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Review
. 2022 Sep 15:14:171-186.
doi: 10.2147/OARRR.S285409. eCollection 2022.

Predicting the Progression of Very Early Systemic Sclerosis: Current Insights

Chiara Bellocchi  1   2 , Augustine Chung  3 , Elizabeth R Volkmann  4
Affiliations
Review

Predicting the Progression of Very Early Systemic Sclerosis: Current Insights

Chiara Bellocchi et al. Open Access Rheumatol. .

Abstract

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease with distinct pathological hallmarks (ie, inflammation, vasculopathy, fibrosis) that may predominate at different stages in the disease course with varying severity. Initial efforts to classify patients with SSc identified a subset of patients with very early SSc. These patients possessed signs of SSc (eg, Raynaud phenomenon, SSc specific autoantibodies and/or nailfold capillary abnormalities) without fulfilling complete SSc classification criteria. Recognizing the inherent value in early diagnosis and intervention in SSc, researchers have endeavored to identify risk factors for progression from very early SSc to definite SSc. The present review summarizes the clinical phenotype of patients with very early and early SSc. Through a scoping review of recent literature, this review also describes risk factors for progression to definite SSc with a focus on the specific clinical features that arise early in the SSc disease course (eg, diffuse cutaneous sclerosis, interstitial lung disease, esophageal dysfunction, renal crisis, cardiac involvement). In addition to clinical risk factors, this review provides evidence for how biological data (ie, serological, genomic, proteomic profiles, skin bioengineering methods) can be integrated into risk assessment models in the future. Furthering our understanding of biological features of very early SSc will undoubtedly provide novel insights into SSc pathogenesis and may illuminate new therapeutic targets to prevent progression of SSc.

Keywords: disease progression; early diagnosis; scleroderma; systemic sclerosis.

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Conflict of interest statement

Dr Elizabeth R Volkmann reports grants, personal fees from Boehringer Ingelheim, grants from Horizon and grants from Kadmon, outside the submitted work; also awarded grants from Prometheus. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A and B) demonstrate nailfold video-capillaroscopy findings in a patient with very early SSc who presented with RP and anticentromere antibodies. Arrows in (A) identify giant capillaries. (B) demonstrates capillary drop-out; the arrow in this panel identifies a microhemorrhage.
Figure 2
Figure 2
The ACR/EULAR 2013 Classification Criteria for SSc, highlighting the criteria for very early SSc. A total score of 9 is sufficient to classify patients with definite SSc.
Figure 3
Figure 3
Flow chart for the evaluation of patients with early SSc by organ system with description of risk factors and diagnostic testing.
Figure 4
Figure 4
Proteins related to very early SSc disease stages.
See this image and copyright information in PMC

References

    1. Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685–1699. doi:10.1016/S0140-6736(17)30933-9 - DOI - PubMed
    1. Wielosz E, Majdan M. Clinical and serological parameters of progression and prognosis in patients with systemic sclerosis - a state of the art review. Wiad Lek. 2020;73(7):1528–1532. - PubMed
    1. Yang C, Tang S, Zhu D, Ding Y, Qiao J. Classical disease-specific autoantibodies in systemic sclerosis: clinical features, gene susceptibility, and disease stratification. Front Med. 2020;7:587773. doi:10.3389/fmed.2020.587773 - DOI - PMC - PubMed
    1. Bellando-Randone S, Matucci-Cerinic M. Very early systemic sclerosis. Best Pract Res Clin Rheumatol. 2019;33(4):101428. doi:10.1016/j.berh.2019.101428 - DOI - PubMed
    1. LeRoy EC, Medsger TA. Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001;28(7):1573–1576. - PubMed