Erupción variceliforme de Kaposi en el contexto de enfermedad de boca-mano-pie en un niño sin dermatitis atópica / Variceliform eruption of Kaposi in the context of hand foot and mouth disease in a child without atopic dermatitis

La erupción variceliforme de Kaposi (EVK) es la diseminación cutánea del virus herpes simple (VHS), siendo la etiología más frecuente el VHS tipo 1. Suele presentarse en pacientes con enfermedades cutáneas de base o por lesiones agudas de la barrera epidérmica. La sospecha clínica se confirma mediante reacción en cadena de la polimerasa, aislamiento del virus en cultivo o mediante anticuerpos monoclonales realizados de una muestra extraída de las lesiones cutáneas. La complicación más frecuente es la sobreinfección bacteriana por Staphylococcus aureus y el tratamiento de elección es aciclovir oral o intravenoso, en función de la gravedad. En la literatura, son múltiples los artículos que asocian la dermatitis atópica con la EVK. Pero estas dos patologías no siempre vienen de la mano, por lo que su diagnóstico en ocasiones puede suponer todo un reto para el pediatra. Presentamos una actualización de los conocimientos de esta enfermedad a raíz de un caso recientemente diagnosticado en nuestro servicio

The variceliform eruption of Kaposi (EVK) is the cutaneous dissemination of the herpes simplex virus (HSV), the most frequent etiology being HSV type 1. It usually occurs in patients with underlying skin diseases or due to a lesion in the epidermal barrier. Clinical suspicion is confirmed by polymerase chain reaction, virus isolation in culture or by monoclonal antibodies made from a sample of skin lesions. The most frequent complication is bacterial superinfection due to Staphylococcus aureus and the treatment of choice is oral or intravenous acyclovir, depending on the severity. In literature, there are many articles that associate atopic dermatitis with the EVK. But these two pathologies do not always come hand in hand, so their diagnosis can sometimes be a challenge for the pediatrician. We present an update on the knowledge of this disease following a case recently diagnosed in our service

Kaposi Varicelliform Eruption Associated With Chickenpox in a Liver Transplant Recipient.

A 43-year-old male patient developed varicella virus (chickenpox) 4 months after receiving a liver transplant. Within 5 days of complete recovery, he presented with widespread cutaneous vesicular eruptions involving the face, back, abdomen, and upper extremities. Tzanck smear showed ground glass inclusions in the nuclei of multinucleated giant cells, suggestive of viral pathology. The patient was subsequently diagnosed with Kaposi varicelliform eruption, a rare dermatologic emergency. He was treated with high-dose intravenous acyclovir and fully recovered.

Frequency and Clinical Features Associated With Eczema Herpeticum in Hospitalized Children With Presumed Atopic Dermatitis Skin Infection.

BACKGROUND: Atopic dermatitis (AD) predisposes to viral skin infections, such as eczema herpeticum (EH), and to bacterial skin infections, such as those caused by Staphylococcus aureus (SA) and group A streptococcus (GAS). This study evaluated clinical features of EH and its frequency of codetection with SA or GAS in children hospitalized for presumed AD skin infection. METHODS: We retrospectively reviewed clinical data for children ≤18 years of age admitted to a large hospital system for AD with presumed skin infection from January 2004 to December 2018. Those with an alternate primary diagnosis or missing microbiologic data were excluded. Encounters with herpes simplex virus testing were identified as AD with EH (ADEH+) or without (ADEH-). Encounters with bacterial skin culture growth were identified as SA or GAS. RESULTS: Among 180 AD encounters with suspected skin infection, 133 (74%) were tested for herpes simplex virus. Clinical findings associated with ADEH+ status (n = 61) included fever on admission (59% vs. 32% in ADEH-; P = 0.002), rash on the neck (30% vs. 13%; P = 0.015) and vesicular rash (70% vs. 49%; P = 0.011). Encounters in the ADEH+ group had a longer hospital length of stay compared with encounters in the ADEH- group [median 4 days (interquartile range 3-5 days) vs. 3 days (interquartile range 2-3 days); P < 0.001]. GAS was identified in only 1 ADEH+ encounter (2%) versus 15 ADEH- encounters (26%), P < 0.001. CONCLUSIONS: Providers should maintain a high index of suspicion for EH in children admitted for presumed AD skin infection. GAS was more commonly associated with ADEH- encounters.

