What is the differential diagnosis for a 23-year-old active duty male with a macular rash on the back, chest, arms, and legs, sparing the scalp, face, feet, and hands?

Differential Diagnosis for Macular Rash Sparing Palms, Soles, Face, and Scalp in a 23-Year-Old Active Duty Male

The most likely diagnoses in this young active duty male with a macular rash distributed on the trunk and extremities while sparing the palms, soles, face, and scalp are viral exanthems (particularly enteroviral infections, EBV, or HHV-6), drug hypersensitivity reactions, and pityriasis rosea, with secondary syphilis being less likely given the distribution pattern. 1, 2

Primary Differential Considerations

Viral Exanthems (Most Likely)

• Enteroviral infections (coxsackievirus, echovirus) commonly cause maculopapular rashes with generalized distribution that typically spare palms and soles 1, 3, 2
• Human herpesvirus 6 (roseola) can present with macular rash following high fever, though more common in children, it occurs in nearly 100% of the population by age 3 and can reactivate 2
• Epstein-Barr virus infection presents with maculopapular rash, particularly if the patient received antibiotics (ampicillin/amoxicillin) 1
• Parvovirus B19 should be considered, presenting with "slapped cheek" appearance on face but can have truncal involvement 1

Drug Hypersensitivity Reactions

• Nonspecific drug eruptions present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches 4
• Query specifically about recent antibiotic use, NSAIDs, anticonvulsants, or any new medications within the past 2-3 weeks 1
• Drug reactions typically show symmetric distribution on trunk and extremities, sparing palms/soles initially 1, 4

Tickborne Rickettsial Diseases (Critical to Exclude)

• Rocky Mountain Spotted Fever (RMSF) initially presents as small blanching pink macules on extremities 2-4 days after fever onset 1, 4
• The classic palm/sole involvement occurs LATE (day 5-6) and only in 50% of cases, so early RMSF can present with the distribution described 1, 4
• Human Monocytic Ehrlichiosis (HME) causes rash in only one-third of adults (up to 66% in children), varying from maculopapular to diffuse erythema, rarely involving palms/soles 1
• Critical point: Up to 20% of RMSF cases have absent or atypical rash 1, 4

Secondary Syphilis

• Less likely given the distribution, as secondary syphilis classically involves palms and soles 1, 5
• However, can present with maculopapular rash on trunk before palm/sole involvement develops 5
• Must obtain sexual history and consider if patient has had recent high-risk exposures 5

Other Infectious Causes

• Mycoplasma pneumoniae infection can cause maculopapular rash with respiratory symptoms 1
• Disseminated gonococcal infection presents with sparse pustular or petechial lesions, typically with arthritis 1
• Leptospirosis should be considered if environmental exposures to contaminated water 1

Key Historical Features to Obtain

Timing and Progression

• Duration of rash and relationship to fever onset (viral exanthems typically show rash after fever resolves; RMSF shows rash 2-4 days after fever begins) 1, 2, 4
• Rate of progression (meningococcemia progresses rapidly; viral exanthems progress slowly) 3

Exposure History

• Tick exposure or outdoor activities in past 14 days, particularly in endemic areas (southeastern and south-central United States for RMSF) 1
• Recent travel, camping, hiking, or field training exercises 1
• Sexual history and recent exposures 5
• Sick contacts with similar symptoms 1

Medication History

• Any new medications in past 2-3 weeks, including over-the-counter drugs and supplements 1
• Recent antibiotic use (particularly relevant for EBV-associated rash) 1

Associated Symptoms

• Fever pattern: High-spiking fever suggests viral exanthem or RMSF; fever with severe headache and myalgias suggests RMSF 1, 2
• Severe headache, confusion, or neurologic symptoms (concerning for RMSF or meningococcemia) 1
• Respiratory symptoms (suggest Mycoplasma or viral infection) 1
• Joint pain or arthritis (consider disseminated gonococcal infection, secondary syphilis) 6

Physical Examination Priorities

Rash Characteristics

• Blanching vs. non-blanching: Petechial (non-blanching) rash suggests RMSF, meningococcemia, or vasculitis 1, 4
• Individual lesion morphology: True macules vs. maculopapules vs. papules 4, 7
• Confluence pattern: Discrete vs. confluent lesions 1

Distribution Verification

• Carefully examine palms and soles to confirm true sparing (early RMSF may not yet involve these areas) 1, 4
• Check for mucosal involvement (suggests Stevens-Johnson syndrome, drug reaction, or viral infection) 1, 4
• Examine for targetoid lesions (erythema multiforme) 4

Systemic Signs

• Vital signs with attention to fever, tachycardia, hypotension (sepsis from RMSF or meningococcemia) 1
• Lymphadenopathy (viral infections, secondary syphilis, drug reactions) 2, 5
• Hepatosplenomegaly (EBV, other viral infections) 1

Diagnostic Approach

Immediate Laboratory Testing

• Complete blood count with differential: Thrombocytopenia suggests RMSF; lymphocytosis suggests viral infection; eosinophilia suggests drug reaction 1
• Comprehensive metabolic panel: Hyponatremia and elevated transaminases suggest RMSF 1
• Rapid plasma reagin (RPR) or VDRL for syphilis screening 5
• Acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum if RMSF/ehrlichiosis suspected (do NOT wait for results to treat) 1

Additional Testing Based on Clinical Suspicion

• Monospot or EBV serology if viral syndrome with pharyngitis 1
• Parvovirus B19 IgM if appropriate clinical context 1
• Blood cultures if patient appears toxic 1
• Skin biopsy if diagnosis remains unclear after initial evaluation, particularly to rule out drug reaction or vasculitis 1

Critical Management Decisions

When to Treat Empirically for RMSF

Initiate doxycycline 100 mg twice daily immediately if: 1

• Fever + rash + headache + tick exposure or endemic area exposure
• Thrombocytopenia and/or hyponatremia present
• Summer months (May-September) in endemic regions
• ANY suspicion of RMSF, as delay in treatment increases mortality significantly

Do not wait for serologic confirmation - early serology is often negative and treatment must begin based on clinical suspicion 1

Red Flags Requiring Urgent Intervention

• Non-blanching petechial rash with fever (treat immediately for meningococcemia and RMSF) 1, 3
• Rapid progression of rash (suggests bacterial infection) 3
• Altered mental status or severe headache (RMSF, meningococcemia) 1
• Mucosal involvement with blistering (Stevens-Johnson syndrome) 1, 4

Common Pitfalls to Avoid

• Assuming absence of palm/sole involvement rules out RMSF - this distribution occurs late and only in 50% of cases 1, 4
• Waiting for positive serology before treating RMSF - acute serology is frequently negative and treatment delay increases mortality 1
• Dismissing the diagnosis because no tick bite was recalled - most RMSF patients do not recall a tick bite 1
• Over-relying on rash appearance alone - many conditions produce similar maculopapular rashes 4, 7
• Missing drug reactions - always obtain complete medication history including recent antibiotics 1