Steroid Taper Research Articles

Rapidly Progressive Aneurysmal Disease Associated with Epstein Barr Virus-Positive Lymphoproliferative Disease in a CVID patient with NFKB-1 Mutation

IntroductionCommon variable immunodeficiency (CVID) is a genetically heterogeneous group characterized by hypogammaglobulinemia and poor immune response to vaccines. CVID patients are at higher risk for autoimmune diseases or malignancy. We demonstrate a rare case of a patient with CVID (NFKB-1 mutation) presenting with features of vasculitis and rapidly progressive aneurysmal disease secondary to an Epstein Barr Virus (EBV)-associated lymphoproliferative disorder. Case descriptionA 36-year-old man with CVID presented with hoarseness and left vocal cord paralysis. Imaging revealed an aortic arch and descending thoracic aorta abnormality concerning for a plaque, vasculitis or focal thrombosed dissection. He later devloped severe back pain and imaging studies demonstrated an abdominal aortic aneurysm, thickening of the common iliac arteries and a focal aneurysm of the right common iliac artery. PET CT scan showed uptake in the upper abdominal aorta extending to the right renal artery and the distal abdominal aorta near the bifurcation extending to the right common iliac artery, concerning for large vessel vasculitis. He was started on high-dose steroids for large vessel vasculitis. One month later, he was hospitalized for disseminated histoplasmosis and disseminated varicella zoster virus (VZV) and started on amphotericin B and acyclovir with steroid taper. Whole exome next-generation sequencing (NGS) revealed NFKB-1 mutation consistent with CVID-12 with autoimmunity. He later developed worsening back pain prompting repeat imaging which showed further progression of his aneurysmal disease. He was also found to have EBV viremia with a titer of 33,700 IU/mL. A left superior gluteal artery biopsy was performed which showed evidence of an EBV+ lymphoproliferative disorder with concern for an EBV-positive fibrin-associated diffuse lymphoproliferative B-cell lymphoma (DLBCL). DiscussionCVID-12 is an autosomal dominant disease resulting from a mutation in NFKB-1. This mutation leads to an impaired immune response associated with recurrent infections and approximately 20% of patients developing lymphomas at some point in their lifetime. However, there are few case reports of CVID associated large vessel aneurysms or vasculitis. Our patient with CVID demonstrated a rare presentation of an EBV-positive lymphoproliferative disorder driving progression of large vessel disease.

Novel Presentation of a Mosaic STAT5B Gain-of-Function Variant

Somatic gain-of-function (GOF) variants in STAT5B have been described in leukemias and lymphomas, and more recently in three patients presenting with nonclonal eosinophilia, atopic dermatitis, diarrhea, and urticaria. Here, we describe a 7-year-old middle-Eastern female presenting with autoimmune adrenal insufficiency and lower extremity weakness. Diagnostic studies revealed CNS demyelination and demyelinating polyneuropathy of the motor nerves. CBC was notable for leukocytosis with eosinophilia, with peak AEC at 3100 cells/cumm. Immunophenotyping demonstrated normal IgG and subclasses and IgA, elevated IgM (233.1 mg/dL), and mildly elevated IgE (135 IU/ml). T cell lymphocytosis was noted on flow cytometry. Extensive infectious and autoantibody testing was unremarkable, and flow cytometry and cytology from CSF, blood, and bone marrow were not concerning for malignancy. She was treated with IV methylprednisolone and steroid taper, followed by rituximab and IVIG. Additional imaging demonstrated an enlarged thymus thought to represent rebound thymic hyperplasia, and splenomegaly. Trio whole exome sequencing performed on a buccal sample was notable for a de novo STAT5B c.1883C>G (p.Thr628Ser) variant present in 13/111 (–12%) of sequencing reads. This STAT5B variant has been reported in T cell prolymphocytic leukemia and studies have shown this variant confers GOF. Clinical evaluation for the STAT5B variant detected mosaicism in buccal swab DNA and near 50% variant allele frequency (VAF) in blood and bone marrow. We then assessed the VAF in various cells on a research basis. The VAF in buccal DNA was 7–9%, 46–48% in whole blood, and 48% in the bone marrow. Cell sorting for CD4+ and CD8+ T cells revealed a VAF of 46–48%. A similar VAF was observed in CD56+ cells (48%) and CD14+ cells (–50%). A fibroblast line was generated from a skin punch biopsy, and the variant allele was absent, suggesting somatic origin. Preliminary data from peripheral blood flow cytometric analysis demonstrated a slight increase in Treg cells, and Th2 skewing of Tregs as implied by cell surface markers. Assessment of pSTAT5 at baseline and after cytokine stimulation suggest increased responsiveness. The patient was started on tofacitinib, a JAK inhibitor primarily targeting JAK1/JAK3. She improved clinically, weaned on steroids, and is being evaluated for HSCT.

A Case of a Relapsing Remitting Macrophage Activating Syndrome After Covid-19 Vaccine In a Teenager with UNC13D Heterozygous Variant of Uncertain Significance

IntroductionMacrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case PresentationA 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron; however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. DiscussionMAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Display omitted] [Display omitted] [Display omitted]

Commentary: Behçet's uveitis - Expanding treatment horizons.

