A fatal case of DRESS induced by strontium ranelate associated with HHV-7 reactivation.

We report the first case of drug rash with eosinophilia and systemic symptoms (DRESS) following strontium ranelate (SR) treatment associated with systemic human HHV-7 reactivation. DRESS syndrome is a severe adverse drug-induced reaction presenting as a diffuse maculopapular skin rash with fever, hematological abnormalities (leukocytosis, eosinophilia, and/or atypical lymphocytosis), and multiorgan involvement. In our patient, diagnosis of DRESS was confirmed by the presence of six of the seven diagnostic criteria established in 2006 by the Japanese Research Committee on Severe Cutaneous Adverse Drug Reaction: maculopapular skin rash developing at least 3 weeks after starting therapy with a limited number of drugs, prolonged clinical symptoms after discontinuation of the causative drug, lymphadenopathy, fever, leukocyte abnormalities, and liver abnormalities. The diagnostic criteria of human herpesvirus (HHV)-6 reactivation have not been fulfilled in our patient, but a HHV-7 active infection was demonstrated by the presence of HHV-7 DNA and IgM in the patient's serum. In fact, in some DRESS instances, reactivation of HHVs other than HHV-6 may be detected, including HHV-7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Our case underlines that not only HHV-6 but also HHV-7 systemic reactivation may be associated with a more severe and even fatal course of this syndrome.

Severe atypical hand-foot-and-mouth disease in adults due to coxsackievirus A6: Clinical presentation and phylogenesis of CV-A6 strains.

BACKGROUND: Typically, hand-foot-and-mouth disease (HFMD) is a mild childhood illness associated with coxsackievirus (CV)-A16, CV-A6, enterovirus (EV)-A71. OBJECTIVES: To identify the viral agents associated with severe cases of atypical HFMD in Italy. STUDY DESIGN: Epidemiologically unrelated cases of severe atypical HFMD admitted to the Emergency Room (ER) of IRCCS San Martino IST (Genoa, Italy) in 2014-2016 were investigated. Serologic screening for viral positivity was performed against exanthem-inducing agents. Ten cases with serology indicative of recent EV infection were selected. Molecular assays were used to detect viral genomes in blood [EVs, Parvovirus B19 (PVB19), herpesviruses (CMV; EBV, HHV-6, -7, -8)]. RESULTS: CV-A6 was detected in 10 cases of severe atypical HFMD. Two cases were also infected with PVB19. Herpesviruses were not detected. Phylogenetic analysis mapped the CV-A6 strains into a single cluster related to two recent isolates from a German and an Asian child. Fever, systemic symptoms, severe vasculitis-like rash, and enanthem were predominant at presentation. Spontaneous recovery occurred in 1-3 weeks. CONCLUSIONS: CV-A6 is emerging as a frequent cause of severe atypical HFMD in Italian adults. This viral agent is disseminating worldwide. Dermatologists must identify the manifold alterations caused by EVs and understand the diagnostic power of current virology methods.

Productive infection of HUVEC by HHV-8 is associated with changes compatible with angiogenic transformations.

Kaposi's Sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8) infection. We have characterized the morphologic and phenotypic modifications of HUVEC in a model of productive HHV-8 infection. HHV-8 replication was associated with ultra-structural changes, flattened soma and a loss of marginal folds and intercellular contacts, and morphologic features, spindle cell conversion and cordon-like structures formation. Phenotypic changes observed on cordon-like structures included partial loss and redistribution of CD31/PECAM-1 and VE-cadherin, uPAR up-regulation and de novo expression of CD13/APN. Such changes demonstrate the induction, in HUVEC, of an angiogenic profile. Most of these findings are directly linked to HHV-8-encoded proteins expression, suggesting that HHV-8 itself may participate to the initial steps of the angiogenic transformation in KS.

An improved method for HLA-B and -C supratyping.

A growing body of evidence links the analysis of the KIR genotype and the presence of their HLA-B and -C ligands to a wide repertoire of human diseases. We noticed that, using a panel of 184 Caucasoid donors, a limited number of HLA alleles were incorrectly supratyped by previously described pyrosequence-based assays. Here we describe a simple implementation of the reported methods that corrects all the discrepancies found with HLA-B and -C molecular typing and allows establishing a quick and high-throughput method for the determination of HLA-Bw4 I(80), Bw4T(80), Bw6 and HLA-C1 or -C2 supratype.

Prevalence of the internalization-associated gene prtF1 in a bacterial population of Streptococcus pyogenes isolated from children with acute pharyngotonsillitis before and after antibiotic therapy.

