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.

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.

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.

EFFECTІVENESS OF LASER THERAPY ІN COMPLEX TREATMENT OF HERPETIC STOMATITIS.

OBJECTIVE: The aim: The purpose of research is to improve the effectiveness of treatment by applying laser in complex treatment in patients with herpetic stomatitis. PATIENTS AND METHODS: Materials and methods: Were examined 47 people (22 men and 25 women) with acute herpetic stomatitis. The patіents' age was from 20 to 72 years. All patients underwent immunological tests such as (T-lymphocytes (CD3 +), T-helpers (CD4 +), cytotoxic T-lymphocytes (CD8 +), the content of immunoglobulins IgM, IgG, IgA and slgA in saliva to assess the іmmunological reactivity of the organism. RESULTS: Results: Clinical observations have shown that when using laser therapy, the results of treatment were better than in the control group. Positive dynamics was observed as early as 1-2 days after the start of laser use and was more pronounced when used in the early stages of the disease. The use of the laser promoted a more rapid suspension of new lesions, a decrease in pain syndrome, and a more rapid regression of herpetic lesions. We have found significant improvements in the arameters of cellular and humoral іmmunity in patients of the main group. CONCLUSION: Conclusions: Treatment of herpetic stomatitis is relevant and requires further improvement and the search for new methods. The use of a laser in the complex treatment of herpetic stomatitis has a positive effect on the course and іmmunological status of patients with herpetic stomatіtis. The manifestations of the disease healed faster, and the pain syndrome was less severe. Duration between іllness and treatment decreased on 19.7% and 26%. It is advіsable to include the method of treatment using a laser in the complex therapy of herpetic stomatitis.

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.

[Chronic mucocutaneous candidiasis with STAT1 gain-of-function mutation associated with herpes virus and mycobacterial infections]. / Candidose cutanéo-muqueuse chronique avec mutation gain-de-fonction du gène STAT1 associée à des infections herpétiques et à mycobactérie.

INTRODUCTION: Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to chronic or recurrent infections with yeasts of the genus Candida affecting the skin, nails and mucous membranes. We describe a Moroccan patient presenting CMC with heterozygous STAT1 gain-of-function (GOF) mutation. PATIENTS AND METHODS: A 5-year-old boy with no consanguinity presented recurrent episodes of oral thrush, chronic nail candidiasis and herpetic gingivostomatitis from the age of 8 months. He also had mycobacterial adenitis secondary to BCG vaccination and atypical rosacea. Genetic analysis revealed GOF mutation of the STAT1 gene. DISCUSSION: CMC was diagnosed in our patient despite poor clinical features. Sequencing of the genome revealed STAT1GOF mutation. This mutation affects production of IL-17, an important cytokine in mucocutaneous defense against Candida. The association with mycobacterial adenitis is rare and continues to be poorly understood. The presence of atypical rosacea in this setting is suggestive of this entity. Antifungal therapy and prevention of complications are necessary to reduce the morbidity and mortality associated with this condition. CONCLUSION: CMC due to STAT1GOF mutation is characterized by a broad clinical spectrum and should be considered in all cases of chronic or recurrent fungal infection, whether or not associated with other infections.

[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.

[Development of a method for evaluating the effectiveness of treatment of children with herpetic stomatitis.]

