Publications by authors named "Christian Lavigne"

54 Publications

Brain abscess caused by Bartonella henselae associated with arteriovenous malformation.

Infect Dis Now 2021 Sep 30;51(6):574-576. Epub 2020 Dec 30.

Department of internal medicine, University hospital of Angers, Angers, France.

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http://dx.doi.org/10.1016/j.idnow.2020.11.012DOI Listing
September 2021

Tear metabolomics highlights new potential biomarkers for differentiating between Sjögren's syndrome and other causes of dry eye.

Ocul Surf 2021 Jul 28;22:110-116. Epub 2021 Jul 28.

Mitolab, MitoVasc Institute, CNRS, 6015, INSERM U1083, University of Angers, France; Department of Biochemistry and Molecular Biology, University Hospital, Angers, France.

Purpose: The lacrimal exocrinopathy of primary Sjögren's syndrome (pSS) is one of the main causes of severe dry eye syndrome and a burden for patients. Early recognition and treatment could prevent irreversible damage to lacrimal glands. The aim of this study was to find biomarkers in tears, using metabolomics and data mining approaches, in patients with newly-diagnosed pSS compared to other causes of dry eye syndrome.

Methods: A prospective cohort of 40 pSS and 40 non-pSS Sicca patients with dryness was explored through a standardized targeted metabolomic approach using liquid chromatography coupled with mass spectrometry. A metabolomic signature predictive of the pSS status was sought out using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the studied population into training, validation and test sets.

Results: Among the 104 metabolites accurately measured in tears, we identified a discriminant signature composed of nine metabolites (two amino acids: serine, aspartate; one biogenic amine: dopamine; six lipids: Lysophosphatidylcholine C16:1, C18:1, C18:2, sphingomyelin C16:0 and C22:3, and the phoshatidylcholine diacyl PCaa C42:4), with robust performances (ROC-AUC = 0.83) for predicting the pSS status. Adjustment for age, sex and anti-SSA antibodies did not disrupt the link between the metabolomic signature and the pSS status. The non-lipidic components also remained specific for pSS regardless of the dryness severity.

Conclusion: Our results reveal a metabolomic signature for tears that distinguishes pSS from other dry eye syndromes and further highlight nine key metabolites of potential interest for early diagnosis and therapeutics of pSS.
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http://dx.doi.org/10.1016/j.jtos.2021.07.006DOI Listing
July 2021

Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients.

J Clin Med 2021 Jun 7;10(11). Epub 2021 Jun 7.

Department of Internal Medicine and Clinical Immunology, Angers University Hospital, 49933 Angers, France.

Post-exertional malaise (PEM), the key feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is characterized by baseline symptom exacerbation after exposure to a stressor, and some patients can experience new or non-typical symptoms. We hypothesized that new or non-typical symptoms occurring long enough before onset of baseline symptom exacerbation could be warning signals predicting PEM. Adult ME/CFS patients who attended the internal medicine department of Angers University Hospital (France) between October 2011 and December 2019 were included in a retrospective medical records review. Patients who experienced one or more new or non-typical symptoms before baseline symptom exacerbation were compared with the rest of the study population for PEM features, epidemiological characteristics, fatigue features, and comorbidities. New or non-typical symptoms preceded baseline symptom exacerbation in 27/197 (13.7%) patients, and the most frequent ones were mood disorders (37%). When compared to the rest of the study population, only PEM intensity was significantly lower in these patients ( = 0.004), even after adjustment for sex and age at disease onset ( = 0.007). New or non-typical symptoms preceding baseline symptom exacerbation in some ME/CFS patients could be warning signals for PEM. Their identification could help preventing PEM occurrences or reducing their intensity leading to improving disease prognosis.
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http://dx.doi.org/10.3390/jcm10112517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201170PMC
June 2021

Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer.

Sci Rep 2021 Jun 25;11(1):13361. Epub 2021 Jun 25.

Department of Internal Medicine and Clinical Immunology, Angers University Hospital, Angers, France.

Elevated plasma vitamin B12 has been associated with solid cancers, based on a single B12 measurement. We evaluated the incidence of solid cancers following B12 measurement in patients with persistent elevated B12, compared to patients without elevated B12 and to patients with non-persistent elevated B12. The study population included patients with at least two plasma B12 measurements without already known elevated-B12-related causes. Patients with elevated plasma B12 (≥ 1000 ng/L) at first measurement (n = 344) were matched for age and sex with patients having 2 normal B12 measurements (< 1000 ng/L) (NN group, n = 344). The patients with elevated plasma B12 at first measurement were split into 2 groups, according to the presence (EE group, n = 144) or the absence (EN group, n = 200) of persistent elevated plasma B12 at second measurement. We compared the cancer-free survival during 60 months between the groups after adjustment for the other elevated-B12-related causes in a survival competing risk model. Compared to the NN group, a persistent elevated plasma B12 ≥ 1000 ng/mL was strongly associated with the occurrence of solid cancer (HR 5.90 [95% CI 2.79-12.45], p < 0.001), contrary to non-persistent plasma B12 elevation (p = 0.29). These results could help to select patients in whom the screening for solid cancers would be of interest.
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http://dx.doi.org/10.1038/s41598-021-92945-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233305PMC
June 2021

Adult-onset diagnosis of urea cycle disorders: Results of a French cohort of 71 patients.

