Intravenous Methylprednisolone Research Articles

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis: A case report

BACKGROUND Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Pulse methylprednisolone therapy triggered sinus bradycardia in two children

Intravenous methylprednisolone is an important therapeutic modality in many conditions, owing to their anti-inflammatory and immune-modulating properties. Along with other side-effects of corticosteroids, cardiovascular side-effects are also seen in varying degree in children. Sinus bradycardia is reported uncommonly in children following high dose intravenous methylprednisolone. We report two paediatric cases without any underlying cardiac problems with asymptomatic bradycardia following high dose intravenous methylprednisolone. Heart rate reduction was seen from 30-40% compared to the baseline heart rate, which returned to its normal value after 24-36 hours of stoppage of the offending drug. A high index of suspicion along with strict cardiovascular monitoring is necessary in patients receiving high dose of methylprednisolone.

#2545 Hemodialysis for salbutamol intoxication: patient case report

Abstract Background and Aims Salbutamol/albuterol is a moderately selective beta-2-adrenergic receptor agonist that acts as an airway smooth muscle relaxant. It is used to prevent and treat acute bronchospasm in various respiratory conditions. Due to its large volume of distribution, it is not considered dialysable. Method This is a clinical case report of inadvertent parenteral administration of salbutamol resulting in acute intoxication. Salvage renal replacement therapy was implemented due to the severity of the patient's clinical condition and the large amount of salbutamol administered. Multiple plasma measurements of salbutamol were taken during hemodialysis, allowing for a correlation to be made with the patient's clinical presentation. Results This case report presents an elderly patient with sepsis, Down syndrome, and liver cirrhosis. The patient required non-invasive ventilation due to worsening respiratory failure and was prescribed intravenous methylprednisolone. However, the patient inadvertently received 5mg of parenteral salbutamol (albuterol), which resulted in immediate severe arrhythmic tachycardia followed by hemodynamic collapse. After unsuccessful cardioversion and treatment with landiolol infusion, salvage hemodialysis was initiated to reduce the suspected highly elevated serum salbutamol levels. After 30 minutes, sinus rhythm with normocardia was observed. No rebound tachycardia was noted after the hemodialysis termination. However, due to severe septic shock, hypotension persisted, and vasoactive medications were adjusted. However, the measured levels of plasma salbutamol do not support the view that hemodialysis was the cause of the described improvement. The total amount of the drug cleared was exceedingly small, only 2.8% of the total dose. Data from the literature support our findings, even in the case of the life-threatening intoxication described. Conclusion The results confirm a large volume of distribution for salbutamol. The measured half-life time during hemodialysis (3.1 hours) is comparable to observed half-life times in therapeutic settings. The observed clinical benefit associated with dialysis appears to be fortuitous. This case report highlights the potential bias towards positive clinical outcomes and unproven therapies.

#3076 A UK parallel cohort study on renal ANCA associated vasculitis outcomes for avacopan exposed and matched unexposed cohorts

Abstract Background and Aims Avacopan was approved in the UK for severe ANCA associated vasculitis (AAV) in December 2022. The ADVOCATE trial found the differential effect of avacopan on kidney function was greatest in patients with the lowest estimated glomerular filtration rate (eGFR), at highest risk of progression to end stage kidney disease (ESKD). Patients with an eGFR <15 ml/min/1.73 m2, pulmonary haemorrhage requiring invasive ventilation, under 12 months prognosis, use of plasma exchange and dual therapy with cyclophosphamide (CYC) and rituximab (RTX) were excluded from ADVOCATE; all common scenarios in real life practice. We aim to provide further information on these subgroups and evaluate 6 month renal outcome data in the UK. Method Parallel cohort study on renal AAV outcomes for avacopan exposed and matched unexposed cohorts, with severe, active GPA or MPA. 120 patients on avacopan from 7 UK centres have been recruited to date. Controls matched by renal function and age will be presented. Comparisons of ESKD, delta eGFR, eGFR recovery, reduction in proteinuria/haematuria, remission, relapse and mortality will be presented, with subgroup analyses for eGFR<15 ml/min/1.73 m2. Steroid exposure will be presented. Results Baseline characteristics of the avacopan cohort are below. Most received oral prednisolone at avacopan initiation (89%, n = 107) and 54% received intravenous methylprednisolone (n = 65). The majority received RTX alone (44%, n = 53) or RTX and CYC combination therapy (43%, n = 52). Fewer received CYC alone (9%, n = 11) and 3% were initiated on alternative immunosuppression (n = 4). 26% (n = 31) underwent plasma exchange and 13% required haemodialysis (n=16). 3% of patients have died. Excluding dialysis dependent patients at presentation, median eGFR was 22ml/min/1.73 m2 (IQR 10-36). eGFR at the time of avacopan initiation was 21ml/min/1.73 m2 (IQR 11-34). Conclusion Avacopan is commonly being used to treat nephritis in patients with a low eGFR, including haemodialysis dependent and elderly patients. Avacopan is frequently used with RTX and CYC combination therapy. 6 month outcome data will provide new data on important patient subgroups excluded from the ADVOCATE trial.

