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Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Elevated levels of faecal calprotectin in primary Sjögren’s syndrome is common and associated with concomitant organic gastrointestinal disease

Authors: Kristofer Andréasson, Bodil Ohlsson, Thomas Mandl

Published in: Arthritis Research & Therapy | Issue 1/2016

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Abstract

Background

Primary Sjögren’s syndrome (pSS) is a systemic rheumatic disease in which gastrointestinal (GI) symptoms are common. Faecal calprotectin (FC) is a non-invasive biomarker that has been suggested to discriminate organic intestinal disease from functional disorders. The purpose of this study was to explore the usefulness of FC testing in patients with pSS.

Methods

In total, 56 consecutive patients with pSS and 29 healthy control subjects were included in this cross-sectional study. FC was measured with a commercially available enzyme-linked immunosorbent assay kit. GI symptoms were evaluated with the Rome III questionnaire and the Visual Analogue Scale for Irritable Bowel Syndrome. In patients with pSS, disease activity was estimated using the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI), and patient-reported outcomes were evaluated with the EULAR Sjögren’s Syndrome Patient-Reported Index.

Results

Patients with pSS had higher levels of FC than healthy control subjects (median 54 μg/g, interquartile range [IQR 20–128]; vs. 20 μg/g [20–43]; p = 0.002). Concomitant organic GI disease was found in 14 patients with pSS and included inflammatory bowel disease (n = 3), colonic adenoma (n = 2) and GI lymphoma (n = 1). Patients with organic GI disease had higher FC levels than the other patients with pSS (median 274 μg/g [IQR 61–363] vs. median 34 μg/g [IQR 20–76]; p < 0.001). Although patients with pSS reported abdominal discomfort more frequently than healthy control subjects did, such symptoms were not associated with organic GI disease or elevated FC levels. FC correlated moderately with ESSDAI. Excluding patients with organic GI disease, we did not identify any significant association between ESSDAI and FC levels.

