Herpes Simplex DNA in Tears of Atypical Dendritic Keratitis and Multiple Punctate Subepithelial Stromal Opacity: A Case Report.

PURPOSE: To report an atypical presentation of herpes simplex virus (HSV) keratitis followed up using expression levels of HSV DNA in tears. METHODS: A 22-year-old Japanese woman with hyperemia and foreign body sensation in her left eye was diagnosed with atypical dendritic keratitis. A slit-lamp examination at presentation indicated the presence of a rush of dendritic lesions with a sparse branching pattern and poor development of terminal bulbs; follicular conjunctivitis was also observed. Positivity for house-dust-mite- and cedar pollen-specific IgE antibodies in her serum indicated atopic diathesis. The HSV DNA levels in her tears were measured by a real-time polymerase chain reaction. RESULTS: At the initial visit, the HSV DNA levels in tears were 6.4 × 10 copies/sample in the right eye and 1.6 × 10 copies/sample in the left eye. The keratitis improved after treatment with topical acyclovir ointment, 5 times a day for 7 days, and systemic valacyclovir 1000 mg/d for 5 days. Multiple punctate subepithelial opacities developed in her left eye on day 7, with undetectable HSV DNA in tears, bilaterally. CONCLUSIONS: We have successfully monitored the HSV DNA levels in tears using quantitative real-time polymerase chain reaction in HSV keratitis where the corneal findings progressed from atypical dendritic keratitis to multiple punctate corneal subepithelial opacities during the treatment period.

Detection of herpes simplex-1 and -2 and varicella zoster virus by quantitative real-time polymerase chain reaction in corneas from patients with bacterial keratitis.

OBJECTIVE:: Bacterial keratitis occurs worldwide, and despite recent developments, it remains a potentially blinding condition. This study assesses the presence of herpes simplex virus (HSV-1 and -2) and varicella zoster virus (VZV) by quantitative real-time polymerase chain reaction (qPCR) in corneal scrapings from patients with bacterial keratitis. METHODS:: A total of 65 patients with clinical diagnoses of infectious corneal ulcers prospectively underwent clinical eye examinations. Corneal scrapings were investigated by Gram staining, Giemsa staining, culture, and qPCR (the study group). Risk factors and epidemiological data were recorded. The control group comprising 25 eyes with typical herpes dendritic keratitis was also analyzed by qPCR. RESULTS:: From the study group (n=65), nine patients (13.8%) had negative smears, cultures, and qPCR findings. Fifty-six (86.2%) patients had positive cultures: 51 for bacteria, 4 for fungi, and 1 for amoebae. Of the patients who had positive bacterial cultures, qPCR identified 10 patients who were also positive for virus: one for VZV and nine for HSV-1. Of the 25 patients in the control group, 21 tested positive for HSV-1 by qPCR analysis. CONCLUSIONS:: Herpes may be present in patients with bacterial corneal ulcers, and qPCR may be useful in its detection.

Detection of herpes simplex-1 and -2 and varicella zoster virus by quantitative real-time polymerase chain reaction in corneas from patients with bacterial keratitis / Detecção de vírus herpes simplex tipo 1 e 2 e varicella zoster por reação em cadeia de polimerase em tempo real em córneas de pacientes com ceratites bacterianas

ABSTRACT Objective: Bacterial keratitis occurs worldwide, and despite recent developments, it remains a potentially blinding condition. This study assesses the presence of herpes simplex virus (HSV-1 and -2) and varicella zoster virus (VZV) by quantitative real-time polymerase chain reaction (qPCR) in corneal scrapings from patients with bacterial keratitis. Methods: A total of 65 patients with clinical diagnoses of infectious corneal ulcers prospectively underwent clinical eye examinations. Corneal scrapings were investigated by Gram staining, Giemsa staining, culture, and qPCR (the study group). Risk factors and epidemiological data were recorded. The control group comprising 25 eyes with typical herpes dendritic keratitis was also analyzed by qPCR. Results: From the study group (n=65), nine patients (13.8%) had negative smears, cultures, and qPCR findings. Fifty-six (86.2%) patients had positive cultures: 51 for bacteria, 4 for fungi, and 1 for amoebae. Of the patients who had positive bacterial cultures, qPCR identified 10 patients who were also positive for virus: one for VZV and nine for HSV-1. Of the 25 patients in the control group, 21 tested positive for HSV-1 by qPCR analysis. Conclusions: Herpes may be present in patients with bacterial corneal ulcers, and qPCR may be useful in its detection.

