Publications by authors named "Alexandra Audemard-Verger"

23 Publications

  • Page 1 of 1

Characteristics and risk factors for poor outcome in patients with systemic vasculitis involving the gastrointestinal tract.

Semin Arthritis Rheum 2021 04 3;51(2):436-441. Epub 2021 Mar 3.

Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France.

Background: Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype.

Aims: This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis.

Methods: Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death.

Results: Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29-7.34), performance status (OR 1.40, 1.05-1.87), use of morphine (OR 2.51, 0.87-7.24), abdominal guarding (OR 3.08, 1.01-9.37), ileus (OR 2.29, 0.98-5.32), melena (OR 2.74, 1.17-6.42), increased leukocytes (per G/L, OR 1.05, 1.00-1.10), low hemoglobin (per g/dL, OR 0.80, 0.71-0.91) and increased CRP (log mg/L, OR 1.21, 0.94-1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well.

Conclusions: Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.002DOI Listing
April 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 Jan 7. Epub 2021 Jan 7.

Université Paris Descartes, Paris, France.

Objectives: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while the disease is 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 hematuria, 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 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
January 2021

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

Clin Rheumatol 2021 May 24;40(5):1933-1940. Epub 2020 Oct 24.

Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France.

Objective: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer.

Methods: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study.

Results: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV.

Conclusion: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.
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http://dx.doi.org/10.1007/s10067-020-05455-zDOI Listing
May 2021

IgA Vasculitis With Underlying Liver Cirrhosis: A French Nationwide Case Series of 20 Patients.

J Rheumatol 2021 May 15;48(5):735-740. Epub 2020 Aug 15.

A. Bigot, MD, F. Maillot, MD, A. Audemard-Verger, MD, PhD, Department of Internal Medicine and Clinical Immunology, CHRU Tours, and University of Tours, Tours;

Objective: Immunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis.

Methods: We conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS).

Results: Twenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, < 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, = 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, = 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12-84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV.

Conclusion: We report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse.
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http://dx.doi.org/10.3899/jrheum.200293DOI Listing
May 2021

Des gangues péri-rénales.

Rev Med Interne 2020 08 19;41(8):567-568. Epub 2020 Jul 19.

Service de Médecine Interne et d'Immunologie Clinique, CHU Tours, Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, France.

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http://dx.doi.org/10.1016/j.revmed.2020.04.009DOI Listing
August 2020

Gastrointestinal involvement in adult IgA vasculitis (Henoch-Schönlein purpura): updated picture from a French multicentre and retrospective series of 260 cases.

Rheumatology (Oxford) 2020 Oct;59(10):3050-3057

Department of Internal Medicine.

Objectives: To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV).

Methods: Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared.

Results: One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia.

Conclusion: GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.
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http://dx.doi.org/10.1093/rheumatology/keaa104DOI Listing
October 2020

Characteristics and outcomes of patients with ophthalmologic involvement in giant-cell arteritis: A case-control study.

Semin Arthritis Rheum 2020 Apr;50(2):335-341

Department of Internal Medicine, Caen University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France. Electronic address:

Purpose: To describe the characteristics and outcome of patients with giant-cell arteritis (GCA)-related ophthalmologic involvement at diagnosis.

Methods: In a retrospective single-center cohort of 409 consecutive patients with GCA, we retrieved 104 patients with visual symptoms at GCA diagnosis and we compared them to 104 age- and sex-matched controls without ophthalmologic involvement. Each visual symptom was associated to an ophthalmologic diagnosis that was centrally re-assessed by an ophthalmologist.

