Eczema herpeticum (EH) is a dermatologic emergency caused by disseminated herpes simplex virus (HSV) infection superimposed on pre-existing skin disease, most commonly atopic dermatitis (AD). It occurs in approximately 3% of AD patients and can be life-threatening if untreated, with historical mortality rates of 10–50% before the acyclovir era. [1-2] The following figure demonstrates the clinical spectrum of EH:
1. History
- Acute onset of painful, burning vesiculopapular eruption in areas of pre-existing eczema [4-5]
- Ask about prior history of atopic dermatitis (severity, age of onset, current treatment) [6]
- Prior episodes of cold sores (HSV-1) or genital herpes (HSV-2) — in the patient or close contacts
- Timing: rapid progression over 1–3 days; may follow a known HSV exposure or AD flare
- Associated symptoms: fever, malaise, lymphadenopathy, cutaneous pain, poor oral intake [7-8]
- Important negatives: no mucosal involvement or target lesions (helps distinguish from SJS), no dermatomal distribution (distinguishes from zoster) [4]
2. Alarm Features
- Periocular involvement — risk of HSV keratoconjunctivitis and corneal scarring (present in ~10% of pediatric cases) [7]
- High fever, tachycardia, or hemodynamic instability suggesting viremia/sepsis
- Rapidly spreading lesions despite antibiotics (suggests missed viral etiology) [5]
- Immunocompromised host (HIV, transplant, chemotherapy) — higher risk of dissemination [4]
- Age <1 year — strongest predictor of hospitalization (OR 7.17) [7]
- Signs of secondary bacterial sepsis (S. aureus bacteremia occurs in ~3.9% of hospitalized cases) [9]
3. Medications
- First-line treatment: Systemic acyclovir — IV acyclovir for severe/hospitalized cases; oral acyclovir (or valacyclovir) for mild, localized disease [2][10-11]
- Oral acyclovir: 200 mg 5× daily for 5–7 days (adults); weight-based dosing in children [10]
- IV acyclovir: 5–10 mg/kg q8h for severe or disseminated disease [12]
- Valacyclovir: alternative oral option with better bioavailability [12]
- Topical corticosteroids should NOT be withheld — they do not prolong hospitalization and help control underlying AD [9][13]
- Topical calcineurin inhibitors (tacrolimus, pimecrolimus) have been associated with increased EH risk and should be held during active infection [1]
- Add empiric antibiotics (e.g., cephalexin, TMP-SMX) if secondary bacterial superinfection is suspected — S. aureus co-infection occurs in ~30% of hospitalized cases [9]
- Avoid: topical antivirals alone are insufficient for EH; systemic therapy is mandatory [11]
4. Diet
- No specific dietary triggers or restrictions
- Ensure adequate hydration, especially in febrile patients and young children with poor oral intake
- Long-term: dietary optimization for AD management (identify individual food triggers if relevant)
5. Review of Systems
- Constitutional: fever, chills, malaise, fatigue
- Skin: pain/burning (more than itch), new vesicles, weeping/crusting, rapid spread
- Eyes: pain, tearing, photophobia, blurred vision (keratoconjunctivitis)
- ENT: oral lesions, dysphagia
- Neuro: headache, altered mental status (concern for HSV encephalitis in severe cases)
- GI: poor oral intake, nausea (especially in children)
6. Collateral History and Family History
- Contact history: recent exposure to individuals with active cold sores or genital herpes
- Family history of atopic disease (eczema, asthma, allergic rhinitis) — the "atopic triad"
- History of filaggrin mutations in family (associated with increased EH risk) [1][14]
- Social context: wrestlers (herpes gladiatorum → EH), daycare exposure [8]
- Prior episodes of EH — recurrence rate ~9% within 1 month, ~16% repeat episodes [7]
7. Risk Factors
- Atopic dermatitis — the dominant risk factor; EH occurs nearly exclusively in AD patients [13]
- Early-onset AD and severe AD (higher total serum IgE) [6]
- Filaggrin gene mutations and impaired skin barrier [1][14]
