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BackgroundSerious infections are more frequently seen in patients with inflammatory rheumatic diseases, being treated with immunosuppressive or biologic disease-modifying antirheumatic drugs (b-DMARDs). Potential harmful effects of immunosuppressive drugs as well as b-DMARDs were a major concern during the early phases of the Coronavirus disease 2019 (COVID-19) pandemic, and preliminary data documented the worse outcome of COVID-19 associated with B cell depleting treatments (1). On the other hand, limited information has been shared about the course of COVID-19 in patients with monogenic autoinflammatory disorders using IL-1 inhibitors.ObjectivesWe herein aimed to evaluate the course of COVID-19 in adult patients with the most common form of inflammasomopathy, Familial Mediterranean Fever (FMF), who were on biologic agents.MethodsIn this cross-sectionally study, FMF patients were evaluated by screening their clinical and electronic records in our database in October 2021. The FMF patients with a record of PCR-confirmed COVID-19 were investigated in more detail in our hospital. Characteristics of FMF findings as well as clinical and laboratory findings associated with COVID-19 were recorded from the outpatient follow-up cards.ResultsWe identified 184 FMF patients using biologic agents, and their baseline characteristics are summarized in Table 1. Among them, 36 had PCR-confirmed COVID-19; 32 of them were currently on b-DMARD along with colchicine (31 anti-IL-1, 1 anti-TNF), and 4 of them had a previous history of b-DMARD treatment. Data about the course of COVID-19 could be reached in 34 patients. Four (11%) patients had an asymptomatic course. Remaining patients with symptomatic COVID-19 had the following symptoms: cough (50%), headache (47.2%), fever (44.4%), loss of taste and smell (41.6%), myalgia (0.6%), dyspnoea (27.8%), diarrhea (25%) abdominal pain (5.6%). Thorax computed tomography was performed in 10 patients, and findings of pneumonia were documented in 6 (16.7%). The mean values of the laboratory parameters were as follows: C-reactive protein 99.48 ± 112.66 mg/L; ferritin 316 ± 208.3; D-Dimer 2445 ± 3917, Lactate Dehydrogenase 253 ± 61, troponin T 26 ± 20, procalcitonin 0.348 ± 0.53. Lymphopenia was detected in 5 (13.9%) patients; mean lymphocyte count was 1080 ± 363. Data about the treatment could be reached in 34 patients. Antiviral therapy was prescribed in 25 (69.4%) patients (favipiravir, n=22; and oseltamivir, n=3). Antibiotics were given to 6 (16.7%) patients, and 6 (16.7%) received hydroxychloroquine. Parenteral steroids were administered to 2 patients during the hospitalization. Six (16.7%) patients required hospitalization, and 2 (5.6%) required oxygen support, non-invasive mechanical ventilation, and one of them followed in the intensive care unit. Twenty-two patients were on anakinra treatment, and none of them required additional dose. Only 1 patient, a 61-year-old male patient with a history of lung lobectomy and renal transplantation, received tocilizumab due to macrophage activation syndrome, and he later died of sepsis. This patient was on anakinra until 2 years before, and it was discontinued due to an allergic reaction. Only 4 patients had a history of vaccination before COVID-19, and none of them developed pneumonia and required hospitalization. Six patients had FMF attacks after recovering from COVID-19. None of the patients developed thromboembolism and secondary bacterial infections.ConclusionThis survey identified 36 biologic b-DMARD receiving FMF patients, who had COVID-19. All but 1 patient had complete recovery, and b-DMARD usage did not negatively affect the COVID-19 course. None of the patients currently on anti-IL-1 or anti-TNF had a worse outcome. Based on these observations, it can be suggested that refractory FMF patients can continue their b-DMARD treatments when they had COVID-19.References[1]Jérôme Avouac, Elodie Drumez, Eric Hachulla, Raphaèle Seror, Sophie Grorgian-Lavialle, et al. COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases trated with rituximab: a cohort study. Lancet Rheumatol 2021 Published Online March 25, 2021, https://doi.org/10.1016/S2665-9913(21)00059-XDisclosure of InterestsNone declared

The COVID-19 pandemic raises many alarms in the rheumatological era. Gianfrancesco et al reported the answer of an important question: the characteristics associated with hospitalization for COVID-19 in people with rheumatic disease.1 The data suggested that patients with rheumatic disease on prednisone dose of ≥10 mg/day were associated with higher odds of hospitalization, and vasculitis was the fourth common rheumatic disease among all of these patients. Another essential concept is to be careful in the differential diagnosis of the patients presenting with symptoms and signs of COVID-19. Physicians should keep in mind the other infectious and inflammatory diseases during diagnostic procedures of these critical patients. Inevitably, COVID-19 ranks first in differential diagnosis of all patients with respiratory symptoms and signs in current pandemic days. The standard of reference for confirming COVID-19 relies on microbiological tests, such as real-time reverse transcription polymerase chain reaction (RT-PCR).2 A systematic review of the accuracy of COVID-19 tests reported false-negative rates up to 29% (equating to a sensitivity of 71–98%), based on negative RT-PCR tests which could turn out positive on repeated testing.3 Chest CT can be used as an auxiliary to RT-PCR for diagnosing COVID-19 pneumonia in the current pandemic context.4 The main CT feature of COVID-19 pneumonia is the bilateral patchy ground-glass opacities (GGOs) with peripheral predominance.5 On the other hand, GGO has many causes and one of these is eosinophilic granulomatosis with polyangiitis (EGPA). Herein, we presented two patients who have been hospitalized with preliminary diagnosis of COVID-19 but diagnosed as EGPA in hospitalisation period for COVID-19. A male patient in his 20s was admitted to the emergency department with complaints of shortness of breath, cough and sputum. In the medical history of the patient, he had asthma for 3 years but he did not receive any asthma …

