In Hemophagocytic Lymphohistiocytosis (HLH), do Creatine Phosphokinase (CPK) and amylase levels increase?

Elevated CPK and Amylase in Hemophagocytic Lymphohistiocytosis (HLH)

Yes, both creatine phosphokinase (CPK) and amylase levels can be elevated in patients with Hemophagocytic Lymphohistiocytosis (HLH) due to the widespread inflammatory response and multi-organ involvement characteristic of this condition.

Laboratory Abnormalities in HLH

HLH is characterized by an uncontrolled hyperinflammatory state that affects multiple organ systems. While the HLH-2004 diagnostic criteria focus on specific laboratory parameters, additional biochemical abnormalities are commonly observed:

• Primary diagnostic criteria (HLH-2004) 1:

  • Fever
  • Splenomegaly
  • Cytopenias affecting ≥2 of 3 lineages
  • Hypertriglyceridemia and/or hypofibrinogenemia
  • Hemophagocytosis in bone marrow, spleen, or lymph nodes
  • Low or absent NK cell activity
  • Hyperferritinemia (>500 μg/L, often >7,000-10,000 μg/L)
  • Elevated soluble IL-2 receptor (sCD25)

• Additional laboratory abnormalities that may occur in HLH:

  • Elevated liver enzymes (AST, ALT) 1
  • Elevated LDH 2
  • Hypoproteinemia and hyponatremia 1
  • Elevated CPK
  • Elevated amylase and lipase 3

Evidence for CPK and Amylase Elevation

The evidence specifically addressing CPK and amylase elevations in HLH is limited but notable:

1. Amylase elevation: A case report documented a 57-year-old patient with HLH who presented with "increased levels of amylase and lipase in absence of radiologic signs of pancreatitis" 3. This suggests that pancreatic enzyme elevation can occur without structural pancreatic damage, likely due to the systemic inflammatory response.

2. Multi-organ involvement: HLH causes widespread inflammation affecting multiple organ systems, including muscle tissue (potentially causing CPK elevation) and the pancreas (causing amylase/lipase elevation) 4, 5.

3. Biochemical profile: The HLH-2004 guidelines and subsequent recommendations acknowledge that various laboratory abnormalities beyond the primary diagnostic criteria can occur in HLH 2, 1.

Clinical Implications

When managing patients with suspected or confirmed HLH:

• Monitor for multi-organ involvement: Elevated CPK may indicate muscle involvement or rhabdomyolysis, while elevated amylase may suggest pancreatic inflammation.

• Differential diagnosis: In patients with elevated pancreatic enzymes, consider HLH in the differential diagnosis, especially when accompanied by other characteristic features (fever, cytopenias, hyperferritinemia) 6.

• Disease monitoring: While ferritin, fibrinogen, platelets, and sCD25 are the primary markers for monitoring disease activity 2, tracking CPK and amylase may provide additional information about specific organ involvement.

Pitfalls and Caveats

• Overlapping presentations: Elevated amylase and CPK can have multiple causes, including direct organ damage from the underlying trigger of HLH (e.g., malignancy, infection).

• Age-related considerations: In adults, particularly those over 60 years, underlying malignancies are a major trigger of HLH (68% have lymphoma) 1, which may independently affect enzyme levels.

• Diagnostic delay: Laboratory findings in HLH can evolve over time, requiring serial testing if HLH is strongly suspected despite not initially meeting full criteria 1.

• Malignancy masking: Distinguishing disease-related abnormalities from HLH can be challenging in patients with known malignancy 1, potentially confounding interpretation of elevated CPK or amylase.

In conclusion, while not part of the primary diagnostic criteria, elevated CPK and amylase can occur in HLH as part of the widespread inflammatory response and multi-organ involvement characteristic of this condition.