsy revealed IgG4-positive plasmacyte infiltration in the coronary wall and a thinned splenic aneurysm wall. This case suggests that early high-dose corticosteroid therapy may be necessary for the treatment of IgG4-related cardiovascular disorders. A minor salivary gland biopsy might facilitate the early diagnosis of IgG4-related disease even if (18)F-fluorodeoxyglucose positron emission tomography provides no inflammatory findings.

Eosinophilic Fasciitis in a Pediatric Patient

We report the case of a pediatric patient with eosinophilic fasciitis, who was successfully treated with early high dose corticosteroids and subsequent use of mycophenolate mofetil. We believe that the early institution of corticosteroids helped to suppress the early inflammatory part of the disease and the subsequent use of mycophenolate mofetil maintained this and may have also helped prevent fibrotic skin changes.

Influence of early cerebrospinal fluid-guided diagnosis and early high-dose corticosteroid therapy on ocular outcomes of Vogt–Koyanagi–Harada disease

To evaluate the importance of early cerebrospinal fluid (CSF)-guided diagnosis and early high-dose corticosteroid therapy on the complications and visual prognosis of Vogt-Koyanagi-Harada (VKH) disease. Charts from patients with VKH disease who had been seen at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital between 1994 and 2002 were retrospectively reviewed. The patients were classified into two groups. The first group (group A) consisted of patients who had received a full work-up including CSF examination and corticosteroid pulse therapy at the acute ophthalmic stage of disease. The second group (group B) consisted of patients who were referred to us by local ophthalmologists long after the disease onset, had not had a CSF examination and had been treated with low-dose systemic corticosteroids or topical corticosteroid therapy. The ocular complications, systemic complications and visual prognosis were compared between the two groups. Twenty-two patients were included in group A and ten patients in group B. The initial diagnosis at the acute ophthalmic stage had been VKH disease in all patients of group A, while, in group B, the diagnosis was idiopathic uveitis in six patients (60%) initially. Frequency of recurrent uveitis and integumentary symptoms were significantly lower in group A. Intensity of sunset glow fundus was significantly more severe in group B. All eyes in group A obtained a final visual acuity of 0.8 or better, whereas 11 eyes (55%) in group B were below this level. The results indicate that early diagnosis, helped by CSF examination and early high-dose corticosteroid therapy, decreased the complication rate and improved the visual prognosis.

Early recognition, evaluation and treatment may prevent blindness in giant cell arteritis

Giant cell arteritis (GCA) is a systemic vasculitis that can cause blindness in the elderly. GCA is a medical emergency since it frequently causes blindness if left untreated. Blindness can even occur in a small percentage of patients who undergo treatment. The etiology remains unknown. Presenting symptoms of GCA vary widely and visual manifestations are an extremely common mode of presentation. All physicians must have a high level of suspicion to diagnose and initiate early and aggressive treatment, which in most patients can arrest but rarely reverses the disease. Early and prolonged high-dose corticosteroids remain the cornerstone of GCA treatment. In symptomatic patients, the combination of abnormal levels of C-reactive protein in addition to Westergren erythrocyte sedimentation rate has 97% specificity in the laboratory diagnosis of GCA. The gold standard for diagnosis is the temporal artery biopsy, but biopsy-negative GCA cases have been reported.

Acute disseminated encephalomyelitis

The authors report 6 children with the diagnosis of acute disseminated encephalomyelitis. Diagnosis was based on clinical and radiological findings. The most common presenting symptoms were fever and disturbed consciousness, followed by cranial nerve abnormalities and pyramidal signs. Brain MRI showed hyperintense signals on T2-weighted images, most commonly in the subcortical and periventricular white matter, brainstem, basal ganglia and thalamus. The lesions were bilateral, asymmetrical and highly variable in size and number. A preceding infection was present in 3 of 6 children. Early high-dose corticosteroids were given to all the patients. All patients recovered clinically. Follow-up ranged from 10 months to 2 years. No relapses were observed during this period. Early high-dose steroid therapy seems to be an effective treatment in acute disseminated encephalomyelitis.

Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome

Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS. We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies. Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS. Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required. Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes. Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention.

Low-dose dexamethasone ameliorates circulatory failure and renal dysfunction in conscious rats with endotoxemia.

