Visible Jaundice and Serum Bilirubin Threshold
Visible jaundice (scleral icterus or skin yellowing) becomes clinically apparent when serum total bilirubin exceeds 2.5 to 3 mg/dL in adults. 1, 2
Clinical Detection Threshold
Jaundice is typically visible when total bilirubin levels reach 3 mg/dL or higher, though the exact threshold varies slightly between 2.5–3 mg/dL depending on individual factors such as skin pigmentation and lighting conditions. 1, 2, 3
Scleral icterus (yellowing of the whites of the eyes) is often the earliest and most reliable clinical sign, appearing before generalized skin jaundice because the sclera has high elastin content with particular affinity for bilirubin. 1, 4
Visual assessment of jaundice severity is unreliable and should never replace objective bilirubin measurement, particularly in patients with darker skin pigmentation where clinical detection is significantly more difficult. 5
Critical Clinical Context
Any visible jaundice warrants immediate laboratory evaluation because it indicates total bilirubin has reached at least 2.5–3 mg/dL, signaling potential serious underlying hepatobiliary disease, hemolysis, or biliary obstruction. 1, 6, 2
The presence of jaundice should prompt fractionation of total bilirubin into direct (conjugated) and indirect (unconjugated) components to differentiate between prehepatic causes (hemolysis), intrahepatic disorders (hepatocellular injury), and posthepatic obstruction (biliary tract disease). 5, 4, 2, 3
Diagnostic Algorithm When Jaundice Is Observed
Immediately obtain total and fractionated bilirubin, complete blood count, liver enzymes (ALT, AST, alkaline phosphatase), GGT, albumin, and INR/PT to determine whether hyperbilirubinemia is conjugated or unconjugated and to assess hepatic synthetic function. 5, 2, 3
If conjugated (direct) bilirubin exceeds 20–35% of total bilirubin, proceed urgently to abdominal ultrasound within 24–48 hours to exclude biliary obstruction, which has 98% positive predictive value for liver parenchymal disease and 65–95% sensitivity for detecting biliary obstruction. 5, 7
If unconjugated (indirect) bilirubin predominates (>70–80% of total), evaluate for hemolysis with peripheral smear, reticulocyte count, haptoglobin, and LDH, and consider Gilbert syndrome if hemolysis workup is negative. 5, 4, 3
Common Pitfalls to Avoid
Do not rely on visual estimation alone—phototherapy "bleaches" the skin in treated patients, and both visual assessment and transcutaneous bilirubin measurements become unreliable during or after treatment. 5
Do not delay obtaining objective bilirubin measurements in patients with suspected jaundice, as the threshold of 2.5–3 mg/dL represents significant hyperbilirubinemia requiring diagnostic evaluation. 1, 2
Do not assume mild jaundice is benign—even bilirubin levels of 3–5 mg/dL can indicate serious conditions such as biliary obstruction, drug-induced liver injury, or hemolytic anemia requiring urgent intervention. 4, 6, 3