What could be causing a patient's complaint of everything looking yellow, considering potential underlying conditions such as liver disease, pancreatic disease, or medication side effects, including antibiotics like rifampicin or antipsychotics like quetiapine?

Yellow Vision (Xanthopsia): Diagnostic Approach and Management

The most critical first step is to determine whether this represents true xanthopsia (yellow vision from ocular toxicity) versus jaundice causing yellow-tinted perception, by immediately examining the sclera and skin for icterus and checking ethambutol exposure, as ethambutol-induced optic neuritis is the most common medication-related cause of yellow vision and requires immediate drug discontinuation to prevent permanent vision loss. 1

Immediate Assessment Required

Distinguish Between Two Primary Mechanisms

Optic nerve toxicity (true xanthopsia):

• Ethambutol causes retrobulbar neuritis manifesting as decreased visual acuity or decreased red-green color discrimination, with yellow vision being a presenting symptom 1
• This is dose-related with minimal risk at 15 mg/kg daily, but risk increases substantially above 30 mg/kg daily 1
• Discontinue ethambutol immediately with any subjective visual loss 1
• Perform immediate red/green color discrimination testing and visual acuity assessment 1
• Arrange urgent ophthalmology evaluation 1

Hyperbilirubinemia (perceived yellow tint):

• Examine sclera and skin for jaundice 2, 3
• Yellow discoloration of vision can occur when severe hyperbilirubinemia causes bilirubin deposition affecting visual perception 4
• Obtain fractionated bilirubin (direct and indirect) immediately to determine conjugated versus unconjugated pattern 2, 3

Medication-Induced Causes to Evaluate

Rifamycins (Rifampin/Rifabutin)

These drugs universally cause orange discoloration of bodily fluids including tears, which can create a yellow-orange visual tint 1

• This is an expected, benign effect that does not require drug discontinuation 1
• Warn patients this will occur and is not harmful 1, 5
• However, rifampin can cause hepatotoxicity (2.7% when combined with isoniazid), leading to jaundice 1, 6
• Check ALT, AST, alkaline phosphatase, and total bilirubin if hepatotoxicity suspected 1, 6

Antipsychotics (Quetiapine, Risperidone)

• Quetiapine has been associated with fulminant hepatic failure causing jaundice and yellow discoloration of sclera 7
• Risperidone can cause hepatocellular damage with AST up to 283 IU/L and ALT up to 778 IU/L 8
• Atypical antipsychotics commonly cause asymptomatic liver enzyme elevations (27.2% in first month) but rarely cause severe hepatotoxicity 9
• Immediately discontinue the antipsychotic if ALT >3× baseline with bilirubin >2× ULN 1

Diagnostic Algorithm

Step 1: Physical Examination (Perform Immediately)

• Inspect sclera and skin for icterus 2, 3
• Check for hepatomegaly and right upper quadrant tenderness 2
• Assess for signs of chronic liver disease 2

Step 2: Laboratory Testing (Obtain Within Hours)

• Complete hepatic panel: ALT, AST, alkaline phosphatase, GGT, albumin, PT/INR 2, 6, 3
• Fractionated bilirubin: Direct and indirect to determine conjugated versus unconjugated pattern 2, 3
• Complete blood count with differential: To assess for hemolysis or infection 2
• Calculate R value: R = (ALT/ULN)/(ALP/ULN) to determine injury pattern 1, 6

Step 3: Ophthalmologic Assessment (If on Ethambutol)

• Immediate visual acuity testing 1
• Red-green color discrimination testing 1
• Urgent ophthalmology referral if any abnormality detected 1

Step 4: Imaging (If Hepatobiliary Pathology Suspected)

• Right upper quadrant ultrasound with Doppler as first-line imaging 2
• CT abdomen with IV contrast if ultrasound inadequate or abscess suspected 2
• MRCP if cholestatic pattern without obvious obstruction 2

Management Based on Etiology

If Ethambutol-Induced Optic Neuritis

Discontinue ethambutol immediately—this is non-negotiable 1

• Peripheral neuropathy from ethambutol is rare but optic neuritis is the primary concern 1
• Recovery of vision depends on early recognition and immediate cessation 1

If Rifamycin-Related (Benign Discoloration)

• Reassure patient this is expected and harmless 1, 5
• Continue medication unless hepatotoxicity develops 1
• Monitor liver enzymes if combined with isoniazid 1, 5

If Drug-Induced Hepatotoxicity

Stop the offending medication immediately if ALT >3× ULN with bilirubin >2× ULN (Hy's Law) 6

• Repeat liver function tests within 2-5 days for hepatocellular pattern 1
• Repeat within 7-10 days for cholestatic pattern 1
• Provide supportive care; most cases resolve with drug withdrawal 7, 8

If Cholestatic Liver Disease

• Urgent ERCP within 24-48 hours if ascending cholangitis suspected 2
• Broad-spectrum antibiotics (ceftriaxone and metronidazole) for systemic inflammatory response 2

Critical Pitfalls to Avoid

• Never continue ethambutol if patient reports visual changes—permanent vision loss can occur 1
• Do not dismiss rifampin's orange tears as the sole cause without checking liver function—rifampin causes both benign discoloration AND hepatotoxicity 1, 6, 5
• Do not assume yellow vision equals jaundice—true xanthopsia from optic nerve toxicity requires different management than hyperbilirubinemia 1, 2
• Do not delay imaging in patients with fever, right upper quadrant pain, and jaundice—acute cholangitis can rapidly progress to septic shock 2
• Do not overlook quetiapine as a cause of fulminant hepatic failure—it is rare but life-threatening 7

Monitoring Strategy

• If ethambutol continued at appropriate doses, perform monthly red-green color discrimination and visual acuity testing 1
• If on rifampin plus isoniazid, monitor liver enzymes at baseline and periodically, especially in first 3 months 1
• If on atypical antipsychotics, obtain baseline liver function tests and monitor at 1 month and 6 months 9
• Repeat liver function tests within 2-3 days if bilirubin ≥2× ULN or ALT/AST >3× ULN 1, 2