BackgroundDemonstration of deposits by non-invasive methods is important especially for organs difficult to sample in amyloidosis. Transient elastography (fibroscan) is a diagnostic method being used to measure liver stiffness (LS) in different chronic liver diseases.ObjectivesWe herein aimed to test the place of fibroscan method for detecting increased LS associated with amyloid deposition in patients (pts) with amyloidosis.MethodsSix categories of pts enrolled into this cross-sectional study; AA amyloidosis (AA-a), AL amyloidosis (AL-a), Familial Mediterranean Fever (FMF) pts without amyloidosis, cirrhotic chronic liver disease, non-cirrhotic chronic hepatitis B infection (CHB) and healthy controls (HC). LS assessment by fibroscan were categorized as normal for kPaResultsA total of 165 pts (AA-a, n=65; AL-a, n=15; FMF, n=20; cirrhotic pts, n=16; CHB, n=22; HC, n=27) constituted the study group. Average age was higher in the AL-a group compared to others. Median LS was highest in cirrhotic pts, and it was also higher in AA-a and AL-a pts compared to FMF and HC. Median LS was numerically higher in AL-a compared to AA-a, but it did not reach statistical significance. Median LS was also higher in FMF pts compared to HC. FIB-4 and APRI scores were lower compared to cirrhotic patients in AA-a and AL-a. ALP levels were higher in AA-a and AL-a groups compared to FMF, CHB and HC. FIB-4 and APRI scores, ALP and GGT levels were correlated with LS both in AA-a (r=0.534***,r=0.485***,r=0.437***, r=0.506***) and, AL-a (r=0.536*, 0.579*, r=0.645*, r=0.752**) and FMF-AA (r=0.584***, r=0.566***,r=0.322*, r=0.306*; *pHigher patient age, age at diagnosis of amylodosis, FIB-4 and LS scores, ALP levels, non-FMF causes of AA were associated with hepatic AA amyloid involvement in biopsy-proven pts. A cut-off value 12.05 kPa of LS provided 100% sensitivity and 85.5% specificity (LR=6.9, AUC=0.901, 95% CI 0.81-0.99) for pts with AA-a.ConclusionIn our single center cohort, we showed a higher median LS by fibroscan in both AL-a and AA-a pts compared to CHB, FMF and HC. It was thought to be that fibroscan may be useful in detecting hepatic amyloid involvement.Table 1.AA-a (n=65)FMF (n=20)AL-a (n=15)Cirrhosis (n=16)Chronic Hepatitis B (non-cirrhotic) (n=22)HC (n=27)p1p2p3p4p5p6Age (years)*46 (19)42.5(13)58 (16)49 (15)45 (21)45 (23)0.40.30.80.50.80.002Gender (n, %)Male38 (59)10 (50)6 (40)10 (62.5)13 (59)17 (55)0.50.810.70.70.2Female27 (41.5)10 (50)9 (60)6 (37.5)9 (40.9)14 (45.2)Diabetes Mellitus (n, %)5 (8)2 (11)2 (13)3 (15)2 (13)3 (10)0.70.60.40.80.90.6Body Mass Index (kg/m2) *25.7 (1.4)25.6 (5.4)24.8 (3.6)26.7 (6.7)25.5 (7)26 (5.7)0.90.410.70.70.3Liver stiffness (kPa)*6.7 (5.6)6.45 (2.7)9.8 (12)26.7 (22)5.7 (5)4.9 (1.6)0.030.16Significant stiffness (kPa≥7)31 (48)11 (55)8 (58)16 (100)4 (18)2 (6.5)0.40.0120.6Advanced stiffness (kPa≥9.5)17 (26)4 (20)7 (50)16 (100)3 (14)00.40.20.0010.020.1S4 stiffness (kPa≥12.5)10 (15)05 (36)16 (100)2 (9)00.0570.40.020.1FIB-4 score0.97 (0.9)0.76 (0.56)1.3 (0.95)2.5 (3.4)0.85 (0.8)0.7 (0.5)0.40.0050.60.1APRI score*0.25 (0.2)0.26 (0.2)0.24 (0.2)0.77 (1.3)0.22 (0.2)0.16 (0.08)0.30.0020.020.4ALP (U/L)*97 (65)79 (55)103 (54)79 (126)76 (39)67 (22)0.50.0020.0020.7GGT (U/L)*18 (18)17 (26)24 (61)24 (51)16 (14)14 (14)0.070.20.20.070.20.08p1: AA-a and FMFp2: AA-a and cirrhosisp3: AA-a and chronic liver diseasep4: AA-a and HCp5: FMF and HCp6: AA-a and AL-a*Median, interquartile of rangeDisclosure of InterestsNone declared

BackgroundPatients with ANCA-associated vasculitis (AAV) reported to have an increased risk of vascular events (VE) compared to general population [1]. However, studies on risk factors for the development of VE in AAV patients (pts) are limited.ObjectivesIn our study we aimed to evaluate the frequency, risk factors and mortality risk of VE pts with AAV.MethodsIn this study we retrospectively evaluated 287 pts with AAV. Patients with EGPA (n=33) were not included and 17 pts were excluded due to missing data. Arterial vascular events (a-VE) were recorded as myocardial infarction, unstable angina pectoris, peripheral artery disease, need for revascularization and cerebrovascular accident. Deep venous thrombosis and pulmonary embolism were recorded as venous thrombotic events (VTE). History of a-VE and/or VTE were grouped as all VE. ANCA test results were analyzed based on IFA and/or Elisa results and divided into two serological groups; c-ANCA/PR3+ (positive) and p-ANCA/MPO+.ResultsData of 237 pts (46 % male) was analyzed. Mean age at diagnosis was 55.6±14 (range; 17-88) years and median disease duration was 77 (range; 3-255) months. Of those pts, 173 (73 %) had GPA and 64 (27 %) had MPA. ANCA results were available in 230 pts; 122 were c-ANCA/PR3+ (53.5 %), 85 were p-ANCA/MPO+ (37 %) and 22 were ANCA negative (ANCA-) (9.5 %). The most common organ involvements were kidneys (75.8 %) and lower respiratory tract (74.4 %).Overall, 22 % (n=52) of the pts developed VE, 17 % (n=40) a-VE, 9 % (n=21) VTE and 3.8 % (n=9) both a-VE and VTE. In univariate analysis; development of VE was significantly higher in males, pts with c-ANCA/PR3 and pts with higher baseline CRP levels, GFR+ [95 % CI:1.06-8.6; OR:3]. Development of VTE was associated with higher VDI score (pIn survival analysis, mortality rate was significantly higher in pts who had a history of VE (Log-Rank: p=0.04).ConclusionOur observational data of more than 5 years of follow-up revealed that, one in five pts with AAV developed VE after diagnosis. The risk of VE was significantly higher in c-ANCA/PR3+ pts, smokers and pts with high VDI scores. Older age increased the risk of a-VE. Mortality was increased in AAV pts with VE after diagnosis. Additional studies needed to delineate the mechanism of VE in AAV and precautions should be undertaken to avoid morbidity and mortality.Table 1.Factors associated with vascular events in pts with AAVUnivariate analysisVariablesVE+ (n=52)VE- (n=185)p value (OR) (95 % CI)Age*58.8±14.554.9±140.08 (0.99-1.04)Gender, male Ɨ31 (60)78 (42)0.03 (5) (1.08-3.8)Diagnosis ƗGPA (n=173)40 (23)133 (77)0.5MPA (n=64)12 (19)52 (81)ANCA status Ɨc-ANCA/PR333 (27)89 (73)0.045 (4) (1.007-4.2)p-ANCA/MPO13 (15)72 (85)Baseline CRP (mg/L)ĸ73 (85)48 (89)0.05 (1-1.009)GFRƗ24 (47)57 (31)0.03 (4.7)BVAS score*19±716.3±70.06 (1-1.1)Smoking history (ever) Ɨ19/45 (42)34/162 (21)0.004 (8.3) (1.4-5.6)Cumulative steroid (MP) dosage (g/12 month) ĸ7.9 (17)7.5 (8)0.8Relapse Ɨ22/49 (45)58/180 (32)0.1Severe infection Ɨ23/46 (50)57/168 (34)0.046 (4) (1.006-3.8)VDI score*4.8±2.72.4±1.7)Remission at 6. month Ɨ19 (56)85 (68)0.2Mortality Ɨ15 (29)27 (14.6)0.02 (5.7) (1.1-4.9)*mean±std devƗ n, %ĸmedian, interquartile range. OR: Odds ratioFigure 1.Comparison of mortality rate between pts had VE and had not.Log-rank: p=0.039References[1]Wallace et al. All-cause and cause-specific.Rheumatology, 2020Disclosure of InterestsNone declared

