High-dose Corticosteroids Research Articles

Fatal rhabdomyolysis and fulminant myocarditis with malignant arrhythmias after one dose of ipilimumab and nivolumab.

Immune checkpoint inhibitors (ICIs) related myocarditis is a rare complication of modern immunotherapy. It can present as an asymptomatic subclinical condition or full-blown fulminant myocarditis with malignant arrythmias and cardiogenic shock. Myositis/rhabdomyolysis and/or myasthenic symptoms can be present concomitantly. We present a case of fatal fulminant myocarditis presenting with cardiac arrythmias and severe systolic dysfunction, with accompanying rhabdomyolysis after the first dose of ipilimumab and nivolumab immunotherapy. First working diagnosis of subacute late presenting acute myocardial infarction (ACS) was incorrect and the correct diagnosis was established only after additional testing and consultation. Treatment consisted of high-dose corticosteroids, intravenous immunoglobulins, sedation with mechanical ventilation, antibiotic coverage, hemodialysis, and sustained low-efficiency daily diafiltration (SLEDD) with CytoSorb or TheraNova membranes, and intra-aortic balloon pump mechanical cardiac support. No tangible improvement in the condition was observed during the whole treatment period and the patient died on the sixth day of intensive care treatment.

Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review

Background: Spontaneous intracranial hypotension (SIH) is a rare and frequently misdiagnosed disorder characterized by a low volume of cerebrospinal fluid (CSF) caused by the leakage of CSF through the spinal dural membrane. Patients with Marfan Syndrome (MS) and other connective tissue disorders are at an increased risk for dural ectasia, which may predispose them to spontaneous CSF leaks due to the structural weakness of their dural membranes. The management of SIH in MS patients is debated. Conservative measures, an epidural blood patch (EBP), and surgical treatments are the options generally provided. Methods: Herein, we report on the case of a 52-year-old female affected by MS, genetically confirmed, with a two-month history of sudden-onset, “thunderclap” headache, worsened in an upright position and horizontal diplopia. A Computed Tomography (CT) scan of the brain showed a bilateral chronic subdural hematoma, slit ventricles, and a caudal descent of the brainstem without overt tonsillar herniation. The Magnetic Resonance Imaging (MRI) scan of the whole spine revealed dural ectasia in the lumbosacral area and presacral perineural cyst without extradural CSF collection. The case was successfully managed with bed rest and high-dose corticosteroid therapy. Then, we discuss the pertinent literature, consisting of 25 papers dealing with the treatment of SIH in patients affected by MS. Results: The literature review yielded 25 papers dealing with SIH management in patients with MS, including 28 patients overall; 21 patients underwent EBP, of whom 7 patients had multiple procedures. Overall, in 23 cases (82%), the symptoms improved. In three cases, the patients were managed conservatively with bed rest. In three of these cases, there was an improvement. In one case, the surgical fenestration of two lumbar intradural spinal meningeal cysts was performed and the patient improved after the procedure. Our patient underwent 15 days of steroid therapy (dexamethasone iv 12 mg/day for 7 days, then reduced to 4 mg/day) and intravenous hydration (Ringer lactate 1500 mL/day). In ten days, the symptoms disappeared. At the 6-month follow-up, the patient was in good clinical condition, and a CT scan showed an almost complete regression of the bilateral subdural hematoma. Conclusions: The management of SIH in MS patients is still challenging. Patients with connective tissue disorders such as MS are at an increased risk for SIH. Few studies have assessed the management of these patients and different strategies. Our case and the available literature provide further data for this type of case.

Invasive Aspergillosis with Cavernous Sinus Thrombosis Following High-Dose Corticosteroid Therapy: A Challenging Case of Rhino-Orbital-Cerebral Mycosis

