Publications by authors named "Michael S Abers"

21 Publications

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An immune-based biomarker signature is associated with mortality in COVID-19 patients.

JCI Insight 2021 01 11;6(1). Epub 2021 Jan 11.

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.
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http://dx.doi.org/10.1172/jci.insight.144455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821609PMC
January 2021

Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Authors:
Paul Bastard Lindsey B Rosen Qian Zhang Eleftherios Michailidis Hans-Heinrich Hoffmann Yu Zhang Karim Dorgham Quentin Philippot Jérémie Rosain Vivien Béziat Jérémy Manry Elana Shaw Liis Haljasmägi Pärt Peterson Lazaro Lorenzo Lucy Bizien Sophie Trouillet-Assant Kerry Dobbs Adriana Almeida de Jesus Alexandre Belot Anne Kallaste Emilie Catherinot Yacine Tandjaoui-Lambiotte Jeremie Le Pen Gaspard Kerner Benedetta Bigio Yoann Seeleuthner Rui Yang Alexandre Bolze András N Spaan Ottavia M Delmonte Michael S Abers Alessandro Aiuti Giorgio Casari Vito Lampasona Lorenzo Piemonti Fabio Ciceri Kaya Bilguvar Richard P Lifton Marc Vasse David M Smadja Mélanie Migaud Jérome Hadjadj Benjamin Terrier Darragh Duffy Lluis Quintana-Murci Diederik van de Beek Lucie Roussel Donald C Vinh Stuart G Tangye Filomeen Haerynck David Dalmau Javier Martinez-Picado Petter Brodin Michel C Nussenzweig Stéphanie Boisson-Dupuis Carlos Rodríguez-Gallego Guillaume Vogt Trine H Mogensen Andrew J Oler Jingwen Gu Peter D Burbelo Jeffrey I Cohen Andrea Biondi Laura Rachele Bettini Mariella D'Angio Paolo Bonfanti Patrick Rossignol Julien Mayaux Frédéric Rieux-Laucat Eystein S Husebye Francesca Fusco Matilde Valeria Ursini Luisa Imberti Alessandra Sottini Simone Paghera Eugenia Quiros-Roldan Camillo Rossi Riccardo Castagnoli Daniela Montagna Amelia Licari Gian Luigi Marseglia Xavier Duval Jade Ghosn John S Tsang Raphaela Goldbach-Mansky Kai Kisand Michail S Lionakis Anne Puel Shen-Ying Zhang Steven M Holland Guy Gorochov Emmanuelle Jouanguy Charles M Rice Aurélie Cobat Luigi D Notarangelo Laurent Abel Helen C Su Jean-Laurent Casanova

Science 2020 10 24;370(6515). Epub 2020 Sep 24.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
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http://dx.doi.org/10.1126/science.abd4585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857397PMC
October 2020

Publisher Correction: Neutrophil swarming delays the growth of clusters of pathogenic fungi.

Nat Commun 2020 05 14;11(1):2492. Epub 2020 May 14.

BioMEMS Resource Center, Massachusetts General Hospital, Boston, MA, 02129, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-16446-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224198PMC
May 2020

Neutrophil swarming delays the growth of clusters of pathogenic fungi.

Nat Commun 2020 04 27;11(1):2031. Epub 2020 Apr 27.

BioMEMS Resource Center, Massachusetts General Hospital, Boston, MA, 02129, USA.

Neutrophils employ several mechanisms to restrict fungi, including the action of enzymes such as myeloperoxidase (MPO) or NADPH oxidase, and the release of neutrophil extracellular traps (NETs). Moreover, they cooperate, forming "swarms" to attack fungi that are larger than individual neutrophils. Here, we designed an assay for studying how these mechanisms work together and contribute to neutrophil's ability to contain clusters of live Candida. We find that neutrophil swarming over Candida clusters delays germination through the action of MPO and NADPH oxidase, and restricts fungal growth through NET release within the swarm. In comparison with neutrophils from healthy subjects, those from patients with chronic granulomatous disease produce larger swarms against Candida, but their release of NETs is delayed, resulting in impaired control of fungal growth. We also show that granulocyte colony-stimulating factors (GCSF and GM-CSF) enhance swarming and neutrophil ability to restrict fungal growth, even during treatment with chemical inhibitors that disrupt neutrophil function.
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http://dx.doi.org/10.1038/s41467-020-15834-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184738PMC
April 2020

Infectious Complications of Immune Checkpoint Inhibitors.

