Malignant catatonia due to anti-NMDA-receptor encephalitis in a 17-year-old girl: case report

Anti-NMDA-Receptor encephalitis is a severe form of encephalitis that was recently identified in the context of acute neuropsychiatric presentation. Here, we describe the case of a 17-year-old girl referred for an acute mania with psychotic features and a clinical picture deteriorated to a catatonic state. Positive diagnosis of anti-NMDA-receptor encephalitis suggested specific treatment. She improved after plasma exchange and immunosuppressive therapy. Post-cognitive sequelae (memory impairment) disappeared within 2-year follow-up and intensive cognitive rehabilitation

Annual direct medical cost of active systemic lupus erythematosus in five European countries.

OBJECTIVES: To evaluate the annual direct medical cost of managing adult systemic lupus erythematosus (SLE) patients with active autoantibody positive disease in Europe. METHODS: A 2-year, retrospective, multicentre, observational study was conducted in five countries (France, Germany, Italy, Spain and the UK). Data included patients' characteristics, disease activity and severity, flare assessments and health resource use (eg, laboratory tests, medications, specialist visits and hospitalisations). Costs were assessed from the public payers' perspective. Cost predictors were estimated by multivariate regression models. RESULTS: Thirty-one centres enrolled 427 consecutive eligible patients stratified equally by disease severity. At baseline, mean (SD) age was 44.5 (13.8) years, 90.5% were women and mean (SD) SLE duration was 10.7 (8.0) years. The SELENA-SLEDAI (11.2 vs 5.3) and SLICC/ACR index (1.0 vs 0.7) scores were higher in severe patients. Over the study period, patients experienced on average 1.02 (0.71) flares/year. The mean annual direct medical cost was higher in severe compared to non-severe patients ( 4748 vs 2650, p<0.001). Medication costs were 2518 in severe versus 1251 in non-severe patients (p<0.001). Medications represented 53% and 47% of the total cost for severe and non-severe patients, respectively, primarily due to immunosuppressants and biologics. Flares, especially severe flares, were identified as the major cost predictor, with each flare increasing the annual total cost by about 1002 (p<0.001). CONCLUSIONS: The annual direct medical cost of SLE patients in Europe is related to disease severity and flares. Medical treatments were the main cost drivers. Severe flares and major organ involvement were identified as important cost predictors

Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus

Objectives To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). Methods Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. Results A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. Conclusion Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability

Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse

International audienceObjectives Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.Methods A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.Results Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.Conclusion Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse

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Letter to the Editor gomery-Asberg Depression Rating Scale, the Brief Psychiatric Rating Scale and the SLE Disease Activity Index (SLEDAI) During the course of the study, 5 patients were admitted with SLE and catatonia. These 5 patients, all female, met the inclusion criteria. All of them (or their families on their behalf) agreed to PE. Three of the patients were teenagers who had been hospitalized for several weeks without any improvement, receiving a treatment regimen combining psychotropic medications, corticoids and immunosuppressors. Three patients exhibited life-threatening complications: 2 were severely malnourished and the third had a pulmonary infection and skin lesions due to immobility. One patient showed a severe renal involvement. The last patient was included because of resistance after 3 weeks of treatment. The mean number of PE that patients received was 7.2 (range: 3-11). We found a significant improvement for all clinical variables. Mean CRS and SLEDAI scores before PE were 15 (range: 11-16) and 18.8 (range: 12-22), respectively. Both scores dramatically decreased after PE to a mean of 1.2 (range: 0-6) and 3.4 (range: 0-12), respectively (Wilcoxon paired test: Z = -2.032, p = 0.042). In particular, 3 patients very much improved on the Clinical Global Impression Scale after the first week of PE. The biological variables paralleled clinical improvement. At follow-up, 4 patients were still doing well; in particular, all the teenagers were able to return to school with minimal treatment for SLE. The last patient (case 4) died in her local hospital as a consequence of a septic shock 3 months after discharge. To date, only a few case studies have reported the possible use of PE in neuropsychiatric SLE The consecutive patients were recruited at Pitié-Salpêtrière Hospital from 2001 to 2004. For inclusion, the diagnosis of SLE was based on the revised criteria of the American College of Rheumatolog

Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients

Immunopathogenesis of Erdheim-Chester disease (ECD), a rare non-Langerhan

Identification of natural killer markers associated with fatal outcome in COVID-19 patients

IntroductionIncreasing evidence has shown that coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunological response. Previous studies have demonstrated that natural killer (NK) cell dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of NK cell markers as a driver of death in the most critically ill patients.MethodsWe enrolled 50 non-vaccinated hospitalized patients infected with the initial virus or the alpha variant of SARS-CoV-2 with moderate or severe illness, to evaluate phenotypic and functional features of NK cells.ResultsHere, we show that, consistent with previous studies, evolution NK cells from COVID-19 patients are more activated, with the decreased activation of natural cytotoxicity receptors and impaired cytotoxicity and IFN-γ production, in association with disease regardless of the SARS-CoV-2 strain. Fatality was observed in 6 of 17 patients with severe disease; NK cells from all of these patients displayed a peculiar phenotype of an activated memory-like phenotype associated with massive TNF-α production.DiscussionThese data suggest that fatal COVID-19 infection is driven by an uncoordinated inflammatory response in part mediated by a specific subset of activated NK cells