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Practical relevanceFeline chronic gingivostomatitis (FCGS) is a debilitating disease for cats and a challenge for veterinarians and cat caregivers alike. Recent literature indicates that the disease is immune-mediated in nature and likely associated with a chronic viral infection in patients with higher alpha diversity of their subgingival microbiome. The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings.Treatment optionsLocalized therapy in the form of surgical extraction of all, or nearly all, teeth continues to be the mainstay of treatment. For cats that do not respond to surgical management, medical management, in the form of immunosuppressive or immunomodulatory therapy, remains an option. Analgesia is of fundamental importance. Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described.AimsThis review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease.Evidence baseThe article draws on the best evidence base at this juncture and is also driven by the authors' collective experience of working on the disease for over a decade.

Feline chronic gingivostomatitis (FCGS) is a painful, immune-mediated, oral mucosal inflammatory disease in cats. The etiology of FCGS remains unclear, with evidence pointing potentially toward a viral cause. Full-mouth tooth extraction is the current standard of care, and cats that are non-responsive to extraction therapy may need lifelong medical management and, in some cases, euthanasia. Adipose-derived mesenchymal stromal cells (adMSCs) have been demonstrated to have advantages in the treatment and potentially the cure of non-responsive FCGS in cats. Therefore, adMSCs have attracted a series of ongoing clinical trials in the past decade. AdMSC therapy immediately after full-mouth tooth extraction was not explored, and we postulate that it may benefit the overall success rate of FCGS therapy. Here, we aim to summarize the current knowledge and impact of adMSCs for the therapeutic management of FCGS and to suggest a novel modified approach to further increase the efficacy of FCGS treatment in cats.

Stem cells represent a very important part of regenerative medicine. They have unprecedented potential for the treatment of various diseases and injuries in both humans and other animals. Furthermore, stem cells are characterized by their ability to both self-renew and differentiate into specialized cell types and these exact abilities can be used in the development, maintenance, and repair of damaged tissues and organs. Stem cells can be classified based on their source and developmental stage, with further categorization according to their differentiation potential. Mesenchymal stem cells (MSCs), particularly those derived from bone marrow and adipose tissue, have attracted significant attention in veterinary medicine due to their versatility and accessibility. This review highlights char-acterisation, sources and therapeutic applications of mesenchymal stem cell therapy in some diseases in the field of veterinary stomatology.

IntroductionMesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes.MethodsThis study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction.ResultsLong-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p

ObjectivesThis study aimed to characterize the clinical, radiographic and histopathologic features of early-onset gingivitis (EOG) and periodontitis in cats.MethodsThe medical records database was searched for cats diagnosed with histologically confirmed EOG or periodontitis from 1997 to 2022. Information such as medical history, lifestyle factors, clinical presentation, radiographic and histopathologic features were included for 27 client-owned cats. Response to treatment and long-term follow-up was also recorded.ResultsModerate-to-severe periodontal disease was radiographically confirmed in 78% (21/27) of cats with moderate-to-severe EOG, compared with the evidence of periodontal disease noted in 30% (8/27) of cases during awake oral examination. Horizontal bone loss, along with missing teeth, were the predominant radiographic features noted in 89% (24/27) of cases. The predominant histopathologic feature was moderate-to-severe, erosive-to-ulcerative, neutrophilic and lymphoplasmacytic inflammation with varying degrees of epithelial and stromal hyperplasia. Two cats developed feline chronic gingivostomatitis (FCGS)-like lesions, and seven cats exhibited worsening of aggressive periodontitis (AP). Lack of improvement in the severity of gingivitis or clinical signs evident at the first follow-up appointment was significantly associated with progression of disease (P = 0.004).Conclusions and relevanceThe results of this study demonstrate the importance of oral evaluations in cats as early as 6 months of age. For cats exhibiting substantial gingivitis, an anesthetized evaluation, periodontal treatment and long-term monitoring are recommended. Given the high frequency of moderate-to-severe periodontitis encountered in these cats, clients should be informed about the potential need for tooth extractions. EOG may progress to AP. Finally, this study suggests that there could be a link between EOG and FCGS; however, further studies are needed to better characterize this condition and establish any potential link between the two entities.

