Kaposi Varicelliform Eruption

Updated: Jun 28, 2022
  • Author: David T Robles, MD, PhD, FAAD; Chief Editor: William D James, MD  more...
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Practice Essentials

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 (AD) and, for this reason, is often referred to as eczema herpeticum (EH). Note the image below.

Erythematous vesicles characteristic of eczema her Erythematous vesicles characteristic of eczema herpeticum with associated impetiginous crust.


Tissue biopsy in Kaposi varicelliform eruption (KVE) shows changes characteristic of herpes virus infection, notably ballooning degeneration of keratinocytes with multinucleated epithelial cells. A viral cytopathic effect occurs in the nucleus, which manifests as peripheral margination of the nucleoplasm creating a basophilic rim at the edge of the nucleus.

Also see Laboratory Studies.


Antivirals are used in the treatment of Kaposi varicelliform eruption (KVE). [1]  See Medication.

Patients with KVE should return for follow-up care in approximately 2 weeks to assess treatment response and to monitor for sequelae.

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.



To date, the pathophysiology of Kaposi varicelliform eruption (KVE) remains unclear. A number of preexisting conditions have been associated with KVE, including atopic dermatitis (AD), pemphigus, Darier disease, seborrheic dermatitis, lupus erythematosus, psoriasis, Wiskott-Aldrich syndrome, congenital ichthyosiform erythroderma, mycosis fungoides, and Sézary syndrome. [2, 3, 4]

Proposed mechanisms to account for the increased susceptibility of individuals with AD to develop KVE or eczema herpeticum (EH) include systemic immune defects involving both cell-mediated and humoral immunity, as well as impairment in cutaneous immune responses that are interrelated with the defective mechanical barrier properties of affected skin in person with AD.

The Th-2 cytokine milieu found in AD appears to be of central importance. In a 2009 study, patients with AD who had a prior history of EH demonstrated more severe disease with a greater Th-2 cytokine predominance. In addition, these patients had greater allergen sensitization, greater frequency of food allergy and/or asthma, and had a much higher frequency of cutaneous infections with pathogens such as Staphylococcus aureus or molluscum contagiosum. [5] Another study found that vaccinia virus inoculated into mouse skin primed with a Th-2-weighted inflammatory response resulted in larger and more erosive primary lesions, more satellite lesions, and higher viral loads than normal or TH-1 weighted skin. [6] Furthermore, the addition of interleukin (IL)–4 and IL-13 (both overexpressed in Th-2 inflammatory reactions) amplified vaccinia virus replication in human skin. [7]

A study from 2014 showed that IL-10 and IL-17 also play a great role in AD patients presenting with disseminated disease. IL-10 induces Th2 responses and regulates T-cell activation. When mice were used to test this theory in association with vaccinia virus, it was found that when an AD exacerbation occurred, there was a concurrent decrease in IL-10. In addition, the neutrophil cutaneous manifestations showed an increase in the amount of IL-17A, IL-17F, and CXCL2, overall showing that a decrease in IL-10 and an increase in IL-17 production resulted in increased systemic viral eruption. [8]

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. [9] Skin from patients with KVE exhibited significantly lower levels of cathelicidin protein expression than skin from patients with AD. [10] An inverse correlation between cathelicidin expression and serum immunoglobulin E levels in patients with AD and patients with KVE has also been found. A high total serum immunoglobulin E level has been identified as a risk factor for the development of KVE. [11]

Skin barrier dysfunction, found in conditions like AD, ichthyosis, pemphigus, and Darier disease, is also a factor in the development of KVE. [4] KVE has also been reported after epidermal disruption caused by vigorous scrubbing, dermabrasion, burns, and skin grafts. [12] Filaggrin is a critical protein involved in formation of an effective skin barrier. Data obtained from a large registry study suggest that certain filaggrin mutations, notably R501X, confer a significant risk of developing KVE in patients with AD. [13]

