Enterovirus Polymerase Chain Reaction Research Articles

Performance of blood enterovirus and parechovirus polymerase chain reaction testing in young febrile infants: a prospective multicentre observational study

ObjectivesTo analyse the performance of blood enterovirus and parechovirus PCR testing (ev-PCR) for invasive bacterial infection (IBI) (isolation of a single bacterial pathogen in a blood or cerebrospinal fluid culture)...

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies >340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was <5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

A baby girl with TBX1 haploinsufficiency who died after elective cardiac repair surgery due to suspected enteroviral meningitis

IntroductionTBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case PresentationA 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient’s irreversible neurological status. The patient was disconnected from ECMO and expired. DiscussionThough we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.

Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) with Direct Cystic Infiltration of the Optic Chiasm and Tracts (P1-9.003)

<h3>Objective:</h3> N/A <h3>Background:</h3> Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare pediatric neoplasm categorized by the WHO in 2016. It is characterized by communicating hydrocephalus, slow tumor growth, CSF with absence of tumor cells, and MRI showing diffuse leptomeningeal enhancement and cystic changes. Here we present, to our knowledge, the first case in which direct cystic tumor infiltration of the optic apparatus was the initial manifestation. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 3-year-old boy developed emesis, altered mental status, bilateral leg weakness, and decreased visual acuity to 20/125 OD and 20/160 OS. MRI showed hydrocephalus and diffuse leptomeningeal enhancement of the brain and spine. Lumbar puncture showed pleocytosis, elevated protein, positive enterovirus PCR, and opening pressure of 55 cm H2O. VP shunt was placed for presumed enterovirus meningitis. Symptoms of hydrocephalus resolved but vision did not improve. Exam showed optic disc pallor bilaterally and no papilledema. OCT demonstrated retinal nerve fiber layer thinning bilaterally. Visual decline progressed despite normalization of ICP. Repeat MRI brain/orbits showed multiple new subpial cysts along the optic tracts and optic chiasm. Filum biopsy showed rare inflammatory cell. Review of the pathology and radiological findings led to a consensus of DLGNT with cysts compressing and infiltrating optic chiasm and nerves. The patient was started on the MEK inhibitor trametinib, with stabilization of MRI findings and vision, but unfortunately without visual improvement. <h3>Conclusions:</h3> Pathologic confirmation of DLGNT can be difficult as safely obtained biopsy samples are typically small. In this case, bilateral optic neuropathy developed due to infiltration of the optic nerves, chiasm and tracts, while papilledema was never seen. MEK inhibitor therapy was initiated with Trametinib leading to stabilization in disease burden. This diagnosis should be considered in pediatric patients with communicating hydrocephalus, diffuse leptomeningeal enhancement, and elevated CSF protein with otherwise normal profile including absence of tumor cells. <b>Disclosure:</b> Dr. Paddock has nothing to disclose. Dr. Dinkin has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for WILSON ELSER MOSKOWITZ EDELMAN &amp; DICKER LLP. Dr. Dinkin has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Rehabilitation Alternative Services, Inc.. Dr. Dinkin has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for AMFS / Medical Experts Nationwide. Dr. Dinkin has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bekman, Marder, Hopper, Malarkey &amp; Perlin, L.L.C.. Dr. Dinkin has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Northwestern Mutual. Dr. Dinkin has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Young Conaway Stargatt &amp; Taylor.

Varicella zoster virus: an under-recognised cause of central nervous system infections?

Varicella zoster virus (VZV) causes infections of the central nervous system (CNS) manifesting as meningitis or encephalitis. It is not commonly tested in CNS infections when compared with enterovirus (EV) and herpes simplex virus 1 (HSV-1) and 2 (HSV-2). Cerebrospinal fluid (CSF) findings of viral CNS infections are thought to be comparable. To describe the manifestations of VZV CNS infections and ascertain if there is a predominant syndrome. To compare CSF parameters of VZV with EV, HSV-1 and HSV-2. Retrospective study at two hospitals in Brisbane, reviewing medical notes and laboratory information system for results between January 2001 and 2019. The following parameters were recorded - disease classification, presence of rash, duration of symptoms prior to hospitalisation, length of admission, duration of antiviral treatment and 30-day mortality. CSF biochemistry, cell count (differential), PCR for VZV, EV, HSV-1 and HSV-2 were recorded. Statistical analysis of CSF parameters included Student's t-test and linear regression. Incidence of meningitis was comparable to encephalitis (44 vs 39%) in 52 cases. CSF protein in VZV was significantly elevated compared with EV (median 1121 vs 569 mg/L; P < 0.001) as was CSF monocytosis (96% vs 61%; P < 0.001). CSF parameters between VZV, HSV-1 and HSV-2 were similar. VZV had a higher incidence than HSV-1 or 2, while it was tested one-third as often. VZV CNS infection cannot be predicted by syndrome. CSF findings are markedly different from EV but like HSV-1 and 2. VZV should be routinely tested with HSV-1 and 2 when viral CNS infection is suspected.