RESUMO Objetivo: Ceratites bacterianas ocorrem mundialmente e apesar dos novos desenvolvimentos permanece como uma condição que pode levar à cegueira. Avaliar a presença de herpes simples (-1 e -2) e vírus varicella zoster (VZV) por reação em cadeia quantitativa de polimerase em tempo real (qPCR) em raspados corneanos de pacientes com ceratite bacteriana. Métodos: Sessenta e cinco pacientes com ceratite infecciosa foram submetidos a raspados corneanos estudados para gram, Giemsa, cultura e qPCR (grupo de estudo). Foram avaliados fatores de risco e epidemiológicos. O grupo controle foi composto por 25 casos de úlcera dendrítica típica por herpes analisados por qPCR. Resultados: Do grupo de estudo (n=65), nove pacientes (13,8%) apresentaram cultura, qPCR e raspado negativos. Cinquenta e seis (86,2%) pacientes apresentaram cultura positiva, 51 para bacteria, 4 para fungo e 1 para ameba. A qPCR identificou 10 pacientes do grupo de cultura positiva para bactéria que também foram positivos para vírus, um VZV e 9 para HSV-1. Dos 25 pacientes que compunham o grupo controle, 21 apresentaram qPCR positivo para HSV-1. Conclusão: Herpes pode estar presente em pacientes com úlceras de córnea bacterianas e a qPCR pode ser útil na sua detecção.

Herpes Simplex Virus Disease of the Anterior Segment in Children.

PURPOSE: To analyze the clinical presentation, characteristics, treatment, recurrences, and final outcomes and complications of herpes simplex virus (HSV) disease of the anterior segment in patients aged 17 years or younger. METHODS: This is an observational and retrospective study with review of the medical records of all the children diagnosed with herpes simplex infection of the anterior segment at an ophthalmologic referral center, from 2002 to 2012. The diagnosis was made on the basis of the history and examination of patients and in specific cases by viral culture and the polymerase chain reaction. Main outcome measurements included final visual acuity, bilateral disease, and recurrence. Recurrent disease was analyzed with Kaplan-Meier curves. RESULTS: A total of 103 patients were included with a median age at presentation of 9 years. Of them, 6 had bilateral and simultaneous disease. The median follow-up time was 18 months (range, 18 days-12 years). The most common clinical manifestations were epithelial dendritic keratitis in 42 eyes (38.5%) and interstitial keratitis in 39 eyes (35.7%), with 15 patients presenting multiple forms of HSV disease. The median final visual acuity in the group of patients was 20/40. Recurrent disease was evident in 42 (38.5%) of the eyes, with a median recurrence time of 15 months (95% confidence interval, 8.1-26.2 months). CONCLUSIONS: In this study, epithelial dendritic and interstitial keratitis were the most frequent forms of disease in the pediatric population with HSV of the anterior segment. A high rate of recurrent disease was present.

Treatment of pseudodendrites in herpes zoster ophthalmicus with topical ganciclovir 0.15% gel.

PURPOSE: There is no standard of treatment for epithelial pseudodendrites in herpes zoster ophthalmicus (HZO). The purpose of this study is to report the topical antiviral drug, 0.15% ganciclovir for treatment of these lesions. METHODS: This is a retrospective, interventional case series of 4 patients who were diagnosed with HZO epithelial pseudodendrites despite being given oral antiviral treatment and who underwent 0.15% ganciclovir gel topical treatment. Main outcome measures included epithelial healing time, visual acuity, and corneal sensation. RESULTS: All 4 patients were immunocompetent and had epithelial lesions unresponsive to antiviral treatment with oral valacyclovir. Treatment with topical 0.15% ganciclovir gel 5 times a day resulted in the lesions healing successfully within 7 days with improved visual acuity in 3 patients and an increase in corneal sensation in 2 of the 4 patients. CONCLUSIONS: Topical 0.15% ganciclovir gel, 5 times a day until pseudodendritic lesion healing and tapering to bid for 2 to 4 weeks thereafter, is an effective treatment for pseudodendrites in HZO-affected cases that are often a challenge to manage with other oral or topical antivirals.

Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers).

Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%. A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days. Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.

Late varicella-zoster virus dendriform keratitis in patients with histories of herpes zoster ophthalmicus.

PURPOSE: To describe the characteristics and course of late varicella-zoster virus (VZV) dendriform keratitis in patients with histories of herpes zoster ophthalmicus (HZO); to describe responses of corneal lesions to antiviral treatment; and to investigate risk factors for recurrence. DESIGN: Retrospective case series. METHODS: Included were patients known to have 1 or more episodes of dendriform lesions beginning at least 2 weeks after HZO in 2 academic practices. Epithelial lesions were evaluated for the presence of VZV DNA by a polymerase chain reaction assay. Demographic, medical, and ophthalmic data were collected for each episode. Responses to treatment with antiviral medications were evaluated. Cumulative risk of recurrence was determined using Kaplan-Meier analysis; potential risk factors for recurrence (age, systemic disease, lesion characteristics, corticosteroids) were evaluated using univariate Cox proportional hazard models. RESULTS: We identified 20 patients (14 women; median age, 65 years) who met inclusion criteria. Dendriform lesions were pleomorphic with thickened, opaque epithelium. Seven patients had systemic diseases characterized by altered immune function. VZV DNA was identified in 15 of 16 cases tested, and all lesions responded to antiviral therapy. The 1-year incidence of first recurrence was 95.8 lesions per 100 person-years of follow-up. Patients had multiple recurrences, but risk of recurrence appeared to decrease over time. No statistically significant risk factors for recurrence were identified. CONCLUSIONS: Late dendriform lesions associated with HZO are foci of productive VZV infection. Lesions can be treated effectively with topical or systemic antiviral agents. Patients can have multiple recurrences of dendriform lesions despite treatment.

Case of bilateral multiple herpetic epithelial keratitis manifested as dendriform epithelial edema during primary Kaposi's varicelliform eruption.

BACKGROUND: Bilateral herpetic keratitis has been reported in patients with atopy, measles, graft-versus-host disease, and altered immune status. We report a serologically verified case of primary, simultaneous onset, bilateral, atypical epithelial herpetic keratitis that manifested as dendriform epithelial edema during a generalized dermatitis incident. CASE: A 37-year-old man with chronic atopic dermatitis developed Kaposi's varicelliform eruption and bilateral dendritic epithelial keratitis with corneal epithelial edema. OBSERVATIONS: The pathogens isolated from both eyes were identified as herpes simplex virus type 1 (HSV-1) by a direct immunofluorescence method. Serological tests obtained on three different occasions over a 5-week period verified a primary HSV infection. CONCLUSIONS: With serological verification, we report a rare case of primary, simultaneous onset, bilateral, dendritic epithelial keratitis at a very early stage with complications of generalized herpetic disease in a patient with atopic dermatitis.

Macrophages are important determinants of acute ocular HSV-1 infection in immunized mice.

