|Ahead of print publication
High-resolution esophageal manometry in systemic sclerosis in the indian population: An observational study
S Kartik1, Dharmendra Kumar2, Gaurav Sikri2, Deepanjan Dey3, AB Srinivasa2, Binit Kumar2
1 Department of Rheumatology, Command Hospital (SC), Pune, Maharashtra, India
2 Department of Physiology, Armed Forces Medical College, Pune, Maharashtra, India
3 Department of Physiology, Army College of Medical Sciences, New Delhi, India
Department of Physiology, Armed Forces Medical College, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Systemic sclerosis (SSc) is a rare multisystemic autoimmune disorder in which the esophagus is the second most common organ to be affected after the skin, leading to dysmotility. Literature available on esophageal dysmotility in SSc is limited. Moreover, studies explaining the spectrum of esophageal dysmotility in the disease in the Indian population are sparse.
Aim: The aim of this study was to characterize esophageal motility disorders in SSc using esophageal high-resolution manometry (HRM) in a representative of the Southwestern Indian population.
Methods: Thirty-two SSc patients participated in the study. All of them met the inclusion and exclusion criteria and underwent esophageal HRM at the Gastrointestinal Physiology Laboratory, Department of Physiology, of our center. The findings were interpreted using the Chicago Classification v3.0 criteria.
Results: Among patients of SSc with a mean age of 42.25 ± 10.45 years, 19 (59.38%) had “absent contractility (AC),” 3 (9.38%) had “ineffective esophageal motility (IEM),” 3 (9.38%) had “type I achalasia, 1 (3.13%) had “esophagogastric junction outflow obstruction,” and 6 (18.75%) had “normal” HRM findings. The HRM parameter of “basal lower esophageal sphincter pressure” differed significantly between “IEM type I achalasia” (P = 0.043) and “type I achalasia AC” groups (P = 0.032), while “median integral relaxation pressure” of “type I achalasia” groups showed significant difference with “normal, IEM, and AC” groups each (P < 0.001).
Conclusions: The findings of the study suggest that varying degrees of esophageal motility disorders are present in SSc using HRM as defined by the Chicago Classification v3.0. Majority (59.38%) of patients had AC, but the rest of them showed other dysmotility patterns.
Keywords: Esophageal motility disorder, high-resolution manometry, lower esophageal sphincter, systemic sclerosis
|How to cite this URL:|
Kartik S, Kumar D, Sikri G, Dey D, Srinivasa A B, Kumar B. High-resolution esophageal manometry in systemic sclerosis in the indian population: An observational study. Indian J Rheumatol [Epub ahead of print] [cited 2020 Apr 1]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=273388
| Introduction|| |
Systemic sclerosis (SSc) is a rare, chronic, multisystem autoimmune and generalized connective tissue disorder of unknown etiology, characterized by fibrosis and vasculopathy. Worldwide, the annual incidence of SSc is 19 per million and its prevalence is 190–750 per million. However, data regarding the Indian subcontinent are scanty. Minz et al. have reported a prevalence of SSc as 120 per million among the age group of 21–40 years in the North Indian population., Females are affected more commonly than males, with ratios of 3:1 and 8:1 in the mid and late childbearing years, respectively.
SSc predominantly affects the skin and various internal organs of the gastrointestinal system, respiratory system, cardiovascular systems, and kidneys. Involvement of the gastrointestinal tract (GIT) is second in frequency only to the skin, affecting about 90% of the patients,, and also the major cause of morbidity and the third most common cause of mortality in patients with SSc. It is the esophagus which is the most commonly affected organ within the GIT, with its involvement in as many as 50%–90% of patients.,,,,,,,,
SSc is mainly classified into two subtypes, based on the extent of skin involvement, namely:
- Limited cutaneous SSc (lcSSc) with essentially limited to the hands and face
- Diffuse cutaneous SSc (dcSSc) with skin involvement proximal to the elbows and knees and/or trunk.
Esophageal high-resolution manometry (HRM) is used to clinically diagnose and assess the quantitative and qualitative motor functions of the esophagus. Usually, it is the distal two-thirds of esophagus, i.e., the smooth muscle part and lower esophageal sphincter (LES) which is affected, leading to absent or lost peristaltic function and reduced basal LES pressure (BLESP) [Figure 1].,,,, BLESP is an integral component of the manometric assessment of LES function. The distribution of esophageal motility disorders is variable in SSc with manifestations, ranging from absent contractility (AC) (56%) to ineffective esophageal motility (IEM) (10%) and reduced BLESP (62%–95%), as reported by various authors.,,,,,,,
|Figure 1: High-resolution manometry images for a normal patient (a) and systemic sclerosis patients (b and c) of the study population|
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Since the neuromuscular apparatus of the GIT shares a common basic feature throughout its length, it appears unlikely that the pathological process should involve different subsections of neuromuscular apparatus in different parts of GIT. In the IEM disorder, the median integral relaxation pressure (IRP) is higher than the BLESP, suggesting a pathological involvement of interneurons which are excitatory to the inhibitory motor neurons (the latter is stronger). IRP is an esophageal pressure topography metric used for assessing the adequacy of esophagogastric junction (EGJ) relaxation in the Chicago Classification of Motility Disorders. It is the mean pressure of 4 s of maximal deglutitive relaxation in the 10-s window beginning at upper esophageal sphincter relaxation.