BackgroundAmyloid storm is an emerging condition which was described recently also associated with poor prognosis in patients (pts) with AA amyloidosis (AA-a).ObjectivesWe herein aimed to evaluate the amyloid storm and its associated factors in pts with AA-a.MethodsWe retrospectively evaluated AA-a pts who followed in our tertiary referral amyloidosis center. Diagnosis of AA-a was made by Congo red straning and immunohistochemistry. Amyloid storm was defined as follows; developing within two weeks, increase in creatinine and proteinuria levels at least two times from baseline or reach the CRP levels more than 10 times [1].ResultsData of 175 pts with AA-a were evaluated and after exclusion of 11 pts who had missing data, 164 pts were included into the analysis. We identified 9 pts (5.5%; of 4 male) who developed amyloid storm. Five pts were FMF-associated AA-a (FMF-AA) and 4 pts were non-FMF-AA (two pts had ankylosing spondylitis, one patient idiopathic and one patient non-FMF periodic fever syndrome) (p=0.1). Median±interquartile range (IQR) patient age, diagnosis age of FMF and amyloidosis were lower in pts had amyloid storm than had not, but they were not statistically different (p=0.2, p=0.3 and p=0.2 respectively). All pts were M694V homozygous among FMF-AA. Etiology of amyloid storm was infection in 5 pts (56%), treatment non-adherence in 3 pts (33%) and surgery in one patient (11%). Overall, 3 pts with amyloid storm died (33%), but mortality was 10% (n=16) in the remaining pts with AA-a. One patient died during the amyloid storm, and others died within one year after the diagnosis of amyloid storm (median 5 months).In univariable analysis, involvement of ≥3 organs, bone marrow involvement and current proteinuria levels (p=0.4, p=0.05 and p=0.04, respectively) were higher; median number of organ involvement and mortality (p=0.09 and p=0.07) were tended to be higher in pts with amyloid storm than those without it. End stage renal disease (ESRD) development was also higher in pts who had amyloid storm (67%; n=6) than in pts who had not (46 % n=71) but did not reach statistical significance (p=0.3). Median±IQR CRP (48 ±77 vs 9 ±17 p=0.08), creatinine (4.8 ±5 vs1.2 ±0.6 p=0.01) and proteinuria (11 ±12 vs 0.85 ±2.3 p=0.02) levels were higher during the amyloid storm than their previous records. In multivariable analysis, amyloid storm was associated with higher mortality (p=0.045 OR 4.6; 95 % CI 1.03-20).In survival analysis, development of amyloid storm tended to be higher in pts with non-FMF-AA compared to FMF-AA (Log-rank p=0.057). Mortality rate was higher in pts who had amyloid storm than those without it (Log-rank p=0.038).ConclusionThis study showed that 5.5% of pts with AA-a may develop amyloid storm, and this condition was associated with higher amyloid burden. Amyloid storm may develop in AA-a pts associated with both FMF and other diseases, and the mortality rate may reach to 33% within one year.References[1]Kukuy et al. (2021). Rheumatology, 60(7), 3235–3242Table 1.Comparison of clinical and laboratory features of pts with and without amyloid stormVariablesAmyloid storm (n=9)Control (n=155)p valueAge*Ɨ37±1045±200.2Gender, male#4 (44)86 (56)0.7Diagnosis#FMF5 (4)122 (96)0.1non-FMF4 (11)33 (89)Organ distribution#Renal9 (100)152 (98)1Gastrointestinal4 (44)33 (21)0.1Heart2/6 (33)32/111 (29)1Liver1 (11)5 (3)0.3Bone marrow2 (22)5 (3)0.05Diagnosis age of FMF* Ɨ17.5±3024±200.3Diagnosis age of AA-a* Ɨ26±2631±220.2Duration of AA-a* Ɨ10±14.611.2±111Number of organ involvement*2±21±10.09≥3 organ involvement#3/5 (60)20/122 (16)0.04Baseline CRP*ĸ proteinuria (g/dL)* creatinine (mg/dL)*10±85.3±4.30.8±0.620±204±5.70.8±0.60.060.90.6Current CRP* ĸ proteinuria* creatinine*2.7±5.2 3.1±231.5±32.7±7.3 0±1.90±1.90.70.040.04Two exon 10 MEFV variant (n=108, %)3 (100)94 (87)0.5M694V homozygous (n=3, %)3 (100)73 (68)0.2ESRD development #6 (67)71 (46)0.3Mortality#3 (33)16 (10)0.07•.*median±IQR Ɨyears #(n, %) ĸmg/LFigure 1.Comparison of survival rate between pts with and without amyloid stormLog-rank: p=0.038Disclosure of InterestsNone declared

BackgroundHaploinsufficiency of A20 (HA20) is a monogenic autoinflammatory disease caused by heterozygous loss-of-function mutations in TNFAIP3 gene and characterized by Behçet disease (BD)-like manifestations such as mucocutaneous, articular, gastrointestinal, ocular symptoms as well as recurrent fever, elevated acute-phase reactants during relapses; and it usually starts during early childhood. Autoimmunity is another component of HA20 with autoantibodies and variable clinical features resembling systemic lupus erythematosus (SLE) and other autoimmune diseases.ObjectivesWe herein present three cases of HA20 with different clinical features and diagnosed during adulthood.MethodsWe used the Ion Torrent platform for deep sequencing.ResultsCase 1: A 51-year old woman diagnosed with BD because of oral and genital aphthous ulcers, arthralgias, erythema nodosum, and pathergy positivity starting from age of 40 in 2012. She developed sudden vision loss (diagnosed with bilateral optic neuropathy), sixth nerve palsy, and entrapment neuropathies in the lower limbs in 2014; and she had flares of neurologic findings between 2014-2020. The only laboratory abnormality was elevated acute-phase reactants, and no pathologic finding was reported for cranial MRI. Pathological examination of sural nerve biopsy revealed chronic inflammatory demyelinating polyneuropathy (CIDP). She received adalimumab and then tofacitinib, and her treatment was switched to certolizumab and IVIG (30 g/6 weeks) in 2020. At the last visit, she was asymptomatic with normal acute phase response, and her examination revealed normal eye movements.Case 2: A 33-year old woman was followed for 12 years with the diagnosis of SLE, based on fever, photosensitivity, alopecia, polyarthritis, serositis, positive anti-nuclear antibody (ANA) at a titer of 1:1280 with a homogeneous pattern, positive anti-dsDNA, anti-Sm, anti-Sm/RNP, and lupus anticoagulant test, and leukopenia, lymphopenia, hypocomplementemia in 2008. She developed shrinking lung syndrome and Jaccoud arthropathy during the disease course. She received several drugs including corticosteroids, hydroxychloroquine, cyclophosphamide, mycophenolate mofetil, belimumab, rituximab, tocilizumab, abatacept, tofacitinib