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Background/Aims Cases of new autoimmune and autoinflammatory conditions have been reported among COVID-19 survivors. A literature review on newonset autoimmune connective tissue diseases (ACTDs) following infection with COVID-19 is lacking.This systematic literature review aimed to evaluate the potential association between COVID-19 infection and the development of new-onset ACTDs in adults. Methods Articles published until September 2022, investigating the association between COVID-19 infection and new-onset ACTDs were included. The ''population'' searched was patients with disease terms for autoimmune connective tissue diseases, including (but not limited to) systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), any idiopathic inflammatory myositis (IIM), antisynthetase syndrome, mixed CTD and undifferentiated CTD (and related MeSH terms), with ''intervention'' as COVID-19 and related terms. For terms for COVID-19, a dedicated search strategy developed by the National Institute for Clinical Excellence was used.Medline, Embase, and Cochrane databases were searched, restricted to English-language articles only. Eligible articles were: case reports and series (of any sample size), observational studies, qualitative studies and randomised controlled trials. Patients developing ACTDs without prior COVID-19 or reporting flares of existing ACTDs were excluded. Information was extracted on patient demographics, new ACTDs' onset time, clinical characteristics, COVID-19 and ACTD treatment, and COVID-19 and ACTDs outcomes. The protocol was registered in PROSPERO (CRD42022358750). Results After deduplication, 2239 articles were identified. After screening title and , 2196 papers were excluded, with 43 proceeding to fulltext screening. Ultimately, 28 articles (all single case reports) were included. Of the 28 included patients, 64.3% were female. The mean age was 51.1 years (range 20-89 years). The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including 4 cases of dermatomyositis);7 (25%) SLE;4 (14.3%) anti-synthetase syndrome;4 (14.3%) SSc;2 (7.1%) other ACTD (one diagnosed with lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) were diagnosed with lupus nephritis. The average onset time from COVID-19 infection to ACTD diagnosis was 23.7days. A third of the patients were admitted to critical care, one for ACTD treatment for SLE with haemophagocytic lymphohistiocytosis (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. The majority (80%) of patients went into remission of ACTD following treatment, while two (10%) patients died- one due to macrophage activation syndrome associated with anti-synthetase syndrome and two from unreported causes. Conclusion Our results suggest a potential association between COVID-19 infection and new-onset ACTDs, predominantly in young females, reflective of wider CTD epidemiology. The aetiology and mechanisms by which ACTDs arise following COVID-19 infection remain unknown and require more robust epidemiological data.
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Background/Aims The immune response to SARS-CoV-2 is known to be reduced in the immunocompromised. However, extent to which immunity is affected by immunosuppression in specific disease cohorts remains poorly characterised. Furthermore, implications of the ongoing vaccination booster programme require further study. Individuals with lupus nephritis (LN) require prolonged high-dose immunosuppression in order to maintain disease control, rendering them important to study in this context. We evaluated SARS-CoV-2 nucleocapsid and spike antibody response in this cohort during the Spring/Summer 2022 booster vaccine campaign. Nucleocapsid antibody indicates previous infection whilst spike antibody indicates previous infection and/or vaccination response. Titre of spike antibody to prevent infection is not known, but presence of antibodies is likely to protect against severe disease. Methods SARS-CoV-2 spike and nucleocapsid antibody were measured in adult patients with LN attending a tertiary centre rheumatology clinic. Data was collected retrospectively on disease, immunosuppression, vaccine status and history of natural exposure. Results 35 cases of LN were investigated, of which LN III, IV and V were predominant biopsy diagnoses. Regarding immunosuppressants, the Eurolupus Cyclophosphamide protocol had been used in the majority of patients to achieve initial control, with 3/35 patients still receiving pulsed courses at data collection. 18/35 were on Mycophenolate Mofetil;a further 13/35 had previously received this. 31/35 took at least 5mg Prednisolone daily;25/35 took Hydroxychloroquine;7/35 took Azathioprine;7/35 had previously been on Methotrexate, 3/35 took Tacrolimus;1/35 took Ciclosporin. Regarding B-cell depleting monoclonal antibody therapy, 13/35 had received Rituximab and 8/35 were receiving Belimumab. Antibody levels were measured between 4 weeks and 13 months after last dose of vaccination;mean duration was 6 months. 11/35 had confirmed COVID-19 infection;a further 8/35 reported a possible history. Of the 35, 32 (91%) had mounted detectable SARS-CoV-2 spike antibody above the bottom 10% of assay detection, indicating some immunity to vaccination or natural exposure. 20 (57%) had detectable nucleocapsid antibody, suggesting natural infection with antibody response. Only 2 (6%) had not mounted any antibody response. Of note, neither were fully vaccinated: one had 1 vaccination with blood test 8 months subsequent;one had 2 vaccinations with blood test 7 months subsequent. The latter was also notably on haemodialysis. All who received 3+ vaccinations had detectable spike antibody responses, as well as 75% of those who had received 2 vaccinations. Conclusion Our study is the first analysis, to our knowledge, of SARS-CoV-2 antibody response in a LN cohort. Whilst neutralising capacity and level of antibody providing protection remains under research, these findings provide at least some reassurance that individuals with LN on immunosuppression are capable of mounting an immune response against SARS-CoV-2. Further work is required to establish extent and duration of protection with serial vaccinations in this cohort.