J Inherit Metab Dis 2021 Sep 7;44(5):1199-1214. Epub 2021 Jun 7.

Laboratoire de Biochimie-Pharmacologie-Toxicologie, CHU Reims, France.

Urea cycle disorders (UCD) are rare diseases that usually affect neonates or young children. During decompensations, hyperammonemia is neurotoxic, leading to severe symptoms and even coma and death if not treated rapidly. The aim was to describe a cohort of patients with adult onset of UCDs in a multicentric, retrospective and descriptive study of French adult patients with a diagnosis after 16 years of age of UCDs due to a deficiency in one of the 6 enzymes (arginase, ASL, ASS, CPS1, NAGS, OTC) or the two transporters (ORNT1 or citrin). Seventy-one patients were included (68% female, 32% male). The diagnosis was made in the context of (a) a metabolic decompensation (42%), (b) family history (55%), or (c) chronic symptoms (3%). The median age at diagnosis was 33 years (range 16-86). Eighty-nine percent of patients were diagnosed with OTC deficiency, 7% CPS1 deficiency, 3% HHH syndrome and 1% argininosuccinic aciduria. For those diagnosed during decompensations (including 23 OTC cases, mostly female), 89% required an admission in intensive care units. Seven deaths were attributed to UCD-6 decompensations and 1 epilepsy secondary to inaugural decompensation. This is the largest cohort of UCDs diagnosed in adulthood, which confirms the triad of neurological, gastrointestinal and psychiatric symptoms during hyperammonemic decompensations. We stress that females with OTC deficiency can be symptomatic. With 10% of deaths in this cohort, UCDs in adults remain a life-threatening condition. Physicians working in adult care must be aware of late-onset presentations given the implications for patients and their families.
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http://dx.doi.org/10.1002/jimd.12403DOI Listing
September 2021

Severe Joint Involvement in VEXAS Syndrome: A Case Report.

Ann Intern Med 2021 07 30;174(7):1025-1027. Epub 2021 Mar 30.

Angers University Hospital, Angers, France.

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http://dx.doi.org/10.7326/L21-0023DOI Listing
July 2021

Symptomatic aortitis at giant cell arteritis diagnosis: a prognostic factor of aortic event.

Arthritis Res Ther 2021 01 7;23(1):14. Epub 2021 Jan 7.

Department of Internal Medicine, CHU Nantes, 1 place Alexis Ricordeau, 44093, Nantes, France.

Background: Giant cell arteritis (GCA) is frequently associated with aortic involvement that is likely to cause life-threatening structural complications (aneurysm, dissection). Few studies have investigated the occurrence of these complications, and no predictive factor has been identified so far. The aim of this study was to investigate factors associated with the risk of aortic complications in a cohort of GCA aortitis.

Methods: Data of all patients managed with aortitis (CT or 18 FDG PET) at the diagnosis of GCA in five hospitals from May 1998 and April 2019 were retrospectively collected. Clinical features were compared according to the presence of aortitis symptoms. The predictive factors of occurrence or aggravation of aortic structural abnormalities were investigated.

Results: One hundred and seventy-one patients with GCA aortitis were included; 55 patients (32%) had symptoms of aortitis (dorsal/lumbar/abdominal pain, aortic insufficiency) at diagnosis. The median follow-up was 38 months. Aortic complications occurred after a median time of 32 months. There were 19 new aortic aneurysms or complications of aneurysm and 5 dissections. Survival without aortic complication was significantly different between the symptomatic and non-symptomatic groups (Log rank, p = 0.0003). In multivariate analysis the presence of aortitis symptoms at diagnosis (HR 6.64 [1.95, 22.6] p = 0.002) and GCA relapse (HR 3.62 [1.2, 10.9] p = 0.02) were factors associated with the occurrence of aortic complications.

Conclusion: In this study, the presence of aortitis symptoms at the diagnosis of GCA aortitis and GCA relapse were independent predictive factors of occurrence of aortic complications during follow-up.
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http://dx.doi.org/10.1186/s13075-020-02396-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792092PMC
January 2021

Impact of aging on phenotype and prognosis in IgA vasculitis.

