Gastritis Differential Diagnosis: A Comprehensive Guide for Clinicians

Gastritis, characterized by the inflammation of the stomach lining, is a prevalent medical condition encountered across diverse clinical settings. Its presentation can vary widely, ranging from asymptomatic to debilitating, underscoring the importance of accurate diagnosis and management. While gastritis itself is a well-defined entity, its symptoms often overlap with a spectrum of other gastrointestinal and systemic disorders. Therefore, establishing a robust differential diagnosis is paramount for clinicians to ensure appropriate patient care and avoid misdiagnosis.

This article aims to provide an in-depth exploration of the differential diagnosis of gastritis, building upon the foundational knowledge of gastritis etiology, epidemiology, pathophysiology, and clinical presentation. By expanding on the conditions that mimic gastritis, this guide will enhance the diagnostic acumen of healthcare professionals, leading to more precise diagnoses and tailored treatment strategies. This comprehensive understanding fosters improved patient outcomes through targeted interventions and the exclusion of alternative diagnoses.

Types and Symptoms of Gastritis: A Brief Overview

Before delving into the intricacies of differential diagnosis, a concise review of gastritis is warranted. Gastritis is broadly classified based on its time course (acute vs. chronic), histological characteristics, anatomical distribution, and underlying causes. Key etiological factors include Helicobacter pylori infection, autoimmune disorders, chemical irritants, and certain medications.

Common symptoms associated with gastritis, often categorized under the umbrella term dyspepsia, include:

• Epigastric pain or discomfort
• Nausea and vomiting
• Bloating and fullness
• Early satiety
• Loss of appetite
• In severe cases, hematemesis or melena

However, it is crucial to recognize that these symptoms are non-specific and can be present in various other conditions affecting the upper abdomen. This symptomatic overlap necessitates a systematic approach to differential diagnosis.

Diagnostic Evaluation of Gastritis

The diagnostic pathway for gastritis typically involves a combination of clinical assessment, endoscopic evaluation, histological examination, and specific laboratory tests. Upper endoscopy with biopsy is considered the gold standard for diagnosing gastritis, allowing for direct visualization of the gastric mucosa and histological confirmation of inflammation.

Key diagnostic modalities include:

• Upper Endoscopy: Visualizes the gastric mucosa, identifies lesions, and allows for biopsy sampling. Endoscopic findings in gastritis can range from mucosal erythema and edema to erosions and ulcerations.
• Histopathology: Microscopic examination of gastric biopsies is essential for confirming gastritis, determining its type and severity, and identifying specific etiological factors like H. pylori. The Sydney System and OLGA/OLGIM staging systems provide standardized frameworks for histological assessment and risk stratification.
• H. pylori Testing: Non-invasive tests like urea breath test and stool antigen test, as well as invasive tests such as biopsy urease test and histology, are crucial for detecting H. pylori infection, a major cause of gastritis.
• Laboratory Tests: Blood tests may be used to assess for complications like anemia (iron deficiency, vitamin B12 deficiency), and to evaluate for autoimmune gastritis (anti-parietal cell antibodies, anti-intrinsic factor antibodies, pepsinogen levels).

While these diagnostic tools are invaluable in confirming gastritis, they are also essential in excluding other conditions in the differential diagnosis.

Gastritis Differential Diagnosis

The differential diagnosis of gastritis is broad and encompasses various gastrointestinal and non-gastrointestinal conditions that can mimic its symptoms. A systematic approach is crucial to differentiate gastritis from these conditions.

1. Functional Dyspepsia

Functional dyspepsia is a common condition characterized by persistent or recurrent dyspeptic symptoms in the absence of any identifiable organic, systemic, or metabolic disease. It is a primary consideration in the differential diagnosis of gastritis due to significant symptom overlap.

