High-dose Steroids Research Articles

P0356 A case of pulmonary nodules in Ulcerative Colitis and primary sclerosing cholangitis: is it drug or disease?

Abstract Background Pulmonary manifestation of inflammatory bowel disease (IBD) is rare, with a broad range of lung diseases including airways, parenchymal, pleural, and pulmonary vascular disease. It is commonly associated with concurrent use of disease-modifying drugs. We present a case of a 26 year old man with ulcerative colitis and primary sclerosing cholangitis (PSC) who developed lung nodules. Methods Case summary: He was diagnosed with PSC in 2017 and ulcerative colitis in 2018. He had active colitis while on an escalated dose of adalimumab, therefore he was switched to vedolizumab. His faecal calprotectin improved but due to ongoing rectal bleeding, the dose of vedolizumab was escalated from 8 to 4 weekly. 5 months after starting vedolizumab he developed night sweats, dry cough, and breathlessness. He has no history of foreign travel, exposure to tuberculosis, industrial exposure, or bird keeping. Results His initial investigations showed a raised CRP and bilirubin. His CT chest showed numerous lung nodules in both lower lobes. His sputum culture, AFB, and fungal blood markers were negative. Samples were also sent from a bronchoalveolar lavage fluid including for pneumocystis jirovecii, which were negative. He was treated with antimicrobials and antifungal, without improvement. He subsequently underwent a lung biopsy, which showed inflammatory changes in an interstitial pattern, which could be related to the biologic therapy, or underlying disease. Staining for fungus, EBV, CMV, HSV were negative. He was treated as bronchiolitis obliterans organising pneumonitis induced by vedolizumab. Vedolizumab was stopped and prednisolone 40mg was started. His symptoms and inflammatory markers improved, and subsequent pulmonary imaging showed a reduction in the size of the lung nodules. Tapering the prednisolone dose to 10mg unfortunately caused a progression in the lung nodules, despite cessation of vedolizumab, which makes it less likely as the culprit drug. Prednisolone was then increased back up to 40mg, resulting in almost complete resolution of the lung nodules, with the plan for a much slower tapering. Despite the high doses of steroid his colitis is still moderately active on colonoscopy. However, further advanced therapy had to be put on hold while waiting for his lung nodules to resolve. Conclusion It remains difficult to determine whether his pulmonary disease is secondary to the biologic drugs, or the underlying disease process of ulcerative colitis. While pulmonary disease associated with IBD has been widely reported, there is currently unclear understanding of its pathophysiology and treatment. Clinicians need to be aware of this rare entity in IBD in order to improve patient outcomes.

Immunotherapy-related secondary hemophagocytosis in a glioblastoma patient: response to cytokine-directed therapy.

Hemophagocytic Lymphohistiocytosis (HLH) is a severe and potentially life-threatening condition characterized by an excessive and uncontrolled activation of the immune system. ICI-related hemophagocytic lymphohistiocytosis (irHLH) is a rare immune-related adverse event with an incidence of 0.03% to 0.4%. Although rare, it can be potentially lethal, with a high mortality rate of up to 50% in some cases. We present a patient with recurrent glioblastoma who developed Hemophagocytic Lymphohistiocytosis s a result of nivolumab treatment and was subsequently managed with cytokine-directed therapy (tocilizumab). Early diagnosis and treatment of Hemophagocytic Lymphohistiocytosis (HLH) associated with immune checkpoint inhibitors (ICIs) are indeed crucial due to the potentially life-threatening nature of the condition.Cytokine-based treatments (such as anti-IL-6) may be appropriate for patients who do not respond to high-dose steroids.

Late-onset Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease (ARD) that results from the dysregulation of multiple innate and adaptive immune pathways. Late-onset SLE (Lo-SLE) is the term used when the disease is first diagnosed after 50-65 years, though the standard age cut-off remains undefined. Defining "late-onset" as lupus with onset after 50 years is more biologically plausible as this roughly corresponds to the age of menopause. Lo-SLE comprises nearly 20% of all cases of lupus. With advancing age, the female predominance of lupus declines to nearly 4:1 to even 1.1:1. The natural history of the disease varies, with lesser major organ involvement like nephritis but higher damage accrual. The latter is possibly owed to the atypical presentation and hesitation among physicians to diagnose SLE at this age, a diagnostic delay with late treatment initiation may accelerate the damage accrual. Multimorbidity is a central issue in these patients, which includes osteoporosis, sarcopenia, accelerated atherosclerosis in the background of existing dyslipidemia, diabetes mellitus, major depression, hypertension, coronary artery disease and other thrombotic events.With the rising ages of populations worldwide, awareness about late-onset lupus is paramount, especially due to the associated diagnostic delays and higher overlap with Sjogren's disease. Also, pharmacotherapeutics must be optimized considering factors associated with ageing like declining glomerular filtration rate (GFR), sarcopenia, osteoporosis, and the associated comorbidities. Measures to minimize the exposure to long-term exposure to high-dose steroids are crucial. Beyond this, it is of essence to adopt non-pharmacological interventions as an adjunct to traditional immunosuppression to improve pain, fatigue, depression, and anxiety, improve cardiovascular health and overall better quality of life with favourable long-term outcomes.

