Biphasic, Refractory, and Persistent Anaphylaxis in Children

Raising the Bar for Asthma Care in the Emergency Department

Antibiotic Use in Acute Exacerbations of Chronic Bronchitis

Objective: Systemic corticosteroid (SCS) usage in specialty care for severe asthma is well documented and on the decline since the introduction of biologics. However, nearly 60% of asthma patients are seen in family medicine. We evaluated SCS usage by family medicine providers in the US for asthma management compared with internal medicine specialists (including allergists and pulmonologists) and its burden of associated comorbidities. Methods: A descriptive, retrospective, real-world database analysis was conducted using a proprietary platform, ImmunoLab, that utilizes Optum's© de-identified Electronic Health Record data set (Optum© EHR) and Optum's de-identified Integrated claims clinical data set (Q4 2019-Q1 2023). “High SCS use” (defined as having ≥6 SCS prescriptions in the last 12 months) in patients with asthma aged 0-65+ were identified and compared to the overall population with asthma. Comparisons were made using demographic data, comorbidities, ethnicity data, laboratory parameters, and medications prescribed by healthcare specialties. Results: In the US, 6.7 million people aged 0-65+ had asthma with 139,500 of them having high SCS use. Asthma prevalence was highest in the 18-39yo group (32.5%). However, the highest percentage of SCS use was noted in the 40-64 group (46.2%). Family medicine providers had higher prescription rates of commonly prescribed corticosteroids compared to internal medicine specialists: oral prednisone 30.2% vs 21.2%, oral methylprednisolone “Medrol Dosepak” 13.9% vs 8.9%, and injectable betamethasone 26.7% vs 8.8% respectively. Macrolide and fluoroquinolone antibiotic use was noted to be higher in the primary care treated patients vs those treated by specialty care, 23.9% vs 14.6% and 21.3% vs 14.3%, respectively. High SCS patients had higher BMI & reported pain episodes. Higher prevalence of elevated HbA1C levels (22.2% vs 18.4%), BUN (11.8% vs 7.5%) and creatinine (16.6% vs 10.7%) levels were noted in the high SCS group compared to the overall asthma population. Patients in the high SCS cohorts also displayed higher rates of smoking and alcohol consumption (3.8% vs 2.6% for 1-10 pack/yr; 14.7% vs 11.8%). Conclusions: Disproportionately higher rates of SCS usage in family medicine when compared to internal medicine specialty care was observed. Patients with higher use of SCS in asthma also had higher antibiotic use, obesity, pain, diabetes, poorer renal function markers, and poor lifestyle choices. Education about the risks of steroid use, improved guidance on step up therapy, need for specialist referral, and increased emphasis on lifestyle changes in the family medicine space may be necessary to address high SCS use.

The corticosteroid-sparing effects of ileocaecal resection have not been thoroughly investigated in a population-based cohort. To investigate systemic corticosteroid use before and after primary ileocaecal resection in patients with Crohn's disease. Through nationwide registries, we identified 1565 patients with Crohn's disease undergoing primary ileocaecal resection in Sweden 2006-2019. We stratified patients according to mean annual systemic corticosteroid (prednisolone equivalents) use in the last 5 years before surgery and compared Crohn's disease treatment after surgery. Some 19% (290/1565) of the patients had a mean annual corticosteroid use of ≥ 1000 mg up to 5 years pre-operatively, of whom 33% (97/290) had ≥ 2000 mg. Mean annual pre-operative CS use did not decrease during the study period (p = 0.35). Compared with patients with < 1000 mg/year pre-operative steroid use, patients with ≥ 1000 mg/year had more frequent previous bowel surgery (10% vs. 16%), exposure to biologics (29% vs. 38%), and immunomodulators (56% vs. 83%). Patients with a pre-operative mean annual corticosteroid use of ≥ 1000 mg had a mean annual reduction in corticosteroid use of 1354 mg after ileocaecal resection (1847 mg pre-operative versus 493 mg post-operative). During follow-up (median 6.8 years), exposure to biologics was similar among patients with different levels of pre-operative corticosteroid use. Our results suggest a significant corticosteroid-sparing effect of ileocaecal resection in Crohn's disease patients with high pre-operative use, indicating a beneficial outcomeof earlier surgical intervention. Despite increasing use of biologics, pre-operative corticosteroid use was consistent over the study period.

ObjectiveTo investigate the impact of baseline and time‐varying factors on the risk of serious adverse events (SAEs) in patients during long‐term certolizumab pegol (CZP) treatment.MethodsSafety data were pooled across 34 CZP clinical trials in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PSO). Cox proportional hazards modeling was used to investigate the association of baseline patient characteristics with risk of serious infectious events (SIEs), malignancies, and major adverse cardiac events (MACEs). Cox modeling for recurrent events assessed the impact of time‐varying body mass index (BMI), systemic corticosteroid (CS) use, and disease activity on SIE risk in RA and SAE risk in PSO.ResultsData were pooled from 8747 CZP‐treated patients across indications. Cox models reported a 44% increase in SIE risk associated with a baseline BMI of 35 kg/m2 or more versus a baseline BMI of 18.5 kg/m2 to less than 25 kg/m2. Baseline systemic CS use, age of 65 years or more, and disease duration of 10 years or longer also increased SIE risk. Older age was the only identified risk factor for malignancies. The risk of MACEs increased 107% for BMI of 35 kg/m2 or more versus BMI of 18.5 kg/m2 to less than 25 kg/m2 and increased 51% for men versus women. Higher disease activity, older age, systemic CS use, BMI of 35 kg/m2 or more, and baseline comorbidities were SIE risk factors in RA. Age and systemic CS use were risk factors for SAEs in PSO.ConclusionAge, BMI, systemic CS use, and disease activity were identified as SIE risk factors in CZP‐treated patients. Risk of malignancies was greater in older patients, whereas obesity and male sex were MACE risk factors.