Orbital radiotherapy with combined intravenous methylprednisolone and mycophenolate mofetil in moderate-to-severe thyroid eye disease

PurposeTo report the clinical outcomes of orbital radiotherapy (ORT) with combined intravenous methylprednisolone (IVMP) and mycophenolate mofetil (MMF) in thyroid eye disease (TED) patients with restrictive myopathy. DesignProspective comparative case series of patients managed at The Chinese University of Hong Kong from 2015 to 2021. MethodsThe primary outcome was the change in Gorman diplopia score at 52 weeks. Secondary outcomes were the changes in extraocular muscle motility (EOMy), area of extraocular muscle (EOM) on MRI, exophthalmos, and marginal reflex distance (MRD) 1 and MRD2 at 52 weeks. ResultsA total of 40 (29 females) TED patients, medium age 56 years, were treated with the double regimen: combined IVMP and MMF (17) or triple regimen: IVMP, MMF, and ORT (23). The triple group has a higher age (P = 0.028). Sex, smoking history, thyroid, and pre-treatment orbital status were comparable between the 2 groups. EOMy improved more after the triple regimen(P = 0.026). Nine patients from the triple group showed a significant reduction in the size of the inferior rectus (both eyes: P < 0.05), while five from the double group showed no significant reduction of any EOM on MRI. The improvement of CAS, diplopia score, exophthalmos, MRD1, and MRD2 were similar. No patient reported any severe or organ-threatening side effects from IVMP, MMF, or ORT requiring discontinuation of treatment. ConclusionThe triple regimen demonstrates better structural and functional outcomes in TED-related restrictive myopathy. Future randomized clinical trials are warranted to clarify the adjuvant role of ORT in this specific indication of TED management.

An unusual case of adult-onset still’s disease complicated with anti-complement factor H antibodies associated atypical haemolytic uraemic syndrome

BackgroundAtypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still’s disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing.Case presentationA 42 years old man was admitted with suspected adult-onset Still’s disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still’s disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml).ConclusionOur case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.

Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) μmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

Severe relapsing autoimmune encephalitis with GABAA receptor, titin and AchR antibodies in a patient with thymoma: a case report

Introduction: We report a challenging case of autoimmune encephalitis in a patient with a thymoma harboring titin and acetylcholine receptor antibodies, who experienced multiple relapses despite thymectomy and aggressive first-line immunotherapy, and for whom GABAA receptor antibodies were ultimately identified. Case presentation: This 40-year-old man presented with headaches, weakness, diplopia, hearing loss and seizures progressing to status epilepticus. Brain MRI showed multifocal cortical and subcortical T2/fluid attenuated inversion recovery hyperintense lesions without enhancement. Initial neural antibody testing identified only acetylcholine receptor and titin antibodies. He presented multiple severe relapses despite complete thymoma resection, intravenous methylprednisolone with immunoglobulins or plasmapheresis, and mycophenolate mofetil. Second-line immunotherapy with rituximab was successful to alleviate symptoms and normalize the EEG and MRI after identification of anti-GABAA receptor antibodies on more comprehensive neural antibody testing for autoimmune encephalitis. Conclusion: This case demonstrates the complexity and importance of identifying pathogenic antibodies and selecting 2nd line treatment accordingly in patients with autoimmune encephalitis when multiple antibodies coexist. Despite tumor resection, aggressive immunotherapy may be needed to prevent further deterioration in anti-GABAA receptor encephalitis.

