Initiation Of Corticosteroids Research Articles

A 10-year retrospective study of 43 female patients presenting with idiopathic granulomatous mastitis

Background: Idiopathic Granulomatous Mastitis (IGM) is a rare inflammatory breast condition affecting middle aged women. IGM typically presents as a unilateral, painful and challenging-to-treat breast mass, with a high recurrence rate. Common treatments include corticosteroids and antibiotics, with surgical excision reserved for resistant cases. However, the absence of a standardized treatment protocol leads to variability in management across different settings and providers. Methods: We present a case series of 43 patients diagnosed with IGM at a community hospital in New York, aiming to facilitate early recognition and treatment of this rare condition. This study identifies risk factors and reviews best practices in imaging and treatment, emphasizing the importance of considering IGM in the differential diagnosis, particularly in cases of recurrent disease. Results: The sample comprised 43 patients with an average age of 34.65 years, 31 (72%) of whom were Hispanic. The most commonly reported symptoms were pain, mass, erythema, and swelling. In all cases, IGM was confirmed by histopathological examination. Treatment modalities included incision and drainage (I and D), corticosteroids, antibiotics, methotrexate and surgical intervention. Conclusions: IGM is a rare condition often mistaken for breast cellulitis, abscess or carcinoma. Maintaining a high index of suspicion is crucial, particularly in Hispanic women who may be at increased risk. Histopathological diagnosis is essential to prevent unnecessary surgical interventions and antibiotic use, thereby reducing recurrence rates. Early initiation of corticosteroids or alternatives like methotrexate can optimize patient outcomes and reduce healthcare costs.

A Propensity Score-Weighted Analysis of Short-Term Corticosteroid Therapy for Refractory Pain Following Spontaneous Subarachnoid Hemorrhage.

Corticosteroids are prescribed for refractory headache in patients with spontaneous subarachnoid hemorrhage (SAH) despite limited supporting evidence. We hypothesized that a short course of corticosteroids would reduce pain. We reviewed all patients who received corticosteroids for refractory headache following spontaneous SAH within our institutional database. Pain was measured by a numeric rating scale (NRS) every 2h. The primary outcome was maximum daily NRS score; secondary outcomes were the mean daily NRS score and daily opioid consumption. Propensity scores were developed using potential predictors of corticosteroid use, including age, sex, pretreatment 24-h pain burden, and the number of analgesics being used to control pain. Inverse probability treatment weighting (IPTW) was used to balance baseline covariate distributions between patients receiving corticosteroids and control patients. Generalized estimating equations were used to analyze longitudinal NRS scores and oral morphine equivalents based on the weighted cohort. A total of 213 patients were included. The mean age was 55 (SD 13) years, and 141 of 213 (66%) were female. Of 213 patients, 195 (92%) had a low clinical grade (i.e., Hunt-Hess grades 1-3). Seventy patients were prescribed corticosteroids on postbleed day 5 (SD 3.3) on average, with an average of 26 (SD 10)mg of dexamethasone over 48h. Patients receiving corticosteroids and controls were well balanced on baseline predictors of treatment status. After IPTW, we found that corticosteroid therapy reduced the daily maximum pain NRS score by 0.59 (SE = 0.39, p = 0.12), 0.96 (SE = 0.42, p = 0.02), and 0.91 (SE = 0.46, p = 0.048) on days 1-3, respectively, after adjusting for control effects. The mean daily pain NRS score and daily opioid use were nonsignificantly reduced in the 3days following corticosteroid initiation after adjusting for control effects. Short-term corticosteroids only slightly reduced maximum pain severity after spontaneous SAH. Other analgesic strategies are required to manage refractory pain in this population.

Otitic hydrocephalus and papilloedema-re-evaluating a treatment paradigm.

Otitic hydrocephalus is increased intracranial pressure without ventricular dilation secondary to mastoiditis and cerebral venous sinus thrombosis (CVST). It is associated with significant visual morbidity, though more detailed data on visual outcomes is lacking. We sought to better characterize the management of increased intracranial pressure and visual outcomes in this population. Retrospective chart review at a quaternary Children's Hospital of patients <18 years of age who were diagnosed with otitic hydrocephalus from January 2009 to July 2023. Data were collected on patient demographics, clinical course, imaging, and treatment outcomes. Fifteen patients were identified with mastoiditis complicated by otitic hydrocephalus. The average age was 5.7 years (range 2-15). Eight patients were male (53%). Six patients (40%) had cranial nerve VI palsy and 14 (93%) developed papilloedema. Eleven patients (73%) developed progressively worsening papilloedema despite improving infection, clot burden, and acetazolamide; of these, three required ventriculostomy catheters. Eight were started on corticosteroids. Six had resolution of papilloedema without the need for shunt placement. Two patients had evidence of optic atrophy from increased ICP and visual loss prior to corticosteroid initiation. Both had stabilization of their condition without further visual loss. This study highlights the importance of systemic corticosteroids as part of the treatment paradigm for otitic hydrocephalus to prevent vision loss in patients otherwise unresponsive to medical management. It also identifies the risk of papilloedema progression and visual morbidity even after the initiation of appropriate medical therapy. Visual outcomes were significantly improved and invasive neurosurgical procedures were avoided with use of corticosteroids.