The present study was planned with an aim to find out the esophageal motor patterns by way of HRM in patients of SSc among a subset of the Indian population.
| Methods|| |
This observational cross-sectional study was carried out at the Gastrointestinal Physiology Laboratory, Department of Physiology, of our center. The aim of this study was to characterize esophageal motility disorders in SSc using high-resolution esophageal manometry in a representative of the Southwestern Indian population. All patients between 16–70 years of age with SSc who visited the rheumatology and gastroenterology departments from 2017 to 2018 and those who fulfilled the “2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis” were included in this study. Patients with evidence of structural lesions of the esophagus on upper gastrointestinal endoscopy or barium swallow and those with a prior upper gastrointestinal surgery were excluded from study. A total of 32 patients of SSc, who fulfilled the above criteria, formed the study group for undergoing HRM.
The study was approved by the Institutional Ethical Committee. Procedure was explained to patients in detail before obtaining informed written consent.
A 16-channel water perfusion HRM assembly with electronic pressure transducers, manufactured by the Royal Melbourne Hospital, Melbourne, Victoria, Australia, was used for the purpose. HRM was performed by introducing the catheter via the nasopharyngeal route. HRM protocol included the BLESP recording, followed by recording ten wet swallows of 5 ml of drinking water, at intervals of 30 s each, in the right lateral recumbent and upright positions. All HRM findings were interpreted using the Chicago Classification v3.0 criteria for esophageal motility disorders.
The results were subjected to statistical analysis using “IBM SPSS Statistics v20.0 software for Window (IBM Corp., Armonk, NY, USA).” Data were presented as mean ± standard deviation. All values were rounded off to the second decimal. Assessment of the difference between anthropometric parameters, across groups based upon HRM findings (i.e., normal motility, type I achalasia, IEM, AC), was made by the application of analysis of variance (ANOVA). If the difference showed statistical significance (i.e., P≤ 0.05), then a post hoc Bonferroni test was performed to find out the groups which were significantly different from each other.
| Results|| |
There were 32 patients who met the inclusion criteria, of which 29 (90.63%) were females and three were males (9.38%). Distribution of anthropometric parameters, i.e., age, height, weight, and body mass index in the whole study population, is given in [Table 1].
|Table 1: Anthropometric characteristic of systemic sclerosis study population|
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The disease duration varied from 1 to 16 years, with a mean value of 5.56 ± 3.62 years among the patients. Of 32 participants, lcSSc was seen in 65.62% (n = 21) and 34.38% (n = 11) participants had dcSSc. All patients had heartburn while 91% (n = 29) had abdomen distention and 34% (n = 11) had dysphagia at the time of HRM evaluation. Distribution of HRM parameters, i.e., BLESP and median IRP with a mean value, showed a wide range of variation in the study population [Table 2] and [Graph 1].
|Table 2: Details of esophageal high-resolution manometry parameters in systemic sclerosis|
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Based on the HRM findings using Chicago v3.0 Classification [Graph 2], 19 (59.38%) patients were diagnosed as “AC,” three (9.38%) as “IEM,” three (9.38%) as “type I achalasia,” one (3.13%) as “EGJ outflow obstruction,” and six (18.75%) as “normal.” The details of anthropometric parameters and HRM parameters with respect to HRM groups were compared using the ANOVA test. Since there was only one case of EGJ outflow obstruction, it was not included in the ANOVA test. Both the HRM parameters, i.e., BLESP (P = 0.026) and median IRP (P = 0.001), showed a statistically difference across the groups [Table 3].
|Table 3: Difference between mean values across the esophageal motility disorders in systemic sclerosis|
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Further comparisons between the pair of groups were made using the post hoc Bonferroni test, to find out the groups which differed significantly from each other [Table 4]. The HRM parameter of BLESP differed significantly between “IEM type I achalasia” (P = 0.043) and “type I achalasia AC” groups (P = 0.032), while median IRP showed a significant difference between “normal-type I achalasia” groups (P < 0.001), “IEM-type I achalasia” groups (P < 0.001), and “type I achalasia-AC” groups (P < 0.001).
|Table 4: Comparisons between pair of esophageal motility disorders in systemic sclerosis by using post hoc Bonferroni test|
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Apart from gastrointestinal system, other systems such as skin (n = 29, 91%), respiratory system (n = 17, 53%), and cardiovascular system (n = 8, 25%) were also involved in SSc patients. Serum autoantibody Antinuclear Antibody (ANA) was found to be positive in all patients by Indirect Immunofluorescence; further ANA profile was not done.
| Discussion|| |
In our study, HRM parameters were recorded in patients of SSc. Classification of esophageal motility disorders was done according to the guidelines laid down by the Chicago v3.0 Classification.
