**Author details**

Sabina Oreska and Michal Tomcik\* Institute of Rheumatology, Department of Rheumatology, Faculty of Medicine, Charles University, Prague, Czech Republic

\*Address all correspondence to: tomcik@revma.cz

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**77**

*Gastrointestinal Involvement in Systemic Sclerosis: Overview, Neglected Aspects, Malnutrition…*

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[10] Hudson M, Lo E, Lu Y, Hercz D, Baron M, Steele R, et al. Cigarette smoking in patients with systemic sclerosis. Arthritis and Rheumatism.

[11] Bodukam V, Hays RD, Maranian P, Furst DE, Seibold JR, Impens A, et al. Association of gastrointestinal

symptoms in patients with systemic sclerosis. Rheumatology (Oxford).

involvement and depressive

[12] Milette K, Hudson M, Korner A, Baron M, Thombs BD, Canadian Scleroderma Research G. Sleep disturbances in systemic sclerosis: Evidence for the role of gastrointestinal symptoms, pain and pruritus. Rheumatology (Oxford).

2013;**33**(11):2943-2948

2011;**63**(1):230-238

2011;**50**(2):330-334

2013;**52**(9):1715-1720

[13] Omair MA, Lee P. Effect of gastrointestinal manifestations on quality of life in 87 consecutive patients with systemic sclerosis. The Journal of Rheumatology. 2012;**39**(5):992-996

[14] Kumar S, Singh J, Rattan S, DiMarino AJ, Cohen S, Jimenez SA. Review article: Pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis. Alimentary Pharmacology & Therapeutics. 2017;**45**(7):883-898

[15] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. The New England Journal of Medicine. 2009;**360**(19):1989-2003

[16] Piasecki C, Chin J, Greenslade L,

McIntyre N, Burroughs AK,

*DOI: http://dx.doi.org/10.5772/intechopen.88286*

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[2] LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): Classification, subsets and pathogenesis.

[3] Sjogren RW. Gastrointestinal features of scleroderma. Current Opinion in Rheumatology. 1996;**8**(6):569-575

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[6] Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis and Rheumatism. 1994;**37**(9):1265-1282

[7] Bacher A, Mittoo S, Hudson M, Tatibouet S. Canadian Scleroderma Research G, Baron M. systemic sclerosis in Canada's north American native population: Assessment of clinical and serological manifestations. The Journal of Rheumatology. 2013;**40**(7):1121-1126

[8] Arnett FC, Howard RF, Tan F, Moulds JM, Bias WB, Durban E, et al. Increased prevalence of systemic sclerosis in a native American tribe in Oklahoma. Association with an Amerindian HLA haplotype. Arthritis and Rheumatism. 1996;**39**(8):1362-1370

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**76**

**Author details**

Sabina Oreska and Michal Tomcik\*

Charles University, Prague, Czech Republic

provided the original work is properly cited.

\*Address all correspondence to: tomcik@revma.cz

Institute of Rheumatology, Department of Rheumatology, Faculty of Medicine,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

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[13] Omair MA, Lee P. Effect of gastrointestinal manifestations on quality of life in 87 consecutive patients with systemic sclerosis. The Journal of Rheumatology. 2012;**39**(5):992-996

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[22] Singh J, Cohen S, Mehendiratta V, Mendoza F, Jimenez SA, Dimarino AJ, et al. Effects of scleroderma antibodies and pooled human immunoglobulin on anal sphincter and colonic smooth muscle function. Gastroenterology. 2012;**143**(5):1308-1318

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[26] Raja J, Denton CP. Cytokines in the immunopathology of systemic sclerosis. Seminars in Immunopathology. 2015;**37**(5):543-557

[27] Manetti M, Neumann E, Muller A, Schmeiser T, Saar P, Milia AF, et al. Endothelial/lymphocyte activation leads to prominent CD4+ T cell infiltration in the gastric mucosa of patients with systemic sclerosis. Arthritis and Rheumatism. 2008;**58**(9):2866-2873

