Roseola Infantum During the COVID-19 Pandemic.

INTRODUCTION: Roseola infantum is always considered to be among the differential diagnosis of young patients with fever and leukopenia whom to be strictly isolated with the preliminary diagnosis of COVID-19 until otherwise proven during the pandemic. RESULTS: Human herpes virus-6 (HHV-6) polymerase chain reaction (PCR) blood test was performed in 4 of 7 patients with a clinical diagnosis of roseola infantum and all found to be HHV-6 PCR positive. The most striking laboratory finding in all patients was leukopenia. HHV-6 PCR tests were found to be positive. Severe acute respiratory syndrome coronavirus-2 testing were found to be negative in all patients. CONCLUSION: During the peak of the pandemic, children continued to present with fever because of viral infections other than COVID-19.

Reduced impact of viral load of HHV-6 in liquor on severity of AESD due to exanthema subitum: A case report and literature review.

BACKGROUND: The most common causative pathogen of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was reported as HHV-6. Although excitotoxic injury with delayed neuronal death is considered to be a possible pathogenesis of AESD, the detailed pathophysiology remains unclear. CASE PRESENTATION: We present a twelve-month-old girl with AESD due to HHV-6 primary infection. She was successfully treated for AESD including targeted temperature management and the administration of vitamin B1, B6, and L-carnitine. Although the viral load of HHV-6 in her liquor was high (12,000 copies/mL), she fully recovered without antiviral agent use. DISCUSSION: There has been no study focusing on the HHV-6 viral load in patients with AESD, and only a few case reports have been published. We reviewed the clinical features and viral load in the liquor of our case and four reported infants with AESD due to HHV-6 primary infection who had real-time PCR tests results. Viral loads in the three patients with a poor prognosis were 31.5, negative, and 3,390 copies/mL, respectively. On the other hand, the copy numbers of HHV-6 DNA in the two patients with no sequelae were 12,000 and 106 copies/mL, respectively, and our case had the highest viral load among the five summarized patients.

Three Adolescents With Primary Human Herpesvirus 7 Infection During a Measles Outbreak.

During local small measles outbreak in Japan, 3 adolescents with febrile skin rash suspected as having measles were diagnosed with primary human herpesvirus (HHV)-7 infection. Primary HHV-7 infection can cause exanthem subitum in not only young children but also adolescents. HHV-7 should be considered as a possible causative agent for adolescent febrile skin rash during the measles outbreak.

Comparison of initial and final diagnoses in children with acute febrile illness: A retrospective, descriptive study: Initial and final diagnoses in children with acute fever.

BACKGROUND: This study aimed to elucidate the etiologies and diagnostic errors of early-phase pediatric fever without an obvious cause. METHODS: This single-center, retrospective, descriptive study included 1334 febrile children hospitalized at Beppu Medical Center in Japan between 2014 and 2018. Eligibility criteria were age ≤12 years, axillary temperature ≥38.0°C, and fever duration ≤7 days at admission. Initial diagnoses on the day of admission and final diagnoses at defervescence were divided into initial fever with identified source (FIS) and initial fever without source (FWS) and final FIS and final FWS, respectively. The etiology of initial FWS and diagnostic discordance between initial FIS and final FIS were investigated. RESULTS: Of the 1334 participants, 94 (7.0%) were diagnosed with initial FWS. Among patients with initial FWS, final diagnoses were confirmed in 40 (43%), including Kawasaki disease in 17, urinary tract infection in 5, bacteremia in 4, exanthem subitum in 3, and the others in 11. Among the 1275 patients diagnosed with final FIS, diagnostic discordances between initial and final diagnoses were observed in 131 patients (10%). The multiple logistic regression analysis identified increased serum C-reactive protein value at admission (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.06-1.13), exanthem subitum (OR: 409; 95% CI: 119-1399), and Kawasaki disease (OR: 14.3; 95% CI: 8.7-23.3) as independent risk factors for diagnostic discordance. CONCLUSION: Exanthem subitum and Kawasaki disease may be undiagnosed or misdiagnosed in febrile children with fever duration ≤7 days.

