What is the differential diagnosis for a patient with continuous vomiting, an elevated white blood cell count, normal inflammatory markers, and no fever?

Differential Diagnosis for Intractable Vomiting with Elevated WBC and Normal Inflammatory Markers

The most likely diagnoses are small bowel obstruction (particularly adhesive or early-stage), cyclic vomiting syndrome, or cannabinoid hyperemesis syndrome, with the elevated WBC suggesting either early bowel ischemia or stress response rather than systemic inflammation. 1, 2

Gastrointestinal Obstructive Causes

Small Bowel Obstruction (Most Critical to Exclude)

• Elevated WBC with normal CRP strongly suggests early or partial small bowel obstruction, potentially with early ischemia 1, 3
• The absence of fever and normal inflammatory markers does not exclude obstruction—physical examination and laboratory tests lack sufficient sensitivity to detect early strangulation or ischemia 1
• Adhesions account for 70% of small bowel obstructions, followed by hernias, malignancies, and Crohn disease 1
• Obtain CT abdomen/pelvis with IV contrast immediately—this has >90% diagnostic accuracy for detecting obstruction, identifying the site and cause, and detecting ischemia 1
• Look for specific CT signs of ischemia: abnormal bowel wall enhancement, intramural hyperdensity, bowel wall thickening, mesenteric edema, ascites, pneumatosis, or mesenteric venous gas 1
• Check serum lactate level—values ≥2.0 mmol/L predict non-viable bowel strangulation 3

Malrotation with Intermittent Volvulus

• Can present with recurrent vomiting episodes separated by symptom-free intervals 4
• Requires urgent imaging to exclude this surgical emergency 1, 4

Functional/Motility Disorders

Cyclic Vomiting Syndrome

• Consider this diagnosis if the patient has stereotypical episodes of acute-onset vomiting lasting <7 days, with at least 3 discrete episodes per year (2 in the prior 6 months), separated by ≥1 week of baseline health 2
• Approximately 65% have prodromal symptoms (median 1 hour before vomiting): fatigue, feeling hot/cold, mental fog, restlessness, anxiety, headache, diaphoresis, or flushing 2
• Most patients (80%) have abdominal pain during episodes—do not dismiss this diagnosis based on pain presence 2
• Elevated WBC can occur due to stress response and hypothalamic-pituitary-adrenal axis activation during episodes 5, 6
• Obtain urine drug screen specifically for cannabis—prolonged use (>1 year) suggests cannabinoid hyperemesis syndrome instead 2

Gastroparesis

• Typically presents with chronic rather than intractable acute vomiting 7
• Consider if symptoms are more chronic and insidious 8, 7

Inflammatory Bowel Disease

Crohn Disease (Active Small Bowel Involvement)

• Can present with vomiting, leukocytosis, and relatively normal CRP in early or predominantly small bowel disease 1
• Obtain CT enterography if patient can tolerate oral contrast—sensitivity 75-90% for detecting active Crohn disease 1
• Look for thickened small bowel with mural stratification, engorged vasa recti, and surrounding inflammatory stranding 1
• Standard CT abdomen/pelvis is acceptable if patient cannot tolerate large volume oral contrast 1

Infectious Causes

Acute Infectious Gastroenteritis with Severe Dehydration

• WBC elevation with normal CRP can occur with viral gastroenteritis causing severe volume depletion 1
• Lymphocytic predominance on differential suggests viral etiology, while neutrophil predominance suggests bacterial 1, 3
• Do not rely on fecal leukocytes—they have poor sensitivity and specificity 9
• Obtain stool culture, C. difficile testing, and consider molecular pathogen panels if infectious etiology suspected 9

Yersinia or Salmonella Infection

• Can cause sustained fever and bacteremia with potential for aortitis or mycotic aneurysms 1
• Consider imaging if there is sustained fever despite adequate therapy or if patient has underlying atherosclerosis 1

Metabolic/Endocrine Causes

Metabolic Disorders

• Aminoacidopathies, organic acidurias, fatty acid oxidation defects, and acute intermittent porphyria can present with cyclic vomiting 4, 6
• Obtain comprehensive metabolic panel, serum glucose, liver function tests, serum lipase, and urinalysis 2, 8
• Consider screening for metabolic disorders if recurrent pattern or family history present 4

Pregnancy

• Always obtain urine pregnancy test in reproductive-age females 8

Neurologic Causes

Increased Intracranial Pressure

• Brain tumor, subdural hematoma, or other space-occupying lesions can present with vomiting and leukocytosis 4
• Obtain non-contrast head CT if any concern for intracranial pathology, especially if headache, altered mental status, or focal neurological signs present 2, 8
• Look for headache worsened by sneezing, coughing, exercise, or postures that raise intracranial pressure 2

Immediate Diagnostic Algorithm

1. Check serum lactate, comprehensive metabolic panel, lipase, and urine pregnancy test 3, 2, 8
2. Obtain CT abdomen/pelvis with IV contrast to exclude obstruction, ischemia, or intra-abdominal pathology 1
3. Obtain urine drug screen for cannabis 2
4. Review WBC differential: neutrophil predominance suggests bacterial/ischemic process; lymphocytic predominance suggests viral 1, 3
5. If CT negative and recurrent pattern present, consider cyclic vomiting syndrome and evaluate for triggers (stress, fasting, menstrual cycle, sleep disturbance) 2, 6

Critical Pitfalls to Avoid

• Never assume normal inflammatory markers exclude bowel ischemia—early ischemia may present with isolated leukocytosis before CRP elevation 1, 3
• Do not delay imaging based on laboratory values alone—physical examination and labs lack sensitivity for detecting strangulation 1
• Always ask about cannabis use directly—patients may not volunteer this information 2
• Do not dismiss abdominal pain as excluding cyclic vomiting syndrome—most CVS patients have pain during episodes 2