A previously healthy 4-year-old boy presented with progressive left eyelid swelling and erythema, without reported animal exposure. Initially diagnosed as impetiginized eczema, the lesion was treated with topical antibiotic and corticosteroid therapy. Due to early clinical worsening, this was subsequently escalated with oral amoxicillin-clavulanate (50 mg/kg/day) and azithromycin (10 mg/kg/day). However, this local and systemic regimen failed and worsened the clinical presentation over a 9-day period. Inflammatory markers and blood cultures remained normal. Due to outpatient treatment failure, an initial periorbital skin and ciliary margin swab was collected on day 9 of oral antibiotics. Two days later, worsening symptoms prompted hospital admission for intravenous broad-spectrum antibiotics (ceftriaxone and clindamycin) and fluconazole. Pending culture results, suspected vesicular lesions led to empirical oral acyclovir (20 mg/kg/dose, 4 times daily); this was discontinued after 3 days when the initial swab returned negative for HSV. Ultimately, after an 8-day incubation, the outpatient swab culture yielded Trichophyton mentagrophytes species complex. Following microbiological identification of the dermatophyte, antifungal treatment was optimized with systemic griseofulvin and topical terbinafine, leading to complete clinical resolution. This case highlights atypical periocular dermatophytosis masquerading as a refractory bacterial and viral infection. Since direct animal exposure was not reported and phenotypic identification alone cannot distinguish between zoophilic (T. mentagrophytes) and anthropophilic (T. interdigitale) subtypes, the exact source of infection remains undetermined. In conclusion, while 'tinea incognito' is well documented, this report illustrates an exceptionally atypical periocular manifestation that mimicked a refractory bacterial cellulitis and simulated a herpetic infection. The novelty of this case lies in its severe clinical mimicry-including the development of chalazion-like lesions-which confounded a multidisciplinary team and led to unnecessary systemic antiviral and broad-spectrum antibiotic therapies, strongly highlighting the clinical importance of considering dermatophytosis in atypical orbital presentations.

Herpes Simplex Virus (HSV) is a double stranded deoxyribonucleic acid (DNA) virus with 2 serotypes, HSV-1 and HSV-2. Neonatal HSV infection is uncommon due to evidence-based interventions for pregnancy, delivery and the newborn. The study assessed whether pregnant women with a history of genital HSV and their infants were managed according to best practice recommendations.

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy in which facial weakness may occur as a cranial neuropathy. Unilateral facial palsy may also prompt a diagnosis of idiopathic Bell's palsy, creating a risk of diagnostic anchoring when broader neurologic symptoms are already present. We report a 32-year-old man with childhood epilepsy who described progressive bilateral upper and lower extremity weakness with paresthesias for approximately two weeks, followed by left facial paralysis about one week later. He also reported co-administration of hepatitis B, influenza, and tetanus vaccines approximately three weeks before presentation; the vaccine products and dates were not independently verified. An outside hospital treated the facial paralysis as presumed Bell's palsy with acyclovir, although the available records do not establish the facial examination pattern, acyclovir regimen, whether corticosteroids were prescribed there, or whether the preceding bilateral limb symptoms were recognized. An outpatient electrodiagnostic study was reportedly interpreted as concerning for GBS, but the complete nerve conduction/electromyography report was unavailable. Cerebrospinal fluid (CSF) showed white blood cells of 5/mm[3], glucose of 59 mg/dL, and protein of 190 mg/dL, supporting albuminocytologic dissociation; a paired serum glucose was unavailable. The patient completed a five-day course of intravenous immunoglobulin (IVIG), and prednisone plus valacyclovir was also documented for the facial palsy, although their exact dose, route, and duration were not recoverable. The source record documented short-term neurologic improvement before discharge. This case emphasizes that unilateral facial palsy should not distract from pre-existing bilateral weakness and paresthesias and that facial weakness in this setting may represent GBS-related cranial neuropathy rather than a separate confirmed Bell's palsy. The temporal association with vaccination does not establish causality.

