Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide
Identifieur interne : 000B70 ( Main/Exploration ); précédent : 000B69; suivant : 000B71Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide
Auteurs : Aleksey Mitev [Allemagne] ; Lisa Christ [Suisse] ; Daria Feldmann [Allemagne] ; Moritz Binder [États-Unis] ; Kim Möller [Royaume-Uni] ; Anna-Maria Kanne [Allemagne] ; Thomas Hügle [Suisse] ; Peter M. Villiger [Suisse] ; Reinhard E. Voll [Allemagne] ; Stephanie Finzel [Allemagne] ; Florian Kollert [Suisse]Source :
- Arthritis Research & Therapy [ 1478-6354 ] ; 2019.
Abstract
Elevated levels of C-reactive protein (CRP) in systemic sclerosis (SSc) have been linked to early inflammatory stages of the disease. This study has been designed to investigate CRP levels longitudinally in a cohort of SSc patients and to correlate these findings with comorbidities and disease characteristics.
In this retrospective study, patients with SSc treated at the outpatient clinic of the Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, were analyzed. Only patients with at least three consecutive visits and at least 1 year follow-up were included in this study. CRP serum levels were measured at every visit and categorized as positive if CRP concentrations were ≥ 5 mg/l. Subjects with elevated CRP levels at more than 80% of visits were defined as inflammatory SSc. The longitudinal CRP profiles were correlated with disease characteristics and comorbidities.
A total of 1815 consecutive visits of 131 SSc patients were analyzed. Over the observed time span (7.6 (1.0–19.5) years), 18.3% (
Inflammatory SSc is characterized by a more severe phenotype, high morbidity, and a large proportion of male patients. Even treatment with CYC does not alter CRP levels in this subpopulation with a high unmet medical need.
Url:
DOI: 10.1186/s13075-019-2057-x
PubMed: 31791379
PubMed Central: 6889646
Affiliations:
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level="a" type="main">Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide</title><author><name sortKey="Mitev, Aleksey" sort="Mitev, Aleksey" uniqKey="Mitev A" first="Aleksey" last="Mitev">Aleksey Mitev</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.5963.9</institution-id><institution>Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center University of Freiburg,</institution><institution>University of Freiburg,</institution></institution-wrap>Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Christ, Lisa" sort="Christ, Lisa" uniqKey="Christ L" first="Lisa" last="Christ">Lisa Christ</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0479 0855</institution-id><institution-id institution-id-type="GRID">grid.411656.1</institution-id><institution>Department of Rheumatology, Immunology, and Allergology, Inselspital,</institution><institution>University Hospital Bern,</institution></institution-wrap>Bern, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Bern</wicri:regionArea></affiliation></author><author><name sortKey="Feldmann, Daria" sort="Feldmann, Daria" uniqKey="Feldmann D" first="Daria" last="Feldmann">Daria Feldmann</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.5963.9</institution-id><institution>Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center University of Freiburg,</institution><institution>University of Freiburg,</institution></institution-wrap>Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Binder, Moritz" sort="Binder, Moritz" uniqKey="Binder M" first="Moritz" last="Binder">Moritz Binder</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0459 167X</institution-id><institution-id institution-id-type="GRID">grid.66875.3a</institution-id><institution>Department of Internal Medicine,</institution><institution>Mayo Clinic,</institution></institution-wrap>Rochester, MN USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Moller, Kim" sort="Moller, Kim" uniqKey="Moller K" first="Kim" last="Möller">Kim Möller</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7486</institution-id><institution-id institution-id-type="GRID">grid.6572.6</institution-id><institution>Rheumatology Research Group, Institute of Inflammation and Ageing,</institution><institution>University of Birmingham,</institution></institution-wrap>Birmingham, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Birmingham</wicri:regionArea></affiliation></author><author><name sortKey="Kanne, Anna Maria" sort="Kanne, Anna