because of fever, arthritis, skin rash, increased acute-phase reactants, pancytopenia, anti-dsDNA positivity. Her fever, red arthritis attacks with high CRP values did not respond, and after the genetic diagnosis of HA20, anakinra was added to treatment. Due to the high dose anakinra requirement, her treatment was switched to canakinumab (150 mg/2 week), and at the last visit, her attacks were significantly reduced.Case 3: A 44-year old woman was evaluated because of recurrent prolonged >38°C fever attacks (2 days-2 weeks duration), arthritis of the elbow, wrist, knee joints, and high acute phase reactant in 2004. She did not have a history of recurrent oral and genital aphthous ulcers, intermittent periorbital edema, rash, any ocular symptoms, or sensorineural hearing loss. ANA, RF, anti-CCP, and MEFV gene mutation were negative on admission. PET-CT demonstrated FDG uptake in the wall of the ascending aorta, aortic arch, and descending aorta in 2011. She had used colchicine in 2004, etanercept between 2009 and 2010, anakinra in 2011, tocilizumab in 2012, and canakinumab in 2013. She repeatedly received IV methylprednisolone pulse therapy, but she experienced a relapse of fever when she reduced the dose of methylprednisolone to ConclusionHA20 can be diagnosed even in adult patients, and the clinical picture of presented cases suggests that monogenic autoinflammatory disorders including HA20 should be suspected in any patient with flares of described manifestations along with strong acute phase response even in adults. Response to corticosteroids and targeted treatments may also be variable.Disclosure of InterestsNone declared

BackgroundGalectin-9, interferon-inducible protein-10 (IP-10) and sialoadhesin (SIGLEC-1) are proteins associated with interferon signature, and considered as potential biomarkers reflecting disease activity in patients with systemic lupus erythematosus (SLE).ObjectivesIn this study, we aimed to investigate the association of serum and urine levels of galectin-9, IP-10 and SIGLEC-1 with disease activity in patients with SLE.MethodsSixty-three patients with active SLE (31 renal and 32 extrarenal) were included in the study. Thirty inactive patients with SLE (15 renal and 15 extrarenal) and 32 healthy volunteers were selected as control groups. Serum (s) and urine (u) levels of galectin-9, IP-10 and SIGLEC-1 were tested using ELISA. Urine levels of biomarkers were normalized by urine creatinine.ResultsGroups were comparable with regard to sex and age distribution. Of 125 participants, 102 (81.6%) were female and median age was 33 (28-44.5) years. Proliferative lupus nephritis (LN) (class III/III+V and IV/IV+V) were found in 22 patients with active renal SLE (70.9%), while 6 patients (19.3%) had pure class V and 3 (9.7%) had class II LN. Levels of sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 were significantly higher in the active SLE group compared to the inactive SLE group (sIP-10 p=0.046, uIP-10 pTable 1.Serum and urine levels of biomarkers across study groups.BiomarkerActive SLE(n=63)Inactive SLE(n=30)Healthy Control(n=32)sGalectin-9 (ng/ml)11.73 (7.52-14.15)8.66 (7.51-10.02)5.61 (4.56-6.6)sIP-10 (pg/ml)279.4 (147.5-430.3)173.4 (142.2-247.9)74.3 (58.8-103)sSIGLEC-1 (pg/ml)181.2 (157.8-213.9)182.5 (169.9-203.1)258.3 (179-602)uGalectin-9 (ng/ml)8.83 (4.07-18.11)11.54 (7.03-15.07)10.63 (5.55-17.4)uIP-10 (pg/ml)34.4 (15.9-73,9)20.8 (9.9-53.3)12.2 (1.8-25.7)uSIGLEC-1 (pg/ml)321 (236.3-370.9)297.6 (247.7-371)290 (205.1-323.5)uGalectin-9 (ng/mgCre)15.50 (9.60-32.05)11.41 (8.78-19.54)13.57 (11.27-22.08)uIP-10 (pg/mgCre)73.4 (40.9-136.9)26.1 (18.1-55.1)16.4 (5-32.5)uSIGLEC-1 (pg/mgCre)619.6 (389.4-1056.5)393.2 (248.6-715.8)425.6 (264.7-925.9)Figure 1.Serum levels of galectin-9 before and after the treatment in 41 patients with active SLE.ConclusionsIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 are associated with disease activity in SLE. None is able to discriminate active renal from active extrarenal disease. sGalectin-9 may be a valuable biomarker to monitor response after treatment for active disease (Funded by Scientific Research Projects Coordination Unit of Istanbul University. Project number: TSA-2019-34218).Disclosure of InterestsNone declared

BackgroundAdenosine Deaminase 2 Deficiency (DADA2) and Haploinsufficiency of A20 (HA20) are two recently described monogenic autoinflammatory diseases (AID). The uncontrolled inflammatory response has been associated with an increased risk of AA amyloidosis in other AID, but there are only two reported patients with DADA2-related amyloidosis so far.1,2ObjectivesWe herein report a patient with AA amyloidosis and AID associated with both DADA2 and HA20.MethodsWe used the Ion Torrent platform for deep sequencing.ResultsCase: A 20-year-old male patient born to consanguineous parents (Figure 1), was admitted to our hospital with fever and abdominal pain in June 2014. Peritonitis, hepatomegaly, and a palpable non-tender mass in the right axillary cavity were detected in physical examination, and his laboratory investigations revealed neutrophilic leukocytosis, high acute phase reactants (APR), and nephrotic range proteinuria. CT angiography showed multiple thrombotic microaneurysms in celiac, splenic, superior, and inferior mesenteric and bilateral renal arteries; and MRI documented an additional aneurysm in anterior communicating artery. No finding was detected in hepatitis serology. He had been diagnosed with polyarteritis nodosa, and prednisolone and azathioprine were started. Renal histopathology confirmed the AA amyloidosis. Genetic analysis revealed no pathogenic MEFV variant. Colchicine and anakinra 100 mg/day were added to his treatment. He experienced 1-2 abdominal episodes annually between 2014-2019, and APR were normal between attacks. In March 2019, he was admitted to the hospital because of abdominal pain, high APR, and iron deficiency anemia. No gross pathology was observed in endoscopic examination of gastrointestinal tract, but histopathological investigation of the gastric mucosa and terminal ileum showed AA amyloidosis. Multiple aneurysms were detected in renal arteries with angiography. Deep sequencing of the targeted genes revealed homozygous p.Pro251Leu in ADA2 gene and heterozygous p.Thr647Pro in TNFAIP3 gene encoding A20, confirming the molecular diagnosis of DADA2 and HA20. The patient described oral recurrent aphthous ulcers starting from his childhood, but he had no uveitis or genital ulcers. His