Behçet’s disease is a complex multisystem disease. A standalone positive typing for HLA-B51 is not considered diagnostic, and the diagnosis of this uveitic entity is based on a myriad of multisystem clinical signs that make up the diagnostic criteria.[1] The genetic predisposition to this disease afforded by HLA-B51 positivity (along with other non-HLA genes) has been postulated to get along with an altered microbiome in the gut of Behçet patients, with an additional possible contribution from infectious agents such as Streptococcus sanguinis, to trigger and then sustain an immune response, which disrupts a previously intact T-cell homeostatic environment. This recent understanding has expanded treatment horizons beyond standard treatment protocols, to include biologic therapy, especially tumor necrosis factor-alpha (TNF-α) antagonists, to achieve control of repeated disrupted immune response.[1] Progressive sight-threatening Behçet’s disease involving the entire uveal tract blinds up to 25% of patients within a course of 10 years, after which the disease progression tends to stabilize.[1,2] This mandates an excellent control of inflammation within this all-important “window period” to save the eye either from the direct inflammatory manifestations of Behçet’s uveitis or its potentially blinding complications.[1] The consensus in uveitis management in Behçet’s disease (according to the European Alliance of Associations of Rheumatology [EULAR] and the American Academy of Ophthalmologists’ guidelines) recommends limitation of steroid administration for control of acute inflammation and substituting steroids with conventional disease-modifying antirheumatic drugs (DMARDs) or biologic therapy. Furthermore, the American Academy of Ophthalmology goes a step further to recommend bypassing the “classic DMARDs” in favor of anti-TNF-α agents in severe, sight-threatening uveitis.[3] Thus, EULAR updated its guidelines in 2018 to recommend administering steroids in posterior segment ocular Behçet’s disease patients, but only in combination with steroid-sparing therapies such as azathioprine (AZA), cyclosporine A (CsA), interferon alpha, or monoclonal anti-TNF antibodies.[3] In the current study[4] of Behçet’s disease with ocular lesions from India, all patients have received steroids and 80% patients have been treated with immunosuppression along with steroids. Randomized controlled trials have shown that the antimetabolite AZA and T-cell inhibitor CsA are effective in the treatment of posterior uveitis in Behçet’s disease. Hence, the updated 2018 EULAR guidelines recommended the use of these two drugs (as against others) in the initial therapy of posterior uveitis.[3] Further, the combined use of AZA and CsA, whether as first- or second-line therapy, has shown efficacy in controlling ocular Behçet’s disease (with more periodic side effect monitoring).[1] In the current study from India, AZA and CsA have been combined in 24% of the patients.[4] In Behçet’s disease, TNF-α production by macrophages, CD4+ and CD8+ T cells, and natural killer cells is increased. The reduction of circulating TNF-α has been shown to result in dramatic improvement in the inflammatory activity of patients with severe pan or posterior uveitis.[1] These anti-TNF-α drugs used are recombinant monoclonal antibodies directed against TNF-α. Due to their potent and fast effects, these agents are now used alone or in combination therapy in refractory ocular Behçet’s cases, or sometimes even as first-line treatment in severe sight-threatening attacks.[3] Adalimumab (ADA) is a fully human monoclonal antibody directed against TNF-α and has been tested against a placebo in both active and quiescent, noninfectious uveitis (VISUAL I and VISUAL II studies, respectively). Ocular Behçet’s disease represented 7% of the uveitic cases enrolled in them.[1] Further, other uncontrolled studies have shown significant results regarding the efficacy of ADA in Behçet’s uveitis.[5] Early initiation of ADA in two children with Behçet’s uveitis succeeded in control of the disease activity, allowing tapering of topical and systemic steroids.[6] Comparative studies have been conducted between ADA and the other agent infliximab (IFX), notably a multicenter study on 177 patients with refractory Behçet’s disease uveitis, which found that both agents gave significantly better control in terms of disease activity as the first-line treatment, but the ADA group had higher percentage of patients with better best corrected visual acuity and fewer drug-related reactions.[7] One must remember that exclusion of tuberculosis and other infectious diseases as well as occult malignancies is mandatory before starting therapy with these agents. Also, an additional immunosuppressant (like methotrexate) may be advisable to prevent anti-chimeric, or antihuman, antibody production, which decreases the efficacy of these agents leading to secondary failure.[1] In the current study from India, biologic agents have been used in 40% of the patients; of which ADA was used in 28% and IFX in 12% of patients.[4] Finally, studies have recently reported success with Janus kinase (JAK) inhibitors in the treatment of noninfectious autoimmune uveitis refractory to conventional DMARDs and anti-TNF-α agents. Successful results have been reported with the JAK inhibitor tofacitinib in refractory Behçet’s disease uveitis,[8] and moving forward, these agents shall most likely further expand our treatment horizons for Behçet’s disease.

Nivolumab-induced Central Nervous System (CNS) Vasculitis Brought on by a Steroid Taper (P12-13.003)