AB0764 SAFETY OF SYSTEMIC CORTICOSTEROIDS IN A SHORT REGIMEN IN PATIENTS WITH PSORIATIC ARTHRITIS. RETROSPECTIVE ANALYSIS OF A LARGE OBSERVATIONAL COHORT.

Some patients with severe community-acquired pneumonia develop fatal complications in the form of acute respiratory distress syndrome and/or septic shock despite the timely adequate antibacterial therapy and presumably due to an excessive uncontrolled systemic inflammatory response and inadequate adrenal response to infection due to the critical illness-related corticosteroid insufficiency (CRICI). Therefore, the additional use of systemic corticosteroids can significantly improve the survival of patients with severe community-acquired pneumonia.Aim. To present the most current preclinical and clinical studies and meta-analyses assessing the effectiveness and safety of the use of systemic corticosteroids for communityacquired pneumonia.The results of these studies demonstrate that the most optimal regimen for the use of systemic corticosteroids in terms of risk and benefit is early (the first 3 days), low-dose (the dose equivalent of 6 mg/day dexamethasone) short-course (5 – 7 days) therapy with immediate withdrawal of the drugs. This regimen produces the best effect in patients with severe community-acquired pneumonia who require ventilation (invasive or non-invasive) with PEEP ≥ 5 cm H2O or high-flow oxygen therapy with FiO2 ≥ 50% and a PaO2/FiO2 ratio less than 300 and/or vasopressor support.Conclusion. Currently, the federal clinical guidelines do not recommend the routine use of corticosteroids in adult patients with community-acquired pneumonia, with the exception of patients with refractory septic shock. However, this narrative review presents evidence supporting the use of adjunctive corticosteroid therapy in adult patients with severe community-acquired pneumonia, particularly when complicated by septic shock, acute respiratory distress syndrome, comorbid asthma and/or chronic obstructive pulmonary disease, provided there is no pulmonary suppuration, severe influenza or mycotic infection. Undoubtedly, this is a compelling argument in favor of revising existing domestic clinical guidelines regarding the use of systemic corticosteroids. Thus, further research is needed to identify subgroups of patients who may benefit from or potentially be harmed by corticosteroids. In addition, it is necessary to determine the optimal regimen for the use of corticosteroids in terms of specific drugs, their dose, routes of administration, frequency and duration of therapy, as well as the withdrawal.

Translated article] Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients With Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City

Update on immunogenicity in severe asthma: Experience with mepolizumab

Anaphylaxis after COVID-19 vaccination: A registry-based study

Are corticosteroids safe in adolescent and adult patients with infectious mononucleosis? A retrospective cohort study

Short courses of systemic corticosteroids are used in the management of a number of acute clinical conditions, including Bell palsy, croup, and pneumonia, but research on associations of corticosteroid use with adverse events (AEs) in children is limited. To document AEs associated with short-term (≤14 days) use of systemic corticosteroids in children and adolescents (1 to younger than 18 years) across different clinical conditions. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to February 2025. Reference lists of eligible articles and related systematic reviews were also searched. Randomized clinical trials evaluating AEs (any unfavorable and unintended signs, symptoms, or syndromes that occurred during the period of using an investigational product) after use of short-course systemic corticosteroids in children and adolescents were included. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline, pairs of reviewers independently reviewed abstracts, extracted data, and assessed risk of bias of eligible trials. Pairwise, fixed-effects meta-analyses were performed using Mantel-Haenszel methods with risk difference (RD). The primary outcomes were serious AEs (events resulting in death, life-threatening conditions, hospitalization, or substantial disability), AEs leading to discontinuation, hyperglycemia, sleep disturbances, change in behavior, and gastrointestinal bleeding. RDs were reported as AEs per 1000 patients with 95% CIs. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence (high, moderate, low, or very low certainty). A total of 45 eligible trials that included 6470 children (mean [SD] age, 5.57 [3.62] years; 3753 male [58%]) were identified. In pooled analysis, there was moderate certainty evidence that compared with usual care, corticosteroids were not associated with serious AEs (RD, 1 fewer AE per 1000 patients [95% CI], 9 fewer to 7 more AEs per 1000 patients]), AEs leading to discontinuation (RD, 4 more AEs per 1000 patients [95% CI, 3 fewer to 11 more AEs per 1000 patients]), or change in behavior (RD, 8 more AEs per 1000 patients [95% CI, 5 fewer to 21 more AEs per 1000 patients]). With moderate certainty evidence, corticosteroids were associated with an increased risk of hyperglycemia (RD, 38 more AEs per 1000 patients [95% CI, 11 to 64 more AEs per 1000 patients]) and sleep problems (RD, 15 more AEs per 1000 patients [95% CI, 1 to 28 more AEs per 1000 patients]). Corticosteroid use was also associated with an increased risk of gastrointestinal bleeding (RD, 13 more per AEs per 1000 patients [95% CI, 3 to 23 more AEs per 1000 patients]), but the certainty of evidence was low. In this systematic review and meta-analysis of randomized trials, there was moderate certainty evidence that corticosteroids were associated with an increased risk of hyperglycemia and sleep problems and low certainty evidence that corticosteroids were associated with increased risk of gastrointestinal bleeding, but these AEs were very seldom serious. These findings suggest that an individualized approach to short-term corticosteroid use may be warranted and that further research is needed to obtain better quality of evidence.