Rheumatology (Oxford) 2021 09;60(9):4245-4251

Université Paris Descartes.

Objectives: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV.

Methods: We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36, 36 ≤ age < 52; 52 ≤ age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset.

Results: Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P < 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P < 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1-38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age.

Conclusion: Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
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http://dx.doi.org/10.1093/rheumatology/keaa921DOI Listing
September 2021

Association of Primary Sjögren's Syndrome and Vitamin B12 Deficiency: A Cross-Sectional Case-Control Study.

J Clin Med 2020 Dec 16;9(12). Epub 2020 Dec 16.

Department of Internal Medicine, Angers University Hospital, 4 Rue Larrey, 49000 Angers, France.

Descriptive and retrospective studies without control groups have suggested a possible association between primary Sjögren's syndrome (pSS) and vitamin B12 (B12) deficiency. This is of importance because several mucosal and neurological features are common to these two conditions and could be prevented or reversed in case of B12 deficiency. We aimed to evaluate the association between pSS and B12 deficiency. We prospectively assessed the B12 status of 490 patients hospitalized in an internal medicine department over a 15-week period. Patients with pernicious anemia were excluded. We extracted patients with pSS and paired them with controls according to age and sex, with a 1:5 ratio. Twenty-one pSS patients were paired with 105 control patients. The median age was 70 years old (51-75) and 95.2% of patients were women. The plasma B12 level was lower in pSS patients (329 (293-521) ng/L vs. 456 (341-587) ng/L, < 0.0001). B12 deficiency was associated with pSS (42.9% among pSS patients vs. 11.4% among controls), even after adjustment for other causes of B12 deficiency (OR 6.45 (95%CI: 2.08-20.0)). In conclusion, pSS appeared to be associated with B12 deficiency, even after the exclusion of pernicious anemia. This justifies screening and treating B12 deficiency in pSS patients.
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http://dx.doi.org/10.3390/jcm9124063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765802PMC
December 2020

Clinical and molecular characterization of adult patients with late-onset MTHFR deficiency.

J Inherit Metab Dis 2021 05 2;44(3):777-786. Epub 2020 Nov 2.

APHP, La Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France.

5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency usually presents as a severe neonatal disease. This study aimed to characterize natural history, biological and molecular data, and response to treatment of patients with late-onset MTHFR deficiency. The patients were identified through the European Network and Registry for Homocystinuria and Methylation Defects and the Adult group of the French Society for Inherited Metabolic Diseases; data were retrospectively colleted. To identify juvenile to adult-onset forms of the disease, we included patients with a diagnosis established after the age of 10 years. We included 14 patients (median age at diagnosis: 32 years; range: 11-54). At onset (median age: 20 years; range 9-38), they presented with walking difficulties (n = 8), cognitive decline (n = 3) and/or seizures (n = 3), sometimes associated with mild mental retardation (n = 6). During the disease course, symptoms were almost exclusively neurological with cognitive dysfunction (93%), gait disorders (86%), epilepsy (71%), psychiatric symptoms (57%), polyneuropathy (43%), and visual deficit (43%). Mean diagnostic delay was 14 years. Vascular events were observed in 28% and obesity in 36% of the patients. One patient remained asymptomatic at the age of 55 years. Upon treatment, median total homocysteine decreased (from 183 μmol/L, range 69-266, to 90 μmol/L, range 20-142) and symptoms improved (n = 9) or stabilized (n = 4). Missense pathogenic variants in the C-terminal regulatory domain of the protein were over-represented compared to early-onset cases. Residual MTHFR enzymatic activity in skin fibroblasts (n = 4) was rather high (17%-58%). This series of patients with late-onset MTHFR deficiency underlines the still unmet need of a prompt diagnosis of this treatable disease.
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http://dx.doi.org/10.1002/jimd.12323DOI Listing
May 2021

Infliximab is an effective glucocorticoid-sparing treatment for Takayasu arteritis: Results of a multicenter open-label prospective study.

Autoimmun Rev 2020 Oct 13;19(10):102634. Epub 2020 Aug 13.

Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, F-67000 Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102634DOI Listing
October 2020

Parietal cell antibodies: evolution of plasma vitamin B12 during oral supplementation to differentiate true and false positives for pernicious anemia.

Pol Arch Intern Med 2020 09 4;130(9):813-815. Epub 2020 Jul 4.

Department of Internal Medicine, University Hospital, Angers, France;

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http://dx.doi.org/10.20452/pamw.15478DOI Listing
September 2020

Epidemiological and clinical factors associated with post-exertional malaise severity in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

J Transl Med 2020 06 22;18(1):246. Epub 2020 Jun 22.