Oral treatment with valacyclovir for HSV-2-associated eczema herpeticum in a 9-month-old infant: A case report.

BACKGROUND: Eczema herpeticum is a rare, severe, and disseminated infection of herpes simplex virus in the setting of eczematous skin diseases. METHODS: We experienced a case of this disease in a 9-month-old infant characterized by a sudden onset of monomorphic vesicles on the head, right lower leg, and two hands. The infant has a 7-month history of atopic dermatitis and his condition was initially regarded as a complication of atopic dermatitis and bacterial infection. After treatment of cefoperazone and dexamethasone, the eruptions got worse. The diagnosis of eczema herpeticum was made according to the clinical features and further confirmed by the findings of herpes simplex virus type 2. RESULTS: The infant was cured by oral treatment with valacyclovir. CONCLUSION: The case highlights that the awareness for the sign of eczema herpeticum when diagnosing children with a sudden onset of disseminated vesicles in the setting of chronic skin disease should be increased. Oral valacyclovir may be an effective and convenient treatment option for pediatric outpatients with eczema herpeticum.

Filaggrin deficiency promotes the dissemination of cutaneously inoculated vaccinia virus.

BACKGROUND: Eczema vaccinatum is a life-threatening complication of smallpox vaccination in patients with atopic dermatitis (AD) characterized by dissemination of vaccinia virus (VV) in the skin and internal organs. Mutations in the filaggrin (FLG) gene, the most common genetic risk factor for AD, confer a greater risk for eczema herpeticum in patients with AD, suggesting that it impairs the response to cutaneous viral infections. OBJECTIVE: We sought to determine the effects of FLG deficiency on the response of mice to cutaneous VV inoculation. METHODS: VV was inoculated by means of scarification of unsensitized skin or skin topically sensitized with ovalbumin in FLG-deficient flaky tail (ft/ft) mice or wild-type (WT) control mice. The sizes of primary and satellite skin lesions were measured, and hematoxylin and eosin staining was performed. VV genome copy numbers and cytokine mRNA levels were measured by using quantitative PCR. RESULTS: VV inoculation in unsensitized skin of ft/ft mice, independent of the matted hair mutation, resulted in larger primary lesions, more abundant satellite lesions, heavier viral loads in internal organs, greater epidermal thickness, dermal cellular infiltration, and higher local Il17a, Il4, Il13, and Ifng mRNA levels than in WT control mice. VV inoculation at sites of topical ovalbumin application amplified all of these features in ft/ft mice but had no detectable effect in WT control mice. The number of satellite lesions and the viral loads in internal organs after cutaneous VV inoculation were significantly reduced in both unsensitized and topically sensitized ft/ftxIl17a(-/-) mice. CONCLUSION: FLG deficiency predisposes to eczema vaccinatum. This is mediated primarily through production of IL-17A.

IL-10 suppresses IL-17-mediated dermal inflammation and reduces the systemic burden of Vaccinia virus in a mouse model of eczema vaccinatum.

Individuals with atopic dermatitis (AD) are susceptible to a severe, potentially fatal, systemic infection and inflammatory response following exposure to Vaccinia virus (VV). IL-10 acts both as an inducer of Th2 responses and as a regulator of T cell activation. It has been shown to limit skin inflammation elicited by contact sensitizers. AD exacerbations have been associated with decreased IL-10 function. We used IL-10(-/-) mice to test the role of the cytokine in VV immunity. They exhibited larger primary lesions and increased cutaneous neutrophil infiltration compared to wild-type (WT) counterparts. This was associated with enhanced production of IL-17A, IL-17F and CXCL2. Paradoxically, despite intact adaptive immune responses, tissue viral burdens were increased in IL-10(-/-) mice. These findings suggest that IL-10 is important in limiting skin inflammation induced by VV and that abnormal IL-17-driven neutrophil recruitment at the primary infection site in the skin results in increased systemic viral dissemination.

IL-25 enhances HSV-1 replication by inhibiting filaggrin expression, and acts synergistically with Th2 cytokines to enhance HSV-1 replication.

