Fixed drug eruption secondary to etoricoxib.

Fixed drug eruptions (FDE) are adverse cutaneous drug reactions and a form of delayed type 4 hypersensitivity reaction characterised by recurrent lesions at the same site each time a specific drug is taken. They most commonly result in cutaneous lesions presenting as an erythematous round or oval macule or plaque. FDEs have rarely been reported to affect oral mucous membranes and tend to have a bullous or aphthous-like appearance with erythema. Almost half of patients report an increase in the severity of symptoms with prolonged exposure to the offending medication. The most commonly attributed classes of drug are antibiotics (tetracyclines and sulphonamides) alongside non-steroidal anti-inflammatory drugs. Cutaneous adverse reactions to etoricoxib, a highly selective COX-2 inhibitor, have been reported. Here we describe an adverse reaction restricted to the oral mucosa.

Cutaneous ulceration in juvenile dermatomyositis with anti-melanoma differentiation-associated gene 5.

This report presents the case of an 11-year-old girl with juvenile dermatomyositis (JDM), anti-MDA5 antibodies and multiple skin ulcers. Treatment with traditional immunomodulators and tofacitinib resulted in healing of the skin ulcers and normalization of muscle enzyme markers. This case highlights the significance of recognizing the association between anti-MDA5 antibodies and cutaneous ulceration in JDM and supports the use of Janus kinase inhibitors as a management option.

Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing.

Probiotics are beneficial bacteria located in the oral cavity which exhibit antimicrobial properties and contribute to the regulation of immune function and the modulation of tissue repair. Fucoidan (FD), a marine prebiotic, may further enhance the ability of probiotics to promote ulcer healing. However, neither FD nor probiotics are attached to the oral cavity and neither are well-suited for oral ulcer healing owing to the wet and highly dynamic environment. In this study, probiotic-loaded calcium alginate/fucoidan composite hydrogels were developed for use as bioactive oral ulcer patches. The well-shaped hydrogels exhibited remarkable wet-tissue adhesion, suitable swelling and mechanical properties, sustained probiotic release, and excellent storage durability. Moreover, in vitro biological assays demonstrated that the composite hydrogel exhibited excellent cyto/hemocompatibility and antimicrobial effects. Importantly, compared to commercial oral ulcer patches, bioactive hydrogels show superior therapeutic capability for promoting ulcer healing in vivo by enhancing cell migration, inducing epithelial formation and orderly collagen fiber deposition, as well as facilitating neovascularization. These results demonstrate that this novel composite hydrogel patch demonstrates great potential for the treatment of oral ulcerations.

Alogliptin Induced Stomatitis: An Adverse Drug Event Case Report.

Background: Dipeptidyl peptidase (DPP)-4 inhibitors are commonly used agents to treat type 2 diabetes mellitus (T2DM). Although generally well tolerated, stomatitis has been previously reported as an adverse event with sitagliptin and linagliptin. Stomatitis with alogliptin has not been reported in post-marketing data to date. Objective: To report a case of suspected drug-induced stomatitis in a patient who received alogliptin for T2DM which resolved upon discontinuation of the offending agent. Summary: A 60-year-old male with T2DM began treatment with a DPP-4 inhibitor, alogliptin. After 4 doses of alogliptin, the patient reported inflammation and irritation along the lateral borders of his tongue, along with open fissures and oral ulcerations on the dorsal surface of the mucosa. He was subsequently diagnosed with stomatitis. Patient discontinued alogliptin and reported improvement in symptoms within 48 hours. Lesions re-epithelialized within 4 weeks after cessation of alogliptin. The Naranjo Algorithm was used to assess causality. The total score was 7, which when interpreted, implicates alogliptin as a "probable" cause of the reaction. Conclusion: A causality assessment determined alogliptin was a "probable" cause of stomatitis experienced by this patient. This adverse effect has not been reported with alogliptin to the authors' knowledge.

A New Hypothesis Describing the Pathogenesis of Oral Mucosal Injury Associated with the Mammalian Target of Rapamycin (mTOR) Inhibitors.