The prevalence of the internalization-associated prtF1 gene was studied in 837 isolates of Streptococcus pyogenes obtained from 713 pediatric patients presenting with acute pharyngotonsillitis before and after antibiotic therapy. Its association with macrolide resistance and with bacteriological treatment failure was determined. The bacterial population isolated from baseline pharyngeal swabs showed an overall prtF1 positivity rate of 33%. A higher prtF1 positivity was found among erythromycin-resistant strains (45%) showing, however, marked differences between the inducible (iMLS), constitutive (cMLS), and efflux pump (M) resistance phenotypes. The prevalence was statistically higher (p < 0.001) in strains belonging to iMLS (84%) and cMLS (67%) phenotypes as compared to the M phenotype (15%). Interestingly, the prevalence of the prtF1 gene was significantly lower (p = 0.04) in strains belonging to M resistance phenotype as compared to erythromycin-susceptible strains (28%). Failed bacterial eradication was demonstrated in 124 patients. The prtF1 positivity rate remained unchanged in strains isolated before and after therapy in patients treated with macrolides (9/54). On the other hand, the positivity rate for the prtF1 gene was significantly higher (p = 0.015) in strains isolated after therapy with beta-lactams (21/70) as compared to baseline isolates (6/70), indicating a differential selection imposed on the organism by these agents. Finally, a high overall eradication rate (88%) of prtF1-positive isolates, belonging to both the erythromycin-susceptible and -resistant phenotypes, was demonstrated following macrolide treatment.

Detection of lymphotropic herpesvirus DNA by polymerase chain reaction in cerebrospinal fluid of AIDS patients with neurological disease.

Cerebrospinal fluid (CSF) samples from 49 acquired immunodefficiency disease syndrome (AIDS) patients with a central nervous system (CNS) disease were examined by polymerase chain reaction (PCR) to evaluate the association between the positivity for cytomegalovirus (CMV) and Epstein-Barr virus (EBV), and clinical diagnosis of a CNS disease. Frequency and clinical relevance of detection of DNA of human herpesviruses 6 (HHV-6), 7 (HHV-7) and 8 (HHV-8) were also determined. DNA of one or more of the following viruses was found in 26 of 49 patients (53%): CMV in 16 (33%), EBV in 13 (27%), human herpesvirus 6 (HHV-6) in 2 (4%), human herpesvirus 7 (HHV-7) in 1 (2%), and human herpesvirus 8 (HHV-8) in 1 (2%). The CMV detection was significantly associated with encephalitis and peripheral neuropathy (7/16 vs. 2/33, p = 0.003), while EBV with primary CNS lymphoma (P-CNSL) (8/13 vs. 0/36, p < 0.0001). HHV-6 DNA was found in CSF of two patients with neuroradiological features suggestive of cerebral lesions. HHV-8 or HHV-7 DNA was detected in the CSF of patients with unexplained neurological symptoms. This study confirms that the PCR analysis of CSF is a valid tool for the diagnosis of neurological diseases associated with CMV and EBV. On the other hand, HHV-6, HHV-7 and HHV-8, instead, were rarely detected in CSF of AIDS patients and have certainly no correlation with the CNS disease found.

Human herpesvirus 6 in cerebrospinal fluid of patients infected with HIV: frequency and clinical significance.

The objective was to evaluate the frequency of human herpesvirus 6 (HHV-6) DNA detection in the CSF of patients infected with HIV and its relation to brain disease and systemic HHV-6 infection. Nested polymerase chain reaction (PCR) was used to analyse CSF samples from 365 consecutive HIV infected patients with neurological symptoms. When available, plasma and brain tissues from patients whose CSF was HHV-6 positive were also studied. HHV-6 was found in the CSF of eight of the 365 patients (2.2%): two had type A and four type B; the HHV-6 variant could not be defined in the remaining two. All eight patients had neurological symptoms and signs related to concomitant opportunistic brain diseases, including cytomegalovirus (CMV) encephalitis in five patients whose CSF was also positive for CMV-DNA. Opportunistic infections but no other unexplained lesions were also found in the brain of all of the four patients who underwent neuropathological examination. Both HHV-6 and CMV were also detected in the plasma of respectively five and seven of seven patients whose CSF was HHV-6 positive. In conclusion, HHV-6 type A or B DNA was infrequently found in the CSF of HIV infected patients, in association with both CMV brain infection and systemic HHV-6 replication. However, no certain relation between HHV-6 and brain disease was found.