What is the differential diagnosis for nausea and vomiting?

Differential Diagnosis of Nausea and Vomiting

Immediate Life-Threatening Causes to Exclude First

Bilious vomiting requires urgent upper GI imaging to exclude malrotation with volvulus or other mechanical obstruction, even if the initial examination is normal. 1

• Bowel obstruction presents with abdominal distention, absent bowel sounds, and colicky pain—this is a life-threatening emergency requiring immediate surgical consultation. 2
• Acute abdomen with peritoneal signs warrants emergent imaging and surgical evaluation. 3

---

Gastrointestinal Causes

Mechanical Obstruction

• Gastric outlet obstruction must be excluded with upper endoscopy before diagnosing any functional or motility disorder. 2
• Malignancy can cause obstruction and should be excluded by endoscopy, particularly in patients ≥55 years with alarm features (weight loss, dysphagia, palpable mass). 2
• Peptic ulcer disease accounts for ~10% of upper GI symptom presentations and requires upper endoscopy for definitive diagnosis. 2

Gastroparesis

• Gastroparesis affects 20-40% of diabetic patients and 25-40% of functional dyspepsia patients, presenting with postprandial vomiting, early satiety, bloating, and nausea. 2
• Gastric emptying scintigraphy performed for at least 4 hours is the gold standard diagnostic test—gastroparesis is confirmed when gastric retention is >10% at 4 hours. 2
• Symptoms correlate poorly with the degree of gastric emptying delay, so testing is essential rather than relying on clinical presentation alone. 2
• Blood glucose must be controlled during testing, as hyperglycemia itself slows gastric emptying and causes false-positive results. 2
• Medications affecting gastric emptying (prokinetics, opioids, anticholinergics) should be withdrawn 48-72 hours before testing. 2

Functional Dyspepsia

• Functional dyspepsia is defined by Rome IV criteria as bothersome epigastric pain, burning, postprandial fullness, or early satiation without structural disease on endoscopy. 2
• When vomiting is prominent in functional dyspepsia, you are likely dealing with the gastroparesis end of the spectrum—these conditions are indistinguishable by symptoms and represent the same spectrum of gastric neuromuscular dysfunction. 2
• Delayed gastric emptying occurs in 25-40% of functional dyspepsia patients. 2
• Rome IV criteria consider persistent or severe vomiting a red flag warranting investigation beyond functional dyspepsia. 2

Cyclic Vomiting Syndrome (CVS)

• CVS has a prevalence of ~2% in US adults and requires at least 3 discrete episodes in the past year, with 2 occurring in the prior 6 months, each lasting <7 days, separated by at least 1 week of complete wellness. 1
• Episodes are stereotypical with prodromal symptoms (impending doom, panic, anxiety, diaphoresis), and personal or family history of migraines supports the diagnosis. 1
• Do not diagnose CVS based on only two episodes—viral gastroenteritis is far more common and this is insufficient to meet diagnostic criteria. 1

Cannabinoid Hyperemesis Syndrome (CHS)

• CHS requires chronic cannabis use (typically >1 year, >4 times weekly) before symptom onset and is characterized by cyclic vomiting with compulsive hot water bathing behavior. 1
• Screen for cannabis use >4 times weekly for >1 year, as this suggests CHS rather than CVS. 1
• Symptoms resolve after 6 months of cannabis cessation. 1
• Do not assume hot water bathing equals CHS—this behavior occurs in nearly half of CVS patients without cannabis use. 1
• Cannabis use has a pooled prevalence of 47% in patients with vomiting syndromes. 2

Other GI Causes

• Gastroesophageal reflux disease (GERD) overlaps significantly with functional dyspepsia—more than 50% of GERD patients have no endoscopic esophagitis. 2
• Constipation occurs in ~50% of patients with advanced cancer and most patients on opioids, and can cause nausea and vomiting. 4

---

Medication and Toxin-Related Causes

• Opioid-induced nausea occurs in 10-50% of patients receiving opioids and worsens gastric emptying—opioids should be avoided in gastroparesis patients. 2
• Check blood levels of digoxin, phenytoin, carbamazepine, and tricyclic antidepressants, as these commonly cause nausea and vomiting. 4
• NSAIDs, anticholinergic drugs (antidepressants, antispasmodics, phenothiazines, haloperidol), and antiemetics themselves can cause nausea. 4
• Chemotherapy-induced nausea and vomiting should be managed per NCCN antiemesis guidelines. 4

---

Metabolic and Endocrine Causes

• Hypercalcemia can cause nausea and vomiting and should be checked in cancer patients. 4
• Diabetic hyperglycemia causes gastric dysmotility. 2
• Thiamin deficiency should be evaluated in patients with persistent vomiting >2-3 weeks to prevent neurological complications. 2
• Pregnancy must be excluded with urine pregnancy testing in women of childbearing age. 3

---

Neurologic Causes

• Central nervous system tumors cause nausea through increased intracranial pressure, typically accompanied by other neurologic signs (headache, focal deficits, altered mental status). 2
• Brain metastases should be considered in cancer patients with new-onset nausea and neurologic symptoms. 4
• Vestibular disturbances can cause acute nausea and vomiting. 5
• Migraine headaches are associated with nausea and vomiting and support a diagnosis of CVS when there is a personal or family history. 1

---

Infectious Causes

• Viral gastroenteritis is the leading cause of acute vomiting, characterized by sudden onset, mild fever, diarrhea, and short duration (<7 days). 1
• Foodborne illness presents with acute onset after contaminated food ingestion. 5

---

Psychiatric and Psychogenic Causes

• Psychogenic disorders should be considered when organic causes are excluded. 2
• Psychiatric comorbidity is associated with CVS, along with younger age and tobacco use. 2
• Eating disorders can cause chronic nausea and vomiting—screen for abnormal eating behaviors (eating too quickly, insufficient chewing, overeating). 2

---

Age-Stratified Diagnostic Algorithm

Patients <55 Years Without Alarm Features

• Adopt an H. pylori test-and-treat strategy using 13C-urea breath test or stool antigen assay. 2
• If H. pylori is negative or symptoms persist after eradication, initiate an empirical high-dose PPI trial (omeprazole 20-40 mg once daily before meals) for 4-8 weeks. 2

Patients ≥55 Years or Any Age With Alarm Features

• Perform upper endoscopy before confirming functional dyspepsia. 2
• Alarm features requiring urgent (2-week wait) endoscopy: unexplained weight loss, dysphagia, upper abdominal mass. 2
• Alarm features requiring non-urgent endoscopy: treatment-resistant dyspepsia, nausea/vomiting with elevated platelet count, hematemesis. 2

---

Common Diagnostic Pitfalls to Avoid

• Do not diagnose functional dyspepsia without endoscopy in adults ≥55 years or those with alarm features—structural disease must be excluded first. 2
• Do not attribute persistent or severe vomiting to functional dyspepsia—Rome IV criteria consider this a red flag for other disorders. 2
• Do not perform gastric emptying studies <4 hours—shorter durations are inaccurate for determining gastroparesis. 2
• Do not overlook medication-induced causes—systematically review all medications, particularly opioids, NSAIDs, and anticholinergics. 4, 2
• Do not miss cannabis use history—this is critical for distinguishing CHS from CVS. 2, 1
• Do not rely solely on symptoms to diagnose gastroparesis—symptoms correlate poorly with gastric emptying delay. 2