Efficacy and safety of apheresis therapy in AQP4 antibody-positive NMOSD attack: A propensity score-matched cohort study.

Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody-positive NMOSD, but high-quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control. Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded. Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50-8.38 vs. 5.00-8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30-0.84 vs. 0.95-1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation. After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile.

Autoimmune hepatitis presenting as severe anemia

AbstractAutoimmune hepatitis (AIH) is relatively rare in children. Herein, our case demonstrates a unique presentation of AIH in a previously healthy 18‐year‐old female presenting with a mild cough, fatigue, and severe anemia (hemoglobin 2.9 g/dL). Initial evaluation revealed jaundice and scleral icterus, prompting transfer of care and further testing, which demonstrated severe microcytic anemia, pancytopenia, elevated liver enzymes, direct hyperbilirubinemia, and marked splenomegaly. Concern for autoimmune hemolytic anemia resulted in a delayed diagnosis. The combination of triple antibody positivity (anti‐nuclear antibodies, anti‐actin, and anti‐liver‐kidney microsomal‐1) and liver histology findings confirmed the diagnosis of AIH. Intravenous methylprednisolone was initiated to induce remission. Due to pancytopenia and persistently elevated INR, tacrolimus was chosen as the maintenance immunosuppression instead of azathioprine. This case highlights several significant considerations for clinicians, including the importance of a timely clinicopathologic diagnosis, the severe anemia presentation secondary to hypersplenism, and the rare finding of triple autoantibody‐positive AIH.

Profile of Multisystem Inflammatory Syndrome in Children (MIS-C) in Infants in North India during the Second Wave of SARS-CoV-2 Pandemic

Background: Multisystem inflammatory syndrome in children (MIS-C) secondary to severe acute respiratory syndrome coronavirus-2 has affected not only older children, adolescents, and adults but also infants, more so during the second wave of the global pandemic. Materials and Methods: All sequentially admitted infants hospitalized during 6 months who fulfilled the World Health Organization criteria for MIS-C or American Heart Association 2017 criteria for Kawasaki disease (KD) (and positive coronavirus disease-2019 [COVID-19] serology) were included in the present study. Results: A total of 19 infants were studied. Thirteen (68.3%) had evidence of recent COVID-19 infection. The median age of presentation was 2 months (interquartile range 25–75th, 0.5–3). The most common presenting symptoms were fever (68.4%), gastrointestinal complaints (63.1%), and edema (36.8%). Other predominant signs were shock (78.9%), myocarditis (52.6%), and neurological complaints (26.3%). Incomplete KD was present in 21% of patients. Elevated C-reactive protein, ferritin, D-Dimer, N-terminal prohormone of brain natriuretic peptide, and reduced fibrinogen were markers of severe illness. All subjects received intravenous immunoglobulin (IVIG) (100%), 31.5% received a second dose of IVIG, and 63.1% received pulse intravenous methylprednisolone. A total of 5 (26.3%) died as a result of the disease process. Conclusion: The spectrum of MIS-C in infants can be varied and is different from older children. A high index of suspicion is therefore needed in infants who present with critical illness and do not respond appropriately to conventional antibiotics and supportive care. The addition of IVIG and corticosteroids to the treatment regimen leads to a favorable outcome.

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland

ObjectivesIn trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of...