- S. aureus skin colonization — promotes HSV replication via α-toxin [1][14]
- Immunosuppression: HIV, organ transplant, immunosuppressive therapy [4]
- Topical calcineurin inhibitor use [1]
- Reduced antimicrobial peptides (LL-37, human β-defensins) [14]
- Dupilumab has been shown to reduce EH risk in AD patients [14]
8. Differential Diagnosis
- Impetigo — the most common misdiagnosis in the ED; honey-crusted lesions without monomorphic vesicles; responds to antibiotics [5]
- Stevens-Johnson syndrome/TEN — target lesions, flaccid bullae, prominent mucosal involvement (absent in EH) [4]
- Disseminated herpes zoster — dermatomal onset before dissemination; VZV PCR distinguishes
- Eczema coxsackium — polymorphous (not monomorphic) vesicles, acral distribution (palms/soles), concurrent oral lesions [13]
- Acute generalized exanthematous pustulosis (AGEP) — drug-related, non-follicular pustules [4]
- Dermatitis herpetiformis — intensely pruritic, grouped papulovesicles on extensor surfaces; associated with celiac disease
- Varicella — diffuse, crops in different stages; no underlying eczematous background
9. Past Medical History
- Atopic dermatitis — severity, duration, age of onset, current therapies
- Prior episodes of eczema herpeticum (recurrence is common) [7]
- History of herpes simplex infections (orolabial or genital)
- Immunodeficiency (HIV, primary immunodeficiency)
- Current immunosuppressive medications (systemic steroids, biologics, calcineurin inhibitors)
- History of S. aureus skin infections (MRSA status)
10. Physical Exam
- Vital signs: fever (present in ~56–59% of cases), tachycardia [7][15]
- Skin: monomorphic, dome-shaped, grouped vesicles and/or "punched-out" erosions concentrated in areas of pre-existing eczema — this is the hallmark finding [6][13]
- Vesicles may become pustular, then rupture leaving hemorrhagic crusts
- Commonly involves head, neck, and trunk [8]
- Look for "punched-out" ulcers with scalloped borders
- Eyes: conjunctival injection, dendritic corneal ulcers on fluorescein exam (10% of pediatric cases) [7]
- Lymphadenopathy: regional or generalized [8]
- Signs of secondary bacterial infection: purulence, expanding cellulitis, warmth
11. Lab Studies
- HSV PCR (NAAT) from vesicle base scraping — gold standard, most sensitive and specific test [12][16]
- Viral culture — less sensitive than PCR but can confirm diagnosis; positive in 1–3 days [12]
- Tzanck smear — rapid bedside test showing multinucleated giant cells; sensitivity ~60–77%, specificity ~100%; useful when PCR is unavailable [17-18]
- Direct fluorescent antibody (DFA) — rapid but sensitivity <75% [12]
- CBC: lymphopenia is associated with EH [6]
- Blood cultures if febrile or toxic-appearing (bacteremia in ~3.9%) [9]
- CRP/ESR: may be elevated; ESR elevation is nonspecific [6]
- Total serum IgE: often markedly elevated in EH patients (reflects severe AD phenotype) [6]
- Wound culture for bacterial superinfection (S. aureus, GAS) [15]
12. Imaging
- Imaging is generally unnecessary for uncomplicated EH
- CT head/MRI brain: only if concern for HSV encephalitis (altered mental status, seizures, focal neurologic deficits)
- Chest X-ray: if concern for disseminated HSV with pulmonary involvement in immunocompromised patients
13. Special Tests
- Tzanck smear: rapid point-of-care test — unroof a fresh vesicle, scrape the base (or preferably the roof), stain with Giemsa/Wright stain; look for multinucleated giant cells and ballooning degeneration [17][19]
- HSV PCR from Tzanck smear debris: can be performed on the same slide, increasing diagnostic yield [17][20]
- Fluorescein eye exam: mandatory if periocular involvement — look for dendritic ulcers indicating HSV keratitis [7]
- Ophthalmology consultation for any periocular disease
14. ECG
- ECG is not routinely indicated for eczema herpeticum
- Consider if the patient is septic or hemodynamically unstable to evaluate for myocarditis or arrhythmia in the setting of systemic infection
