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Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases., (© 2023. The Author(s).)

Osteopathy in rheumatology can either be primary a condition as a consequence of inflammatory rheumatic diseases but can also be drug induced. The most severe clinical manifestations are insufficiency fractures and osteonecrosis. The risk of fractures is highest for patients treated with glucocorticoids depending on the daily intake, the cumulative glucocorticoid dosage and the duration of administration. An incidence rate of nearly 13% was reported after administration of glucocorticoids lasting > 1 year. Cases of osteonecrosis under glucocorticoids are, in contrast, less frequent and not associated with glucocorticoid-induced osteoporosis. The antiresorptive substances bisphosphonates and denosumab, as well as romosumab are effective and important in treating osteoporosis; however, they can also cause atypical fractures, particularly of the femur as well as osteonecrosis of the jawbone. According to the most recent guidelines the benefits of bisphosphonate treatment have only been verified for 3-5 years and for denosumab for 3 years. There are clear preventive recommendations to avoid osteonecrosis of the jaw. Ultimately, the disease-modifying antirheumatic drugs (DMARD) methotrexate and leflunomide also affect the metabolism of bones. There is a rare but very characteristic form of osteopathy associated with methotrexate, mainly occurring in cases of long-term treatment. The typical manifestations are insufficiency fractures, particularly of the distal tibia, which persist for many years under continuous methotrexate administration. The treatment is the discontinuation of methotrexate and in most cases the fractures will heal within 3-4 months. Leflunomide has been associated with cases of persisting pseudarthrosis that only disappeared after a wash-out of the active metabolite., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

Antisynthetase syndromes (ASS) are rare autoimmune diseases. Characteristic is the presence of at least one of the three main symptoms myositis, interstitial lung disease (ILD) and arthritis with possible accompanying symptoms, such as mechanic's hands and feet, Raynaud's disease and/or fever in combination with detection of an aminoacyl-tRNA synthetase antibody in peripheral blood. In addition to myositis, ILD is a frequent and often predominant organ involvement and is responsible for morbidity and mortality. Autoantibodies to 11 aminoacyl-tRNA synthetases are known of which 8 have so far been associated with the clinical manifestation of ASS. The Jo-1 antibody is by far the most frequent one. The antibodies differ in the rate and severity of the main and accompanying symptoms. Treatment with selected immunosuppressive medication depends on the extent and severity of organ involvement. With a 5-year survival rate of approximately 90%, the Jo-1 syndrome has the best prognosis.

Objective: To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease., Methods: We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures., Results: NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP., Conclusion: NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Synovitis is the main pathology and can lead to a progressive destruction of the joints. It is often said that RA "burns out", implying that the inflammation decreases spontaneously in the long term, mostly severe course of RA and reaches a stage with a stable absence of joint inflammation, even without treatment. To test this concept we analyzed the published evidence. Data of historic long-term inception cohorts of patients who have never been treated with antirheumatic drugs and patients who received conventional disease-modifying antirheumatic drugs (DMARD), show that the disease stays active with sustained radiological progression in the majority of patients. At best, the disease can show a milder course with time or a stage of absence of joint inflammation can be reached if patients responded very well to initial drug treatment. Terminating DMARD treatment in this situation bears the risk of a latent progressive joint destruction, the appearance of extra-articular manifestations and an increase in the cardiovascular risk. Hence there is no evidence for the existence of a "burnt out" RA with stable inactive disease without drug treatment in the long-term course. In a modern treatment strategy of RA following the treat-to-target principle and aiming at remission, the term "burnt out" RA should no longer be used.

Objectives: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD)., Methods: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2)., Results: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005)., Conclusions: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.

Objective: Rituximab (RTX) has been used successfully for the treatment of severe Jo1 antibody-associated antisynthetase syndrome. The aim of this retrospective study was to evaluate the effect of RTX in severe Jo1 antisynthetase syndrome and determine predictive factors for response., Methods: There were 61 patients with Jo1 antisynthetase syndrome identified; 18 of these received RTX. One patient was lost to followup. The remaining 17 patients and 30 out of 43 patients who were treated with conventional immunosuppressive (IS) drugs were followed for a mean of 35 months and 84 months, respectively., Results: Polymyositis/dermatomyositis (95%) and interstitial lung disease (ILD; 66%) were the dominant clinical manifestations. Detection of anti-Ro52 antibodies (43%) was significantly associated with acute-onset ILD (p = 0.016) with O2 dependency, and patients with high concentrations of anti-Ro52 (20%) had the highest risk (p = 0.0005). Sixteen out of 18 patients (89%) showed a fast and marked response to RTX. Among those patients who were highly positive for anti-Ro52, response to RTX was seen in 7 out of 7 cases (100%), but no response to cyclophosphamide (n = 4), cyclosporine A (n = 3), azathioprine (n = 9), methotrexate (n = 5), or leflunomide (n = 2) was observed. One patient treated with RTX died of pneumonia., Conclusion: RTX is effective in the treatment of severe forms of Jo1 antisynthetase syndrome. In our retrospective study, the presence of high anti-Ro52 antibody concentrations predicts severe acute-onset ILD and nonresponse to IS drugs. In contrast to conventional IS, RTX is equally effective in patients with Jo1 antisynthetase syndrome, independent of their anti-Ro52 antibody status.