Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive skin and internal organ fibrosis, with various degrees of severity according to the disease subtype. Although skin fibrosis is the hallmark of the disease, it is the visceral damage that is responsible for increased morbidity and mortality.1 The clinical presentation of SSc is heterogeneous, ranging from mild fibrosis of acral portions of extremities and organs, to extensive generalized fibrosis and severe organic damage.1 The two major SSc subsets are limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc). In patients with lcSSc, skin thickening occurs in distal extremities, whereas in patients with dcSSc skin thickening occurs proximally to the elbows or knees and often extends to the trunk.1 Visceral involvement varies between subtypes; lcSSc is more frequently associated with pulmonary arterial hypertension and severe gut disease,1 whereas dcSSc involves a higher risk of interstitial lung disease2 and renal damage.3

The disease has a low prevalence worldwide, affecting between 7.2 and 33.9 per 100,000 in Europe and North America, respectively.4 As also seen in other autoimmune diseases, the natural history and clinical phenotype of SSc may vary across geographic regions, races and ethnicities.5 For example, African American patients have an earlier onset of disease, more severe clinical manifestations and more aggressive lung disease as compared to Caucasian patient populations.6

In Latin America some studies seem to indicate a lower prevalence of the disease relative to the other world regions7,8 as well as differences in its natural history. For example, the mean age at the time of disease onset was 32 years in Dominican patients, comparable to that of their African American counterparts, and lower than in Caucasian patients.9 Also, Mexican patients showed a lower frequency of renal crisis, higher prevalence of pulmonary arterial hypertension (PAH), as well as a higher frequency of anticentromere antibodies (ACA) and anti-topoisomerase antibodies (ATA) than in the African American patient population.10 A cohort of Argentinean patients had a lower prevalence of ATA, compared to other cohorts from Europe and USA.11

To our knowledge, there are few studies on the clinical and serological characteristics of SSc patients in Venezuela. In a study of rheumatic disorders in a population of a native indigenous population in eastern Venezuela, the prevalence of SSc was estimated at 0.06% per 100.12 The aim of our study was to investigate the demographic and clinical characteristics of urban Venezuelan SSc patients seen in a tertiary hospital.

In the present study, we looked at the sociodemographic and clinical characteristics in a sample of Venezuelan patients with SSc seen in a tertiary hospital. Differences in the demographic and clinical characteristic of those with the limited and diffuse subsets were described. Several differences were observed in the phenotypic expression and natural history of the disease compared to other populations. In contrast to results reported in Mexican10 and African American patients,3,17 our cohort showed a higher mean age, higher mean age at disease onset and higher disease duration, more comparable to the results reported in white patients of the EULAR Scleroderma Trials And Research18 (EUSTAR) and the Genetic versus Environment In Scleroderma Outcome Study19 (GENISOS) cohort studies. The female/male ratio in our study was 23:1, higher than that reported in other cohorts.4,9,11 This trend may be a result of cultural factors (for example, male patients are less likely than female patients to attend to outpatient health centers20,21) or it may be a random effect due to the relative small population studied.

Similar to the Mexican10 and Argentinean11 studies, our cohort showed a lower proportion of dcSSc cases as compared to those seen in African American patients,17 the ethnic group with the highest proportion of this SSc subset.3,17,22 The mean disease duration in our patients with dcSSc were markedly lower than in lcSSc patients, which may be explained by an earlier consultation due to the more severe clinical manifestations in patients with of dcSSc.3,22

The prevalence of ILD in our patients was 45.2%, comparable to that of Mexican10 and Caucasian EUSTAR18 patients and that of African American patients from a US cohort.17 It was also higher than that reported in the Asian, Caucasian and Hispanic patients from Northern California reported by Schmajuk et al.23 Unlike other racial/ethnic groups, in which lung damage predominated in dcSSc, in African American patients the pulmonary condition was distributed equally in both subsets.17 In our cohort, patients with dcSSc showed a higher prevalence of ILD and a lower level of FVC than patients in the lcSSc subset, as expected by the association of dcSSc with severe lung disease.2

Results of autoimmune serology showed a high frequency of ANA (92.9%), as previously reported in other cohorts.3,10,18 A close relationship was observed between ACA and the lcSSc subtype, with a similar frequency to that reported in other populations.10,17,24 Venezuelan patients had a lower frequency of ACA (15% vs 29%) but similar frequency of ATA as compared to Mexicans.10 The presence of ATA in SSc patients has been estimated to vary between 9.4% and 42%,25 which is in line with our observed prevalence of 22.7%. We found a lower frequency of ACA (15% vs 30%) and ATA (26% vs 37%) than that observed in a cohort of Caucasian patients,18 but similar to those reported in Japanese patients.24

Our study has some limitations. It was carried out in a single referral hospital, limiting the generalizability of the study, and it was based in a small sample population. There were also limitations in the extent of evaluation, such as the lack of capillaroscopic examination and a wider profile of autoantibodies due to the current humanitarian crisis and its impact on the health system in Venezuela.26 Also, we might have missed some early-onset SSc patients, some of them with nailfold capillary abnormalities.27 The strengths include the additional data to supplement the relatively scant information on the clinical expression of this disease in Latin America, and the ethnic homogeneity of the population studied.

In summary, this sample of Venezuelan patients with scleroderma presented with a clinical and serological phenotype with minor differences but otherwise comparable to other patient sample populations. The autoantibody pattern profile contributes to distinguishing the two main SSc subgroups and can help in the prediction of lung involvement.

Venezuelan patients with SSc show a demographic and clinical pattern of expression comparable to that described in other races and ethnicities and in patient populations in different geographic latitudes. Unlike in other autoimmune conditions, the uniformity of clinical expression of the disease may suggest a relatively constrained number of shared genetic and environmental factors contributing to the triggering and development of the disease worldwide.

The study was approved by the Ethics Committee of the University Hospital of Caracas. All procedures performed in our studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki.

Informed consent was obtained from all individual participants included in the study.

The authors received no financial support for the research, authorship, and/or publication of this article.

Authors declare no conflict of interest.