In systemic sclerosis (SSc), absent contractility (AC) rather than ineffective esophageal motility on manometry is associated with a severe esophageal and extraintestinal phenotype. We sought to determine whether slow esophageal transit on scintigraphy associates with a comparable clinical phenotype to that of AC on manometry, as scintigraphy may serve as a noninvasive approach to risk-stratify patients with SSc.

Clinical, demographic, and serologic features were compared between patients with and without delayed esophageal transit on scintigraphy. University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract (GIT) 2.0 scores measured GI symptoms, Medsger scores measured physician-assessed SSc disease severity, and the Composite Autonomic Symptom Score 31 survey evaluated dysautonomia symptoms.

Of 131 patients, 79 (60%) had delayed esophageal transit by scintigraphy. Patients with delayed esophageal transit were more likely to have diffuse SSc (24 [32%] vs 11 [22%]; P = 0.024), severe lung involvement (22 [41%] vs 7 [19%]; P = 0.034), severe Raynaud (36 [47%] vs 15 [31%]; P = 0.063), and a higher median (interquartile range [IQR]) diarrhea GIT score (0.5 [IQR 0-1] vs 0 [IQR 0-1]; P = 0.050). Lower diffusing capacity of the lungs for carbon monoxide values correlated with a higher esophageal transit time (ρ = -0.32; P = 0.014). After adjusting for disease duration, delayed esophageal transit was significantly associated with severe Medsger lung scores, severe Raynaud phenomenon, and higher modified Rodnan skin scores.

Patients with delayed esophageal transit by scintigraphy have a more severe SSc phenotype, similar to patients with AC, on esophageal manometry. Further studies should validate esophageal scintigraphy as a tool to identify patients with SSc with AC who may develop specific GI and extraintestinal complications.

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.

Systemic sclerosis (SSc) is considered by many to be one of the most severe autoimmune rheumatic diseases with lower prevalence observed in Northern Europe. No previous studies on the prevalence of SSc in Latvia have been conducted and the aim was to study the demographic and clinical data of patients with SSc in northeastern Europe country.

This study was conducted in two main Latvian hospitals for adults and includes patients with SSc who were consulted between 2016 and 2021.

During the study period, 159 patients with SSc were consulted. The point prevalence on 1 January 2021 was 84.0 per million. Female to male ratio was 4.67:1, and highest gender ratio was observed in the age group 70-79-year (6.75:1). Antinuclear antibodies were present in 82.58% of patients, without gender difference. Centromere pattern was more frequently observed in females (40.19% vs. 19.04%), in contrast to speckled pattern (50.98% vs. 57.14%). At disease onset females tended to be younger (46.51 ± 13.52) than males (50.5 ± 16.64). Males had more diffuse cutaneous subtype, interstitial lung disease, pulmonary hypertension and esophageal dysmotility. More than half of patients received treatment with glucocorticoids at any point of the disease (68.31%), without gender difference.

Systemic sclerosis is less common in Latvia than in other countries and regions. Due to its location, the data from Latvia are consistent with a north-south gradient in Europe. Gender ratio differences persisted in older age groups as well. Antinuclear antibodies presence did not differ between genders, but in female's centromere pattern was much more likely to be present. Males had more severe disease course, but in both genders more than half of patients received treatment with GCs at any point of the disease.

Systemic Sclerosis (SSc) is a rare connective tissue disorder characterized by autoimmunity, fibrosis, and vasculopathy that affects the skin and internal organs, including the gastrointestinal tract, particularly the esophagus. This article highlights the characteristics and clinical symptoms of esophageal involvement in patients with SSc.

This study was conducted between November 2022 to August 2023, including 26 already diagnosed cases of SSc in the Department of Rheumatology and Rehabilitation and Kurdistan Center for Gastroenterology and Hepatology-Sulaymaniyah, Iraq. Esophageal involvement was investigated using esophageal manometry, esophagogastroduodenoscopy (EGD), and 24-hour impedance-pH monitoring.

Females were significantly predominant (P = 0.019) regarding the symptoms; 76.9% of the patients had heart burn, 76.9% dysphagia, 73.1% water brush, and 69.2% regurgitation. In total, 69.2% of the patients showed erosive gastrointestinal reflux disease (GERD) on EGD, 76.9% had decreased lower esophageal sphincter pressure (DLESP) and decreased distal esophageal peristaltic contractions (DDEPC) on esophageal manometry, and 84.6% had reflux on pH monitoring. Raynaud's phenomenon is the most common and typically the earliest clinical manifestation of SSc. The presence of erosive GERD was found to significantly increase the risk of developing dysphagia (B = 4.725, P = 0.014, OR = 3.482) and regurgitation (B = 3.521, P = 0.006, OR = 4.030).

It is crucial to take gender-specific considerations into account when diagnosing and managing esophageal complications in patients with systemic sclerosis (SSc). Additionally, employing various diagnostic assessments to detect esophageal involvement during SSc is essential. Erosive GERD has been identified as a risk factor that contributes to the development of dysphagia and regurgitation in individuals with SSc.

To describe the severity and impact of gastrointestinal involvement in patients with systemic sclerosis (SSc) and identify associated factors.

Non-controlled cross-sectional study of patients with SSc (2013 American College of Rheumatology/European League Against Rheumatism criteria). The main variables were severity of gastrointestinal involvement according to the University of California, Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument (UCLA SCTC GIT 2.0) and dysphagia according to the Eating Assessment Tool-10 (EAT-10). We evaluated reflux, distension, diarrhoea, faecal soilage, constipation, emotional well-being and social functioning, as well as dysphagia. Clinical and epidemiological data were collected using the Mini Nutritional Assessment Short Form (MNA-SF) and the EuroQol-5D-3L. The degree of skin fibrosis was assessed using the modified Rodnan skin score (mRSS). Multivariate models were constructed to analyse factors associated with gastrointestinal involvement and dysphagia.