<h3>Objective:</h3> To illustrate a case of nivolumab-induced CNS vasculitis that developed while tapering steroids and was successfully treated expectantly without immunosuppression <h3>Background:</h3> Immune checkpoint inhibitors (ICIs) with anti-PD-1/PD-L1 and anti-CTLA4 activity are associated with CNS vasculitis. Generally, both intra- and extracranial vasculitides are treated with steroids <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 75 year-old male received two months of concurrent chemoradiation with weekly carboplatin/paclitaxel for esophageal adenocarcinoma. Esophagectomy was considered, but the patient opted for active surveillance. Three years later, enlarging lung nodules heralded recurrent, metastatic esophageal cancer. Treatment with FOLFOX and nivolumab was initiated. Six months later, due to worsening fatigue, he was transitioned to nivolumab monotherapy. Over the following two weeks, he developed progressive dyspnea. Work-up suggested ICI-associated pneumonitis, and he was started on 50 mg prednisone, with weekly taper. A month later, at 30 mg daily, he developed confusion and was hospitalized. A brain MRI revealed multifocal lesions, some with ring-enhancement, concerning for metastases or abscess. Cerebellar biopsy demonstrated small-vessel CNS vasculitis, but given clinical improvement without treatment the patient was managed expectantly and returned back to baseline over two weeks <h3>Conclusions:</h3> This case of biopsy-proven ICI-associated CNS vasculitis developed while tapering steroids, and was treated conservatively. Steroids are first-line treatment for vasculitis; the development of vasculitis while tapering steroids thus raises the possibility of a rebound effect facilitating the development of vasculitis. Cases of CNS vasculitis that started while tapering steroids have been infrequently reported in the literature, but to our knowledge this is the first description of this phenomenon with ICI-associated CNS vasculitis. Additionally, this patient underwent biopsy with concern for metastasis or abscess, but ultimately did not necessitate treatment for vasculitis. This raises the possibility that active surveillance is a reasonable management strategy in cases of self-resolving ICI-associated CNS vasculitis <b>Disclosure:</b> Dr. Karbhari has nothing to disclose. Dr. Galindo Mendez has nothing to disclose. Dr. Robbins has received personal compensation in the range of $0-$499 for serving as a Consultant for Guidepoint Global Inc. The institution of Dr. Robbins has received research support from Diamond Endowment Fund. The institution of Dr. Robbins has received research support from Reeves Endowment Fund. The institution of Dr. Robbins has received research support from Institute for Ethnomedicine. The institution of Dr. Robbins has received research support from Dartmouth Hitchcock Swigart Ethics Fellowship. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Neurohospitalist with Hayes Locums. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vickery &amp; Shepherd. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vaccine Injury Compensation Program. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Kraft Davies PLLC. Dr. Robbins has received personal compensation in the range of $500-$4,999 for serving as a Medical Expert with Northwestern University.

Rare Case of Neurosarcoidosis presenting as Isolated Longitudinal Extensive Transverse Myelitis (LETM). (P9-5.006)

<h3>Objective:</h3> NA <h3>Background:</h3> Neurosarcoidosis is seen in only 5–16% of the patients with sarcoidosis. Incidence of longitudinal extensive transverse myelitis (LETM) in neurosarcoidosis is even rarer. <h3>Design/Methods:</h3> 37-year-old male with history of recurrent LETM and seizure disorder was admitted for worsening lower extremity weakness and unresponsiveness. History was significant for transverse myelitis diagnosed 8 months ago after presenting with lower extremity weakness and urinary incontinence. MRI of the spine at that time revealed focus of abnormal T2 signal in upper thoracic spinal cord extending from the mid T3 level inferiorly through the T5–6 level, with associated cord expansion. <h3>Results:</h3> Repeat MRI of the spine and brain showed progression of disease in the spine with nodular leptomeningeal enhancement most prominent within the posterior fossa. Extensive workup including neuromyeltitis optica, paraneoplastic panel, anti-aquaporin Ab and Anti-MOG Ab testing was negative. Patient was treated with steroids and plasmapheresis treatment (PLEX). PLEX treatments were held due to concern for infection. He was switched to steroid taper and biweekly Rituximab infusion. Rituximab infusions were stopped due to side effects and patient was trialed on mycophenolate mofetil. However, patient was transitioned back to steroid taper and rituximab infusion after worsening of symptoms. Patient eventually underwent meningeal biopsy which showed granulomatous leptomeningitis and parenchymal microglial activation. With strong suspicion for Neurosarcoidosis now based on accumulated evidence the patient was restarted on IV methylprednisolone and subsequent steroid taper. Improvement of his symptoms with partial recovery of strength was noted. Patient was subsequently transitioned to Leflunomide, infliximab infusions and steroid taper. Follow up MRI of the brain and spinal cord showing improvement in areas of enhancement. <h3>Conclusions:</h3> Our patient presented with neurosarcoidosis manifesting as LETM with no prior diagnosis of sarcoidosis or evidence of system involvement on further thorough workup. The diagnosis was challenging confirmed after a neural biopsy given absence of non-neurological manifestations. <b>Disclosure:</b> Dr. Khosa has nothing to disclose. Dr. Anandaram has nothing to disclose. Dr. Khosa has nothing to disclose. Dr. Buttar has nothing to disclose.

Amyloid beta-related angiitis in a patient with light chain systemic Amyloidosis: A rare co-morbidity. (P9-5.013)