Simple Summary: Feline chronic gingivostomatitis (FCGS) remains a poorly understood clinical condition with significant impact on the quality of life of affected cats. An understanding of the pathogenesis of this inflammatory disease will enable the development of improved and targeted therapeutics beyond full-mouth extractions. Here, we collected sterile noninvasive plaque samples at ten distinct sites within the oral cavity in cats with FCGS (n = 12), healthy cats (n = 9), or cats with other oral conditions (n = 11). We used 16S rRNA gene sequencing (V1–V9) to profile bacteria in the oral microbiome. We found that the microbiomes of cats with FCGS were distinct from those of healthy cats at multiple oral sites, indicating that dysbiosis is present throughout the oral cavity. The microbiomes of cats varied depending on their oral diagnoses, confirming that the various dental diseases impact the microbiome in different ways. Lastly, microbiome data obtained from swabs of the oral cavity were similar to those obtained using endodontic paper point plaque samples, suggesting this approach as another valuable method of sampling. Given these additional insights, future studies can focus on targeted therapeutics so that extraction of healthy teeth will no longer be the standard of care for this challenging condition. Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis (n = 12), healthy cats (n = 9), and cats with tooth resorption or periodontitis (n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method. Collectively, our work furthers our understanding of the dysbiosis and composition of bacteria in the oral microbiome in FCGS, with hopes of contributing to the prevention, diagnosis, and treatment of this challenging condition in felines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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ObjectivesThe aim of this pilot study was to determine the safety, efficacy and immunomodulatory function of systemically administered adipose-derived mesenchymal stem cells (ASCs) in cats affected by feline chronic gingivostomatitis (FCGS) prior to full-mouth tooth extractions.MethodsFive client-owned cats affected with FCGS that did not undergo full-mouth tooth extractions for FCGS treatment received two intravenous injections of 20 million fresh, allogeneic or autologous ASCs. An oral examination with photographs, a complete blood count, blood immune cell phenotyping and a biochemical profile were completed at 0 and 6 months after treatment.ResultsFour cats completed the study and one cat exited the study 3 months after treatment. While the treatment was determined to be clinically safe, no positive clinical response was observed in three cats and a mild response was noted in two cats. Furthermore, none of the cats exhibited immune modulation, as evidenced by no alteration in circulating CD8+ T cells, normalization of the CD4:CD8 ratio or neutrophil counts.Conclusions and relevanceUnlike the reported efficacy of ASCs in treating cats with non-responsive FCGS after full-mouth tooth extraction, the systemic administration of ASCs prior to full-mouth tooth extraction lacks substantial clinical efficacy and is not recommended at this time.

Introduction: Among viral diseases, herpes occupies a prominent position, currently considered to be the most prevalent infection in humans. It manifests in various clinical forms, affecting the skin, mucous membranes, eyes, nervous system and internal organs. The wide range of clinical manifestations warrants its recognition as a crucial medical and social issue. Case presentation: An adult patient presented with a case of acute herpetic stomatitis, localized in the oral cavity and facial area. The patient underwent comprehensive treatment in collaboration with an infectious disease specialist. After 8 days of effective treatment, the lesions were absent. Upon subsequent visits after 6, 12, and 18 months, no signs or manifestations of the disease in the oral cavity and face were observed. Conclusion: This clinical case substantiates the efficacy of a comprehensive treatment approach for acute herpetic stomatitis, involving collaboration with an infectious disease specialist, and underscores its paramount significance in attaining optimal patient outcomes. [ABSTRACT FROM AUTHOR]

BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases.

Feline chronic gingivostomatitis is a frustrating disease to manage owing to its elusive etiopathogenesis and its subsequently suboptimal treatment options. Nevertheless, efforts to shed light on the disease over the past few decades have advanced the knowledge on its potential etiopathogenesis and the success rates of available treatment options. Further research is ongoing, with promising attempts to better understand and treat this, likely, multifactorial disease.

IntroductionMesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes.MethodsThis study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction.ResultsLong-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p

Objectives: This study investigated the prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea and analysed its risk factors. Methods: Three hundred and forty-five feral cats that visited the hospital for neutering using a trap–neuter–return approach were screened for feline chronic gingivostomatitis based on clinical criteria. In addition, we determined if body weight, sex and the presence of tongue lesions are risk factors for feline chronic gingivostomatitis. The difference in severity due to the presence or absence of risk factors, and the relationship between gross findings and histopathological lesions, were analysed by grading lesion severity. Results: Feline chronic gingivostomatitis was diagnosed in 92 cats. Disease prevalence did not significantly differ with body weight and sex but was significantly related to tongue lesions. Conclusions and relevance: The prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea was 26.6%. It was significantly more prevalent in cats that had tongue lesions. Severity was also significantly associated with tongue lesions. Feline chronic gingivostomatitis may be associated with an infectious agent that causes tongue lesions. [ABSTRACT FROM AUTHOR]

Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis (n = 12), healthy cats (n = 9), and cats with tooth resorption or periodontitis (n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method. Collectively, our work furthers our understanding of the dysbiosis and composition of bacteria in the oral microbiome in FCGS, with hopes of contributing to the prevention, diagnosis, and treatment of this challenging condition in felines.

Primary herpetic gingivostomatitis (PHGS) represents the most observed clinical feature of primary herpes infection with the simplex virus (HSV). It is often caused by HSV‐1 and affects children most of the time. Unlike, the majority of primary HSV infections that is asymptomatic. It may be preceded by some prodromal symptoms like fever, anorexia, irritability, malaise, and headache. After the resolution of the primary infection, the virus remains latent in a nervous ganglion. The aim of the present paper was to report a case of severe PHGS with herpetic whitlow in a 10‐year‐old child. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710-1722.

Abstract Primary herpetic gingivostomatitis (PHGS) represents the most observed clinical feature of primary herpes infection with the simplex virus (HSV). It is often caused by HSV‐1 and affects children most of the time. Unlike, the majority of primary HSV infections that is asymptomatic. It may be preceded by some prodromal symptoms like fever, anorexia, irritability, malaise, and headache. After the resolution of the primary infection, the virus remains latent in a nervous ganglion. The aim of the present paper was to report a case of severe PHGS with herpetic whitlow in a 10‐year‐old child.

UnlabelledMesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n=3) or substantial clinical improvement (n=2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6-24 months). In this study, cats with 15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype.SignificanceThis study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings demonstrate that this therapy resulted in complete clinical and histological resolution or reduction in clinical disease severity and immune modulation in most cats. This study also identified a potentially useful biomarker that could dictate patient enrollment and shed light on immune modulation mechanism. As a naturally occurring animal model, FCGS also provides a strategic platform for potentially translatable therapy for the treatment of human oral inflammatory disease.

Allergic reactions sometimes participate in the development of perioral and oral diseases, indicating the need for appropriate allergen assessment. This review discusses current knowledge on the potential allergic reactions to different dental materials in patients with oral and perioral diseases. Aside from allergies to various dental materials, similar non-allergic, non-immune contact reactions (irritant or toxic) can occur. Among dental materials, the most frequent allergens are alloys, followed by rubber materials, polymers and acrylates. Allergic reactions to dental alloys that contain nickel, cobalt and amalgam are especially frequent since dentists use them for prosthetic and other restorations. There is a broad spectrum of clinical presentations of oral and perioral diseases possibly related to allergies, such as lichenoid reactions, cheilitis, perioral dermatitis, burning sensations, etc. Despite some limitations, patch test is crucial in the diagnosis and recognition of causative allergens because it reveals contact allergies, and is still superior in differentiating allergic and irritant contact reactions. It is important to examine patient medical histories (e.g., occurrence of symptoms after dental therapy or food consumption), and in consultation with their dentist, carry out allergy tests to specific dental allergens which are used or planned to be used in subsequent treatment.