Of the 75 patients with SSc included, 58.7% had moderate, severe or very severe reflux, 57.4% had constipation according to UCLA SCTC GIT 2.0 and 49.7% had abdominal distension. Gastrointestinal symptoms interfered significantly with social functioning (42.7%) and emotional well-being (40.0%). Dysphagia (EAT-10≥3) was recorded in 52% of patients, and according to MNA-SF poor nutrition in 30.7%, and clear malnutrition requiring a nutritional intervention in 5.3%. Multivariate adjustment revealed an association between severity of gastrointestinal symptoms according to the mRSS (β=0.249; p=0.002) and Visual Analogue Scale 3-Level EuroQol-5D (VAS-EQ-5D-3L) (β=-0.302; p=0.001), whereas presence of dysphagia was associated with the mRSS (OR=2.794; p=0.015), VAS-EQ-5D-3L (OR=0.950; p=0.005) and malnutrition (MNA-SF≤7; OR=3.920; p=0.041).

Patients with SSc frequently present severe gastrointestinal symptoms. These are associated with poor quality of life, more severe skin involvement and malnutrition.

Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan.

A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE.

Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone.

Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

Absent contractility (AC), a motility disorder characterized by the absence of esophageal contractions while maintaining normal lower esophageal sphincter relaxation, is recognized as a distinctive major disorder of peristalsis on esophageal high-resolution manometry that warrants comprehensive understanding. This unique motility disorder often co-occurs with connective tissue, rheumatologic or autoimmune diseases, with scleroderma being the classic example. Symptoms of gastroesophageal reflux are common. AC can profoundly impact patients' lives and result in a spectrum of complications, including erosive esophagitis, esophageal candidiasis, Barrett's esophagus, and malnutrition. To address the intricate complexities of AC and its multifaceted complications, a multidisciplinary approach is paramount. This approach considers the distinct clinical presentation and underlying rheumatologic conditions of the individual patient, recognizing the inherent diversity within this disorder. While medical management of gastroesophageal reflux remains the cornerstone of AC treatment, emerging surgical and endoscopic interventions offer additional therapeutic options for those grappling with this challenging condition. This comprehensive review provides an in-depth evaluation of recent advances in our understanding of AC and its management. It endeavors to offer valuable insights into therapeutic strategies for AC and its associated issues.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation and progressive fibrosis, typically affecting the skin, with variable internal organ involvement. Interstitial lung disease (ILD), with a prevalence between 35 and 75%, is the leading cause of death in patients with SSc, indicating that all newly diagnosed patients should be screened for this complication. Some patients with SSc-ILD experience a progressive phenotype, which is characterized by worsening fibrosis on high-resolution computed tomography (HRCT), a decline in lung function, and premature mortality. To assess progression and guide therapeutic decisions, regular monitoring is essential and should include pulmonary function testing (PFT), symptom assessment, and repeat HRCT imaging when indicated. Multidisciplinary discussion allows a comprehensive evaluation of the available information and its consequences for management. There has been a shift in the approach to managing SSc-ILD, which includes the addition of targeted biologic and antifibrotic therapies to standard immunosuppressive therapy (particularly mycophenolate mofetil or cyclophosphamide), with autologous hematopoietic stem-cell transplantation and lung transplantation reserved for refractory cases.

Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).

Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.

Among 112 participants with follow-up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C-index of 0.72 (95% confidence interval 0.60-0.84).

The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc-ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc-ILD cohorts to confirm its predictive power.

Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD).

We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan-Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with GERD vs without GERD (SSc and SSc-ILD), and PPI vs no PPI use (SSc-ILD only). Progression was defined as a decrease in either percentage predicted forced vital capacity of ≥10% or single-breath diffusing capacity for carbon monoxide of ≥15%, or death.

It was found that 2693/4306 (63%) registered patients with SSc and 1204/1931 (62%) with SSc-ILD had GERD. GERD was not associated with decreased OS or decreased PFS in patients in either cohort. In SSc-ILD, PPI use was associated with improved OS vs no PPI use after 1 year [98.4% (95% CI: 97.6, 99.3); n = 760 vs 90.8% (87.9-93.8); n = 290] and after 5 years [91.4% (89.2-93.8); n = 357 vs 70.9% (65.2-77.1); n = 106; P < 0.0001]. PPI use was also associated with improved PFS vs no PPI use after 1 year [95.9% (94.6-97.3); n = 745 vs 86.4% (82.9-90.1); n = 278] and after 5 years [66.8% (63.0-70.8); n = 286 vs 45.9% (39.6-53.2); n = 69; P < 0.0001].

GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD. Controlled, prospective trials are needed to confirm this finding.

To investigate whether symptoms of gastroesophageal reflux disease and radiographic measures of esophageal dilation are associated with radiographic progression of systemic sclerosis-related interstitial lung disease (SSc-ILD).

Participants of the Scleroderma Lung Study II, which compared mycophenolate versus cyclophosphamide for SSc-ILD, completed the reflux domain of the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 at baseline. The diameter and area of the esophagus in the region of maximum dilation was measured by quantitative image analysis. Univariate and multivariable linear regression analyses were created to evaluate the relationship between these measures of esophageal involvement and progression of SSc-ILD over 2 years, based on the radiologic quantitative interstitial lung disease (QILD) and quantitative lung fibrosis (QLF) in the lobe of maximum involvement (LM). All multivariable models controlled for the treatment arm, baseline ILD severity, and proton-pump inhibitor use.