• Overlap with Gastritis: Functional dyspepsia shares symptoms like epigastric pain, nausea, bloating, and early satiety with gastritis. Many patients presenting with dyspeptic symptoms may initially be suspected of having gastritis.
• Differentiation from Gastritis:
  • Endoscopy and Histology: The key differentiating factor is the absence of endoscopic and histological evidence of gastric mucosal inflammation in functional dyspepsia. Upper endoscopy is typically normal or shows only minimal, non-specific findings. Biopsies will not reveal significant inflammation characteristic of gastritis.
  • H. pylori Status: While H. pylori infection can be present in patients with functional dyspepsia, eradicating H. pylori may not always resolve symptoms in functional dyspepsia, unlike in H. pylori-induced gastritis.
  • Rome IV Criteria: Functional dyspepsia is diagnosed based on symptom-based criteria outlined in the Rome IV classification, focusing on symptom type, frequency, and duration in the absence of organic disease.
  • Absence of Alarm Features: The absence of alarm symptoms (weight loss, bleeding, dysphagia, anemia) in functional dyspepsia further distinguishes it from conditions like gastric cancer or peptic ulcer disease, which might also be considered in the differential of gastritis symptoms.

2. Peptic Ulcer Disease (PUD)

Peptic ulcer disease, encompassing gastric and duodenal ulcers, is another crucial consideration in the differential diagnosis of gastritis. Both conditions can present with epigastric pain and dyspepsia.

• Overlap with Gastritis: Epigastric pain is a prominent symptom in both gastritis and PUD. Nausea, vomiting, and bloating can also be present in both. H. pylori is a common etiological factor for both conditions.
• Differentiation from Gastritis:
  • Pain Characteristics: Peptic ulcer pain often has distinct characteristics. Gastric ulcer pain may be exacerbated by eating, while duodenal ulcer pain is often relieved by food and may worsen at night. Gastritis pain is typically less related to meals and more diffuse. However, these are not always reliable differentiators.
  • Endoscopy: Upper endoscopy is crucial for differentiation. PUD is characterized by discrete mucosal breaks (ulcers) in the stomach or duodenum, which are distinct from the diffuse mucosal inflammation seen in gastritis.
  • Location of Lesions: Gastritis is characterized by inflammation of the gastric mucosa, while PUD involves ulceration, which is a deeper mucosal defect.
  • Complications: PUD can lead to complications like bleeding, perforation, and obstruction, which are less common in uncomplicated gastritis. Hematemesis or melena is more suggestive of PUD or a more severe form of erosive gastritis.

3. Gastric Cancer

Gastric cancer, although less common than gastritis or functional dyspepsia, is a critical condition to exclude in the differential diagnosis, especially in patients with persistent dyspeptic symptoms or alarm features.

• Overlap with Gastritis: Early gastric cancer can present with non-specific dyspeptic symptoms similar to gastritis, including epigastric pain, nausea, and early satiety. Atrophic gastritis, a chronic form of gastritis, is a known risk factor for gastric cancer, making the differentiation even more important.
• Differentiation from Gastritis:
  • Alarm Symptoms: The presence of alarm symptoms such as unintentional weight loss, persistent vomiting, dysphagia, anemia, or gastrointestinal bleeding is highly suggestive of gastric malignancy and warrants urgent investigation.
  • Age and Risk Factors: Older age and risk factors for gastric cancer (family history, smoking, high salt intake, H. pylori infection, atrophic gastritis, intestinal metaplasia) increase the suspicion for malignancy.
  • Endoscopy with Biopsy: Upper endoscopy with multiple biopsies is essential to rule out gastric cancer. Endoscopic findings suggestive of malignancy include masses, ulcers with irregular borders, and mucosal nodularity. Biopsies should be taken from any suspicious areas and from the recommended sites as per the Sydney protocol to detect atrophic gastritis and precancerous lesions.
  • Histopathology: Histopathological examination of biopsies is definitive in diagnosing gastric cancer.

