Publications by authors named "Eric Hachulla"

367 Publications

Epidemiology of Idiopathic Inflammatory Myopathies in Africa: A Contemporary Systematic Review.

J Clin Rheumatol 2021 Apr 9. Epub 2021 Apr 9.

From the Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Yaoundé, Cameroon Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia Rheumatology Unit, Yaoundé Central Hospital, Yaoundé, Cameroon Department of Internal Medicine and Clinical Immunology, CHRU Lille, Referral Centre for rare systemic autoimmune diseases North and Northwest of France, Univ. Lille, INSERM U995, LIRIC-Lille Inflammation Research International Centre, Lille, France.

Background: The epidemiology of idiopathic inflammatory myopathies (IIMs) has been extensively studied in America, Europe, and Asia, but remains unclear in Africa.

Objective: The aim of this review was to summarize available data on the epidemiology of IIMs in Africa.

Methods: We searched MEDLINE, EMBASE, and African Journals Online for studies published up to December 30, 2020, and reporting epidemiological data on IIMs in Africa. Data were combined through narrative synthesis. The review protocol was registered with PROSPERO, CRD42020186781.

Results: We included 39 studies reporting 683 cases (71.7% adults) of IIMs. Incidence rates of ~7.5/1,000,000 person-years and 1.2/1,000,000 person-years were estimated for dermatomyositis (DM), whereas polymyositis (PM) had an incidence rate of 8.8/1,000,000 person-years. Prevalence estimates of 11.49/100,000 and 11/100,000 (95% confidence interval, 0-32) were provided for IIMs and the PM subtype, respectively. Mean age at diagnosis ranged from 7.9 to 57.2 years, and 50% to 100% of the patients were females. Main subtypes of adult-onset IIMs were DM (21%-93%) and PM (12%-79%), whereas the commonest juvenile subtype was juvenile DM (5.8%-9%). Skeletal muscle involvement (56%-100%) was the main disease feature, and esophagus was the most commonly affected internal organ (6%-65.2%). Anti-Jo1/histidyl tRNA synthetase (7%-100%) and anti-Mi2 (17%-45%) antibodies were the most frequent myositis specific antibodies. Early mortality was high (7.8%-45%), and main death causes were infections, cancers and organ damage in respiratory and cardiovascular domains.

Conclusions: Apart from a potential younger age at onset of adult IIMs in Africa, current sparse data mostly suggest a similar epidemiology between Africa and other regions. Further high-quality studies are required to validate these findings.
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http://dx.doi.org/10.1097/RHU.0000000000001736DOI Listing
April 2021

Is the presence of antiphospholipid antibodies a poor prognostic factor for patients with HELLP syndrome?

Am J Obstet Gynecol 2021 Apr 1. Epub 2021 Apr 1.

Univ. Lille, Inserm, Service de Médecine Interne et d'Immunologie clinique, CHU Lille, Centre de Référence des maladies Autoimmunes systémiques rares du Nord et du Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases (ReCONNECT), U1167 RID-AGE, F-59000 Lille, France.

Background: The characteristics of antiphospholipid syndrome (APS)-associated HELLP syndrome are poorly described, likely due to the low frequency of this combination of syndromes.

Objective: To compare the characteristics and prognosis of HELLP syndrome in patients with and patients without APS.

Study Design: In this multicentric case-control study, adult women diagnosed with HELLP syndrome before 34 weeks' gestation, and who were also tested for antiphospholipid antibodies according to international diagnostic recommendations, were included. Cases ("HELLP-APS+") were defined as patients who fulfilled the international classification criteria for APS syndrome; they were retrospectively recruited by screening the 672 APS patients in our APS database; Controls ("HELLP-APS-") were defined as patients who did not fulfill APS criteria; they were retrospectively recruited from our hospital admission database.

Results: Overall, 71 patients were included (mean age, 30±5 years), 23 patients in the HELLP-APS+ group and 48 patients in the HELLP-APS- group. The live birth rate was significantly lower for HELLP-APS+ patients compared to HELLP-APS- patients (43.5% versus 89.4%; P<0.001). The HELLP-APS+ patients gave birth prematurely more often than the HELLP-APS- patients: 24 weeks' gestation (22.0-28.0) versus 30 weeks' gestation (27.0-33.0) (P<0.001). Among HELLP-APS+ patients, 39% required an induced abortion due to HELLP syndrome severity versus 8.5% of HELLP-APS- patients (P=0.006). The intensive care unit admission rate was 61.9% in HELLP-APS+ patients, which was significantly higher than the 27.7% rate in HELLP-APS- patients (P=0.007). No mother died.

