Elsevier

Autoimmunity Reviews

Volume 16, Issue 3, March 2017, Pages 253-257
Autoimmunity Reviews

Review
Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study

https://doi.org/10.1016/j.autrev.2017.01.008Get rights and content

Abstract

Objective

Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients.

Methods

Anti-Jo1 positive patients presenting with incomplete ASSD (no > 2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients.

Results

165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15 months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19 months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p = 0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p = 0.002).

Conclusion

Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Introduction

Anti-synthetase syndrome (ASSD) is a connective disease mainly affecting adults at any age, characterized by a strict association with aminoacyl-transfer RNA synthetase (ARS) antibodies and by a highly variable clinical picture [1]. Interstitial lung disease (ILD), myositis and arthritis represent the classic clinical triad of the disease, with frequencies ranging from 60% to 95% of cases [2], [3], [4], [5], [6], [7], [8]. Recently, it has been shown that in anti-Jo1 positive ASSD, the clinical triad of the disease is rarely observed at disease onset, and that patients presenting with just one or two classic triad findings (for a practical purpose defined as incomplete forms) frequently will develop additional triad features during the follow-up [9], [10], [11]. The later appearance of initially absent classic triad findings during the follow-up is common and, of interest, is particularly increased in patients with a single triad finding onset, depicted in up to 50% of anti-Jo1 positive ASSD [10]. Other ASSD typical clinical features, like fever, Raynaud phenomenon (RP) and mechanic's hands (MHs), are less frequently observed in comparison to the classic triad findings and have been reported in approximately 40% of cases [10], [11], [12]. Although the presence of MHs is a relevant clinical clue for the diagnosis of ASSD [13], the implications and clinical predictive value of the development of fever, MHs and RP during the course of the disease in patients without the classic triad at disease onset have not been evaluated yet. Thus, the aim of this multicenter, international and retrospective study was to assess whether the development of RP, fever or MHs during the follow-up may predict the subsequent occurrence of the baseline absent classic triad manifestations in one of the largest cohort of anti-Jo1 positive ASSD [10].

Section snippets

Patients and methods

Patients were selected from a retrospective large database of ASSD patients regularly followed at twenty-four Rheumatology centers from Italy (14), Spain (6), Germany (3), and USA (1), as previously described [10]. Patients were eligible if they had at least two anti-Jo1 positive tests and presented, at disease onset, with an incomplete ASSD (just one or two findings between arthritis, myositis and ILD). Signed informed consent as approved by the local Institutional Ethics Board was required

Results

One-hundred and sixty-five (123 women, 42 men) with incomplete ASSD were selected. The median age at disease onset was 53 years (IQR 42–64) and the median follow-up 94 months (IQR 49–156).

Discussion

To the best of our knowledge, results of the present study provide the first demonstration that anti-Jo1 positive ASSD patients with incomplete forms at disease onset who during the follow-up develop non-classic accompanying ASSD clinical features have an almost four-fold increased risk for new classic triad manifestation occurrence when compared to those patients who do not develop accompanying features. Indeed, the diagnosis of ASSD is still challenging because symptoms are often non-specific

Take-home messages

  • Interstitial lung disease, arthritis and myositis represent the classical triad manifestations of anti-synthetase syndrome (ASSD).

  • The classical triad manifestations are rarely contemporary observed at disease onset and an incomplete form, with one or two classic triad manifestations, characterizes about 80% of patients at disease presentation. Nevertheless, the appearance of the complete classic triad manifestations is common during the follow-up of the disease.

  • Studies aimed at establishing

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosures: None to declare.

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