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


Overall Patient Characteristics

To compare demographic and serological parameters, we used data of the initial visit. For determining organ manifestations, clinical symptoms and medication data from all follow-up visits were analysed. Among all 3281 SSc patients, 54.2% (1777/3281) suffered from lcSSc, 34.8% (1142/3281) from dcSSc, and 11.0% (362/3281) from SSc overlap syndromes. The gender analysis revealed 79.7% (2568/3281) female patients, and 20.3% (655/3281) male patients. The mean age of SSc onset of the entire SSc cohort was 49.1 ± 14.0 years. Overall, 24.5% of patients developed first non-RP symptoms at the age of <40 years, 53.0% between the age of 40–60 years, and 22.5% were older than 60 years of age (Table 1). The mean age at disease onset in the early disease onset cohort (<40 years) was 30.5 ± 7.0 years, in the standard disease onset cohort (40–60 years) 50.0 ± 5.8 years, and in the late disease onset cohort (>60 years) 67.4 ± 5.2 years. The mean follow-up time was 4.9 (3.5) years and 2200 (67.1%) patients had at least 2 registered visits.

Age-related Clinical Manifestations Within the Entire SSc Cohort and Within Each SSc Subset

SSc patients with a late disease onset (>60 years) developed the lcSSc subtype significantly more often (65.0%) compared with dcSSc (25.7%), and 9.3% of SSc overlap syndromes (P < 0.001). Significantly more elderly patients (>60 years) were female compared with the younger cohort (P = 0.008) (Table 1). The antibody distribution matched also to the distribution of the subsets; here, SSc patients with a late disease onset were significantly less often positive for Scl-70, but significantly more often positive for ACA antibodies (P < 0.001). Accordingly, these patients had a significantly lower mRSS (9.4 (8.4), P = 0.023), but all three main SSc subsets developed first skin changes significantly earlier compared with patients with an early disease onset (<40 years). Patients with the diffuse form and SSc overlap syndromes developed first skin changes after a mean duration of 3.1 ( 3.5) years whereas lcSSc patients showed fist skin fibrosis after 4.0 (3.5) years (P < 0.001).

Furthermore, compared with the early disease onset cohort, the elderly cohort suffered overall significantly more often from PH (19.2%, P < 0.001), heart involvement (14.8%, P = 0.030) as well as significantly less often from oesophageal (48.3%, P = 0.01), and musculoskeletal involvement (31.3%, P = 0.005) (Table 2). Of these, the elderly lcSSc (17.6%) and dcSSc patients (24.9%) developed significantly more often PH (P < 0.001), but only the elderly dcSSc patients more frequently lung fibrosis (73.5%, P < 0.001) and heart involvement (23.8%, P = 0.005) compared with the younger cohort. In contrast, elderly SSc patients developed musculoskeletal involvement less often compared with the younger cohort, which was significant for SSc overlap patients (37.3%; P = 0.011) (Table 2 and Table 3).

Furthermore, patients with a late disease onset compared with patients with an early disease onset had digital ulcers significantly less often (P < 0.001) and significantly more often arterial hypertension (P < 0.001), which consists for all SSc subsets. Elderly patients diagnosed with lcSSc and dcSSc suffered more frequently from dyspnea (P < 0.001), and only lcSSc patients from proteinuria (P = 0.006) (Table 3).

No significant difference was found for the use of corticosteroids within the three age groups. However, fewer patients older than 60 years at disease onset underwent immunosuppressive treatment (35.1%; 244/696; P = 0.017) compared with patients younger than 40 years (42.0%, 319/759). Only the elderly dcSSc cohort had been treated significantly more often with corticosteroids (P = 0.026) compared with younger patients with dcSSc. Otherwise, no significant difference for corticosteroids and other disease-modifying agents within other SSc subsets was present (Table 3).

Age-related Disease Progression Within the Three SSc Subtypes (Follow-up Time >10 Years)

Across all three subsets, patients with a late disease onset had a significantly higher and earlier incidence of an organ manifestation, e.g. PH, lung fibrosis or heart involvement (P < 0.001; Figure 1), except the musculoskeletal system and the gastrointestinal involvement (Figure 1A–D). The proportion of patients free of organ manifestation after 10 years was lower in the late onset cohort (>60 years) compared with the early onset cohort (<40 years) for PH (61.8% vs 90.5%), lung fibrosis (47.8% vs 56.7%) and heart involvement (67.6% vs 84.3%) (Table 4).

Figure 1.

(A–D) Kaplan–Meier curves showing the time to onset of organ manifestations
Kaplan–Meier curves showing the time to onset of organ manifestations (PH, lung fibrosis, heart, musculoskeletal and gastrointestinal involvement) in three age subgroups at disease onset (<40 years, 40–60 years and >60 years) for all SSc patients and according to the SSc subset (lcSSc, dcSSc and SSc overlap syndromes). P-values correspond to log rank tests. Number at risk and cumulative number of events are given at starting point (SSc diagnosis) and every 5 years of follow-up.

This trend was also evident for each SSc subset (dcSSc, lcSSc and SSc overlap syndromes); patients diagnosed with late onset dcSSc showed the most pronounced organ manifestation, followed by the SSc overlap syndromes and the lcSSc patients. In contrast, the proportion-free rate of gastrointestinal (GI) involvement rate was almost the same for all SSc subsets (74.5% for dcSSc, 74.4% for lcSSc and 70.6% for SSc overlaps). Deviating from all other organ manifestations, musculoskeletal involvement occurred significantly earlier and more frequently in SSc overlap patients (proportion-free of organ involvement, 51.8% for dcSSc; 60.9% for lcSSc; and 34.2% for SSc overlap syndromes). Nevertheless, no significant difference for musculoskeletal involvement between early and late disease onset could be demonstrated (Figure 1A–D).