Determination of four homogeneous subgroups of patients with antiphospholipid syndrome: a cluster analysis based on 509 cases.

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.

Six medico-psycho-social dimensions of a pedagogical model used to define clusters of patients with Sjögren's syndrome and intentionality to participate in a patient education programme.

OBJECTIVES: Sjögren's syndrome (SS) is an autoimmune disease with an impact on quality of life (QoL). The aim of patient education (PE) is to improve patients' QoL. The main objective of this study was to describe the medico-psycho-social characteristics defining the six spheres of an allosteric educational model in order to characterise clusters of patients with SS and intentionality for patients to participate in a programme of patient education. METHODS: A self-administered questionnaire was proposed to 408 patients with SS followed in the Department of Internal Medicine of the University Hospital of Lille, France with the aim of assessing the six spheres of the allosteric model: intentional, perceptual, affective, cognitive, infra-cognitive and meta-cognitive. Sub objectives were to determine factors that can influence intentionality to participate in a PE programme and to determine, using cluster analysis, similar characteristics of patients with SS. RESULTS: 127 patients (31%) agreed to participate and were included in the study; 96% were women and the median age was 51 years (±14.5). They mostly reported dry syndrome and fatigue, had a good knowledge of SS, and presented anxiety symptoms. They mainly had problem-centred coping strategies, internal locus of control and low self-esteem. SS had an impact on their social interactions. Considering intentionality to participate in a PE programme, the patients were significantly younger, had a shorter duration of the disease, more frequently had disabled status, reported more fatigue, more self-reported symptoms and a poorer QoL. Two clusters of patients could be individualised, with one group including 75 (59%) patients presenting a higher global impact of the disease, including a more severe impairment for the scores of the perceptual, emotional and infra-cognitive spheres, worse physical QoL, and a higher intentionality to participate in a PE programme. CONCLUSIONS: Our study described an SS population in terms of the different spheres of an allosteric model applicable to the practice of PE. A cluster of patients appeared to present more impact of the disease and more intentionality to participate in a programme of PE. There was no difference between the two groups in terms of the cognitive sphere (i.e. knowledge of the disease), thus indicating that motivation to participate in a PE programme is influenced by non-cognitive factors. Considering intentionality to participate in a PE programme, duration disease, age of the patient and QoL should be more considered to propose to patients to participate in a PE programme. Use of the allosteric model appears promising for future research in PE.

Dyslipidemia is insufficiently treated in antiphospholipid syndrome patients.

OBJECTIVES: Although dyslipidemia is a strong risk factor for thrombosis in antiphospholipid syndrome (APS), it has been poorly studied. This study aimed to assess lipids profile and risk factors for unachieved cholesterol levels in a real-life APS population. METHODS: Inclusion criteria were: APS diagnosis according to international classification criteria, referring to the out-patients clinic of our tertiary care center for their follow-up, and having a blood sample collection for lipids levels determination. Cholesterol level targets for each patient were defined according to 2019 ESC/EAS guidelines for the management of dyslipidemia. RESULTS: Between January 2020 and April 2021, 114 APS patients were included (male 37 (32.5%); mean age 49 ± 14 years). Among them, 40 (35.1%) had a history of dyslipidemia, 48 (42.1%) were under lipid-lowering therapies, and 59 (51.8%) had a history of cardiovascular disease (CVD). Mean levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride were, respectively, 110 ± 40 mg/dL, 60±20 mg/dL, and 120 (80-190) mg/dL. Unachieved LDL-C levels were found in 77 (67.5%) patients of whom 53 had history of CVD. Overall, 90 (78.9%) had protective HDL-C and 31 (27.2%) had hypertriglyceridemia. In the multivariate analysis, independent risk factors for unachieved LDL-C levels were older age and history of CVD; triple aPL negativity, defined as complete disappearance of aPL over time in APS patients who were previously positive in accordance to international criteria, was an independent protective factor for unachieved LDL-C. CONCLUSION: Our finding suggested that dyslipidemia is frequent in APS patients and mainly insufficiently treated, especially in patients with history of CVD, who are at highest risk of future CV events.

Neuralgic amyotrophy triggered by cytomegalovirus: to be aware of this clinical diagnosis.

