Patients were seen at the Rheumatology department of the Hospital Regional Universitario José María Cabral y Baez in the period between March 2002 and May 2013 (n=1.609); we selected those that met the EULAR/ACR 2012 classification criteria for systemic sclerosis (SS),8 and who were compiled in the Dominican population EUSTAR database. For classification into subtypes we followed the recommendations of EULAR/ACR criteria for classification of SS and localized disease subtypes.9,10Fig. 1 summarizes the classification.

Fig. 1.

Overall scleroderma classification. Adapted from: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee 9 to Kreuter et al.10

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Patients with overlap (n=1) syndromes, including mixed connective tissue disease (n=3) were excluded from this study. SS patients were divided into those with the diffuse form of the disease and those with the limited form (which included CREST syndrome); there were no patients with SS sine scleroderma. Patients of all age ranges were included because there is no pediatric rheumatology service in the region. Clinical and demographic information was obtained retrospectively from the department database and medical records; information at diagnosis was used. High resolution computed tomography (HRCT) and pulmonary function tests for the detection of interstitial lung disease were performed.

All patients signed informed consent; in the case of minors, the legal representative signed the informed consent, with the minor also signing the informed consent. The protocol was approved by the institutional ethics committee.

The demographic variables analyzed were gender and age, both at diagnosis and at the time of onset of related symptoms. The age at diagnosis was calculated using the date on which the final diagnosis was made and the date of birth of the individual; the age at onset of symptoms was obtained through directed interrogation.

Regarding the disease subtype, these were determined according to EULAR criteria/ACR 2013.8 The modified Rodnan scale (mRSS) was used to assess the extent of disease; the prognosis of the patients was considered according to a consensus of EUSTAR experts.11 We inquired about clinical manifestations of cutaneous, pulmonary, gastrointestinal and renal involvement. Ischemic heart disease, peripheral vascular disease, hypertension, dyslipidemia, diabetes mellitus, chronic renal failure, osteoporosis (because of its high prevalence in the population) and toxic habits (which included smoking, alcohol, physical inactivity and obesity) were investigated.

Autoimmune serology was performed, consisting of antinuclear antibodies (ANA), anticentromere antibodies, anti-Scl-70, anti-RNP, anti-Sm, anti-SSA, anti-SSB, anti-Jo-1 and anti-dsDNA, in a subgroup of patients, using an electrochemiluminescent immunoassay method. Pulmonary artery pressure, pulmonary or tricuspid regurgitation and diastolic dysfunction were sought using echocardiography. The results of pulmonary function tests were divided into the following patterns: obstructive, restrictive and mixed. The presence of pulmonary fibrotic changes on the posteroanterior chest X-ray was investigated. HRCT was performed in 15 patients and the results were classified as normal, ground glass pattern, honeycomb pattern and others.

The focus of this study was to describe the findings in a series of patients with SS, so no treatment information was included.

Categorical data are expressed in percentages, whereas continuous variables are presented using means±standard deviation (SD) when the distribution was normal, and using median and ranks when it was not.

Normality was assessed using the Shapiro–Wilk test. For the relationship between categorical variables we employed Fisher's exact test (FET). The relationship between a categorical variable and a continuous variable was determined by ANOVA or Kruskal–Wallis. All analyses were performed using α=0.05. The statistical package used was SPSS, v.20.

Limited SS was found in 12 patients (43%), while the remaining patients (n=14) had diffuse SS. At the time that this study was performed, the average time of evolution (calculated using the age at onset of symptoms) was 6.8±4.3 years.

The extent of skin disease was determined using the mRSS which did not follow a normal distribution (Shapiro–Wilk P=.003). In patients with limited SS, the median was 14, with a range of 15 (minimum=6). When considering the division suggested by the EUSTAR consensus of experts in Paris, 2009, in this group of patients we found that 5.3% of patients have a high probability of remission (mRSS≤10); the rest have a 50% likelihood of improvement in symptoms (mRSS: 11–35). In patients with diffuse SS, median mRSS was 23, with a range of 39 (minimum value=6), with a minimum of 6; although 21.4% of patients had mRSS≤10 64.3% were found to have values in the range of 11–35. There was no statistically significant association between SS subtype and mRSS (H [1]=2.600; P=.107, mean range for limited SS=10.68, mean range for diffuse SS=15.57).

