CONTINUING MEDICAL EDUCATION Kaposi’s Varicelliform Eruption: A Case Report and Review of the Literature Sasha C. Kramer, MD; Chadwick J. Thomas, MD; William B. Tyler, MD; Dirk M. Elston, MD GOAL To gain a thorough understanding of Kaposi’s varicelliform eruption OBJECTIVES Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Recognize Kaposi’s varicelliform eruption. 2. Distinguish herpetic from vaccine-associated forms of Kaposi’s varicelliform eruption. 3. Manage Kaposi’s varicelliform eruption in affected patients. CME Test on page 123. This article has been peer reviewed and is accredited by the ACCME to provide continuing approved by Michael Fisher, MD, Professor of medical education for physicians. Medicine, Albert Einstein College of Medicine. Albert Einstein College of Medicine designates Review date: January 2004. this educational activity for a maximum of 1 This activity has been planned and implemented category 1 credit toward the AMA Physician’s in accordance with the Essential Areas and Policies Recognition Award. Each physician should claim of the Accreditation Council for Continuing Medical only that hour of credit that he/she actually spent Education through the joint sponsorship of Albert in the activity. Einstein College of Medicine and Quadrant This activity has been planned and produced in HealthCom, Inc. Albert Einstein College of Medicine accordance with ACCME Essentials. Drs. Kramer, Thomas, Tyler, and Elston report no conflict of interest. The authors report discussion of off-label use for intravenous vaccinia immune globulin under an investigational new drug protocol. Dr. Fisher reports no conflict of interest. Disseminated herpes or vaccinia in the setting of eczema herpeticum in a woman with a long- underlying skin diseases is known as Kaposi’s standing history of atopic dermatitis (AD). This varicelliform eruption (KVE). Patients typically report also reviews the literature on eczema her- present with disseminated vesicopustules in the peticum and eczema vaccinatum (EV), summa- areas of the most severe involvement of their rizes clinical and histopathologic characteristics underlying skin disease. We report a case of and treatment, and discusses the recommenda- tions of the Centers for Disease Control and Accepted for publication December 23, 2003. Prevention for smallpox vaccination. Drs. Kramer and Thomas are residents from the Department of Cutis. 2004;73:115-122. Dermatology, Dr. Tyler is an Associate in Pathology, and Dr. Elston is an Associate in Dermatology and Laboratory Medicine from atients with chronic inflammatory skin dis- the Departments of Dermatology and Pathology, Geisinger eases, particularly atopic dermatitis (AD), are Medical Center, Danville, Pennsylvania. at risk for dissemination of cutaneous viral Reprints: Dirk M. Elston, MD, Department of Dermatology, P Geisinger Medical Center, MC 14-06, 100 N Academy Ave, infections. Infection is most commonly caused by Danville, PA 17822 ([email protected]). herpes simplex virus (HSV); however, it also may VOLUME 73, FEBRUARY 2004 115 Kaposi’s Varicelliform Eruption Figure 1. Confluent eroded vesicopapules on the cheek and chin. occur with coxsackievirus or vaccinia. The term Figure 2. Numerous vesicles with prominent erosion Kaposi’s varicelliform eruption (KVE) is used synony- and crusting present on the trunk. mously with eczema herpeticum when HSV infects eczematous skin. When KVE occurs in a patient who has received or has come in close contact with some- Results of a bacterial culture yielded Staphylococcus one who has received the smallpox vaccination, it and Streptococcus species. Biopsy results confirmed also is referred to as eczema vaccinatum (EV). The cytopathic changes diagnostic of herpesvirus infec- pathogenesis of KVE may be related to impaired tion with focal keratinocyte necrosis and acantholysis immune surveillance or simply may represent a (Figures 4 and 5). mechanical phenomenon secondary to decreased epithelial barrier function. As the threat of bioter- Comment rorism with smallpox increases, physicians must KVE was first described in 1887 by Moritz Kaposi who address the question of safety when vaccination is was Professor and Chairman of Dermatology at the considered in individuals with a history of atopy. University of Vienna School of Medicine.1 Kaposi initially thought the condition was secondary to a Case Report fungal infection, but the discovery of inclusion bodies A 40-year-old woman with long-standing AD pre- histologically suggested a viral etiology.2 The term sented with a 5-day history of painful vesicles that KVE is now used to describe disseminated herpes sim- had started on her right arm and gradually spread to plex, vaccinia, or coxsackievirus in the setting