Abnormalities in Blood Parameters in Athletes Taking Anabolic Androgenic Steroidal Agents; an Observational Clinical Study.

Many studies indicate that high and multiple doses of anabolic-androgenic steroids (AAS) for athletic enhancement can result in serious and irreversible adverse effects. A study that includes laboratory blood testing to evaluate the direct effects of AAS agents among users has not been previously undertaken. The purpose of this study was to investigate the adverse effects of the use of AAS by athletes and to determine whether AAS use leads to changes in certain blood parameters. This is an observational study consisting of two stages. First, the participants completed an online questionnaire assessing sociodemographic characteristics, and knowledge and attitudes towards AAS. Second, volunteers underwent laboratory blood testing. Analysis was conducted using frequency distributions and percentages of responses across various variables. Thirty-one individuals completed the online questionnaire, 18 of whom continued to stage 2, where blood samples were taken to trace any changes in blood parameters. All the participants were male, with an age range of 24-45 years. The results showed that 94% of the participants used AAS for nontherapeutic purposes. Most participants reported that they take a combination of AAS (96%), as well as in combination with other supplements (74%). The most used combination was testosterone plus growth hormone (45%), and the most used supplements were liver protectors (84%). Seventy-four percent of the participants reported side effects, and 28% had received a medical diagnosis, such as hypertension, hyperlipidemia or an infertility. High levels of testosterone, prolactin, alanine transaminase (ALT), aspartate transferase (AST) and lipid profile, and low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were observed. The unsupervised use of AAS alone or in combination with other hormones and/or supplements may lead to adverse effects. Further studies with larger samples are needed to draw significant conclusions about the safety of using AAS.

The relationship between steroid treatment and mortality in patients with COVID-19 followed up in an intensive care unit.

Optimal treatment of the coronavirus disease (COVID-19) is still unclear. It has been reported that the use of different doses of corticosteroid treatments may reduce mortality. In our study, we aimed to find the effect of corticosteroid treatment dose on mortality of patients followed up in intensive care due to COVID-19. Our retrospective, descriptive and single-centre study included 102 patients diagnosed with COVID-19 who were followed up in intensive care unit, 28 of whom received pulse steroids and 74 of whom received high dose steroids. Laboratory values, duration of intensive care unit and mortality rates of the patients were evaluated. Mortality was found to be statistically significantly lower in the group receiving pulse steroid compared to the group receiving high dose steroid. In multivariate logistic regression analysis, age and pulse steroid were found to be independent predictors of mortality. According to this analysis, each 10-year increase in age increased mortality by 4.8%, whereas pulse steroid decreased mortality by 79.4%. In our study, we found that mortality was statistically significantly lower in the group of patients receiving pulse steroids than in the group receiving high dose steroids. We found that the number of patients using pulse steroids was statistically significantly lower in the group with mortality. We found that age and pulse steroid independently determined the patients with mortality.

MACROPHAGE ACTIVATION SYNDROME (MAS) SECONDARY TO MYCOBACTERIUM BOVIS CYSTITIS FOLLOWING INTRAVESICAL INSTILLATION OF BACILLUS CALMETTE-GUERIN (BCG) VACCINE: A CASE REPORT WITH REVIEW OF LITERATURE

