OVERVIEW: What every practitioner needs to know
Are you sure your patient has eczema herpeticum? What are the typical findings for this disease?
Patients with Kaposi varicelliform eruption (eczema herpeticum) present with painful red vesicles or “punched-out” erosions in an area of a preexisting dermatosis (Figure 1, Figure 2, Figure 3). In primary infection, associated fever, lymphadenopathy, and general malaise are common. In secondary or recurrent epidoses, systemic symptoms are less likely.
What other disease/condition shares some of these symptoms?
The clinical differential diagnosis includes:
Chickenpox (primary varicella infection)
Herpes zoster (reactivated varicella infection)
Irritant or allergic contact dermatitis
Autoimmune blistering disease
What caused this disease to develop at this time?
Kaposi varicelliform eruption occurs when herpes simplex virus (HSV) infects a preexisting dermatosis. Similar eruption has also been reported after exposure to other viruses (vaccinia, coxsackievirus).
Patients are infected by close contacts or by reactivation of virus harbored in the skin, mucosa, or dorsal root ganglia.
The most common underlying dermatitis is atopic dermatitis/eczema (hence the term “eczema herpeticum”). However, many other diseases that disrupt the normal skin barrier may also predispose to this eruption, including Darier disease, pemphigus, psoriasis, ichthyoses, contact dermatitis, and thermal burns.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Evaluation of blister fluid or infected keratinocytes confirms the diagnosis. If keratinocytes are being sampled, they should be obtained by vigorous scraping of the base of a “fresh” or recently developed lesion to increase the sensitivity of the test. If there is overlying crust, it should be removed before sampling so that the base of the erosion can be accessed.
There are several diagnostic tests available:
Direct fluorescent antibody testing is accurate; can distinguish between HSV 1, HSV 2, and varicella; and results can be obtained rapidly (several hours)
Viral culture is also diagnostic. Results are accurate and reliable, and can distinguish between different viruses. However, results are slow (2 days).
Tzanck smear requires a skilled observer to interpret, but results are immediate on examination of the smear. A Tzanck preparation is performed by placing scrapings from the base of a blister or erosion on a glass slide, staining with Wright or Giemsa stain, and examining under light microscopy for characteristic “Tzanck” cells (multinucleate keratinocytes). Tzanck cells can be seen in herpes, varicella, and cytomegalovirus infections.
Polymerase chain reaction may be helpful in when the cutaneous lesions are old or atypical and viral particles are few in number.
Biopsy is not necessary but can be diagnostic. Characteristic viral cytopathic changes of the epidermis and follicular epithelium are present on hematoxylin and eosin (H & E)-stained tissue. Special stains are not usually required. However, immunohistochemical studies can be performed on paraffin-embedded tissue to distinguish HSV-1, HSV-2, and varicella, which is not possible with routine H & E staining.
Would imaging studies be helpful? If so, which ones?
Imaging studies are not indicated.
If you are able to confirm that the patient has eczema herpeticum, what treatment should be initiated?
Treatment with systemic antiviral agents should be initiated as soon as a diagnosis of Kaposi varicelliform eruption is suspected.
Oral acyclovir is the preferred first-line treatment in otherwise healthy, immunocompetent pediatric patients, at a dose of 30 mg/kg/d divided five times daily for 7-10 days.
Intravenous acyclovir is recommended for patients with systemic involvement or in patients who are immunocompromised (15-30 mg/kg/d divided three times daily). Foscarnet should be used in patients with acyclovir-resistant infection. Valacyclovir is efficacious and can be dosed only twice daily, an advantage over daily multiple dosing of acyclovir. However, it is cost-prohibitive for some patients.
Two topical ophthalmic preparations, trifluridine and vidarabine, are available for use in patients with ophthalmic involvement. Immediate opthalmologic consultation is recommended for any patient with potential ocular infection.
What are the adverse effects associated with each treatment option?
Intravenous acyclovir should be administered with aggressive hydration to prevent renal crystalline precipitates.
What are the possible outcomes of eczema herpeticum?
Kaposi varicelliform eruption has in past decades led to significant mortality. With widespread use of acyclovir, current mortality is estimated at approximately 10% and is most common in immunocompromised patients. Significant morbidity results from cutaneous scarring, keratoconjunctivitis, and subsequent ocular scarring and, rarely, multisystem organ involvement. For these reasons, treatment with systemic antiviral agents is recommended. The risks of complications from Kaposi varicelliform eruption far outweigh the risks from antiviral therapy, which is generally safe and well tolerated.