<h3>Objective:</h3> To report a rare comorbidity of amyloid beta-related angiitis (ABRA) and systemic light chain amyloidosis (AL) <h3>Background:</h3> ABRA is a rare central nervous system (CNS) disorder with overlapping features of primary angiitis of the CNS and cerebral amyloid angiopathy. ABRA pathophysiology differs from extremely rare CNS involvement in AL. This is the first report of ABRA and AL comorbidity. <h3>Design/Methods:</h3> Case Report <h3>Results:</h3> A 73 year old Caucasian female with AL, prior autologous stem cell transplantation followed by relapse and daratumumab therapy resulting in complete response, presented with subacute development of headaches, global dysphasia and right sided homonymous hemianopia. Brain magnetic resonance imaging (MRI) demonstrated an increased T2/Fluid attenuated inversion recovery signal along the left parietal occipital cortex with mild restricted diffusion and microhemorrhages. Cerebrospinal fluid (CSF) studies showed: pleocytosis (30 nucleated cells/mm3) consisting of mature granulocytes, small mature lymphocytes and rare plasma cells, no monotypic B-cell, overtly aberrant T-cell, or expanded large granular lymphocyte population, no malignant cells; hyperproteinorachia (214 mg/dL); and no markers of intrathecal immunoglobulin G synthesis. Infectious CSF studies, CSF autoimmune encephalopathy panel and rheumatological work up were unremarkable. Steroid treatment (methylprednisolone, 1000 mg/day for 5 days intravenously, followed by a slow oral taper) led to a resolution in visual field deficit and a significant improvement in speech patterns. New microhemorrhages with new foci of restricted diffusion in the left posterior parietal/occipital region and posterior right centrum semiovale were shown on brain MRI three months later. Brain biopsy was performed with no neurological complications and pathology was consistent with ABRA. Liquid chromatography-tandem mass spectrometry of the brain tissue detected a peptide profile consistent with amyloid-beta precursor type amyloid deposition. The patient continued on oral steroid taper and is starting cyclophosphamide. <h3>Conclusions:</h3> Although ABRA is pathophysiologically distinct from and unrelated to AL, those two conditions may rarely co-exist. <b>Disclosure:</b> Dr. Javed has nothing to disclose. The institution of Dr. Jensen has received research support from ASCO / Conquer Cancer Foundation. The institution of Dr. Jensen has received research support from AHRQ. Dr. A Tuchman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shattuck Labs. Dr. A Tuchman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. An immediate family member of Dr. Allenzara has received personal compensation for serving as an employee of Atai . An immediate family member of Dr. Allenzara has stock in Atai company stock . An immediate family member of Dr. Ishizawar has received personal compensation for serving as an employee of EMD MilliporeSigma. Dr. Cho has nothing to disclose. Dr. Yap has nothing to disclose. The institution of Dr. Dujmovic Basuroski has received research support from Alexion Pharmaceuticals, Inc. The institution of Dr. Dujmovic Basuroski has received research support from Biogen MA Inc. The institution of Dr. Dujmovic Basuroski has received research support from EMD Serono Research and Development Institute, Inc . The institution of Dr. Dujmovic Basuroski has received research support from Celgene Corporation/Bristol-Myers Squibb. The institution of Dr. Dujmovic Basuroski has received research support from The Bodford Family Transverse Myelitis Center Fund.

HSV-2 Retinitis and Encephalitis Masquerading as Giant Cell Arteritis and Acute Ischemic Stroke of the Midbrain (P12-10.002)

<h3>Objective:</h3> To describe a unique case of stroke mimicry. <h3>Background:</h3> Non-vascular causes of acute neurological symptoms may clinically and radiographically mimic ischemic strokes. In the brainstem, such considerations are generally restricted to neoplastic, demyelinating, or infectious etiologies. HSV-2 may very rarely cause isolated mesencephalitis. <h3>Design/Methods:</h3> We describe a patient who presented with headache, arthralgias, and visual dysfunction who was initially diagnosed with giant cell arteritis (GCA) but was eventually found to have HSV-2 infection. <h3>Results:</h3> A 75-year-old man with past medical history notable for atrial fibrillation (on apixaban), hypertension, hyperlipidemia, and rheumatoid arthritis (on adalimumab) presented for evaluation of gait instability. Four weeks prior to presentation, he developed bitemporal headaches without visual symptoms and arthralgias. His rheumatologist checked an ESR (40) and ordered a temporal artery biopsy. He presented the day his apixaban was held prior to biopsy (1 week prior to this presentation) with right eye inferior visual field loss. Fundoscopy revealed disc edema felt consistent with anterior ischemic optic neuropathy. He was treated with pulse-dose steroids out of concern for GCA and underwent bilateral temporal artery biopsy before being discharged home on an oral steroid taper and resumed anticoagulation. CT, CTA, and MRI were reportedly normal and the biopsies were ultimately negative. He then presented this admission with gait instability and MRI exhibited a diffusion restricting lesion with T2-FLAIR hyperintensity without hemorrhage in the left cerebral peduncle. His visual symptoms progressed and he underwent right eye anterior chamber paracentesis with fluid resulting PCR positive for HSV-2. Subsequent CSF sampling also revealed lymphocytic pleocytosis and HSV-2 positivity. Despite maximal medical therapy, he lost vision in both eyes over a matter of weeks before developing Charles-Bonnet syndrome. <h3>Conclusions:</h3> HSV-2 encephalitis may cause mesencephalic, non-hemorrhagic, restricting lesions mimicking acute ischemic stroke. HSV may also cause a necrotizing retinitis, initially mimicking ischemic, even arteritic, optic neuropathy. <b>Disclosure:</b> Dr. Sutherland has received personal compensation in the range of $0-$499 for serving as a Consultant for McGraw-Hill. Dr. Gummerson has nothing to disclose. Dr. De Havenon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Integra. Dr. De Havenon has stock in Certus. The institution of Dr. De Havenon has received research support from NIH/NINDS. The institution of Dr. De Havenon has received research support from Regeneron Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMAG Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMGEN. Dr. De Havenon has received publishing royalties from a publication relating to health care.