Background: Intravesical Bacillus Calmette-Guerin (BCG) vaccine instillation is widely used for the treatment of superficial bladder cancer. While mild non-infectious problems have mostly been reported with intravesical BCG instillation, significant local and systemic complications, albeit low, have also been documented. Macrophage activation syndrome (MAS) is a potentially serious condition characterized by a hyperinflammatory state occurring secondary to infections, malignancies, and autoimmune diseases. Intravesical BCG is internalized into tumor cells, initiating local and systemic immune responses, leading to MAS. Case Summary: We report the case of a 61-year-old male patient with high-grade papillary bladder carcinoma who was diagnosed with macrophage activation syndrome (MAS) in association with Mycobacterium bovis (M bovis) cystitis following the fifth dose of intravesical BCG instillation. He was put on high-dose oral steroids prednisolone 1mg/kg/day for MAS along with antitubercular targeting M bovis infection. There was a dramatic clinical responsefrom Day 7 of treatment with a drastic reduction in serum ferritin levels from day 12. There are only 6 cases of MAS in association with intravesical BCG instillation reported in the literature to date. All were male patients with the median age being 67 years which was similar to our patients age. Intravenous Immunoglobulin (IVIG) (5/6, 83.33%), high-dose steroids (6/6, 100%), and antitubercular drugs (2/6, 33.33%), Vinblastine (1/6, 16.66%) were used in these cases for the treatment of the same. Conclusion: The diagnosis of MAS in a setting of intravesical BCG immunotherapy requires a high index of suspicion as MAS has been rarely found to be associated with BCG therapy and there is an increased risk of mortality when this condition remains untreated.

Intralesional Steroid Injection Therapy of the Benign Vocal Fold Lesions

Voice therapy and laryngeal microsurgery are the main treatment options for benign vocal fold lesions. However, if patients are unable to endure lengthy voice therapy, or refuse surgery under general anesthesia, clinicians need to try other methods. Recently local steroid injection directly into the true vocal folds (TVF) benign lesions has been focused on alternative treatment options, and good results have been reported. Local steroid injection into the TVF was first described in 1964 by Dr. Yanagihara. Although this initial technique was inaccurate, however, with the advancement of modern endoscopy, recent emerging articles have proposed for the effectiveness of in-office awake vocal fold steroid injection in the treatment of benign vocal fold lesions. Based on previous studies of vocal fold steroid injection in the treatment of benign vocal fold lesions, I will summarize and suggest as follows. Various corticosteroids (triamcinolone acetonide, methylprednisolone, dexamethasone sodium phosphate) are used for the intralesional injection in the treatment of benign vocal fold lesions. The steroid injection approach can be transoral, transcutaneous or via flexible endoscope with operating channel, and injection route depends mainly on availability and individual experience. Intralesional corticosteroid injection significantly reduces benign vocal fold lesion volume and improves voice quality, at least transiently. There are many unresolved issues remain regarding the problem of vocal fold atrophy after steroid injection. Nevertheless, to minimize the risk of vocal atrophy, it is advisable to pay attention to repeating short interval steroid injection or administrating high dose of steroid. And, in case where repeated steroid injections are necessary for benign vocal fold lesions such as vocal nodule, vocal polyp, Reinke’s edema, I suggest that 12 weeks intervals would be safe to prevent vocal fold atrophy. And, to prevent recurrence of benign vocal fold lesions after steroid injection therapy, it is recommended to add post-procedural voice therapy, including vocal hygiene.

Tissue-based Gene Expression Diagnosis of Mild and Moderate T-cell-mediated Rejection to Guide Therapy in Kidney Transplants.

Mild histologic lesions of tubulo-interstitial inflammation could represent a "response-to-wounding" rather than allorecognition. Tissue gene expression may complement histopathology for T-cell-mediated rejection (TCMR) diagnostics. We report on the incorporation of tissue gene expression testing using a Molecular Microscope Diagnostic System into the management of kidney transplant biopsies with suspected TCMR. Patients (N = 209) were divided into 3 groups based upon diagnosis and TCMR therapy (with high-dose steroids and/or anti-thymocyte globulin): Group 1: Untreated histologic TCMR with molecular quiescence (H+M-); Group 2: Treated histologic and molecular TCMR (H+M+); and Group 3: Controls, with no histologic or molecular (H-M-) rejection. At biopsy, estimated glomerular filtration rate was worse (P = 0.006) in H+M+ (N = 35; 33 ± 22 mL/min/1.73 m2) and H+M- (N = 30; 40 ± 18 mL/min/1.73 m2) groups; compared with H-M- (N = 144; 47 ± 24 mL/min/1.73 m2) group. In H+M- biopsies, mean molecular acute kidney injury scores (0.33 versus 0.10; P = 0.03) were higher than in H-M-; while molecular TCMR was lower compared with H+M+ (0.04 versus 0.54; P < 0.001). At 12 m postbiopsy estimated glomerular filtration rate remained low (P < 0.001) in H+M+ (38 ± 22 mL/min/1.73 m2) but improved in untreated H+M- (44 ± 22 mL/min/1.73 m2) and H-M- (50 ± 23 mL/min/1.73 m2) groups. At a mean follow-up of 2.1 ± 1.2 y post-index biopsy, death-censored graft survival was lower in H+M+ (74%) than in H+M- (90%) and H-M- (92%; P = 0.001). H+M+ cases had numerically higher rejection on follow-up biopsy (20%) than H+M- (7%) (P = 0.12) and de novo donor-specific antibody formation (H+M+ 24%; H+M- 10%; P = 0.13). In this large single-center study, biopsies with untreated histological TCMR and molecular quiescence had comparable clinical outcomes to cases with no rejection, whereas those with histologic and tissue gene expression confirmed TCMR had inferior outcomes.