What causes this disease and how frequent is it?
Kaposi varicelliform eruption affects male and female patients equally and can occur in any age group. The causative virus is transmitted by direct contact with infected secretions or from reactivation of virus from cutaneous nerves.
Kaposi varicelliform eruption occurs in patients with a variety of preexisting dermatoses, including atopic dermatitis, congenital ichthyoses, Darier disease, pemphigus vulgaris, psoriasis, lupus erythematosus, and cutaneous T-cell lymphoma. Many authors postulate that these patients have defects in cell-mediated or humoral immunity that predispose them to cutaneous viral infection. Compared with patients with atopic dermatitis alone, patients with Kaposi varicelliform eruption exhibit the following:
Increased Th2 cytokine levels
Increased incidence of food allergies and asthma
Increased incidence of cutaneous infections such as molluscum contagiosum and staphylococcal infections
Decrease in cutaneous cathelicidin (antimicrobial peptide) protein expression
Higher serum and skin levels of IgE
Recent data also suggest that a genetic mutation in fillaggrin
(R501X) may predispose patients with atopic dermatitis to the development of Kaposi varicelliform eruption.
Activities or exposure that disrupt the skin’s normal mechanical barrier can also dispose to the development of Kaposi varicelliform eruption, including dermabrasion or other epidermal trauma from cosmetic procedures, burns, skin grafts, and mechanical trauma (scrubbing, scraping, or peeling from external agents or injury).
How do these pathogens/genes/exposures cause the disease?
Disruption of the mechanical skin barrier, in combination with decreased local cell–mediated and humoral immune responses, predisposes to viral infection and easy dissemination.
What complications might you expect from the disease or treatment of the disease?
Kaposi varicelliform eruption is considered by many to be a true dermatologic emergency because of the potential for irreversible ocular scarring (in rare cases of ocular involvement). It can also lead to multisystem organ involvement (including lung, liver, and brain infection) in patients who are immunocompromised or have severe primary infection. Patients with Kaposi varicelliform eruption are also likely to experience secondary staphylococcal infection of the affected skin.
How can eczema herpeticum be prevented?
Patients with a known preexisting dermatosis should be counseled about the signs and symptoms of Kaposi varicelliform eruption. In cases of recurrent herpes labialis or herpes genitalis, prophylactic therapy with daily systemic antiviral agents may be indicated. These patients should also be treated with preprocedure systemic antiviral therapy before scheduled dermabrasion or other cutaneous procedures that will disrupt the epidermal barrier.
Vaccination is not available for HSV, and genetic counseling for potential fillaggrin or other gene mutations is not currently available.
What is the evidence?
Freyschmidt, EJ, Mathias, CB, Diaz, N. “Skin inflammation arising from cutaneous regulatory T cell deficiency leads to impaired viral immune responses”. J Immunol. vol. 185. 2010. pp. 1295-302.
Frisch, S, Siegfried, EC. “The clinical spectrum and therapeutic challenge of eczema herpeticum”. Pediatr Dermatol. vol. 28. 2011. pp. 46-52.
Gao, PS, Rafaels, NM, Hand, T. “Fillaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum”. J Allergy Clin Immunol. vol. 124. 2009. pp. 507-13.
Goodyear, HM, MeLeish, P, Randall, S. “Immunological studies of herpes simplex virus infection in children with atopic eczema”. Br J Dermatol. vol. 134. 1996. pp. 85-93.
Hata, TR, Kotol, P, Boguniewicz, M. “History of eczema herpeticum is associated with the inability to induce human beta-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis”. Br J Dermatol. vol. 163. 2010. pp. 659-61.
Ongoing controversies regarding etiology, diagnosis, treatment
Some authors have postulated that chronic topical corticosteroid or calcineurin inhibitor use in patients with atopic dermatitis may lead to increased risk of Kaposi varicelliform eruption, but this has not been proved.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has eczema herpeticum? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- If you are able to confirm that the patient has eczema herpeticum, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of eczema herpeticum?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- What complications might you expect from the disease or treatment of the disease?
- How can eczema herpeticum be prevented?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment