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.

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.

Mycophenolate Mofetil for a Flare Child Lupus Nephritis: A Case Reports

Renal involvement is the most common complication of systemic lupus erythematosus(SLE) and is also an important predictor of patient mortality. The incidence of flaresis estimated at 65% each year in patients with lupus nephritis. Therapy in lupusnephritis with flare also uses high doses of steroid agents and strongimmunosuppression agent. Mycophenolate mofetil (MMF) as a immunosuppressionagent tends to favor for flare in lupus nephritis. We describe a patient who had flarein lupus nephritis that resolved with high-dose steroid and MMF. The combination ofimmunosuppression agent and high-dose corticosteroid is an effective for control ofactive diseases. Cyclophosphamide as the steroid sparing agent was discontinuedbecause of adverse effect as well as hematuria. Partial remission was later achievedand maintained with MMF and corticosteroid after five month with protocol treatment.Thus, MMF while maintaining the steroid dose may induce remission for this case.

Reversible blindness after erroneous prescription of closantel: A case report

A 20-year-old girl referred with vision loss upon closantel use. Plasma exchange and high-dose corticosteroid pulse therapy were administered. A 2.5-year follow-up showed improved vision and increased layer thickness of the peripheral nerve fiber. Early treatment with plasma exchange and high-dose corticosteroid therapy can be beneficial to reverse closantel toxicity.

The Controversy About the Effects of Different Doses of Corticosteroid Treatment on Clinical Outcomes for Acute Respiratory Distress Syndrome Patients: An Observational Study

Background: Corticosteroid usage in acute respiratory distress syndrome (ARDS) remains controversial. We aim to explore the correlation between the different doses of corticosteroid administration and the prognosis of ARDS.Methods: All patients were diagnosed with ARDS on initial hospital admission and received systemic corticosteroid treatment for ARDS. The main outcomes were the effects of corticosteroid treatment on clinical parameters and the mortality of ARDS patients. Secondary outcomes were factors associated with the mortality of ARDS patients.Results: 105 ARDS patients were included in this study. Corticosteroid treatment markedly decreased serum interleukin-18 (IL-18) level (424.0 ± 32.19 vs. 290.2 ± 17.14; p = 0.0003) and improved arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (174.10 ± 65.28 vs. 255.42 ± 92.49; p &lt; 0.0001). The acute physiology and chronic health evaluation (APACHE II) score (16.15 ± 4.41 vs. 14.88 ± 4.57, p = 0.042) decreased significantly on the seventh day after systemic corticosteroid treatment. Interestingly, the serum IL-18 decreased significantly (304.52 ± 286.00 vs. 85.85 ± 97.22, p &lt; 0.0001), whereas the improvement of PaO2/FiO2 (24.78 ± 35.03 vs. 97.17 ± 44.82, p &lt; 0.001) was inconspicuous after systemic corticosteroid treatment for non-survival patients, compared with survival patients. Furthermore, the receiver operating characteristic (ROC) model revealed, when equivalent methylprednisolone usage was 146.5 mg/d, it had the best sensitivity and specificity to predict the death of ARDS. Survival analysis by Kaplan–Meier curves presented the higher 45-day mortality in high-dose corticosteroid treatment group (logrank test p &lt; 0.0001). Multivariate Cox regression analyses demonstrated that serum IL-18 level, APACHE II score, D-dimer, and high-dose corticosteroid treatment were associated with the death of ARDS.Conclusion: Appropriate dose of corticosteroids may be beneficial for ARDS patients through improving the oxygenation and moderately inhibiting inflammatory response. The benefits and risks should be carefully weighed when using high-dose corticosteroid for ARDS.Trial registration: This work was registered in ClinicalTrials.gov. Name of the registry: Corticosteroid Treatment for Acute Respiratory Distress Syndrome. Trial registration number: NCT02819453. URL of trial registry record: https://register.clinicaltrials.gov.