The baseline mean patient-reported reflux score was 0.57, indicating moderate reflux (n = 141). Baseline mean maximal esophageal diameter and area were 22 mm and 242 mm2 , respectively. Baseline reflux scores were significantly associated with the change in QLF-LM and QILD-LM in the univariate and multivariable models. Neither radiographic measure of esophageal dilation was associated with the change in radiographic measures of lung involvement.

Severity of reflux symptoms as measured by an SSc-specific questionnaire was independently associated with the change in the radiographic extent of ILD and fibrosis over 2 years in patients with SSc-ILD. Two objective measures of esophageal dilation were not associated with radiographic progression of ILD, highlighting the need for improved objective measures of esophageal dysfunction in SSc.

The gastrointestinal tract is commonly involved in patients with systemic sclerosis (SSc) with varied manifestations. As our understanding of SSc gastrointestinal disease pathogenesis and risk stratification is limited, we sought to investigate whether patterns of esophageal dysfunction associate with specific clinical phenotypes in SSc.

Patients enrolled in the Johns Hopkins Scleroderma Center Research Registry who completed high-resolution esophageal manometry (HREM) studies as part of their clinical care between 2011 and 2020 were identified. Associations between esophageal abnormalities on HREM (absent contractility [AC], ineffective esophageal motility [IEM], hypotensive lower esophageal sphincter [hypoLES]) and patient demographic information, clinical characteristics, and autoantibody profiles were examined.

Ninety-five patients with SSc had HREM data. Sixty-five patients (68.4%) had AC (37 patients with only AC, 28 patients with AC and a hypoLES), 9 patients (9.5%) had IEM, and 11 patients (11.6%) had normal studies. AC was significantly associated with diffuse cutaneous disease (38.5% versus 10.0%; P < 0.01), more severe Raynaud's phenomenon, including digital pits, ulcers, or gangrene (56.9% versus 30.0%; P = 0.02), and reduced median diffusing capacity of lung for carbon monoxide (50.6% versus 72.2%; P = 0.03). AC was observed in most of the patients who died (13 of 14; P = 0.06). These findings were not seen in patients with IEM.

Among patients with SSc, AC is associated with a significantly more severe clinical phenotype. IEM may associate with a milder phenotype. Further studies are needed to evaluate AC, IEM, and their clinical impact relative to the timing of other end-organ complications in SSc.

Absent contractility is considered a disorder of peristalsis. The literature about the etiology and clinical characteristics is scarce and the evidence on systemic diseases associated with this esophageal disorder is limited. Therefore, we aimed to determine the etiology of absent contractility in our population using the clinical algorithm recently described in the literature.

We conducted a retrospective, descriptive study at a single tertiary hospital of all patients diagnosed of absent contractility between May 2018 and February 2020. Data on demographic characteristics, medication, comorbidities, and laboratory and paraclinical tests were recorded from clinical records.

A total of 72 patients with absent contractility were included for analysis. There was a predominance of female sex (n=43, 59.7%), with a mean age of 55.4 (±15.0) years. We identified a systemic disorder associated with absent contractility in 64 (88.9%) patients. From these, 31 (43.1%) patients were diagnosed with a systemic autoimmune disease, 26 (36.1%) patients were considered to have absent contractility secondary to pathological exposure to acid-reflux and 15 (20.8%) patients were diagnosed with other non-autoimmune systemic disorders. In the remaining eight (11.1%) patients, there were no underlying systemic disorders that could justify the diagnosis of absent contractility.

A systematic approach to search for an underlying cause in patients diagnosed with absent contractility is warranted. Up to 90% of patients with absent contractility have a systemic disorder associated with this condition.

Esophageal dysmotility is a common and neglected complication of systemic sclerosis (SSc) associated with poor prognosis, while the assessment remains a challenge. We aimed to develop a diagnostic model for esophageal dysmotility in SSc patients that provides individualized risk estimates.

Seventy-five SSc patients who underwent high-resolution manometry (HRM) were included in the study. Esophageal widest diameter (WED) was measured on a chest CT scan. Esophageal parameters between patients with and without esophageal dysmotility were compared. Multivariate logistic regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to fit the model. The diagnostic model was evaluated by discrimination and calibration. Internal validation was estimated using the enhanced bootstrap method with 1000 repetitions.

Sixty-one systemic sclerosis patients (81.3%) were diagnosed with esophageal dysmotility according to the Chicago Classification v 3.0. The diagnostic model for evaluating the probability of esophageal dysmotility integrated clinical and imaging features, including disease duration, ILD, and WED. The model displayed good discrimination with an area under the curve (AUC) of 0.923 (95% CI: 0.837-1.000), a Brier score of 0.083, and good calibration. A high AUC value of 0.911 could still be achieved in the internal validation.

The diagnostic model, which combines the disease duration, ILD, and imaging feature (WED), is an effective and noninvasive method for predicting esophageal dysmotility in SSc patients.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by heterogeneous changes involving numerous organs and systems. The currently available data indicate that muscle injury (both smooth and striated muscles) is widespread and leads to significant morbidity, either directly or indirectly. From the consequences of smooth muscle involvement in the tunica media of blood vessels or at the level of the digestive tract, to skeletal myopathy (which may be interpreted strictly in the context of SSc, or as an overlap with idiopathic inflammatory myopathies), muscular injury in scleroderma translates to a number of notable clinical manifestations. Heart involvement in SSc is heterogenous depending on the definition used in the various studies. The majority of SSc patients experience a silent form of cardiac disease. The present review summarizes certain important features of myocardial, as well as smooth and skeletal muscle involvement in SSc. Further research is needed to fully describe and understand the pathogenic pathways and the implications of muscle involvement in scleroderma.

