Does typhoid fever cause icterus (jaundice)?

Does Typhoid Fever Cause Jaundice?

Yes, typhoid fever can cause jaundice, occurring in approximately 12-37% of cases, though it is not a typical presenting feature and indicates more severe hepatic involvement with worse clinical outcomes.

Epidemiology and Clinical Significance

• Jaundice occurs in 12.2% to 36.8% of typhoid fever patients, representing a clinically significant complication that indicates more severe hepatic injury 1, 2
• When jaundice develops, fever typically precedes the appearance of icterus by 8-27 days, distinguishing it from acute viral hepatitis where jaundice appears earlier in the disease course 1
• Mortality is higher in icteric typhoid patients (19.4%) compared to non-icteric patients (12.1%), though with appropriate antibiotic therapy, complete recovery is expected 1, 2

Clinical Presentation and Diagnostic Features

Key Physical Findings

• Hepatosplenomegaly occurs in 87.1% of jaundiced typhoid patients, making this a critical physical examination finding 1
• Right upper quadrant tenderness and upper abdominal pain are significantly more common in icteric versus anicteric typhoid patients 2
• Confusion and altered mental status occur more frequently when jaundice is present 2

Laboratory Pattern

• Mixed hepatocellular and cholestatic pattern with elevated conjugated bilirubin (mean 95 μmol/L, range 31-150 μmol/L) 1, 3
• Serum transaminases are moderately elevated: AST mean 180 IU/L, ALT mean 105 IU/L (range 100-620 IU/L in children) 1, 4
• Alkaline phosphatase elevation (mean 136 IU) indicates cholestatic component 1
• Lower serum albumin and total protein in icteric patients compared to anicteric patients 2
• Low prothrombin index is significantly associated with jaundiced typhoid patients 2

Critical Differential Diagnosis

The ACIP guidelines emphasize that typhoid fever must be differentiated from other tropical causes of fever with jaundice, including viral hepatitis, malaria, leptospirosis, yellow fever, and Q fever 5

Distinguishing Typhoid from Other Tropical Causes

According to Praxis Medical Insights, when evaluating tropical infections causing jaundice:

• Enteric fever (typhoid) is the most common serious tropical disease requiring treatment in travelers from Asia after malaria is excluded, accounting for 3-17% of febrile jaundice cases in Asian returnees 6
• Malaria must be excluded first with three thick films/rapid diagnostic tests over 72 hours, as it accounts for 28-47% of febrile jaundice in African returnees 6
• Leptospirosis presents with proteinuria and hematuria on urinalysis, which are not typical of typhoid hepatitis 6
• Rickettsial infections show relatively low AST/ALT elevation despite jaundice, whereas typhoid shows moderate transaminase elevation 6

Key Differentiating Features

• Prolonged fever (8-27 days) before jaundice onset favors typhoid over acute viral hepatitis 1
• Hepatosplenomegaly with tender hepatomegaly is characteristic of typhoid hepatitis 1, 4
• Blood culture positive for Salmonella typhi confirms diagnosis, though bone marrow culture has higher sensitivity 1, 3, 7
• Abdominal ultrasound shows normal biliary system (unlike obstructive causes), but may reveal mesenteric lymphadenopathy and terminal ileum thickening 3

Clinical Implications and Complications

• Jaundice in typhoid indicates more severe hepatic injury and predicts higher risk of complications 2
• Glomerulonephritis occurs significantly more frequently in icteric typhoid patients 2
• Acute liver failure is exceptionally rare but life-threatening, requiring intensive care and may necessitate consideration for liver transplantation 3
• Female gender is associated with higher rates of jaundice in typhoid fever 2

Management Approach

Immediate Actions

• Initiate empiric fluoroquinolone therapy (or ceftriaxone/azithromycin as alternatives) even before blood culture results are available when typhoid hepatitis is suspected 1, 7
• Obtain blood cultures before antibiotics (two sets), as this confirms diagnosis 6, 3
• Perform abdominal ultrasound to exclude biliary obstruction and evaluate for hepatosplenomegaly 6, 3

Laboratory Workup

• Complete blood count, fractionated bilirubin, AST, ALT, alkaline phosphatase, prothrombin time, albumin 6, 1, 2
• Urinalysis to exclude leptospirosis (proteinuria/hematuria absent in typhoid) 6
• Three malaria thick films over 72 hours to exclude malaria in endemic areas 6

Antibiotic Selection

• Fluoroquinolones are first-line empiric therapy for typhoid fever 7
• Ceftriaxone or meropenem for severe cases or multidrug-resistant strains 3, 7
• Azithromycin is an alternative when fluoroquinolones are contraindicated 7
• Complete 2 weeks of appropriate antibiotic therapy with clinical and microbiologic monitoring 3

Common Pitfalls to Avoid

• Don't assume viral hepatitis based solely on jaundice and fever—the prolonged fever duration (8-27 days) before jaundice onset distinguishes typhoid 1
• Don't delay antibiotics waiting for culture results when clinical suspicion is high, as early treatment prevents progression to liver failure 1, 3
• Don't miss multidrug-resistant typhoid, which is increasingly common and requires broader-spectrum antibiotics like ceftriaxone or meropenem 3, 7
• Don't overlook travel history—most U.S. cases occur in returning travelers from the Indian subcontinent, Africa, Asia, or Latin America 7
• Don't forget that classic typhoid findings (rose spots, relative bradycardia, stepwise fevers) are frequently absent, especially when jaundice is present 7