PURPOSE: To determine the effect of macrophage depletion on herpes simplex virus type (HAV)-1 replication in the eye and on the establishment of latency in trigeminal ganglia (TG) of immunized and ocularly infected mice. METHODS: BALB/c mice were immunized with five HSV-1 glycoprotein DNA genes or were sham immunized. The virulent HSV-1 strain KOS was used as a positive vaccine control. Immunized mice were depleted of their macrophages by dichloromethylene diphosphonate (Cl(2)MDP) injection. After ocular infection with the HSV-1 strain McKrae, virus replication in the eye, blepharitis, corneal scarring, and dermatitis were determined. Finally, the copy numbers of latency-associated transcript (LAT) and CD4(+) and CD8(+) T-cell transcripts in the TGs of surviving mice 30 days after infection were determined by RT-PCR. RESULTS: Depletion of macrophages in immunized mice increased HSV-1 replication in the eye of infected mice between days 1 and 5 after ocular infection. Depletion of macrophages did not alter the HSV-1-induced death or corneal scarring in immunized mice. Macrophage depletion, however, resulted in increased blepharitis in immunized mice. Finally, macrophage depletion had no effect on the establishment of latency in immunized mice, as the TGs from both depleted and mock-depleted mice were negative for the presence of the LAT transcript. CONCLUSIONS: In immunized mice during primary HSV-1 ocular infection, macrophages play an important role in vaccine efficacy against HSV-1 replication in the eye and blepharitis in infected mice. During the latent stage of HSV-1 infection, however, macrophage depletion failed to have any observable effect on HSV-1 latency in the TGs of infected mice.

Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation.

PURPOSE: To report a case of acyclovir-resistant herpes simplex virus (HSV) keratitis after long-term, inconsistent use of topical acyclovir and fluorometholone. METHODS: A 70-year-old man with dendritic keratitis caused by an acyclovir-resistant HSV strain was examined. The 50% inhibitory concentration of different antiviral agents against the isolated virus and the DNA sequence of viral thymidine kinase were determined. RESULTS: The 50% inhibitory concentration of acyclovir and trifluorothymidine for the isolated HSV strain was 13.75 and 0.28 microg/mL, respectively, indicating that the virus was resistant to acyclovir. DNA sequencing of the viral thymidine kinase revealed that this virus had a frameshift mutant with a G insertion in the 7Gs homopolymer. Topical trifluorothymidine was effective, and the epithelial lesion was completely resolved within 2 weeks. CONCLUSION: A typical form of dendritic keratitis was caused by an acyclovir-resistant HSV with frameshift mutation in a 7Gs homopolymer region.

"Steel wool keratopathy": a clinical sign of chronic inflammation.

PURPOSE: To introduce into the clinical nomenclature a sign frequently observed in our patients with persistent corneal inflammation associated with herpetic stromal keratitis. METHODS: Case reports and review of the literature. RESULTS: Four representative patients with herpesvirus stromal keratitis are presented. Herpes simplex virus-1 (HSV-1) was confirmed by culture in 1 case and by polymerase chain reaction in a second case. In the remaining 2 cases, the diagnosis was made based on characteristic clinical findings for herpes simplex virus and varicella zoster virus (VZV). On clinical examination, all 4 representative cases of stromal keratitis revealed a well-defined, localized region of intertwined, metallic-like, polychromatic material in the corneal stroma, a sign we have termed steel wool keratopathy. We have only rarely observed this finding in patients with stromal keratitis not caused by a herpesvirus. CONCLUSION: Steel wool keratopathy seems to represent a focal region of stromal degeneration or deposition associated with chronic inflammation. Although we most often observe this finding in patients with stromal keratitis secondary to HSV or VZV, we cannot exclude the possibility that this sign represents the sequelae of chronic/recurrent inflammation rather than a specific pathologic response to herpetic antigens.

Effect of oral valaciclovir on herpetic keratitis.

PURPOSE: To examine the efficacy of valaciclovir (VACV) oral formulation as an alternative to topical treatments in a case of herpetic keratitis. METHODS: The patient was a 61-year-old man who presented with dendritic keratitis in his left eye. After recognizing his difficulty in using eye ointment, we prescribed oral VACV 500 mg tablets twice daily for 7 days. We also describe our experiments with orally administered VACV in a mouse model of this disease. In this study, 143 Balb/c mice were inoculated with herpes simplex virus type 1 (HSV)-1 in each eye and treated with oral VACV 50 or 100 mg/kg twice daily, oral acyclovir (ACV) 50 mg/kg 5 times/d, 3% ACV eye ointment (ACV-O) 5 times/d, 3% ACV eye drops 5 times/d, or control for 5 days. RESULTS: After 7 days, the patient's lesion was observed healed. Corrected left visual acuity was also improved, and HSV DNA was below detectable level. In the mouse study, slit-lamp examination on days 3, 4, 5, and 7 revealed that all 5 ACV and VACV treatment groups were significantly more effective in improving symptoms of herpetic epithelial keratitis versus control (P < 0.05). Moreover, VACV 100 mg/kg was superior to other treatments. Viral titers in mouse eyeball and trigeminal ganglia were lowest in the VACV 100 mg/kg group versus other treatment groups. CONCLUSION: Our case example suggests that when frequent application, blurred vision, and foreign body sensation after ACV-O application cause difficulty for patients to follow treatment, oral VACV might be an effective and safe option for patients with herpetic keratitis.

