Background Hyperinflammation (HI) developing in 2 nd week of COVID‐19 contributes to the worse outcome. Because of relatively milder laboratory findings, available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome could not be helpful. Methods Discovery cohort included symptomatic COVID‐19 patients from Turkey, followed at hospital during the initial wave. Replication cohort consisted of hospitalized patients from a later period; all required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel and the majority received tocilizumab or anakinra. Daily clinical and laboratory data were recorded, and data of treatment start day were compared with the 5 ‐ 6 th day data of other patients. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. Results 685 patients were analyzed in discovery and 156 in replication cohorts; of whom 150 and 61 received treatment for HI, respectively. Mortality rate was higher in HI patients of discovery cohort (23.3%) compared to the rate of other patients (3.7%), and it was much lower in replication cohort for both groups. The 12‐item criteria were developed to define HI of COVID‐19 (HIC), and score of 35 provided 85.3% sensitivity, 81.7% specificity. The same criteria gave 90.0% sensitivity for HIC in replication cohort, but lower specificity values were observed, due to the inclusion of milder cases of HIC responding only glucocorticoids. Conclusions The new criteria are expected to define patients with HIC better with reasonable sensitivity and specificity and enable us to start treatment as early as possible. This article is protected by copyright. All rights reserved.

Background:Recently developed EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) have important differences compared to the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria and the revised 1997 American College of Rheumatology (ACR) criteria: The obligatory entry criterion of antinuclear antibody (ANA) positivity is introduced and a “weighted” approach is used1. Sensitivity and specificity of these three criteria have been debated and may vary in different populations and clinical settings.Objectives:We aim to compare the performances of three criteria sets/rules in a large cohort of patients and relevant diseased controls from a reference center with dedicated clinics for SLE and other autoimmune/inflammatory connective tissue diseases from Turkey.Methods:We reviewed the medical records of SLE patients and diseased controls for clinical and laboratory features relevant to all sets of criteria. Criteria sets/rules were analysed based on sensitivity, positive predictive value, specificity and negative predictive value, using clinical diagnosis with at least 6 months of follow-up as the gold standard. A subgroup analysis was performed in ANA positive patients for both SLE patients and diseased controls. SLE patients that did not fulfil 2012 SLICC criteria and 2019 EULAR/ACR criteria and diseased controls that fulfilled these criteria were evaluated.Results:A total of 392 SLE patients and 294 non-SLE diseased controls (48 undifferentiated connective tissue disease, 51 Sjögren’s syndrome, 43 idiopathic inflammatory myopathy, 50 systemic sclerosis, 52 primary antiphospholipid syndrome, 15 rheumatoid arthritis, 15 psoriatic arthritis and 20 ANCA associated vasculitis) were included into the study. Hundred and fourteen patients (16.6%) were ANA negative.Sensitivity was more than 90% for 2012 SLICC criteria and 2019 EULAR/ACR criteria and positive predictive value was more than 90% for all three criteria (Table 1). Specificity was the highest for 1997 ACR criteria. Negative predictive value was 76.9% for ACR criteria, 88.4% for SLICC criteria and 91.7% for EULAR/ACR criteria.In only ANA positive patients, sensitivity was 79.6% for 1997 ACR criteria, 92.2% for 2012 SLICC criteria and 96.1% for 2019 EULAR/ACR criteria. Specificity was 92.6% for ACR criteria, 87.8% for SLICC criteria 85.2% for EULAR/ACR criteria.Eleven clinically diagnosed SLE patients had insufficient number of items for both 2012 SLICC and 2019 EULAR/ACR criteria. Both criteria were fulfilled by 16 diseased controls: 9 with Sjögren’s syndrome, 5 with antiphospholipid syndrome, one with dermatomyositis and one with systemic sclerosis.Table 1.Sensitivity, positive predictive value, specificity and negative predictive value of 1997 ACR, 2012 SLICC and 2019 EULAR/ACR classification criteriaSLE (+)SLE (-)Sensitivity (%)Positive Predictive Value (%)Specificity (%)Negative Predictive Value (%)1997 ACR(+) 308(-) 841527978.695.494.976.92012 SLICC(+) 357(-) 352626891.193.291.288.42019 EULAR/ACR(+) 368(-) 242826693.892.990.591.7Conclusion:In this cohort, although all three criteria have sufficient specificity, sensitivity and negative predictive value of 1997 ACR criteria are the lowest. Overall, 2019 EULAR/ACR and 2012 SLICC criteria have a comparable performance, but if only ANA positive cases and controls are analysed, the specificity of both criteria decrease to less than 90%. Some SLE patients with a clinical diagnosis lacked sufficient number of criteria. Mostly, patients with Sjögren’s syndrome or antiphospholipid syndrome are prone to misclassification by both recent criteria.References:[1]Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019;78:1151-1159.Disclosure of Interests:None declared