Infect Dis Clin North Am 2020 06 23;34(2):235-243. Epub 2020 Apr 23.

Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 9000 Rockville Pike, Building 10/Room 12C103A, Bethesda, MD 20892, USA. Electronic address:

The clearance of both tumors and microbes depends on highly coordinated immune responses that are sufficiently potent to kill malignant or microbial cells while avoiding immunopathology from an overly exuberant inflammatory response. A molecular understanding of the immune pathways that regulate these responses paved the way for the development of checkpoint inhibitors (CPIs) as a therapeutic strategy to boost endogenous antitumor immunity. CPIs have demonstrated survival benefits across a wide spectrum of cancers. While infectious complications of CPIs are uncommon, immune-related adverse events occur frequently and often require immunosuppressive therapies that increase the risk of infection.
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http://dx.doi.org/10.1016/j.idc.2020.02.004DOI Listing
June 2020

Checkpoint Inhibition and Infectious Diseases: A Good Thing?

Trends Mol Med 2019 12 4;25(12):1080-1093. Epub 2019 Sep 4.

Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center (UT-MDACC), Houston, TX, USA.

The mammalian immune system has evolved the capacity to detect and destroy tumor cells. Tumors utilize multiple strategies to evade host immune surveillance, including the induction of the checkpoint molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to suppress antitumor immunity. Pharmacologic blockade of these molecules with checkpoint inhibitors (CPIs) restores T cell function and prolongs survival in patients with various malignancies. Emerging evidence suggests that the same checkpoint pathways may play a crucial role during infections. Indeed, CPIs appear promising as immunotherapeutic agents in infectious diseases, although their efficacy varies depending on pathogen-, cell-, and organ-specific factors. More research will be necessary to clarify the effects and safety of CPIs on clinically relevant outcomes of human infection.
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http://dx.doi.org/10.1016/j.molmed.2019.08.004DOI Listing
December 2019

Acute Infection and Myocardial Infarction. Reply.

N Engl J Med 2019 04;380(15):e21

Ottawa Hospital Research Institute, Ottawa, ON, Canada.

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http://dx.doi.org/10.1056/NEJMc1901647DOI Listing
April 2019

Acute Infection and Myocardial Infarction.

N Engl J Med 2019 01;380(2):171-176

From the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston (D.M.M.); National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (M.S.A.); and the Ottawa Hospital Research Institute and University of Ottawa, Ottawa (V.F.C.-M.).

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http://dx.doi.org/10.1056/NEJMra1808137DOI Listing
January 2019

Low procalcitonin, community acquired pneumonia, and antibiotic therapy.

Lancet Infect Dis 2018 05;18(5):496-497

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

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http://dx.doi.org/10.1016/S1473-3099(18)30215-9DOI Listing
May 2018

Reply to Horowitz.

Clin Infect Dis 2018 07;67(3):482

Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1093/cid/ciy124DOI Listing
July 2018

Procalcitonin as a Marker of Etiology in Community-Acquired Pneumonia.

Clin Infect Dis 2018 05;66(10):1639

Department of Medicine, Baylor College of Medicine, Houston, Texas.

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http://dx.doi.org/10.1093/cid/cix1089DOI Listing
May 2018

Evolving Understanding of the Causes of Pneumonia in Adults, With Special Attention to the Role of Pneumococcus.

Clin Infect Dis 2017 Oct;65(10):1736-1744

Johns Hopkins University School of Medicine, Baltimore, Maryland.

Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia in adults. After 1950, the proportion of pneumonia caused by pneumococcus began to decline. Pneumococcus has continued to decline; at present, this organism is identified in fewer than fewer10%-15% of cases. This proportion is higher in Europe, a finding likely related to differences in vaccination practices and smoking. Gram-negative bacilli, Staphylococcus aureus, Chlamydia, Mycoplasma, and Legionella are each identified in 2%-5% of patients with pneumonia who require hospitalization. Viruses are found in 25% of patients, up to one-third of these have bacterial coinfection. Recent studies fail to identify a causative organism in more than 50% of cases, which remains the most important challenge to understanding lower respiratory infection. Our findings have important implications for antibiotic stewardship and should be considered as new policies for empiric pneumonia management are developed.
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http://dx.doi.org/10.1093/cid/cix549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108120PMC
October 2017

Serial Procalcitonin as a Predictor of Bacteremia and Need for Intensive Care Unit Care in Adults With Pneumonia, Including Those With Highest Severity: A Prospective Cohort Study.