Dysgeusia is the first recognized oral symptom of novel coronavirus disease (COVID‐19). In this review article, we described oral lesions of COVID‐19 patients. We searched PubMed library and Google Scholar for published literature since December 2019 until September 2020. Finally, we selected 35 articles including case reports, case series and letters to editor. Oral manifestations included ulcer, erosion, bulla, vesicle, pustule, fissured or depapillated tongue, macule, papule, plaque, pigmentation, halitosis, whitish areas, hemorrhagic crust, necrosis, petechiae, swelling, erythema, and spontaneous bleeding. The most common sites of involvement in descending order were tongue (38%), labial mucosa (26%), and palate (22%). Suggested diagnoses of the lesions were aphthous stomatitis, herpetiform lesions, candidiasis, vasculitis, Kawasaki‐like, EM‐like, mucositis, drug eruption, necrotizing periodontal disease, angina bullosa‐like, angular cheilitis, atypical Sweet syndrome, and Melkerson‐Rosenthal syndrome. Oral lesions were symptomatic in 68% of the cases. Oral lesions were nearly equal in both genders (49% female and 51% male). Patients with older age and higher severity of COVID‐19 disease had more widespread and sever oral lesions. Lack of oral hygiene, opportunistic infections, stress, immunosuppression, vasculitis, and hyper‐inflammatory response secondary to COVID‐19 are the most important predisposing factors for onset of oral lesions in COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if the onset of primary herpetic gingivostomatitis (PHG) is shifting toward an adult age and compare the clinical characteristics of PHG between children and adults. Method and Materials: The charts of patients diagnosed with PHG in an oral medicine clinic in Bucharest, Romania, over a 10-year period were revisited. Diagnosis was based on history, clinical data, and laboratory confirmation (Tzanck cytology, polymerase chain reaction [PCR], or immunofluorescence). Seventy-three cases (38 females, 35 males) were included. The age range was between 22 months and 53 years, with a mean age of 18.6 years. All patients were healthy with no suspicion of HIV infection or immunodeficiency. Results: Nearly 48% (47.94%) of the sample were in the young adult group. General symptoms (fever, malaise, and lymphadenopathy) were equally present in children and adults. The most involved areas were the gingiva, vermilion border, and tongue. No differences in the extent of lesions were observed between children and adults. Inflammatory gingivitis and pharyngotonsillitis were more frequent in children than in adults although their frequency was less than expected. Conclusions: PHG was more frequently observed in young adults than in children. No significant differences between children and adults in the severity of infection were observed. Most of the patients presented widespread lesions. [ABSTRACT FROM AUTHOR]

Abstract Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune‐mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose‐derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti‐fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710–1722

Abstract Acute gingivostomatitis is relatively frequent in children; of viral origin, its diagnosis is usually straightforward. Acute gingivostomatitis is very painful and for many years, codeine, whose use was restricted in 2013, was widely employed in this context. The aim of this study was to ascertain the prevalence of acute stomatitis in pediatric emergency care, to evaluate the pain caused by stomatitis, and to determine the analgesic resources deployed both in the emergency department and at discharge, over the 5-year period preceding restriction of the use of codeine. Methods This was a retrospective study conducted in a pediatric emergency department (PED) of a university hospital between August 2008 and June 2013. Results A total of 702 children (372 herpetic gingivostomatitis [HGS], 149 herpangina [H], 181 hand, foot, and mouth disease [HFMD]) were included. Over the 5 years, one case of gingivostomatitis was identified for 303 visits to the PED. A total of 548 (78.1%) children were aged less than 36 months and the median age was 22 months. For 501 of 702 (71.4%) children, parents reported pain and/or feeding difficulties; in the HGS group, 314 of 372 (84.4%) patients had these symptoms. Of the 702 children, 48 (6.8%) were admitted to hospital. Overall, 457 (65.1%) of 702 children were given codeine before the PED visit, during the PED visit, or as a medication to take after discharge. The corresponding figures were 314 of 372 (84.4%) for the HGS group, 67 of 149 (45.0%) for the H group, and 76 of 181 (42.0%) for the HFMD group, P < 0.001. Conclusions Acute gingivostomatitis is a relative frequent reason for PED visits, and the pain and feeding difficulties that it elicits are a real challenge. Before codeine restriction, this medication played a major role in the analgesic strategy for this disease. It is essential that analgesic regimens at least as effective as codeine replace it. Morphine combined with paracetamol or the association of ibuprofen with paracetamol are options that are recommended by the French National Health Authority (HAS). [ABSTRACT FROM AUTHOR]