Neuralgic amyotrophy (NA) is a multifocal inflammatory neuropathy. Although the exact etiopathogenesis of the latter is unknown, the literature reports frequent associations with immunological events such as different infectious diseases. Our case reveals a rarely described etiology of NA. NA is mainly a clinical diagnosis. The etiology shown in our case study is interesting for the scientific community, because CMV is an ubiquitous disease. NA is frequently under-recognized and misdiagnosed. This is particularly common in the early phase of the disease, when neurologic signs have not yet developed.

Consideration of coping strategies for patients suffering from systemic lupus erythematosus: reflection for a personalised practice of patient education.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune multi-organ disease with an unpredictable course. SLE causes functional disability, changes in body appearance, and psychological distress. When faced with SLE, patients have to implement coping strategies. Therefore, the aim of this study was to describe patients' coping strategies, consider the implications for a personalised practice of patient education and evaluate patients' adherence to HCQ treatment. METHODS: One hundred and fifty-eight SLE patients receiving hydroxychloroquine (HCQ) treatment entered a prospective, non-comparative, longitudinal study aimed at describing patients' coping strategies and evaluating their adherence to the HCQ regimen. Coping strategies were evaluated using an abbreviated French version of the WCC-27 exploring 3 dimensions of coping: problem-centered coping, emotion-centered coping and search for social support. Adherence was assessed by the MASRI, the MMAS-8 and also objectively assessed by the patient's serum level of HCQ. Data collected at study entry also included disease activity: SLEDAI, and disease extent: SLICC damage index. The prevalence of anxious and depressive symptoms was evaluated with the HADS. Quality of life was evaluated using the LupusQoL questionnaire. RESULTS: Patients were clustered using an unsupervised hierarchical classification based on coping strategies. Four clusters of patients were individualised. The cluster of patients with low problem-centered coping, high emotion-centered coping and the lowest search for social support had worse quality of life and more psychological distress. We did not find any inter-cluster differences in terms of compliance to HCQ. CONCLUSIONS: Patients' knowledge is not the only parameter to consider for a personalised educational therapy: psychological parameters such as coping must also be considered to ensure the best possible quality of life. For educational therapy purposes, it is important not to group patients with the same coping style; heterogenous groups will enable patients to share their experiences and learn from the coping strategies of others.

Styloidogenic compression of the internal jugular vein, a new venous entrapment syndrome?

Internal jugular vein (IJV) thrombosis is mainly related to central venous catheter, malignancy, and ovarian hyperstimulation syndrome. We report a case of IJV thrombosis possibly related to IJV compression between the styloid process and the first cervical vertebra (C1) transverse process. To support this hypothesis, we perform radiological assessment of the IJV and examine its relationship with the styloid process and C1 transverse process in 34 controls. Our results showed a strong correlation between IJV diameter and styloid process-C1 transverse process distance. Compared to control subjects, our patient had a short styloid process-C1 transverse process distance, which suggests its involvement in IJV thrombosis.

Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients.

OBJECTIVE: The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis. METHODS: First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients. Exclusion criteria were the presence of RF, the presence of ACPA and overlap with another CTD. RESULTS: In the single-centre study, polyarthritis was the first manifestation in 12 of 45 ASS patients (27%). An additional 28 patients were collected for the multicentre study, resulting in a total population of 40 ASS patients who presented with polyarthritis. The mean delay from polyarthritis onset to ASS diagnosis was 27 months (s.d. 40). Pulmonary and muscle symptoms were uncommon at ASS diagnosis (40% and 32.5%, respectively) and were dramatically delayed [mean delay after polyarthritis onset of 41 months (s.d. 53) and 21 months (s.d. 14), respectively]. Mechanic's hands and cutaneous signs of DM occurred in 25% and 22.5%, respectively, with a mean delay of 10 months (s.d. 10) and 31 months (s.d. 21), respectively. When present (32%), RP was the earliest non-articular manifestation [mean delay 3 months (s.d. 23) after polyarthritis onset]. On HEp-2 cells, antinuclear and/or cytoplasmic fluorescence was found in 70% of cases, with specificity for various anti-aminoacyl tRNA synthetase (anti-ARS) antibodies. CONCLUSION: ASS may be revealed by polyarthritis. To decrease the delay in diagnosis of ASS, pulmonary and muscle symptoms and anti-ARS antibodies might usefully be searched for in seronegative polyarthritis patients, especially in those with RP.

