Discontinuation Of Corticosteroids Research Articles

P0783 High risk of adrenal insufficiency in patients with Inflammatory Bowel Disease treated with a conventional course of systemic corticosteroids: Results from a prospective study

Abstract Background Corticosteroids (CS) remain the first-line treatment for inflammatory bowel disease (IBD) although they can cause adrenal insufficiency (AI) due to the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Assessing this risk is essential, as these patients are often in stressful situations, and AI can mimic IBD symptoms, leading to misdiagnosis. However, there is a lack of studies adequately assessing adrenal function in these patients. The objectives of this study were to determine the proportion of IBD patients who present HPA axis suppression following CS treatment, assess the time required for axis recovery, and identify risk factors for AI. Methods A prospective observational study was conducted including adult patients with active IBD who started systemic CS treatment and with no exposure to CS within the last 6 months. They all followed a pre-defined regimen of 1 mg/kg/day of prednisone (maximum 60mg) for 2 weeks, tapering by 10 mg weekly until reaching 20 mg, then tapering by 5 mg weekly. The HPA axis was assessed 24 hours after CS discontinuation by the measurement of baseline cortisol and ACTH, and cortisol 30 and 60 minutes after stimulation with 250 mcg of ACTH. HPA axis recovery was evaluated 3 and 6 months after CS discontinuation. The association between clinical and demographic variables and the occurrence of AI was analysed. Results Ninety-two patients were included (58% Crohn's disease, 39% ulcerative colitis, mean age 39.8±16 years, 50% women), who received a total CS dose of 2000.7±543.1 mg for 63.5±14.1 days. Forty patients (43.5%) were diagnosed with AI (32 partial, 8 complete). The recovery test was not performed in 10/40 patients (5 due to loss of follow-up, 5 due to need of a new course of CS). 23/30 patients recovered the adrenal function 3 months after stopping CS, and 27/30 patients after 6 months. In the univariate analysis, only fecal calprotectin at the end of CS treatment was associated with AI (P=0.026). Conclusion A high proportion of IBD patients treated with a conventional CS treatment schedule develop HPA axis suppression, although most of them recover adrenal function within six months. The development of AI was not associated with any of the studied variables, except for faecal calprotectin levels. Our results highlight the potential risks associated with prolonged CS use and underscore the importance of considering AI in this context, particularly when the patient faces physical stress.

Efficacy Assessment of Biological Treatments in Severe Asthma.

Uncontrolled, severe asthma remains a significant clinical challenge, affecting a small proportion of asthma patients worldwide. Despite advancements in treatment options, a subset of patients continues to experience frequent exacerbations, uncontrolled symptoms, and impaired quality of life. The advent of biological therapies has revolutionized the management of severe asthma, offering targeted treatments that address specific inflammatory pathways. This review provides a comprehensive overview of the efficacy and response criteria of biological treatments in severe asthma, focusing on clinical, functional, and inflammatory markers used to help in the evaluation of the biologic treatment. Key response criteria include symptom control, reduction in exacerbations, improvement in lung function, and a reduction in or the discontinuation of oral corticosteroids. Biomarkers such as blood eosinophils and exhaled nitric oxide (FeNO) are essential tools in guiding treatment adjustments. Real-world studies underscore the importance of personalized treatment strategies, as variability in response to biological therapies can be significant. The emergence of tools such as the FEOS score and EXACTO questionnaire offer quantitative measures for assessing biological response and guiding clinical decisions. Additionally, predictive factors for better or poorer responses, such as pre-treatment lung function and comorbidities, like obesity and rhinosinusitis, are critical in patient selection. This review highlights the need for ongoing reassessments and potential modifications of therapy in cases of suboptimal response. Practical considerations for switching biological therapies are discussed, emphasizing the importance of tailoring treatments to individual patient profiles and disease phenotypes. With the continued development of personalized medicine, the outlook for patients with severe asthma is improving, selecting specific biomarkers to improve the selection of the biologic treatment.

Clinical outcomes in peripheral ulcerative keratitis.