4. Cholecystitis and Biliary Colic

Biliary tract diseases, such as cholecystitis (inflammation of the gallbladder) and biliary colic (gallbladder pain due to gallstones), can sometimes mimic gastritis due to the proximity of the gallbladder to the stomach and the shared innervation.

• Overlap with Gastritis: Epigastric or right upper quadrant pain, nausea, and vomiting can be present in both gastritis and biliary tract diseases.
• Differentiation from Gastritis:
  • Pain Location and Radiation: Biliary pain is typically located in the right upper quadrant or epigastrium and may radiate to the right shoulder or back. Gastritis pain is more often localized to the epigastrium.
  • Pain Characteristics: Biliary colic is characterized by episodic, severe, cramping pain, often triggered by fatty meals. Cholecystitis pain is more constant and may be associated with fever and right upper quadrant tenderness. Gastritis pain is usually less severe and less colicky.
  • Physical Examination: Right upper quadrant tenderness, Murphy’s sign (inspiratory arrest on palpation of the right subcostal area during deep inspiration) are suggestive of cholecystitis.
  • Imaging Studies: Abdominal ultrasound is the primary imaging modality for diagnosing gallbladder disease, revealing gallstones, gallbladder wall thickening, and pericholecystic fluid. CT scan or MRI may be used for further evaluation if ultrasound is inconclusive or to rule out other conditions.
  • Liver Function Tests: Elevated liver enzymes (AST, ALT, alkaline phosphatase, bilirubin) may be present in biliary obstruction or cholecystitis, which are not typically seen in gastritis unless there is associated liver disease.

5. Pancreatitis

Pancreatitis, both acute and chronic, can present with upper abdominal pain that may be mistaken for gastritis.

• Overlap with Gastritis: Epigastric pain, nausea, and vomiting are prominent symptoms in both conditions.
• Differentiation from Gastritis:
  • Pain Characteristics and Location: Pancreatitis pain is typically severe, constant, and located in the upper abdomen, often radiating to the back. Gastritis pain is usually less severe and less likely to radiate to the back.
  • Aggravating and Relieving Factors: Pancreatitis pain is often worsened by lying supine and relieved by sitting up and leaning forward. Gastritis pain is less influenced by posture.
  • History of Risk Factors: Risk factors for pancreatitis, such as alcohol abuse, gallstones, hypertriglyceridemia, and certain medications, increase the suspicion for pancreatitis.
  • Physical Examination: Epigastric tenderness, guarding, and decreased bowel sounds may be present in pancreatitis. In severe cases, signs of systemic inflammation like fever, tachycardia, and hypotension may be present.
  • Laboratory Tests: Elevated serum amylase and lipase levels are diagnostic hallmarks of pancreatitis. These enzymes are typically normal in gastritis.
  • Imaging Studies: Abdominal CT scan is the imaging modality of choice for diagnosing pancreatitis and assessing its severity and complications. Ultrasound may also be used, particularly for detecting gallstones as a cause of pancreatitis.

6. Zollinger-Ellison Syndrome (ZES)

Zollinger-Ellison syndrome is a rare condition characterized by gastrin-secreting tumors (gastrinomas), leading to excessive gastric acid production and peptic ulcers. While ulcers are the hallmark, the associated dyspepsia can be mistaken for gastritis.

• Overlap with Gastritis: Dyspeptic symptoms, including epigastric pain, heartburn, nausea, and bloating, can occur in both ZES and gastritis.
• Differentiation from Gastritis:
  • Severity and Refractoriness to Treatment: ZES-related symptoms are often severe, refractory to standard gastritis treatments (like PPIs at usual doses), and ulcers are frequently multiple, large, and located in atypical locations (e.g., distal duodenum, jejunum). Gastritis symptoms usually respond to standard acid-suppressing therapy.
  • Diarrhea: Chronic diarrhea is a common symptom in ZES due to excessive acid production overwhelming intestinal bicarbonate secretion and causing malabsorption. Diarrhea is not typically a feature of gastritis.
  • Recurrent Peptic Ulcers: Recurrent peptic ulcers despite H. pylori eradication and NSAID avoidance should raise suspicion for ZES.
  • Elevated Gastrin Levels: The key diagnostic test for ZES is measuring fasting serum gastrin levels. Markedly elevated gastrin levels (>1000 pg/mL) in the setting of gastric acid hypersecretion are diagnostic. A secretin stimulation test can further confirm the diagnosis in borderline cases.
  • Gastric pH: Gastric pH studies will reveal very low gastric pH (<2) despite PPI therapy in ZES, indicating acid hypersecretion.

