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

Abstract and Introduction


Objectives: Systemic sclerosis is a heterogeneous, multisystem disease. It can occur at any age, but most patients develop the disease between the age of 40 to 50 years. There is controversial evidence on whether/how the age at disease onset affects their clinical phenotype. We here investigate the relationship between age at disease onset and symptoms in a large cohort of SSc patients (lcSSc, dcSSc and SSc-overlap syndromes).

Methods: Clinical data of the registry of the German Network for Systemic Scleroderma including 3281 patients were evaluated and subdivided into three age groups at disease onset (<40 years, 40–60 years, >60 years).

Results: Among all SSc patients, 24.5% developed their first non-Raynaud phenomenon symptoms at the age <40 years, and 22.5% were older than 60 years of age. In particular, older patients at onset developed the lcSSc subset significantly more often. Furthermore, they had pulmonary hypertension more often, but digital ulcerations less often. Remarkably, the course of the disease was more rapidly progressing in the older cohort (>60 years), except for gastrointestinal and musculoskeletal involvement. No significant difference was found for the use of corticosteroids. However, significantly, fewer patients older than 60 years received immunosuppressive treatment.

Conclusion: In this large registry, ~25% of patients developed SSc at an age above 60 years with an increased frequency of lcSSc. In this age group, an onset of internal organ involvement was significantly accelerated across all three subsets. These findings suggest that, in the elderly cohort, more frequent follow-up examinations are required for an earlier detection of organ complications.


Systemic sclerosis (SSc) is a complex and heterogeneous multisystem disease, which affects the skin together with many internal organs, such as the cardiopulmonary system, the gastrointestinal tract, the musculoskeletal system and the kidney.[1] The disease is characterized by endothelial cell damage, altered regulation of the immune system, and an extensive deposition of collagen and other extracellular matrix proteins leading to fibrosis.[1] Importantly, SSc is a heterogeneous disease and different SSc subsets are associated with distinct expression of organ manifestations/clinical features and a divergent progression of the disease. This has also been shown for patients with SSc overlap syndromes who, despite their limited skin involvement, develop a completely different course of disease, distinct from lcSSc and dcSSc patients.[2]

The majority of SSc patients develop initial clinical symptoms between the age of 40 to 50 years.[3,4] However, there is a very broad range of disease onset and also much younger and older patients can develop SSc.[3,5] Furthermore, various authors have observed that elderly patients express different clinical features, which is reflected by characteristic autoantibodies.[3,5–11] There is, however, still a controversial discussion; several studies indicate that older patients have a more severe course of the disease including different organ involvement and a worse prognosis. Recently, a more progressive disease with a poor prognosis and a higher mortality rate compared with younger SSc patients was reported.[5] In particular, although elderly patients (>60 years) have a lower prevalence of digital ulcers, they developed cardiac involvement more frequently[5,9,12] with an increased mortality.[6–11,13,14] Furthermore, Nihtyanova and colleagues reported that a greater age at disease onset predicts a higher risk for both lung fibrosis and pulmonary hypertension (PH).[15] This is supported by an analysis of a SSc cohort by the Johns Hopkins University. It has been demonstrated that patients older than 65 years have not only a greater risk for PH, but for renal, cardiac and musculoskeletal involvement.[3] Apart from the organ involvement, it is controversial whether older patients more frequently belong to a certain SSc subset with a rather limited[6,7] or diffuse skin involvement.[16–18] On the other hand, the Spanish Scleroderma Study Group have shown in their SSc cohort of 1037 patients that younger patients (age ≤30 years) had a higher prevalence of oesophageal and musculoskeletal involvement, but a lower prevalence of anti-centromer antibodies (ACA). Furthermore, the mortality ratio was higher in younger patients.[10,14]

To further evaluate the controversial situation regarding the relationship between the age at disease onset, disease course and clinical characteristics, we here present data from an independent, very large cohort of patients with different SSc subsets, which have been carefully analysed with many consecutive visits over 15 years.