Favorable outcome in children with dense deposit disease with the use of long-term mycophenolate mofetil and high-dose alternate-day steroids.

This study aimed to evaluate the response to therapy and outcome with long-term daily mycophenolate mofetil (MMF) and high-dose alternate-day steroids (HADS) in children with dense deposit disease (DDD). Children with DDD who received long-term MMF (1200mg/m2/day) and HADS (1.5-2mg/kg AD) with slow tapering were retrospectively evaluated for their clinico-pathological presentation, response to therapy (complete, partial, no remission) and outcome (patient and renal survival). Six out of eight children with DDD seen over 10years (3 boys, 3 girls) aged 6-13years received the above therapy. Clinical presentation was nephrotic syndrome (1/6), gross hematuria (2/6), and nephritic onset of nephrotic syndrome (3/6). Serum creatinine was elevated at presentation in 3/6; C3 levels were low in all. None had crescentic changes on biopsy. The duration of therapy was 2-3years. On therapy, haematuria resolved by 3months, and proteinuria decreased to non-nephrotic range by 12 to 18months in all six. Serum creatinine normalized, and all showed complete remission during treatment. Three had sustained remission. Two children relapsed while tapering steroids and attained partial remission on increasing the steroid dose. One patient relapsed, 1year after therapy completion and did not respond to restarting the same treatment. Over a mean follow-up period of 5years, patient and renal survival was 100%. Long-term treatment with MMF and HADS showed a beneficial effect in the resolution of proteinuria with preservation of renal function and survival in the medium term in children with DDD with nephritic/nephrotic presentation.

Serious infections and tuberculosis adversely impact outcomes of juvenile onset systemic lupus erythematosus in India.

Infections are a major cause of morbidity and mortality in juvenile systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in juvenile SLE. A retrospective review of 225 patients of juvenile SLE (ACR 1997 criteria) with age <18years visiting the rheumatology clinic at a single centre between 2000 to 2020 was done from case records and the hospital electronic health records. Serious infection was defined as the need for hospitalization, or infection resulting in disability or death. Cox regression was used to determine factors associated with a serious infection and the effect of serious infection on overall survival. We reviewed 225 children (197 girls, mean age 13.89 ± 3.42years) with a cumulative follow up of 1153.45 person-years. Eighty serious infections occurred in 63 (28% of the cohort) children at a rate of 69.35 serious infections per 1000 person-years. A second serious infection occurred in 12 children and 5 of them developed three infections.Among the cases with known etiology (78.75% of cases), bacterial infections were most common (N = 33) including S. Aureus (11), E. Coli (7), K. Pneumoniae (3), E. Fecalis (3), S. Pneumoniae (2), Acinetobacter spp. (2), Citrobacter (2), Salmonella (2) and P. Aeruginosa (1). Twenty six (32.5%) opportunistic infections occurred: Mycobacterium tuberculosis (18), Cytomegalovirus (3), disseminated Herpes zoster (4) and invasive candidiasis (1) with 15 (83.3%) of the tuberculosis cases being extrapulmonary. On multivariate analysis, fever (HR 8.51, 1.17-61.44), gastrointestinal involvement (HR 4.73, 1.13-19.94), current steroid dose (HR 1.36,1.14-1.62), average cumulative steroid dose per year (HR 1.004, 1.002-1.005) and cyclophosphamide (HR 2.22, 1.11-4.46) were associated with serious infection.Hospitalization rates were significantly higher in those with any serious infection (Rate-ratio 2.79, 1.81-3.77) as was damage accrual (SLICC damage index 1.04 vs 0.22). Serious infection-free survival at 1 year and 5 years was 84% (79.1-89.2) and 72% (65.4-79.2). There were 19 deaths with infection attributable mortality in 10 (52.6%). Serious infection predisposed to higher overall mortality with recurrent infections conferring a hazard ratio of 36.02 (8.07-160.62). Serious infections are a major cause of mortality and damage in SLE. Constitutional symptoms, gastrointestinal involvement, current and cumulative steroid dose and cyclophosphamide predict serious infections. TB prophylaxis in patients with SLE should be considered in endemic areas, especially when using high-dose steroid therapy.

