Introduction
Peptic Ulcer Disease (PUD) is a prevalent gastrointestinal disorder characterized by sores or ulcers forming in the lining of the stomach or the first part of the small intestine (duodenum). Effective management of PUD requires a thorough understanding of its diagnosis, treatment, and prevention strategies. This blog combines insights from recent key studies to provide a comprehensive guide to managing PUD.
Diagnosis of Peptic Ulcer Disease
Clinical Presentation
Patients with PUD often present with epigastric pain, which can be described as burning, gnawing, or hunger-like. The pain typically occurs on an empty stomach and may be relieved by food or antacids. Other symptoms include bloating, nausea, vomiting, and in severe cases, hematemesis (vomiting blood) or melena (black tarry stools), indicating gastrointestinal bleeding. Weight loss and appetite changes may also be observed.
Diagnostic Testing
- Endoscopy: The gold standard for diagnosing Peptic Ulcer Disease (PUD) is esophagogastroduodenoscopy (EGD). This procedure allows for direct visualization of the ulcers and the ability to obtain biopsies for histopathological examination. EGD is essential for confirming the presence of an ulcer, assessing its severity, and ruling out malignancy.
- H. pylori Testing: Testing for H. pylori can be performed using urea breath tests, stool antigen tests, and biopsy-based methods such as rapid urease tests, histology, and culture. Post-treatment confirmation of eradication is crucial.
- Laboratory Tests: Blood tests to check for anemia, a complete blood count (CBC), and stool tests for occult blood can help assess the presence of bleeding.
- Non-invasive Tests: Urea breath test and stool antigen test are non-invasive methods to detect H. pylori infection.
Differential Diagnosis
Differential diagnosis includes gastroesophageal reflux disease (GERD), functional dyspepsia, gastritis, gastric cancer, and pancreatitis. Conditions such as irritable bowel syndrome (IBS) and gallbladder disease should also be considered.
Treatment of Peptic Ulcer Disease
Pharmacological Therapy
- Proton Pump Inhibitors (PPIs): The cornerstone of PUD treatment involves the eradication of H. pylori and the use of proton pump inhibitors (PPIs) to reduce gastric acid secretion. PPIs are highly effective in promoting ulcer healing and preventing recurrence.
- Drug Combinations and Regimens:
- Triple Therapy: PPI + amoxicillin + clarithromycin. Dosage: PPI double dose every 12 hours, 1000 mg amoxicillin every 12 hours, 500 mg clarithromycin every 12 hours. Duration: 14 days.
- Quadruple Non-Bismuth-Based Therapy: PPI + amoxicillin + clarithromycin + metronidazole. Dosage: PPI standard dose every 12 hours, 1000 mg amoxicillin every 12 hours, 500 mg clarithromycin every 12 hours, 500 mg metronidazole every 12 hours. Duration: 14 days.
- Bismuth-Based Quadruple Therapy: PPI + bismuth subcitrate + tetracycline + metronidazole. Dosage: PPI standard dose every 12 hours, 120 mg bismuth subcitrate every 6 hours, 500 mg tetracycline every 6 hours, 500 mg metronidazole every 8 hours. Duration: 14 days.
- Fluoroquinolone-Based Triple Therapy: PPI + amoxicillin + levofloxacin with or without bismuth. Dosage: PPI standard dose every 12 hours, 1000 mg amoxicillin every 12 hours, 500 mg levofloxacin every 24 hours, 240 mg bismuth every 12 hours. Duration: 14 days.
- Rifabutin-Based Triple Therapy: PPI + amoxicillin + rifabutin. Dosage: PPI standard dose every 12 hours, 1000 mg amoxicillin every 12 hours, 150 mg rifabutin every 12 hours. Duration: 10 days.
Management of Complications
- Endoscopic Therapy: Complications of PUD, such as bleeding, perforation, and gastric outlet obstruction, are serious and require prompt management. Endoscopic therapy is highlighted as the primary intervention for peptic ulcer bleeding, offering both diagnostic and therapeutic benefits. Techniques such as injection therapy, thermal coagulation, and hemoclipping can effectively control bleeding.
- Surgical Intervention: Surgical options are reserved for refractory cases where endoscopic therapy fails or for complications like perforation and obstruction that cannot be managed conservatively. Procedures include vagotomy, antrectomy, and pyloroplasty.
Prevention of Peptic Ulcer Disease
Strategies for Prevention
Preventing ulcer recurrence is the most important long-term goal to reduce morbidity and mortality. Eradication of H. pylori infection is key to healing peptic ulcers and preventing relapse without the need for maintenance acid suppressive therapy. However, antibiotic resistance makes H. pylori treatment challenging. The effectiveness of PPI-based triple therapy (PPI, clarithromycin, and amoxicillin or metronidazole) has decreased from over 90% to less than 70% due to rising antibiotic resistance. Treatment should ideally be based on antimicrobial susceptibility tests, but in their absence, first-line therapies should consider local antibiotic resistance rates. PPI-based triple therapy containing clarithromycin should be avoided if resistance is over 15%. In areas with low clarithromycin resistance or confirmed individual susceptibility, PPI-clarithromycin-amoxicillin or PPI-clarithromycin-metronidazole can be used. High-dose PPI (double the standard dose) and extending therapy duration to 14 days can improve eradication rates.