Conclusion: Our results suggest that presence of APS is a poor prognostic factor for HELLP syndrome, for both the mother and fetus.
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http://dx.doi.org/10.1016/j.ajog.2021.03.039DOI Listing
April 2021

Calcinosis in systemic sclerosis.

Joint Bone Spine 2021 Mar 31:105180. Epub 2021 Mar 31.

Univ. Lille, Inserm, CHU Lille, Service de Médecine Interne et Immunologie Clinique, Centre de référence des maladies autoimmunes systémiques rares du Nord et Nord-Ouest de France (CeRAINO), U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France.

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http://dx.doi.org/10.1016/j.jbspin.2021.105180DOI Listing
March 2021

Systemic Pulmonary Events Associated with Myelodysplastic Syndromes: A Retrospective Multicentre Study.

J Clin Med 2021 Mar 10;10(6). Epub 2021 Mar 10.

Department of Internal Medicine and Clinical Immunology, National Reference Centre for Rare Systemic Autoimmune Disease North and North-West of France, University of Lille, CHU Lille, F-59000 Lille, France.

Although pulmonary events are considered to be frequently associated with malignant haemopathies, they have been sparsely studied in the specific context of myelodysplastic syndromes (MDS). We aimed to describe their different types, their relative proportions and their relative effects on overall survival (OS). We conducted a multicentre retrospective cohort study. Patients with MDS (diagnosed according to the 2016 WHO classification) and pulmonary events were included. The inclusion period was 1 January 2007 to 31 December 2017 and patients were monitored until August 2019. Fifty-five hospitalized patients were included in the analysis. They had 113 separate pulmonary events. Thirteen patients (23.6%) had a systemic autoimmune disease associated with MDS. Median age at diagnosis of MDS was 77 years. Median time to onset of pulmonary events was 13 months. Pulmonary events comprised: 70 infectious diseases (62%); 27 interstitial lung diseases (23.9%), including 13 non-specific interstitial pneumonias and seven secondary organizing pneumonias or respiratory bronchiolitis-interstitial lung diseases; 10 pleural effusions (8.8%), including four cases of chronic organizing pleuritis with exudative effusion; and six pulmonary hypertensions (5.3%). The median OS of the cohort was 29 months after MDS diagnosis but OS was only 10 months after a pulmonary event. The OS was similar to that of the general myelodysplastic population. However, the occurrence of a pulmonary event appeared to be either an accelerating factor of death or an indicator for the worsening of the underlying MDS in our study. More than a third of pulmonary events were non-infectious and could be systemic manifestations of MDS.
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http://dx.doi.org/10.3390/jcm10061162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999053PMC
March 2021

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study.

Lancet Rheumatol 2021 Mar 25. Epub 2021 Mar 25.

Service de Rhumatologie, Centre de Référence des Maladies Autoimmunes Systémiques Rares de l'Est et du Sud-Ouest de France, CHU de Bordeaux and UMR-CNRS 5164, Université de Bordeaux, Bordeaux, France.

Background: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.

Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.

Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).

Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases.

Funding: None.
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http://dx.doi.org/10.1016/S2665-9913(21)00059-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993930PMC
March 2021

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

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

Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France. Electronic address:

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
March 2021

F-FDG positron emission tomography scanning in systemic sclerosis-associated interstitial lung disease: a pilot study.

Arthritis Res Ther 2021 03 6;23(1):76. Epub 2021 Mar 6.

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

Background: Interstitial lung disease is a common complication of systemic sclerosis (SSc-ILD), and it remains difficult to accurately predict its course. Progressing ILD could be more metabolically active, suggesting that the F-FDG tracer could be a tool in the managing of SSc-ILD.

Methods: In our center, SSc patients and controls (non-Hodgkin lymphoma cured after first-line regimen) who had received a PET/CT were screened retrospectively. The FDG uptake (visual intensity, pattern, SUV) was systematically recorded in > 30 regions of interest (ROIs) linked to SSc in a blind reviewing by 2 independent nuclear medicine physicians using a standardized form.

