Multidimensional tracking of phenotypes and organ involvement in a complete nationwide systemic sclerosis cohort

Abstract

Objective: SSc is a severe, heterogeneous multi-organ disease where population-based estimates on phenotypic spectrum, overall disease burden and societal impact are largely missing. Here the objective was to provide the first-ever complete national-level data on phenotype and major organ afflictions in SSc.

Methods: A stepwise strategy was applied to find and characterize every SSc patient resident in Norway from 2000 to 2012. First we identified every case in the country registered with an International Classification of Diseases, Tenth Revision code for SSc (M34). Next we manually reviewed all cases coded as M34 to determine whether they met the 1980 ACR and/or 2013 ACR/EULAR classification criteria for SSc and could be included in the Norwegian SSc cohort (Nor-SSc). Finally, all disease features from SSc onset to study end were reviewed.

Results: The Nor-SSc cohort included 815 SSc patients. The mean age at diagnosis was 53 years, with 84% females and 77% limited cutaneous SSc. The estimated incidence increased from 4 per million in 2000 to 13 per million in 2012. We identified high cumulative frequencies of internal organ involvement, coexistence of multiple organ afflictions across disease subsets and autoantibody status and stable frequencies of pulmonary arterial hypertension across haemodynamic definitions, but indications of referral-related differences in pulmonary hypertension detection rates across the study area.

Conclusion: This nationwide cohort study provides new, unbiased evidence for a high disease burden in SSc patients of Caucasian descent and indicates the existence of hurdles preventing equality of assessment across the SSc population.

Keywords: epidemiology; gastrointestinal involvement; interstitial lung disease; pulmonary hypertension; systemic sclerosis.

Fig. 1

Case-finding strategy and patient inclusion in the Nor-SSc cohort Stepwise case-finding strategy (yellow boxes) and number of excluded patients (red boxes) and the number of identified SSc patients in the Nor-SSc cohort segregated by prevalent and incident cases (green boxes).

Fig. 2

Prevalence and incidence in the Nor-SSc cohort (A) The number of newly diagnosed SSc patients per year from 2000 to 2012. (B) Point prevalence of SSc in Norway each year from 2000 to 2012. (C) Mean time (in months) from RP to first non-RP symptom (green) and time from first non-RP symptom to diagnosis (red). (D) Distribution of SSc-related serum antibodies in the cohort. (E) Distribution of SSc according to skin involvement. (F) Frequencies of skin and renal involvement and other organ manifestations. (G) Frequencies of GI involvement. (H) Assessment of pre-capillary PH, with estimates for definite PH diagnosed by RHC and possible PH by echocardiography and clinical parameters.

Fig. 3

Cumulative coexistence of six major disease features Cumulative coexistence of six major disease features including GI involvement, skin affection, lung fibrosis, digital ulcers, PH and SRC stratified by antibody status or disease subtype with (A) all patients, (B) patients positive for anti-topoisomerase I antibody, (C) patients positive for ACAs, (D) patients positive for anti-RNA polymerase III antibody, (E) lcSSc patients and (F) dcSSc patients.

Fig. 4

Frequency of PH assessed by RHC (A) Cumulative incidence of PH subsets during the study period according to the current PH definition. (B) Cumulative incidence of PAH, PH-ILD and borderline PH in patients with available PVR values (n = 155) and the number of patients fulfilling the newly proposed pre-capillary PH definition and PVR >2.5 WU and >2.0 WU.