Specific Viral Etiology Research Articles

Expression of HLA and Autoimmune Pathway Genes in Liver Biopsies of Young Subjects With Autoimmune Hepatitis Type 1.

Objectives:To test the hypothesis that autoimmune hepatitis (AIH type I) in young subjects is due to genetic differences in proinflammatory genes responding to viral triggers in patients and controls.Methods:Intrahepatic gene expression was compared between AIH type I (n = 24, age 9–30 years) patients (hereafter referred to as the AIH group) and controls (n = 21, age 4–25 years). RNA sequencing was performed on complementary DNA (cDNA) libraries made from total RNA extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsy samples. Gene expression levels were quantified, and differentially expressed genes were functionally analyzed. Pathway analysis was performed using the databases Kyoto Encyclopedia of Genes and Genomes (KEGG) and PANTHER. The remaining sequences were mapped to the RefSeq complete set of viral genomes.Results:Differential gene analysis identified 181 genes that were significantly differentially expressed (136 upregulated in the AIH group). Autoimmune pathway genes such as CD19 and CD20 which are important in B cell regulation and maturation as well as, CD8 and LY9, which are T-cell related, were upregulated in our AIH group. Genes implicated in AIH pathogenesis including CXCL10, which is thought to be associated with AIH severity and progression, complement genes (C1QA, C1QB, and C1QC), and human leucocyte antigen (HLA) genes (HLA-DRB1, HLA-DRA, HLA-B, and HLA-C) were upregulated in samples from the AIH group. Specific viral etiologies were not found.Conclusions:Unbiased next-generation sequencing and differential gene expression analysis of the AIH group has not only added support for the role of B cells in the pathogenesis and treatment of AIH but also has introduced potential new therapeutic targets: CXCL10 (anti-CXCL10) and several complement system–related genes.

Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma.

BackgroundConjunctivitis is a known comorbidity of atopic dermatitis. Dupilumab clinical trials for moderate-to-severe atopic dermatitis in adults showed a higher conjunctivitis incidence for dupilumab-treated patients than placebo-treated patients, whereas trials for uncontrolled asthma reported lower rates for both dupilumab and placebo.ObjectiveThe objective of this study was to evaluate the incidence and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma.MethodsWe evaluated the incidence of conjunctivitis in adolescents (aged 12 to < 18 years) in three phase III trials. Ocular events were diagnosed and treated based on patient-reported symptoms and an external eye examination by study investigators, in most cases without an ophthalmologic referral. In LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blinded trial), adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients < 60 kg at baseline; 300 mg, ≥ 60 kg at baseline). In LIBERTY AD PED-OLE (open-label extension), pediatric patients from previous dupilumab atopic dermatitis trials received dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks. In LIBERTY ASTHMA QUEST (randomized, double-blinded, placebo-controlled trial), patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on therapy with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo.ResultsIn ADOL, more dupilumab-treated (17/165; 10.3%) than placebo-treated patients (4/85; 4.7%) reported one or more conjunctivitis event. All events were mild to moderate in severity; 12 (7.3%) dupilumab-treated and 4 (4.7%) placebo-treated patients received treatment. Most patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved during the treatment period. The risk of conjunctivitis showed no relationship with dupilumab serum concentration. In PED-OLE, 12/275 adolescents (4.4%) reported one or more conjunctivitis event. Most conjunctivitis events were mild to moderate. Ten patients received treatment for conjunctivitis. Ten patients recovered/resolved during the study. In QUEST, similar low proportions of dupilumab-treated (2/68, 2.9%) and placebo-treated (1/39, 2.6%) adolescents reported one or more conjunctivitis event. All events were mild to moderate. One dupilumab-treated patient received treatment for conjunctivitis. All cases recovered/resolved during the study. No patients in these trials discontinued study treatment temporarily or permanently because of conjunctivitis. In ADOL, one case of unspecified viral keratitis (specific viral etiology not known) in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis in the placebo group were reported; both events resolved during the treatment period, and neither led to treatment discontinuation.ConclusionsDupilumab-treated adolescents in atopic dermatitis trials had a higher incidence of conjunctivitis than placebo-treated patients, whereas overall rates of conjunctivitis among adolescents in the asthma trial were lower than in atopic dermatitis trials and were similar for dupilumab- and placebo-treated patients. Most events were mild to moderate, most recovered/resolved, and none prompted study withdrawal. These results are similar to those reported in adult trials and support a drug–disease interaction.ClinicalTrials.gov IdentifiersNCT03054428, NCT02612454, NCT02414854. Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma (MP4 18453 kb)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-020-00577-1.