It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. Among the most common issues is the development of ulcers of the oral mucosa (mTOR-inhibitor associated stomatitis; mIAS). These lesions are distinct from those of other anti-cancer agents, occur with regularity, and impact patient outcomes. mIAS' pathogenesis has been the subject of speculation, and its similar presentation to recurrent aphthous stomatitis (RAS) has led to the hypothesis that it might serve as a surrogate to better understand RAS. Based on a review of the literature, the current manuscript provides a hypothesis regarding the mechanisms by which mTORis uniquely initiate mucosal injury and an explanation for the observation that steroids (also an immunosuppressive) are effective in its treatment through a non-immunologic mechanism. Unexplained unique features of mIAS are discussed in this review in the context of future investigation.

Clinical Performance Evaluation of a Hyaluronic Acid Dental Gel for the Treatment of Traumatic Ulcers in Patients with Fixed Orthodontic Appliances: A Randomized Controlled Trial.

BACKGROUND: A newly available gel containing hyaluronic acid (HA) and polyvinylpyrrolidone was tested for efficacy on traumatic oral ulcers (TOU) caused by fixed orthodontic appliances. METHODS: A double-blind RCT was conducted to test the new gel versus a placebo. According to the sample size calculation, a total of 60 patients were considered sufficient and randomly allocated to one of the two groups out of a pool of 100 total patients who initially agreed to participate in the study. A VAS scale test and lesion measurements at T0, T1, and T2 were performed on the patients. RESULTS: A total of 70 patients developed TOU, with 8 drop-outs; the intergroup comparison showed a statistically significant greater dimension of the lesion in the control group at T2 when compared to the test group. The pain experienced by the patients belonging to the test group was significantly lower than the pain in the patients in the control group Conclusions: Under the limitations of the study, the new formula might provide faster healing with less pain experienced by the patient when compared to a placebo.

An Update on Feline Calicivirus.

INTRODUCTION: Feline Calicivirus (FCV) is one of the most common viral pathogens in domestic cats worldwide. The first report of FCV dates back to 1957, when FCV was isolated from the gastrointestinal tract of cats in New Zealand. Subsequent reports recognised FCV as a cause of respiratory disease in cats, and at present, feline practitioners worldwide are daily confronted with cats suffering from suspected FCV. The highly mutagenic nature of FCV and its high genetic plasticity enable the virus to successfully survive in the feline population, and pose a special challenge as regards the diagnosis, treatment, and prevention of FCV-induced disease. Upper respiratory tract disease has been considered a common clinical sign of FCV infection. A study from Switzerland demonstrated that oral ulcerations, salivation and gingivitis-stomatitis were more commonly associated with FCV infection than upper respiratory tract disease, and less than half of the cats suspected to have FCV infection were found to be FCV-positive. Furthermore, a study investigating FCV isolates from Switzerland found some evidence that the genetic background of cats might influence their susceptibility to FCV infection. This review article provides a comprehensive summary of the FCV literature, and integrates the results of recent research on FCV's genetic characteristics, the cellular and humoral immunity evoked by FCV vaccination and infection, the diagnosis of FCV, FCV prevention/vaccination, the risk factors associated with FCV, and the hygienic measures necessary in FCV-contaminated areas. After each section, the key points are summarised, and relevant information is outlined to help feline practitioners in FCV diagnosis, treatment and prevention.

INTRODUCTION: Le calicivirus félin (FCV) est l'un des agents pathogènes viraux les plus courants chez les chats domestiques dans le monde. Le premier signalement de FCV remonte à 1957, lorsque le FCV a été isolé du tractus gastro-intestinal de chats en Nouvelle-Zélande. Des rapports ultérieurs ont reconnu le FCV comme une cause de maladie respiratoire chez les chats et, à l'heure actuelle, les praticiens félins du monde entier sont quotidiennement confrontés à des chats suspectés de FCV. La nature hautement mutagène du FCV et sa haute plasticité génétique permettent au virus de survivre avec succès dans la population féline et posent un défi particulier en ce qui concerne le diagnostic, le traitement et la prévention de la maladie induite par le FCV. La maladie des voies respiratoires supérieures a été considérée comme un signe clinique courant d'infection par le FCV. Une étude réalisée en Suisse a démontré que les ulcérations buccales, la salivation et la gingivite-stomatite étaient plus fréquemment associées à une infection à FCV qu'à une autre maladie des voies respiratoires supérieures et moins de la moitié des chats suspectés d'avoir une infection à FCV se sont avérés positifs pour le FCV. De plus, une étude portant sur des isolats de FCV en Suisse a trouvé des preuves que le profil génétique des chats pourrait influencer leur sensibilité à l'infection par le FCV. Cet article de synthèse fournit un résumé complet de la littérature sur le FCV et intègre les résultats de recherches récentes sur les caractéristiques génétiques du FCV, l'immunité cellulaire et humorale évoquée par la vaccination et l'infection au FCV, le diagnostic du FCV, la prévention/vaccination contre le FCV, les facteurs de risque associés avec le FCV et les mesures d'hygiène nécessaires dans les zones contaminées par le FCV. Après chaque section, les points clés sont résumés et des informations pertinentes sont décrites pour aider les praticiens félins dans le diagnostic, le traitement et la prévention du FCV.

