Publications by authors named "Anne-Laure Fauchais"

66 Publications

High incidence of giant cell arteritis during the COVID-19 pandemic: no causal relationship but possible involvement of stress.

Clin Exp Rheumatol 2021 Apr 1. Epub 2021 Apr 1.

Bacteriology-Virology-Hygiene Department, Dupuytren University Hospital, Limoges, and UMR INSERM 1092 RESINFIT, University of Limoges, France.

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April 2021

An immunohistochemical analysis of fibroblasts in giant cell arteritis.

Ann Diagn Pathol 2021 Mar 1;52:151728. Epub 2021 Mar 1.

Department of Internal Medicine, Dupuytren Hospital, Limoges, France; EA3842-CaPTuR, Contrôle de l'Activation Cellulaire, Progression Tumorale et Résistance thérapeutique, Faculty of Medicine, Limoges, France.

Background: Giant cell arteritis (GCA) is a systemic vasculitis of large and medium vessels characterized by an inflammatory arterial infiltrate. GCA begins in the adventitia and leads to vascular remodeling by promoting proliferation of myofibroblasts in the intima. The morphology of the fibroblasts in the adventitia in GCA is unclear. Access to temporal artery biopsies allows morphological studies and evaluation of the microenvironment of the arterial wall. We evaluated the distribution of vascular fibroblasts and of markers of their activation in GCA.

Methods: Formalin-fixed paraffin-embedded tissue sections from 29 patients with GCA and 36 controls were examined. Immunohistochemistry was performed for CD90, vimentin, desmin, alpha-smooth muscle actin (ASMA), prolyl-4-hydroxylase (P4H), and myosin to evaluate the distribution of fibroblasts within the intima, media, and adventitia.

Results: Temporal arteries from patients with GCA showed increased levels of CD90, vimentin, and ASMA in the adventitia and intima compared to the controls. Desmin was expressed only in the media in both groups. P4H was expressed similarly in the adventitia and intima in the two groups. Adventitial and intimal CD90 cells co-expressed P4H, ASMA, and myosin at a high level in GCA.

Conclusion: The results suggest a role for adventitial fibroblasts in GCA. Inhibiting the differentiation of adventitial fibroblasts to myofibroblasts has therapeutic potential for GCA.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151728DOI Listing
March 2021

Epidemiology of cutaneous involvement in Sjögren syndrome: Data from three French pSS populations (TEARS, ASSESS, diapSS).

Joint Bone Spine 2021 Feb 19;88(4):105162. Epub 2021 Feb 19.

Inserm 1227, LabEx IGO, rhumatologie, centre de référence maladies rares CERAINO, université de Bretagne Occidentale, CHU de Brest, 29200 Brest, France. Electronic address:

Objective: To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS).

Methods: We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100).

Results: Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P<0.001), muscular (P<0.01), haematological (P<0.05), biological (P<0.05), history of arthritis (P<0.01), splenomegaly (P<0.05) and higher gamma globulin levels (P<0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P<0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS>50; 48.2%) and found that patients with dry skin had higher VAS pain (P<0.01) and drought (P<0.01) scores.

Conclusion: ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.
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http://dx.doi.org/10.1016/j.jbspin.2021.105162DOI Listing
February 2021

Abdominal symptoms during Sjogren's syndrome: a pilot study.

Adv Rheumatol 2021 01 19;61(1). Epub 2021 Jan 19.

Internal Medicine Department, Limoges University Hospital, 16 rue du Professeur Bernard Descottes, 87042, Limoges, France.

Background: Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease.

Methods: One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected.

Results: Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ± 5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each).

Conclusions: The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms.

Trial Registration: NCT03157011 . Date of registration: July 17, 2017.
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http://dx.doi.org/10.1186/s42358-021-00164-wDOI Listing
January 2021

Giant cell arteritis or polymyalgia rheumatica after influenza vaccination: A study of 12 patients and a literature review.

Autoimmun Rev 2021 Feb 14;20(2):102732. Epub 2020 Dec 14.

