What is the best course of action for a patient presenting with a rash on both legs, headaches, and joint pain, with laboratory results showing leukopenia (low white blood cell count), normal hemoglobin and platelet counts, and slightly elevated lymphocytes, and normal urinalysis, electrolytes, and liver function?

Empiric Treatment for Tickborne Rickettsial Disease

Start doxycycline 100 mg orally twice daily immediately without waiting for confirmatory testing, as this presentation is highly concerning for a tickborne rickettsial disease (ehrlichiosis or anaplasmosis), and delay in treatment significantly increases morbidity and mortality. 1, 2

Critical Diagnostic Features Present

Your patient's constellation of findings is classic for tickborne rickettsial disease:

• Leukopenia with relative lymphocytosis - This combination is particularly suggestive of ehrlichiosis (HME) or anaplasmosis (HGA), occurring in up to 53% and 94% of patients respectively 1
• Rash on both legs - While rash occurs frequently in Rocky Mountain spotted fever and occasionally in ehrlichiosis, it is rare in anaplasmosis 1
• Headache and joint pain - These are cardinal features of all tickborne rickettsial diseases 1
• Normal platelets - Note that thrombocytopenia occurs in up to 94% of ehrlichiosis/anaplasmosis cases, but its absence does NOT exclude the diagnosis 1

Why Immediate Treatment is Critical

• Up to 50% of Rocky Mountain spotted fever deaths occur within 9 days of illness onset 1
• Early serologic testing is typically negative - IgM and IgG antibodies are not detectable before the second week of illness, so waiting for laboratory confirmation will delay life-saving treatment 1, 2
• Most patients (up to 40%) do not recall a tick bite, so absence of tick exposure history should never exclude this diagnosis 1, 2
• Standard broad-spectrum antibiotics are ineffective - Penicillins, cephalosporins, aminoglycosides, erythromycin, and sulfa drugs do not treat rickettsial diseases 1

Essential Next Steps

Obtain blood smear examination immediately - Look for morulae (intracellular inclusions) in leukocytes, though these are only visible in 1-20% of ehrlichiosis cases and their absence does not rule out disease 1, 2

Send serologic testing and PCR - Order acute phase serology for Ehrlichia chaffeensis and Anaplasma phagocytophilum, but do NOT wait for results before starting treatment 1, 2

Obtain detailed exposure history:

• Recent outdoor activities in wooded or grassy areas 2
• Geographic location and season (primarily April-September for tick activity) 1
• Pet exposure or contact with animals 1

Monitoring and Follow-up

• Reassess within 24-48 hours - If the patient fails to improve or worsens on doxycycline, consider coinfection with Borrelia burgdorferi (Lyme disease) or Babesia microti, as the same tick vector transmits multiple pathogens 1
• Watch for complications - Severe manifestations can include meningoencephalitis, acute respiratory distress syndrome, and multiorgan failure, particularly in immunocompromised patients 1
• Obtain convalescent serology - Repeat serologic testing 2-4 weeks after acute illness to confirm diagnosis retrospectively 1

Common Pitfalls to Avoid

• Never delay doxycycline while awaiting laboratory confirmation - Treatment decisions must be based on clinical findings, not serology 2
• Do not assume viral etiology based on "normal" labs - Leukopenia with lymphocytosis in the setting of rash, headache, and joint pain should trigger immediate empiric treatment 1, 2
• Do not exclude rickettsial disease based on geography - While more common in south central and south Atlantic states, these diseases should be considered endemic throughout the contiguous United States 1