Corticosteroids have long been proposed as a therapeutic adjuvant in septic renal dysfunction because of their anti-inflammatory properties and favorable results from animal experiments. However, some reports suggested the potential for harm associated with the administration of early high-dose corticosteroids in patients with severe sepsis and septic shock. Thus, we examined the effects of low-dose dexamethasone (0.01 and 0.1 mg/kg) on hemodynamics and renal function in conscious rats with endotoxemia. Intravenous injection of rats with endotoxin (E. coli lipopolysaccharide, LPS, 1 mg/kg) caused hypotension, vascular hyporeactivity, and tachycardia as well as renal dysfunction. Circulatory failure and renal dysfunction caused by LPS were significantly attenuated in the dexamethasone 0.1 mg/kg-treated group. The nitric oxide (NO) production in plasma and renal tissue and the iNOS protein expression in the kidney were suppressed by cotreatment of LPS rats with dexamethasone, 0.1 mg/kg. Light microscopy showed that 0.1 mg/kg dexamethasone reduced marked infiltration of neutrophils in renal tissues from LPS rats. Moreover, the survival rate at 18 h was significantly increased in the dexamethasone 0.1 mg/kg-treated group when compared with the LPS group. These results suggest that the beneficial effects of low-dose dexamethasone (0.1 mg/kg) in conscious rats with endotoxic shock are associated with amelioration of circulatory failure and renal dysfunction, and this is attributed to inhibition of NO production.

Pharmacologic Treatments for Acute Respiratory Distress Syndrome and Acute Lung Injury

Multiple pharmacologic treatments have been studied for patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Our objective was to systematically evaluate this literature to determine the effects of these interventions on important clinical outcomes. We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966-week 2, January 2004), EMBASE (1980-week 4, 2004), CINAHL (1982-week 2, January 2004), and HEALTHSTAR (1995-December 2003); proceedings from four conferences (1994-2003); and bibliographies of review articles and included studies. We included randomized controlled trials (RCTs) of pharmacologic treatments compared with no therapy or placebo for established ARDS and ALI in adults admitted to an intensive care unit, with measurement of early mortality, late mortality, duration of ventilation, ventilator-free days, non-pulmonary organ dysfunction, or adverse events. We excluded trials in other populations incorporating subgroup analyses of patients with ARDS and ALI and studies of nitric oxide, partial liquid ventilation, and fluid and nutritional interventions. Two reviewers independently screened studies and abstracted data from studies included in the analysis. Data were pooled using random effects models where appropriate. We retrieved 75 potentially relevant articles and abstracts, of which 33 trials randomizing 3272 patients met our selection criteria. Meta-analysis showed no effect on early mortality for alprostadil ([prostaglandin E(1)] seven studies; 693 patients; relative risk [RR] 0.95; 95% confidence interval [CI], 0.77, 1.17), acetylcysteine (five studies; 235 patients; RR 0.89; 95% CI, 0.65, 1.21), early high-dose corticosteroids (two studies; 180 patients; RR 1.12; 95% CI, 0.72, 1.74), or surfactant therapy (nine studies; 1418 patients; RR 0.93; 95% CI, 0.77, 1.12). Most trials of alprostadil, early high-dose corticosteroids, and surfactant therapy showed more adverse events in the active therapy arm. Single small RCTs demonstrated lower hospital mortality (24 patients, RR 0.20; 95% CI, 0.05, 0.81) with corticosteroids for late phase ARDS and lower 1-month mortality (30 patients, RR 0.67; 95% CI, 0.47, 0.95) with pentoxifylline for patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show beneficial effects on prespecified outcomes. Effective pharmacotherapy for ARDS is extremely limited. Corticosteroids for late phase ARDS and pentoxifylline for patients with metastatic cancer and ARDS reduced mortality in single small studies. However, further research is required to investigate their potential benefit in the treatment of ALI/ARDS.

Steroids for Septic Shock : Back From the Dead? (Pro)

The use of corticosteroids as adjunctive therapy for severe sepsis and septic shock has been a source of controversy for the past 35 years. Despite a wealth of preclinical data supporting both survival and physiologic benefit for early steroid use, the data in human sepsis have been much less convincing. There have even been reports suggesting the potential for harm associated with the administration of early high-dose corticosteroids in patients with severe sepsis and septic shock. Recent trials have reported hemodynamic and survival benefits associated with the use of more physiologic steroid replacement therapy in patients with vasopressor-dependent septic shock. These results coupled with the observation of "relative adrenal insufficiency" in some patients with severe sepsis and septic shock may once again establish a defined role for corticosteroid therapy in the management of severe sepsis and septic shock.