High-dose Intravenous Steroids Research Articles

Serum neurofilament light chains in progressive multiple sclerosis patients treated with repeated cycles of high-dose intravenous steroids.

Background and objectives: In progressive multiple sclerosis (MS) patients, CNS inflammation trapped behind a closed blood brain barrier drives continuous neuroaxonal degeneration, thus leading to deterioration of neurological function. Therapeutics in progressive MS are limited. High-dose intravenous glucocorticosteroids (HDCS) can cross the blood-brain barrier and may reduce inflammation within the CNS. However, the treatment efficacy of HDCS in progressive MS remains controversial. Serum neurofilament light chains (sNfL) are an established biomarker of neuroaxonal degeneration and are used to monitor treatment responses. We aimed to investigate whether repeated cycles of intravenous HDCS reduce the level of sNfL in progressive MS patients. Methods: We performed a monocentric observational study of 25 patients recruited during ongoing clinical routine care who were treated with repeated cycles of intravenous HDCS as long-term therapy for their progressive MS. sNfL were measured in 103 repeated blood samples (median time interval from baseline 28 weeks, range 2-55 weeks) with the Single Molecular Array (SiMoA) technology. The Expanded Disability Status Score (EDSS) was documented at baseline and follow-up. Results: The median age of patients was 55 years (range 46-77 years) with a median disease duration of 26 years (range 11-42 years). sNfL baseline levels at study inclusion were significantly higher in progressive MS patients compared to age-matched healthy controls (median 16.7 pg/ml vs 11.5 pg/ml, p=0.002). sNfL levels showed a positive correlation with patient age (r=0.2, p=0.003). The majority of patients (72%, 16/23) showed reduced sNfL levels ≥20 weeks after HDCS compared to baseline (median 13.3 pg/ml, p=0.03). sNfL levels correlated negatively with the time interval from baseline HDCS therapy (r=-0.2, p=0.03). This association was also evident after correction for treatment with disease-modifying drugs (adjusted R2=0.10, p=0.001). The EDSS remained stable (median 6.5) within a median treatment duration of 26 weeks (range 13-51 weeks). Conclusion: Although larger studies are needed to confirm our findings, we were able to demonstrate that HDCS treatment reduces sNfL levels and therefore may slow down neuroaxonal damage in a subgroup of patients with progressive MS. Moreover, a stable EDSS was observed during therapy. Findings suggest that HDCS may be beneficial for the treatment of progressive MS.

927: DABBING LUNG INJURY MANAGED BY VV ECMO

Introduction: E-cigarette or vaping-associated lung injury (EVALI) is an uncommon complication of e-cigarettes or vaping. Most cases are associated with tetrahydrocannabinol (THC) containing products. “Dabbing” refers to the process of ingesting high concentrations of THC-containing oils or waxes with butane solvents to vaporize cannabinoids for inhalation. Another distinction is the presence of impurities and unpurged butane in the vapors inhaled by the users. Description: A 29-year-old male presented with cough, dyspnea, and fever seven days prior to admission. He reported smoking marijuana but denied vaping. Initial chest radiograph demonstrated multifocal pneumonia. PCR for SARS-CoV-2 was negative. He required four liters of supplemental oxygen. Physical exam was remarkable for diffuse pulmonary crackles. Broad spectrum antibiotics for pneumonia were initiated. Oxygen requirements rapidly increased, prompting intubation 48 hours from presentation. Ventilator settings escalated to a positive end-expiratory pressure of 18 cm H2O with 100% FiO2. Computed tomography angiography ruled out pulmonary embolism, however showed diffuse patchy nodular and confluent opacities. Respiratory cultures grew commensal flora and blood cultures were negative. Comprehensive laboratory investigations for an infectious etiology and autoimmune vasculitis were negative. In further discussion with the patient’s wife, he has been “dabbing” for the past six months. High dose intravenous steroids were initiated. The patient continued to have refractory hypoxemic and hypercapnic respiratory failure with ARDS requiring prone positioning. The patient ultimately required transition to veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patient received 12 days of VV-ECMO and was eventually liberated after 19 days of ventilator support. At discharge he was asymptomatic, at his baseline level of function, and required no supplemental oxygen. He was discharged on daily steroids with a taper and outpatient follow-up. Discussion: The necessity of VV-ECMO utilization in “dabbing” associated acute lung injury represents a rare severe presentation. Dabbing is emerging as a trend among young adults and represents an under-investigated cause of severe inhalational lung injury.