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Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023
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Introduction: Early in the pandemic various lockdown measures were implemented to decrease spreading of Covid-19. This resulted in many clinics and hospitals observing a decrease in the usual numbers of patients accessing care. Patients have also expressed fears and challenges with accessing care at health clinics and hospitals during this time. Since May 2020, there has been a gradual decrease in the restrictions and stay at home orders for Covid-19 by the government in Jamaica and more persons have begun to access care again at health facilities. The impact of the Covid-19 pandemic in patients with chronic kidney disease especially those who were not admitted with Covid-19 is limited. This study seeks to determine why patients were not accessing care early in the pandemic and the possible longer-term impact of the Covid-19 pandemic on the care and prognosis of patients with chronic kidney disease. Method(s): All patients who attended Renal clinic, Kingston Public Hospital (KPH) from April 20th to July 14th 2021 were eligible for inclusion in the study. Those who consented to participate in the study had an interview with the researcher at the Renal clinic where a questionnaire was administered. Demographic data was collected as well as whether they were a new or follow-up patient and number of appointments missed was noted. Their renal diagnosis and labs were obtained from their dockets by the researchers. The data was analysed using Microsoft excel and Epi info software Results: There were 185 participants. 45.7% of the participants were 51 to 70 years old. 61.1% were females and 38.9% were males. Follow-up patients accounted for 76.2% of the participants whilst 23.8% were new patients. 92.2% of the follow-up patients reported attending clinic in the past year. 15.1% of the participants reported missing at least one appointment in the past year. Most common reasons given for missing appointments were forgot date of appointment, afraid of coming to hospital, was sick at home or admitted to hospital. 2.7% of the participants reported having had Covid-19. Only 7.0% of the study participants were on dialysis. 76.9% of those receiving dialysis were started on haemodialysis since March 2020. 93.0% reported receiving all or most of their medications through the free public health care system during the pandemic. 44.3% of the participants reported working in the past year. Most common reasons given for not working in the past year were medical condition, receiving family support or retired. Only 3.6% reported being sent home by an employer due to the pandemic. The most common renal diagnoses were diabetic nephropathy and hypertensive nephrosclerosis followed by lupus nephritis and sickle cell nephropathy. 49.2% were CKD stage 3b to Stage 5. 14.6% of those who were CKD stage 3 near to March 2020 progressed to CKD stage 4 or 5 by a year later. Conclusion(s): During the pandemic, attendance of patients at Renal clinic, Kingston Public Hospital and their access to medications remained high. Approximately 15% of those with CKD stage 3 near the onset of the pandemic progressed to CKD stage 4 or 5 by a year later. This warrants further study. No conflict of interestCopyright © 2023
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The 2019 Coronavirus disease (COVID-19) vaccine is a major weapon in the fight against the severe acute respiratory syndrome brought about by coronavirus 2 (SARS-CoV-2). The vaccine significantly reduces the risk and severity of infection by SARS-CoV-2. Patients with systemic lupus erythematosus (SLE) need protection from vaccine-preventable diseases including COVID-19. SLE patients have higher rates of severe infections due to immunosuppressive therapies and multiple immunologic defects - both of which are capable of blunting the immune responses after vaccination. In the management of COVID-19, recommendations have been developed to guide adjustments and/or continuation of immunosuppressive therapies for an effective immune response following vaccination with mRNA-based or viral vector-delivered vaccines. Monoclonal antibodies have also become available since December 2021. Here we present three cases of SLE patients who contracted COVID-19 after vaccination. One was managed in ambulatory settings and two required inpatient hospital admission.Copyright © 2022
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Introduction: Patients with systemic lupus erythematosus (SLE) are at increased risk of the Coronavirus disease 2019 (COVID-19), whereas vaccines against the COVID-19 increase type I interferon and may trigger SLE flares. Lupus nephritis (LN) is common in adolescents with SLE and usually more severe than in adults. The incidence and severity of renal flare among these patients following COVID-19 mRNA vaccination are limited. Method(s): Adolescents, aged 12-18 years, with SLE and ever biopsy-proven lupus nephritis who had renal remission were prospectively studied following the COVID-19 (BNT162b2) mRNA vaccination. Renal remission was defined as having stable renal function and normal urinalysis at recruitment. SLE disease activity index 2000 (SLEDAI-2K) scores during the last 3 months prior to the vaccination were reviewed, and