Endoscopic Features of Upper Gastrointestinal Tract in Patients with Systemic Sclerosis Compared to the Healthy Control

Jun Won Park; Jihye Kim; Eun Ae Kang; Min Jung Kim; Joo Sung Kim; Eun Bong Lee

doi:10.4078/jrd.2019.26.1.66

Journal List > J Rheum Dis > v.26(1) > 1122091

Go to TopGo to Top Go to BottomGo to Bottom

This article has been corrected. See "Erratum: Endoscopic Features of Upper Gastrointestinal Tract in Patients with Systemic Sclerosis Compared to the Healthy Control" in Volume 26 on page 147.

TOOLS

Park, Kim, Kang, Kim, Kim, and Lee: Endoscopic Features of Upper Gastrointestinal Tract in Patients with Systemic Sclerosis Compared to the Healthy Control

Original Article

J Rheum Dis 2019;26(1):66-82.

Published online: 31 January 2019

DOI: https://doi.org/10.4078/jrd.2019.26.1.66

Endoscopic Features of Upper Gastrointestinal Tract in Patients with Systemic Sclerosis Compared to the Healthy Control

Jun Won Park¹, Jihye Kim^2,³, Eun Ae Kang³, Min Jung Kim¹, Joo Sung Kim³, Eun Bong Lee¹

¹Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

²Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea

³Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

Corresponding to: Eun Bong Lee http://orcid.org/0000-0003-0703-1208 Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. E-mail: leb7616@snu.ac.kr

Received 24 November 201829 November 2018 Accepted 30 November 2018

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To characterize the endoscopic features of upper gastrointestinal tract in patients with systemic sclerosis (SSc) compared with those in the healthy controls.

Methods

Data on esophagogastroduodenoscopy (EGD) in 180 patients with SSc (SSc group) were compared with that from the 181 age- and sex-matched healthy control who underwent EGD for routine checkup (control group). Clinical data of participants at the time of EGD (defined as baseline) were collected from electric medical record. Endoscopic findings were evaluated by two experts with blinded to their clinical features. Primary outcome of the study was prevalence of each endoscopic lesion between the two groups.

Results

The mean±standard deviation age and disease duration in the SSc group at baseline were 55.3±11.8 and 2.9±3.7 years, respectively. Compared to the control group, SSc group more frequently showed reflux esophagitis (32.8% vs. 9.4%, p＜0.001). In contrast, prevalence of atrophic gastritis was significantly lower in the SSc group (8.3% vs. 29.3%, p＜0.001). This result was consistent in the multivariable analysis where patients' age and concomitant proton pump inhibitor use were adjusted. There was no case of gastric antral vascular ectasia (GAVE) in both groups. However, 29 (16.1%) patients in SSc group showed a clinically significant anemia (hemoglobin ＜10 mg/dL), with none of the endoscopic features showed significant associations with the outcome.

Conclusion

Patients with SSc showed significantly lower prevalence of atrophic gastritis. There was no case of GAVE, which suggests that clinical phenotype of the SSc could be different according to the ethnicity or geographic region.

Keywords: Scleroderma, Systemic, Endoscopy, Gastritis, Gastric antral vascular ectasia

REFERENCES

1. Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017; 390:1685–99.

2. Forbes A, Marie I. Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology (Oxford). 2009; 48(Suppl 3):iii36–9.

3. Altman RD, Medsger TA Jr, Bloch DA, Michel BA. Predictors of survival in systemic sclerosis (scleroderma). Arthritis Rheum. 1991; 34:403–13.

4. Hunzelmann N, Genth E, Krieg T, Lehmacher W, Melchers I, Meurer M, et al. The registry of the German network for systemic scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford). 2008; 47:1185–92.

5. Alastal Y, Hammad TA, Renno A, Khalil B, Pierre J, Kwaah B, et al. Gastrointestinal manifestations associated with systemic sclerosis: results from the nationwide inpatient sample. Ann Gastroenterol. 2017; 30:498–503.

6. McFarlane IM, Bhamra MS, Kreps A, Iqbal S, Al-Ani F, Saladini-Aponte C, et al. Gastrointestinal manifestations of systemic sclerosis. Rheumatology (Sunnyvale). 2018; 8:pii: 235.

7. Savarino E, Furnari M, de Bortoli N, Martinucci I, Bodini G, Ghio M, et al. Gastrointestinal involvement in systemic sclerosis. Presse Med. 2014; 43:e279–91.

8. Watson M, Hally RJ, McCue PA, Varga J, Jiménez SA. Gastric antral vascular ectasia (watermelon stomach) in patients with systemic sclerosis. Arthritis Rheum. 1996; 39:341–6.

9. Ghrénassia E, Avouac J, Khanna D, Derk CT, Distler O, Suliman YA, et al. Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study. J Rheumatol. 2014; 41:99–105.

