Atypical herpetic ulcerations in COVID-19 positive patients: A report of three cases.

Since the global COVID-19 pandemic, numerous reports have been made regarding oral lesions seen in COVID-19 patients. It remains unclear whether or not these are true manifestations of COVID-19. Here we present 3 patients who were hospitalized for COVID-19 and who developed atypical herpetic ulcerations during their treatment with remdesivir (Veklury) and steroids. In healthy patients, recurrent infection by herpes simplex virus (HSV) presents as lesions only on the lips and the attached oral mucosa. Atypical herpetic ulcerations are seen in immunocompromised patients. They present as large, stellate shaped ulcerations with raised borders and may involve movable mucosa. The 3 cases presented in this report resembled the atypical herpetic ulcerations typically seen in patients with immunosuppression. Through our report, we aimed to introduce the possibility of atypical herpetic ulcers in patients being treated for COVID-19, to allow for their timely diagnosis and to raise awareness of the underlying immunocompromised state.

Terapias oncoespecíficas en pacientes con virus del herpes simple bucal / Oncospecific therapies in patients with herpes simplex virus

Se efectuó un estudio descriptivo y transversal de 25 pacientes con cáncer infectados por el virus del herpes simple bucal, quienes tenían el sistema inmunológico deteriorado debido al tratamiento oncoespecífico, atendidos en la consulta estomatológica del Policlínico de Especialidades del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba, desde enero de 2014 hasta igual mes de 2016, a fin de evaluar los resultados del diagnóstico clínico y citopatológico de esta afección. En la casuística prevalecieron el sexo masculino, el dolor como sintomatología clínica, el bermellón del labio inferior como el sitio de mayor incidencia y la quimioterapia como la modalidad terapéutica de mayor reactivación de este agente viral. La citología exfoliativa confirmó la presencia de células epiteliales gigantes multinucleadas con cuerpos de inclusiones intranucleares y necrosis de células infectadas, respectivamente, siendo estos los hallazgos microscópicos más significativos

A descriptive and cross-sectional study of 25 patients with cancer infected by the oral herpes simplex virus was carried out. They had the immunologic system damaged due to oncospecific treatment, assisted in the stomatological service of the Specialties Polyclinic of Saturnino Lora Torres Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, from January, 2014 to the same month in 2016, in order to evaluate the results of the clinical and cytopathologic diagnosis of this disorder. In the case material the male sex and pain as clinical symptomatology, the vermilion of the lower lip as the place of more incidence and chemotherapy as the therapeutic modality of this viral agent higher reactivation prevailed. The exfoliative cytology confirmed the presence of multinucleous giant epithelial cells with bodies of intranuclear inclusions and infected cells necrosis, respectively, being these the most significant microscopic findings

Estomatitis herpética y coinfección HIV-1 y P. Jiroveci en una adolescente: informe de un caso / Herpetic stomatitis and HIV-1 and P. Jiroveci co-infection in a female adolescent: report of a case

La infección por el HIV-1 cursa con enfermedades oportunistas asociadas. En referencia a los virus herpes, la asociación más conocida es con el HVS-2. La coinfección HIV-1, HVS-1 y P. jiroveci constituye un cuadro clínico de alta morbilidad y baja frecuencia. Caso clínico: una paciente de 17 años de edad fue derivada a la consulta con sintomatología compatible con gingivoestomatitis herpética recurrente resistente a la terapia con aciclovir p.o. 200 mg cada 5 hs y tratada con amoxicilina-clavulánico p.o. (875 mg-125 mg) cada 12 hs por 20 días. Al ingreso presentaba adenitis cervical, odinofagia, disnea, fiebre (38.2ºC), pulso: 120/min, presión arterial: 120/75 mm Hg, frecuencia respiratoria: 24/min y deterioro generalizado. Se solicitó hacer la serología para el HIV y estudio RX de tórax. La serología para HIV-1 resultó positiva y los valores de CD4+ y carga viral fueron 320/mm3 y 25.000 copias/ml, respetivamente. El estudio RX de tórax reveló neumonía por P. jiroveci que se confirmó posteriormente por fibrobroncoscopía. Se realizó el tratamiento farmacológico de la infección herpética con foscarnet (i.v) 60mg /kg cada 12 hs. durante 3 días, mientras que la neumonía se trató con trimetropima 160 mg y sulfametoxazol p.o. 800 mg cada 6 horas durante 14 días. La remisión de la sintomatología bucal se oservó a los 15 días postratamiento. Conclusión: la población femenina adolescente evidencia una mayor vulnerabilidad biológica y social en relación a la transmisión del HIV. El odontólogo responsable deberá calibrarse en el reconocimiento y diagnóstico precoz de las manifestaciones bucales de dicha infección viral. Ante la presencia de cepas de HVS-1 aresistentes deberá contemplarse la posibilidad de otras infecciones oportunistas simultáneas