Prognostic Factors for Visual Outcomes in Acute Anterior Optic Neuritis Using Optical Coherence Tomography

Purpose: To identify the clinical characteristics and predictors of visual outcomes in acute anterior optic neuritis patients treated with high-dose steroid pulse therapy using spectral domain optical coherence tomography (SD-OCT).Methods: In this study, the medical records of 34 acute anterior optic neuritis patients treated with intravenous high-dose steroid pulse therapy and followed-up for at least 3 months were retrospectively reviewed. The patients were divided into two groups based on the final best-corrected visual acuity (BCVA); group 1 (n = 23) had a final BCVA ≥20/32, while group 2 (n = 11) had a final BCVA <20/32. Clinical characteristics and optical parameters obtained using SD-OCT were evaluated to identify factors influencing the final visual outcome.Results: There were no statistically significant differences in clinical or demographic data between the two groups. Peripapillary retinal nerve fiber layer (pRNFL) swelling at initial presentation was less common (p = 0.015), and the time to pRNFL thickness stabilization was longer (p = 0.016), in group 1. Multivariate logistic regression demonstrated better final visual acuity for patients in whom pRNFL thickness stabilization took longer, as well as in those with a smaller reduction in macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and those without recurrence (p = 0.002, 0.016, and 0.035, respectively).Conclusions: Intravenous high-dose steroid pulse therapy much improved long-term visual outcomes in acute anterior optic neuritis patients with delayed pRNFL thickness stabilization, a smaller mGCIPL thickness reduction, and no recurrence. This suggests that inner retinal layer thickness and recurrence after stabilization may serve as biomarkers for final visual acuity after intravenous steroid treatment in acute anterior optic neuritis.

P33 The successful use of Belimumab in recurrent small bowel obstruction secondary to Lupus Enteritis

P33 The successful use of Belimumab in recurrent small bowel obstruction secondary to Lupus Enteritis

Clinical Characteristics of Patients with Euthyroid Thyroid-associated Ophthalmopathy

Purpose: To compare clinical features between thyroid-associated ophthalmopathy (TAO) patients with hyperthyroidism and euthyroidism.Methods: Between September 2015 and January 2021, we enrolled 96 TAO patients with euthyroidism (n = 16) or hyperthyroidism (n = 80). We recorded the age, sex, smoking status, presence of hypertension and diabetes, total follow-up period, unilateral involvement, eyelid edema, lid lag and retraction, clinical activity score (CAS), modified NOSPECS score, exophthalmometry, Hess test, area of extraocular muscles on orbital computed tomography (CT), treatment with systemic and subconjunctival steroids and radiotherapy, and serum levels of free thyroxine, thyroid-stimulating hormone (TSH), anti-thyroglobulin antibody (anti-Tg Ab), anti-thyroid peroxidase antibody (anti-TPO Ab), TSH receptor antibody (TSHR Ab), and thyroid stimulating antibody.Results: Unilateral involvement was significantly more common in the euthyroid group, while conjunctival injection, CAS, extraocular muscle movement restriction within 10° on the Hess chart, maximum cross-sectional area of the inferior rectus on orbital CT, and treatment with intravenous high-dose steroid were significantly more common in the hyperthyroid group. Furthermore, the modified NOSPECS score and levels of free thyroxine, anti-Tg Ab, anti-TPO Ab, and TSHR Ab were significantly higher in the hyperthyroid than euthyroid group.Conclusions: Compared to hyperthyroid TAO patients, those with euthyroid TAO were more likely to have unilateral involvement. They also had lower clinical activity and severity, milder enlargement of extraocular muscles (EOMs), and lower rates of EOM movement restriction and treatment with intravenous high-dose steroid. Euthyroid TAO patients had lower levels of free thyroxine, anti-Tg Ab, anti-TPO Ab, and TSHR Ab compared to hyperthyroid TAO patients.

