Gastrointestinal Involvement in Systemic Sclerosis

Methods

The following initial search terms (01/07/2016–05/10/2018) were used in PubMed: 'scleroderma gastrointestinal' (denominator 77); 'systemic sclerosis gastrointestinal' (denominator 107), 'treatment gastrointestinal dysmotility' (denominator 85), 'fecal incontinence systemic sclerosis' (denominator 11), and 'fecal incontinence scleroderma' (denominator 7) and 'treatment gastrointestinal motility' (denominator 625). We identified 81 studies of interest based on their relevance to the diagnosis and treatment of gastrointestinal disease in systemic sclerosis, including key review articles whose reference lists were screened for additional relevant manuscripts.

Table 1. Promotility agents and available data in scleroderma
Drug	Use in GI disease	Mechanism of action	Common or significant adverse events	Data for use in SSc GI disease
Metoclopramide	Esophageal dysmotility, hypotensive LES, gastroparesis, small bowel dysmotility	Dopamine 2 receptor antagonist, 5HT4 agonist, weak 5HT3 antagonist	Dyskinesia and acute dystonia	Case series [28–30]
Domperidone	Esophageal dysmotility, hypotensive LES, gastroparesis	Dopamine 2 antagonist	Cardiac arrhythmia (QT prolongation), hyperprolactinemia	RCT; open-label trial [22,31]
Pyridostigmine	Esophageal dysmotility, gastroparesis, small bowel and large bowel dysmotility	Acetylcholinesterase inhibitor	Abdominal pain and diarrhea	Case series [27]
Bethanechol	Esophageal dysmotility,	Parasympathetic choline carbamate that selectively stimulates muscarinic receptors	Abdominal pain and diarrhea	None
Buspirone	Esophageal dysmotility, hypotensive LES	5HT1 receptor agonist; preferential full agonist of presynaptic 5HT1A receptors which are inhibitor autoreceptors and a partial agonist of postsynaptic 5HT1A	Dizziness, drowsiness, nausea	Open label trial [23,31]
Sildenafil	Hypotensive LES, colonic dysmotility	Phosphodiesterase inhibitor	Headache, lightheadedness, dizziness	None
Cisapride	Esophageal dysmotility, gastroparesis, small bowel dysmotility	Serotonin 5HT4 receptor agonist; indirectly acts as a parasympathomimetic	Cardiac arrhythmia, headache, rash, abdominal cramps, diarrhea,	Double-blind, placebo-controlled trial; case series [32–35]
Prucalopride	Large bowel dysmotility	Selective high affinity 5HT4 receptor agonist	Headache, nausea, abdominal pain, diarrhea	Randomized cross-over study, case series [26,36]
IVIG	Gastroparesis	May inhibit pathogenic antibodies to M3R receptors	Aseptic meningitis	Case series [24,25,37–40]
Remorelin	Gastroparesis	Ghrelin agonist	Flushing, upset stomach, nausea, fatigue	None
Octreotide	Small bowel dysmotility	Somatostatin mimic	Arrhythmia, tachyphylaxis, hyperglycemia, dizziness, abdominal pain, diarrhea, flatulence	RCT; case series [40,41]
Neostigmine	Small/large bowel dysmotility	Anticholinesterase agent	Arrhythmia, dizziness, diarrhea, dysphagia, nausea, crams, salivation, lacrimation, bronchospasm	Randomized placebo crossover study; case series [42,43]
Linaclotide	Colonic dysmotility	Guanylate cyclase 2C agonist on intestinal epithelial cells	Diarrhea, abdominal pain flatulence, URI	None
Plecanatide	Colonic dysmotility	Activates guanylate cyclase C on intestinal endothelial cells	Dizziness, diarrhea, abdominal distention	None
Lubiprostone	Colonic dysmotility	Activates CIC-2 chloride channels in GI epithelial cells	Headache, nausea, diarrhea	None
Misoprostol	Colonic dysmotility	Prostaglandin analogue	Diarrhea, abdominal pain, headache	None
Colchicine	Colonic dysmotility	Inhibitors microtubule polymerization;	Diarrhea, nausea, vomiting	None