To evaluate clinical and treatment outcomes in patients with peripheral ulcerative keratitis (PUK). Retrospective, case series SUBJECTS: Patients diagnosed with PUK at the Wilmer Eye Institute between January 2003 and October 2022. Data collected included demographics, presence of systemic disease, disease laterality, duration of disease, PUK activity, presence of corneal perforation, and treatments. Outcomes of interest included: disease control, corticosteroid-sparing success, corticosteroid-discontinuation success, sustained drug-free remission, disease reactivation, occurrence of perforation, and need for surgery. Fifty-seven patients with PUK were identified. The median age was 53 years, with 46% of patients being Black. Most patients (56%) had an associated systemic diagnosis. The median duration of symptoms prior to presentation was 3 months and 42% of patients presented with bilateral disease. Of the 81 affected eyes, 7 had perforated prior to presentation. During a median follow-up of 3 years, 76% of patients received oral prednisone and 80% received at least one immunosuppressive drug. Disease control was achieved in all patients within a median of 1.3 months. The rates of corticosteroid-sparing success and corticosteroid discontinuation were 0.44 per patient-year (/PY) and 0.27/PY, respectively. Sustained drug-free remission was achieved in only 6% of patients. During follow-up, the rate of corneal perforation was 0.009/EY. The rate of disease reactivation was 0.07/EY, with a median time to reactivation of ∼2 years. Over a moderate amount of follow-up, systemic therapy achieved disease control, corticosteroid-sparing and corticosteroid discontinuation. However, sustained drug-free remission was infrequent in our cohort.

Pediatric Topical Steroid Withdrawal Syndrome: What Is Known, What Is Unknown.

Topical steroid withdrawal syndrome (TSW) is a debated condition marked by burning erythema, severe itching, and dry skin following the discontinuation of topical corticosteroids (TCS). This study reviewed reported pediatric TSW cases. With a total of 21 cases reported (inconsistent data provided), 60% (6/10) used TCS on the face; 69% (9/13) were associated with an escalation in potency of TCS and 75% (3/4) were the erythematoedematous variant. Overall, data on TSW in children is lacking and standardized diagnostic criteria are needed.

Allergic Contact Dermatitis in Pediatric Practice.

Allergic contact dermatitis (ACD) is prevalent among pediatric population, adolescent and young adults. Patients with ACD experience a lot of sociopsychological and qualityof- life (QoL) difficulties. Children and their caregivers alike are vulnerable to the burden of ACD. We have, in this paper, provided an overview of ACD and discussed common and unusual causes of ACD. We performed an up-to-date literature review in the English language on "allergic contact dermatitis" via PubMed Clinical Queries, using the keywords "allergic contact dermatitis" in August 2022. The search included meta-analyses, randomized controlled trials, clinical trials, casecontrol studies, cohort studies, observational studies, clinical guidelines, case series, case reports, and reviews. The search was restricted to English literature and children. ACD may be acute or chronic and it affects more than 20% of children and adults with significant quality-of-life impairments. ACD is manifested by varying degrees of cutaneous edema, vesiculation, and erythema. The hypersensitivity reaction is one of the most prevalent forms of immunotoxicity in humans. Localized acute ACD lesions can be managed with high-potency topical steroids; if ACD is severe or extensive, systemic corticosteroid therapy is often required to provide relief within 24 hours. In patients with more severe dermatitis, oral prednisone should be tapered over 2-3 weeks. Rapid discontinuation of corticosteroids can result in rebound dermatitis. Patch testing should be performed if treatment fails and the specific allergen or diagnosis remains unknown. ACD is common and can be a physically, psychologically, and economically burdensome disease. Diagnosis of ACD is primarily based on history (exposure to an allergen) and physical examination (morphology and location of the eruption). Skin patch test can help determine the causative allergen. Allergen avoidance is the cornerstone of management. Topical mid- or highpotency corticosteroids are the mainstay of treatment for lesions on less than 20% of the body area. Severe cases of ACD may require treatment with systemic corticosteroids.