Isolated Central Nervous System Vasculitides in COVID-19: A Systematic Review of Case Reports and Series

Cerebral vasculitides, both isolated or in systemic disorders, could be triggered by infections, and few cases have been associated to coronavirus disease 2019 (COVID-19). This study searched for publications in Pubmed, EMBASE, and Cochrane library databases for case reports and series of isolated central nervous system (CNS) vasculitides triggered by severe acute respiratory syndrome coronavirus-2. We included 12 studies (published from June 2020 to July 2022) and collected 39 adult patients (5/39 pathologically or radiologically proven, 34/39 suggestive for primary CNS vasculitis or PCNSV). All cases had a positive real-time polymerase chain reaction on a nasopharyngeal swab or a respiratory tract specimen. About the 85% of the included cases were males, and disease onset occurred later than 50 years old in all but three subjects. In total, 33/39 patients presented severe COVID-19 pneumonia, frequently requiring intensive care unit care. The most common neurological features were headache, obnubilation, and coma. PCNSV was suspected mainly on radiological findings, whereas the cerebrospinal fluid analysis was minimally altered. Magnetic resonance imaging showed vessel wall enhancement in 32/39 cases, generally with the concomitant presence of microbleeds, subarachnoid haemorrhages, and/or multiple ischemic lesions. Despite the severe respiratory and neurological disease course, most cases (93%) improved spontaneously or after a course of high-dose intravenous steroids with no need for immunosuppression. In conclusion, PCNSV could rarely relate to COVID-19 and independently from pulmonary disease severity. Adults with COVID-19-related PCNSV could have a favourable prognosis.

A Case of Choroidal Folds in a Patient with Immunoglobulin G4-related Ophthalmic Disease

Purpose: To report a case of choroidal folds caused by enlargement of the extraocular muscles (EOM) and orbital fat in a patient with immunoglobulin (Ig) G4-related ophthalmic disease. A full recovery was achieved after steroid administration.Case summary: A 56-year-old male received intravenous high-dose steroids to treat IgG4-related ophthalmic disease presenting with bilateral eyelid edema, hypertrophy of all EOM, and mild exophthalmos. After 3 months, only slight improvement was observed and azathioprine was initiated. The patient exhibited only a minimal response over the next 2 months; all medications were therefore stopped. One month later, the patient presented with aggravation of the swelling (both eyelids), exophthalmos, and visual impairment of the left eye. The corrected vision was 1.0 in the right eye and 0.2 in the left eye; choroid folds were observed in the posterior pole of the left eye. Intravenous steroid (500 mg) was given once and oral steroids prescribed as maintenance therapy. After 2 weeks, the corrected visual acuity recovered to 1.0 in both eyes, the eyelid edema and exophthalmos improved and the choroidal folds resolved completely.Conclusions: Choroidal folds associated with enlargement of EOM and orbital fat tissue can cause visual impairment in patients with IgG4-related ophthalmic disease. Steroids are effective in the acute phases and prevent irreversible visual impairment.

Traumatic Optic Neuropathy Aggravated by Orbital Emphysema after Orbital Fracture

Purpose: To report a case of traumatic optic neuropathy aggravated by orbital emphysema after an orbital fracture.Case summary: A 19-year-old man with no specific medical history was referred for a right orbital fracture caused by blunt trauma to the supraorbital rim of the right eye. Computed tomography (CT) showed a right orbital fracture involving the inferomedial wall and inferomedial strut. The corrected visual acuity was 0.4 in the right eye (RE) and 1.0 in the left and the intraocular pressure was 15 and 18 mmHg, respectively. Restriction on downgaze, abduction, and an indefinite relative afferent pupillary defect (RAPD) were observed in the RE. Fundus exam was non-specific other than commotio retinae on the temporal side of the macula in the RE. After 12 hours post trauma, the visual acuity of the RE had decreased to light perception. Definite RAPD was observed with optic disc swelling on the fundus photo and optical coherence tomography. Orbital CT showed air shadows, which were not seen on the initial evaluation, adjacent to the optic disc. We diagnosed traumatic optic neuropathy aggravated by orbital emphysema. High-dose intravenous steroid was given for 3 days. Despite a lateral canthotomy and cantholysis to decompress the right orbit, visual acuity did not improve above counting fingers.Conclusions: Increased intraorbital pressure and congestion caused by orbital emphysema may exacerbate traumatic optic neuropathy. Therefore, close observation is required.

Gastric cancer complicated by paraneoplastic neurological syndrome which presented with extremity numbness: a case report