Antimicrobial use for pediatric acute respiratory tract infections and the subsequent emergence of multi-drug resistant bacteria

Background: Viruses cause the majority of acute respiratory tract infections (ARTIs). On clinical grounds, differentiation of bacterial vs. viral ARTIs is difficult and warrant costly investigations. In Sri Lanka, ARTIs are commonly treated by family physicians (FP), and severe patients seek inward care. This study was conducted to evaluate the use of antibiotics by FP and by hospital care and the development of antimicrobial resistance (AMR) in children with viral ARTIs. Methods and materials: Nasopharyngeal aspirates of inward patients (1-month to 5-years) with ARTIs were collected in Teaching Hospital, Anuradhapura from March-2013 to August-2014. Using immunofluorescence assay (IFA) specific viral etiology was detected. Phenotypically multi-drug resistant (MDR) bacteria were detected. The use of antibiotics and the development of infectious diseases in the past six months, in the current episode and follow up to 6 months was assessed using questionnaires, telephone interviews, and demonstration of antimicrobials. Multivariate analysis was performed to assess risk factors for the development of MDR microbes. Results: Out of 413 viral etiologies were detected in 40% (165/413). Antibiotics were prescribed in the health care facility for 100% (165/165) of patients with viral ARTIs. Initially, 120 patients were treated by FP, and 100% were on antimicrobials. Following admission, 84 of them were treated with antibiotics. Out of 120, 80 were on co-amoxiclav, 38 were on cephalosporin (cefixime-28; cefuroxime-10), and 2 were on macrolides monotherapy. Everyone was presented to FP on day 1 of illness. Mean ± SD hospital stay for viral ARTIs with and without antimicrobials was 4 ± 1.6 and 4.1 ± 1.8 days and is not significant. Eighty had two episodes of ARTI in the earlier 6-months, and every occasion was treated with antibiotics by FP. In follow up, 102 (75%) and 20 (14.7%) extended-spectrum of beta-lactamases (ESBL) and carbapenemase producers (CRE) were isolated in patients with urinary and other infections. Conclusion: The use of viral diagnostic by FP and in hospitals would be an essential factor in reducing the unnecessary use of antibiotics. The rational antibiotic use will invariably contribute to reduce the cost and to prevent the emergence of ESBL and CRE.

Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome.

Infectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respiratory distress syndrome is unknown. We aimed to characterize the epidemiology of viral pneumonia in pediatric acute respiratory distress syndrome and compare characteristics and outcomes between pneumonia subjects with and without viruses. Secondarily, we examined the association between specific viruses and outcomes. We performed a secondary analysis of a prospectively enrolled pediatric acute respiratory distress syndrome cohort. Subjects with pneumonia acute respiratory distress syndrome underwent testing of respiratory secretions for viruses and culture for bacteria and fungi and were stratified according to presence or absence of a virus. Tertiary care children's hospital. Children with acute respiratory distress syndrome. None. Of 544 children with acute respiratory distress syndrome, 282 (52%) had pneumonia as their inciting etiology, of whom 212 were virus-positive. In 141 of 282 (50%) pneumonia acute respiratory distress syndrome cases, a virus was the sole pathogen identified. Virus-positive pneumonia had fewer organ failures but worse oxygenation, relative to virus-negative pneumonia, with no differences in antibiotic use, ventilator duration, or mortality. Subjects with respiratory syncytial virus-associated acute respiratory distress syndrome had lower mortality (0%), and subjects with influenza-associated acute respiratory distress syndrome had shorter ventilator duration, relative to other viral acute respiratory distress syndrome. Nonadeno herpesviruses, tested for exclusively in immunocompromised subjects, had greater than 80% mortality. Pneumonia was the most common cause of pediatric acute respiratory distress syndrome, and viruses were commonly isolated as the sole pathogen. Respiratory syncytial virus and influenza were associated with better outcomes relative to other viral etiologies. Viral pneumonias in immunocompromised subjects, particularly nonadeno herpesviruses, drove the mortality rate for pneumonia acute respiratory distress syndrome. Specific viral etiologies are associated with differential outcomes in pediatric acute respiratory distress syndrome and should be accounted for in future studies.

Central Nervous System Disease and Adenoviruses

Research Article| March 01 2019 Central Nervous System Disease and Adenoviruses AAP Grand Rounds (2019) 41 (3): 35. https://doi.org/10.1542/gr.41-3-35 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Central Nervous System Disease and Adenoviruses. AAP Grand Rounds March 2019; 41 (3): 35. https://doi.org/10.1542/gr.41-3-35 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: adenoviruses, central nervous system dysfunction, adenovirus infections Source: Schwartz KL, Richardson SE, MacGregor D, et al. Adenovirus-associated central nervous system disease in children. J Pediatr. 2018 6 November [published online ahead of print]; doi: https://doi.org/10.1016/j.jpeds.2018.09.036Google Scholar Investigators from The Hospital for Sick Children (SickKids) in Toronto conducted a retrospective observational study to characterize adenovirus-associated central nervous system (CNS) disease in children. Three data sources were used: the SickKids microbiology and encephalitis databases (which include children who had been admitted to SickKids during 2000–2016 and 1996–2016, respectively) and a literature search. Children in the SickKids databases were eligible for the study if they were previously healthy; were 1 month to 18 years old; had neurologic symptoms; did not have a preexisting neurologic disorder; and had adenovirus detected by direct fluorescent antibody staining, culture, or polymerase chain reaction (PCR). Child cases identified from the literature search were eligible if they had a neurologic diagnosis other than febrile seizures and had microbiologic or serologic evidence of acute adenovirus infection. Clinical and demographic characteristics of identified children were abstracted from each data source. Using SickKids microbiology data, investigators determined the frequency and spectrum of neurologic complications of adenovirus disease. Using SickKids encephalitis data, investigators determined the frequency of adenovirus among children with encephalitis. Cases identified by literature search were then pooled with children identified in the SickKids databases (excluding those with febrile seizures) to characterize the adenovirus-associated CNS disease spectrum further. Multivariable logistic regression was used to identify risk factors associated with death or neurologic impairment. Of the 977 cases of adenovirus infection in the SickKids microbiology database, 32 (3.3%) had neurologic symptoms. Of these, 26 had febrile seizures, 4 had encephalitis, 1 had acute demyelinating encephalomyelitis, and 1 had aseptic meningitis. Of the 431 children in the SickKids encephalitis database, 8 (1.9%) had adenovirus (including the 4 with encephalitis identified in the SickKids microbiology database). There were 16 studies identified by the literature search involving 38 children, resulting in a pooled total of 48 cases. Of these, the median age was 2 years, and 40% were female. The most common prodromal symptoms were upper respiratory illness (48%), vomiting (22%), and diarrhea (19%). Hepatitis developed during hospitalization in 40%. There were 10 (21%) deaths, and 8 (17%) had permanent neurologic impairment. Children who developed seizures during their illness course had greater odds of death or permanent neurologic impairment (adjusted OR, 7.3; 95% CI, 1.69–31.45). The investigators conclude that adenovirus is a rare cause of CNS disease in children but can be fatal. Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Adenoviruses are common, accounting for at least 5%–10% of respiratory infections in children.1 Vomiting and diarrhea are often present concurrently.2 A specific viral etiology is usually not sought in children with these self-limited symptoms, so the incidence of adenovirus infections is difficult to ascertain. In the current study, the authors reviewed rare CNS manifestations of... You do not currently have access to this content.