The interaction between the respiratory and gastrointestinal systems, and the role of the latter in the development of respiratory pathology, has been examined with a focus on gastro-oesophageal reflux disease (GORD). However, little data exists examining the link between oesophageal motility and respiratory disease.

In this study, we examined patterns in oesophageal motility using high-resolution oesophageal manometry (HROM) in patients with refractory respiratory symptoms.

Data were collected retrospectively for all patients that were investigated using HROM at a single centre for refractory respiratory symptoms between January 1st, 2011-December 1st, 2021. Patients were selected for investigation based on airway reflux symptoms, measured by the Hull Airways Reflux Questionnaire (HARQ).

441 patients were investigated with HROM (64% female, mean age = 56.5 [SD = 13.9]). The commonest diagnoses of these patients were Chronic Cough (77%, n = 339), Asthma (10%, n = 44), and Interstitial Lung Disease (7%, n = 29). The prevalence of oesophageal dysmotility was 66% in our cohort. Those with oesophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs 35.3, p < 0.001) and there was a significant inverse correlation between HARQ scores and distal contractile integral (DCI), a measure of oesophageal contractility.

Two-thirds of patients with refractory respiratory symptoms were found to have oesophageal dysmotility on HROM. These findings suggest motility disorders of the oesophagus may contribute to the development and progression of respiratory disease. This study highlights the need for further prospective study of the relationship between oesophageal dysmotility and respiratory disease.

(1) Background: Absent contractility (AC) is an esophageal motility disorder defined as a normal integrated relaxation pressure with 100% failed peristalsis. We sought to clarify the natural history of this disorder and its relationship with rheumatologic diseases, such as systemic sclerosis (scleroderma). (2) Methods: We retrospectively identified patients with AC based on high-resolution manometry findings at three referral institutions and then matched them with controls with esophageal complaints who had normal manometries. (3) Results: Seventy-four patients with AC were included (mean age 56 years; 69% female). Sixteen patients (21.6%) had a rheumatologic disease. Compared to controls, patients with AC were significantly more likely to present with heartburn, dysphagia, vomiting, and weight loss. During follow-up, they were also more likely to be seen by a gastroenterologist, be diagnosed with gastroesophageal reflux disease, take a proton pump inhibitor, and undergo repeat upper endoscopies. No AC patients developed a new rheumatologic disease during follow-up. No significant differences were noted in the clinical presentation or course of AC patients with rheumatologic disease compared to those without. (4) Conclusions: Patients with AC have more esophageal symptoms and require more intense gastrointestinal follow-up than controls. Only a minority of patients with AC have underlying rheumatologic disease. Those without rheumatologic disease at baseline did not subsequently develop one, suggesting that a rheumatologic evaluation is likely unnecessary. The clinical course of AC in patients with rheumatologic disease and those without appears to be similar.

Systemic sclerosis (SSc) is a chronic and generalized disease affecting the connective tissue of the skin and many internal organs, in particular the gastrointestinal tract. The esophagus is involved in up to 80% of the cases and represents a major cause of serious morbidities that deeply impact on the quality of life and survival of patients. Indeed, the presence of esophageal dysfunction is a good prognostic indicator in SSc, primarily due to its impact on pulmonary disease. Thus, the detection of esophageal motility alterations plays a critical role to prevent the development of both esophageal and pulmonary complications and to improve the survival of these patients. Currently, this diagnostic work-up has been limited to the use of esophageal manometry, which is considered the gold standard for the evaluation of motor physiology and pathophysiology of this organ in different clinical situations. However, in recent years, new equipments such as high-resolution (-impedance) manometry and functional luminal imaging probe have been developed and used in many esophageal clinical settings, including SSc. In this mini-review, we summarize current evidence regarding esophageal dysmotility, in the light of new data on secondary peristalsis published in this issue of the journal.

Although esophageal dysmotility is common in systemic sclerosis (SSc)/scleroderma, little is known regarding the pathophysiology of motor abnormalities driving reflux severity and dysphagia. This study aimed to assess primary and secondary peristalsis in SSc using a comprehensive esophageal motility assessment applying high-resolution manometry (HRM) and functional luminal imaging probe (FLIP) Panometry.

A total of 32 patients with scleroderma (28 female; ages 38-77; 20 limited SSc, 12 diffuse SSc) completed FLIP Panometry and HRM. Secondary peristalsis, i.e., contractile responses (CR), was classified on FLIP Panometry by pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), or absent (ACR). Primary peristalsis on HRM was assessed according to the Chicago classification.

The manometric diagnoses were 56% (n = 18) absent contractility, 22% (n = 7) ineffective esophageal motility (IEM), and 22% (n = 7) normal motility. Secondary peristalsis (CRs) included 38% (n = 12) ACR, 38% (n = 12) IDCR, 19% (n = 6) BCR, and 15% (n = 5) NCR. The median (IQR) esophagogastric junction (EGJ) distensibility index (DI) was 5.8 mm² /mmHg (4.8-10.1) mm² /mmHg; EGJ-DI was >8.0 mm² /mmHg in 31%, and >2.0 mm² /mmHg in 100% of patients. Among 18 patients with absent contractility on HRM, 11 had ACR, 5 had IDCR, and 2 had BCR. Among 7 patients with IEM, 1 had ACR, 5 had IDCR, and 1 NCR. All of the patients with normal peristalsis had NCR or BCR.

This was the first study assessing combined HRM and FLIP Panometry in a cohort of SSc patients, which demonstrated heterogeneity in primary and secondary peristalsis. This complementary approach facilitates characterizing esophageal function in SSc, although future study to examine clinical outcomes remains necessary.