compared to SLEDAI-2K scores at 1, and 3 months after two-dose primary series. Renal flare included new onset significant proteinuria, abnormal urine sediment, and/or significant increased serum creatinine. Result(s): 35 adolescents (female 88.6%), with mean age of 15.4 +/-1.6 years, were included. Median (IQR) duration of SLE was 41.4 (18.9, 70.4) months. LN included class II (2, 5.7%) class III (2, 5.7%), class IV (12, 34.3%) class V (7, 20.0%), and class III/IV + V (10, 28.6%). Median daily dose of prednisolone prior to vaccination was 5 (2.5, 5) mg. SLEDAI-2K scores at pre-vaccination, 1-, and 3-months post vaccination were not significantly different [2 (0.25,4), 2 (0, 4) and 2 (0, 4);p=0.06). Three (8.6%) patients had renal flare within 3 months post vaccination. One had mild microscopic hematuria and mild proteinuria but improved after increased prednisolone to 0.5 mg/kg/day. Two patients had severe renal flare with biopsy proven LN class IV (1 with class V and 1 with thrombotic microangiopathy). Moreover, one patient developed COVID-19 at 2 months post vaccination without renal flare. Conclusion(s): Within 3 months post COVID-19 mRNA vaccine in adolescents with remission of LN, incidence of renal flare was 8.6%. Renal flare could be severe and required increasing immunomodulatory treatment. Larger population and longer follow-up are needed. No conflict of interestCopyright © 2023
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The proceedings contain 539 papers. The topics discussed include: advances in the understanding and management of atherosclerosis in inflammatory arthritis;long-term safety and efficacy of voclosporin in Asian patients with lupus nephritis;clinical profile of four children with juvenile dermatomyositis and anti-SAE antibody positivity: a single center experience from north India;the MMP degraded and citrullinated vimentin (VICM) is a diagnostic and treatment response biomarker;incidence and outcome of covid-19 in AIRD patients on concomitant treatment with tofacitinib- results from KRA covid cohort (KRACC) subset;are we treating-to-target in spondyloarthritis (SPA)? a cross-sectional analysis from the Asia Pacific league of associations for rheumatology (APLAR) SPA registry;utilities of low-dose computed tomography (LDCT) on identifying patient with axial psoriatic arthritis (AXPSA) a cross-sectional study;age-related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis;and MICRORNA-27a-3p inhibits lung and skin fibrosis of systemic sclerosis by negatively regulating SPP1.
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The proceedings contain 68 papers. The topics discussed include: post-transplant lymphoproliferative disorder (PTLD) in a patient with rheumatoid arthritis;cancer, covid and control of RA - a toxic combination?;continuation of golimumab (anti-TNF) in a patient with SpA and low-risk prostate cancer, what is the right decision?;orbital lymphoma in a 72-year-old lady with rheumatoid arthritis: an argument for rituximab;a case of cancer mimicking inflammatory arthritis;managing relapsing and refractory lupus nephritis in juvenile systemic lupus erythematosus: a case report;a case of juvenile systemic lupus erythematosus with pyrexia of unknown origin;recurring brachial plexopathy- the zebra among the horses;and Neisseria meningitidis as a cause of isolated bilateral polyarticular native knee joint septic arthritis.
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Background: We report a 40-year- old female with co-existent lupus nephritis and thymoma who developed severe lupus flare (worsening nephritis, new onset hemolytic anemia) following SARS-CoV- 2 vaccine. Case: This 40 year old female has had stable lupus nephritis (LN) while maintained on mycophenolate mofetil and hydroxychloroquine for several years. A co-existent thymoma was likewise stable and did not require any added therapy apart from the management of the LN. She received the first dose of inactivated vaccine for SARS-CoV- 2 without event. Two weeks following the second dose, she developed Coombs positive hemolytic anemia (hemoglobin 64 g/L) with leukopenia (WBC 2.3 x 109/L), worsening nephritis (3+ proteinuria with uPCR 1.0, active urine sediments), hypocomplementemia, and elevated anti-dsDNA. She received methylprednisolone pulse therapy then maintained on prednisone 40mg/day with clinical improvement. Two weeks thereafter, she was admitted due to severe COVID-19 pneumonia accompanied by severe anemia requiring blood transfusion;she received a regimen of bevacizumab, dexamethasone, and remdesivir and was discharged recovered, without overt sequelae at the time of this report. Discussion(s): Vaccines are highly effective in reducing hospitalization and death attributable to SARS-CoV- 2 infection. There are concerns however regarding autoimmune disease flares following SARS-CoV- 2 vaccine, reported to occur in about 4% patients with autoimmune disorders. It is also possible that this patient's reaction may have been further aggravated by the co-existent thymoma. While there was apparent sub-optimal protection of the vaccine against moderate to severe COVID-19 infection in this patient, it may be conjectured that her significant recovery and response to the anti-viral combined with immunosuppressive regimen may be due to the high dose steroid treatment given for the post-vaccine autoimmune reaction.
