Incidence, prevalence, and mortality of localized scleroderma in Quebec, Canada: a population-based study

Abstract

Background: Localized scleroderma is an understudied autoimmune disease characterized by fibrosis of the skin and/or subcutaneous tissue. To date, only 6 articles reported on the incidence and/or prevalence estimates globally, with significant design limitations and risk of bias. None of the studies originated from Canada or investigated mortality/geospatial epidemiology. We aimed to study the incidence, prevalence, mortality and spatiotemporal trends of localized scleroderma in Quebec, Canada, stratified by sex and age.

Methods: Quebec populational health administrative databases were used to identify localized scleroderma cases from 1989 to 2019. Crude incidence rate, age-standardized incidence rate, prevalence and mortality analyses were conducted using negative binomial random walk models. Spatial analyses were conducted using a Poisson Besag-York-Mollié regression model.

Findings: There were 6063 incident localized scleroderma cases identified over the total period of the study (mean age 53.0, standard deviation [SD] 20.2 years at diagnosis). The overall age and sex-standardized incidence rate was 3.25/100,000 person-years [95% Confidence Interval (CI) 3.17-3.33]. Among 6063 incident cases, 4510 (74.4%) were female and 1553 (25.6%) were male, yielding a female-to-male ratio of approximately 3:1. In females, we noted an initial increase in age-standardized incidence rate followed by a plateau and a decrease after 2013 (average annual percent change -2.0 [95% CI -3.7 to -0.2]%). In males, a steady decrease in age-standardized incidence rate was observed (average annual percent change -3.3 [95% CI -5.0 to -1.8]%). The highest incidence rate was observed in the 60-79 year-old age group for females and the 80+ group for males. Age-standardized incidence rate varied geographically with hotspots identified in the south of Quebec. The average prevalence was 24.5/100,000 [95% CI 24.3-24.8]. The overall standardized mortality ratio was comparable for females (1.04 [95% CI 0.95-1.14]) and males (1.14 [95% CI 0.98-1.33]) and decreased steadily over time for both sexes (from 1.31 [95% CI 1.06-1.58] in 1996 to 0.81 [95% CI 0.66-0.98] in 2019). Standardized mortality ratio analysis revealed excess death only in females aged 40-59 years.

Interpretation: From 1989 onward, we report an initial increase in the age and sex-standardized incidence rate of localized scleroderma in Quebec followed by a recent decrease after 2013, as well as a generally increasing prevalence from 1996 to 2019. Standardized mortality ratio analysis confirmed the clinical observation that localized scleroderma is a morbid rather than life-threatening disease. We demonstrate an uneven geographic distribution of localized scleroderma incidence in Quebec.

Funding: This project was funded by Canadian Dermatology Foundation, National Scleroderma Foundation and Canadian Institutes of Health Research. Dr. Netchiporouk received FRQS Junior 1 Clinician Scientist Salary Award.

Keywords: Epidemiology; Incidence; Localized scleroderma; Morphea; Prevalence; Quebec.

Fig. 1

Age standardized incidence rate (ASIR) over time (1996–2019) for females, males, and both. The grey areas represent the 95% confidence intervals for the annual point estimates from the model.

Fig. 2

Crude incidence rate over time (1996–2019) per age group (0–19, 20–39, 40–59, 60–79, 80+) for females (A) and males (B). The grey areas represent the 95% confidence intervals for the annual point estimates from the model.

Fig. 3

Prevalence rates over time (1996–2019) for females, males, and both. The peak prevalence for females was 47.1/100,000 persons with a 3.7 [95% Confidence Interval, CI 3.4–4.2]% average annual percent increase. The peak prevalence for males was 13.6/100,000 persons with a 0.4 [95% CI −0.04 to 0.9]% average annual percent increase. The grey areas represent the 95% CI for the annual point estimates from the model. The points around the curve represent the true observed values for each year.

Fig. 4

Number of deaths per cause of death among study individuals.

Fig. 5

Trends in standardized mortality ratio (SMR), standardized by age and sex, over time (1996–2019) for females and males. The grey areas represent the 95% confidence intervals. The Y axis is a logarithmic scale.

Fig. 6

Standardized mortality ratio (SMR) over the study period per age group and sex. The lines for each point represent the 95% confidence interval. The Y axis is a logarithmic scale.

Fig. 7

A. Geographic distribution of standardized incidence ratios in Quebec (1996–2019). B. Clustered hot spots in Quebec (1996–2019).