Oral chronic graft-versus-host disease: What the general dental practitioner needs to know.

BACKGROUND: Long-term survivors of allogeneic hematopoietic cell transplantation will increasingly seek care from dental providers. METHODS: The authors highlight the importance of minimizing oral symptoms and complications associated with oral chronic graft-versus-host-disease (cGVHD). RESULTS: Chronic GVHD is the result of an immune response of donor-derived cells against recipient tissues. Oral cGVHD can affect the mucosa and damage salivary glands and cause sclerotic changes. Symptoms include sensitivity and pain, dry mouth, taste changes, and limited mouth opening. Risk of developing caries and oral cancer is increased. Food intake, oral hygiene, and dental interventions can represent challenges. Oral cGVHD manifestations and dental interventions should be managed in close consultation with the medical team, as systemic treatment for cGVHD can have implications for dental management. CONCLUSIONS: General dental practitioners can contribute substantially to alleviating oral cGVHD involvement and preventing additional oral health deterioration. PRACTICAL IMPLICATIONS: Frequent examinations, patient education, oral hygiene reinforcement, dry mouth management, caries prevention, and management of dental needs are indicated. In addition, oral physical therapy might be needed. Invasive dental interventions should be coordinated with the transplantation team. Screening for oral malignancies is important even years after resolution of GVHD symptoms. Management of the oral manifestations of cGVHD might require referral to an oral medicine professional.

Exploring the role of oral microorganisms in the pathogenesis of mucositis by assessing their impact on metabolic activity and reproductive capacity of epithelial cells in vitro.

PURPOSE: Clinical and in vitro studies showed selected oral microorganisms to be related to delayed wound healing and ulcerative oral mucositis. However, it is not known whether this effect is due to reduced metabolism and/or the reduced reproductive capacity of epithelial cells. Therefore, we studied the influence of the oral microorganisms Porphyromonas gingivalis, Candida glabrata, and Candida kefyr on cell metabolism and reproductive capacity of oral epithelial cells, aimed to further unravel the pathogenesis of oral mucositis. METHODS: Oral epithelial cells were exposed to different concentrations of P. gingivalis, C. glabrata, and C. kefyr as mono-infections or mixed together. An MTT assay was performed to determine the effect on cell metabolism. A clonogenic assay was used to study the effect on the reproductive capacity of oral epithelial cells. RESULTS: The metabolism of oral epithelial cells was reduced when the microorganisms were present in high concentrations: P. gingivalis at a multiplicity of infection (MOI) of 1000 and the Candida spp. at MOI 100. No statistical difference was observed in the ability of a single epithelial cell to grow into a colony of cells between control and P. gingivalis, C. glabrata, and C. kefyr, independent of the concentrations and combinations used. CONCLUSION: P. gingivalis, C. glabrata, and C. kefyr lowered the metabolic activity of oral epithelial cells in high concentrations, yet they did not influence the reproductive capacity of epithelial cells. Their impact on ulcerative oral mucositis is likely due to an effect on the migration, proliferation, and metabolism of epithelial cells.

Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients.

The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.

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.