Older Age Onset of Systemic Sclerosis

Accelerated Disease Progression in All Disease Subsets

Pia Moinzadeh; Kathrin Kuhr; Elise Siegert; Ulf Mueller-Ladner; Gabriela Riemekasten; Claudia Günther; Ina Kötter; Jörg Henes; Norbert Blank; Gabriele Zeidler; Christiane Pfeiffer; Aaron Juche; Ilona Jandova; Jan Ehrchen; Marc Schmalzing; Laura Susok; Tim Schmeiser; Cord Sunderkoetter; Jörg H. W. Distler; Margitta Worm; Alexander Kreuter; Thomas Krieg; Nicolas Hunzelmann


Rheumatology. 2020;59(11):3380-3389. 

In This Article


This study revealed that approximately one quarter of patients developed SSc after the age of 60 years with a significantly higher proportion of women in the late disease onset cohort. The main finding of the present study is a shift in the distribution of subsets. This was also reflected by the antibody distribution, with significantly more ACA and less ATA within the elderly cohort. Moreover, SSc overlap syndromes show a significantly different age distribution within the late-onset cohort.

The second main finding is that, independent of the subsets, older patients, although having a significantly lower modified Rodnan Skin Score, developed significantly earlier first skin changes as well as specific organ manifestations, compared with patients with the early disease onset. This is in line with recent observations that the disease progression was significantly faster in lcSSc patients with late disease onset compared with the early-onset cohort.[6,7] Nevertheless, diffuse cutaneous SSc patients showed the most rapidly progressing subtype independent from disease onset groups compared with the other two subsets.

In terms of organ manifestation, our data suggest that PH and heart involvement occurred significantly more often within the late-onset cohort, which is in line with other reports.[3,15] However, a more detailed analysis of the development of clinical symptoms and organ manifestations within the different subsets showed that late-onset lcSSc and dcSSc patients developed significantly more often PH, while only late-onset dcSSc patients suffered more frequently from lung fibrosis and heart involvement. In addition, the analysis of all follow-up data over >15 years, using Kaplan–Meier analyses confirmed the results that late onset scleroderma patients in all subsets had a significantly higher and especially earlier incidence of organ manifestation, e.g. PH, lung fibrosis and heart involvement with the exception of the musculoskeletal system and the gastrointestinal involvement. It is interesting to note that SSc overlap patients characterized by more intense musculoskeletal involvement compared with the other two subsets developed those complications more often in the early disease onset cohort. This supports the notion that these patients represent a specific subset with a different disease course as suggested earlier.[2]

Basically, our findings are in line with previous publications but also extend these observations. The EULAR Scleroderma Trials and Research Group (EUSTAR) published their data recently regarding the association between age subgroups and clinical characteristics; they also showed that patients with a late disease onset suffered more frequently from the limited subtype, with ACA positivity and PH/cardiac involvement.[23]

However, it has not been reported so far that we determined no difference for the use of corticosteroids within the three age groups and significantly fewer patients older than 60 years at disease onset who underwent disease-modifying/immunosuppressive treatment.

Although it has also been observed in other studies, it remains unclear why our patients had significantly fewer digital ulcers at late disease onset,[3,24,25] but demonstrated a more severe course of the disease with more extensive PH.[3,23] This observation may be explained by the increased use of vasodilators due to arterial hypertension and/or PH in older patients. It should also be mentioned that in a retrospective study it was shown that digital amputation was associated with older age, long history of RP, long disease duration and presence of anticentromere antibody. This could probably be explained by the coexistence of other micro/macrovascular disease processes.[26] Our observation that vasculopathic organ manifestations, except digital ulcers, were more common in the late onset cohort, and inflammatory symptoms more frequent in the early onset cohort support this conclusion. This is also in agreement with the relatively rare use of immunosuppressive drugs in patients with later disease onset; however, the fact that elderly patients are more vulnerable to risks of immunosuppressive therapies, especially to infections and malignancies, and that physicians might be more reluctant to prescribe immunosuppressive drugs in the elderly might also contribute to this observation. Our data support the suggestion of several other studies to use the older age at disease onset as an independent prognostic factor, together with the diffuse subset, lung involvement, PH and renal crisis[10,26,27] for a poor prognosis.

This study contributes further important and unique findings due to the well-defined patient cohort of 3281 patients and >8000 follow-up visits. The presentation of the course of the disease on the basis of Kaplan–Meier curves nicely presents the variation in disease expression and progression in all three different SSc subsets. In contrast to other studies, our data clearly show differences between the individual SSc subsets, the lcSSc, dcSSc and SSc overlap syndromes together with a new contribution of therapeutic approaches in different age groups.

The following limitations of our study need to be discussed. It should be noted, that, as in many other studies, the data within this register are pre-collected and definitions have been established when the register was established in 2003. Specific data that turned out to be interesting during the analysis could not be collected retrospectively. Missing data were fortunately only <10% for all main variables, except for some variables (e.g. FVC, FEV1) that have been added after revision of the questionnaire in 2014. A further general limitation in the interpretation of register-based studies is that only data of included patients are considered, leaving an unclear number of unrecorded patients. However, assuming a prevalence of SSc of 100–200 patients per million, our data are based on 25–50% of all patients in Germany indicating a high reliability of the findings.

In summary, our findings may have an important impact for recommendations on the number of follow-up visits and additional diagnostics in SSc patients. Not only the specific SSc subset,[2] but also the patients with an older age at disease onset represent subgroups at risk and should be examined more frequently regarding potential organ manifestations. Importantly, an older age at disease onset is an additional risk factor for disease progression in addition to well-known risk factors such as SSc subsets, specific antibodies and specific organ manifestations.