Kaposi varicelliform eruption in Darier disease

Dear Editor, Darier disease (DD) is a rare autosomal-dominant acantholytic skin disorder caused by mutations in the ATP2A2 gene. This mutation disrupts intracellular calcium signaling, leading to the breakdown of desmosomes, which impairs cell adhesion.[1] The disease features greasy keratotic papuloplaques in seborrheic and intertriginous areas and can be exacerbated by heat, sweating, ultraviolet light, and mechanical trauma.[2] The altered skin barrier predisposes patients to relapsing bacterial, viral, and fungal infections.[3] Kaposi varicelliform eruption (KVE), or eczema herpeticum, is a disseminated herpes simplex virus (HSV) superinfection in preexisting dermatologic diseases, including acantholytic, papulosquamous, and autoimmune bullous dermatoses, particularly in patients with atopic dermatitis.[4] Here, we report a case of KVE in an adolescent with poorly controlled DD. A 17-year-old boy with biopsy-confirmed DD was lost to follow-up for months. He presented to the emergency department with a 4-day history of painful skin lesions on his face and neck. Accompanying symptoms included intermittent fever, progressive malaise, and fatigue. He denied headache, shortness of breath, or other systemic symptoms, neither recent travel history nor contact history. The patient applied topical betamethasone for exacerbations and took oral antihistamines for itch but denied new topical agents before the episode. Physical examination revealed diffused umbilicated vesicles and pustules with perivesicular erythema, covered with honey-colored crusts on the face and neck [Figure 1a-e]. There was no lymphadenopathy. The body temperature was 38.3°C, and laboratory tests showed leukocytosis and elevated levels of C-reactive protein (122.08 mg/L). KVE was diagnosed by detection of multinucleated giant cells on a Tzanck smear, a positive viral culture of HSV-1, and detection of HSV-1 DNA in vesicles by polymerase chain reaction (PCR). The patient was then admitted and received systemic antiviral therapy, starting with 1 week of intravenous acyclovir (500 mg three times a day), followed by 1 week of oral acyclovir (400 mg three times a day). In addition, an intravenous antibiotic with cefazolin (1 g three times a day) was initiated for a suspected secondary bacterial infection. Ophthalmologic examination showed no ocular involvement. The antibiotic was switched to intravenous piperacillin–tazobactam (4.5 g four times a day) based on positive cultures of methicillin-sensitive Staphylococcus aureus and Pseudomonas aeruginosa. The blood culture results were negative. Fever and symptoms gradually subsided during hospitalization. Following 2 weeks of treatment, all lesions healed with residual erythematous macules and patches [Figure 1f]. Acitretin 25 mg/day was prescribed for underlying DD after successful infection management, leading to a satisfactory outcome.Figure 1: (a-c) Diffuse umbilicated vesicles and pustules with peripheral erythema and serous crusting on the face and neck. (d) Typical presentation in Darier disease by confluent greasy keratotic papuloplaques on the posterior neck, along with the presence of umbilicated vesicles resembling herpetic lesions noted in the peripheral area. (e) The close-up picture of diffuse vesicles and pustules with peripheral erythema and serous crusting on the neck and upper chest, some with umbilicated feature. (f) Residual erythematous macules and patches on the face and neck after 2 weeks of systemic antiviral therapy.DD complicated by KVE is a less common occurrence but constitutes a dermatologic emergency due to its potentially high mortality if misdiagnosed or delayed treatment.[5] The underlying mechanism of KVE in DD remains unclear. Besides altered skin barrier function, a defect in cell-mediated immunity has been postulated as a consequence of KVE in DD, although some studies have failed to confirm an immunologic derangement.[2] An in vitro study demonstrated that silencing the ATP2A2 gene disrupted the skin barrier, facilitating HSV-1 invasion into the deep epidermal layers and reducing the production of interferon-β and other antiviral factors.[6] A recent study suggested a potential relationship between pro-inflammatory cytokines (e.g. interleukin-6 and tumor necrosis factor-alpha) and the development of severe KVE by promoting HSV growth.[7] Clinically, patients with KVE often present with clusters of monomorphic dome-shaped vesicles that develop into umbilicated or crusted erosions in preexisting lesions, frequently accompanied by fever, malaise, or lymphadenopathy.[8] It is sometimes difficult to differentiate KVE from a vesiculobullous variant of DD since DD could manifest as blistering with ulcerations. HSV infection should always be considered in patients experiencing sudden worsening, especially with changes in pain or itch in the underlying eruption, followed by the appearance of monomorphic dome-shaped vesicles and pustules.[2,3] Subsequent complications of KVE include HSV keratoconjunctivitis, secondary bacterial wound infection, septicemia, viremia, meningitis, or encephalitis, which are potentially lethal. This emphasizes the importance of prompt diagnosis and management. Diagnosis can be supported by multinucleated giant cells on a Tzanck test and confirmed by positive HSV viral culture or PCR for HSV DNA from blister fluid.[5,8] Once KVE is diagnosed, timely systemic antiviral therapy should be initiated to reduce morbidity and mortality.[8] In patients with DD, the presence of moderate-to-severe disease has been reported to be associated with the development of KVE.[2] Therefore, in addition to avoiding possible exacerbating factors, patient education with appropriate treatment of the underlying DD and good medication compliance are believed to be the most effective strategies to prevent KVE. This case demonstrates the presentation of an emergent condition with toxic signs in DD and emphasizes the importance of precise diagnosis and timely treatment to avoid potentially fatal complications. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest Dr. Chun-Bing Chen, the Deputy Editor at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.