Heterogeneity and evolution of thymidine kinase and DNA polymerase mutants of herpes simplex virus type 1: implications for antiviral therapy.

BACKGROUND: Infections caused by acyclovir-resistant isolates of herpes simplex virus (HSV) after hematopoietic stem cell transplantation (HSCT) are an emerging concern. An understanding of the evolutionary aspects of HSV infection is crucial to the design of effective therapeutic and control strategies. METHODS: Eight sequential HSV-1 isolates were recovered from an HSCT patient who suffered from recurrent herpetic gingivostomatitis and was treated alternatively with acyclovir, ganciclovir, and foscavir. The diverse spectra and temporal changes of HSV drug resistance were determined phenotypically (drug-resistance profiling) and genotypically (sequencing of the viral thymidine kinase and DNA polymerase genes). RESULTS: Analysis of 60 clones recovered from the different isolates demonstrated that most of these isolates were heterogeneous mixtures of variants, indicating the simultaneous infection with different drug-resistant viruses. The phenotype/genotype of several clones associated with resistance to acyclovir and/or foscavir were identified. Two novel mutations (E798K and I922T) in the viral DNA polymerase could be linked to drug resistance. CONCLUSIONS: The heterogeneity within the viral populations and the temporal changes of drug-resistant viruses found in this HSCT recipient were remarkable, showing a rapid evolution of HSV-1. Drug-resistance surveillance is highly recommended among immunocompromised patients to manage the clinical syndrome and to avoid the emergence of multidrug-resistant isolates.

The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

[Improvement of treatment of inflammatory diseases in oral cavity].

In order to determine the anti-pathogenic clinical efficacy of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis, medical examination and treatment of these disorders have been carried out in a group of 80 patients. It is established that the use of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis decreases the infectious load in parodontal recess, reduces the manifestations of local inflammation, normalizes the immunity indices, and decreases the level of endogenous intoxication, which ensures the acceleration of recuperation processes and lowers the frequency of recurrences.

Herpetic geometric glossitis in an immunocompetent patient with pneumonia.

Herpetic geometric glossitis is an uncommon, clinically distinctive presentation of oral herpes simplex virus infection that affects the tongue. All published reports have been in patients who are immunocompromised. We present an immunocompetent woman with viral pneumonia who developed painful linear fissures on the back of the tongue suggestive of herpetic geometric glossitis. The diagnosis was confirmed by both biopsy specimen and immunohistochemistry. As in other cases, the patient promptly responded to treatment with antiviral therapy. The morphology, laboratory findings, and similarities to herpetic corneal dendrites are discussed. Herpetic geometric glossitis should no longer be considered as a diagnosis only in immunosuppressed individuals, but in immunocompetent persons as well.

Gengivoestomatite herpética aguda / Acute herpetic gingivostomatitis: report of a case

Gengivoestomatite Herpética Aguda (GEHA) representa uma doença infecto-contagiosa causada pelo vírus herpes simples. Revela relevante freqüência entre as crianças de zero a seis anos de idade, apresentando sintomatologia prodrômica e manifestação clínica autolimitada entre dez a quatorze dias. O conhecimento desta patologia por parte do cirurgião dentista é de fundamental importância, em decorrência do potencial de contaminação, morbidade e baixa no estado geral do paciente, somadas às possíveis complicações, observadas, sobretudo, em pacientes imunocomprometidos ou imunologicamente imaturos.

Acute Herpetic Gingivostomatitis (AHG) is an infect-contagious disease caused by a virus called Herpes simplex. This illness demonstrates important frequency among very young children (varying age from 0 to 6), presenting specific symptoms and auto-limited clinical manifestations during a period of ten to fourteen days. The knowledge of the referred pathology is of fundamental importance to the dentist, even more its contamination levels, morbidity and down general patient health condition plus the possible adversed progression of the AHC in immunocompromised or immunologic immature patients.