OA26 Atypical Multisystem Inflammation related to infection or just plain old polyarteritis nodosa?

Abstract Introduction We present the case of a 5-year-old boy with episodes of pyrexia of unknown origin associated with polyarthritis, central neuroinflammation and mucocutaneous manifestations. His skin biopsy demonstrated a nodular vasculitis which could be consistent with polyarteritis nodosa. Interestingly though, he had additional atypical rashes, ocular inflammation and evidence of acute and past streptococcal infection and his fever and CRP normalised prior to corticosteroid initiation. Case description A five-year-old British African male presented with five-week history of persistent fever, headaches, joint pain and bilateral eye pain. He was transferred to a tertiary paediatric infectious disease’s unit due to unrelenting fever with no fixed pattern, despite nine days of broad-spectrum intravenous antibiotics. He was diagnosed with neuroinflammation of uncertain aetiology, evidenced by leptomeningeal enhancement and bilateral papillitis on brain MRI. CSF microbiology and autoimmune profiles were negative. There was no evidence of primary malignancy. The fever resolved with pulsed IV methylprednisolone and the child was discharged home on a weaning regime of oral prednisolone. After stopping steroid treatment, he represented with high-grade fever, limping, anterior uveitis and new-onset non tender cutaneous lesions, plaques over eyelids and cheek and annular lesions over arms, legs and buttocks. Repeat MRI of the brain and spine showed resolution of previous neuroinflammation. Blood tests revealed raised ANA, IgG and ASOT titre, and his throat swab was positive for Group A Streptococcus. He completed 10 days of intravenous antibiotics and oral high dose ibuprofen (10 mg/kg TDS). On review by tertiary paediatric rheumatology, he was identified to have pleomorphic skin rash and subcutaneous nodules. Skin and deep tissue biopsy confirmed lobular and septal panniculitis with necrotising vasculitis, consistent with a nodular vasculitis. Treatment with high-dose steroid and mycophenolate mofetil (MMF) was initiated, but his CRP and fever had resolved prior to his first dose. He experienced improvement in systemic symptoms and arthritis; however, skin lesions persisted, with appearance of new lesions and hyperpigmentation, on reduction of steroid dose. His course was complicated by acute varicella infection, requiring oral aciclovir. Further treatment trials included topical tacrolimus and topical corticosteroids for his skin lesions. At one biopsy site, he experienced significant delay in wound healing. The genetic panel for primary immunodeficiency panel (R15) demonstrated no pathological variants. Discussion This case report highlights that, whilst the biopsy may be consistent with nodular vasculitis, such as PAN, the clinical manifestations are not perfectly aligned. Discussion within the rheumatology community would support optimal patient care. Childhood-onset Polyarteritis Nodosa (c-PAN) is a rare systemic vasculitis. Although the aetiology is unknown, associations with infections like group A streptococcus and hepatitis B suggest a postinfectious autoimmune response. There are no clear genetic links to PAN, but PAN-like vasculitis is part of reported monogenic autoinflammatory conditions. Key atypical features in this case include uveitis at presentation, nonspecific central neuroinflammation, unusual cutaneous lesion morphology, improvement of acute phase reactants before immunomodulatory treatment, and delayed biopsy wound healing. While ocular findings in PAN may include episcleritis, scleritis, keratitis, retinal vascular occlusions, and ocular ischemic syndrome, uveitis has not been reported in c-PAN. The patient also showed nonspecific inflammatory changes on initial MRI. Neurological involvement in c-PAN typically includes cerebrovascular accidents, cranial nerve palsies, and mononeuritis multiplex, with meningeal involvement being less common (reported 4% in a study of 69 children). Additionally, the patient experienced delayed wound healing following the biopsy, which is undocumented in c-PAN, but may be related to immune modulating treatment. A positive streptococcal throat swab could suggest an immune reaction as part of bacterial tonsilitis, or Acute Rheumatic Fever. However, he did not meet Jones Criteria, there was no response to prolonged antibiotics and the chronic remitting nature made these less likely. An autoinflammatory disorder, Deficiency of Adenosine Deaminase 2 (DADA2), was also considered but he had no evidence of livedo racemosa, strokes and no CECR1 mutation was identified. Our case has been discussed within a multidisciplinary team and we speculate that it could represent a previously undefined immune sensitivity within the autoimmune, autoinflammatory and immune deficiency spectrum giving an exaggerated response to infection. Key learning points • This case presents a significant diagnostic challenge due to its atypical clinical features and inconclusive extensive investigations, including immunologic testing, tissue biopsy, and genetic analysis. • While the patient’s symptoms improved with high-dose steroids and MMF, the recurrence of symptoms upon tapering steroids underscores the persistent inflammatory nature of the disease. • The detection of group A Streptococcus in the patient’s throat swab suggests a potential postinfectious autoimmune trigger, highlighting the role infections can play in the pathogenesis of vasculitis. The negative results from the R15 Primary Immunodeficiency panel suggest that more advanced genetic and immunologic testing may be beneficial. • We invite discussion on whether additional genetic or immunologic testing could optimise this patient’s care and contribute to the broader understanding of atypical vasculitis syndromes.