of involve the rest of her body. She had been evaluated certain underlying skin diseases.1 by a physician and had been placed on prednisone, Eczema herpeticum is a term often used synony- cephalexin, and triamcinolone without improve- mously with HSV-associated KVE because eczema is ment. The patient did not have any preceding history the most common underlying skin condition seen in of oral ulcerations or erosions but did report a history KVE.1 KVE also has been reported to occur in the set- of intermittent “cold sores.” On examination, her ting of Darier disease,3,4 cutaneous T-cell lymphoma,5 face, chest, arms, abdomen, back, and upper thighs pityriasis rubra pilaris,6 familial benign chronic pem- were packed with confluent vesicopapules; some areas phigus,7 congenital ichthyosiform erythroderma, seb- were eroded and weeping a yellow serous fluid (Fig- orrheic dermatitis, Wiskott-Aldrich syndrome,8 ures 1 through 3). Direct fluorescent antibody (DFA) psoriasis, and lupus erythematosus.9 Additionally, test yielded positive results of HSV-1 and HSV-2. A KVE has been reported in patients who have disrup- diagnosis of eczema herpeticum was made, and treat- tion of the epidermal barrier either as a result of irri- ment with valacyclovir and cephalexin was initiated. tant contact dermatitis caused by vigorous scrubbing 116 CUTIS® Kaposi’s Varicelliform Eruption A B Figure 3. Individual umbilicated vesicopustules (A and B). of the face with a facial cleanser,10 following a skin Prior to the availability of antiviral therapy, deaths graft,11 in the setting of second-degree burns,12 or occurred secondary to rhabdomyolysis and renal fail- after dermabrasion.2 It also has been reported to occur ure.18 Bacterial infection of the eroded skin can in the setting of multiple myeloma.13 progress to bacterial sepsis. The literature presents conflicting data regarding immunologic defects in response to herpesvirus Differential Diagnosis and Diagnosis infection in patients with AD. Although it has been The differential diagnosis of eczema herpeticum suggested that patients with AD have depressed includes impetigo, varicella-zoster virus, and EV.1 A cell-mediated immunity to HSV, studies have failed diagnosis of eczema herpeticum should be consid- to confirm this.14,15 Some authors have postulated ered in the presence of multiple umbilicated that decreased numbers of circulating natural killer papules, vesicopustules, or erosions in a patient with cells and a decrease of IL-2 receptors cause patients underlying skin disease. The presence of herpesvirus with atopic eczema to be more susceptible to her- infection often can be confirmed by the presence of petic infection.15 It may be that the spread of infec- ballooning degeneration and nuclear cytopathic tion is related purely to mechanical factors rather effect in multinucleated cells seen on a Tzanck test. than to immune surveillance. The characteristic nuclear cytopathic effect KVE can present in a primary form or a recurrent includes peripheral margination of nucleoplasm so form.16 The primary form presents with clusters of that it creates a basophilic rim at the edge of the umbilicated vesicles and vesicopustules that usually nucleus. When possible, samples should be obtained occur in areas where skin has been most affected by from the floor of a freshly unroofed vesicopustule.19 the underlying skin disease.17 The lesions gradually More specific identification of the causative agent spread and are accompanied by systemic symptoms can be confirmed by viral culture or DFA testing of such as fever, malaise, and lymphadenopathy.1 Milder a smear. Smears for DFA testing generally are cases may have lesions limited to the head and obtained with a No. 15 blade from the floor of a neck.16 Over time, the vesicles may become hemor- fresh vesicle. A round smear requires fewer drops of rhagic and later develop into erosions that can reagent than a long thin smear and is therefore more become secondarily infected.17 More severe cases can cost-effective. DFA results generally can be result in scarring. Recurrent cases usually are more obtained within 1 to 4 hours. limited with fewer systemic symptoms.16 Biopsy results of eczema herpeticum will show Herpetic keratitis is a serious ocular sequela. For- changes characteristic of herpesvirus infection; tunately, despite the frequent involvement of vesi- namely ballooning degeneration of keratinocytes copustules on the face, ocular herpetic infection is with multinucleated epithelial cells and nuclear cyto- rare in the setting of KVE.18 One study reported pathic effect.19 Polymerase chain reaction from tissue 3 patients with KVE with positive HSV conjunctival or smears may be performed to extract herpes DNA culture results