What are the likely causes of hyperlipasemia and neutropenia in a previously healthy 16-year-old female?

Differential Diagnosis of Elevated Lipase and Neutropenia in a Previously Healthy 16-Year-Old Female

In a previously healthy adolescent presenting with both hyperlipasemia and neutropenia, the most critical immediate considerations are acute infection (particularly sepsis or infectious colitis), drug/toxin exposure, and underlying autoimmune or inflammatory conditions, with malignancy being less likely but requiring exclusion given the combination of findings.

Primary Diagnostic Considerations

Infectious Etiologies (Most Likely)

Sepsis with multi-organ involvement represents the most concerning and potentially life-threatening cause of this combination:

• Sepsis can cause both neutropenia (through consumption and bone marrow suppression) and elevated lipase (through systemic inflammation and reduced clearance) 1
• Approximately 27.7% of non-pancreatic hyperlipasemia cases are associated with sepsis, and the presence of sepsis significantly deteriorates diagnostic accuracy of lipase for pancreatitis 1
• Neutropenia in sepsis occurs through multiple mechanisms including increased margination, consumption at infection sites, and bone marrow suppression 2
• The combination carries high mortality risk, with in-hospital mortality of 22.4% in patients with non-pancreatic hyperlipasemia 1

Infectious colitis is a specific entity that can produce this exact combination:

• Infectious colitis has been documented to cause elevated lipase without pancreatic inflammation 3
• Gastrointestinal infections can cause neutropenia through bone marrow suppression or increased peripheral consumption 4
• This diagnosis should be strongly considered if the patient has diarrhea, abdominal pain (particularly left-sided), or recent gastrointestinal symptoms 3

Inflammatory Bowel Disease

Crohn's disease or ulcerative colitis can present with both findings:

• Inflammatory bowel disease is associated with elevated lipase levels even without pancreatitis 3, 5
• Autoimmune conditions can cause neutropenia through immune-mediated destruction or bone marrow suppression 2
• This is particularly relevant in adolescent females, as IBD commonly presents in this age group

Drug or Toxin Exposure

Medication-induced causes must be systematically excluded:

• Certain medications can cause both neutropenia (chemotherapy agents, immunosuppressants, antibiotics) and elevated lipase 2
• Organophosphate poisoning has been documented to cause hyperlipasemia 5
• A detailed medication and exposure history is essential

Metabolic/Genetic Disorders

Glycogen Storage Disease Type Ib should be considered:

• GSD Type Ib characteristically presents with neutropenia, impaired neutrophil function, and recurrent bacterial infections 2
• While primarily causing hypoglycemia and hepatomegaly, GSD I can be associated with acute pancreatitis when severe hypertriglyceridemia (>1,000 mg/dL) develops 2
• Neutropenia in GSD Ib results from impaired glucose-6-phosphate transport affecting neutrophil function 2
• This diagnosis is less likely if there is no history of hypoglycemia, hepatomegaly, or growth delay

Acute Kidney Injury

Renal dysfunction can cause isolated hyperlipasemia:

• Acute kidney injury is present in 33.2% of non-pancreatic hyperlipasemia cases due to reduced renal clearance 1
• However, AKI alone would not explain neutropenia unless part of a systemic process 5

Critical Diagnostic Algorithm

Immediate Assessment (Within 2 Hours)

Determine if true acute pancreatitis is present:

• Lipase level ≥666 U/L has 71.4% sensitivity and 88.8% specificity for acute pancreatitis 1
• Lipase >532 U/L provides optimal diagnostic accuracy with 77.4% sensitivity and 78.0% specificity in critically ill patients 6
• The presence of sepsis or AKI significantly reduces the diagnostic accuracy of lipase for pancreatitis 1

Assess for sepsis immediately:

• Check vital signs for fever, tachycardia, hypotension
• Obtain blood cultures before antibiotics
• Calculate neutrophil-to-lymphocyte ratio (NLR): NLR >10.37 is an independent risk factor for mortality (OR: 3.71) in non-pancreatic hyperlipasemia 1
• If sepsis is suspected, initiate broad-spectrum antibiotics within 2 hours 4

Laboratory Evaluation

Essential initial tests:

• Complete blood count with differential to quantify absolute neutrophil count (ANC <500/µL defines neutropenia) 4
• Comprehensive metabolic panel including renal function, albumin (decreased albumin is associated with mortality in hyperlipasemia) 1
• Amylase level: amylase >244 U/L is an independent risk factor for mortality in non-pancreatic hyperlipasemia 1
• Lipid panel to assess for severe hypertriglyceridemia (>1,000 mg/dL suggests pancreatitis risk) 2, 7
• Liver function tests
• C-reactive protein and inflammatory markers

Secondary diagnostic tests based on clinical presentation:

• Blood cultures if febrile or sepsis suspected
• Stool studies including culture, ova and parasites, Clostridioides difficile if diarrhea present 3
• Autoimmune serologies (ANA, anti-dsDNA, complement levels) if autoimmune disease suspected
• Vitamin E level if abetalipoproteinemia considered (though this typically presents with neurological symptoms) 8

Imaging Strategy

Abdominal imaging is essential to differentiate pancreatic from non-pancreatic causes:

• CT abdomen/pelvis with IV contrast is the gold standard: 69.1% of acute pancreatitis cases are confirmed by CT 9
• Look specifically for pancreatic inflammation, colitis, hepatosplenomegaly, lymphadenopathy
• Ultrasound can identify gallstones, hepatomegaly, or nephromegaly (suggestive of GSD I) 2

Risk Stratification

High-Risk Features Requiring Immediate Intervention

The following indicate need for ICU-level care:

• ANC <100/µL (10-20% risk of bloodstream infection) 2, 4
• Signs of sepsis or hemodynamic instability
• NLR >10.37 1
• Lipase >666 U/L with imaging-confirmed pancreatitis 1
• Presence of both sepsis and AKI together 1

Duration of Neutropenia

Prolonged neutropenia (>10 days) significantly increases infection risk and mortality 4:

• If neutropenia persists, consider bone marrow evaluation for primary hematologic disorder
• Fungal infections (particularly Candida) become more likely with prolonged neutropenia 2, 4

Common Pitfalls to Avoid

Do not assume all elevated lipase represents acute pancreatitis:

• Only 38.1% of critically ill patients with hyperlipasemia actually have acute pancreatitis 6
• In one study, only 6.3% of patients with lipase <3× ULN had confirmed pancreatitis 9
• Non-pancreatic hyperlipasemia is associated with higher mortality (22.4%) than actual pancreatitis (5.1%) 1

Do not overlook infectious colitis:

• This is the first documented cause of elevated lipase without pancreatitis in infectious colitis 3
• Left lower quadrant pain with diarrhea should prompt evaluation for colitis even with elevated lipase 3

Do not delay antibiotics if neutropenic fever is present:

• Empirical broad-spectrum antibiotics must be given within 2 hours of presentation in febrile neutropenia 4
• Approximately 50-60% of febrile neutropenic patients have an established or occult infection 2, 4

Do not miss GSD Type Ib in patients with chronic neutropenia:

• Ask specifically about history of hypoglycemia, hepatomegaly, recurrent infections, or growth delay 2
• GSD Ib patients have both neutropenia and risk of pancreatitis from severe hypertriglyceridemia 2