Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Impairment of quality of life in patients with antiphospholipid syndrome.

OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). CONCLUSION: Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient's perspective and to provide patients with the support they need.

Screening of human papillomavirus infection in women with systemic sclerosis.

OBJECTIVES: High risk human papilloma-viruses (HR HPV) are associated with risk of cervical dysplasia and carcinoma. The risk is increased in patients with immune deficiency or auto-immune disease as systemic lupus erythematosus. Currently, no data are available about the human papillomavirus status in women with systemic sclerosis (SSc). METHODS: Thirty-one women with SSc were evaluated for cervical HPV infection and dysplasia, and compared to fifty age-matched control. Cervical swabs were tested by the INNO-LiPA assay®. Serum antibodies against HPV 16 and 18 were assessed using enzyme-linked immunosorbent assay in the SSc group. RESULTS: The overall HPV frequency was comparable between SSc and controls (32% vs. 38%), as well as the HR HPV frequency (28% vs. 34%), but infection by ≥2 HPV was two times more frequent in the SSc group (50% vs. 26% of the HPV positive samples). The most prevalent genotype was 52 in the SSc group (12%), and 52/53 in the control group (8% for both). Pap smears were within the normal range. Seropositivity for HPV 16 and 18 was 13% and 6.5%, respectively. A diffuse systemic sclerosis and a younger age at first intercourse were more frequent in cases of overall HPV positivity. Current smoking and a higher number of sexual partners were only observed in cases of seropositivity. CONCLUSIONS: This is the first study to evaluate HPV status in women with SSc. HR HPV52 was the most common genotype with a greater multi-HPV infection rate. This result needs to be confirmed in a larger study.

Electrostatic wipes as simple and reliable methods for influenza virus airborne detection.

The performance of an in-house protocol for virus detection on commercialized electrostatic wipes (EWs) was assessed experimentally by impregnating them with suspensions of cytomegalovirus, adenovirus, and influenza virus, and by determining the recovery efficiency, repeatability, and detection limit of the protocol. The protocol was sensitive enough to detect 4 log10 gene copies of virus. At room temperature, influenza RNA was stable on EWs for at least four days. When EWs were placed high in 32 influenza-infected patients' rooms, influenza RNA was detectable in 75% (N = 24) of EWs, suggesting that EWs are simple and reliable methods for influenza virus airborne detection.

[Kappa light chain deposition disease, presenting as Sjögren's syndrome, successfully treated by high-dose melphalan and autologous blood stem transplantation]. / Maladie de Randall, simulant une maladie de Gougerot-Sjögren, traitée avec succès par chimiothérapie et autogreffe de moelle osseuse.

INTRODUCTION: Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy. CASE REPORT: We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation. CONCLUSION: Light chain deposition disease should be recognized as an aetiology of sicca syndrome and peripheral neuropathy. Further studies should assess the prevalence of sicca syndrome in light chain deposition disease and better characterise the neurological manifestations.

[Eosinopenia in 2018]. / L'éosinopénie en 2018.

Since 1893, eosinopenia is a biological test to help a diagnosis of bacterial infection. Several publications have confirmed this hypothesis, particularly in the intensive care, pneumology and pediatric units. The value of this marker has been identified in vascular cerebral diseases and coronary bypass. Its contribution seems as relevant as procalcitonin, without extra cost. The diagnostic performance of this test was reinforced by a composite score (CIBLE score) that may improve its value in daily routine. Finally, monitoring eosinopenia appears to be a reliable mortality marker.

Incidence of amyloidosis over 3 years: the AMYPRO study.

OBJECTIVES: There is a lack of epidemiological information concerning amyloidosis, particularly in France. We started a 3-year prospective study (AMPYRO) to analyze the epidemiological features of amyloidosis in the eastern part of France. METHODS: From 2003 to 2005, all patients with a tissue sample showing amyloid deposits, were included in this study. Immunohistochemistry using anti-P component, anti-SAA, anti-light chains immunoglobulins and anti-transthyretin was applied for each tissue sample. For each patient, past and present medical histories along with biological features were recorded. RESULTS: Seventy-six patients with amyloid were identified over 3 years. The age-standardized incidence rate of amyloidosis was estimated at 14 cases per million person-years. The final entire population included in the AMYPRO study was composed of 66 patients with a mean age of 71.7+/-11.5 years old. The amyloid typing after clinical, biological and immunohistochemistry revealed senile amyloid in 40 cases (60.6%), AL amyloid in 13 (19.7%) and AA amyloid in 9 (13.6%). Neither clinical nor biological features differed significantly between the transthyretin-positive and transthyretin-negative populations. CONCLUSION: Regarding only tissue samples, senile amyloid was the most prominent amyloid type identified. Therefore, the clinician needs to be aware that in most of the amyloid cases identified on the pathologic examination there is no need for additional examination unless there are clinical or biological signs of a primary or secondary amyloidosis.