The safety and feasibility of colchicine uptitration in the management of idiopathic recurrent pericarditis

Abstract Introduction Colchicine is recommended first line in the management of idiopathic recurrent pericarditis (IRP) at low doses (0.5 - 1 mg/24h). In cases refractory to low dose colchicine, corticosteroid use is common, despite an increased risk of disease recurrence and the risk of complications resulting from corticosteroid dependence. Biologic agents that block interleukin-1, anakinra and rilonacept, are highly effective in IRP, but their use is limited by expertise and cost. Colchicine uptitration is recommended by consensus international guidance in familial Mediterranean fever, a disease characterised by recurrent serositis, and, hence, offers an accessible steroid sparing approach to the management of treatment-refractory idiopathic recurrent pericarditis Purpose To explore the safety and feasibility of colchicine uptitration in patients with IRP refractory to low dose colchicine (0.5-1 mg/24h). Methods Retrospective review of electronic medical records of all patients with IRP and familial Mediterranean fever reviewed at a tertiary centre 2013-2023. Treatment-refractory IRP cases were defined as active disease despite colchicine 1mg/24h or disease requiring other prophylactic drugs, and corticosteroid dependence as daily corticosteroid use for 6 months. Results Of 121 IRP cases, 77 (63.6%) were treatment refractory at first review. Median follow up was 24 months (IQR 6 – 36). Corticosteroid dependence complicated 34/77 (44.2%) cases. Of treatment-refractory cases without corticosteroid dependence, 42/43 (97.7%) were treated with colchicine uptitration and 4/43 (9.3%) with anti-interleukin-1 biologic(s); none became corticosteroid dependent. Of corticosteroid dependent cases, 30/34 (88.2%) were treated with colchicine uptitration and 13/34 (38.2%) with anti-interleukin-1 biologic(s). Corticosteroids were fully discontinued in 25/34 (73.5%): 8/25 (32.0%) weaned with colchicine uptitration alone, 14/25 (56.0%) with anti-interleukin-1 biologic(s) and 3/21 (14.3%) with azathioprine. Median corticosteroid duration was 17.5 months (IQR 13 - 44.25) and corticosteroid toxicity occurred in 8/34 (23.5%). Among the 76/77 cases (98.7%) treated with colchicine (median maintenance dose 2 mg/24h (IQR 1.5-2)), permanent discontinuation was uncommon (3/76, 3.9%) and due to gastrointestinal symptoms. Self-limiting liver transaminase elevation was common (29/76, 38.2%) but did not lead to discontinuation in any case. The prevalence of liver transaminase elevation among patients with familial Mediterranean fever on life long colchicine was 181/568 (31.9%). Conclusions In this treatment-refractory pericarditis cohort, colchicine uptitration enabled avoidance of new corticosteroid dependence, facilitated corticosteroid discontinuation and was well tolerated. This contrasts with the frequent toxicity seen with prolonged corticosteroid use and offers an accessible steroid sparing approach to IRP management that warrants prospective investigation.

Molecular, Pathophysiological, and Clinical Aspects of Corticosteroid-Induced Neuropsychiatric Effects: From Bench to Bedside.

Corticosteroids are frequently prescribed across medical disciplines, yet they are associated with various adverse effects, including neuropsychiatric symptoms, documented since their introduction over 60 years ago. The cellular mechanisms underlying neuropsychiatric symptoms are complex and somewhat obscure, involving multiple pathways. Notably, they include changes in excitability, cellular death of hippocampal and striatal neurons, and increased inflammation and oxidative stress. Clinical presentation varies, encompassing affective disorders (anxiety, euphoria, depression), psychotic episodes, and cognitive deficits. It is crucial to note that these manifestations often go unnoticed by treating physicians, leading to delayed detection of severe symptoms, complications, and underreporting. Discontinuation of corticosteroids constitutes the cornerstone of treatment, resolving symptoms in up to 80% of cases. Although the literature on this topic is scant, isolated cases and limited studies have explored the efficacy of psychotropic medications for symptomatic control and prophylaxis. Pharmacological intervention may be warranted in situations where corticosteroid reduction or withdrawal is not feasible or beneficial for the patient.

Efficacy and safety of tocilizumab in Chinese patients with systemic juvenile idiopathic arthritis: a multicentre phase IV trial

ObjectivesGiven the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.MethodIn this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.ResultsSixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.ConclusionThis is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life.

