Systemic sclerosis (SSc) is an autoimmune disease of unknown cause characterized by microvasculopathy, fibroblast activation, and excessive production of collagen.1

Involvement of the gastrointestinal (GI) tract in SSc is second in frequency only to the skin, and it is characterized by esophageal dysmotility in 75–90%, stomach involvement in 50%, small bowel involvement in 40–70%, colon involvement in 20–50%, and anorectal involvement in 50–70%.2 The mortality rate attributable to GI involvement is 6–12%.3–7

The great impact of esophageal involvement in the morbi-mortality of SSc is related to its association with interstitial lung disease,8 weight loss and malnutrition, Barrett's esophagus9,10 and its progression to adenocarcinoma.11 Around 18–40% of patients are asymptomatic despite the objective documentation of esophageal disease.10 Esophageal manometry is considered the method of choice for evaluation of esophageal motility in SSc patients, even when they are asymptomatic.

A new technique called high resolution manometry (HRM) in which catheters with 36 pressure sensors separated by 1cm are used to measure intraesophageal pressure from the hypopharynx to the stomach, was introduced recently. The result is a color picture of the topography of esophageal pressure, where the duration, amplitude and velocity of esophageal contractions (including the function of the upper and lower esophageal sphincter) are plotted.12 Traditionally, manometric findings were reported as rated by Spechler and Castell.13 From 2008 onwards (and with the introduction of the HRM) a new classification (The Chicago classification) was described, and is currently the most widely used classification.14,15 The aim of this study was to categorize esophageal motor disorder in patients with SSc by HRM and to describe its association with upper GI symptomatology.

We included 21 patients, 19 with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Seventeen patients (80.9%) had less than three years of being diagnosed. Most patients were female (95.2%) with mean age of 44.9 (SD 14) years, a mean weight of 61.9kg (SD 14.4) and height of 1.57 (SD 0.8) m; the other clinical and demographic variables are in Table 1. We found 17 (80.9%) patients with limited SSc. The mean mRSS for all patients was 9.7 (SD 7.4). Raynaud's phenomenon was reported in 18 (85.7%) patients.

We found a normal HRM in 6 (28.5%) patients and an abnormal HRM in 15 (71.4%) patients. Patients with an abnormal HRM were: 1 (6.6%) patient with distal esophageal spasm, 5 (33.3%) patients with absent peristalsis, 4 (26.6%) patients with weak peristalsis with small peristaltic defects, and 3 (20%) patients with frequent failed peristalsis. Only 2 (13.3%) patients in whom an abnormal HRM was found could not be classified.

The association between upper GI symptoms and HRM results is shown in Table 2. Dysphagia and heartburn were the most frequent symptoms reported by the patients, but in general, symptom frequency did not vary between groups with or without HRM abnormalities. Only regurgitation was found to be more frequent in patients with a normal HRM. Additionally, neither the Carlsson–Dent questionnaire nor dysphagia severity was different between groups. Two patients with limited SSc who were asymptomatic (one patient with absent peristalsis and the other with weak peristalsis with small peristaltic defects) showed an abnormal HRM. The two variant SSc patients (scleroderma sine scleroderma and morphea) had a normal HRM.

In this cohort of SSc patients, an abnormal HRM was found in 71.4%. Dysphagia and heartburn were the most common esophageal symptoms reported, which is similar to other published series.8–10 We did not find any association between clinical-demographic variables and the outcome of the HRM, or between upper GI symptoms and HRM findings, except for regurgitation, which was found to be more frequent in patients with a normal HRM.

There had been a previous study assessing the clinical features of Mexican scleroderma patients; Santos-Navarro et al.19 studied 60 patients and found hypotensive lower esophageal sphincter (LES) in 95%. Aperistalsis (41%), slight hypomotility (30%), and severe hypomotility (27%) with different gastric manifestations as: early satiety 45%, abdominal pain 35%, nausea 20% and vomiting 10%. In contrast with our study they did not intent to correlate the clinical findings with manometry ones. Also they performed standard manometry versus high resolution in our patients. Even tough, they found a high prevalence of manometry alterations, maybe explained by age differences between cohorts, and the established disease by ten years of more.