Departments of Internal Medicine, University Hospital of Limoges, Limoges Cedex, France.

Introduction: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are inflammatory rheumatic diseases common in people over the age of 50 years. Seasonal influenza vaccination (IV) is strongly recommended in this population, among whom it is considered to be effective and well tolerated. IV-induced GCA or PMR are thought to be exceptional.

Patients And Methods: We retrieved all post-IV cases from an inception cohort of patients with newly diagnosed GCA. We also included two patients with post-IV PMR and reviewed all published reports of post-IV GCA or PMR, with selection of cases demonstrating disease onset within 1 month following IV. We compared the results of HLA-DRB1 typing, performed in seven patients with post-IV GCA or PMR, with those of 11 GCA patients with familial aggregation and 16 randomly selected GCA patients without a reported trigger.

Results: Of 358 GCA recruited since 2002, 10 (2.8%) qualified for post-IV GCA, of whom two also showed familial aggregation. Thirty-two patients (19 with GCA and 13 with PMR) including our patients were reviewed; their mean age was 71.8 ± 7.4 years and the M/F ratio was 0.8. Six patients (19%) had a history of PMR. Patients with post-IV GCA/PMR had the DRB1*13:01 haplotype more frequently compared to those with familial GCA (5/7 vs. 2/11, p = 0.048) or with GCA without a known trigger (3/16, p = 0.026). Post-IV PMR generally appeared self-limited, whereas post-IV GCA often displayed a more protracted course (chronic relapsing disease in one-third of the patients).

Conclusion: Post-IV onset of GCA/PMR is not an exceptional occurrence and may be part of the spectrum of the autoimmune syndrome induced by adjuvants (ASIA). IV can trigger GCA or PMR, especially in persons at higher spontaneous risk, such as those with a personal or familial history of GCA/PMR. Whether the presence of the DRB1*13:01 allele further increases the risk of post-IV GCA/PMR through a stronger vaccine-induced immune reaction deserves further investigation. Unlike PMR, GCA can be a serious complication of IV.
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http://dx.doi.org/10.1016/j.autrev.2020.102732DOI Listing
February 2021

Risk profiling for a refractory course of giant cell arteritis: The importance of age and body weight: "Risk profiling for GC resistance in GCA".

Semin Arthritis Rheum 2020 12 28;50(6):1252-1261. Epub 2020 Sep 28.

Departments of 1Internal Medicine, University Hospital of Limoges, France.

Background: Giant cell arteritis (GCA) is a disease that relapses often, and some patients run a refractory course. Although prompt recognition of resistant GCA is a major issue, there is no well-recognized, baseline risk factor for poor response to glucocorticoid (GC) treatment.

Methods: We included all patients consecutively diagnosed with GCA and homogeneously treated since 1976 in a single department and regularly followed-up for at least 18 months. Using a set of customized criteria defining response to GCs, we separated patients into highly responsive, usually responsive, dependent on GCs, and resistant to GCs. We determined which of the baseline variables were associated with GC-resistance and conducted factor analyses of mixed data and decision tree analyses. We also determined whether being GC-resistant was associated with poorer tolerance to GCs and higher death rates.

Results: In all, 455 patients were followed for 93.4 ± 67.6 (standard deviation) months; 41 (9%) and 21 (4.6%) patients developed GC-dependent and GC-resistant disease, respectively. Factor analyses suggested an association between clinical pattern and degree of responsiveness to GCs; The decision tree analyses, built on an age at GCA onset 〈 66 years and body weight 〉 71 kg, delineated a high risk profile (44% of the patients who featured both characteristics were GC-resistant vs. less than 3% who featured neither, p < 0.001). Infections were more prevalent in the GC-resistant or GC-dependent patients, but without decreasing their survival.

Conclusion: Extra-cranial, large-vessel GCA may be associated with prolonged GC requirements. A simple combination of age and body weight defined a subgroup of patients at high risk for developing GC resistance. Our findings need confirmation in prospective controlled studies.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.009DOI Listing
December 2020

[Low-dose methotrexate].

