World Workshop on Oral Medicine VII: Oral adverse effects to biologic agents in patients with inflammatory disorders. A scoping review.

BACKGROUND: Biologic agents are rapidly emerging as an effective therapy to treat autoimmune and other chronic diseases. The use of these agents is poorly characterized, resulting in a lack of guidance for dental practitioners. Case reports of oral adverse events have begun to emerge. However, their scope and frequency have not been summarized and analysed to date. The objective of this review was to characterize the literature on oral adverse effects associated with biological therapy when used for autoimmune and inflammatory disorders. METHODS: This review was developed in accordance with scoping review recommendations. Search strategies were developed and employed for six databases. Studies were selected using a systematic search process but with broad inclusion of study types given the paucity of information available. Reports of oral adverse events were analysed descriptively according to agent, mechanism of action, underlying disease, and oral adverse effect observed. RESULTS: Our search returned 2080 articles and 51 met our inclusion criteria, of which most were case reports. The most frequent adverse effects included angioedema, oral lichenoid lesions, osteonecrosis of the jaw, and oral infections. There were also cases of oral malignancies associated with use of biologic agents. Less common effects such as pigmentation were also described. CONCLUSIONS: Oral adverse events have been reported in patients on biologic therapy, albeit in small numbers to date. This limits the generalizability of these results, which should not be used to generate a clinical guideline as they are based primarily on case reports. However, this study presents the first review characterizing the adverse effects observed. Large multi-center studies will be necessary to further define the oral and dental complications caused by biologic agents.

Association between autoimmune rheumatic diseases and head and neck cancer: Systematic review and meta-analysis.

BACKGROUND: Personal history of autoimmune rheumatic diseases has been implicated in the development of malignant neoplasms. Our aim was to assess the risk of head and neck (H&N) cancers in patients with autoimmune rheumatic diseases. METHODS: The articles search included PubMed, EMBASE, LILACS, The Cochrane Library, CINAHL, Scopus, Web of Science, and Google Scholar with no language restrictions for studies published from inception of the databases to August 20, 2022, assessing the risk of H&N cancer in patients with autoimmune rheumatic diseases. Studies were included if they reported the standardized incidence ratio (SIR) with corresponding 95% confidence intervals (CIs). The primary outcome was risk of H&N cancers in patients with autoimmune rheumatic diseases compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of H&N cancers varied according to study site. RESULTS: Our search identified 5378 records, of which 32 cohort studies were eligible for systematic review and 24 for meta-analysis (including 273 613 patients). A significant association was found between H&N cancer and autoimmune rheumatic diseases (SIR = 2.35; 95% CI: 1.57-3.50; p < 0.01, I2  = 94%). CONCLUSION: Our study suggests that patients with autoimmune rheumatic diseases had a significantly increased risk of H&N cancer compared with the general population, including thyroid, oral, and nasopharyngeal cancers. These findings have implications for the individualized screening of these patients and the planning of oncology units. The protocol is registered with PROSPERO, number CRD42020197827.

Association between axial spondyloarthritis and temporomandibular disorders: A systematic review.

This study aimed to assess the frequency of temporomandibular disorders (TMDs) in patients with axial spondyloarthritis (axSpA) compared with the healthy individuals. We systematically searched PubMed, Embase, Scopus, Web of Science, CINAHL, and Google Scholar databases from their inception until 2022, without language restriction. A standardized dataset was used to extract data from the observational studies. Patients were required to have axial spondyloarthritis and clinical and/or radiographic evidence of temporomandibular joint dysfunction. Meta-analysis was performed with a random effects model. A systematic review was registered under number CRD42020206283. We identified seven relevant studies, which provided data for 745 patients and 216 temporomandibular disorders events. The combined odds ratio (OR) showed that the risk of temporomandibular disorders in individuals with axial spondyloarthritis was higher than the control group (pooled OR = 5.26, 95% CI 2.50-11, 06; p < 0.02; I2  = 58%). Also, these individuals do not appear to refer possible temporomandibular joint symptoms to the rheumatologist or dentist. The results of this systematic review and meta-analysis suggest that patients with axial spondyloarthritis have an increased frequency of temporomandibular disorders. TMDs seem to be secondary to postural alterations rather than direct involvement of the temporomandibular joints (TMJs).

Adverse post-operative events of salivary gland biopsies: A systematic review and meta-analysis.

