What is the differential diagnosis and management for rashes following fever?

Differential Diagnosis for Rashes After Fever

When evaluating a patient with rash following fever, immediately consider life-threatening conditions first: Rocky Mountain Spotted Fever (RMSF), meningococcemia, toxic shock syndrome, and Kawasaki disease in children, as these require urgent intervention to prevent mortality and severe morbidity. 1

Critical Timing and Rash Characteristics

The timing of rash onset relative to fever is diagnostically crucial:

• Rash appearing 2-4 days after fever onset suggests RMSF, which begins as blanching pink macules on ankles, wrists, or forearms, progressing to maculopapular and potentially petechial lesions involving palms and soles by days 5-6 1
• Rash within 5 days of fever occurs in Kawasaki disease, typically presenting as diffuse maculopapular eruption with perineal accentuation 1
• Rash appearing later (median 5 days) suggests ehrlichiosis, though rash occurs in only ~30% of adults and ~60% of children 1

Life-Threatening Conditions Requiring Immediate Recognition

Rocky Mountain Spotted Fever

• High mortality (5-10%) if untreated 1
• Classic triad of fever, rash, and tick bite present in only a minority at initial presentation 1
• Critical pitfall: Up to 20% never develop rash; absence of rash should NOT exclude diagnosis 1
• Associated findings: thrombocytopenia, hyponatremia, elevated transaminases 1
• Start empiric doxycycline immediately if suspected, before confirmatory testing 1

Meningococcemia

• Begins as maculopapular rash progressing rapidly to petechial/purpuric lesions 1
• Progresses more rapidly than RMSF 1
• Requires immediate antibiotics and supportive care

Kawasaki Disease (Children)

• Requires diagnosis within 10 days to prevent coronary artery aneurysms 1
• Diagnostic criteria: ≥5 days fever PLUS ≥4 of: polymorphous exanthem, bilateral conjunctival injection, oral/lip changes, extremity changes, cervical lymphadenopathy 1
• Rash typically extensive, involving trunk/extremities with perineal accentuation 1
• Bullous or vesicular rashes exclude Kawasaki disease 1

Systematic Approach by Rash Morphology

Maculopapular Rashes

Most common presentation with broad differential 1, 2:

Infectious causes:

• Viral: measles, roseola (HHV-6), parvovirus B19, enteroviruses (coxsackie, echovirus), EBV, adenovirus 1
• Bacterial: secondary syphilis, leptospirosis, Mycoplasma pneumoniae, disseminated gonococcal infection 1
• Rickettsial: RMSF, ehrlichiosis 1

Non-infectious causes:

• Drug hypersensitivity reactions (most common non-infectious cause) 1, 2
• Kawasaki disease 1
• Adult-onset Still's disease 2
• Immune complex-mediated illness 1

Petechial/Purpuric Rashes

Immediately life-threatening until proven otherwise:

• Meningococcemia 1
• RMSF (late presentation, days 5-6) 1
• Enteroviral infections 1
• Immune thrombocytopenic purpura 1
• Thrombotic thrombocytopenic purpura 1
• Post-streptococcal (after group A strep pharyngitis) 1

Scarlatiniform Rashes

• Scarlet fever (group A streptococcus) 1
• Toxic shock syndrome (staphylococcal or streptococcal) 1
• Kawasaki disease variant 1

Vesicular Rashes

• Varicella (chickenpox) 2
• Herpes zoster (disseminated)
• Rickettsia parkeri rickettsiosis (vesiculopapular with eschar) 1

Essential Diagnostic Clues

Geographic and Exposure History

• Tick exposure: Consider RMSF, ehrlichiosis, anaplasmosis 1
• Travel to western US with leukopenia/thrombocytopenia: Colorado tick fever 1
• Forest/natural environment exposure: Various tickborne diseases 3

Rash Distribution Patterns

Palms and soles involvement (not pathognomonic but suggestive):

• RMSF (typically late, days 5-6, only ~50% of cases) 1
• Secondary syphilis 1
• Meningococcemia 1
• Ehrlichiosis (rare) 1
• Certain enteroviruses 1
• Infective endocarditis 1

Centripetal spread (extremities to trunk):

• RMSF characteristic pattern 1

Perineal accentuation with early desquamation:

• Kawasaki disease 1

Laboratory Findings

Thrombocytopenia + leukopenia:

• Ehrlichiosis (up to 94% thrombocytopenia) 1
• Anaplasmosis 1
• Tickborne viral fevers 1

Thrombocytopenia + hyponatremia + normal/slightly elevated WBC:

• RMSF 1

Elevated transaminases:

• Common in rickettsial diseases 1

Critical Management Pitfalls

1. Never wait for the complete triad (fever, rash, tick bite) before treating suspected RMSF—present in only a minority initially 1
2. Do not exclude RMSF based on absence of rash—up to 20% never develop rash, and <50% have rash in first 3 days 1
3. Rash on palms/soles is NOT pathognomonic for RMSF and occurs in multiple conditions 1
4. In children with prolonged fever and rash, always consider Kawasaki disease to prevent coronary complications 1
5. Petechial rash requires immediate evaluation for meningococcemia and other life-threatening causes 1

Diagnostic Algorithm Priority

1. Assess for immediate life threats: Signs of sepsis, meningitis, rapidly progressive petechial rash → empiric antibiotics immediately
2. Obtain complete blood count: Thrombocytopenia + leukopenia suggests ehrlichiosis/anaplasmosis; thrombocytopenia + hyponatremia suggests RMSF 1
3. Document rash characteristics: Morphology, distribution, timing relative to fever onset
4. Epidemiologic clues: Tick exposure, travel history, medication history, animal contacts 3
5. Age-specific considerations: Kawasaki disease in children <5 years; viral exanthems more common in children 1