Leflunomide therapy for IgA vasculitis with nephritis in children

Background Henoch-Schönlein purpura (HSP), also called IgA vasculitis, is a systemic vasculitis characterized by deposits of immunoglobulin A in blood vessels. Renal impairment of these patients is the main determinant of prognosis. The optimal treatment of HSP nephritis (HSPN) in children remains controversial, but many clinicians administer an immunosuppressive agent with a corticosteroid. A previous study reported that leflunomide (LEF) with a corticosteroid was effective for adult patients with HSPN and nephrotic proteinuria. However, data on this treatment in pediatric patients is limited. Methods We described our experience at a single center on the use of LEF in 5 pediatric patients who had IgA vasculitis with proteinuria that was nearly 50 mg/kg (nephrotic range) and remained high despite administration of intravenous steroid, and biopsy-proven nephritis. All patients had class II to IIIb lesions based on the International Study of Kidney Disease in Children (ISKDC). Results We successfully treated all 5 children who had IgA vasculitis with nephritis using LEF with a corticosteroid. Four patients achieved a complete remission of proteinuria, and 1 patient had significantly reduced proteinuria. The children received LEF for 6 months to 12 months, and none of them had severe adverse events. Conclusions To our knowledge, this is the first case series to report successful treatment of pediatric HSPN with LEF in combination with a corticosteroid.

Narrative review of neuraxial potassium chloride administration errors: clinical features, human factors, and prevention measures

BackgroundAdministration of the wrong drug via the epidural or intrathecal route can cause devastating consequences. Because of the commonality of potassium replacement therapy coupled to its potential neurotoxic profile, we suspected that injuries related to this drug error would be present in the literature.ObjectivesWe aimed to identify clinical characteristics associated with the inadvertent administration of potassium chloride (KCl) during neuraxial anesthesia. Our secondary objective was to identify human factors that may have been associated.Evidence reviewPublished reports of neuraxial administration of KCl in humans were searched using Medline and Google Scholar. Error reports in any language were included.Findings25 case reports/series reported administration of KCl via epidural (25 patients) or intrathecal routes (three patients). There were six cases during interventional pain procedures, five cases in operating rooms and 17 in wards or intensive care units. Neuraxial KCl caused paraplegia in 22 patients. Mechanical ventilation was instituted in 11 of 28 patients. Three patients died. Epidural (eight patients) and spinal (two patients) lavage were performed to minimize consequences. A correctly prepared KCl infusion was connected to the epidural catheter for nine patients on wards (32%; 95% upper confidence limit: 48%) due to epidural–intravenous line confusion. Among the other 19 errors, KCl was confused with normal saline for 13 patients or local anesthetic in three patients. A wide range of concentrations and doses of KCl were administered. Variable use of intravenous steroid (13 patients) and epidural saline (eight patients) was found among patients who received epidural KCl. Human factors identified included incorrect visual perception, inadequate monitoring of infusions and substandard practice related to neuraxial anesthesia or analgesia.ConclusionsKCl administration via epidural or intrathecal route has been reported to cause catastrophic consequences.

Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic

Objective: Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL. Methods: Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment. Results: In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure. Conclusion: There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.

The Clinical Effects of Steroids Therapy in the Preserving Residual Hearing after Cochlear Implantation with the OTICON Neuro Zti EVO

Background: A prospective clinical study was conducted to investigate whether two different pharmacotherapy strategies of steroid administration impact hearing preservation in adult patients who underwent cochlear implantation with the Oticon Medical Neuro cochlear implant system. Methods: Twenty nine adult participants were included. Pure tone audiometry was performed before implantation, during processor activation and 12 months after activation. There were three treatment groups: (1) intravenous steroid therapy (standard steroid therapy with dexamethasone administrated intravenously at the dose 0.1 mg/kg body mass twice a day); (2) combined oral and intravenous steroid therapy (extended steroid therapy with dexamethasone administrated intravenously at the dose 0.1 mg/kg b.m. twice a day and prednisone (orally) at the dose 1 mg/kg body mass/24 h), and (3) no steroid therapy (a control group). Patients’ hearing thresholds before implantation were on average 103 dB HL, 89 dB HL, and 93 dB HL, respectively. Results: Deterioration of hearing thresholds was observed in all three patients’ groups. Twelve months after surgery the patients with and without steroid therapy had similar hearing thresholds. Conclusions: The steroid regimen used in this study did not play a significant role in patients with non-functional residual hearing, who underwent cochlear implantation with the Oticon Medical Neuro cochlear implant system.

