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Background/objectives: The large number and heterogeneity of causes of uveitis make the etiological diagnosis a complex task. The clinician must consider all the information concerning the ophthalmological and extra-ophthalmological features of the patient. Diagnostic machine learning algorithms have been developed and provide a correct diagnosis in one-half to three-quarters of cases. However, they are not integrated into daily clinical practice. The aim is to determine whether machine learning models can predict the etiological diagnosis of uveitis from clinical information., Methods: This cohort study was performed on uveitis patients with unknown etiology at first consultation. One hundred nine variables, including demographic, ophthalmic, and clinical information, associated with complementary exams were analyzed. Twenty-five causes of uveitis were included. A neural network was developed to predict the etiological diagnosis of uveitis. The performance of the model was evaluated and compared to a gold standard: etiological diagnosis established by a consensus of two uveitis experts., Results: A total of 375 patients were included in this analysis. Findings showed that the neural network type (Multilayer perceptron) (NN-MLP) presented the best prediction of the etiological diagnosis of uveitis. The NN-MLP's most probable diagnosis matched the senior clinician diagnosis in 292 of 375 patients (77.8%, 95% CI: 77.4-78.0). It achieved 93% accuracy (95% CI: 92.8-93.1%) when considering the two most probable diagnoses. The NN-MLP performed well in diagnosing idiopathic uveitis (sensitivity of 81% and specificity of 82%). For more than three-quarters of etiologies, our NN-MLP demonstrated good diagnostic performance (sensitivity > 70% and specificity > 80%)., Conclusion: Study results suggest that developing models for accurately predicting the etiological diagnosis of uveitis with undetermined etiology based on clinical information is feasible. Such NN-MLP could be used for the etiological assessments of uveitis with unknown etiology., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims: To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis., Methods: Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation., Results: 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 -not reached) vs 8.4 months (3.1-22.9) with MMF and 16.8 months (8.0-90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively., Conclusion: In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile., Competing Interests: Competing interests: Bahram Bodaghi: Alimera, Abbvie, Optos, Zeiss, Thea, Horus, Active biotech. Laurent Kodjikian: Alimera, Abbvie, Novartis, Bayer, Roche, Horus, Krys. Sara Touhami: Allergen, Novartis, Horus, Bayer pharma. Pascal Sève: Abbvie, Pfizer, Sanofi, Lilly, GSK, UCB Pharma., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: The 2017 reform of the third cycle of medical studies (R3C) was accompanied by modifications in the formats and number of specialty diplomas. The aim of this study was to investigate the evolution of the choice of the internal medicine and clinical immunology specialty before and after 2017., Methods: We used the median ranking and its evolution, as well as incoming and outgoing remorse rights, as markers of attractiveness. Data on the number of position offered, rankings and affectation were collected from decrees published in the French "Journal Officiel" each year. A survey conducted by the "Amicale des Jeunes Internistes" investigated the reasons for the outgoing or incoming rights to remorse., Results: Before 2017, internal medicine was accessible to 52% of students on average, with a median rank of 1118 [339-2640]. From 2017 onwards, the internal medicine specialty was accessible to an average of 76.6% of students, with a median rank of 2772 [1039-5155]. The balance of incoming and outgoing remorse rights was -4.7% before 2017 and varied between -4.1 and -12.4% from 2017., Conclusion: Since 2017, the median and cut-off ranks of students choosing internal medicine specialty have increased, and balance of incoming and outgoing remorse rights was increasingly negative. A reflection on the attractiveness of the internal medicine specialty is undertaken by the National College of Internal Medicine Teachers in order to make the richness of the specialty and its different modes of practice known to future residents., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Determining uveitis etiology is a challenge. It is based primarily on demographic data and the characteristics of eye examination. It is not clear to what extent extraocular physical signs contribute to elucidating the etiology. This study aimed to establish the contribution of the clinical extra-ophthalmological features for the assessment of the underlying etiology of uveitis., Methods: We retrospectively reviewed 1307 patients with uveitis referred to our tertiary center between 2003 and 2021. Uveitis was classified according to the Standardization of Uveitis Nomenclature. Clinical features were collected at diagnosis by internists before the etiological diagnosis was made. The main outcome description was the contribution of clinical features., Results: Clinical extra-ophthalmological features contributed to the assessment of the underlying etiology of uveitis in 363 (27.8%) patients. The joint and the skin examinations were the most useful for etiological investigations, respectively in 12.3% and 11.8% of patients. Five etiologies of uveitis accounted for 80% of the cases: sarcoidosis, HLA-B27-related uveitis, Behçet's disease, multiple sclerosis, and Vogt-Koyanagi-Harada disease. Clinical extra-ophthalmological features were particularly important in the etiological diagnosis of acute bilateral anterior uveitis and panuveitis., Conclusion: This study suggests that clinical extra-ophthalmological features are essential for the etiological diagnosis of uveitis in more than a quarter of patients. It demonstrates once again the value of collaboration between ophthalmologists and other specialists experienced in performing extra-ophthalmological clinical examinations, particularly in patients with acute bilateral anterior uveitis and panuveitis.

