Can Lyme disease or other chronic infections cause hyperammonemia?

Hyperammonemia in Lyme Disease and Other Chronic Infections

There is no evidence in the medical literature supporting that Lyme disease or other chronic infections directly cause elevated blood ammonia levels (hyperammonemia). Based on available guidelines and research, hyperammonemia is primarily associated with liver dysfunction, kidney disease, and specific metabolic disorders rather than chronic infections like Lyme disease.

Pathophysiology of Hyperammonemia

• Hyperammonemia is characterized by elevated levels of ammonia in the blood, typically resulting from impaired capacity of the body to excrete nitrogenous waste 1
• Normal blood ammonia levels range between 11 and 50 μM; levels may exceed 1 mM in pathological conditions 2
• Ammonia is primarily metabolized by the liver through the urea cycle, and liver dysfunction is the most common cause of hyperammonemia 3
• Elevated ammonia is strongly associated with disruption of potassium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation, and dysregulation of neurotransmission 3

Lyme Disease and Liver Function

• While Lyme disease can cause mild liver function abnormalities, there is no evidence that it directly causes hyperammonemia 4
• In a prospective study of 115 patients with early Lyme disease, 40% had at least one liver test abnormality, primarily elevated gamma-glutamyl transpeptidase (28%) and alanine transaminase (27%) 4
• Liver function abnormalities in Lyme disease are typically mild, often asymptomatic, and resolve with appropriate antibiotic treatment 4
• Patients with disseminated Lyme disease are more likely to have elevated liver function tests (66%) compared to those with localized disease (34%) 4

Clinical Manifestations of Lyme Disease

• Lyme disease primarily manifests with erythema migrans (characteristic rash), fever, headache, fatigue, and musculoskeletal pain 5
• Cardiac involvement occurs in approximately 4-10% of patients, typically presenting as atrioventricular heart block or myopericarditis 6
• Neurological manifestations include meningitis, cranial neuropathy (particularly facial nerve palsy), and radiculopathy 5
• Joint involvement typically presents as monoarthritis or oligoarthritis, most commonly affecting the knee 5

Conditions Associated with Hyperammonemia

• Primary causes of hyperammonemia include:
  • Liver dysfunction (cirrhosis, acute liver failure) 3
  • Urea cycle disorders and other inborn errors of metabolism 1
  • Reye's syndrome 1
  • Kidney dysfunction 3
• Hyperammonemia is a hallmark of hepatic encephalopathy in patients with cirrhosis and liver failure 3
• Elevated ammonia levels are uncommon in patients with metabolic dysfunction-associated steatotic liver disease 3

Coinfections in Lyme Disease

• Coinfection with Anaplasma phagocytophilum (causing Human Granulocytic Anaplasmosis) or Babesia microti should be considered in patients with:
  • High-grade fever persisting >48 hours despite appropriate antibiotic therapy 5
  • Unexplained leukopenia, thrombocytopenia, or anemia 5
  • Resolution of erythema migrans but worsening of viral infection-like symptoms 5
• Laboratory abnormalities in anaplasmosis include thrombocytopenia, leukopenia, elevated hepatic transaminases, and mild anemia, but not hyperammonemia 5
• Coinfection with A. phagocytophilum has been reported in <10% of patients with Lyme disease 5

Clinical Implications

• When evaluating a patient with suspected Lyme disease and abnormal liver function tests, consider:
  • The pattern and severity of liver enzyme elevations 4
  • Presence of disseminated disease, which increases likelihood of liver involvement 4
  • Alternative causes of liver dysfunction 1
• For patients with unexplained hyperammonemia, focus on evaluating liver and kidney function, metabolic disorders, and medication effects rather than chronic infections 3, 1

Conclusion

Based on current medical evidence, there is no established link between Lyme disease or other chronic infections and hyperammonemia. While Lyme disease can cause mild liver function abnormalities, these typically resolve with appropriate antibiotic treatment and are not associated with significant ammonia elevation. When encountering hyperammonemia, clinicians should focus on evaluating liver function, kidney disease, and metabolic disorders as the most likely causes.