P126 Older adults with acute severe ulcerative colitis have similar steroid failure and colectomy rates as younger adults

Background There is paucity of data on the outcomes of Acute Severe Ulcerative Colitis (ASUC) in older adults (≥60 years of age). The primary objective of our study was to assess steroid failure rate. The secondary outcomes assessed were need for colectomy during same admission, at 3 and 12months; mortality during admission for ASUC, at 3 months and 12months. Outcomes were compared with younger adults (< 60 years). Methods All admissions for ASUC (fulfilling Truelove and Witts Criteria) between January 1, 2013 and July 31st, 2020 at two Australian tertiary IBD centres were retrospectively analysed. Review of electronic medical records was performed and clinical, endoscopic, laboratory data were collected. Non-parametric data were compared using Kruskal-Wallis test. Parametric data were compared using paired t-test. Results 226 episodes of ASUC were analysed, 45 episodes were in patients who were ≥ 60 years of age at the time of ASUC event. Median Charlston comorbidity index was 3 (IQR: 2–4). In older adults, 19 (42.2%) failed intravenous steroid therapy and required rescue therapy. 2 (10.5%) episodes underwent direct colectomy, 17 episodes received medical rescue therapy (11 infliximab, 6 ciclosporin); 7 (63.6%) episodes received IFX 5mg/kg, 4 episodes (36.4%) received IFX 10mg/kg. 6 (13.3%) episodes had a colectomy during the admission for ASUC; 9 (20.9%) episodes had colectomy within 3 months and 9(20.9%) episodes underwent colectomy within 12 months. In patients < 60 years of age, steroid failure rate was 46.9% (85/181), 10.5% (19/181) underwent colectomy during the same admission, 17.6% (30/181) underwent colectomy by 3 months and 28.8% (42/181) had undergone colectomy at 12 months. In older adults, mortality during same admission occurred in 1 (2.2%) patient, 3-month mortality was 6.8% (3 patients) and 12-month mortality was 11.4% (5 patients). There was no mortality in patients < 60 years of age. Conclusion In older adults, steroid failure, the need for colectomy during the same admission and colectomy at 12 months is similar to a population <60 years of age. Mortality (at 3 and 12 months) is significantly higher.

Epidemiology and risk of invasive fungal infections in systemic lupus erythematosus: a nationwide population-based cohort study

Introduction: Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited. Methods: Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan’s National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs. Results: A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 [95% confidence interval (CI): 9.8–12.6] relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9–86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30–36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes. Conclusion: Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE. Plain Language Summaries Patients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections. Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens. Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.

FRI0549 RISK OF INVASIVE FUNGAL INFECTION IN SYSTEMIC LUPUS ERYTHEMATOSUS: A NATIONWIDE POPULATION-BASED STUDY IN TAIWAN

Background:Infectious disease is one of the leading causes of mortality in systemic lupus erythematosus (SLE). Among these infections, invasive fungal infection (IFI) carries high mortality rate (25-70%), but the literature of IFI in SLE is limited.Objectives:To investigate the epidemiology and risk factors of invasive fungal infection and its subtypes, including candidiasis, aspergillosis, and cryptococcosis, in SLE patients.Methods:All patients with newly diagnosed SLE between 1997-2012 were enrolled from Taiwan National Health Insurance Research Database, with an age- and sex-matched non-SLE control group in a ratio of 1:10. IFI was identified by ICD9 codes1from discharge record and validated by use of systemic anti-fungal agents. The incidence rate (IR), incidence rate ratio (IRR), cause mortality rate of IFI and its subtypes were compared. A Cox multivariate model with time-dependent covariates was applied to analyse the independent risk factors of IFI.Results:A total of 269 951 subjects (24 541 SLE and 245 410 control) were included. There were 445 episodes of IFI in SLE group. Candida was the most common pathogen (52.8%), followed by cryptococcus and aspergillus. The IR of IFI in SLE was 20.83 per 10,000 person-years with an IRR of 11.1 (95% CI 9.8-12.6) compared to the control (figure 1). Kaplan-Meier curve also disclosed a lower IFI-free survival in SLE (figure 2). The all-cause mortality rate was similar between SLE and the control (26.7 vs 25.7%). In SLE, treatment with mycophenolate mofetil (HR=2.24, 95% CI 1.48-3.37), cyclosporin (HR=1.65, 95% CI 1.10-1.75), cyclophosphamide (HR=1.37, 95% CI 1.07-1.75), oral daily dose of steroid>5 mg prednisolone (HR=1.26, 95% CI 1.01-1.58), and intravenous steroid therapy (HR=29.11, 95% CI 23.30-36.37) were identified as independent risk factors of IFI. Similar analyses were performed for subtypes of IFI. Distinctive risk factors were found between different subtypes of IFI (table 1).Conclusion:SLE patients have a higher risk of IFI. Intravenous steroid therapy is the most important risk factor of IFI. This study provides crucial information for risk stratification of IFI in SLE.References:[1] Winthrop KL, Novosad SA, Baddley JW, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015 Dec; 74(12):2107-2116.Disclosure of Interests:None declared