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2-3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Granulomatous myositis is a clinical-pathological entity, which has been rarely reported, mostly described in sarcoidosis. Currently, no clear and simple prognostic factor has been identified to predict granulomatous myositis evolution. The clinical, anatomopathological, imaging, and biological characteristics of 26 patients with granulomatous myositis were retrospectively collected to describe clinical presentation and outcomes of this condition. Twenty-six patients with granulomatous myositis were included (14 males) with a median age of symptom onset of 65 years. 54 % of patients presented a severe form of the disease defined as a Rankin score ≥2 at last follow-up visit or a progressive form of the disease (no improvement under treatment). Etiology were sarcoidosis (n = 14), inclusion body myositis (n = 4), autoimmune disease (n = 1), hematological malignancy (n = 1), and idiopathic (n = 6). Distal deficit and amyotrophy were more frequent among those with a severe disease. Corticosteroids led to improvement in 75 % of cases, but 66 % of responders relapsed. Methotrexate appeared as a promising second line therapy with clinical improvement in 50 % of patients, and no relapse in responders. Granulomatous myositis is often a severe and difficult-to-treat disease in which patients frequently progress towards severe disability. The presence of muscle atrophy and distal weakness appears to be frequently associated with a severe form of the disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures., Methods: We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS., Results: A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0-100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains., Conclusions: RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The study aims to determine the impact of initial management in Vogt-Koyanagi-Harada syndrome (VKHS)., Methods: Patients diagnosed with a VKHS between January 2001 and December 2020 in two French tertiary centers were included in a retrospective study., Results: Fifty patients were included with a median duration of follow-up of 29.8 months. All patients received oral prednisone after methylprednisolone in all but four of them. Five patients received at least one associated immunosuppressive therapy (IST) within the first 6 months and 26 patients received IST during the entire follow-up period. Twenty-eight patients presented at least one relapse at a median of 5.4 months from diagnosis. Multivariate analyses demonstrated a significant association between relapse and delayed treatment (>26 days) (HR = 3.69, CI95% 1.30-10.47, p = .01), whereas no association was observed between relapse and the number of corticosteroid pulses at initial management., Conclusion: An early corticosteroid treatment within the first 26 days of symptoms decreased the relapse rate.

Background: Recurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking., Methods: We performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality., Results: Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death., Conclusion: This study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia., Methods: We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x10 9 /L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations., Results: Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x10 9 /L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x10 9 /L in all cases (n=4)., Discussion: This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AVM declared a shared parent affiliation with the author LL to the handling editor at the time of review., (Copyright © 2024 Chapuis, Bousquet, Viallard, Terrier, Amoura, Batani, Brézin, Cacoub, Caminati, Chazal, Comarmond, Durieu, Ebbo, Grall, Ledoult, Losappio, Mattioli, Mékinian, Padoan, Regola, Schroeder, Seluk, Trefond, Wechsler, Lefevre, Kahn, Sève and Groh.)

Purpose: To describe an unusual case of Whipple's disease (WD) complicated by uveitis, and subsequent paradoxical worsening after effective antibiotic treatment targeting Tropheryma whipplei (TW)., Methods: Case report., Results: A 53-year-old male presented with bilateral knee arthritis, weight loss, chronic low-grade fever, and cognitive disorders. He was under treatment with tumor necrosis factor α inhibitors (TNFi) for seronegative spondyloarthritis. Given this unusual clinical presentation, further investigations were performed and revealed blood, saliva, stool, synovial fluid and cerebrospinal fluid positivity for TW, confirming the diagnosis of systemic WD. Ophthalmologic examination revealed bilateral posterior uveitis and an aqueous humor sample confirmed the presence of intraocular TW. TNFi were stopped, and the patient was subsequently treated with adequate antibiotics (ceftriaxone, followed by doxycycline and hydroxychloroquine), and subconjunctival corticosteroid injections. After a transient improvement of the ocular symptoms, he presented a recurrence of posterior segment inflammation, leading to repeated PCR testing for TW which were negative. Therefore, paradoxical worsening of the inflammation in the context of immune recovery uveitis (IRU) was thought to be the culprit. The patient was treated with systemic corticosteroid therapy, allowing for rapid improvement of the ocular findings., Conclusions: This case underlines the possibility of IRU complicating WD. Ophthalmologists, rheumatologists, and internists should be aware of this rare complication, particularly in the context of previous immunosuppressive therapy., (© 2024. The Author(s).)