Rev Prat 2020 03;70(3):239-245

Service de médecine interne A, hôpital universitaire Dupuytren, Limoges, France.

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March 2020

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

Rheumatology (Oxford) 2021 02;60(2):675-681

Service de Rhumatologie, CNR RESO, CHU Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Objectives: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS).

Methods: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed.

Results: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission.

Conclusions: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.
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http://dx.doi.org/10.1093/rheumatology/keaa257DOI Listing
February 2021

BDNF belongs to the nurse-like cell secretome and supports survival of B chronic lymphocytic leukemia cells.

Sci Rep 2020 07 28;10(1):12572. Epub 2020 Jul 28.

Equipe Accueil 3842 CAPTuR, Faculty of Medicine, Limoges University, 2, Rue du Docteur Marcland, 87025, Limoges Cedex, France.

Evading apoptosis and sustained survival signaling pathways are two central hallmarks of B-cell chronic lymphocytic leukemia (B-CLL) cells. In this regard, nurse-like cells (NLC), the monocyte-derived type 2 macrophages, deliver stimulatory signals via B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and the C-X-C Motif Chemokine Ligand 12 (CXCL12). Previously, we demonstrated that brain-derived neurotrophic factor (BDNF) protects B-CLL cells from spontaneous apoptosis by activating the oncogenic complex NTSR2-TrkB (neurotensin receptor 2-tropomyosin-related kinase receptor B), only overexpressed in B-CLL cells, inducing anti-apoptotic protein Bcl-2 (B-cell lymphoma 2) expression and Src kinase survival signaling pathways. Herein, we demonstrate that BDNF belongs to the NLC secretome and promotes B-CLL survival. This was demonstrated in primary B-CLL co-cultured with their autologous NLC, compared to B-CLL cells cultured alone. Inhibition of BDNF in co-cultures, enhances B-CLL apoptosis, whereas its exogenous recombinant activates pro-survival pathways in B-CLL cultured alone (i.e. Src activation and Bcl-2 expression), at a higher level than those obtained by the exogenous recombinant cytokines BAFF, APRIL and CXCL12, the known pro-survival cytokines secreted by NLC. Together, these results showed that BDNF release from NLC trigger B-CLL survival. Blocking BDNF would support research strategies against pro-survival cytokines to limit sustained B-CLL cell survival.
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http://dx.doi.org/10.1038/s41598-020-69307-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387561PMC
July 2020

Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis.

Arthritis Res Ther 2020 02 18;22(1):30. Epub 2020 Feb 18.

Univ. Lille, Institute for Translational Research in Inflammation (INFINITE), F-59000, Lille, France.

Background: Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival.

Methods: From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes.

Results: A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1-6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2-5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5.

Conclusions: Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.
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http://dx.doi.org/10.1186/s13075-020-2113-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029583PMC
February 2020

Features and prognosis of giant cell arteritis in patients over 85 years of age: A case-control study.

Semin Arthritis Rheum 2019 10 2;49(2):288-295. Epub 2019 Mar 2.

Department of Internal Medicine, Caen University Hospital, Caen, France.

Background: We examined the initial features, course, and prognosis of giant cell arteritis (GCA) in patients ≥ 85 years of age (≥85 year) and compared them to those of younger patients.

Methods: The present retrospective study included all patients who were newly diagnosed with GCA in the Internal Departments of two French University Hospitals from 1976 or 1998 to 2017 and who were followed up for at least 6 months. Logistic regression analyses were conducted to identify baseline and prognostic characteristics associated with being ≥85 year.