15. Assessment
EH is a dermatologic urgency that is frequently misdiagnosed as impetigo or an AD flare in the ED, leading to delayed antiviral therapy. [5] The classic presentation is a patient with known AD who develops monomorphic, painful vesicles or punched-out erosions with fever and systemic illness. Key clinical pearl: the lesions are painful (not just pruritic), monomorphic (uniform size), and concentrated in areas of active eczema. [6][13]
Severity stratification
- Mild/localized: limited vesicles, no fever, well-appearing → may be managed outpatient
- Moderate/severe: widespread eruption, fever, systemic symptoms, age <1 year, periocular involvement → requires hospitalization [7]
- Critical: signs of viremia, sepsis, encephalitis, or multiorgan involvement → ICU admission (~3.8% of hospitalized cases) [9]
Complications: secondary bacterial sepsis (S. aureus), HSV keratoconjunctivitis/keratitis, HSV encephalitis, multiorgan failure, scarring, recurrence [7][9]
16. Treatment Plan
Initial stabilization
- IV access, fluid resuscitation if dehydrated or septic
- Antipyretics for fever
Antiviral therapy — start immediately; do not wait for confirmatory testing: [2][9]
- IV acyclovir 5–10 mg/kg q8h for severe, disseminated, or hospitalized cases [11-12]
- Oral acyclovir 400 mg 5× daily (adults) or valacyclovir 1 g BID for mild, localized disease [10]
- Pediatric dosing: IV acyclovir 10–20 mg/kg q8h (age-dependent); oral valacyclovir 20–25 mg/kg BID–TID [12]
- Duration: typically 7–14 days depending on severity and response
Adjunctive therapy
- Continue topical corticosteroids for underlying AD — this does NOT worsen EH and should not be withheld [9][13]
- Empiric antibiotics if bacterial superinfection suspected (cephalexin, TMP-SMX, or IV antibiotics if septic) [9][15]
- Hold topical calcineurin inhibitors during active infection [1]
- Ophthalmology consult for periocular involvement [7]
- Pain management as needed
17. Disposition
Admit if
- Fever or systemic symptoms [7]
- Age <1 year [7]
- Widespread/generalized eruption
- Periocular involvement
- Immunocompromised host
- Unable to tolerate oral medications
- Signs of secondary bacterial sepsis
- Concern for HSV encephalitis or disseminated HSV
Discharge criteria
- Localized disease, afebrile, well-appearing, tolerating oral medications
- Reliable follow-up within 24–48 hours
- Access to oral antiviral medication
ICU admission: hemodynamic instability, encephalitis, multiorgan involvement [9]
Consult triggers: Dermatology (all cases if available), Ophthalmology (periocular disease), Infectious Disease (immunocompromised or refractory cases)
18. Follow Up / Return Precautions
- Follow-up in 24–48 hours for outpatient cases to assess treatment response
- Dermatology follow-up within 1–2 weeks for all patients to optimize AD management and reduce recurrence risk
- Return immediately for: worsening rash despite antivirals, new fever, eye pain/vision changes, altered mental status, poor oral intake, or signs of spreading infection
- Expected course: lesions should begin crusting and improving within 2–3 days of antiviral initiation; full resolution typically in 1–2 weeks [5][10]
- Recurrence counseling: ~9% recurrence within 1 month, ~16% repeat episodes; prior EH significantly increases risk of future episodes [7]
- Infection control: lesions are contagious until fully crusted; avoid contact with immunocompromised individuals and neonates
- Long-term AD optimization: aggressive skin barrier care, consider dupilumab for severe AD (reduces EH risk) [14]
References
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2. Guidelines of Care for the Management of Atopic Dermatitis: Section 3. Management and Treatment With Phototherapy and Systemic Agents. — Sidbury R, Davis DM, Cohen DE, et al. Journal of the American Academy of Dermatology. 2014.
