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Objectives: To evaluate the ability of 18 FDG PET/CT, at diagnosis of giant cell arteritis (GCA) and during follow-up, to predict occurrence of relapse in large-vessel GCA (LV-GCA)., Methods: We conducted a retrospective study using the French Study Group for Large-Vessel Vasculitis (GEFA) network. Data from patients with LV-GCA diagnosed by PET/CT and who had PET/CT in the following year were collected. For each PET/CT, PET vascular activity score (PETVAS) and total vascular score (TVS) were assessed, and their ability to predict the occurrence of subsequent relapse was assessed., Results: A total of 65 LV-GCA patients were included, of whom 55 had undergone a follow-up PET/CT 3 to 12 months after the diagnosis of GCA. Patients for whom the second PET/CT (PET2) was performed during active GCA were excluded. PETVAS and TVS decreased between PET1 and PET2 in all patients (p < 0.001). There was no correlation between vascular activity scores in PET2 and time to prednisone taper. For relapse prediction, at PET1, the AUC of the TVS and PETVAS were respectively 51.9 and 41.9 at 6 months, 55.3 and 49.7 at 1 year, 55 and 55.7 at 2 years. For PET2, the AUC were respectively 46.1 and 46.7 at 6 months, 52.1 and 48.9 at 1 year, 58.4 and 52.3 at 2 years., Conclusion: PET vascular activity scores at diagnosis and at follow-up PET/CT performed outside a period of GCA activity do not display high performance to predict the occurrence of subsequent relapse in LV-GCA patients., Competing Interests: Disclosures Maxime Samson: Argenx (consulting), Boerhinger Ingelheim (consulting), Chugai (consulting), CSL Vifor (consulting), Fresenius Kabi (consulting), GSK (consulting), Novartis (consulting and research grant), (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Inaugural axial muscle involvement, defined as dropped head syndrome (DHS) and/or camptocormia (CC), is poorly described in inflammatory myopathies (IM). This study aimed to further characterize IM patients with inaugural DHS/CC, their outcome and care management., Methods: This retrospective study included IM patients diagnosed between 2000 and 2021. The main inclusion criterion was IM revealed by axial muscle deficit (DHS/CC)., Results: Twenty-seven patients were included; median (IQR) age at first symptoms was 66.0 years (55.5-75.0); 21 were female (77.8%). There were nine IBM, 33.3%, nine overlap myositis (OM, 33.3%), five DM, 18.5%, two immune checkpoint inhibitor-related myositis (7.4%), one focal myositis (3.7%) and one myositis with anti-Hu antibodies (3.7%). Age at first symptoms was ≤70 years in 16 patients (59.3%), including all DM patients and 8/9 OM patients (88.9%). In this group, partial remission of the disease was obtained in 9/16 (56.3%) and complete remission in 1/16 patients (6.3%); regression of DHS/CC was achieved in 3/16 patients (18.8%). Conversely, in the group of 11 patients aged >70 years at first symptoms, there were eight IBM (72.7%). Partial remission was obtained in 5/11 patients (45.5%), the disease was stable in 6/11 patients (54.5%); no complete remission was obtained nor regression of DHS/CC., Conclusion: The analysis of IM patients with inaugural DHS/CC delineates two groups of patients according to the age at first symptoms in terms of clinical and outcome specificities, and proposes an adapted diagnostic and care management approach to prevent long-term complications., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking., Methods: This retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed., Results: 196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12-3.08), gastrointestinal involvement (1.95; 95% CI1.09-3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24-3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23-6.37), necrotic purpura (HR 4.16; 95%CI 1.62-10.70), acute kidney injury (HR 4.89; 95% 1.71-13.99) and secondary PAN (HR 2.98; 95%CI 1.29-6.85) were independently associated with mortality., Conclusion: Landscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes., Methods: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjögren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjögren's syndrome flare (≥3-point increase in EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjögren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquête Nationale Périnatale 2016)., Findings: 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjögren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of ≥1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjögren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjögren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [4%] of 51 pregnancies; p=0·023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjögren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjögren's syndrome (odds ratio 1·31, 95% CI 0·53-2·98; p=0·52)., Interpretation: Pregnancies in women with primary Sjögren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes., Funding: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge., Competing Interests: Declaration of interests NC-C reports an unrestricted research grant from UCB to her institution. GN reports grants from la Société Française de Rhumatologie and Arthritis Foundation; consulting fees from Biogen, Pfizer, Novartis, Lilly, and Amgen; support for attending meetings and travel from Amgen; and is an advisory board member for Boehringer Ingelheim. AM reports an unrestricted research grant from Pfizer to her institution; consulting fees from Janssen and Gilead; and honoraria for presentations or speaker bureaus from AbbVie, Bristol Myers Squibb, Biogen, Pfizer, UCB, and Lilly; support from AbbVie, Janssen, Bristol Myers Squibb, and Pfizer for attending meetings or travel; and is an advisory board member for Janssen and UCB. CR reports consulting fees from Novartis and UCB. MM received grants from GSK and received support for travel and attending meetings from Novartis and LFB. LR reports support for attending meetings from Novartis and Otsuka. XM reports consulting fees from AstraZeneca, Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. VLG reports honoraria for presentations or speaker bureaus from Bristol Myers Squibb; consulting fees from Novartis; and support from AstraZeneca–MedImmune for attending meetings and travel. RS reports consulting fees from GlaxoSmithKline, Bristol Myers Squibb, Boehringer Ingelheim, and Janssen; honoraria for presentations or speaker bureaus from GlaxoSmithKline, Bristol Myers Squibb, Fresenius Kabi, Boehringer Ingelheim, Janssen, Pfizer, and Roche; and support for attending meetings and travel from Amgen and GlaxoSmithKline. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to report the association of focal myositis (FM) and Behçet's disease (BD) and to analyse the main characteristics of such an association., Methods: This is a retrospective multicentre study of patients with BD and FM (BD + FM+ group) and those without FM (BD - FM+ group). Clinical, laboratory, radiological, pathological, treatment and outcome data were analysed., Results: The BD + FM+ group included 10 patients; the median [interquartile range] age at BD diagnosis was 25 [16-35] years, and at FM diagnosis, it was 30 [26-42] years. The diagnosis of BD preceded FM in the majority of cases (n = 8/10). FM occurrence was associated with BD flare-ups in three cases. The creatine kinase levels remained normal or slightly increased. Histological analyses identified relatively preserved muscle tissue, associated with vasculitis (n = 5/6). All patients required treatment; most patients relapsed (n = 9/10). The BD - FM+ group included 35 patients. A comparison of the groups identified a trend towards a younger median age at diagnosis of FM among those with BD (p = 0.063) and more frequent focal muscle swelling in the BD + FM+ group (p = 0.029). The pathological analysis identified significantly less frequent muscle alterations in the BD + FM+ group (muscle fibre size heterogeneity, p = 0.021; necrosis, p = 0.007; and fibrosis, p = 0.027). BD + FM+ patients had a higher frequency of relapse (p = 0.003) and systematic treatment (p = 0.042)., Conclusions: FM occurring during BD appears to be part of the systemic vasculitis process and presents as a vasculitis-associated focal myopathy with a specific clinico-histological pattern. Patients with this association require long-term follow-up and adapted management. This case series also highlights the need for research on BD diagnostic criteria in cases of FM., (© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Objective: Dermatomyositis associated with anti-MDA5 autoantibodies (DM-MDA5+) is a rare autoimmune disease usually characterized by skin involvement, often-severe lung involvement, and general features. Several reports of infections have been described, sometimes early after the introduction of immunosuppressive therapy. We studied the infection risk in a DM-MDA5+ population. Methods: A retrospective cohort study comparing the number and type of infections during the follow-up of 19 patients with DM-MDA5+ and 37 patients with another type of inflammatory myopathy was analyzed. Patients in both groups were matched on initial immunosuppressive therapy. We described and compared significant infectious complications (SIC) in each group. Results: Patients DM-MDA5+ had more SIC: 27 events in the DM-MDA5+ group versus 6 in the controls (HR 7.08, 95% CI 2.50−20.04, p < 0.0001). The number of SIC per patient was higher in DM-MDA5+ (1.4 ± 1.57 vs. 0.16 ± 0.44, p < 0.001). These were mainly lung (n = 13, 48%) and skin infections (n = 6, 22%), more often infections of an undetermined infectious agent (n = 11, 41%) or of bacterial origin (n = 9, 33%). A few cases of opportunistic infections were reported. The median duration of follow-up without SIC event in the DM-MDA5+ cohort was 3.5 months. Conclusion: Patients with DM-MDA5+ have an increased infection risk compared to others inflammatory myopathies irrespective of immunosuppressive therapy exposure. These results highlight the importance of monitoring for infection during patient follow-up.

