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

Immediate Assessment and Life-Threatening Conditions

The American College of Physicians recommends immediate initiation of doxycycline for presumed Rocky Mountain spotted fever (RMSF) if the patient has fever, systemic symptoms, or recent tick exposure, as this carries 5-10% mortality if untreated and increases dramatically with delayed treatment 1, 2, 3
The Centers for Disease Control and Prevention (CDC) suggests checking for fever, headache, and tick exposure history within the past 2 weeks to rule out Rocky Mountain spotted fever, which has a maculopapular rash spreading to palms and soles 2-4 days after fever onset 1, 2, 3
The Infectious Diseases Society of America recommends considering Ehrlichiosis, which presents similarly with fever, headache, and rash involving palms/soles in 30% of adults and 60% of children, with 3% case-fatality rate 3
The American College of Obstetricians and Gynecologists (ACOG) advises measuring 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, if the patient is pregnant 2

The British Association of Dermatologists suggests considering Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) if there is recent medication exposure (within 1-3 weeks), with involvement of palms and soles, which can be prominent and may blister 4, 5, 6
The American Academy of Pediatrics recommends considering urticaria pigmentosa (cutaneous mastocytosis) in children, which presents as red to brown to yellow macules measuring a few mm to 1-2 cm in diameter, with less common involvement of palms, soles, scalp, and face compared to trunk and extremities 7

The American College of Physicians advises initiating doxycycline empirically before awaiting test results if the patient has fever or systemic symptoms, and to continue for at least 3 days after fever subsides and until evidence of clinical improvement, typically 5-7 days total 1, 2, 3
The British Association of Dermatologists recommends immediately discontinuing all potentially causative medications and transferring to a burn unit or intensive care setting for supportive care if Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is diagnosed 4, 5, 6
The American College of Obstetricians and Gynecologists (ACOG) suggests treating secondary syphilis with benzathine penicillin G 2.4 million units IM single dose for early syphilis, or doxycycline 100 mg PO twice daily for 14 days if penicillin-allergic and not pregnant 2

The Centers for Disease Control and Prevention recommends initiating doxycycline immediately if the patient has fever, headache, malaise, or tick exposure within the past 2 weeks, even before diagnostic confirmation, as mortality increases from 5-10% to potentially fatal with delayed treatment of Rocky Mountain spotted fever (RMSF) 8
The American Academy of Pediatrics notes that children under 15 years develop the rash more frequently and earlier than adults in RMSF 8
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 in RMSF 8

The American Heart Association recommends considering Kawasaki disease in children with fever for 5 days plus erythema of palms and soles with firm, painful induration of hands or feet, which requires at least 4 of 5 principal criteria: extremity changes, polymorphous exanthem, bilateral conjunctival injection, oral/lip changes, and cervical lymphadenopathy 9
The American College of Cardiology notes that periungual desquamation typically begins 2-3 weeks after fever onset in Kawasaki disease 9
The presence of palm and sole involvement narrows the differential significantly to RMSF, secondary syphilis, Kawasaki disease (in children), ehrlichiosis, and rat bite fever, according to the Centers for Disease Control and Prevention and the American Heart Association 8, 9