What is the first‑line treatment for gastro‑oesophageal reflux disease and esophageal spasm in patients with systemic sclerosis?

Treatment of Esophageal Reflux and Spasm in Scleroderma

Proton pump inhibitors at high doses should be used as first-line therapy for gastroesophageal reflux disease in systemic sclerosis, with prokinetic agents (domperidone, prucalopride, or buspirone) added for symptomatic motility disturbances that persist despite adequate acid suppression. 1

First-Line Therapy: High-Dose PPIs

• High-dose PPI therapy is mandatory for scleroderma-related GERD, as standard doses are frequently insufficient to achieve adequate acid suppression and prevent progression to Barrett's esophagus and strictures. 2

• The 2023 EULAR guidelines explicitly recommend PPIs for treatment of gastroesophageal reflux disease and prevention of esophageal ulcers and strictures in systemic sclerosis, despite acknowledging that PPIs may be only partially effective in controlling esophagitis or abnormal acid exposure. 1

• Evidence shows that approximately 54% of scleroderma patients have partial response to high-dose PPIs (omeprazole 20 mg twice daily), indicating the need for aggressive dosing from the outset. 1

Second-Line Therapy: Prokinetic Agents

When to add prokinetics:

• Add prokinetic drugs when patients have symptomatic motility disturbances (dysphagia, regurgitation, persistent reflux symptoms) despite adequate high-dose PPI therapy. 1, 3

• Ensure patients are already on high-dose PPIs before adding prokinetics, as the strongest RCT evidence evaluated prokinetics as adjuncts to ongoing PPI therapy. 3

Specific prokinetic selection:

• Domperidone is supported by the highest quality recent evidence (RCT of 148 scleroderma patients), showing 86.8% response rate for GERD symptoms when added to ongoing high-dose PPIs. 1, 3

• Prucalopride (5-HT4 receptor agonist) is effective for both upper and lower GI symptoms, with particular benefit when constipation coexists with reflux symptoms. 1, 3

• Buspirone (5-HT1A receptor agonist) increases lower esophageal sphincter pressure and reduces heartburn/regurgitation scores, making it useful for refractory lower esophageal sphincter dysfunction. 1, 3

• Avoid metoclopramide for long-term use due to significant adverse effects including tardive dyskinesia. 3

Essential Non-Pharmacologic Measures

• Rigorous anti-reflux lifestyle modifications are mandatory because they directly reduce nocturnal reflux and aspiration risk, thereby mitigating interstitial lung disease progression and mortality. 2

• Specific measures include: head-of-bed elevation, avoidance of food after dinner, thorough chewing, slow eating, drinking water with meals, and avoidance of trigger foods. 2

Management of Small Intestinal Bacterial Overgrowth (SIBO)

• Use rotating antibiotics for symptomatic SIBO, which frequently complicates chronic intestinal dysmotility in scleroderma patients on long-term therapy. 1, 3, 4

• Rotating antibiotic courses (every 2-6 weeks with 1-2 week antibiotic-free periods) help prevent antimicrobial resistance while managing recurrent symptoms. 1, 4

Critical Clinical Caveats

• Aggressive treatment of GERD is mandatory in scleroderma because aspiration of refluxate worsens interstitial lung disease and increases mortality. 2

• Prokinetic agents are most useful in early stages of scleroderma when gastrointestinal musculature is still intact; they become less effective as smooth muscle atrophy progresses. 3

• Approximately 17% of patients do not respond to combination PPI plus prokinetic therapy, requiring escalation of care. 1

• Long-term PPI safety concerns exist in the general population, but the benefits in preventing esophageal complications in scleroderma outweigh these risks. 1

• Patients with severe esophageal symptoms (frequent aspiration, nocturnal reflux, marked dysphagia) require intensified monitoring for pulmonary complications. 2

Algorithm for Treatment Escalation

1. Start high-dose PPI (e.g., omeprazole 20 mg twice daily or equivalent) plus rigorous lifestyle modifications. 1, 2

2. If partial response after 4 weeks, add prokinetic agent:

   • Domperidone for predominantly upper GI symptoms 3
   • Prucalopride for mixed upper/lower GI symptoms or constipation 3
   • Buspirone for refractory lower esophageal sphincter dysfunction 3

3. If symptoms persist, evaluate for SIBO with breath testing and treat with rotating antibiotics if confirmed. 1, 4

4. Monitor for pulmonary complications in all patients with severe symptoms. 2