The clinical manifestations at the onset of antisynthetase syndrome: A chameleon with multiple faces

Abstract

The antisynthetase syndrome (ASS) is clinically characterized by fever, myositis, interstitial lung disease, joint involvement, mechanic’s hands, or Raynaud’s phenomenon, and the presence of antisynthetase autoantibodies. These clinical manifestations may not occur simultaneously. Therefore, the aim of this study was to analyze the sequence in which these clinical manifestations can develop at the onset of ASS. This retrospective, single-center cohort study enrolled 55 ASS patients. Their mean age at the onset of ASS symptoms was 42.3±11.8 years. There was a predominance of female patients (75.9%) and white patients (72.7%). At initial presentation, 41.8% of the patients had fever, 43.6% had joint symptoms, 38.2% had myositis, 36.4% had interstitial lung disease, 18.2% had Raynaud’s phenomenon, and 16.4% had mechanic’s hands. Subsequent clinical symptoms emerged at varying time points. In two out of 55 cases, joint, muscle, and lung manifestations developed simultaneously. The median time between the onset of symptoms and the complete ASS clinical manifestation was 19.9 (4.0-60.2) months; whereas, the timeframe between the onset of symptoms and the ASS diagnosis was 29.0 (11.0-63.0) months. The confounding misdiagnoses interfering with the initial diagnosis were polymyositis (52.7%), dermatomyositis (29.1%), nonspecific interstitial pneumopathy (23.6%), rheumatoid arthritis (18.2%), and others (10.9%). Clinical features at the onset of ASS are highly variable. Consequently, confounding factors can lead to significant delays for the final and definitive diagnosis of ASS. Therefore, ASS should be considered a differential diagnosis in patients with initial symptoms of joint, lung, and/or muscle involvements, as well as fever, mechanic’s hands, and/or Raynaud’s phenomenon manifestations.

Difficulties in the diagnosis of antisynthetase syndrome

“…Over time, however, most patients developed further symptoms, and by the end of the follow-up, the vast majority of patients had either the classic triad of symptoms or at least two symptoms coexisting [14]. The different timing of symptom onset was also demonstrated in a retrospective study analysing 55 patients with antisynthetase syndrome hospitalised in a Brazilian centre [18]. In the described cohort, the most common first symptom of the disease was joint complaints, observed in 43.6% of patients.…”

“…Diagnosis of the disease is complicated by the fact that not all symptoms are necessarily present in every patient, and complaints may appear at different times [14,18,19]. A trend towards the progression of the clinical picture over time was noted in an observational study on a group of 828 patients with antisynthetase antibodies from the AENEAS (American and European NEtwork of Antisynthetase Syndrome) registry [14].…”

“…Subsequent clinical symptoms appeared at different time points in individual patients. In the cohort described above, the median time between the onset of first symptoms and the development of fully-symptomatic antisynthetase syndrome was 19.9 months, reaching 60.2 months in the case with the maximum time to fully symptomatic disease [18]. A multicentre study of Spanish patients with antisynthetase syndrome analysed the course of the disease in 148 individuals [19].…”

A case of antisynthetase syndrome with chilblains‐like lesions and microangiopathy

“…The anti-JO1 is the most frequently identified. More rarely, anti-PL-12, PL-7, EJ, OJ, KS, ZO, YRS, JS, and SC can be involved [1][2][3]7 Specific MSA identification is important because of their association with clinical specificities, forming clinical subgroups. 3,4 Muscle biopsy (after magnetic resonance imaging) can be useful when the diagnosis is difficult and shows relatively homogeneous anomalies regardless of the ASS subgroup.…”

High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome

“…Antisynthetase syndrome (ASSD) is a rare systemic autoimmune myopathy that is defined by the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) autoantibodies. Clinically, ASSD is characterized by myositis, arthritis, and interstitial pneumopathy, in addition to "mechanic's hands," Raynaud's phenomenon, or fever (1)(2)(3)(4). Myositis has a broad phenotypic spectrum among individuals with ASSD, ranging from increased serum levels of muscle enzymes in asymptomatic patients or isolated myalgia to severe muscle weakness in bedridden patients (5).…”