Esophageal motility disorders are prevalent in 90% of patients with systemic sclerosis [scleroderma (SSc)], with an increased mortality rate in patients with severe esophageal involvement. Esophageal smooth muscle damage caused by ischemia, nerve damage, and inflammatory factors may be responsible for discomfort and various complications in these patients. The clinical manifestations are diverse. Most hospitals still use traditional esophageal manometry and 24-h pH monitoring to diagnose esophageal function in patients with SSc. The aim of this review article is to provide an overview of SSc-related esophageal motility disorders and related research progress, including the pathogenesis and clinical features of these disorders and the progress made in endoscopic diagnosis. We also discuss the possible pathogenesis and potential therapeutic targets.

The gastrointestinal tract is the second largest organ system in the body and is often affected by connective tissue disorders. Scleroderma is the classic rheumatologic disease affecting the esophagus; more than 90% of patients with scleroderma have esophageal involvement. This article highlights esophageal manifestations of scleroderma, focusing on pathogenesis, clinical presentation, diagnostic considerations, and treatment options. In addition, this article briefly reviews the esophageal manifestations of other key connective tissue disorders, including mixed connective tissue disease, myositis, Sjogren syndrome, systemic lupus erythematosus, fibromyalgia, and Ehlers-Danlos syndrome.

Systemic sclerosis is an autoimmune disease characterized by vascular disease, fibrosis of the skin, and internal organ dysfunction. Gastrointestinal involvement is the most frequent complication of internal organs, impacting up to 90% of patients. Gastrointestinal involvement can affect any region of the gastrointestinal tract from the mouth to the anus, with a predominance of disorders being observed at the level of the upper digestive tract. The gastrointestinal involvement primarily involves the esophagus, small bowel, and rectum. The severity of gastrointestinal involvement affects quality of life and is a marker of worse prognosis and mortality in these patients. In this review, we describe the current findings regarding gastrointestinal involvement by this entity.

The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis (SSc). Esophageal involvement may lead to a significant reduction in patient quality of life. The exact pathophysiology is complex and not yet fully elucidated. Ultimately, esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus. Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility. Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease. No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc, though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc. Further exploration can be made by high resolution manometry and pH-impedance study. Proton pump inhibitors remain the mainstay of treatment, while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances. Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage, and new therapeutic modalities are emerging. The role of surgical treatment is restricted and should only be preserved for resistant cases.

Jackhammer esophagus (JE) is a newly described esophageal motility disorder. However, there are limited data on JE and this entity remains misunderstood.

We performed a systematic review of clinical series on JE through MEDLINE, EMBASE, and Web of Science. Data from included studies were then extracted, and random-effects meta-analyses were performed.

Thirty-eight studies met inclusion criteria. The pooled prevalence of JE was 1.97% [95% CI: 1.39%-2.78%] among patients referred for high-resolution manometry (HRM). The mean age at diagnosis was 60.8 years [95% CI: 57.1-64.4] and 65% [95% CI: 58%-72%] of patients were female. JE was significantly more prevalent in postlung transplant patients and morbidly obese patients undergoing HRM (23.99% [95% CI: 9.00%-38.97%] and 5.18% [95% CI: 1.76%-14.3%] respectively). Dysphagia was the most common presentation of JE (64% [95% CI: 52%-77%]) followed by gastroesophageal reflux disease (46% [95% CI: 26%-67%]). The pooled mean distal contractile integral (DCI) of all standard HRM swallows was 9249 mm Hg·s·cm [95% CI: 7834-10 663], and the pooled mean integrated relaxation pressure (IRP) was 13.9 mm Hg [95% CI: 8.2-19.7]. Overall, 73.6% [95% CI: 64.0%-83.1%] of JE patients who underwent treatment achieved clinical symptom improvement (79% [95% CI: 74%-85%] for endoscopic treatment and 63% [95% CI: 47%-79%] for medical treatment). The pooled clinical success rate of peroral endoscopic myotomy (POEM) specifically was 82% [95% CI: 75%-90%].

JE is a new motility disorder most commonly presenting with dysphagia. High clinical suspicion is important because the diagnosis can only be made through HRM.

Systemic sclerosis (SSc) has the potential to affect any component of the gastrointestinal (GI) tract. GI involvement in SSc is a leading cause of morbidity and overall decreased quality of life in this patient population, identifying a need for a concise approach to work-up. This literature review aims to present a systematic, anatomical approach and differential diagnosis of GI involvement in SSc for the general internist and rheumatologist. Each component of the luminal GI tract has its own specified section, beginning with a review of a clinical approach to diagnosis that includes a differential for clinicians to consider, followed by a discussion of the literature surrounding objective evaluation of these conditions (i.e. serologic studies, imaging, endoscopy). Additionally there is a focused discussion on an approach to GI bleeding in the patient with SSc.

Our study aims to characterize esophageal motor function; evaluate the relationships among esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM), and 24-hour esophageal multichannel intraluminal impedance monitoring combined with pH-metry (MII-pH); and elucidate the determinants of esophageal symptom perception in South Koreans with systemic sclerosis (SSc).

We reviewed prospectively collected HRM (n = 46), EGD (n = 41), and MII-pH (n = 37) data from 46 consecutive patients with SSc (42 females; mean age 50.1 years) who underwent esophageal tests between June 2013 and September 2018.

