Drug-Related Pyroglutamic Acidosis: Systematic Literature Review

Area of Science:

• Metabolic Disorders
• Toxicology
• Clinical Medicine

Background:

• Inborn errors of glutathione metabolism can lead to pyroglutamic acid accumulation and high anion gap metabolic acidosis.
• Acquired cases of pyroglutamic acidosis, unrelated to genetic defects, have been reported since 1988.
• Predisposing factors, clinical presentation, and prognosis of acquired pyroglutamic acidosis remain poorly understood.

Purpose of the Study:

• To systematically review and characterize acquired pyroglutamic acidosis.
• To identify predisposing factors, clinical features, management strategies, and outcomes.

Main Methods:

• Systematic literature review conducted across major biomedical databases (NLM, EMBASE, Web of Science, Google Scholar).
• Inclusion of 131 reported cases of acquired pyroglutamic acidosis.
• Analysis of patient demographics, comorbidities, drug exposures, clinical signs, laboratory findings, treatments, and mortality.

Main Results:

• The majority of patients were adult females (79%), over 51 years old (66%), with comorbidities (74%) like undernutrition or alcohol use disorder, and often had concurrent infections (69%).
• Common clinical features included altered consciousness (60%) and Kussmaul breathing (56%).
• Frequent drug exposures included prolonged paracetamol use (>10 days) (92%), beta-lactamase-resistant penicillin (32%), and vigabatrin (2.3%).
• Associated findings included hypokalemia (24%) and acute kidney injury (41%).
• Management involved drug withdrawal (100%), bicarbonate (63%), acetylcysteine (42%), and renal replacement therapy (18%).
• The overall fatality rate was 18%, significantly lower when acetylcysteine was administered (11% vs. 24%).

Conclusions:

• Acquired pyroglutamic acidosis is a rare but potentially fatal metabolic complication.
• Paracetamol use, often combined with beta-lactamase-resistant penicillin or vigabatrin, is a common trigger.
• Risk factors include advanced age, female sex, comorbidities, and infection.
• Prompt recognition and treatment with acetylcysteine are crucial for improving patient outcomes.