Department of Internal Medicine, University Hospital, 49000, Angers, France.

Background: Post-exertional malaise (PEM), the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), occurs generally after exposure to a stressor. It is characterized by the worsening of ME/CFS symptoms and results in aggravating the course of the disease and the quality of life of patients. Due to its unpredictable onset, severity, and recovery time, identifying patients with higher risk for severe PEM would allow preventing or reducing its occurrence. We thus aimed at defining possible factors that could be associated with PEM severity.

Methods: Adult patients fulfilling ME international consensus criteria who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2019 were included retrospectively. All patients were systematically hospitalized for an etiological workup and overall assessment. We reviewed their medical records for data related to the assessment: epidemiological data, fatigue features, clinical manifestations, and ME/CFS precipitants. PEM severity was appreciated by the Center for Disease Control self-reported questionnaire. The study population was classified into quartiles according to PEM severity scores. Analyses were performed with ordinal logistic regression to compare quartile groups.

Results: 197 patients were included. PEM severity was found to be positively associated with age at disease onset ≥ 32 years (OR 1.8 [95% CI 1.1-3.0] (p = 0.03)), recurrent infections during the course of the disease (OR 2.1 [95% CI 1.2-3.7] (p = 0.009)), and when ME/CFS was elicited by a gastrointestinal infectious precipitant (OR 5.7 [1.7-19.3] (p = 0.006)).

Conclusion: We identified some epidemiological and clinical features, which were positively associated with PEM severity in subsets of ME/CFS patients. This could help improving disease management and patients' quality of life.
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http://dx.doi.org/10.1186/s12967-020-02419-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309998PMC
June 2020

Differences in clinical features between small fiber and sensitive large fiber neuropathies in Sjögren's syndrome.

Eur J Intern Med 2020 09 27;79:58-62. Epub 2020 May 27.

Department of Internal Medicine, University Hospital, Angers, 49000, France. Electronic address:

Background: To distinguish large (LFN) and small fiber neuropathies (SFN) in Sjögren's syndrome (SS) requires electroneuromyography (EMG) first, but this is time-consuming and has sometimes a limited accessibility, which can lead to a diagnostic delay. We aimed to identify clinical features that could distinguish SFN from sensitive LFN in SS.

Methods: The study included patients with SS who were monitored in the internal medicine and neurology departments at Angers University Hospital between 2010 and 2016, and who were tested for suspected peripheral neuropathy. Patients with clinical motor involvement were excluded. LFN diagnosis was based on EMG. SFN diagnosis was based on intraepidermal nerve fiber density on skin biopsies in patients with no abnormality on EMG.

Results: LFN and SFN were diagnosed respectively in 22 (6.9%) and 17 (5.4%) patients among 317 patients with SS. Prevalence of anti-SSA antibodies was lower in the SFN group compared to the LFN group (p=0.002). The types of paresthesia did not differ between the 2 groups. After adjustment for age and sex, SFN was associated with dysautonomia (p=0.01, OR 8.4 [CI 95%: 1.7-42.4]) and without length-dependent topography (p=0.03, OR 0.2 [0.04-0.8] in comparison with the LFN group.

Conclusions: An association of non-length-dependent pattern and dysautonomia seems to predict the absence of LFN in SS and encourages the search for SFN. In contrary, patients with length-dependent involvement and without dysautonomia should be prioritized for EMG.
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http://dx.doi.org/10.1016/j.ejim.2020.05.004DOI Listing
September 2020

Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease.

PLoS One 2020 22;15(5):e0233460. Epub 2020 May 22.

Internal Medicine Department, Reference Center for Lysosomal Storage Disorders, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France.

Backgroud: Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy. A nonclassical phenotype has been described with an almost exclusive cardiac involvement. Specific therapies with enzyme substitution or chaperone molecules are now available depending on the mutation carried. Numerous clinical and fundamental studies have been conducted without stratifying patients by phenotype or severity, despite different prognoses and possible different pathophysiologies. We aimed to identify a simple and clinically relevant way to classify and stratify patients according to their disease severity.

Methods: Based on data from the French Fabry Biobank and Registry (FFABRY; n = 104; 54 males), we applied unsupervised multivariate statistics to determine clusters of patients and identify clinical criteria that would allow an effective classification of adult patients. Thanks to these criteria and empirical clinical considerations we secondly elaborate a new score that allow the severity stratification of patients.

