What is the cause of a 3-day history of fever, myalgia, nausea, and a maculopapular rash that began on the wrists and ankles and spread to the hands, particularly the palms, in a patient with leukopenia, anemia, thrombocytopenia, hyponatremia, hypochloremia, and elevated liver enzymes, who lives in [STATE]?

Rocky Mountain Spotted Fever (RMSF)

This patient has Rocky Mountain Spotted Fever until proven otherwise, and doxycycline must be initiated immediately without waiting for laboratory confirmation. The combination of fever, myalgia, nausea, maculopapular rash beginning on wrists/ankles and spreading to palms, along with leukopenia, thrombocytopenia, hyponatremia, and elevated transaminases creates a classic presentation that demands urgent empiric treatment. 1, 2

Critical Clinical Features Supporting RMSF

The presentation matches the CDC's established criteria for RMSF with remarkable precision:

• Rash pattern: The maculopapular rash appearing 2-4 days after fever onset, starting on wrists and ankles before spreading to palms, is pathognomonic for RMSF when present. 1 This centripetal progression distinguishes RMSF from most viral exanthems, which spare palms and soles. 3

• Laboratory constellation: The triad of thrombocytopenia (platelets 90,000), hyponatremia (sodium 128), and elevated hepatic transaminases (AST 80, ALT 120) occurs in the majority of RMSF patients. 1 The leukopenia (WBC 3,000) further supports a tickborne rickettsial disease rather than a typical bacterial infection. 1

• Timeline: The 3-day history fits the typical incubation period of 3-12 days for RMSF. 1

Why This Cannot Wait

Mortality increases dramatically with each day of delayed treatment—50% of RMSF deaths occur within 9 days of illness onset, and the case-fatality rate is 5-10% overall. 1, 2 Lack of rash or late-onset rash is associated with delays in diagnosis and increased mortality. 1 Approximately 40% of patients report no tick bite history, so absence of recalled tick exposure does not exclude RMSF. 2, 4

Differential Diagnosis Considerations

While RMSF is the primary concern, other diagnoses warrant brief consideration:

• Ehrlichiosis (E. chaffeensis): Presents with similar laboratory findings (leukopenia, thrombocytopenia, elevated transaminases, hyponatremia) but rash occurs in only 30% of adults and appears later (median 5 days after onset), rarely involving palms and soles. 1, 3 The prominent early rash with palm involvement makes this less likely.

• Meningococcemia: Can present with petechial rash and systemic toxicity, but progresses more rapidly than RMSF and typically shows a different rash distribution pattern. 1, 2

• Secondary syphilis: Can cause palmar/plantar rash but lacks the acute febrile presentation and laboratory abnormalities seen here. 4

Immediate Management Algorithm

Step 1: Initiate doxycycline 100 mg orally or intravenously twice daily immediately—do not wait for serologic confirmation. 1, 2, 4

Step 2: Obtain diagnostic studies without delaying treatment:

• Complete blood count with differential (looking for thrombocytopenia, leukopenia, increased immature bands) 1
• Comprehensive metabolic panel (confirming hyponatremia, elevated transaminases) 1
• Acute serology for Rickettsia rickettsii (though initial serology is often negative) 1
• Peripheral blood smear examination 1

Step 3: Continue doxycycline for at least 3 days after fever subsides and until evidence of clinical improvement, typically 5-7 days total. 4

Step 4: Monitor for clinical response within 24-48 hours. 3 Expect defervescence and clinical improvement if RMSF is the correct diagnosis.

Critical Pitfalls to Avoid

• Do not exclude RMSF based on geography alone—while more common in south central and south Atlantic states, RMSF should be considered endemic throughout the contiguous United States. 1

• Do not wait for the classic triad of fever, rash, and tick bite—this is present in only a minority of patients at initial presentation. 2

• Do not use broad-spectrum antibiotics like penicillins, cephalosporins, aminoglycosides, or sulfa-containing drugs, as these are ineffective against rickettsiae. 1

• Do not delay treatment in children <8 years old due to concerns about doxycycline—the mortality risk of untreated RMSF far outweighs the minimal risk of dental staining from a short course. 2

Expected Clinical Course

If RMSF is correctly diagnosed and treated, clinical improvement should occur within 24-48 hours of initiating doxycycline. 3 Failure to improve should prompt consideration of alternative diagnoses or complications such as meningoencephalitis, acute renal failure, ARDS, or shock. 1 Severe manifestations are more common in immunosuppressed patients, elderly (≥60 years), and children <10 years. 3