Objective: Immunoglobulin A vasculitis (IgAV) usually occurs following viral respiratory tract infection. In the context of the global coronavirus disease 2019 (COVID-19) pandemic, we describe a case series of patients who developed IgAV following SARS-CoV-2 infection., Methods: This national multicenter retrospective study included patients with IgAV following SARS-CoV-2 infection from January 1, 2020, to January 1, 2022. Patients had histologically proven IgAV and reverse transcription PCR (RT-PCR)-proven SARS-CoV-2 infection. The interval between infection and vasculitis onset had to be < 4 weeks., Results: We included 5 patients, 4 of whom were women with a mean age of 45 years. Four patients had paucisymptomatic infections and 1 required a 48-hour low-flow oxygen treatment. All 5 patients had purpuric skin involvement. Arthritis was observed in 2 patients, 3 had IgA glomerulonephritis, and 2 had digestive involvement. Three renal biopsies were performed and showed mesangial IgA deposits without any extracapillary proliferation. Median C-reactive protein was 180 (range 15.1-225) mg/L, median serum creatinine level was 65 (range 41-169) µmol/L, and 2 patients had a glomerular filtration rate < 60 mL/min. Four patients received first-line treatment with glucocorticoids. All patients had a favorable progression and 2 patients experienced minor skin relapses, one after COVID-19 vaccination., Conclusion: This series describes the emergence of IgAV closely following COVID-19; we were not able to eliminate an incidental link between these events. Their disease outcomes were favorable. In most of our patients, the SARS-CoV-2 infection was paucisymptomatic, and we recommend RT-PCR tests to look for COVID-19 in patients without any evident triggers for IgAV., (Copyright © 2022 by the Journal of Rheumatology.)