ThP8.12 - To do or not to do-Temporal artery Biopsy in Giant Cell arteritis

Abstract Aims Temporal artery biopsy (TAB) remains the gold-standard diagnostic test for giant cell arteritis (GCA). Our aim is to evaluate the correlation between initiation of corticosteroid therapy, timing of biopsy, and histological diagnosis of GCA through TAB. Moreover, analyse the usefulness of this practice. Methods Operative notes of TABs performed by a Vascular Surgery department at a teaching hospital between August 2021 and January 2023 were reviewed. We looked into the relationship between histological findings and the timing of corticosteroid treatment initiation prior to TAB. Results A total of eight patients had a TAB, with a male-to-female ratio of 2:6. The median age of the patients was 68-years-old (range 53-84). TABs were performed within 16 days of the referral (range 2-16). All were performed on elective theatre lists and none on emergency theatre lists (CEPOD). All patients had started corticosteroids by the time they had TAB, with a median duration of 11.5 days before TAB (range 2-16). The histopathology report was positive for active GCA in 1 case (12.5%) where the TAB was performed on day 3. In another performed on day 16, histopathology showed signs of healed inflammation (12.5%). In all other cases the report was negative (75%). All patients completed a full weaning course of steroids regardless of histological findings. Conclusion GCA is a systemic inflammatory vasculitis. Prompt initiation of high-dose corticosteroids is the mainstay management to reduce risks of ischaemic-related complications. Our work suggests the timing of biopsy is a key determinant of histological diagnosis of GCA.

Early Intestinal Ultrasound in Severe Ulcerative Colitis Identifies Patients at Increased Risk of 1-Year Treatment Failure and Colectomy

Abstract Background and Aims Reliable and easily accessible objective markers of disease activity to predict long-term treatment outcomes in severe ulcerative colitis [UC] are missing. We aimed to investigate if intestinal ultrasound [IUS] might predict long-term outcomes in hospitalised patients with severe UC, treated with intravenous [IV] corticosteroids. Methods Hospitalised patients with severe UC and IUS inflammation (bowel wall thickness [BWT] &amp;gt; 3.0 mm) starting IV corticosteroids were recruited at three university hospitals in Denmark. IUS was performed before treatment and 48 ± 24 h, 6 ± 1 days, and 3 months after treatment initiation. Time until colectomy or need for new interventions was registered together with Mayo score at 3 months and partial Mayo score [pMayo] at 12 months. Follow-up time was 12 months. Results In the final analysis, 56 patients were included; 45 [80%] patients needed intervention, including nine colectomies, during the 12-month follow-up. After 48 ± 24 h, no patient with a BWT &amp;lt; 3 mm needed a colectomy, p = 0.04. BWT ≥ 4 mm showed an increased risk of colectomy {odds ratio 9.5 (95% confidence interval [CI] 1.5–186), p = 0.03}, whereas a BWT ≥ 3 mm showed an increased risk of intervention (3.6 [1.1–12.5], p = 0.03). A BWT ≥ 4 mm resulted in a significantly shorter time until both colectomy, p = 0.03, and treatment intensification (mean days 75 [95% CI 24–127] vs 176 [119–233], p = 0.005). However, neither IUS parameters nor pMayo score, C-reactive protein [CRP], haemoglobin, or p-albumin could predict remission at 3 and 12 months. Conclusion BWT, assessed at 48 h post intravenous corticosteroid initiation in patients hospitalised with severe UC, may identify patients with an increased risk of short- and long-term colectomy and predict a more aggressive short-term disease course.

A Case of Gougerot Sjögren Syndrome (SGS) Discovered by Chronic Pulmonary Impairment at the Nianankoro Fomba Hospital in Segou

Introduction: Sjögren's syndrome (SS) is a systemic autoimmune disease whose target is the epithelium of the exocrine glands and in particular the salivary glands. SS affects women more often with a sex ratio of 9 women to 1 man and the peak frequency is around age 50. It is mainly described in Western literature where it seems to come second after RA. In Africa, it is mainly reported in the Maghreb. We report a case, revealed by pulmonary damage at the Nianankoro Fomba hospital in Ségou. Observation: This was a patient, aged 50, without any particular ATCD, who had consulted for chronic cough with mucco-purulent sputum and dyspnea, which had been present for more than four (4) months. Faced with the failure of a trial anti-tuberculosis treatment despite the negativity of the sputum testing for BARR in the Pneumophthisiology department, she decided to consult internal medicine. Clinical examination revealed NYHA stage III dyspnea. A chest CT concluded with bilateral pulmonary parenchymal interstitial syndrome associated with inflammatory bronchopathy with bronchiectasis. The immunological assessment revealed positive anti–SSA and anti–SSB Abs. Clinical improvement was obtained after initiation of corticosteroids and immunosuppressants. Conclusion: This observation illustrates the interest of looking for latent SS in the etiological assessment of a persistent cough.

Outcomes of patients with acute severe autoimmune hepatitis: Predictors of non-response to corticosteroids and need for liver transplantation.