Perception of aesthetic impairment in patients with systemic sclerosis determined using a semi-quantitative scale and its association with disease characteristics.

Background: Systemic sclerosis is a fibrotic disease. Body image assessments could be key in optimizing care; however, data are scarce. The main objective was to assess the perception of aesthetic impairment using a visual aesthetic evaluation scale in patients with systemic sclerosis compared with healthy subjects. The secondary objectives were to assess associations between the perception of aesthetic impairment and scores on standardized questionnaires for aesthetic impairment as well as clinical, psychological/quality of life, and functional parameters of patients with systemic sclerosis. Methods: This study evaluated and compared the perception of aesthetic impairment in two populations: patients with systemic sclerosis from a referral center at Lille Hospital, France, and healthy controls. Results: This study included 88 patients (69 (78.4%) women) with a median age of 52 years and 88 controls (49 (55.7%) women) with a median age of 45 years. The perception of aesthetic impairment assessed using the aesthetic evaluation scale was poorer in systemic sclerosis patients than in controls (3.7 ± 0.3 vs 2.8 ± 0.3, p = 0.028) and was statistically correlated with assessments using the adapted satisfaction with appearance, a specific aesthetic impact assessment questionnaire for patients with systemic sclerosis. Patients with anxiety or depressive symptoms had significantly higher aesthetic evaluation scale scores. Systemic sclerosis patients with facial involvement and pitting scars had a worse perception of aesthetic impairment. Compared with healthy controls, systemic sclerosis patients had a worse perception of aesthetic impairment, especially systemic sclerosis patients with anxiety or depression and those with facial and hand involvement. Conclusion: The aesthetic evaluation scale appears to be an easy-to-use tool to evaluate body image. Correlations of the aesthetic evaluation scale score with psychological and quality of life parameters reflect the importance of these parameters for body image evaluation and its complex assessment. Trial registration: Clinical Trial NCT03271320 (Registered 9 January 2017, https://www.clinicaltrials.gov/ct2/show/NCT03271320?term=NCT03271320&cntry=FR&draw=2&rank=1).

Giant cell arteritis-related cerebrovascular ischemic events: a French retrospective study of 271 patients, systematic review of the literature and meta-analysis.

BACKGROUND: Cerebrovascular ischemic events (CIE) are among the most severe complications of giant cell arteritis (GCA). Heterogeneity between different studies in the definition of GCA-related CIE leads to uncertainty regarding their real prevalence. The aim of our study was to evaluate the prevalence and describe the characteristics of GCA-related CIE in a well-phenotyped cohort completed by a meta-analysis of the existing literature. METHODS: In this retrospective study performed in the Lille University Hospital, all consecutive patients with GCA according to American College of Rheumatology (ACR) diagnostic criteria were included from January 1, 2010, to December 31, 2020. A systematic review of the literature using MEDLINE and EMBASE was performed. Cohort studies of unselected GCA patients reporting CIE were included in the meta-analysis. We calculated the pooled summary estimate of GCA-related CIE prevalence. RESULTS: A total of 271 GCA patients (89 males, mean age 72 ± 9 years) were included in the study. Among them, 14 (5.2%) presented with GCA-related CIE including 8 in the vertebrobasilar territory, 5 in the carotid territory, and 1 patient having multifocal ischemic and hemorrhagic strokes related to intra-cranial vasculitis. Fourteen studies were included in the meta-analysis, representing a total population of 3553 patients. The pooled prevalence of GCA-related CIE was 4% (95% CI 3-6, I2 = 68%). Lower body mass index (BMI), vertebral artery thrombosis on Doppler US (17% vs 0.8%, p = 0.012), vertebral arteries involvement (50% vs 3.4%, p < 0.001) and intracranial arteries involvement (50% vs 1.8%, p < 0.001) on computed tomography angiography (CTA) and/or magnetic resonance angiography (MRA), and axillary arteries involvement on positron emission computed tomography (PET/CT) (55% vs 20%, p = 0.016) were more frequent in GCA patients with CIE in our population. CONCLUSIONS: The pooled prevalence of GCA-related CIE was 4%. Our cohort identified an association between GCA-related CIE, lower BMI, and vertebral, intracranial, and axillary arteries involvement on various imaging modalities.