Still's disease (SD) is a heterogeneous autoinflammatory disorder for which several phenotypes have been described. We conducted a retrospective study to re-evaluate the dichotomous view of the disease, to compare the juvenile and adult forms, and to look for prognostic factors. We collected data from ten French centers, seeking patients with a diagnosis of adult-onset SD (AOSD) or systemic juvenile idiopathic arthritis (sJIA). We identified 238 patients, 152 (64%) of whom had AOSD while 86 (36%) had sJIA. The median age at SD onset was 26.6 years. In patients with identifiable patterns, the course of SD was systemic in 159 patients (74%), chronic in 55 (26%). Sore throat and myalgia were more frequent in patients with AOSD. Abnormal liver tests, serum ferritin and C-reactive protein levels were higher in AOSD group. Fever and skin rash were predictive of complete remission or recovery and high lactate dehydrogenase level was a poor prognosis factor. Symptoms such as splenomegaly, skin rash, high polymorphonuclear neutrophils count and macrophage activation syndrome were predictive of a systemic phenotype. Overall, there were no major differences between sJIA and AOSD. Our results are consistent with the "biphasic" model of an autoinflammatory disease that can progress to chronic arthritis if not treated early.

Objective: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients., Methods: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE., Results: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred &gt;20 years earlier (P &lt; 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]., Conclusion: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Distinguishing between macrophage activation syndrome (MAS) and a simple flare of Still's disease (SD) may be challenging. We sought to clarify the clinical features and outcome of MAS in SD and to explore predictive factors of MAS development. Demographic and clinical data, treatments, and outcomes were recorded in a cohort of 206 SD patients. SD patients with and without MAS were compared. To explore predictive factors for the development of MAS, patients were compared at the time of SD diagnosis. Twenty (9.7%) patients experienced MAS, which was inaugural in 12 cases. Patients with MAS were more likely to have hepatomegaly (OR, 3.71; 95% CI, 1.14-11.2; p = 0.03) and neurological symptoms (OR, 4.43; 95% CI, 1.08-15.3; p = 0.04) than patients without MAS. Cytopenias, abnormal liver tests, and coagulation disorders were significantly more frequent in patients with MAS; lactate dehydrogenase and serum ferritin levels were significantly higher. An optimized threshold of 3500 μg/L for serum ferritin yielded a sensitivity (Se) of 85% and a negative predictive value (NPV) of 97% for identifying patients with/without MAS. Survival analysis showed that a high ferritin level at the time of SD diagnosis was predictive of MAS development ( p < 0.001). Specific factors, including neurological symptoms, cytopenias, elevated LDH, and coagulopathy, may contribute to the early detection of MAS. Extreme hyperferritinemia at the onset of SD is a prognostic factor for the development of MAS.

Aims: To assess vision-related (VR-QOL) and health-related quality of life (HR-QOL) in a large series of patients with de novo uveitis at baseline and 6-month follow-up., Methods: Non-inferiority, prospective, multicentre, cluster randomised controlled trial registered under the Unique Identifier: NCT01162070. VR-QOL and HR-QOL were assessed by the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and the Medical Outcomes Study 36-item Short Form Survey (SF-36)., Results: At inclusion, 466 patients completed the VFQ-25. The mean composite score was 80.0 (±16.7). In multivariate analysis, higher age, female sex and insidious onset were significantly associated with lower QOL. At 6 months, 138 patients completed the VFQ-25, with a significantly higher mean composite score of 82.6 (±16.7). SF-36 mental component was 42.9 (±11.3) and physical component was 47.2 (±8.5) at inclusion (n=425). HR-QOL improvement at 6 months was not clinically significant., Conclusion: QOL seems relatively well preserved in this cohort; only VR-QOL improved significantly at 6 months, especially in patients with low initial visual acuity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Recently, concerns have been raised about an increased risk of cardiac sarcoidosis in patients with sarcoid uveitis. While cardiac sarcoidosis has a high mortality burden, there is still a lack of precise data on this association. The objective of this study is to describe the frequency and type of cardiac complications associated with sarcoidosis of a large cohort of patients with sarcoid uveitis. We analyzed the cardiac outcomes of a monocentric retrospective cohort of consecutive adults with a diagnosis of sarcoid uveitis between January 2004 and March 2020 in a tertiary French university hospital. A total of 294 patients with a final diagnosis of sarcoid uveitis were included. At final follow-up, seven (2.4%) patients of the cohort had cardiac sarcoidosis. Cardiac sarcoidosis was more frequent among patients with previously reported systemic sarcoidosis ( p = 0.008). The prevalence of cardiac sarcoidosis among patients with sarcoid uveitis is low, but patients with previously diagnosed sarcoidosis or those who develop systemic sarcoidosis during follow-up appear to be at increased risk.

