Critical Reviews in Oral Biology & Medicine

Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host’s immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response—in particular, CD4⁺ T-cells—plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host’s tissue destruction. In particular, studies of the pathogen-specific CD4⁺ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4⁺ T-cell-mediated osteoclastogenic factor, ‘RANK-L’, which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8⁺ T-cells, and CD4⁺ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

Abbreviations used in the paper are as follows: Antibody, Ab; antigen, Ag; antigen-presenting cells, APC; Actinobacillus actinomycetemcomitans, A. actinomycetemcomitans or Aa; β₂-microglobulin, β₂m; cytotoxic CD8⁺ αβ T-lymphocytes, CTL; dendritic cells, DC; delayed-type hypersensitivity, DTH; immunoglobulin, Ig; Fc receptor, Fc-R; interferon-γ, IFN-γ; receptor activator of NF-κB ligand, RANK-L; molecular weight, MW; Porphyromonas gingivalis, P. gingivalis or Pg; localized juvenile periodontitis, LJP; lipopolysaccharide, LPS; mouse mammalian tumor virus, MMTV; non-obese diabetic and severe combined immunodeficiency mice, NOD/SCID mice; osteoclast, OC; T-helper cells, Th; superantigen, SAg; transforming growth factor-β, TGF-β; secretory-IgA, s-IgA; T-cell receptor, TCR; T cytotoxic-1 cells, Tc1; and T cytotoxic-2 cells, Tc2.

Chronic hyperplastic candidosis/candidiasis (CHC; syn. candidal leukoplakia) is a variant of oral candidosis that typically presents as a white patch on the commissures of the oral mucosa. The major etiologic agent of the disease is the oral fungal pathogen Candida predominantly belonging to Candida albicans, although other systemic co-factors, such as vitamin deficiency and generalized immune suppression, may play a contributory role. Clinically, the lesions are symptomless and regress after appropriate antifungal therapy and correction of underlying nutritional or other deficiencies. If the lesions are untreated, a minor proportion may demonstrate dysplasia and develop into carcinomas. This review outlines the demographic features, etiopathogenesis, immunological features, histopathology, and the role of Candida in the disease process. In the final part of the review, newer molecular biological aspects of the disease are considered together with the management protocols that are currently available, and directions for future research.

Oral fungal infections (mycoses) have come into particular prominence since the advent of infection with Human Immunodeficiency Virus (HIV), and recognition of the Acquired Immune Deficiency Syndrome (AIDS), as well as the phenomenal increase in world travel with increased exposure to infections endemic in the tropics. Paracoccidioidomycosis is a rare mycosis worldwide but common in Brazil and some other areas in Latin America. It can be life-threatening and can manifest with a spectrum of clinical presentations, including frequent oral lesions. This paper reviews the more recent information on Paracoccidioidomycosis, emphasizing those areas most relevant in dental science.

Burning Mouth Syndrome (BMS) is a chronic pain syndrome that mainly affects middle-aged/old women with hormonal changes or psychological disorders. This condition is probably of multifactorial origin, often idiopathic, and its etiopathogenesis remains largely enigmatic. The present paper discusses several aspects of BMS, updates current knowledge, and provides guidelines for patient management. There is no consensus on the diagnosis and classification of BMS. The etiopathogenesis seems to be complex and in a large number of patients probably involves interactions among local, systemic, and/or psychogenic factors. In the remaining cases, new interesting associations have recently emerged between BMS and either peripheral nerve damage or dopaminergic system disorders, emphasizing the neuropathic background in BMS. Based on these recent data, we have introduced the concepts of “primary” (idiopathic) and “secondary” (resulting from identified precipitating factors) BMS, since this allows for a more systematic approach to patient management. The latter starts with a differential diagnosis based on the exclusion of both other orofacial chronic pain conditions and painful oral diseases exhibiting muco-sal lesions. However, the occurrence of overlapping/overwhelming oral mucosal pathologies, such as infections, may cause difficulties in the diagnosis ("complicated BMS"). BMS treatment is still unsatisfactory, and there is no definitive cure. As a result, a multidisciplinary approach is required to bring the condition under better control. Importantly, BMS patients should be offered regular follow-up during the symptomatic periods and psychological support for alleviating the psychogenic component of the pain. More research is necessary to confirm the association between BMS and systemic disorders, as well as to investigate possible pathogenic mechanisms involving potential nerve damage. If this goal is to be achieved, a uniform definition of BMS and strict criteria for its classification are mandatory.

Present tooth-bleaching techniques are based upon hydrogen peroxide as the active agent. It is applied directly, or produced in a chemical reaction from sodium perborate or carbamide peroxide. More than 90% immediate success has been reported for intracoronal bleaching of non-vital teeth, and in the period of 1–8 years’ observation time, from 10 to 40% of the initially successfully treated teeth needed re-treatment. Cervical root resorption is a possible consequence of internal bleaching and is more frequently observed in teeth treated with the thermo-catalytic procedure. When the external tooth-bleaching technique is used, the first subjective change in tooth color may be observed after 2–4 nights of tooth bleaching, and more than 90% satisfactory results have been reported. Tooth sensitivity is a common side-effect of external tooth bleaching observed in 15%-78% of the patients, but clinical studies addressing the risk of other adverse effects are lacking. Direct contact with hydrogen peroxide induced genotoxic effects in bacteria and cultured cells, whereas the effect was reduced or abolished in the presence of metabolizing enzymes. Several tumor-promoting studies, including the hamster cheek pouch model, indicated that hydrogen peroxide might act as a promoter. Multiple exposures of hydrogen peroxide have resulted in localized effects on the gastric mucosa, decreased food consumption, reduced weight gain, and blood chemistry changes in mice and rats. Our risk assessment revealed that a sufficient safety level was not reached in certain clinical situations of external tooth bleaching, such as bleaching one tooth arch with 35% carbamide peroxide, using several applications per day of 22% carbamide peroxide, and bleaching both arches simultaneously with 22% carbamide peroxide. The recommendation is to avoid using concentrations higher than 10% carbamide peroxide when one performs external bleaching. We advocate a selective use of external tooth bleaching based on high ethical standards and professional judgment.

Dental clinicians are confronted with an increasing number of medically compromised patients who require implant surgery for their oral rehabilitation. However, there are few guidelines on dental implant therapy in this patient category, so that numerous issues regarding pre- and post-operative management remain unclear to the dental clinician. Therefore, the aim of the present review is to offer a critical evaluation of the literature and to provide the clinician with scientifically based data for implant therapy in the medically compromised patient. This review presents the current knowledge regarding the influence of the most common systemic and local diseases on the outcome of dental implant therapy, e.g., abnormalities in bone metabolism, diabetes mellitus, xerostomia, and ectodermal dysplasias. Specific pathophysiologic aspects of the above-mentioned diseases as well as their potential implications for implant success are critically appraised. In line with these implications, guidelines for pre- and post-operative management that may assist in the successful implant-supported rehabilitation of this patient category are proposed.