Results: We observed that the absence of acroparesthesia or cornea verticillata is sufficient to classify males as having the nonclassical phenotype. We did not identify criteria that significantly cluster female patients. The classical phenotype was associated with a higher risk of severe renal (HR = 35.1; p <10-3) and cardiac events (HR = 4.8; p = 0.008) and a trend toward a higher risk of severe neurological events (HR = 7.7; p = 0.08) compared to nonclassical males. Our simple, rapid and clinically-relevant FFABRY score gave concordant results with the validated MSSI.

Conclusion: Acroparesthesia and cornea verticillata are simple clinical criteria that efficiently stratify Fabry patients, defining 3 different groups: females and males with nonclassical and classical phenotypes of significantly different severity. The FFABRY score allows severity stratification of Fabry patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233460PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244174PMC
August 2020

Coagulation Parameters in Adult Patients With Type-1 Gaucher Disease.

J Hematol 2019 Sep 30;8(3):121-124. Epub 2019 Sep 30.

Internal Medicine Department, Tours University Hospital, University of Tours, UMR INSERM 1253, 37044 Tours, France.

Background: Gaucher disease is a rare inborn error of lysosomal metabolism, characterized by lysosomal storage of the β-glucosylceramide. Bleedings observed in type-1 Gaucher disease (GD1) are commonly attributed to a low platelet count, but they can also occur when the platelet count is normal or slightly low. Abnormal platelet function has been described and deficiencies in coagulation factors too, such as factors II, V, VII, VIII, IX, X, XI, XII, and von Willebrand factor. However, studies are few in number, involving few patients and having varying conclusions. The aim of this study was to analyze clotting factor deficiencies in a larger cohort of French patients with GD1.

Methods: This is an observational national study. The coagulation parameters were collected during routine GD1 monitoring and described retrospectively.

Results: We highlighted low levels of various coagulation factors in 46% of the patients with GD1. The most frequent coagulation abnormalities encountered were factor V, X, XI, and XII deficiencies. Deficits were usually mild and coagulation abnormalities tended to be more frequent in non-splenectomized patients.

Conclusions: In conclusion, frequent and varied coagulation abnormalities were found in a high proportion of GD1 patients.
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http://dx.doi.org/10.14740/jh543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153659PMC
September 2019

Unstimulated whole saliva flow for diagnosis of primary Sjögren's syndrome: time to revisit the threshold?

Arthritis Res Ther 2020 02 24;22(1):38. Epub 2020 Feb 24.

Department of Internal Medicine, University Hospital, 4 rue Larrey, 49000, Angers, France.

Background: Unstimulated whole saliva (UWS) flow rate is one of the ACR/EULAR 2016 criteria for primary Sjögren's syndrome (pSS). With a single threshold of ≤ 0.1 mL/min, UWS flow does not take into account the age- and sex-related physiological variations. Furthermore, it has a low sensitivity for the diagnosis of pSS (about 50%), contrary to the screening test for xerophthalmia, Schirmer's test (sensitivity of about 70%). We aimed to identify UWS thresholds allowing better performances for a screening test for pSS comparable to Schirmer's test, and considering age- and sex-related variations.

Methods: A prospective cohort of 185 patients with oral and/or ocular dryness was classified into 3 groups: men, women < 50 (< 50 years old), and women ≥ 50 (≥ 50 years old). The diagnostic performances of UWS flow rate in these groups were compared in terms of sensitivity, specificity, positive and negative predictive values, and ROC curves. The identification of thresholds that optimize diagnostic performances was carried out using Youden's index.

Results: The diagnostic performances of UWS flow rate varied according to age and sex. UWS had poor diagnostic performances whatever the threshold in the women ≥ 50 group. The threshold of 0.2 mL/min had a sensitivity of ≥ 70% and a specificity of ≥ 50% in both men and women < 50 groups. In the whole population and compared to the current cutoff, a threshold of 0.2 mL/min increased sensitivity (+ 19.8%) and positive (+ 2.3%) and negative (+ 7.0%) predictive values, with a better specificity (65.2%) than Schirmer's test.

Conclusion: For objective assessment of xerostomia, raising the threshold of the UWS flow rate to 0.2 mL/min would optimize its screening performances for pSS.
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http://dx.doi.org/10.1186/s13075-020-2132-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041275PMC
February 2020

Strength of the Association of Elevated Vitamin B12 and Solid Cancers: An Adjusted Case-Control Study.

J Clin Med 2020 Feb 9;9(2). Epub 2020 Feb 9.

Department of Internal Medicine, Angers University Hospital, 49933 Angers, France.

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 ≥ 1000 ng/L with 785 controls matched for sex and age with B12 < 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 ≥ 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.
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http://dx.doi.org/10.3390/jcm9020474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073937PMC
February 2020

Pasteurella bacteraemia: Impact of comorbidities on outcome, based on a case series and literature review.