mother and brother also had recurrent oral aphthous ulcers. Genetic analyses showed heterozygous p.Pro251Leu variant in ADA2 gene in his mother, and heterozygous p.Gln703Lys variant in NLRP3 gene as well as heterozygous p.Thr647Pro TNFAIP3 variant and heterozygous p.Pro251Leu ADA2 in his brother. An improvement in his findings was observed within 2 weeks after switching his anakinra to adalimumab 40 mg every other week. At his last visit in February 2021, the patient had no complaints with normal APR, and urinalysis analysis showed 200 mg/day proteinuria, which was regressed from 3 g/day.ConclusionThis is the first case of AA amyloidosis associated with ADA2 and TNFAIP3 (A20) variants. ADA2 p.Pro251Leu variant has previously been validated as likely pathogenic, and our patient’s clinical findings were mainly compatible with DADA2. On the other hand, TNFAIP3 gene p.Thr647Pro mutation has been reported as variant of unknown significance, but it may have contributed to the DADA2 associated increased risk of amyloidosis. A better response of proteinuria to adalimumab treatment indicates superiority of anti-TNFs in DADA2 patients compared to anti-IL-1 drugs.References[1]Ekinci RMK, Balci S, Bisgin A, et al. Renal amyloidosis in deficiency of adenosine deaminase 2: successful experience with canakinumab. Pediatrics 2018;142.[2]Batu ED, Karadag O, Taskiran EZ, et al. A case series of adenosine deaminase 2-deficient patients emphasizing treatment and genotype-phenotype correlations. The Journal of rheumatology 2015;42:1532-4.Disclosure of InterestsNone declared

BackgroundAA amyloidosis (AA-a) is a rare condition while the most common cause is Familial Mediterranean Fever (FMF) in Turkey. There is limited evidence about the impact of AA-a burden on prognosis and outcome in AA-a.ObjectivesWe herein aimed to evaluate the AA-a burden and its association with outcome in patients (pts) with FMF-associated AA-a (FMF-AA)MethodsWe retrospectively evaluated FMF-AA pts from our AA-a cohort. Diagnosis of AA-a was confirmed by histologically. Heart involvement (inv.) was defined by documenting increased (>12 mm) septal wall thickness (CSWT) and at least one of three appropriate echocardiography findings (decreased ejection fraction, increased granular echogenicity or valvulopathy, diastolic dysfunction). The pts were divided in three groups according to AA-a burden: pts had only renal inv. (Group 1, G1), renal and gastrointestinal (GIS) (Group 2, G2); renal and GIS and heart (Group 3, G3)ResultsData of 137 pts with FMF-AA (55% male) were analyzed. We classified 79 pts in G1, 20 in G2, and 14 in G3. CSWT, troponin (trop) and pro-BNP levels were higher in G3 than G1 and G2 but trop levels were not statistically (sts) significant (sig.) between G3 and G2. Overall mortality was in 15.3 %. While mortality rate increased gradually with higher AA-a burden (10 % in G1, 15 % in G2 and 43 % in G3), the difference was sts sig. between G3 and G1.The number of MEFV variants was lower in pts with higher AA-a burden, especially those with M694V homozygosity were 93% and 72% in G1, 83% and 67% in G2, and 75% and 50% in G3 rsp; but the differences were not sts sig. (p=0.2 and p=0.7 for G1-G2, p=0.06 and p=0.2 for G1-G3, p=0.6 and p=0.4 for G2-G3).The number of organ inv. was correlated with CSWT (r=0.559’ ‘pROC analyses revealed 56% sensitivity (SS) and 70 % specificity (SP) for bsl Cre (cut off value [COV] 0.95, AUC=0.726 p=0.03 95% CI 0.56-0.9), 83.3 % SS and 74 % SP for trop (COV 35.5 AUC=0.864 p=0.006 CI 0.73-0.99), 100 % SS and 85.5 % SP for pro-BNP (COV 7246 AUC=0.897 p=0.024 CI 0.79-1.0), 79% SS and 58 % SP for CSWT (COV 11.5 AUC=727 p=0.007 CI 0.61-0.84) to be able to predict higher mortality.ConclusionThis study showed the association of AA-a burden with higher morbidity such as ESRD and higher mortality in pts with FMF-AA. Bsl Cre, prt, trop and pro-BNP levels were correlated with extent of AA-a burden and predicted higher mortality. Lower frequency of pts with two exon 10 variants or M694V homozygosity in pts with higher AA-a burden indicates that additional genetic and environmental factors may play a role in the development and progression of AA-a in FMF.Table 1.Clinical and laboratory features of pts with FMF-AA according to AA-a burdenVariablesG1 (n=79)G2 (n=20)G3 (n=14)p1 (OR)p2p3Age * Ɨ42.8±1343.2±1348.9±110.90.10.2Gender, male**36 (45.6)15 (75)7 (50)0.02 (5.5)0.80.1Diagnosis age of AA-a * Ɨ30.7±1334.1±1434.9±150.30.30.9Duration of AA-a * Ɨ13.8±910.8±614.3±80.150.80.2BaselineCRP (mg/L) Ɨ20±1324±1913±70.40.050.07Prt (g/dL) Ɨ Ɨ3.8 (5.8)12.4 (16)5 (4.2)0.030.30.2Cre (mg/dL) Ɨ0.8±0.41.5±11.8±1.30.6e-GFR Ɨ#104±31104±3159±390.020.0040.5CRF at admission**28/74 (38)13/19 (68)9/12 (75)0.02 (5.7)0.03 (6)0.7ESRD at admission**7/62 (11)6/18 (33)4/11 (36)0.03 (5)0.03 (4.6)0.9CSWT Ɨ10.2±1.710.6±1.113.9±1.60.3Trop ĸ Ɨ Ɨ9 (13)28 (68)75 (85)0.40.0050.1pro-BNP ĸ Ɨ Ɨ288 (1040)766 (1967)4968 (33800)0.50.0030.026ESRD (overall)**35 (45)10 (50)13 (93)0.70.001 (11)0.01 (7)Duration of b-DMARD (months) Ɨ##66±2967.7±3741.8±300.90.020.08Mortality **8 (10)3 (15)6 (43)0.50.006 (10)0.1#estimated glomerular filtration ratep1: G2-G1p2: G3-G1p3: G2-G3Ɨ mean±std dev. Ɨ Ɨmedian (IQR) *years ** n, % ĸ pg/mLFigure 1.Comparison of survival rate between G3 and G1Log-Rank: p=0.007Disclosure of InterestsNone declared

BackgroundA hyperinflammatory response compatible with features of macrophage activation syndrome (MAS) contributes to this worse outcome in patients with Coronavirus Disease 2019 (COVID-19). Glucocorticoids have become the standard of care for those requiring oxygen support or mechanical ventilation. More targeted anti-inflammatory treatments with tocilizumab and anakinra have also been shown to be effective.ObjectivesMore studies are being awaited to clarify the features of patients who would benefit more, and we investigated the characteristics of the surviving and dead patients who received anakinra.MethodsThe records of hospitalized adult patients between March 2020 and May 2021 in a tertiary referral center were evaluated. Diagnosis of COVID-19-related MAS was based on the expert opinion and preliminary criteria developed by our group that patients with a score of ≥45 were accepted COVID-19-related MAS.1 Patients who received anakinra constituted the study group. Anakinra dose was determined according to the clinical and inflammatory parameters; and doses varied between daily 100-300 mg SC to 400-800 mg IV.Laboratory data of surviving