[28] Manetti M, Neumann E, Milia AF, Tarner IH, Bechi P, Matucci-Cerinic M, et al. Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients. Arthritis and Rheumatism. 2007;**56**(10):3442-3447

[29] Manetti M, Rosa I, Messerini L, Guiducci S, Matucci-Cerinic M, Ibba-Manneschi L. A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis. Journal of Cellular and Molecular Medicine. 2014;**18**(2):253-262

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[40] Kirby DF, Chatterjee S. Evaluation and management of gastrointestinal manifestations in scleroderma. Current Opinion in Rheumatology.

[41] Derk CT, Rasheed M, Spiegel JR, Jimenez SA. Increased incidence of carcinoma of the tongue in patients with systemic sclerosis. The Journal of Rheumatology. 2005;**32**(4):637-641

[42] Ntoumazios SK, Voulgari PV, Potsis K, Koutis E, Tsifetaki N, Assimakopoulos DA. Esophageal involvement in scleroderma:

Gastroesophageal reflux, the common problem. Seminars in Arthritis and Rheumatism. 2006;**36**(3):173-181

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related to systemic sclerosis: A 3-year EULAR Scleroderma trials and Research prospective follow-up study. Rheumatology (Oxford).

2011;**50**(8):1440-1444

2012;**32**(1):165-168

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[35] Veale BJ, Jablonski RY, Frech TM, Pauling JD. Orofacial manifestations of systemic sclerosis. British Dental Journal. 2016;**221**(6):305-310

[36] Jung S, Martin T, Schmittbuhl M, Huck O. The spectrum of orofacial manifestations in systemic sclerosis: A challenging management. Oral Diseases.

[37] Avouac J, Sordet C, Depinay C, Ardizonne M, Vacher-Lavenu MC, Sibilia J, et al. Systemic sclerosisassociated Sjogren's syndrome and relationship to the limited cutaneous subtype: Results of a prospective study of sicca syndrome in 133 consecutive patients. Arthritis and Rheumatism.

2017;**23**(4):424-439

2006;**54**(7):2243-2249

[38] Auluck A, Pai KM, Shetty C, Shenoi SD. Mandibular resorption in progressive systemic sclerosis: A report of three cases. Dento Maxillo Facial Radiology. 2005;**34**(6):384-386

Research & Therapy. 2016;**18**:11

2014;**124**(4):1622-1635

*Gastrointestinal Involvement in Systemic Sclerosis: Overview, Neglected Aspects, Malnutrition… DOI: http://dx.doi.org/10.5772/intechopen.88286*

International Journal of Colorectal Disease. 2001;**16**(5):271-275

*New Insights into Systemic Sclerosis*

1995;**36**(5):654-656

2000;**27**(5):1203-1206

[18] Russell ML, Friesen D, Henderson RD, Hanna WM. Ultrastructure of the esophagus in scleroderma. Arthritis and Rheumatism. 1982;**25**(9):1117-1123

[19] Kumar S, Singh J, Kedika R, Mendoza F, Jimenez SA, Blomain ES, et al. Role of muscarinic-3 receptor antibody in systemic sclerosis: Correlation with disease duration and effects of

2016;**310**(11):G1052-G1060

[20] Goldblatt F, Gordon TP, Waterman SA. Antibody-mediated gastrointestinal dysmotility in scleroderma. Gastroenterology.

[21] Singh J, Mehendiratta V, Del Galdo F, Jimenez SA, Cohen S, DiMarino AJ, et al. Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells. American Journal of Physiology. Gastrointestinal and Liver Physiology.

2002;**123**(4):1144-1150

2009;**297**(6):G1206-G1213

2012;**143**(5):1308-1318

[22] Singh J, Cohen S, Mehendiratta V, Mendoza F, Jimenez SA, Dimarino AJ, et al. Effects of scleroderma antibodies and pooled human immunoglobulin on anal sphincter and colonic smooth muscle function. Gastroenterology.