OBJECTIVES: The study aimed to perform a systematic review and meta-analysis of the complications following major and minor salivary gland biopsy. MATERIALS AND METHODS: Observational studies assessing postoperative complications of minor salivary gland biopsy and indexed at Medline/PubMed, EMBASE, Cinahl, LILACS, or Scopus were selected. This review was registered under the protocol number: CRD42020211169. The level of significance considered was 0.05, and the R software (The R Foundation) was used for the meta-analysis. RESULTS: Twenty-seven studies reporting 3208 patients were included in this review. The combined prevalence of postsurgical complications was 11% (95% CI, 8 to 13%, p = 0.01). The percentage of the combined prevalence of neurological complications was 3% (95% CI, 1-6%, p = 0.01). The surgical technique did not influence the frequency of overall and neurological complications. CONCLUSION: Minor salivary gland biopsies are a safe and predictable procedure that should be performed on the lower lip. Postoperative complications are more common than previously reported, but permanent complaints are uncommon.

Antagonist effect of probiotic bifidobacteria on biofilms of pathogens associated with periodontal disease.

The in vitro antagonist growth effect of bifidobacteria were evaluated on periodontal bacteria. Bifidobacterium longum, Bifidobacterium lactis and Bifidobacterium infantis biofilms were grown in single, double or triple combinations with putative periodontal pathogens P. gingivalis and F. nucleatum or beneficial bacteria S. oralis for 24, 72 and 168 h and the total counts were analyzed by checkerboard DNA-DNA hybridization. The results showed that B. infantis and B. lactis, as single species, demonstrated the best antagonist effect on F. nucleatum and P. gingivalis and no influence on S. oralis growth at 168 h. All the double combinations of bifidobacteria tested demonstrated an inhibitory effect on F. nucleatum (72 h) and P. gingivalis (168 h) and did not affect S. oralis counts at any time. In conclusion, B. lactis and B. infantis alone or in double combinations have antagonist effect on periodontopathogens biofilms, at different time points, and minimal influence on S. oralis growth.

Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries.

BACKGROUND: Early childhood caries (ECC) is an aggressive condition that can affect teeth of young children. This study aimed to evaluate genotypic diversity and phenotypic traits of S. mutans isolated from dental biofilms of children with different caries status in comparison with caries free (CF) children. METHODS: Streptococcus mutans strains were isolated from supragingival biofilm samples of CF, ECC and severe-ECC (S-ECC) children and genotyped by arbitrary-primer polymerase chain reaction - AP-PCR. S. mutans genotypes were tested for their ability to reduce the suspension pH through glycolysis, to tolerate extreme acid challenge and by their ability to form biofilm. Response variables were analyzed by ANOVA/Tukey or Kruskal-Wallis/Mann-Whitney tests at a 5% of significance. RESULTS: There was an increase in the prevalence of Streptococcus mutans in biofilms with the severity of dental caries. No differences in genotypic diversity and in acidogenicity of genotypes were found among CF, ECC and S-ECC children. S mutans strains with genotypes more characteristic for ECC and S-ECC children formed more biofilms than those identified in CF children. The strains isolated from S-ECC children were highly acid tolerant. CONCLUSION: Although S. mutans genotypic diversity was similar among the groups of children, phenotypic traits of S. mutans, especially the acid tolerance response, could explain the severity of early childhood caries.

Gram-negative periodontal pathogens and bacterial endotoxin in metallic orthodontic brackets with or without an antimicrobial agent: an in-vivo study.