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Background and Objective: This study describes the prevalence, characteristics, and outcomes of COVID-19 infection among patients with autoimmune rheumatic diseases (AIRD) seen in a tertiary hospital in Manila, Philippines. Method(s): This cross sectional study included patients diagnosed with AIRD seen over a 24-month period from March 2020 to February 2022 confirmed with COVID-19 infection. We collected data from patients' electronic records, clinic and hospital charts and analyzed underlying AIRD characteristics including disease activity, medications, severity, and outcomes including hospitalization and mortality. Result(s): Of the 565 patients with AIRD, 67 patients reported to be positive for COVID-19. The most common underlying AIRD was systemic lupus erythematosus (SLE) in 53 patients followed by rheumatoid arthritis and dermatomyositis. Cough, fever, dyspnea, diarrhea, anosmia, ageusia and sore throat were the common presenting symptoms. Three were asymptomatic, 52 had mild symptoms, 3 patients had moderate and 9 had severe COVID-19 infection. Nineteen patients (28%) were subjected to hospitalization and admission and 48 (72%) were confined at home or in an isolation facility. Use of methotrexate, mycophenolate mofetil, prednisone <10 mg/day and hydroxychloroquine did not affect the risk for moderate to severe COVID-19 infection, hospitalization and mortality. However, the use of azathioprine increases the risk for moderate to severe COVID-19 infection but not for hospitalization and mortality. Four (6%) patients died of severe COVID-19 pneumonia: an elderly rheumatoid arthritis patient with co-morbidity of asthma, a lupus nephritis patient with end stage renal disease on hemodialysis, another lupus nephritis patient with malignancy who underwent radiotherapy and lastly, a patient with overlap dermatomyositis and SLE with restrictive lung disease due to severe dextroscoliosis. Conclusion(s): This single-center experience on AIRD patients with COVID-19 infection showed that patients with active disease, co-morbidities, especially lung diseases, and use of high dose glucocorticoid had higher risk for moderate to severe COVID-19 infection, hospitalization and mortality.
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Background: Blockade of JAK, preferably JAK1, by upadacitinib is a feasible approach to achieve erosion repair as it (1) is approved for the treatment of rheumatoid arthritis (RA), (2) effectively controls the inflammation and (3) targets pathogenic pathways that influence local bone homeostasis in the joint. To address the question whether inhibition of JAK1 could lead to erosion repair in patients with active RA, we performed a pilot non-randomized study comparing the changes in bone erosions on high-resolution peripheral quantitative computer tomography (HR-pQCT) before and after upadacitinib. Method(s): This is a 24-week, single-centered, prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA (Disease activity score 28-C- reactive protein [DAS28-CRP] > 3.2) and >=1 bone erosion on HR-pQCT. They were given upadacitinib 15mg once daily for 6 months. HR-pQCT of the 2-4 metacarpophalangeal (MCP) head was done at baseline and 6 months. The primary outcome was the change of erosion volume on HR-pQCT. Secondary outcomes included change in RA disease activity and predictors of response to treatment. Erosion regression was defined as decrease in volume exceeding the smallest detectable change. Result(s): The baseline clinical characteristics of the recruited patients were shown in Table 1. Of the 20 patients, 11 (55%) patients failed to respond to 3 or more csDMARDs. At 24-week, there was significant improvement in mean DAS28 (-1.75, P < 0.001). Erosion regression was seen in 8 (40%) patients on HR-pQCT (Figure 1). Although no significant change in overall median erosion volume before and after upadacintinib (0.07 [-0.90 to 0.76 mm3] mm3, P = 0.904) was noted, the deterioration was less obvious compared to a historic cohort of 20 patients with similar age and disease activity on csDMARDs (median erosion volume change in 6 months: 0.67 mm3). When patients were stratified according to whether or not they had failed multiple csDMARDs, significantly high proportion of patients in the non-multiple- DMARDs failure group had volume regression in at least one erosion compared to those in the failure group (75% vs 25%, P = 0.04). There was improvement in mean total erosion volume in the non-failure group (-0.33 +/- 1.33 mm3), whereas mean erosion volume in the failure group worsened (2.09 +/- 7.62 mm3). One patient developed chest infection requiring hospitalization and withdrew from the study. No other serious adverse event was noted. Conclusion(s): The results of the study suggest upadacitinib is clinically efficacious in refractory RA disease and can retard erosion progression. Regression of erosion is possible, particularly in those with limited csDMARDs exposure. Whether early JAK1 inhibition could lead to better structural outcome warrants further investigations. (Figure Presented).
