Eczema Herpeticum (2024)

Continuing Education Activity

Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus that develops in a patient with atopic dermatitis. EH typically presents as a sudden onset eruption of monomorphic vesicles and "punched-out" erosions with hemorrhagic crusts over eczematous areas. Patients may have systemic symptoms, such as fever, lymphadenopathy, or malaise. This activity reviews the evaluation and treatment of eczema herpeticum and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

  • Identify the etiology of eczema herpeticum.

  • Outline the typical presentation of eczema herpeticum.

  • Describe the management options available for eczema herpeticum.

Access free multiple choice questions on this topic.

Introduction

Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus that develops in a patient with atopic dermatitis.[1]EH typically presents as a sudden onseteruption of monomorphic vesicles and "punched-out" erosions with hemorrhagic crusts over eczematous areas. Patients may have systemic symptoms, such as fever, lymphadenopathy, or malaise.[2]Presentation ranges from mild and self-limiting in healthy adults to life-threatening in children, infants, and immunocompromised patients. Early treatment with antiviral therapy canshorten the duration of mild disease and prevent morbidity and mortality in severe cases.[3]

Etiology

Eczema herpeticum is due to cutaneous superinfection with herpes simplex virus (HSV), usually HSV-1, in patients with atopic dermatitis. Cases due toreactivation of HSV are more common than primary infection.[4]Patients with atopic dermatitis are prone torecurrent bacterial and viral skin infections due to impaired epidermal barrier function and immune dysregulation.[5]Disseminated cutaneous HSV infection can also occur in patients with otherforms of dermatitis that impair the skin barrierand is known as Kaposi varicelliform eruption (KVE).KVE has been reported in patients with Darier disease, Hailey–Hailey disease, immunobullous diseases, burns, irritant contact dermatitis, mycosis fungoides, Sézary syndrome, ichthyoses, and pityriasis rubra pilaris.[6][7]

Risk factors associated with the development of EHare more severe atopic skin disease, decreased epidermal expression of filaggrin, and decreased production of cathelicidin and other antimicrobial peptides.[8]EH patients exhibit biomarkers associated with T-helper type 2 (Th2) cell responses, such as reduced interferon levels, elevated eosinophil count, and increased serum IgE levels.[5]EH patients are more likely to have food and environmental allergies, asthma, early onset of atopic dermatitis before age five, and history of Staphylococcus aureus and molluscum contagiosum infections.[5]The HLA-B7 allele has been found to be associated with an increased risk of EH.[9]Increased interleukin-10 (IL-10) and local IL-25 expression is found in EH patients and may play a role in the development of EH.[10]The Th2 shift of the immune system in EH patients is associated with decreased antimicrobial peptides in the epidermis and reduced defense against cutaneous HSV infection.

Epidemiology

Eczema herpeticum occurs in less than 3% of atopic dermatitis patients, affecting infants and children more than adults.[5]Atopic dermatitis is the most common chronic inflammatory skin disease in the world, affecting 10to 20% of children in developed countries and 7to 10% of adults in the United States.[11][12]Given the prevalence of HSV exposure, the comparativerarity of EH in atopic dermatitis patients suggests many host factors play an important role in the development of EH. A study of pediatric EH patients in Canada found that predictors of hospitalization includedmale sex, age less than one year, fever, and systemic symptoms at presentation.[13]

Another study in the United States found that the average age of hospitalized pediatric patients with EH was 3.26+/- 0.1 years,and41.8% of patients were female.[13]This study also reported higher prevalence, length of hospital stay, and cost of care occurring in Asian pediatric patients.[13]The epidemiology of EH in non-hospitalized and adult patients is not well defined.

History and Physical

Eczema herpeticum presents as a sudden onset eruption of monomorphic, dome-shaped, grouped, 2to 3 mm vesicles on an erythematous base. Lesions are superimposed on areas of pre-existing atopic dermatitis, most commonly on the face, neck, and upper trunk. The lesions are pruritic, painful, and may spread to involve normal skin over seven to 10 days.[14]Within two weeks, the vesicles ruptureand form characteristic "punched-out" erosions with the hemorrhagic crust. Small erosions may coalesce to form a larger erosion or ulceration with a scalloped border.