Results: Compared to controls, patients with visual symptoms showed less fever (p = 0.0006), less polymyalgia rheumatica (p = 0.02) and lower acute phase reactants (p = 0.004). Blurred vision (in 60% of patients), amaurosis fugax (in 18%), diplopia (in 13%) and permanent visual loss (in 9%) were the four visual symptoms described by patients before GCA diagnosis. Anterior ischemic optic neuropathy (AION) was found in 47 (45%) patients, followed by central retinal artery occlusion (CRAO) in 15 (15%). Two patients had both involvements. The delay of glucocorticoids initiation was not different between patients with and without visual symptoms (p = 0.06). Among the 60 patients with initial AION and/or CRAO, 39 (65%) kept definite blindness or important visual damage, although 45 (75%) had received intravenous (IV) pulses of methylprednisolone. A new ischemic event (AION in all cases) occurred in 4% of patients with visual symptoms despite the initiation of treatment.

Conclusion: Ophthalmologic involvement was observed in one-quarter of our GCA patients. AION is still associated with the worst visual prognosis, and IV methylprednisolone pulses did not reduce the risk of blindness in our study.
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http://dx.doi.org/10.1016/j.semarthrit.2019.09.008DOI Listing
April 2020

Sustained Response and Rationale of Programmed Cell Death-1-Targeting for Progressive Multifocal Leukoencephalopathy.

Open Forum Infect Dis 2019 Oct 30;6(10):ofz374. Epub 2019 Sep 30.

Department of Internal Medicine and Clinical Immunology, CHU de Caen, Caen, France.

In this study, we report a complete (clinical, radiological, and virological) sustained (1 year) response after nivolumab salvage therapy in a progressive multifocal leukoencephalopathy patient. Analyses of the cells infiltrate in a pretreatment brain biopsy suggest that parenchymal programmed cell death-L1 macrophages could be the T-cells partnership in immune exhaustion and virus escape.
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http://dx.doi.org/10.1093/ofid/ofz374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767972PMC
October 2019

Complex regional pain syndrome type I masquerading as fasciitis.

Joint Bone Spine 2020 03 25;87(2):185-186. Epub 2019 Sep 25.

Service de médecine interne, centre hospitalo universitaire de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France. Electronic address:

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http://dx.doi.org/10.1016/j.jbspin.2019.09.012DOI Listing
March 2020

Intra-Alveolar Haemorrhage Complicating IgA Vasculitis: A Case Report, Literature Review and Discussion of Treatment.

Eur J Case Rep Intern Med 2019 25;6(4):001083. Epub 2019 Mar 25.

Department of Internal Medicine and Clinical Immunology, CHU de Caen Côte de Nacre, Caen, France.

Introduction: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis with IgA-dominant immune deposits. IgAV frequently involves the skin, gastrointestinal tract, joints and kidneys. In contrast to other types of small-vessel vasculitis, IgAV is rarely complicated by intra-alveolar haemorrhage (IAH).

Methods/results: We describe a patient with relapsing bladder cancer who presented with IAH during the course of IgAV successfully treated with corticosteroids alone.

Conclusion: This case report reminds us that IgAV can manifest with IAH. There are no robust data to support the systematic use of cyclophosphamide or plasma exchange as first-line therapy for IgAV with IAH.

Learning Points: Intra-alveolar haemorrhage in IgA vasculitis is an uncommon but important condition.The treatment strategies for IgA vasculitis and intra-alveolar haemorrhage and their rare association are discussed with reference to the literature.
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http://dx.doi.org/10.12890/2019_001083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499093PMC
March 2019

Recruitment of CXCR3 T cells into injured tissues in adult IgA vasculitis patients correlates with disease activity.

J Autoimmun 2019 05 8;99:73-80. Epub 2019 Feb 8.

Paris Descartes University, Cochin Institute, CNRS UMR8104, INSERM U1016, Paris, France. Electronic address:

Objectives: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients.

Methods: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cytometry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by immunohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age- and sex-matched healthy controls.

Results: We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria.

Conclusion: Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity.
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http://dx.doi.org/10.1016/j.jaut.2019.01.012DOI Listing
May 2019

Profiling the lymphoid-resident T cell pool reveals modulation by age and microbiota.

Nat Commun 2018 01 4;9(1):68. Epub 2018 Jan 4.

Paris Descartes Université, Sorbonne Paris Cité, Institut Cochin, CNRS UMR8104, INSERM U1016, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.