Acute severe autoimmune hepatitis (AS-AIH) is an evolving concept and the outcomes and optimal treatment have been less studied. In this study, we aimed to investigate the outcomes of patients with AS-AIH and predictors of non-response to corticosteroid therapy and need for liver transplantation. In a retrospective cohort, we included patients with AS-AIH admitted to our liver center. We defined AS-AIH based on the international autoimmune hepatitis group score as acute presentation of AIH with an international normalized ratio (INR)≥1.5 and without liver cirrhosis and hepatic encephalopathy. All patients received high dose corticosteroid therapy. Treatment response was defined as liver transplant free survival at 4months after presentation. Factors associated with response to corticosteroids and survival of patients were studied. In total, 61 patients with AS-AIH were included. Forty-seven patients responded to corticosteroid therapy. In the multivariate regression model, baseline INR (odds ratio [OR]: 0.184; 95% confidence interval [CI]: 0.048-0.699; p=0.013) and delayed versus early initiation of corticosteroid (after vs. before 5days of presentation) (OR: 0.189; 95% CI: 0.039-0.919; p=0.039) were independent predictors of clinical non-response to corticosteroid therapy. In the multivariable Cox regression model, baseline INR level (hazard ratio [HR]: 2.542; 95% CI: 1.188-5.440; p=0.016) and delayed initiation of corticosteroids (HR: 3.578; 95% CI: 1.084-11.812; p=0.036) were independent predictors of liver transplant free survival at 6months after diagnosis. Delayed initiation of corticosteroid therapy might be predictive of clinical non-response to medical therapy and need for liver transplantation in patients with AS-AIH.

The Association Between Early Initiation of Systemic Corticosteroids and the Hospital Length of Stay in Patients With Multisystem Inflammatory Syndrome in Children.

Patients with multisystem inflammatory syndrome in children (MIS-C) often require hospital admission. Treatment of MIS-C has included intravenous immunoglobulin, systemic corticosteroids, and/or immunomodulators. There is no standardized approach to when steroids should be initiated during treatment. The study objective was to determine whether early initiation of steroids in patients with MIS-C is associated with the duration of hospital length of stay (LOS). This is a single-center retrospective cohort study of patients younger than 21 years who were hospitalized with MIS-C between March 2020 and September 2021 and received steroids. Cases were obtained from an institutional MIS-C log. Patients with culture proven sepsis and/or those who received intravenous immunoglobulin or steroids within the previous 30 days were excluded. We used a multivariable linear regression model, controlling for potential confounders, to assess the association between early steroids and LOS. A total of 56 patients hospitalized with MIS-C were identified; 38 received systemic corticosteroids and were included in the study. The mean time from admission to steroid administration was 9.8 hours (SD = 7.7) in the early group and 44.6 hours (SD = 14.2) in the late group. There was a statistically significant difference in baseline characteristics of patients receiving early versus late steroids in initial C-reactive peptide, procalcitonin, brain natriuretic peptide, and cardiac dysfunction. After controlling for confounders, initiating steroids within 24 hours of admission for MIS-C was associated with a decreased hospital LOS: in patients treated with early steroids, LOS was 58.3 hours less (95% confidence interval, -100.0 to -16.6; P = 0.007) than in those who received late steroids. Among patients with MIS-C, initiating systemic corticosteroids within 24 hours of admission was associated with decreased hospital LOS.

THE PREVALENCE AND RISK FACTORS FOR ARTERIAL HYPERTENSION IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME

Objective: Arterial hypertension (AH) is claimed to be an uncommon finding in children with idiopathic nephrotic syndrome (INS). The study aimed to analyze blood pressure, prevalence, and risk factors of AH in children with INS. Design and method: In 153 children with INS (9.32±3.84 years, 100 boys), we evaluated systolic and diastolic blood pressure (mm Hg, Z-scores), age at onset of the disease, anthropometric data, response to steroids, results of kidney biopsy, number of INS relapses, and medications. Results: The mean age at disease onset was 4.39±2.38 years; 67 patients had steroid-sensitive nephrotic syndrome (SSNS), 12 frequently relapsing nephrotic syndrome (FRNS), 58 steroid-dependent nephrotic syndrome (SDNS), and 16 steroid-resistant nephrotic syndrome (SRNS). Kidney biopsy was performed in 26: 5 – minimal change disease, 11 – mesangial proliferation, 10 – focal and segmental glomerulosclerosis. AH at disease onset was found in 10 (6.5%) patients in the following 11 (7.2%) after corticosteroid initiation. The observation period was 4.93±3.80 years, and AH was found in 31 (20.3%) – in 3 (4.5%) patients with SSNS, 2 (16.7%) with FRNS, 20 (34.5%) with SDNS, and 6 (37.5%) with SRNS. Patients with AH had lower height Z-score (-0.46±1.20 vs. 0.18±1.15, p=0.006), higher BMI Z-score (1.15±1.10 vs. 0.41±1.09, p&lt;0.001), number of INS relapses (8.32±6.78 vs. 4.41±3.82, p&lt;0.001), and current prednisone dose (0.49±0.67 vs. 0.18±0.29 [mg/kg/24h], p&lt;0.001). Systolic blood pressure Z-score at the end of observation correlated with age (r=-0.192, p=0.017), BMI Z-score (r=0.368, p&lt;0.001), and present prednisone dose [mg/kg/24h] (r=0.186, p=0.021), diastolic blood pressure Z-score with BMI Z-score (r=0.231, p=0.004), and number of INS relapses (r=0.163, p=0.044). In Cox Proportional Hazard presence of SDNS and SRNS were the only predictors of AH (SDNS: HR=4.80, 95CI(1.30-17.75), SRNS: HR=4.77, 95CI(1.06-21.53)). Conclusions: 1. Approximately one-third of patients with SDNS and SRNS develop arterial hypertension in the course of the disease. 2. Steroid dependence and steroid resistance are the strongest predictors of AH in children with INS. Other determinants of blood pressure elevation in this group of patients are high BMI and a high number of relapses.

