Supportive care and antiviral treatments in primary herpetic gingivostomatitis: a systematic review.

OBJECTIVES: Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic gingivostomatitis (PHGS), often a self-limiting infection; however, it can limit the ability to drink/eat with, sometimes, the need for hospitalization. Multiple therapeutic methods have been proposed. This systematic review aims to collect and critically appraise the available evidence about the clinical management of PHGS. MATERIALS AND METHODS: Literature search including three databases (PubMed, Scopus, Embase), study design, and data analysis were performed following PRISMA guidelines, according to the PICO tool (PROSPERO n° CRD42023391386). Risk of bias was assessed with RoB 2 and ROBINS-I. RESULTS: Five studies on a total of 364 patients (average age: 7.6 years) were identified. The treatment regimens were summarized in acyclovir; acyclovir + honey; fluids and analgesic; maalox + diphenhydramine; lidocaine; chlorhexidine (CHX); CHX + ialuronic acid; CHX + Mucosyte®; antimicrobial photodynamic therapy (aPDT); topical antiviral; topical antiviral + aPDT; and others. CONCLUSIONS: Although PHGS is a disease with a high worldwide prevalence, the lack of consensus about therapeutic management indicates gaps in existing evidence. Most of the proposed treatment consists in symptomatic drugs with empiric regimens which are ineffective for the viral replication. The main limit to realize randomized clinical trial is due to the rapid onset and remission of the disease. In fact, the diagnostic delay, estimated in 72 h, decreases the effectiveness of any antiviral drugs. CLINICAL RELEVANCE: Out of the five studies included in this systematic review, only one was able to provide some weak evidence that ACV is an effective treatment, improving healing of oral lesions and reducing duration of symptoms.

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.

Severe pediatric oral mucositis.

We initially suspected primary herpetic gingivostomatitis. But the patient's lab work, persistent fever, and cough led us in a different direction.

Efficacy of antimicrobial photodynamic therapy versus antiviral therapy in the treatment of herpetic gingivostomatitis among children: Aa randomized controlled clinical trial.

AIM: The aim of the present study was to evaluate the effect of antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to topical antiviral therapy for the treatment of children having herpetic gingivostomatitis. MATERIALS AND METHODS: 45 individuals (age group 12-18 years) with herpetic gingivostomatitis (HG) were divided into three groups on the basis of provision of treatment. (a) Group A: topical anti-viral therapy (TAT) (n = 14, mean age = 17.0 years) (b) Group B: antimicrobial photodynamic therapy (aPDT) (n = 15, mean age =17.7 years) and (c) Group C: topical anti-viral therapy + adjunctive aPDT (n = 16, mean age = 18.0 years) respectively. Pain scores [visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ)] were assessed and HSV-1 was quantified. ENZYME LINKED IMMUNOSORBENT ASSAY (ELISA) was used to compute the pro-inflammatory cytokine including interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The analysis of the mean values and inter group comparisons were evaluated with the Mann-Whitney test. The Friedman test was used to establish the comparison of the changes observed in HSV quantification, pain scores, and pro-inflammatory cytokines. ANOVA tests were employed for the quantification of differences observed at follow-ups. The assessments for the clinical trial were done at baseline, immediate after post-op, two, and four weeks, and three and six months respectively. RESULTS: According to the analysis of the data obtained after the clinical assessment, the three groups reported a decrease in the pain scores, HSV-1 quantification and levels of the pro-inflammatory cytokines. However, Group C (TAT + aPDT) reported improvement in the observed parameters which was statistically significant in comparison to Group A (TAT) and Group B (aPDT) respectively. CONCLUSION: Antimicrobial photodynamic therapy (aPDT) in conjunction with topical antiviral therapy (TAT) helped in reducing the pain scores and pro-inflammatory cytokine levels in herpetic gingivostomatitis among children.

ACUTE HERPETIC STOMATITIS: CLINICAL MANIFESTATIONS, DIAGNOSTICS AND TREATMENT STRATEGIES.

OBJECTIVE: The aim: To evaluate the recent scientific articles concerning peculiarities of this oral pathology. The goal is to carry out a literature review by evaluating all signs and clinical symptoms related to this disease, so as to provide the clinician with a useful tool for an early diagnosis and treatment of the disease. PATIENTS AND METHODS: Materials and methods: The collection of relevant data were done using the scientific databases Pubmed, Google Scholar. A manual search on Dentistry and Pharmacological sources was also conducted for relevant studies published. The selected key words: ("Herpes virus" OR "HSV") AND ("oral" OR "oral lesions") were used for collecting the data. CONCLUSION: Conclusions: The article presents clinical peculiarities of herpetic stomatitis depending on disease severity and course. Primary herpetic stomatitis appears as spherical clustered vesicles on the gingival and adjacent mucosa. Soon after eruption of elements of lesion they rupture forming painful halo like aphtae / ulcers. Typical symptoms are: pain from ruptured vesicles, lymphadenitis, fever etc. Early diagnosis of disease is important and treatment with antiviral medicaments can modify the course of the disease by reducing symptoms and potentially reducing recurrences. Management of acute herpetic stomatitis include antiviral medicaments intake, maintenance of fluids and electrolytes level in a body. The treatment principles based on etiotropic, pathogenetic and symptomatic therapy are considered in manuscript.