Int J Infect Dis 2020 Mar 8;92:89-96. Epub 2020 Jan 8.

Department of Internal Medicine, Angers University Hospital, 4, rue Larrey, 49933 Angers, France. Electronic address:

Objectives: Pasteurella bacteraemia is rare, but has been associated with a high mortality rate. The aim of this study was to estimate the impact of comorbidities on patients with Pasteurella bacteraemia.

Methods: All cases of Pasteurella bacteraemia in adults treated in our centre between January 2008 and December 2017 were included retrospectively and compared with cases identified in a systematic review of the literature via MEDLINE covering the years 1951-2017. The epidemiological, bacteriological, and clinical data were collected, as well as the instances of death after 30 days.

Results: Twenty cases of Pasteurella bacteraemia identified in our centre and 99 cases from the literature review were included. A major comorbidity was found in 80/119 (67.2%) patients. The death rate at 30 days was 31.1%. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Age was not associated with mortality. On multivariate analysis, the only factor associated with mortality was a major comorbidity (odds ratio 2.78, 95% confidence interval 1.01-7.70; p = 0.04).

Conclusions: This study confirms the high mortality rate and highlights the importance of the host background, independent of age, in Pasteurella bacteraemia. Clinicians should be aware of the comorbidities in cases of Pasteurella infection, due to the poor prognosis of bacteraemia.
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http://dx.doi.org/10.1016/j.ijid.2020.01.003DOI Listing
March 2020

Granulomatosis-associated myositis: High prevalence of sporadic inclusion body myositis.

Neurology 2020 03 27;94(9):e910-e920. Epub 2019 Dec 27.

From the Département d'Immunologie Clinique et Médecine Interne (Y.D.) and Département de Rhumatologie (J.-E.G., J.S., A.M.), Centre de Référence des Maladies Auto-immunes Rares, Département d'Immunobiologie (B.N.), Département de Pathologie (B.L.), Département de Neurologie, Centre de Référence des Maladies Neuro-musculaires (A.E.-L.), and Institut de Physiologie EA 3072, Service de Physiologie et d'Explorations Fonctionnelles (B.G., A.M.), Hôpitaux Universitaires de Strasbourg; Département de Médecine Interne et Immunologie Clinique (Y.A., O.B., B.H., K.M.), Centre de Référence des Maladies Neuro-Musculaires Paris Est, Assistance Publique-Hôpitaux de Paris (AP-HP), DHU I2B, Sorbonne Universités UPMC Univ Paris 06, Inserm, UMR 974, Centre de Recherche en Myologie, Hôpital Universitaire Pitié-Salpêtrière; Département de Neuropathologie (S.L.-L.), Centre de Référence des Maladies Neuro-Musculaires Paris Est, Hôpital Universitaire Pitié-Salpêtrière; Fédération de Médecine Translationnelle de Strasbourg (B.L., J.-E.G., B.G., J.S., A.M.), Université de Strasbourg; Département de Rhumatologie (D.W.), Hôpital Universitaire de Besançon, France; Département de Rhumatologie (C.V.F.), Hôpital Universitaire Sart-Tilman, Liège, Belgium; Departement de Rhumatologie (N.P.), Hôpital Universitaire de Bordeaux; Departement de Médicine Interne (E.M.), Hôpital Universitaire Louis Mourier, Colombes; Departement de Médicine Interne et Maladies Vasculaires (C.L.), Hôpital Universitaire d'Angers; Departement de Médicine Interne (O.H.), Hôpital Emile Muller, Mulhouse; Departement de Médicine Interne (J.M.), Hôpital Universitaire de Tours, France.

Objective: To refine the predictive significance of muscle granuloma in patients with myositis.

Methods: A group of 23 patients with myositis and granuloma on muscle biopsy (granuloma-myositis) from 8 French and Belgian centers was analyzed and compared with (1) a group of 23 patients with myositis without identified granuloma (control-myositis) randomly sampled in each center and (2) a group of 20 patients with sporadic inclusion body myositis (sIBM) without identified granuloma (control-sIBM).

Results: All but 2 patients with granuloma-myositis had extramuscular involvement, including signs common in sarcoidosis that were systematically absent in the control-myositis and the control-sIBM groups. Almost half of patients with granuloma-myositis matched the diagnostic criteria for sIBM. In these patients, other than the granuloma, the characteristics of the myopathy and its nonresponse to treatment were similar to the control-sIBM patients. Aside from 1 patient with myositis overlapping with systemic sclerosis, the remaining patients with granuloma-myositis did not match the criteria for a well-defined myositis subtype, suggesting pure sarcoidosis. Matching criteria for sIBM was the sole feature independently associated with nonresponse to myopathy treatment in patients with granuloma-myositis.