Pharmacologic Management of Obesity in Neuro-oncology: A Case Report

Introduction: Brain tumors are the most common solid tumors in pediatric oncology. Advances in the treatment of childhood brain tumors have led to increased survival; however, treatment-related morbidity remains high. The risk of developing overweight/obesity or significant weight gain is commonly observed in children with a brain tumor often due to hypothalamic damage as a result of radiation therapy, surgery, or the tumor itself. This may be accompanied by endocrinopathies such as diabetes insipidus and central precocious puberty in survivors of a childhood brain tumor. Lifestyle intervention strategies are often ineffective in preventing and managing obesity. Patients have difficulty with adherence to dietary interventions due to prolonged exposure to high-dose steroids, compromised physical health due to the disease process, or limitations in mobility as a result of excessive weight gain or the sequelae of the tumor management. There are no effective interventions to prevent or manage obesity in this patient population. Case Presentation: We describe a case report of a 11-year-old female who underwent treatment for a ganglioglioma, WHO grade 1 and, simultaneously, experienced nearly 100-kilogram weight gain. After several unsuccessful attempts at lifestyle interventions, she was referred to endocrinology and prescribed a GLP-1 receptor agonist, semaglutide. Following treatment with semaglutide, significant weight loss was observed. Importantly, the patient reported enhanced quality of life and social activity. Conclusion: Anti-obesity medications are promising treatment options for this vulnerable patient group. Additional research is warranted to examine their use for the prevention and treatment of obesity in children with a brain tumor.

Refractory hypoglycemia is sensitive to octreotide therapy: is it triggered by sorafenib or hepatocellular carcinoma?

Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia through extensive tumor infiltration and the presence of insulin-like growth factor 2 precursors. In this article, a patient whose persistent hypoglycemia did not improve despite long-term intravenous glucose and high-dose steroid treatment and who was successfully treated with octreotide is described. A 50-year-old male patient with a diagnosis of metastatic HCC was admitted to the emergency department due to symptomatic hypoglycemia. His blood glucose level was found to be 40 mg/dl and he was hospitalized in our clinic for treatment. The patient, who had been on sorafenib treatment for 2 weeks due to HCC, was started on intravenous dextrose for hypoglycemia and steroid, glucagon, and octreotide treatments, respectively. The patient's sorafenib treatment was discontinued and a second-line palliative chemotherapy was initiated. The patient responded dramatically to octreotide treatment and the need for intravenous glucose gradually decreased. Following approximately six weeks after hospitalization, the patient's requirement for intravenous glucose was no longer necessary. HCC and its treatment is a complex process involving the activation or inhibition of various mechanisms, and refractory hypoglycemia may rarely be seen in patients with HCC. But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.

Sudden sensorineural hearing loss in diabetes mellitus patients receiving intra-tympanic steroid injections.

Sudden sensorineural hearing loss is an acute hearing disorder typically managed using steroids. However, prognostic factors of diabetes mellitus (DM) patients undergoing intra-tympanic steroid injections (ITSIs) are unclear. We explored the prognostic factors for ITSI in DM patients with unilateral SSNHL. This retrospective study enrolled 89 DM patients with unilateral SSNHL from July 2016 to June 2022. All patients received ITSIs, and their clinical and audiological data were analyzed. The patients' mean age was 49.31±16.26years. After ITSI, the mean hearing level gain was 14.91±20.28dB, the mean speech reception threshold (SRT) gain was 15.78±32.16dB, and the mean speech discrimination score (SDS) gain was 16.94±35.06%. Based on Siegel's criteria, 8 patients (8.98%) had complete recovery, 14 (15.73%) had partial recovery, 16 (17.98%) had slight recovery, and 51 (57.31%) had no improvement. Older age (odds ratio [OR]=0.970, 95% confidence interval [CI]: 0.941-0.999, p=0.043) and profound hearing loss on pure-tone audiometry (PTA; OR=0.058, 95% CI: 0.007-0.462, p<0.001) were adverse prognostic factors in univariate analyses. Older age (OR=0.963, 95% CI: 0.932-0.994, p=0.023) and profound hearing loss (OR=0.048, 95% CI: 0.005-0.395, p=0.004) were independent negative prognostic factors in a multivariate analysis. ITSI is effective and avoids side effects of high-dose steroids in patients with SSNHL and DM. Among 89 DM SSNHL patients who underwent ITSI, older age and profound hearing loss were negative prognostic factors. Prompt and active management is necessary for DM patients with these risk factors.