An unusual case of cluster of differentiation 30-positive T-cell lymphoproliferative disorder manifesting as mandibular gingival ulceration: A case report.

BACKGROUND: Primary cutaneous cluster of differentiation 30-positive (CD30+) T-cell lymphoproliferative disorders are the second most common type of skin T-cell lymphoma. The lesions exhibit an indolent course, with a morphology resembling high-grade T-cell lymphoma. CASE DESCRIPTION: A 67-year-old healthy man sought treatment for a large nonhealing ulcer on the buccal gingiva of the mandibular right premolars. He reported a history of recurrent cutaneous lesions, for which he was seen 1 year earlier at a hospital. Results of incisional biopsy showed a dense lymphoid cell infiltrate composed of atypical CD30+ T-cells intermixed with eosinophils. The diagnosis was updated to CD30+ T-cell lymphoproliferative disorder, which was similar to the cutaneous lesion diagnosis. The lesion area healed completely, and there were no signs of recurrence at 18-month follow-up. PRACTICAL IMPLICATIONS: Oral CD30+ T-cell lymphoproliferative disorder has a favorable outcome, but it is commonly misdiagnosed. Biopsy is crucial and should be combined with clinical examination to avoid chemotherapeutic treatments intended for high-grade lymphoma.

The 30th birthday of chronic ulcerative stomatitis: A systematic review.

OBJECTIVES: Chronic ulcerative stomatitis (CUS) is a chronic, ulcerative condition of the oral cavity, clinically and histologically similar to oral lichen planus (OLP), first described as a new disease entity in 1990 by Parodi et al. In this review, 30 years after our first description of CUS, we aimed to systematically review the literature of CUS cases reported ever since. METHODS: We present a systematic review of CUS literature cases, performed in compliance with the PRISMA statement. RESULTS: Of 125 retrieved articles, 20 satisfied inclusion criteria. These described 76 CUS cases, all presenting orally evident disease: erosions (55%), white lesions (49%), erythema (49%), ulcerations (34%) were the most frequent signs; 54% experienced discomfort/pain. Topographically, buccal mucosa (68%) and gingiva (54%) were the most affected locations, followed by tongue (42%), hard palate (27%), labial mucosa (22%), and widespread involvement (15%). Great diagnostic delay (6.3 years) was evidenced highlighting CUS is an entity too often misdiagnosed. Histopathology found lichenoid features (46%) and non-specific inflammation (54%). Extra-oral involvement was reported in 21%, especially as LP (69%). Of DIF, 97% were positive; 3% negative, compensated by positive IIF, permitting diagnosis. Of patients on steroids, only 12% reported therapeutic success; most steroid-non-responsive patients passed to antimalarials, with 91.66% success when used alone, 100% success in combination therapy. CONCLUSION: Dermatologists should suspect CUS in chronic steroid-unresponsive erosive/ulcerative stomatitis. In these cases, to diagnose CUS, the presence of stratified epithelium-specific antinuclear antibodies (SES-ANA) should be investigated through immunofluorescence. Once diagnosed, CUS can be treated with antimalarials, which are an effective treatment contrarily to corticosteroids.

Vesiculobullous disease with Cutaneous Systemic Lupus Erythematosus Treated by Rituximab: A case report.

Vesiculobullous lesions in systemic lupus erythematosus (SLE) are a rare cutaneous manifestation of cutaneous and/or systemic LE with variable presentation. The diagnosis of SLE-associated vesiculobullous diseases remains challenging, due to the poorly defined similarities and nosology in immunohistopathological and clinical and features.

Mandibular osteonecrosis following herpes zoster infection: Report of a rare case with a literature review.

Any patient with a herpes zoster infection of the mandibular branch of the trigeminal nerve should benefit from early oral monitoring, especially in elderly population where traumatic dental prostheses are common, because osteonecrosis can occur.