7. Myocardial Ischemia

Although less common, myocardial ischemia (angina or heart attack) can sometimes present with epigastric pain, particularly in elderly individuals, diabetics, and women. This can be misdiagnosed as gastritis or other gastrointestinal conditions.

• Overlap with Gastritis: Epigastric pain is the primary overlapping symptom. Nausea and vomiting can also occur in myocardial ischemia.
• Differentiation from Gastritis:
  • Pain Characteristics: Anginal pain is often described as chest discomfort, pressure, tightness, or squeezing, which may radiate to the jaw, left arm, or back. Epigastric pain from myocardial ischemia may be less typical and more easily mistaken for gastrointestinal pain.
  • Associated Symptoms: Symptoms like shortness of breath, sweating, dizziness, and palpitations are more suggestive of cardiac ischemia.
  • Risk Factors for Heart Disease: Risk factors for coronary artery disease (age, smoking, hypertension, hyperlipidemia, diabetes, family history) should raise suspicion for cardiac etiology in patients presenting with epigastric pain.
  • ECG: Electrocardiogram (ECG) is crucial to rule out myocardial ischemia. ST-segment elevation or depression, T-wave inversions, or new Q waves can indicate acute myocardial ischemia.
  • Cardiac Enzymes: In cases of myocardial infarction, cardiac enzymes (troponin) will be elevated.

8. Gastric Lymphoma

Gastric lymphoma, a malignancy of the lymphatic tissue in the stomach, can mimic gastritis clinically and endoscopically.

• Overlap with Gastritis: Dyspeptic symptoms like epigastric pain, nausea, vomiting, and weight loss can be present in both gastric lymphoma and gastritis. H. pylori infection is implicated in the pathogenesis of some types of gastric lymphoma (MALT lymphoma). Endoscopically, gastric lymphoma can present with mucosal thickening, folds, or ulcerations that can be non-specific and resemble gastritis.
• Differentiation from Gastritis:
  • Persistent Symptoms and Lack of Response to Treatment: Symptoms of gastric lymphoma may be persistent and less responsive to typical gastritis treatments.
  • B Symptoms: Systemic symptoms like fever, night sweats, and unintentional weight loss (B symptoms) are more suggestive of lymphoma.
  • Endoscopy with Biopsy: Endoscopy with deep biopsies is essential to differentiate gastric lymphoma from gastritis. Lymphoma may involve the submucosa, requiring deeper biopsies for diagnosis. Immunohistochemistry and flow cytometry on biopsy samples are crucial for lymphoma diagnosis and subtyping.
  • H. pylori Eradication Response: MALT lymphoma, a subtype of gastric lymphoma, is often associated with H. pylori infection and can regress with H. pylori eradication therapy. However, not all gastric lymphomas respond to eradication, and persistent symptoms after eradication require further investigation.

9. Celiac Disease

Celiac disease, an autoimmune disorder triggered by gluten in genetically susceptible individuals, primarily affects the small intestine but can also present with upper gastrointestinal symptoms that overlap with gastritis.