Studies present conflicting data with regard to HSV-specific immune defects in patients with AD. One study failed to show any HSV-specific immune defect, either cell-mediated or humoral, in children with AD. In contrast, another study found that the skin in patients with AD is rich in IL-4–producing CD4+ T cells. This increase in IL-4 inhibits Th-1 cells and thus suppresses interferon-gamma secretion. Decreased interferon-gamma may contribute to increased susceptibility to HSV infection in atopic skin. [14]

Additional evidence for viral susceptibility in patients with AD was demonstrated in a study that found keratinocytes of ADEH patients had significantly decreased expression of a specificity protein 1 (Sp1) over AD patients without a history of EH and nonatopic dermatitis patients. Central to this finding is that Sp1 gene knockdown was associated with enhanced replication of both vaccinia and HSV-1 viruses. [15]

Furthermore, an additional study has shown that patients who are ADEH positive have a specific immune response post HSV-1 exposure, through the inhibition of IRF3 and IRF7. This inhibition correlates to the innate immune pathway that creates an increased predisposition to disseminated viral infection. [16, 17] A link has been established between defective IFN-gamma and CD8+ T cells contributing to the ADEH-positive phenotype. [18]

The genetics underlying the predisposition of certain AD patients to EH are reflective of the complex relationship between the skin and the immune system. Proposed genetic factors include the following:

  • Mutations in interferon regulatory factor 2, which contribute to the markedly reduced levels of interferon-gamma found in ADEH patients [19]

  • Polymorphisms in the STAT6 gene, which leads to overexpression of IL-4 and IL-13 and increased vaccinia virus replication in keratinocytes [20]

  • Mutations in claudin-1, a tight junction adhesive protein, which was associated with more widespread HSV skin infections in AD patients [21]

A study published in 2021 used whole genome sequencing to identify novel genetic mutations associated with KVE in the following 8 genes: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. [22]



Kaposi varicelliform eruption (KVE) is caused primarily by HSV-1, but can also be caused by 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 (AD). For this reason, it is also referred to as eczema herpeticum (EH).

KVE has also been associated with the following:

Case reports have stated that KVE occurred as a drug reaction without a previous dermatosis, once to phenytoin and the other post everolimus treatment for metastatic renal cell carcinoma. [28, 29]



The incidence of Kaposi varicelliform eruption (KVE) has increased since 1980, likely secondary to the increased incidence of HSV infections. [30]  KVE affects men and women equally.

Originally thought to be a disorder of infants, KVE is now known to occur in children of any age and in adults. The Nationwide Inpatient Sample, 2002-2012, surveyed a 20% sample of all US hospitals and concluded that the incidence of hospitalization per million children ranged from 4.03-7.30 and increased significantly during the study. The mean length of a stay was 3.86 days (±9 d) and the cost of care was $5737 (±$160.60). [31] 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. [32] In one study, the mean age of onset of AD was lower (5.6 y) in patients with KVE compared with atopic dermatitis controls (9.6 y).



Significant morbidity and mortality can be associated with Kaposi varicelliform eruption (KVE) due to HSV infection. However, with the introduction of intravenous acyclovir, in addition to systemic/topical antibiotic treatment, the mortality rate from KVE has decreased from as high as 50% to less than 10%. Significant complications may arise from keratoconjuctivitis, and rare cases of multiple-organ involvement with meningitis and encephalitis have been reported. [33]

Corticosteroid treatment has been suggested as a risk factor for developing KVE. Yet, a retrospective analysis of 100 cases showed that greater than 75% of patients had not received corticosteroid treatment in the 4 weeks before the onset of KVE. [32] This seems to argue against a role for topical steroids in the development of KVE. However, KVE has been reported to occur in atopic dermatitis patients treated with topical calcineurin inhibitors, such as tacrolimus. [34] Whether this is causally related remains unknown.

A recent retrospective cohort study concluded that delay in treatment with acyclovir increased hospital length of stay (LOS), ranging from an 11% increase when treatment was delayed only 1 day to an 98% increase in LOS when started on day 4-7. The study noted that there were no associated deaths during the nearly 10-year study period. [35]