The most common HRM diagnosis was normal (39.1%), followed by ineffective esophageal motility (23.9%) and absent contractility (21.7%). Erosive esophagitis was observed in 12.2% of total SSc patients, with a higher frequency in patients with absent contractility than those with normal motility (44.5% vs 0.0%, P = 0.01). Pathologic acid exposure was observed in 6 patients (20.0%) and positive symptom association in 18 patients (60.0%) in MII-pH tests of symptomatic patients. The proportion of SSc patients with esophageal symptoms not explained by reflux or mucosal or motor esophageal abnormalities was 33.0%.

Esophageal involvement among South Koreans with SSc was characterized by heterogeneous motility patterns, with a higher prevalence of normal motility and lower prevalence of erosive esophagitis. Reflux hypersensitivity or functional heartburn might be partly attributed to the perception of esophageal symptoms in SSc patients who have neither gastroesophageal reflux disease nor esophageal dysmotility.

Gastroesophageal reflux disease (GERD) is a common clinical condition for which our understanding has evolved over the past decades. It is now considered a cluster of phenotypes with numerous anatomical and physiological abnormalities contributing to its pathophysiology. As such, it is important to first understand the underlying mechanism of the disease process for each patient before embarking on therapeutic interventions. The aim of our paper is to highlight the mechanisms contributing to GERD and review investigations and interpretation of these results. Finally, the paper reviews the available treatment modalities for this condition, ranging from medical intervention, endoscopic options through to surgery and its various techniques.

In this review, the authors discuss systemic sclerosis-associated interstitial lung disease (SSc-ILD) with a focus on recent developments in diagnosis, surveillance, and management.

With advances in the management of SSc, the importance of ILD has been increasingly recognized and is the leading cause of mortality. Early detection is essential, and a combination of lung function testing and chest imaging are key tools in diagnosis and surveillance. The foundation of treatment is immunomodulation with recent studies identifying several potential new agents. The use of therapies targeting pro-fibrotic pathways have demonstrated significant effects on lung function decline and represent the latest advance in therapy for SSc-ILD.

Recent studies support the use of newer therapies in SSc-ILD including antifibrotic agents. The identification and management of comorbidities is important, and lung transplantation is a viable option for patients with advanced disease.

Absent esophageal contractility (AC) is distinguished from type 1 achalasia (ACH1) during high-resolution manometry (HRM) on the basis of normal or elevated deglutitive integrated relaxation pressure (IRP) values. However, IRP measurements are subject to pressure recording error. We hypothesized that distinctive responses to pharmacologic provocation using amyl nitrite (AN) and cholecystokinin (CCK) could reliably distinguish AC patients from those with ACH1.

To compare esophageal response with AN and CCK in a well-defined cohort of ACH1 and AC patients.

All available clinical, radiographic, endoscopic, and manometric information in 34 patients with aperistalsis was reviewed to determine the final diagnosis of ACH1 and AC. The differences in response to provocative challenges with the rapid drink challenge (RDC) test and administration of AN and CCK were compared between these two groups.

Eighteen patients were diagnosed with ACH1 and sixteen with AC. While IRP values were significantly higher in ACH1, the standard criterion value misclassified four AC patients as having ACH1 and five ACH1 patients as having AC. IRP values on the RDC did not accurately segregate AC from ACH1, but we were able to identify AN and CCK esophageal motor response criteria that allowed correct classification of ACH1 and AC patients.

Nearly a quarter of AC and ACH1 patients may be misdiagnosed based on manometric IRP criteria alone. Differences in the esophageal motor responses to AN and CCK have the potential to facilitate the correct diagnosis in these challenging patients.

Standard high-resolution manometry (HRM) protocols are based on 10 single water swallows acquired in the supine position.

To assess the impact of position, rapid drink challenge and solid test meal on the diagnosis of oesophageal motility disorders.

Seventy-two healthy volunteers (20-76 years) and 366 consecutive patients (18-90 years) completed HRM with 10 single water swallows in the supine and upright positions. Rapid drink challenge was performed twice, before and after the solid test meal. Diagnosis based on single water swallows in the supine position (Chicago Classification v3.0) was compared with results in the upright position and with provocative tests.

Overall, diagnostic agreement in the supine and upright positions was present in 296/438 (67.6%) subjects. This increased to 90.0% when ineffective oesophageal motility was considered with normal motility. Integrated relaxation pressure was 4 mm Hg higher in the supine position. There was a higher prevalence of inconsistent, likely false positive, diagnoses of outlet obstruction in the supine compared to the upright position (16/20 vs 1/4 patients, P = 0.0007). Similarly, the difference in concordance for the diagnosis of oesophago-gastric junction obstruction or achalasia between single water swallows in the supine and upright positions with solid test meal was significant (12/29 (41.4%) vs 12/14 (85.7%), P = 0.0087).

Diagnostic agreement for oesophageal motility disorders based on single water swallows in the upright and supine positions was moderate, with frequent discordant findings for ineffective motility and outlet obstruction. HRM studies can be performed in either position, using appropriate reference values. Rapid drink challenge or solid test meal can resolve diagnostic discrepancies.

Systemic sclerosis (SSC) is an autoimmune disorder that affects several organs of unknown etiology, characterized by vascular damage and fibrosis of the skin and organs. Among the organs involved are the esophagus and the lung.

To relate the profile of changes in esophageal electromanometry (EM), the profile of skin involvement, interstitial pneumopathy (ILD), and esophageal symptoms in SSC patients.

This is an observational, cross-sectional study carried out at the SSC outpatient clinic of the Hospital de Clínicas of the Federal University of Uberlândia. After approval by the Ethics Committee and signed the terms of consent, 50 patients were initially enrolled, from 04/12/2014 to 06/25/2015. They were submitted to the usual investigations according to the clinical picture. The statistical analysis was descriptive in percentage, means, and standard deviation. The Chi-square test was used to evaluate the relationship between EM, high-resolution tomography, and esophageal symptoms.