Reacciones adversas de los diez fármacos más notificados. Matanzas 2014 al 2017 / Adverse reactions to the ten most reported drugs in Matanzas 2014-2017

RESUMEN Introducción: la toxicidad de los fármacos es compleja y difícilmente valorable, por la cantidad de factores que intervienen en su producción, como modo de aparición, duración y gravedad de las reacciones adversas. La importancia de estas reacciones está dada por la frecuencia y gravedad con que un fármaco o familia de fármacos las producen. Objetivo: caracterizar las principales reacciones adversas que provocan los medicamentos, los grupos de edades con más riesgos, los sistemas de órganos que se afectan, la frecuencia, imputabilidad y la intensidad de las mismas. Materiales y métodos: estudio observacional, descriptivo, de serie de casos en farmacovigilancia. El universo fue las reacciones adversas de los 10 fármacos más notificados por la Unidad Coordinadora Provincial de Farmacovigilancia en Matanzas, en el periodo 2014-2017. Se estudiaron las variables: medicamentos, grupo farmacológico, datos demográficos, nivel de atención, tipo de efecto adverso, intensidad, imputabilidad y frecuencia. Resultados: se notificaron 10 fármacos con 2 216 reacciones. La vacuna pentavalente fue la más notificada, con un 17,6 %, seguido por la amoxicilina y las penicilinas. Predominó el sexo femenino con 1 279 reportes, (59,1 %) y los adultos, con 1 010 notificaciones, (46,6 %). La atención primaria de salud fue la de mayor número de notificaciones, 2 082 reportes, (96,1 %). Las principales reacciones fueron: la erupción cutánea, la fiebre y la urticaria. Predominaron reacciones moderadas; 1 972 reportes, (91,1 %), aquellas clasificadas como probables, 1 887 reportes, (87,1 %) y las frecuentes con 1 284 reportes, (59,2 %). Conclusiones: el sistema de farmacovigilancia en la provincia proporcionó sistemáticamente información sobre la seguridad de los medicamentos, lo que permitió el conocimiento de la relación beneficio-riesgo de los medicamentos presentes en el mercado, así como los más usados.

ABSTRACT Introduction: drugs toxicity is complex and of difficult assessment, due to the quantity of factors intervening in its production, like emergency way, duration, and seriousness of the adverse reactions. The importance of these reactions is given by the frequency and seriousness a drug or a drug family produces them. Objective: to characterize the main adverse reactions caused by medicines, the age groups having higher risk, the most affec6ted systems of organs, frequency, imputability and intensity. Material and methods: descriptive, observational study of a series of cases in pharmacovigilance. The universe was the adverse reactions of the ten drugs most reported by the Provincial Coordinating Unit of Pharmacovigilance in the period 2014-2017. The studied variables were: drugs, pharmacological group, demographic data, health care level, kind of adverse effect, intensity, imputability and frequency. Results: ten drugs were reported with 2 216 reactions. The pentavalent vaccine was the most reported one, with 17.6 %, followed by amoxicillin and penicillin. There was a predominance of the female sex with 1 279 reports (59.1 %), and adult people with 1 010 reports (46.6 %). The highest number of reports was made by the primary health care, 2 082 (96.1 %). The main reactions were skin rash, fever and urticaria. There was a predominance of mild reactions: 1 972 reports (91.1 %); reactions classified as probable: 1 887 reports (87.1 %): ands frequent ones: 1 284 reports (59.2 %). Conclusions: the pharmacovigilance system in the province systematically provided information on drugs´ safeness that allowed knowing the benefit-risk relation of the medicines that are in the market, and also which are the most used ones.

Leukocytoclastic Vasculitis Associated with HHV6-A/ciHHV6-A and HHV6-B Coinfection in an Immunocompetent Woman.

BACKGROUND AND OBJECTIVE: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis that can be limited to the skin but may also affect other organs. Often, its cause is unknown. LCV has previously been reported to occur with the reactivation of human herpesvirus 6 (HHV-6). Here, we report a second instance of HHV-6 reactivation in a 43-year-old woman with idiopathic cutaneous LCV. CASE DESCRIPTION: In this case, the patient was immunocompetent, and testing revealed that she had inherited chromosomally integrated human herpesvirus 6 variant A (iciHHV6-A) with a parallel skin infection of HHV-6B. The integrated ciHHV-6A strain was found to be transcriptionally active in the blood, while HHV-6B late antigen was detected in a skin biopsy. The patient's rash was not accompanied by fever nor systemic symptoms and resolved over four weeks without any therapeutic intervention. CONCLUSION: In light of the transcriptional activity documented in our case, further examination of a possible role for HHV-6 in the etiology of LCV is warranted.