Sudden sensorineural hearing loss related to Streptococcus suis meningitis

Background: Streptococcus suis meningitis is caused by Streptococcus suis, gram positive bacteria which is a pathogen mainly in pigs. It is an emerging zoonosis globally with highest incidence in Southeast Asia. The main risk factors are contact with infected pigs and consumption of raw or moderately cooked pork. Bilateral sudden sensorineural hearing loss is a remarakable symptom in this disease. Early initiation of antibiotic and systemic corticosteroids is recommended to improve clinical outcome and reduce complications. Even so, despite adequate treatment, sensorineural hearing loss related to S. suis meningitis is usually irreversible. We report two male patients consulted to otorhinolaryngology department regarding decreased hearing in both ears. Both patients was previously admitted because of altered mental status, accompanied with fever and headache. History of eating traditional Balinese pork dish before the onset was noted. Pure-tone audiometry revealed bilateral sensorineural hearing loss in both patients. Diagnosis of S. suis meningitis was established and treatment was prompted. Clinically, both patients showed improvement but evaluation audiometry showed no remarkable improvement in hearing threshold. Therefore, transmission avoidance, infection prevention, hygiene practice and educational activities are essential.

Shorter Intervals of Antenatal Corticosteroid Administration Can Influence Short- and Long-Term Outcomes in Premature Infants

Background: Studies examining shorter intervals between antenatal corticosteroid administration (ACS) and delivery are limited. This study analyzed effects of the timing of ACS on short-term and long-term outcomes in premature infants. Methods: This retrospective cohort study analyzed 534 deliveries between 220/7 and 296/7 gestational weeks, from January 2008 through December 2015, at the Department of Obstetrics and Gynecology of the University Hospital in Ulm, Germany. The initiation of antenatal corticosteroids to delivery was categorized using cutoffs of &gt;/≤24 hours. The study reported on gestational age, birthweight, the time interval between the first ACS and delivery, Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score, umbilical pH, delivery mode, incidences of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), the use of surfactant, as well as the neurodevelopment after 2 years (mental development index (MDI) and psychomotor development index (PDI)), and mortality. Results: Gestational ages were significantly advanced in the &gt;24 hours group (p &lt; 0.001). The incidences of BPD and IVH were significantly higher in neonates with less than 24 hours to delivery (BPD: 51.0% vs. 41.2%, p = 0.045; IVH: 10.5% vs. 3.0%, p = 0.001). There were no significant differences in ROP (p = 0.083), NEC (p = 0.856), or neurodevelopment after 2 years (MDI: p = 0.465, PDI: p = 0.116). Conclusions: Complications such as NEC and ROP, along with long-term neurological outcomes, do not seem to be influenced by shorter ACS intervals. In contrast, BPD, IVH, and surfactant administration appear to occur more frequently with ACS &lt;24 hours.

P408 Complete endoscopic healing, the future therapeutic target in Crohn's disease? Results of a prospective multicenter study

Abstract Background The STRIDE II guidelines recognize endoscopic healing (EH), defined by an SES-CD score ≤2 or a CDEIS score &amp;lt;3, as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, complete endoscopic healing could reduce the risk of long-term complications in CD. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic healing achieved. Methods We conducted a prospective multicenter study that included all patients with CD undergoing colonoscopy for EH assessment or dysplasia screening between September 2019 and September 2022 in one university hospital, one general hospital and one private center. Two groups were compared: patients with complete EH (CDEIS = 0) and those with partial EH (CDEIS &amp;lt;4). The primary endpoint was CD relapse, defined as the need for drug intensification and/or initiation of corticosteroid and/or CD-related hospitalization and/or development of a fistula (luminal or perianal) or abscess, and/or the need for bowel resection. Patients were followed up every 6 months for two years. Based on previously published data, 138 patients were expected to demonstrate a 13% difference with a two-sided alpha risk of 5% and a power of 80%. Results A total of 133 patients were included. The majority of patients were female (55%), non-smokers (63%), with a median disease duration of 10 (IQR, 4-19) years. Fifty-seven (43%) patients had ileocolonic location and 81 (61%) an inflammatory (B1) behavior. Patients had been on treatment for a median of 18.0 months (IQR 8.6-52) prior to colonoscopy, with no difference between the two groups. There was no significant difference between the two groups apart from BMI. Eighty-four (63%) patients had complete EH. After adjustment for BMI, the risk of relapse was significantly higher in the CDEIS&amp;gt;0 group (23% vs. 41%, HR = 2.05; IC95% = [1.09 - 3.87]; p=0.027). After a median follow-up of 23.3 months, the number of drug intensification, hospitalizations, use of corticosteroids, occurrence of abscess, fistula, or bowel resection in the CDEIS 0 and CDEIS &amp;gt; 0 and &amp;lt;4 groups were 20% and 35% (p=0.065), 2.4 and 16% (p=0.005), 2.4% and 10% (p=0.10), 3.6% and 18% (p=0.009), 7.1% and 18% (p=0.048), 7.1% and 18% (p=0.048) respectively. Conclusion This prospective multicenter study confirms that complete endoscopic healing is associated with better long-term outcomes than partial endoscopic healing in patients with CD, as well as fewer surgeries and hospitalizations and an overall decreased risk of treatment failure.