Determining Normative Values for Cerebrospinal Fluid Profiles in Infants.

Previous studies of reference values for cerebrospinal fluid (CSF) profiles have been limited by small sample size and few exclusion criteria. To determine age-specific normative CSF white blood cell count (WBC), glucose, and protein values in infants ≤90 days old. Performed a retrospective cross-sectional study of infants ≤90 days old who had a diagnostic lumbar puncture between 2008 and 2016. Infants with bacterial meningitis, bacteremia, UTI, positive CSF herpes simplex virus polymerase chain reaction (PCR) result, traumatic lumbar puncture, ventriculoperitoneal shunt, prematurity, recent seizure, previous antibiotic use, and history of a complex chronic condition were excluded for calculations to determine normative values. Data on demographics and CSF values (WBC with differential, protein, glucose, enterovirus PCR) were collected. CSF values were compared by age and by enterovirus PCR results using Kruskal-Wallis and Wilcoxon rank tests. A total of 1029 out of 2000 patients were included and divided into 3 age groups: 0 to 28 days, 29 to 60 days, 61 to 90 days. CSF WBC values were significantly greater for 0- to 28-day old infants (median: 3, 95th percentile: 14) than for 29- to 60-day and 61- to 90-day old infants (median: 2 and 2; 95th percentile: 7 and 11, respectively) (P < .001). With each month of life, the median CSF protein significantly decreased and glucose significantly increased. In the CSF WBC differential, monocytes were found to be prevalent. We determined age-specific normative components for CSF profile values for infants 0 to 90 days.

AKI In Suspected Meningitis/Encephalitis May Be "Avoidable Kidney Injury".

AKI In Suspected Meningitis/Encephalitis May Be "Avoidable Kidney Injury".

CHRONIC PANCREATIC DISEASE IN THE LESSER KUDU (TRAGELAPHUS IMBERBIS): A REPORT OF 16 CASES IN THE UNITED STATES.

A review of archival cases at Northwest ZooPath from 1995-2018 identified 16/96 (17%; eight females, eight males) lesser kudus (Tragelaphus imberbis) with chronic pancreatic disease (CPD) from three institutions, all of which originated from an initial founder stock of 12 animals. Ages at time of death or euthanasia ranged from 2 to 132 mo (average age = 69 mo). All cases had varying degrees of pancreatic acinar cell depletion, ductular hyperplasia, and fibrosis. Serum fructosamine, glucose, insulin, and insulin to glucose ratio collected close to time of death from 13 affected animals were not significantly different from controls (n = 19). Of these analytes, receiver operating characteristic analysis identified fructosamine as the best-performing analyte with an area under the curve 0.671 (95% confidence interval = 0.480-0.828; sensitivity = 58.3%, specificity = 84.2%; cutoff point >352 µmol/L) in the diagnosis of CPD. With a 15% prevalence, there was a positive predictive value of 41% and a negative predictive value of 92%, indicating that the probability of false positives is high, but of false negatives is low. An etiologic agent was not identified by histology (n = 16), transmission electron microscopy (n = 1), or enterovirus PCR (n = 2). Serum zinc and hepatic heavy metal analyses were judged to be within normal limits. Chronic pancreatic disease is considered an important cause of morbidity and mortality in the lesser kudu; serum chemistry analysis warrants further investigation in its use for diagnosis. The etiopathogenesis is not understood, but the absence of obvious causes, the occurrence also in very young animals, and the inbred lineage of lesser kudus in the United States suggest a genetic basis for this disease.

Blood enterovirus polymerase chain reaction testing in young febrile infants

ObjectiveTo analyse the impact of blood enterovirus and human parechovirus PCR (ev-PCR) testing in young infants with fever without a source (FWS).DesignObservational study, subanalysis of a prospective registry.SettingPaediatric emergency department.PatientsInfants...