10. Hung EW, Mayes MD, Sharif R, Assassi S, Machicao VI, Hosing C, et al. Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial. J Rheumatol. 2013; 40:455–60.

11. Marie I, Levesque H, Ducrotté P, Denis P, Hellot MF, Benichou J, et al. Gastric involvement in systemic sclerosis: a prospective study. Am J Gastroenterol. 2001; 96:77–83.

12. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013; 72:1747–55.

13. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988; 15:202–5.

14. Rey JF, Lambert R. ESGE Quality Assurance Committee. ESGE recommendations for quality control in gastrointestinal endoscopy: guidelines for image documentation in upper and lower GI endoscopy. Endoscopy. 2001; 33:901–3.

15. Aabakken L, Barkun AN, Cotton PB, Fedorov E, Fujino MA, Ivanova E, et al. Standardized endoscopic reporting. J Gastroenterol Hepatol. 2014; 29:234–40.

16. Marques S, Bispo M, Pimentel-Nunes P, Chagas C, Dinis-Ribeiro M. Image documentation in gastrointestinal endoscopy: review of recommendations. GE Port J Gastroenterol. 2017; 24:269–74.

17. Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med. 2002; 21:2409–19.

18. Kanfer EJ, Nicol BA. Haemoglobin concentration and erythrocyte sedimentation rate in primary care patients. J R Soc Med. 1997; 90:16–8.

19. Tiev KP, Cabane J. Digestive tract involvement in systemic sclerosis. Autoimmun Rev. 2011; 11:68–73.

20. Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther. 2009; 29:938–46.

21. Kim HS, Baik SJ, Kim KH, Oh CR, Lee JH, Jo WJ, et al. Prevalence of and risk factors for gastrointestinal diseases in Korean Americans and native Koreans undergoing screening endoscopy. Gut Liver. 2013; 7:539–45.

22. Lee HJ, Yang HK, Ahn YO. Gastric cancer in Korea. Gastric Cancer. 2002; 5:177–82.

23. Ntoumazios SK, Voulgari PV, Potsis K, Koutis E, Tsifetaki N, Assimakopoulos DA. Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem. Semin Arthritis Rheum. 2006; 36:173–81.

24. Denaxas K, Ladas SD, Karamanolis GP. Evaluation and management of esophageal manifestations in systemic sclerosis. Ann Gastroenterol. 2018; 31:165–70.

25. Triadafilopoulos G. Proton pump inhibitors for Barrett's oesophagus. Gut. 2000; 46:144–6.

26. Kahrilas PJ. Gastroesophageal reflux disease. JAMA. 1996; 276:983–8.

27. Ebert EC, Hagspiel KD. Gastrointestinal and hepatic manifestations of rheumatoid arthritis. Dig Dis Sci. 2011; 56:295–302.

28. Kuo CF, Luo SF, Yu KH, Chou IJ, Tseng WY, Chang HC, et al. Cancer risk among patients with systemic sclerosis: a nationwide population study in Taiwan. Scand J Rheumatol. 2012; 41:44–9.

29. Kang KY, Yim HW, Kim IJ, Yoon JU, Ju JH, Kim HY, et al. Incidence of cancer among patients with systemic sclerosis in Korea: results from a single centre. Scand J Rheumatol. 2009; 38:299–303.

30. Hashimoto A, Arinuma Y, Nagai T, Tanaka S, Matsui T, Tohma S, et al. Incidence and the risk factor of malignancy in Japanese patients with systemic sclerosis. Intern Med. 2012; 51:1683–8.

31. Joo YE, Park HK, Myung DS, Baik GH, Shin JE, Seo GS, et al. Prevalence and risk factors of atrophic gastritis and intestinal metaplasia: a nationwide multicenter prospective study in Korea. Gut Liver. 2013; 7:303–10.

32. Thonhofer R, Siegel C, Trummer M, Graninger W. Early endoscopy in systemic sclerosis without gastrointestinal symptoms. Rheumatol Int. 2012; 32:165–8.

33. Shibukawa G, Irisawa A, Sakamoto N, Takagi T, Wakatsuki T, Imamura H, et al. Gastric antral vascular ectasia (GAVE) associated with systemic sclerosis: relapse after endoscopic treatment by argon plasma coagulation. Intern Med. 2007; 46:279–83.

34. Yamamoto M, Takahashi H, Akaike J, Suzuki C, Naishiro Y, Yamamoto H, et al. Gastric antral vascular ectasia (GAVE) associated with systemic sclerosis. Scand J Rheumatol. 2008; 37:315–6.

35. McColl KE. Effect of proton pump inhibitors on vitamins and iron. Am J Gastroenterol. 2009; 104(Suppl 2):S5–9.

Supplementary Figure 1.