Table 1. Promotility agents and available data in scleroderma

Drug

Use in GI disease

Mechanism of action

Common or significant adverse events

Data for use in SSc GI disease

Metoclopramide

Esophageal dysmotility, hypotensive LES, gastroparesis, small bowel dysmotility

Dopamine 2 receptor antagonist, 5HT4 agonist, weak 5HT3 antagonist

Dyskinesia and acute dystonia

Case series [28–30]

Domperidone

Esophageal dysmotility, hypotensive LES, gastroparesis

Dopamine 2 antagonist

Cardiac arrhythmia (QT prolongation), hyperprolactinemia

RCT; open-label trial [22,31]

Pyridostigmine

Esophageal dysmotility, gastroparesis, small bowel and large bowel dysmotility

Acetylcholinesterase inhibitor

Abdominal pain and diarrhea

Case series [27]

Bethanechol

Esophageal dysmotility,

Parasympathetic choline carbamate that selectively stimulates muscarinic receptors

Abdominal pain and diarrhea

None

Buspirone

Esophageal dysmotility, hypotensive LES

5HT1 receptor agonist; preferential full agonist of presynaptic 5HT1A receptors which are inhibitor autoreceptors and a partial agonist of postsynaptic 5HT1A

Dizziness, drowsiness, nausea

Open label trial [23,31]

Sildenafil

Hypotensive LES, colonic dysmotility

Phosphodiesterase inhibitor

Headache, lightheadedness, dizziness

None

Cisapride

Esophageal dysmotility, gastroparesis, small bowel dysmotility

Serotonin 5HT4 receptor agonist; indirectly acts as a parasympathomimetic

Cardiac arrhythmia, headache, rash, abdominal cramps, diarrhea,

Double-blind, placebo-controlled trial; case series [32–35]

Prucalopride

Large bowel dysmotility

Selective high affinity 5HT4 receptor agonist

Headache, nausea, abdominal pain, diarrhea

Randomized cross-over study, case series [26,36]

IVIG

Gastroparesis

May inhibit pathogenic antibodies to M3R receptors

Aseptic meningitis

Case series [24,25,37–40]

Remorelin

Gastroparesis

Ghrelin agonist

Flushing, upset stomach, nausea, fatigue

None

Octreotide

Small bowel dysmotility

Somatostatin mimic

Arrhythmia, tachyphylaxis, hyperglycemia, dizziness, abdominal pain, diarrhea, flatulence

RCT; case series [40,41]

Neostigmine

Small/large bowel dysmotility

Anticholinesterase agent

Arrhythmia, dizziness, diarrhea, dysphagia, nausea, crams, salivation, lacrimation, bronchospasm

Randomized placebo crossover study; case series [42,43]

Linaclotide

Colonic dysmotility

Guanylate cyclase 2C agonist on intestinal epithelial cells

Diarrhea, abdominal pain flatulence, URI

None

Plecanatide

Colonic dysmotility

Activates guanylate cyclase C on intestinal endothelial cells

Dizziness, diarrhea, abdominal distention

None

Lubiprostone

Colonic dysmotility

Activates CIC-2 chloride channels in GI epithelial cells

Headache, nausea, diarrhea

None

Misoprostol

Colonic dysmotility

Prostaglandin analogue

Diarrhea, abdominal pain, headache

None

Colchicine

Colonic dysmotility

Inhibitors microtubule polymerization;

Diarrhea, nausea, vomiting

None

Gastrointestinal Involvement in Systemic Sclerosis

Diagnosis and Management

Methods

Comments

Most Popular Articles

What to Read Next on Medscape

Special Coverage: COVID-19

About

Membership

Apps

WebMD Network

Editions

Gastrointestinal Involvement in Systemic Sclerosis

Diagnosis and Management

Methods

Tables

References

Authors and Disclosures

Authors and Disclosures

Sidebar

Sidebar

Key Points

Comments

Most Popular Articles

What to Read Next on Medscape

Special Coverage: COVID-19

More from This Journal

Latest News & Perspective

Recommended Reading

Drugs Related to Scleroderma

Most Popular Articles

Recommendations

Email This

Find Us On

About

Membership

Apps

WebMD Network

Editions