Background: Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype., Aims: This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis., Methods: Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death., Results: Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29-7.34), performance status (OR 1.40, 1.05-1.87), use of morphine (OR 2.51, 0.87-7.24), abdominal guarding (OR 3.08, 1.01-9.37), ileus (OR 2.29, 0.98-5.32), melena (OR 2.74, 1.17-6.42), increased leukocytes (per G/L, OR 1.05, 1.00-1.10), low hemoglobin (per g/dL, OR 0.80, 0.71-0.91) and increased CRP (log mg/L, OR 1.21, 0.94-1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well., Conclusions: Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE., Method: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed., Results: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE., Conclusion: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Sarcoidosis is one of the leading causes of uveitis. To date, no studies have assessed the factors specifically related with recovery in ocular sarcoidosis. In this study, we aimed to determine factors associated with ocular and extraocular recovery in patients with sarcoid uveitis., Methods: A retrospective study of sarcoid uveitis, with a three-year minimum follow-up in Lyon University Hospital between December 2003 and December 2019. Patients presented biopsy-proven sarcoidosis or presumed sarcoid. Recovery was defined by a disease-free status, spontaneously or despite being off all treatments for three years or more., Results: 143 patients were included: 110 with biopsy-proven and 33 with presumed sarcoid uveitis. Seventy-one percent were women, the median age at presentation was 53 years, and 71% were Caucasian. Chronic uveitis was the main clinical presentation (75%), mostly panuveitis (48%) with bilateral involvement (82%). After a median follow-up of 83.5 months, recovery was reported in 26% of patients. In multivariable analysis, Caucasian ethnicity ( p = 0.007) and anterior uveitis ( p = 0.008) were significantly associated with recovery, while increased intraocular pressure was negatively associated ( p = 0.039)., Conclusion: In this large European cohort, one quarter of patients recovered. Caucasian ethnicity and anterior uveitis are associated with ocular and extraocular recovery.

Background: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients., Methods: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL., Results: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL)., Conclusions: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

Background: Uveitis is a frequent and early feature of sarcoidosis. As BTNL2 (butyrophilin-like 2) gene polymorphism was found linked with the susceptibility to sarcoidosis, we investigated whether a specific genotype of BTNL2 gene G16071A (or rs2076530) single-nucleotide polymorphism (SNP) would be associated with the risk of sarcoid uveitis in all patient subgroups., Methods: The study compared the genotype frequencies of SNP G16071A of 135 patients with sarcoid uveitis (Sa + Uv + ) with those of 196 patients with sarcoidosis without uveitis (Sa + Uv - ), 81 patients with uveitis without sarcoidosis (Sa - Uv + ), and 271 controls with no sarcoidosis nor uveitis (Sa - Uv - ). Three hypothetical subgroups of patients with sarcoid uveitis (Sa + Uv + cases) were considered: (1) subgroup I: patients aged <45 years of both sexes and all ethnic origins; (2) subgroup II: Caucasian women aged >45 years; and (3) subgroup III: all other patients., Results: A statistically significant difference in genotype frequencies was found between the groups Sa + Uv - and Sa - Uv - (p=3.2×10 -6 ) and between the groups Sa + Uv + and Sa + Uv - (p=7.1×10 -3 ). There was no difference between the three subgroups of Sa + Uv + patients. There was a statistically significant difference in genotype frequencies between Sa + Uv - and Sa + Uv + subgroup II (p=0.005) but no difference between Sa + Uv - and Sa + Uv + subgroup I., Conclusion: No association was found between G16071A and the susceptibility to sarcoid uveitis. BTNL2 gene G16071A SNP seems to be a predisposing factor for sarcoidosis except in Caucasian postmenopausal women with sarcoid uveitis in whom the GG genotype prevails. These and future results will help in understanding differences between particular subgroups of patients with sarcoid uveitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the ophthalmological and extra-ophthalmological clinical characteristics and visual prognosis of patients with sarcoid uveitis in different ethnic groups., Methods: We retrospectively analysed the data from patients with sarcoid uveitis seen at two departments of Ophthalmology between December 2003 and December 2017. Patients presented biopsy-proven sarcoidosis and/or presumed sarcoid uveitis based on the following criteria: compatible thoracic imaging, associated with elevated angiotensin-conversion enzyme (ACE) and/or lymphocytic alveolitis on bronchoalveolar lavage fluid analysis (> 15% lymphocytes and CD4/CD8 > 3.5). Ophthalmological and general characteristics, as well as visual and global prognoses, were compared in three pre-defined ethnic groups: White Europeans, North Africans and Afro-Caribbeans., Results: A total of 194 patients were included: 145 with biopsy-proven and 49 with presumed sarcoid uveitis. Overall, 68% were White Europeans while 20.6% were North Africans and 11.3% were Afro-Caribbeans. Sixty-nine per cent were women and the median age at presentation was 52.1 years. Median ages at first ocular manifestation of the disease in Afro-Caribbeans and North Africans were respectively 34.3 and 43.1 years, while it was 57.8 years in White Europeans (p < 0.001). Ocular involvement was bilateral in 77.8% (n = 151) of the cases and nearly half of the patients had panuveitis (48.5%). Anterior uveitis was more frequent in Afro-Caribbeans (59.1%; p < 0.0001), while White Europeans presented more frequently with intermediate uveitis. There was a significantly higher frequency of systemic involvement of sarcoidosis in North Africans while White Europeans showed a higher frequency of isolated ocular involvement at onset and during follow-up. Afro-Caribbeans, who had a complete visual recovery in 72.7% of the cases, had a better visual prognosis than other ethnic groups (p = 0.025)., Conclusion: In this large European series of sarcoid uveitis, we observed ethnicity-related differences regarding uveitis clinical presentation and visual outcome. Although good overall, the visual prognosis seems to be better in Afro-Caribbeans than in other ethnic groups.