Chronic recurrent varicella-zoster virus keratitis confirmed by polymerase chain reaction testing.

PURPOSE: To report a case of chronic recurrent varicella virus epithelial keratitis in a child. DESIGN: Case report. METHODS: Clinical examination and polymerase chain reaction analysis of corneal epithelium. RESULTS: A 10-year-old healthy child developed chronic recurrent varicella virus keratitis with pseudodendrites after recovering from systemic varicella. Analysis of the debrided pseudodendrites was repeatedly positive for VZV DNA and negative for HSV DNA. Treatment with oral acyclovir and topical corticosteroid drops was effective in eliminating the pseudodendrites; however, recurrences occurred once the medications were discontinued. CONCLUSIONS: Varicella virus epithelial keratitis in children can be a recurrent chronic condition requiring prolonged treatment.

Improved protection from primary ocular HSV-1 infection and establishment of latency using multigenic DNA vaccines.

PURPOSE: To compare the effectiveness of immunization with "naked" DNA corresponding to the genes encoding five HSV-1 glycoproteins, gB, gC, gD, gE, and gI (5gP DNA), with immunization with the five glycoproteins (5gP protein). Also, to compare immunization of 5gP protein in Montanide ISA 720 (SEPPIC, Paris, France), an adjuvant recently approved for use in humans, with immunization of 5gP protein in Freund's adjuvant. METHODS: BALB/c mice were vaccinated with 5gP DNA or 5gP protein emulsified in ISA 720 or Freund's adjuvant. Neutralizing antibody titers were determined by plaque-reduction assays. IL-2, -4, and -12 and IFN-gamma levels were determined by ELISA after in vitro stimulation of spleen cells. After ocular challenge with 2 x 10(5) plaque-forming units [pfu] per eye of HSV-1 strain McKrae, virus replication in the eye, survival, blepharitis, corneal scarring, and latency were determined. RESULTS: Neutralizing antibody titers (approximately 1:800-1:1200), corneal scarring (trace) and survival (100%) were similar for all vaccine groups, including 5gP DNA. Compared with the other vaccine groups, the 5gP DNA group had less ocular virus replication, as judged both by maximum virus titer and time of viral clearance. ISA 720 appeared more effective than Freund's against ocular virus replication and eye disease. The 5gP DNA-vaccinated mice had less blepharitis and latency than any other group and had the highest levels of IL-12 and IFN-gamma. All vaccine groups had similar levels of IL-2. CONCLUSIONS: The 5gP DNA vaccine appeared to be more effective than the corresponding protein subunit vaccine, regardless of adjuvant. Emulsification of the 5gP protein in ISA 720 appeared to be more effective than emulsification in Freund's adjuvant.

Estudio clínico y virológico en un grupo de niños chilenos con herpes ocular: análisis genómico de las cepas / Clinical-virological study in chilean children with ocular herpes: genomic analysis of strains