Numerous vesicles may appear in successive crops, and multiple morphologies may be present at the same time.Lesions that are secondarily impetiginizedmay have an overlying honey-colored crust. In patients with severe or poorly-controlled atopic dermatitis, the characteristic morphology may be difficult to recognize and can be misdiagnosed as an exacerbation of eczematous dermatitis.[15] Patientsmayhave systemic symptoms, such as fever, malaise, and lymphadenopathy.[3]EH lesions generally heal without scarring within six weeks.[16]

Evaluation

The diagnosis ofeczema herpeticum can be made clinically if characteristic morphology is present. Viral polymerase chain reaction (PCR) canbe performed on vesicle fluid to confirm the diagnosis and determine the type of herpesvirus with high sensitivity and specificity.

If PCR is not available, a Tzank smear, direct fluorescent antibody (DFA) testing, and viral cultures can confirm HSV infection.Bacterial culture should be done if there is a concern for impetiginization. If the clinical presentation is atypical, a skin biopsy may be indicated. Laboratory tests may reveal lymphopenia and an increased erythrocyte sedimentation rate.[14]

Treatment / Management

Eczema herpeticum patients should betreated promptly with systemic acyclovir or valacyclovir tominimize the risk of complications and prevent progression to severe disease.

  • Mild cases can be treated with oral acyclovir or valacyclovir for 7-21 days or until all lesions are crusted over.[17]The recommended dosage for oral acyclovir is 30-60 mg/kg/d divided into three doses per day in childrenand 400 mg3 times per day in adults.[16][18]The dosage for oral valacyclovir is 20 mg/kg/d in children and 500mg 3 times per day in adults.[4]

  • Severe cases or immunocompromised patients should be hospitalized for intravenous acyclovir 5-10 mg/kg every 8 hours.Patients can be transitioned to oral acyclovir once there is clinical improvement, and the lesions start to crust over.[15]Supportive care with gentle emollients and cool compresses can provide symptomatic relief.

  • Critically ill patientsmay needintravenous fluids, electrolyte repletion, wound care, pain control, and nutritional support. Patients should be counseled about the risk of autoinoculation, and frequent handwashing should be encouraged. EH lesions are considered infectious untilcrusted over.

  • Contact precautions should be initiated for hospitalized patients, including patient isolation and the use of face masks and gowns for healthcare providers.[18]Patients should be monitored for the development of secondary bacterial infections and treated with systemic antibiotics according toculture and susceptibility results.[18]

Differential Diagnosis

The differential diagnosis foreczema herpeticum includes impetigo, hand-foot-and-mouth disease, eczema coxsackium, primary varicella infection, disseminated herpes zoster, disseminated molluscum contagiosum, acute generalized exanthematous pustulosis, dermatitis herpetiformis, cellulitis, and erysipelas. Misdiagnosis of EH can lead to delayed initiation of antiviral treatment and subsequent complications. Diagnostic clues that favorEH arepainful lesions, monomorphic size of the lesions, and characteristic "punched-out" erosions in areas of pre-existing atopic dermatitis. Unlike herpes zoster, EH does not respect dermatomal boundaries.

Prognosis

Eczema herpeticum is a potentially life-threatening disease with mortality risk due to complications of systemic viremia, bacteremia, and fungal infection leading to multi-organ failure.[19] Prior to the use of acyclovir, mortality rates in EH patients were reportedly 10% to 50%[20]Since the widespread implementation of systemic antiviral treatment, mortality rates have decreased significantly.