Relationships of interleukin-17 polymorphisms with recurrent aphthous ulcer risk in a Han Chinese population.

OBJECTIVE: Interleukin (IL)-17 is a multifunctional cytokine with important roles in inflammatory and autoimmune diseases. This case-control study explored the relationships of IL-17A rs2275913 and IL-17F rs763780 single-nucleotide polymorphisms (SNPs) with recurrent aphthous ulcer (RAU) morbidity and severity. METHODS: IL-17A rs2275913 and IL-17F rs763780 SNPs were measured in 125 patients with RAU and 116 healthy control participants. The genotype distributions, disease risks, and relationships with RAU severity were analyzed. RESULTS: RAU risk was associated with rs2275913 after adjustment for age, body mass index, sex, smoking status, and drinking status (AA vs. GG: odds ratio [OR], 2.759; 95% confidence interval [CI], 1.381-5.512; A allele vs. G allele: OR, 1.783; 95% CI, 1.242-2.560). TC and CC genotypes in rs763780, and the corresponding C allele, demonstrated greater prevalence among patients with RAU, compared with the TT genotype (TC vs. TT, OR: 1.895; 95% CI: 1.088-3.301; CC vs. TT, OR: 4.080, 95% CI: 1.079-15.425; C allele vs. T allele, OR: 1.969, 95% CI: 1.257-3.083). Serum IL-17 concentrations were also higher in patients with RAU than in control participants. These concentrations were associated with IL-17 polymorphisms. CONCLUSIONS: IL-17 polymorphisms might be associated with greater risk of RAU pathogenesis.

Spontaneous oral ulceration with bone sequestration: its relevance in current clinical practice.

Oral ulceration associated with bony exposure and sequestration is uncommon and often related to well-recognised conditions. In a small group of patients no obvious aetiological factors can be elucidated, and various terminologies have been utilised to describe these lesions. We report six cases of spontaneous oral ulceration with bone sequestration as a specific entity and review the pertinent literature. We retrospectively reviewed patients presenting in the period 2013-2018. Data collected included demographic details, relevant medical, drug, and radiotherapy history; presentation, investigations, management, and outcome. Six patients with an age range of 49-65 years were identified with spontaneous oral ulceration with bone sequestration in the study period. All were males, and none had any relevant history. Five lesions occurred over the mylohyoid ridge and one was related to a lingual mandibular torus. The most common presentation was a painful ulcer with exposed bone, which had been present for 6 - 12 weeks. Occlusal radiographs demonstrated focal rarefaction in two patients. All were managed conservatively and by removal of the loose sequestrum. Healing occurred successfully in all cases, and this was earlier when the loose sequestrum was removed. Spontaneous oral ulceration with bone sequestration is a distinct lesion that most often presents over the prominence of the mylohyoid ridge. It is currently an uncommon entity (0.02%), but this could well be due to a lack of recognition and under-reporting. It should be considered as a diagnosis only when other causes have been excluded. Lesions heal successfully with conservative management and surgical intervention, and this occurs earlier following removal of the loose sequestrum.

A Rare Case Report of Dabigatran Induced Oral Ulcers.

BACKGROUND: Dabigatran is a novel oral anticoagulant molecule which is a direct thrombin (Factor IIa) inhibitor and is used for prevention of stroke and systemic embolism. It is easy to administer as compared to warfarin therapy as it does not require routine laboratory monitoring and has fewer drug interactions. OBJECTIVE: To present a rare case of oral ulcers secondary to dabigatran in a patient with deep vein thrombosis. CASE REPORT: A 68-year-old female presented with painful oral ulcers, retrosternal pain and difficulty in swallowing. She had been taking capsule Dabigatran for the prevention of systemic embolism for 2 months. She had experienced symptoms of onset taking dabigatran for 7 days. Clinical examination revealed three tender, well-defined, clean looking ulcers of various sizes present over the dorsum of the tongue. Dabigatran was withdrawn and the patient was on oral proton pump inhibitors. Patient showed remarkable improvement in oral ulcers after 2 weeks. CONCLUSION: Patient education and counseling should be done regarding this side effect of dabigatran and proper intake of this medicine.

A review and guide to drug-associated oral adverse effects-Oral mucosal and lichenoid reactions. Part 2.