Based on the HRM findings, majority of the patients were diagnosed as “AC,” but a significant number of patients also showed other esophageal motility patterns, such as “IEM,” and “type I achalasia,” and one patient had “EGJ outflow obstruction.”
Aggarwal et al. had also reached a similar conclusion in their study, which had found that approximately 60% of patients of SSc had “AC” while the rest had atypical manometric findings. This suggests the heterogeneity of the pathological processes affecting the GIT, leading to the manifestation of the “opposite end of esophageal motility spectrum,” i.e., AC on the one end and type I achalasia on the other end. SSc could affect neurons, connective tissues, and vascular tissues, to different extent in different organ systems. It is likely that in some patients, the smooth muscles are predominantly affected, resulting in total disruption of motility, e.g., in IEM or AC. In others, however, the “enteric nervous system (ENS)” is mainly affected, resulting in disruption of both motility and motor coordination, e.g., in type I achalasia or EGJ obstruction. On the other hand, a small subsection of people may have their esophagus unaffected, and they comprise the normal motility group.
It is well known that achalasia develops because of loss of “inhibitory motor neurons” and the interstitial cells of Cajal, and this loss is throughout the GIT albeit to different extents. Similarly, IEM could be the outcome of involvement of both smooth muscles and “ascending and descending interneurons” (which are involved in smooth progression of peristaltic movement), thereby leading to weak peristalsis. Furthermore, in IEM, the median IRP increased above the BLESP. This suggests pathological involvement of predominantly those interneurons, which stimulates the “inhibitory motor neurons” (there are both excitatory and inhibitory descending inputs at the LES, with the latter being stronger) responsible for causing relaxation of LES during swallowing. Involvement of “inhibitory motor neurons” results in failure of LES relaxation which manifests as high Median IRP. The AC could have resulted from the involvement of mainly smooth muscles and excitatory interneurons, leading to complete failure of peristalsis and high BLESP. In addition, the AC group showed a reduction in median IRP as compared to BLESP, suggesting a sparing of the interneurons and “inhibitory motor neurons” involved in relaxation of LES.
The comparison of BLESP between groups showed that, even though it was highest in type I achalasia group, it was significantly different only from the IEM group and AC group, but not with the normal group. On comparing the median IRP, we found that, except in type I achalasia where it was significantly higher, the value was normal in other groups, i.e., normal, IEM, and AC.
Another particular finding was that, in the IEM group, the median IRP was higher than the BLESP. This further supports the view of relative sparing of the GIT in the normal group, leading to normal relaxation of LES and hence lower median IRP than BLESP. However, involvement of “inhibitory motor neurons” in type I achalasia group will explain higher BLESP and absence of LES relaxation, leading to higher median IRP. In the IEM group, involvement of smooth muscle could explain lower BLESP. This along with involvement of interneurons, which stimulates “inhibitory motor neurons,” could elucidate both weak peristalsis and higher IRP (although in normal range) than BLESP. Similarly, involvement of interneurons, which stimulates “excitatory motor neurons,” along with smooth muscle, will lead to picture of “AC,” i.e., completely failed peristalsis, low BLESP, but normal IRP–BLESP relationship. Even though logical, we cannot firm up our argument in the absence of histological and immunohistochemical investigations, which would have been able to tell in detail about the involvement of smooth muscles and ENS under different conditions.
The study has been limited by a small sample size (n = 32), which was due to the rarity of SSc cases reporting to us within the limited period of the study. It would have been much better if histological and immunohistochemical examination was also included, which could have firmed up or refuted our arguments. The absence of adequate clinical and serological data is another limitation of this study.
| Conclusion|| |
Esophageal motility patterns, based on HRM recordings as defined by the Chicago v3.0 Classification, show wide variability. Majority of patients in a representative of the Indian population had AC, but the rest of them showed other dysmotility patterns as “IEM,” “type I achalasia,” “EGJ outflow obstruction,” and “normal.” The understanding of its pathophysiology is limited and is still evolving. The pathological involvement of the esophagus in SSc appears to be heterogeneous, affecting different sections/subsections of the neuromuscular apparatus.
Further evaluation using histological and immunohistochemical methods are suggested to get a more accurate picture of these pathological involvements. Furthermore, varieties of tests, such as impedance–pH metry and autonomic function tests, may be performed to find out or rule out any possible association with GIT symptoms.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]