A 2011 study of 1331 hospitalized pediatric EH patients in the United States found no deaths and concluded that the mortality rate of hospitalized patients is low.The median length of hospital stay was three days, with 9.2% of patients requiring hospitalization longer than one week, and 3.8% required ICU admission.[21]A study in 2018 of 4655 hospitalized children with EH found a mortality rate of 0.1%, with 98.1% of patients classified as minor mortality risk. Only 4.5% of patients were classified as having major loss of function, while 33.1% had moderate, and the majority had a minor loss of function.[13]

Complications

Potential complications of EH include cutaneous superinfection with Staphylococcus aureus (S. aureus), Streptococcus pyogenes, and molluscum contagiosum virus.[22][23]The study by Aronson et al. foundS. aureusinfection in 30.3% of hospitalized pediatric EH patients with9.2% due to methicillin-resistantS aureus and3.9% with bacteremia. 86.4% of patients were treated with oral or intravenous antibiotics.[21]Additional complications include meningoencephalitis and herpetic keratoconjunctivitis, which can result in scarring and blindness.[4]Disseminated systemic infections of HSV leading to bone marrow suppression, disseminated intravascular coagulation, and death has been reported.[15]

Deterrence and Patient Education

Patients with eczema herpeticum should be counseled that they are infectious until all lesions have crusted over and thus avoid close contact with others until then. Encourage patients to avoid scratching and wash hands frequently due to the risk of autoinoculation. Patients diagnosed with mild EH and treated as outpatients should be cautioned to seek emergency care if they develop systemic symptoms or worsening rash, as they may require hospitalization, intravenous acyclovir treatment, or antibiotic coverage.

Enhancing Healthcare Team Outcomes

Eczema herpeticum is considered a medical emergency and should be treated promptly with systemic antivirals, as misdiagnosis and delay in treatment can result in serious complications. An ophthalmologic evaluation is warranted in cases of EH involving the face and eyelids. A dermatology consult may be beneficial to confirm the diagnosis. Clinicians should beaware of the risk factors associated with EH, including severe or poorly controlled atopic dermatitis, food and environmental allergies, asthma, the onset of atopic dermatitis before age five, and history ofS. aureus and molluscum contagiosum infections.

Patients with systemic symptoms or widespread involvement should be promptly referred to the Emergency Department. To improve patient outcomes and prevent morbidity and mortality, healthcare providers should have a high index of suspicion for EHin patients with a history of atopic dermatitis presenting with a sudden onset, vesicular, monomorphic rash in areas of pre-existing dermatitis.

Eczema Herpeticum (1)

Figure

Eczema, Herpeticum DermNet New Zealand

References

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2.

Seegräber M, Worm M, Werfel T, Svensson A, Novak N, Simon D, Darsow U, Augustin M, Wollenberg A. Recurrent eczema herpeticum - a retrospective European multicenter study evaluating the clinical characteristics of eczema herpeticum cases in atopic dermatitis patients. J Eur Acad Dermatol Venereol. 2020 May;34(5):1074-1079. [PubMed: 31733162]

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Vera-Kellet C, Hasbún C. Eczema herpeticum: A medical emergency in patients with atopic dermatitis. IDCases. 2020;19:e00663. [PMC free article: PMC7093737] [PubMed: 32226756]

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Wollenberg A, Wetzel S, Burgdorf WH, Haas J. Viral infections in atopic dermatitis: pathogenic aspects and clinical management. J Allergy Clin Immunol. 2003 Oct;112(4):667-74. [PubMed: 14564342]

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Leung DY. Why is eczema herpeticum unexpectedly rare? Antiviral Res. 2013 May;98(2):153-7. [PMC free article: PMC3773952] [PubMed: 23439082]

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Lehman JS, el-Azhary RA. Kaposi varicelliform eruption in patients with autoimmune bullous dermatoses. Int J Dermatol. 2016 Mar;55(3):e136-40. [PubMed: 26500144]

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Walker K, Martini A, Philips H, Sharp L, Thomas K, Tarbox M. Darier disease with disseminated herpes simplex virus type 2 infection. Dermatol Online J. 2019 Apr 15;25(4) [PubMed: 31046908]

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Hata TR, Kotol P, Boguniewicz M, Taylor P, Paik A, Jackson M, Nguyen M, Kabigting F, Miller J, Gerber M, Zaccaro D, Armstrong B, Dorschner R, Leung DY, Gallo RL. History of eczema herpeticum is associated with the inability to induce human β-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis. Br J Dermatol. 2010 Sep;163(3):659-61. [PMC free article: PMC2966528] [PubMed: 20545685]

9.

