Background The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. MethodsWe did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case-control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. Findings Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55-76] years vs 57 [49-67] years; p=0•0010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2•8 [95% CI 1•3-6•1]; p=0•031) and obesity (11 [17%] vs 1 [2%]; OR 11•0 [1•3-83•4]; p=0•0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78•8 years [IQR 75•3-81•3] vs 65•5 years [53•3-74•0]; p=0•0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case-control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died...

Interstitial lung disease (ILD) represents one of the most severe extra-muscular features of idiopathic inflammatory myositis (IIM). We aimed to identify any clinical and serological predictors of ILD in a monocentric cohort of 165 IIM patients. ILD+ patients were defined as having restrictive impairment in lung function tests and signs of ILD at chest high-resolution computed tomography (HRCT). Available HRCT images were centralized and classified in different ILD patterns: non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), usual interstitial pneumonia-like (UIP), indeterminate for UIP, and interstitial lung abnormalities (ILA). Lung function test data were recorded at onset, at 1 and 5 years after ILD diagnosis. ILD was found in 52 IIM patients (31.5%): 46.2% was affected by anti-synthetase syndrome (ARS), 21% by polymyositis (PM), 19% by dermatomyositis (DM), and 13.5% by overlap myositis. Most of ILD+ showed NSIP (31.9%), OP (19%), indeterminate for UIP (19%), and UIP (12.8%) patterns. At multivariate analysis, ILD was predicted by anti-Ro52 (p: 0.0026) and dyspnea (p: 0.015) at IIM onset. Most of ILD onset within is 12 months after IIM. In five cases, ILD occurs after 12 months since IIM diagnosis: these patients more frequently show dry cough and anti-Ku antibodies. Anti-Ro52 + ILD patients showed a significant increase of DLCO at 1 and 5 years of follow-up, compared with anti-Ro52 negative cases. ILD occurs in about one third of IIM and was predicted by dyspnea at onset and anti-Ro52 antibodies. Anti-Ro52 defines a subgroup of ILD showing a significant improvement of DLCO during follow-up. This retrospective study has been approved by local ethic committee (ASST-Spedali Civili of Brescia, Italy); protocol number: NP3511

Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad’s phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of “seronegative” SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2–7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients’ stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns’ interpretation. The gold-standard technique for autoantibodies’ identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients.

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BackgroundIdiopathic inflammatory myositis (IIM) is a group of heterogeneous autoimmune diseases, characterized by myositis-specific (MSA) or myositis-associated autoantibodies (MAA). Muscle biopsy is the diagnostic gold standard, but correlations with elevated creatine level (CK) or MSA/MAA are unclear.ObjectivesTo evaluate the association between specific histological findings and clinical and/or serological features in IIM patients from a single tertiary Rheumatology referral center.MethodsWe retrospectively analyzed demographic and clinical data from medical charts, of 184 patients affected by IIM followed-up for >1 year. Muscle biopsies of 89 IIM patients were retrieved from deltoid, biceps or quadriceps muscle, snap-frozen and stored at -80°C and processed for routine histology and histochemistry.ResultsThe majority of our muscle biopsy cohort was represented by Dermatomyositis (DM) (39.3%), Polymyositis (PM) (29.2%) and Anti-synthetase syndrome (ASS) (13.5%), whereas the rest was composed of Overlap Syndrome (OS), Immune-Mediated Necrotizing Myopathy (IMNM) and Inclusion-Body Myositis (IMB) (13.5%, 2.2% and 2.2% respectively).DM presented perifascicular atrophy in 85% of cases and perivascular and perifascicular infiltration in only 40% of cases, similar to other types of IIMs. The overall histology finding was characterized by minimal inflammation and/or necrosis but major atrophy. In comparison, Polymyositis showed more endomysial infiltration and necrosis (Table 1). ASS was characterized by atrophy and perifascicular necrosis in 83% of cases, with perimysial and perivascular infiltration in 67% of cases. Those characteristics were observed both in anti-Jo-1+ (13.9%) as well as non-Jo-1+ ASS patients (13.2%). Non-Jo-1+ ASS patients presented endomysial infiltration, invading or enveloping the muscle fibers (not present in anti Jo-1+) (p: 0.036), with addition of rimmed vacuoles and aspecific clinical presentation. Moreover, in DM, anti-Mi2+ antibodies (9.3%) were significantly associated with perifascicular regeneration and endomysial infiltration, in comparison to both anti-TIF1γ+ (5.8%) and anti-NXP2+ patients (4.6%). No significant histopathological features were found in patients with anti-Ro52 autoantibodies (37.2%), that represented the most frequent MAA in our cohort.Table 1.BIOPSY CHARACTERISTICSASS 12 (%)PM 35 (%)DM 26 (%)p [OR] ASS vs PMp [OR] PM vs DMdiffuse atrophy3 (25)34 (97.1)8 (30.8)<0.0001 [0.010 (0.001-0.106)]<0.0001 [76.5 (8.8-660.6)]perifascicolar degeneration----29 (82.9)15 (57.7)----0.044 [3.544 (1.09-11.5)]prevalent necrosis----10 (28.6)1 (3.8)----0.017 [10 (1.19-84)]Jo1 12 (%)PL7/PL12 5 (%)p [OR]endomysial infiltration (invading fibers)03 (60)0.015 [inf]Mi2 8 (%)TIF1γ 5 (%)NXP2 4 (%)p [OR] Mi2 vs TIF1γp [OR] Mi2 vs NXP2perifascicolar regeneration8 (100)1 (20)00.007 [inf]0.002 [inf]endomysial infiltrate (surrounding fibers)6 (75)----0----0.061ConclusionNo significant associations emerged between CK levels, different types of IIM and MSA. Some histological features seem to define subtypes of DM. A precise definition of autoantibody profile in IIM could define not only a clinical phenotype but also the muscle damage distribution.Disclosure of InterestsNone declared