Aseptic meningitis and Fabry disease.

OBJECTIVE: Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features. METHODS: We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases. RESULTS: Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis. INTERPRETATION: Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.

Limb arteries involvement assessed by FDG/PET CT at diagnosis of giant cell arteritis and risk of relapse: An observational study.

INTRODUCTION: Steroids and anti-IL6 biotherapy are highly effective in obtaining remission in patients with giant cell arteritis (GCA) but the risk of relapses remains high. We aimed to identify predictors of relapse in GCA. METHODS: All consecutive patients admitted with a new diagnosis of GCA - according to the 2022 American College of Rheumatology/EULAR (ACR/EULAR) classification criteria - between May 2011 and May 2022 were eligible for this study. The primary outcome was the GCA relapse rate over the 36-months follow up. Factors associated with the primary outcome and time to first relapse were analyzed. RESULTS: One hundred and eight patients (74 [69-81] years, 64.8% women) with a new diagnosis of GCA were studied. GCA was biopsy-proven in 65 (60.2%) cases. Ninety-eight (90.7%) FDG/PET CT scans performed at diagnosis were available for review. All patients received steroids given for 21.0 [18.0-28.5] months, associated with methotrexate (n=1, 0.9%) or tocilizumab (n=2, 1.9%). During a median follow-up of 27.5 [11.4-35.0] months, relapse occurred in 40 (37%) patients. Multivariable Cox regression model, including general signs, gender, aortic wall thickness, FDG uptake in arterial wall and IV steroid pulse as covariates, showed that both general signs (HR 2.0 [1.0-4.0, P<0.05) and FDG uptake in limb arteries (HR 2.7 [1.3-5.5], P<0.01) at diagnosis were associated with GCA relapse. CONCLUSION: FDG uptake in limb arteries at diagnosis is a predictor of relapse in newly diagnosed GCA.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis.

INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.

Prognostic factors in giant cell arteritis associated aortitis with PET/CT and CT angiography at diagnosis.

BACKGROUND: Prognosis data on giant-cell arteritis (GCA)-associated aortitis are scarce and heterogeneous. The aim of this study was to compare the relapses of patients with GCA-associated aortitis according to the presence of aortitis on CT-angiography (CTA) and/or on FDG-PET/CT. METHODS: This multicenter study included GCA patients with aortitis at diagnosis; each case underwent both CTA and FDG-PET/CT at diagnosis. A centralized review of image was performed and identified patients with both CTA and FDG-PET/CT positive for aortitis (Ao-CTA+/PET+); patients with positive FDG-PET/CT but negative CTA for aortitis (Ao-CTA-/PET+), and patients solely positive on CTA. RESULTS: Eighty-two patients were included with 62 (77%) of female sex. Mean age was 67±8 years; 64 patients (78%) were in the Ao-CTA+/PET+ group; 17 (22%) in the Ao-CTA-/PET+ group and 1 had aortitis only on CTA. Overall, 51 (62%) patients had at least one relapse during follow-up: 45/64 (70%) in the Ao-CTA+/PET+ group and 5/17 (29%) in the Ao-CTA-/PET+ group (log rank, p = 0.019). In multivariate analysis, aortitis on CTA (Hazard Ratio 2.90, p = 0.03) was associated with an increased risk of relapse. CONCLUSION: Positivity of both CTA and FDG-PET/CT for GCA-related aortitis was associated with an increased risk of relapse. Aortic wall thickening on CTA was a risk factor of relapse compared with isolated aortic wall FDG uptake.

Venous thromboembolism during systemic inflammatory and autoimmune diseases associated with myelodysplastic syndromes, chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasms: a French multicentre retrospective case-control study.

OBJECTIVES: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE. METHODS: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders. RESULTS: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83). CONCLUSIONS: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Acute myocarditis revealing autoimmune and inflammatory disorders: Clinical presentation and outcome.

