Pathological contributors to organ damage and mortality in systemic sclerosis: a nationwide matched case-control study.

BACKGROUND

Mortality is increased in systemic sclerosis (SSc), including a 10-15-fold increase in sudden cardiac death. Limited histopathology data exist to understand the pathogenesis of this excess. This study aimed to compare heart, lung and renal histopathology at autopsy between SSc and controls.

METHODS

A matched case-control study was performed using autopsy data from the Australian National Coronial Information System. SSc cases were selected via keyword search, and age- and sex-matched to controls identified from motor vehicle accidents. Cause of death, antemortem comorbidities and autopsy findings were extracted. Odds ratios were calculated with 95 % confidence intervals (CI).

FINDINGS

Fifty-nine SSc cases (64 years, 81 % female) were matched to 59 controls (62 years, 81 % female). Myocardial fibrosis was 11-times more common in SSc (95 %CI 4-29, p < 0.01), inflammation 39-times more common (95 %CI 2-672, p = 0.01) and small vessel vasculopathy 27-times more common (95 %CI 2-485, p = 0.02), despite no difference in epicardial coronary artery disease (p = 0.24). Two-thirds of SSc cases had myocardial fibrosis with no identifiable secondary cause (e.g., coronary/valvular lesions). Pulmonary fibrosis, inflammation and vasculopathy ranged from 23 to 100-times more common in SSc. Renal fibrosis/scarring, inflammation/infiltrates and vasculopathy were 3-6-times more common in SSc. Among SSc cases, combined pathologies (≥2 of fibrosis, inflammation or vasculopathy) were seen concurrently in 31 % of hearts, 41 % of lungs and 45 % of kidneys.

INTERPRETATION

The high frequency of unexplained myocardial fibrosis in SSc provides insights into the mechanism of excess mortality and sudden cardiac death observed in SSc. This matched autopsy study demonstrates the mechanisms and complexity of organ damage in SSc, with 30-45 % of organs displaying multiple concurrent pathologies.