A Rare Case of Bilateral Optic Perineuritis, Scleritis and Uveitis in a Pediatric Patient Following Influenza Vaccination (P1-9.007)

<h3>Objective:</h3> To present a rare case of bilateral optic perineuritis, scleritis and uveitis in a pediatric patient following influenza vaccination. <h3>Background:</h3> Optic perineuritis is a rare orbital inflammatory disease that typically presents with unilateral symptoms, but may be bilateral and is rare in children. Bilateral uveitis and scleritis are uncommon in children. Rarely, perineuritis, sceritis and uveitis have been reported following influenza vaccination. To our best knowledge, optic perineuritis, scleritis and uveitis occurring simultaneously following vaccination has not been reported. A seven-year-old female patient presented with two months of bilateral eye pain, vision loss, extreme photophobia and sleepiness that started two weeks following influenza vaccination. At presentation she had decreased visual acuity (VA) bilaterally (right, 20/100; left, 20/80), bilateral scleral erythema, and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain showed bilateral scleritis and optic perineuritis (left greater than right), with classic tram-track sign on axial view and donut sign on coronal view of the optic nerves. No other brain or cervical/thoracic lesions were seen. Serum antibodies to aquaporin 4, myelin oligodendrocyte glycoprotein, rheumatological work up and infectious studies were unremarkable. C-reactive protein and erythrocyte sedimentation rate were elevated. Routine cerebrospinal fluids findings were normal. The patient was treated with 2 g/kg of intravenous immunoglobulins (IVIG) followed by 30 mg/kg methylprednisolone intravenously (given insufficient response to IVIG), and oral steroid taper that is still ongoing (current dose: 12.5 mg/day). Methotrexate was started due to uveitis (25 mg once a week). Follow-up MRI of the brain one month after treatment initiation showed a significantly improved bilateral optic per neural enhancement and scleritis. Current VA is 20/30 bilaterally. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> Bilateral optic perineuritis, scleritis and uveitis can occur in a single pediatric patient and can potentially represent a post-vaccinal phenomenon. Timely recognition and treatment is important for visual outcomes. <b>Disclosure:</b> Dr. Wooten has nothing to disclose. The institution of Dr. Dujmovic Basuroski has received research support from Alexion Pharmaceuticals, Inc. The institution of Dr. Dujmovic Basuroski has received research support from Biogen MA Inc. The institution of Dr. Dujmovic Basuroski has received research support from EMD Serono Research and Development Institute, Inc . The institution of Dr. Dujmovic Basuroski has received research support from Celgene Corporation/Bristol-Myers Squibb. The institution of Dr. Dujmovic Basuroski has received research support from The Bodford Family Transverse Myelitis Center Fund. Dr. Sarkissian has nothing to disclose. Dr. Kostic has nothing to disclose. Dr. Javed has nothing to disclose. Jordan Broman-Fulks has nothing to disclose.

A Case of CNS Lymphoma Imitating Post-Vaccination ADEM (P14-13.003)

<h3>Objective:</h3> NA <h3>Background:</h3> A previously healthy 42-year-old male presented acutely with slurred speech, confusion and urinary incontinence several weeks after receiving a COVID booster and Tdap vaccination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> Initial workup revealed multifocal enhancing T2 white matter hyperintensities in the bilateral frontal/parietal lobes, corpus callosum and bilateral midbrain, sparing the cerebellum and spinal cord. Contrast enhanced CT of the chest, abdomen and pelvis showed no masses or lymphadenopathy. Cerebrospinal fluid analysis showed a mild lymphocytic pleocytosis (12) with normal RBC, protein, glucose, negative meningitis/encephalitis PCR, cytology and autoimmune encephalitis antibodies. Serum testing was negative for HIV, RPR, NMO, MOG and antinuclear antibodies. Working diagnosis of acute disseminated encephalomyelitis was made and he was started on IV methylprednisolone 1g daily for 5 days followed by an oral steroid taper with a weekslong improvement in symptoms to his neurologic baseline followed by relapse. We repeated MRI brain which demonstrated mixed response to treatment and two repeat CSF analyses showed 2 WBC with negative cytology. Given symptom recurrence, 1g daily IV methylprednisolone was re-administered for 5 days with another brief improvement, followed by IVIG 2g/kg over 5 days. Despite aggressive immunotherapy, his symptoms continued to worsen, and he was referred for brain biopsy confirming the diagnosis of primary diffuse large B-cell lymphoma of the CNS. At the direction of neuro-oncology, the patient underwent 6 cycles of systemic high-dose methotrexate and rituximab and 2 cycles of temozolomide with PET/MRI evidence of complete response (no lesion enhancement). His performance status improved significantly, and he underwent autologous hematopoietic stem cell transplant for consolidative therapy. <h3>Conclusions:</h3> CNS lymphoma should be considered in the differential for contrast-enhancing FLAIR hyperintensities and can be steroid responsive. Brain biopsy should not be delayed in cases where CNS lymphoma is a leading differential as it can guide early disease management and help improve patient outcomes. <b>Disclosure:</b> Dr. Frank has nothing to disclose. Dr. Alalami has nothing to disclose. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of an immediate family member of Dr. Livingston has received research support from Vertex. The institution of an immediate family member of Dr. Livingston has received research support from Roche. The institution of an immediate family member of Dr. Livingston has received research support from AstraZeneca. The institution of an immediate family member of Dr. Livingston has received research support from Enanta. Dr. Hu has nothing to disclose. Dr. Shadbehr has nothing to disclose.