3. Viral infections. — Rook's Dermatology Handbook. 2023.
4. Eczema Herpeticum in an Immunocompetent Man. — Chang-Chieh L, Shen-Han C, Yu-Han F, Chi-Ta H. Diagnostic Microbiology and Infectious Disease. 2024.
5. Eczema Herpeticum: Making the Diagnosis in the Emergency Department. — Studdiford JS, Valko GP, Belin LJ, Stonehouse AR. The Journal of Emergency Medicine. 2011.
6. Predisposing Factors and Clinical Features of Eczema Herpeticum: A Retrospective Analysis of 100 Cases. — Wollenberg A, Zoch C, Wetzel S, Plewig G, Przybilla B. Journal of the American Academy of Dermatology. 2003.
7. Eczema Herpeticum in Children: Clinical Features and Factors Predictive of Hospitalization. — Luca NJ, Lara-Corrales I, Pope E. The Journal of Pediatrics. 2012.
8. Eczema Herpeticum in a Wrestler. — Shenoy R, Mostow E, Cain G. Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine. 2015.
9. Delayed Acyclovir and Outcomes of Children Hospitalized With Eczema Herpeticum. — Aronson PL, Yan AC, Mittal MK, Mohamad Z, Shah SS. Pediatrics. 2011.
10. Treatment of Eczema Herpeticum With Oral Acyclovir. — Niimura M, Nishikawa T. The American Journal of Medicine. 1988.
11. Recurrent Herpes Labialis in Adults: New Tricks for an Old Dog. — Rosen T. Journal of Drugs in Dermatology : JDD. 2017.
12. Guidelines for the Prevention and Treatment of Opportunistic Infections in Children With and Exposed to HIV. — Bill G. Kapogiannis, Franklin Yates, Wei Li, et al Office of AIDS Research Advisory Council (2025). 2025.
13. Atopic Dermatitis: Update on Skin-Directed Management: Clinical Report. — Schoch JJ, Anderson KR, Jones AE, Tollefson MM. Pediatrics. 2025.
14. Eczema Herpeticum in Atopic Dermatitis. — Traidl S, Roesner L, Zeitvogel J, Werfel T. Allergy. 2021.
15. Frequency and Clinical Features Associated With Eczema Herpeticum in Hospitalized Children With Presumed Atopic Dermatitis Skin Infection. — Hemani SA, Edmond MB, Jaggi P, Cooley A. The Pediatric Infectious Disease Journal. 2020.
16. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
17. Comparison of Tzanck Smear, Viral Culture, and DNA Diagnostic Methods in Detection of Herpes Simplex and Varicella-Zoster Infection. — Nahass GT, Goldstein BA, Zhu WY, et al. The Journal of the American Medical Association. 1992.
18. Comparison of the Tzanck Test and Polymerase Chain Reaction in the Diagnosis of Cutaneous Herpes Simplex and Varicella Zoster Virus Infections. — Ozcan A, Senol M, Saglam H, et al. International Journal of Dermatology. 2007.
19. Detection of Multinucleated Giant Cells in Differentiated Keratinocytes With Herpes Simplex Virus and Varicella Zoster Virus Infections by Modified Tzanck Smear Method. — Yamamoto T, Aoyama Y. The Journal of Dermatology. 2021.
20. Detection of Herpes Simplex and Varicella-Zoster Infection From Cutaneous Lesions in Different Clinical Stages With the Polymerase Chain Reaction. — Nahass GT, Mandel MJ, Cook S, Fan W, Leonardi CL. Journal of the American Academy of Dermatology. 1995.