Results: Of the 865 patients assessed in this study, 87 were ≥85 year. Compared to younger patients, patients ≥ 85 year had more comorbid conditions (odds ratio [OR] = 1.11-1.74, p < 0.01), less often exhibited polymyalgia rheumatica (PMR; OR = 0.33-0.96, p = 0.04), and more often developed permanent visual loss (OR = 1.29-3.81, p < 0.01). The older patients also showed less dependence on glucocorticoid (GC) medications (OR = 0.23-0.94, p = 0.04), had fewer relapses (OR = 0.31-0.87, p = 0.015), less often recovered from GCA (OR = 0.22-0.69, p < 0.01), and more often died during treatment (OR = 1.45-4.65, p = 0.001) compared to younger patients. Being ≥85 year was the only factor associated with an increased 1-year mortality (hazard ratio = 1.77-5.81, p = 0.0001) for the whole cohort.

Conclusions: GCA in very elderly patients was characterized by a higher rate of severe ischemic complications and an increased risk for early death compared to younger patients. Thus, there is a need for the early diagnosis of GCA and close clinical monitoring in this unique population.
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http://dx.doi.org/10.1016/j.semarthrit.2019.02.011DOI Listing
October 2019

Regulatory Roles of Sortilin and SorLA in Immune-Related Processes.

Front Pharmacol 2018 7;9:1507. Epub 2019 Jan 7.

Faculty of Medicine, University of Limoges, Limoges, France.

Sortilin, also known as Neurotensin Receptor-3, and the sorting-related receptor with type-A repeats (SorLA) are both members of the Vps10p domain receptor family. Initially identified in CNS cells, they are expressed in various other cell types where they exert multiple functions. Although mostly studied for its involvement in Alzheimer's disease, SorLA has recently been shown to be implicated in immune response by regulating IL-6-mediated signaling, as well as driving monocyte migration. Sortilin has been shown to act as a receptor, as a co-receptor and as an intra- and extracellular trafficking regulator. In the last two decades, deregulation of sortilin has been demonstrated to be involved in many human pathophysiologies, including neurodegenerative disorders (Alzheimer and Parkinson diseases), type 2 diabetes and obesity, cancer, and cardiovascular pathologies such as atherosclerosis. Several studies highlighted different functions of sortilin in the immune system, notably in microglia, pro-inflammatory cytokine regulation, phagosome fusion and pathogen clearance. In this review, we will analyze the multiple roles of sortilin and SorLA in the human immune system and how their deregulation may be involved in disease development.
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http://dx.doi.org/10.3389/fphar.2018.01507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330335PMC
January 2019

Is early-onset primary Sjögren's syndrome a worse prognosis form of the disease?

Rheumatology (Oxford) 2019 07;58(7):1163-1167

Service de médecine interne, CHU Claude Huriez, Lille Cedex, France.

Objectives: Onset of primary SS is usually between 40 and 60 years of age, with severe systemic complications in 15% of cases. We sought to determine whether early-onset disease is related to a specific phenotype and if it is predictive of a poor outcome.

Methods: Biological and clinical data from 393 patients recruited in the ASSESS cohort, a French multicentre prospective cohort, were compared according to age at diagnosis.

Results: Fifty-five patients had early-onset disease, defined as age ⩽35 years at diagnosis, and presented a significantly higher frequency of salivary gland enlargement (47.2% vs 33.3%, P = 0.045), adenopathy (25.5% vs 11.8%, P = 0.006), purpura (23.6% vs 9.2%, P = 0.002) and renal involvement (16.4% vs 4.4%, P = 0.003). They had a higher frequency of hypergammaglobulinaemia (60.8% vs 26.6%, P < 0.001), RF positivity (41.5% vs 20.2%, P < 0.001), low C3 level (18.9% vs 9.1%, P = 0.032), low C4 level (54.7% vs 40.2%, P = 0.048) and autoantibodies [84.6% with anti-SSA vs 54.4% (P < 0.001) and 57.7% with anti-SSB vs 29.7% (P < 0.001)]. The change in ESSDAI scores between baseline and the 5-year follow-up was significantly different (P = 0.005) with a trend for worsening in the early-onset group (0.72, P = 0.27) and a significant improvement in the later onset group (-1.27, P < 0.0001).