Conclusions

GI symptoms are frequent in pSS. Contrary to patient-reported outcomes, elevated FC levels in pSS indicate possible organic GI disease that warrants further investigation.
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Literature
1.
go back to reference Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554–8.PubMedPubMedCentralCrossRef Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554–8.PubMedPubMedCentralCrossRef
2.
go back to reference Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, et al. EULAR Sjögren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjögren’s syndrome. Ann Rheum Dis. 2010;69(6):1103–9. A published erratum appears in Ann Rheum Dis. 2011;70(5):880.PubMedPubMedCentralCrossRef Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, et al. EULAR Sjögren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjögren’s syndrome. Ann Rheum Dis. 2010;69(6):1103–9. A published erratum appears in Ann Rheum Dis. 2011;70(5):880.PubMedPubMedCentralCrossRef
3.
go back to reference Tsianos EB, Vasakos S, Drosos AA, Malamou-Mitsi VD, Moutsopoulos HM. The gastrointestinal involvement in primary Sjögren’s syndrome. Scand J Rheumatol Suppl. 1986;61:151–5.PubMed Tsianos EB, Vasakos S, Drosos AA, Malamou-Mitsi VD, Moutsopoulos HM. The gastrointestinal involvement in primary Sjögren’s syndrome. Scand J Rheumatol Suppl. 1986;61:151–5.PubMed
4.
go back to reference Ostuni PA, Germana B, Di Mario F, Rugge M, Plebani M, De Zambiasi P, et al. Gastric involvement in primary Sjögren’s syndrome. Clin Exp Rheumatol. 1993;11(1):21–5.PubMed Ostuni PA, Germana B, Di Mario F, Rugge M, Plebani M, De Zambiasi P, et al. Gastric involvement in primary Sjögren’s syndrome. Clin Exp Rheumatol. 1993;11(1):21–5.PubMed
5.
go back to reference Sheikh SH, Shaw-Stiffel TA. The gastrointestinal manifestations of Sjögren’s syndrome. Am J Gastroenterol. 1995;90(1):9–14.PubMed Sheikh SH, Shaw-Stiffel TA. The gastrointestinal manifestations of Sjögren’s syndrome. Am J Gastroenterol. 1995;90(1):9–14.PubMed
6.
go back to reference Hammar O, Ohlsson B, Wollmer P, Mandl T. Impaired gastric emptying in primary Sjögren’s syndrome. J Rheumatol. 2010;37(11):2313–8.PubMedCrossRef Hammar O, Ohlsson B, Wollmer P, Mandl T. Impaired gastric emptying in primary Sjögren’s syndrome. J Rheumatol. 2010;37(11):2313–8.PubMedCrossRef
7.
go back to reference Barton A, Pal B, Whorwell PJ, Marshall D. Increased prevalence of sicca complex and fibromyalgia in patients with irritable bowel syndrome. Am J Gastroenterol. 1999;94(7):1898–901.PubMedCrossRef Barton A, Pal B, Whorwell PJ, Marshall D. Increased prevalence of sicca complex and fibromyalgia in patients with irritable bowel syndrome. Am J Gastroenterol. 1999;94(7):1898–901.PubMedCrossRef
8.
go back to reference Lidén M, Kristjánsson G, Valtysdottir S, Venge P, Hällgren R. Cow’s milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren’s syndrome. Clin Exp Allergy. 2008;38(6):929–35.PubMedPubMedCentralCrossRef Lidén M, Kristjánsson G, Valtysdottir S, Venge P, Hällgren R. Cow’s milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren’s syndrome. Clin Exp Allergy. 2008;38(6):929–35.PubMedPubMedCentralCrossRef
9.
go back to reference Ohlsson B, Scheja A, Janciauskiene S, Mandl T. Functional bowel symptoms and GnRH antibodies: common findings in patients with primary Sjögren’s syndrome but not in systemic sclerosis. Scand J Rheumatol. 2009;38(5):391–3.PubMedCrossRef Ohlsson B, Scheja A, Janciauskiene S, Mandl T. Functional bowel symptoms and GnRH antibodies: common findings in patients with primary Sjögren’s syndrome but not in systemic sclerosis. Scand J Rheumatol. 2009;38(5):391–3.PubMedCrossRef
10.
go back to reference Kjellén G, Fransson SG, Lindström F, Sökjer H, Tibbling L. Esophageal function, radiography, and dysphagia in Sjögren’s syndrome. Dig Dis Sci. 1986;31(3):225–9.PubMedCrossRef Kjellén G, Fransson SG, Lindström F, Sökjer H, Tibbling L. Esophageal function, radiography, and dysphagia in Sjögren’s syndrome. Dig Dis Sci. 1986;31(3):225–9.PubMedCrossRef
11.
go back to reference Maury CP, Törnroth T, Teppo AM. Atrophic gastritis in Sjögren’s syndrome: morphologic, biochemical, and immunologic findings. Arthritis Rheum. 1985;28(4):388–94.PubMedCrossRef Maury CP, Törnroth T, Teppo AM. Atrophic gastritis in Sjögren’s syndrome: morphologic, biochemical, and immunologic findings. Arthritis Rheum. 1985;28(4):388–94.PubMedCrossRef
12.
go back to reference Iltanen S, Collin P, Korpela M, Holm K, Partanen J, Polvi A, et al. Celiac disease and markers of celiac disease latency in patients with primary Sjögren’s syndrome. Am J Gastroenterol. 1999;94(4):1042–6.PubMed Iltanen S, Collin P, Korpela M, Holm K, Partanen J, Polvi A, et al. Celiac disease and markers of celiac disease latency in patients with primary Sjögren’s syndrome. Am J Gastroenterol. 1999;94(4):1042–6.PubMed
