Clinical heterogeneity and prognostic factors of anti-synthetase syndrome: a multi-centered retrospective cohort study.

OBJECTIVE: Anti-synthetase syndrome (ASyS) patients have heterogeneous clinical manifestations with different initial presentations, complications, and outcomes. This study aimed to assess the clinical characteristics and complications in patients with ASyS, and to identify factors that were associated with the survival of ASyS patients. METHODS: This was a retrospective multicentre longitudinal study. Patients fulfilling either the Connor's criteria or Solomon's criteria for ASyS were recruited. Electronic health records were reviewed until October 2022. Multivariate Cox-regression analysis was used to determine the independent prognostic factors. Auto-antibodies were checked by commercial immunoassays. RESULTS: A total of 205 patients (anti-Jo-1 49.3%, anti-PL-7 19.0%, anti-EJ 11.2%, anti-PL-12 10.2% and anti-OJ 3.4%) were included. The median follow-up time was 4 years. The time from symptoms onset to diagnosis was significantly longer for non-anti-Jo1 patients (median 5 vs 3 months). Common initial presentations included myositis (56.1%), arthritis (54.6%), and interstitial lung disease (ILD) (54.1%). Patients with anti-Jo-1 had significantly higher muscle enzyme levels and more arthritis. All patients with anti-EJ would develop ILD on follow-up and malignancy was noted in 28.6% of the anti-OJ positive patients. 15.6% of the patients died and pulmonary diseases (ILD or pneumonia) were the major causes. Age at diagnosis, malignancy and rapidly progressive-ILD were independently associated with mortality, while joint manifestation was a protective factor. CONCLUSION: In view of the heterogeneity of clinical presentation of ASyS, high index of suspicion and early checking of specific autoantibodies might help prompt diagnosis of ASyS and detection of related complications.

Pyroglutamic Acidosis - An Underrecognised Entity Associated with Acetaminophen Use.

Pyroglutamic acidosis (PGA) is an underrecognized entity characterised by raised anion gap metabolic acidosis (RAGMA) and urinary hyper-excretion of pyroglutamic acid. It is frequently associated with chronic acetaminophen (APAP) ingestion. We report the case of a 73-year-old man with invasive pulmonary aspergillosis treated with voriconazole and APAP for analgesia with a cumulative dose of 160 g over 40 days. PGA was suspected as he developed severe RAGMA and common causes were excluded. Diagnosis was confirmed via urinary organic acid analysis which showed significant hyper-excretion of pyroglutamic acid. APAP was discontinued, and N-acetylcysteine (NAC) was administered. His RAGMA rapidly resolved following treatment.