Conclusion: Early-onset primary SS is associated with a specific phenotype defined by clinical and biological features known to be predictive factors of severe systemic disease. Interestingly, we showed a different evolution of the ESSDAI score depending on the age at disease onset, patients with early-onset disease tending to worsen over time.
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http://dx.doi.org/10.1093/rheumatology/key392DOI Listing
July 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

Tocilizumab as an add-on therapy to glucocorticoids during the first 3 months of treatment of Giant cell arteritis: A prospective study.

Eur J Intern Med 2018 11 24;57:96-104. Epub 2018 Jul 24.

Department of Internal Medicine and Clinical Immunology, CHU Dijon Bourgogne, Dijon, France; University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-21000 Dijon, France.

Background: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA).

Methods: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded.

Results: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study.

Conclusion: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis.

Trial Registration: ClinicalTrials.gov (NCT01910038).
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http://dx.doi.org/10.1016/j.ejim.2018.06.008DOI Listing
November 2018

Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function.

Endoscopy 2019 01 12;51(1):40-49. Epub 2018 Jun 12.

Service de Médecine Nucléaire, CHU Limoges, Limoges, France.

Background: Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM.

Methods: 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months.

Results: Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5;  < 0.001), quality of life, and gastric emptying (T½: 100 vs. 345 minutes,  < 0.001; %H2: 56.0 % vs. 81.5 %,  < 0.001; %H4: 15.0 % vs. 57.5 %,  = 0.003) at 3 months. The clinical success of G-POEM using the functional imaging probe inflated to 50 mL had specificity of 100 % and sensitivity of 72.2 % ( = 0.04; 95 % confidence interval 0.51 - 0.94; area under the curve 0.72) at a distensibility threshold of 9.2 mm/mmHg.

Conclusion: G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.
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http://dx.doi.org/10.1055/a-0628-6639DOI Listing
January 2019

Rapid Push vs Pump-Infused Subcutaneous Immunoglobulin Treatment: a Randomized Crossover Study of Quality of Life in Primary Immunodeficiency Patients.

J Clin Immunol 2018 05 31;38(4):503-512. Epub 2018 May 31.

Centre Hospitalier Edouard Herriot, Lyon, France.

Purpose: Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient's life quality index (LQI).

Methods: This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%.

Results: Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p = 0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump.

Conclusions: Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician's armamentarium which is preferred by some patients and is cost-effective. CLINICALTRIALS.

Gov Identifier: NCT02180763 CLINICAL IMPLICATIONS: Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week. This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician's armamentarium.
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http://dx.doi.org/10.1007/s10875-018-0507-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028863PMC
May 2018

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

Autoimmun Rev 2018 Jul 3;17(7):653-659. Epub 2018 May 3.

National Referral Centre for rare Juvenile Rheumatological and Autoimmune Diseases, Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, Claude Bernard University Lyon 1, Lyon, France. Electronic address:

Objective: The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown.

Results: Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time.

Conclusion: Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.
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http://dx.doi.org/10.1016/j.autrev.2018.01.022DOI Listing
July 2018

Development of Giant Cell Arteritis after Treating Polymyalgia or Peripheral Arthritis: A Retrospective Case-control Study.

J Rheumatol 2018 05 15;45(5):678-685. Epub 2018 Mar 15.

From the Department of Internal Medicine, University Hospital of Limoges; Functional Unit of Clinical Research and Biostatistics, Limoges School of Medicine, Limoges Cedex; Department of Internal Medicine, Caen University Hospital, Caen, France.

Objective: We investigated the development of giant cell arteritis (GCA) in patients with prior diagnoses of isolated polymyalgia rheumatica and/or peripheral arthritis (PMR/PA), and the potentially relevant characteristics of both illnesses in such patients.

Methods: We retrospectively compared the features of 67 patients at the onset of PMR/PA, and their outcomes, to those of a random group of 65 patients with PMR/PA who did not develop late GCA. We also compared the features and outcomes of patients with late GCA to those of a random sample of patients with more usual GCA (65 with concurrent PMR/PA and 65 without).