Activities of Clinical Expertise and Research in a Rare Disease Referral Centre: A Place for Telemedicine beyond the COVID-19 Pandemic?

INTRODUCTION: Rare disease referral centres are entrusted with missions of clinical expertise and research, two activities that have to contend with numerous obstacles. Providing specialist opinions is time-consuming, uncompensated and limited by difficulties in exchanging medical data. Clinical research is constrained by the need for frequent research protocol visits. Our objective was to determine whether telemedicine (TLM) can overcome these difficulties. METHODS: To better characterise the activity of clinical expertise provided by our French centre, each opinion delivered by our team was reported on a standardised form. To investigate our clinical research activity, investigators and patients were asked to complete a questionnaire on the acceptability of research protocol teleconsultations. RESULTS: Regarding clinical expertise, our team delivered 120 opinions per week (representing a total of 21 h), of which 29% were delivered to patients and 69% to medical practitioners. If these were delivered using TLM, it would represent a potential weekly income of EUR 500 (tele-expertise) and EUR 775 (teleconsultations). Regarding the research activity, 70% of investigators considered the frequency of visits to be a limiting factor for patient inclusions; nearly half of the patients surveyed would be in favour of having teleconsultations in place of (40%) or in addition to (56%) in-person visits. CONCLUSION: Whereas TLM has become widely used as a back-up procedure to in-person consultations during the COVID-19 pandemic, the solutions it provides to the problems encountered in performing expertise and research activities have made it a new conventional follow-up modality for patients with rare diseases.

Cutaneous Involvement in Catastrophic Antiphospholipid Syndrome in a Multicenter Cohort of 65 Patients.

Importance: Catastrophic antiphospholipid syndrome (CAPS) is a severe, rare complication of antiphospholipid syndrome (APS), but cutaneous involvement has not yet been adequately described. Objective: To describe cutaneous involvement during CAPS, its clinical and pathological features, and outcomes. Design, Setting, and Participants: This cohort study was a retrospective analysis of patients included in the French multicenter APS/systemic lupus erythematosus register (ClinicalTrials.gov: NCT02782039) by December 2020. All patients meeting the revised international classification criteria for CAPS were included, and patients with cutaneous manifestations were analyzed more specifically. Main Outcomes and Measures: Clinical and pathological data as well as course and outcome in patients with cutaneous involvement during CAPS were collected and compared with those in the register without cutaneous involvement. Results: Among 120 patients with at least 1 CAPS episode, the 65 (54%) with skin involvement (43 [66%] women; median [range] age, 31 [12-69] years) were analyzed. Catastrophic antiphospholipid syndrome was the first APS manifestation for 21 of 60 (35%) patients with available data. The main lesions were recent-onset or newly worsened livedo racemosa (n = 29, 45%), necrotic and/or ulcerated lesions (n = 27, 42%), subungual splinter hemorrhages (n = 19, 29%), apparent distal inflammatory edema (reddened and warm hands, feet, or face) (n = 15, 23%), and/or vascular purpura (n = 9, 14%). Sixteen biopsies performed during CAPS episodes were reviewed and showed microthrombi of dermal capillaries in 15 patients (94%). These lesions healed without sequelae in slightly more than 90% (58 of 64) of patients. Patients with cutaneous involvement showed a trend toward more frequent histologically proven CAPS (37% vs 24%, P = .16) than those without such involvement, while mortality did not differ significantly between the groups (respectively, 5% vs 9%, P = .47). Conclusions and Relevance: In this cohort study, half the patients with CAPS showed cutaneous involvement, with a wide spectrum of clinical presentations, including distal inflammatory edema. Skin biopsies confirmed the diagnosis in all but 1 biopsied patient.

Association between Routine Laboratory Parameters and the Severity and Progression of Systemic Sclerosis.

