BackgroundBehçet’s disease (BD) may present with different clinical phenotypes. Ocular and Neurobehçet’s Disease (NBD) are severe complications [1-4]. Data on NBD epidemiology, clinical phenotype and therapy are scarce and controversial.ObjectivesIn a wide unselected single-center series of BD our aims were to assess a) NBD prevalence, b) associations with other clinical clusters and c) treatment.MethodsCross-sectional study of all 120 patients diagnosed with BD in Northern Spain, between January 1, 1999 to December 31, 2019. Finally, 96 patients were included in this study according to 2014 International Criteria for Behçet Disease (ICBD) [5]. NBD was diagnosed according to the International Consensus Recommendation (ICR) criteria [4].ResultsNBD was diagnosed in 23 of 96 (24%) patients (15 women/8 men) (mean age: 44±13.9 years). NBD was classified as parenchymatous (n=10, 43.5%), non-parenchymatous (n=10, 43.5%) and mixed (n=3, 13%). HLAB51 was positive in 5 out of 13 (38.4%) patients tested. The main cluster of clinical associations were oral aphthae (n=20, 87%); ocular (n=14, 60.9%), cutaneous (n=10, 43.5%), articular (n=9, 39.1%), vascular (n=4, 17.4%) and intestinal (n=1, 8.7%) involvement (Figure 1).Figure 1.Clusters of clinical associations of NBDTreatments were oral corticosteroids (n=16; 69.6%; mean maximum dose 42±12.5 mg/ day, conventional immunosuppressants (n=13, 56.5%) and Biological Therapy (BT) (n= 7; 30.4%). BT was used in patients who were refractory to conventional immunosuppressants. Monoclonal anti-TNFα were used as the first option in all patients who received BT. In 3 out of 7 (42.7%) patients BT was switched due to inefficacy. Table 1 shows the main NBD clinical subtypes and treatment.Table 1.Main clinical features and treatment of 23 patients with NBDn (%)Mean maximum oral prednisone dose, (SD) mg/dayConventional immunosuppressants, n (%)monoclonal anti-TNFα, n (%)Tocilizumab, n (%)Anakinra, n (%)Parenchymal phenotype10 (43.5)51.7±19.36 (46.2)4 (57.1)00-Hemiparesis5 (50)52.5±7.52 (50)3 (75)-Optic neuropathy-Encephalopathy3 (30)1 (10)52.3±26.3452 (66.7)1 (16.7)00-Ophtalmoparesis1 (10)01 (16.7)1(25)Non-parenchymal phenotype10 (43.5)42±12.55 (38.5)2 (28.6)00-Aseptic meningitis10 (43.5)42±12.55 (38.5)2 (28.6)Mixed3 (13)45±152 (15.4)1(14.3)1 (14.3)1 (14.3)-Aseptic meningitis and ophtalmoparesis1 (33.4)600000-Aseptic meningitis and other cranial nerve involvement1 (33.4)01 (50)000-Encephalopathy and intracranial hypertension1 (33.4)301(50)1(100)1(100)1(100)Complete remission was achieved in 18 of 23 cases (78.2%), partial response in 2 out of 23 cases (8.7%). No severe adverse effects were observed.ConclusionNBD was observed in 24% of patients with BD. The most frequent clinical clusters of NBD were oral aphthae and ocular involvement. All patients treated with either conventional immunosuppressant or BT achieved clinical remission.References[1]Martín-Varillas JL, et al. Ophthalmology 2018 Sep;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020.[2]Atienza-Mateo B, et al. Arthritis Rheumatol 2019 Dec;71(12):2081-2089. doi: 10.1002/art.41026.[3]Santos-Gómez M, et al. Clin Exp Rheumatol 2016 Sep-Oct;34(6 Suppl 102): S34-S40.[4]Kalra S, et al. Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations. J Neurol. 2014 Sep;261(9):1662–76.[5]International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD). J Eur Acad Dermatol Venereol. 2014 Mar;28(3):338-47.Disclosure of InterestsAlba Herrero-Morant: None declared, Carmen Álvarez-Reguera: None declared, Lara Sanchez-Bilbao: None declared, David Martínez-López: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Guillermo Suárez-Amorín: None declared, Raúl Fernández Ramón: None declared, M. Cristina Mata Arnaiz: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Roche, Sanofi, Lilly, Celgene, Sobi, and MSD, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, BMS, Janssen, and MSD, Grant/research support from: Abbvie, MSD, and Roche