Internal medicine is a medical specialty that is often poorly understood by the general public and sometimes misidentified. In an era of increasing subspecialization and high technicality, it is characterized by a comprehensive approach centered on clinical evaluation. Unlike what is observed in most developed countries, where systemic autoimmune diseases are managed by organ specialists based on their mode of presentation, French internists are at the forefront for diagnosing and managing these diseases. Their multidisciplinary training gives them legitimacy to justify this role. Internists also play a crucial role in the management of patients requiring unplanned hospitalizations downstream from emergency departments and in connection with primary care. Internists primarily practice in a hospital setting, with a specific position in the French healthcare system aligned with the training frameworks of all medical specialties. To better define internal medicine, its role in care activities, as well as in education and research, internists organized a General Assembly of internal medicine that took place on September 28, 2023, in Paris. Structured around think tanks focusing on care, education, and research activities, the general assembly aimed to improve visibility on internal medicine and internists. This article recounts the discussions that animated this meeting and highlights the main ideas that emerged. These general assemblies constitute a foundational step and will be followed by a Consultation Conference in order to better identify and promote internal medicine and internists, regardless of their types and places of practice., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: To evaluate the contribution of chest X-ray and chest CT for the diagnosis of sarcoid uveitis., Methods: Retrospective study on consecutive patients with uveitis of unknown etiology, who underwent both chest X-ray and CT during uveitis diagnosis workup in a tertiary French university hospital., Results: A total of 914 patients were included. Systemic sarcoidosis was identified in 23.1%. The probability of discordance between chest X-ray and CT increased with age at diagnosis ( p  < 0.001). In patients 30 years of age and younger, the probability of discordance was 5% or less, and 0.8% if the ACE level was normal. After 78.3 years of age, the probability of discordance was 20% or more., Conclusion: We recommend not to perform CT in patients under 30 years of age with a normal chest X ray and ACE level, and suggest performing chest CT first in the elderly.

Sarcoidosis is a multisystemic disease characterized by non-caseating granuloma infiltrating various organs. The form with symptomatic muscular involvement is called muscular sarcoidosis. The impact of immune cells composing the granuloma on the skeletal muscle is misunderstood. Here, we investigated the granuloma-skeletal muscle interactions through spatial transcriptomics on two patients affected by muscular sarcoidosis. Five major transcriptomic clusters corresponding to perigranuloma, granuloma, and three successive muscle tissue areas (proximal, intermediate, and distal) around the granuloma were identified. Analyses revealed upregulated pathways in the granuloma corresponding to the activation of T-lymphocytes and monocytes/macrophages cytokines, the upregulation of extracellular matrix signatures, and the induction of the TGF-β signaling in the perigranuloma. A comparison between the proximal and distal muscles to the granuloma revealed an inverse correlation between the distance to the granuloma and the upregulation of cellular response to interferon-γ/α, TNF-α, IL-1,4,6, fibroblast proliferation, epithelial to mesenchymal cell transition, and the downregulation of muscle gene expression. These data shed light on the intercommunications between granulomas and the muscle tissue and provide pathophysiological mechanisms by showing that granuloma immune cells have a direct impact on proximal muscle tissue by promoting its progressive replacement by fibrosis via the expression of pro-inflammatory and profibrosing signatures. These data could possibly explain the evolution towards a state of disability for some patients.

Background and Aim: Granulomatous hepatitis (GH) is associated with various aetiologies, especially inflammatory and infectious disorders. Sarcoidosis is a granulomatous disease in which the liver is the fourth most affected organ. Since epithelioid cell granulomas are not specific to sarcoidosis and since most patients with hepatic sarcoidosis are asymptomatic, valuable diagnostic biomarkers are needed to support the diagnosis of sarcoidosis. This study proposes to assess the diagnostic value of serum angiotensin converting enzyme (sACE) and lymphopenia in GH for sarcoidosis., Methods: We retrospectively analyzed the records of 90 patients referred to the internal medicine or hepatogastroenterology departments of the Lyon University Hospital (Lyon, France) between March 2002 and January 2020 in a context of GH., Results: In our tertiary center, 38 patients with sarcoidosis were identified among 73 patients with GH. Lymphopenia had a high specificity (85.7%), which increased when combined with elevated (97.0%). Interestingly, specificity increased in patients under 50 years old (100%)., Conclusions: Those results suggests that lymphopenia and sACE may be valuable biomarkers for sarcoidosis diagnosis in GH when combined, especially in younger patients.