Aims: To determine the long-term visual and systemic outcomes of uveitis patients with biopsy-proven sarcoidosis., Methods: A retrospective study of biopsy-proven sarcoid uveitis, with a 3-year minimum follow-up, seen at Lyon University Hospital, between April 2004 and January 2016., Results: A total of 83 patients were included, with a median age at onset of 52 (37-62) years and an unbalanced gender ratio (women 77.1%). Thirty-one patients had original systemic sarcoidosis in addition to ocular localisation, whereas 52 initially presented with isolated sarcoid uveitis. Among the latter, 7.7% (n=4) developed an extraocular disease after a median follow-up duration of 60 (44-110) months. The systemic spread in these patients included cutaneous sarcoids (n=2), arthritis (n=1) and multiple mononeuritis (n=1). Complete visual recovery was obtained for 60.2% of all patients and 89.2% had retrieved best-corrected visual acuity (BCVA) >20/50 in both eyes. A unilateral loss of BCVA of worse than 20/200 was documented in two patients in the isolated sarcoid uveitis group. No patient suffered from bilateral severe visual impairment or blindness. Factors linked to a poor visual prognosis, defined by BCVA ≤20/50 in at least one eye, were chronic macular oedema (p=0.009) and persistent ocular inflammation (p=0.0005)., Conclusions: In this large European series of biopsy-proven sarcoidosis to date, with a prolonged follow-up, sarcoid uveitis was suggestive of a favourable systemic and visual outcome. Clinically isolated uveitis that revealed sarcoidosis remained a strictly ocular condition in most cases., Competing Interests: Competing interests: None., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE., Methods: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2)., Results: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1)., Conclusions: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE., (© The Author(s) 2016.)

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.

Objective: To analyze the factors associated with response to anti-tumor necrosis factor (anti-TNF) treatment and compare the efficacy and safety of infliximab (IFX) and adalimumab (ADA) in patients with refractory noninfectious uveitis., Methods: This was a multicenter observational study of 160 patients (39% men and 61% women; median age 31 years [interquartile range 21-42]) with uveitis that had been refractory to other therapies, who were treated with anti-TNF (IFX 5 mg/kg at weeks 0, 2, 6, and then every 5-6 weeks [n = 98] or ADA 40 mg every 2 weeks [n = 62]). Factors associated with complete response were assessed by multivariate analysis. Efficacy and safety of IFX versus ADA were compared using a propensity score approach with baseline characteristics taken into account. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (95% CIs) were calculated., Results: The main etiologies of uveitis included Behçet's disease (BD) (36%), juvenile idiopathic arthritis (22%), spondyloarthropathy (10%), and sarcoidosis (6%). The overall response rate at 6 and 12 months was 87% (26% with complete response) and 93% (28% with complete response), respectively. The median time to complete response was 2 months. In multivariate analysis, BD and occurrence of >5 uveitis flares before anti-TNF initiation were associated with complete response to anti-TNF (SHR 2.52 [95% CI 1.35-4.71], P = 0.004 and SHR 1.97 [95% CI 1.02-3.84], P = 0.045, respectively). Side effects were reported in 28% of patients, including serious adverse events in 13%. IFX and ADA did not differ significantly in terms of occurrence of complete response (SHR 0.65 [95% CI 0.25-1.71], P = 0.39), serious side effects (SHR 0.22 [95% CI 0.04-1.25], P = 0.089), or event-free survival (SHR 0.55 [95% CI 0.28-1.08], P = 0.083)., Conclusion: Anti-TNF treatment is highly effective in refractory inflammatory uveitis. BD is associated with increased odds of response. IFX and ADA appear to be equivalent in terms of efficacy., (© 2016, American College of Rheumatology.)

