What is the diagnosis and treatment for an adult or adolescent patient with no significant past medical history presenting with a pruritic maculopapular rash on the hands and feet?

Pruritic Maculopapular Rash on Hands and Feet: Diagnosis and Treatment

The most critical diagnosis to exclude immediately is Rocky Mountain Spotted Fever (RMSF), which requires empiric doxycycline without delay, as 50% of deaths occur within 9 days and treatment delay significantly increases mortality. 1

Immediate Clinical Assessment

Life-Threatening Diagnoses to Rule Out First

Start empiric doxycycline immediately if RMSF cannot be excluded based on clinical presentation, even before confirmatory testing. 1 The classic presentation includes:

• Fever, severe headache, and myalgias with rash appearing by day 5-6 of illness 1
• Rash begins as small blanching pink macules on ankles, wrists, or forearms, evolving to maculopapular lesions with central petechiae 1
• Involvement of palms and soles indicates advanced disease and severe illness 1, 2
• Up to 20% of RMSF cases lack rash entirely, so absence does not exclude diagnosis 1
• Tick exposure history is present in only 60% of cases 1

Critical pitfall: Do not wait for the classic triad of fever, rash, and tick bite—it is present in only a minority of patients at initial presentation. 1, 2

Additional Serious Infectious Causes

If meningococcemia cannot be excluded, add ceftriaxone to doxycycline immediately. 1 Look for:

• Rapidly progressive petechial or purpuric rash with high fever, severe headache, and altered mental status 1
• Systemic toxicity: tachycardia, confusion, hypotension 1

Differential Diagnosis for Pruritic Maculopapular Rash on Hands/Feet

Infectious Causes

Secondary syphilis (Treponema pallidum) should be considered with:

• Maculopapular rash involving palms and soles 3, 1
• Sexual exposure history
• Associated lymphadenopathy

Ehrlichiosis (E. chaffeensis) presents with:

• Rash in approximately one-third of patients, occurring later in disease course (median 5 days after onset) 3
• Rash rarely involves palms and soles 3
• Leukopenia (up to 53%), thrombocytopenia (up to 94%), and elevated liver transaminases 3

Enteroviral infections (including Enterovirus 71) cause:

• Lesions on hands, feet, and mouth 3
• More gradual progression than bacterial causes 4

Rat-bite fever (Streptobacillus moniliformis) can involve palms and soles 3, 1

Non-Infectious Causes

Drug hypersensitivity reactions:

• Ampicillin causes maculopapular rash in 5-10% of patients, considerably more frequent with concurrent viral illness 5
• This is typically a benign, nonallergic phenomenon that resolves spontaneously 5
• Drug reactions can involve palms and soles 1

Kawasaki disease (primarily pediatric):

• Erythema of palms and soles with firm, painful induration of hands/feet in acute phase 3
• Desquamation begins periungually within 2-3 weeks after fever onset 3
• Requires ≥5 days of fever plus ≥4 of 5 principal clinical criteria 3

Essential Diagnostic Workup

Obtain immediately if systemic illness suspected: 3, 1

• Complete blood count with differential (assess for leukopenia, thrombocytopenia, bandemia)
• Comprehensive metabolic panel (check for hyponatremia, elevated hepatic transaminases)
• Peripheral blood smear examination
• Blood cultures before antibiotics if possible, but do not delay treatment 1

Laboratory findings suggestive of specific diagnoses:

• RMSF: Normal WBC with increased bands, thrombocytopenia, mild transaminase elevations, hyponatremia 3
• Ehrlichiosis: Leukopenia (up to 53%), thrombocytopenia (up to 94%), modest transaminase elevations 3

Treatment Algorithm

If Systemic Toxicity Present (fever, headache, myalgias, altered mental status):

1. Start doxycycline immediately (even in children <8 years old due to high RMSF mortality if treatment delayed) 1
2. Add ceftriaxone if meningococcemia cannot be excluded 1
3. Hospitalize for systemic toxicity, rapidly progressive rash, or diagnostic uncertainty 1

If No Systemic Toxicity:

• Consider secondary syphilis: obtain RPR/VDRL and treponemal testing
• Consider drug reaction: review medication history, particularly recent antibiotics
• Consider enteroviral infection: supportive care, typically self-limited
• Consider ehrlichiosis if tick exposure and appropriate laboratory abnormalities

Key Historical Elements to Elicit:

• Recent outdoor activities in grassy/wooded areas (RMSF peaks April-September) 1
• Tick exposure (though absence does not exclude RMSF) 1
• Sexual exposure history (secondary syphilis)
• Recent medication use, especially ampicillin or other antibiotics 5
• Travel to endemic areas 1
• Time course: RMSF rash appears day 5-6; hand-foot-mouth disease peaks spring to fall 1

In darker-skinned patients, petechial rashes may be difficult to recognize, increasing risk of delayed diagnosis. 2