Objectives: Mediation analyses were conducted to measure the extent to which musculoskeletal (MSK) flares and depression affected physical health through excessive fatigue., Methods: Mediation analyses were performed in a large multicentre cohort of SLE patients. Domains of the LupusQoL and SLEQOL questionnaires were selected as outcomes, MSK flares according to the SELENA-SLEDAI flare index (SFI-R) score and depression defined by Center for Epidemiologic Studies-Depression scale (CES-D) scale as exposures and different fatigue domains from MFI-20 and LupusQoL questionnaires as mediators. For each model, total, direct, indirect effects and proportion of effect mediated by fatigue (i.e. proportion of change in health-related quality of life) were determined., Results: Of the 336 patients, 94 (28%) had MSK flares at inclusion and 99 (29.5%) were considered with depression. The proportion of the total effect of MSK flares on physical health impairment explained by fatigue ranged from 59.6% to 78% using the LupusQOL 'Physical health' domain and from 51.1% to 73.7% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. The proportion of the total effect of depression on physical health impairment explained by fatigue ranged from 68.8% to 87.6% using the LupusQOL 'Physical health' domain and from 79.3% to 103.2% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected., Conclusions: The effect of MSK flares and depression on physical health impairment is largely mediated by fatigue. Thus, the patient's perception of disease activity as measured by physical health is largely influenced by fatigue. In addition, fatigue has a significant negative impact on quality of lifeof SLE patients with depression., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Declaration of interests PS declares competing interests with Abbvie and Chugai. LK declares competing interest with Abbvie, Novartis, Bayer, Roche, Alimera, Horus, and Thea. All other authors declare no competing interests.

Purpose: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids., Methods: We included 39 BSCR patients that were followed for ≥1 year. We analyzed their progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. In order to determine the efficiency of initial loading doses, patients were classified into two groups according to their initial treatment: methylprednisolone followed by prednisone (n = 28) and prednisone alone (n = 11)., Results: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day., Conclusions: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Aim: To report on the prevalence and clinical implications of positive QuantiFERON-TB (QFT) test results in the diagnostic evaluation of a cohort of consecutive sarcoid uveitis patients in France., Design: Retrospective cross-sectional study., Methods: This study included consecutive sarcoid uveitis patients who all underwent QFT testing., Results: A total of 234 patients were included in the study, among them 28 (12%) were QFT-positive. Previously treated tuberculosis (TB) was documented in 2 patients. QFT-positive patients were older (59 ± 16 years vs. 51 ± 18 years, p = .025) and more in proportion to suffer from chronic uveitis and panuveitis compared to QFT-negative patients. Moderate and severe visual impairment were significantly more frequent in the QFT-positive group (35.7% vs. 18.9%, p = .049 and 25.0% vs. 9.2%, p = .022, respectively)., Conclusion: The significant proportion of QFT-positive patients (12%) in this large series of sarcoid uveitis patients makes us suggest not to exclude the diagnosis of sarcoidosis in case of positive QFT in a low-endemic country for tuberculosis, and to manage these patients early by initiating without delay systemic steroids associated with latent tuberculosis therapy.

Recent years have seen the emergence and application of artificial intelligence (AI) in diagnostic decision support systems. There are approximately 80 etiologies that can underly uveitis, some very rare, and AI may lend itself to their detection. This synthesis of the literature selected articles that focused on the use of AI in determining the diagnosis, classification, and underlying etiology of uveitis. The AI-based systems demonstrated relatively good performance, with a classification accuracy of 93-99% and a sensitivity of at least 80% for identifying the two most probable etiologies underlying uveitis. However, there were limitations to the evidence. Firstly, most data were collected retrospectively with missing data. Secondly, ophthalmic, demographic, clinical, and ancillary tests were not reliably integrated into the algorithms' dataset. Thirdly, patient numbers were small, which is problematic when aiming to discriminate rare and complex diagnoses. In conclusion, the data indicate that AI has potential as a diagnostic decision support system, but clinical applicability is not yet established. Future studies and technologies need to incorporate more comprehensive clinical data and larger patient populations. In time, these should improve AI-based diagnostic tools and help clinicians diagnose, classify, and manage patients with uveitis.