In both subtypes of SS, the process of induration was more severe in the fingers of the upper extremities, bilaterally, as evidenced by a median of 3 in the value of mRSS at this location. In both hands, the degree of general affection was moderate to severe, with values 2 and 3 for the median and mode of mRSS, respectively; however, in most patients, the left tended to be worse than its right counterparts regarding induration. In both arms, the median mRSS was 1.5 while the mode was 2, pointing to a mild-moderate condition in this location; both arms were equally affected.

In general, in the diffuse subtype of SS, the face and both feet were affected with mild (median and mode 1) induration, with no cases of moderate and severe disease. In the limited form of SS, facial skin involvement was rare (2 cases showed mild and 2 moderate induration), but the mild involvement of both feet was (median and mode 1) the norm.

The delay from the time of first symptom to the time of diagnosis had a mean of 2.6±2.7 years. Most patients (60%) were diagnosed in the year after disease began or the next; 5 patients took more than 5 years to be diagnosed after the first symptom. There was no relationship between the first symptom and diagnosis, and patient SS subtype (H [1]=0.480, P=.488; mean range for limited SS=14.14, mean range for diffuse SS=12.11).

The most common clinical sign found was Raynaud's phenomenon; it was found in all patients with diffuse SS, but only in 54.5% of patients with the limited form. Localized calcinosis was found in 2 patients with diffuse disease; in patients with limited disease, 2 cases of localized calcinosis occurred, one case of diffuse calcinosis and another in a patient with visceral affection. In patients with diffuse SS, digital ulcers were found occasionally in 33.3% of cases and frequently in 13.3%; in patients with limited scleroderma, digital ulcers occurred frequently in 2 patients. The phenomenon of pitting was found in 46.7% of the patients with diffuse SS, but not in patients with limited SS.

Regarding respiratory symptoms, 66.7% of the patients with diffuse SS reported no dyspnea; of the 6 patients with dyspnea, 3 had dyspnea on moderate exertion. In patients with limited SS, one patient had great efforts dyspnea, while 2 had dyspnea on slight exertion. Cough was low in frequency, being present in only one patient with diffuse SS and in 2 patients with limited SS.

The most common clinical manifestation was gastrointestinal reflux, but appeared more frequently in patients with limited SS (54.5%) than in diffuse SSc patients (46.7%). Dysphagia was present in 26.7% of patients with diffuse SS, but only in 2 patients with limited SS. Clinical signs of malabsorption were found in a patient with diffuse disease and 2 patients with the limited form; constipation followed a similar distribution.

Renal manifestations were rare. No casts or azotemia was found. Three patients had albuminuria, and 2 with diffuse scleroderma. Erythrocyturia was found in a patient with diffuse disease. No patient had scleroderma renal crisis.

Fig. 2 summarizes the frequency of clinical manifestations in the patients with diffuse and limited SS.

Fig. 2.

Clinical manifestations in patients with scleroderma. The main clinical manifestations in this population (n=26) are presented in this graph; the most frequent were Raynaud's phenomenon and gastroesophageal reflux. SS, systemic sclerosis.

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Additionally, the presence of comorbidities and toxic habits in this group of patients was studied. Consistently with the age range (73.1% of the population is under 50 years old) and the prevalence of female gender, the number of comorbidities was low. Fig. 3 summarizes the findings.

Fig. 3.

Comorbidities and toxic habits in patients with scleroderma. The number of comorbidities in this population (n=26) was low, probably due to the fact that it was a predominantly young population. The most common comorbidity was hypertension. SS, systemic sclerosis.

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The comorbidity that was found more frequently in patients with both subtypes of SS was arterial hypertension: 26.7% and 45.5% of cases of diffuse and limited SS presented it, respectively. Dyslipidemia was found in 2 patients, one with diffuse SS and one with limited SS. Diabetes mellitus type 2 was found in 2 patients, one with diffuse SS and one with limited SS; there were no cases of obesity.

Cardiovascular disorders were observed in patients with limited SS: 2 had ischemic heart disease, and 3, peripheral vascular disease. There were no patients with diffuse SSc and cardiovascular disease.

Osteoporosis was found in a patient with diffuse SS and 3 patients with limited SS. Chronic kidney disease was demonstrated in a patient with limited SS.