Results: Among the 545 SSc patients followed up in our center, 36, including 22 SSc-ILDs, had a PET/CT, whose indication was cancer screening in most cases. The mean ± SD age was 57.9 ± 13.0 years with 20/36 females. Fourteen patients had a disease duration of less than 2 years. A third had anti-centromere antibodies and 27.8% had anti-topoisomerase antibodies. Pulmonary FDG uptakes were higher in SSc patients than in controls (n = 89), especially in those with ILD compared with those without ILD. Pulmonary FDG uptakes were positively correlated with the ILD severity (fibrosis extent, %FVC, and %D). No significant difference was found in the FDG uptakes from extrathoracic ROIs. Progressing SSc-ILDs within the 2 years after PET/CT (n = 9) had significant higher pulmonary FDG uptakes at baseline than stable SSc-ILDs (n = 13).

Conclusion: PET/CT could be a useful tool in the assessment of the severity and the prediction of pulmonary function outcome of SSc-ILD.
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http://dx.doi.org/10.1186/s13075-021-02460-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936499PMC
March 2021

Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic).

Arthritis Res Ther 2021 03 3;23(1):70. Epub 2021 Mar 3.

MEDSENIC, SAS, a company with CNRS participation, Strasbourg, France.

Background: Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE.

Methods: This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS).

Results: Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P < 0.01). In the long term, 6 patients attained LLDAS at W52, which continued at last follow-up (median LLDAS duration 3 years, range 2-4).

Conclusions: A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy.

Trial Registration: ClinicalTrials.gov, NCT01738360  registered 30 November 2012.
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http://dx.doi.org/10.1186/s13075-021-02454-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927234PMC
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

Granulomatosis with polyangiitis: Study of 795 patients from the French Vasculitis Study Group registry.

Semin Arthritis Rheum 2021 Feb 10;51(2):339-346. Epub 2021 Feb 10.

National Referral Center for Rare Systemic Autoimmune Diseases, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), 27, rue du faubourg Saint-Jacques, Paris, Cedex 14 75679, France. Electronic address:

Objective: To describe the characteristics and long-term outcomes of patients with granulomatosis with polyangiitis (GPA) from the French Vasculitis Study Group database.

Methods: Patients' clinical and laboratory characteristics, Birmingham Vasculitis Activity Score (BVAS)-assessed disease activity, malignancies, opportunistic infections, and vital status were collected at diagnosis and each visit. Estimated probabilities and predictors of overall (OS) and relapse-free survival (RFS) were analyzed by Cox regression.

Results: We enrolled 795 newly diagnosed patients, followed for a median of 3.5 years. Initial clinical manifestations involved ear, nose & throat (ENT; 80%), lungs (68%) and kidneys (56%). Among the 728 available ELISA results, 75.0% were PR3-ANCA-positive, 16.5% MPO-ANCA-positive and 62 (8.5%) ANCA-negative. Relapses occurred in 394 (50%) patients, involving ≥1 organ(s) affected at onset in 179 (46%), mainly ENT, lungs and kidneys, with mean BVAS 10.2 points below that at diagnosis (p<0.001). Five- and 10-year RFS rates were 37% and 17%, respectively. PR3-ANCA-positivity independently predicted relapse (p = 0.05) and prolonged survival (p = 0.038). OS-but not RFS-improved significantly over time (p<0.001); 10-year OS reached 88.2% (95% CI 83.9 to 92.7) for the 660 patients diagnosed after 2000. Infections were the main causes of death. Malignancy or opportunistic infection each occurred in ≤5% of the patients.

Conclusion: Survival has improved dramatically over the last decades but the high relapse rate remains a major concern for GPA patients, once again stressing the need for therapeutic strategy optimization to lower it. PR3-ANCA-positivity was associated with increased probability of relapse and survival.
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http://dx.doi.org/10.1016/j.semarthrit.2021.02.002DOI Listing
February 2021

The clinical phenotype of Systemic Sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort.

Rheumatology (Oxford) 2021 Feb 12. Epub 2021 Feb 12.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy.

Objective: To evaluate clinical associations of anti-PM/Scl antibodies in patients with Systemic Sclerosis (SSc) in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (SRC), malignancies, and functional outcome of interstitial lung disease (ILD).

Methods: (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared to 7,202 anti-PM/Scl-, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case-control study: additional data were collected for 165 anti-PM/Scl+ SSc (85 from the EUSTAR registry), and compared to 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration, and age at SSc onset.