Aims: To determine the clinical features of patients with uveitis with biopsy-proven sarcoidosis, document differences in these features according to ethnicity, age and sex, and assess the diagnostic value of biochemical and imaging examinations., Methods: Retrospective study of 83 biopsy-proven sarcoid uveitis cases seen at two Departments of Internal Medicine and two Departments of Ophthalmology between April 2004 and March 2014., Results: Caucasian patients presented with uveitis at a later age than non-Caucasian (58 years vs 41 years; p=0.001) and had more often a chronic form (78.3% vs 43.8%; p=0.01). Women had higher rates of chronic macular oedema than men (48.3% vs 14.3%; p=0.01). There were no statistically significant differences between patients aged ≤50 years and patients aged >50 years. ACE levels were high (>62 U/L) in 61.7% and lysozyme levels high (>16.7 mg/L) in 83.9% of tested patients. Chest X-rays and CTs were suggestive of sarcoidosis in 62.8% and 91.2% of cases, respectively. Among 21 patients with positive tomography and negative X-rays, 13 were Caucasian women >50 years. Endoscopic ultrasound-guided fine-needle aspiration of intrathoracic nodes contributed to the diagnosis in 7 patients with normal labial salivary gland and transbronchial biopsies. Any of the enzyme tests together with any of the imaging tests identified 100% of the patients., Conclusions: In this largest European series of biopsy-proven sarcoidosis to date, the outstanding diagnostic ability of enzyme test plus imaging test couple suggests that the recourse to invasive procedures should be limited to patients with ocular involvement that would justify systemic treatments., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD)., Methods: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]., Results: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases., Conclusion: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations., Methods: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded., Results: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001)., Conclusion: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians., (© 2015, American College of Rheumatology.)

Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database.Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been treated by cyclophosphamide.Pituitary disease in GPA occurs mostly several months or years after diagnosis. There is no correlation between hormonal, radiologic, and systemic outcome. Although immunosuppressive drugs improve the systemic disease, hormonal deficiencies usually persist. It is therefore important to shorten diagnostic delays and treat these patients early in the course of disease before irreversible damage occur.

Introduction: Syphilis, caused by Treponema pallidum agent, results in polymorphic and non-specific ocular manifestations. Early diagnosis and institution of individualized treatment play a large role in the prognosis. The increase in syphilis over the past several years requires the ophthalmologist to consider this diagnosis in the setting of any intraocular inflammatory involvement., Purpose: To describe epidemiological, clinical and paraclinical features and natural history of syphilitic uveitis., Materials and Methods: Retrospective, descriptive and non-comparative study of a series of patients hospitalized between 2007 and 2013 in our department of ophthalmology for management of ocular inflammation associated with a positive syphilitic serology., Results: Thirteen patients of mean age 52.5 years ± 12.9 (33-82 years) were included. All were male and were followed for six months. Co-infection with human immunodeficiency virus (HIV) was present in four of them. Other risk factors discovered on history were unprotected sexual relations, multiple partners, homosexual relations, co-infection with another sexually transmitted disease (STD) or an occupational risk. Decreased visual acuity (VA) was present in all patients, with an average initial VA of 0.71 ± 0.81 LogMAR, i.e. 2/10. Involvement was bilateral in 38% (n=5) of cases. Papilledema was present in 10 patients. Seven patients exhibited vasculitis, 6 patients a necrotizing retinitis, 2 patients with placoid lesions, 7 patients with panuveitis and 2 patients with macular edema. We did not find any patients with isolated anterior uveitis. Three patients exhibited concomitant extraocular involvement with cutaneous palmoplantar lesions. Spectral domain optical coherence tomography (SD-OCT) found a fragmentation of the external limiting membrane and a disorganization of the ellipsoid line in two patients. Cerebrospinal fluid was studied for all patients. Eight of them exhibited lymphocytic meningitis, and we found the presence of anti-Treponema pallidum hemagglutination assay antibody (TPHA) in 9 patients and anti-veneral disease research laboratory antibody (VDRL) in 1 patient. Syphilis polymerase chain reaction (PCR) in the aqueous humor was positive in 50% (n=6) of studied cases and the PCR for Epstein Barr virus came back positive in four specimens out of eight. False positive reactions were observed for Lyme disease in eight patients. The four HIV-positive patients showed bilateral lesions more frequently, but less severe and with a favorable outcome. Antibiotic treatment with ceftriaxone (2 grams per day intramuscularly for 15 to 21 days) and local treatment (corticoids and mydriatics) in the case of inflammation of the anterior segment, allowed a regression of the inflammation in all of our patients as well as an improvement in VA (average final VA 0.09 ± 0.17 LogMAR, i.e. approximately 8/10). One Jarisch Herxheimer reaction occurred and was resolved with systemic corticosteroid therapy. A change in the retinal pigment epithelium was the main sequela in 44% of cases (n=8 eyes)., Conclusion: Every structure of the eye may be involved with syphilis; therefore, syphilis must be systematically sought during the etiologic assessment of ocular inflammation even in the absence of historical risk factors. HIV-positive patients must be handled in the same way as immunocompetent patients. Collaboration with the internist is essential for the diagnosis, monitoring, and staging, especially in search of neurosyphilis. The clinical course is favorable with early treatment., (Crown Copyright © 2014. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups., Methods: Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361)., Results: The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22)., Conclusions: We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

Introduction: Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares., Patients and Methods: [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up., Results: Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12)., Conclusions: Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.

