Two pediatric cases of influenza B-induced rash and mucositis: Stevens-Johnson syndrome or expansion of the Mycoplasma pneumoniae-induced rash with mucositis (MIRM) spectrum?

We present two pediatric cases of recurrent mucositis associated with influenza B infection, both in patients with prior episodes of Stevens-Johnson syndrome (SJS) due to Mycoplasma. Influenza B is an uncommon cause of both rash and mucosistis and SJS.

Brincidofovir clearance of acyclovir-resistant herpes simplex virus-1 and adenovirus infection after stem cell transplantation.

Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance. A subsequent Epstein-Barr virus disease with relevant meningoencephalitis responded to rituximab.

Correlation between different genotypes of human cytomegalovirus and Epstein-Barr virus and peri-implant tissue status.

BACKGROUND: The purpose of this study was to estimate the prevalence of different genotypes of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in peri-implantitis and mucositis sites, and to evaluate the correlation between herpesvirus presence and clinical parameters. METHODS: A total of 80 dental implants (mean time of loading, 4.16 ± 1.8 years) were evaluated during the course of the study (30 peri-implantitis, 25 mucositis and 25 healthy peri-implant sites). The following clinical parameters were assessed: visible plaque index, bleeding on probing, suppuration and probing depth. A polymerase chain reaction (PCR) assay was used to identify the presence of different HCMV and EBV genotypes in peri-implant tissue plaque samples. RESULTS: HCMV-2 was detected in 53.3% and EBV-1 in 46.6% of the 30 peri-implantitis sites evaluated. By contrast, HCMV-2 was not detected in healthy periodontal sites and EBV-1 was detected in one healthy site. A statistically significant correlation was found between the presence of HCMV-2 and EBV-1 genotypes and clinical parameters of peri-implantitis. CONCLUSIONS: The results from the present study confirmed the high prevalence of HCMV-2 and EBV-1 in the peri-implant tissue plaque of peri-implantitis sites and suggests a possible active pathogenic role of the viruses in peri-implantitis.

Functional interaction between herpes simplex virus type 2 gD and HVEM transiently dampens local chemokine production after murine mucosal infection.

Herpes virus entry mediator (HVEM) is one of two principal receptors mediating herpes simplex virus (HSV) entry into murine and human cells. It functions naturally as an immune signaling co-receptor, and may participate in enhancing or repressing immune responses depending on the natural ligand used. To investigate whether engagement of HVEM by HSV affects the in vivo response to HSV infection, we generated recombinants of HSV-2(333) that expressed wild-type gD (HSV-2/gD) or mutant gD able to bind to nectin-1 (the other principal entry receptor) but not HVEM. Replication kinetics and yields of the recombinant strains on Vero cells were indistinguishable from those of wild-type HSV-2(333). After intravaginal inoculation with mutant or wild-type virus, adult female C57BL/6 mice developed vaginal lesions and mortality in similar proportions, and mucosal viral titers were similar or lower for mutant strains at different times. Relative to HSV-2/gD, percentages of HSV-specific CD8(+) T-cells were similar or only slightly reduced after infection with the mutant strain HSV-2/gD-Δ7-15, in all tissues up to 9 days after infection. Levels of HSV-specific CD4(+) T-cells five days after infection also did not differ after infection with either strain. Levels of the cytokine IL-6 and of the chemokines CXCL9, CXCL10, and CCL4 were significantly lower in vaginal washes one day after infection with HSV-2/gD compared with HSV-2/gD-Δ7-15. We conclude that the interaction of HSV gD with HVEM may alter early innate events in the murine immune response to infection, without significantly affecting acute mortality, morbidity, or initial T-cell responses after lethal challenge.

Prevalence of oral herpes simplex virus reactivation in cancer patients: a comparison of different techniques of viral detection.

BACKGROUND: Oral reactivation of latent Herpes simplex virus (HSV) infection may easily occur in cancer patients. Virus reactivation can cause oral mucosa damage, worsen already existing lesions caused by stomatotoxic effect of cancer therapy and, whether symptomatic or asymptomatic, ample spreading and promote viral transmission. METHODS: Polymerase chain reaction (PCR), cell-culture and direct immunofluorescence have been used to determine the frequency of oral HSV reactivation in 60 patients undergoing chemotherapy for different malignancies. RESULTS: By means of PCR, the presence of viral DNA was detected in 71.7% of patients prior to chemotherapy and in 85.0% after chemotherapy. 33.3% of patients before and 40.0% after chemotherapy were viral-culture positive, while 3.3% of patients before and 11.7% after chemotherapy were positive as shown by direct immunofluorescence. No significant difference in HSV-1 reactivation was found before and after chemotherapy. In addition, no significant difference was found when comparing HSV-1 reactivation in patients with and without mucositis. HSV-2 was not detected in any of the patients. CONCLUSIONS: Reactivation of latent HSV is exceptionally frequent in cancer patients. The results of this study suggest that virus reactivation occurs independently of cancer chemotherapy. The potential role of HSV reactivation in oral mucosa damage remains unclear.

Herpes simplex virus in febrile neutropenic children undergoing chemotherapy for cancer: a prospective cohort study.

BACKGROUND: The primary objective of this study was to determine the prevalence of oral herpes simplex virus (HSV) as detected by polymerase chain reaction, in pediatric oncology patients with febrile neutropenia. Our secondary objectives were to describe the association between oral HSV and prolonged fever, neutropenia, mucositis, and response to initial antimicrobial therapy. METHODS: In this prospective cohort study, we obtained a mouth swab and blood specimen from oncology patients with febrile neutropenia, and tested them for HSV by polymerase chain reaction. Prolonged fever was defined as the presence of fever 48 hours after initiation of broad-spectrum antibiotic therapy. RESULTS: Of the 75 oral and blood specimens obtained, only 7 oral swabs (9%) and 2 blood samples (3%) were positive for HSV. Oral HSV was not associated with prolonged fever or neutropenia. However, oral HSV was associated with longer median duration of mucositis (8 days; interquartile range, 0-12 days) compared with negative episodes (0 days; interquartile range, 0-2.5 days); P = 0.005. Oral HSV also was associated with inferior successful response to initial antimicrobial therapy (1 of 7, 14.3%) compared with negative episodes (51 of 67, 76.1%); P = 0.002. CONCLUSIONS: The prevalence of HSV infection in pediatric oncology patients with febrile neutropenia was low and was not associated with prolonged fever. However, oral HSV was associated with prolonged mucositis and poorer response to initial therapy. It is unknown whether early intervention with acyclovir can alter these associations.

Mucositis in the cancer patient and immunosuppressed host.

Oral mucositis is a serious complication of cancer therapy and in severely immunosuppressed patients. In immunosuppressed patients, the signs and symptoms of infection often are muted because of limited host response, and accurate diagnosis and appropriate treatment may be difficult. Prevention of mucosal breakdown, suppression of microbial colonization, control of viral reactivation, and effective management of severe xerostomia are all critical steps to reducing the overall morbidity and mortality of oromucosal infections.