INTRODUCTION: High levels of periodontal pathogens can cause periodontal alterations. The presence of endotoxin might be responsible for the occurrence and progression of tissue inflammation and bone resorption. The aims of this study were to use checkerboard DNA-DNA hybridization and limulus amebocyte lysate assay to evaluate in metallic orthodontic brackets (1) the presence of 16 gram-negative periodontal pathogenic microorganisms of the orange complex and red complex +Treponema socranskii, (2) the amount of bacterial endotoxin, and (3) the efficacy of 0.12% chlorhexidine gluconate mouthwash in reducing bacterial contamination and endotoxin amount. METHODS: Thirty-three patients (ages, 11-33 years) under orthodontic treatment with fixed appliances had 3 new metallic brackets bonded to 3 different premolars. Sixteen patients used a 0.12% chlorhexidine gluconate mouthwash (Periogard, Colgate-Palmolive, São Bernardo do Campo, São Paulo, Brazil) (experimental group), and 17 patients used a placebo mouthwash (control group) twice a week. After 30 days, the brackets were removed, and the samples were obtained. The data were analyzed statistically by Mann-Whitney, Kruskal-Wallis, and Dunn tests (α = 0.05). RESULTS: The 0.12% chlorhexidine gluconate group accumulated significantly lower levels of microorganisms than did the placebo group (P = 0.01). When each microbial complex was analyzed separately, a statistically significant difference between the experimental and control groups was found for the orange complex (P = 0.04). A greater amount of bacterial endotoxin was detected in the 0.12% chlorhexidine gluconate group than in the control group (P = 0.02). CONCLUSIONS: The 0.12% chlorhexidine gluconate oral rinses can be useful to reduce the levels of gram-negative periodontal pathogenic microorganisms in patients with fixed orthodontic appliances. Considering the increased amount of bacterial endotoxin after chlorhexidine gluconate use, further research is necessary to develop clinical procedures or antimicrobial agents with action against bacterial endotoxin adhering to metallic brackets.

Effect of S. mutans combinations with bifidobacteria/lactobacilli on biofilm and enamel demineralization.

The present study evaluated the ability of Bifidobacterium and Lactobacillus species associated with streptococci to increase insoluble extracellular polysaccharide (EPS) production and initial caries lesion progression. Bovine enamel blocks (n = 190; 4 mm x 4 mm) were prepared, selected according to initial surface hardness (SH), and divided into two groups: a) double combinations: S. mutans with Bifidobacterium or Lactobacillus, and b) triple combinations: S. mutans and S. sobrinus with Bifidobacterium or Lactobacillus species. The blocks were exposed to the bacterial associations for 7 days. Subsequently, quantity of EPS from biofilms and caries lesion depth were determined by means of colorimetric and cross-sectional enamel hardness (ΔKHN) analysis. The data were submitted to one-way analysis of variance, followed by the Bonferroni test (p < 0.05). S. mutans with B. animalis or B. dentium produced a higher quantity of EPS; S. mutans + B. animalis led to the highest ∆KHN. S. mutans + S. sobrinus + B. longum induced greater EPS and ∆KHN values. In conclusion, associations of B. animalis and B. longum with streptococci promoted EPS production and caries lesion progression.

Comparative in vitro investigation of the cariogenic potential of bifidobacteria.

OBJECTIVE: This study aimed to assess the in vitro cariogenic potential of some Bifidobacterium species in comparison with caries-associated bacteria. DESIGN: Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium dentium, Lactobacillus acidophilus, Lactobacillus casei, Actinomyces israelii, Streptococcus sobrinus and Streptococcus mutans were tested for acidogenicity and aciduricity by measuring the pH of the cultures after growth in glucose and bacterial growth after exposure to acid solutions. Biofilm biomass was determined for each species either alone or associated with S. mutans or S. mutans/S. sobrinus. Enamel hardness was analyzed before and after 7-days biofilm formation using bacterial combinations. RESULTS: B. animalis and B. longum were the most acidogenic and aciduric strains, comparable to caries-associated bacteria, such as S. mutans and L. casei. All species had a significantly increased biofilm when combined either with S. mutans or with S. mutans/S. sobrinus. The greatest enamel surface loss was produced when B. longum or B. animalis were inoculated with S. mutans, similar to L. casei and S. sobrinus. All strains induced similar enamel demineralization when combined with S. mutans/S. sobrinus, except by B. lactis. CONCLUSION: The ability to produce acidic environments and to enhance biofilm formation leading to increased demineralization may mean that Bifidobacterium species, especially B. animalis and B. longum, are potentially cariogenic.

