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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 12  |  Issue : 6  |  Page : 156-166

Gastro-intestinal involvement in systemic sclerosis


1 Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
2 Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA

Date of Web Publication23-Nov-2017

Correspondence Address:
Saurabh Kedia
Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.219088

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  Abstract 


The gastrointestinal (GI) tract can be involved in up to 90% of patients with systemic sclerosis (SSc) and is the leading cause of morbidity and third most common cause of mortality in these patients. The GI involvement can occur in the absence of cutaneous manifestations in 10% of patients. Vasculopathy, cellular and humoral immunity, and diffuse fibrosis are the principal pathogenetic mechanisms in SSc and begin with autoantibody-mediated neuronal damage followed by muscular damage and fibrosis. This leads to progressive dysmotility of the entire GI tract from mouth to anus and is responsible for the clinical manifestations including gastroesophageal reflux disease and dysphagia due to esophageal involvement, gastroparesis, small intestinal bacterial overgrowth and chronic intestinal pseudo-obstruction, and constipation due to colonic and fecal incontinence due to anorectal involvement. The clinical features resulting from the involvement of these organs often overlap and multiple areas may be involved simultaneously. The treatment remains mostly symptomatic because effective disease-modifying therapies are lacking. These patients are at a risk of malnutrition and nutritional screening, and thus rehabilitation is very important. Refractory cases require nutritional support in the form of enteral nutrition and/or home parenteral nutrition. Future research is needed in the pathogenesis, development of biomarkers for early identification of GI involvement at the asymptomatic stage, and targeted disease-modifying therapies, which can alter/halt the disease progression.

Keywords: esophageal dysmotility, fecal incontinence, fibrosis, gastroparesis, pseudoobstruction


How to cite this article:
Kedia S, Chhaparia A, Garg P. Gastro-intestinal involvement in systemic sclerosis. Indian J Rheumatol 2017;12, Suppl S1:156-66

How to cite this URL:
Kedia S, Chhaparia A, Garg P. Gastro-intestinal involvement in systemic sclerosis. Indian J Rheumatol [serial online] 2017 [cited 2017 Dec 18];12, Suppl S1:156-66. Available from: http://www.indianjrheumatol.com/text.asp?2017/12/6/156/219088




  Introduction Top


Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by diffuse fibrosis of skin and internal organs. The prevalence of disease varies from 443/1,000,000 and 277/1,000,000 population in the USA and Europe to 120/1,000,000 population in India.[1],[2],[3] The peak age of disease onset is 30–50 years and it is 2–4 times more common in females than in males.[4] SSc is classified into diffuse and limited subtypes, with the skin thickening being distal to elbow and knees in the limited subtype.[5] The gastrointestinal (GI) involvement occurs (GI-SSc) in up to 90% of patients with SSc and may also occur in the absence of overt cutaneous manifestations in 10%.[6] It can involve any region of the GI tract, with esophageal involvement being the earliest and most common occurring in up to 70% of patients. GI involvement is the leading cause of morbidity and the third leading cause of mortality in SSc after cardiopulmonary and renal involvement.[7],[8] The present review will focus on the pathogenesis, clinical features, and management of GI manifestations in patients with SSc.


  Pathogenesis of Gastrointestinal Involvement in Systemic Sclerosis Top


The pathogenesis of SSc is possibly a complex interaction of genetics, environment, and aberrant immune damage along with increased fibrogenesis.[9] Smoking [10] and Helicobacter pylori[11] infection have been the only recognized environmental triggers till date. Evidence for genetic predisposition stems from a study demonstrating more severe GI involvement in Canadian North American native patients as compared to Caucasian Americans.[12]

The pathogenetic manifestations of SSc are a consequence of three distinct processes: vasculopathy, immune aberrations (both humoral as well as cellular), and fibrogenesis [Figure 1].
Figure 1: Pathogenesis of gastro-intestinal manifestations of systemic sclerosis