Dental practitioners and other health professionals commonly encounter and manage adverse medicine effects that manifest in the orofacial region. Numerous medicines are associated with a variety of oral adverse effects. However, due to lack of awareness and training, these side effects are not always associated with medicine use and are underreported to pharmacovigilance agencies by dentists and other health professionals. This article aims to inform health professionals about the various oral adverse effects that can occur and the most commonly implicated drugs to improve the management, recognition and reporting of adverse drug effects. This article follows on from Part 1; however, the focus here is on lichenoid reactions and oral mucosal disorders including oral aphthous-like ulceration, mucositis and bullous disorders such as drug-induced pemphigus, pemphigoid, Stevens-Johnson syndrome and toxic epidermal necrolysis.

A case report of a tongue ulcer presented as the first sign of occult tuberculosis.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease with considerable fatality, typically affecting the pulmonary system and, rarely, other body organs including the oral cavity. Due to the rarity of oral TB, it is frequently overlooked in differential diagnosis of oral lesions. Despite a declining trend in TB incidence in recent years, it is still a major public health problem with high contagiousness, thereby requiring the early diagnosis and prompt treatment. CASE PRESENTATION: A 57-year-old male patient presented with chief complaint of painful ulcer on tip of his tongue. He reported that the ulcer developed without any remarkable event such as mechanical trauma, vesicle formation or systemic illness. His past medical history revealed the TB over 40 years ago, which had reportedly healed after pharmacological treatments. As the ulceration persisted after topical steroid application and careful education about avoiding possible mechanical stimuli, biopsy was performed and histological finding showed typical findings of oral tuberculosis including intense granulomatous inflammatory features with small red rods of mycobacterial organisms as well as epithelioid cells and Langhans giant cells. After suitable antituberculosis treatments, oral tuberculosis ulcer was almost completely healed. We present a case of oral TB affecting tip of the tongue in a patient with a history of pulmonary TB and emphasize the understanding of intraoral manifestations for early diagnosis and prompt treatment of TB. CONCLUSIONS: The present case represented the importance of understanding oral tuberculosis manifestations for dental clinicians who might be frequently the first health care professionals to encounter various oral lesions.

Candida and Porphyromonas gingivalis: the effect on wound closure in vitro.

Microorganisms play a role in oral mucositis after cancer therapy. The current study explored the hypothesis that Candida spp. alone and together with Porphyromonas gingivalis cause delayed healing of oral ulcerations due to the inhibition of wound closure. An in vitro scratch assay model was used to study the influence of viable and heat-killed Candida glabrata, Candida kefyr, and Candida albicans on cell migration of oral epithelial cells. Separately, the effect of conditioned medium of Candida spp. and the effect of a mixed infection of Candida spp. with P. gingivalis on wound closure was studied. In the presence of 10 viable C. glabrata or C. kefyr versus one epithelial cell, with a multiplicity of infection (MOI) of 10, the relative closure of the scratch was 26% and 17%, respectively. At a MOI of 1, this was 60% for C. glabrata and 78% for C. kefyr. The inhibition of oral epithelial cell migration challenged with either C. glabrata or C. kefyr together with P. gingivalis was stronger than the inhibition caused by one of both organisms separately. Candida spp. inhibit cell migration in vitro. A combination of Candida spp. and P. gingivalis inhibited cell migration more than either microorganism separately.

Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. METHODS: A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. RESULTS: In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. CONCLUSIONS: The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.

Estomatitis por metotrexate: Breve revisión del tema / Methotrexate stomatitis: A brief review

El empleo de metotrexate como inmunoimodulador y antimetabolito, ha ido en aumento debido a su efectividad terapéutica, bajo costo y su esquema sencillo de dosis única semanal. Sin embargo, recientemente se han reportado efectos adversos graves relacionados con su administración, entre ellos la estomatitis. Las úlceras bucales son el efecto adverso oral más frecuente y se relacionan con la falta de administración complementaria de ácido fólico, iatrogenias ocasionadas por errores en la ingestión o interacciones farmacológicas.

The use of methotrexate as immunomodulator and antimetabolite has been increasing because of its therapeutic effectiveness, low cost, and simple scheme single dose weekly. However, have recently been reported serious adverse effects related to administration, including stomatitis. Mouth ulcers are the most frequent oral adverse effect and relate to the lack of supplemental folic acid, iatrogenic errors caused by ingestion or drug interactions.