Severe pneumonia with multiple microbial detections can make etiologic attribution and rescue decisions difficult. We report a 42-year-old man with obesity (body mass index, 36.3 kg/m[2]) who was admitted with rapidly progressive pneumonia, sepsis, acute hypoxemic respiratory failure, and multiorgan dysfunction [Sequential Organ Failure Assessment (SOFA) score, 9]. Despite invasive ventilation, one approximately 28-h prone-positioning session, and broad-spectrum antimicrobials, oxygenation deteriorated; immediately before extracorporeal support, PaO2 was 52 mmHg on FiO2 1.0 (PaO2/FiO2, 52 mmHg). The course included blood-tinged secretions, suspected alveolar hemorrhage without a documented progressively bloody serial lavage pattern, and complete left lung atelectasis. Bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) detected Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Legionella pneumophila, and a high Epstein-Barr virus (EBV) sequence burden. Admission blood cultures and conventional sputum culture showed no bacterial growth. On hospital day 3, venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated at 3,510 rpm, with blood flow 5.0 L/min and sweep gas flow 4.5 L/min. Adjunctive intravenous acyclovir (0.75 g every 8 h for 7 days) was administered because of the high EBV burden, although its clinical benefit in EBV pulmonary disease is unproven. VV-ECMO was discontinued on hospital day 18, extubation occurred on hospital day 24, and the patient subsequently returned to normal daily life. The clinical value of this case lies in management of a compound, potentially reversible phenotype rather than proof of any single microbial cause: severe pneumonia with polymicrobial mNGS detections, high EBV burden of uncertain significance, suspected hemorrhagic lung injury, unilateral atelectasis, and obesity-related respiratory mechanics successfully bridged with VV-ECMO.

Encephalitis guidelines recommend repeating a lumbar puncture (LP) 3-7 days after an initial negative cerebrospinal fluid (CSF) herpes simplex virus (HSV) polymerase chain reaction (PCR) test in patients with high suspicion for HSV or varicella zoster virus (VZV), but this subgroup has not been specified. Retrospective observational study of 602 adults with encephalitis from 2002 to 2023 from two large U.S. healthcare systems. Multivariate logistic regression models were developed and internally validated to identify clinically relevant and statistically significant features predicting HSV, VZV, and combined HSV/VZV encephalitis. HSV and VZV encephalitis were diagnosed in 103 (17.1%) and 43 (7.14%), respectively. Independent predictors for HSV acute presentation, new temporal lobe abnormalities on MRI, and hemorrhage on brain MRI. For VZV, predictors were immunosuppression, Charles Comorbidity Index > 2, and absence of seizures on presentation. For HSV/VZV, predictors included age ≥ 50 years, immunocompromise, acute presentation, CSF lymphocytosis, new temporal lobe abnormalities on MRI, hemorrhage on brain MRI, and Glasgow Coma Scale (GCS) ≥ 13 (P < 0.05). Patients were classified into 3 categories: low-risk (0 points), intermediate-risk (1 point), and high-risk (≥ 2 points). The area under the receiver operating curve was 0.675, 0.734, and 0.583 for the HSV, VZV, and HSV/VZV models, respectively. The risk score can help identify patients with an initial negative PCR who would benefit from a repeat LP (intermediate- or high-risk) and may support discontinuing acyclovir in low-risk patients.

Herpes simplex esophagitis (HSE) rarely occurs in immunocompetent patients. Eosinophilic esophagitis (EoE) may predispose to herpes simplex virus superinfection through epithelial barrier disruption. We present an immunocompetent woman with previous EoE managed with dietary modifications without pharmacologic therapy who developed severe odynophagia. Endoscopy showed erosive esophagitis mimicking candidiasis and active EoE, histologically consistent with HSE without eosinophilic inflammation or fungal organisms. Empiric antifungals and corticosteroids were discontinued, and intravenous acyclovir was initiated with rapid improvement. Follow-up endoscopy confirmed complete mucosal healing. This case highlights the diagnostic complexity of HSE complicating EoE and the indispensable role of histopathologic evaluation.