Adalimumab to treat noninfectious pediatric chronic anterior uveitis: a case series

PurposeEvaluate the response to adalimumab (ADA) in pediatric chronic anterior uveitis (pCAU).MethodsRetrospective chart review of pCAU patients treated with ADA. Outcomes evaluated included the proportion of patients achieving zero ocular inflammation and discontinuation of topical corticosteroids, visual outcomes, and incidence of uveitis recurrences after ≥ 12 months of prescribing ADA. Incidence and risk factors for developing anti-adalimumab antibodies (AAAs) were also evaluated.ResultsOf 27 children aged 11 years, 16 (59%) were Caucasian and 6 (22%) African Americans. Thirteen (48%) patients had idiopathic pCAU, 12 (44%) had juvenile idiopathic arthritis (JIA) related pCAU, and 2 (7%) had tubulointerstitial nephritis and uveitis syndrome. At baseline, African American children had worse visual acuity (p = 0.026). At 1 year, 21 (78%) children achieved zero ocular inflammation (remission). Risk factors associated with non-remission were being African American (20% vs. 94%, p = 0.003) and experiencing ≥ 1 episode of uveitis recurrence (100% vs. 0%, p < 0.001). Six episodes of uveitis recurrence were documented in five children, four of whom were African American. Topical corticosteroids were discontinued in 83% of children, and visual acuity remained stable for 1 year. Twelve children were tested for AAAs due to arthritis or uveitis flare-ups, with five (42%) being positive. No significant factors were associated with the development of AAAs.ConclusionsWe found that ADA is effective in controlling inflammation, reducing the need for topical corticosteroids, and maintaining visual acuity in pCAU. There appears to be racial differences in African American children who had worse baseline disease and poorer outcomes. Studies are necessary to understand better and address these disparities.

Response to Upadacitinib in Patients with Inflammatory Bowel Disease Previously Treated with Tofacitinib.

Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure. This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels. A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04). Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC.

FDG altered biodistribution in white adipose tissue, a rare entity: case report and review of the literature

PurposeAltered 18F-fluorodeoxyglucose (FDG) biodistribution due to patient factors such as exercise and inadequate fasting are well established causes of limited diagnostic efficacy. In addition, medications such as G-CSF are known to affect uptake of FDG by bone marrow and spleen. In this study, we present a case of increased white adipose uptake in a pediatric lymphoma patient who recently received high dose dexamethasone and review the relevant literature regarding this rare and poorly understood pattern of altered FDG biodistribution.MethodsA 14-year-old male patient diagnosed with B-cell lymphoblastic lymphoma underwent FDG-PET/CT for restaging shortly after completing an induction chemotherapy regimen. Images revealed diffuse FDG uptake localizing to white adipose tissue, attributed to the 29-day course of dexamethasone which was completed two days prior. A diagnostically adequate study with relative normalization of FDG biodistribution was obtained seven days later.ResultsIn our review of the literature, diffuse FDG uptake by white fat is a rare occurrence and has only been reported by a few case reports and early observational studies. In addition to patients receiving corticosteroids, other cases of medication-induced adipose remodeling such as patients receiving highly active antiretroviral therapy have been documented with similar patterns of increased white adipose tissue activity.ConclusionCorticosteroid-induced white fat uptake of FDG is a rare phenomenon that can limit diagnostic accuracy of FDG-PET/CT and necessitate repeat imaging. Current evidence suggests that a wait period of at least one week after discontinuation of corticosteroids is sufficient to allow for decreased white fat uptake and increased diagnostic accuracy.