BackgroundNeurosarcoidosis (NS) is a serious and relative uncommon complication of sarcoidosis [1].Data on incidence is scarce and varies worldwide.ObjectivesTo estimate NS epidemiology in Northern Spain.MethodsPatients diagnosed with sarcoidosis at a University hospital in Northern Spain, between January 1999 and December 2019 were assessed. Sarcoidosis diagnosis was established according to ATS/ERS/WASOG criteria as follows: compatible clinical and radiological presentation, histopathologic confirmation, and exclusion of other granulomatous diseases. NS was diagnosed according to the NS Consortium Consensus Group [2].Demographic and clinical data were collected. The incidence of sarcoidosis between 1999-2019 was estimated by gender, age, and year of diagnosis.ResultsNS was observed in 30 of 234 (12.8%) (19 women/ 11 men) (mean age: 55.0±15.8 years) patients with sarcoidosis. The underlying neurological manifestations were chronic headache (n=13, 43.4%), peripheral neuropathy (n=6, 20.0%), cranial neuropathy (n=5, 16.7%), spinal cord abnormalities (n=3, 10.0%) and aseptic meningitis (n=3, 10.0%).A comparison between different geographical areas is summarized inTable 1. There are wide variations in frequency (US:4.8% to France:33.9%), gender predominance and age at diagnosis (31 to 55 years) depending on the geographical area. Nevertheless, most of the patients were diagnosed in the 5thdecade of life.Annual incidence of NS in our population area in the 1999-2019 period was 0.11 per 100,000 people, 95% (CI:0.11-0.26); 0.08 (0.07-0.24) in men, 0.13 (0.09-0.24) in women. There were variations in annual incidences, ranging from a minimum value of 0.08 in 2013-2014 to a maximum of 0.19/100,000 people in 1999-2000. A downward trend in annual incidence over time was observed. Nevertheless, the correlation was weak (r2=0.1135) (Figure 1).ConclusionThe epidemiological characteristics of NS is very different in frequency. Frequency estimated in this study was similar to that of other countries.References[1] Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol 2014; 32:275-84. PMID:24321604.[2] Stern BJ, et al. JAMA Neurol. 2018;75:1546-1553.Table 1.Main clinical features and treatment of neurosarcoidosis in different geographical areasAuthor, yearCountrycasesMale n (%)Age at onset years mean ± SDSNS%SNSSNSGascón-Bayarri et. al., 2011Spain445306.7ND10 (33.4)ND48.3±NDLeonhard et. al, 2016The NetherlandsND52NDND22 (48.0)44±ND43.0±NDJoubert et. al, 2017France69023433.9ND117 (50.0)ND31.5±NDDorman et. al, 2019USA1706824.8691 (40.6)43 (52.4)49±10.845.0±11.4Arun et. al, 2020UKND80NDND35 (44.0)ND47.8±NDGoel et al., 2020IndiaND12NDND4 (33.4)ND44.0± 9.2Sambon et. al, 2022Belgium1802212.2ND14 (64.0)ND40.5±NDByg et al., 2022DenmarkND20NDND11 (55.0)ND51.6±NDPresent study, 2023Spain2343012.8105 (44.9)11 (36.7)48.4±14.855.0±15.8Abbreviations:ND: non data, NS: neurosarcoidosis, S: SarcoidosisFigure 1.Trends in age at neurosarcoidosis diagnosis in Cantabria, Spain, in 1999-2019 by genderAcknowledgements:NIL.Disclosure of InterestsAlba Herrero-Morant: None declared, Lara Sanchez-Bilbao: None declared, Iñigo Gonzalez-Mazon: None declared, David Martínez-López: None declared, Carmen Álvarez-Reguera: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Raúl Fernández-Ramón: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Lilly, Bristol-Myers, Janssen, Galapagos and MSD, Consultant of: Abbvie, Pfizer, Roche, Lilly, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD, Novartis and Roche.