Folliculocentric Herpes: A Clinicopathological Study of 28 Patients.

The cutaneous manifestations of herpes infection are primarily in the context of active infection and of the post-herpetic zosteriform eruption. The former manifests cytopathic alterations diagnostic of herpes. The latter includes lichen planus-like and granuloma annulare-like eruptions and lymphocytoma cutis. We encountered skin biopsies from 28 patients whose acute or chronic herpetic or post-herpetic zosteriform lesions manifested folliculocentricity. The clinical appearance of the lesions was correlated with the histopathologic and immunohistochemical features of paraffin-embedded skin biopsies to determine the specific viral etiology. A history of underlying medical disease was noted if present. There were 16 men and 12 women with a folliculocentric eruption occurring after a known herpetic eruption or manifesting cytopathic changes and/or immunohistochemical findings compatible with herpes virus in lesional skin biopsies. Underlying immune dysregulatory states were present in most cases, namely, malignancy, anticonvulsant or antidepressant therapy, diabetes mellitus, psoriasis, Crohn disease, and other conditions. All biopsies demonstrated dense lymphohistiocytic infiltrates in or around hair follicles with variable necrosis, while active infections also showed cytopathic and/or immunohistochemical evidence of herpetic alterations, most commonly varicella zoster. Other features included interfollicular interface dermatitis, lymphocytic eccrine hidradenitis, neuritis, and folliculocentric vasculitis. Cutaneous herpetic eruptions can evoke a predominantly folliculocentric mononuclear cell reaction and vasculitis; there is an association with underlying endogenous and/or iatrogenic immune dysregulation. Most cases are secondary to reactivation of varicella zoster. The histomorphology suggests a role for cell-mediated immunity. Antigenic homology of an endogenous 72-kd heat shock protein in follicles with that of a herpetic heat shock protein, in concert with an intrafollicular proliferative response of γ-δ T lymphocytes, may explain the follicular localization and composition of the infiltrate.

Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk

Viral respiratory wheezing illnesses are common in early childhood, and many children who wheeze subsequently develop asthma. In the Childhood Origins of ASThma (COAST) cohort, we previously reported that the development of rhinovirus (RV) wheezing illnesses in infancy and early childhood is the most robust predictor of subsequent asthma development in high-risk children at age 6 years, regardless of aeroallergen sensitization or other risk factors.1 However, a study in a similar high-risk birth cohort recently reported that the number of lower-respiratory episodes in the first 3 years of life, as opposed to a specific viral or bacterial etiology, was associated with asthma risk, and suggested that the specific microbiologic trigger is not important for the risk for later asthma development.

Abstract 2211: Viral subtypes in hepatocellular carcinoma are associated with different mechanisms of WNT/CTNNB1 alteration

