The Dilemma of D-Lactic Acidosis in Inflammatory Bowel Disease

Background: Chronic intestinal failure is a feared complication of Crohn’s disease, as a result of multiple small bowel resections for stricturing or penetrating disease manifestations. Short bowel syndrome is defined as intestinal failure with less than 200 cm of small bowel remaining. Patients often present with nutrient deficiencies, dehydration, and malnutrition requiring total parenteral nutrition (TPN). We report a rare presentation of acute intoxication related to D-lactic acidosis in a patient with short bowel syndrome. Methods: We report a case of a 50-year-old male with a history of fibrostenotic and fistulizing Crohn’s disease requiring multiple small bowel resections, now with short bowel syndrome (90 cm small bowel remaining), and mild peripheral primary sclerosing cholangitis. For the last year, he has been maintained on upadacitinib with no disease activity shown on CT enterography and colonoscopy. He first reported episodes of ‘feeling intoxicated’ with symptoms of ataxia, slurred speech, brain fog and bloating with baseline loose stools. He denied ascites, edema, fevers, jaundice, hematochezia, or melena. He does not drink alcohol and drug screening was negative. These episodes were causing a strain on his marriage as his partner thought the only reasonable explanation for his behavior was substance use. He discontinued TPN for 3 months and lost 20 lbs. unintentionally. Medications included upadacitinib 30 mg daily, ursodiol 500 mg daily, and a multivitamin. Results: Due to concern for nutritional deficiency versus d-lactic acidosis versus auto-brewery syndrome he underwent further testing. His laboratory evaluation was notable for a hemoglobin of 11.5 g/dL, AST 36 U/L, ALT 71 U/L, alkaline phosphatase 161 U/L, albumin 4.1 g/dL, potassium 3.7 mmol/L, sodium 144 mmol/L, chloride 108 mmol/L (high), bicarbonate 24 mmol/L, anion gap 12, creatinine 0.9 mg/dL, vitamin b12 247 ng/L, folate 12 mcg/L, magnesium 1.4 mg/dL (low), thiamine normal, ethanol serum < 10 mg/dL, pH 7.18 (low), pCO2 66 mmHg (venous), bicarbonate 20 mmol/L, serum d-lactate 3.22 mmol/L (elevated from reference range 0.25 mmol/L), urine d-lactate 19.78 mmol/L (elevated from reference range 0.25 mmol/L). Bacterial and fungal aspirates from a normal upper endoscopy grew Klebsiella pneumoniae >100,000 cfu/mL and Candida albicans >100,000 cfu/mL. Our patient met with nutrition to restart TPN while adhering to a low simple CHO diet, avoiding fructose/sugar/alcohol, and ensuring adequate hydration. His frequency of symptoms has improved since starting cycling antibiotics and targeted treatment with anti-fungal therapy. Conclusions: Our patient had evidence of metabolic acidosis with positive d-lactic acidosis in the setting of small intestinal bacterial overgrowth with Klebsiella and Candida. IBD physicians should have a low index of suspicion for diagnosing d-lactic acidosis in high-risk patients (short bowel syndrome, Roux-en-Y gastric bypass) presenting with metabolic acidosis (+/- elevated anion gap) and encephalopathy of unclear etiology. D-lactate is not detected on standard laboratory testing and requires a specialty lab test of urine or serum to be taken during an episode. Bacteria are almost always the predominant generator of d-lactate, especially E. coli, Klebsiella pneumoniae, Candida freundii, Lactobacillus, and Bifidobacterium.