Invasive aspergillosis is a rare but severe fungal infection primarily affecting immunocompromised individuals. The Coronavirus Disease-2019 (COVID-19) pandemic has introduced new complexities in managing aspergillosis due to the widespread use of corticosteroids for treating COVID-19-related respiratory distress, which can increase susceptibility to fungal infections. Here, we present a challenging case of progressive cerebral aspergillosis complicated by cavernous sinus thrombosis (CST) in a 67-year-old male with a history of COVID-19. The patient, initially misdiagnosed with temporal arteritis, received pulse corticosteroid therapy twice before presenting with persistent left-sided headaches and vision loss. Cranial imaging revealed findings consistent with fungal sinusitis, Tolosa–Hunt syndrome, and orbital pseudotumor, which progressed despite initial antifungal therapy. Subsequent magnetic resonance imaging indicated an invasive mass extending into the left cavernous sinus and other intracranial structures, raising suspicion of aspergillosis. A transsphenoidal biopsy confirmed Aspergillus infection, leading to voriconazole therapy. Despite aggressive treatment, follow-up imaging revealed significant progression, with extension to the right frontal region and left cavernous sinus. The patient then developed visual impairment in the right eye and was diagnosed with CST secondary to fungal sinusitis. Management included a combination of systemic antifungals and antibiotics; however, the patient declined surgical intervention. This case underscores the diagnostic challenges and rapid progression associated with cerebral aspergillosis in post-COVID-19 patients treated with corticosteroids. This report highlights the need for heightened clinical suspicion and prompt, targeted interventions in similar cases to improve patient outcomes. Further research is required to understand the optimal management of invasive fungal infections.

Spesolimab Response in a Patient With Steroid-Resistant Sweet Syndrome.

This case report describes a patient with Sweet syndrome whose condition improved with spesolimab after failure of high-dose corticosteroids.

Longer duration of high-dose corticosteroids provides benefit for hospitalized COVID-19 patients with high oxygen requirement

The optimal corticosteroids dose in patients with coronavirus disease 2019 (COVID-19) requiring high oxygen remains unknown. In this retrospective study of patients with COVID-19 requiring high oxygen and receiving corticosteroids, the efficacy, safety, and duration of high-dose treatment were evaluated. The primary outcome was all-cause mortality during follow-up. Safety outcomes included infection, gastrointestinal bleeding, and venous thromboembolic events. 210 patients were included, with 126 in Group A (corticosteroids at a equivalent dose <1 mg/kg/d prednisone), 44 in Group B (corticosteroids at a equivalent dose ≥1 mg/kg/d prednisone for ≤5 days), and 40 in Group C (corticosteroids at a equivalent dose ≥1 mg/kg/d prednisone for >5 days). The all-cause mortality risk was lower in Group C but higher in Group B than in Group A. Safety outcomes did not differ significantly, except for Group C, which had the highest venous thromboembolism rate. Our results suggest that high-dose corticosteroids for a longer course decrease mortality with comparable safety outcome.