DOP21 Histo-endoscopic remission (HEMR) Predicts Future Relapse in Patients with Ulcerative Colitis and is Associated with Lower Colectomy Risk

Abstract Background Treating beyond clinical and endoscopic remission, aiming for histological remission, is an aspiring target in ulcerative colitis [UC]. Hence, combined histo-endoscopic endpoints are increasingly being embraced. We assessed different degrees of histologic remission in patients with UC and their association with long-term outcomes. Methods UC patients achieving endoscopic improvement (Mayo endoscopic score [MES] ≤1) were recruited at colonoscopy. Clinical data were retrospectively collected from medical records. Endoscopies were video-recorded and biopsies from the most affected segment were collected for histological assessment and RNAseq (in case of MES 0 rectosigmoid biopsies were collected according to previous disease extent). Geboes Score [GS] and Robarts Histopathology Index [RHI] were determined for each biopsy by two pathologists blinded to the endoscopic scores. Non-histo-endoscopic remission [NHR], histo-endoscopic mucosal remission [HEMR] and histo-endoscopic mucosal normalization [HEMN] were defined as GS ≥2B.1, GS &amp;lt;2B.1 and GS ≤0.1. Clinical relapse was defined as the need for dose optimization, switching therapy or initiation of corticosteroids during follow-up. Long-term outcomes were analysed using log-rank test and Cox regression. Results Between 2016 and 2022, a total of 172 UC patients were included (Table). Endoscopic remission (MES 0) was achieved in 104 (60.4%) patients. NHR, HEMR and HEMN were observed in 15 (14.4%), 69 (85.6%), 51 (49.0%) of MES 0 patients and 32 (47.1%), 36 (52.9%), 18 (26.5%) of MES 1 patients. During a median [IQR] follow-up of 2.8 (1.9-3.9) years, 51 (29.7%) patients relapsed, and 7 (4.0%) patients needed colectomy. Relapse- and colectomy-free survival (Figure) were significantly higher when comparing HEMR to NHR (p&amp;lt;0.001 for both). This difference was not observed for endoscopic score (MES 0 vs. 1) or different degrees of histologic remission (HEMN vs. HEMR). The univariate Cox regression showed that histo-endoscopic activity, clinical activity (i.e., patient reported outcomes (PRO-2) for stool frequency or rectal bleeding &amp;gt; 0) and prior advanced therapy failure were associated with an increased risk of relapse. The multivariate Cox regression identified histo-endoscopic activity as the only risk factor for relapse (adjusted hazard ratio [HR]) = 3.01, 95% confidence interval [1.69-5.34], p&amp;lt;0.001). Conclusion In this cohort of UC patients with endoscopic improvement, 14.4% of MES 0 and 47.1% of MES 1 patients still showed signs of histologic activity (i.e., presence of neutrophils in the lamina propria or epithelium. Histologic remission was a superior predictor of future outcome (relapse, colectomy) when compared to endoscopic remission and showed to be the sole predictor of relapse.

P570 Efficacy and safety of Adalimumab in Very Early-onset IBD- A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Patients with very early onset inflammatory bowel disease (VEOIBD) often present with severe disease course and require escalation to biologics. Exclusion of pediatric patients from clinical trials lead to scarcity of efficacy and safety data on TNFa antagonists therapy in VEOIBD. We aimed to assess safety and efficacy of adalimumab (ADM) induction and maintenance therapy in patients with VEOIBD. Methods This was a retrospective study involving 31 sites affiliated with the IBD Porto Group and IBD Interest Group of ESPGHAN, as well as centers in North America. Demographic, clinical and laboratory data were collected from patients diagnosed with VEOIBD who commenced ADM therapy before 6 years of age between 2014 to 2023. Results We identified 77 VEOIBD patients with a median age at diagnosis of 2.6 years (interquartile range [IQR] 1.3–4.1), of whom 29 (38%) were diagnosed at age &amp;lt;2 years (infantile-onset IBD). Thirty-seven (48%) patients were diagnosed with Crohn’s disease, 25 (32%) with ulcerative colitis and 15 (20%) with IBD-unclassified. Five (9%) from those genetically tested were diagnosed with monogenic disease. Median age at initiation of ADM was 4.2 (IQR 2.8-5.1) years. Forty-four patients (57%) were Infliximab experienced, discontinued mainly due to pharmacokinetic (20 [45%]) and pharmacodynamic (13 [30%]) failures. At initiation of ADM, concomitant corticosteroids and immunomodulators were given in 37 (48%) and 29 (37%) patients, respectively. The median wPCDAI and PUCAI scores at baseline were 45 [37.5-60] and 45 [27.5-57.5], respectively. Median follow-up time was 85.4 (IQR 40.4-139.2) weeks. While patients with CD showed significant clinical improvement after 26 and 52 weeks (PCDAI decreased to 10 [0-33.4], p&amp;lt;0.001, and 10 [0-25], p&amp;lt;0.05, respectively), No significant improvement in PUCAI score was observed among patients with UC (Figure 1). Inflammatory markers and calprotectin showed a gradual decrease over time (Figure 1). Weight and Height Z scores did not differ significantly throughout the follow-up period. ADM discontinuation rates after 1 and 3 years were 40% and 65%, respectively, mainly due to primary non-response (14, 29.8%) and loss of response (19, 40.4%). Drug discontinuation rates were not dependent on concomitant immunomodulator treatment or ADM initiation or on age (less or above 3 years). Four patients (5.2%) developed severe infections, including a patient with TTC7A mutation who died following septic shock. Conclusion Adalimumab therapy was relatively safe and seemed more effective in young patients with Crohn’s disease, but not in those with ulcerative colitis. Durability was relatively low due to high rates of primary non-response and secondary loss of response.