Mathias RA, Weinberg A, Boguniewicz M, Zaccaro DJ, Armstrong B, Schneider LC, Hata TR, Hanifin JM, Beck LA, Barnes KC, Leung DY. Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells. Br J Dermatol. 2013 Sep;169(3):700-3. [PMC free article: PMC8609667] [PubMed: 23600999]

10.

Damour A, Garcia M, Seneschal J, Lévêque N, Bodet C. Eczema Herpeticum: Clinical and Pathophysiological Aspects. Clin Rev Allergy Immunol. 2020 Aug;59(1):1-18. [PubMed: 31836943]

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Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in children: clinical features, pathophysiology, and treatment. Immunol Allergy Clin North Am. 2015 Feb;35(1):161-83. [PMC free article: PMC4254569] [PubMed: 25459583]

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Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013 Nov;132(5):1132-8. [PubMed: 24094544]

13.

Hsu DY, Shinkai K, Silverberg JI. Epidemiology of Eczema Herpeticum inHospitalized U.S. Children: Analysis ofaNationwide Cohort. J Invest Dermatol. 2018 Feb;138(2):265-272. [PubMed: 28927889]

14.

Wollenberg A, Zoch C, Wetzel S, Plewig G, Przybilla B. Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. J Am Acad Dermatol. 2003 Aug;49(2):198-205. [PubMed: 12894065]

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Zhuang K, Wu Q, Ran X, Ran Y, Ding L, Xu X, Lei S, Lama J. Oral treatment with valacyclovir for HSV-2-associated eczema herpeticum in a 9-month-old infant: A case report. Medicine (Baltimore). 2016 Jul;95(29):e4284. [PMC free article: PMC5265786] [PubMed: 27442669]

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Luca NJ, Lara-Corrales I, Pope E. Eczema herpeticum in children: clinical features and factors predictive of hospitalization. J Pediatr. 2012 Oct;161(4):671-5. [PubMed: 22575249]

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Atherton DJ, Harper JI. Management of eczema herpeticum. J Am Acad Dermatol. 1988 Apr;18(4 Pt 1):757-8. [PubMed: 3372774]

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Sohail M, Khan FA, Shami HB, Bashir MM. Management of eczema herpeticum in a Burn Unit. J Pak Med Assoc. 2016 Nov;66(11):1357-1361. [PubMed: 27812048]

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Wollenberg A. Eczema herpeticum. Chem Immunol Allergy. 2012;96:89-95. [PubMed: 22433376]

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Wheeler CE, Abele DC. Eczema herpeticum, primary and recurrent. Arch Dermatol. 1966 Feb;93(2):162-73. [PubMed: 4159394]

21.

Aronson PL, Yan AC, Mittal MK, Mohamad Z, Shah SS. Delayed acyclovir and outcomes of children hospitalized with eczema herpeticum. Pediatrics. 2011 Dec;128(6):1161-7. [PMC free article: PMC3387896] [PubMed: 22084327]

22.

Beck LA, Boguniewicz M, Hata T, Schneider LC, Hanifin J, Gallo R, Paller AS, Lieff S, Reese J, Zaccaro D, Milgrom H, Barnes KC, Leung DY. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum. J Allergy Clin Immunol. 2009 Aug;124(2):260-9, 269.e1-7. [PMC free article: PMC3056058] [PubMed: 19541356]

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Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Ann Allergy Asthma Immunol. 2018 Jan;120(1):66-72.e11. [PMC free article: PMC5745030] [PubMed: 29273131]

Disclosure: Anny Xiao declares no relevant financial relationships with ineligible companies.

Disclosure: Arline Tsuchiya declares no relevant financial relationships with ineligible companies.

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