Outcomes of COVID-19 in a cohort of pediatric patients with rheumatic diseases

Background There are few reports of COVID-19 in pediatric patients with rheumatic diseases. This study describes the clinical presentation and outcomes of COVID-19 in this population. Methods We analyzed a single-center case series of pediatric patients with rheumatic diseases and laboratory-confirmed COVID-19. Demographic, baseline and COVID-19 associated clinical features were compared between ambulatory and hospitalized patients using univariate analysis. Results Fifty-five cases were identified: 45 (81.8%) in the ambulatory group and 10 (18.2%) hospitalized. African American race (OR 7.78; 95% CI [1.46–55.38]; p = 0.006) and cardiovascular disease (OR 19.40; 95% CI 2.45–254.14; p = 0.001) predominated in hospitalized patients. Active rheumatic disease (OR 11.83; 95% CI 1.43–558.37; p = 0.01), medium/high-dose corticosteroid use (OR 14.12; 95% CI [2.31–106.04]; p = 0.001), mycophenolate use (OR 8.84; 95% CI [1.64–63.88]; p = 0.004), rituximab use (OR 19.40; 95% CI [2.45–254.14]; p = 0.001) and severe immunosuppression (OR 34.80; 95% CI [3.94–1704.26]; p = < 0.001) were associated with increased odds of hospitalization. Fever (OR 7.78; 95% CI [1.46–55.38]; p = 0.006), dyspnea (OR 26.28; 95% CI [2.17–1459.25]; p = 0.003), chest pain (OR 13.20; 95% CI [1.53–175.79]; p = 0.007), and rash (OR 26.28; 95% CI [2.17–1459.25]; p = 0.003) were more commonly observed in hospitalized patients. Rheumatic disease flares were almost exclusive to hospitalized patients (OR 55.95; 95% CI [5.16–3023.74]; p < 0.001).. One patient did not survive. Conclusions Medium/high-dose corticosteroid, mycophenolate and rituximab use, and severe immunosuppression were risk factors for hospitalization. Fever, dyspnea, chest pain, and rash were high-risk symptoms for hospitalization. Rheumatic disease activity and flare could contribute to the need for hospitalization.

Risk of asthma in children diagnosed with bronchiolitis during infancy: protocol of a longitudinal cohort study linking emergency department-based clinical data to provincial health administrative databases

IntroductionThe Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) and the Bronchiolitis Severity Cohort (BSC) study enrolled infants with bronchiolitis during the first year of life. The CanBEST trial suggested that treatment of infants with a combined therapy of high-dose corticosteroids and nebulised epinephrine reduced the risk of admission to hospital. Our study aims to—(1) quantify the risk of developing asthma by age 5 and 10 years in children treated with high-dose corticosteroid and epinephrine for bronchiolitis during infancy, (2) identify risk factors associated with development of asthma in children with bronchiolitis during infancy, (3) develop asthma prediction models for children diagnosed with bronchiolitis during infancy.Methods and analysisWe propose a longitudinal cohort study in which we will link data from the CanBEST and BSC study with routinely collected data from provincial health administrative databases. Our outcome is asthma incidence measured using a validated health administrative data algorithm. Primary exposure will be treatment with a combined therapy of high-dose corticosteroids and nebulised epinephrine for bronchiolitis. Covariates will include type of viral pathogen, disease severity, medication use, maternal, prenatal, postnatal and demographic factors and variables related to health service utilisation for acute lower respiratory tract infection. The risk associated with development of asthma in children treated with high-dose corticosteroid and epinephrine for bronchiolitis will be assessed using multivariable Cox proportional hazards regression models. Prediction models will be developed using multivariable logistic regression analysis and internally validated using a bootstrap approach.Ethics and disseminationOur study has been approved by the ethics board of all four participating sites of the CanBEST and BSC study. Finding of the study will be disseminated to the academic community and relevant stakeholders through conferences and peer-reviewed publications.Trial registration numberISRCTN56745572; Post-results.