What are the differential diagnoses of viral infections causing palmoplantar (skin on the palms and soles) skin rashes?

Viral Infections Causing Palmoplantar Rashes

Direct Answer

The most common viral infections causing palmoplantar (palm and sole) rashes are enteroviruses, particularly coxsackievirus A16 and enterovirus 71 causing hand-foot-and-mouth disease, though certain enteroviruses like coxsackievirus and echovirus can also involve these areas. 1, 2

Primary Viral Causes of Palmoplantar Rash

Hand-Foot-and-Mouth Disease (Most Common)

• Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) are the major etiological agents causing maculopapular or papulovesicular rash specifically on palms and soles of feet 1, 2
• Coxsackievirus A6 (CV-A6) and CV-A10 are additional causative agents that can produce palmoplantar involvement 2
• Echovirus 4 has been documented to cause hand-foot-and-mouth disease with palmoplantar eruptions, though less commonly 3
• The rash presents as papulovesicular lesions on hands and soles, accompanied by painful oral ulcerations and low-grade fever 1
• Lesions typically resolve in 7-10 days without specific antiviral treatment 1

Other Enteroviral Infections

• Certain enteroviruses (coxsackievirus and echovirus) can cause palmoplantar involvement, though most enteroviral infections spare palms, soles, face, and scalp 4, 5
• These infections are the most common cause of maculopapular rashes overall but palmoplantar distribution is less typical 5

Critical Non-Viral Differential Diagnoses

Life-Threatening Bacterial/Rickettsial Causes (Must Rule Out First)

Rocky Mountain Spotted Fever (RMSF)

• Initial presentation shows small blanching pink macules on ankles, wrists, or forearms appearing 2-4 days after fever onset 4, 5
• Rash progresses to maculopapular with central petechiae, spreading centripetally to involve palms and soles in approximately 50% of cases 4
• Critical red flag: fever + rash + headache + tick exposure requires immediate doxycycline 100 mg twice daily without waiting for laboratory confirmation 5
• Mortality rate is 5-10% with delays in treatment significantly increasing death risk 5
• Up to 20% never develop a rash, making diagnosis challenging 4, 5

Human Monocytic Ehrlichiosis (HME)

• Rash occurs in only approximately 30% of adults (up to 66% in children) 4, 5
• Rash patterns vary from petechial or maculopapular to diffuse erythema 4, 5
• Palmoplantar involvement is rare, appearing later in disease course (median 5 days after onset) 4
• Mortality rate is 3% 5

Other Infectious Causes with Palmoplantar Distribution

Secondary Syphilis (Treponema pallidum)

• Maculopapular rash characteristically involves palms and soles 4, 6
• Requires RPR/VDRL testing and sexual history evaluation 6

Meningococcemia (Neisseria meningitidis)

• Rapidly progressive petechial rash that can evolve to purpura fulminans 4, 6
• Requires immediate empiric treatment if cannot be ruled out 6

Rat-Bite Fever (Streptobacillus moniliformis)

• Can present with palmoplantar rash 4

Infective Endocarditis

• Petechial rash on extremities with fever and new heart murmur 6
• Requires blood cultures and echocardiography 6

Most Common Rash Patterns by Viral Etiology

Hand-Foot-and-Mouth Disease Pattern

• Papulovesicular lesions specifically on palms, soles, hands, knees, and elbows 1, 2
• Oral vesicles producing multiple small superficial ulcers 2
• Distribution pattern is pathognomonic when combined with oral lesions 1

General Enteroviral Pattern (Non-HFMD)

• Maculopapular rash on trunk and extremities while sparing palms, soles, face, and scalp 5, 6
• This is the more typical presentation for most enteroviral infections 5

Human Herpesvirus 6 (Roseola)

• Macular rash following high fever, more common in children 5, 7
• Does not typically involve palms and soles 8

Epstein-Barr Virus

• Maculopapular rash, especially if patient received ampicillin or amoxicillin 5, 7
• Does not characteristically involve palms and soles 8

Parvovirus B19

• "Slapped cheek" appearance on face with possible truncal involvement 5, 7
• Palmoplantar involvement is not typical 8

Immediate Diagnostic Algorithm for Palmoplantar Rash

Step 1: Assess for Life-Threatening Causes

• If fever + headache + tick exposure (or endemic area) + thrombocytopenia/hyponatremia present: initiate doxycycline immediately 5, 6
• Obtain complete blood count with differential looking for leukopenia, thrombocytopenia 4, 5
• Obtain comprehensive metabolic panel looking for hyponatremia, elevated hepatic transaminases 4, 5
• Obtain acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum 5, 6

Step 2: Characterize Rash Distribution and Morphology

• Papulovesicular lesions on palms/soles + oral ulcerations = hand-foot-and-mouth disease 1, 2
• Maculopapular progressing to petechial with centripetal spread = consider RMSF 4, 5
• Petechial rash with rapid progression = consider meningococcemia 6

Step 3: Obtain Relevant History

• Tick exposure or travel to endemic areas (RMSF, ehrlichiosis) 4, 5
• Recent antibiotic use, particularly ampicillin/amoxicillin (drug reaction, EBV) 5, 7
• Sexual history (secondary syphilis) 6
• Exposure to young children or daycare settings (hand-foot-and-mouth disease) 1
• Recent chemotherapy, particularly capecitabine (drug-induced palmoplantar erythrodysesthesia) 9

Critical Pitfalls to Avoid

• Do not exclude RMSF based on absence of tick bite history, as 40% of patients do not report tick exposure 6
• Do not wait for serologic confirmation before starting doxycycline if RMSF is suspected 5, 6
• Do not assume all palmoplantar rashes are viral; drug hypersensitivity reactions can present similarly 4, 6
• Less than 50% of RMSF patients have rash in the first 3 days of illness, and lack of rash is associated with delays in diagnosis and increased mortality 5
• Hand-foot-and-mouth disease can rarely progress to severe complications including meningitis, encephalitis, and polio-like paralysis 2