BACKGROUND: Acute myocarditis (AM) may be the heralding manifestation of autoimmune and inflammatory disorders (AIID). We aimed to describe the clinical presentation and outcome of patients with AM revealing AIID. METHODS: All consecutive adult patients with AM admitted in a department of Cardiology (Bichat Hospital, Paris, France) from January 2011 to January 2019 were included. Diagnosis of AM was based on clinical manifestations, elevated Troponin, myocardial inflammation on CMR and no evidence for coronary artery disease. AIID were classified using international criteria. RESULTS: Two-hundred and eighteen (35.3 [26.4-47.1] years, 75.2% males) patients with AM were included. Overall, AM revealed AIID in 15 (6.9%), including systemic lupus erythematosus (n = 3), adult onset Still's disease (n = 3), sarcoidosis (n = 2), mixed connective tissue disease (n = 1), anti-Jo1 syndrome (n = 1), eosinophilic granulomatosis with polyangiitis (n = 1), antiphospholipid syndrome (n = 1), reactive arthritis (n = 1), Graves' disease (n = 1) and Crohn's colitis (n = 1). Left ventricular ejection fraction (LVEF) at onset was <30% in 5 (33.3%) patients with AIID. All but 2 patients with AIID were treated with steroids, immunosuppressive and/or immunomodulatory drugs and LVEF normalized in all by the end of follow-up. By comparing patients with AIID to patients with idiopathic AM (n = 203), multivariable analysis showed that pericardial effusion, lack of chest pain and high CRP level at onset were independently associated with AIID. CONCLUSION: Acute myocarditis revealing AIID may be life-threatening at the acute phase but has an overall good prognosis under specific treatment. Pericardial effusion and CRP level at admission suggest an AIID as the cause for AM.

Persistent FDG/PET CT uptake in idiopathic retroperitoneal fibrosis helps identifying patients at a higher risk for relapse.

BACKGROUND: The aim of this study was to evaluate the prognostic value of persistent retroperitoneal fibrosis FDG uptake using FDG/PET CT in patients with idiopathic retroperitoneal fibrosis (IRF). METHODS: In this monocentric retrospective cohort study, all patients admitted for IRF from January 2009 to December 2017 underwent a FDG/PET CT at diagnosis and during follow up. Metabolic activity of IRF was assessed by retroperitoneal fibrosis FDG uptake measured as maximal standardized uptake value (SUVmax). The primary outcome was IRF relapse rate during follow-up. RESULTS: 23 consecutive patients (54.7 [36.9-89] years, 73.9% of men) diagnosed with IRF had FDG/PET CT imaging performed at diagnosis, 3.1 [1-8.7] months (i.e 1st evaluation) and 10.4 [4.9-17.5] months (i.e 2nd evaluation) after diagnosis. High FDG retroperitoneal fibrosis uptake was present in all patients at diagnosis (SUVmax 6.5 [3.8-11.9]) and persisted in 16 (69.6%; SUVmax 3.65 [2.1-5.4]) and 12 (52.2%; SUVmax 3.75 [2.7-7.8]) patients, at 1st and 2nd evaluation respectively. All but one patient had received steroids at IRF diagnosis and 21 (91.3%) were in complete remission at both 1st and 2nd evaluation. During a median follow-up period of 38.7 [3-106.9] months, 6 (26.1%) patients suffered IRF relapse that occurred 15.7 [9.2-42.8] months after diagnosis. Multivariate analysis showed that only persistent retroperitoneal fibrosis FDG uptake at 2nd evaluation was associated with IRF relapse (p = .046). CONCLUSIONS: In IRF, persistent retroperitoneal fibrosis FDG uptake during follow up is associated with clinical outcome. FDG/PET CT may help to better stratify the risk of relapse and target therapy in IRF.

Increased FDG-PET/CT pericardial uptake identifies acute pericarditis patients at high risk for relapse.

OBJECTIVES: We aimed to evaluate the prognostic value of FDG pericardial uptake using FDG-PET/CT in patients admitted for acute pericarditis with pericardial effusion. METHODS: In this monocentric retrospective cohort study, all patients admitted for idiopathic acute pericarditis with pericardial effusion from January 2009 to December 2016 who underwent a FDG-PET/CT at diagnosis were considered. Pericardial FDG uptake was measured by generating a volume of interest to calculate the maximal standardized uptake value. The primary outcome was the pericarditis relapse rate during follow-up. RESULTS: FDG-PET/CT was performed 23 [7-99] days after diagnosis in 39 patients (52 [18-83] years, 43.6% of women) admitted for acute pericarditis with pericardial effusion. During a median follow-up period of 7.6 [2.4-77.2] months, 7 (17.9%) patients suffered pericarditis relapse that occurred 3.8 [1.6-14.6] months after FDG-PET CT. In the multivariable analysis, pericardial FDG uptake at diagnosis (OR: 16.6; 95% confidence interval [CI]: 1.25 to 220.8; p = 0.033) was independently associated with pericarditis relapse. Eventually, patients with pericardial FDG uptake at diagnosis had a higher recurrence rate during follow up (p = 0.047). CONCLUSIONS: In acute pericarditis with pericardial effusion, increased FDG-PET/CT pericardial uptake is associated with a higher risk for relapse.

