How should I treat a previously healthy adult presenting with acute fever, headache, maculopapular rash and a necrotic eschar after recent outdoor exposure in a scrub‑typhus endemic area?

Treatment of Scrub Typhus in Previously Healthy Adults

Initiate doxycycline 100 mg orally or intravenously twice daily immediately upon clinical suspicion—do not wait for laboratory confirmation, as delayed treatment increases mortality to 4%. 1

Immediate Empiric Treatment

• Start doxycycline immediately when a patient presents with fever, headache, maculopapular rash, and eschar after outdoor exposure in an endemic area, even before diagnostic confirmation. 1
• The standard adult dose is doxycycline 100 mg twice daily (oral or IV), which is FDA-approved for rickettsial diseases including scrub typhus. 2
• Doxycycline is the drug of choice for all ages, including children under 8 years (at 2.2 mg/kg body weight twice daily for those under 45 kg). 1
• Expect fever to resolve within 24–48 hours after starting doxycycline in early disease; this rapid defervescence is characteristic and helps confirm the diagnosis. 1

Alternative Antibiotic Options

• Chloramphenicol (12.5–25 mg/kg every 6 hours IV) can be used as an alternative agent, though doxycycline remains first-line. 1
• Azithromycin may be considered for mild cases, but supporting evidence is limited compared to doxycycline. 1

Diagnostic Workup (Do Not Delay Treatment)

While treatment should never be delayed, obtain the following tests to support diagnosis:

• Serological testing is the primary diagnostic method, with paired serum samples 2–4 weeks apart showing ≥4-fold antibody titer rise providing definitive confirmation. 1
• Complete blood count with differential (looking for thrombocytopenia, leukocytosis). 1
• Comprehensive metabolic panel (checking for hyponatremia, elevated liver transaminases). 1
• Blood cultures before initiating therapy when feasible. 1

Clinical Presentation Recognition

Key features that should trigger immediate doxycycline therapy:

• Eschar: A painless necrotic lesion with black crust and surrounding erythema at the chigger bite site—present in only 60% of cases, so its absence does not exclude scrub typhus. 1
• Fever is the most consistent symptom, typically beginning 6–10 days after the chigger bite. 1
• Maculopapular rash on trunk and extremities, though this may be absent or subtle. 1
• Headache, myalgia, and malaise are common accompanying symptoms. 1
• Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain) occur frequently. 1
• Respiratory symptoms including cough and pneumonia occur in up to 28% of cases. 1

Reassessment if No Response

If fever persists beyond 48 hours after starting doxycycline, reassess the diagnosis and consider:

• Alternative or co-infecting pathogens such as malaria, dengue, enteric fever, or leptospirosis. 1
• Severely ill patients with multi-organ dysfunction may require >48 hours before clinical improvement. 1
• Consider hospitalization for patients showing evidence of organ dysfunction. 1

Potential Complications Requiring Monitoring

• Central nervous system involvement (meningitis/meningoencephalitis) occurs in approximately 20% of patients. 1
• Pulmonary complications including pneumonitis (up to 36%) and ARDS (15%) are common. 1
• Acute renal failure develops in 9% of cases and may require renal replacement therapy. 1
• Cardiovascular complications including myocarditis, pericarditis, and arrhythmias (including atrial fibrillation) can occur. 3
• Hemorrhagic complications may develop even without typical skin lesions. 4
• Septic shock with multi-organ failure represents the most severe presentation. 5

Critical Pitfalls to Avoid

• Never delay doxycycline while awaiting serologic confirmation—mortality increases significantly with treatment delay, and the dramatic response to therapy within 24–48 hours serves as a diagnostic clue. 1, 6
• Do not exclude scrub typhus based on absence of eschar—it is present in only 60% of confirmed cases. 1
• Avoid relying on Weil-Felix testing, which has poor sensitivity despite good specificity; IgM ELISA or microimmunofluorescence assays are superior when available. 6
• Do not dismiss the diagnosis in areas not traditionally considered endemic—scrub typhus is expanding beyond the historical "Tsutsugamushi Triangle" and is now recognized globally. 7
• Children aged <10 years have higher mortality risk if treatment is delayed, making early empiric therapy even more critical in pediatric cases. 1

Supportive Care Considerations

• Careful fluid management is essential—avoid overhydration as pulmonary complications occur in up to 36% of cases. 1
• Patients with multi-organ failure require hospitalization and intensive monitoring. 1
• Outcome is primarily determined by severity of illness at presentation and adequacy of supportive care. 1