OA25 Not so “savy” afterall

Abstract Introduction Interferonopathies (IFN’s) are a constellation of diseases that cause recurrent pathogenic inflammation, arising primarily through antigen-independent hyperactivation of immune pathways¹. It is primarily due to abnormal production or signalling of type I IFNs². A disorder of both the innate and adaptive immune system, this condition is relatively new with the term only coined in 2011. Currently there are more than 20 interferonopathies recognized, with new interferonopathies being identified like Sting associated vasculopathy with onset in infancy (SAVI). Case description Our patient first presented with a severe panniculitis rash, Raynaud’s, swelling of her limbs and hepatosplenomegaly at five weeks of age. She developed significant respiratory distress requiring non-invasive ventilation. A CT Thorax revealed diffuse groundglass opacification suggestive of interstitial lung disease. She had elevated inflammatory markers (CRP 24 mg/L, ferritin 1448 ng/ml, ESR 88 mm/hr), a transaminitis (ALT 193 U/ml, AST 356 U/L). She had multiple positive auto antibodies (Table 1) Clinically SAVI was suspected as the most likely diagnosis. Her interferon signature gene assay demonstrated exaggerated IFI 27 and IFI44L levels. A Trio exome sequencing and IKBKG sequencing however have not been indicative of any currently recognised interferonopathy. Further genetic analysis has been requested to explore possible novel pathogenic mutations. A reasonable clinical response was seen with corticosteroid therapy in combination with Jak Inhibition. With worsening of her cutaneous disease and an increasing need for corticosteroid use a trial of anti IL-6 therapy was initiated. This was subsequently discontinued when she presented with severe acute digital ischemia. It was managed with escalating doses of ruxolitinib, pulse high dose corticosteroids and epoprostenol infusion. Her interferon signature gene assay demonstrated exaggerated IFI 27 and IFI44L levels. A Trio exome sequencing and Inhibitor of nuclear factor kappa B gene (IKBKG) sequencing however have not been indicative of any currently recognised interferonopathy. Further genetic analysis has been requested to explore possible novel pathogenic mutations. A reasonable clinical response was seen with corticosteroid therapy in combination with Jak Inhibition. With worsening of her cutaneous disease and an increasing need for corticosteroid use a trial of anti IL-6 therapy was initiated. This was subsequently discontinued when she presented with severe acute digital ischemia. It was managed with escalating doses of ruxolitinib, pulse high dose corticosteroids and epoprostenol infusion. Discussion This case enhances our current understanding of interferonopathies. Although the phenotype and course of the disease is compatible with SAVI³, genetic testing is negative to date. Presently there are eleven heterozygous gain-of-function (GoF) variants for SAVI4. With JAK inhibition as the most successful therapeutic option to date5. Our case possibly represents an as yet unreported genetic variant, further studies are awaited.This case enhances our current understanding of interferonopathies. Although the phenotype and course of the disease is compatible with SAVI³, genetic testing is negative to date. Presently there are eleven heterozygous gain-of-function (GoF) variants for SAVI4. With JAK inhibition as the most successful therapeutic option to date5. Our case possibly represents an as yet unreported genetic variant, further studies are awaited.This case enhances our current understanding of interferonopathies. Although the phenotype and course of the disease is compatible with SAVI³, genetic testing is negative to date. Presently there are eleven heterozygous gain-of-function (GoF) variants for SAVI4. With JAK inhibition as the most successful therapeutic option to date5. Our case possibly represents an as yet unreported genetic variant, further studies are awaited. Key learning points • Early suspicion for an interferonopathy in very young infants with interstitial lung disease • Expanding the potentially new genetic variants of this condition • Challenge of treatment management

Phenytoin-induced DRESS syndrome: A multidisciplinary case study in precision medicine and advanced therapeutics

This case report aims to examine the diagnostic and therapeutic approach for phenytoin-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome in a pediatric patient, emphasizing the importance of early recognition and intervention. A 17-year-old male presented with a pruritic rash, fever, lymphadenopathy, and elevated liver enzymes one month after starting phenytoin for epilepsy. Diagnosis was confirmed using the RegiSCAR scoring system, which objectively assessed clinical and laboratory findings. The patient received high-dose corticosteroids and N-acetylcysteine (NAC) after discontinuing phenytoin, with regular monitoring of clinical and laboratory parameters. Timely withdrawal of phenytoin, along with corticosteroid and NAC therapy, led to the resolution of symptoms without long-term complications. The RegiSCAR scoring system proved invaluable for accurate and swift diagnosis, supporting its utility in pediatric DRESS cases. This case also suggests the potential of genetic screening, particularly HLA typing, for identifying high-risk individuals, although it was not utilized here. Early diagnosis and multidisciplinary management are critical for favorable outcomes in pediatric DRESS cases. Routine HLA screening could help prevent DRESS syndrome in patients prescribed high-risk medications, though further studies are needed to assess feasibility and cost-effectiveness. This case underlines the value of standardized treatment protocols and personalized medicine in managing drug hypersensitivity reactions effectively.

The impact of high dose corticosteroid treatment affect on cardiac abnormalities in patients with multiple sclerosis

Aims: High-dose corticosteroids to control acute relapses of multiple sclerosis, leveraging their anti-inflammatory effects. However, these treatments can lead to cardiovascular side effects. Understanding the pathophysiology of corticosteroid induced bradycardia is paramount for healthcare providers. Our aim in this study are to identify risk factors for cardiac side effects and assess the timing of cardiac complications relative to treatment. Methods: Patients who met the McDonald's criteria for definite MS and patients requiring admission for pulse steroid treatment with an acute recurrence were included.Individuals taking cardiac medications, or with a heart illness were excluded.Patients were given 1 g IV methylprednisolone in 2 hours for five to seven days in order to treat acute relapses. Results: We studied with 23 patients(6 males and 17 females, 26.1/73.9% respectively).The mean±SD age of the patients was 34.6±9.9 (18-43) years and the mean±SD duration of disease was 5.5±4.9 years.Most of the patients were relapsing–remitting MS in 73.9%, primary progressive in 4.4% and secondary progressive in 21.7%.The most common cardiac arhythmia during corticosteroid pulse therapy was sinus bradycradia(n=6). Conclusion: The combination of direct effects on cardiac myocytes, electrolyte disturbances, autonomic dysfunction, and individual genetic factors can contribute to the development of bradycardia in MS patients treated with high-dose methylprednisolone. Close monitoring and prompt intervention are crucial to manage this adverse effect and optimize patient safety.