Diagnosis of systemic inflammatory diseases among patients admitted for acute pericarditis with pericardial effusion.

AIMS: Acute pericarditis may be the heralding manifestation of various systemic inflammatory diseases (SIDs). The aim of this study was to identify clinical indicators for SIDs in patients admitted for acute pericarditis with pericardial effusion. METHODS: All consecutive adult patients hospitalized in a Department of Internal Medicine over a 10-year period for acute pericarditis with pericardial effusion were retrospectively reviewed. Patients with cancer and tuberculosis were excluded. A structured clinical panel for extra-cardiac symptoms of SIDs was applied. SIDs were classified using current international criteria. RESULTS: Ninety-nine patients were admitted for acute pericarditis with pericardial effusion. After exclusion, 74 (49.7 ±â€Š19.7 years, 56.7% women) patients were analyzed. Among them, 23 (23.2%) patients had a SID that was revealed by pericarditis in 12 cases. Systemic lupus erythematosus, undifferentiated connective-tissue disease, and Sjogren's syndrome accounted for 75% of the SID. Patients with SIDs were younger (P < 0.001), more frequently of female sex (P = 0.025), and had a higher frequency of extra-cardiac symptoms (P < 0.001) including arthralgia, myalgia, Raynaud phenomenon, and skin rash, as compared with patients with idiopathic pericarditis (n = 51). Overall, after exclusion of neoplasm and tuberculosis, the probability of SIDs in patients admitted with an acute pericarditis with pericardial effusion was 89.7% in patients younger than 50 who had extra-cardiac symptoms. Conversely, the probability fell to 8.4% in patients older than 50 with no extra-cardiac symptoms. CONCLUSION: Both age and extra-cardiac symptoms suggest an underlying SID as a possible cause of acute pericarditis.

Cystic lung disease in Sjögren's syndrome: An observational study.

OBJECTIVES: To analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögren's syndrome (SS). METHODS: From June 2010 to February 2015, 90 consecutive SS patients [60.1±14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records. RESULTS: Twenty-one (23.3%) patients had cysts on CT scan performed 40.5±54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3±15.3 versus 58.5±14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1±17.7months), no patient developed specific lung disease or lymphoproliferative disorders. CONCLUSIONS: Cystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS.

Positron emission tomography and computed tomography angiography for the diagnosis of giant cell arteritis: A real-life prospective study.

The use of 18F-fluoro-deoxyglucose positron emission tomography scan (FDG-PET) and computed tomography angiography (CTA) to improve accuracy of diagnosis of giant cell arteritis (GCA) is a very important clinical need. We aimed to compare the diagnostic performance of FDG-PET and CTA in patients with GCA.FDG-PET and CTA were acquired in all consecutive patients suspected for GCA. Results of FDG-PET and CTA were compared with the final diagnosis based on clinical judgment, temporal artery biopsy (TAB) findings, and ACR criteria. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method.Twenty-four patients suspected for GCA were included. Fifteen (62.5%) were ultimately diagnosed as having GCA. Among them, all fulfilled ACR criteria and 6 had biopsy-proven GCA. Strong FDG uptake in large vessels was found in 10 patients who all had GCA. Mean maximal standard uptake values (SUVmax) per patient measured at all the arterial territories were of 3.7 (range: 2.8-4.7). FDG uptake was negative in 14 patients including 9 and 5 patients without and with GCA, respectively. Mural thickening suggestive of aortitis or branch vessel arteritis was observed on CTA in 11 patients with and 2 patients without GCA. No mural thickening was observed in 11 patients including 7 patients without and 4 patients with GCA. Overall, sensitivity was 66.7% and 73.3%, specificity was 100% and 84.6%, NPV was 64.3% and 64.6%, and PPV was 100% and 84.6% of FDG-PET and CTA, respectively.Both FDG-PET and CTA have a strong diagnostic yield for the diagnosis of GCA. FDG-PET appeared to have a higher PPV as compared to CTA and may be the preferred noninvasive technique to explore patients with suspected GCA.