Background:COVID-19 runs a severe disease associated with acute respiratory distress syndrome in a subset of patients, and a hyperinflammatory response developing in the second week contributes to the worse outcome. Inflammatory features are mostly compatible with macrophage activation syndrome (MAS) observed in other viral infections despite resulting in milder changes. Early detection and treatment of MAS may be associated with a better outcome. However, available criteria for MAS associated with other causes have not been helpful.Objectives:To identify distinct features of MAS associated with COVID-19 using a large database enabling to assess of dynamic changes.Methods:PCR-confirmed hospitalized COVID-19 patients followed between March and September 2020 constituted the discovery set. Patients considered to have findings of MAS by experienced physicians and given anakinra or tocilizumab were classified as the MAS group and the remaining patients as the non-MAS group. The MAS group was then re-grouped as the cases with exact-MAS and borderline-MAS cases by the study group. Clinical and laboratory data including the Ct values of the PCR test were obtained from the database, and dynamic changes were evaluated especially for the first 14 days of the hospitalization. The second set of 162 patients followed between September-December 2020 were used as the replication group to test the preliminary criteria. In the second set, hospitalization rules were changed, and all patients required oxygen support and received dexamethasone 6mg/day or equivalent glucocorticoids. Daily changes were calculated for the laboratory items in MAS, borderline, and non-MAS groups to see the days differentiating the groups, and ROC curves and lower and upper limits (10-90%) of the selected parameters were calculated to determine the cutoff values.Results:A total of 769 PCR-confirmed hospitalized patients were analysed, and 77 of them were classified as MAS and 83 as borderline MAS patients. There was no statistically significant difference in the baseline viral loads of MAS patients compared to the non-MAS group according to the Ct values. Daily dynamic changes in the MAS group differed from the non-MAS group especially around the 6th day of hospitalization, and more than a twofold increase in ferritin and a 1.5-fold increase in D-dimer levels compared to the baseline values help to define the MAS group. Twelve items selected for the criteria are given in Table 1 below. The total score of 45 provided 79.6% sensitivity for the MAS (including borderline cases) and 81.3% specificity around days 5 and 6 in the discovery set, and a score of 60 increased the specificity to 94.9% despite a decrease in sensitivity to 40.8%. The same set provided a similar sensitivity (80.3%) in the replication, but a lower specificity (47.4-66% on days 6 to 9) due to a group of control patients with findings of MAS possibly masked by glucocorticoids.Table 1.Preliminary Criteria for Macrophage Activation Syndrome Associated with Coronavirus Disease-191.Fever (>37.0 °C)2.Ferritin concentration > 550 ng/mL3.More than 2 times increase of ferritin concentration within 7 days of disease onset4.Neutrophil count > 6000 cell/mm35.Lymphopenia < 1000 cell/mm36.Neutrophil/lymphocyte ratio > 67.D-dimer concentration > 1000 ng/ml8.More than 50% increase of D-dimer concentration within 7 days of disease onset9.CRP concetration > 50 mg/L10.LDH concentration > 300 U/L11.ALT or AST concentration > 50 U/L12.Procalcitonin concentration < 1.21 point for each positive item assessed on Days 5-7Score calculation: Total points / 12 x 100Possible MAS ≥45 and Definite MAS ≥60Conclusion:This study defined a set of preliminary criteria using the most relevant items of MAS according to the dynamic changes in the parameters in a group of COVID-19 patients. A score of 45 would be helpful to define a possible MAS group with reasonable sensitivity and specificity to start necessary treatments as early as possible.Disclosure of Interests:None declared.

Background:Serious infections (SI) are one of the main complications in patients with ANCA associated vasculitis (AAV).Objectives:We planned to investigate the prevalence, features and risk factors of SI in our AAV cohort during follow-up.Methods:Outpatient and hospital data of patients diagnosed with granulomatous polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatous polyangiitis (eGPA) between 1999 and 2019 according to Chapel Hill Consensus Criteria and followed up at least 6 months in our vasculitis clinic were evaluated. Development of sepsis, requirement for intravenous (IV) antibiotherapy and / or hospitalization during infection episodes were considered as SI. Chi-square, student’s t-test and logistic regression analysis were used for statistical analysis.Results:Study was conducted with 186 (53.6% female) patients with adequate follow-up data. Mean age of diagnosis was 54.3±14,5 (23-79), mean follow-up duration was 86,4 ± 54,3 (6-251) months. Number of GPA, MPA and eGPA patients were 132 (71%), 42 (22,5%) and 12 (6,5%), respectively. IV cyclophosphamide (CYC) was used in 148 (79,6%), azathioprin in 105 (56,5%), rituximab (RTX) in 69 (%37,1), methotrexate in 29 (15,6%) and mycophenolate mofetil in 14 (7,5%) patients. Number of patients developed SI was 66 (34.7%), total SI episode was 86, patients who had multiple episodes was 15. All SI is shown in Table-1. Bacterial pneumonia was the most common diagnosis and 26 of SI (30.2%) were considered as opportunistic (systemic viral, parasite, fungus) infections. Thirty-one of patients developed SI (40,7%) in the first year after diagnosis. SI were observed more frequently in the presence of major organ involvement (kidney, lung, neurological) (65/173 vs. 1/13 p = 0.02 OR = 8.7 95% CI 1.06-64.4). Diffuse alveolar hemorrhage (DAH) was associated with SI in multivariate analysis (12/52 vs. 0/34 p=0.007 OR=1.6 95% CI 1.3-1.96). Cumulative CYC dose was significantly higher in patients with SI (14,2±21 vs. 8.2±13.9 p=0.045). During maintenance, patients treated with RTX had significantly more SI (18/53 vs. 17/99 p=0.19 OR=3,3 95% CI 1,55- 7,07). Hypogammaglobulinemia (HIgG) (IgG<700 mg/dL) was present in 12 (14%) SI episodes. HIgG was associated with SI in RTX-treated patients (5/13 vs. 7/47 p=0.03 OR=4.2, CI=1-16.5). Hospitalization need for SI was 65%. Disease flares (34/128 vs. 32/62 p = 0.001 %95 CI = 2.9 95% CI 1.6-5.6) and organ damage presence were more common (64/65 vs. 109/125 p = 0.01 95% OR= 8.9 95% CI 1.1-68.9) in patients with a history of SI in multivariate analysis. SI was confirmed as cause of death in three cases.Conclusion:Long-term follow-up results of a single center cohort of AAV patients revealed that approximately one third of patients developed SI, most frequently in the first year of treatment. During the maintenance period, the risk of SI continues. Cumulative CYC dosage and maintanence with RTX is associated with SI, especially in patients who developed hIgG. Major organ involvement, disease flares and organ damage are significant risk factors for SI. In this regard, protection measures (vaccination, prophylaxis) should be reviewed and the quality of follow-up should be improved.Table 1.Serious infections in AAV patients.BACTERIALNFUNGALNVIRALNPROTOZOANNPneumonia37PJP7Zoster Zona3Intramuscular abscess (Nocardiosis)1Urinary Tract Infection (UTI)8Aspergilloma1CMV Pneumonia1Gr (-) sepsis2Invasive Fungal Infection3CMV Colitis1Perianal abscess2Candida Eosephagitis4CMV Gastritis1Intraabdominal abscess2Candidemia2HSV Eosephagitis1Catheter infection2UTI1Sellulitis1Fungal otitis1Orbital sellulitis1Maxillary sinüs abscess1Mastoiditis1Prosthesis infection1Septic artrhitis1Lung tuberculosis1Disclosure of Interests:None declared

No abstract