IVIG. American Journal of Physiology. Gastrointestinal and Liver Physiology.

McCormick PA. Endoscopic detection of ischaemia with a new probe indicates low oxygenation of gastric epithelium in portal hypertensive gastropathy. Gut. [23] Cohen S, Fisher R, Lipshutz W, Turner R, Myers A, Schumacher R. The pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease. The Journal of Clinical Investigation.

[24] Chizzolini C, Boin F. The role of the acquired immune response in systemic sclerosis. Seminars in Immunopathology. 2015;**37**(5):519-528

[25] O'Reilly S, Hugle T, van Laar JM. T cells in systemic sclerosis: A

reappraisal. Rheumatology (Oxford).

[26] Raja J, Denton CP. Cytokines in the immunopathology of systemic sclerosis.

[27] Manetti M, Neumann E, Muller A,

[28] Manetti M, Neumann E, Milia AF, Tarner IH, Bechi P, Matucci-Cerinic M, et al. Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients. Arthritis and Rheumatism.

[29] Manetti M, Rosa I, Messerini L, Guiducci S, Matucci-Cerinic M, Ibba-Manneschi L. A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis. Journal of Cellular and Molecular Medicine.

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Schumpelick V. Increased distribution of collagen type III and reduced

expression of matrix metalloproteinase 1 in patients with diverticular disease.

Seminars in Immunopathology.

Schmeiser T, Saar P, Milia AF, et al. Endothelial/lymphocyte activation leads to prominent CD4+ T cell infiltration in the gastric mucosa of patients with systemic sclerosis. Arthritis and Rheumatism.

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2012;**51**(9):1540-1549

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[37] Avouac J, Sordet C, Depinay C, Ardizonne M, Vacher-Lavenu MC, Sibilia J, et al. Systemic sclerosisassociated Sjogren's syndrome and relationship to the limited cutaneous subtype: Results of a prospective study of sicca syndrome in 133 consecutive patients. Arthritis and Rheumatism. 2006;**54**(7):2243-2249

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2014;**66**(11):1725-1730

validity and ease of use of the

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[96] Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. American College of G. clinical guideline: Management of gastroparesis. The American Journal of Gastroenterology.

2013;**108**(1):18-37. quiz 8

2014;**26**(7):753-760

[97] Ghoshal UC, Srivastava D, Ghoshal U, Misra A. Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture. European Journal of Gastroenterology & Hepatology.

[91] Marighela TF, Genaro Pde S, Pinheiro MM, Szejnfeld VL, Kayser C. Risk factors for body

2015;**10**(9):e0137912

2013;**32**(7):1037-1044

2014;**30**(2):204-209

2014;**33**(1):77-82

quiz 29

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levels in systemic sclerosis. PLoS One. 2015;**10**(9):e0137912

*New Insights into Systemic Sclerosis*

[75] Cavazzana I, Ceribelli A, Taraborelli M, Fredi M, Norman G, Tincani A, et al. Primary biliary cirrhosis-related autoantibodies in a large cohort of Italian patients with systemic sclerosis. The Journal of Rheumatology. 2011;**38**(10):2180-2185

2006;**55**(3):388-394

2012;**59**(1):48-52

2011;**30**(1):129-132

[76] Rigamonti C, Shand LM, Feudjo M, Bunn CC, Black CM, Denton CP, et al. Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis. Gut.

Becker C, Schneider U, et al. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Annals of the Rheumatic Diseases.

2010;**69**(11):1951-1957

2011;**40**(2):e111-e119

S42-S46

2015;**1**(1):82-105

[84] Baubet T, Ranque B, Taieb O, Berezne A, Bricou O, Mehallel S, et al. Mood and anxiety disorders in systemic sclerosis patients. Presse Médicale.