Results: Patients with late GCA represented 7.4% of all patients with GCA included in a large hospital-based inception cohort. PMR/PA preceded overt GCA by 27 months on average. Permanent visual loss developed in 10 patients, including 8 of 48 (17%) patients featuring cranial arteritis. A questionable female predominance was the only distinguishing feature of PMR/PA evolving into GCA; late GCA more often featured subclinical aortitis (OR 6.42, 95% CI 2.39-17.23; p < 0.001), headache (OR 0.44, 95% CI 0.19-1.03; p = 0.06), and fever (OR 0.29, 95% CI 0.13-0.64; p = 0.002) less often compared to the more usual form of GCA. Patients with either form of GCA experienced similar outcomes.

Conclusion: A cranial arteritis pattern of late GCA is associated with a significant risk for ischemic blindness. However, compared to the usual form of GCA, late GCA is often less typical, with a higher frequency of silent aortitis. Patients with relapsing/refractory PMR may not be at increased risk for late GCA.
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http://dx.doi.org/10.3899/jrheum.170455DOI Listing
May 2018

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

Ann Rheum Dis 2018 04 6;77(4):563-570. Epub 2018 Jan 6.

UCL Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK.

Objectives: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).

Methods: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).

Results: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.

Conclusions: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.

Trial Registration Number: NCT02339441.
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http://dx.doi.org/10.1136/annrheumdis-2017-211912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890636PMC
April 2018

Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.

Rheumatology (Oxford) 2018 02;57(2):370-381

Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.

Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.

Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).

Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.
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http://dx.doi.org/10.1093/rheumatology/kex410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850714PMC
February 2018

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS).

Ann Rheum Dis 2017 Jul 10;76(7):1207-1218. Epub 2017 Feb 10.

UCL Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK.

Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.

Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.

Results: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.

Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.

Trial Registration Number: NCT02339441.
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http://dx.doi.org/10.1136/annrheumdis-2016-210503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530354PMC
July 2017

A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren's syndrome.

Rheumatology (Oxford) 2017 Mar;56(3):362-370

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris.

Objective.: Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment.

Methods.: We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement.

Results.: A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study.

Conclusion.: Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.
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http://dx.doi.org/10.1093/rheumatology/kew376DOI Listing
March 2017

Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis: A single-center, retrospective study of 70 patients.

Medicine (Baltimore) 2016 Oct;95(42):e4974

Department of Internal Medicine, University Hospital of Limoges Functional unit of Clinical Research and Biostatistics, Limoges School of Medicine, Limoges Cedex, France.

Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group). Of these 70 patients, 63 belonged to an inception cohort of 478 patients, whereas the remaining 7 were referred to our department for resistant GCA. In all, 52 patients were assessable for DDS efficacy. The baseline characteristics of the DDS-1 patients were similar to those of 395 GCA patients (control group) who received prednisone alone. DDS-1 patients had a more sustained decrease in GC dose with a lower mean prednisone dose at 12 months, and they comprised higher proportions who achieved GC withdrawal within the first year, who stopped prednisone treatment, and who recovered from GCA (P < 0.001 for each variable). Patients in the DDS-2 group achieved a mean rate of prednisone reduction of 65% and a prednisone dose reduction of 16.9 ± 13.3 mg/d. The monthly decreases in the prednisone dose were 2.4 and 1.25 mg in DDS-1 and DDS-2 patients, respectively. DDS-induced side effects were recorded in 44 (64%) assessable patients. These side effects led to lowering of the DDS dose by 25 mg/d in 11 (16%) patients and permanent cessation of DDS in 14 patients (20%), due to allergic skin rash in 7, agranulocytosis in 2, icteric hepatitis in 2, and excessive hemolysis in 2 patients. DDS is a potent GC-sparing agent in GCA that should be evaluated in prospective studies. However, DDS use should be restricted to refractory GCA patients due to its toxicity, and close clinical and laboratory monitoring for 3 months is necessary.
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http://dx.doi.org/10.1097/MD.0000000000004974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079312PMC
October 2016

Amaigrissement à tous les âges.

Rev Prat 2016 Sep;66(7):e299-e304

Service de médecine interne A, CHU Dupuytren, 87000 Limoges, France.