Maria" uniqKey="Kanne A" first="Anna-Maria" last="Kanne">Anna-Maria Kanne</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.5963.9</institution-id><institution>Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center University of Freiburg,</institution><institution>University of Freiburg,</institution></institution-wrap>Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Hugle, Thomas" sort="Hugle, Thomas" uniqKey="Hugle T" first="Thomas" last="Hügle">Thomas Hügle</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0423 4662</institution-id><institution-id institution-id-type="GRID">grid.8515.9</institution-id><institution>Rheumatology,</institution><institution>University Hospital Lausanne (CHUV),</institution></institution-wrap>Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Villiger, Peter M" sort="Villiger, Peter M" uniqKey="Villiger P" first="Peter M." last="Villiger">Peter M. Villiger</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0479 0855</institution-id><institution-id institution-id-type="GRID">grid.411656.1</institution-id><institution>Department of Rheumatology, Immunology, and Allergology, Inselspital,</institution><institution>University Hospital Bern,</institution></institution-wrap>Bern, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Bern</wicri:regionArea></affiliation></author><author><name sortKey="Voll, Reinhard E" sort="Voll, Reinhard E" uniqKey="Voll R" first="Reinhard E." last="Voll">Reinhard E. Voll</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.5963.9</institution-id><institution>Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center University of Freiburg,</institution><institution>University of Freiburg,</institution></institution-wrap>Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Finzel, Stephanie" sort="Finzel, Stephanie" uniqKey="Finzel S" first="Stephanie" last="Finzel">Stephanie Finzel</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.5963.9</institution-id><institution>Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center University of Freiburg,</institution><institution>University of Freiburg,</institution></institution-wrap>Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Kollert, Florian" sort="Kollert, Florian" uniqKey="Kollert F" first="Florian" last="Kollert">Florian Kollert</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0479 0855</institution-id><institution-id institution-id-type="GRID">grid.411656.1</institution-id><institution>Department of Rheumatology, Immunology, and Allergology, Inselspital,</institution><institution>University Hospital Bern,</institution></institution-wrap>Bern, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Bern</wicri:regionArea></affiliation></author></analytic><series><title level="j">Arthritis Research & Therapy</title><idno type="ISSN">1478-6354</idno><idno type="eISSN">1478-6362</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background/purpose</title><p id="Par1">Elevated levels of C-reactive protein (CRP) in systemic sclerosis (SSc) have been linked to early inflammatory stages of the disease. This study has been designed to investigate CRP levels longitudinally in a cohort of SSc patients and to correlate these findings with comorbidities and disease characteristics.</p></sec><sec><title>Methods</title><p id="Par2">In this retrospective study, patients with SSc treated at the outpatient clinic of the Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, were analyzed. Only patients with at least three consecutive visits and at least 1 year follow-up were included in this study. CRP serum levels were measured at every visit and categorized as positive if CRP concentrations were ≥ 5 mg/l. Subjects with elevated CRP levels at more than 80% of visits were defined as inflammatory SSc. The longitudinal CRP profiles were correlated with disease characteristics and comorbidities.