Results: Patients with isolated anti-PM/Scl positivity, as compared with anti-Pm/Scl-, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of dermatomyositis, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls.In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed.

Conclusion: The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous dermatomyositis, calcinosis, and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.
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http://dx.doi.org/10.1093/rheumatology/keab152DOI Listing
February 2021

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

Ann Rheum Dis 2021 Jan 27. Epub 2021 Jan 27.

National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, University College London Hospitals National Health Service (NHS) Trust, London, UK

Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases.

Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.

Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.

Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.
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http://dx.doi.org/10.1136/annrheumdis-2020-219498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843211PMC
January 2021

Acquired Hemophilia A in IgG4-Related Disease: Case Report, Immunopathogenic Study, and Review of the Literature.

Front Immunol 2020 18;11:558811. Epub 2020 Dec 18.

CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.

We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII antibodies titers, consistent with acquired hemophilia A (AHA). Histological work-up of a cervical lymphadenopathy revealed benign follicular hyperplasia with IgG4 lymphoplasmacytic infiltration; and serum IgG4 levels were markedly elevated, compatible with IgG4-related disease (IgG4-RD). He was successfully treated with a 9-month course of prednisone, secondarily associated with rituximab when an AHA relapse occurred. As this patient presented with an unusual association of rare diseases, we wondered whether there was a link between the two conditions. Our first hypothesis was that the anti-FVIII autoantibodies could be directly produced by the proliferating IgG4 plasma cells as a result of broken tolerance to autologous FVIII. To test this assumption, we determined the anti-FVIII IgG subclasses in our patient and in a control group of 11 AHA patients without IgG4-RD. The FVIII inhibitor was mostly IgG4, with an anti-FVIII IgG4/IgG1 ratio of 42 at diagnosis and 268 at relapse in our patient; similar values were observed in non-IgG4-RD AHA patients. As a second hypothesis, we considered whether the anti-FVIII activity could be the result of a non-specific autoantibody production due to polyclonal IgG4 plasma cell proliferation. To test this hypothesis, we measured the anti-FVIII IgG4/total IgG4 ratio in our patient, as well as in several control groups: 11 AHA patients without IgG4-RD, 8 IgG4-RD patients without AHA, and 11 healthy controls. We found that the median [min-max] ratio was higher in AHA-only controls (2.4 10 [5.7 10-1.79 10]), an oligoclonal setting in which only anti-FVIII plasma cells proliferate, than in IgG4-RD-only controls (3.0 10 [2.0 10-6.0 10]), a polyclonal setting in which all IgG4 plasma cells proliferate equally. Our patient had intermediate ratio values (2.7 10 at diagnosis and 1.0 10 at relapse), which could plead for a combination of both mechanisms. Although no definitive conclusion can be drawn, we hypothesized that the anti-FVIII autoantibody production in our IgG4-RD AHA patient could be the result of both broken tolerance to FVIII and bystander polyclonal IgG4 plasma cell proliferation.
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http://dx.doi.org/10.3389/fimmu.2020.558811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793697PMC
December 2020

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

Nat Rev Rheumatol 2021 03 6;17(3):177-184. Epub 2021 Jan 6.

Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.
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http://dx.doi.org/10.1038/s41584-020-00565-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786339PMC
March 2021

French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides).

Orphanet J Rare Dis 2020 12 29;15(Suppl 2):351. Epub 2020 Dec 29.

Internal Medicine, CHU Cochin, AP-HP, Paris, France.

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3-6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12-48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.
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http://dx.doi.org/10.1186/s13023-020-01621-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771069PMC
December 2020

Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial.

Ann Rheum Dis 2020 Nov 18. Epub 2020 Nov 18.

Rheumatology, CHU Strasbourg, Centre National de Référence des maladies auto-immunes et systémiques rares Est/Sud-Ouest (RESO), Strasbourg, Alsace, France

Objectives: No immunomodulatory drug has been approved for primary Sjögren's syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren's syndrome-related systemic complications.

Methods: Multicentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren's syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren's Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician's global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment.

Results: 110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of -11.4% (95% credible interval -30.6 to 9.0) (Pr[Toc >Pla]=0.14).

Conclusion: Among patients with primary Sjögren's syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo.