E026 Severe odynophagia due to cricoarytenoid arthritis in a patient with rheumatoid arthritis and systemic lupus erythematosus

Abstract Background/Aims A 65-year-old man with a 20-year history of rheumatoid arthritis (RA) presented with dysphagia, odynophagia, polyarthralgia and significant weight loss. Methods - Results In addition to raised markers of inflammation, he was anti-nuclear antibody, anti-dsDNA antibody, anti-chromatin antibody and rheumatoid factor positive. He was initiated on 20mg once daily prednisolone but reported continued dysphagia and odynophagia. Computerised tomography (CT) of the neck revealed sclerosis at both cricoarytenoid joints with positron emission tomography (PET-CT) imaging identifying focal FDG uptake in the right hemiglottis projected over the posterior right true cord. Direct visualisation showed reduced mobility of the arytenoids with incomplete glottic closure in the absence of other abnormalities. He was diagnosed with cricoarytenoid (CA) joint arthritis on a background of RA and systemic lupus erythematosus overlap, with the resolution of his symptoms following intravenous methylprednisolone. Conclusion CA arthritis is an increasingly rare manifestation of autoimmune disease, and severe ongoing odynophagia an atypical presentation. This case highlights the need for continued awareness of laryngeal manifestations of autoimmune disease and demonstrates the benefit of PET-CT in cases where the diagnosis is uncertain or delayed. Disclosure J.S. Berry: None. J. Robinson: None. W. Ng: Consultancies; Expert advice in the area of Sjogren’s syndrome to GlaxoSmithKline, MedImmune, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, Sanofi, Novartis and BMS.

Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration.

Background: Epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early onset, and unfavorable developmental outcomes. This article discusses the use of intravenous methylprednisolone (IVMP) pulse therapy in pediatric patients with EE to evaluate its efficacy and tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction > 50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: The study included 21 patients, with a responder rate of 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Variables significantly predicting favorable outcome were etiology (p = 0.0475) and epilepsy type (p = 0.0475), with the best outcome achieved in patients with genetic epilepsy and those with encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES). All patients evidenced improvements in QoL at the last follow-up, with no relevant adverse events reported. Conclusions: Our study confirmed the efficacy and high tolerability of IVMP pulse therapy in pediatric patients with EE. Genetic epilepsy and ESES were positive predictors of a favorable clinical outcome. QOL, EEG tracing, and postural-motor development showed an improving trend as well. IVMP pulse therapy should be considered earlier in patients with EE.

E031 Retinal vasculitis with Libman-Sacks endocarditis as presenting features of a systemic lupus erythematosus with antiphospholipid antibody syndrome patient

Abstract Background/Aims Ocular manifestations of systemic lupus erythematosus (SLE) are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with the active generalised disease. We report a case of a 22-year-old lady who was diagnosed with SLE with antiphospholipid antibody syndrome (APS) as the initial presentation of retinal vasculitis and Libman-Sacs endocarditis. Methods A 22-year-old lady with a background history of benign hypermobility spectrum disorder, presented to the eye casualty with a 4-week history of right-sided visual disturbances and was diagnosed with retinal vasculitis associated with uveitis, central retinal vein occlusion with multiple emboli in the retinal artery of the right eye and a single embolus in the left eye. In terms of family history, both father and brother were diagnosed with spondyloarthropathy, and the maternal uncle had Sjogren’s syndrome. She was then referred to the medical team for proper evaluation. On query, she mentioned photosensitive rash on her face getting worse in sunlight, a history of Raynaud’s phenomenon, significant hair loss, and one miscarriage before the 10 weeks of gestation. On examination, mild alopecia and a faint butterfly rash on the face were noted. Cardiac auscultation revealed pansystolic murmur. The rest of the systemic examinations were unremarkable. Results The blood test showed thrombocytopenia (130 u/L), positive antinuclear antibody (1:80, speckled pattern) with anti-double stranded DNA (26 IU/L), low complement (C3-0.74, C4- 0.12), markedly raised anticardiolipin antibody IgG (2016 u/ml), anti beta 2 glycoprotein 1 IgG ( &amp;gt;6100 u/ml) including presence of lupus anticoagulant. Her urinary protein creatinine ratio was 66mg/mmol. 3 sets of blood cultures came back negative. Transthoracic echo showed vegetation on the posterior mitral valve leaflet (0.95x 1.2cm) with moderate mitral regurgitation while transesophageal echo additionally found the possibility of perforation at the junction of leaflets of the mitral valve which was later confirmed by cardiac magnetic resonance imaging (MRI). The head MRI scan did not show any central nervous system abnormality. She was initially treated with 500mg intravenous methylprednisolone for 3 days followed by 20mg oral prednisolone daily with gradual tapering. Hydroxychloroquine and mycophenolate mofetil were added. Her case was discussed in the cardiology multidisciplinary team meeting and an opinion from the cardiothoracic surgery was taken to consider valve replacement in the future. Due to aspirin allergy, only warfarin was considered for APS. She had 2 sessions of pan-retinal photocoagulation as well. In subsequent follow-up, it was noted significant improvements in terms of her symptoms. Conclusion Vaso-occlusive retinopathy is a rare, potentially vision-threatening initial manifestation of SLE, which can be an indicator of active disease. Early identification of patients is necessary for timely intervention and multidisciplinary team involvement is required for comprehensive treatment plans. Disclosure M. Islam: None. S. Quddus: None. M. Hughes: None. R. Kumar: None.