(1) Background: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease with a high mortality and morbidity rate. Identification of biomarkers that can predict the evolution of SSc is a key factor in the management of patients. The aim of this study was to assess the association of routine laboratory parameters, widely used in practice and easily available, with the severity and progression of SSc. (2) Methods: In this retrospective monocentric cohort study, 372 SSc patients were included. We gathered clinical and laboratory data including routine laboratory parameters: C-reactive-protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count, serum sodium and potassium levels, creatinin, urea, ferritin, albumin, uric acid, N-terminal pro-brain natriuretic peptide (NTproBNP), serum protein electrophoresis, and liver enzymes. Associations between these routine laboratory parameters and clinical presentation and outcome were assessed. (3) Results: Median (interquartile range) age was 59.0 (50.0; 68.0) years. White blood cell, monocyte, and neutrophil absolute counts were significantly higher in patients with diffuse cutaneous SSc and with interstitial lung disease (ILD) (p < 0.001). CRP was significantly higher in patients with ILD (p < 0.001). Hemoglobin and ferritin were significantly lower in patients with pulmonary hypertension (PH) including pulmonary arterial hypertension and ILD associated PH (p = 0.016 and 0.046, respectively). Uric acid and NT pro BNP were significantly higher in patients with PH (<0.001). Monocyte count was associated with ILD progression over time. (4) Conclusions: Overall, our study highlights the association of routine laboratory parameters used in current practice with the severity and progression of SSc.

Pneumocystis jirovecii colonization in patients with systemic autoimmune diseases: prevalence, risk factors of colonization and outcome.

OBJECTIVES: To determine the rate and identify risk factors of Pneumocystis jirovecii (P. jirovecii) colonization among patients with systemic autoimmune diseases. METHODS: We conducted an observational study in patients with systemic autoimmune diseases in an internal medicine department. Each week, five patients with systemic diseases were randomly selected for colonization screening. Patients complaining of recent respiratory symptoms were excluded. P. jirovecii PCR was performed on induced sputum samples. Univariate and multivariate logistic regression analyses of clinical and biological data were performed to determine predictors of Pneumocystis colonization. Pneumocystis pneumonia occurrence in P. jirovecii-positive PCR patients was recorded during a 1-year follow-up. RESULTS: P. jirovecii was detected in 11/67 (16%) subjects. Comparing the features in P. jirovecii-positive and P. jirovecii-negative PCR patients, only male gender was significantly associated with Pneumocystis colonization. In multivariate analysis with regard to gender, the higher prevalence of P. jirovecii colonization in men was largely explained by higher daily CSs [odds ratio (OR) = 1.6; 95% CI 1.1, 2.3] and lower total lymphocyte level (OR = 0.9; 95% CI 0.8, 0.99). No P. jirovecii-positive PCR patient developed Pneumocystis pneumonia during the 1-year follow-up, but corticosteroid amounts were significantly lower at the end of follow-up than on inclusion. CONCLUSION: This is the first study on P. jirovecii colonization in patients with systemic autoimmune diseases. We found a high prevalence of colonization and identified CS therapy and lymphocyte counts as risk factors for colonization. We recommend screening for P. jirovecii colonization in patients with systemic autoimmune diseases receiving immunosuppressant treatment. Further studies are needed to determine the role of subclinical colonization in disease transmission and the persistence of Pneumocystis colonization.

Extended myositis-specific and -associated antibodies profile in systemic sclerosis: A cross-sectional study.

OBJECTIVE: In systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), auto-antibodies are used in daily practice as potent biomarkers of clinical phenotypes. This study aimed at estimating the prevalence of myositis-specific (MSA) and myositis-associated (MAA) auto-antibodies in a well-characterised SSc patients cohort using two different immunoblot assays, and studying their clinical associations. METHODS: In this cross-sectional study, the sera of 300 consecutive patients were tested at the same time with myositis antibodies Euroimmun® and D-tek® immunoblot assays. RESULTS: Prevalence of MSA/MAA, MSA and MAA were 17.0%, 8.0% and 9.7%, respectively. When combining results of both tests, anti-PM/Scl 100 were found in 5.0% (95% confidence interval 2.8; 8.1); anti-PM/Scl 75 and anti-TIF1γ in 3.7% (1.8; 6.5); anti-Ku 3.0% (1.4; 5.6); anti-MDA5 in 1.3% (0.4; 3.4); anti-Mi-2 ß, anti-NXP2, anti-PL-7 and anti-SRP in 0.7% (0.08; 2.4); anti-EJ and anti-PL-12 in 0.3% (0.01; 1.8) of patients. No reactivity against SAE1, Jo-1 or OJ was observed. Anti-PM/Scl 75 antibodies were associated with interstitial lung disease (80% vs. 42%) and myositis (27% vs. 3%); anti-Ku antibodies were associated with myositis (33% vs. 3%). CONCLUSION: In this cross-sectional study of 300 SSc patients, the prevalence of MSA/MAA, MSA and MAA using immunoblot assays were 17.0%, 8.0% and 9.7%, respectively. MAA positivity was associated with ILD and myositis, but this study did not highlight any clinical associations with MSA positivity.