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Background: People with systemic lupus erythematosus (SLE) are at greater risk of developing infections, including COVID-19. This study describes the characteristics and outcomes of COVID-19 infection among patients with SLE seen in a tertiary hospital in Manila, Philippines. Method(s): This cross-sectional study included patients with diagnosed SLE seen over 24 months from March 2020 to February 2022, who were confirmed with COVID-19 infection. We collected data from patients' electronic records and clinic charts and analyzed underlying SLE characteristics including disease activity and medications, COVID-19 involvement, vaccination status and outcomes including hospitalization and mortality. Result(s): Of the 507 patients with SLE, 53 patients reported positive for COVID-19. Cough, fever, dyspnea, diarrhea, anosmia, ageusia, and sore throat were the common presenting complaints. Three were asymptomatic, 41 had mild symptoms, 2 had moderate, and 7 had severe COVID-19 infection. Sixteen patients (30%) were hospitalized, and 37 (70%) were confined at home or an isolation facility. More than half of patients were unvaccinated during the time of COVID-19 infection (28, 54%), 3 (6%) were partially vaccinated and 21 (40%) were fully vaccinated. Use of methotrexate, mycophenolate mofetil, prednisone <10 mg/day, and hydroxychloroquine did not affect the risk for moderate to severe COVID-19 infection. Patients in low disease activity or remission tended to have asymptomatic to mild COVID-19 infection. Two (4%) died with severe COVID 19 infection: a lupus nephritis patient with end-stage renal disease on hemodialysis and a lupus nephritis patient with concomitant double gynecologic malignancy (vulval and cervical) who underwent 35 cycles of radiotherapy prior to COVID-19 infection. Conclusion(s): This study on SLE patients with COVID-19 infection showed that patients with high disease activity, co-morbidity especially ESRD and the use of high dose glucocorticoid had higher risk for moderate to severe COVID-19 infection and hospitalization. Use of immunosuppressants and prednisone <10 mg/day did not appear to contribute to increased severity of COVID-19 infection, hospitalization and mortality.
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Background: Presenting features for glomerular disease can be varied, including but not exclusively, acute kidney injury, nephrotic syndrome or haemo-proteinuria. At our regional tertiary centre we conducted a retrospective study to see whether clinical presentations of glomerular diseases had changed during the COVID-19 pandemic. Method(s): In this study, new and repeat native renal biopsies were included from January 2018 to October 2021. Glomerular pathologies of interest included minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis and pauciimmune glomerulonephritis. We looked at three periods of time: prior to the start COVID-19 pandemic in 2018/19;during the COVID-19 pandemic in 2020;and after the introduction of COVID-19 vaccines in 2021. Result(s): 263 biopsies were identified over the 4-year period. IgA nephropathy - n = 13. Lupus nephritis - n = 43. The different classes of lupus nephritis are shown in (see figure 1) Minimal change disease - n = 57. All presented with the nephrotic syndrome. Between 6-25% over the study period presented with AKI (mean 19%) Pauci-immune glomerulonephritis - n = 85. Between 81%-91% over the study period presented with AKI, or AKI on CKD (mean 84%) Membranous glomerulopathy - n = 66. 50%, presented with the nephrotic syndrome. 20% presented with AKI in addition to proteinuria. Conclusion(s): Our analysis has not shown a significant change in clinical presentations of glomerular disease. There has not been an increased propensity in presenting with AKI in minimal change disease or membranous nephropathy. We saw the highest proportion of class IV lupus nephritis in 2021.