Comparison of the Efficacy of Omalizumab and Mepolizumab in Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease

Introduction: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous in both phenotypes and endotypes. Due to insufficient head-to-head comparison studies, it is hard to decide which biological to initiate. This study aimed to compare the efficacy of omalizumab and mepolizumab which can be used in the treatment of patients with severe eosinophilic asthma diagnosed with N-ERD. Methods: The population of this observational, cross-sectional study comprised of N-ERD patients who received omalizumab or mepolizumab for at least 6 months for severe asthma. Outcomes included the asthma control test (ACT), and sino-nasal outcome test scores (SNOT-22), blood eosinophil counts at initiation of biological treatment (T0, baseline) and at the end of 6th months (T6). Adverse effects related to biological treatment and changes of oral corticosteroids dose was recorded. Results: The study included a total of 22 patients, of whom 11 received mepolizumab and 11 received omalizumab. The change in ACT, SNOT-22, eosinophil counts, and adverse effects related to biologicals were similar at T6 (p = 0.606, p = 0.168, p = 0.05, p = 0.053, respectively). However, when examining the SNOT-22 and ACT based on the cumulative distribution curve (SUCRA), mepolizumab (SUCRA value: 0.61, 0.72, respectively) demonstrated greater efficacy compared to omalizumab (SUCRA value: 0.19, 0.35, respectively). The oral corticosteroids discontinuation rate was similar between the two groups (p = 0.05). Conclusion: We found both omalizumab and mepolizumab to be effective in treatment; however, we determined that mepolizumab may have a potential superiority in efficacy.

Real-world experience with fostamatinib in patients with immune thrombocytopenia: Results of an observational study (FORTE).

e23289 Background: Immune thrombocytopenia (ITP) is an autoantibody-mediated disease in which platelets are prematurely phagocytosed by Fcg-receptor-bearing macrophages in a spleen tyrosine kinase (SYK)-dependent signaling pathway. Corticosteroids (CS) are used to suppress the immune response, but long-term use carries a heavy burden of toxicity. Subsequent treatments for ITP include fostamatinib, a potent oral SYK inhibitor approved in 2018 based on two randomized, placebo-controlled, phase 3 trials. In trial patients, who received fostamatinib as second-line therapy following CS with or without immunoglobulins (IVIG), 25 of 32 (78%) patients achieved a platelet response of ≥50,000/µL, which was sustained for a median of 83% of treatment days. Here, we report real-world experience with fostamatinib as second-line therapy for ITP from a multi-center, prospective, observational study. Methods: The study (FORTE; NCT04904276) enrolled adult patients with ITP and an insufficient response to prior CS and/or IVIG. Patients were treated according to their clinician’s discretion, and data were collected for up to 12 months at clinic visits. Results: Sixteen patients were enrolled, and 15 were treated. Of the 15, 9 (60%) were female and the median age was 48 years (range, 20-92). 12 (80%) patients had prior CS and 6 (40%) prior IVIG. 7 (47%) patients completed the study and 8 discontinued treatment due to adverse events (4), lack of efficacy (2), and patient decision (2). After initiation of fostamatinib, 93% (14/15) of patients achieved ≥1 platelet count ≥50,000/μL. Median platelet count increased over time from 43,000/μL (IQR 19,000-105,000) at baseline to 167,000/μL (IQR 96,000-180,000) at Month 12. The median cumulative duration of elevated platelet count was 32 weeks (IQR 6.4-49.4). Concomitant CS were used by 7 (47%) patients at baseline, all of whom were able to taper as early as Month 1 and discontinue their dose by Month 3 in 4 patients, Month 6 in 2 patients, and Month 9 in 1 patient. Five patients had ITP-related AEs (4 Grade 1 and 1 Grade 2): gingival bleeding (2), mucosal haemorrhage (2), fatigue (1), contusion (3), headache (1) and epistaxis (1). There were 3 serious AEs in 2 patients: Grade 3 diarrhea in 1 and Grade 2 dyspnea and chills in 1. Overall safety results were consistent with previous studies of fostamatinib. Conclusions: Real world use of fostamatinib as documented in this observational study demonstrated efficacy and safety as second-line therapy for ITP. Fostamatinib allowed successful tapering and discontinuation of CS while maintaining platelet counts above 50,000/μL. Clinical trial information: NCT04904276 .

Red blood cell distribution width is a useful biomarker to predict bleeding and thrombosis risks in patients with immune thrombocytopenic purpura.

Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks before ITP treatment to optimize therapy and appropriately manage these complications. We performed a retrospective cohort study of 120 patients with primary ITP to identify a biomarker to predict bleeding and thrombosis. We compared blood test results at diagnosis between patients with and without bleeding or thrombosis episodes. The standard deviation of red blood cell distribution width (RDW-SD) differed significantly between those with and without bleeding and between those with and without thrombosis, leading us to identify it as a variable representative of risk. RDW-SD was significantly associated with patient age and with histories of several vascular diseases. Multivariate regression analyses showed that RDW integrated several variables associated with vascular risks. RDW-SD was significantly associated with difficulty with corticosteroid discontinuation (hazard ratio [HR], 2.22, p=0.01), incidence of bleeding (HR, 2.75, p< 0.01), incidence of thrombosis (HR, 2.67, p< 0.01) and incidence of infection (HR, 1.78, p=0.04). The RDW-SD value at the time of ITP diagnosis is a useful biomarker to predict the risks of bleeding, thrombosis, and other complications.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BackgroundCefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. MethodsWe identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. ResultsThe rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. ConclusionsIn this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. Level of EvidenceIII.

E043 Fast track giant cell arteritis service in a district general hospital using ultrasound doppler imaging

Abstract Background/Aims Giant cell arteritis (GCA) is the commonest large and medium artery vasculitis, a multisystem condition that results in significant comorbidity and mortality. Corticosteroids are pivotal in remission induction and maintenance therapy, but complications can arise either due to delayed treatment, or unnecessary treatment of GCA mimics. This renders quick diagnosis of GCA vital. Temporal artery biopsy (TAB) has traditionally been the golden standard diagnostic modality, but it requires a surgical setting, resulting in delays. Temporal artery ultrasound doppler scanning (TA UDS), however, has now been incorporated by both BSR and EULAR in their recommendations, offering a diagnostic tool with high specificity and sensitivity. Aims 1. To set up a fast track GCA diagnostic service in an one-stop-shop outpatient clinical setting with inhouse ultrasound; 2. To limit dependence of GCA diagnosis on TAB Methods We set up a dedicated GCA clinic at Eastbourne District General Hospital aiming to see patients within five days of referral. In the clinic, patients were categorised to low, moderate or high GCA risk via a pre-test probability score, and had TA UDS by an expert rheumatologist. We collected data on number of UDS performed, scan outcomes, and TAB requests over a 17-month period. Results Total number of referrals with suspected GCA was 147, mainly via general practice and ophthalmology, with 117 already having been started on corticosteroids by the referrer. Overall, 93% of patients were seen within five days of initial referral, with 32% within 72 hours of steroid commencement. We scanned 138 patients (94%) and diagnosed GCA in 41 (30%) of them. Of the nine we did not scan, six had very low probability score and were given alternative diagnoses; two were out of the window for diagnostics and GCA was diagnosed clinically; and one could not be scanned due to technical reasons, so a TAB was requested. Crucially, this was the only TAB requested during this period. Conclusion Our fast track service has facilitated prompt review of GCA referrals with the use of ultrasound, limiting the need for a TAB. The pathway enables both prompt commencement of appropriate steroid-weaning regimens in confirmed GCA, but also facilitates timely discontinuation of corticosteroids in patients with excluded GCA, thus minimising future complications either way. Typically, it takes more than three weeks to arrange a TAB. Moreover, ultrasound use avoids an invasive procedure with potential for surgical complications. From a healthcare system point of view, there are certain cost-saving implications in using ultrasound for GCA diagnosis. These can range from reduced demand for outpatient clinics, theatre slots and theatre staff, to minimisation of any future complications be it post-op, disease- or steroid- related. Finally, a service user survey, aiming to improve our pathway, documented improved patient satisfaction. Disclosure P. Kamperidis: None. A. Hall: None. H. Perera: None. S. Panthakalam: None.

The CORE syndrome: an overlap of severe asthma, obstructive sleep apnea, rhinosinusitis, and esophageal reflux.