The occurrence of a macular hole due to posterior uveitis is infrequently reported. We report the evolution of three cases of macular holes secondary to posterior segment inflammation. A complete inflammatory and infectious assessment found one case of toxocariasis, one of sarcoidosis, and one of syphilis. After medical etiological treatment, macular hole closure was rapidly obtained in all the cases and confirmed by spectral domain optic coherence tomography, with visual acuity improvement. Fibrous scarring developed in two cases, and foveal photoreceptor complex normalization was observed in the sarcoidosis case. These observations demonstrate that macular holes secondary to posterior uveitis frequently resolve without surgical intervention and so could be underdiagnosed if the patient is not evaluated at the time of onset before spontaneous hole closure.

Background: This was an evaluation of intra-individual variation of the cuff-leak test (ΔCLT) immediately post-intubation and pre-extubation, as a predictor of post-extubation stridor., Methods: Prospective, clinical investigation in the ICU of a non-university hospital. CLTs were performed immediately after intubation (T0) and before extubation (T1) to evaluate the differences in cuff leak (ΔCLT = CL(T1) - CL(T0))., Results: We included 104 mechanically ventilated subjects in the study over a 12-month period. The incidence of post-extubation stridor was 6.7%. Stridor was more common in females of short stature. ΔCLT was considered as significant when CL(T1) - CL(T0) was negative. The sensitivity and the specificity of the test were 86% and 48%, respectively. When we tested the pre-extubation CLT alone with a threshold of 130 mL as a predictor of post-extubation stridor, the sensitivity and the specificity of the test were 86% and 76%, respectively., Conclusions: The intra-individual variation of CLT immediately post-intubation and pre-extubation does not improve the accuracy of a standard pre-extubation CLT to predict post-extubation stridor. Moreover, the standard pre-extubation CLT did not appear in our study to be an ideal test to detect post-extubation stridor. Larger studies should be performed before generalizing these preliminary results.

Erdheim-Chester disease is a rare form of systemic non-Langerhans cell histiocytosis characterized by infiltration by lipid-laden or foamy histiocytes. Osseous involvement, major diagnostic criteria, is constant and characteristic. It presents as metaphyseal and diaphyseal osteosclerosis, mainly affecting the long bones of the lower limbs. A few cases with axial skeleton involvement have been reported. Extra-osseous lesions may affect the retroperitoneum, lungs, skin, heart, brain and orbits. Prognosis depends mainly on the extra-osseous disease, mainly heart and lung involvement. Diagnosis is based on the combination of radiographic features, nuclear medicine features and nearly pathognomonic immunohistochemical profile., (Copyright © 2011 Elsevier Masson SAS and Éditions françaises de radiologie. All rights reserved.)

Purpose: To report atypical ocular manifestations in two patients with undiagnosed Hodgkin lymphoma., Methods: Observational case report., Results: The first patient, a 27-year-old man, presented with bilateral acute angle-closure glaucoma secondary to uveal effusion. Histopathology of chest lymph nodes obtained by mediastinoscopy revealed nodular sclerosing Hodgkin lymphoma. Ocular signs resolved after systemic chemotherapy. The second patient, a 56-year-old man, presented with bilateral multifocal choroiditis. Extensive biologic and microbiologic examinations were negative. Pathologic lymph nodes were detected in the anterior mediastinum. The histopathologic examination of the nodes after mediastinoscopy revealed nodular sclerosing Hodgkin lymphoma. Systemic chemotherapy was instituted. The patient encountered a major increase in the multifocal choroiditis within 3 days after the second chemotherapy injection. High-dose intravenous corticosteroid therapy was initiated. No recurrence of choroidal lesions was observed after the treatment completion., Conclusion: These two patients presented with bilateral paraneoplastic uveal tract involvement as initial presentation of Hodgkin lymphoma. Systemic corticosteroid therapy may be associated with systemic chemotherapy to obtain complete remission of the ocular inflammatory activity.

Purpose: To report the additional clinical value of real-time Polymerase chain reaction (PCR) in the detection of Treponema pallidum in aqueous humor., Methods: A real-time (RT) PCR assay targeting the polymerase 1 gene of Treponema pallidum was performed in aqueous humor samples collected in consecutive patients with ocular syphilis., Results: Five patients presenting with optic neuritis (1), posterior placoid chorioretinitis (1), or panuveitis with retinitis (3) were tested. The PCR results were positive in the 3 cases of panuveitis and negative in the 2 other cases., Conclusion: RT-PCR for Treponema pallidum in aqueous humor is useful to confirm syphilitic panuveitis.

Treatment of hepatitis C (HCV)-mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m(2)) once a week for 1 month followed by Peg-interferon-alpha (Peg-IFN-alpha; 2a, 180 microg or 2b, 1.5 microg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-alpha/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-alpha/ribavirin, rituximab plus Peg-IFN-alpha/ribavirin-treated patients had a shorter time to clinical remission (5.4 +/- 4 vs 8.4 +/- 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69(+) B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-alpha/ribavirin is well tolerated and more effective than Peg-IFN-alpha/ribavirin in HCV-MC.