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September 2016

Contribution of dot-blot assay to the diagnosis and management of myositis: a three-year practice at a university hospital centre.

Clin Exp Rheumatol 2016 Sep-Oct;34(5):918-924. Epub 2016 Aug 2.

Department of Internal Medicine, Limoges University Hospital, France.

Objectives: Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases with wide clinical spectrum that may lead to delayed diagnosis. The aim of this study was to examine the impact of IIM-specific dot-blot assay on diagnostic process of patients presenting with muscular or systemic symptoms evocating of IIM.

Methods: We collected all the prescriptions of an IIM specific dot-blot assay (8 autoantigens including Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, PM/Scl and Scl-70) over a 38-month period.

Results: 316 myositis dot-blot assays (MSD) were performed in 274 patients (156 women, mean age 53±10.6 years) referring for muscular and/or systemic symptoms suggesting IIM. The timing of dot prescription through the diagnostic process was highly variable: without (35%), concomitantly (16%) or after electromyographic studies (35%). Fifty-nine patients (22%) had IIM according to Bohan and Peter's criteria. Among them, 29 (49%) had positive dot (8 Jo-1, 6 PM-Scl, 5 PL-12, 5 SRP, 2 Mi-2, 2 PL-7 and 1 Ku). Various other diagnoses were performed including 35 autoimmune disease or granulomatosis (12%), 19 inflammatory rheumatic disease (7%), 16 non inflammatory muscular disorders (6%), 10 drug-induced myalgia (4%), 11 infectious myositis (4%). Except 11 borderline SRP results and one transient PM-Scl, MSD was positive only in one case of IIM. Dot allowed clinicians to correct diagnosis in 4 cases and improved the diagnosis of IIM subtypes in 4 cases.

Conclusions: This study reflects the interest of myositis dot in the rapid diagnosis process of patients with non-specific muscular symptoms leading to various diagnoses including IIM.
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January 2017

Venous thrombosis in patients with giant cell arteritis: Features and outcomes in a cohort study.

Joint Bone Spine 2017 May 17;84(3):323-326. Epub 2016 Jun 17.

Faculté de médecine de Limoges, centre d'épidémiologie, de biostatistique et de méthodologie de la recherche, 87025 Limoges cedex, France.

Objectives: To describe the features and outcomes of patients with giant cell arteritis who developed venous thrombosis.

Methods: Inception cohort study including 428 newly diagnosed patients of giant cell arteritis from 1976 to 2014. Clinical and biological data and outcomes were analysed by comparing patients with and without venous thrombosis.

Results: Twenty-six patients (6%) developed venous thrombosis, 12 of whom presented with pulmonary embolism. The mean time between the onset of giant cell arteritis symptoms and venous thrombosis occurrence was 248.8±215.0 days. No difference was observed between the two groups in clinical or laboratory data collected at diagnosis. The mean time from the start of prednisone to venous thrombosis diagnosis was 187.7±217.0 days. The average dose of prednisone at venous thrombosis onset was 21.5mg/day. The venous thrombosis group had a higher number of glucocorticoid-related adverse effects (mean, 3.1 vs 1.1; P<0.0001), a higher mortality rate (58% vs 33%, P=0.01) and a higher proportion of deaths occurring during glucocorticoid treatment (31% vs 14%, P=0.03). Death was related to venous thrombosis in four patients.

Discussion: The occurrence of overt venous thrombosis is more than anecdotal among patients treated for giant cell arteritis. Venous thrombosis does not rely on the active phase of giant cell arteritis, but could be associated with long-term use of glucocorticoids. Because venous thrombosis may be associated with an increased mortality risk in patients with giant cell arteritis, a high index of suspicion should be applied in appropriate settings, especially in patients experiencing multiple glucocorticoid-related adverse effects.
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http://dx.doi.org/10.1016/j.jbspin.2016.04.011DOI Listing
May 2017

Is rituximab an effective treatment of refractory calcinosis?

