What causes jaundice (yellowing of the skin) aside from hyperbilirubinemia (elevated bilirubin levels)?

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From the Guidelines

Yellowing of the skin can be caused by several factors besides bilirubin, including carotenemia, certain medications, uremia, liver diseases, genetic disorders, and external factors. These conditions can lead to a yellowish discoloration of the skin, which may be similar to jaundice but can be distinguished by the absence of yellowing in the whites of the eyes. Some of the key factors that can cause yellowing of the skin besides bilirubin include:

  • Carotenemia, a condition resulting from excessive consumption of carotene-rich foods like carrots, sweet potatoes, and squash, which can turn the skin yellow-orange, particularly on the palms, soles, and face 1
  • Certain medications such as quinacrine, chloroquine, and phenothiazines, which may cause yellow skin discoloration as a side effect 1
  • Medical conditions like uremia (kidney failure), which can lead to a yellowish-gray skin tone due to the buildup of urochrome pigments 1
  • Liver diseases not directly related to bilirubin elevation, such as primary biliary cholangitis, which can cause jaundice-like yellowing 1
  • Rare genetic disorders like Dubin-Johnson syndrome, which can affect pigmentation 1
  • External factors including excessive turmeric consumption or application of saffron-based products, which can temporarily stain the skin yellow 1 It's essential to seek medical evaluation to determine the underlying cause of unexplained yellowing of the skin, as it can be a symptom of an underlying condition that requires treatment.

From the FDA Drug Label

Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces will occur, and its intensity is proportional to the amount ingested. The FDA drug label does not answer the question.

From the Research

Causes of Yellowing of Skin

Besides bilirubin, there are several other factors that can cause yellowing of the skin, including:

  • Hemolysis, which leads to elevated levels of unconjugated (indirect) bilirubin 2
  • Hematoma resorption, which also leads to elevated levels of unconjugated (indirect) bilirubin 2
  • Intrahepatic disorders, such as alcohol, infectious hepatitis, drug reactions, and autoimmune disorders, which can lead to unconjugated or conjugated hyperbilirubinemia 2
  • Posthepatic disorders, such as gallstone formation, biliary tract infection, pancreatitis, and malignancies, which can cause conjugated hyperbilirubinemia 2
  • Alcoholic liver disease, biliary strictures, choledocholithiasis, drug-induced liver injury, and hepatitis, which can also cause jaundice 3

Diagnostic Approach

To determine the underlying cause of yellowing of the skin, a comprehensive medical history, review of systems, and physical examination are essential 3. Initial laboratory evaluation should include assays for bilirubin (total and fractionated), a complete blood cell count, aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline phosphatase, albumin, prothrombin time, and international normalized ratio 3. Imaging modalities such as ultrasonography of the abdomen, computed tomography with intravenous contrast media, and magnetic resonance cholangiopancreatography may also be necessary to determine the underlying cause of jaundice 3.

Laboratory and Imaging Modalities

Laboratory and imaging modalities are crucial in evaluating patients with jaundice, as they can help differentiate between various causes of hyperbilirubinemia 4, 5, 2, 3. A stepwise approach to evaluation can be cost and time saving, as well as a framework to improve patient outcomes 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Jaundice in the adult patient.

American family physician, 2004

Research

Evaluation of Jaundice in Adults.

American family physician, 2025

Research

A Systematic Approach to Patients with Jaundice.

Seminars in interventional radiology, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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