Atopic dermatitis (AD) is characterized by epidermal barrier defects and recurrent microbial skin infections. AD patients with a history of eczema herpeticum (ADEH+) have more severe skin disease and more highly T helper type 2 (Th2)-polarized immune responses as compared with uncomplicated AD (ADEH-). However, the mechanisms linking epidermal barrier defects and viral skin infection are not well understood. Recently, it has been reported that interleukin-25 may play a role in augmenting Th2 responses. We examined protein expression of IL-25 in the skin biopsies from normal subjects (n=10), ADEH- (n=18), ADEH+ (n=7), and psoriasis (n=9). IL-25 expression was increased in the skin from ADEH-, ADEH+, and psoriasis as compared with normal skin, and was significantly greater in lesional ADEH+ skin than in lesional ADEH- skin. Importantly, we demonstrated that IL-25 enhances herpes simplex virus (HSV)-1 and vaccinia virus replication by inhibiting filaggrin expression, and IL-25 acts synergistically with IL-4 and IL-13 to enhance HSV-1 replication in vitro. In contrast, IFN-γ inhibited HSV-1 replication in vitro. In addition, we demonstrate that filaggrin is a critical protein to inhibit HSV-1 replication because filaggrin small interfering RNA knockdown enhances HSV-1 replication in vitro. Filaggrin breakdown products, however, inhibited HSV-1 replication in vitro.

Eczema herpeticum with herpetic folliculitis after bone marrow transplant under prophylactic acyclovir: are patients with underlying dermatologic disorders at higher risk?

We present an unreported coexistence: eczema herpeticum (EH) with histopathological findings of herpetic folliculitis (HF) after allogeneic bone marrow transplantation (BMT). A patient with atopic dermatitis (AD) underwent allogeneic BMT for idiopathic acquired aplastic anemia. She had been receiving cyclosporine (150 mg/12 h) and acyclovir (400 mg/12 h) for 6 months. A facial rash was observed, composed of monotonous erythematous, umbilicated papulo-vesicles and papulo-crusts <4 mm in size. The histopathological study showed herpetic cytopathic changes within the epidermis that extended into the hair follicle epithelium. Interestingly, microscopic HF has not previously been associated with post-transplant patients or EH. However, it is reasonable to hypothesize that the coexistence of these herpes simplex virus-related events may be underreported in the literature. Although further studies are necessary, we suggest that the prophylactic antiviral dose after BMT be enhanced in patients with underlying dermatologic diseases, especially in those with AD.

Eczema herpeticum.

Atopic dermatitis (AD) patients tend to develop viral infections such as herpes simplex, molluscum contagiosum or verrucae vulgares more frequently than nonatopic patients. In addition, disseminated viral infections occur in the skin lesions of AD. Though these diseases are relatively rare and little is known about their specific pathogenesis, some of them are among the true medical emergencies in dermatology. This contribution covers eczema herpeticum, the disseminated viral infection of an eczematous skin disease with the herpes simplex virus, as it is the clinically most important viral complication of AD.

Eczema vaccinatum.

Eczema vaccinatum (EV) is a complication of smallpox vaccination that can occur in persons with eczema/atopic dermatitis (AD), in which vaccinia virus disseminates to cause an extensive rash and systemic illness. Because persons with eczema are deferred from vaccination, only a single, accidentally transmitted case of EV has been described in the medical literature since military vaccination was resumed in the United States in 2002. To enhance understanding of EV, we review its history during the era of universal vaccination and discuss its relationship to complications in persons with other diseases or injuries of the skin. We then discuss current concepts of the pathophysiology of AD, noting how defective skin barrier function, epidermal hyperplasia, and abnormal immune responses favor the spread of poxviral infection, and identify a number of unanswered questions about EV. We conclude by considering how its occurrence might be minimized in the event of a return to universal vaccination.

A case of pityriasis rubra pilaris with associated focal acantholytic dyskeratosis complicated by Kaposi's varicelliform eruption.