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Vasculopathy

Vasculopathy is manifested by fibroproliferative lesions in the microvasculature because of endothelial damage. Studies have demonstrated reduced blood supply to the gastric and duodenal mucosa, basement membrane thickening of the arterioles along with perivascular infiltrates in patients with GI-SSc.[13],[14]

Immune aberrations

There is a role of both humoral and cellular immunity in the pathogenesis of GI-SSc. Eaker et al.[15] demonstrated a prolongation in the activity front duration and interval after injection of antibodies from patients with SSc into an immunosuppressed rat model. Another study [16] showed that carbachol (a muscarinic agonist)-induced M3-muscarinic receptor-mediated contractions in the mouse colon longitudinal muscle were inhibited by Ig fractions from patients with scleroderma. Kawaguchi et al.[17] showed that anti-muscarinic-3 acetylcholine receptor antibodies in patients with GI-SSc correlated with the severity of GI involvement. A study showed eosinophils and mast cells in close association with Meissner's and Auerbach's plexuses in the intestinal mucosa of patients with early GI-SSc.[18] Further, a recent study demonstrated CD4 + T cell infiltration in the gastric mucosa of patients with SSc along with an increased CD4+/CD8+T cell ratio.[19]

Fibrosis

Fibrosis disrupts the normal tissue architecture leading to GI dysfunction. Fibrosis results from a complex interaction between multiple pro-fibrogenic cytokines [20] such as transforming growth factor (TGF-), connective tissue growth factor, endothelin-1, platelet-derived growth factor, and profibrotic cells including fibroblasts and myofibroblasts.[21] A study demonstrated high amount of collagen in the lamina propria that increased toward the muscularis mucosae along with muscular atrophy and peri-mysial, peri-glandular, and peri-vascular fibrosis.[22]

The pathogenesis of GI-SSc is progressive beginning with neuronal followed by muscular damage and subsequently fibrosis [23],[24] [Figure 1].


  Clinical Features Top


Esophagus

The esophageal involvement can be asymptomatic or present as dysphagia (61%–80%), odynophagia, heartburn (77%–78%), regurgitation, and/or vomiting.[25],[26],[27],[28] Patients can also present with atypical symptoms of gastroesophageal reflux disease (GERD) such as chronic cough and asthma. The severity of GERD has been correlated with Raynaud's phenomenon, pulmonary artery hypertension, increasing age, disease duration, interstitial lung disease, and one study negatively correlated it with H. pylori infection.[29],[30],[31] The correlation between the severity of esophageal involvement and diffuse versus limited SSc has been heterogeneous.[30],[32],[33]

Manometry is the most sensitive technique to demonstrate esophageal involvement.[34] The typical manometric changes include deceased lower esophageal sphincter (LES) pressure (62%–95%), diminished esophageal amplitude with aperistalsis (41%), absent contractility (56%), slight hypomotility (30%), severe hypomotility (27%), and ineffective esophageal motility (10%).[26],[27],[28] These changes have been demonstrated in almost all patients with esophageal symptoms/esophagitis and ~60% of asymptomatic patients.[27] Endoscopic involvement (esophagitis) has been demonstrated even in asymptomatic patients [35] and in 32%–97% of symptomatic patients.[25],[27],[32],[33],[36] Other endoscopic abnormalities include hiatus hernia (60%), stricture (29%), loose hiatus (15%), and Barrett's esophagus (13%–18%)[26],[37] [Figure 2]. Radiologic abnormalities (dilated and patulous esophagus) have been documented in up to 68% of patients.[33]
Figure 2: Upper gastrointestinal endoscopy showing esophageal ulcers with dilated esophagus in patients with systemic sclerosis