Recommended Standard First-line Therapy
Either a bismuth-containing quadruple therapy for 14 days (PPI, a bismuth salt, tetracycline, and metronidazole) or a non-bismuth-based quadruple concomitant therapy (PPI, clarithromycin, amoxicillin, and metronidazole) for 14 days; both regimens have an eradication rate of more than 90%.
Sequential Therapy
Consists of a 5-day dual therapy with a PPI and amoxicillin followed by a 5-day triple therapy with a PPI, clarithromycin, and tinidazole or metronidazole. Overall, the eradication rate of sequential therapy is better than that of 7-day and 10-day triple therapy regimens but not better than the eradication rate of 14-day triple therapy, bismuth-based therapy, and non-bismuth-based concomitant therapy, and this treatment is not recommended.
Hybrid Quadruple Therapies
Combine 10−14 days of dual therapy with PPI and amoxicillin with 7 days of treatment with clarithromycin and metronidazole. Hybrid quadruple therapy has shown similar effectiveness to quadruple concomitant or sequential quadruple therapy, and is more effective in non-Italian populations than in other populations studied.
Rescue Therapy
- Levofloxacin-Containing Triple Therapy: Achieves 74–81% eradication rates as a second-line therapy in areas with low (<10%) quinolone resistance. However, a rapid increase in primary quinolone resistance to H. pylori reduces the effectiveness of levofloxacin-containing therapy.
- Bismuth-Containing Quadruple Therapy: Effective as a second-line therapy after failure of standard triple therapies, with eradication rates of 77–93%. Adding bismuth to levofloxacin-containing triple regimens turns them into quadruple-therapy regimens.
- Susceptibility Testing: Strongly recommended after one treatment failure or after two consecutive treatment failures.
- Rifabutin-Based Triple Therapy: Used when culture of H. pylori is not available or after three failed treatments, with 66–70% eradication rates for 10 days.
Management of Bleeding Peptic Ulcers
Risk Stratification and Initial Management
- Risk Stratification: Glasgow-Blatchford and Rockall scores help identify high-risk patients for early intervention and reduce hospital stay for low-risk patients. A Glasgow-Blatchford score of zero accurately identifies patients not requiring treatment in the hospital.
- Acid Suppression: Maintaining a neutral gastric pH is crucial to prevent platelet disaggregation and clot lysis over a bleeding ulcer. Intravenous administration of PPIs offers faster onset and better bioavailability compared to oral administration.
- Pre-emptive PPIs: High-dose intravenous PPIs before endoscopy can reduce high-risk endoscopic stigmata and the need for endoscopic treatment. However, they should not delay early endoscopy for high-risk patients.
Endoscopic Treatment
- Early Endoscopy: Performing endoscopy within 24 hours provides important prognostic information and effective therapy. It reduces rebleeding, surgery, and mortality rates.
- Endoscopic Therapy: Indicated for ulcers showing active bleeding, a non-bleeding visible vessel, or an adherent clot. Combining a second modality with epinephrine injection is more effective than epinephrine alone in reducing recurrent bleeding, surgery, and mortality.
- Post-Endoscopic Therapy: High-dose PPI therapy post-endoscopy is crucial for preventing recurrent bleeding. Both continuous infusion and intermittent high-dose PPI therapy are effective.
Management of Recurrent Bleeding
- Further Endoscopic Treatment vs. Surgery: Early surgery or angiographic embolization are options for patients with uncontrolled or recurrent bleeding. Repeat endoscopy may be preferable to surgery, as it has fewer complications.
- Antithrombotic Therapy: Managing patients on antiplatelet or anticoagulant therapy is challenging and should be individualized based on bleeding severity and thromboembolic risk. Continuing aspirin in patients with ulcer bleeding can reduce all-cause mortality despite the increased risk of recurrent bleeding.
Conclusion
Effective management of Peptic Ulcer Disease involves a comprehensive approach that includes accurate diagnosis, appropriate pharmacological therapy, lifestyle modifications, and regular monitoring. Understanding the multifactorial nature of PUD and addressing all contributing factors can significantly improve patient outcomes and prevent recurrence. By implementing these strategies, healthcare providers can ensure optimal care for patients with PUD.
References
- Lanas, Angel, and Francis KL Chan. "Peptic ulcer disease." The Lancet 390.10094 (2017): 613-624.
- Kavitt, Robert T., et al. "Diagnosis and treatment of peptic ulcer disease." The American journal of medicine 132.4 (2019): 447-456.
- Sverdén, Emma, et al. "Peptic ulcer disease." BMJ 367 (2019).