[Nosologic descriptions of lesions of the oral mucosa]. / Description nosologique des lésions de la muqueuse orale.

This article describes extensively and systematically oral mucosa diseases. Macroscopical aspects are particularly described in order to give the dentist all important elements of differential diagnosis. This nosological description is based on a clinical approach: white and pigmented lesions are distinguished from ulcerated and benign so as malignant tumoral lesions. Specifically on the oral mucosa located lesions and oral mucosa lesions of systemic diseases are described.

The clinical characteristics of intraoral herpes simplex virus infection in 52 immunocompetent patients.

OBJECTIVE: Intraoral herpes simplex virus infection is commonly mistaken for recurrent aphthous stomatitis. The purpose of this study was to describe the clinical features of intraoral herpes simplex virus infection. STUDY DESIGN: Fifty-two immunocompetent patients with culture-positive intraoral herpes simplex virus infection were studied. RESULTS: The median age of the patients was 42 years. One third of the patients exhibited single ulcers; the remaining patients displayed multiple lesions. In 47 of 52 cases, the ulcers occurred on keratinized surfaces of the oral cavity; however, 5 patients had persistent ulcerations on nonkeratinized mucosa, a typical feature of herpetic ulcers in immunosuppressed patients. Of 27 patients with histories of recurrences, 22 were previously incorrectly diagnosed with recurrent aphthous stomatitis. CONCLUSIONS: Herpes simplex virus infection of the oral cavity can usually be differentiated from other causes of recurrent oral ulcerations on the basis of its clinical appearance and distribution. The recognition of atypical features may prevent unnecessary and costly treatments for unrelated though clinically similar-appearing disorders.

Immunocytochemical detection of autoantibody deposits in Tzanck smears from patients with oral pemphigus.

Eighteen patients, ten affected by pemphigus vulgaris and four affected by herpes simplex of the oral mucosa, together with four healthy patients as controls, were investigated by cytologic examination of Papanicolaou stained smears obtained by scraping the oral mucosa. In all cases additional smears were immunostained with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies against human heavy IgG chains and lambda light chains. The results have shown that, for a cytological diagnosis of pemphigus, this technique can be used as an easy substitute for the immunofluorescence test and does not require any specialized training or equipment. The findings are clearly detectable by light microscopy and allow, together with the immunostaining, an adequate visualization of cell morphology.

Autopsy findings in the tongues of 20 patients with AIDS.

An extensive examination of the tongue was performed at autopsy in 20 consecutive patients who had died with AIDS. Abnormalities in the tongue were detected in 18 (90%) of the cases; the commonest lesions were ulceration (11), candidosis (8) and small foci of hyperkeratosis (10). The most extensive lesions were caused by Aspergillus infection (1), non-Hodgkin's lymphoma juxtaposed with Kaposi's sarcoma (1), herpetic infection (1) and candidosis (5). The disease causing death was identified in the tongue in two cases. There was a surprisingly low prevalence of oral hairy leukoplakia, which may be related to anti-viral or retroviral therapy.

Oral recrudescent herpes simplex virus infection.

OBJECTIVE: The objective of this study is to determine the frequency of involvement of different intraoral sites by oral recrudescent herpes simplex virus in immunocompromised patients and whether keratinized intraoral sites are always affected by this virus. STUDY DESIGN: The records of 30 hospitalized patients who had oral ulcers culture positive for herpes simplex virus were reviewed for the location of oral ulcers, febrile episodes, and medical diagnoses. RESULTS: The data revealed that oral recrudescent herpes simplex virus may involve any intraoral site in immunocompromised patients with nonkeratinized sites representing approximately half of all sites; this is more frequent than has been previously reported. Twenty-six (86.7%) of 30 patients had no evidence of herpes labialis, and 13 (43.3%) of 30 patients were afebrile. CONCLUSION: It is recommended that all oral ulcers, in immunocompromised patients should be cultured for herpes simplex virus regardless of their location. Early diagnosis reduces patient morbidity because effective treatment in the form of acyclovir is readily available.

Small, freshly arrived histiocytes in cutaneous and mucosal herpetic lesions.