Adolescents and primary herpetic gingivostomatitis: an Italian overview.

AIM: The aim of this study was to investigate the therapies administered to Italian adolescents with primary herpetic gingivostomatitis (PHGS) METHODS: The medical records of 74 adolescents with PHSG were reviewed. The following data were recorded: age, gender, day of onset, type of treatment, lesions' severity, pain scoring, eating, and drinking ability. The oral examination was performed at the first evaluation (T0) and after one week (T1). RESULTS: All patients showed up at the first visit at least 48 h after the onset of symptoms. No patient was prescribed an antiviral therapy. An antibiotic therapy was prescribed in order to prevent secondary bacterial infections. Fifteen patients had been treated with non alcoholic chlorhexidine rinses (group A), 29 patients with non alcoholic chlorhexidine rinses plus hyaluronic acid gel (group B); 30 patients with non alcoholic chlorhexidine rinses plus Mucosyte® (group C). A significant improvement of the pain scoring and lesions' severity was noted in group C. CONCLUSION: In Italian adolescents, PHGS is diagnosed at least 48 h after onset and the antibiotic therapy is widely prescribed in order to prevent overinfections. Among topical therapies, an association of verbascoside and sodium hyaluronhate seems to favour a faster healing.

Prevalence and Likelihood Ratio of Six Objective Signs among Good Responders to Natrum muriaticum: Multi-centre Observational Assessment.

BACKGROUND: The reliability of homeopathic prescriptions may increase through resource to objective signs and guiding symptoms with significant positive likelihood ratio (LR). We estimated LR for six objective signs attributed to the homeopathic medicine Natrum muriaticum (Nat-m). METHODS: In this multi-centre observational assessment, we investigated the prevalence of six signs in the general patient population and among good responders to Nat-m in daily homeopathic practice. Next, we calculated LR for these six signs. RESULTS: Data from 36 good responders to Nat-m and 836 general population patients were compared. We found statistically significant positive LR (95% confidence interval) for signs such as lip cracks (1.94; 1.15 to 3.24), recurrent herpes (2.29; 1.20 to 4.37), hairline eruptions (2.07; 1.03 to 4.18), and dry hands (2.13; 1.23 to 3.69). CONCLUSIONS: Objective signs with significant positive LR might increase the reliability of homeopathic prescriptions. Further studies are warranted to confirm the validity of this approach.

[STUDY OF ANTIVIRAL AND IMMUNECORRECTIVE EFFECTS OF LAZOLEX IN PATIENTS WITH RECURRENT HERPETIC STOMATITIS].

At present, our country continues intensive research to find and introduce into practice new natural medicinal preparations made from ecologically clean endemic plants of Georgia. An example of such studies in the Iveria-Pharma company is the domestic drug Lazolex (extract of the pericarpium of an unripe walnut), which has passed the necessary preclinical tests and began to be used in the clinic as an antiherpetic agent. On healthy volunteers, we found positive immunotropic effects of Lazolex. Therefore, we considered it necessary to study the antiviral effect of the drug and its immunomodulatory properties in a clinical setting, specifically in chronic herpetic stomatitis. First of all, it was shown that the state of the patients' immune system was in a clear correlation with the severity of the herpes process, i.e. the most severe immunosuppression was recorded in patients with severe stomatitis. The double effect of the drug is to significantly increase the results of antiviral treatment and immunorehabilitation of patients. As a result of a parallel study of Zovirax and Lazolex, a high clinical activity of both drugs was recorded. However, the presence of pronounced immuno-corrective properties in Lazolex manifested itself in an improvement in the quality of patient treatment: active tissue regeneration and a significant decrease in the timing of exacerbation of local herpetic lesions, an increase in the duration of remission. Conducted clinical, laboratory and immunological studies allow us to recommend Lazolex for active use in dental practice for viral diseases.

Clinical features of gingivostomatitis due to primary infection of herpes simplex virus in children.