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, especially in Asia, and regions of endemic hepatitis infection. The primary risk factors for HCC are chronic hepatitis infection by hepatitis C (HCV) or hepatitis B (HBV). We performed whole exome sequencing on 549 matched tumor and normal samples from three centers (BCM HGSC, RCAST, NCC) to identify somatic changes in protein coding regions and changes in copy number. Here we describe variants associated with specific viral etiologies in HCC. We found TP53, CTNNB1, ARID1A, ARID2, and AXIN1 to be among the most frequently mutated genes in the entire dataset, implicating DNA damage, WNT signaling, and chromatin remodeling as recurrently altered pathways in HCC. Our validation rate for mutations in significantly mutated genes was over 95%. We identified 18 genes which differed significantly (p &amp;lt; 0.05) in mutation frequency between viral subtypes. Of these, AXIN1 was mutated in over 15% of HBV-associated HCC but less than 5% of HCV and non-viral-associated HCC. Additionally, we performed GISTIC analysis based on read depth from our whole exome sequencing data. We found that WNT3A and MYC were significantly amplified and AXIN1 and TP53 were significantly deleted in HCV-associated HCC but not HBV or non-virus-associated HCC. Our findings indicate that WNT/beta-catenin signaling is a frequently altered pathway in HCC. While aberrations in this pathway were present in all viral etiologies, HBV-associated HCC tended to mutate AXIN1 while HCV-associated HCC tended to have AXIN1 deletion. These differences may result from virus-specific oncogenic processes. Citation Format: Kyle R. Covington, Lawrence A. Donehower, Chad Creighton, Betty L. Slagle, John A. Goss, Ronald T. Cotton, Marie-Claude Gingras, Eve Shinbrot, Jacfranz J. Guiteau, Thao N. Nguyen, Theresa R. Harring, Donna M. Muzny, Kimberly Walker, HarshaVardhan Doddapaneni, Richard A. Gibbs, Hiroyuki Aburatani, Tatsuhiro Shibata, David A. Wheeler, Japan ICGC HCC Project. Viral subtypes in hepatocellular carcinoma are associated with different mechanisms of WNT/CTNNB1 alteration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2211. doi:10.1158/1538-7445.AM2014-2211

Serum cathelicidin level is associated with viral etiology and severity of bronchiolitis

Serum cathelicidin level is associated with viral etiology and severity of bronchiolitis

Advances in pediatric neurovirology.

Viral infections of the pediatric central nervous system (CNS) encompass a broad spectrum of both perinatally and postnatally acquired diseases with potentially devastating effects on the developing brain. In children, viral infections have been associated with chronic encephalopathy, encephalitis, demyelinating disease, tumors, and epilepsy. Older diagnostic techniques of biopsy, viral culture, electron microscopy, gel-based polymerase chain reaction (PCR), and viral titer quantification are being replaced with more rapid, sensitive, and specific real-time and microarray-based PCR technologies. Advances in neuroimaging technologies have provided for earlier recognition of CNS injury without elucidation of specific viral etiology. Although the mainstay therapy of many pediatric neurovirologic diseases, aside from HIV, includes intravenous acyclovir, much work is being done to develop novel antiviral immunotherapies aimed at both treating and preventing pediatric CNS viral disease.

Association of Tumor Necrosis Factor-Alpha Gene Promoter Polymorphisms with Acute Viral Hepatitis in the Indian Population

The key elements that determine the host response to either the self-limited or a severe fulminant form of liver disease are unclear. We have investigated the potential association of single nucleotide polymorphisms (SNPs) in the promoter region of tumor necrosis factor-alpha (TNFalpha) in their susceptibility to acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) patients exhibiting specific viral etiology. A total of 124 individuals including 64 cases comprising 27 FHF, 37 AVH, and 60 healthy controls were recruited. SNPs at -238 (G/A), -308 (G/A), -857 (C/T), and -863 (C/A) of TNFalpha were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing. Serum levels of TNFalpha were determined at admission and death or recovery. Association between the TNFalpha genotype and susceptibility to FHF was not evident; however, carrier genotypes in relation to the -308 (GA/AA) and -857 (CT/TT) loci were found to be significantly (P < or = 0.05) associated with susceptibility to AVH in relation to controls. The mean TNFalpha serum levels at admission were significantly higher (P < 0.001) in FHF than AVH patients, but no marked difference was observed between FHF-E (expired; n = 17) and FHF-S (survivors; n = 10), though the former were comparatively higher. This study suggests that SNPs at -308 and -857 of the TNFalpha promoter may represent an increased risk for the development of AVH but not for FHF in the Indian population.