Trial Registration Number: NCT01782235.
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http://dx.doi.org/10.1136/annrheumdis-2020-218467DOI Listing
November 2020

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database.

Arthritis Res Ther 2020 10 28;22(1):257. Epub 2020 Oct 28.

Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.

Background: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression.

Methods: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime.

Results: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc.

Conclusions: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.
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http://dx.doi.org/10.1186/s13075-020-02329-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592571PMC
October 2020

Exploring patient education unmet needs for rare and complex connective tissue and musculoskeletal diseases: A survey of health care providers' and patients' expectations in Europe.

Chronic Illn 2020 Oct 22:1742395320968618. Epub 2020 Oct 22.

Department of Internal Medicine and Clinical Immunology, Hôpital Claude Huriez, University of Lille, Lille, France.

Objective: The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases involves health care providers (HCPs) from 8 European countries and 7 patients' representatives of European Patient Advocacy Groups. The objective was to evaluate current practice and unmet needs for patient education (PE) in Europe.

Methods: A questionnaire was sent to HCP members asking about the PE practices and another, to enquire about their needs, was sent to patients' associations in the different countries.

Results: The questionnaire was completed by 33 HCPs. Half had no specific staff members dedicated to PE. For HCPs with dedicated staff, 83.3% (n = 11) considered that care providers were insufficient to meet patients' needs. Most of HCPs would like to see the practice of PE standardized. Sixty eight percent (n = 1093) of patients suffering from connective tissue diseases completed the questionnaire had never heard about PE. Most of them were interested in taking part in a PE program.

Discussion: Our survey revealed a strong interest in PE among patients and HCP and heterogeneity of practice. PE appeared important for both HCPs and patients. An online course for medical students in Europe will be developed in partnership with EULAR to respond to these unmet needs.
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http://dx.doi.org/10.1177/1742395320968618DOI Listing
October 2020

Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database.

Ann Rheum Dis 2021 02 28;80(2):219-227. Epub 2020 Sep 28.

Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland

Objectives: To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up.

Methods: Eligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models.

Results: 826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms.

Conclusion: SSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage.
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http://dx.doi.org/10.1136/annrheumdis-2020-217455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815627PMC
February 2021

Clinical practice guidelines adherence, knowledge and awareness in rare and complex connective tissue diseases across Europe: results from the first ERN ReCONNET survey.

RMD Open 2020 08;6(2)

Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

Introduction: The European Reference Network (ERN) ReCONNET is the ERN aimed at improving the management of rare and complex connective tissue and musculoskeletal diseases (rCTDs) across the European Union (EU). In the mission of ERN ReCONNET, clinical practice guidelines (CPGs) play a crucial role, representing a valid tool towards the harmonisation of the management of rCTDs while improving effectiveness and quality of care delivered to patients.

Methods: ERN ReCONNET developed two surveys to map the adherence to rCTDs CPGs among healthcare providers and to assess the knowledge and awareness of CPGs for their diseases among patients, family members and caregivers.

Results: The results of the surveys highlighted that healthcare professionals find it useful to apply CPGs in clinical practice (93%), while 62% of them experience difficulties and barriers in the application in their centres. Healthcare professionals also highlighted the need to develop CPGs for all rCTDs and to implement the use of the existing CPGs in clinical practice. On the other hand, patients, families and caregivers are relatively aware of the purpose of CPGs (51%) and 62% of them were aware of the existence of CPGs for their disease. Patient-friendly versions of CPGs and patients' lifestyle guidelines should be systematically developed contributing to the empowerment of patients in the disease management.

Conclusion: ERN ReCONNET is addressing the main issues identified in the results of the survey, promoting practical actions for the local adaptation of CPGs across Europe, improving their routine clinical use and increasing the awareness on CPGs among rCTDs patients, family members and caregivers.
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http://dx.doi.org/10.1136/rmdopen-2020-001344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507993PMC
August 2020

Hand ultrasound for the diagnosis of scleroderma: a scoring strategy including US items and items from the EULAR/ACR classification.

Clin Exp Rheumatol 2020 May-Jun;38 Suppl 125(3):140-147. Epub 2020 Aug 27.

Department of Internal Medicine and Clinical Immunology, CHU Rennes, Université de Rennes; and Université de Rennes, CHU Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France.

Objectives: To evaluate the diagnostic value of hand ultrasound (US) in systemic sclerosis (SSc) and to explore its relevance within a combined diagnostic approach.