BackgroundNeurosarcoidosis (NS) is one of the most severe manifestations of sarcoidosis [1].NS diagnosis is difficult since clinical features and cranial imaging findings are often unspecific and central nervous system biopsy is unfrequently performed. Flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) is emerging as a powerful tool for the evaluation of sarcoidosis. Data on the role of 18F-FDG PET-CT in NS is scarce.ObjectivesTo assess the utility of 18F-FDG PET-CT in patients with suspected NS.MethodsPatients diagnosed with sarcoidosis at a University hospital in Northern Spain, between January 1999 and December 2019 were assessed. Sarcoidosis was diagnosed according to ATS/ERS/WASOG criteria as follows: compatible clinical and radiological presentation, histopathologic confirmation, and exclusion of other granulomatous diseases. NS was diagnosed according to the NS Consortium Consensus Group [2].Receiver Operating Characteristic (ROC) curve for Chest Computed Tomography (CT) and 18F-FDG PET-CT were compared.ResultsNS was suspected in 30 (19 women/11 men) patients out of 384 (7.8%) (mean age; 55.0±15.8 years). The underlying neurological manifestations were chronic headache (n=13; 43.4%), peripheral neuropathy (n=6, 20%), cranial neuropathy (n=5, 16.7%), spinal cord abnormalities (n=3, 10%) and aseptic meningitis (n=3, 10%). Complementary study’s findings are described inTable 1.18F-FDG PET-CT was performed in 10 (33.4%) patients. 18F-FDG PET-CT were abnormal in 9 (90%) patients. Abnormalities suggestive of NS were found in 7 (70%) patients. These were located in lymph nodes (n=7, 100%), parotid gland (n=1, 14.3%) and bone (n=1, 14.3%). Other abnormalities were found in 2 (20%) patients in vocal cord (n=1, 50%) and rectum (n=1, 50%). Only 1 (10%) patient had no abnormalities in 18F-FDG PET-CT. All patients (n=2, 100%) in which chest radiography and chest CT were negative, had pathological findings suggestive of NS in 18F-FDG PET-CT. After whole-body 18F-FDG PET-CT, all patients with accessible abnormalities suggestive of sarcoidosis underwent biopsy in lymph node (n=5, 71.4%), parotid gland (n=1, 14.3%) and skin (n=1, 14.3%). In all of them non-necrotizing granulomas were found. 18F-FDG PET-CT and chest CT diagnostic ability was compared (Figure 1). 18F-FDG PET-CT had a higher Area Under the Curve (AUC) (0.94 [95% CI: 0.78-1]) than chest CT (0.75 [95% CI: 0.28-1]).Conclusion18F-FDG PET-CT seems to be a useful tool in the evaluation of patients with suspected NS specially when the chest CT is negative or inconclusive.References:[1] Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol 2014; 32:275-84.[2] Stern BJ, et al. JAMA Neurol. 2018;75:1546-1553.Table 1.Complementary studies in 30 patients with suspected neurosarcoidosis in the 1999-2019 period in a University hospital in Northern Spain.Ancillary investigationWith 18F-FDG PET-CT (n=10; 33.4%)Without 18F-FDG PET-CT (n=20; 66.6%)Total (n=30; 100%)•Laboratory tests, No./No. assessed (%) - ACE >70 U/L3/9 (33.3)9/13 (60)12/24 (50) - CRP >0.5 mg/dL3/10 (30)8/10 (80)11/20 (55) - ESR >20 mm/h5/10 (50)7/15 (46.7)12/25 (48) - CD4/CD8 >3.51/2 (50)0/1 (0)1/3 (33.4)•Imaging studies suggestive of sarcoidosis, No./No. assessed (%) - Chest radiograph8/10 (80)16/20 (80)24/30 (80) - Chest CT9/10 (90)16/20 (80)25/30 (83.4) - Gammagraphy6/9 (66.7)10/18 (55.6)16/27 (59.3)Abbreviations:18F-FDG PET-CT: Flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography, ACE: Angiotensin-Converting Enzyme, CRP: C-reactive protein, CT: computerized tomography, ESR: Erythrocyte Sedimentation Rate.Figure 1.Receiver Operating Characteristic (ROC) curve of Chest CT and 18F-FDG PET-CTAcknowledgements:NIL.Disclosure of InterestsAlba Herrero-Morant: None declared, Lara Sanchez-Bilbao: None declared, Iñigo Gonzalez-Mazon: None declared, David Martínez-López: None declared, Carmen Álvarez-Reguera: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Raúl Fernández-Ramón: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Lilly, Bristol-Myers, Janssen, Galapagos and MSD, Consultant of: Abbvie, Pfizer, Roche, Lilly, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD, Novartis and Roche.