Scatter plot indicating the degree of relationship between the ESR and hemoglobin levels. ESR: erythrocyte sedimentation rate, HB: hemoglobin.

Figure 1.

Prevalence of reflux esophagitis, atrophic gastritis and their advanced lesions between the systemic sclerosis (SSc) and the control groups.

Supplementary Table 1.

Reliability of endoscopic evaluation between the two readers

Endoscopic lesions	Kappa (95% CI)
Reflux esophagitis	0.92 (0.87 to 1.00)
Barrett esophagus	0.66 (0.30 to 1.00)
Esophageal stricture	0.80 (0.52 to 1.00)
Chronic superficial gastritis	0.92 (0.87 to 0.97)
Erosive gastritis	0.96 (0.92 to 1.00)
Atrophic gastritis	0.97 (0.94 to 1.00)
Intestinal metaplasia	0.87 (0.71 to 1.00)
GAVE	1.00
Gastric ulcer	1.00
Duodenal ulcer	1.00
Hyperplastic polyp	0.96 (0.89 to 1.00)
Adenomatous polyp	0.75 (0.41 to 1.00)
Early gastric cancer	1.00

CI: confidence interval, GAVE: gastric antral vascular ectasia.

Supplementary Table 2.

Prevalence of endoscopic lesion between the two groups in the subgroup of the patients without PPI

Endoscopic lesions	Control group (n=174)	SSc group (n=79)	p-value
Reflux esophagitis	16 (9.2)	18 (22.8)	0.003
Low grade (LA-A or B)	16 (100.0)	11 (51.1)
High grade (LA-C or D)	0 (0.0)	7 (38.9)
Barrett esophagus	0 (0.0)	1 (1.3)	0.137
Esophageal stricture	0 (0.0)	3 (3.8)	0.010
Chronic superficial gastritis	40 (23.0)	17 (21.5)	0.795
Erosive gastritis	38 (21.8)	8 (10.1)	0.025
Atrophic gastritis	52 (29.9)	6 (7.6)	＜0.001
Intestinal metaplasia	8 (4.6)	1 (1.3)	0.185
GAVE	0 (0.0)	0 (0.0)	NA
Gastric ulcer	0 (0.0)	1 (1.3)	0.137
Duodenal ulcer	3 (1.7)	3 (3.8)	0.315
Hyperplastic polyp	5 (2.9)	1 (1.3)	0.436
Adenomatous polyp	1 (0.6)	2 (2.5)	0.183
Early gastric cancer	1 (0.7)	0 (0.0)	0.500

Values are presented as number (%). PPI: proton pump inhibitor, SSc: systemic sclerosis, LA: Los Angeles classification criteria for reflux esophagitis, GAVE: gastric antral vascular ectasia, NA: non-applicable.

Supplementary Table 3.

Prevalence of endoscopic lesion between the two groups after excluding the PACS data with low resolution which was taken before 2007

Endoscopic lesions	Control group (n=181)	SSc group (n=158)	p-value
Atrophic gastritis	53 (29.3)	15 (9.3)	＜0.001
Intestinal metaplasia	8 (4.4)	2 (1.3)	0.087

Values are presented as number (%). PACS: picture archiving and communication system, SSc: systemic sclerosis.

Table 1.

Clinical features of the included patients with systemic sclerosis (n=180)

Clinical feature	Value
Age (yr)	53.3±11.8
Male sex	23 (12.8)
Time from the onset of Raynaud phenomenon (yr)	5.6±6.6
Time from the onset of non-Raynaud phenomenon symptom (yr)	3.4±4.0
Disease duration (yr), (n=179)	2.9±3.7
Disease duration less than 5 years (n=179) 1	140 (77.8)
Ever-smokers	15 (8.3)
Diffuse subtype	88 (48.9)
Limited subtype	92 (51.1)
Anti-scl70 antibody positive (n=171)	72 (48.0)
Anti-centromere antibody positive (n=171)	38 (25.3)
Anti-U1RNP antibody positive (n=154)	23 (16.9)
Telangiectasia (n=145)	32 (22.1)
Interstitial lung disease 1	110 (61.1)
GI manifestations
Dysphasia	44 (24.4)
Reflux	72 (40.0)
Early satiety	45 (25.0)
Vomiting	10 (5.6)
Diarrhea	29 (16.1)
Constipation	13 (7.2)
Abdominal pain	26 (14.4)
Melena	1 (0.6)
Anemia*	73 (40.6)
Significant anemia^†	29 (19.1)
NSAID use at baseline (n=179)	27 (15.1)
Steroid use at baseline (n=179)	59 (33.0)
PPI use at baseline (n=170) 1	101 (56.1)
ESR (mm/hr)	34.0±26.1

Values are presented as mean±standard deviation or number (%). GI: gastrointestinal, PPI: Proton-pump inhibitor, ESR: erythrocyte sedimentation rate.