BACKGROUND: Primary herpetic gingivostomatitis (PHGS) in children, though usually self-limited, might mimic bacterial and enteroviral pharyngitis clinically. We conducted a study to define the clinical features of PHGS in children. METHODS: Between January 2012 and December 2016, 282 inpatients aged less than 19 years with cell culture-confirmed herpes simplex virus (HSV) infection in a medical center were identified from the virologic laboratory logbook. Clinical data were retrospectively collected. RESULTS: Among the 282 inpatients, 185 cases were considered as PHGS and were included for analysis. Fever was present in 99.5%. The mean duration of fever was 5.11 days (±2.24) with the longest being 17 days. Common oral manifestations included oral ulcers (84.3%), which equally resided in the anterior and posterior part of the oral cavity (65.4% vs. 63.2%), gum swelling and/or bleeding (67.6%), and exudate coated tonsils (16.8%). Leukocytosis (WBC count > 15,000/uL3) was noted in 52 patients (28.1%) and a serum C-reactive protein level > 40 mg/L in 55 patients (29.7%). Fixty-five patients (35%) were diagnosed with PHGS on admission and were significantly more likely to have ulcers over the anterior oral cavity (76.1% vs. 26.7%) and gum swelling/bleeding (76.2% vs. 7.5%, p-value all < 0.001) on admission and were significantly less likely to receive antibiotic treatment (16.9 vs. 36.7%, p-value < 0.01) than others. Forty-six patients (25%) undiagnosed as PHGS on discharge were significantly more likely to have exudate coated on the tonsils, to receive antibiotic treatment and significantly less likely to have gum swelling/bleeding and oral ulcers (all p-values < 0.01). CONCLUSIONS: Meticulously identifying specific oral manifestations of gum swelling/bleeding and ulcers over the anterior oral cavity in children can help making the diagnosis of PHGS earlier and subsequently reduce unnecessary prescription of antibiotics.

[Complex treatment of recurrent herpetic stomatitis with dysbiosis]. / Analiz kompleksnoi metodiki lecheniia retsidiviruiushchego gerpeticheskogo stomatita s disbakteriozom.

Research objective was to study the effectiveness of complex treatment of recurrent herpetic stomatitis with dysbiosis. The study included 147 patients aged from 18 to 45 years with recurrent herpetic stomatitis (RGS) and disbyosis divided in 3 groups. Group 1 received conventional antiviral and symptomatic treatment of RGS, in group 2 complex immunoglobulins (IgA (15-25%), IgM (15-25%) and Ig (50-70%)) were added to conventional therapy, group 3 received immunoglobulins only. Clinical and immunological efficiency was estimated by values of oral local immunity (SlgA, lysozyme), humoral immunity (IgE and IgG) and cellular immunity (RBTL with FGA, defined T-lymphocytes). Significant (p<0.05) increase of lisozyme and SlgA, RBTL with FGA, number of T-lymphocytes and IgG concentration was observed in group 2. The obtained data allow improving quality of treatment of recurrent herpetic stomatitis with related dysbiosis.

The alpha-herpesviridae in dermatology : Herpes simplex virus types I and II.

This review on herpes simplex virus type I and type II (HSV­I, HSV­II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV­I infection; HSV-related folliculitis; verrucous HSV­I and HSV­II lesions; the role of recurrent HSV­I infection in burning mouth syndrome; HSV­I and HSV­II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV­I or HSV­II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV­I and anti-HSV­II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV­I and HSV­II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

What do Clinicians Perceive as a Successful "Trial of Fluids"?: A Secondary Assessment of a Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to explore physician perceptions of the amount of fluid that demonstrates a successful "trial of fluids" (adequate fluid intake) in the emergency department in children who have had insufficient fluid intake at home. METHODS: This is a secondary analysis of a randomized placebo-controlled trial of viscous lidocaine versus placebo in children aged 6 months to 8 years with acute infectious ulcerative mouth conditions (gingivostomatitis, ulcerative pharyngitis, or hand foot and mouth disease) and poor oral fluid intake. We measured the amount of fluid ingested in 60 minutes after administration of the intervention and related physician perception of adequate intake to measured intake. Given that there was little difference in oral intake between the treatment groups, the 2 arms were pooled for this analysis. RESULTS: One hundred participants were recruited (50 per treatment group), all of whom completed the 60-minute trial period. At baseline, 72% were mildly dehydrated, 21% were not dehydrated, and 5% were moderately dehydrated. The participants drank a median of 8.6 mL/kg (interquartile range [IQR], 3.7-14). Clinicians perceived 58% of the participants to have an adequate intake within the first hour after intervention. The median consumption of those whose oral intake was deemed as adequate was 12.6 mL/kg (IQR, 9.4-18.4); for those whose oral intake was not deemed adequate, the median consumption was 2.7 mL/kg (IQR, 0.7-5.3) (rank sum, P < 0.001). CONCLUSIONS: In children undergoing trial of fluids, we found that most clinicians perceived a fluid intake greater than 9 mL/kg as adequate and lower than 5 mL/kg as inadequate.

Acyclovir for herpetic gingivostomatitis in children.

QUESTION: Every year I see preschool children with gingivostomatitis. There seems to be quite a substantial burden of illness with this condition. Because it is caused by herpes simplex virus type 1, should I prescribe antiherpetic therapy with oral acyclovir? ANSWER: While most children with primary gingivostomatitis will be asymptomatic, some will experience considerable pain and discomfort and are at risk of dehydration. There are no large, well designed studies to clearly determine appropriate therapy for all children. Based on a single randomized study, treatment should be started only within the first 72 hours of symptom onset if substantial pain or dehydration are documented.