[Usefulness of antineutrophil cytoplamic antibodies in giant cell arteritis]. / Valeur des anticorps anticytoplasme des polynucléaires neutrophiles dans la maladie de Horton.

PURPOSE: The relevance of antineutrophil cytoplasmic antibody (ANCA) during giant cell arteritis is not established. The purpose of our study was to estimate the ANCA frequency and their impact on disease course of giant cell arteritis. METHODS: Thirty patients were followed-up for giant cell arteritis and had a detection of ANCA. RESULTS: Nine patient had positive ANCA (30%). These patients had no significant differences regarding clinical and biological data or number of relapses in comparison with patients having negative ANCA testing. However, the relapse occurred earlier in the presence of ANCA (six months versus 31.5 months). CONCLUSION: In giant cell arteritis, detection of ANCA seems predictive of a premature relapse and should be associated with an acute monitoring of ANCA positive patients.

[A predictive bacterial infection score according to eosinophil level: An observational study]. / Proposition d'un score prédictif d'infection bactérienne selon le taux d'éosinophiles : étude observationnelle.

INTRODUCTION: Several studies have shown that eosinopenia less than 0.04g/L is a marker of bacterial infection in the presence of unexplained inflammatory syndrome. The aim of our study was to test this hypothesis and to propose a predictive score for bacterial infection (score CIBLE, C reactive protein, bacterial infections, levels of leucocytes and eosinophils). PATIENTS AND METHODS: This was a single-center observational study of patients admitted to an internal medicine department in the year 2015 and presenting with an inflammatory biological syndrome. Patients were divided into 2 groups: bacterial infections (group 1) and nonbacterial inflammatory diseases (group 2). RESULTS: One hundred and ninety patients were included: 92 men (48.4 %) and 98 women (51.6 %). Mean age was 73.5±18.2 years [19-104]. Group 1 consisted of 124 patients (65.2 %) and group 2 of 66 patients (34.8 %). ROC analysis confirmed a cut-off level for eosinophils count at 0.04g/L as discriminant to predict bacterial infection. In a multivariate analysis, the eosinophil/neutrophil ratio, a history of COPD, the C reactive protein concentration, patient age and initial temperature were the most significant variables. They were used to build the CIBLE score. For a score higher than or equal to 87, the probability of a bacterial infection is at least 70 %. CONCLUSION: The CIBLE score appears to be a relevant and inexpensive tool to establish a probability for bacterial infection.

[Transthyretin amyloidoses]. / Les amyloses à transthyrétine.

PURPOSE: Transthyretin amyloidoses are the most common form of amyloidosis. Two different types of transthyretin amyloidoses are described, one is rare, familial, its precursor is the mutated transthyretin, this type is called transthyretin amyloid, the other is more common, its precursor is wild transthyretin, this second type is called senile amyloid. The review describes the molecular, clinical and evolutives features of both types. CURRENT KNOWLEDGE AND KEY POINTS: Transthyretin is a naturally beta-pleated protein. Reported mutations increase its proteolysis resistance and its ability to form amyloid deposits. While transthyretin amyloid is clinically aggressive (neuropathy, cardiomyopathy, nephropathy, and vitreous deposits), senile amyloid is slightly symptomatic (rarely congestive heart failure). The differential diagnosis is essentially based on molecular biology. FUTURE PROSPECTS AND PROJECTS: Liver transplantation is an effective treatment of transthyretin amyloid because it switches the mutated protein synthesis to the wild protein synthesis. Liver transplantation is sometimes associated with cardiac or kidney transplantation depending of the clinical presentation. Concerning a specific treatment, P component analogous are developed for inhibiting amyloid deposits formation. Tetrameric transthyretin structure stabilisators are in development.

[Pseudo-myasthenic myopathy in a woman with anorexia nervosa]. / Pseudomyasthénie grave chez une anorexique.

Skeletal myopathy, although foreseeable in severe malnutrition, has been rarely reported in patients with anorexia nervosa. We report a case of oculo-oropharyngeal myopathy mimicking myasthenia in a 42-year-old woman with an history of anorexia nervosa, completely reversible after refeeding with carbohydrate diet, mainly chocolate. Nutritional myopathies are not well known and therefore rarely looked for in patients with anorexia nervosa. Classical presentation is a myogenic syndrome with severe type 2 fibre atrophy and biochemical characteristics similar to Mac Ardle's disease. A clinical form mimicking myasthenia gravis has never been reported. Refeeding programme leads to total recovery within a few days.