Frequency of malignancy is high in patients admitted for a first venous thromboembolism episode: an observational study.

Patients with a cancer at time of first venous thromboembolism (VTE) have not been thoroughly analyzed. Our study aimed to (1) determine the frequency of cancer diagnosed in patients hospitalized for a first VTE episode, (2) investigate the characteristics of VTE and cancer in such patients. All consecutive adults patients hospitalized over a 6-years period for a first VTE episode in a tertiary care hospital were considered. Patients with congenital or acquired thrombophilia were excluded. Demographic, medical history, and follow up data were retrieved from medical records. 216 patients (63.6 ± 19.7 years, 63.4 % females) hospitalized for a first VTE were analyzed. Among them, 64 patients (29.6 %) had cancer, either revealed (n = 26) or already known (n = 38) at VTE diagnosis. Cancer was in an advanced stage in 26 patients (40.6 %). Patients with cancer were older and displayed a higher frequency of vena cava thrombosis, as compared to patients without cancer. VTE was more recurrent and mortality was higher in patients with cancer. Cancer occurred after VTE diagnosis in only 2 (2/127, 1.6 %) cases during a protracted follow-up of 24.1 ± 22.5 months. Overall, VTE preceded cancer diagnosis in only 3 % (2/66) of cases. Frequency of cancer is high among patients hospitalized for a first VTE. In such setting, VTE often involved unusual sites such as vena cava. In most cases, cancer was either already known or diagnosed at time of VTE, with a poor prognosis.

Development and multi-centre evaluation of a method for assessing the severity of potential harm of medication reconciliation errors at hospital admission in elderly.

BACKGROUND: Medication reconciliation is a powerful process to correct medication errors (ME) resulting from miscommunicated information at transitions of care. This study aims to develop and evaluate a scoring method for assessing the severity of potential harm of ME intercepted by medication reconciliation at hospital admission in elderly. METHODS: The development of the scoring method was based on a literature search and the creation of a list of high-risk drugs used in outpatient care. The evaluation of the method was carried out in 7 French hospitals and was based on two criteria: the inter-rater reliability and acceptability. The assessment of the inter-rater reliability was based on intra-class correlation coefficient (ICC) calculations. Each hospital prospectively enrolled the 10 first patients aged 65 or older presenting with at least one ME. Seven blocks of 10 patients were formed. After randomization, each block was rated by practitioners from 3 hospitals. The assessment of the acceptability was based on a satisfaction questionnaire. RESULTS: A clinical algorithm was developed. The inter-rater reliability of the method was validated by the overall agreement of the 7 hospitals ratings. The agreement was at least substantial (ICC>0.60) and in most of cases almost perfect (ICC>0.80). The acceptability of the method was judged as satisfactory. CONCLUSION: This multi-centre project has validated an instrument for assessing the severity of potential harm of ME intercepted by medication reconciliation. This will allow studies to be conducted with large cohorts of patients in order to develop epidemiological databases of ME of potential clinical significance.

Medication reconciliation: a prospective study in an internal medicine unit.

BACKGROUND: Medication reconciliation has proved its effectiveness at improving drug-prescription safety. This study was undertaken to assess the impact of an intervention aimed at decreasing the discrepancies between a patient's usual treatment(s) and medications prescribed at admission. METHODS: Our study was conducted from November 2010 to May 2011. Discrepancies between home medication( s) and drugs prescribed to every patient aged C65 years, transferred from the Emergency Department and hospitalized in the Internal Medicine Unit, were analyzed. RESULTS: During this 6-month period, 170 patients were prospectively included, with a total of 1,515 medicines reconciled. The unintentional discrepancy rate declined from 4.3 to 0.9 % after the intervention. The main sources of discrepancies concerned alimentary tract and metabolism (25.7 %), cardiovascular (24 %), and nervous system drugs (19.4 %). CONCLUSIONS: The results of this study demonstrated that acquisition of patients' medication history is often incomplete or incorrect. Pharmacists seem to be especially well suited to help medical teams rectify this situation. However, the cost effectiveness of this intervention needs further assessment.