Chimeric antigen receptor T-cell toxicities - using steroids to spare steroids?

Background/Objectives: This study aimed to evaluate the clinical outcomes of biologic switching in patients with severe asthma in real-world settings. Methods: In this retrospective study, asthma exacerbations, systemic corticosteroid use, asthma control, and spirometric parameters were compared before and one year after biologic switching in adults with severe asthma. All patients were analyzed as a single cohort, with additional subgroup analyses performed according to the type of biologic switch (omalizumab to mepolizumab, mepolizumab to benralizumab, and omalizumab to benralizumab). Results: Among 29 patients who underwent biologic switching, the median annual exacerbation rate decreased from 2.0 (IQR, 1.5–2.5) to 0 (IQR, 0–1) at one year (p < 0.001), while systemic corticosteroid use declined from 69.0% (n = 20) to 34.5% (n = 10) (p = 0.002). A total of 38.0% of patients (n = 11) were switched from mepolizumab to benralizumab, 58.6% (n = 17) from omalizumab to mepolizumab, and 3.4% (n = 1) from omalizumab to benralizumab. In patients switched from omalizumab to mepolizumab, significant reductions were observed in annual exacerbations and in both the rate and dose of systemic corticosteroid use, along with improved asthma control (p = 0.002, p = 0.008, p = 0.002, and p = 0.001, respectively). In contrast, among patients switched from mepolizumab to benralizumab, exacerbation rates decreased significantly (p = 0.019), with no significant changes in systemic corticosteroid use (p = 1.000) or dose (p = 0.102). Only one patient was switched from omalizumab to benralizumab and showed improvements in exacerbation frequency, asthma control, systemic corticosteroid use, and spirometric parameters. The mean age of the patients was 53.24 ± 10.74 years (range, 33–73), with 51.7% being female (n = 15). Conclusions: Biologic switching was associated with favorable clinical outcomes, including fewer exacerbations and improved asthma control, in selected patients with severe asthma who showed an inadequate response to their current biologic therapy.

BackgroundSystemic corticosteroid use in type 2 inflammation-associated diseases including asthma, atopic dermatitis, allergic rhinitis, and chronic rhinosinusitis has been associated with adverse outcomes, and corticosteroid-sparing treatments are available.ObjectiveAssess temporal changes in systemic corticosteroid use and the impact of type 2 inflammation multimorbidity (eg multiple concurrent type 2 inflammation-associated diseases) and specialist assessment on systemic corticosteroid exposure.MethodsUsing nationwide databases, all Danish adults with asthma, atopic dermatitis, allergic rhinitis, or chronic rhinosinusitis, based on hospital diagnoses or redeemed prescriptions between 1997 and 2021 were included in an open, serial cross-sectional cohort.ResultsOver 25 years, a total of 2,151,209 Danish adults were included. Of those with a single diagnosis (type 2 inflammation monomorbidity),13.9% had asthma, 19.2% allergic rhinitis, 52.9% atopic dermatitis, and 14.0% chronic rhinosinusitis. In terms of type 2 inflammation multimorbidity, 75.1% of included individuals had one, 21.3% two and 3.5% three diagnoses, respectively. Overall, 9.6% of type 2 monomorbid individuals redeemed systemic corticosteroids, with asthma (16.5%) and atopic dermatitis (6.0%) having the highest and lowest prevalence of use. Systemic corticosteroid use peaked in 2006 (10.6%) and was lowest in 2020 (7.2%). Exposure > 5 mg prednisolone/day was constant around 15% overall among users. Type 2 inflammation multimorbidity was associated with increases in systemic corticosteroid use at 9.6%, 16.0% and 20.9% for one, two and three diagnoses, respectively. A median referral delay of 4.1 [8.1] years from first systemic corticosteroid redemption to specialist assessment was seen. Specialist assessment led to a 64.9% reduction in median annual systemic corticosteroid exposure overall.ConclusionIn type 2 inflammation associated diseases, systemic corticosteroid use remains common despite the introduction of corticosteroid-sparing treatments. Timely referrals to specialist assessment could reduce the overall systemic corticosteroid exposure.