Feline chronic gingivostomatitis (FCGS) has an unclear pathogenesis with the oral microbiome and viral infections, such as feline immunodeficiency virus (FIV), thought to contribute. Although the relationship between the FIV status and FCGS is not clear, one theory is FIV-induced immune dysregulation could contribute to oral dysbiosis, promoting FCGS development. To further understand the relationship between FCGS, FIV infection, and the oral microbiome, oral cavities of forty cats fitting within 4 groups (FIV- without gingivitis, FIV+ without gingivitis, FIV- with gingivitis, FIV+ with gingivitis) were swabbed. Next generation sequencing targeting the V4 region of the 16s rRNA gene was performed for bacterial community profiling. No differences in diversity were observed, however, analysis of the data in terms of gingivitis revealed differences in the relative abundance of taxa and predicted functional output. Odoribacter spp., a bacteria associated with oral disease, was found in higher relative abundances in cats with the highest gingivitis grade. Cats with gingivitis were also found to harbor communities more involved in production of short-chain fatty acids, which have been connected with oral disease. Significant findings associated with the FIV status were few and of low impact, suggesting any connection between the FIV status and FCGS is likely not related to the oral microbiota.

Vedolizumab is a humanized monoclonal antibody that binds to the human a4ß7 integrin and is approved for use in inflammatory bowel diseases. We describe a patient with severe, refractory erosive gingivostomatitis, which appeared a few days after the first dose of vedolizumab and resolved after discontinuation of the drug. We believe the gingivostomatitis to be a direct side effect of vedolizumab, rather than an extraintestinal manifestation of the underlying inflammatory bowel diseases. The clinicians need to be aware of this adverse event, which could be mistakenly considered as an extraintestinal manifestation of inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

ObjectiveThis study was performed to assess the relationship between oral Feline calicivirus (FCV) load and severity of lesions at the time of presentation of cats suffering from feline chronic gingivostomatitis (FCGS) (part 1) and treatment outcome after dental extractions (part 2). We hypothesized that a higher FCV viral load would be positively correlated with the severity of lesions at presentation and negatively correlated with treatment outcome. In addition, the effect of dental extractions on outcome and the influence of preoperative severity of lesions on the outcome were investigated.Materials and methodsCats with FCGS were included in the study if they had been diagnosed with caudal stomatitis, had been tested positive for FCV using a real-time reverse transcriptase-PCR test on oropharyngeal swab, and had dental extractions performed within the authors’ department. General practitioners provided all previous medical treatments. Cats with recheck examinations were included in part 2 of the study. Multivariate statistical analysis was performed to assess the relationship between the different parameters.ResultsOne hundred four cats met the requirements for part 1 and 56 cats for part 2 of the study. Data collected from patients’ record included patient history, viral testing results, extent and severity of oral lesions, extent of teeth extraction. Signalment, history, preoperative treatment, and severity of caudal and alveolar stomatitis score were not associated with FCV load (P > 0.05). Presence of lingual ulcers was significantly correlated with FCV load (P = 0.0325). Clinical cure (32.1%) or very significant improvement (19.6%) was achieved in 51.8% of cats within 38 days. Concomitantly, 60.7% of the owners considered their cat cured (41.1%) or significantly improved (19.6%). Extent of teeth extraction was not found to influence the clinical outcome (P > 0.05).ConclusionThe results of this study did not support the hypothesis that FCV oral load is correlated with the severity of oral lesions or with the outcome following dental extractions. In addition, the severity of caudal inflammation was not correlated with healing time or achievement of cure.