Use of corticosteroids and antibiotics for the treatment of asthma exacerbations at a quaternary care respiratory institute: A descriptive cohort study

Rationale The Global Initiative for Asthma guidelines recommend 50 mg prednisone for 5-7 days for asthma exacerbations and avoiding antibiotics. Management following failed home action plans is not addressed. Objectives The objectives of this study were to describe management of asthma exacerbations at the Montreal Chest Institute - Day Hospital (MCI-DH). Methods We retrospectively reviewed patients presenting to the MCI-DH for asthma exacerbations from January 2019 to June 2020. Data pertaining to demographics, treatments, and adverse events were collected and presented descriptively without statistical comparison. Measurements and Main Results Most patients present to the MCI-DH with an asthma exacerbation following a failed home action plan. A total of 107 patients (130 visits) were included in the analysis. Systemic corticosteroids were initiated in 119/130 (91.5%) visits, with 30 (25.2%) patients receiving the full course as oral therapy, whereas 89 (74.8%) were transitioned to oral therapy from intravenous. A daily dose of 50 mg of prednisone was observed in 34/119 (28.6%) treatment courses. The mean total corticosteroid duration was 12 days (SD 8), with only 18/119 (15.1%) treatment courses prescribed for 5-7 days. Corticosteroids were tapered over a mean of 14 days (SD 15) in 66 (55.5%) patients. Antibiotics were initiated in 18/130 (13.9%) visits, and 5/18 (27.8%) had no documented rationale. No adverse drug events were recorded in the 90 days following treatments. Conclusions The MCI-DH serves a complex population of patients often presenting following a failed action plan. Clinical judgment appears to have led to longer course high dose corticosteroids for many. Salvage therapy following a failed action plan requires further study.

Ischemic Stroke Unveiling Takayasu Arteritis Complicated by Coronary Arteritis: A Case Study

Context: We present the case of a 38-year-old woman admitted for ischemic stroke. Etiological evaluation revealed halo signs on transesophageal echocardiography (TEE), suggestive of Takayasu arteritis. Case Presentation: During hospitalization, the patient developed chest pain, elevated troponin levels (300 ng/L), left ventricular hypokinesia on echocardiography, and T-wave inversions on electrocardiogram (ECG), indicating coronary arteritis. High-dose corticosteroid therapy led to rapid improvement in inflammatory markers. The diagnosis of Takayasu arteritis was confirmed based on the American College of Rheumatology (ACR) criteria. This case highlights the variable clinical presentation of Takayasu arteritis, including coronary involvement, and underscores the effectiveness of corticosteroid therapy in controlling inflammation. Conclusion: Takayasu arteritis, though rare, can manifest with ischemic stroke and coronary arteritis. Prompt recognition and corticosteroid treatment are essential in managing this potentially life-threatening condition.

Outcomes Associated with the use of High Dose Corticosteroids and IL-6 Inhibitors for the Treatment of Acute Respiratory Distress Syndrome Secondary to SARS COV-2.