Contribution of Sex Steroids in Management of Tall Stature: Is It Effective or Not?

Reduction in adult height by high-dose sex steroids was introduced decades ago. Here, we present the impact of lower doses of sex steroids on the predicted adult height (PAH) in children with tall stature. This single-center retrospective observational study included 22 tall children treated with low-dose sex steroids. Patients with familial tall stature, constitutional advance of growth, or Marfan syndrome were included. Anthropometric measurements at the commencement of treatment, six-monthly intervals on treatment, cessation of treatment, and at final assessment, were evaluated. Bone age (BA) determination, and PAH were made using both the tables of Bayley-Pinneau (BP) and Tanner-Whitehouse (TW) mark II methods. The final height was significantly lower than the predicted height in girls whereas it was not significantly lower than predicted height in boys. In patients with Marfan syndrome, the final height was only lower than the prediction of TW rather than BP. Non-Marfan cases had significantly lower final height than both the predicted heights. Conversely, although there was a decrease in height SDS over time, this difference was not statistically significant in the study cohort. Starting treatment at early BA (<10 years) did not affect the last height SDS or the difference between predicted height and final height. Sex difference, sex steroid dosage, differences in treatment duration and differences in BA measurement method, PAH method, BA and chronological age at the start of treatment may all influence the therapy response. Shortcomings about these influences can be overcome in future prospective studies with a larger sample size.

Severe Cutaneous Toxicity in A 67-Year-Old Patient with Metastatic Urothelial Carcinoma Undergoing Therapy with Enfortumab Vedotin and Pembrolizumab.

Enfortumab vedotin (EV) combined with pembrolizumab (EV+P) is a promising first-line therapy for metastatic urothelial carcinoma. While it has shown significant efficacy, severe cutaneous adverse events such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. We present this case as another example of severe skin off-target toxicity associated with this treatment, emphasising the importance of recognising this potential complication. A 67-year-old male with metastatic urothelial carcinoma, chronic kidney failure and liver cirrhosis presented with fever, respiratory symptoms and a pruritic rash after two doses of EV+P. The rash rapidly worsened, leading to extensive skin desquamation affecting 20-30% of his body surface area. Skin biopsies confirmed SJS with early-stage TEN (SJS/TEN overlap). The patient was treated with high-dose intravenous steroids, empirical antibiotics for neutropenia and intensive topical care. Significant re-epithelialisation occurred by day 13, and the patient was discharged on day 15 with cessation of EV+P therapy. This case demonstrates the potential for severe cutaneous toxicity in patients receiving EV+P, especially those with complex comorbidities. Early recognition and prompt, aggressive management with systemic corticosteroids are essential for improving outcomes. The case highlights the need for vigilance in monitoring for such adverse events and reporting them to improve patient safety. High clinical suspicion recognition of early signs of dermolysis is essential in managing severe cutaneous toxicity associated with enfortumab vedotin.A multidisciplinary approach the management of Stevens-Johnson syndrome/toxic epidermal necrolysis should involve a multidisciplinary team, especially in patients with complex comorbidities.Pharmacovigilance continuous monitoring and prompt reporting of adverse events to health authorities are vital for improving patient safety and therapeutic outcomes.

Lung Toxicity Occurring During Enfortumab Vedotin Treatment: From a Priming Case Report to a Retrospective Analysis.

Background/Objectives: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) that combines monomethyl auristatin E (MMAE), a potent cytotoxic agent, with a monoclonal antibody targeting Nectin-4. It has emerged as a promising therapy for metastatic urothelial carcinoma (mUC), either as monotherapy or in combination with pembrolizumab, improving significantly the overall survival of these patients. EV is associated with common adverse events, including skin reactions, glucose imbalance, and peripheral neuropathy, which are usually mild in severity and easily manageable. Methods: Following an initial case of pleuro-pneumopathy occurring in a patient treated with EV, we conducted a retrospective analysis of EV effects on pulmonary imaging. Results: In a cohort of 20 all-comers mUC patients, we identified three cases of potentially EV-related lung toxicity, resulting in a pleuro-pneumopathy rate of 15%. Two of these cases appeared highly symptomatic and required high steroid doses, with a rapid resolution of symptoms and normalization of radiological findings. In one patient, rechallenge of EV was associated with reoccurrence of pneumopathy. We described the clinical and radiological features of these cases, as well as their evolution after EV discontinuation and rechallenge. Conclusions: This case series underscores the importance of close pulmonary monitoring during EV treatment.