BackgroundNeurosarcoidosis (NS) is a severe complication of sarcoidosis [1,2]. NS may be classified according to several subtypes [1]. Data on therapy, including biological therapy (BT) is scarce.ObjectivesTo assess efficacy and safety of BT in refractory NS subtypes.MethodsStudy of NS from a large cohort (n=234) of all consecutive patients diagnosed with sarcoidosis in a single university hospital from January 1, 1999 to December 31, 2019. Diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria [3].Efficacy was considered as complete or partial response and no-response according to the resolution of the neurological syndrome (signs and/or symptoms) after the BT onset.ResultsNS was observed in 30 (19 women/11 men) of 234 (12.8%) patients; mean age, 55.0±15.8 years. NS subtypes were chronic headache (n=13, 43.4%), peripheral neuropathy (n=6, 20%), cranial neuropathy (n=5, 16.7%), spinal cord abnormalities (n=3, 10%) and aseptic meningitis (n=3, 10%). A total of 26 (86.7%) patients received oral corticosteroids (CT) (mean maximum dose: 50±19.2 mg/dL) and 7 (23.3%) IV CT. In addition, conventional immunosuppressants were administered to 18 (60%) patients and BT to 12 (40%) patients. No treatment was administered to 4 (13.3%) patients. Table 1 shows treatment according to NS subtypes.Table 1.Treatment of 30 patients with neurosarcoidosisNeurosarcoidosis subtypen (%)Other clinical manifestationsn (%)Conventional immunosuppressant,N=23n (%)monoclonal anti-TNFα, N=22 n (%)Etarnecept, N=1n (%)Tocilizumab, N=1n (%)Secukinumab, N=1 n (%)Rituximab, N=1 n (%)Chronic headache*13 (43.4)P (n=9, 69.2%)A (n=9, 69.2%)C (n=6, 46.2%) O (n=4, 30.8%)D (n=4, 30.8%)MTX (n=6, 26.1%) AZA (n=1, 4.3%)IFX (n=1, 4.5%)ADA (n=1, 4.5%)GLM (n=1, 4.5%)0 (0)01 (4.5)1 (4.5)Peripheral neuropathy6 (20.0)P (n=5, 83.3%)A (n=3, 50%)O (n=3, 50%) C (n=2, 33.3%)MTX (n=4, 17.4%) AZA (n=2, 8.7%)IFX (n=3, 13.6%)ADA (n=2, 9.1%)GLM (n=1, 4.5%)1 (4.5)000Cranial neuropathy5 (16.7)P (n=4, 80%) O (n=3, 60%)C (n=1, 20%)A (n=1, 20%)D (n=1, 20%)AZA (n=4, 17.4%)MTX (n=3, 13.1%)IFX (n=3, 13.6%)ADA (n=1, 4.5%)0000Spinal cord abnormalities3 (10.0)P (n=3, 100%)O (n=1, 33.3%)C (n=1, 33.3%)A (n=1, 33.3%)MTX (n=1, 4.3%)IFX (n=1, 4.5%)GLM (n=1, 4.8%)0000Aseptic meningitis3 (10.0)P (n=2, 66.7%)O (n=1, 33.3%)C (n=1, 33.3%)A (n=1, 33.3%)MTX (n=2, 8.7%)IFX (n=2, 9.1%)ADA (n=1, 4.5%)01 (4.5)00TOTAL(n= 30)30 (100)P (n=23, 76.7%)A (n=15, 50%)O (n=12, 40%)C (n=11,36.7%)D (n=5, 16.7%)MTX (n=16, 69.6%) AZA (n=7, 30.4%)IFX (n=10, 45.5%)ADA (n=5, 22.7%)GLM (n=3, 13.6%)1 (4.5)1 (4.5)1 (4.5)1 (4.5)Abbreviations: A: Articular, ADA: Adalimumab, AZA: Azathioprine, C: Cutaneous, D: Digestive, GLM: Golimumab, IFX: Infliximab, MTX: Methotrexate, O: Ocular, P: Pulmonar*With MRI, CSF, and/or EMG/NCS findings typical of granulomatous inflammation of the nervous system after rigorous exclusion of other causes and not meeting criteria for other neurosarcoidosis subtypes.A total of 12 patients received treatment with 22 BT. Most used BT were monoclonal anti-TNFα (n=18, 81.8%), infliximab (IFX) (n= 10, 45.5%) and adalimumab (ADA) (n=5, 22.7%). After 12 months since the initiation of BT, complete, partial or no response was observed in 14 of 17 (82.4%), 2 (11.8%) and 1 patient (5.9%), respectively (Figure 1). Severe allergic reaction was observed in one patient on both IFX and ADA. No more severe adverse events were observed.Figure 1.Neurological clinical response to biological therapyConclusionBT, especially monoclonal anti-TNFα, seems to be effective and safe in NS, regardless of subtype.References[1]J. Bradshaw M, et al. Neurol Neuroimmunol Neuroinflamm 2021;8:e1084. doi:10.1212/NXI.0000000000001084[2]Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol. 2014 Mar-Apr;32(2):275-84. PMID: 24321604.[3]Statement on Sarcoidosis. Am J Respir Crit Care Med [Internet] 1999;160(2): 736–55. https://doi.org/10.1164/ajrccm.160.2.ats4-99Disclosure of InterestsAlba Herrero-Morant: None declared, David Martínez-López: None declared, Lara Sanchez-Bilbao: None declared, Iñigo Gonzalez-Mazon: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Raúl Fernández Ramón: None declared, Carmen Álvarez-Reguera: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Roche, Sanofi, Lilly, Celgene, Sobi, and MSD, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, BMS, Janssen, and MSD, Grant/research support from: Abbvie, MSD, and Roche