OA16 Clinical and biochemical improvement following daratumumab therapy for anti-MDA5 antibody positive dermatomyositis with rapidly progressive interstitial lung disease: a case report

Abstract Background/Aims Anti-melanoma differentiation-associated 5 gene autoantibody (anti-MDA5) positive dermatomyositis (DM) with rapidly progressive interstitial lung disease (RP-ILD) represents the most severe and difficult-to-treat form of autoimmune myositis with unfavourable 6-month survival rates despite intensive treatment strategies of combination therapy with glucocorticoids, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil and rituximab. We describe a case of anti-MDA5 positive DM with RP-ILD that was refractory to intensive combination therapy, requiring courses of rescue plasmapheresis, before eventually responding to intravenous daratumumab. Methods A 30-year-old non-smoking Chinese man who was previously well was hospitalised after 3 weeks of intermittent pyrexia, non-productive cough, lethargy, rashes and myalgia. Examination revealed typical cutaneous changes of dermatomyositis, bilateral mid-to-lower zone inspiratory crepitations in his chest with no proximal muscle weakness or synovitis. Initial investigations demonstrated elevations in creatine kinase, C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, ferritin and neutrophil-to-lymphocyte ratio. Although an initial chest radiograph was normal, CT thorax 4 days later showed non-specific ground-glass opacities with consolidation in both lower lobes. Anti-MDA5 antibodies were strongly positive on EUROLINE Inflammatory Myopathies 16 Ag (IgG) commercial line immunoblot. He was transferred to our centre for further care one week after hospitalisation and was intubated on arrival for type I respiratory failure. He was initiated on combination therapy of intravenous methylprednisolone, intravenous rituximab, hydroxychloroquine, tofacitinib and was also treated with plasmapheresis to remove pathogenic anti-MDA5 antibodies. Although his condition improved initially with successful extubation within one week, the disease remained active in the following months with several admissions for infection-related issues and progression of RP-ILD. Despite various combinations of immunosuppressives and further courses of plasmapheresis, at 6 months post-diagnosis he continued to require a minimum daily prednisolone dose of 45mg (0.625mg/kg/day), remaining positive for anti-MDA5 antibodies on the immunoblot assay, with persistently elevated serum ferritin and transaminases. As such, he was treated with four doses of intravenous daratumumab in an attempt to deplete the long-lasting plasma cells that may be driving the disease. Results Following daratumumab treatment, the anti-MDA5 antibody turned negative on the immunoblot assay with normalisation of ferritin and transaminases, with corresponding improvement in lung function tests and chest radiograph findings. 3 months post-daratumumab, he remains clinically well on hydroxychloroquine, tofacitinib and nintedanib, with successful continuing taper of prednisolone. Conclusion Daratumumab is an anti-CD38 monoclonal antibody licensed for the treatment of multiple myeloma which has been used off-label for other refractory autoimmune conditions such as SLE. It is postulated that besides CD19/20 positive B cells, CD38 positive long-lived autoantibody-secreting plasma cells are essential drivers of chronic inflammation in these autoimmune diseases. In our patient with anti-MDA5 DM and RP-ILD, the use of daratumumab was well-tolerated and led to definite clinical and biochemical improvement. Disclosure L. Koh: None. G. Chai: None. M. Manghani: None. X. Lim: None. B.P.L. Leung: None. C. Chua: None.