Methods: 224 patients with suspected SSc were consecutively included. They all had US evaluation assessing the presence of fibrotic tenosynovitis (fibrotic TS) and ulnar artery occlusion (UAO). The final diagnosis of SSc was based on the clinical evaluation of a board of experts independently of any pre-established classification criteria.

Results: 166 patients were finally diagnosed as SSc according to the experts as reference standard. 62 SSc and 8 non-SSc patients had UAO (uni or bilateral) (p=0.001). 23 SSc patients and 1 non-SSc patient had US fibrotic TS (p=0.007). A US SSc-pattern (presence of UAO and/or fibrotic TS) was reported in 73 SSc patients and 9 non-SSc patients (p<0.001). UAO had an area under ROC curve (AUC) for the diagnosis of SSc of 0.618 (95%CI 0.539- 0.697); with Se=0.373 (0.304-0.449) and Sp=0.862 (0.751-0.928). Fibrotic TS had an AUC of 0.561 (0.480-0.643); with Se=0.139 (0.094-0.199) and Sp=0.983 (0.909-0.997). The US-SSc pattern had a AUC of 0.641 (0.563- 0.695), with Se=0.440 (0.367-0.516) and Sp=0.845 (0.731-0.916). A scoring system including these US parameters and items from ACR/EULAR classification criteria had an AUC of 0.979 (0.962-0.996)) and allows the substitution of capillaroscopy by US parameters with similar performances.

Conclusions: The use of hand US parameters may help to refine the diagnostic strategy of SSc and their inclusion in a combined diagnostic approach could be discussed.
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September 2020

Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study.

RMD Open 2020 08;6(2)

Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Paris, France

Objective: To compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome.

Patients And Methods: Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.

Results: A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination.

Conclusion: Several non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.
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http://dx.doi.org/10.1136/rmdopen-2020-001340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507995PMC
August 2020

Infliximab is an effective glucocorticoid-sparing treatment for Takayasu arteritis: Results of a multicenter open-label prospective study.

Autoimmun Rev 2020 Oct 13;19(10):102634. Epub 2020 Aug 13.

Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, F-67000 Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102634DOI Listing
October 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

Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis.

J Clin Oncol 2020 10 30;38(28):3252-3260. Epub 2020 Jul 30.

Amyloidosis Research and Treatment Center "Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo," Pavia, Italy.

Purpose: Oral melphalan and dexamethasone (MDex) were considered a standard of care in light-chain (AL) amyloidosis. In the past decade, bortezomib has been increasingly used in combination with alkylating agents and dexamethasone. We prospectively compared the efficacy and safety of MDex and MDex with the addition of bortezomib (BMDex).

Methods: This was a phase III, multicenter, randomized, open-label trial. Patients were stratified according to cardiac stage. Patients with advanced cardiac stage (stage IIIb) amyloidosis were not eligible. The primary end point was hematologic response rate at 3 months. This trial is registered with ClinicalTrials.gov identifier NCT01277016.

Results: A total of 109 patients, 53 in the BMDex and 56 in the MDex group, received ≥ 1 dose of therapy (from January 2011 to February 2016). Hematologic response rate at 3 months was higher in the BMDex arm (79% 52%; = .002). Higher rates of very good partial or complete response rates (64% 39%; hazard ratio [HR], 2.47; 95% CI, 1.30 to 4.71) and improved overall survival, with a 2-fold decrease in mortality rate (HR, 0.50; 95% CI, 0.27 to 0.90), were observed in the BMDex arm. Grade 3 and 4 adverse events (the most common being cytopenia, peripheral neuropathy, and heart failure) were more common in the BMDex arm, occurring in 20% versus 10% of cycles performed.

Conclusion: BMDex improved hematologic response rate and overall survival. To our knowledge, this is the first time a controlled study has demonstrated a survival advantage in AL amyloidosis. BMDex should be considered a new standard of care for AL amyloidosis.
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http://dx.doi.org/10.1200/JCO.20.01285DOI Listing
October 2020

Extended myositis-specific and -associated antibodies profile in systemic sclerosis: A cross-sectional study.

Joint Bone Spine 2021 01 9;88(1):105048. Epub 2020 Jul 9.