Abstract 4124430: Calcinosis Cutis and Heart Failure---A Rare Manifestation Which Should Never Be Ignored!

Introduction: Heart failure can be a manifestation of underlying immune mediated myopathies like dermatomyositis/polymyositis which can present in broad range of clinical manifestations and sometimes dermatologic lesions can be the only manifestation of these underlying pathologies without typically involving the muscle weakness. Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue. There are five subtypes of calcinosis cutis, dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Case summary: 70-year-old female was evaluated for bilateral lower extremity swelling. Past medical history was significant for Graves’ disease, atrial fibrillation, mechanical aortic valve on warfarin, hypertension, hyperlipidemia, ascending aortic aneurysm. Work up showed BNP of 4700 pg/ml with normal cardiac enzymes. Transthoracic echocardiogram revealed newly reduced ejection fraction of 25—30% with severely dilated left ventricle. Patient refused cardiac catheterization. Nuclear stress test showed no evidence of ischemia. Patient was started on guideline directed medical therapy and biventricular Implantable cardioverter defibrillator device was placed as per cardiology recommendation. Six months later patient developed multiple calcinosis cutis lesions on abdominal wall requiring surgical excisions. Endocrine work up including PTH, serum Ca level was normal, however creatin kinase level was high normal (150 U/L). Serum aldolase was ordered which was found to be elevated(25U/L). Muscle biopsy was performed as per recommendations of rheumatology which was diagnostic of dermatomyositis. Patient was started on high dose steroids and methotrexate and eventually IV immunoglobulins as per rheumatology recommendation. Follow up echocardiogram revealed improved ejection fraction to 40--45% with resolution of any further lesion of calcinosis cutis afterwards. Conclusion: Cardiac involvement such as congestive heart failure can be a part of presentation of underlying untreated myopathies. Calcinosis cutis can be the only clinical manifestation of dermatomyositis affecting heart. Etiology of calcinosis cutis in patients with heart failure should be worked up properly. Dystrophic calcinosis cutis is the subtype associated with underlying autoimmune connective tissue diseases.

Abstract 4135360: Eosinophilic Myocarditis: An Atypical Presentation with a Labile Course: A Case Report

Case presentation: A 64-year-old man presented with one day of chest pain. Initial evaluation showed elevated cardiac enzymes (CE) and normal eosinophil count. Electrocardiogram (EKG) was unremarkable. Transthoracic echocardiogram (TTE) showed an ejection fraction (EF) of 40% and a moderate-large pericardial effusion with signs of tamponade. Pericardiocentesis was deferred due to the lack of a safe window. Left and right heart catheterization showed no occlusive disease or chamber pressure equalization. The patient developed worsening shock, raising suspicion for myocarditis and prompting an endomyocardial biopsy (EMB). He was placed on extracorporeal membrane oxygenation (ECMO) on day 3. The EMB resulted as eosinophilic myocarditis (EM), and high dose Methylprednisolone was started. He was decannulated from ECMO on day 10. Intra-operative transesophageal echocardiogram (TEE) post-decannulation showed a normal EF without segmental abnormalities. Three hours later, a rise in CEs was noted, and EKG showed ST elevations inferiorly. TTE showed a reduced EF with multiple segmental abnormalities concerning for myocardial infarction. A repeat coronary angiogram was unremarkable. Due to the residual pericardial effusion, the patient underwent a pericardial window draining 200 cc of serosanguinous fluid. Intra-operative TEE showed an EF of 20% with no improvement after drainage. He had a cardiac arrest during the procedure and was placed back on ECMO. High-dose steroids were resumed along with intravenous immunoglobulin. Despite interventions, the patient continued to deteriorate and he ultimately expired. Discussion: EM has high mortality and a variable course, often requiring EMB for diagnosis. As in our case, about 25% of cases present without peripheral eosinophilia. Pericardial effusion occurs in 34% of cases and tamponade in 6%. A distinct feature of this case is the decompensation associated with ST elevation and segmental abnormalities, thought initially to be myocardial infarction (MI), after an initial response to steroids. While the etiology of such decompensation is unclear, relapsing EM in the setting of tapering steroids is one explanation, as myocarditis and MI can share similar clinical features. Another explanation is cardiac tamponade, which has also been reported to mimic MI and myocarditis. Air embolism from ECMO decannulation is another possibility, though air embolisms may include cerebrovascular pathology, which was not observed.

