What is the likely diagnosis for a patient with fever, rash on the trunk, relative bradycardia, splenomegaly, hepatomegaly, diarrhea, and a positive Widal test?

Differential Diagnosis: Typhoid Fever is the Primary Diagnosis

Based on this clinical constellation—5 days of continuous fever, trunk rash, relative bradycardia, hepatosplenomegaly, diarrhea, and positive Widal test—typhoid fever (enteric fever caused by Salmonella typhi) is the most likely diagnosis. 1, 2, 3

Primary Diagnosis: Typhoid Fever

The clinical presentation matches the classic CDC case definition for typhoid fever, which describes sustained fever, headache, malaise, anorexia, relative bradycardia, and either constipation or diarrhea. 1, 3 This patient demonstrates the pathognomonic triad that strongly suggests typhoid:

• Relative bradycardia with fever is a highly characteristic finding, with likelihood ratios of 5.9-10 for typhoid fever when splenomegaly is present. 1, 4
• Hepatosplenomegaly occurs commonly in typhoid fever, with splenomegaly present in 13-57% of cases and serving as a strong predictor (LR+ 5.9-10). 1, 5, 6
• Trunk rash may represent rose spots, which occur in 5-30% of typhoid cases, though this classic finding is often absent in modern presentations. 5, 6
• Diarrhea is present in 33% of typhoid cases, though constipation is equally common. 1, 5, 6

Critical Diagnostic Considerations

Widal Test Limitations

The positive Widal test supports but does NOT confirm the diagnosis—blood culture is mandatory for definitive diagnosis. 1, 7 The CDC explicitly states that serologic evidence alone is insufficient, as the Widal test has poor sensitivity and specificity, particularly in endemic areas where background antibody levels are elevated. 7 False positives occur with prior vaccination, previous typhoid infection, or cross-reactions with other Salmonella species. 7

Required Confirmatory Testing

• Blood cultures (2-3 sets of 20 mL each) must be obtained immediately before starting antibiotics, as this has 80% sensitivity and is the gold standard for diagnosis. 1, 2, 3
• Blood culture yield is highest in the first week of symptoms (this patient is at day 5). 3, 7

Alternative Diagnoses to Consider

While typhoid fever is most likely, the differential diagnosis includes:

Malaria

• Must be excluded urgently in any febrile traveler from tropical regions, as it can present with fever, splenomegaly, and hepatomegaly. 1, 8
• Three thick blood films over 72 hours are required to exclude malaria with confidence. 1
• However, relative bradycardia is NOT typical of malaria, making typhoid more likely. 8

Dengue Fever

• Can present with fever, rash, hepatosplenomegaly, and thrombocytopenia. 1
• More common in travelers from Asia (LR+ 2-8 for Asian travel). 1
• Typically causes leucopenia and thrombocytopenia rather than the pattern seen in typhoid. 1

Rickettsial Infections (Typhus)

• Can present with fever, rash, and hepatosplenomegaly. 9
• Skin rash has LR+ of 3.8 for rickettsioses, and skin ulcer/eschar has LR+ of 11.1. 1
• Co-infection with typhoid has been reported. 9

Leptospirosis

• Presents with fever, hepatosplenomegaly, and can cause relative bradycardia. 1
• More likely with history of freshwater exposure. 1
• Typically causes proteinuria and hematuria on urinalysis. 1

Amoebic Liver Abscess

• Can cause fever, hepatomegaly, and right upper quadrant pain. 1
• Ultrasound would show liver lesion. 1
• Less likely without localized abdominal pain. 1

Immediate Management Algorithm

Step 1: Obtain Diagnostic Studies BEFORE Antibiotics

• Blood cultures (2-3 sets) immediately. 2
• Malaria thick films and rapid diagnostic test (three over 72 hours). 1
• Complete blood count (expect possible leukopenia, lymphopenia, or thrombocytopenia). 1, 3
• Liver function tests (95% of typhoid patients have elevated transaminases). 5
• Stool culture if diarrhea persists. 1

Step 2: Initiate Empiric Antibiotic Therapy

For severe presentation with documented fever ≥38.5°C and clinical features of sepsis, start IV ceftriaxone 2-4 g daily immediately after cultures. 2, 3 This is critical because:

• Intestinal perforation can occur in the third week if untreated. 3
• Encephalopathy and septic shock are life-threatening complications. 3, 8

For uncomplicated cases from South/Southeast Asia (high fluoroquinolone resistance), use azithromycin 500 mg daily for 7-14 days. 2

Step 3: Supportive Care and Monitoring

• Serial neurologic examinations to detect encephalopathy (occurs in 10-15% of cases). 2
• Contact precautions with gloves, gowns, and hand hygiene. 2
• Monitor for complications: intestinal perforation, gastrointestinal bleeding, septic shock. 3

Step 4: Public Health Notification

• Typhoid fever is a nationally notifiable disease—report immediately to local/state health department. 2
• Submit isolates for antimicrobial susceptibility testing and molecular typing. 2

Common Pitfalls to Avoid

• Do not rely on Widal test alone—it has poor diagnostic accuracy and requires blood culture confirmation. 1, 7
• Do not miss malaria—it can be fatal and must be excluded in all febrile travelers from tropical regions. 1, 8
• Do not delay antibiotics in severe cases—waiting for culture results can lead to perforation or death. 2, 3
• Do not assume classic "step-ladder" fever pattern—it is not reliably present in modern cases. 3
• Do not overlook travel history—typhoid is most common in travelers from South/Southeast Asia. 1, 3, 4