During the COVID-19 pandemic, treatment strategies evolved rapidly. The RECOVERY trial established corticosteroids as the standard care for reducing mortality in COVID-19 patients. However, some critical care clinicians began using doses higher than those recommended in RECOVERY. To characterize the use of high-dose corticosteroids and IL-6 inhibitors in critically ill COVID-19 patients and examine their association with adverse drug events (ADEs). A retrospective cohort study of 320 electronic health records (January 1, 2020 - June 30, 2022) was conducted on COVID-19 patients requiring high-flow oxygen or mechanical ventilation. Patients were categorized based on corticosteroid dose: "high dose dexamethasone" (daily dose greater than 12 mg and/or for longer than 10 days), "low dose dexamethasone" (daily dose 12 mg or less for 10 days or less), and "no dexamethasone" (no corticosteroid therapy). Subgroups were created based on IL-6 inhibitor use. High-dose dexamethasone was associated with increased odds of ADEs compared to low dose (OR 2.55, 95% CI 1.45 to 4.49) and no dexamethasone (OR 6.29, 95% CI 2.08 to 19.03). No additional efficacy benefit was observed in patients receiving high dose corticosteroids when compared to low dose corticosteroids. Patients receiving both an IL-6 inhibitor and high-dose dexamethasone had further increased odds of ADEs. High-dose dexamethasone was also associated with increased mortality compared to low dose (OR 3.78, 95% CI 1.97-7.25) and no dexamethasone (OR 15.22, 95% CI 3.27-70.74). Acknowledging the risk for residual confounding, higher doses of dexamethasone were associated with increased ADEs and mortality. These findings highlight the need for careful consideration of the use of high-dose dexamethasone.

Severe hypersensitivity reactions to 2 immunotherapy agents in a patient with cutaneous squamous cell carcinoma.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. There is currently limited data on cross-sensitivity between immunotherapy agents. In this case study, we report a case of severe anaphylaxis to both pembrolizumab and cemiplimab. Pembrolizumab (Keytruda) and cemiplimab (Libtayo) are both approved for the treatment of metastatic cutaneous squamous cell carcinoma. Infusion reactions occur rarely with immunotherapy agents. However, if infusion reactions are severe, the treatment should be discontinued, and there is no guidance as to whether another immunotherapy agent may be used. An 87-year-old-male was diagnosed with metastatic cutaneous squamous cell carcinoma expressing a PD-L1 combined positive score of 81%-90%. He was treated with pembrolizumab and, 15 minutes after completion of the first infusion, developed swelling of the eyelids, ears, and tongue in addition to a whole-body rash without pruritus. Due to the severity of the reaction, pembrolizumab was permanently discontinued and the patient was then started on cemiplimab. The patient received a high-dose corticosteroid as premedication before the first infusion of cemiplimab and tolerated the treatment without any adverse effects. However, when the corticosteroid premedication dose was decreased before the second cycle, the patient had a severe infusion reaction to cemiplimab requiring discontinuation. A patient with metastatic cutaneous squamous cell carcinoma developed a severe hypersensitivity reaction to pembrolizumab and subsequently to cemiplimab, despite premedication.

Corticosteroid Use in Randomized Clinical Trials of Biologics and Small Molecules in Inflammatory Bowel Disease: A Systematic Review.

This systematic review aims to elucidate the use of corticosteroids in randomized clinical trials (RCTs) evaluating biologics and small molecules for inflammatory bowel disease (IBD). We analyzed corticosteroid use during both the induction and maintenance phases, highlighting areas needing standardization and improvement in clinical research. We selected placebo-controlled phase 3 RCTs involving adults with moderate to severe IBD. These studies included detailed reports on corticosteroid use during induction and maintenance phases, with clinical remission and/or corticosteroid-free clinical remission (CSF-CR) as primary endpoints. Initially, 324 studies were identified and refined to 26 RCTs after screening. Analysis revealed variability in corticosteroid administration. Over time, corticosteroid use showed a decreasing trend (Spearman ρ = -0.42, P = .045). Studies allowing higher corticosteroid doses (up to 40mg/day of prednisone or equivalent) reported a higher proportion of corticosteroid users (51.8%, range: 42.9%-61%) compared to those excluding patients on doses >20mg/day (37.5%, range: 31.6%-51.8%; P = .007) or >30mg/day (41.1%, range: 29.6%-53.7%; P=.023). Trials with mandatory tapering protocols showed a narrower gap between overall clinical remission and CSF-CR rates, with an average difference of 6% in the group without mandatory tapering and 1.2% in the group with forced tapering (T-test P=.038; Cohen's d ≈ 1.1). This review highlights the variability in corticosteroid use across RCTs and its impact on evaluating new IBD therapies. Standardizing tapering protocols and defining CSF-CR are essential for accurate outcomes.

Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma: Results From the Real-World US PATRIOT-II Study

IntroductionIn JAVELIN Bladder 100, avelumab first-line maintenance (1LM) improved overall survival (OS) and progression-free survival (PFS) in patients with locally advanced/metastatic urothelial carcinoma (la/mUC) without progression following 1L platinum-based chemotherapy (PBC) versus best supportive care. PATRIOT-II describes real-world outcomes with avelumab 1LM. Patients and MethodsThis observational, retrospective study of avelumab 1LM in US community/academic centers used medical record data collected from avelumab initiation for ≥12 months to assess survival, safety, and healthcare resource utilization; analyses are descriptive. ResultsThe study included 160 patients from 37 centers (median age, 70 years; 77% male). Avelumab 1LM was initiated at a median of 4 weeks (IQR 3-6) after PBC completion. Median follow-up from avelumab 1LM was 16 months (IQR 11-21). At study end, 19.4% of patients continued avelumab; 73.7% had discontinued due to progression, adverse events (AEs), or performance status deterioration. Median PFS and OS from avelumab initiation were 5.4 months (95% CI, 3.8-6.9) and 24.4 months (95% CI, 20.4-28.4), respectively. Grade ≥3 treatment-related AEs (TRAEs) occurred in 15 patients (9.4%); 35 (21.9%) had any-grade immune-related AEs, and 23 (14.3%) received high-dose systemic corticosteroids for AEs. Forty-four patients (27.5%) were hospitalized during the avelumab treatment period, of whom 13 (8.1%) were hospitalized due to TRAEs. Limitations of this study include a small sample size, potential selection bias, and missing/unknown data. ConclusionThese results align with the JAVELIN Bladder 100 clinical trial and other real-world studies, supporting avelumab 1LM use in patients with la/mUC without progression following 1L PBC.

The effect of corticosteroids in developing active pulmonary tuberculosis among patients with COVID-19.

Corticosteroids can reduce the mortality rate among patients with severe COVID-19 pneumonia. However, opportunistic infections such as Mycobacterium tuberculosis are of concern, especially among those on high doses of corticosteroids. It is unknown whether the risk of developing subsequent TB infection is high or not among COVID-19 patients on high doses of corticosteroids. Hence, this study was conducted to address this gap of knowledge. We conducted a retrospective, cross-sectional study at the King Chulalongkorn Memorial Hospital from October 12, 2022 to June 30, 2023. Two hundred forty-three participants with documented COVID-19 diagnosis on high dose corticosteroids were enrolled into the study. Baseline characteristics and risk factors of developing TB were collected. The prevalence of TB was significantly different among participants with chronic kidney disease (CKD) stages 2-4 and chronic lung diseases. The incidence of TB post 1-year diagnosis of COVID-19 was 4 out of 243 patients (1.6%) or 1,646 cases per 100,000 person-year. The mortality rate among subsequent TB group was significantly much higher than the non-TB group (50% vs 0.4%; p-value = 0.001). COVID-19 participants on high doses of corticosteroids also were co-infected with other infections such as bacteria (37.1%), fungi (5.3%), and Pneumocystis jirovecii (PJP) (1.2%). We found that the incidence of TB in participants with COVID-19 on high doses of corticosteroids was 11 times higher than the general population. Therefore, we recommend screening for latent TB among these patients to prevent/early diagnose TB disease.

Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma

We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 92.5 days (range: 22–210 days) after CAR-T therapy and a median of 85 days after cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis and villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR T-cell presence was confirmed within the lamina propria. Systemic corticosteroids were initiated in 10 patients (71%) a median of 25.5 days following symptom onset, with symptom improvement in 40%. Subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. Five patients (36%) have died from bowel perforation or treatment-emergent sepsis. In conclusion, IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1–3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.