BMJ Case Rep 2016 May 31;2016. Epub 2016 May 31.

Internal Medicine Department, Limoges University Hospital, Limoges, France.

Calcinosis, the deposition of calcified material in soft tissues, is frequently seen in systemic sclerosis and dermatomyositis. Treatment options are limited, with disappointing results. Some recent case reports suggest that rituximab may be an attractive therapeutic option. In case 1, a 54-year-old woman who presented with rheumatoid arthritis in association with scleromyositis was treated with rituximab for rheumatoid arthritis. Despite this, she developed multiple progressive calcinosis, necessitating extracorporeal shock wave lithotripsy to limit calcinosis extension and pain. In case 2, a 38-year-old man, previously treated for an anti-Pm/Scl-positive polymyositis/scleroderma overlap syndrome, presented with multiple tumoural periarticular calcinosis, which progressed despite bisphosphonates, sodium thiosulfate and thalidomide. We decided to start rituximab. Progression of calcinosis was still evident 6 and 12 months after anti-CD20 treatment. Many treatments have been tried to treat calcinosis without demonstrated effectiveness. Presently, rituximab cannot be recommended for this indication in the absence of successful controlled trials.
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http://dx.doi.org/10.1136/bcr-2015-213179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904422PMC
May 2016

Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

J Autoimmun 2016 08 25;72:73-83. Epub 2016 May 25.

INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France; Department of Internal Medicine and Clinical Immunology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France. Electronic address:

CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands.
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http://dx.doi.org/10.1016/j.jaut.2016.05.008DOI Listing
August 2016

Risk Factors for Permanent Visual Loss in Biopsy-proven Giant Cell Arteritis: A Study of 339 Patients.

J Rheumatol 2016 07 1;43(7):1393-9. Epub 2016 May 1.

From the Department of Internal Medicine, Le centre hospitalier et universitaire (CHU) Limoges, Limoges, France.E. Liozon, MD, Department of Internal Medicine, CHU Limoges; F. Dalmay, PhD, Department of Internal Medicine, CHU Limoges; F. Lalloue, PhD, Department of Internal Medicine, CHU Limoges; G. Gondran, MD, Department of Internal Medicine, CHU Limoges; H. Bezanahary, MD, Department of Internal Medicine, CHU Limoges; A.L. Fauchais, MD, PhD, Department of Internal Medicine, CHU Limoges; K.H. Ly, MD, PhD, Department of Internal Medicine, CHU Limoges.

Objective: To determine the risk factors for permanent visual loss (PVL) in patients with biopsy-proven giant cell arteritis (GCA) and the usefulness of the factors in clinical practice.

Methods: From 1976 through 2015, the clinical charts and laboratory results of 339 patients with biopsy-proven GCA were recorded prospectively at the time of diagnosis. We used multivariable logistic regression analysis to determine which of 24 pretreatment characteristics were associated with PVL.

Results: Visual ischemic manifestations occurred in 108 patients, including PVL in 53 (16%), bilaterally in 15 patients (28%). The independent predictors associated with an increased risk of PVL were age (OR 1.06, 95% CI 1.01-1.12, p = 0.01), a history of transient visual ischemic symptoms (OR 2.62, 95% CI 1.29-5.29, p < 0.01), and jaw claudication (OR 2.11, 95% CI 1.09-4.10, p = 0.03). The presence of fever (OR 0.30, 95% CI 0.14-0.64, p < 0.01) and rheumatic symptoms (OR 0.23, 95% CI 0.10-0.57, p = 0.001) were associated with a markedly reduced risk of developing visual loss (3.7% if features were both present). No laboratory variables were independently associated with PVL.

Conclusion: The visual ischemic risk of untreated GCA can be readily estimated upon simple clinical findings, but not laboratory variables. However, we did not identify a subgroup of patients carrying no risk of developing visual loss. Glucocorticoid treatment remains, therefore, urgent for any patient with a high clinical suspicion index.
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http://dx.doi.org/10.3899/jrheum.151135DOI Listing
July 2016