Conclusion: Patients with granuloma-myositis should be carefully screened for sIBM associated with sarcoidosis in order to best tailor their care.
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http://dx.doi.org/10.1212/WNL.0000000000008863DOI Listing
March 2020

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome.

Sci Rep 2019 12 11;9(1):18817. Epub 2019 Dec 11.

Department of internal medicine, University Hospital, Angers, 49000, France.

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate. Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment. We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.
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http://dx.doi.org/10.1038/s41598-019-55473-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906377PMC
December 2019

Mutations in MTHFR and POLG impaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis.

J Hum Genet 2020 Jan 23;65(2):91-98. Epub 2019 Oct 23.

INSERM UMR_S 1256, NGERE-Nutrition, Genetics, and Environmental Risk Exposure and Reference Centre for Inherited Metabolic Diseases (ORPHA67872), University Hospital of Nancy and Faculty of Medicine of Nancy, University of Lorraine, Nancy, France.

Hereditary spastic paraplegias (HSPs) are characterized by lower extremity spasticity and weakness. HSP is often caused by mutations in SPG genes, but it may also be produced by inborn errors of metabolism. We performed next-generation sequencing of 4813 genes in one adult twin pair with HSP and severe muscular weakness occurring at the same age. We found two pathogenic compound heterozygous variants in MTHFR, including a variant not referenced in international databases, c.197C>T (p.Pro66Leu) and a known variant, c.470G>A (p.Arg157Gln), and two heterozygous pathogenic variants in POLG, c.1760C>T (p.Pro587Leu) and c.752C>T (p.Thr251Ile). MTHFR and POLG mutations were consistent with the severe muscle weakness and the metabolic changes, including hyperhomocysteinemia and decreased activity of both N(5,10)methylenetetrahydrofolate reductase (MTHFR) and complexes I and II of the mitochondrial respiratory chain. These data suggest the potential role of MTHFR and POLG mutations through consequences on mitochondrial dysfunction in the occurrence of spastic paraparesis phenotype with combined metabolic, muscular, and neurological components.
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http://dx.doi.org/10.1038/s10038-019-0689-yDOI Listing
January 2020

Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.

J Inherit Metab Dis 2019 03 17;42(2):333-352. Epub 2019 Feb 17.

Hospital Infantil Miguel Servet, Zaragoza, Spain.

Aim: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry.

Results: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities.

Conclusion: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.
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http://dx.doi.org/10.1002/jimd.12041DOI Listing
March 2019

Arthritis in primary Sjögren's syndrome: Characteristics, outcome and treatment from French multicenter retrospective study.

Autoimmun Rev 2019 Jan 5;18(1):9-14. Epub 2018 Nov 5.

Service de médecine interne, Hôpital Saint-Antoine, APHP, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), F-75012 Paris, France. Electronic address:

Objective: To describe the characteristics and the outcome of primary Sjögren Syndrome (pSS) associated arthritis and to compare the efficacy of different therapeutic regimen.

Methods: We conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of pSS and at least one episode of clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls).

Results: 57 patients (93% women) were included with a median age of 54 years [45-63]. Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p = .007) and a higher ESSDAI score (8 [6-12] vs. 2 [1-4], p < .0001). There was no difference concerning CRP levels, rheumatoid factor and cyclic citrullinated peptide (CCP)-antibodies positivity. Among 57 patients with synovitis, 101 various treatment courses have been used during the follow-up of 40 [22.5-77] months. First treatment course consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). HCQ, MTX, and RTX were associated with a significant reduction of tender and swollen joint count, and a significant steroids-sparing effect. No difference could be shown for the joint response between these treatment regimens.

Conclusion: pSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined.
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http://dx.doi.org/10.1016/j.autrev.2018.06.015DOI Listing
January 2019

Deep characterization of the anti-drug antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY.

Orphanet J Rare Dis 2018 07 31;13(1):127. Epub 2018 Jul 31.

Sorbonne Université, INSERM, UMR 974, Centre of Research in Myology, Association Institut de Myologie, Pitié-Salpêtrière University Hospital, 75013, Paris, France.

Background: Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies (ERT) have been available. We aimed to determine the epidemiology and the functional characteristics of anti-drug antibodies. Patients from the French multicenter cohort FFABRY (n = 103 patients, 53 males) were prospectively screened for total anti-agalsidase IgG and IgG subclasses with a home-made enzyme-linked immunosorbent assay (ELISA), enzyme-inhibition assessed with neutralization assays and lysoGb3 plasma levels, and compared for clinical outcomes.