Sexually transmitted viral infections disproportionately affect women and have adverse outcomes on maternal and fetal health. Since they are acquired through the vaginal tract, the vaginal epithelium is an important site to study host-viral interactions. An in vitro model of mouse vaginal epithelial organoids that can be infected by herpes simplex virus was recently established. Here, we used multiple vaginal organoid systems and studied their response to infection by herpes simplex virus type 2 (HSV-2) and Zika virus (ZIKV), both of which can be sexually transmitted and result in adverse effects on maternal and fetal health. We showed that mouse vaginal organoids support the replication of HSV-2 and ZIKV and respond to interferon treatment. We also established human vaginal spheroids from VK2/E6E7 cells that contain distinct apical and basal cell layers and are also susceptible to HSV-2 and ZIKV infection. Acyclovir treatment reduced HSV-2 replication in both mouse organoids and VK2 spheroids. However, ZIKV was restricted by remdesivir in VK2 spheroids but not in mouse organoids, indicating differences in antiviral activity depending on the organoid system. Finally, we established apical-out mouse vaginal organoids that were also susceptible to HSV-2 and ZIKV infection. Altogether, our results show that vaginal organoids and spheroids are useful in vitro models to study vaginal viral infections and effects of antiviral drugs.IMPORTANCEThe vaginal epithelium is the site of acquisition of sexually transmitted viral infections in women but has been historically understudied. 3D vaginal organoids that model the vaginal epithelium can be used to study virus-host interactions and provide novel insights. We demonstrated that vaginal organoids derived from mouse tissues could be infected with herpes simplex virus type 2 (HSV-2) and Zika virus (ZIKV), and these organoids are also capable of expressing immune genes. We then generated "flipped" mouse organoids that better represent the natural orientation of the vaginal epithelial lining. We also developed spheroids from human vaginal epithelial cells and showed that they can also be infected with HSV-2 and ZIKV. Finally, we showed that antiviral drugs reduced viral infection in these vaginal organoid and spheroid models. Our findings show that vaginal organoids and spheroids possess characteristics that make them useful models to study viral infections, as well as to test antiviral drugs.

We report an infant with HSV-1 encephalitis presenting with multifocal extra-temporal hemorrhagic lesions and complete temporal lobe sparing on neuroimaging. This case highlights the importance of considering herpes simplex encephalitis and initiating empirical acyclovir therapy even in the absence of the characteristic temporal pattern.

Herpes simplex virus type 1 (HSV-1) is highly prevalent, but emerging drug-resistant strains against nucleoside analogs like acyclovir demand novel therapeutics. This study employed an in silico drug repurposing approach to screen 41 beta-blockers as potential non-nucleoside inhibitors targeting HSV-1 thymidine kinase (TK). Molecular docking, 100 ns molecular dynamics (MD) simulations, MM/GBSA binding free energy calculations, per-residue energy decomposition, and ADMET analysis were performed. Docking results revealed several beta-blockers surpassed acyclovir (-5.20 kcal/mol) in binding energy, with bopindolol emerging as the top candidate (-9.32 kcal/mol). Interaction analysis showed bopindolol forms stable hydrogen bonds with Gln125, Arg163, and Arg222, alongside stabilizing hydrophobic interactions. MD simulations confirmed the structural stability of the bopindolol-HSV-1 TK complex, evidenced by stable RMSD, low residue fluctuations, persistent hydrogen bonding, and consistent protein compactness. MM/GBSA calculations yielded a favourable delta G binding of -53.08 ± 3.57 kcal/mol. Energy decomposition indicated binding is driven by van der Waals and electrostatic interactions, with key contributions from Arg222, Tyr172, Met128, and Gln125. Furthermore, ADMET analysis demonstrated favourable pharmacokinetic properties for bopindolol. Overall, bopindolol represents a promising non-nucleoside inhibitor scaffold targeting HSV-1 TK, warranting further experimental validation.