Staphylococcal TSST-1 Association with Eczema Herpeticum in Humans.

Atopic dermatitis (AD) is a condition affecting 30 million persons in the United States. AD patients are heavily infected with Staphylococcus aureus on the skin. A particularly severe form of AD is eczema herpeticum (ADEH), where the patients' AD is complicated by S. aureus and herpes simplex virus (HSV) infection. This study examined the S. aureus strains from 15 ADEH patients, provided blinded, and showed a high association of ADEH with strains that produce toxic shock syndrome toxin-1 (TSST-1; 73%) compared to 10% production by typical AD isolates from patients without EH and those from another unrelated condition, cystic fibrosis. The ADEH isolates produced the superantigens associated with TSS (TSST-1 and staphylococcal enterotoxins A, B, and C). This association may in part explain the potential severity of ADEH. We also examined the effect of TSST-1 and HSV-1 on human epithelial cells and keratinocytes. TSST-1 used CD40 as its receptor on epithelial cells, and HSV-1 either directly or indirectly interacted with CD40. The consequence of these interactions was chemokine production, which is capable of causing harmful inflammation, with epidermal/keratinocyte barrier disruption. Human epithelial cells treated first with TSST-1 and then HSV-1 resulted in enhanced chemokine production. Finally, we showed that TSST-1 modestly increased HSV-1 replication but did not increase viral plaque size. Our data suggest that ADEH is associated with production of the major TSS-associated superantigens, together with HSV reactivation. The superantigens plus HSV may damage the skin barrier by causing harmful inflammation, thereby leading to increased symptoms. IMPORTANCE Atopic dermatitis (eczema, AD) with concurrent herpes simplex virus infection (eczema herpeticum, ADEH) is a severe form of AD. We show that ADEH patients are colonized with Staphylococcus aureus that primarily produces the superantigen toxic shock syndrome toxin-1 (TSST-1); however, significantly but to a lesser extent the superantigens staphylococcal enterotoxins A, B, and C are also represented in ADEH. Our studies showed that TSST-1 uses the immune costimulatory molecule CD40 as its epithelial cell receptor. Herpes simplex virus (HSV) also interacted directly or indirectly with CD40 on epithelial cells. Treatment of epithelial cells with TSST-1 and then HSV-1 resulted in enhanced chemokine production. We propose that this combination of exposures (TSST-1 and then HSV) leads to opening of epithelial and skin barriers to facilitate potentially serious ADEH.

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.

Empiric antibiotics and outcomes of children hospitalized with eczema herpeticum.

Although patients with eczema herpeticum often receive antibiotics for presumed bacterial coinfection, the effect of empiric antibiotic therapy is unknown. Our objective therefore was to determine the association between empiric antibiotics and outcomes in children hospitalized with eczema herpeticum. We conducted a multicenter retrospective cohort study of 1,150 children ages 2 months to 17 years admitted with eczema herpeticum between January 1, 2001, and March 31, 2010, to 42 tertiary care children's hospitals in the Pediatric Health Information System. All patients received antibiotics during the hospitalization. Multivariable linear regression models determined the association between empiric antibiotic therapy and the main outcome measure: hospital length of stay (LOS). There were no deaths during the study period. Receipt of empiric antibiotics was not associated with a change in the LOS on unadjusted or multivariable analysis. The class of empiric antibiotic was not associated with the LOS except for receipt of vancomycin, which was associated with a longer LOS (21% adjusted longer LOS, 95% confidence interval (CI) = 8-35%; p = 0.001). When restricted to patients with a bloodstream infection, receipt of empiric antibiotics was associated with a 51% adjusted shorter LOS (95% CI = -24 to -68%; p = 0.002). In children hospitalized with eczema herpeticum, empiric antibiotic therapy was not associated with a shorter LOS overall, but was associated with a shorter LOS in patients with a bloodstream infection. These findings highlight the importance of early recognition of systemic bacterial illness in children with eczema herpeticum. Empiric antibiotics did not affect mortality, which is low.

Fatal outcome due to bacterial superinfection of eczema herpeticum in a patient with mycosis fungoides.

Kaposi varicelliform eruption or eczema herpeticum is well known to be associated with several chronic dermatoses, including atopic dermatitis, foliaceus pemphigus, seborrheic dermatitis, Darier disease, and congenital ichthyosiform erythroderma. Although less frequently, it has also been described in cases of mycosis fungoides and Sèzary syndrome. We would like to report an extremely rare case of a woman with a T-cell cutaneous lymphoma who developed disseminated cutaneous herpes simplex with S. aureus sepsis and a fatal outcome.

Secondary bacterial infections complicating skin lesions.