[85] Baron M, Bernier P, Cote LF, Delegge MH, Falovitch G, Friedman G,

et al. Screening and therapy for malnutrition and related gastro-

[86] Nagaraja V, McMahan ZH, Getzug T, Khanna D. Management of gastrointestinal involvement in scleroderma. Current Treatment Options in Rheumatology.

[87] Tanner SB, Moore CF Jr. A review of the use of dual-energy X-ray

and Reviews. 2012;**4**:99-107

2004;**63**(3):326-327

[88] Frediani B, Baldi F, Falsetti P, Acciai C, Filippou G, Spreafico A, et al. Bone mineral density in patients with systemic sclerosis. Annals of the Rheumatic Diseases.

[89] Carbone L, Tylavsky F, Wan J, McKown K, Cheng S. Bone mineral density in scleroderma. Rheumatology

(Oxford). 1999;**38**(4):371-372

[90] Corrado A, Colia R, Mele A, Di Bello V, Trotta A, Neve A, et al. Relationship between body mass

composition, bone mineral density, skin fibrosis and 25(OH) vitamin D serum

absorptiometry (DXA) in rheumatology. Open access Rheumatology : Research

intestinal disorders in systemic sclerosis: Recommendations of a north American expert panel. Clinical and Experimental Rheumatology. 2010;**28**(2 Suppl 58):

[77] Assandri R, Monari M, Montanelli A. Development of systemic sclerosis in patients with autoimmune hepatitis: An emerging overlap syndrome. Gastroenterology and Hepatology from

Bed to Bench. 2016;**9**(3):211-219

[78] You BC, Jeong SW, Jang JY, Goo SM, Kim SG, Kim YS, et al. Liver cirrhosis due to autoimmune hepatitis combined with systemic sclerosis. The Korean Journal of Gastroenterology.

[79] Skare TL, Nisihara RM, Haider O, Azevedo PM, Utiyama SR. Liver autoantibodies in patients with scleroderma. Clinical Rheumatology.

[80] Shawis TN, Chaloner C, Herrick AL, Jayson MI. Pancreatic function in systemic sclerosis. British Journal of Rheumatology. 1996;**35**(3):298-299

[81] Abraham AA, Joos A. Pancreatic necrosis in progressive systemic sclerosis. Annals of the Rheumatic Diseases. 1980;**39**(4):396-398

[82] Caporali R, Caccialanza R, Bonino C, Klersy C, Cereda E, Xoxi B, et al. Disease-related malnutrition in outpatients with systemic sclerosis. Clinical Nutrition. 2012;**31**(5):666-671

[83] Krause L, Becker MO, Brueckner CS, Bellinghausen CJ,

**82**

[91] Marighela TF, Genaro Pde S, Pinheiro MM, Szejnfeld VL, Kayser C. Risk factors for body composition abnormalities in systemic sclerosis. Clinical Rheumatology. 2013;**32**(7):1037-1044

[92] Rosato E, Gigante A, Gasperini ML, Molinaro I, Di Lazzaro GG, Afeltra A, et al. Nutritional status measured by BMI is impaired and correlates with left ventricular mass in patients with systemic sclerosis. Nutrition. 2014;**30**(2):204-209

[93] Caramaschi P, Biasi D, Caimmi C, Barausse G, Gatti D, Ferrari M, et al. Relationship between body composition and both cardiovascular risk factors and lung function in systemic sclerosis. Clinical Rheumatology. 2014;**33**(1):77-82

[94] Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. The American Journal of Gastroenterology. 2013;**108**(3):308-328. quiz 29

[95] Ebert EC. Esophageal disease in scleroderma. Journal of Clinical Gastroenterology. 2006;**40**(9):769-775

[96] Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. American College of G. clinical guideline: Management of gastroparesis. The American Journal of Gastroenterology. 2013;**108**(1):18-37. quiz 8

[97] Ghoshal UC, Srivastava D, Ghoshal U, Misra A. Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture. European Journal of Gastroenterology & Hepatology. 2014;**26**(7):753-760