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Background: Glomerular disease carries a significant burden of morbidity and mortality. There is emerging evidence of the impact of the COVID-19 pandemic and COVID-19 vaccination on glomerular disease. The aim of the study was to retrospectively analyse our experience of the incidence of glomerular disease between 2018 and 2021. Method(s): Native renal biopsy results were reviewed to compare the incidence of glomerular disease prior to the COVID-19 pandemic (2018/19);prior to development of COVID-19 vaccination (2020);and after the introduction of COVID-19 vaccines (2021). Biopsy data from January 2018 to October 2021 were collated from pathology records for all glomerular disease patients in our unit. We focused on the incidence of IgA nephropathy, lupus nephritis, minimal change disease, membranous nephropathy and pauci-immune glomerulonephritis. Result(s): 263 native biopsies were performed;45 biopsies in 2018, 75 in 2019, 65 in 2020 and 78 in the first ten months of 2021. The proportional incidence of each disease is shown in figure 1. The incidence of membranous nephropathy was noted to be higher in 2021, coinciding with the introduction of the COVID-19 vaccine programme in the UK, from an average of 23% of cases between 2018-2020, to 31% in the first ten months of 2021. The overall incidence of glomerular disease, excluding vasculitis, seemed to have fallen during 2020. Conclusion(s): The emergence of COVID-19 does not appear to have caused a significant increase in the overall incidence of glomerular disease in our population. We noted an increase in the incidence of membranous nephropathy following the introduction of the COVID-19 vaccination programme in 2021. The relatively lower incidence in 2020 could be related to limited access to primary health care practitioners and consequent reduction in referrals to secondary care at the time.
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SESSION TITLE: Autoimmune Diseases Gone Wild: Rare Cases of Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Post-Covid-19 Multisystem Inflammatory Syndrome (MIS) is a severe hyperinflammatory syndrome associated with either the acute or recovery phase of covid-19 infection affecting multiple organ systems requiring hospitalization. This syndrome has been described in both children (MIS-C) and adults (MIS-A). Several case reports and systematic reviews have reported an association between post-covid-19 MIS-A and several autoimmune diseases. CASE PRESENTATION: We herein report a case of a 27-year-old female with no known chronic medical condition and a non-contributory family history who was diagnosed with post-covid-19 multisystem inflammatory syndrome in adults (MIS-A). She presented with generalized partial thickness erythematous skin ulcerations with tender blistering and painful erosion of her mucus membranes (oral and vaginal mucosa). This was diagnosed as Steven Johnsons syndrome. She was pulsed with intravenous methylprednisone. During this therapy, she progressed to severe acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (fig 1). Bronchoscopy revealed mild pulmonary hemorrhage fig 2a&b). Serological testing heralded a new onset systemic lupus erythematosus in light of positive antinuclear antibodies, anti Ds DNA and anti Smith antibodies. Her course was complicated by significant proteinuria and an active renal cast suggestive of lupus nephritis. This necessitated further treatment for active lupus. She was successfully extubated and discharged home. DISCUSSION: We arrived at the diagnosis of post-covid-19 multisystem inflammatory syndrome in adults (MIS-A) in light of her presenting with fever, hypotension, persistent sinus tachycardia and new onset atrial fibrillation), acute pancreatitis, acute kidney injury, elevation in transaminases, new onset skin rash, elevated inflammatory markers and a recent history of positive SARS-CoV-2 infection. Covid-19 has been reported to induce wide spread vasculitis resulting in MIS-A or MIS-C by triggering type 3 hypersensitivity (1). Also, multiple case reports and systemic reviews have reported a direct association between MIS-A and several autoimmune diseases including SLE, SJS (2). The patient recovered with high dose corticosteroid and supportive therapy indicating her severe ARDS was most likely due associated to SJS, SLE and MIS-A. Clinicians should also keep in mind that SARS-CoV-2 PCR swab may be negative at the time patient presents with symptoms of MIS-A as the infection might have occurred about 4-5weeks prior just as in our patient(3) CONCLUSIONS: We cannot underscore enough the importance of clinicians having a high index of suspicion for this syndrome in patients with acute or recent covid-19 infection, with or without a positive PCR covid-19 test. Early involvement of a multidisciplinary approach and appropriate management is essential to mitigate morbidity and mortality in these patients. Reference #1: Roncati L, Ligabue G, Fabbiani L, Malagoli C, Gallo G, Lusenti B, et al. Type 3 hypersensitivity in COVID-19 vasculitis. Clin Immunol Orlando Fla. 2020 Aug;217:108487. Reference #2: Gracia-Ramos AE, Martin-Nares E, Hernández-Molina G. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells [Internet]. 2021 Dec 20 [cited 2022 Mar 22];10(12):3592. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700122/ Reference #3: Morris SB. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep [Internet]. 2020 [cited 2022 Mar 22];69. Available from: https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm DISCLOSURES: No relevant relationships by Isaac Ikwu No relevant relationships by Anthony Lyonga Ngonge No relevant relationships by Alem Mehari No relevant relationships by Noordeep Panesar no disclosure on file for Vis al Poddar;No relevant relationships by Emnet Yibeltal
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Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest
ABSTRACT
Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.