We report on the predominance of a special type of small histiocyte in the inflammatory infiltrate accompanying herpetic bullae. These histiocytes, which have previously been taken to be neutrophils, are freshly arrived cells with a hitherto unknown function. Until now, they have been found only in Sweet's syndrome and erythema nodosum where they form Miesscher's radial granulomas. Similar small histiocytes were found in half of those herpetic lesions with intact bullae, and in over two-thirds of ulcerated lesions in which these cells formed a palisade in the fibrinoid material covering the floor of the ulcerated vesicles. Small histiocytes, admixed with neutrophils, were in close proximity to virally infected keratinocytes. Immunohistochemical analysis confirmed their histiocytic nature. With the exception of ecthyma contagiosum (orf), similar small histiocytes were not found in other viral infections or in nonspecific ulcers of the skin. In cases of herpetic folliculitis, small histiocytes showed massive epidermotropism towards hair follicle epithelium. We conclude that cutaneous and oral herpetic infections represent yet another disease in which small, freshly arrived histiocytes occur. They may be involved in antigen presentation, or in killing of infected keratinocytes.

Oral manifestations of infectious diseases.

The oral manifestations of infectious diseases is a major topic since the prevalence rate has increased, and usually poses diagnostic and therapeutic dilemmas to the oral clinician. The clinical features of the most common and important oral infectious diseases are discussed.

Herpesviridae-associated persistent mucocutaneous ulcers in acquired immunodeficiency syndrome. A clinicopathologic study.

Persistent mucocutaneous ulcers in AIDS represent a variety of disease entities. The purpose of this study was to characterize clinicopathologic features of persistent oral ulcers associated with cytomegalovirus and herpes simplex virus in AIDS. Forty-seven persons infected with HIV with persistent ulcers (mean, 2.4 ulcers/person) were included in this study. A biopsy specimen from a representative ulcer was taken from each patient. Hematoxylin-eosin, periodic acid-Schiff, cytomegalovirus, and herpes simplex virus immunocytochemical stains were performed on tissue sections. The most common sites of involvement were the buccal/labial mucosa (27%), tongue (25%), and gingiva (18%). Mean ulcer size was 1.8 cm with a mean duration of 5.6 weeks. The ulcerogenic viral agents were cytomegalovirus alone in 53% of cases, cytomegalovirus and herpes simplex virus coinfection in 28% of cases, and herpes simplex virus alone in 19% of cases. Treatment response to ganciclovir with or without topical steroids resulted in lesion resolution in the cytomegalovirus and cytomegalovirus/herpes simplex virus groups; however, recurrence/resistance was relatively high (23%). Herpes simplex virus/cytomegalovirus ulcers responded to oral acyclovir in combination with systemic ganciclovir. Increasing the oral acyclovir dosage resulted in resolution of herpes simplex virus-only ulcers in all but one case. Cytomegalovirus and herpes simplex virus are associated with persistent mucocutaneous ulcers in AIDS. These lesions responded to systemic antiviral therapy but are difficult to differentiate from other ulcerogenic diseases such as aphthous major, necrotizing stomatitis, and ulcerations not otherwise specified without biopsy and histopathologic examination.

Herpes simplex and cytomegalovirus coinfected oral ulcers in HIV-positive patients.

Four HIV-positive patients with herpes simplex virus and cytomegalovirus coinfected oral ulcers are presented. All patients had persistent oral pain associated with nonhealing mucosal ulcers. Lesions occurred on the palate, retromolar pad, tongue, and lip, and the clinical appearance of the ulcers was nonspecific. Histologic and immunohistochemical stains showed herpes simples virus alterations in keratinocyte nuclei and cytomegalovirus alterations in mesenchymal/endothelial cell nuclei and cytoplasm. Lesions in one patient responded to ganciclovir therapy. One patient improved with acyclovir, and another healed normally after excisional biopsy. Each virus alone has been described as causing oral ulcerations; their appearance together in the same lesion would suggest a synergistic relationship.

Alteraçöes dos tecidos moles da boca. Parte 1: doenças vesicobolhosas, condiçöes ulcerativas e lesöes verrucosas papilares / Alterations of bucal soft tissues. Part 1: vesicobullous diseases, ulcerative conditions and verrucous papilars lesions

Os autores iniciam o desenvolvimento do tema alteraçoes de tecidos moles da boca, esclarecendo à classe médica sobre as principais doenças vesicobolhosas, condiçoes ulcerativas e lesoes verrucosas papilares.