Effect of S. mutans combinations with bifidobacteria/lactobacilli on biofilm and enamel demineralization

Abstract The present study evaluated the ability of Bifidobacterium and Lactobacillus species associated with streptococci to increase insoluble extracellular polysaccharide (EPS) production and initial caries lesion progression. Bovine enamel blocks (n = 190; 4 mm x 4 mm) were prepared, selected according to initial surface hardness (SH), and divided into two groups: a) double combinations: S. mutans with Bifidobacterium or Lactobacillus, and b) triple combinations: S. mutans and S. sobrinus with Bifidobacterium or Lactobacillus species. The blocks were exposed to the bacterial associations for 7 days. Subsequently, quantity of EPS from biofilms and caries lesion depth were determined by means of colorimetric and cross-sectional enamel hardness (ΔKHN) analysis. The data were submitted to one-way analysis of variance, followed by the Bonferroni test (p < 0.05). S. mutans with B. animalis or B. dentium produced a higher quantity of EPS; S. mutans + B. animalis led to the highest ∆KHN. S. mutans + S. sobrinus + B. longum induced greater EPS and ∆KHN values. In conclusion, associations of B. animalis and B. longum with streptococci promoted EPS production and caries lesion progression.

Papel de cepas de Streptococcus mutans e Bifidobacterium spp. na etiologia ou proteção contra doenças bucais / The role of Streptococcus mutans strains and Bifidobacterium spp. in the etiology or protection against oral diseases

A boca é um ecossistema complexo composto por centenas de espécies microbianas que apresentam características genotípicas e fenotípicas distintas que permitem sua adaptação e sobrevivência às adversidades desse ambiente. Streptococcus mutans é a espécie bacteriana mais relacionada à etiologia da cárie dentária, devido principalmente ao seu potencial acidogênico, acidúrico e na aderência e formação de biofilme dental. Outras espécies bacterianas, como as bifidobactérias, foram detectadas em diversos sítios bucais incluindo lesões cariosas iniciais ou cavitadas e estão sendo relacionadas à etiologia da cárie precoce da infância (CPI). Contrariamente, efeito benéfico na prevenção da doença periodontal tem sido observado para as bifidobactérias pelo fato dessas espécies competirem e interferirem na aderência e formação do biofilme de patógenos periodontais. Assim, ambiguidade em relação ao papel das bifidobactérias na etiologia ou prevenção de doenças bucais está sendo observada na literatura. Este trabalho foi dividido em três capítulos. Os objetivos foram: 1) avaliar a diversidade genotípica e as características fenotípicas de cepas de S. mutans, isoladas do biofilme dental de crianças CPI e CPI-severa (CPI-S) em comparação com crianças livres de cárie (LC); 2) avaliar a capacidade de produzir e tolerar ácidos, de formar biofilme e de induzir lesões iniciais de cárie in vitro por espécies de bifidobactérias comparadas à de espécies bacterianas já reconhecidas no contexto da cárie dentária e 3) investigar o efeito antagonista in vitro de algumas espécies de bifidobactérias sobre biofilmes de Fusobacterium nucleatum, Porphyromonas gingivalis e Streptococcus oralis. No capítulo 1, cepas de S. mutans de amostras de biofilme de crianças com CPI, CPI-S e LC foram isoladas em meio Agar Mitis Salivarius com bacitracina e avaliadas geneticamente pelo método de AP-PCR (Reação em Cadeia da Polimerase usando Iniciadores Arbitrários) e fenotipicamente pelos métodos de...

The mouth is a complex ecosystem composed of hundreds of microbial species with different genotypic and phenotypic characteristics that allow their adaptation and survival in the adversity of that environment. Streptococcus mutans is the bacterial species more closely related to the etiology of dental caries, mainly due to its acidogenic and aciduric potential and adherence and formation of dental biofilm. Other bacterial species, such as bifidobacteria, have been detected in oral sites including initial and cavitated carious lesions and have been related to the etiology of early childhood caries (ECC). In contrast, beneficial effect of bifidobacteria in the prevention of periodontal disease has been observed because they compete and interfere with the adherence and biofilm formation by periodontal pathogens. Thus, ambiguity regarding the role of bifidobacteria in the etiology or prevention of oral diseases has been observed in the literature. This work was divided into three chapters. The objectives were: 1) to evaluate the genotypic diversity and phenotypic characteristics of S. mutans strains isolated from dental biofilm of ECC and severe-ECC (S-ECC) children compared to caries-free children (CF); 2) to evaluate the ability to produce and tolerate acids, to form biofilm and inducing in vitro initial carious lesions by species of bifidobacteria compared to the bacterial species already recognized in the context of dental caries and 3) to investigate the in vitro antagonistic effect of some bifidobacteria species on biofilms of Fusobacterium nucleatum, Porphyromonas gingivalis and Streptococcus oralis. In Chapter 1, S. mutans strains from biofilm samples of children with ECC, S-ECC and CF were isolated in Agar Mitis Salivarius with bacitracin and genetically evaluated by AP-PCR method (Arbitrary Primers - Polymerase Chain Reaction) and phenotypically by acidogenicity methods, verifying the final pH of the cultures after exposure to high glucose concentration...