ABSTRACT
Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of severe COVID-19 due to the underlying disease, comorbidities and use of immuno-suppressants (IS). An alternative option would be to adopt telemedicine (TM) to maintain medical care while minimizing exposure. Despite being widely adopted during the pandemic, the evidence supporting the use of TM in rheumatology has been limited. Objectives: We primarily aimed to evaluate the effectiveness to maintain disease activity control using TM delivered care compared to conventional in-person follow-up in patients with lupus nephritis (LN). The secondary objectives were to compare the patient reported outcomes, safety and cost-of-illness from the patient's perspective between the 2 modes of health care delivery. Methods: This was a 1-year, single-center, RCT conducted at a regional hospital in Hong Kong. From May 2020, consecutive adult patients with a SLE according to the 2019 EULAR/ACR classifcation criteria followed up at the LN clinic were invited to participate in the study. Participants were randomized 1:1 to either TM (TM group) or standard FU (SF group). Patients randomized to receive TM FU were scheduled for a video consultation via a commerical software ZOOM. Patients in the SF group received standard in-person outpatient care. SLE disease activity at each consultation was assessed by SLEDAI-2k and physician global assessment (PGA). Results: A total of 144 patients with LN were randomized and 3 patients self-withdrew from the study. The mean age was 44.5±11.4 years and the median time from diagnosis to randomization was 168 months (range: 1-528). Most of the patients had class III, IV or V LN (87.2%) and were on prednisolone (89.4%, median dose 5mg daily). Many of them (68.1%) were on IS. While 66.0% of the patients were in lupus low disease activity state (LLDAS), none had disease remission. There were no baseline differences, including demographics, SLEDAI-2k (TM: 3.8±2.3, SF: 3.2±2.2, p=0.13, PGA (TM: 6.2±6.5, SF: 4.6±5.9, p=0.13) and SLE damage index (TM: 1.1±1.3, SF: 0.8±1.1, p=0.10), between the 2 groups. At one year, 80.0% and 80.2% of the patients in the TM group and SF group were in LLDAS or remission respectively. SLE disease activity indices including SLEDAI-2k, PGA, proteinuria amount and serum anti-ds-DNA level remained similar between the 2 groups. Within the study period, 28 (40%) patients in the TM group and 21 (29.6%) patients in the SF group had disease fare (p=0.20). There were no differences in the SF-36, lupusQoL and HADS scores between the 2 groups at the end of the study. The overall patient satisfaction score was higher in the TM group with a signifcantly shorter waiting time before seeing doctors. At the end of the study, 67.9% of the overall participants agreed to (versus 15.0% who did not agree to) use TM as a mode of future FU. The mean indirect costs of illness (HKD26,681 vs HKD12,016, p=0.20) and the out-of-pocket costs for health care services were similar between the 2 groups (TM: HKD13,547 vs SF: HKD12,297, p=0.83) in one year. The total number of FU was similar (TM: 6.0±2.0, SF: 5.7±1.7, p=0.40). However, signifcantly more patients in the TM group (29/70, 41.4% vs 4/71, 5.6%;p<0.01) requested change mode of FU. The proportion of patients requiring hospitalization during the study period was also higher in the TM group (TM: 23/70, 32.9% vs 11/71, 15.5%;p=0.02). After adjusting for age and pred-nisolone dosage, not being in LLDAS at baseline was the predictor of hospitalization (OR 3.4, 95%CI 1.20-9.65). None of the participants was tested positive for COVID-19. Conclusion: TM FU resulted in similar 1-year disease activity control and better satisfaction in patients with LN compared to standard care. However, a signifcant proportion of patients cared by TM required in-person visits or were hospitalized. The results of the study suggest that TM delivered care could help minimizing exposure to COVID-19, but it needs to be complemented by physical visits, particularly in those with unstable d sease.