13.
go back to reference Palm Ø, Moum B, Gran JT. Estimation of Sjögren’s syndrome among IBD patients: a six year post-diagnostic prevalence study. Scand J Rheumatol. 2002;31(3):140–5.PubMedCrossRef Palm Ø, Moum B, Gran JT. Estimation of Sjögren’s syndrome among IBD patients: a six year post-diagnostic prevalence study. Scand J Rheumatol. 2002;31(3):140–5.PubMedCrossRef
14.
go back to reference Liang Y, Yang Z, Qin B, Zhong R. Primary Sjögren’s syndrome and malignancy risk: a systematic review and meta-analysis. Ann Rheum Dis. 2014;73(6):1151–6.PubMedCrossRef Liang Y, Yang Z, Qin B, Zhong R. Primary Sjögren’s syndrome and malignancy risk: a systematic review and meta-analysis. Ann Rheum Dis. 2014;73(6):1151–6.PubMedCrossRef
15.
go back to reference Røseth AG, Fagerhol MK, Aadland E, Schjønsby H. Assessment of the neutrophil dominating protein calprotectin in feces: a methodologic study. Scand J Gastroenterol. 1992;27(9):793–8.PubMedCrossRef Røseth AG, Fagerhol MK, Aadland E, Schjønsby H. Assessment of the neutrophil dominating protein calprotectin in feces: a methodologic study. Scand J Gastroenterol. 1992;27(9):793–8.PubMedCrossRef
16.
go back to reference Røseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol. 1999;34(1):50–4.PubMedCrossRef Røseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol. 1999;34(1):50–4.PubMedCrossRef
17.
go back to reference Waugh N, Cummins E, Royle P, Kandala NB, Shyangdan D, Arasaradnam R, et al. Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation. Health Technol Assess. 2013;17(55). doi:10.3310/hta17550. Waugh N, Cummins E, Royle P, Kandala NB, Shyangdan D, Arasaradnam R, et al. Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation. Health Technol Assess. 2013;17(55). doi:10.​3310/​hta17550.
18.
go back to reference Manz M, Burri E, Rothen C, Tchanguizi N, Niederberger C, Rossi L, et al. Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study. BMC Gastroenterol. 2012;12:5.PubMedPubMedCentralCrossRef Manz M, Burri E, Rothen C, Tchanguizi N, Niederberger C, Rossi L, et al. Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study. BMC Gastroenterol. 2012;12:5.PubMedPubMedCentralCrossRef
19.
go back to reference Burri E, Manz M, Schroeder P, Froehlich F, Rossi L, Beglinger C, et al. Diagnostic yield of endoscopy in patients with abdominal complaints: incremental value of faecal calprotectin on guidelines of appropriateness. BMC Gastroenterol. 2014;14:57.PubMedPubMedCentralCrossRef Burri E, Manz M, Schroeder P, Froehlich F, Rossi L, Beglinger C, et al. Diagnostic yield of endoscopy in patients with abdominal complaints: incremental value of faecal calprotectin on guidelines of appropriateness. BMC Gastroenterol. 2014;14:57.PubMedPubMedCentralCrossRef
20.
go back to reference Norman GL. Fecal calprotectin: an inflammatory biomarker with emerging importance in the clinical laboratory. MLO Med Lab Obs. 2015;47(5):24–6.PubMed Norman GL. Fecal calprotectin: an inflammatory biomarker with emerging importance in the clinical laboratory. MLO Med Lab Obs. 2015;47(5):24–6.PubMed
21.
go back to reference Burri E, Manz M, Rothen C, Rossi L, Beglinger C, Lehmann FS. Monoclonal antibody testing for fecal calprotectin is superior to polyclonal testing of fecal calprotectin and lactoferrin to identify organic intestinal disease in patients with abdominal discomfort. Clin Chim Acta. 2013;416:41–7.PubMedCrossRef Burri E, Manz M, Rothen C, Rossi L, Beglinger C, Lehmann FS. Monoclonal antibody testing for fecal calprotectin is superior to polyclonal testing of fecal calprotectin and lactoferrin to identify organic intestinal disease in patients with abdominal discomfort. Clin Chim Acta. 2013;416:41–7.PubMedCrossRef
22.
go back to reference Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006;15(3):237–41.PubMed Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006;15(3):237–41.PubMed
23.
go back to reference Bengtsson M, Hammar O, Mandl T, Ohlsson B. Evaluation of gastrointestinal symptoms in different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS). BMC Gastroenterol. 2011;11:122.PubMedPubMedCentralCrossRef Bengtsson M, Hammar O, Mandl T, Ohlsson B. Evaluation of gastrointestinal symptoms in different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS). BMC Gastroenterol. 2011;11:122.PubMedPubMedCentralCrossRef
24.
go back to reference Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, et al. EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjögren’s syndrome. Ann Rheum Dis. 2011;70(6):968–72.PubMedCrossRef Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, et al. EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjögren’s syndrome. Ann Rheum Dis. 2011;70(6):968–72.PubMedCrossRef
25.
