Footprint-like urinary leucine crystals in alkaline urine during pediatric SJS/TEN overlap syndrome: a multimodal case-based study

Leucine crystalluria is a rare pathological urinary sediment finding traditionally associated with severe hepatobiliary dysfunction or amino-acid metabolic disorders. Its recognition usually relies on the classical yellow-brown, concentrically laminated or radially striated morphology, traditionally described in urine with lower pH values. Atypical forms may therefore be misclassified, particularly in bilirubin-rich urine. We conducted a retrospective case-based morphological and analytical study of unusual urinary crystals detected in a 12-year-old boy with SJS/TEN overlap syndrome complicated by persistent cholestatic hepatitis and biochemical abnormalities associated with pancreatitis. Clinical data, serial laboratory indices, and urinalysis results were reviewed. Fresh urine sediment was examined by bright-field, phase-contrast, and polarized microscopy. Copper sulfate staining and LC-MS/MS were used as supportive tests, while FTIR spectroscopy was used for compositional confirmation. A literature-based comparison was constructed to contextualize the present case against previously reported urinary leucine crystals. At the time of crystal detection, the patient exhibited persistent cholestatic and metabolic injury, with total bilirubin 160.8 µmol/L, direct bilirubin 140.4 µmol/L, γ-glutamyl transferase 1121 U/L, total bile acids 170.2 µmol/L, total cholesterol 15.13 mmol/L, triglycerides 5.86 mmol/L, urine bilirubin 3+, and urine pH 7.5. Microscopy revealed yellow to yellow-brown crystals with a reproducible footprint-like morphology, weak birefringence, and no dominant classical pattern of concentric rings or radial striations. Copper sulfate staining produced a green colour reaction, chemically compatible with leucine. LC-MS/MS demonstrated a peak with a retention time closely matching an L-leucine standard under a leucine-compatible MRM transition, and FTIR showed absorption bands compatible with leucine. Together, these findings supported the identification of the crystals as leucine-compatible crystals, with FTIR serving as the principal compositional confirmation method despite the atypical morphology. This study broadens the morphological and clinical spectrum of urinary leucine crystals. In a pediatric SJS/TEN overlap context, footprint-like leucine crystals were detected in alkaline urine and their composition was confirmed by FTIR. This finding should be interpreted as a rare urinary indicator of severe hepatobiliary metabolic disturbance, rather than as a specific diagnostic marker of SJS/TEN. For atypical yellow-brown urinary crystals, a multimodal approach integrating morphology, urine pH, supportive chemical testing, supportive LC-MS/MS evidence, and FTIR confirmation can prevent misclassification and enhance diagnostic confidence. Not applicable