What is the differential diagnosis for acute gastritis?

Differential Diagnosis for Acute Gastritis

When evaluating acute gastritis, the differential diagnosis must systematically exclude life-threatening conditions first, then distinguish between upper GI pathologies with overlapping presentations, including peptic ulcer disease, GERD, acute mesenteric ischemia, and various infectious or autoimmune etiologies.

Immediate Life-Threatening Conditions to Exclude First

• Perforated peptic ulcer presents with sudden severe epigastric pain, fever, abdominal rigidity, and carries mortality rates up to 30% if treatment is delayed 1, 2
• Acute mesenteric ischemia should be considered when epigastric pain is accompanied by severe symptoms, particularly in patients with atrial fibrillation, recent MI, or diffuse atherosclerotic disease 3
• Acute pancreatitis presents with severe epigastric pain radiating to the back and requires urgent evaluation with elevated amylase (noting that elevated amylase occurs in roughly half of mesenteric ischemia patients, potentially causing misdiagnosis) 3, 1

Upper Gastrointestinal Pathologies with Overlapping Presentations

Peptic Ulcer Disease (PUD)

• PUD involves focal mucosal breaks extending through the epithelial lining into the submucosal layer, with incidence of 0.1-0.3%, primarily caused by Helicobacter pylori infection (42% of cases) and NSAID use (36% of cases) 1, 4
• Epigastric pain is the predominant symptom, often with nocturnal timing particularly for duodenal ulcers 4
• Hemorrhage is the most common complication (73% of complicated cases) with 30-day mortality of 8.6%, manifesting as hematemesis or melena 1, 2
• Endoscopy reveals focal ulcer craters with discrete margins and ulceroproliferative features 4

Gastroesophageal Reflux Disease (GERD)

• GERD results from reflux of gastric contents into the esophagus causing troublesome symptoms, often mediated through transient lower esophageal sphincter relaxations 4
• Regurgitation of gastric contents is characteristic, typically worsening after meals and when supine 4
• CT imaging may show distal esophageal wall thickening ≥5 mm (sensitivity 56%, specificity 88% for reflux esophagitis) 1
• Correlation between reflux symptoms and endoscopy-positive GERD is poor, requiring endoscopic confirmation 4

Acute Hemorrhagic Gastritis

• Acute hemorrhagic gastritis accounts for approximately one-fourth of upper GI bleeding in endoscopic studies 5
• Predisposing conditions include alcohol abuse, portal hypertension, short- or long-term NSAID use, and physiologic stress in ICU patients 5
• Presents with diffuse mucosal bleeding making endoscopic therapy more difficult than focal ulcer bleeding 5

Infectious Etiologies

Helicobacter pylori Acute Gastritis

• H. pylori acute gastritis can mimic gastric carcinoma or lymphoma endoscopically, requiring histology and organism detection for accurate diagnosis 6
• Histological examination shows edema, hyperemia, and intense polymorphonuclear leukocyte infiltration (neutrophils and eosinophils) in the lamina propria, mucus layer, and inside glands 6
• Treatment with amoxicillin (2 g/day for 2 months) plus metronidazole (750 mg/day for 15 days) produces dramatic symptom reduction 6

Other Infectious Causes

• Viral infections including cytomegalovirus (CMV) or Epstein-Barr virus (EBV) should be considered in the differential 7
• Bacterial infections such as Enterococcus and Treponema pallidum can cause gastritis 7

Chronic Gastritis Presentations Mimicking Acute Disease

Autoimmune Atrophic Gastritis

• Autoimmune gastritis is defined as loss of gastric glands with or without metaplasia in the setting of chronic inflammation, confirmed by histopathology 3
• Antiparietal cell antibodies and anti-intrinsic factor antibodies assist with diagnosis 3
• Evaluate for vitamin B-12 and iron deficiencies, particularly in corpus-predominant disease 3
• Screen for concomitant autoimmune thyroid disease 3

Lymphocytic Gastritis

• Lymphocytic gastritis represents a distinct chronic, noninfectious entity that must be differentiated from H. pylori gastritis 8

Inflammatory Bowel Disease Involvement

• IBD (particularly Crohn's disease) can affect the stomach, but typically presents with diarrhea rather than primarily vomiting 1
• Focal chronic inflammation and architectural abnormalities in biopsies favor Crohn's disease over peptic ulcer disease 1
• In children, granulomas are identified in 67% at initial colonoscopy 1
• The predominant epigastric location and retrosternal pain are more consistent with upper GI pathology rather than the colonic/terminal ileal involvement typical of IBD 1

Medication-Induced Gastropathy

• Gastropathy refers to structural alterations of the mucosa with paucity of inflammatory signs, distinguishing it from true gastritis 9
• Common medications causing gastropathy include antibiotics used for H. pylori eradication and NSAIDs 7
• Proton pump inhibitor (PPI) use can mask H. pylori, which may only be found within parietal cells in such cases 7

Critical Diagnostic Pitfalls to Avoid

• Symptoms are nonspecific and overlap extensively between GERD, gastritis, esophagitis, and peptic ulcer disease, requiring careful history and often endoscopic evaluation 1, 4
• False-negative H. pylori results can occur if both antral and oxyntic mucosa are not sampled, if insensitive stains are used, or in the presence of marked reactive changes such as intestinal, pseudo-pyloric, or pancreatic metaplasia 7
• Do not assume benign disease without histologic confirmation when ulceroproliferative features are present, as malignancy can mimic PUD 4
• Elevated amylase can occur in mesenteric ischemia, potentially leading to misdiagnosis as pancreatitis and delay in critical interventions 3

Diagnostic Algorithm

When H. pylori is not detected but morphology suggests infection:

• Ensure both antral and oxyntic mucosa are present in biopsies 7
• Use sensitive stains and identify marked reactive changes suggesting atrophic gastritis 7
• Consider PPI use masking H. pylori within parietal cells 7
• If organism remains undetected, consider lymphocytic gastritis, IBD, vasculitis, granulomatous disease, viral infections, or medication-induced gastropathy 7
• When all known causes are excluded, use the term "idiopathic focal/diffuse gastritis" 7

For patients with alarm features (bleeding, perforation signs, fever with tachycardia):

• Upper endoscopy is first-line for diagnosis and therapy 1
• Obtain topographical biopsies from body and antrum in separately labeled jars for risk stratification 3
• At least two biopsy samples from both antrum and body improve H. pylori detection sensitivity 1
• If peritoneal signs develop, immediate surgical consultation is mandatory 1