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Stomach

The symptoms of gastric involvement include early satiety (45%), abdominal pain (35%), nausea (20%), and vomiting (10%) which may progress to complete food intolerance, severe weight loss, and malnutrition.[26] Patients may also present rarely with GI bleeding and iron deficiency anemia. Functional abnormalities include delayed gastric emptying (10%–75%), altered gastric compliance, and reduced antral motility.[38],[39],[40],[41] Patients with diffuse SSc have been demonstrated to have a slower gastric emptying than patients with limited SSc.[42] The structural changes demonstrated on upper GI (UGI) endoscopy include nonerosive gastropathy (40%), erosive gastropathy (30%), nodular gastropathy (10%), dehiscent pylorus, and gastric antral vascular ectasia (GAVE).[26],[43],[44] GAVE has been demonstrated in up to 5%–22% patients of GI-SSc.[45] In a study of 264 patients, 5.7% patients had GAVE, and SSc preceded the onset of GAVE in 87%.[46] The most common manifestation of GAVE was iron deficiency anemia (87%), while two patients presented with UGI bleeding. The typical endoscopic features were “watermelon stomach” characterized by prominent, erythematous stripes, radiating in a spoke-like fashion from the antrum to the pylorus.

Intestine

Small intestine

It is the second most common site of GI involvement in GI-SSc. The major manifestations include small intestinal bacterial overgrowth (SIBO), chronic intestinal pseudo-obstruction (CIPO), pneumatosis cystoides intestinalis (PCI), and jejunal diverticulae. The manometric findings include reduced proximal small-bowel postcibal motility and incoordianted fasting or postcibal hypermotility, suggestive of neuropathy.[47] These changes are progressive as evidenced by a 5-year follow-up study which showed progressive deterioration of small-bowel motor activity on manometry.[48] Caserta et al.[49] showed increased intestinal permeability in one-third of patients with SSc and it correlated with the degree of GI involvement. Due to hypomotility and delayed intestinal transit, there is increased prevalence of SIBO in patients with GI-SSc (21%–50%) and it manifests as bloating, diarrhea, steatorrhea, and features of malabsorption.[50],[51] The diagnosis of SIBO is usually made by a positive glucose/lactulose H2 breath test which has a poor sensitivity and moderate specificity of 44% and 64%, respectively.[52] The jejunal aspirate and culture sensitivity is invasive, cumbersome, and has very poor sensitivity.[53] A positive response to a broad-spectrum antibiotic in a patient suspected to have SIBO also confirms the diagnosis in the absence of any investigation.[54]

Intestinal pseudo-obstruction is one of the most severe complications of GI-SSc. In a study, it was responsible for 5.4% admissions (n = 10,386) over a period of 10 years (2002–2011) in the USA and was associated with a significant in-hospital mortality of 7.3%.[55] CIPO may present with recurrent acute episodes or chronic symptoms of pain abdomen, distension, nausea/vomiting, constipation, and obstipation. In one study, antroduodenojenunal manometry revealed signs of intestinal pseudo-obstruction in 80% of patients.[56]

PCI is characterized by intramural clusters of gas in the small and large bowel wall on X-ray or computed tomography and may be accompanied by free intraperitoneal air.[57],[58] Symptoms of PCI are nonspecific including abdominal pain, bloating, nausea, vomiting, and constipation. Treatment approach to PCI is mostly conservative: intestinal rest, parenteral nutrition, antibiotics, fluid and electrolyte supplementation, and inhaled oxygen. Surgical intervention should be performed only in cases of bowel perforation, ischemia, or necrosis.

Studies have also reported fructose and lactose malabsorption in up to 40% patients with SSc.[59],[60]

Jejunal diverticulae develop because of protrusion of the intestinal wall at points of muscle atrophy. Although they are asymptomatic, they can sometimes cause SIBO or rarely cause intestinal perforation.[25]

Radiological findings in patients with small-bowel involvement reveal features of megaduodenum, small-bowel dilatation and/or diverticulae, and hide-bound appearance of small bowel on computed tomography.[25],[61]

Colon

Colonic involvement commonly presents as chronic constipation because of colonic hypomotility;[62],[63] diverticulae and telangiectasias are other manifestations. In a study of 401 consecutive patients with SSc, 45% patients experienced weekly constipation.[64] Occasionally, constipation can be severe enough to cause fecal impaction and rarely colonic perforation. Colonic diverticulae in SSc are wide mouthed, usually asymptomatic, and less likely associated with diverticulitis.