The clinical and histopathological diagnosis of pityriasis rubra pilaris (PRP) can be difficult because clinical findings are often subtle in early stages, and microscopic findings can overlap with those of other skin diseases. Focal acantholytic dyskeratosis (FAD) can rarely be seen in PRP and can mimic Darier's disease, Grover's disease or other disorders characterized by these histopathologic features. Kaposi's varicelliform eruption is a widespread infection due to herpes simplex virus (HSV) types 1 and 2, coxsackievirus A16 or vaccinia virus, occurring in a preexisting dermatosis; only one case has been reported in PRP. We report a patient with PRP whose biopsies showed both herpes simplex infection and FAD. A complete understanding of the mechanism behind this eruption evolved gradually, aided in great measure by the histopathologic findings.

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections. OBJECTIVE: We sought to determine why a subset of patients with AD have an increased risk of disseminated viral skin infections. METHODS: Human subjects with AD with a history of eczema herpeticum (EH) and various control groups were enrolled. Vaccinia virus (VV) expression was measured by means of PCR and immunofluorescent staining in skin biopsy specimens from each study group after incubation with VV. Transgenic mice with a constitutively active signal transducer and activator of transcription 6 gene (STAT6) were characterized for response to VV skin inoculation. Genotyping for 10 STAT6 single nucleotide polymorphisms (SNPs) was performed in a white patient sample (n = 444). RESULTS: VV gene and protein expression were significantly increased in the skin of patients with EH compared with other subject groups after incubation with VV in vitro. Antibody neutralization of IL-4 and IL-13 resulted in lower VV replication in patients with a history of EH. Mice that expressed a constitutively active STAT6 gene compared with wild-type mice had increased mortality and satellite lesion formation after VV skin inoculation. Significant associations were observed between STAT6 SNPs and EH (rs3024975, rs841718, rs167769, and rs703817) and IFN-γ production. The strongest association was observed for a 2-SNP haplotype (patients with AD with a history of EH vs patients with AD without a history of EH, 24.9% vs 9.2%; P = 5.17 × 10(-6)). CONCLUSION: The STAT6 gene increases viral replication in the skin of patients with AD with a history of EH. Further genetic association studies and functional investigations are warranted.

Protective murine and human monoclonal antibodies against eczema vaccinatum.

BACKGROUND: Eczema vaccinatum is the most common severe pathology associated with smallpox vaccination (vaccinia virus), occurring at high rates among individuals with a previous history of atopic dermatitis (atopic eczema). METHODS: Monoclonal antibodies capable of neutralizing vaccinia virus, anti-H3 and anti-B5, were developed as a potential therapy for treatment of human eczema vaccinatum. RESULTS: Using a small animal model of eczema vaccinatum, we demonstrated that both murine and fully human monoclonal antibodies effectively limited eczema vaccinatum disease, foreshortening both the disease kinetics and the severity of the erosive viral skin lesions. CONCLUSIONS: These neutralizing antibodies would likely be effective at reducing or eliminating clinical disease in people with eczema vaccinatum or other severe side effects of the smallpox vaccine.

Atopic dermo-respiratory syndrome is a correlate of eczema herpeticum.

BACKGROUND: Factors favoring the emergence of eczema herpeticum (EH) in patients with atopic dermatitis (AD) remain elusive. The aim of this work was to identify changes in clinical and laboratory parameters in acute EH patients, before and after 6 weeks of treatment, as well as differences between AD patients with and without a history of EH. METHODS: A total of 235 adult subjects were included and subdivided into six groups: (i) AD patients with acute EH, (ii) AD patients with history of EH, (iii) AD without EH but with recurrent herpes simplex virus (HSV) infections, (iv) AD without EH or recurrent HSV infections and healthy non-AD controls (v) with and (vi) without recurrent HSV infections. Clinical examination of AD, assessment of atopic status and severity were performed. Total IgE, allergen-specific IgE and differential blood count were analyzed. Clinical diagnosis of acute EH was confirmed by PCR. RESULTS: More male patients with AD were affected by EH than female patients. Acute episodes of EH are characterized by lower levels of lymphocytes and higher levels of monocytes. AD patients with history of EH display higher total IgE serum levels (ADEH(+) HSV(+) vs ADEH(-) HSV(+) , P < 0.001) and higher sensitization profiles and stronger severity of AD (EASI and SCORAD; ADEH(+) HSV(+) vs ADEH(-) HSV(+) , P < 0.001). Concomitant asthma and rhinitis were identified as correlates of EH. CONCLUSION: From these data, we conclude that AD patients with EH display a distinct clinical and biological phenotype.