Purpose: The study aims to describe the course and management of non-infectious uveitis during pregnancy and postpartum period in European populations., Methods: A retrospective observational study in two tertiary centers in France was performed. Pregnant patients during the follow-up of a non-infectious uveitis as well as those with new-onset uveitis were included. The medical records were analyzed with a systematic collection of the characteristics of the uveitis, the treatment and evolution of the uveitis, and the course of the pregnancy including obstetric complications., Results: Seventy-nine pregnancies in 59 women were included: 48 patients (68 pregnancies) were followed for uveitis and 11 had a new-onset uveitis diagnosis. Most patients had idiopathic uveitis (32.2%) or sarcoid uveitis (27.1%). Among the patients followed for uveitis at the time of conception, there were 18 relapses (26.5%) requiring treatment escalation. Relapses occurred mainly in the two first trimester (n = 12) or during the postpartum period (n = 5) and were significantly associated with an active uveitis at the time of conception (OR = 9.2, 95% CI [1.57-48.4], p = 0.01). The characteristics of the new-onset uveitis were similar to those already existing before pregnancy. Obstetric complications occurred in 25 pregnancies (31.6%), mainly gestational hypertension and gestational diabetes., Conclusion: The frequency of non-infectious uveitis relapses decreases as pregnancy progresses, in agreement with data from other non-European studies. However, multidisciplinary monitoring should be advised, especially to uncontrolled patients at the time of conception., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sarcoidosis is an inflammatory disease that involves the eyes in 10-55% of cases, sometimes without systemic involvement. All eye structures can be affected, but uveitis is the most common ocular manifestation and causes vision loss. The typical ophthalmological appearance of these uveitis is granulomatous (in cases with anterior involvement), which are usually bilateral and with synechiae. Posterior involvement includes vitritis, vasculitis and choroidal lesions. Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas. The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas. However, due to the technical difficulty and yield of biopsies, the diagnosis of ocular sarcoidosis is often based on clinico-radiological features. The international criteria for the diagnosis of ocular sarcoidosis have recently been revised. Corticosteroids remain the first-line treatment for sarcoidosis, but up to 30% of patients require high doses, justifying the use of corticosteroid-sparing treatments. In these cases, immunosuppressive treatments such as methotrexate may be introduced. More recent biotherapies such as anti-TNF are also very effective (as they are in other non-infectious uveitis etiologies).

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disorder. FMF is caused by mutations in the MEFV gene, encoding pyrin, an inflammasome sensor. The best characterized pathogenic mutations associated with FMF cluster in exon 10. Yet, mutations have been described along the whole MEFV coding sequence. Exon 10 encodes the B30.2 domain of the pyrin protein, but the function of this human-specific domain remains unclear. Pyrin is an inflammasome sensor detecting RhoA GTPase inhibition following exposure to bacterial toxins such as TcdA. Here, we demonstrate that the B30.2 domain is dispensable for pyrin inflammasome activation in response to this toxin. Deletion of the B30.2 domain mimics the most typical FMF-associated mutation and confers spontaneous inflammasome activation in response to pyrin dephosphorylation. Our results indicate that the B30.2 domain is a negative regulator of the pyrin inflammasome that acts independently from and downstream of pyrin dephosphorylation. In addition, we identify the central helical scaffold (CHS) domain of pyrin, which lies immediately upstream of the B30.2 domain as a second regulatory domain. Mutations affecting the CHS domain mimic pathogenic mutations in the B30.2 domain and render the pyrin inflammasome activation under the sole control of the dephosphorylation. In addition, specific mutations in the CHS domain strongly increase the cell susceptibility to steroid catabolites, recently described to activate pyrin, in both a cell line model and in monocytes from genotype-selected FMF patients. Taken together, our work reveals the existence of two distinct regulatory regions at the C-terminus of the pyrin protein, that act in a distinct manner to regulate positively or negatively inflammasome activation. Furthermore, our results indicate that different mutations in pyrin regulatory domains have different functional impacts on the pyrin inflammasome which could contribute to the diversity of pyrin-associated autoinflammatory diseases., (© 2023. The Author(s).)

Sarcoidosis is one of the leading causes of inflammatory eye disease. All ocular structures can be affected, but uveitis is the main manifestation responsible for vision loss in ocular sarcoidosis. Typical sarcoid anterior uveitis presents with mutton-fat keratic precipitates, iris nodules, and posterior synechiae. Posterior involvement includes vitritis, vasculitis, and choroidal lesions. Cystoid macular edema is the most important and sight-threatening consequence of sarcoid uveitis. Patients with clinically isolated uveitis at diagnosis rarely develop other organ involvement. Even though, ocular sarcoidosis can have a severe impact on visual prognosis, early diagnosis and a wider range of available therapies (including intravitreal implants) have lessened the functional impact of the disease, particularly in the last decade. Corticosteroids are the cornerstone of treatment for sarcoidosis, but up to 30% of patients achieve remission with requiring high-dose systemic steroids. In these cases, the use of steroid-sparing immunosuppressive therapy (such as methotrexate) is unavoidable. Among these immunosuppressive treatments, anti TNF-α drugs have been a revolution in the management of non-infectious uveitis., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome with an overall mortality rate of 40%. A multiple-cause-of-death analysis allows for the characterization of mortality and associated causes over an extended period. Death certificates, collected between 2000 and 2016 by the French Epidemiological Centre for the Medical Causes of Death (CepiDC, Inserm), containing the ICD10 codes for HLH (D76.1/2), were used to calculate HLH-related mortality rates and to compare them with the general population (observed/expected ratios, O/E). HLH was mentioned in 2072 death certificates as the underlying cause of death (UCD, n = 232) or as a non-underlying cause of death (NUCD, n = 1840). The mean age at death was 62.4 years. The age-standardized mortality rate was 1.93/million person-years and increased over the study period. When HLH was an NUCD, the most frequently associated UCDs were hematological diseases (42%), infections (39.4%), and solid tumors (10.4%). As compared to the general population, HLH decedents were more likely to have associated CMV infections or hematological diseases. The increase in mean age at death over the study period indicates progress in diagnostic and therapeutic management. This study suggests that the prognosis of HLH may be at least partially related to coexisting infections and hematological malignancies (either as causes of HLH or as complications).