Open Forum Infect Dis 2017 4;4(1):ofw238. Epub 2017 Jan 4.

Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.

Background: Procalcitonin (PCT) is a prohormone that rises in bacterial pneumonia and has promise in reducing antibiotic use. Despite these attributes, there are inconclusive data on its use for clinical prognostication. We hypothesize that serial PCT measurements can predict mortality, intensive care unit (ICU) admission, and bacteremia.

Methods: A prospective cohort study of inpatients diagnosed with pneumonia was performed at a large tertiary care center in Boston, Massachusetts. Procalcitonin was measured on days 1 through 4. The primary endpoint was a composite adverse outcome defined as all-cause mortality, ICU admission, and bacteremia. Regression models were calculated with area under the receiver operating characteristic curve (AUC) as a measure of discrimination.

Results: Of 505 patients, 317 patients had a final diagnosis of community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP). Procalcitonin was significantly higher for CAP and HCAP patients meeting the composite primary endpoint, bacteremia, and ICU admission, but not mortality. Incorporation of serial PCT levels into a statistical model including the Pneumonia Severity Index (PSI) improved the prognostic performance of the PSI with respect to the primary composite endpoint (AUC from 0.61 to 0.66), bacteremia (AUC from 0.67 to 0.85), and need for ICU-level care (AUC from 0.58 to 0.64). For patients in the highest risk class PSI >130, PCT was capable of further risk stratification for prediction of adverse outcomes.

Conclusion: Serial PCT measurement in patients with pneumonia shows promise for predicting adverse clinical outcomes, including in those at highest mortality risk.
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http://dx.doi.org/10.1093/ofid/ofw238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414101PMC
January 2017

A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis.

Open Forum Infect Dis 2016 Jan 12;3(1):ofw036. Epub 2016 Feb 12.

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital; Harvard Medical School.

Prolonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients.
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http://dx.doi.org/10.1093/ofid/ofw036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800458PMC
January 2016

Abnormal movements in critical care patients with brain injury: a diagnostic approach.

Crit Care 2016 Mar 14;20:60. Epub 2016 Mar 14.

Neurosciences Critical Care Division, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

Abnormal movements are frequently encountered in patients with brain injury hospitalized in intensive care units (ICUs), yet characterization of these movements and their underlying pathophysiology is difficult due to the comatose or uncooperative state of the patient. In addition, the available diagnostic approaches are largely derived from outpatients with neurodegenerative or developmental disorders frequently encountered in the outpatient setting, thereby limiting the applicability to inpatients with acute brain injuries. Thus, we reviewed the available literature regarding abnormal movements encountered in acutely ill patients with brain injuries. We classified the brain injury into the following categories: anoxic, vascular, infectious, inflammatory, traumatic, toxic-metabolic, tumor-related and seizures. Then, we identified the abnormal movements seen in each category as well as their epidemiologic, semiologic and clinicopathologic correlates. We propose a practical paradigm that can be applied at the bedside for diagnosing abnormal movements in the ICU. This model seeks to classify observed abnormal movements in light of various patient-specific factors. It begins with classifying the patient's level of consciousness. Then, it integrates the frequency and type of each movement with the availability of ancillary diagnostic tests and the specific etiology of brain injury.
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http://dx.doi.org/10.1186/s13054-016-1236-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791928PMC
March 2016

Postobstructive Pneumonia: An Underdescribed Syndrome.

Clin Infect Dis 2016 Apr 21;62(8):957-61. Epub 2016 Feb 21.

Medical Care Line (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center Department of Medicine and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.

Background: Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP).

Methods: We prospectively studied patients hospitalized for CAP; 5.4% had PO-CAP, defined as a pulmonary infiltrate occurring distal to an obstructed bronchus. Sputum and blood cultures, viral polymerase chain reaction, urinary antigen tests, and serum procalcitonin (PCT) were done in nearly all cases. Clinical and laboratory characteristics of patients with PO-CAP were compared to those of patients with B-CAP.