BackgroundParaneoplastic neurological syndromes refer to a group of neurological disorders, which occur as distant effects of malignant tumors and are not caused by metastasis, nutritional disorders, or side effects of antitumor drugs.Case presentationA 70-year-old woman complained of a 1-month history of extremity numbness. Upon presentation to our hospital, she had worsening numbness, and experienced staggering and falling. Physical examination revealed diminished tendon reflexes in both lower limbs, stocking and glove-type abnormal sensation, and left-sided dominant high-steppage gait due to weakness of the bilateral tibialis anterior muscles. Blood tests indicated anemia, and upper gastrointestinal endoscopy revealed gastric cancer, leading to laparoscopic distal gastrectomy. A nerve conduction velocity test showed demyelinating peripheral neuropathy. Further blood tests and imaging studies ruled out nutritional disorders, such as vitamin deficiency, diabetes-related diseases, connective tissue diseases, and central nervous system metastasis, leading to the suspicion of paraneoplastic neurological syndrome. After laparoscopic distal gastrectomy, the progression of symptoms stopped, and with intravenous high-dose immunoglobulin and steroid therapy, the symptoms improved to only minor numbness in the peripheral limbs as of the 18-month follow-up. As of the 2-year follow-up, there has been no cancer recurrence or metastasis.ConclusionsWhen paraneoplastic neurological syndrome is suspected, early diagnosis and a multidisciplinary approach, including surgical treatment, are important before irreversible neurological damage occurs.

P047 The triple M threat of check-point inhibitors - an emerging overlap syndrome

Abstract Background/Aims The objective of this abstract is to raise awareness on an emerging overlap syndrome of life-threatening immune-related adverse events, manifesting as a triad of myositis, myocarditis and myasthenia gravis in immune check-point inhibitor (ICI) treated patients. It highlights the success of combination, aggressive and prompt immunosuppression with high dose intravenous steroid, cyclophosphamide, rituximab and intravenous immunoglobulin therapy, in two patients presenting at Guy’s and St Thomas’s Hospital, London with this overlap syndrome following pembrolizumab therapy. Methods Case presentation. Case 1: 75-year-old Caucasian gentleman receives one dose of pembrolizumab for metastatic melanoma. Two weeks later, he presents with myalgia, weakness, elevated CK 10,000. Troponin T is raised 459, ECG shows right bundle branch block (RBBB) and on day 3, he rapidly descends into complete heart block then cardiac arrest. Return of spontaneous circulation is obtained and a permanent pacemaker (PPM) inserted. On day 6, myocardial biopsy confirms acute myocarditis. He develops progressive muscle weakness, dysphagia and Type 2 respiratory failure. He receives 3 doses of IV methylprednisolone, in addition to intravenous immunoglobulins (IVIG) and intravenous cyclophosphamide. EMG shows mild myopathic features, positive AChR antibody, SSA/Ro60 and myositis-specific SRP antibodies and he becomes dependent on non-invasive ventilation. He commences pyridostigmine for myasthenia gravis. On day 19 two doses 1g Rituximab two weeks apart is administered. Monthly IVIG continues for three months and he completes 6 cycles of 500mg cyclophosphamide. A year following discharge, he is maintained on prednisolone 5mg OD with no additional immunosuppression and significantly improved muscle strength. Case 2: 77-year-old Caucasian gentleman receives one dose of pembrolizumab for metastatic melanoma. Four weeks later, he presents with myalgia, bilateral ptosis, muscle weakness and breathlessness. Bloods show CK 6467, troponin T 1058. He promptly receives 3 doses of IV methylprednisolone in addition to IVIG. A PPM is inserted electively as ECGs show RBBB and intermittent bradyarrhythmias. His anti-Ro/SSA-52 antibody is positive and AChR and myositis-specific antibodies are negative. He trials neostigmine due to persistent ptosis. On Day 6, muscle biopsy confirms immune-mediated necrotising myositis and he commences intravenous cyclophosphamide 500mg followed by 5 further cycles. On day 7, 1g intravenous rituximab is administered and repeated two weeks later, additional to monthly IVIG for five months. 6 months later, his CK has normalised and he has no residual muscle weakness. Results n/a Conclusion Although a rare complication of ICIs, this triad of myositis, myocarditis and myasthenia gravis can be potentially severe and fatal. With ICI reshaping the prognosis of several cancers and pembrolizumab gaining recent further approvals, we will increasingly encounter this therapeutic challenge. Therefore, raising awareness of this overlap syndrome amongst rheumatologists is even more critical to allow for prompt recognition and treatment with immunosuppression. Disclosure A. Mootoo: None. A. Masood: None. P. Maghsoudlou: None. D. D'Cruz: None.