Introduction: The definite diagnosis of neurosarcoidosis is challenging since it requires a compatible histology of the nervous system. When neurosarcoidosis is suspected, other systemic manifestations are investigated to confirm the diagnosis. A minor salivary gland biopsy (MSGB) is often performed since it is minimally invasive. The objective of the present study was to assess its performance for the diagnosis of neurosarcoidosis., Methods: A retrospective single-center study included patients who underwent a MSGB in a tertiary neurological university hospital (Lyon, France) between 2015 and 2018. Clinical presentations unlikely to be compatible with neurosarcoidosis were excluded. Positive cases of neurosarcoidosis were defined as definite, probable, and possible cases, according to the latest international neurosarcoidosis diagnostic criteria from the Neurosarcoidosis Consortium Consensus Group., Results: A total of 529 patients underwent a MSGB for clinical manifestations compatible with neurosarcoidosis. Among the 13 who fulfilled the criteria for neurosarcoidosis, only one had a positive MSGB. The sensitivity of MSGB was 7.7% (95% CI [0.2-36.0%]) and the specificity was 100.0% (95% CI [99.3-100%])., Conclusion: Considering the low sensitivity of MSGB for the diagnosis of NS, MSGB should be performed in selected indications, including a suspicion of spinal cord sarcoidosis, or when there is a strong clinical, laboratory, and radiological suspicion of NS. MSGB should rather not be performed when the chest CT-scan does not show signs of pulmonary or lymph node sarcoidosis., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Sarcoidosis is a systemic granulomatosis of unknown etiology, characterized by the presence of immune granulomas. Liver damage is a relatively common extra-pulmonary manifestation, occurring in 3.6-30% of cases. Some patients can develop symptomatic portal hypertension (PH). Few series have evaluated the prognosis of symptomatic PH as well as the efficacy and safety of specific treatment on this complication., Methods: This is a multicenter retrospective study of cases of histologically proven hepatic sarcoidosis with symptomatic PH (ascites, digestive hemorrhage) and/or hepatic encephalopathy. Demographic characteristics, comorbidities, clinical manifestations of sarcoidosis, biological data, imaging study of the liver, treatment, and clinical outcomes were collected., Results: Twelve patients were identified, with a mean follow-up of 140 months. The M/F ratio was 1 and Caucasian origin was the most represented (75%). Seven patients presented with hepatic comorbidities: metabolic syndrome, chronic alcoholism or chronic viral hepatitis. Apart from hepatic involvement, mediastino-pulmonary involvement was the most common followed by osteoarticular and skin. Liver damage was inaugural in two thirds of cases. Nine patients developed ascites, six presented esophageal varices complicated by gastrointestinal bleeding. Three patients presented with both ascites and variceal bleeding. One case of hepatic encephalopathy was observed. Five patients presented signs of hepatocellular insufficiency during follow-up, of whom three had hepatic comorbidities. Eight out of 12 patients required second-line treatment after failure of corticosteroids, three patients underwent ligation of esophageal varices but with recurrent digestive bleeding in all cases. Two patients benefited from a transjugular intrahepatic portosystemic shunt (TIPS), also with poor result. At the end of follow-up, five patients were alive and seven patients died. Two patients received a liver transplant, with good result and without recurrence of sarcoidosis on the transplant thereafter. Two patients had quiet sarcoidosis on low dose of corticosteroids and one patient was lost to follow-up., Conclusion: Symptomatic PH related to hepatic sarcoidosis is a severe complication, with high morbidity and mortality, and frequent failure of specific treatments of PH. Early management of these patients, with detection of hepatic comorbidities seems important. In case of therapeutic failure, liver transplantation is an option to consider., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fauter, Rossi, Drissi-Bakhkhat, Latournerie, Gerfaud-Valentin, Durieu, Jamilloux, Bailly, Mahevas and Sève.)

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.

