What is the differential diagnosis for a new blanchable rash involving the trunk but sparing the arms in an otherwise healthy adult?

Differential Diagnosis for Blanchable Truncal Rash Sparing Arms

The most likely diagnosis is a viral exanthem, particularly enteroviral infection, which characteristically presents with trunk and extremity involvement while sparing the arms, palms, soles, face, and scalp. 1

Immediate Life-Threatening Conditions to Exclude First

Before considering benign causes, you must rule out Rocky Mountain Spotted Fever (RMSF), which carries a 5-10% mortality rate and requires immediate empiric doxycycline 100 mg twice daily without waiting for laboratory confirmation. 1 However, several features make RMSF less likely in your case:

• RMSF typically begins on ankles, wrists, or forearms 2-4 days after fever onset, then spreads centripetally to trunk while involving palms and soles—the opposite pattern of arm-sparing. 1
• Fever is present in virtually all RMSF cases. 1
• Only 50% of patients have rash in the first 3 days, and up to 20% never develop a rash at all. 1

If fever, headache, or tick exposure are present, initiate doxycycline immediately—do not wait for laboratory confirmation. 1, 2 Critical red flags requiring immediate treatment include thrombocytopenia or hyponatremia on labs. 1

Most Likely Diagnoses (Benign)

Viral Exanthems

Enteroviral infections are the most common cause of maculopapular rashes and characteristically spare palms, soles, face, and scalp—consistent with arm-sparing. 1, 3

Additional viral considerations:

• Human herpesvirus 6 (roseola) presents with macular rash following high fever, though more common in children. 1
• Epstein-Barr virus causes maculopapular rash, especially if the patient received ampicillin or amoxicillin. 1, 3
• Parvovirus B19 presents with "slapped cheek" appearance on face with possible truncal involvement. 1

Drug Eruptions

Drug hypersensitivity reactions present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches, and are the leading differential for blanchable rash in the absence of fever. 3

• Query about any new medications within the past 2-3 weeks, particularly antibiotics, NSAIDs, or anticonvulsants. 3
• Drug-induced urticaria is most commonly caused by penicillins, sulfonamides, and nonsteroidal anti-inflammatory drugs, occurring within 24 hours of drug ingestion. 4
• Up to 40% of patients may not recall or report new medications, so probe carefully. 3

Less Common but Important Considerations

Kawasaki Disease (Pediatric Patients)

If the patient is a child with fever ≥5 days, consider Kawasaki disease, which causes coronary artery aneurysms if untreated. 1, 2

• The rash is typically truncal with accentuation in the perineal/groin region where early desquamation may occur. 5
• Diagnostic criteria require fever ≥5 days plus 4 of 5 features: bilateral conjunctival injection, oral mucosal changes, cervical lymphadenopathy ≥1.5 cm, extremity changes, and polymorphous rash. 5, 1

Human Monocytic Ehrlichiosis

HME rash occurs in only approximately 30% of adults and appears later in disease course (median 5 days after onset), rarely involving palms and soles. 1

• HME carries a 3% case-fatality rate. 1
• Rash varies from petechial or maculopapular to diffuse erythema. 1

Diagnostic Workup

Obtain complete blood count with differential to evaluate for thrombocytopenia, leukopenia, or eosinophilia. 1, 3

Obtain comprehensive metabolic panel looking for hyponatremia and elevated hepatic transaminases, which are present in up to 94% and 53% of RMSF/ehrlichiosis cases respectively. 1

If RMSF or ehrlichiosis is suspected, obtain acute serology for Rickettsia rickettsii, Ehrlichia chaffeensis, and Anaplasma phagocytophilum immediately. 1

Critical Pitfalls to Avoid

The absence of fever does not exclude viral exanthems, as fever may have resolved or been mild. 3

Up to 40% of RMSF patients report no tick bite history, so do not exclude RMSF based solely on absence of recalled tick exposure. 1, 2

In darker-skinned patients, blanchable rashes may be difficult to recognize, increasing risk of delayed diagnosis. 3

Management Based on Most Likely Diagnosis

If viral exanthem is suspected, provide supportive care with antihistamines for pruritus and monitor for development of classic viral syndrome features. 3

If drug reaction is suspected, discontinue the offending agent immediately and provide symptomatic treatment with antihistamines. 3

Red flags requiring immediate re-evaluation include development of fever, progression to purpura or ecchymoses, development of systemic symptoms, and involvement of palms and soles. 3

If clinical response to doxycycline is delayed in a treated patient, consider coinfection with Borrelia burgdorferi or Babesia microti in appropriate epidemiologic settings. 1