• Overlap with Gastritis: Nausea, vomiting, abdominal pain, and bloating can be present in both celiac disease and gastritis.
• Differentiation from Gastritis:
  • Diarrhea and Malabsorption: Celiac disease typically presents with symptoms of malabsorption, including chronic diarrhea, weight loss, fatigue, and nutrient deficiencies. These are less common in gastritis unless it is severe and chronic.
  • Extra-intestinal Manifestations: Celiac disease can have various extra-intestinal manifestations, such as dermatitis herpetiformis, anemia, osteoporosis, and neurological symptoms, which are not typically associated with gastritis.
  • Serology: Serological tests for celiac disease, including tissue transglutaminase IgA antibody (tTG-IgA) and endomysial antibody (EMA), are highly sensitive and specific.
  • Upper Endoscopy with Duodenal Biopsy: Upper endoscopy with biopsies of the duodenum is the gold standard for diagnosing celiac disease. Histopathology typically shows villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes in the duodenal mucosa. Gastric biopsies in celiac disease may show lymphocytic gastritis, but duodenal findings are more characteristic.
  • Gluten-Free Diet Response: Clinical improvement with a gluten-free diet is a key diagnostic and therapeutic feature of celiac disease.

10. Multiple Endocrine Neoplasia (MEN) Syndromes

Certain MEN syndromes, particularly MEN type 1, can be associated with gastrointestinal manifestations that can mimic gastritis. ZES, already discussed, is a component of MEN1.

• Overlap with Gastritis: Dyspeptic symptoms, including epigastric pain and nausea, can occur in MEN syndromes, particularly due to the development of peptic ulcers and acid hypersecretion in ZES, which can be part of MEN1.
• Differentiation from Gastritis:
  • Associated Endocrine Tumors: MEN syndromes are characterized by tumors in multiple endocrine glands. MEN1 typically involves tumors of the parathyroid glands, pituitary gland, and pancreas (including gastrinomas). MEN2 involves medullary thyroid carcinoma, pheochromocytoma, and parathyroid adenoma (MEN2A) or mucosal neuromas and Marfanoid habitus (MEN2B).
  • Family History: A family history of MEN syndrome is a significant risk factor.
  • Hypercalcemia: Hyperparathyroidism, a common feature of MEN1 and MEN2A, leads to hypercalcemia, which can cause gastrointestinal symptoms and should prompt consideration of MEN.
  • Elevated Hormone Levels: In addition to gastrin levels in ZES, other hormone levels may be elevated depending on the specific MEN syndrome and the endocrine tumors involved (e.g., parathyroid hormone in hyperparathyroidism, prolactin in pituitary adenomas).
  • Genetic Testing: Genetic testing for MEN1 or RET gene mutations can confirm the diagnosis in suspected cases.

11. Other Conditions

Beyond these primary differentials, other less common conditions may also need to be considered depending on the specific clinical context:

• Gastroesophageal Reflux Disease (GERD): While primarily esophageal, GERD can cause epigastric pain and nausea, though heartburn and regurgitation are more typical symptoms. Endoscopy may show esophagitis, and gastric biopsies are typically normal unless there is co-existing gastritis.
• Irritable Bowel Syndrome (IBS): IBS can sometimes present with upper abdominal discomfort and bloating, although lower abdominal pain and altered bowel habits are more characteristic. IBS is a functional disorder, and endoscopy and biopsies are normal.
• Gastroparesis: Delayed gastric emptying can cause nausea, vomiting, and early satiety, mimicking gastritis. Gastric emptying studies are diagnostic. Gastroparesis can be secondary to diabetes, post-surgical, or idiopathic.
• Medication-induced Gastropathy: NSAIDs, aspirin, corticosteroids, and potassium supplements can cause gastropathy and symptoms similar to gastritis. History of medication use is crucial. Endoscopy may show erosions or ulcers, but histopathology may show gastropathy rather than true gastritis in some cases.

Prognosis and Management Implications

Accurate differential diagnosis is not only crucial for identifying the underlying cause of a patient’s symptoms but also has significant implications for prognosis and management. Misdiagnosing a serious condition like gastric cancer as gastritis can lead to delayed treatment and adverse outcomes. Conversely, incorrectly diagnosing gastritis when the patient has functional dyspepsia can lead to unnecessary investigations and treatments.