Post-infectious Epilepsy from Probable Neurocysticercosis in a 32 Year Old Pregnant Female (P14-10.003)

<h3>Objective:</h3> To report a case of neurocysticercosis management in a first trimester pregnant female. <h3>Background:</h3> Neurocysticercosis is a parasitic infection known to be endemic to some countries and is a leading cause of acquired epilepsy worldwide. Available data on the diagnosis and management of neurocysticercosis infection in pregnancy remains limited. <h3>Design/Methods:</h3> Case report <h3>Results:</h3> A 32-year-old female presented with headaches after a camping trip in the Ozarks. MRI head revealed leptomeningeal hyperintensity in the left parieto-occipital junction. Three weeks later, she presented again with seizures and was 11 weeks pregnant. The semiology was right hand somatosensory to focal clonic, then generalized. She had recently travelled to South America. Neurological exam was significant for concentration difficulty, right pronator drift, finger extension weakness, and bradykinesia with dysdidokinesia in the right hand. MRI with and without contrast demonstrated one multi-cystic lesion in the left parietal lobe without a discernable scolex, with extensive surrounding vasogenic edema. Work up demonstrated peripheral eosinophilia, and unremarkable lumbar puncture (WBC 3). Lesion biopsy demonstrated eosinophils, demyelination, and inflammation of the meninges. Given the clinical and radiographic findings, suspicion for a parasitic infection was high on the differential and a diagnosis of probable Neurocysticercosis was made. Patient was managed with levetiracetam (with high dose folate), high dose IV steroids, and a prolonged oral steroid taper for vasogenic edema. Surveillance MRIs revealed slow improvement over weeks and complete resolution to a gliotic scar without calcification by six months. <h3>Conclusions:</h3> Neurocysticercosis represents a treatment challenge in pregnancy, given the teratogenicity of antiparasitic agents and the potential for acute worsening of peri-lesional edema. Symptomatic treatment aimed at controlling seizures and the inflammatory response can help support the immunocompetent pregnant patient in the right clinical setting, while the cysts undergo natural involution. <b>Disclosure:</b> Dr. Shamim has nothing to disclose. Dr. Nwabueze has nothing to disclose. Dr. Leever has nothing to disclose. Dr. Gronseth has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Brain &amp; Life. Dr. Gronseth has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. Dr. Gronseth has received personal compensation in the range of $0-$499 for serving as a Member/EBM consultant Guideline Development Subcommittee with AAN.

P029 Ocular syphilis: a mimicker for giant cell arteritis

Abstract Background/Aims Syphilis has seen a resurgence in the United Kingdom in recent years. It is a sexually transmitted disease caused by Treponema pallidum spirochaete infection, and typically presents as painless genital ulceration in its primary stage; left untreated it can progress rapidly to secondary and tertiary stages with multi-system involvement and wide-ranging symptoms, hence it being labelled ‘the great imitator’. We report a case of a patient presenting with classical features of giant cell arteritis (GCA), ultimately being diagnosed with neuro-ocular syphilis. Methods A 65-year-old man with a background of hypertension and migraines presented to our hospital with a 3-week history of temporal headache, scalp tenderness and jaw ache. He described lethargy, weakness and weight loss. On examination he had a prominent left temporal artery, with concurrent scalp tenderness; neurological and general medical examination were otherwise normal. Blood tests showed an erythrocyte sedimentation rate (ESR) of 66 and a C-reactive protein (CRP) of 115, leading to a strong clinical suspicion of GCA. He was commenced on 60mg of oral prednisolone with immediate improvement of his symptoms at this dose. Subsequent temporal artery ultrasound and temporal artery biopsy were negative for GCA. On tapering his steroids to 40mg he experienced partial relapse of his symptoms. Following Neurology review his steroid taper was adjusted to decrease more slowly. On 20mg of prednisolone the patient began experiencing stabbing retro-orbital pain and visual blurring, and was assessed by Ophthalmology with no local cause for his symptoms identified - he was therefore pulsed with intravenous methylprednisolone for a flare of GCA. Despite an initial response, the patient continued to experience intermittent symptoms on steroids; imaging with PET-CT did not show evidence of inflammation or malignancy and an MRI of his brain and orbits was normal. Results The patient eventually re-presented to Ophthalmology with floaters, pain and decreased vision and a spot diagnosis of posterior placoid chorioretinitis was made after retinal examination. Characteristic yellowish ovoid lesions confluent in the macular area were noted, as well as ellipsoid zone loss with nodular retinal pigment epithelium on optical coherence tomography (OCT) imaging. This condition is pathognomonic of neuro-ocular syphilis and serological testing confirmed the diagnosis, with a high rapid plasma reagin (RPR) titre of 1:512. He was treated with a course of intramuscular Ceftriaxone with a rapid resolution of his symptoms, and was successfully weaned off all steroid therapy. Conclusion Diagnosing GCA remains a clinical challenge for rheumatologists, especially in cases with typical symptoms and signs but negative confirmatory testing on imaging and histology. There are a wide range of conditions that resemble GCA, and neuro-ocular syphilis is one such diagnosis that has been reported in the literature as a mimic, as demonstrated by this important case. Disclosure S. Ali: None. S. Lekh: None. C. Tench: None.

Thygeson's superficial punctate keratitis in children.