Despite being implicated in non-lymphoid tissues, non-recirculating T cells may also exist in secondary lymphoid organs (SLO). However, a detailed characterization of this lymphoid-resident T cell pool has not yet been done. Here we show that a substantial proportion of CD4 regulatory (Treg) and memory (Tmem) cells establish long-term residence in the SLOs of specific pathogen-free mice. Of these SLOs, only T cell residence within Peyer's patches is affected by microbiota. Resident CD4 Treg and CD4 Tmem cells from lymph nodes and non-lymphoid tissues share many phenotypic and functional characteristics. The percentage of resident T cells in SLOs increases considerably with age, with S1PR1 downregulation possibly contributing to this altered homeostasis. Our results thus show that T cell residence is not only a hallmark of non-lymphoid tissues, but can be extended to secondary lymphoid organs.
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http://dx.doi.org/10.1038/s41467-017-02458-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754350PMC
January 2018

Calcium-mediated shaping of naive CD4 T-cell phenotype and function.

Elife 2017 12 14;6. Epub 2017 Dec 14.

Institut Cochin, Paris Descartes Université, CNRS UMR8104, INSERM U1016, Paris, France.

Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on calcineurin activation. Accordingly, in vivo calcineurin inhibition leads the most self-reactive naive CD4 T cells to adopt the phenotype of their less self-reactive cell-counterparts. Collectively, our findings demonstrate that calcium-mediated activation of the calcineurin pathway acts as a rheostat to shape both the phenotype and effector potential of naive CD4 T cells in the steady-state.
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http://dx.doi.org/10.7554/eLife.27215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747519PMC
December 2017

Macrophages Induce Long-Term Trapping of γδ T Cells with Innate-like Properties within Secondary Lymphoid Organs in the Steady State.

J Immunol 2017 09 4;199(6):1998-2007. Epub 2017 Aug 4.

Institut Cochin, CNRS UMR8104, INSERM U1016, Paris Descartes Université, 75014 Paris, France;

So far, peripheral T cells have mostly been described to circulate between blood, secondary lymphoid organs (SLOs), and lymph in the steady state. This nomadic existence would allow them to accomplish their surveying task for both foreign Ags and survival signals. Although it is now well established that γδ T cells can be rapidly recruited to inflammatory sites or in certain tumor microenvironments, the trafficking properties of peripheral γδ T cells have been poorly studied in the steady state. In the present study, we highlight the existence of resident γδ T cells in the SLOs of specific pathogen-free mice. Indeed, using several experimental approaches such as the injection of integrin-neutralizing Abs that inhibit the entry of circulating lymphocytes into lymph nodes and long-term parabiosis experiments, we have found that, contrary to Ly-6CCD44 and Ly-6CCD44 γδ T cells, a significant proportion of Ly-6CCD44 γδ T cells are trapped for long periods of time within lymph nodes and the spleen in the steady state. Specific in vivo cell depletion strategies have allowed us to demonstrate that macrophages are the main actors involved in this long-term retention of Ly-6CCD44 γδ T cells in SLOs.
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http://dx.doi.org/10.4049/jimmunol.1700430DOI Listing
September 2017

Positive predictive value of hospital discharge diagnosis code to identify immunoglobulin A vasculitis in France: A validation study.

Eur J Intern Med 2017 09 23;43:e18-e19. Epub 2017 Jun 23.

CHU de Caen, Department of Internal Medicine, Caen F-14000, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2017.05.025DOI Listing
September 2017

Characteristics and Management of IgA Vasculitis (Henoch-Schönlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey.

Arthritis Rheumatol 2017 09;69(9):1862-1870

Department of Internal Medicine, Hôpital de Bondy, AP-HP, Paris, France.

Objective: Data on adult IgA vasculitis (Henoch-Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models.

Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10-12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28-10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29-2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00-3.20; P = 0.049).

Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first-line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.
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http://dx.doi.org/10.1002/art.40178DOI Listing
September 2017

Is it relevant to screen young women hospitalized in psychiatric department for neuropsychiatric systemic lupus erythematosus (NPSLE)?: A prospective study of 100 psychiatric inpatients.

Medicine (Baltimore) 2016 Nov;95(47):e5288

Departement of internal medicine, CHU de Caen, France Caen University, Caen, France Immunology departement, Caen , France Department of Psychiatry, CHU de Caen, Caen Department of Immunology, Institut Cochin, Paris, France.

On the basis that diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is sometimes difficult and systemic lupus erythematosus (SLE) can present with isolated psychiatric symptoms, we initiated a survey in a psychiatric department to screen for NPSLE in young female inpatients.We prospectively studied consecutive young female patients referred to the department of psychiatry. Antinuclear antibodies (ANA), anti-deoxyribonucleic acid (DNA), and antiextractable soluble nuclear antigens (ENA) in the serum of patients were screened. In case of positive anti-DNA or anti-ENA, the patient was referred to the department of internal medicine.One hundred patients were enrolled, mean age 33.1 ± 8.4 years. Most patients presented underlying psychiatric disorders: depression (46%), schizophrenia (13%), anxiety disorder (6%), and personality disorder (10%). A quarter of the cohort did not display underlying psychiatric disorders before hospitalization. Positive ANA ≥1:160 were found in 32 of the 100 patients tested (32%). No patients presented anti-DNA antibodies. One patient had positive anti-sjogrën's syndrome related antigen A (SSA), but did not present any features of SLE or Sjögren syndrome.Thus, systematic screening of SLE is not relevant in young women hospitalized in psychiatric department. However, clinicians should keep in mind that SLE can present with pure psychiatric symptoms.
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http://dx.doi.org/10.1097/MD.0000000000005288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134858PMC
November 2016

Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

PLoS One 2016 22;11(3):e0151696. Epub 2016 Mar 22.

Department of Internal Medicine, CHU Grenoble, Grenoble, France.

Objective: To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST).

Methods: We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline.

Results: Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed.

Conclusion: This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803192PMC
August 2016

Risk of thrombosis in patients with primary immune thrombocytopenia and antiphospholipid antibodies: A systematic review and meta-analysis.

Autoimmun Rev 2016 Mar 19;15(3):203-9. Epub 2015 Dec 19.

Internal Medicine Department, Toulouse University Hospital; UMR 1027 Inserm-University of Toulouse; CIC 1436, Toulouse University Hospital, France.

Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β2GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40-10.99]; it was 2.14, 95% CI [1.11-4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-β2GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies.
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http://dx.doi.org/10.1016/j.autrev.2015.11.001DOI Listing
March 2016

IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects.

Autoimmun Rev 2015 Jul 14;14(7):579-85. Epub 2015 Feb 14.

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Descartes, Paris, France.

Immunoglobulin A (IgA) vasculitis, formerly called Henoch-Schönlein purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. IgA vasculitis is more common among children than adults, with more severe disease in adults. Gastrointestinal and renal involvements represent the principal causes of morbidity and mortality in adults. Factors associated with long-term end-stage renal disease (ESRD) include baseline renal function impairment and baseline proteinuria >1 or 1.5 g/day, and on renal biopsy degree of interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis. Management of IgA vasculitis in adults is rendered difficult for clinicians because of the absence of correlation between initial presentation and long-term renal outcome, and the possible occurrence of spontaneous remission in patients with severe presentation or, in contrast, possible evolution to ESRD in patients with mild symptoms. Treatment is often symptomatic because disease course is usually benign. Treatment of severe involvement, including severe gastrointestinal complications or proliferative glomerulonephritis, remains controversial, with no evidence that corticosteroids or immunosuppressive agents improved long-term outcome. Prospective, randomized, controlled trials are thus needed to analyze the benefit-risk ratio of such treatments.
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http://dx.doi.org/10.1016/j.autrev.2015.02.003DOI Listing
July 2015
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