Appropriate management hinges on the correct diagnosis. For example:

• Gastritis: Management focuses on treating the underlying cause (e.g., H. pylori eradication, acid suppression for reactive gastritis), dietary modifications, and lifestyle changes.
• Functional Dyspepsia: Management is centered on symptom relief with medications like PPIs, H2 blockers, prokinetics, neuromodulators, and lifestyle and dietary modifications.
• Peptic Ulcer Disease: Treatment involves acid suppression, H. pylori eradication if present, and avoidance of NSAIDs.
• Gastric Cancer: Requires oncological management including surgery, chemotherapy, and radiation therapy depending on the stage.
• Biliary Tract Disease, Pancreatitis, Myocardial Ischemia, ZES, Celiac Disease, Gastric Lymphoma, MEN Syndromes: Each of these conditions requires specific and targeted management strategies distinct from gastritis treatment.

Conclusion

The differential diagnosis of gastritis is a complex clinical challenge due to the non-specificity of dyspeptic symptoms and the overlap with a wide range of gastrointestinal and systemic conditions. A thorough clinical evaluation, judicious use of diagnostic modalities including endoscopy, histopathology, and specific laboratory tests, and a systematic approach to considering alternative diagnoses are essential for accurate diagnosis and optimal patient care. This comprehensive guide highlights the key conditions in the differential diagnosis of gastritis, emphasizing the clinical and diagnostic features that help distinguish them from gastritis and ensure appropriate management. By mastering the nuances of Gastritis Differential Diagnosis, clinicians can significantly improve diagnostic precision and ultimately enhance patient outcomes.

Image: Histopathological view of chronic gastritis exhibiting gastric mucosal atrophy and dense lymphocytic infiltration, demonstrating key microscopic features for diagnosing chronic gastritis.

Image: Microscopic visualization of Helicobacter pylori in gastritis, stained with hematoxylin and eosin, showcasing the spiral-shaped bacteria responsible for H. pylori-associated gastritis.

References

1. Kayaçetin S, Güreşçi S. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol. 2014 Jun;25(3):233-47. [PubMed: 25141310]
2. Chia JK, Chia AY. Acute gastritis associated with enterovirus infection. Arch Pathol Lab Med. 2010 Jan;134(1):16-7. [PubMed: 20073596]
3. Sipponen P, Maaroos HI. Chronic gastritis. Scand J Gastroenterol. 2015 Jun;50(6):657-67. [PMC free article: PMC4673514] [PubMed: 25901896]
4. Pennelli G, Grillo F, Galuppini F, Ingravallo G, Pilozzi E, Rugge M, Fiocca R, Fassan M, Mastracci L. Gastritis: update on etiological features and histological practical approach. Pathologica. 2020 Sep;112(3):153-165. [PMC free article: PMC7931571] [PubMed: 33179619]
5. Sipponen P, Price AB. The Sydney System for classification of gastritis 20 years ago. J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:31-4. [PubMed: 21199511]
6. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P., faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015 Sep;64(9):1353-67. [PMC free article: PMC4552923] [PubMed: 26187502]
7. Moayyedi P, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol. 2017 Jul;112(7):988-1013. [PubMed: 28631728]
8. Fischbach W, Malfertheiner P. Helicobacter Pylori Infection. Dtsch Arztebl Int. 2018 Jun 22;115(25):429-436. [PMC free article: PMC6056709] [PubMed: 29999489]
9. Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021 Oct;161(4):1325-1332.e7. [PMC free article: PMC8740554] [PubMed: 34454714]
10. Varbanova M, Frauenschläger K, Malfertheiner P. Chronic gastritis – an update. Best Pract Res Clin Gastroenterol. 2014 Dec;28(6):1031-42. [PubMed: 25439069]