Multi‐institutional retrospective review of acute generalized exanthematous pustulosis (AGEP) induced by hydroxychloroquine

AbstractBackgroundAcute generalized exanthematous pustulosis (AGEP) is a rare and severe cutaneous drug eruption. Hydroxychloroquine (HCQ) is one of the known culprit drugs with less than 60 cases reported in the literature, and may have a more severe clinical presentation compared to AGEP induced by other drugs. There are no standardized management strategies for HCQ‐induced AGEP outside of drug discontinuation.ObjectivesCharacterize the clinical presentation of HCQ‐induced AGEP and management strategies.MethodsRetrospective chart review of nine patients clinically diagnosed with HCQ‐induced AGEP using the EuroSCAR score from 2017 to 2022 at four academic medical centres in the United States.ResultsAll patients in our series were female and the median age was 52. Four patients initially presented with fever, and eight patients had neutrophilia. Median time to rash was 15 days. Biopsies obtained in six patients showed typical characteristics of AGEP. In most patients, rash morphology consisted of generalized pinpoint pustules atop atypical targetoid lesions and annular plaques. Five patients were hospitalized for AGEP. All patients were treated with methylprednisolone and/or prednisone, and the average days treated with systemic corticosteroids was 35.ConclusionsOur case series is the largest to date describing HCQ‐induced AGEP. Clinicians should be wary that HCQ‐induced AGEP may present with a longer latency period after drug initiation and with atypical targetoid and annular lesions. Early initiation of systemic corticosteroids should be considered due to the severity of this drug reaction with addition of cyclosporine in refractory cases.

Early Versus Late Initiation of Hydrocortisone in Patients With Septic Shock: A Prospective Study.

Introduction The optimal timing of corticosteroid initiation in septic shock patients is debatable. The Surviving Sepsis Campaign Guidelines recommended adding hydrocortisone to septic shock patients who require a vasopressor with a dose of norepinephrine ≥ 0.25 mcg/kg/min for at least four hours. Nevertheless, the best time to initiate hydrocortisone remains uncertain. Objective Assessing the impact of early (≤3 hours) versus late (>3 hours) initiation of hydrocortisone in septic patients. Methodology We compared the outcomes of septic shock patients who received hydrocortisone within three hours versus those who started treatment after three hours. The inclusion criteria encompassed septic shock patients aged 18 or older who received at least one dose of hydrocortisone. Exclusion criteria included pregnancy, do-not-resuscitate orders, the absence of empirical intravenous antibiotics, recent corticosteroid use, recent cardiac arrest, and a history of adrenal insufficiency. Results Eighty-one patients were included (54% were males). The mean age was 59 years, and 56.8% of patients were in the early group. The time needed to discontinue vasopressors was 25 and 37 hours for the early and late groups, respectively (p = 0.009), and more patients achieved reversal of shock (35 vs. 24 patients) and had shorter ICU stays (17 days vs. 20 days). Conclusion Initiating hydrocortisone early, within three hours, reduced the time needed to discontinue vasopressors among the study population. However, both early and late initiation strategies yielded comparable outcomes in terms of ICU mortality, ICU length of stay, and shock reversal.

Natural history of Duchenne muscular dystrophy in the United Kingdom: A descriptive study using the Clinical Practice Research Datalink.

Duchenne muscular dystrophy (DMD) is a rare, muscle-degenerative disease predominantly affecting males. Natural history models capture the full disease pathway under current care and combine with estimates of new interventions' effects to assess cost-effectiveness by health technology decision-makers. These models require mortality estimates throughout a patient's lifetime, but rare disease datasets typically contain relatively few patients with short follow-ups. Alternative (published) sources of mortality data may therefore be required. The Clinical Practice Research Datalink (CPRD) was evaluated as a source of mortality and natural history data for future economic evaluations of health technologies for DMD and rare diseases in general in the UK population. This retrospective longitudinal cohort study provides flexible parametric estimates of mortality rates and survival probabilities in the current UK DMD population through primary/secondary records in the CPRD since 1990. It also investigates clinically significant milestones such as corticosteroid use, spinal surgery, and cardiomyopathy in these patients. A total of 1121 male patients were included in the study, observed from 0.7 to 48.9 years. Median life expectancy was 25.64 years (95% confidence interval 24.73, 26.47), consistent with previous global estimates. This has improved to 26.47 (25.16, 27.89) years in patients born after 1990. The median ages at corticosteroid initiation, spinal surgery, ventilation, and cardiomyopathy diagnosis were 6.06 years (5.77, 6.29), 14.79 years (14.29, 15.09), 16.97 years (16.50, 18.31), and 15.26 years (14.22, 16.70), respectively. Estimates of mortality in UK-based DMD patients are age-specific in a uniquely large and nationally representative sample from the CPRD.