ABSTRACT
Background: Voclosporin (VCS), a novel calcineurin inhibitor, was approved in the US in January 2021 for the treatment of adult patients with active lupus nephritis (LN) in combination with background immunosuppressive therapy. The Phase 3 AURORA 1 study showed that the addition of VCS to mycophenolate mofetil (MMF) and low-dose steroids in patients with LN signifcantly increased rates of complete renal response at 52 weeks. Objectives: Here we report the results of the completed continuation study, AURORA 2, which assessed the long-term safety and tolerability of VCS compared to placebo in patients with LN receiving treatment for an additional 24 months following completion of the AURORA 1 study Methods: Key inclusion criteria for the parent AURORA 1 study included a diagnosis of biopsy-proven active LN (Class III, I V, or V ± III/IV), proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V) and estimated glomerular fltration rate (eGFR) >45 mL/min/1.73 m2. Patients who completed AURORA 1 and who elected and were eligible to enter AURORA 2 continued on the same blinded therapy as at the end of AURORA 1 (either VCS or placebo twice daily in combination with MMF and low-dose steroids). Safety and tolerability were monitored, and eGFR, serum creatinine (SCr), and urine protein creatinine ratio (UPCR) were also assessed. Results: In total, 116 and 100 patients in the VCS and control arms enrolled in AURORA 2, with 92 (79.3%) and 73 (73.0%) patients in each respective arm receiving treatment to the end of AURORA 2. There were no unexpected safety signals in the VCS arm compared to control, with similar rates of serious adverse events reported in both arms (VCS [18.1%] vs. control [23.0%];Table 1). Eight patients in each arm experienced serious adverse events of infection;serious coronavirus infections were observed in 2 patients in the voclosporin arm and 5 patients in the control arm. There were 4 and 2 adverse events by preferred term of renal impairment reported in the VCS and control arms, respectively, none of which were considered serious, and no reports of acute kidney injury by preferred term in either arm. There were no deaths in the VCS arm during AURORA 2;four deaths were reported in the control arm (pulmonary embolism [n=1], coronavirus infection [n=3]). Mean eGFR and SCr levels remained stable through the end of AURORA 2. The difference between the VCS and control arms in LS mean change from baseline in eGFR was 2.7 mL/min/1.73 m2 at 4 weeks following study drug discontinuation (Figure 1). The mean reductions in UPCR observed in patients treated with VCS in AURORA 1 were maintained in AURORA 2 with no increase in UPCR noted at the follow-up visit 4 weeks after study drug discontinuation. Conclusion: Voclosporin was well-tolerated over 3 years of treatment with no unexpected safety signals detected. Further, eGFR remained stable throughout the study period, and the signifcant and meaningful reductions in proteinuria achieved in AURORA 1 were maintained. These data provide evidence of a longterm treatment beneft of VCS in patients with LN. Includes adverse events starting on or after the frst dose of study drug in AURORA 2 up to 30 days after the last dose and all events of death reported during study follow-up. Adverse events were aggregated by System Organ Class and Preferred Term and coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0. AE, adverse event.
ABSTRACT
Background: Numerous immune-mediated diseases fare or new disease onset after SARS-CoV2-vaccination have been reported. There were case reports showed the immune-mediated disease fare post vaccination but study on new disease occurs post Covid-19 vaccination is still lacking. Objectives: To describe two SLE cases that diagnosed post Covid-19 vaccination. Methods: Case report Results: 14 years old girl, post Covid-19 vaccination 1st dose 3 weeks ago presented with 2 day history of giddiness, breathlessness, vomiting and diarrhea prior to admission. She also complained of frothy urine for the past 1 week associated with lower limbs swelling and facial puffiness. Clinical examination noted she had sparse hair, oral ulcers and discoid lupus at the ear concha. She also noted to have periorbital puffiness with pedal edema. Lung auscultation noted bi-basal crepitations. Blood investigation noted ANA positive (1:640, speckled) with low complement 3 (0.1g/L). Her full blood count showed leucopenia (3100 UL) with low lymphocyte count of 810UL. UFEME noted protein of 3 + and red blood cell of 2+ with normal renal profile. Her serum albumin was 22g/L. Chest x ray showed clear lung field with no cardiomegaly. Her 24-hour urine protein showed proteinuria of 2.345g/dl and her renal biopsy showed mesangial proliferative lupus nephritis class iI. She was given intravenous methyl-prednisolone 500mg OD for 3 days and discharged with tapering dose of prednisolone, hydroxychloroquine, calcium supplements, perindopril and frusemide. Another case was a 17 year-old female, post covid-19 vaccination 10 weeks, presented with 3 weeks history of bilateral lower limbs weakness with difficulty in getting up from chair. She also had fever on and off with cough for 1 week. There was no alopecia, oral ulcer, facial rash or photosensitivity. No joints pain. Clinical examination noted presence of proximal myopathy with stable vital signs. Other systemic examinations were unremarkable. Blood investigation noted ANA positive (1: 640, homogenous and speckled) with low complements level (C3 0.19g/L and C4 0.049 g/L).Her creatine kinase was 2367U/L and EMG showed evidence of irritable myopathic process which is consistent with inflammatory myositis. Her TFT was normal. Myositis panel showed anti-Ku and anti-Ro 52 were positive. She was treated as SLE with myositis and intravenous methylprednisolone was given. She discharge well with tapering dose of prednisolone and azathioprine. Her creatine kinase showed improvement with immunosuppression therapy and she was advised on intensive physiotherapy. Conclusion: The onset of these two SLE cases were occurred within the 2 month of post covid-19 vaccination. Whether Covid-19 vaccination direct contribute to the occurrence of SLE remained inconclusive. More studies are required to show its correlation between onset of SLE and Covid-19 vaccination.