What are the differential diagnoses for an elderly African American woman presenting with a pruritic rash over the face, torso, extremities, and palms of hands, accompanied by fever, with normal laboratory results and a normal computed tomography (CT) scan?

Differential Diagnoses for Pruritic Rash with Fever in an Elderly African American Woman

The most critical differential to consider immediately is Rocky Mountain Spotted Fever (RMSF), which requires urgent empiric doxycycline treatment without waiting for laboratory confirmation, given the rash involving palms, fever onset after rash, and the 5-10% mortality risk if treatment is delayed. 1

Life-Threatening Infectious Causes Requiring Immediate Action

Tickborne Rickettsial Diseases (Highest Priority)

Rocky Mountain Spotted Fever (RMSF) is the most concerning diagnosis given the clinical presentation:

• The rash involving palms indicates advanced disease and is associated with severe illness 2
• RMSF classically presents with small blanching pink macules on ankles, wrists, or forearms that evolve to maculopapular lesions with central petechiae, spreading to palms, soles, arms, legs, and trunk 1
• Critical pitfall: In darker-skinned patients like this African American woman, petechial rashes may be difficult to recognize, increasing risk of delayed diagnosis 2
• The CDC recommends initiating doxycycline 100 mg twice daily immediately if fever + rash + any endemic area exposure is present, without waiting for laboratory confirmation 1
• Normal labs do NOT exclude RMSF—up to 20% of cases never develop the expected thrombocytopenia or hyponatremia 1

Human Monocytic Ehrlichiosis (HME) should also be considered:

• Rash occurs in only 30% of adults and varies from petechial to maculopapular to diffuse erythema 1
• Rash appears later in disease course (median 5 days after onset) and rarely involves palms and soles 1
• Carries a 3% case-fatality rate 1

Other Serious Infectious Causes

Meningococcemia (Neisseria meningitidis):

• Causes petechial or purpuric rash that can rapidly progress to purpura fulminans 2
• Typically appears alongside high fever, severe headache, and altered mental status 2
• Up to 50% of early cases lack rash 1

Secondary Syphilis (Treponema pallidum):

• Can present with rash involving palms and soles 2
• Important consideration given the demographic and distribution pattern 2

Bacterial Endocarditis:

• Petechiae on palms and soles can occur with endocarditis 2
• Consider if any cardiac risk factors present 2

Viral Exanthems

Common viral causes that present with maculopapular rashes:

• Human herpesvirus 6 (roseola) presents with macular rash following high fever 1
• Parvovirus B19 presents with "slapped cheek" appearance on face with possible truncal involvement 1
• Epstein-Barr virus causes maculopapular rash, especially if patient received ampicillin or amoxicillin 1
• These are generally self-limited but should be considered after excluding life-threatening causes 3, 4

Drug Hypersensitivity Reactions

Drug-induced eruptions are important differentials:

• Can cause petechial rash on palms and soles 2
• Present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches 1
• Obtain detailed medication history including any new medications started in past 2-4 weeks 4

Autoimmune and Vasculitic Causes

Adult-Onset Still's Disease (AOSD):

• Can present with vasculitic purpuric rash characterized by perivascular inflammation 2
• Consider if periodic fever pattern or systemic symptoms present 5

Critical Clinical Algorithm

Immediate actions required:

1. Initiate empiric doxycycline 100 mg twice daily immediately if any suspicion for RMSF/ehrlichiosis exists—do not wait for laboratory confirmation 1

2. Obtain urgent laboratory testing:

   • Complete blood count with differential (looking for leukopenia, thrombocytopenia) 1
   • Comprehensive metabolic panel (looking for hyponatremia, elevated hepatic transaminases) 1
   • Acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum 1
   • Blood cultures if endocarditis suspected 2

3. Expect clinical improvement within 24-48 hours of initiating doxycycline if rickettsial disease is present 1

4. Monitor for severe complications including meningoencephalitis, ARDS, and multiorgan failure, which occur if treatment is delayed 1

Key Clinical Pitfalls to Avoid

• Do not wait for the classic triad of fever, rash, and tick bite in RMSF—it is present in only a minority of patients at initial presentation 2
• Normal laboratory results do NOT exclude serious disease—less than 50% of RMSF patients have rash in the first 3 days, and up to 20% never develop thrombocytopenia 1
• Rash on palms and soles is not pathognomonic for any single condition—consider RMSF, meningococcemia, secondary syphilis, endocarditis, and drug reactions 2
• In this African American patient, petechial components may be subtle or missed entirely, leading to delayed diagnosis and increased mortality 2