What is the diagnosis and treatment for a patient presenting with red and brown macules on the palms and soles?

Diagnosis and Management of Red and Brown Macules on Palms and Soles

Immediate Assessment

The most critical first step is to determine if the patient has fever, systemic symptoms, or recent tick exposure—if present, immediately initiate doxycycline for presumed Rocky Mountain spotted fever (RMSF), as this carries 5-10% mortality if untreated and increases dramatically with delayed treatment. 1, 2, 3

Life-Threatening Conditions to Rule Out First

• Rocky Mountain spotted fever: Check for fever, headache, and tick exposure history within the past 2 weeks. The maculopapular rash spreads to palms and soles 2-4 days after fever onset. Do not wait for the classic triad (fever, rash, tick bite)—only a minority present with all three initially. 1, 2, 3

• Ehrlichiosis: Presents similarly with fever, headache, and rash involving palms/soles in 30% of adults and 60% of children, with 3% case-fatality rate. 3

• If pregnant: Measure serum bile acids immediately to exclude intrahepatic cholestasis of pregnancy, which predominantly affects palms and soles with pruritus worse at night and confers risk of stillbirth. 2

Differential Diagnosis for Non-Emergent Cases

Secondary Syphilis

Secondary syphilis is the most likely diagnosis for isolated red and brown macules on palms and soles without systemic symptoms. The classic presentation consists of reddish-brown macules and papules on palms and soles, often with papules and plaques on the torso and proximal extremities. 4

• The rash is typically diffuse, nonpruritic, and contagious. 4
• May also present with warty lesions, mucous membrane involvement, or patchy alopecia. 4
• Obtain RPR/VDRL and confirmatory treponemal testing (FTA-ABS or TP-PA). 4

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

Consider if there is recent medication exposure (within 1-3 weeks). Involvement of palms and soles can be prominent and may blister. 5

• Look for purpuric macules or flat atypical targets with dark red centers surrounded by pink rings. 5
• Check for mucous membrane involvement (eyes, mouth, nose, genitalia) with erosive and hemorrhagic mucositis. 5
• Assess for positive Nikolsky sign (gentle lateral pressure causes epidermis to slide over dermis). 5

Cutaneous Mastocytosis (in children)

If the patient is a child, consider urticaria pigmentosa, which presents as red to brown to yellow macules measuring a few mm to 1-2 cm in diameter. 5

• Less commonly affects palms, soles, scalp, and face compared to trunk and extremities. 5
• Check for Darier's sign (wheal and flare formation after stroking lesions). 5
• Most cases develop lesions during the first year of life and resolve by age 10. 5

Rat Bite Fever

Consider if there is history of rodent exposure. The rash can involve palms and soles, similar to RMSF and secondary syphilis. 1

• Rash typically appears 2-10 days after rat bite or exposure. 1
• May be nonspecific and mimic drug reactions, viral exanthems, or endocarditis. 1

Other Considerations

• Volar melanotic macules: Asymptomatic light brown or tannish-gray macules, more common in dark-skinned individuals but can occur in whites. 6, 7
• Tinea nigra: Asymptomatic, unilateral, well-defined brown to black macules caused by Hortaea werneckii. 8
• Chemotherapy-induced hand-foot syndrome: If on capecitabine, 5-FU, doxorubicin, or multikinase inhibitors. 3

Diagnostic Workup

History

• Medication history (within past 3 weeks for SJS/TEN, current chemotherapy for hand-foot syndrome). 5, 3
• Tick exposure or travel history. 2, 3
• Rodent exposure. 1
• Sexual history and risk factors for syphilis. 4
• Pregnancy status. 2

Physical Examination

• Assess body surface area involvement and presence of blistering or epidermal detachment. 5
• Examine all mucous membranes (eyes, mouth, nose, genitalia). 5
• Check for Nikolsky sign if blistering present. 5
• Check for Darier's sign if considering mastocytosis in children. 5
• Look for lymphadenopathy, condyloma lata, or other signs of secondary syphilis. 4

Laboratory Testing

• If fever/systemic symptoms: Initiate doxycycline empirically before awaiting test results. 1, 2, 3
• Syphilis serology: RPR/VDRL with confirmatory treponemal testing. 4
• If pregnant with pruritus: Serum bile acids. 2
• KOH preparation: If considering tinea nigra (reveals pigmented yeast and hyphae). 8
• Skin biopsy: If diagnosis unclear after initial workup. 4, 7

Treatment

For Secondary Syphilis (Most Likely Non-Emergent Diagnosis)

• Benzathine penicillin G 2.4 million units IM single dose for early syphilis (primary, secondary, or early latent <1 year duration). 4
• If penicillin-allergic and not pregnant: Doxycycline 100 mg PO twice daily for 14 days.
• If pregnant and penicillin-allergic: Desensitization followed by penicillin treatment.

For RMSF (If Suspected)

• Doxycycline 100 mg PO twice daily (or IV if unable to take oral) immediately, even in children and pregnant women. 1, 2, 3
• Continue for at least 3 days after fever subsides and until evidence of clinical improvement, typically 5-7 days total.

For SJS/TEN (If Diagnosed)

• Immediately discontinue all potentially causative medications. 5
• Transfer to burn unit or intensive care setting for supportive care. 5
• Fluid resuscitation, wound care, nutritional support, and ophthalmologic consultation. 5

Critical Pitfalls to Avoid

• Never dismiss fever with palmar rash as simple dermatitis—RMSF mortality increases dramatically with delayed doxycycline treatment. 2, 3
• Do not wait for the classic triad (fever, rash, tick bite) before treating suspected RMSF. 2, 3
• Do not confuse excoriations from scratching with primary rash in pregnant patients—cholestasis has no primary rash, only secondary excoriations. 2
• Secondary syphilis can have highly variable presentations, including rupioid (warty) forms, making histologic diagnosis challenging. 4