Systemic sclerosis (SSc) is a rare autoimmune disease, with a prevalence in Europe ranging from 7.2 to 33.9 cases per 100,000 individuals.1 This disease is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. It primarily involves the microcirculation and Raynaud's phenomenon (RP) is typically the first and most prevalent manifestation of the disease, occurring in more than 90% of patients.2

Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC), which is a simple, safe and non-invasive technique that allows a detailed assessment of nailfold capillaries.3 NVC shows a variety of morphological changes, including microhemorrhages, enlarged and giant capillaries, impaired capillary architecture, loss of capillaries with or without avascular areas and the presence of abnormal shapes.4 Some authors have disclosed specific capillaroscopic patterns in SSc patients, known as “scleroderma patterns”. These patterns not only aid in the diagnostic process, but also appear to correlate with consecutive stages of capillary damage.4,5 The three NVC scleroderma patterns (early, active and late) seem to reflect the evolution of SSc microangiopathy and may be useful in assessing microvascular damage. Therefore, NVC can be a diagnostic and a follow-up parameter to track microvascular changes over time.

However, there has been limited research and understanding regarding the impact of the severity of microvascular damage in predicting overall disease severity. With the aim of assessing NVC as a marker of overall disease severity, this study was conducted to evaluate microvascular damage using NVC among patients with SSc at disease onset and to assess associations between these changes and systemic involvement over a 3-year follow-up period.

NVC is a unique, non-invasive and easy technique that allows the morphological evaluation of the nailfold capillaries.3 Its major role in rheumatology is to aid in the differential diagnosis of primary and secondary Raynaud's phenomenon. Capillaroscopic changes can be observed in several connective tissue diseases, namely in SSc, systemic lupus erythematosus (SLE), dermatomyositis, mixed connective tissue disease (MCTD), undifferentiated connective tissue disease, rheumatoid arthritis and overlap syndromes.12 In SSc, these capillaroscopic changes are specific and detectable in the vast majority of patients.4,5 It is noteworthy that “scleroderma” type capillaroscopic changes have been validated and accepted as diagnostic criterion in the current 2013 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SSc.6

Beyond its crucial role in SSc diagnosis, NVC may also serve as a valuable indicator of disease activity and severity, as suggested by previous studies.13–15 However, most of these studies only examined specific manifestations of the disease and have not explored the association between the capillaroscopic changes and the overall disease severity.

In our study, we identified a moderate correlation between the severity of microvascular damage, as indicated by the worsening of the NVC patterns, and the global measure of disease severity, determined by the summation of the Medsger DSS for each domain. Notably, patients exhibiting a late scleroderma pattern had a significantly higher disease severity score and this pattern was predictive of a worse global disease severity score. To the best of our knowledge, only one other study, conducted by Avouac et al., has explored the correlation between the NVC changes and the global disease severity score using the Medsger DSS.16 Avouac et al. reported that a reduction in the number of capillaries and the presence of neoangiogenesis were associated with the worsening of the Medsger DSS.16 Ingegnoli et al. found that in cases of less severe organ involvement, the early or active scleroderma patterns were more commonly observed, whereas in more severe forms of the disease, the late scleroderma pattern became more prevalent.17 These findings, along with our own research, strongly emphasize the crucial role of NVC as a predictor of the extent of internal organ involvement and the disease severity.

Regarding each specific manifestation, we observed that patients exhibiting a late pattern in the NVC had a significantly increased risk of developing digital ulcers. Additionally, we identified a correlation between the severity of microvascular damage and the severity of peripheral vascular involvement. These findings are in agreement with previous reports. Avouac et al. found that a reduction in the number of capillaries and the presence of neoangiogenesis were associated with the onset of new digital ulcers, while other authors have reported that the risk of developing digital ulcers was significantly higher in patients with a late pattern.14,18,19

Regarding calcinosis, we found that patients exhibiting a late pattern in the NVC had a significantly higher risk of development of calcinosis and that the late scleroderma pattern was a predictor of calcinosis in both univariate and multivariate analyses. Calcinosis was a relatively underexplored topic in previous research. However, two previous studies, conducted by Morardet et al. and Baron et al., also found that calcinosis is independently associated with the late scleroderma pattern, and particularly, with severe capillary loss.20,21

Furthermore, we found that patients with a late pattern in the NVC had a significantly increased risk of severe skin involvement. We also identified a moderate correlation between the severity of microvascular damage and the extent of skin involvement. These findings are well-supported in the literature, as previous studies have reported that late patterns are associated with a more extensive skin involvement and a reduction in the number of capillaries may predict the progression of skin thickness.3,14,16,18

Moreover, a weak correlation between the extent of microvascular damage and the severity of muscle involvement was found in our study. Additionally, a late scleroderma pattern appears to predict muscular involvement in SSc patients. To the best of our knowledge, only one study, conducted by Smith et al., has explored the link between NVC patterns at baseline and the severity of muscle involvement, and no significant association was reported. Given the limited number of patients in this study who exhibited muscle involvement, we recommend caution in the interpretation of these results.

Contrary to previous reports, our findings did not reveal any noteworthy correlation between the severity of microvascular damage and lung involvement, including both ILD and PAH.14,15,22,23 Most of our patients with lung involvement exhibited either an active or a late scleroderma pattern, but no significant difference was found among the different NVC patterns. It's worth noting that the absence of this association may be related to the limited number of patients with lung involvement, particularly those with PAH.

Our study had some limitations that should be acknowledged. Major limitations are related to the single-centre retrospective nature of the study. Other limitation includes the small number of patients with cardiac and muscle involvement, so generalization in these cases should be done cautiously. Since we did not have any patient with renal involvement, it was not possible to assess the association with NVC patterns. Furthermore, we did not assess the potential influence of medications taken prior to the NVC, which could eventually interfere with the results of the NVC.

Further prospective studies with larger samples size are warranted, especially to investigate the possible association between capillaroscopic changes and the overall disease severity, as well as the possible associations between different organ involvement, including muscle, renal and cardiac involvement, which have been poorly studied before.

In our study, the overall disease severity in SSc is associated with the worsening of NVC pattern. Also, the severity of peripheral vascular involvement and extension of skin involvement was associated with worsening of NVC pattern. Additionally, the late scleroderma pattern seems to predict the presence of digital ulcers, calcinosis, muscular involvement and severe disease.

This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement. It may aid the physicians in risk stratification, ensuring a careful monitoring and more aggressive treatment for patients at higher risk of a severe disease.

None to declare.