Background/Purpose:

The Le Roy et al. classification of SSc into limited and diffuse cutaneous subtype remains the most commonly used. Nevertheless, autoantibodies are much better predictors of organ involvement. Although more sophisticated approaches exist, a simple classification, using antibodies and skin subset is relevant to clinical practice and could help risk stratification.

Methods:

Initially subjects were divided into 12 groups, based on skin subset and autoantibodies – ACA, anti-Scl-70 antibodies, anti-RNA polymerase antibodies (ARA), anti-U3RNP antibodies, anti-PmScl antibodies and a group with other antibodies, including rarer specificities, ANA+ ENA- and ANA negative patients.

Kaplan-Meier (KM) estimation of survival and cumulative incidence of organ complications were calculated for each subgroup. Subgroups were ranked in terms of endpoint estimates and those showing similar ranking in multiple endpoints, were merged.

Results:

The cohort consisted of 1025 SSc patients. Mean age at disease onset was 47 years and 16% were male. Diffuse cutaneous (dc)SSc was diagnosed in 35% of the subjects. Antibody characteristics included ACA in 31%, Scl-70 in 22%, ARA in 11%, U3RNP in 5% and PmScl in 4% of the subjects. For the whole cohort, at 20 years from onset, estimated survival was 60%, incidence of significant pulmonary fibrosis (PF) was 44%, pulmonary hypertension (PH) 25%, scleroderma renal crisis (SRC) 7% and cardiac SSc 6%.

The final classification included 7 subgroups. Group 1 (29%) consisted of ACA+ lcSSc patients. This was the subgroup with the highest survival (72%), the lowest incidence of PF (13%) and SRC (no cases) at 20 years from onset. The incidence of PH was similar to the average for the whole cohort.

Group 2 (11%) consisted of all ARA+ subjects and it had the highest incidence of SRC (32% at 20 years), while other organ complications and survival were similar to the cohort average.

Group 3 (11%) included Scl-70+ lcSSc patients and although incidence of PF in this group was the second highest (69% at 20 years), other complications were rare. The group had the lowest incidence of PH (6%) and the second lowest incidence of SRC (3%) at 20 years.

On the other hand, Scl-70+ dcSSc patients (group 4, 11%), had a very poor prognosis with the highest incidence of PF (91%), cardiac scleroderma (14%) and the worst survival (41%) at 20 years.

Group 5 included all U3RNP+ patients (5%). Although survival in this group was not bad (70% at 20 years), this group had the highest PH incidence (40%) and the second highest incidence of cardiac SSc (11%) at 20 years.

Groups 6 and 7 (22% and 11% respectively) included lcSSc and dcSSc patients with other antibody specificities. Group 6 had low overall risk of SRC and cardiac SSc, while other outcomes were similar to the cohort average. Conversely, group 7 had poor prognosis, with the second lowest survival (42% at 20 years) and above average rates of organ disease, particularly PF and SRC.

Conclusion:

We propose a simple classification scheme, combining autoantibody specificity and extent of skin involvement, which is easy to apply in a clinical setting and distinguishes well between patient groups at risk of serious complications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-practical-classification-of-systemic-sclerosis-using-subset-and-autoantibodies-for-the-purpose-of-early-risk-stratification/