and died patients were comparatively analyzed by using the ANCOVA method on the relevant days (baseline, anakinra-onset day, first response to anakinra treatment, and discharge or death). The temporal variation (drug onset day-first response day, drug onset day-discharge, or death day) was evaluated using the ANOVA method. A 50% reduction of CRP compared to the anakinra start day was accepted as the first response to the treatment.ResultsOut of 1080 hospitalized patients, 218 (151 male, 67 female, mean age 60.0±14.1) who received anakinra were identified. Among them, 125 (57.3%) patients were followed in the ward, 21 (9.6%) did not need oxygen treatment during the hospitalization; 69 (31.6%) patients were followed at ICU, 40 of them were intubated, 30 (13.7%) died in ICU. Anakinra had been started in a mean of 4.8 days of hospitalization. Twenty had tocilizumab initially and then received anakinra because of ongoing inflammatory parameters. The majority (83.5%) received steroid treatment (79.5% methylprednisolone, 5% of dexamethasone), and 6 received one IV pulse 250 mg of methylprednisolone; 36 (16.5%) were followed before September 2020 and received anakinra without steroids because of the standard of care at that period. Only CRP was different between the alive and dead patients for the baseline parameters (p=0.05). On the first day of drug treatment, CRP and procalcitonin values were significantly higher in dead patients (Table 1). A 50% decrease in CRP level was achieved in 3.1 days in survivors and 4.7 days in dead patients. D-dimer (p=0.018), CRP (p=0.006), LDH (p=0.003), procalcitonin (p=0.005), creatinine kinase (p=0.001), and fibrinogen levels (p=0.05) were significantly different between the surviving and dead patients when the measurements between the first drug administration day and response day were compared. Neutrophil, lymphocyte count, ferritin, D-dimer, CRP, LDH, AST, procalcitonin, creatinine kinase, and fibrinogen levels were significantly different between the patients when the parameters between the first drug administration day and discharge/death day were compared. Dead patients had higher CRP values and they did not show a continuing CRP decrease with the steroids and anakinra (Figure 1).ConclusionRetrospective analysis of 218 patients suggests that starting anakinra earlier in hospitalized patients may provide better results, and a decrease in CRP, ferritin, D-dimer values, as well as an increase in lymphocyte count, are associated with favorable outcomes. Increasing values of D-dimer and troponin during treatment are associated with worse outcomes, possibly indicating cardiovascular and thrombotic pathologies not responding to anakinra. Changes in the CRP values are found to help monitor the response to anakinra. Other inflammatory pathways could be targeted in those who are not responding to appropriate doses of anakinra within 5 days.Disclosure of InterestsNone declared

Background:The negative impact of COVID-19 in patients with ANCA associated vasculitis (AAV) and patients on rituximab (RTX) treatment have been reported (1). Risk factors for severe course of COVID-19 and increased mortality in these patients are unclear.Objectives:To evaluate the course of COVID-19 in our AAV cohort and identifying risk factors for mortality.Methods:Patients with AAV who were classified according to CHCC and whose scheduled last visit were after December 2019 were screened and evaluated for COVID-19 either by phone call or in the clinic. Records of patients with a history of hospital admission due to COVID-19 were evaluated. Cumulative clinical findings and treatment history were noted. Hypogammaglobulinemia (hIgG) was defined as IgG level below 700 mg/dl. All inpatients with a diagnosis of COVID-19 were screened for hIgG and IVIG was administered if necessary.Results:Eighty-nine patients (47.2% female, mean age 56 + 12.5 (28-81)) were included into the study. The diagnosis was GPA in 56 (62.9%) and MPA in 33 (37.1%) patients. Mean follow up time was 91 + 53.4 (26-272) months. Anti-PR3 and anti-MPO were positive in 46 (51.7%) and 32 (35.9%) patients, respectively. Lower respiratory tract (LRT) involvement was present in 72 (80.9%) and 10 patients had a history of diffuse alveolar haemorrhage (DAH). Sixty-one patients (68.2%) had a history of rapidly progressive glomerulonephritis (RPGN) and 21 (23.6%) had peripheral nervous system (PNS) involvement.Fifteen (16.9%) patients had COVID-19; 14 of them were PCR positive, one patient had symptoms and thorax CT findings compatible with COVID-19. Pulmonary infiltrates were observed in 13 patients (86.7%); 9 (60%) had severe pneumonia. Twelve patients (85.7%) were hospitalized, 6 patients (42.9%) needed ICU admission and 5 patients (35.7%) died. Tocilizumab and anakinra for hyperinflammation during COVID-19 were used in 1 (6.7%) and 4 (26.7%) patients, respectively.Four out of five deceased patients (3 on RTX treatment, 1 with renal transplant) were in remission at the time of COVID-19. COVID-19 was detected in a patient with disease flare and DAH, during treatment with high dose steroids and plasmapheresis. hIgG was detected in all deceased patients from COVID-19 during hospital admission (mean IgG: 495±113.2 mg/dL).Symptomatic COVID-19 was more frequent in patients with a history of DAH, RPGN and hIgG. hIgG during the follow-up was significantly associated with COVID-19 in multivariable analysis (p=0.01, OR=20,6 %95 CI (2-210). Comparison of patients who died of COVID-19 and survived showed that female sex, PNS involvement and hIgG during the clinical course and hospital admission were risk factors for increased mortality (Table 1). Age, smoking, treatments, history of flares or serious infections, remission status and chronic renal insufficiency did not differ between groups.Conclusion:The frequency and mortality from COVID-19 is found to be high in our AAV cohort compared to previous reports (1). Patients with serious lung or renal involvement are prone to symptomatic COVID-19. Previously reported severe outcomes on RTX therapy might be related to consequent hIgG. High dose IVIG treatment may not be sufficient in improving survival in AAV patients with severe COVID-19 and hIgG.References:[1]Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients. 2020:annrheumdis-2020-218310.Table 1.Comparison of risk factors for CI and mortality in patients with AAVCOVID-19 (n=15)Non-infected (n=74)pORDeath (n=5)Survive (n=10)p2OR2Age53.4±11.956.6±12.6NS51.2±12.654.6±12.1NSSex (female)635NS420.03614 (0.9-207)LRT Involvement1458NS59NSDAH460.0384.1 (1-16.9)13NSRPGN15460.0048.5 (1-68.4)57NSPNS involvement318NS300.0059 (1.4 - 57)RTX treatment1033NS37NShIgG in outpatient visits670.026.3 (1.8-23.3)420.0216(1.5-234)hIgG during hospitalization due to CI----540.0252.5 (1.2-5.4)Flares≥1725NS43NSChronic Renal Insufficiency722NS43NSDisclosure of Interests:None declared