Papel de cepas de Streptococcus mutans e Bifidobacterium spp. na etiologia ou proteção contra doenças bucais / The role of Streptococcus mutans strains and Bifidobacterium spp. in the etiology or protection against oral diseases

A boca é um ecossistema complexo composto por centenas de espécies microbianas que apresentam características genotípicas e fenotípicas distintas que permitem sua adaptação e sobrevivência às adversidades desse ambiente. Streptococcus mutans é a espécie bacteriana mais relacionada à etiologia da cárie dentária, devido principalmente ao seu potencial acidogênico, acidúrico e na aderência e formação de biofilme dental. Outras espécies bacterianas, como as bifidobactérias, foram detectadas em diversos sítios bucais incluindo lesões cariosas iniciais ou cavitadas e estão sendo relacionadas à etiologia da cárie precoce da infância (CPI). Contrariamente, efeito benéfico na prevenção da doença periodontal tem sido observado para as bifidobactérias pelo fato dessas espécies competirem e interferirem na aderência e formação do biofilme de patógenos periodontais. Assim, ambiguidade em relação ao papel das bifidobactérias na etiologia ou prevenção de doenças bucais está sendo observada na literatura. Este trabalho foi dividido em três capítulos. Os objetivos foram: 1) avaliar a diversidade genotípica e as características fenotípicas de cepas de S. mutans, isoladas do biofilme dental de crianças CPI e CPI-severa (CPI-S) em comparação com crianças livres de cárie (LC); 2) avaliar a capacidade de produzir e tolerar ácidos, de formar biofilme e de induzir lesões iniciais de cárie in vitro por espécies de bifidobactérias comparadas à de espécies bacterianas já reconhecidas no contexto da cárie dentária e 3) investigar o efeito antagonista in vitro de algumas espécies de bifidobactérias sobre biofilmes de Fusobacterium nucleatum, Porphyromonas gingivalis e Streptococcus oralis. No capítulo 1, cepas de S. mutans de amostras de biofilme de crianças com CPI, CPI-S e LC foram isoladas em meio Agar Mitis Salivarius com bacitracina e avaliadas geneticamente pelo método de AP-PCR (Reação em Cadeia da Polimerase usando Iniciadores Arbitrários) e fenotipicamente pelos métodos de...

The mouth is a complex ecosystem composed of hundreds of microbial species with different genotypic and phenotypic characteristics that allow their adaptation and survival in the adversity of that environment. Streptococcus mutans is the bacterial species more closely related to the etiology of dental caries, mainly due to its acidogenic and aciduric potential and adherence and formation of dental biofilm. Other bacterial species, such as bifidobacteria, have been detected in oral sites including initial and cavitated carious lesions and have been related to the etiology of early childhood caries (ECC). In contrast, beneficial effect of bifidobacteria in the prevention of periodontal disease has been observed because they compete and interfere with the adherence and biofilm formation by periodontal pathogens. Thus, ambiguity regarding the role of bifidobacteria in the etiology or prevention of oral diseases has been observed in the literature. This work was divided into three chapters. The objectives were: 1) to evaluate the genotypic diversity and phenotypic characteristics of S. mutans strains isolated from dental biofilm of ECC and severe-ECC (S-ECC) children compared to caries-free children (CF); 2) to evaluate the ability to produce and tolerate acids, to form biofilm and inducing in vitro initial carious lesions by species of bifidobacteria compared to the bacterial species already recognized in the context of dental caries and 3) to investigate the in vitro antagonistic effect of some bifidobacteria species on biofilms of Fusobacterium nucleatum, Porphyromonas gingivalis and Streptococcus oralis. In Chapter 1, S. mutans strains from biofilm samples of children with ECC, S-ECC and CF were isolated in Agar Mitis Salivarius with bacitracin and genetically evaluated by AP-PCR method (Arbitrary Primers - Polymerase Chain Reaction) and phenotypically by acidogenicity methods, verifying the final pH of the cultures after exposure to high glucose concentration...