ObjectivesGingivostomatitis is a common, painful pediatric presentation, and yet, few studies are available to guide management. We aimed to describe pediatric emergency physicians’ current practice patterns, with respect to analgesic use in children with acute gingivostomatitis, in order to inform future studies.MethodsA national survey was conducted at all 15 national academic pediatric centres.Electronic surveys were distributed to pediatric emergency physicians using a modified Dillman protocol; non-respondents received paper surveys via post. Data were collected regarding demographic characteristics, clinical behaviour, factors that may influence practice, and future directions.ResultsResponse rate was 74% (150/202). Most physicians (72%) preferred the combination of acetaminophen and ibuprofen to either agent alone (ibuprofen 19%, acetaminophen 7%). The preferred second-line analgesics were oral morphine (48%, 72/150) and compounded topical formulas (42%, 64/150). The most commonly cited compounded agent was Benadryl plus Maalox (23%, 35/150). Clinical experience with a medication had the greatest influence on practice pattern, with 52% (78/149) strongly agreeing. The most commonly cited barrier to adequate analgesia was difficulty in the administration of topical or oral medication to children.ConclusionsAs with many other painful conditions, the combination of acetaminophen and ibuprofen was preferred, followed by either agent alone. Oral morphine and topical compounded agents were also frequently prescribed. Regardless of patient age, physicians preferred oral morphine as a second-line agent to treat pain from severe gingivostomatitis. Future research will focus on determining which analgesic and route (oral or topical) is the most effective and best-tolerated choice. [ABSTRACT FROM PUBLISHER]

The article describes the case of a two-year-old boy with three days of high fever and poor feeding and whose physical examination showed gingivostomatitis. Topics discussed include his admission at the hospital for rehydration, findings on his second right finger, and discussion on his diagnosis of Herpetic Whitlow (HW), a cutaneous herpes simplex virus (HSV) infection of the pulp or nail bed of a finger.

Introduction: Mesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes., Methods: This study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction., Results: Long-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment ( p  = 0.871) or the severity of the SDAI at entry ( p  = 0.848) or exit ( p  = 0.166), or the delta SDAI between entry and exit ( p  = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p  < 0.041). Most clients were satisfied with the treatment and outcomes, with 90.6% willing to pursue treatment again, given a similar situation., Discussion: The results of this study support the use of both autologous and allogeneic MSC as an efficacious and safe therapeutic option for refractory FCGS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soltero-Rivera, Hart, Blandino, Vapniarsky and Arzi.)

Background: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. Results: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCVsuspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). Conclusions: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multicat environments, reduction of group size in addition to the generally recommended vaccination are advocated. [ABSTRACT FROM AUTHOR]

• Assessment of topical antiviral therapy (TAT) with adjunctive antimicrobial photodynamic therapy (aPDT) was executed in the present study. • The selected individuals were divided into three study groups: Topical antiviral therapy (TAT); antimicrobial photodynamic therapy (aPDT) and combination of topical antiviral therapy and antimicrobial photodynamic therapy (aPDT). • Pain scores reported reduced values at follow-ups for Group C (TAT + aPDT). • Pro-inflammatory cytokines IL-6 and TNF-α were assessed. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Herpetic gingivostomatitis represents the most commonly observed clinical manifestation of primary herpes simplex virus (HSV) infection. HSV-1 has been associated with oro-labial disease, with most infections occurring during childhood, and HSV-2 with genital disease. However, it is possible for HSV-2 to cause oro-labial herpes and HSV-1 to cause genital herpes. An unusual case of acute herpetic gingivostomatitis (AHGS) that presented as extremely painful multiple ulcerations of the gingiva and hard palate in a 32-year-old male patient is presented. The association of HSV-2 in the etiology of oral lesions is highlighted. The clinical presentation, course, differential diagnosis and management of AHGS are discussed. [ABSTRACT FROM AUTHOR]

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Abstract: Pharyngitis is an acute inflammatory infection of pharynx and/or tonsils, most cases are caused by viruses and occur as part of common cold syndromes. As there is marked overlap between clinical findings of viral and bacterial pharyngitis and it is difficult to distinguish GABHS from viral causes clinicians tend to prescribe antibiotics for any sore throat and therefore pharyngitis has become the raison d'être for antibiotic misuses. Although clinical findings may not specifically differentiate the various pharyngitis pathogens yet many of these pathogens have clinical markers which could give us some clues to clinical suspicion. A good picture is equal to thousand words, believing in this axiom article presents few simple clinico-pictorial clues which could help suspecting pharyngitis pathogens, this in turn may boost clinical confidence to avoid unnecessary antibiotic prescriptions. [Copyright &y& Elsevier]