ObjectivesThe association between mutations in TNFAIP3, encoding the NF-kB regulatory protein A20, and a new autoinflammatory disease has recently been recognised. This study aims at describing the clinical phenotypes and disease course of patients with A20 haploinsufficiency (HA20).MethodsData for all cases from the initial publication, and additional cases identified through collaborations since, were collected using standardised data collection forms.ResultsA total of 16 patients (13 female) from seven families with a genetic diagnosis of HA20 were included. The disease commonly manifested in early childhood (range: first week of life to 29 years of age). The main clinical symptoms were recurrent oral, genital and/or gastrointestinal ulcers (16/16), musculoskeletal (9/16) and gastrointestinal complaints (9/16), cutaneous lesions (8/16), episodic fever (7/16), and recurrent infections (7/16). Clinical phenotypes varied considerably, even within families. Relapsing-remitting disease course was most common, and one patient died. Laboratory abnormalities included elevated acute-phase reactants and fluctuating presence of various autoantibodies such as antinuclear antibodies (4/10 patients tested) and anti-dsDNA (2/5). Tissue biopsy of different sites revealed non-specific chronic inflammation (6/12 patients tested), findings consistent with class V lupus nephritis in one patient, and pustules and normal results in two patients each. All patients were treated: 4/16 received colchicine and 12/16 various immunosuppressive agents. Cytokine inhibitors effectively suppressed systemic inflammation in 7/9 patients.ConclusionsEarly-onset recurrent oral, genital and/or gastrointestinal ulcers are the hallmark feature of HA20. Frequency and intensity of other clinical manifestations varied highly. Treatment regimens should be based on disease severity, and cytokine inhibitors are often required to control relapses.

Background:Infection is a remarkable cause of morbidity and mortality in patients with SLE.Objectives:We aimed to determine the clinical course of COVID-19 infection in our patients with SLE and the factors affecting this courseMethods:SLE patients (2012 SLICC criteria) diagnosed with COVID-19 infection by a positive PCR test and/or typical findings of lung involvement in CT (computed tomography) imaging were included. Data regarding cumulative clinical and laboratory characteristics, histopathology results, autoantibody profiles, immunsuppressives and damage (SLICC damage index/SDI)) were retrieved from the existing database and revised. SLE Disease Activity Index (SLEDAI-2K) was determined at the time of infection.Results:Sixteen SLE patients with COVID-19 infection were identified. Most (87.5%) of these patients were female. Seventy % (n=11) had lupus nephritis. Twenty-five % had thrombotic antiphospholipid syndrome.PCR was positive in 70% (n=11) of the patients. Pulmonary parenchymal findings compatible with COVID-19 were observed in 56% (n=9) of those patients. Regarding complaints upon admission, 50% (n=8) had fever, 44% (n=7) cough, 44% (n=7) dyspnea, 19% (n=3) myalgia, 12.5% (n=2) headache, 12.5% (n=2) nausea /vomiting, 6% (n=1) diarrhea, and 6 % (n=1) had anosmia. Eight patients were hospitalized. Six of these patients needed oxygen therapy via nasal cannula. None needed a follow-up in the intensive care unit. The mean hospitalization duration was 14 ± 5 (8-25) days.Regarding disease activity at the time of infection, 9 had inactive disease with a SLEDAI-2K score of 0 whilst in 5 patients SLEDA-2K score was ≥4. The mean SLEDAI-2K score at the time of infection was 1.7 ± 2.3 (0-6). System/organwise, 1 patient with chronic thrombocytopenia presented with a worsening platelet count accompanied by serologic activity. This patient was a non-adherent to treatment who had stopped taking mycophenolic acid months before COVID19. Three patients 2 of whom had proliferative nephritis experienced nephritic flares.1 patient who had a history of cutaneous lupus and was in remission presented with oral ulcer, leukopenia and hypocomplementemia during infection. Of 16 patients, 7 had system damage at the time of infection. The mean SDI score of the patients was 1.4±1.8. Comparison of patients with and without damage revealed no significant differences in disease activity, symptoms associated with COVID, in the need for hospitalization, hospitalization duration, and the requirement for oxygen therapy. However,CT findings compatible with COVID19, were more common in patients with damage (87% vs.33%,p=0.04) and their mean CRP levels were higher at diagnosis (65 ± 47 vs.22 ± 48 mg/l;p=0.032).All patients received similar treatment for COVID-19 except active patients who required high dose steroids (2 with active renal, 1 with thrombocytopenia and 1 with oral ulcer, leukopenia and hypocomplementemia).The patient with thrombocytopenia also received intravenous immunoglobulin and 1 with cutaneous active disease received tocilizumab as she developed macrophage activation syndrome. Six patients (37.5%) had received rituximab (RTX) in the last 6 months before COVID. No significant difference, in terms of hospitalization and need for oxygen therapy due to COVID19 was found between patients who had received RTX vs who had not. No hypogammaglobulinemia was detected in patients who received RTX despite lower levels of IgG (998 ± 184 vs 1481± 51 mg/dl, p=0.02)Conclusion:Although half of the patients in our series of COVID19 infected SLE patients required hospitalization, there were no mortalities. More patients with damage (none pulmonary) displayed CT findings compatible with COVID19 and further follow up will reveal whether they will suffer from fibrotic lung disease. Patients can experience disease flares during COVID. But it is also important to consider that some manifestations such as thrombocytopenia may also be a sign of severe infection. Immunosupressive agents may not have a negative impact on the course of infection.*the first two authors contributed equallyDisclosure of Interests:None declared.