Encefalopatía por virus herpes 6 como complicación de exantema súbito / Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

[Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication]. / Encefalopatía por virus herpes 6 como complicación de exantema súbito.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

Viral exanthems: An update on laboratory testing of the adult patient.

Although classic viral exanthems of childhood are well described, they are rarely differentiated in adults. Laboratory techniques for viral identification have advanced without substantial literature to suggest how a dermatologist ought to conduct a cost-effective and diagnostic viral panel. Certain clinical features such as petechiae, vesicles, and dusky macular or morbilliform exanthems point strongly toward a viral exanthem. Differentiation of drug and viral causes of morbilliform eruptions has proven difficult. It is possible that with further diagnostic refinement that unnecessary and fruitless workups of an exanthem and unneeded discontinuation of drugs can be avoided. We review viral exanthems based on clinical features and discuss the available and optimal laboratory techniques to assist the dermatologist in a targeted workup.

[A case of dysfibrinogenemia without hemorrhagic diathesis or thromboembolism linked to a new mutation p.H103N in fibrinogen γ chain]. / Un cas de dysfibrinogénémie sans complication hémorragique ni thrombotique lié à une nouvelle mutation p.H103N de la chaîne γ du fibrinogène.

This work describes a dysfibrinogenemia linked to a new mutation in the gene coding for fibrinogen γ chain. Dysfibrinogenemia was fortuitously discovered in a 9-year old boy consulting for symptoms suggesting meningitis. DNA was extracted from blood, the fibrinogen genes coding for Aα, Bß and γ chains were sequenced, and compared with consensus sequences. Apart from the patient, dysfibrinogenemia and the mutation p.H103N in the γ chain of fibrinogen with heterozygous status were found in his mother, without any symptom. This mutation is unknown in fibrinogen variant databases and seems to affect mostly fibrin polymerisation. The reporting of this new p.H103N mutation in the γ chain has a great interest for improving the knowledge of the fibrinogen gene and its expression. Even if no haemorrhage was observed in this case, the expression of this mutation impaired the function of the molecule, particularly polymerisation, and could induce bleeding during an important surgery.

Differentiating roseola infantum with pyuria from urinary tract infection.

BACKGROUND: The aim of this study was to identify factors for differentiating roseola infantum from urinary tract infection (UTI) and to describe a cohort of infants diagnosed with roseola infantum and sterile pyuria. METHODS: The medical records of infants diagnosed with roseola infantum or UTI were examined. Multivariate analysis was performed to identify factors associated with UTI. Demographic and clinical variables were compared between infants who had roseola infantum with or without sterile pyuria. RESULT: There were 301 infants included: 158 in the roseola group (21, 13.3% with sterile pyuria) and 143 in the UTI group. The relative risk of UTI over roseola infantum: increased with leukocytosis (white blood cell [WBC] count >10,000/mm(3), odds ratio [OR] = 85.62) and pyuria (OR = 18.97); decreased with age (OR = 0.90); increased in boys (OR = 2.48); increased with WBC count 4000-10,000/mm(3) (OR = 4.24); and decreased with duration of fever (OR = 0.84). There was a significantly higher proportion of girls in the roseola pyuria group (81.0%) compared with the no pyuria group (44.5%, P = 0.002). A significantly higher proportion of infants in the roseola pyuria group (76.2%) received antibiotics than infants in the no pyuria group (38.0%, P = 0.002). CONCLUSION: Leukocytosis is the strongest predictor of UTI over roseola infantum. Sterile pyuria may occur in infants with roseola infantum.

[Chromosomal integration of the sixth human herpes virus (HHV-6)]. / Chromozomální integrace sestého lidského herpesviru (HHV-6).

Two closely related and commonly found human herpesviruses HHV-6 A and HHV-6 B are classified into the sixth human herpes virus complex (HHV-6). Primary infection with HHV-6 often takes place in early childhood and it can be either asymptomatic or manifests itself as sixth disease (caused by HHV-6 B). HHV-6 remains present in a latent form in the body with the potential for virus reactivation. The article points out the phenomenon of chromosomal integration of HHV-6 (Ci-HHV-6) which is found in about 1% of the population and, unlike the commonly spread HHV-6 infection, has become hereditary, with its pathological potential in Ci-HHV-6 DNA carriers remaining unknown. Therefore, the focus on clinical consequences of Ci-HHV-6 is of high relevance to the therapeutic strategy for patients with high HHV-6 positivity in molecular biological tests.