This is not the first study to find a lack of an association between esophageal dysmotility evaluated by HRM and upper GI symptomatology in patients with SSc. Roman et al. studied HRM findings in 51 patients with SSc, and found that 67.3% had HRM abnormalities (most commonly hypotensive esophagogastric junction). However, up to 87% of patients had esophageal symptoms that were not predictive of HRM alterations.20 Later, Tang et al. associated HRM findings with phenotypic and GI symptoms in 28 patients with SSc, and could not find a clear association between dysphagia and HRM findings.21 Recently, Raja et al. reported the finding of a study on 31 patients with SSc who underwent HRM.22 They found that upper GI symptoms were absent in the majority of their patients, even when they had severe esophageal involvement according to HRM findings. The same basic results were reported in another recent study involving 79 patients with SSc.23

It has been known for some time that the severity of upper GI symptoms does not always correlate with objective measures of esophageal dysmotility, and this may include HRM. In a retrospective study of over 250 patients who underwent HRM due to upper GI symptoms, these were not found to be related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position.24 The discordance that we observed in our study might not be limited to patients with SSc. Other studies on populations with systemic diseases that usually involve the esophagus, such as Chagas disease, have similarly found a lack of an association between HRM findings and upper GI symptomatology.25 Additionally, in our study, 95.2% of patients at the time of evaluation were treated with proton pump inhibitors (PPIs). The lack of association between the symptoms and the results of HRM may be also partly explained by the high percentage of patients using PPIs at the time of evaluation, or even the use of other non-prescription medications for heartburn that could mask the symptoms evaluated. This limitation was also seen in other study.21

On the other hand, there are certain features of SSc that have been more consistently associated with HRM alterations. Patients with SSc and Raynaud phenomenon have been found to have lower amplitude of distal esophageal contractions21 as well as with more hypotensive lower esophageal sphincter22 compared to those without. Degree of skin involvement has also been positively correlated with esophageal dysmotility according to HRM as well as with more severe dysphagia.21,23 The latter were not found in our cohort. The presence of pulmonary fibrosis in SSc patients was also found to be associated with more absent contractility in HRM as well as with more symptoms of gastroesophageal reflux.22,23 At least one study found that alterations in HRM were correlated to presence of Scl70 and absence of anti-centromere antibodies,20 but these findings were not replicated in another recent study.23 In our study we did not assess lung function, and neither the severity of skin involvement or presence of Raynaud phenomenon was significantly associated with HRM abnormalities, although there was a trend toward more alterations in patients with Raynaud phenomenon.

The patients with morphea and scleroderma sine scleroderma we included both had a normal HRM. Recently, Arif et al. evaluated SSc and morphea patients with upper gastrointestinal endoscopy, esophageal manometry and 24-h pH monitoring, and found that of the 31 patients with morphea, none had manometric findings, although only four patients had symptoms. The authors concluded that in morphea, an assessment of GI manifestations is not necessary, unlike SSc.26 We also observed two patients with SSc without esophageal symptoms but with an abnormal HRM. Previously, Thonhofer et al. conducted a retrospective study, where they evaluated patients with SSc and Mixed Connective Tissue Disease (MCTD) without GI symptoms. The patients underwent a baseline evaluation and follow-up at three to six months. In all thirteen SSc patients, significant pathology of the upper GI-tract was found. In patients with esophageal abnormalities, starting treatment led to favorable results, which was confirmed in the follow-up study. The authors suggest that the GI evaluation must be performed early in patients diagnosed with SSc, even if they do not report typical symptoms,27 an opinion that we share considering our results.

We consider that the strengths of the study are: a population with a relatively early diagnosis of SSc, the use of HRM and the Chicago classification. The limitations include: cross-sectional study design, small cohort of patients, heterogeneity in the treatment of patients, lack of description of other comorbidities that could affect the outcome of the HRM, as well as lack of further studies to complement the manometry result, such as pH monitoring or endoscopy.

In conclusion, we found a high prevalence of esophageal symptoms but a lack of association between these and the presence of an abnormal HRM, which is in accordance to other published, studies.19–22 This suggests that it is important to perform a systematic approach to GI symptomatology in SSc patients at diagnosis irrespective of objective procedures of motility evaluation. This will identify early GI abnormalities, help alleviate symptoms and thereby lessen the impact on morbidity and mortality generated by this condition.

None.

Arana-Guajardo AC: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; obtained funding; administrative, technical, or material support.

Barrera-Torres G: acquisition of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.

Villarreal-Alarcón MA: study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; study supervision.

Vega-Morales D: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis; study supervision.

Esquivel-Valerio JA: analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.

None declared.