Anorectal

The clinical features of anorectal involvement, seen in 50%–70% patients with SSc, include constipation, fecal impaction, painful defecation, and fecal incontinence.[65] Fecal incontinence affects up to 40% patients of SSc and can occur because of impaired anal sphincter function, reduced rectoanal sensation, abnormal rectoanal wall properties, altered GI transit, constipation with overflow, rectal prolapse, reduced rectal compliance, and diarrhea resulting from small- or large-bowel dysmotility and malabsorption.[66] Anorectal involvement is manifested by abnormal anal sphincter resting pressures, impaired rectal capacity and wall compliance on anorectal manometry, lower mean resting pressure, maximal voluntary squeeze effort, squeeze vector volume, and greater squeeze asymmetry.[62],[67],[68],[69] Endoanal ultrasound has revealed thin and atrophic internal anal sphincter even in asymptomatic patients.[70] The recto-anal inhibitory reflex is impaired in patients with constipation and fecal incontinence, and it correlates with attenuated anal sensory threshold.[71],[72]

GI bleeding

In a study of 144 patients, 15% had at least one episode of GI bleeding. Mucosal telangiectasias were the most common cause (41%) followed by peptic ulcer disease (32%) and erosive gastritis. Bleeding telangiectasias occurred in the entire GI tract, including oral cavity, esophagus, stomach, duodenum, ileum, cecum, and colon.[73]

There is a negative impact of these GI symptoms on the quality of life of patients with SSc,[74],[75],[76] with depression being one of the common mediators, and anti-depressant use has been reported in up to 26% patients with SSc.[77]

Hepatic

The hepatic manifestations of GI-SSc include primary biliary cholangitis (PBC), nodular regenerative hyperplasia,[78] autoimmune hepatitis,[79] and primary sclerosing cholangitis. PBC is the most common liver disorder associated with SSc, reported in 2%–22% patients with SSc.[80],[81]

Pancreatic

Exocrine pancreatic insufficiency has been associated with diffuse SSc, and in a study of 16 consecutive SSc patients, 7 patients had evidence of exocrine insufficiency on investigations.[82]

Malnutrition

Patients with SSc are at risk for malnutrition because of poor oral intake, delayed gastric emptying, malabsorption, and cachexia due to chronic inflammation. Oral intake is reduced because of decreased mouth opening, symptomatic esophageal dysmotility, persistent nausea and vomiting, early satiety, and abdominal pain. Malabsorption and maldigestion can occur because of SIBO, intestinal ischemia due to vascular involvement, bile acid malabsorption,[83] carbohydrate intolerance, and intestinal failure as a result of fibrotic infiltration and chronic intestinal dysmotility. Associated depression in these patients can also decrease their appetite. In a study of 586 patients with SSc, 28% were at risk for malnutrition, as assessed by “Malnutrition Universal Screening Tool” (MUST) and this risk correlated with the number of GI symptoms, shorter disease duration, diffuse disease, hemoglobin, oral aperture, and physician global assessment of disease severity.[84] In another study, the prevalence of malnutrition was 15% and was independently associated with disease activity.[85]


  Diagnosis and Management Top


The diagnosis and management of GI-SSc involves a multidisciplinary approach that involves a gastroenterologist, rheumatologist, and a dietician [Supplementary Table 1] [Additional file 1] . For most GI manifestations, there is no specific treatment which can alter the natural history or disease course, and the treatment is focused mainly on symptomatic improvement, the evidence for which is mostly extrapolated from indications in other disorders.