A Fatal Case of Nocardia Bacteremia in a Lung Transplant Recipient

<h3>Introduction</h3> <i>Nocardia</i> bacteremia is an extremely rare disease. Although closely associated with immunocompromised states, only a few cases have been reported after lung transplant (LT). <h3>Case Report</h3> We present a case of <i>Nocardia</i> bacteremia in a 75-year-old man after bilateral LT (11/2017) for combined pulmonary fibrosis and emphysema. Nearing 3 years posttransplant, pulmonary function tests (PFTs) revealed an obstructive pattern with downtrending FEV₁ from baseline; work-up for acute cellular rejection, infection, and antibody-mediated rejection was unremarkable. Serial PFTs ultimately suggested CLAD-BOS phenotype, and he received photopheresis with some stabilization. However, over the next 2 months, he required 2 hospital admissions with need for high-dose intravenous steroids given hypercapnia in the setting of underlying rejection. At 38 months posttransplant, he developed lower extremity cellulitis and new-onset anorexia, generalized weakness, and rapid decline in mental status with need for a third hospitalization and mechanical ventilation with vasopressor support. Infectious work-up and empiric broad-spectrum antibiotic coverage were initiated. Within 12 hours, both blood cultures were positive for <i>Nocardia cyriacigeorgica</i> (Gram stain, <b>Figure A</b>). Meropenem and trimethoprim/sulfamethoxazole were substituted without clinical improvement over the next several days. Brain MRI ruled out cerebral nocardiosis; chest CT showed bibasilar consolidations with air space opacities. An echocardiogram estimated a left ventricular ejection fraction between 20-25% with severe diffuse hypokinesis, likely stress-induced cardiomyopathy, with no evidence of vegetations. Bronchoscopy revealed superinfection with pan-sensitive <i>Pseudomonas</i> spp, without isolation of <i>Nocardia</i> spp. The patient deteriorated and died 39 months after transplant. <h3>Summary</h3> <i>Nocardia</i> bacteremia, scarcely reported in LT recipients, portends a poor prognosis despite aggressive combination antimicrobial therapy.

Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders-Experience from Tertiary Care Center in North India.

Therapeutic plasma exchange (TPE) is indicated in the acute presentation of neuromyelitis optica spectrum disorders (NMOSD) as category II indication as per American Society for Apheresis guidelines 2016. To assess the efficacy of TPE in symptomatic patients of NMOSD not responding to high dose intravenous steroids. We retrospectively reviewed the record of TPE procedures in NMOSD patients over a period of 3 years (2013-2016). TPEs were done on Cobe® spectra (Terumo BCT, Lakewood Co., USA) using 5% human serum albumin or fresh frozen plasma as replacement fluid. Clinical improvement was recorded post-procedure and adverse reactions if any was noted. We performed TPE in 11 clinically diagnosed patients of NMOSD. Three (27%) patients had only visual symptoms, five (46%) had both visual as well as muscular symptoms, whereas three (27%) patients presented with only muscular symptoms. Out of seven tested, three patients were aquaporin-4-immunoglobulin-G-positive (AQP4-IgG positive). Visual symptoms improved from no vision pre-TPE therapy to finger counting or 6/24 post-therapy.The muscle power of the limbs improved by grade one to grade two post-therapy. Adverse events were observed in 8% (5/62) of the procedures; allergic reactions to replacement fluid as the most common event (n = 3) followed by hypotension (n = 2). Follow-up was available in 81% (9/11) patients. Two patients died at 3 and 12 months of follow-up. One patient had relapsed and underwent a second TPE cycle. The addition of TPE as a part of therapy is effective and safe in acute exacerbations of NMOSD.

A prospective study on tryptophan immunoadsorption in AQP4 antibody-positive neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) is a rare inflammatory demyelinating disease of the central nervous system. NMOSD pathogenesis is mainly mediated by antibodies directed against aquaporin4 (AQP4 antibody). Immunoadsorption (IA) could specifically remove pathogenic antibody to alleviate the disease. Until now, prospective studies concerning the efficacy of IA on NMOSD are scarce. This study aims to prospectively evaluate the efficacy and safety of IA in the treatment of NMOSD. We included patients with AQP4 antibody-positive NMOSD who were hospitalized from September 2019 to September 2020, with no significant improvement in symptoms after 1 week of high-dose intravenous steroid therapy. Tryptophan IA therapy was initiated with five sessions on alternate days. Expanded Disability Status Scale (EDSS), visual acuity, and laboratory values were measured before and after IA, with a follow-up of 6months. Spinal magnetic resonance imaging (MRI) characteristics were collected. Related side effects were recorded. Seven patients were enrolled in the present study. After five IA, the patients' EDSS decreased from 5.71 ± 2.04 to 4.64 ± 2.29, P=.006. The visual acuity of the three visually impaired patients was improved. AQP4-IgG decreased significantly from 80.00 (interquartile range [IQR], 21.00-80.00) (U/mL) to 9.72 (IQR, 5.21-55.57) (U/mL) (P=.018). MRI of the spinal cord showed the scope of the myelopathy was narrowed and no significant enhancement was observed on postcontrast T1-weighted image at 90 days after treatment. Only one patient had transient hypotension. Tryptophan IA therapy effectively and safely improved neurological function and visual acuity, and reduced the AQP4 antibody concentration in patients with NMOSD.