Acute Parvovirus B19 (PVB19) infection is responsible for erythema infectiosum in children and non-specific polyarthralgias in immunocompetent adults associated with skin lesions and rarer manifestations (hepatic, neurological, cardiac or nephrological). In immunocompromised patients, cytopenias are more frequent and in some cases, viremia persists and is responsible for PVB19 chronic infection. PVB19 is responsible for pure red cell aplasia during chronic hemolytic diseases. Acute PVB19 infection is a differential diagnosis of some autoimmune diseases and has been suspected to be a trigger for some autoimmune diseases because of its ability to promote the emergence of autoimmune markers. Mechanisms of molecular mimicry, induction of apoptosis and activation of enzymes have been demonstrated, explaining in part the production of autoantibodies during infection. However, the demonstration of a causal relationship in the triggering of autoimmune disease remains to be done. This review provides a synthesis of the PVB19 infection clinical data in adults with a particular focus on these links with autoimmunity., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this study was to compare primary versus secondary forms of multiple evanescent white dot syndrome (MEWDS) at T0 (baseline) and T1 (1-4 months after the onset of symptoms)., Methods: A total of 101 eyes in 100 patients were included in a multicentric retrospective study., Results: Secondary MEWDS was defined as MEWDS associated with underlying chorioretinal inflammatory pathologies, mainly multifocal choroiditis and punctuate inner choroidopathy. Patients with secondary MEWDS were older (P = 0.011). The proportion of women (P = 0.8), spherical equivalent (P = 0.3), and best-corrected visual acuity at T0 (P = 0.2) were not significantly different between the two groups. The area of MEWDS lesions on late-phase indocyanine green angiography was significantly smaller in secondary MEWDS (P = 0.001) and less symmetrical with respect to both horizontal (P = 0.003) and vertical (P = 0.004) axis. At T0, neither the clinical (P = 0.5) nor the multimodal imaging (P = 0.2) inflammation scores were significantly different between the groups. At T1, the multimodal imaging inflammation score was higher in secondary MEWDS (P = 0.021)., Conclusion: In secondary MEWDS, outer retinal lesions are less extensive and located close to preexisting chorioretinal lesions. Mild signs of intraocular inflammation on multimodal imaging are more frequent in secondary MEWDS during recovery. These findings suggest that chorioretinal inflammation may trigger secondary MEWDS.

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.

Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by uncontrolled activation of immune cells and mediators. Two diagnostic tools are widely used in clinical practice: the HLH-2004 criteria and the Hscore. Despite their good diagnostic performance, these scores were constructed after a selection of variables based on expert consensus. We propose here a machine learning approach to build a classification model for HLH in a cohort of patients selected by glycosylated ferritin dosage in our tertiary center in Lyon, France. On a dataset of 207 adult patients with 26 variables, our model showed good overall diagnostic performances with a sensitivity of 71.4% and high specificity, and positive and negative predictive values which were 100%, 100%, and 96.9%, respectively. Although generalization is difficult on a selected population, this is the first study to date to provide a machine-learning model for HLH detection. Further studies will be required to improve the machine learning model performances with a large number of HLH cases and with appropriate controls.

The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defenses against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identifies etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step 2 activators. High concentrations of these metabolites fully and rapidly activate pyrin, in a human specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) and familial Mediterranean fever (FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, display increased responses to these metabolites. This study identifies an unconventional pyrin activation mechanism, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and explains the "steroid fever" described in the late 1950s upon steroid injection in humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify multidimensional phenotypes of sarcoid uveitis patients., Design: Retrospective cohort., Methods: Consecutive patients with biopsy-proven, presumed, or probable sarcoid uveitis between December 2003 and December 2020 in Lyon were recruited. Data were collected from the clinical notes, and consisted in laboratory and imaging findings, systemic treatments and outcome. Systemic sarcoidosis was diagnosed according to the Abad's modified criteria and uveitis was classified according to the Standardization of Uveitis Nomenclature. A hierarchical cluster analysis was performed. The main outcome measure was identification of different phenotypes of sarcoid uveitis patients., Results: A total of 299 patients were included. Three clusters were identified: (1) younger non-Caucasian patients who presented acute (75.3%), anterior (55.6%) uveitis, and systemic manifestations (87.8%), requiring oral corticosteroids (75.3%) along with immunosuppressive therapy (17.2%) and who were more prone to experience complete visual recovery (84.1%); (2) middle-aged Caucasian patients who presented chronic (91.7%), panuveitis (79.5%), and isolated uveitis at diagnosis (74.8%), requiring systemic treatment with corticosteroids (74.0%) but less frequently immunosuppressive therapy (9.8%) and a worse prognosis (45.3% complete visual recovery); and (3) middle-aged Caucasian patients, without preferential chronic or acute uveitis, isolated uveitis at diagnosis (81.4%), more homogenous in terms of eye involvement repartition, requiring less corticosteroids or immunosuppressive therapy (respectively 54.1% and 13.1%) and having a prognosis close to cluster 2 patients (55.3% complete visual recovery)., Conclusions: This retrospective study suggested the existence of several phenotypes of sarcoid uveitis patients with different progressions and prognoses. Further studies are needed to determine the genetic and environmental factors that could explain these results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening cytokine storm syndrome. There are no definitive guidelines for the management of secondary HLH (sHLH). A recent report by a National Health Service (NHS) clinical panel has recommended anakinra as a treatment option. We aimed to analyse the efficacy and safety of anakinra for the treatment of all-cause sHLH. We conducted a multicentric retrospective study in two French University hospitals and included all patients who had a diagnosis of sHLH and who received anakinra. Among 21 patients (median age, 45 years), 13 were men. Anakinra was used as first-line therapy in 10 patients, and as monotherapy in 5 patients. We found that anakinra was effective in 19/21 patients (90.5%), with fever resolution in 19 patients (90.5%) within a median of 1.0 day (1, 2). At the Day 7 assessment, the mean CRP concentration decreased significantly (p < 0.001), as did the mean ferritin (p = 0.011). Anakinra was generally safe and well tolerated and was discontinued for side effects in only three patients (14.3%). Anakinra is an efficient and safe treatment to control sHLH of various causes. These data, together with the recent report of the NHS panel, call for the rapid conduct of prospective randomized clinical trials.