The viral aetiology of acute encephalitis in children in Vietnam

Background Acute encephalitis is an important and severe disease in children in South-Vietnam, but relatively little is known about the etiology. Knowledge about the etiology of encephalitis would benefit future studies aiming at prevention and treatment of the disease. To identify specific viral etiologies of encephalitis, we conducted a descriptive study between Jan 2004 and Jan 2005 at a referral children hospital, the Pediatric Hospital Number One located at centre of Ho Chi Minh City.

Prise en charge diagnostique et thérapeutique des rétinites nécrosantes herpétiques

To study the viral cause and present the management of necrotizing herpetic retinopathies. Charts of patients presenting with acute retinal necrosis (ARN) or progressive outer retinal necrosis (PORN) diagnosed between March 1997 and June 2001 were retrospectively reviewed. Intraocular specimens were obtained in 33 cases to determine the viral cause using polymerase chain reaction-based assays and/or detection of intraocular antibody production. The mean age was 43.4 Years. Herpesvirus genome was identified in 29 patients (80.5%). In the ARN group (32 patients, 38 eyes), herpes simplex virus (HSV) DNA was found in 11 patients (34.4%), varicella-zoster virus (VZV) in nine patients (28.1%), and cytomegalovirus (CMV) in four patients (12.5%). One patient (3.1%) presented an Epstein-Barr virus (EBV) infection. ARN was bilateral at initial examination in six patients and secondary bilateralization was observed in four patients. In the PORN group (four patients, eight eyes), the retinitis was bilateral and VZV DNA was detected in all cases. Two patients were treated with intravenous acyclovir, six with foscarnet alone, ten with intravenous foscarnet + acyclovir, 18 with intravenous foscarnet and intravitreous ganciclovir injections. Complications of necrotizing herpetic retinitis were cataract (26%), optic nerve atrophy (23.9%), and retinal detachment (17.4%). Final visual acuity was less or equal to 20/200 in 47.8% of cases. It is important to determine the specific viral etiology since progression and prognosis may be different in herpetic necrotizing retinitis caused by HSV, VZV, or CMV. Visual prognosis is improved by intensive antiviral therapy, but remains poor if complications occur.

Viral etiology of frequently recurring respiratory tract infections in children.

The viral etiology of frequently recurring respiratory tract infection (FRRI) in children aged <2 years was studied. Altogether, 329 children were followed from 2 to 24 months of age in the Finnish Otitis Media Cohort Study. Children with FRRI were defined as having > or =9 episodes of upper respiratory tract infection (URI) and/or > or =4 episodes of acute otitis media during follow-up. Nasopharyngeal aspirates, middle ear fluid specimens, and serum samples were analyzed for 8 common respiratory viruses. Of 1358 URI episodes, 642 (47%) occurred in the 78 children with FRRI. At least 1 virus was associated with 62% of these episodes, whereas the corresponding figure for children without FRRIs was 54%. The frequency of different viruses was similar in both groups, but the relative proportion of rhinovirus infections was slightly higher among children with FRRI. In conclusion, a specific viral etiology does not explain the excess of URI episodes in children with FRRI.