Prospective case‐control study of enterovirus detection differences in children’s cerebrospinal fluid between multiplex PCR and real‐time RT‐PCR assay

BackgroundViral encephalitis is common in childhood. It is an acute brain parenchymal inflammation caused by a variety of viral infection, and enterovirus accounts for the majority. Due to atypical clinical manifestations, pathogenic testing is important for assisting clinical diagnosis. The purpose of this study was to evaluate the performance of the multiplex PCR assay compared with quantitative real‐time PCR for enterovirus detection.MethodsA prospective case‐control study was performed involving 103 pediatric patients suspected for viral encephalitis and cerebrospinal fluid (CSF) samples were collected and tested for 9 pathogens using multiplex PCR assay during April to November in 2018. In parallel, an aliquot of samples was tested for enterovirus infection by real‐time PCR assay.ResultsThere were 85.4% children were confirmed as viral encephalitis on discharge, the remaining ones were diagnosed as other CNS diseases, such as epilepsy. The specificity of the two methods was the same as that of the clinical diagnosis, but the sensitivity and consistency with clinical diagnosis of multiplex PCR were both higher than the real‐time PCR. Besides of enterovirus, multiplex PCR could also detect coinfection of enterovirus with Epstein‐Barr virus and mumps virus.ConclusionResults of multiplex PCR method are more consistent with the clinical diagnosis and are superior to real‐time PCR for detecting enterovirus in CSF.

Molecular Characterization and Clinical Description of Non-Polio Enteroviruses Detected in Stool Samples from HIV-Positive and HIV-Negative Adults in Ghana.

In the post-polio eradication era, increasing attention is given to non-polio enteroviruses. Most of the data about enteroviruses in sub-Saharan Africa are related to acute flaccid paralysis surveillance and target the pediatric population. This study aimed to investigate the presence of enterovirus in PLHIV (people living with HIV) and HIV-negative individuals in Ghana. Stool samples from HIV-positive individuals (n = 250) and healthy blood donors (n = 102) attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana, were screened by real-time PCR for enterovirus. Molecular typing of the VP1 region was performed. Enterovirus-positive samples were tested for norovirus, adenovirus, rotavirus, sapovirus, and cosaviruses. Twenty-six out of 250 HIV-positive subjects (10.4%) and 14 out of 102 HIV-negative individuals (13.7%) were detected enterovirus-positive, not showing a significant different infection rate between the two groups. HIV-negative individuals were infected with Enterovirus C strains only. HIV-positive participants were detected positive for species Enterovirus A, Enterovirus B, and Enterovirus C. Co-infections with other viral enteric pathogens were almost exclusively detected among HIV-positive participants. Overall, the present study provides the first data about enteroviruses within HIV-positive and HIV-negative adults living in Ghana.

Teaching NeuroImages: Hopkins syndrome: A rare differential diagnosis of neurogenic monomelic amyotrophy.

An 11-year-old Brazilian boy presented with worsening left thigh weakness. At age 2 years, he presented with left lower limb weakness after 4 days of a severe asthma episode. Examination showed amyotrophy, weakness, and areflexia of the left lower limb (figure). Spine MRI and CSF analysis (including serology and PCR for herpesvirus, enterovirus, and arbovirus) were unremarkable. Neurophysiologic studies exhibited ongoing denervation and chronic reinnervation changes involving the left lower limb muscle groups. Our patient was diagnosed with Hopkins syndrome, a rare childhood-onset lower motor neuron disease presenting with monomelic amyotrophy after an acute asthma attack.1,2

Clinical validity of enterovirus PCR testing of skin swabs samples

Background: Enteroviruses cause a diverse spectrum of diseases. In 2018, enterovirus PCR was included in the standard panel of skin swabs investigations, which already included HSV and VZV. Here we show evidence that positive PCR results for enterovirus correlate with clinical data obtained through retrospective review. Method: A retrospective search of laboratory records for all skin swabs between July 18 and March 19 was performed. Enterovirus PCR positive results were correlated with clinical information from request forms and electronic patient records. A subset of positive samples was sent to the reference laboratory for genotyping by Sanger sequencing of the VP1 gene. Results: Of 1159 specimens tested, 108 were positive for enterovirus, 194 were positive for HSV 1, 70 for HSV 2, 167 for VZV. Median age for enterovirus positive patients was 1 year, compared with 29 years for HSV and VZV positive patients. 99 enterovirus positive results correlated clinically, 2 did not correlate, and 7 had no clinical information available. Those with clinical correlation had a higher PCR cycle threshold (CT), than those without (mean 27.4 vs. 38). 12 samples were sent to the reference laboratory. Of the 6 that could be successfully genotyped, all were Coxsackie A6. Conclusions Positive enterovirus PCR in skin swabs correlated well with clinical signs, demonstrating validity. The identification of Coxsackie A6 on all sub-typed isolates further supports the validity of a positive result, as does the younger median patient age for patients testing positive for enterovirus compared to other viral infections.

