What does a rash with red and brown macules on the palms and soles indicate?

Red and Brown Macules on Palms and Soles: Diagnostic Approach

A rash with red and brown macules on the palms and soles most urgently indicates Rocky Mountain spotted fever (RMSF) if accompanied by fever and systemic symptoms, requiring immediate empiric doxycycline treatment before awaiting test results, as mortality increases from 5-10% to potentially fatal with delayed treatment. 1, 2

Life-Threatening Conditions Requiring Immediate Action

Rocky Mountain Spotted Fever (RMSF)

• Initiate doxycycline immediately if the patient has fever, headache, malaise, or tick exposure within the past 2 weeks, even before diagnostic confirmation. 1, 2
• The maculopapular rash appears 2-4 days after fever onset and spreads to involve palms and soles, though up to 10-15% of patients never develop a rash. 1
• Children under 15 years develop the rash more frequently and earlier than adults. 1
• Continue doxycycline for at least 3 days after fever subsides and until clinical improvement occurs, typically 5-7 days total. 2
• Critical pitfall: Do NOT wait for the classic triad of fever, rash, and documented tick bite—only a minority present with all three initially, and this delay increases mortality. 1, 3

Ehrlichiosis

• Consider this diagnosis if the patient presents with fever, headache, and systemic symptoms with recent tick exposure. 1, 2
• Rash involving palms and soles occurs in 30% of adults and 60% of children, appearing a median of 5 days after illness onset. 1
• Case-fatality rate is 3%, making this another urgent consideration. 1, 2

Pregnancy-Specific Emergency

• If the patient is pregnant, measure serum bile acids immediately to exclude intrahepatic cholestasis of pregnancy, which predominantly affects palms and soles with pruritus worse at night and carries risk of stillbirth. 2

Secondary Syphilis: The Classic Mimic

Clinical Presentation

• Secondary syphilis characteristically presents with reddish-brown to copper-colored macules and papules on palms and soles. 4, 5
• The rash is typically painless, nonpruritic, and highly contagious. 4, 5, 6
• Associated findings include generalized lymphadenopathy, mucous membrane lesions ("mucous patches"), condyloma lata, and patchy alopecia. 1, 7
• In HIV-positive patients, secondary syphilis may present atypically with more severe, persistent, or unusual manifestations including rupioid (oyster shell-like) lesions. 7, 4, 8

Diagnostic Approach

• Obtain both non-treponemal (RPR or VDRL) and treponemal tests (TPPA or FTA-ABS) for confirmation. 8, 5
• Skin biopsy shows perivascular lymphoplasmacytic infiltrate with endothelial swelling; spirochetal stains can identify organisms. 7, 6

Treatment

• Treat with benzathine penicillin G 2.4 million units intramuscularly as a single dose for early syphilis. 2, 5
• For penicillin-allergic non-pregnant patients, use doxycycline 100 mg orally twice daily for 14 days. 2

Other Important Differential Diagnoses

Kawasaki Disease (Pediatric Patients)

• Consider in children with fever for 5 days plus erythema of palms and soles with firm, painful induration of hands or feet. 1
• Requires at least 4 of 5 principal criteria: extremity changes, polymorphous exanthem, bilateral conjunctival injection, oral/lip changes, and cervical lymphadenopathy. 1
• Periungual desquamation typically begins 2-3 weeks after fever onset. 1
• Critical distinction: RMSF is included in the differential diagnosis of Kawasaki disease, emphasizing the importance of ruling out RMSF first. 1

Rat Bite Fever

• Consider with appropriate exposure history (rodent contact). 9
• Rash involves palms and soles, appearing 2-10 days after exposure. 9
• Can mimic RMSF, secondary syphilis, and other conditions, making diagnosis challenging. 9

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

• Suspect if recent medication exposure occurred within 1-3 weeks. 2
• Palm and sole involvement can be prominent and may blister. 2
• Immediately discontinue all potentially causative medications and transfer to burn unit or ICU for supportive care if diagnosed. 2

Algorithmic Approach to Diagnosis

1. First: Assess for fever and systemic symptoms

   • If present with palm/sole rash → Start doxycycline empirically for presumed RMSF 1, 2
   • Check for tick exposure history within past 2 weeks 1, 2

2. Second: If no fever/systemic symptoms, obtain sexual history

   • If positive sexual exposure → Test for syphilis (RPR/VDRL and treponemal tests) 8, 5
   • Examine for other signs: lymphadenopathy, mucous patches, condyloma lata 4, 5

3. Third: Consider patient-specific factors

   • Pregnant → Check serum bile acids urgently 2
   • Child with fever → Evaluate for Kawasaki disease criteria 1
   • Recent medication exposure → Consider SJS/TEN 2
   • Rodent exposure → Consider rat bite fever 9

4. Fourth: If diagnosis remains unclear

   • Perform skin biopsy with special stains (spirochetal, immunohistochemistry) 7, 6
   • Consider less common causes based on additional clinical features

Key Clinical Pearls

• The presence of palm and sole involvement narrows the differential significantly to RMSF, secondary syphilis, Kawasaki disease (in children), ehrlichiosis, and rat bite fever. 1, 2, 9
• Lack of rash or late-onset rash in RMSF is associated with delays in diagnosis and increased mortality—treat empirically based on clinical suspicion. 1
• Skin pigmentation may make rashes difficult to recognize in some patients, requiring heightened clinical suspicion. 1
• In HIV-positive patients, secondary syphilis can present with atypical features that may mimic other conditions like Kaposi sarcoma. 7, 4