Nontypical Henoch-Sch??nlein Purpura

To the Editor: The observation by A. Hakim (1) of four patients who had atypical skin rash is interesting. There are some similarities in those patients to the ones we described previously (2). There are also differences. The features which are similar are recurrent abdominal pain which was severe enough to cause crying and require a surgical consult. In contrast to our patients, however, all of the four patients described by Hakim had a rash. The rash was described as atypical. If the skin rash in Henoch-Schönlein purpura (HSP) is atypical, a skin biopsy should be done to look for the classic leukocytoclastic vasculitis. If such an examination was done, it was not reported by the authors. A rash in Henoch-Schönlein purpura is not always the presenting manifestation and as Hakim has stated, the rash may not be typical. Physicians understand the challenge in diagnosing HSP in patients in the absence of a rash. Our report and others have raised awareness of HSP in certain clinical situations and have suggested modalities for making an appropriate diagnosis. The dictum we learned from our patients is that if we have a young child with colicky abdominal pain of 1 to 2 weeks duration and there is no surgical cause think of HSP, particularly if the stools are positive for occult blood. In that situation, an upper GI endoscopy is helpful and may show the typical findings of HSP. Colonoscopy may also aid in the diagnosis. Regarding the etiology, prodromal viral illness has been described as an etiology of HSP. Though there is a higher occurrence of HSP in the late fall and spring, some patients are seen throughout the year. The observation of Hakim about the high incidence during winter may also suggest a specific viral etiology leading to the vasculitis. To use different ways of writing HSP reflecting the severity of the skin rash is interesting. Hakim is proposing that we use HSP if it is with a typical rash, HSp if it is with an atypical rash. We add that we use HSP-P (HSP minus P) if there is no rash in this condition. T. S. Gunasekaran M.D. James Berman M.D.

Treatment recommendations for specific viral etiologies

Treatment recommendations for specific viral etiologies

Viral encephalitis.

Viral encephalitis.

Sudden infant death syndrome, child sexual abuse, and child development.

Since the introduction of the Back to Sleep Campaigns, there has been a dramatic reduction in sudden infant death syndrome in this country. Steven Blatt and Victoria Meguid review the literature surrounding sleep position. Investigators have continued efforts to find other modifiable risk factors of sudden infant death syndrome. A prospective study of more than 33,000 neonates found a link between a prolonged QT electrocardiogram interval and sudden infant death syndrome. Also discussed are investigations seeking to explain the relationship between smoking and sudden infant death syndrome. Ann Botash, Florence Jean-Louis and Mongkae Ploy Siripornsawan review the latest thinking on genital warts and their relation to specific viral etiologies and child sexual abuse. Other symptoms and signs of sexual abuse are the focus of a number of articles that can help the practitioner care for these unfortunate children. Catherine Church reviews medication options for children diagnosed with pervasive developmental disorders or autism spectrum disorders. Finally, in this article, risperidone, fluoxetine and naltrexone are reviewed.

Are human herpes viruses or measles virus associated with esophageal achalasia?

In order to test the hypothesis that esophageal achalasia may be due to neurotropic viral damage to the esophageal myenteric plexus, esophageal tissue with or without achalasia was analyzed by polymerase chain reaction for the presence of human herpes virus DNA or measles virus RNA. The DNA and RNA were extracted from the esophageal muscle of 12 patients with achalasia and six patients with upper esophageal carcinoma. Peripheral blood mononuclear cells from eight adult volunteers and two samples of umbilical blood mononuclear cells were also used as controls. PCR amplification with a pair of primers specific for herpes simplex type 1 and 2 viruses identified 92-bp fragments in nearly all specimens, including those without achalasia. Each 92-bp fragment was confirmed to be identical to a single herpes simplex virus sequence by automated DNA sequence analysis. No amplification for five other herpes viruses or measles virus was detected. Therefore, a specific viral etiology for achalasia was not identified in this study.

A Cluster of Young Patients With Burkitt's Lymphoma and Nasopharyngeal Carcinoma in Central Texas

During a five-month period in 1982, diagnoses were made of Burkitt's lymphoma in three children and nasopharyngeal carcinoma in three teenagers who were residents of a small geographic area of central Texas. The observed number of these two Epstein-Barr virus-related cancers was significantly greater than the number expected in young patients based on Surveillance, Epidemiology, and End Results incidence rates. No epidemiologic associations were found linking any of the patients. Environmental studies including serological assays to determine a specific viral etiology were unrevealing. A search for new agents and the preservation of materials for future studies should continue to be a high priority in the evaluation of cancer clusters.