Case of multiple sclerosis presenting as unilateral internuclear ophthalmoplegia

A 30-year-old female presented with complaints of decreased vision and diplopia since 1 week along with headache and gait disturbances. Examination revealed medial restriction of ocular movements in the right with left abducting nystagmus suggestive of right-sided internuclear ophthalmoplegia and right-sided facial palsy. The patient was admitted under neurology as a suspected case of demyelinating disorder. Magnetic resonance imaging with gadolinium contrast revealed features suggestive of probably multiple sclerosis (MS). The patient was given 5 days of high-dose intravenous steroids following which the patient showed improvement and was discharged on multivitamins. Subsequent follow-up showed significant improvement in symptoms, visual acuity, and ocular movements. Hereby presenting a rare case of MS presenting as unilateral internuclear ophthalmoplegia.

Successful Treatment with ALVR105 for Disseminated Adenovirus Infection in an Infant after Allogeneic Hematopoietic Cell Transplantation: A Case Report

Background: Adenovirus (AdV) disease is one of the most difficult-to-manage complications in infants and children who have received allogeneic hematopoietic cell transplantation (HCT). Cidofovir has been used off-label as preemptive anti-adenoviral therapy. It is the current standard of care treatment, but data supporting its therapeutic value are lacking, and its use is limited by severe renal toxicity.Case: A 10-month-old male with infantile osteopetrosis underwent a single-unit umbilical cord blood transplant (TNC = 21.78 × 10 7/kg, CD34 = 10.5 × 10 5/kg) after myeloablative conditioning (busulfan, cyclophosphamide, and anti-thymocyte globulin). Cyclosporine and mycophenolate mofetil (MMF) were used for graft versus host disease (GVHD) prophylaxis. A positive test for adenovirus from a respiratory viral panel pre-transplant delayed conditioning for six weeks until the patient had two negative tests, one week apart. His post-transplant course was complicated by severe veno-occlusive disease starting on day +3, with secondary respiratory and renal failure. The patient was started on continuous renal replacement therapy along with intravenous defibrotide and high-dose steroids. Neutrophil engraftment did not occur until day +38. Post-engraftment, the patient developed a skin rash diagnosed as GVHD by biopsy, which was treated with corticosteroids at 2 mg/kg/day. As part of viral infection surveillance, the patient received a weekly blood PCR test for adenovirus; on day +25 it was noted he had reactivated adenovirus. He had been demonstrating overall clinical improvement, including declining hepatic transaminases and bilirubin, and reduced respiratory support requirements until day +39, when he developed fever with an increased need for respiratory support and rising transaminases. The respiratory viral panel showed that the patient was positive for adenovirus. Further workup also showed adenovirus PCR positive in stool and increase in quantitative adenoviremia, all consistent with disseminated adenoviral infection. The use of cidofovir was contraindicated in this patient due to renal toxicity.ALVR105 (Viralym-M), an allogeneic, off-the-shelf, multivirus-specific T-cell therapy (VST) that can target AdV, BKV, CMV, EBV, HHV-6, and JCV, was provided by AlloVir on a compassionate-use basis. A cell line that was HLA matched to the patient at 2 out of 8 HLA-A, HLA-B, HLA-DR, and HLA-DQ alleles was identified. After emergency IND approval, institutional review board approval, and family consent, one ALVR105 dose of 0.7 × 10 7 cells was infused on day +48. The dosage was calculated based on the patient's age, weight (8.5 kg), body surface area (0.35 m 2), and the dosing regimen used in a previous phase 2 trial. The patient developed fever and low blood pressure around 30 hours post-infusion, requiring an increase in his existing inotropic support and stress dose hydrocortisone. This was likely associated with underlying post-transplant complications, but a possible association with ALVR105 infusion could not be ruled out.The patient's viral load decreased substantially in the following weeks (Table 1). Concurrently, his liver enzymes, pulmonary secretions, and respiratory support requirements all improved. His respiratory secretions became negative for adenovirus PCR at day +28 post-infusion of ALVR105.At the time of writing, the patient was day +100 post-transplant (day +56 post-infusion of ALVR105), and his veno-occlusive disease had improved. Supplemental oxygen was no longer required, but volume-assured pressure was still in use, likely due to hepatosplenomegaly. The patient had detectable adenovirus viremia but below the threshold of quantitative measurement (<190 copies/ ml). The patient remains well-engrafted with evidence of persistent ALVR105 (Viralym-M) as illustrated in Table-2, but the % of Allovir cells are below our lab's 5% validation threshold. The patient's GVHD has resolved. MMF dosing was stopped on day + 31 from transplant, and the patient is receiving only cyclosporine and physiologic doses of hydrocortisone.Conclusion: In this infant with post allogeneic HCT disseminated adenovirus infection, ALVR105 appeared to be safe and was temporally associated with marked clinical improvement, suggesting VSTs may be of value in very young patients with adenovirus infection. This represents the first use of ALVR105 in an infant (< 1-year-old) patient. [Display omitted] DisclosuresMoon: Allovir: Current Employment, Current equity holder in publicly-traded company. OffLabel Disclosure:Virus specific cell therapy, used against adenovirus infection in post-transplant setting.