P013 A case report of posterior orbital inflammation associated with VEXAS(Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome

Abstract Background/Aims VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly recognised adult-onset acquired autoinflammatory disease caused by somatic mutations of the UBA1 gene in the blood precursor cells. It is characterised by systemic inflammation and haematologic abnormalities. Methods Here we report a case of a 66 year old male who presented with orbital inflammation as one of the striking features of his underlying VEXAS. Results Our patient has a history of type 1 insulin dependent diabetes, otitis externa and recurrent lower limb distal venous thrombosis. He presented to Eye Emergency in May 2023 with rapid onset painful diplopia, left retrobulbar pain and peri-orbital swelling. He had recently been referred to Haematology with new anaemia and constitutional symptoms. MRI demonstrated inflammatory changes of some left extraocular muscles and cranial nerves. He was pulsed with three days of intravenous methylprednisolone with significant clinical response. Bone marrow biopsy reported reactive morphology and no clear myelodysplasia. In August 2023, the patient re-attended eye clinic with right sided facial swelling. Rheumatology were consulted for further opinion. The patient had previously been known to the department over 10 years ago, after presenting with arthritis labelled as diabetic cherioarthropathy. Extensive autoimmune panel was requested, including normal IgG subclass, weakly positive c-ANCA with a negative PR3. The patient had a new macrocytic anaemia (Hb 103 g/L, MCV 103 fl) and previous thrombocytopenia. Inflammatory markers were raised, CRP between 8-180, ESR 60 to 110 and Ferritin 878. Ultrasound of neck showed normal parotid and small reactive lymph nodes. Urgent PET-CT reported bone marrow reactivation with no significant findings. Prednisolone 40mg was given with marked resolution of the facial swelling. Opinion was sought by Haematology about any features of VEXAS on previous myelodysplasia screening. A week later, we received the result of the genetic testing showing a mutation of the UBAE gene, consistent with the diagnosis of VEXAS. The patient had re-occurrence of his inflammatory symptoms on several occasions [including diplopia, headache, rash, ocular pain, or periocular swelling] which were all steroid responsive. After discussion with multiple specialities, including Haematology, Ophthalmology and Immunology colleagues with a specialist interest in VEXAS, Tocilizumab was felt to be the most appropriate initial treatment. The patient is due for their first infusion in October 2023. Conclusion We report a unique case of VEXAS who presented with orbital inflammation, a less well-characterised feature of VEXAS. VEXAS is perhaps not as exceptionally rare as we first thought, it is likely more similar cases will present and we need to have a high degree of clinical suspicion in patients with unexplained systemic inflammation, especially those presenting initially with ocular inflammation. These patients require a multi-disciplinary approach to ensure best management of a very challenging condition. Disclosure C.A. Zollinger-Read: None. A. Zewar: None. L. Dunkley: None. J. Jefferis: None.

Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Superior oblique palsy as the initial manifestation of anti-contactin-1 IgG4 autoimmune nodopathy: A case report

Autoimmune nodopathy (AN) is a group of peripheral neuropathies caused by antibodies targeting the nodes of Ranvier or paranodes. It typically presents with sensory ataxia, distal limb weakness, and tremor, and often has a subacute onset, with limited response to immunoglobulin or corticosteroids. We report a case of anti-contactin-1 neuropathy initially manifesting as isolated superior oblique palsy, aiming to broaden the clinical spectrum of the disease. A 68-year-old male with well-controlled diabetes, hypertension, and hyperlipidemia developed acute binocular vertical diplopia, progressing over two months to include distal paresthesia, sensory ataxia, ageusia, and dysarthria. Concurrent nephrotic syndrome was identified. Nerve conduction studies supported demyelination. Despite treatment with intravenous methylprednisolone followed by long-term immunosuppression, some disability persisted. Serum archived during his admission tested positive for anti-contactin-1 IgG, with IgG4 as the predominant subclass, in the flow cytometry assay for AN. This case extends the clinical spectrum of AN. Some cases of isolated cranial nerve palsies, especially in the relevant context like nephrotic syndrome, may be attributed to AN. Prompt initiation of more effective therapies, such as rituximab, could significantly improve outcomes.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.