What are the differential diagnoses and initial management for a 30‑year‑old woman with persistent nausea and vomiting, leukopenia (white‑cell count 3.7 ×10⁹/L) and mildly elevated C‑reactive protein (18 mg/L)?

Differential Diagnosis and Management of Persistent Nausea and Vomiting in a 30-Year-Old Woman with Leukopenia and Elevated CRP

In a 30-year-old woman with persistent nausea and vomiting, leukopenia (WCC 3.72), and mildly elevated CRP (18), the most critical initial step is to obtain a pregnancy test, complete metabolic panel, liver function tests, lipase, and urinalysis to exclude pregnancy, metabolic derangements, hepatobiliary disease, and infection—while simultaneously initiating rehydration and empiric antiemetic therapy with metoclopramide or ondansetron. 1, 2

Immediate Diagnostic Priorities

Laboratory Evaluation

• Obtain urine pregnancy test immediately in any woman of childbearing age, as pregnancy (including hyperemesis gravidarum) is the most common endocrinologic cause of nausea and vomiting in this demographic 3, 4
• Complete blood count with differential to characterize the leukopenia (lymphopenia vs. neutropenia) and assess for thrombocytopenia or anemia 1, 2
• Comprehensive metabolic panel including electrolytes, glucose, calcium, and renal function to identify hypokalemia, hypochloremia, metabolic alkalosis, hypercalcemia, or Addison's disease 1, 5
• Liver function tests (AST, ALT, bilirubin, alkaline phosphatase) to evaluate for hepatitis, cholestasis, or pregnancy-related liver disease 1, 2
• Lipase and amylase to exclude pancreatitis 6, 5
• Thyroid-stimulating hormone if clinically indicated by other symptoms 1, 6
• Urinalysis with culture to assess for urinary tract infection or ketones 1, 2

Critical History Elements

• Cannabis use history is essential given the patient's age; Cannabis Hyperemesis Syndrome (CHS) should be suspected if heavy cannabis use preceded symptom onset, though diagnosis requires 6 months of cessation or 3 typical cycle lengths without vomiting 1
• Medication and toxin exposure, including over-the-counter drugs, supplements, and recent antibiotic use 2, 5
• Timing and pattern of symptoms: cyclic pattern suggests CVS or CHS; constant symptoms suggest structural or metabolic causes 6, 7
• Relationship to food intake: early satiety and postprandial vomiting suggest gastroparesis or gastric outlet obstruction 2, 5
• Associated symptoms: abdominal pain (pancreatitis, obstruction), headache (CNS causes, migraine), fever (infection), diarrhea (gastroenteritis) 2, 6

Differential Diagnosis Framework

Infectious/Inflammatory Causes (Most Likely Given Elevated CRP)

• Viral gastroenteritis or post-infectious gastroparesis—though leukopenia is atypical 2, 4
• COVID-19 gastrointestinal manifestations—can present with nausea, vomiting, and leukopenia 3
• Hepatitis (viral, autoimmune, drug-induced)—check liver enzymes 1, 2

Pregnancy-Related Causes (Must Exclude First)

• Hyperemesis gravidarum—occurs in 0.35-2% of pregnancies, typically first trimester, with abnormal liver enzymes in ~50% of cases 3
• HELLP syndrome or acute fatty liver of pregnancy—though these typically occur in third trimester with more severe laboratory abnormalities 3

Metabolic/Endocrine Causes

• Hypercalcemia, hypothyroidism, or Addison's disease—all can present with nausea, vomiting, and leukopenia 1, 4
• Diabetic ketoacidosis (if diabetic)—check glucose and ketones 6, 5

Gastrointestinal Structural Causes

• Gastroparesis—consider if postprandial symptoms predominate 2, 5
• Gastric outlet obstruction or small bowel obstruction—though typically presents with abdominal pain 3, 8
• Peptic ulcer disease or gastritis—common but usually doesn't cause leukopenia 2, 4

Toxin/Medication-Induced

• Cannabis Hyperemesis Syndrome—increasingly common in this age group 1
• Medication adverse effects—review all medications including recent additions 2, 5

Functional/Psychiatric Causes

• Cyclic Vomiting Syndrome—characterized by stereotypical episodes with symptom-free intervals, often misdiagnosed for years 7
• Eating disorders or somatization—consider if other features present 4, 6

Hematologic/Oncologic (Less Likely but Important)