</p></sec><sec><title>Results</title><p id="Par3">A total of 1815 consecutive visits of 131 SSc patients were analyzed. Over the observed time span (7.6 (1.0–19.5) years), 18.3% (<italic>n</italic> = 24) of patients had continuously elevated CRP levels (inflammatory SSc), whereas in 29% (<italic>n</italic> = 38), CRP levels were always in the normal range. There was no association between disease duration and CRP levels at first visit. Inflammatory SSc was associated with male gender (<italic>p</italic> = 0.022), anti-Scl-70 antibodies (<italic>p</italic> = 0.009), diffuse cutaneous SSc (<italic>p</italic> = 0.036), pulmonary fibrosis (<italic>p</italic> < 0.001), rheumatoid arthritis (<italic>p</italic> = 0.007), and cardiac arrhythmia (<italic>p</italic> = 0.048). Moreover, patients with inflammatory SSc revealed higher modified Rodnan skin scores (<italic>p</italic> < 0.001); lower forced vital capacity (FVC) (<italic>p</italic> < 0.001), total lung capacity (<italic>p</italic> = 0.001), and diffusing capacity (<italic>p</italic> = 0.008); and faster decline of FVC per year (<italic>p</italic> = 0.007). Even treatment with cyclophosphamide (CYC) did not decrease CRP levels (<italic>p</italic> = 0.754).</p></sec><sec><title>Conclusion</title><p id="Par4">Inflammatory SSc is characterized by a more severe phenotype, high morbidity, and a large proportion of male patients. Even treatment with CYC does not alter CRP levels in this subpopulation with a high unmet medical need.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Van Den Hoogen, F" uniqKey="Van Den Hoogen F">F van den Hoogen</name></author><author><name sortKey="Khanna, D" uniqKey="Khanna D">D Khanna</name></author><author><name sortKey="Fransen, J" uniqKey="Fransen J">J Fransen</name></author><author><name sortKey="Johnson, Sr" uniqKey="Johnson S">SR Johnson</name></author><author><name sortKey="Baron, M" uniqKey="Baron M">M Baron</name></author><author><name sortKey="Tyndall, A" uniqKey="Tyndall A">A Tyndall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Laar, Jm" uniqKey="Van Laar J">JM van Laar</name></author><author><name sortKey="Farge, D" uniqKey="Farge D">D Farge</name></author><author><name sortKey="Sont, Jk" uniqKey="Sont J">JK Sont</name></author><author><name sortKey="Naraghi, K" uniqKey="Naraghi K">K Naraghi</name></author><author><name sortKey="Marjanovic, Z" uniqKey="Marjanovic Z">Z Marjanovic</name></author><author><name sortKey="Larghero, J" uniqKey="Larghero J">J Larghero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sullivan, Km" uniqKey="Sullivan K">KM Sullivan</name></author><author><name sortKey="Goldmuntz, Ea" uniqKey="Goldmuntz E">EA Goldmuntz</name></author><author><name sortKey="Keyes Elstein, L" uniqKey="Keyes Elstein L">L Keyes-Elstein</name></author><author><name sortKey="Mcsweeney, Pa" uniqKey="Mcsweeney P">PA McSweeney</name></author><author><name sortKey="Pinckney, A" uniqKey="Pinckney A">A Pinckney</name></author><author><name sortKey="Welch, B" uniqKey="Welch B">B Welch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denton, C P" uniqKey="Denton C">C.P. 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Szamosi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li><li>Suisse</li><li>États-Unis</li></country><region><li>Minnesota</li></region></list><tree><country name="Allemagne"><noRegion><name sortKey="Mitev, Aleksey" sort="Mitev, Aleksey" uniqKey="Mitev A" first="Aleksey" last="Mitev">Aleksey Mitev</name></noRegion><name sortKey="Feldmann, Daria" sort="Feldmann, Daria" uniqKey="Feldmann D" first="Daria" last="Feldmann">Daria Feldmann</name><name sortKey="Finzel, Stephanie" sort="Finzel, Stephanie" uniqKey="Finzel S" first="Stephanie" last="Finzel">Stephanie Finzel</name><name sortKey="Kanne, Anna Maria" sort="Kanne, Anna Maria" uniqKey="Kanne A" first="Anna-Maria" last="Kanne">Anna-Maria Kanne</name><name sortKey="Voll, Reinhard E" sort="Voll, Reinhard E" uniqKey="Voll R" first="Reinhard E." last="Voll">Reinhard E. Voll</name></country><country name="Suisse"><noRegion><name sortKey="Christ, Lisa" sort="Christ, Lisa" uniqKey="Christ L" first="Lisa" last="Christ">Lisa Christ</name></noRegion><name sortKey="Hugle, Thomas" sort="Hugle, Thomas" uniqKey="Hugle T" first="Thomas" last="Hügle">Thomas Hügle</name><name sortKey="Kollert, Florian" sort="Kollert, Florian" uniqKey="Kollert F" first="Florian" last="Kollert">Florian Kollert</name><name sortKey="Villiger, Peter M" sort="Villiger, Peter M" uniqKey="Villiger P" first="Peter M." last="Villiger">Peter M. Villiger</name></country><country name="États-Unis"><region name="Minnesota"><name sortKey="Binder, Moritz" sort="Binder, Moritz" uniqKey="Binder M" first="Moritz" last="Binder">Moritz Binder</name></region></country><country name="Royaume-Uni"><noRegion><name sortKey="Moller, Kim" sort="Moller, Kim" uniqKey="Moller K" first="Kim" last="Möller">Kim Möller</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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