AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Kaposi varicelliform eruption (KVE) is the name given to a distinct cutaneous eruption caused by herpes simplex virus (HSV) type 1, HSV-2, coxsackievirus A16, or vaccinia virus that infects a preexisting dermatosis. Most commonly, it is caused by a disseminated HSV infection in patients with atopic dermatitis.

Pathophysiology

To date, the pathophysiology of KVE remains unclear. Several proposed mechanisms involve both cell-mediated and humoral defects in persons with atopic dermatitis that could account for their susceptibility.

• T-cell–mediated immunity is important in the control of primary and recurrent HSV infections, and an HSV-specific, cell-mediated immune defect has been found in adults following KVE.
• Antibodies against HSV appear to limit the severity of infection and play a role in cell-mediated cytotoxicity. A persistently low enzyme-linked immunosorbent assay titer (1:1600) after infection has been reported following KVE.
• Natural killer (NK) cells provide a first-line defense against HSV infection, and reduced NK activity in atopic dermatitis has been reported. The reduced number of NK cells and a decrease in interleukin 2 receptors, a marker for lymphocyte activation, have been proposed to contribute to the susceptibility of children with atopic dermatitis.

Recent studies present conflicting data with regard to HSV-specific immune defects in patients with atopic dermatitis. One study failed to show any HSV-specific immune defect, either cell-mediated or humoral, in children with atopic dermatitis. In contrast, one study found that the skin in patients with atopic dermatitis is rich in interleukin 4 (IL-4)–producing CD4⁺ T cells. This increase in IL-4 can inhibit Th-1 cells and thereby suppress interferon-gamma secretion, leading to increased susceptibility to HSV infection in atopic skin.

The cathelicidin family of antimicrobial peptides is an integral component of the innate immune response that exhibits activity against bacterial, fungal, and viral pathogens. The importance of cathelicidins in antiviral skin host defense was confirmed by the observation of higher levels of HSV-2 replication in cathelicidin-deficient mouse skin compared with that seen in skin from their wild-type counterparts. Skin from patients with KVE exhibited significantly lower levels of cathelicidin protein expression than skin from patients with atopic dermatitis. An inverse correlation between cathelicidin expression and serum immunoglobulin E levels in patients with atopic dermatitis and patients with KVE has also been found. A high total serum immunoglobulin E level may also be a risk factor for the development of KVE.

Frequency

United States

The incidence of KVE has increased since 1980, likely secondary to the increased incidence of HSV infections.

Mortality/Morbidity

Significant morbidity and mortality can be associated with KVE due to HSV infection. However, with the introduction of intravenous acyclovir, in addition to systemic/topical antibiotic treatment, the mortality from KVE has decreased from as high as 50% to less than 10%.

Corticosteroid treatment has been suggested as a risk factor for developing KVE. However, a retrospective analysis of 100 cases of KVE showed that more than 75% of patients had not received corticosteroid treatment in the 4 weeks before the onset of KVE. This seems to argue against a role for topical steroids in the development of KVE. However, recent reports have described KVE occurring in atopic dermatitis patients treated with topical calcineurin inhibitors, such as tacrolimus, who subsequently developed KVE. Whether this is causally related remains unknown.

Sex

KVE affects men and women equally.

Age

• Originally thought to be a disorder of infants, it is now known to occur in children of any age and in adults.
• In a German study of 75 patients with KVE, the age of onset ranged from 5 months to 69 years. Most patients (56%) were aged 15-24 years.
• In one study, the mean age of onset of atopic dermatitis was lower (5.6 y) in patients with KVE compared with atopic dermatitis controls (9.6 y).

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

• KVE begins as clusters of umbilicated vesiculopustules in areas where the skin has been affected by a preexistent dermatitis. Frequently, a delay in diagnosis occurs because the eruption is confused with the underlying disease until the characteristic umbilicated vesiculopustules appear. The eruption continues to spread over 7-10 days and may be associated with a high temperature, malaise, and lymphadenopathy.
• The primary episode of KVE runs its course and heals in 2-6 weeks.
• The average duration of illness is 16 days.
• Transmission occurs through contact with a person who is infected or by dissemination of primary or recurrent herpes.
• Recurrent episodes may also occur but are milder and not usually associated with systemic symptoms.
• Some studies have shown a high frequency of HSV DNA in the oral cavity of patients with KVE.
• In severe cases of KVE, lesions may heal with scarring.

Physical

• Umbilicated vesiculopustules that progress to punched-out erosions in the setting of a widespread dermatosis is virtually pathognomonic for KVE.
• The eruption is most commonly disseminated in the areas of dermatitis, with a predilection for the upper body and the head. Localized forms also exist.
• The vesicles often become hemorrhagic and crusted and can evolve into extremely painful erosions with a punched-out appearance.
• These erosions may coalesce to form large, denuded areas that frequently bleed and can become secondarily infected with bacteria.

