Description and Analysis of a Novel Subtype of the Anti-Synthetase Syndrome Characterized by Frequent Attacks of Fever and Systemic Inflammation in a Single-Center Cohort Study

Abstract

ObjectivesThe aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation.MethodsA retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype.ResultsOut of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0–1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% vs. 21% and 40% vs. 9%, respectively, both p<0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (>=3) were much higher in the high-inflammation group (60% vs. 26%), while biological agents, i.e., rituximab and tocilizumab, showed better “drug survival” for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort.ConclusionsASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.

Anakinra for the Treatment of Antisynthetase Syndrome: A Monocentric Case Series and a Systematic Literature Review

“…4,5 As shown by both our case series and SLR, these manifestations are prominent features of AS, and they identify a difficult-to-treat disease phenotype that may not even respond to RTX. 3 Hence, the encouraging findings of our study are in line with the plausible pathogenic role of IL-1 in AS. Further, patients featuring biochemical (ie, increased acute-phase reactants) and clinical (ie, fever, myocarditis, and interstitial lung disease) signs of prominent inflammation possibly represent a disease subset that could benefit the most from this approach.…”

“…2 Further, this therapy may not effectively induce remission in some patients with AS. 3 Hence, alternative drugs for patients with refractory AS are necessary. Interleukin (IL)-1 blockade with anakinra might represent a suitable option due to its potent antiinflammatory properties and favorable safety profile.…”

Idiopathic inflammatory myopathies: one year in review 2022

“…Patients with two or more non-infectious fever attacks and within the upper three quartiles of attack frequency were defined as the high-inflammation ASS subgroup (78). These patients had an average of 1.12 attacks/patient-year and were most commonly anti-Jo1 or anti-PL7-positive (78).…”

“…Patients with two or more non-infectious fever attacks and within the upper three quartiles of attack frequency were defined as the high-inflammation ASS subgroup (78). These patients had an average of 1.12 attacks/patient-year and were most commonly anti-Jo1 or anti-PL7-positive (78). Compared to the low-inflammation ASS group, defined by at most a single attack and a frequency lower than 0.5 attacks/patient-year, the high-inflammation ASS group had a higher occurrence of fever and RP-ILD as the disease presentation (78).…”

A multidisciplinary approach to the diagnosis of antisynthetase syndrome

“…Fever when present should prompt investigation for infection, although the reported prevalence in ASyS ranges from 21 to 66% ( 23 , 71 ). A Chinese cohort study identified more pyrexial episodes with acute phase response in anti-PL7 (50%) and anti-Jo1 (30%) positive cases, with a more inflammatory phenotype predictive of rapidly progressive ILD (RP-ILD) ( 72 ). The large 2014 meta-analysis demonstrated more fever in non-anti-Jo1 patients as opposed to anti-Jo1 positive patients ( 18 ).…”