The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.

Objectives: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE., Methods: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2., Results: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment., Conclusion: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Glycosylated ferritin (GF) has been reported as a good diagnostic biomarker for adult-onset Still’s disease (AOSD), but only a few studies have validated its performance. We performed a retrospective study of all adult patients with at least one GF measurement over a 2-year period in one hospital laboratory. The diagnosis of AOSD was based on the expert opinion of the treating physician and validated by two independent investigators. Patients’ characteristics, disease activity, and outcome were recorded and compared. Twenty-eight AOSD and 203 controls were identified. Compared to controls, the mean GF was significantly lower (22.3% vs. 39.3, p < 0.001) in AOSD patients. GF had a high diagnostic accuracy for AOSD, independent of disease activity or total serum ferritin (AUC: 0.674 to 0.915). The GF optimal cut-off value for AOSD diagnosis was 16%, yielding a specificity of 89% and a sensitivity of 63%. We propose a modified diagnostic score for AOSD, based on Fautrel’s criteria but with a GF threshold of 16% that provides greater specificity and increases the positive predictive value by nearly 5 points. GF is useful for ruling out differential diagnoses and as an appropriate classification criterion for use in AOSD clinical trials.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi-Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

Objectives: The clinical value of cryoglobulinemia (CG) in systemic lupus erythematosus (SLE) is largely unknown. The aim of this retrospective study was to describe the characteristics of CG in SLE, its impact on SLE phenotype, and the features associated with cryoglobulinemic vasculitis (CryoVas) in SLE patients., Methods: This retrospective study conducted in a French university hospital reviewed the data from 213 SLE patients having been screened for CG between January 2013 and December 2017. SLE patients positive for CG were compared to SLE patients without CG. Patients were classified as CryoVas using the criteria of De Vita et al. RESULTS: Of the 213 SLE patients included (mean age 29.2 years, female sex 85%), 142 (66%) had at least one positive CG in their history, 67% of them having a persistent CG at follow-up. CG was type III in 114 (80%) cases and type II in 27 (19%) cases. The mean concentration of the cryoprecipitate was 40mg/L (range 0-228). Patients with CG had significantly more C4 consumption. Among patients with CG, 21 (15%) developed a CryoVas. The clinical manifestations of patients with CryoVas were mainly cutaneous (purpura, ulcers, digital ischemia) and articular, without any death at follow-up. Severe manifestations of CG included glomerulonephritis in 1/21 (5%) patients and central nervous system involvement in 4/21 (19%) patients. A response to first-line treatments was observed in 12/13 (92%) patients, but relapses were observed for 3 of them., Conclusion: CG is frequent in SLE, but mostly asymptomatic. CryoVas features involve mostly joints, skin, and general symptoms. CryoVas in SLE appears to be a specific condition, with a low prevalence of neuropathy, membranoproliferative glomerulonephritis, and severe manifestations., (© 2022. The Author(s).)

Sarcoidosis can develop into a chronic disease in about 30% of cases. When general treatment is indicated, corticosteroids are the first-line treatment. More than one third of patients treated with corticosteroids receive a steroid-sparing agent. Although methotrexate is the most commonly used sparing agent, synthetic antimalarials have been used for more than fifty years on the basis of small, randomised, therapeutic trials. Despite this low level of evidence, chloroquine or more often hydroxychloroquine are used in daily practice, particularly to treat skin, bone and joint sarcoidosis, as well as hypercalcemia and certain types of uveitis. This review summarises the state of knowledge on steroid-sparing therapy in sarcoidosis, particularly in its extra-pulmonary form. These data support the need for good quality therapeutic trials to validate the use of hydroxychloroquine in this specific indication., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)