[Amyloidosis: Up-to-date]. / Actualités sur les amyloses.

Amyloidosis is mainly a systemic disease belonging to protein-folding diseases. The past 10 years have shown significant progress in typing and the clinical management of amyloidosis, in the identification of novel prognostic markers for risk-stratification, and also in the development of new therapeutic agents. Biological molecular techniques are now able to type amyloidosis which were unidentified. Cardiac MRI and biomarkers allow a precise risk-stratification, especially in AL amyloidosis. If necessary, this prognostic evaluation may lead to rapid changes in the chemotherapy treatment. Emerging treatments rely on biotherapies, gene therapy, immunotherapy and blocking analogous agents. They give hope about an increase of survival of patients with systemic amyloidosis.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Clinical features of pulmonary embolism in elderly: a comparative study of 64 patients]. / Particularités cliniques de l'embolie pulmonaire chez la personne âgée : étude comparative de 64 patients.

PURPOSE: To date only a few studies regarding pulmonary embolism (PE) in elderly have been published. The aim of this study was to determine the clinical features of PE in elderly patients (≥ 75 years). METHODS: All patients hospitalized for PE in our internal medicine department from January 2005 to December 2010 were included in the study. The aim was to compare the features of PE in elderly patients (≥ 75 years) to those of patients younger than 75 years. The following data were recorded: past medical history, risk factors for venous thrombo-embolism (VTE), clinical features, and PE etiologies. RESULTS: The population was composed of 64 patients (women 56%) with a median age of 82 years (IQR: 13.5). There was no statistical difference for risk factors of VTE. Syncope was more frequent in elderly patients (33% versus 7%, P=0.04) whereas thoracic pain predominated in younger patients (36,5% versus 7%, P=0.005). Chronic obstructive pulmonary disease was more frequent in the past medical history of elderly patients. The diagnostic of PE was less suspected in elderly patients (47% versus 72%, P=0.035). The etiologies were similar between the two groups. CONCLUSION: Our study highlights the frequency of syncope as the presenting feature of PE in elderly, whereas thoracic pain is uncommon. We confirmed the difficulty to diagnose PE in elderly population.

[Guidelines for the probabilistic treatment of community-acquired pneumonia: compared experience between internal medicine and emergency departments in the University Hospital of Besançon, France]. / Application des référentiels concernant la prise en charge probabiliste des pneumopathies communautaires non sévères: expérience comparée du service de médecine interne et du service des urgences adultes du CHU de Besançon.

INTRODUCTION: The objective of this study was to assess the application of local and national recommendations in the management of community-acquired pneumonia in an internal medicine department with an antibiotic referent physician and in an emergency department. PATIENTS AND METHODS: This was a retrospective single-center study including patients admitted with community-acquired pneumonia in the internal medicine department of the University Hospital of Besançon after an initial admission in the emergency department. RESULTS: One hundred patients (58 women and 42 men) were included. The mean age was 79 ± 11 years. The prescriptions done in the emergency department were in accordance with local recommendations or Société de pathologie infectieuse de langue française (SPILF) recommendations in 62% of cases. The prescriptions followed the recommendations in 94% of cases in internal medicine department (P<0.05). The lack of initial antibiotic treatment had no influence on morbidity and mortality. CONCLUSION: The guidelines for infectious diseases treatment were significantly more often applied in a department where a referent physician was designated for this.

[Contribution of cerebral magnetic resonance imaging to etiological investigation of uveitis]. / Place de l'imagerie par résonance magnétique cérébrale dans le bilan étiologique des uvéites.

PURPOSE: Uveitis is a disorder for which etiologic assessment procedures are still not codified. Clinical presentation is heterogenous, with poor correlation between symptoms and neurological involvement. The aim of our study was to assess the contribution of cerebral magnetic resonance imaging (MRI) in the management of uveitis. METHODS: Seventy-one patients, 26 men and 45 women, were included between January 1st, 2000 and March 31st, 2008, in two groups "contributory MRI" and "not contributory MRI" according to diagnostic contribution of MRI. Clinical characteristics of uveitis, inflammatory, immunological and infectious biological features, and cerebral MRI were analyzed. RESULTS: A diagnostics was established in 38 (53.5%) patients. Five patients with multiple sclerosis and one case of Behçet's disease were diagnosed using cerebral MRI. CONCLUSION: This study points out cerebral MRI contribution as a second-line examination for the etiological diagnosis of uveitis especially in case of suspicion of multiple sclerosis or Behçet's disease.