The high frequency of herpes infection in children determines the need to search for new diagnostic markers, evaluate treatment efficacy and predict relapse of the disease. The purpose of the work is to assess the possibility of using biochemical analysis of oral fluid to assess the effectiveness of treatment of children with acute herpetic stomatitis. In the oral fluid and blood plasma of 28 children of patients with acute herpetic stomatitis in the dynamics of the disease, the content of total protein, proteins of the acute phase of inflammation, as well as the concentrations of calcium, magnesium, copper and zinc was determined spectrophotometrically. Oral fluid and blood plasma of 45 practically healthy children were used as a control. In acute herpetic stomatitis, the content of C-reactive protein, orosomucoid, α1-antitrypsin, ceruloplasmin, prealbumin and microalbumin, as well as magnesium, calcium and zinc, increases in the oral fluid of children, but the level of total protein and transferrin decreases. In this blood plasma, the level of ceruloplasmin, orosomucoid, C-reactive protein, α1-antitrypsin is higher, and zinc is lower than in healthy children. The copper content in the oral fluid and blood plasma of children increases with moderate herpetic stomatitis, and significantly decreases with severe herpetic stomatitis. The degree of changes in the content of the proteins of acute phase of inflammation and indicators of mineral metabolism of the oral fluid and blood plasma of children with a herpetic infection of the oral cavity correlates with the severity of the disease. Highly significant correlations were revealed when comparing the concentrations of proteins of the acute phase of inflammation, electrolytes between the oral fluid and the blood plasma of children with acute herpetic stomatitis. After treatment of children with acute herpetic stomatitis, the content of minerals and proteins of the acute phase of inflammation in the oral fluid returned to normal only with a mild disease severity. A method has been developed for evaluating the effectiveness of treatment of children with acute herpetic stomatitis by determining the content of minerals in the oral fluid. The ratio of copper to calcium in the oral fluid of children more than 45 should be considered an indicator of effective treatment of children with herpetic stomatitis.

The controversial natural history of oral herpes simplex virus type 1 infection.

The natural history of oral herpes simplex virus type 1 (HSV-1) infection in the immunocompetent host is complex and rich in controversial phenomena, namely the role of unapparent transmission in primary infection acquisition, the high frequency of asymptomatic primary and recurrent infections, the lack of immunogenicity of HSV-1 internalized in the soma (cell body) of the sensory neurons of the trigeminal ganglion, the lytic activity of HSV-1 in the soma of neurons that is inhibited in the sensory neurons of the trigeminal ganglion and often uncontrolled in the other neurons, the role of keratin in promoting the development of recurrence episodes in immunocompetent hosts, the virus-host Nash equilibrium, the paradoxical HSV-1-seronegative individuals who shed HSV-1 through saliva, the limited efficacy of anti-HSV vaccines, and why the oral route of infection is the least likely to produce severe complications. The natural history of oral HSV-1 infection is also a history of symbiosis between humans and virus that may switch from mutualism to parasitism and vice versa. This balance is typical of microorganisms that are highly coevolved with humans, and its knowledge is essential to oral healthcare providers to perform adequate diagnosis and provide proper individual-based HSV-1 infection therapy.

Honey can help in herpes simplex gingivostomatitis in children: Prospective randomized double blind placebo controlled clinical trial.

PURPOSE: Herpes simplex gingivostomatitis (HSGS) in children is a common painful infectious disease. This study aims to examine the combined efficacy of honey with acyclovir suspension compared to acyclovir alone for treating HSGS in young children. MATERIAL AND METHODS: This Randomized double blind placebo controlled study was conducted from June 2015 to September 2017 in a tertiary referral hospital. One hundred children aged 2-8 years with HSGS were randomly classified into 2 groups; study group: treated with honey plus oral acyclovir and control group: treated with oral acyclovir alone. Severity of oral lesions, Fever, eating and drinking ability, pain scores and need for analgesics were compared between 2 groups on day 3, 5 and 7 after starting treatment. RESULTS: Children receiving honey plus acyclovir (i.e. study group) had significantly earlier disappearance of herpetic oral lesions; median 3 days vs. 6 days in control group (P = 0.022), drooling; 2 days vs. 4 days (P = 0.030) and eating difficulty; 3 days vs. 8 days (P = 0.001). Study group also had significantly lower pain scores, better eating and drinking ability and significantly less need for analgesics at 3 time-points of assessment. Fever disappeared in both groups with no statistically significant difference. CONCLUSIONS: The combined use of honey with oral acyclovir can produce favorable outcome than acyclovir alone in children with Primary herpetic gingivostomatitis.

[Complex treatment of recurrent herpetic stomatitis in employees of industrial enterprises]. / Kompleksnoe lechenie retsidiviruiushchego gerpeticheskogo stomatita u rabotnikov promyshlennykh predpriiatii.