Fatal Enterovirus-related Myocarditis in a Patient with Devic's Syndrome Treated with Rituximab.

Enteroviruses are a frequent source of infection and among the most common central nervous system viral pathogens. Enteroviruses - in particular, the Coxsackie B viruses - are a known cause of myocarditis. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody. Many reports in the literature suggest a higher risk of infection following repeated rituximab therapy, including viral infection. However, observations of enterovirus-related myocarditis in the context of rituximab treatment are scarce. The authors describe the case of a patient with neuromyelitis optica spectrum disorder who developed severe and fatal enterovirus-related myocarditis after rituximab therapy with a difficult differential diagnosis of autoimmune or giant-cell myocarditis. This case highlights the importance of complete diagnostic workup in difficult cases of myocarditis, including endomyocardial biopsies.

Adalimumab and myositis: A case report and review of the French and international Pharmacovigilance Databases.

TNFα inhibitors, including adalimumab, are widely used in inflammatory rheumatologic and bowel diseases. Well-known adverse effects include: opportunistic infections, immunogenicity and new inflammatory manifestations. Myositis is an inflammatory disease, which manifests with muscle symptoms and can be life-threatening. Little is known about drug-induced myositis. We aimed to describe a case of myositis induced by adalimumab and reviewed national and international pharmacovigilance databases for other cases until 01/02/2019. This was a 63 years old woman with Crohn's disease, who developed muscle weakness, and rhabdomyolysis 3 months after starting adalimumab. Diagnosis of myositis was suspected and confirmed with electromyography and muscle biopsy. Improvement in muscle symptoms was observed after stopping adalimumab and starting corticosteroids. Muscular adverse effects are well-known and usually benign with adalimumab. However, five cases of myositis during treatment with adalimumab were registered in French PharmacoVigilance Database (FPVD) with muscle symptoms observed 3 months to 7 years after starting adalimumab. In VigiBaseⓇ, 90 cases of myositis associated with adalimumab with some similar characteristics were registered. When a patient treated with adalimumab complains of muscular symptoms, inflammatory myopathies should be considered. This adverse effect should be mentioned in a 'Summary of Product Characteristics' to alert healthcare professionals.

Clinical Characteristics and Outcome of Patients with Infective Endocarditis Diagnosed in a Department of Internal Medicine.

Clinical manifestations of infective endocarditis (IE) can be highly non-specific. Our objective was to describe the clinical characteristics of patients initially referred to a department of internal medicine for a diagnostic work-up, and eventually diagnosed with IE. We retrospectively retrieved adult patients admitted to the department of internal medicine at Lille University Hospital between 2004 and 2015 who fulfilled Duke Classification criteria for definite IE. Thirty-five patients were included. The most frequently involved bacteria were non-hemolytic streptococci. Most patients presented with various systemic, cardiac, embolic, rheumatic, and immunological findings, with no sign or symptom displaying high sensitivity. The first transthoracic echocardiogram was negative in 42% of patients. Furthermore, definite diagnosis required performing at least 2 transesophageal examinations in 24% of patients. We observed a trend towards decreased survival in the subgroup of patients in whom the delay between onset of symptoms and diagnosis was >30 days. In conclusion, patients who are initially referred to internal medicine for a diagnosis work-up and who are ultimately diagnosed with IE have non-specific symptoms and a high percentage of initial normal echocardiography. Those patients require prolonged echocardiographic monitoring as a prolonged delay in diagnosis is associated with poorer outcomes such as death.