Objetivo: Caracterizar el diagnóstico de infección ocular por virus herpes simples (HSV) en un grupo de niños chilenos, mediante el estudio clínico y de laboratorio virológico. Métodos: La población estudiada comprendió niños menores de 15 años, con diagnóstico clínico de herpes ocular, que fueron atendidos por los autores y un grupo de oftalmólogos entrenados especialmente para el estudio. Junto con detallar el tipo de infección herpética, a todos los pacientes se les tomaron muestra para estudio virológico que incluyó estudio de cultivos celulares y posteriormente técnica de reacción en cadena de polimerasa (PCR), con el fin de tipificar las cepas y características genómicas del virus infectante. Resultados: El estudio enroló 18 niños, cuyas edades fluctuaron entre los 40 días y 13 años, con una media de 6 años. De las formas clínicas observadas, la más frecuentes fueron la blefaritis y la queratitis dendrítica constituyendo en 27 y 22 por ciento de los casos, respectivamente. El diagnóstico de HSV fue confirmado en 15 de 18 pacientes, constituyendo un 83 por ciento de positividad. 14 de 15 casos correspondieron a HSV tipo 1, y en un niño se diagnóstico infección por HSV tipo 2. Los antecedentes clínicos de este caso confirmaron que se trataba de una infección perinatal, lo que permitió instaurar el tratamiento en forma oportuna. El estudio permitió identificar un caso de excreción ocular viral asintomática, lo que sumando a un cuadro de recurrencias múltiples obligó a indicar terapia profiláctica permanente con aciclovir. Conclusiones: La blefaritis y queratitis herpética constituyeron en conjunto el 70 por ciento de los casos. El rendimiento celular y PCR fue elevado en los casos con alto índice de replicación viral, como la queratitis y blefaritis. En los casos con menor replicación, como queratitis estromal o conjuntivitis, el estudio PCR demostró una mayor sensibilidad que el estudio en cultivo celular. La presencia de un caso de infección perinatal por HSV-2 pudiera ser indicativo de un aumento en la frecuencia de esta forma de presentación.

Identification of a herpes simplex virus-induced dendrite in an eye-bank donor cornea.

PURPOSE: To demonstrate the presence of an active herpetic dendrite in an eye-bank cornea. CASE REPORT: One eye-bank cornea was studied. Viral cultures and polymerase chain reaction (PCR) testing were performed 4 days after tissue preservation. The presence or absence of herpes simplex virus (HSV) type 1 was investigated. RESULTS: The presence of an active HSV dendrite in an eye-bank cornea was verified. HSV type 1 was confirmed using PCR amplification and restriction endonuclease DNA fragment analysis. CONCLUSION: This case suggests that HSV may remain viable in stored corneal tissue at 4 degrees C.

Early epithelial changes in recurrent herpes simplex virus keratitis: a non-contact photomicrographic study in vivo in the human cornea.

PURPOSE: To examine early corneal epithelial changes in recurrent herpes simplex virus (HSV) type 1 keratitis. MATERIAL AND METHODS: Three patients presenting early (< or =18, < or =24 and < or =29 hours) after the onset of symptoms were examined by means of non-contact in vivo photomicrography. RESULTS: Case 1 (< or =18 hours) showed about 60 rounded or irregularly shaped and partly confluent intraepithelial lesions. In case 2 (< or =24 hours) similar lesions and a dendritic figure with a broken pattern were present. Case 3 (< or =29 hours) showed four separate lesions and a large dendrite. Some lesions appeared as dark protrusions in the fluorescein stained tear film, others stained green; of these, some additionally showed fluorescein diffusion into the surroundings. The smallest discernible entities were abnormal cells of about 10 microm in diameter, present both within the lesions and scattered elsewhere, and clearly swollen cells of about 15 microm of diameter. CONCLUSIONS: The distribution of the precursors shows the multifocal origin of HSV dendritic figures. The dark protruding lesions with abnormal cells covered by intact overlying cell layer(s) seem to be the earliest HSV epithelial changes so far captured in the living human cornea. The protrusions are probably the result of cell swelling representing the incipient stage of HSV cytopathic effect, and the subsurface location of the abnormal cells suggests that the initial virus target are the deeper epithelial layers. The morphological features of the remaining lesions are consistent with successive stages of cell degeneration, i.e. cell swelling leading to surface disruptions, burst of the cells, and cell desquamation resulting in surface ulcerations. The contemporaneous presence of all these stages is typical of recurrent HSV type 1 infections.