Research ebjective was to study assessment of quality organization of work treatment recurrent herpetic stomatitis in patients of industrial enterprises from employees.172 patients on the industrial enterprises from 25 to 54 year were treated recurrent herpetic stomatitis. Clinical efficiency of immunomodulator quality therapy of recurrent herpetic stomatitis for assessment organization of work in employees industrial is proved by estimation of oral cavity local immunity (SIgA, lisozyme). After treatment of recurrent herpetic stomatitis in employees signifie and (p<0,005) inerease of lisozyme and SIgA. The obtaiquality of treatment of recurrent herpetic stomatitis et employees of industrial enterprises.

Recurrent Herpes Labialis in Adults: New Tricks for an Old Dog.

Herpes labialis remains a common worldwide affliction. Recent advances in understanding the basic pathogenesis have led to new therapeutic intervention, both on-label and off-label. Aside from reducing the duration and symptomatology of acute outbreaks, another goal of treatment is to decrease the frequency of future episodes. Oral and topical acyclovir and its analogues are the mainstay of both chronic suppressive and episodic therapy. A new muco-adhesive formulation of acyclovir provides a decrease in outbreaks, probably due to a diminution of herpesvirus load in all reservoir sites. Acyclovir-resistant strains are rare in immunocompetent hosts; parenteral foscarnet and cidofovir are administered in this situation. Parenteral acyclovir is the drug of choice for eczema herpeticum, which may begin as herpes labialis in an atopic dermatitis patient. Thermotherapy may be beneficial, and a certified device to deliver heat is available outside the United States.

J Drugs Dermatol. 2017;16(3 Suppl):s49-53.

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.

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.

[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.

Low-level Laser Therapy: A Review of Its Applications in the Management of Oral Mucosal Disorders.

Due to its analgesic, anti-inflammatory, and biostimulating effects, low-level laser therapy (LLLT) has been widely used for oral disorders, such as oral lichen planus (OLP), xerostomia, recurrent aphthous stomatitis (RAS), herpes labialis, burning mouth syndrome (BMS), and oral mucositis (OM). The research team for the present study has reviewed the literature on the subject, with an emphasis on the applicability of LLLT in general and of its various clinical protocols for the management of those oral disorders. In lesions such as the ones occurring in OM, RAS, herpes labialis, and OLP, the course of wound healing and the pain have been shown to decrease, with a few, or most often, no adverse side effects. The literature shows that LLLT can also be effective in reducing symptoms in patients with BMS. For the treatment of hyposalivation and xerostomia, the use of LLLT has been described in the literature, but no consensus has resulted. Very few controlled clinical studies with well-established therapeutic protocols have occurred, except for OM, for which LLLT has been widely researched. Although information on the use of the laser for some lesions has already been consolidated, further research is needed, especially randomized, controlled clinical trials with long-term follow-up. Those studies will allow the safe use of LLLT, permitting the creation of care protocols for the management of oral disorders.

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.

Atypical Presentation of Zoster Mimicking Headache and Temporomandibular Disorder: A Case Report.

Herpes zoster in the prodromal stage may be mistaken for other diseases characterized by pain in the area of prodrome, such as dental pain. We report on a case of trigeminal herpes zoster, which presented as sudden onset headache and acute temporomandibular pain in the prodromal phase.

[Prevention of the recurrent herpetic stomatitis in employees of Kazan city industrial enterprises frequently suffering from acute respiratory viral infections]. / Profilaktika retsidiviruyushchego gerpeticheskogo stomatita u rabotnikov promyshlennykh predpriyatii goroda Kazani, chasto boleyushchikh ostrymi respiratornymi zabolevaniyami.

Research objective was to study the efficacy of ingavirin for prevention of recurrent herpetic stomatitis in employees of Kazan city industrial enterprises frequently suffering from acute respiratory viral infections. 128 employees aged from 18 to 56 years were included in the study. Clinical and immunological efficiency of ingavirin prevention of recurrent herpetic stomatitis is proved by estimation of oral cavity local immunity (SlgA, lisozyme), humoral immunity (IgE and IgG) and cellular immunity (RBTL with FGA, defined T-lymphocytes). After administration of ingavirin significant (p<0.05) increase of lisozyme and SlgA, RBTL with FGA, number of T-lymphocytes and IgG concentration was observed. The obtained data allow to recommend ingavirin for prevention of recurrent herpetic stomatitis.