Kaposi Varicelliform Eruption

Updated: Aug 20, 2015
  • Author: David T Robles, MD, PhD; Chief Editor: William D James, MD  more...
  • Print
Overview

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 (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.
Next:

Pathophysiology

To date, the pathophysiology of Kaposi varicelliform eruption (KVE) remains unclear. A number of preexisting conditions have been associated with KVE, including AD, pemphigus, Darier disease, seborrheic dermatitis, lupus erythematosus, psoriasis, Wiskott-Aldrich syndrome, congenital ichthyosiform erythroderma, mycosis fungoides, and Sézary syndrome. [1, 2, 3]

Proposed mechanisms to account for the increased susceptibility of individuals with AD to develop KVE or 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. [4] 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. [5] Furthermore, the addition of interleukin (IL)–4 and IL-13 (both overexpressed in Th-2 inflammatory reactions) amplified vaccinia virus replication in human skin. [6]

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. [7]

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. [8] Skin from patients with KVE exhibited significantly lower levels of cathelicidin protein expression than skin from patients with AD. [9] 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. [10]

Skin barrier dysfunction, found in conditions like AD, ichthyosis, pemphigus, and Darier disease, is also a factor in the development of KVE. KVE has also been reported after epidermal disruption caused by vigorous scrubbing, dermabrasion, burns, and skin grafts. [11] 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. [12]

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. [13]

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. [14]

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. [15] A link has been established between defective IFN-gamma and CD8+ T cells contributing to the ADEH-positive phenotype. [16]

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 [17]
  • Polymorphisms in the STAT6 gene, which leads to overexpression of IL-4 and IL-13 and increased vaccinia virus replication in keratinocytes [18]
  • Mutations in claudin-1, a tight junction adhesive protein, which was associated with more widespread HSV skin infections in AD patients [19]
Previous
Next:

Epidemiology

Frequency

The incidence of Kaposi varicelliform eruption (KVE) has increased since 1980, likely secondary to the increased incidence of HSV infections. [20]

Sex

Kaposi varicelliform eruption (KVE) affects men and women equally.

Age

Originally thought to be a disorder of infants, Kaposi varicelliform eruption (KVE) 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. [21] In one study, the mean age of onset of AD was lower (5.6 y) in patients with KVE compared with AD controls (9.6 y).

Previous