title: In antisynthetase syndrome, ACPA are associated with severe and erosive arthritis: an overlapping rheumatoid arthritis and antisynthetase syndrome.
abstract: Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case-control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P < 0.0001). The number of swollen joints was significantly higher (7.0 ± 5.0 vs 2.9 ± 3.9, P < 0.005), with a distribution resembling that of RA. Radiographic damages were also more frequent in ACPA-positive ASS patients (87% vs 11%, P < 0.0001). Aside from a significantly higher transfer factor for carbon monoxide in ACPA-ASS patients, lung, muscle, and skin involvements had similar incidences, patterns, and severity in both groups. Although Nonbiologic treatments were similarly used in both groups, ACPA-positive patients received biologics more frequently (59% vs 12%, P < 0.0008), mostly due to refractory arthritis (n = 9). Eight patients received anti-Cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) with good efficacy and tolerance, whereas 2 of the 5 patients treated with antitumor necrosis factor drugs had worsened myositis and/or interstitial lung disease. After a >7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA-ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements.
authors.affiliation: From the Service de Rhumatologie-Centre de Référence des Maladies Autoimmunes et Systémiques Rares (AMe, JS), Hôpitaux Universitaires de Strasbourg, Fédération de Médecine Translationnelle; Service de Physiologie et d'Explorations Fonctionnelles (AM, BG), Centre Hospitalo-Universitaire de Strasbourg; EA 3072 (AM, BG), "Mitochondrie, Stress Oxydant et Protection Musculaire", Faculté de Médecine, Université de Strasbourg et Fédération de Médecine Translationnelle (FMTS), Strasbourg; Service de Médecine Interne-Centre de Référence des Maladies Autoimmunes et Systémiques Rares (GL, EH), CHRU Lille, Université Lille 2, Lille; Service de Radiologie (GB), Hôpitaux Universitaires de Strasbourg, Strasbourg; Service de Rhumatologie (AD), Hôpital Général de Dôle, Dôle; Service de Rhumatologie (SO, OM), Hôpital Bichat, APHP, Paris; Service de Rhumatologie (AT), Hôpitaux Universitaires de Clermont-Ferrand, Clermont-Ferrand; Service de Rhumatologie (BLG), Hôpitaux Universitaires de Nantes, Nantes; Service de Rhumatologie (LM), Hôpital Général de Colmar, Colmar; Service de Médecine Interne (ALB), Hôpital Général de Douai, Douai; Service de Rhumatologie (MDB); Service de Médecine Interne (CD), Hôpitaux Universitaire de Fort de France, Fort de France; Service de Pneumologie et Réanimation Médicale (MD), Hôpital Pitié-Salpêtrière, APHP, Paris; Service de Rhumatologie et Néphrologie (PC), Centre Hospitalier de Béthune, Béthune; Department de Rhumatologie (GF), Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Avicenne-Jean Verdier-René Muret; INSERM UMR1125 (GF); Sorbonne Paris Cité-Université Paris 13 (GF), Bobigny; Service de Rhumatologie Hôpitaux Universitaires de Lille (RMF), Université de Lille 2, Lille; Service de médecine interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Hôpital Pitié Salpêtrière, APHP, Paris, F-75013 (AMa, ZA) ; Département de médecine interne et immunologie clinique, Centre de Référence Maladies Neuro-Musculaires - DHU i2B, Hôpital Pitié- Salpêtrière, APHP, Paris, F-75013 (BH, OB) INSERM UMR-S 1135 (BH, AMa, ZA) & INSERM UMRS974 (BH, OB) Sorbonne Universités, UPMC Univ Paris 06, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Meyer
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lefevre
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bierry
authors.forename: Aurélie
authors.initials: A
authors.lastname: Duval
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ottaviani
authors.forename: Olivier
authors.initials: O
authors.lastname: Meyer
authors.forename: Anne
authors.initials: A
authors.lastname: Tournadre
authors.forename: Benoit
authors.initials: B
authors.lastname: Le Goff
authors.forename: Laurent
authors.initials: L
authors.lastname: Messer
authors.forename: Anne Laure
authors.initials: AL
authors.lastname: Buchdahl
authors.forename: Michel
authors.initials: M
authors.lastname: De Bandt
authors.forename: Christophe
authors.initials: C
authors.lastname: Deligny
authors.forename: Matthieu
authors.initials: M
authors.lastname: Dubois
authors.forename: Pascal
authors.initials: P
authors.lastname: Coquerelle
authors.forename: Géraldine
authors.initials: G
authors.lastname: Falgarone
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Flipo
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Baptiste
authors.initials: B
authors.lastname: Hervier
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009220:Myositis / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology; D011859:Radiography; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D011795:Surveys and Questionnaires
chemical_list: D001323:Autoantibodies