To describe the first paediatric case series of Thygesons' superficial punctate keratitis (TSPK) with management outcomes. A retrospective chart review was done for all children either diagnosed at initial presentation or referred with TSPK from 01/2012 to 08/2021 at a tertiary children's hospital. Records were assessed for signs, symptoms, diagnosis, steroid and cyclosporine 0.05% use. The main outcome measures were visual acuity, treatment response and total steroid exposure. Fifteen children (7 females), mean age at presentation 8 ± 4 years were included. All had bilateral disease and a BCVA of >20/40 in the better eye. All patients received topical fluorometholone 0.1%, (FML) initially. 80% had a good response to FML. Corneal scraping was done to exclude infectious causes in four cases due to poor initial response or clinical suspicion. All 4 needed EUA for scraping and anterior segment OCT, after which 2 had molecularly confirmed TGFBI-related stromal dystrophy. For the rest, slow steroid taper was done every 4-6 weeks and recurrences were treated by increasing steroid frequency. Cyclosporine 0.05% was started in nine patients (69%), 8 ± 6 months after initial presentation. The decrease in total steroid exposure per week after starting cyclosporine was statistically significant (p < 0.05). Children with TSPK respond quickly to steroids, however, recurrences are common, necessitating a slow taper. Non-response to steroid needs careful reconsideration of the diagnosis and may necessitate the use of an EUA. Using cyclosporine 0.05% reduces the total steroid exposure in TSPK.

Choroidal Mass in a Patient with Undiagnosed Pulmonary Langerhans’ Cell Histiocytosis

ABSTRACT Background Langerhan cell histiocytosis (LCH), although not a common cause, should be kept in the differential diagnosis for a patient that presents with a choroidal mass. Case presentation A 28-year-old female presented with a 4-day history of vision loss and associated pain in her right eye. Examination and investigations A dilated fundus examination revealed a deep subretinal, orange, mottled lesion with associated serous retinal detachment. Ultrasonography demonstrated a solid mass at the posterior pole. Fluorescein angiography revealed corresponding, small, punctate, hyperfluorescent areas with leakage and pooling in the late phase outlining the subretinal fluid. Optical coherence tomography confirmed the choroidal elevation and subretinal fluid. In addition to starting oral steroids for addressing the patient’s acute symptoms, a metastatic workup was ordered due to the lesion’s appearance. Diagnosis: Computed tomography (CT) of the chest showed nodular lesions and subsequent lung biopsy was S-100 and CD1a positive, diagnostic of Langerhan’s cell histiocytosis (LCH). Treatment and outcome The patient was treated with six cycles of vinblastine and prednisolone therapy followed with a subsequent taper of steroids. Complete resolution of signs and symptoms was noted. Discussion A review of all reported cases of ophthalmic LCH with or without choroidal involvement was conducted. Diagnostic and therapeutic approaches described in these reportshave been summarized in the current manuscript. This case highlights the importance of pursuing a systemic workup in patients with uveal mass lesions. LCH should be considered in the differential of every choroidal mass.

Polyarteritis nodosa: a case report of isolated large bowel involvement and surgical intervention

Polyarteritis nodosa (PAN) is a necrotizing vasculitis commonly affecting small-sized vessels and medium-sized vessels. We present the case of surgical resection for ischemic colitis secondary to PAN. A 26-year-old woman presented with left lower quadrant pain, diarrhea and bloody stools. Colonoscopy showed diffuse circumferential ulceration and necrotic lining from the sigmoid colon to the splenic flexure. A subsequent computed tomography angiography (CTA) revealed left colonic wall thickening, hypoenhancement and multiple inferior mesenteric artery aneurysms, concerning for vasculitis. Ensuing laboratory workup all returned negative. Worsening pain, left-sided peritonitis, tachycardia and rising white blood cell necessitated a colectomy from the proximal descending to upper rectum with an end colostomy. Surgical pathology showed features consistent with PAN. The patient improved significantly after surgery and was discharged on a steroid taper and later started on mycophenolate mofetil. This case is a unique presentation of isolated large intestinal involvement and was treated with both medical and surgical interventions.

Steroid Use in the NICU: Treatment and Tapering

The adrenal gland cortex produces life-sustaining steroid hormones that are critical for the development and survival of the fetus and neonate. Antenatal and postnatal administration of steroids has critical therapeutic effects in preterm infants. However, prolonged postnatal steroid therapy for more than 1 to 2 weeks is associated with iatrogenic adrenal insufficiency and should prompt consideration of a steroid taper and stress dose precautions. In this review, we will describe fetal adrenal development and steroidogenesis, the effect of antenatal exogenous steroids, the therapeutic role of postnatal steroids, evaluation and treatment of adrenal insufficiency, and the role of steroid tapers after prolonged steroid treatment.

A Case of Bilateral Optic Neuropathy Following COVID-19 Infection

Purpose: To report a case of bilateral optic neuropathy after COVID-19 infection.Case summary: Thirty-four-year-old woman presented with bilateral ocular pain, visual disturbance, and decreased visual acuity after contracting COVID-19 infection 16 days ago. At the initial visit, best-corrected visual acuity was 0.8 in the right eye, and 0.7 in the left eye. Left eye had relative afferent papillary defect and visual field tests revealed enlarged blind spot in both eyes. Fundus exam showed bilateral optic disc swelling and peripapillary retinal hemorrhage along with vitreous hemorrhage in the left eye. Fluorescein angiography revealed bilateral leakage of dye from the optic disc with area of hypofluorescence corresponding to retinal hemorrhage around the optic disc in both eyes. Brain magnetic resonance imaging (MRI) showed ill-defined left optic nerve enhancement. A diagnosis of bilateral optic neuropathy was made, and the patient was treated with high dose IV steroid 1 g per day for 3 days and oral steroid tapering for 2 weeks. Disc swelling and retinal hemorrhage were improved 1 month after treatment along with enhanced visual acuity to 1.0.Conclusions: Bilateral optic neuropathy following COVID-19 infection showed improvement after steroid treatment.

