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

BackgroundIgG4-related disease (IgG4-RD) is an inflammatory and fibrosing entity with very heterogeneous clinical manifestations. Its pathogenesis remains unknown, clinical features are heterogeneous and unspecific, and recently released classification criteria are invaluable in early recognition of the disease. Therefore, regrettably IgG4 related disease continues underdiagnosed.Objectivesa) To evaluate the clinical characteristics of patients diagnosed with IgG4-RD in a single University hospital;b) To compare with other large series.MethodsStudy of patients from a referral hospital and literature review of cases diagnosed with IgG4-RD. Diagnosis was made accordingly to these criteria: a) Okazaki;b) Umehara;c) ACR/EULAR 2020; and/ord) clinical, laboratory and imaging suggestive findings(ref. 1-3). For the literature review, we searched PubMed and the Cochrane library from its inception until 31 December 2022, selecting the largest series.ResultsWe include 11 patients (7 females/4 males) (mean±SD age; 61.2±15.6 years) diagnosed with IgG4-RD. The organs affected at diagnosis were: aorta (n=5), pleura/lung (n=4), lymph nodes (n=3), salivary glands (n=2), retroperitoneum (n=2), lacrimal glands (n=1), bile duct (n=1), kidney (n=1), orbit (n=1), subglottis (n=1), pericardium (n=1), mesentery (n=1), maxillary sinuses (n=1). IgG4 values were increase in 2 (18%) patients (median [IQR]; 250.5 [201.0-300.1] mg/dL) (normal value <135 mg/dL). Blood plasmablasts were increased in 8 (73%) patients (median; 831 [785-1218] cells/mL) (normal values <653 cells/mL). In the literature review, 6 series of more than 100 patients each were selected. The main data from the different series are listed intable 1.Thefigureshows the most frequently affected organs in the different series. The pancreas was one of the most frequently involved. In contrast, in our series, aortic involvement followed by lung/pleura were the most frequent.ConclusionIgG4-RD is a very heterogeneous disease with involvement of virtually every organ of the anatomy, usually presenting with involvement of more than one organ. Despite the name of the entity, serum IgG4 is not always elevated.References[1]Okazaki K et al. Int J Rheumatol. 2012. PMID: 22690221[2]Umehara H, et al. Mod Rheumatol. 2012. PMID: 21881964[3]Wallace ZS et al. Arthritis Rheumatol. 2020. PMID: 31793250Table 1.Main features in series of more than 100 patients and in current seriesReferenceCasesSex Female (F)/ Male (M)Age, median [IQR] or mean±SDDiagnosis criteriaNumber of organs affectedLevel of serum IgG4 (mg/dL), median [IQR]Lanzillotta et al. Rheumatology 2020131F (n=36),M (n=95)62 [53-70]-Umehara: possible (46%), probable (2%), definitive (52%)-1 organ (26%)-More of 1 organ (74%)224 [115-382]An et al.Orphanet J Rare Dis 2022127F (n=35),M (n=92)63 [55-69]-Umehara: possible (82.6%), probable (2.3%), definitive (11.8%)-1 organ (20%)-2-4 organs (68%)-More of 5 organs (9%)980 [390-1520]Zongfei et al.Clin Rheumatol 2021102F (n=25),M (n=77)62 [54.1-65.8]-Okazaki (100%)Median [IQR]: 2 [1-3]399 [199-776]Wang et al.Arthritis Res Ther 2018215F (n=67),M (n=148)54 [46-62]-Umehara: possible (47.9%), probable (4.7%), definitive (47.4%)-1-2 organs (36%)-3-4 organs (47%)-5 or more organs (17%)896 [350-1860]Inoue et al.Medicine (Baltimore) 2015235F (n=189), M(n=46)67-Symptoms+laboratory +image/ Compatible histology (100%)-1 organ (41%)-2 or more organs (59%)470 [ND]Wallace et al.Arthritis Rheumatol 2015125F (n=49),M (n=76)50.3±14.9- Symptoms+laboratory +image/ Compatible histology (100%)-1 organ (38%)-2 organs (24%)-3 or more organs (38%)NDCurrent series11F (n=7),M (n=4)57 [54.5-73.5]-Okazaki: 45%-Umehara: possible (18%), probable (18%), definitive (9%)-ACR/EULAR 2020 (9%)-Symptoms+laboratory +image/ Compatible histology (54%)-1 organ (36%)-2 organs (27%)-3 or more organs (36%)66.3 [22.2-116.3]Figure 1.Involved organs in series of more than 100 patients and in current series (%)Acknowledgements:NIL.Disclosure of InterestsLara Sanchez-Bilbao: None declared, Javier Loricera Speakers bureau: Roche, Novartis, UCB Pharma, MSD, Celgene, and Grünenthal, Carmen Álvarez-Reguera: None declared, Alba Herrero-Morant: None declared, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD, Grant/research support from: AbbVie, MSD, 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