Reactive hemophagocytic syndrome (RHS) is a rare, life-threatening, and little-known complication of rheumatic diseases. This disorder is characterized by fever, pancytopenia, liver failure, coagulopathy, and neurologic symptoms. RHS may develop in patents who have lymphoma, organ transplantation, serious infection, and rheumatic diseases, most notably systemic lupus erythematosus and adult-onset Still disease (AOSD). Observations of specific cases of RHS in AOSD remain rare, and the significance of this syndrome during the course of AOSD remains unknown. We retrospectively studied 16 episodes of AOSD-associated RHS in 8 patients. To determine whether RHS is associated with a particular phenotype of AOSD, we conducted a case-control study from the cohort of AOSD patients seen during the same period. The estimated frequency of RHS in AOSD patients from our cohort was 15.3% (8/52). The median age at RHS diagnosis was 44.5 years. We collected clinical and laboratory data. RHS was the first manifestation of AOSD in 7 cases. The main symptoms were fever (n = 8), salmon rash (n = 6), arthralgia (n = 7), lymphadenopathy (n = 6), and shock (n = 4). Serum ferritin concentration was consistently elevated (>1000 microg/L in 8 cases), and the level of glycosylated ferritin was low in all cases (<5% in 7 cases, 15% in 1 case). Six patients presented with coagulopathy; hypertriglyceridemia was found in 6 cases. Admission to the intensive care unit was required in 4 cases. Treatment included corticosteroids (n = 8) and intravenous immunoglobulin (n = 6), cyclophosphamide in 2 cases, infliximab in the same 2 cases, and cyclosporine in 1 case. With a follow-up ranging from 2 to 15 years, the patients were in remission with prednisone plus methotrexate (n = 4), prednisone plus infliximab (n = 2), and low-dose prednisone alone (n = 2). We compared the 8 patients included in this study with 44 control patients with AOSD without RHS. Low haptoglobin levels, very high ferritin levels (>10,000 microg/L), and a normal or low neutrophil count seem to be predictive factors of the occurrence of RHS in AOSD.

Objectives: To report the results of a pilot study using rituximab combined with Peg-interferon (IFN) alpha2b-ribavirin in severe refractory hepatitis C virus (HCV) related mixed cryoglobulinaemia (MC) vasculitis., Methods: Sixteen consecutive patients with severe HCV-MC vasculitis that were resistant (n = 11) or relapser (n = 5) to a previous combination treatment with standard (n = 10) or Peg-IFNalpha2b (n = 6) plus ribavirin were included. They were treated with rituximab (375 mg/m2 intravenously weekly for 4 weeks) combined with Peg-IFNalpha2b (1.5 mug/kg per week subcutaneously) plus ribavirin (600-1200 mg/day orally) for 12 months., Results: Fifteen patients (93.7%) showed clinical improvement, 10 of whom (62.5%) were clinical complete responders (CR). HCV RNA and serum cryoglobulin became undetectable in all the clinical CR. Peripheral blood B cell depletion was achieved in all patients (CD19+ cells, 111 (SD 32)/mm3 at baseline versus 2(2)/mm3 after the fourth infusion of rituximab) with reconstitution starting at the end of antiviral treatment. Compared with clinical CR, the partial or non-responders had a 3.6 times longer duration of vasculitis prior to treatment and a lower rate of early virological response. Treatment was well tolerated with no infectious complications. After a mean follow-up of 19.4 (SD 3.6) months, two patients experienced clinical relapse associated with a simultaneous reappearance of HCV RNA and cryoglobulin and an increase in the number of B cells., Conclusions: Rituximab combined with Peg-IFNalpha2b-ribavirin represents a safe and effective treatment option in severe refractory HCV-MC vasculitis.

Churg-Strauss syndrome (CSS) is an extremely rare disease, and even less common in women of childbearing age. Patients with severe disease or those who are un-responsive to corticosteroids are usually treated with cytotoxic drugs, especially cyclophosphmide. Intravenous immunoglobulin (IVIg) has became a promising, but not completely accepted, form of treatment for systemic vasculitis that is un-responsive to standard therapy. We report a case of a woman who presented with a CSS flare during pregnancy. Because of mono-neuritis, treatment with IVIg was instituted with successful results. Our case not only supports the beneficial effect of IVIg in CSS, but it also illustrates its successful and safe use in a patient who was pregnant. We discuss the indication of IVIg during the course of anti-neutrophil cytoplasm antigen (ANCA) vasculitis during the pregnancy.

Monoclonal gammopathy has been reported rarely in association with infectious diseases. Viral infection has been the most frequently reported. We report a case of Bartonella quintana endocarditis in a 45-year-old homeless male associated with a monoclonal IgG kappa gammopathy. The gammopathy disappeared after 8 months of antibiotics while the Bartonella antibody titre was decreasing. This correlation suggests a causative role for B. quintana for the monoclonal gammopathy. To the best of our knowledge, this the first report of monoclonal gammopathy in the course of B. quintana infection., (2006 Wiley-Liss, Inc.)