Results: In a 2-year period, we identified 30 patients with PO-CAP. Compared to patients with B-CAP, patients with PO-CAP had longer duration of symptoms (median, 14 vs 5 days;P< .001). Weight loss and cavitary lesions were more common (P< .01 for both comparisons) and leukocytosis was less common (P< .01) in patients with PO-CAP. A bacterial pathogen was implicated in only 3 (10%) PO-CAP cases. PCT was <0.25 ng/mL in 19 (63.3%) patients. Although no differences were observed in disease severity or rates of intensive care unit admissions, 30-day mortality was significantly higher in PO-CAP vs B-CAP (40.0% vs 11.7%;P< .01).

Conclusions: Although there is substantial overlap, PO-CAP is a clinical entity distinct from B-CAP; a bacterial cause was identified in only 10% of patients. Our study has important implications for the clinical recognition of patients with PO-CAP, the role of microorganisms as etiologic agents, and the use of antibiotic therapy.
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http://dx.doi.org/10.1093/cid/civ1212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803103PMC
April 2016

A comparison of the microbiologic profile of indwelling versus external urinary catheters.

Am J Infect Control 2014 Jun;42(6):682-4

Houston VA Center for Innovations in Quality, Effectiveness, and Safety, Houston, TX; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX; Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX. Electronic address:

We studied the microbiology reports of urine cultures collected from external (condom catheters) versus indwelling (Foley) catheters. The equal prevalence of Enterobacteriaceae and Enterococci in samples from both catheter types calls into question the practice of switching from indwelling to external catheters to decrease catheter-associated bacteriuria.
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http://dx.doi.org/10.1016/j.ajic.2014.02.028DOI Listing
June 2014

The yield of sputum culture in bacteremic pneumococcal pneumonia after initiation of antibiotics.

Clin Infect Dis 2014 Jun 5;58(12):1782-3. Epub 2014 Mar 5.

Baylor College of Medicine Medical Care Line, Infectious Diseases Section, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.

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http://dx.doi.org/10.1093/cid/ciu140DOI Listing
June 2014

Neurological and psychiatric adverse effects of antiretroviral drugs.

CNS Drugs 2014 Feb;28(2):131-45

Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA,

Antiretroviral drugs are associated with a variety of adverse effects on the central and peripheral nervous systems. The frequency and severity of neuropsychiatric adverse events is highly variable, with differences between the antiretroviral classes and amongst the individual drugs in each class. In the developing world, where the nucleoside reverse transcriptase inhibitor (NRTI) stavudine remains a commonly prescribed antiretroviral, peripheral neuropathy is an important complication of treatment. Importantly, this clinical entity is often difficult to distinguish from human immunodeficiency virus (HIV)-induced peripheral neuropathy. Several clinical trials have addressed the efficacy of various agents in the treatment of NRTI-induced neurotoxicity. NRTI-induced neurotoxicity is caused by inhibition of mitochondrial DNA polymerase. This mechanism is also responsible for the mitochondrial myopathy and lactic acidosis that occur with zidovudine. NRTIs, particularly zidovudine and abacavir, may also cause central nervous system (CNS) manifestations, including mania and psychosis. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is perhaps the antiretroviral most commonly associated with CNS toxicity, causing insomnia, irritability and vivid dreams. Recent studies have suggested that the risk of developing these adverse effects is increased in patients with various cytochrome P450 2B6 alleles. Protease inhibitors cause perioral paraesthesias and may indirectly increase the relative risk of stroke by promoting atherogenesis. HIV integrase inhibitors, C-C chemokine receptor type 5 (CCR5) inhibitors and fusion inhibitors rarely cause neuropsychiatric manifestations.
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http://dx.doi.org/10.1007/s40263-013-0132-4DOI Listing
February 2014

Central nervous system vasculitis secondary to systemic sclerosis.

J Clin Neurosci 2013 Aug 8;20(8):1168-70. Epub 2013 May 8.

Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.

Systemic sclerosis (SSc) or scleroderma is a connective tissue disease with a diverse array of clinical manifestations secondary to underlying fibrosis and autoimmunity. Central nervous system (CNS) impairment is uncommon in SSc. Here we report the fourth known patient with CNS vasculitis caused by SSc. In each previous report, the patient was a middle-aged to elderly female. Our patient was 24 years old at the time of presentation, significantly younger than the other reported patients. Importantly, our patient's rapidly progressive clinical course and poor response to immunosuppression have not been reported in patients with CNS vasculitis secondary to scleroderma. Although CNS vasculitis is extremely rare in SSc, our report suggests that clinicians should consider this diagnosis in the differential of SSc patients with neurologic impairment.
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http://dx.doi.org/10.1016/j.jocn.2012.09.022DOI Listing
August 2013