Monitoring of Patients with Autoimmune Cytopenias during Sars-Cov-2 Vaccination Campaign: The Experience of a Reference Center

▪SARS-CoV-2 infection and vaccination have raised concern in immune mediated diseases, including autoimmune cytopenias (AIC, i.e. autoimmune hemolytic anemia, AIHA; autoimmune thrombocytopenia, ITP; autoimmune neutropenia, AIN; aplastic anemia, AA; and their combination, termed Evans syndrome, ES). The latter are highly heterogeneous conditions with variable severity and a clinical course marked by several relapses often triggered by immune-activating events (infections, traumas, surgery, etc.) including vaccines. Some reports of ITP and AIHA post-SARS-CoV-2 vaccines have been described but no population studies have been conducted in AIC patients. Here we systematically studied a large series of 100 patients with AIC (44 AIHA, 38 ITP, 7 AIN, 6 ES, and 5 AA) prospectively followed at a reference center in Milan, Italy, who underwent SARS-CoV-2 vaccination from 24 th of March until the end of June 2021. Patients (median age 62 years, range 25-89, female/male ratio 1.7) were monitored with whole blood counts and LDH testing the week before and the week after each vaccination dose. Importantly, ongoing AIC therapy (38% of cases, including steroids, cyclosporine, eltrombopag, and complement inhibitor sutimlimab) were kept stable within the 2 weeks before vaccination. Patients mainly received Pfizer-BioNtech vaccine (N=88), followed by Moderna (N=10), and Astra-Zeneca (N=2). Table 1 summarizes hematologic trends and side effects observed after each dose in patients with ITP and AIHA. Regarding the former, a delta percentage reduction of 10% or higher was observed in up to 13% of cases after the first and the second dose, requiring therapy adjustment in 2 patients. They were two elderly male subjects on low dose eltrombopag treatment and experienced a severe/moderate relapse (platelets 28 and 21x10^9/L) with mucosal bleeding, after the 2 nd dose of Pfizer vaccine. Both had a concomitant trigger (1 hip fracture and 1 bronchitis reactivation) and were rescued by increasing eltrombopag dose and with the addition of prednisone 1 mg/Kg day. Regarding AIHA, 3 elderly patients experienced a clinically significant relapse (>10% Hb decrease): 1 female patient experienced an Hb reduction from 10.4 to 9.1 g/dL after the first dose of Pfizer vaccine, that required a slight increase of steroid dose (to 5 mg day prednisone) and remained stable after the second dose; 1 male subject had an Hb reduction from 13.9 to 9.1 g/d>L after the first dose of Moderna vaccine, requiring prednisone 0.5 mg/kg day; the third male patient experienced a severe relapse (Hb reduction by 47%, from 14 to 7.4 g/dL) with LDH increase to 2.3 x ULN after the second dose of Pfizer vaccine. The patient required high dose intravenous steroids and hemolysis improved in about 1 week. All patients had warm type AIHA and had complained no other triggers or non-hematologic adverse events. Patients with AIN, AA and ES had no significant changes in their hematologic values (1 AIN had a neutrophil decrease by 30% but was consistent with previous oscillations; 2 ES had a platelet or neutrophil decrease within the normal range) and required no treatment changes. Finally, the following non-hematologic adverse events were observed: fever (7%), pain at the injection site (15%) and arthralgia (<5%), without significant differences between the first and the second dose.These data show that SARS-CoV-2 vaccination may be associated with a mild decrease of hematologic values in about 10% of AIC cases. However, true ITP and AIHA relapses occurred in 5% of cases only, sometimes in the presence of a concomitant trigger, and were rapidly rescued with treatment adaptation. Overall, the hematologic monitoring of SARS-CoV-2 vaccine adopted in our survey appears appropriate to early detect and manage AIC reactivation, ensuring a safe vaccination campaign in this patient population. [Display omitted] DisclosuresFattizzo: Annexon: Consultancy; Alexion: Speakers Bureau; Kira: Speakers Bureau; Momenta: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Apellis: Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Bianchi: Agios pharmaceutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Barcellini: Novartis: Honoraria; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Honoraria; Agios: Honoraria, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