Causes

• KVE is caused by HSV-1, HSV-2, coxsackievirus A16, or vaccinia virus infecting a preexisting dermatosis.
• Most commonly, it is caused by a disseminated HSV infection in patients with atopic dermatitis. For this reason, it is also referred to as eczema herpeticum.
• KVE has also been associated with mycosis fungoides, pityriasis rubra pilaris, neurodermatitis, irritant contact dermatitis, congenital ichthyosiform erythroderma, ichthyosis vulgaris, pemphigus foliaceus, benign familial pemphigus (Hailey-Hailey disease), Darier disease, Wiskott-Aldrich syndrome, Sézary syndrome, seborrheic dermatitis, skin grafts, burns, cowpox, and rosacea.

DIFFERENTIALS

Section 4 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Varicella-zoster virus
Eczema vaccinatum

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• Viral cultures of fresh vesicular fluid and the direct observation of infected cells scraped from ulcerative lesions by direct fluorescent antibody (DFA) stain are the most useful and reliable diagnostic tests available.
• • When cultures are taken, swabbing should be vigorous because HSV is cell associated and a paucity of extracellular virus particles may be present.
  • DFA staining of scrapings from an early vesicular or crusted lesion is as accurate as viral culture in differentiating HSV-1, HSV-2, and varicella-zoster virus. Furthermore, the results from DFA staining can be available in a few hours.
• A Tzanck smear of an opened vesicle or erosion can provide rapid diagnosis when it shows the characteristic epithelial multinucleated giant cells and acantholysis.
• If the lesions are atypical, equivocal, or old, biopsy or the polymerase chain reaction (PCR) should be considered. A biopsy can establish a diagnosis that may not have been thought of clinically, whereas PCR can detect minute amounts of viral DNA in tissue through amplification.

Procedures

• As indicated above, biopsy of the affected area can aid in the diagnosis of KVE.

Histologic Findings

Tissue biopsy shows changes characteristic of herpes virus infection, which is ballooning degeneration of keratinocytes with multinucleated epithelial cells. A viral cytopathic effect occurs on the nucleus, which manifests as peripheral margination of the nucleoplasm such that it creates a basophilic rim at the edge of the nucleus.

TREATMENT

Section 6 of 10  

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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Consultations

Consultation with an ophthalmologist is indicated when eye involvement is suspected. Herpetic keratitis can lead to scarring. Fortunately, ocular herpetic infection in the setting of KVE is rare.

MEDICATION

Section 7 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antivirals

Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Outpatient Care

• Patients should return for follow-up care in approximately 2 weeks so that the response to treatment can be evaluated.

Complications

• Systemic viremia with multiple organ involvement is the major cause of morbidity and mortality. The organ systems involved include the liver, the lungs, the brain, the gastrointestinal tract, and the adrenal glands.
• Septicemia from secondary bacterial infections of skin lesions also contributes to the morbidity and mortality of patients. Staphylococcus aureus, alone or mixed with group A beta-hemolytic streptococci, Pseudomonas aeruginosa, and Peptostreptococcus species were found to be the major isolates from patients with secondary bacterial infections.
• When KVE due to HSV involves the face, a risk of ocular involvement leading to blepharitis, conjunctivitis, keratitis, and uveitis exists. Herpetic keratitis can lead to blindness due to stromal scarring. Interestingly, very few reported cases of ocular herpetic disease in KVE have occurred, even when positive conjunctival HSV cultures are present.

Patient Education

• For excellent patient education resources, visit eMedicine's Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Eczema.

MULTIMEDIA

Section 9 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Characteristic umbilicated vesiculopustules on the thigh of a child with a preexisting atopic dermatitis.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

• Bork K, Brauninger W. Increasing incidence of eczema herpeticum: analysis of seventy-five cases. J Am Acad Dermatol. Dec 1988;19(6):1024-9. [Medline].
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• Vestey JP, Howie SE, Norval M, Maingay JP, Neill WA. Immune responses to herpes simplex virus in patients with facial herpes simplex and those with eczema herpeticum. Br J Dermatol. Jun 1988;118(6):775-82. [Medline].
• Vestey JP, Howie SE, Norval M, Maingay JP, Neill WA. Severe eczema herpeticum is associated with prolonged depression of cell-mediated immunity to herpes simplex virus. Curr Probl Dermatol. 1989;18:158-61. [Medline].
• Wheeler CE Jr, Abele DC. Eczema herpeticum, primary and recurrent. Arch Dermatol. Feb 1966;93(2):162-73. [Medline].
• 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. Aug 2003;49(2):198-205. [Medline].
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Article Last Updated: Aug 29, 2007