Outcome measurement in gastrointestinal-systemic sclerosis

Khanna et al.[86] modified the previously developed Scleroderma Gastrointestinal Tract 1.0 (SSC-GIT 1.0) questionnaire in 2009 to make a uniform assessment tool for evaluating the GI symptoms and their impact in patients with SSc. Of the initial 53 items in the SSC-GIT 1.0, 20 items were excluded and 1 item was added to assess rectal incontinence, leaving a 34-item revised instrument (the University of California, Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 [UCLA SCTC GIT 2.0]).[87] The questionnaire includes items in seven domains. Participants who rate their GI disease as mild have lower scores on a 0–3 scale on all seven scales [Supplementary Table 2] [Additional file 2] .

Recently, a new scale has been developed by the National Institutes of Health: Patient-Reported Outcomes Measurement Information System GI symptom item bank which contains sixty items, that cover eight GI-specific domains [88] and includes the additional domains of difficult swallowing and nausea/vomiting in comparison with UCLA SCTC GIT 2.0.

Management of esophageal involvement

Gastroesophageal reflux disease

The management of GERD involves life style measures and pharmacological therapy.[89] The life style measures include small frequent meals, weight reduction, head end elevation of the bed during sleeping, avoiding lying down after meals for 2 h, early dinner, low fat diet, and avoidance of alcohol and smoking. The pharmacological agents include proton pump inhibitors (PPIs), prokinetics, and H2 receptor inhibitors (H2RIs) [Supplementary Table 3] [Additional file 3] . PPIs have not been studied specifically in GERD with SSc, except for a small randomized control trial (RCT) of lansoprazole, in which lansoprazole was found efficacious till 6 months, but there was no evidence of long-term benefit.[90] Patients may require double dose of PPIs to control their symptoms. Nocturnal H2RIs can be added in patients who are nonresponsive to high-dose PPIs. These patients often require long-term therapy with PPIs, because of their protracted symptoms. Due to increasing concern of side effects with long-term PPI use (osteopenia, interaction with anti-platelets, interstitial nephritis, SIBO),[91] patients should be tried to be weaned off PPI, or at least a minimum possible dose in combination with H2RI or a prokinetic should be used.

The prokinetics are agents which increase the GI motility through their actions on various GI receptors [Supplementary Table 3]. Prokinetics can act in two ways: it increases the LES pressure and fastens gastric emptying (delayed gastric emptying seen in up to 50% of GI-SSc has been shown to increase GERD). Cisapride and metoclopramide have shown to alleviate the symptoms of GERD in combination with PPIs in patients with SSc.[92],[93],[94] Acotiamide, a cholinesterase inhibitor, approved for functional dyspepsia in adults, showed efficacy in a patient with severe GERD refractory to PPI and conventional prokinetic.[95] There is no evidence on the role of anti-reflux surgery in GERD associated with SSc, and considering the associated dysmotility, surgery should best be avoided as it can precipitate dysphagia.

Dysphagia

Dysphagia in SSc can either be because of esophageal dysmotility or esophageal stricture secondary to GERD and reflux esophagitis. There is limited role of pharmacological therapy in dysmotility-associated dysphagia. Evidences for nonpharmacological therapies include one study on low-frequency electrical acupuncture stimulation.[96] However, this was an old study, and there is no recent literature on this aspect. In patients with refractory dysphagia, feeding through a percutaneous endoscopic gastrostomy (PEG, if stomach is spared) or feeding jejunostomy may be performed. GERD stricture-related dysphagia requires aggressive PPI therapy and endoscopic dilatation.

Stomach

Gastroparesis

The evidence for treatment modalities for gastroparesis in SSc comes mostly from other conditions such as diabetes.[97] Nonpharmacological interventions include low residue and low fat diets and small frequent meals. A 4-week administration of erythromycin showed clinical improvement and accelerated gastric emptying [98] in patients with SSc-related gastroparesis. However, the efficacy was only maintained till midterm, and data beyond 33 weeks are lacking.[99] Other prokinetics can also be considered, given the evidence for their efficacy in other conditions. One short-term study of transcutaneous electric nerve stimulation showed efficacy in patients with this condition,[100] but further data are required. In patients with refractory gastroparesis, feeding jejunostomy (in the presence of normal intestinal transit) or home parenteral nutrition (HPN) can be considered.