Results: Among the patients exposed to agalsidase, 40% of men (n = 18/45) and 8% of women (n = 2/25) had antibodies with a complete cross-reactivity towards both ERTs. Antibodies developed preferentially in men with non-missense GLA mutations (relative risk 2.88, p = 0.006) and classic phenotype (58.6% (17/29) vs 6.7% (1/16), p = 0.0005). Specific anti-agalsidase IgG1 were the most frequently observed (16/18 men), but the highest concentrations were observed for IgG4 (median 1.89 μg/ml, interquartile range (IQR) [0.41-12.24]). In the men exposed to agalsidase, inhibition was correlated with the total IgG titer (r = 0.67, p < 0.0001), especially IgG4 (r = 0.75, p = 0.0005) and IgG2 (r = 0.72, p = 0.001). Inhibition was confirmed intracellularly in Fabry patient leucocytes cultured with IgG-positive versus negative serum (median: 42.0 vs 75.6%, p = 0.04), which was correlated with IgG2 (r = 0.67, p = 0.017, n = 12) and IgG4 levels (r = 0.59, p = 0.041, n = 12). Plasma LysoGb3 levels were correlated with total IgG (r = 0.66, p = 0.001), IgG2 (r = 0.72, p = 0.004), IgG4 (r = 0.58, p = 0.03) and IgG1 (r = 0.55, p = 0.04) titers. Within the classic group, no clinical difference was observed but lysoGb3 levels were higher in antibody-positive patients (median 33.2 ng/ml [IQR 20.6-55.6] vs 12.5 [10.1-24.0], p = 0.005).

Conclusion: Anti-agalsidase antibodies preferentially develop in the severe classic Fabry phenotype. They are frequently associated with enzyme inhibition and higher lysoGb3 levels. As such, they could be considered as a hallmark of severity associated with the classic phenotype. The distinction of the clinical phenotypes should now be mandatory in studies dealing with Fabry disease and its current and future therapies.
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http://dx.doi.org/10.1186/s13023-018-0877-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069887PMC
July 2018

Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients.

J Autoimmun 2018 07 17;91:55-60. Epub 2018 Apr 17.

Sorbonne Universités, UPMC Université Paris 06, UMR 7211, Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, National center for Autoimmune and Systemic rare disease, National center for Autoinflammatory diseases and amyloidosis, F-75013, Paris, France. Electronic address:

Objectives: To assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).

Methods: We conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score).

Results: Forty-six patients with TA were included, with a median age of 43 years [29-54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2-3] at baseline to 0 [0-1] and 0 at 3 and 6 months, respectively; p < 0.0001). The daily prednisone dose also decreased from 15 mg [8-19] at baseline to 4 mg [5-21] and 5 mg [4.5-9] at 3 and 6 months, respectively (p < 0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% [CI 95%; 0.7-0.95], 72% [CI 95%; 0.55-0.95] and 48% [CI 95%; 0.2-0.1] at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 [CI 95%; 1.08-29], p = 0.041), and C-reactive protein level (HR 1.16 [CI 95%; 1.01-1.31], P = 0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (p = 0.02).

Conclusion: This large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.
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http://dx.doi.org/10.1016/j.jaut.2018.04.002DOI Listing
July 2018

Intra-venous bevacizumab in hereditary hemorrhagic telangiectasia (HHT): A retrospective study of 46 patients.

PLoS One 2017 30;12(11):e0188943. Epub 2017 Nov 30.

Médecine Interne - Maladies Multi-Organiques, Hôpital Saint Eloi, Montpellier, France.

Background: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France.

Methods: Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network.

Results: Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect's duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients.

Conclusion: Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188943PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708634PMC
January 2018

Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review.

Autoimmun Rev 2017 Dec 14;16(12):1219-1223. Epub 2017 Oct 14.

AP-HP, Hôpital Saint-Antoine, service de médecine interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC University, Paris 06, F-75012, Paris, France. Electronic address:

Background: Cogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.

Patients And Methods: We conducted a French nationwide retrospective study of patients with Cogan syndrome (n=40) and a literature review of cases (n=22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists.

Results: We included 62 patients (31 females) (median age 37years [range 2-76]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n=43; 70%) or associated with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95% confidence interval 1.65; 260], p=0.019).

Conclusion: Infliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.
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http://dx.doi.org/10.1016/j.autrev.2017.10.005DOI Listing
December 2017

Pulmonary hypertension subtypes associated with hereditary haemorrhagic telangiectasia: Haemodynamic profiles and survival probability.

PLoS One 2017 5;12(10):e0184227. Epub 2017 Oct 5.

Service de Médecine interne, CHRU de Lille, Université de Lille, Lille, France.

Background: Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT).

Methods And Results: We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH.

Conclusion: This study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184227PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628806PMC
October 2017
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