What are the most common exanthematous diseases in the United States?

Main Exanthematous Diseases in the United States

Most Common Viral Exanthems

The most common exanthematous diseases in the United States are viral in origin, with enteroviral infections (coxsackievirus and echovirus) being the predominant cause, followed by human herpesvirus 6 (roseola), parvovirus B19 (erythema infectiosum), Epstein-Barr virus, and respiratory viruses. 1, 2, 3

Enteroviral Infections

• Enteroviruses are the most frequent cause of maculopapular rashes in the U.S., typically presenting with trunk and extremity involvement while characteristically sparing palms, soles, face, and scalp 1
• These infections can occasionally produce petechial manifestations that may mimic serious bacterial infections like meningococcemia 1, 4
• The rash distribution is more generalized and less likely to involve palms and soles compared to tickborne diseases 4

Human Herpesvirus 6 (Roseola Infantum)

• Roseola presents with high fever lasting 3-5 days, followed by the appearance of a pink-rose colored macular rash after fever resolution 1, 5
• The rash characteristically spares palms, soles, and face 5
• This is most common in children, though it can occur across age groups 1, 2

Parvovirus B19 (Erythema Infectiosum/Fifth Disease)

• Parvovirus B19 causes the classic "slapped cheek" appearance on the face with possible truncal involvement 1, 6
• School-aged children (4-10 years) are most commonly affected 6
• The rash evolves through three stages: initial facial erythema, followed by spread to trunk and extremities with a characteristic lacy or reticulated pattern, then evanescence and recrudescence 6
• In adults, only approximately 20% develop facial erythema, with the rash more frequently appearing on legs, trunk, and arms 6
• Pruritus occurs in approximately 50% of cases 6

Epstein-Barr Virus

• EBV causes maculopapular rash, particularly when patients receive ampicillin or amoxicillin during acute infection 1
• This drug-induced rash is a classic presentation that helps distinguish EBV from other viral exanthems 1

Other Viral Causes

• Respiratory viruses commonly cause nonspecific viral exanthems 7
• Measles (rubeola) and rubella, while less common due to vaccination, remain reportable diseases with 764 and 6 cases respectively in recent surveillance data 8, 2, 3

Critical Life-Threatening Exanthematous Diseases Requiring Immediate Recognition

Rocky Mountain Spotted Fever (RMSF)

• RMSF presents initially as small (1-5 mm), blanching, pink macules on ankles, wrists, or forearms appearing 2-4 days after fever onset 8, 1
• The rash progresses to maculopapular with potential central petechiae, spreading to palms, soles, arms, legs, and trunk while typically sparing the face 8, 1
• Less than 50% of patients have rash in the first 3 days of illness, and up to 20% never develop a rash, making early diagnosis challenging 1
• The case-fatality rate is 5-10%, with 50% of deaths occurring within 9 days of illness onset 1
• Up to 40% of patients report no tick bite history, so absence of tick exposure should never exclude this diagnosis 1, 5
• The CDC recommends initiating doxycycline 100 mg twice daily immediately without waiting for laboratory confirmation if fever + rash + headache + tick exposure or endemic area exposure are present 1

Meningococcemia

• Meningococcemia presents with rapid progression from maculopapular to petechial rash with clinical deterioration 5, 4
• This requires urgent intramuscular ceftriaxone pending blood cultures if it cannot be excluded 5
• Bacterial causes typically show elevated white blood cell count with left shift and markedly elevated inflammatory markers 4

Human Monocytic Ehrlichiosis (HME)

• HME rash occurs in only approximately 30% of adults (up to 66% in children), varying from petechial or maculopapular to diffuse erythema 8, 1
• The rash appears later in disease course (median 5 days after onset) and rarely involves palms and soles 8, 1
• The case-fatality rate is 3% 1

Bacterial Exanthems

Scarlet Fever

• Scarlet fever presents with a sandpaper-textured rash appearing during active fever, spreading from the upper trunk 5
• It is associated with pharyngitis and tonsillar exudates, distinguishing it from viral causes 5

Non-Infectious Exanthematous Conditions

Drug Eruptions

• Nonspecific drug eruptions present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches 1
• DRESS syndrome can present with elevated liver enzymes and hyperbilirubinemia 1

Kawasaki Disease

• Kawasaki disease causes coronary artery aneurysms if left untreated and presents with truncal rash with accentuation in the groin region 1
• Diagnostic criteria include fever for ≥5 days plus 4 of 5 features: bilateral conjunctival injection, oral mucosal changes, cervical lymphadenopathy ≥1.5 cm, extremity changes, and polymorphous rash 1

Key Diagnostic Approach

Critical Red Flags

• Never dismiss a petechial rash without thorough evaluation, as meningococcemia requires urgent treatment 5, 4
• Thrombocytopenia and/or hyponatremia are critical red flags for RMSF or ehrlichiosis 1
• The timing of rash relative to fever is the single most important distinguishing feature between viral exanthems 5

Essential Laboratory Workup for Suspected Tickborne Disease

• Complete blood count with differential (looking for leukopenia, thrombocytopenia) 1
• Comprehensive metabolic panel (looking for hyponatremia, elevated hepatic transaminases) 1
• Acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum 1
• Note that early serology for RMSF is typically negative, so negative early testing does not exclude diagnosis 5

Common Pitfalls to Avoid

• Do not rely on tick bite history to exclude RMSF, as 40% of patients have no reported bite 1, 5
• Geography should not exclude RMSF, as cases occur nationwide 5
• Lack of rash or late-onset rash is associated with delays in diagnosis and increased mortality for RMSF 1