Abstract 16249: A Case of Myocarditis and Pneumonitis Associated With Pembrolizumab Therapy

Introduction: Immune checkpoint inhibitors (ICI) are a novel therapy that activates antitumor immunity but can have varied immune-related adverse effects. As ICI therapy is used to treat malignancy, cases of autoimmune myocarditis and heart failure increase, thought to be due to PD-1 inhibition, which may be potentially fatal. Case presentation: A 37 yo female with history of autoimmune hepatitis and stage III melanoma on Pembrolizumab (ninth cycle 1.5 months prior) presented with chest pain, tachycardia, fatigue, dyspnea, and fever. Lab studies were notable for elevated troponin, lactic acidosis, and disseminated intravascular coagulation (DIC). CT thorax showed asymmetric ground glass opacities, concerning for ICI pneumonitis. Echocardiogram showed an LVEF of 15% with global hypokinesis. She was treated for severe sepsis, DIC, and respiratory failure, temporarily requiring intra-aortic balloon pump. Heart failure guideline-directed medical therapy (GDMT) was started. Clinical presentation was concerning for acute myocarditis related to ICI therapy as a cause for new cardiomyopathy. A cardiac MRI (CMR) revealed subepicardial late gadolinium enhancement (LGE) along the basal inferior/inferolateral wall segments concerning for myocarditis. Corticosteroids with a prolonged taper were started. Endomyocardial biopsy of the septum (EMB) was negative. Her clinical status improved and repeat echo showed LVEF recovery up to 45%. Discussion: Endomyocardial biopsy (EMB) provides definitive diagnosis of myocarditis and is recommended (Class I) for new-onset heart failure with hemodynamic compromise and/or arrhythmias. Although our patient’s EMB was negative (likely due to limitation of sample location), she met the 2013 ESC guideline diagnostic criteria for myocarditis with elevated troponin, functional and structural abnormalities on cardiac imaging. With increased utilization of ICI therapy in the management of aggressive malignancies, it is important to monitor for potentially adverse effects such as autoimmune myocarditis. Standard treatment is prompt initiation of corticosteroids, though newer studies report successful treatment with immunomodulators, such as abatacept and ruxolitinib, if steroids are unsuccessful.

Incidence and treatment of checkpoint inhibitor induced immune related adverse events in the emergency department.

438 Background: Immune checkpoint inhibitors (ICPis) are currently indicated for the treatment of various types of cancers. Through inhibition of the cancer cell’s checkpoint mediated T-cell evasion, ICPis allow for sustained T-cell activation and proliferation, resulting in increased cancer cell death. However, due to increased activation and proliferation of cytotoxic T-cells, ICPis have been associated with a wide spectrum of adverse effects, known as immune related adverse effects (irAEs). Although recently updated, the 2018 NCCN and ASCO guidelines state that treatment is based on the location and severity of irAEs. In general, grade 3 toxicities warrant suspension of ICPis and initiation of high-dose corticosteroids. Corticosteroids should then be tapered over the course of at least 4-6 weeks. The diagnosis of an irAE is challenging, toxicities may be misdiagnosed as there is a diverse familiarity with ICPis and their associated irAEs. Subsequently, care may be delayed, and patients may not receive appropriate guideline directed care. Methods: This multi-center chart review included 7 hospitals within a large health system. Our electronic health record was utilized to compile a report of patients who had received ICPIs within 12 months of presentation to an ED within the health system between 9/1/2019 and 9/1/2022. Assessed outcomes included incidence and type of irAE, time between last ICPi dose and presentation to the ED, steroid used for treatment, time to steroid, treatment driver, and the action that deviated from the 2018 ASCO/NCCN guideline directed treatment if applicable. Results: Of the 241 patients receiving an ICPi, 26 (10.8%) experienced an irAE that prompted a visit to an ED within our health system. Guideline directed treatment of irAE(s) was followed 76.9% of the time, with the steroid dose being too low (15.4%) and the steroid taper occurring too quickly (7.7%) being the two reasons for discordant treatment. Treatment started a median of 1.1 after presentation to an ED, with colitis as the most prevalent irAE in 11 patients (42%) presenting. For all patients, there was an average of 20 days between the last ICPi dose and presentation to ED. The main steroid used was methylprednisolone (42%). Conclusions: The 10.8% of patients who experienced an irAE that prompted a visit to an ED within our health system is a lower rate than what has been described in the literature previously, where rates of presentation to an ED due to an irAE ranged from 25-37%. This could be due to previous data coming from before or shortly after the publication of ASCO and NCCN guidelines in 2018, or because our outpatient medical staff has become more aware of irAEs and their appropriate treatment. Limitations include this review was retrospective, no patients had an irAE that was refractory to steroids, and the study period being soon after national guidelines were published.