Univ. Lille, U1286 - Infinite - Institute for Translational Research in Inflammation, 59000 Lille, France; Inserm, U1286, 59000 Lille, France; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), 59000 Lille, France. Electronic address:

Objective: In systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), auto-antibodies are used in daily practice as potent biomarkers of clinical phenotypes. This study aimed at estimating the prevalence of myositis-specific (MSA) and myositis-associated (MAA) auto-antibodies in a well-characterised SSc patients cohort using two different immunoblot assays, and studying their clinical associations.

Methods: In this cross-sectional study, the sera of 300 consecutive patients were tested at the same time with myositis antibodies Euroimmun® and D-tek® immunoblot assays.

Results: Prevalence of MSA/MAA, MSA and MAA were 17.0%, 8.0% and 9.7%, respectively. When combining results of both tests, anti-PM/Scl 100 were found in 5.0% (95% confidence interval 2.8; 8.1); anti-PM/Scl 75 and anti-TIF1γ in 3.7% (1.8; 6.5); anti-Ku 3.0% (1.4; 5.6); anti-MDA5 in 1.3% (0.4; 3.4); anti-Mi-2 β, anti-NXP2, anti-PL-7 and anti-SRP in 0.7% (0.08; 2.4); anti-EJ and anti-PL-12 in 0.3% (0.01; 1.8) of patients. No reactivity against SAE1, Jo-1 or OJ was observed. Anti-PM/Scl 75 antibodies were associated with interstitial lung disease (80% vs. 42%) and myositis (27% vs. 3%); anti-Ku antibodies were associated with myositis (33% vs. 3%).

Conclusion: In this cross-sectional study of 300 SSc patients, the prevalence of MSA/MAA, MSA and MAA using immunoblot assays were 17.0%, 8.0% and 9.7%, respectively. MAA positivity was associated with ILD and myositis, but this study did not highlight any clinical associations with MSA positivity.
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http://dx.doi.org/10.1016/j.jbspin.2020.06.021DOI Listing
January 2021

Outcomes of pregnancy and associated factors in sub-Saharan African women with systemic lupus erythematosus: a scoping review.

Lupus Sci Med 2020 06;7(1)

Department of Internal Medicine and Clinical Immunology, CHU and Univerisity of Lille, Lille, France.

Objective: To scope and summarise available literature on the outcomes of pregnancy and associated factors in sub-Saharan African women with SLE.

Methods: Electronic databases and reference lists of retrieved articles were searched to identify relevant studies published from 1 January 2000 to 28 October 2019. Data were combined through narrative synthesis.

Results: We included four studies retrospectively reporting a total of 137 pregnancies in 102 women over a 26-year period. Mean age at conception ranged from 27.2 to 39.9 years. Kidney damage, the predominant organ manifestation before conception, was reported in 43 (42.2%) patients. Ninety-seven (70.8%) pregnancies resulted in 98 live births. SLE flares occurred in 44 (32.2%) pregnancies, mainly skin (20.4%) and renal (18.2%) flares. Major adverse pregnancy outcomes (APOs) were preterm birth 38.8%, low birth weight 29.8%, pregnancy loss 29.2% and pre-eclampsia 24.8%. The main factors associated with APOs were nephritis and SLE flares.

Conclusion: Over two-thirds of pregnancies resulted in live birth in this cohort of sub-Saharan African women with SLE. The main APOs and associated factors described in other parts of the world are also seen in this region, but with high rates of APOs. A large prospective multinational study is warranted for more compelling evidence.
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http://dx.doi.org/10.1136/lupus-2020-000400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295444PMC
June 2020

Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial.

Ann Intern Med 2020 08 2;173(3):179-187. Epub 2020 Jun 2.

Cochin Hospital, Paris Descartes University, Paris, France (P.C., C.V., X.P., B.T., L.M., L.G.).

Background: Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Objective: To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen.

Design: Randomized controlled trial. (ClinicalTrials.gov: NCT02433522).

Setting: 39 clinical centers in France.

Patients: 68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy.

Intervention: Rituximab or placebo infusion every 6 months for 18 months (4 infusions).

Measurements: The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0.

Results: From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) ( = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) ( = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group.

Limitation: Potential selection bias based on previous rituximab response and tolerance.

Conclusion: Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy.

Primary Funding Source: French Ministry of Health and Hoffmann-La Roche.
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http://dx.doi.org/10.7326/M19-3827DOI Listing
August 2020