Feline chronic gingivostomatitis (FCGS) is a painful inflammatory disease of the oral cavity. Treatment options for FCGS are very limited and little is known regarding its aetiology. The aim of this study was to investigate the presence of putative novel species in the oral cavity of cats with and without FCGS. Bacterial DNA was extracted from oral swabs and identified by 16S rRNA gene sequencing. The 16S rRNA genes of 54 clones representing distinct potentially novel species were sequenced (1202-1325 base pairs). Obtained sequences were compared to the BLAST database, aligned using the ClustalW2 alignment tool and a phylogenetic tree created. Twenty-two clones (18 from control and four from FCGS samples) had a similarity of less than 97% and were considered novel. The proportion of novel phylotypes in each group was 19.6% (control) and 2.3% (FCGS). In the derived phylogenetic tree, 15 novel phylotypes clustered together and branched away from known species and phyla. This suggests the presence of a group of novel, previously unidentified bacteria that are associated with the feline oral cavity in both health and disease. [ABSTRACT FROM AUTHOR]

The article discusses on erosive oral lesions that can be sub divided into punctate and bullous ulcers depending on the extent of tissue destruction. It focuses on the manifestations of and therapy for punctate lesions. It states that a variety of herpesviruses and enteroviruses can produce ulcerative lesions in the oral cavity, such as herpes labialis, herpes zoster and herpes simplex virus. It also mentions on a range of infections, including mycotic infection, Behcet's syndrome and Reiter's syndrome. It concludes that a majority of traumatic ulcers have an identifiable cause.

Summary: Histological and immunohistochemical studies were performed on samples of the glossopalatine mucosa from 30 cats with feline chronic gingivostomatitis (FCGS). Immunohistochemical labelling and computer-assisted morphometric analysis were used to identify expression of CD3, CD4, CD8, CD79a, IgG, IgM, IgA, leucocyte antigen 1 (L1) and class II molecules of the major histocompatibility complex (MHC) in tissue sections. Mast cells were detected by toluidine blue staining. The microscopical lesions were graded by severity of inflammation and although this grading correlated significantly with the severity of mucosal inflammation assessed at clinical examination, sites assessed as clinically normal or mildly inflamed were poorly predictive of the histopathological grade in the corresponding tissue sample. The number of CD79a+ cells (mostly plasma cells), L1+ cells (mostly neutrophils) and CD3+ T cells, and the level of MHC class II expression, tended to correlate with the severity of the inflammation. In general, CD8+ T cells were more numerous than CD4+ T cells. The majority of the plasma cells were of the IgG isotype and fewer IgA+ and IgM+ plasma cells were present. In some cases MHC class II expression by mucosal epithelium, salivary duct epithelium or skeletal muscle fibres was observed. Relative to equivalent oral mucosal samples from healthy cats, the number of cells labelled for CD3, CD4, CD8, CD79a, IgG, IgM, IgA or L1, and the number of mast cells, within the lamina propria/submucosa were significantly increased. Limited analysis of the epithelial compartment also found more CD3+ T cells compared with healthy cats. These findings indicate that the glossopalatine mucosal lesions in FCGS represent a complex, chronic and destructive inflammatory process affecting the epithelium and lamina propria, with frequent extension into submucosal tissues. The predominance of CD8+ cells over CD4+ cells suggests the induction of an underlying cytotoxic cell-mediated immune response, which could be consistent with a viral aetiology. [Copyright &y& Elsevier]

Primary herpetic gingivostomatitis (PHGS) represents the clinically apparent pattern of primary herpes simplex virus (HSV) infection, since the vast majority of other primary infections are symptomless. PHGS is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. The disease presents as numerous pin-head vesicles, which rupture rapidly to form painful irregular ulcerations covered by yellow–grey membranes. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings. Following resolution of the lesions, the virus travels through the nerve endings to the nerve cells serving the affected area, whereupon it enters a latent state. When the host becomes stressed, the virus replicates and migrates in skin, mucosae and, in rare instances, the central nervous system. A range of morbidities, or even mortality, may then occur, i.e., recurrent HSV infections, which are directly or indirectly associated with PHGS. These pathological entities range from the innocuous herpes labialis to life-threatening meningoencephalitis. [ABSTRACT FROM AUTHOR]