91.9% of the patients had some manometric alterations. 37.8% had involvement of the esophageal body and lower esophageal sphincter. 37.8% had ILD. 24.3% presented the diffuse form of SSC. No association was found between manometric changes and clinical manifestations (cutaneous, pulmonary, and gastrointestinal symptoms).

The present study confirms that esophageal motility alterations detected by EM are frequent in SSC patients, but may not be related to cutaneous extension involvement, the presence of ILD, or the gastrointestinal complaints of patients.

Systemic sclerosis (SSc) affects the upper gastrointestinal (GI) system in 90% of patients. High-resolution manometry (HRM) assesses esophageal dysmotility, but its role in diagnosis and follow-up remains unclear. The objectives of this systematic review were to investigate the role of HRM in the assessment of SSc-associated upper GI involvement and to evaluate the correlation between HRM abnormalities and clinical characteristics and the effects of therapeutic interventions on HRM findings. Fifteen articles were included. Most (11/15) studies were of very good or good quality. Most studies assessed correlations between esophageal symptoms and esophageal dysmotility. Two studies assessed the effectiveness of buspirone and reported HRM findings. Studies assessing upper GI symptoms using validated questionnaires, such as the University of California Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 or Gastrointestinal Symptoms Severity Index score, found an association between absent contractility on HRM and upper GI symptoms, but even asymptomatic patients often have esophageal body dysmotility on HRM. Esophageal dysmotility positively correlates with the presence of interstitial lung disease on high-resolution computed tomography and reduced diffusion capacity (< 0.8 of predicted value). Trials investigating the effect of buspirone demonstrate both increased lower esophageal sphincter resting pressure and reduced upper GI symptoms. Most studies report on limited patient numbers and retrospective data. Potential bias was minimized using quality appraisal. HRM findings correlate to upper GI symptoms when assessed by validated questionnaires and can detect response to therapy in buspirone trials. Esophageal body dysmotility on HRM positively correlates with the presence of interstitial lung disease. KEY POINTS: • Esophageal body dysmotility on HRM correlates with presence of ILD. • HRM findings seem to correspond to clinical symptom alleviation in interventional trials, but data are still limited. • At present HRM, a procedure with a high negative burden to the patient, offers little to no role in the therapeutic strategy.

Esophageal motility abnormalities (EMAs) and interstitial lung diseases (ILDs) are often seen in patients with systemic sclerosis (SSc). Gastroesophageal reflux disease (GERD) could be associated with ILDs, but it is not fully understood if ILDs are caused by GERD or SSc itself.

A total of 109 patients with SSc who underwent high-resolution manometry were enrolled. Esophageal motility was diagnosed with the Chicago classification v3.0. The severity of skin thickness was evaluated by the modified Rodnan total skin thickness score (mRSS). The severity of ILDs was assessed with the chest high-resolution computer tomography (HRCT) scoring system. Relationships between EMAs, GERD, autoantibodies, skin thickness and ILDs were evaluated.

44 patients had normal esophageal motility, eight had esophago-gastric junction outflow obstruction, one had distal esophageal spasm, 27 had ineffective esophageal motility and 29 had absent contractility (AC). Patients with AC had more GERD than those with normal esophageal motility (p < 0.05). The mRSS score in patients with AC was significantly higher than that in those with normal esophageal motility (p < 0.05). The HRCT score in patients with AC tended to be higher than that in those with normal esophageal motility (p = 0.05). A multivariable analysis showed that severe skin thickness was a significant predictor of AC. GERD was not a significant predictor for ILDs.

There were significant correlations between EMAs and severe skin thickness. GERD is not an etiology of ILDs.

Over 90% of patients with systemic sclerosis suffer from gastroesophageal reflux. Esophageal motility disturbances are associated with a reduced life quality and may force interstitial lung disease progression. We wanted to determine whether we can improve gastroesophageal reflux in these patients by esophageal stem-cell injection.

We performed a pilot study including eights patients with systemic sclerosis and symptomatic gastroesophageal reflux. Sampling of adipose tissue was performed by an experienced plastic surgeon under local anesthesia. The collected fat was injected into the submucosa of the distal esophagus, each time 1 ml in all four quadrants starting 2, 4 and 6 cm proximal to the Z line (ending up to a total volume of 12 ml). Before the intervention, 3, 6 and finally 12 months after the procedure, patients answered the Gastroesophageal Reflux Disease Health-Related Quality of Life Questionnaire (GERD HRQL) and a high-resolution manometry was performed to quantify changes in motility function.

All patients showed an improvement in the GERD HRQL score after the stem-cell injection and a lower dosage of proton-pump inhibitors. The manometric findings showed no change throughout the time. A serious adverse event occurred, as one patient developed multiple cerebellar embolic infarcts.

Because of the favorable effect in all patients, a safe route for esophageal fat injection needs to be developed.

Esophageal dysfunction is common in systemic sclerosis (SSc) patients. Limited treatment options are available for scleroderma esophageal disease. Here, we discuss recent updates on the diagnosis, treatment, and characterization that have been made in patients with scleroderma esophageal disease.

In the past few years, novel diagnostic tools have provided insight into esophageal dysmotility in SSc patients. New drugs are being tested and might improve symptoms and quality of life in SSc patients with esophageal dysfunction. Molecular stratification methods have facilitated the identification of molecular signatures in the esophagus of SSc patients. The Friend leukemia integration 1 (Fli1) conditional knockout mouse is the first animal model to report an esophageal phenotype with SSc features. The clinical presentation in SSc patients with esophageal dysfunction is heterogeneous, complicating diagnosis and management. The improvement of diagnostic tools for esophageal symptoms and dysfunction and the use of molecular approaches in SSc mouse models and patient biopsies offer an opportunity to improve the characterization of SSc esophageal disease, which should help improve management and treatment decisions.