^* Anemia was defined as the hemoglobin level less than 12 g/dL.

^† Significant anemia was defined as the hemoglobin level less than 10 g/dL.

Table 2.

Prevalence of endoscopic lesion between the two groups

Endoscopic lesions	Control group (n=181)	SSc group (n=180)	p-value
Reflux esophagitis	17 (9.4)	59 (32.8)	＜0.001
Low grade (LA-A or B)	17 (100.0)	45 (75.0)
High grade (LA-C or D)	0 (0.0)	15 (25.0)
Barrett esophagus	0 (0.0)	3 (1.7)	0.081
Esophageal stricture	0 (0.0)	3 (1.7)	0.081
Chronic superficial gastritis	42 (23.2)	31 (17.2)	0.157
Erosive gastritis	38 (21.0)	21 (11.7)	0.017
Atrophic gastritis	53 (29.3)	15 (8.3)	＜0.001
Intestinal metaplasia	8 (4.4)	2 (1.1)	0.055
GAVE	0 (0.0)	0 (0.0)	NA
Gastric ulcer	0 (0.0)	4 (2.2)	0.044
Duodenal ulcer	3 (1.7)	5 (2.8)	0.470
Hyperplastic polyp	5 (2.8)	9 (5.0)	0.271
Adenomatous polyp	1 (0.6)	2 (1.1)	0.559
Early gastric cancer	1 (0.6)	1 (0.6)	0.997

Values are presented as number (%). SSc: systemic sclerosis, LA: Los Angeles classification criteria for reflux esophagitis, GAVE: gastric antral vascular ectasia, NA: non-applicable.

Table 3.

Clinical features associated with atrophic gastritis on baseline EGD

Variable	Univariable analysis		Multivariable analysis*
Variable	OR (95% CI)	p-value	Adjusted OR (95% CI)	p-value
Age	1.06 (1.03 to 1.09)	＜0.001	1.06 (1.04 to 1.09)	＜0.001
Male sex	1.05 (0.48 to 2.31)	0.892	†
Disease duration	0.95 (0.81 to 1.12)	0.532	†
Ever-smokers	0.31 (0.27 to 2.44)	0.707	†
PPI use at baseline	0.35 (0.17 to 0.72)	＜0.001	1.23 (0.46 to 3.26)	0.681
Systemic sclerosis (vs. normal control)	0.22 (0.12 to 0.410	＜0.001	0.17 (0.07 to 0.38)	＜0.001

EGD: esophagogastroduodenoscopy, OR: odds ratio, CI: confidence interval, PPI: proton pump inhibitor.

^* Clinical factors with a significant association (p＜0.1) were included in the multivariable model.

^† Does not included in the multivariable model as a covariate.

Table 4.

Clinical features associated with significant anemia at baseline

Variable	Univariable analysis		Multivariable analysis^*,‡
Variable	OR (95% CI)	p-value	Adjusted OR (95% CI)	p-value
Age	1.05 (1.02 to 1.09)	0.006	1.02 (0.98 to 1.07)	0.351
Female sex^‡	10.78 (1.42 to 1,384.20)	0.014	5.59 (0.531 to 781.39)	0.179
Disease duration	1.09 (0.99 to 1.20)	0.098	1.11 (0.98 to 1.26)	0.084
Ever-smokers^‡	0.15 (0.001 to 1.17)	0.076	0.76 (0.01 to 11.69)	0.866
ESR	1.04 (1.02 to 1.06)	＜0.001	1.04 (1.02 to 1.06)	＜0.001
PPI use at baseline	0.58 (0.26 to 1.30)	0.184	†
Reflux esophagitis	1.10 (0.47 to 2.53)	0.831	†
Barrett esophagus	2.66 (0.23 to 30.35)	0.431	†
Chronic superficial gastritis	0.31 (0.07 to 1.39)	0.126	†
Erosive gastritis	0.85 (0.23 to 3.11)	0.809	†
Atrophic gastritis	0.79 (0.17 to 3.69)	0.760	†
Intestinal metaplasia^‡	1.01 (0.01 to 12.88)	0.993	†
Retained food in stomach	2.66 (0.23 to 30.35)	0.431	†
Gastric ulcer^‡	0.56 (0.004 to 5.43)	0.673	†
Duodenal ulcer^‡	0.45 (0.003 to 4.16)	0.553	†

OR: odds ratio, CI: confidence interval, ESR: erythrocyte sedimentation rate, PPI: proton pump inhibitor.

^* Clinical factors with a significant association (p＜0.1) were included in the multivariable model.

^† Does not included in the multivariable model as a covariate.

^‡ Firth penalized maximum likelihood was used due to complete separation of outcome.

TOOLS

Similar articles