Refractory Bell’s palsy responding to late treatment with high-dose intravenous steroids

Bell’s palsy is an acute peripheral facial paralysis with no detectable cause. Although the prognosis of Bell’s palsy is generally good, some patients experience poor recoveries and there is no established treatment for those that do not recover even after receiving the conventional treatment. Here we present two cases of refractory Bell’s palsy with facial nerve enhancement in magnetic resonance imaging who showed symptomatic improvement after the late administration of high-dose intravenous methylprednisolone.

Long-term remission of AIDS-related primary central nervous system lymphoma in a patient under antiretroviral therapy: a case report and review of the literature

BackgroundAIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/μl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2–3 months if left untreated.Case descriptionA 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT.ConclusionNowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.

Posterior Ischemic Optic Neuropathy after Cervical Spine Surgery

Purpose: To describe a patient with posterior ischemic optic neuropathy (PION) after cervical spine surgery who recovered after treatment.Case summary: A 51-year-old woman presented with eye pain and decreased visual acuity in the left eye, which had begun 8 hours after cervical spine surgery in the prone position. Her best-corrected visual acuity (BCVA) was 20/20 in the right eye and hand motion in the left eye; a relative afferent pupillary defect was present in the left eye. Ductions and versions were normal with pain in the left eye. The results of slit lamp examination, fundoscopic examination, fluorescein angiography, and optical coherence tomography were unremarkable in both eyes. Brain and orbital magnetic resonance imaging showed no abnormal findings in the visual pathway, such as brain infarction or intracranial artery stenosis. The patient was diagnosed with PION in the left eye. Because postoperative anemia had developed with a rapid decrease in hemoglobin from 14.7 g/dL to 9.9 g/dL, red blood cell (RBC) transfusion was performed together with intravenous high-dose steroid therapy and subcutaneous epoetin alfa injection. After 3 weeks, the patient’s BCVA improved to 20/22 in the left eye.Conclusions: Unilateral PION developed after cervical spine surgery in the prone position. Visual improvement was observed after RBC transfusion, intravenous high-steroid therapy, and subcutaneous epoetin alfa injection.

Immunoglobulin G4-related Ophthalmic Disease with Peripheral Eosinophilia and Elevated Immunoglobulin E Levels

Purpose: To report a case with peripheral eosinophilia and elevated immunoglobulin (Ig) E levels, subsequently diagnosed as IgG4-related ophthalmic disease involving the extraocular muscles.Case summary: A 56-year-old male visited the allergy department presenting with systemic urticaria and bilateral eyelid swelling that began 5 months prior. Laboratory examinations showed elevated levels of serum eosinophil and IgE, 1,309 IU/uL and 1,793 IU/mL, respectively. Orbital computed tomography revealed that all extraocular muscles and the bilateral exophthalmos were enlarged, and the patient was referred to the ophthalmology department. Eye alignment was orthophoric for all gaze directions, and limited abduction (-1) was noted in both eyes. An incisional biopsy of the extraocular muscles was conducted. Histopathological findings showed lymphoid aggregates, diffuse fibrosis, and an increased IgG4+/IgG+ plasma cell ratio of 40%, which led to the diagnosis of IgG4-related ophthalmic disease. An elevated IgG4 serum level (1,710 mg/dL) was also noted. The patient received high-dose intravenous steroids and eyelid swelling improved after two months. Levels of serum eosinophil, IgE, and IgG4 all decreased after three months.Conclusions: IgG4-related ophthalmic disease may be accompanied by eosinophilia and elevated IgE. These findings may facilitate future diagnoses of this disease.