Human herpes virus type 6 can cause skin lesions at the BCG inoculation site similar to Kawasaki Disease.

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. We present an 11-month-old boy who developed fever with redness of the BCG site due to infection with human herpes virus type 6 (HHV6). At the age of 3 months, the patient received BCG. His fever remitted 7 days after the onset of skin redness, with sequential desquamation at the BCG site and extremities, which is not a common feature of HHV6 infection that typically lasts for 3 days. The final diagnosis was exanthema subitum. Characteristically, the HHV6 infection in our patient appeared to be associated with the invigoration of the T cell system, as represented by the elevated serum levels of soluble interleukin-2 receptor (3,490 U/ml vs. normal range 145-519 U/ml). This patient clearly showed redness and crusting at the BCG inoculation site, suggesting that HHV6 infection might cause skin changes similar to those of KD via an unknown mechanism. In addition, we suggest that the activation of the T cell system may account for the skin lesions in KD, characterized by redness and subsequent crusting of the BCG inoculation site and desquamation of the extremities.

Development of quantitative RT-PCR assays for detection of three classes of HHV-6B gene transcripts.

The monitoring of active human herpesvirus 6 (HHV-6) B infection is important for distinguishing between the reactivation and latent state of the virus. The aim of this present study is to develop a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay for diagnosis of active viral infection. Primers and probes for in house quantitative RT-PCR methods were designed to detect the three kinetic classes of HHV-6B mRNAs (U90, U12, U100). Stored PBMCs samples collected from 10 patients with exanthem subitum (primary HHV-6B infection) and 15 hematopoietic stem cell transplant recipients with HHV-6B reactivation were used to evaluate reliability for testing clinical samples. Excellent linearity was obtained with high correlation efficiency between the diluted RNA (1-100 ng/reaction) and C(t) value of each gene transcript. The U90 and U12 gene transcripts were detected in all of the peripheral blood mononuclear cells (PBMCs) samples collected in acute period of primary HHV-6B infection. Only one convalescent PBMCs sample was positive for the U90 gene transcript. Additionally, the reliability of HHV-6B quantitative RT-PCRs for diagnosis of viral reactivation in hematopoietic transplant recipients was evaluated. Relative to virus culture, U90 quantitative RT-PCR demonstrated the highest assay sensitivity, specificity, positive predictive value, and negative predictive value. Thus, this method could be a rapid and lower cost alternative to virus culture, which is difficult to perform generally, for identifying active HHV-6B infection.

Development of a human herpesvirus 6 species-specific immunoblotting assay.

In order to assess the full spectrum of human herpesvirus 6A (HHV-6A)- and HHV-6B-associated diseases, we sought to develop an HHV-6 species-specific serological assay based on immunoblot analysis. The immunodominant proteins encoded by open reading frame U11, p100 for HHV-6A (strain U1102) and 101K for HHV-6B (strain Z29), were selected to generate virus species-specific antigens. Recombinant p100 and 101K were produced in a prokaryotic expression system. The expression of these proteins was confirmed by using anti-His tag and 101K-specific monoclonal antibodies. HHV-6 species-specific antibodies were detected by immunoblotting in patient sera. Eighty-seven serum samples obtained from various subjects were utilized to determine the reliability of the method for clinical use. Ten of twelve exanthem subitum convalescent-phase sera reacted exclusively with 101K, whereas none of twelve acute-phase sera reacted with either protein. Two of three sera collected from HHV-6A-infected patients reacted with p100 and 101K. Although all five acute and convalescent-phase sera obtained from transplant recipients reacted exclusively with 101K, two of six convalescent-phase sera obtained from patients with drug-induced hypersensitivity syndrome reacted with both p100 and 101K. Of 38 sera obtained from healthy adults, 31 were positive for 101K antibody, while 4 reacted with both proteins. However, PCR analysis of peripheral blood mononuclear cells and saliva from these subjects did not detect HHV-6A DNA. In conclusion, this novel serological assay based on immunoblot analysis using recombinant HHV-6A p100 and HHV-6B 101K allowed us to discriminate between HHV-6A- and HHV-6B-specific antibodies.