Gastroesophageal reflux disease (GERD) is frequently implicated as a cause for respiratory disease. However, there is growing evidence that upper gastrointestinal dysmotility may play a significantly larger role in genesis of respiratory symptoms and development of underlying pulmonary pathology. This paper will discuss the differential diagnosis for esophageal and gastric dysmotility in aerodigestive patients and will review the key diagnostic and therapeutic interventions for this dysmotility.

Previous studies have shown an association between GERD and pulmonary pathology in children with aerodigestive disorders. Recent publications have demonstrated the presence of esophageal and gastric dysfunction, using fluoroscopic and nuclear medicine studies, in aerodigestive patients who commonly present to pulmonary and otolaryngology clinics. High-resolution impedance manometry (HRIM) has revolutionized our understanding of esophageal dysmotility and its role in pathogenesis of aspiration and esophageal dysfunction and subsequent respiratory compromise.

Esophageal and gastric dysmotility have a profound effect on development of respiratory symptoms and pulmonary sequalae in aerodigestive patients. However, our understanding of the pathophysiology is in its infancy. Prospective studies in are needed to address key clinical questions such as: What degree of dysmotility initiates respiratory compromise? What diagnostic tests and therapeutic options best predict aerodigestive outcomes?

Systemic sclerosis (SSc) is a multisystem connective tissue disease, characterized by chronic inflammation and vascular changes that result in esophageal smooth muscle atrophy and fibrosis. Subsequent progressive loss of peristalsis in the distal esophagus and loss of lower esophageal sphincter function lead to problems with the protective barrier and exposure of sensitive tissues to the gastroduodenal contents, a disorder called reflux disease. Areas covered: Depending on the range, nature and symptoms of the disease, the term 'reflux disease' may refer to gastroesophageal reflux, laryngopharyngeal reflux, microaspiration into the airways and silent reflux. Despite the links between these visceral complications, this connection remains controversial. This is due to a lack of complete understanding, the asymptomatic nature of the disease and the limited diagnostic accuracy of tests, which can delay diagnosis. Such delays are problematic, given that the early detection of GERD in SSc patients, the timing of assessment, the treatment of the organs involved are critical aspects of patient prognosis and disease outcome. Expert commentary: This review summarizes the most recent knowledge about the pathophysiology, diagnosis and prospective treatment of GERD in SSc patients and highlights how innovative technologies applied through an integrative, interdisciplinary approach may soon lead to effective treatment strategies.

This study assessed whether high-resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression.

This prospective, longitudinal cohort study recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR, American College of Rheumatology /EULAR, The European League against Rheumatism 2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR 2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of SSc) and 72 healthy controls. HRM evaluated esophageal motility for water swallows and a solid test meal.

Systemic sclerosis patients had less frequent effective esophageal contractions during the test meal compared to healthy controls even in very early disease (0.15, 1.0, 2.1 per minute for groups #1, #2, and #3, vs 2.5 per minute in health; P < 0.001, P < 0.001, and P < 0.0085, respectively). Ineffective motility at HRM was associated with a higher modified Rodnan skin score at baseline. Moreover, at mean 18 (10-31) months of follow-up, the presence of ineffective motility at baseline was associated with progression of skin disease (P = 0.01). Cox proportional hazard regression analysis identified hypotensive peristalsis in the test meal (<15% effective solid swallows) and low distal contractile integral (DCI; <400 mm Hg·cm·s) as predictors for skin aggravation, but not for new organ involvement.

Ineffective motility during a test meal is present already in patients with very early SSc. Findings on HRM studies are associated with disease severity at baseline, and low percentage of effective swallows in test meal and low mean DCI are both predictors of skin progression during follow-up.

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

This study aims to investigate pre-clinical esophageal involvement in systemic sclerosis (SSc) by high-resolution impedance manometry (HRiM), its associations with disease features including lung involvement, and its predictivity of esophageal symptoms overtime. Charts of 45 asymptomatic (no heartburn/regurgitation/dysphagia) SSc patients (96% females; mean age 46 years) with at least one follow-up (FU) visit and complete clinical, serological, functional, and radiological assessment, including high-resolution computed tomography (HRCT) of the chest and lung function tests, that had undergone esophageal HRiM were retrospectively evaluated. Esophagogastric junction-contractile integral (EGJ-CI) and esophageal body motility, as evaluated by mean distal contractile integral (DCI), were assessed. SSc patients had a normal esophageal motility in 7/45 cases, a defective EGJ-CI in 28, an ineffective esophageal motility (IEM) in 17, and aperistalsis in 12. Defective EGJ-CI was associated with IEM/aperistalsis in 20 cases, while 9 patients had isolated IEM. Defective EGJ-CI and/or IEM/aperistalsis were associated with a diffusing lung capacity for CO < 80% of predicted value (all p < 0.05), while defective EGJ-CI was also associated with interstitial lung disease on HRCT (p = 0.03). Prevalence of any HRiM abnormality was higher in anti-centromere antibody negative patients (all p < 0.05). IEM/aperistalsis independently increased the risk of esophageal symptoms by 2.3-fold (95% CI 1.1-5.7) and was associated with their higher cumulative incidence with respect to patients with other HRiM patterns at FU (χ² = 4.63; p = 0.03). SSc patients asymptomatic for esophageal involvement can have HRiM abnormalities in up to 84% of cases. A baseline-impaired motility is a risk factor for symptomatic esophageal disease.