Infections à entérovirus de l’adulte traité par rituximab : un nouveau cas de méningite et myofasciite chronique et revue de la littérature

IntroductionChronic enterovirus infections can occur in primary immunodeficiency with hypogammaglobulinemia. They usually associate meningitis and myofasciitis. Such infections have also been described in adults with rituximab-induced hypogammaglobulinemia. Case reportWe report the case of a 33-year-old woman who was given rituximab for immune thrombocytopenia and developed rituximab-induced hypogammaglobulinemia (IgG 4.4g/L). One year after the last rituximab infusion, she developed lower limbs myofasciitis, followed two months later by a chronic lymphocytic meningitis. PCR in the serum and the cerebrospinal fluid at the time of the meningitis and the myofasciitis were positive to the same enterovirus (echovirus 11) while it was negative in the fascia biopsy. Under treatment with intravenous immunoglobulins, all symptoms and laboratory abnormalities improved and enterovirus PCR became negative. ConclusionWe report a case of chronic enterovirus infection associating meningitis and myofasciitis in an adult with rituximab-induced hypogammaglobulinemia. Outcome was favorable under treatment with intravenous immunoglobulins.

Impact of decreasing cerebrospinal fluid enterovirus PCR turnaround time on costs and management of children with suspected enterovirus meningitis.

To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9–7.6). Median hospital LOS was 5 days (IQR 3–12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33–0.68) and 0.67 days (95%CI 0.42–0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14–517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.

An unusual case of enterovirus causing Gianotti Crosti syndrome

A 15-month-old child presented to the emergency department with a papular acrally distributed erythematous rash of unknown cause. The eruption was unusually florid but consistent with a diagnosis of Gianotti Crosti syndrome, a self-limiting skin condition of childhood. The child had not been unwell, nor recently vaccinated, but tested positive for enterovirus polymerase chain reaction (PCR). Although numerous viruses, such as Epstein-Barr and Coxsackie B, have been associated with Gianotti Crosti syndrome, this is one of the few published cases specifically discussing the presentation of enterovirus induced Gianotti Crosti syndrome.

Screening for enteroviral meningitis in infants and children-Is it useful in clinical practice?

Enteroviral meningitis in infants and children commonly leads to hospital admission. Diagnosing viral meningitis can be difficult clinically. We examined the usefulness of enteroviral polymerase chain reaction (PCR) testing using cerebrospinal fluid (CSF) samples on clinical practice by comparing positive enteroviral CSF PCR cases (n = 39/136) to negative controls using both clinical outcomes and laboratory parameters. A positive result correlated with a reduced admission to high dependency unit, reduced the duration of antibiotics and a shorter length of stay (P < .05). Adjusted CSF white cell count > 5/μL correlated with positive PCR (P < .05) but would have missed 32% of cases of enteroviral meningitis. Following these findings, an algorithm for the management of suspected viral meningitis has been introduced.

The Mechanism of Onychomadesis (Nail Shedding) and Beau's Lines Following Hand-Foot-Mouth Disease.

Background: Nail changes, including onychomadesis (nail shedding) and Beau’s line, following hand-foot-mouth disease (HFMD) are a common emergence at the stage of late complications of HFMD. However, the exact mechanism is still unknown. Therefore, we conducted this study to elucidate the mechanism of nail changes following HFMD. Methods: We collected 11 patients suffering from onychomadesis following HFMD. Nail samples from all of them were collected. Real time reverse transcription polymerase chain reaction (RT-PCR) and sequencing for human enteroviruses (HEV) were performed. Throat swabs for RT-PCR and sequencing for HEV were performed for three cases. Results: RT-PCR demonstrated the presence of Coxackievirus A6 (CVA6) in nail samples from three patients and one with Echovirus. Conclusion: In conclusion, we believe that the major cause of onychomadesis following HFMD is that certain novel viruses, mostly CVA6, are virulent and may damage nail matrix. Direct injury caused by cutaneous lesions of HFMD around nail matrix is a minor cause. There are still other virulent HEV which may result in onychomadesis. In addition, the novel strain of CVA6 also causes atypical clinical presentations, such as adult involvement and delayed-onset palmar and plantar desquamation. Physicians should be familiar with atypical presentations caused by novel viruses to avoid misdiagnosis and even inform patients of the possibility of onychomadesis that may take place weeks later to reassure patients.

64-Year-Old Man With Subacute Altered Mental Status and Headache

64-Year-Old Man With Subacute Altered Mental Status and Headache