New insights into the use of high dose corticosteroids and plasmapheresis in persons with MOGAD and NMOSD

BackgroundAnti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and neuromyelitis optica spectrum disease (NMOSD) are antibody mediated diseases characterized by neurological symptoms including recurrent relapses of optic neuritis and/or myelitis, as well as other less frequent syndromes. The current treatment for acute attacks of NMOSD/MOGAD are based on clinical studies for other demyelinating diseases(i.e. Multiple Sclerosis). In NMOSD, high dose corticosteroids (HDS) are considered the standard first line therapy, with emerging evidence supporting the use of plasmapheresis (PLEX) as an acute therapy. In MOGAD, being a relatively new clinical syndrome, the consensus on acute treatments is yet to be reached. The objective of our study was to assess the efficacy of treatment regimens (no treatment vs. HDS vs. HDS and PLEX) on disability outcomes in persons with NMOSD and MOGAD-optic neuritis and myelitis. MethodsWe retrospectively extracted data from the MuSicaL-NeMo database using a mixed Natural Language Processing followed by investigators verification. We assessed the change in Expanded Disability Status Scale (EDSS) and Visual Acuity (VA) following HDS and PLEX, in persons with MOGAD and NMOSD following myelitis and optic neuritis. We used the novel statistical measure Wilcoxon-Mann-Whitney Odd (WMW-Odd) to calculate the change through all the spectrum of each ordinal scale (VA and EDSS). ResultsEleven myelitis and 12 optic neuritis in 22 persons with MOGAD and 30 myelitis and 12 optic neuritis in 20 persons with NMOSD were included(15 Aquaporin-4 seropositive). In persons with MOGAD-optic neuritis the group receiving HDS had a WMW-Odd of 15.33(p ≤ 0.001), however those not receiving treatment also tended to improve (WMW-Odd=3.17, p = 0.06). NMOSD-optic neuritis treated with HDS only improve 33.3 % of the times (p=NS). Persons with MOGAD-myelitis receiving HDS significantly improved (WMW-Odd=7.33, p = 0.002). Persons with NMOSD-myelitis treated with HDS had an WMW-Odd of 2.56 (p = 0.002) and those treated with PLEX plus HDS (PLEX+), had similar WMW-Odd of 2.51 (p = 0.03). When correcting for disease severity by restricting inclusion to persons with NMOSD with EDSS≥4, both treatments showed a higher WMW-Odd, however the group receiving HDS continued to show higher WMW-Odd than the PLEX+ group(WMW-Odd= 3.75, p = 0.002 vs. WMW-Odd =3.05, p = 0.02, respectvely) ConclusionOur study suggests that persons with MOGAD-optic neuritis improve without acute treatments, however they have very marked improvement when using HDS, as previously suggested. Patient with MOGAD-myelitis are also very responsive to HDS, however, as compared to MOGAD-optic neuritis, they displayed less improvement, if not treated. In the NMOSD group the use of PLEX in addition to HDS did not demonstrate any significant difference in EDSS outcomes. Contrary to previous suggestions, when adjusting for group differences (by only including EDSS ≥4), the use of HDS and PLEX+ did not show better results than the group using HDS.

Fatal Case of Immune-Related Myocarditis and Myositis Due to Treatment with Immune Checkpoint and Tyrosine Kinase Inhibitors.

Immune checkpoint inhibitor and tyrosine kinase inhibitor combinations have become the new standard of care in the first-line treatment of metastatic clear cell renal cell carcinoma. However, there is a growing concern regarding severe immune-related adverse events. A 78-year-old man with metastatic clear cell renal cell carcinoma, treated with pembrolizumab and axitinib, was admitted to the emergency department 30 days after initiating treatment due to rapidly progressive myositis. Myocarditis with severe ventricular dysfunction was identified. Muscular biopsy findings were compatible with inflammatory myopathy associated with immune checkpoint inhibitors. Initial treatment with high-dose corticosteroids showed an insufficient response. Therapeutic escalation on the third day with methylprednisolone, immunoglobulin, and abatacept resulted in clinical improvement. On the eleventh day, a sudden malignant arrhythmia occurred, followed by cardiac arrest. This represents one of the first case reports describing myocarditis and myositis during treatment with pembrolizumab-axitinib. While immune checkpoint inhibitor may play a major role, it is also possible that the tyrosine kinase inhibitor, while attempting to promote immune modulation, also increases severe toxicities.