Gastric antral vascular ectasia

The treatment of GAVE-induced anemia depends on the severity, with conservative management (iron supplementation) for mild cases. In patients with GI bleeding or patients with iron refractory anemia, endoscopic therapy with argon plasma coagulation (APC) is indicated.[45] In patients with APC refractory GAVE,[101] intravenous cyclophosphamide may be considered as evidenced by benefit in two case series of two and three patients, respectively.[102],[103]

Intestine

Small intestinal bacterial overgrowth

The treatment of SIBO involves broad-spectrum empirical antibiotics as positive culture is difficult to obtain. The recommended antibiotics include amoxicillin, quinolones, tetracycline, metronidazole, rifaximin, and cotrimoxazole.[53] No antibiotic is superior over the other and a 10–14 day course of any of these antibiotics is recommended. The response is monitored by clinical improvement, given the poor sensitivity of breath test. In patients with a background of recurrent SIBO, cyclical course of antibiotics, i.e., 10–14 days of a different antibiotic every month in rotation may be recommended. A small case series of ten patients with severe bloating/distension showed improvement with 2 months of probiotics containing Bifidobacterium infantis at a dose of 109 colony-forming unit/capsule.[104]

Constipation

The treatment of constipation involves administration of agents which increase colonic motility.[105] These include stimulant laxatives such as senna, bisacodyl, or sodium picosulfate. In the absence of renal involvement, adequate fluid intake should be advised. Prokinetics such as cisapride, metoclopramide, and prucalopride have been shown to increase colonic motility,[106] and prucalopride has been recently approved for the treatment of functional constipation.[107] There is also one case report of improvement in refractory constipation with oxygen therapy in a woman with SSc and lung involvement when she was administered oxygen for hypoxemia.[108] Surgery (resection ± stoma formation) is a difficult option in these patients because of concerns for poor wound healing and prolonged ileus, but can be considered in patients with complications (obstructed defecation/perforation) or drug refractory constipation.[109]

Intestinal pseudo-obstruction

In a case–control series of 64 patients with CIPO associated with SSc, one-fourth required HPN, 9% underwent surgical resection, and the overall mortality was 16%.[110] The treatment depends on the onset: for an acute episode, management consists of proper hydration, intravenous antibiotics, analgesia, and bowel decompression by nasogastric (NG) tube placement. Intravenous neostigmine at a dose of 2 mg can be given to relieve acute obstruction,[111] but cardiac and cholinergic side effects should be considered, especially in frail patients. For patients with chronic bowel dilatation and symptoms, recommended agents include prokinetics, cholinesterase inhibitors such as pyridostigmine, and a somatostatin analog octreotide. Prucalopride showed benefit in SSc-related CIPO in a placebo-controlled 1-year follow-up study.[112] Multiple studies in GI-SSc-associated CIPO have shown efficacy of octreotide (dose: 50–200 μg/24 h) in inducing spontaneous migrating motor complexs (MMCs) and intestinal motility, along with reduction of SIBO and improvement in abdominal symptoms.[113],[114],[115],[116] In patients who show loss of response, increasing the dose has led to improvement.[116] Long-acting octreotide (octreotide LAR) has also shown efficacy in this situation and in patients who lost response on subcutaneous octreotide.[117] There is also one case report and a case series of 14 patients which showed improvement on a combination of erythromycin and octreotide.[118],[119] Surgery should be avoided in these cases because there is no mechanical lesion and surgery is not curative. Parenteral nutrition at home should be considered in refractory cases.

Fecal incontinence

Effective management of fecal incontinence involves treatment of precipitating factors. For patients with loose stools, correction of underlying cause and fiber supplement can help. Patients with constipation and fecal impaction can be helped by rectal suppositories and laxatives. Pelvic floor biofeedback, although not evaluated in SSc, can help these patients. Sacral nerve stimulation has shown benefits in anorectal dysfunction unrelated to SSc [120] in one small study of five patients with SSc-associated fecal incontinence.[121] However, another study of ten patients did not show any benefit with this therapy.[122] However, given the heterogeneous results of neuromodulation and small number of patients with limited follow-up, further long-term studies are required to confirm the efficacy of neuromodulation therapies.