Effect of Intravitreal Dexamethasone Implant Injection in a Patient with Recurrent Nodular Anterior Scleritis

Purpose: To report the use of intravitreal dexamethasone implant injection in a patient with recurrent nodular anterior scleritis.Case summary: A 16-year-old patient presented with persistent eye pain and conjunctival injection in the left eye, which were diagnosed as nodular anterior scleritis. The clinical features improved with topical and systemic steroid treatment, but the patient developed side effects related to steroid use, including elevated intraocular pressure and skin rash. The steroid dose was reduced which led to frequent recurrence. Immunosuppressive agents were added to the treatment regimen, but there was no improvement; the patient developed intermediate uveitis and vitreous hemorrhage. Scleritis and intermediate uveitis continued despite vitrectomy; therefore, intravitreal dexamethasone implant injection was performed. There was no scleritis recurrence within 1 year after injection, which allowed tapering of steroids and immunosuppressive drugs.Conclusions: Intravitreal dexamethasone implant injection may be effective for recurrent nodular anterior scleritis in patients who exhibit complications, such as intermediate uveitis.

A242 DELAYED STEROID TAPER MAY REDUCE RISK OF RELAPSE IN PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR ASSOCIATED HEPATOTOXICIT

Abstract Background Immune checkpoint inhibitors (ICI) have become the cornerstone of treatment of certain malignancies. However, they can result in systemic toxicities including hepatitis. Societal guidelines recommend initial management with high dose steroids, then a slow taper as hepatitis resolves. However, there is significant variation in steroid response with some patients experiencing a relapse of hepatitis as steroid doses are tapered (“steroid relapse”). Purpose Identify clinical features that predict relapse, and to explore variations in steroid management, in patients with ICI hepatotoxicity. Method Patients receiving ICI in early phase clinical trials at Princess Margaret Cancer Centre, or treated at the Toronto Centre for Liver Disease for ICI hepatotoxicity, were included. Patients with CTCAE Grade (G)3 ICI hepatotoxicity (ALT &amp;gt;5 x ULN) were identified and clinical records reviewed for management and outcomes. Patients with an alternate cause for ALT elevation; who did not receive corticosteroids; or with HCC or viral hepatitis, were excluded. Result(s) Between August 2012 and December 2021, 36 patients with G3 ICI hepatotoxicity were identified. Most (23; 64%) had metastatic melanoma. Thirteen received anti-CTLA-4/PD-1; 18 anti-PD-1 or anti-PD-L1, and 5 anti-CTLA-4 monotherapy. All patients initially received corticosteroids (1-2mg/kg/day methylprednisone equivalent). Thirteen patients (36%) were steroid relapsers. Consistent steroid response was seen in 18 (50%). Age, sex, liver metastases, prior ICI exposure, peak ALT or starting dose of steroids (≤1.5 vs &amp;gt;1.5mg/kg/day methylprednisolone equivalents) did not predict relapse, although relapsers were more likely to have been treated with combination anti-CTLA-4/PD-1 (7 (54%) relapsers, vs 3 (16%) responders, p = 0.02). Relapse occurred after a median of 14.5 days (range 8-111), and after taper to median 54% (5-100) of initial steroid dose. In responders, ALT normalisation occurred after median 14 days (range 3-56). In 27 patients where sufficient data were available, societal guidelines on ALT thresholds to initiate steroid taper were followed in 13 (48%; 6 relapsers and 7 responders). However, initiation of steroid taper was delayed in responders compared to relapsers (after median 7 days (2-15) in responders vs 4 days (range 2-9) in relapsers, p = 0.04). Overall, 5 relapsers responded to re-escalation of steroids. Eight required additional treatment with MMF, and 4 required 3rd line therapy with Tacrolimus. Ultimately, hepatitis resolved in all patients. Conclusion(s) In patients with ICI hepatotoxicity, combination ICI therapy confers a higher risk of steroid relapse than monotherapy. There is significant heterogeneity in management of steroid dosing in patients with ICI hepatotoxicity. Delayed initiation of steroid taper may be associated with a reduced risk of relapse and warrants prospective evaluation as part of a standardised management algorithm. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Clinical Features and Outcomes of Japanese Patients with Giant Cell Arteritis: A Comparison with Takayasu Arteritis.

Giant cell arteritis (GCA) and Takayasu arteritis (TA) are distinct types of large-vessel vasculitis; however, the clinical features of the diseases have some similarities. Limited data are available regarding Japanese patients with GCA and TA. The present study aimed to compare the clinical features and outcomes of Japanese patients with GCA and TA and the effects of large vessel involvement (LVI). We performed a retrospective cohort study of the patients with GCA (n = 15) and TA (n = 30) who visited our department from April 2012 to June 2022. Signs and symptoms attributed to the disease, treatment, clinical outcomes, and mortality were recorded using a standardized database. The median age of onset was significantly higher in the GCA group at 24 years (range, 16-72 years) in the TA group and 77 years (range, 57-89 years) in the GCA group (p < 0.001). There were no significant differences in survival rates or the cumulative rates of cardiovascular events between the GCA and TA groups. However, relapse-free survival rates were significantly higher in patients with GCA than in patients with TA. Seven of the 15 patients with GCA had large vessel involvement, which did not affect the survival rates. Prednisolone (PSL) doses were significantly decreased after induction therapy in both groups, and the rates of achieving steroid tapering (PSL < 5.0 mg/day) were significantly higher in patients with GCA compared with those in patients with TA. Our study demonstrated no significant difference in the survival rates of Japanese patients with GCA and TA. The relapse-free survival rates were significantly higher in the GCA group than in the TA group. LVI may not be associated with disease relapse or survival rate in Japanese patients with GCA.