Adult-onset Still’s disease masquerading as acute coronary syndrome: a case report and review of the literature

IntroductionAdult-onset Still’s disease is a rare systemic autoinflammatory disease. We present a case of a young man with a constellation of symptoms and myopericarditis as a complication of this disease.CaseA 36-year-old Hispanic man with no significant past medical history developed a quotidian fever pattern following an upper respiratory tract infection. He initially presented with chest pain concerning for myocardial infarction and underwent cardiac catheterization, which revealed non-obstructive coronary artery disease. He was found to have myopericarditis, significant neutrophilic leukocytosis, and hyperferritinemia. He improved on high-dose corticosteroids but developed steroid-induced psychosis, and 4 months from symptom onset, he finally received tocilizumab, which eventually induced remission without adverse reactions.DiscussionAdult-onset Still’s disease should be considered in a patient with fevers of undetermined origin. Due to its multisystemic involvement, adult-onset Still’s disease is often a diagnosis arrived at after an extensive cardiac, hematologic, malignant, and infectious workup. Imaging, laboratory testing, and bone marrow biopsy were necessary to rule out alternative etiologies of this patient’s presentation. Steroids are the mainstay of treatment because they are easily affordable, although the high risk of adverse effects makes them less desirable. Interleukin-1 inhibitors (anakinra or canakinumab) and interleukin-6 inhibitor tocilizumab are the steroid-sparing biologic agents of choice but are cost-prohibitive.ConclusionAdult-onset Still’s disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays.

8264 An Interesting Case of Hypophysitis in a Young Woman

Abstract Disclosure: A. Garcia: None. R. Sharma: None. C.M. Knight: None. Background Hypophysitis is an uncommon disorder and presents with clinical signs and symptoms along with biochemical abnormalities. Herein, we present a case of hypophysitis that responded well to high dose steroids. Case An 18 y.o black, adopted woman presented to hospital with complaints of headache and vision disturbances. Endocrinology was consulted for pituitary macroadenoma. Symptoms started a month prior. She had extensive work-up at an outside hospital including brain imaging, CSF analysis, and bloodwork. No definitive diagnosis was made and she was sent home on topiramate. Her symptoms continued to worsen prompting her to seek another opinion. No family history as she is adopted. She has a history of depression controlled with medication. MRI Brain showed 1.8x1.1x1.6 cm T2-enhancing mass with suprasellar extension deforming the midline optic chiasm. Initially, a diagnosis of macroadenoma was made and Endocrinology and Neurosurgery services consulted. Patient denied galactorrhea, menstrual abnormality, polyuria, polydipsia, cold intolerance, orthostasis, or weight gain. Bloodwork was significant for low TSH (0.045 uIU/ml; normal 0.35-4.94), low free T4 (0.58 ng/dl; normal 0.76-1.79). Thyroid functions were normal approximately one year prior. Cortisol was very low at 1.8 mcg/dL and ACTH inappropriately low-normal at 12 pg/ml (normal 6-50). LH and estradiol were low, while FSH was low normal. Prolactin, GH, IGF-1, sodium, glucose and creatinine were normal. Endocrine reviewed the previous MRI brain done four weeks ago that was reported as normal. Discussion with previous outside hospital radiologist suggested that pituitary was indeed not normal but was fuller with convexity towards chiasm although no definitive adenoma was found. Since it is unlikely that such adenoma would develop over 4 weeks, Endocrinology reached out to our radiologist who assessed this as pituitary enlargement due to likely hypophysitis, especially when compared to imaging 4 weeks ago. Further work up showed mildly-elevated ESR, and normal ACE, dsDNA, ANA, and Sjogren’s antibody levels. Tests for pregnancy, Lyme disease, tuberculosis, EBV and syphilis were negative. SARS-CoV-2 was negative for COVID. IgG4 levels were normal. CSF analysis was normal. She was started on levothyroxine and high-dose corticosteroids with improvement in her symptoms. Repeat imaging after 5 days of corticosteroids showed about 30% decrease in pituitary size. A diagnosis of likely lymphocytic hypophysitis was made and pituitary surgery averted for time being. Conclusion We present a case of possible lymphocytic hypophysitis in a young woman who avoided pituitary surgery due to diligent history and examination, in addition to a multidisciplinary team approach. It is very important to have prompt multidisciplinary approach if there is any doubt about a diagnosis as in this case. Presentation: 6/3/2024