[98] Quigley EM. Small intestinal bacterial overgrowth: What it is and what it is not. Current Opinion in Gastroenterology. 2014;**30**(2):141-146

[99] Khanna D, Hays RD, Park GS, Braun-Moscovici Y, Mayes MD, McNearney TA, et al. Development of a preliminary scleroderma gastrointestinal tract 1.0 quality of life instrument. Arthritis and Rheumatism. 2007;**57**(7):1280-1286

[100] Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the University of California, Los Angeles Scleroderma clinical trial consortium gastrointestinal tract instrument. Arthritis and Rheumatism. 2009;**61**(9):1257-1263

[101] Spiegel BM, Hays RD, Bolus R, Melmed GY, Chang L, Whitman C, et al. Development of the NIH patientreported outcomes measurement information system (PROMIS) gastrointestinal symptom scales. The American Journal of Gastroenterology. 2014;**109**(11):1804-1814

[102] Nagaraja V, Hays RD, Khanna PP, Spiegel BM, Chang L, Melmed GY, et al. Construct validity of the patientreported outcomes measurement information system gastrointestinal symptom scales in systemic sclerosis. Arthritis Care Res (Hoboken). 2014;**66**(11):1725-1730

[103] Stratton RJ, Hackston A, Longmore D, Dixon R, Price S, Stroud M, et al. Malnutrition in hospital outpatients and inpatients: Prevalence, concurrent validity and ease of use of the 'malnutrition universal screening tool' ('MUST') for adults. The British Journal of Nutrition. 2004;**92**(5):799-808

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**Chapter 4**

**Abstract**

**1. Introduction**

**2.1 Introduction**

Systemic Sclerosis Mimics

Many clinical conditions are presenting with sclerosis of the skin and with tissue fibrosis. These conditions may be confused with systemic sclerosis (SSc, scleroderma). These diseases and disabilities are generally referred to as systemic sclerosis mimics or scleroderma-like syndromes. These disorders have very different etiologies and often an unclear pathogenetic mechanism. Distinct clinical characteristics, skin histology, and disease associations may allow distinguishing these conditions from systemic sclerosis and from each other. A histopathological examination with clinicopathological correlation for diagnosis is important to spare the patients from ineffective treatments and inadequate management. In this chapter, we discussed localized scleroderma, lichen sclerosus, nephrogenic systemic fibrosis, eosinophilic fasciitis, scleromyxedema, and scleredema. These are often detected in the primary care setting and referred to rheumatologists for further evaluation. Rheumatologists, or preferably in collaboration with a dermatologist, must be able to promptly recognize them to provide valuable prognostic information and appropriate treatment options for affected patients.

**Keywords:** localized scleroderma, lichen sclerosus, eosinophilic fasciitis,

In this chapter, we discuss the groups of disorders classified as systemic sclerosis mimics. Localized and sometimes generalized skin stiffness is typical for this group of diseases. However, quite incongruous pathogenesis, underlying disease mechanisms and distinct organ involvement are significantly different in these conditions. This chapter describes the pathogenesis, clinical manifestation, histopathology findings, and therapeutic possibilities of the most common diseases that may cause

Localized scleroderma is a clinically distinct inflammatory disease, primarily of the dermis and also subcutaneous fat [1]. The inflammation leads to scar-like sclerosis. Inflammatory infiltrates and changes of small vessels are similar in morphea and systemic sclerosis (SSc), but morphea has more asymmetric or linear skin localization and distribution than SSc, which has symmetrical distribution. Generalized morphea can prevent and mimic diffuse cutaneous SSc, but this clinical variant does not have Raynaud's phenomenon, digital sclerosis and lung, and

nephrogenic systemic fibrosis, scleromyxedema, scleredema

difficulties in the differential diagnosis of systemic sclerosis.

**2. Localized scleroderma, morphea**

*Ondřej Kodet and Sabína Oreská*