Considering the role of humoral immunity (anti-M3 antibodies) in the pathogenesis of SSc, there have been two case series of 2 and 15 patients which showed improvement in their GI symptoms after intravenous immunoglobulins administration.[123],[124]

Nutritional management

Patients with GI-SSc are at a risk for malnutrition with the disease onset and this risk increases with disease progression. Therefore, screening for malnutrition is very important in these patients, and screening is recommended at diagnosis/ first hospital visit with the MUST.[125],[126],[127] MUST screens for malnutrition risk on three domains: body mass index, percentage unexplained weight loss in 3–6 months, and acute disease effect.[128] For each domain, the score ranges from 0 to 2 points. The sum of scores from these three domains gives the overall risk for malnutrition: 0 (no risk), 1 (medium risk), 2 or more (high risk). After the initial screening, repeat screening at yearly intervals with MUST is recommended by an expert panel. In addition to screening by MUST, the panel has also recommended the following investigations: hemogram, serum levels of folic acid, ferritin, Vitamin B12, and Vitamin A.

The first step in the nutritional management is the correction of underlying precipitating factors which would include pharmacological treatment of dysphagia and GERD, gastroparesis, SIBO, intestinal dysmotility, CIPO, and constipation [Figure 3]. Oral hygiene can be improved in consultation with a dentist and functional limitations can be overcome by the help of an occupational therapist. In addition, dietetic counseling with a dietician may also help in nutritional rehabilitation. In a study of 18 GI-SSc patients with unintentional weight loss, a 6-week intervention with medical nutritional therapy which consisted of dietary advice on increased calorie and protein intake, modified textures, and lifestyle modifications improved the nutritional symptom scores and body composition.[129]
Figure 3: Flowchart for nutritional management of patients with systemic sclerosis with gastrointestinal involvement

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In patients not responding to these measures, artificial nutritional support is recommended. It usually begins with enteral nutrition which consists of tube feeding of liquid meal in the GI tract. The tolerance to enteral feeds is first tested with NG/nasojejunal tube feeding for some time. Jejunal feeding is beneficial in patients with gastroparesis and has minimal risk of aspiration. Percutaneous placement of enteral tubes (gastric/jejunal) is recommended in patients who can tolerate nasal feeds and have improvement in their nutritional status. The procedures include PEG, percutaneous endoscopic jejunostomy, or direct surgical jejunostomy.

Parenteral nutritional is recommended in patients who are intolerant to enteral nutrition or derive no benefit from enteral nutrition. Parenteral nutritional can be a short-term measure to bridge or support enteral nutrition or can be a lifelong nutritional support for patients in whom all other means of nutrition have failed, and this can be managed at home in support with a specialist nurse, termed as HPN. There have been five case series on HPN in GI-SSC. In the first case series of 15 patients, Ng et al.[130] reported improvement in 11 patients, and only two episodes of catheter-related sepsis and two episodes of superior vena cava obstruction were documented over 15,700 catheter use days. The two latest series of eight and five patients also showed symptomatic improvement over long-term use (median duration: 40 months) along with only two episodes of line infections over 13,851 catheter use days in the former series.[131],[132]


  Conclusion Top


GI involvement in SSc is associated with considerable morbidity and definite mortality, which has remained unchanged over the years, possibly because of the lack of disease-modifying therapy in any form of SSc. The treatment till date remains mostly symptomatic and is therefore not effective in all the patients, leading to a significant nutritional compromise, which results in the use of artificial nutritional support systems, which have their own complications. This is also compounded by the lack of good studies on the cellular and molecular pathogenesis of the disease which would guide in the development of effective targeted therapies. Thus, there is a need for future research into the pathogenesis, effective disease-modifying therapies, and biomarkers for early disease identification.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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