Abstract 4134417: Cardiotoxicity Conundrum: Distinguishing Immune Checkpoint Inhibitor Myocarditis from Fluorouracil Cardiotoxicity in Concurrent Therapy

Case Description: The patient is a 37-year-old male with metastatic gastroesophageal junction adenocarcinoma presenting with chest pain and dyspnea two days after initiation of leucovorin, fluorouracil, oxaliplatin (FOLFOX), and nivolumab therapy. He was tachycardic and hypotensive with elevated cardiac biomarkers and globally reduced left ventricular systolic function. Suspecting immune checkpoint inhibitor (ICI) myocarditis versus fluorouracil (5-FU) cardiotoxicity, he was treated simultaneously for both. After starting high-dose steroids and before uridine triacetate, he had improved symptoms, cardiac function, biomarkers, and invasive hemodynamics. Though his endomyocardial biopsy did not show inflammatory cell infiltrates, his CMR demonstrated increased T1 and T2 relaxation times consistent with myocarditis. Testing revealed normal dihydropyrimidine dehydrogenase (DPD) activity. He completed uridine triacetate and was discharged on a steroid taper. At follow-up, he remained clinically stable, tolerating oxaliplatin and docetaxel (FLOT) initiation and nivolumab rechallenge without 5-FU. Discussion: This case is challenging as the presentation does not conclusively identify a causative agent. The patient’s symptom severity suggests ICI myocarditis, while the early onset points to 5-FU cardiotoxicity. His quick recovery of cardiac function after medication cessation suggests 5-FU-associated Takotsubo cardiomyopathy. His improvement after steroids raises concern for an adverse immunologic response as in ICI myocarditis or idiosyncratic reactions to oxaliplatin with 5-FU. This patient received ICI therapy and chemotherapy, increasing his risk for cardiac immune-related adverse events. His protracted 5-FU infusion increased his risk for 5-FU cardiotoxicity, but his normal DPD activity mitigates this risk. Although his biopsy was negative, it cannot exclude ICI myocarditis. By the IC-OS 2021 consensus, he meets the criteria for ICI myocarditis presenting 48 hours after nivolumab exposure with cardiogenic shock, elevated cardiac biomarkers, decline in cardiac function, and CMR with elevated T1 and T2 relaxation times. Yet, his biomarkers remained normal with nivolumab rechallenge, arguing against ICI myocarditis and suggesting 5-FU as the culprit. Early recognition and differentiation of the culprit in concurrent therapies impact management and future treatment options. Rechallenge carries risk and requires interdisciplinary collaboration to ensure patient safety.

Rheumatoid Arthritis: A Rare Cause of Pachymeningitis and Optic Neuritis.

Rheumatoid pachymeningitis and optic neuritis are rare complications of rheumatoid arthritis (RA) and are a diagnosis of exclusion. A 75-year-old male with a history of seronegative RA presented to the emergency department with left eye pain and blurry vision lasting two days. He had been diagnosed with seronegative RA around nine months previously. His blood pressure was elevated at 204/75 mmHg upon arrival. Physical examination revealed left conjunctival injection, mild ptosis, painful extraocular movements and tenderness over the orbit and sinuses. Initial treatments included painkillers and intravenous labetalol, which alleviated his symptoms and decreased his blood pressure. Laboratory tests showed a C-reactive protein of 2.5 mg/dl and an erythrocyte sedimentation rate of 32 mm/h, with other blood work unremarkable. A computed tomography (CT) angiogram of the head and neck showed no high-grade stenosis. Given his RA history, initial concerns included scleritis. A magnetic resonance imaging (MRI) of the brain and orbit revealed inflammation around the left optic nerve, and pachymeningitis at the left cerebral convexity and interhemispheric fissure, suggesting hypertrophic pachymeningitis. An ophthalmologic examination was unremarkable. Treatment was adjusted to include pulse doses of intravenous methylprednisolone for optic neuritis, resulting in significant pain relief. Though inadequate for complete testing, a lumbar puncture indicated an inflammatory disorder with elevated glucose (199 mg/dl), protein (109 mg/dl), and unremarkable WBC/RBC and Gram staining. Cytology and culture were unremarkable. The most likely diagnosis at this point was rheumatological meningitis and rheumatological optic neuritis. The patient improved markedly with high-dose steroids over four days and was discharged on prednisone. In cases of optic neuritis and pachymeningitis, RA should remain on the differential in patients with or without a prior diagnosis. Rheumatoid arthritis (RA) is a systemic disease but can rarely cause neurological involvement.Pachymeningitis is an inflammation of the dura mater, rarely caused by RA.Optic neuritis can also rarely be caused by RA and responds to steroids.