go back to reference Andréasson K, Saxne T, Scheja A, Bartosik I, Mandl T, Hesselstrand R. Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren’s syndrome and rheumatoid arthritis. Arthritis Res Ther. 2014;16(1):R46.PubMedPubMedCentralCrossRef Andréasson K, Saxne T, Scheja A, Bartosik I, Mandl T, Hesselstrand R. Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren’s syndrome and rheumatoid arthritis. Arthritis Res Ther. 2014;16(1):R46.PubMedPubMedCentralCrossRef
26.
go back to reference Wang S, Wang Z, Shi H, Heng L, Juan W, Yuan B, et al. Faecal calprotectin concentrations in gastrointestinal diseases. J Int Med Res. 2013;41(4):1357–61.PubMedCrossRef Wang S, Wang Z, Shi H, Heng L, Juan W, Yuan B, et al. Faecal calprotectin concentrations in gastrointestinal diseases. J Int Med Res. 2013;41(4):1357–61.PubMedCrossRef
27.
go back to reference Carswell KA, Vincent RP, Belgaumkar AP, Sherwood RA, Amiel SA, Patel AG, et al. The effect of bariatric surgery on intestinal absorption and transit time. Obes Surg. 2014;24(5):796–805.PubMedCrossRef Carswell KA, Vincent RP, Belgaumkar AP, Sherwood RA, Amiel SA, Patel AG, et al. The effect of bariatric surgery on intestinal absorption and transit time. Obes Surg. 2014;24(5):796–805.PubMedCrossRef
28.
go back to reference Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128(5):1172–8.PubMedCrossRef Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128(5):1172–8.PubMedCrossRef
29.
go back to reference Brun JG, Cuida M, Jacobsen H, Kloster R, Johannesen AC, Høyeraal HM, et al. Sjögren’s syndrome in inflammatory rheumatic diseases: analysis of the leukocyte protein calprotectin in plasma and saliva. Scand J Rheumatol. 1994;23(3):114–8.PubMedCrossRef Brun JG, Cuida M, Jacobsen H, Kloster R, Johannesen AC, Høyeraal HM, et al. Sjögren’s syndrome in inflammatory rheumatic diseases: analysis of the leukocyte protein calprotectin in plasma and saliva. Scand J Rheumatol. 1994;23(3):114–8.PubMedCrossRef
30.
go back to reference Prell C, Nagel D, Freudenberg F, Schwarzer A, Koletzko S. Comparison of three tests for faecal calprotectin in children and young adults: a retrospective monocentric study. BMJ Open. 2014;4(5):e004558.PubMedPubMedCentralCrossRef Prell C, Nagel D, Freudenberg F, Schwarzer A, Koletzko S. Comparison of three tests for faecal calprotectin in children and young adults: a retrospective monocentric study. BMJ Open. 2014;4(5):e004558.PubMedPubMedCentralCrossRef
31.
go back to reference Dhaliwal A, Zeino Z, Tomkins C, Cheung M, Nwokolo C, Smith S, et al. Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cut-offs should we apply? Frontline Gastroenterol. 2015;6(1):14–9.PubMedPubMedCentralCrossRef Dhaliwal A, Zeino Z, Tomkins C, Cheung M, Nwokolo C, Smith S, et al. Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cut-offs should we apply? Frontline Gastroenterol. 2015;6(1):14–9.PubMedPubMedCentralCrossRef
32.
go back to reference Szodaray P, Barta Z, Lakos G, Szakáll S, Zeher M. Coeliac disease in Sjögren’s syndrome—a study of 111 Hungarian patients. Rheumatol Int. 2004;24(5):278–82. Szodaray P, Barta Z, Lakos G, Szakáll S, Zeher M. Coeliac disease in Sjögren’s syndrome—a study of 111 Hungarian patients. Rheumatol Int. 2004;24(5):278–82.
33.
go back to reference Montalto M, Santoro L, Curigliano V, D’Onofrio F, Cammarota G, Panunzi S, et al. Faecal calprotectin concentrations in untreated coeliac patients. Scand J Gastroenterol. 2007;42(8):957–61.PubMedCrossRef Montalto M, Santoro L, Curigliano V, D’Onofrio F, Cammarota G, Panunzi S, et al. Faecal calprotectin concentrations in untreated coeliac patients. Scand J Gastroenterol. 2007;42(8):957–61.PubMedCrossRef
34.
go back to reference Klingberg E, Carlsten H, Hilme E, Hedberg M, Forsblad-d’Elia H. Calprotectin in ankylosing spondylitis – frequently elevated in feces, but normal in serum. Scand J Gastroenterol. 2012;47(4):435–44.PubMedCrossRef Klingberg E, Carlsten H, Hilme E, Hedberg M, Forsblad-d’Elia H. Calprotectin in ankylosing spondylitis – frequently elevated in feces, but normal in serum. Scand J Gastroenterol. 2012;47(4):435–44.PubMedCrossRef
35.
go back to reference Marie I, Leroi AM, Menard JF, Levesque H, Quillard M, Ducrotte P. Fecal calprotectin in systemic sclerosis and review of the literature. Autoimmun Rev. 2015;14(6):547–54.PubMedCrossRef Marie I, Leroi AM, Menard JF, Levesque H, Quillard M, Ducrotte P. Fecal calprotectin in systemic sclerosis and review of the literature. Autoimmun Rev. 2015;14(6):547–54.PubMedCrossRef
Metadata
Title
Elevated levels of faecal calprotectin in primary Sjögren’s syndrome is common and associated with concomitant organic gastrointestinal disease
Authors
Kristofer Andréasson
Bodil Ohlsson
Thomas Mandl
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0907-8

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