Secondary bacterial infection in skin lesions is a common problem. This review summarises a series of studies of the microbiology of several of these infections: scabies, psoriasis, poison ivy, atopic dermatitis, eczema herpeticum and kerion. Staphylococcus aureus and group A beta-haemolytic streptococci were the most prevalent aerobes and were isolated from all body sites. In contrast, organisms that reside in the mucous membranes close to the lesions predominated in infections next to these membranes. In this fashion, enteric gram-negative bacilli and Bacteroides spp. were found most often in buttock and leg lesions. The probable sources of these organisms are the rectum and vagina, where they normally reside. Group A beta-haemolytic streptococci, pigmented Prevotella and Porphyromonas spp. and Fusobacterium spp. were most commonly found in lesions of the head, face, neck and fingers. These organisms probably reached these sites from the oral cavity, where they are part of the normal flora. This review highlights the polymicrobial aerobic-anaerobic microbiology of secondarily infected skin lesions.

Diagnosis of zoster and evaluation of varicella vaccine with a passive haemagglutination assay.

A passive haemagglutination (PHA) assay for the detection of varicella-zoster virus (VZV) antibody was prepared with purified viral glycoproteins. Serum samples from vaccinees with live attenuated varicella vaccine, and of zoster patients, were measured for antibody titres against VZV with PHA, complement fixation (CF) and immune adherence haemagglutination (IAHA) assays, and the results compared. Antibody development could be detected as early as 3 weeks after vaccination, by both PHA and IAHA tests, but not with the CF test. Significant rises in VZV antibody in zoster patients were detected by both PHA and CF tests several days after onset. No cross-reaction was observed using HSV PHA among the vaccinees and the zoster patients. The VZV PHA assay could be used as a monitor of vaccination and a tool for differential diagnosis.

Detection of herpes simplex viral DNA in Kaposi's varicelliform eruption using in situ hybridization method.

Herpes simplex viral DNA was detected in biopsy specimens obtained from four patients with Kaposi's varicelliform eruption using an in situ hybridization technique with biotinylated complementary DNA probes. Herpes simplex viral DNA was consistently found almost exclusively in the nuclei of giant cells and balloon cells in vesicles during day 2, 5 and 7 of the disease. In the nuclei, the viral DNA staining pattern was granular or agglomerate. No positive staining was observed in the cytoplasm.

[Participation of vaccinia virus in the pathogenesis of different clinical forms of postvaccinal complications. I. Frequency of vaccinia virus detection in the vaccinted who have usual and complicated reactions to vaccination]. / Ob uchastii virusa vaktsiny v patogeneze razlichnykh klinicheskikh form postvaktsinal 'nykh oslozhnenii. Soobshchenie I. Chastota obnaruzheniia virusa vaktsiny u privitykh s obychnoi i oslozhnennoi reaktsiei na vaktsinatsiiu.

The virological examination of 1365 samples taken from 469 children vaccinated against smallpox revealed considerable differences in the frequency and the time of vaccinia virus detection in different clinical forms of postvaccinal pathology as compared with uncomplicated vaccinal process. During the postvaccinal period taking its normal course vaccinia virus was isolated from 7.3% of children only from the pharynx till day 8 following vaccination. In generalized and creeping vaccinia the virus was isolated from 71.4% of children, in postvaccinal encephalitis from 57.1% of children, in vaccinal angina frove-mentioned complications vaccinia virus was detected in the samples obtained from the patients till days 24, 35, 15 and 24 respectively. The etiopathogenetic role of vaccinia virus in a number of postvaccinal complications is discussed.

Kaposi's varicelliform eruption in mycosis fungoides.

Kaposi's varicelliform eruption, caused by herpes simplex type 1, developed in a patient with mycosis fungoides four days after initiation of photochemotherapy with methoxsalen plus long-wave ultraviolet light (PUVA). He had a history of recurrent localized herpes infection. Vidarabine (adenine arabinoside) was used as treatment. Rechallenge with PUVA did not provoke another herpes infection. Kaposi's varicelliform eruption is rare in mycosis fungoides. Vidarabine may prove to be useful in the treatment of widespread herpes simplex.

Cutaneous dissemination of herpes simplex virus in individuals fifteen years of age and older.

We have reported the case histories of two individuals with underlying atopic dermatitis who developed extensive vesicular eruptions. In both cases herpes simplex virus type l was isolated from skin lesions and both individuals ultimately recovered. These two cases represent only the third and fourth instances of this syndrome proven to be caused by herpes simplex virus type l that have been reported in older individuals. In addition we have reviewed the literature relative to cutaneous disseminated herpes simplex virus infections occurring in individuals over the age of 15 and have presented a comprehensive overview of this disease.