The patients studied reported low risk lifestyles. The degree of physical inactivity in the population was low: only 4 patients reported sedentary life styles, 2 in each subtype of the disease. Regular use of tobacco was only seen in patients with limited SS. None of the patients reported regular intake of alcohol.

As part of the study protocol, all the patients included in the study were evaluated using echocardiography. 2 cases of pulmonary arterial hypertension, a case of diastolic dysfunction and a case of pericarditis (none of these was the same patient) were found in the subgroup of patients with diffuse SS. The ejection fraction of the left ventricle was above 60% in all patients. 2 cases with pulmonary arterial hypertension and 3 with diastolic dysfunction were found in the subgroup of patients with limited SS; 2 patients showed isolated tricuspid regurgitation. There were no cases of pericarditis. Similar to the patients with diffuse mode, the ejection fraction of the left ventricle was above 60% in all patients. No statistically significant association between the presence of abnormalities on echocardiography and subtype of SS was observed (FET exact P=.680) or value of the mRSS (F[1,22]=0.239; P=.630).

The pulmonary function tests were normal in 6 patients (23.1%), 4 of these with limited scleroderma. Of the patients with diffuse SS, 60% had a restrictive pattern; there was one case with isolated obstructive pattern and a case with mixed pattern. In this group of patients, the mean values±SD for FVC, FEV1 and FVC/FEV1 were 69.5%±19.1%; 73.9% 22.7±107.4 and 16.6%, respectively. In the patients with limited SS it was found that 36.4% had normal spirometry, 36.4% had a restrictive pattern, 9.1% an obstructive pattern and 9.1% a mixed pattern. Mean±SD values for FVC, FEV1 and FVC/FEV1 in this subgroup of patients were 76.6%±24.4%; 84.1% 31.7±125.1 and 57.3%. There was no statistically significant association between the subtype of scleroderma and the development of a restrictive pattern (FET exact P=.408).

The posteroanterior chest X-ray images were suggestive of fibrotic changes in the lungs of 80% of the population with diffuse SS; in patients with limited disease, this finding was found in 54.5% of patients. For economic reasons, HRCT was performed only in 14 patients. Patients with diffuse SS on HRCT were 10, of which only one had a normal HRCT. Four patients (26.7%) had a standard “honeycomb” pattern; there were no patients with frosted glass pattern. In 5 patients there were other findings (bronchiectasis, pachypleuritis, increased pulmonary insterstitial images, emphysema and atelectasis). Of the 4 patients with limited SS in whom HRCT was performed, only one had no evidence of lung disease. A “honeycomb” pattern was found in one patient and a frosted glass pattern in another; other findings (bronchiectasis, pachypleuritis, increased pulmonary interstitium, emphysema and atelectasis) were found in 3 patients.

Until last year, there was no videocapillaroscopy equipment in the country and it currently remains a high cost study, not covered by social security; as a result, only 7 patients have videocapillaroscopy. Three patients with diffuse SS had videocapillaroscopy performed; one patient had no pathologic data, another had an active pattern and the third pattern had a late pattern. In the group of patients with limited SS, 2 had an active pattern, one an early pattern and one a late pattern.

An “autoimmune panel” composed of ANA, anticentromere, anti-Scl-70, anti-RNP, anti-Sm, anti-SSA, anti-SSB, anti-Jo-1 and anti-dsDNA antibodies was offered at a price subsidized by private institutions to help low-income population; anti-PM-Scl are not available in the country. Thirteen patients agreed to have autoimmune serology tests performed. Negative serology was found in one patient, who had limited SS. Tables 3 and 4 give details about the presence of each of these autoantibodies.

ANA titers were investigated in 15 patients, 5 with limited SS and 11 with diffuse SS. All patients with diffuse disease had presence of ANA. In this group of patients there was a similar distribution between nucleolar (27.3%), speckled (45.5%) and homogeneous patterns (27.3%); there were no patients with anticentromere pattern. Four of the 5 patients with limited SS had ANA. In 2 cases, a homogeneous pattern was found; the other 2 patients had anticentromere mottled patterns.

The authors declare that this research has not performed experiments on humans or animals.

The authors declare that they have followed the protocols of their workplace on the publication of data from patients and all the patients included in the study have received sufficient information and gave written informed consent to participate in the study.

The authors have obtained informed consent from patients and/or subjects referred to in the article. This document is in the possession of the corresponding author.