• Leukemia or lymphoma—leukopenia with systemic symptoms warrants consideration 2
• Bone marrow suppression from toxins or medications 5

Initial Management Algorithm

Immediate Stabilization (First 1-2 Hours)

• Assess hydration status and initiate isotonic IV fluids (lactated Ringer's or normal saline) if moderate-to-severe dehydration, altered mental status, or inability to tolerate oral intake 1, 8
• Correct electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, which are common with prolonged vomiting 1, 8
• Administer thiamine 100 mg IV before glucose-containing fluids to prevent Wernicke's encephalopathy in patients with persistent vomiting 3, 1

Empiric Antiemetic Therapy (Initiate Immediately)

• First-line: Dopamine receptor antagonist 1, 8

  • Metoclopramide 10 mg IV/PO every 6-8 hours (promotes gastric emptying, particularly useful if gastroparesis suspected) 1, 8
  • OR Prochlorperazine 10 mg IV/PO every 6-8 hours 3, 8
  • OR Haloperidol 0.5-2 mg IV/PO every 4-6 hours 9, 8

• If symptoms persist after 4 weeks or are severe, add 5-HT3 antagonist 1, 8

  • Ondansetron 4-8 mg IV/PO every 8 hours (sublingual formulation available for actively vomiting patients) 1, 8
  • Monitor for QTc prolongation, especially with concurrent use of other QT-prolonging agents 1

• For anxiety-related component, consider adding 3, 8

  • Lorazepam 0.5-1 mg PO/IV every 4-6 hours as needed 3, 9

• Administer antiemetics on a scheduled basis rather than PRN, as prevention is easier than treating established vomiting 1, 8

Supportive Care

• Proton pump inhibitor (omeprazole 20-40 mg daily) if gastritis or GERD suspected 9, 8
• Small, frequent meals and avoidance of high-fat, high-sugar foods once oral intake tolerated 1, 2
• Ensure adequate fluid intake of at least 1.5 L/day once tolerating oral intake 1

Imaging and Further Evaluation (Based on Initial Results)

When to Obtain Imaging

• Upper GI imaging or esophagogastroduodenoscopy (EGD) should be performed once to exclude obstructive lesions, gastric malignancy, or peptic ulcer disease—but avoid repeated endoscopy unless new symptoms develop 1, 6
• Abdominal CT if concern for obstruction, pancreatitis, or intra-abdominal pathology based on examination or laboratory findings 6, 5
• Head CT only if neurologic symptoms present (headache, altered mental status, focal deficits) 6, 5

Gastric Emptying Study

• Consider if gastroparesis suspected based on postprandial symptom pattern and after structural causes excluded 6, 5

Critical Pitfalls to Avoid

• Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension 1, 8
• Do not dismiss cannabis use history—CHS is increasingly common and often misdiagnosed; offer treatment even with ongoing use, as therapies can still be effective 1
• Avoid repeated endoscopy or imaging unless new symptoms develop 1
• Monitor for extrapyramidal symptoms with dopamine antagonists, particularly in young patients; treat with diphenhydramine 50 mg IV if they occur 1, 8
• Do not overlook pregnancy testing—this is the single most important initial test in a woman of childbearing age 3, 4
• Leukopenia with elevated CRP is unusual for simple gastroenteritis—maintain high suspicion for systemic infection (including COVID-19), hematologic disorder, or medication/toxin effect 3, 2

Refractory Symptoms (If No Response After 48-72 Hours)

• Add second antiemetic from different drug class rather than replacing the first agent 1, 8
• Consider olanzapine 2.5-5 mg PO daily, which has shown superior efficacy for refractory symptoms 9, 8
• Dexamethasone 4-8 mg IV/PO twice daily if CNS involvement or severe symptoms 3, 1
• Dronabinol 2.5-7.5 mg PO every 4-6 hours for refractory nausea unresponsive to conventional antiemetics 1, 8
• Consider continuous IV or subcutaneous infusion of antiemetics for intractable symptoms 3, 8

Follow-Up and Reassessment

• If liver chemistry abnormalities persist despite symptom resolution, investigate alternative etiologies including viral hepatitis, autoimmune hepatitis, or drug-induced liver injury 3
• If leukopenia persists or worsens, obtain hematology consultation to exclude primary bone marrow disorder 2
• If symptoms follow a cyclic pattern, consider CVS and initiate prophylactic therapy with amitriptyline 50 mg nightly 7