Background:Retinol binding protein 4 (RBP4) is a plasma retinol transporter that transports retinol from liver to periphery. RBP4 has been studied as a biomarker in metabolic and neoplastic conditions, however its association with inflammation is not clear. Serum amyloid A (SAA), another retinol binding protein, has been known as a sensitive biomarker of inflammation in familial Mediterranean fever (FMF) and other autoinflammatory disorders. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and SAA are commonly used as acute phase reactants, but they are not successful in differentiating non-infectious inflammatory conditions from infections.Objectives:We aimed to evaluate the potential of serum RBP4 as a biomarker of acute phase response and to determine its performance in differentiation of inflammation of patients with FMF and AA amyloidosis from infections.Methods:A total of 169 participants in 5 groups, consisting of FMF (n = 60), FMF with AA amyloidosis (n = 58), non-FMF AA amyloidosis (n = 23), infections (n = 10, 3 pneumonia, 3 sepsis, 1 pyelonephritis, 1 fungal infection, 1 cellulitis, 1 disseminated zoster), and healthy controls (HC) (n = 18), were included and evaluated cross sectionally. Hemogram and serum CRP, ESR, SAA, ferritin, creatinine, AST, ALT, albumin levels were recorded from the patient charts. FMF and FMF + amyloidosis patients were evaluated during attack-free period. Serum RBP4 levels were investigated by ELISA (Elabscience, USA). Mean values and relative changes compared to healthy controls were evaluated for SAA, CRP, RBP4 levels in all groups.Results:Serum RBP4 level was found to be higher in FMF group compared to the patients with infection (p = 0.002) and HC (p Table 1.Demographic features and laboratory findings of the participantsVariablesFMF(n=60)FMF- Amyloidosis(n=58)Non-FMF-AA Amyloidosis(n=23)Infection(n=10)Healthy control(n=18)Female/Male46/1433/258/153/78/10Age (SD)*38±13(18-74)43±11(21-69)53±1365±1533±9Creatinine (mg/dL)*0,8±0,21,7±1,72,0±1,61,7±1,00,7±0,2Albumin(mg/dL)*4,7±0,44,3±0,63,3±0,93,0±0,94,8±0,2Ferritin (ng/mL)*70±94245±315139±168554±3883±72RBP4 (ng/mL)*772±183671±214666±256512±204524±117RBP4 (median)770(434-1142)653(227-1259)645(331-1214)487(226-876)498(566-738)CRP (mg/L)*16±47,112,8±32,825,7±36,469±36,81,2±1,2SAA (mg/dL)*10,3±31,45,0±13,97,1±14,140,2±18,50,3±0,1ESR*15±1319±1641±2945±427±5Relative RBP4 increase1,47±0,351,28±0,411,27±0,490,98±0,39Relative CRP increase13,4±39,210,6±27,321,4±30,357,7±30,6Relative SAA increase34,5±104,816,0±45,723,7±47,1133,9±61,7*mean, RBP4 (Retinol Binding Protein 4), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Serum Amyloid A (SAA).Conclusion:This preliminary study showed that RBP4 levels may be increased about 1.5 times in FMF and to lesser extent in AA amyloidosis patients despite no significant change during acute phase response of different infections. Patients with infections show strong CRP and SAA response, and the differential response of RBP4 in FMF patients warrants further analysis in larger group of patients with different clinical characteristics.Disclosure of Interests:None declared

Background:COVID-19 runs a variable course resulting in acute respiratory distress syndrome and death in a subset of patients. The entry of SARS-CoV-2 into the cell stimulates innate immunity including NLRP3 inflammasome and lead to development of adaptive immunity later. Hyperinflammatory response with the release of proinflammatory cytokines including IL-1β and IL-6 results in cytokine storm in some patients with a worse outcome. Colchicine acts on NLRP3 inflammasome and inhibits and IL-1 mediated inflammatory attacks in gout and familial Mediterranean fever (FMF) patients. Patients with inadequate response to colchicine may benefit from anti-IL-1 biologic agents such as anakinra and canakinumab. Recently, favourable effects of anakinra have been observed in COVID-19 patients with findings of cytokine storm.Objectives:We aimed to evaluate the impact of COVID-19 among refractory FMF patients followed-up in tertiary referral with the treatment of biologic agents and also document the course of COVID-19 in these patients.Methods:We searched out database of FMF patients to identify those using biologic agents (anti-IL-1, anti-IL-6 or anti-TNF) for colchicine-refractory FMF. We interviewed the patients using a standard questionnaire by phone call for symptomatic COVID-19 and evaluated those patients who described findings of COVID-19 further by their hospital records or inviting them to the hospital for additional investigations.Results:We identified 183 patients and contacted 106 of them by phone in May-October 2020. A history of symptomatic COVID-19 was documented in 7 FMF patients who were on a biologic agent. Six were on anti-IL-1 and one was on anti-TNF, and one of the patients was not taking his biologic agents for 1 year. All of 7 patients had a favourable outcome. All but 1 patient followed at home and none of them developed findings of cytokine storm, thromboembolism and secondary bacterial infection. Hospitalized patient did not require intensive care unit (ICU) support or mechanical ventilation, and he was not given additional anti-inflammatory medications.Conclusion:This series of refractory FMF patients with potentially higher inflammatory characteristics showed COVID-19 did not result in a worse outcome in those patients during the first phase of the pandemic, and none developed findings of cytokine storm. Observations in these patients supports further that biologic agents blocking IL-1 and possibly TNF may contribute to the uneventful course of COVID-19 by preventing the development of hyperinflammatory response. Data collection from a larger group of patients, especially those with amyloidosis, will clarify the protective effects of colchicine and contribution of anti-IL-1 treatments on the favourable disease course during the second phase of the pandemic.Patient 1Patient 2Patient 3Patient 4Patient 5Patient 6Patient 7Age (years)45483953323731MEFV variantsUnknownM694V/M680IUnknownM694V/ M694VM694V/ M694VM694V/ M694VM694V/ M694VAmyloidosisNoNoNoNoNoNoNoBiologic agentsAnakinra100 mg/dayNot takenfor 1 yearAdalimu-mabCanakinumab150 mg/monthAnakinra100 mg/dayCanakinumab150 mg/monthAnakinra100 mg/dayPrednisone (mg/day)5NoNoNoNoNoNoColchicine(mg/day)21,51,51,51,52,02,0RT-PCR positivityYesYesYesYesYesYesYesChest CT signsYesYesNot doneNot doneNot doneNot doneNot doneHospitalisationNoNoNoYesNoNoNoAntiviral therapyOseltamivirOseltamivirNoFavipravirFavipravirFavipravirFavipravirHCQ useYesYesYesYesNoNoNoNew FMF attackduring COVID-19NoNoNoNoNoNoNoDisclosure of Interests:None declared