Romain Paule

Stratifying the risk of death in systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution computed tomography (HRCT) is often assessed by a visual semi-quantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning based algorithm allowing for automated quantification of ILD on HRCT in patients with SSc. We correlated the extent of ILD with the occurrence of death during follow-up and evaluated the additional value of ILD extent to predict death based on a prognostic model including well-known risk factors in SSc. We included 318 patients with SSc among which 196 had ILD; median follow-up was 94 months (interquartile range 73–111). Mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased 4% (hazard ratio 1.04, 95%CI 1.01–1.07, p = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival (p = 0.007) but its discrimination only marginally. However, it improved the ability to predict 2-year mortality (difference in time-dependent AUC 0.043, 95%CI 0.002–0.084, p = 0.040). The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.

Objective: To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy. Methods: We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment. Results: We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone. Conclusion: In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.

Objective: APS is a heterogeneous disease with different phenotypes. Using an unsupervised hierarchical cluster analysis, we aimed to determine distinct homogeneous phenotypes among APS patients. Methods: We performed an observational, retrospective study of APS patients enrolled in the French multicentre ‘APS and SLE’ registry who met the Sydney classification criteria. The clustering process involved an unsupervised multiple correspondence analysis followed by a hierarchical ascendant clustering analysis; it used 27 variables selected to cover a broad range of APS clinical and laboratory manifestations. Results: These analyses included 509 patients, mainly women (77.8%). Mean (s.d.) age at APS diagnosis was 36.2 (14.6) years, and mean follow-up since diagnosis 10.3 (8.5) years. This hierarchical classification cluster analysis yielded four homogeneous groups of patients: cluster 1, mostly with venous thromboembolism without any associated autoimmune disease; cluster 2, older, lowest proportion of women, history of arterial events, and/or with migraines, arterial hypertension, diabetes mellitus, or dyslipidaemia; cluster 3, younger, highest proportion of women, associated SLE or other autoimmune diseases, and a history of venous thromboembolism or pregnancy morbidity; and cluster 4, mainly with a history of catastrophic antiphospholipid syndrome, aPL-associated nephropathy, and pregnancy morbidity, with frequent triple positivity and more deaths (16.7%). Conclusions: Our study applied an unsupervised clustering method to distinguish four homogeneous APS patient subgroups that were predominantly venous; arterial; associated with SLE or another autoimmune disease; and arterial microthrombotic. Heterogeneous pathophysiological mechanisms may explain these findings.

Purpose: Uveitis can be associated with meningitis (uveomeningitis) and the inflammation shared with the central nervous system. We aimed to describe the characteristics and outcome of uveomeningitis. Methods: We retrospectively analyzed 110 consecutive adult patients with uveomeningitis. Results: The main causes of uveomeningitis were Vogt–Koyanagi–Harada (31%), syphilis (16%), sarcoidosis (12%), Behçet’s disease (7%), and multiple sclerosis (5%). Sixteen percent of uveomeningitis remained of undetermined origin. Compared to etiology-matched uveitis without meningitis, patients with uveomeningitis were younger, had more frequent neurological manifestations, and had more frequent abnormal cerebral magnetic resonance imaging findings. In contrast, no ocular feature upon examination was significantly associated with the presence of meningitis. Patients with uveomeningitis were more frequently treated with immunosuppressants but uveitis relapse and systemic complications did not differ between groups. Conclusion: Uveomeningitis is associated with a limited spectrum of diseases. Meningitis does not seem to impact ocular and extraocular outcomes. Therefore, lumbar puncture should be performed on an individual basis during the diagnostic workup of uveitis.

In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term - yet promising - experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the “cytokine storm”, prevent ICU admission and the requirement for mechanical ventilation. Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU.

Background: This study aimed to assess the diagnostic relevance of CD4/CD8 ratio in cerebrospinal fluid (CSF) for the etiological diagnosis work-up of uveitis. Methods: We consecutively included patients who were referred to our department for the diagnostic workup of intermediate and/or posterior uveitis. Etiological diagnoses were established in a blind manner regarding CD4/CD8 ratio. Results: Fifty-two patients were included. A diagnosis of ocular sarcoidosis was made in 15 (29%) patients, 21% had another determined diagnosis while 50% remained of undetermined origin. Median CD4/CD8 ratio in CSF was 4.57 (IQR 3.39–5.47) in ocular sarcoidosis, 1.74 (1.60–3.18) in uveitis due to other determined cause (P = .008), and 2.83 (2.34–3.54) in those with uveitis of undetermined origin (P = .007). CD4/CD8 ratio >3.23 was associated with a diagnosis of ocular sarcoidosis. Conclusion: Determination of CD4/CD8 ratio in CSF can be useful for diagnosis work-up since a CD4/CD8 ratio >3.23 in CSF is associated with ocular sarcoidosis.