Asthma, obstructive sleep apnea (OSA), rhinosinusitis, and esophageal reflux are conditions that may overlap, forming a syndrome known as CORE. Whenever clinical remission of severe asthma (SA) is not achieved, it is essential to investigate the presence of comorbidities, in particular the presence of OSA that may lead to the diagnosis of CORE syndrome. The study was conducted on naive patients with SA and concomitant rhinosinusitis and esophageal reflux, referred to our institute since 2018. Patients who did not experience clinical remission were investigated for OSA through a home sleep apnea test. Subsequently, for those diagnosed with OSA, continuous positive airway pressure (CPAP) was proposed and was re-evaluated after 12months. Six patients with CORE syndrome were enrolled. The mean apnea-hypopnea index (AHI) was 33.25 ± 20.13 events/h, oxygen desaturation index (ODI) was 28.95 ± 19.95 events/h, and time in bed with SaO2 < 90% (T90) was 26.40 ± 27.22% for which continuous positive airway pressure (CPAP) treatment was proposed but only 3 out of 6 patients accepted. After 12months, all CPAP-treated patients manifested a significant reduction in daytime sleepiness (ESS score was 6.33 ± 3.8), an improvement in ACT score (+ 8 (+ 32%), + 9 (+ 36%), and + 14 (+ 56%) points), a discontinuation of oral corticosteroids (OCS), an absence of exacerbations, and an improvement of lung function leading to clinical remission of asthma. Whenever facing SA patients, non-responders to therapy, it is important to suspect the presence of CORE syndrome; in particular, the detection and subsequent treatment of OSA would seem to improve the outcome of such patients.

Daptomycin-induced eosinophilic pneumonia.

Daptomycin-induced eosinophilic pneumonia (DIEP) is a rare complication of daptomycin use. Manifestations most commonly include fever, hypoxia, dyspnea, cough, eosinophilia, and lung changes on radiographs and CT. Patients typically have had recent daptomycin exposure and develop fever, dyspnea, infiltrates on chest radiograph, more than 25% eosinophils on bronchoalveolar lavage, and improvement of symptoms after withdrawal of daptomycin. Treatment includes discontinuation of daptomycin, corticosteroids, and supportive measures such as supplemental oxygen. Clinicians should have a high index of suspicion for DIEP in patients who develop new onset of pulmonary and systemic signs and symptoms after initiation of daptomycin.

Histopathological Diagnosis of Primary Central Nervous System Lymphoma after Therapy with Corticosteroids or Anticoagulants.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessments is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p = 0.049), it was only necessary in less than 10% of the cases with preoperative (but discontinued) corticosteroid treatment. Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p = 0.015). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p = 0.02). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for early surgical intervention. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after the discontinuation of CS remains a case-by-case decision. The effect of anticoagulation and dual antiplatelet therapy on diagnostic accuracy might have been underestimated and should be examined closely in future investigations.

Development of Crystalline Corneal Opacities (Steroid Keratopathy) in Dogs After Treatment With Ophthalmic Corticosteroids.

To retrospectively evaluate and describe the relationship between the use of topical corticosteroids and the development of crystalline corneal opacities (steroid keratopathy) in a colony of research Beagles and Beagle-derived dogs. Medical records of 73 purpose-bred Beagles and Beagle-derived dogs were reviewed from June 2012 to May 2021. All dogs were treated with topical ophthalmic corticosteroids for at least 21 days. In addition to regular ophthalmic examination, some dogs also had a systemic lipid profile (n = 6) performed to work up further and characterize the crystalline corneal opacities. Globes of 3 dogs were examined histopathologically. Axial stromal crystalline corneal opacities were appreciated in 25 eyes of 14 dogs after a median of 141 days after initiating treatment (35-396 days). Multiple corticosteroids were used, including neomycin-polymyxin b-dexamethasone 0.1% ophthalmic ointment, prednisolone acetate 1% ophthalmic suspension, and difluprednate 0.05% ophthalmic emulsion (Durezol). Resolution of corneal opacity was documented in 4 of 25 eyes when ophthalmic corticosteroids were discontinued after a median of 406.5 days (271-416 days). Histopathologic examination revealed a dense band of acellular material, poorly staining with periodic acid-Schiff, subtending the corneal epithelium, and being surrounded by spindle cells. This case series documents the onset of steroid keratopathy in Beagles and Beagle-derived dogs after treatment with ophthalmic corticosteroids. Clinical resolution of steroid keratopathy lesions may be possible after discontinuation of ophthalmic corticosteroids.