Systemic use of non‐biologic agents in orofacial diseases: other immunomodulatory agents

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most importantly the corticosteroids (steroids). Previous articles by us in this series have discussed systemic use of corticosteroids and purine synthesis inhibitors; the other immunomodulating agents (calcineurin inhibitors, thalidomide, dapsone, colchicine and cyclophosphamide) are reviewed in this final article.     

Systemic use of non‐biologics in orofacial diseases: 2. Purine synthesis inhibitors

Systemic non‐biological agents (NBAs) have been extensively used for immunosuppression in clinical medicine, often with considerable efficacy, although sometimes accompanied with adverse effects as with all medicines. With the advent of biological agents, all of which currently are restricted to systemic use, there is a rising need to identify which agents have the better therapeutic ratio. The NBAs include a range of agents, most especially the corticosteroids (corticosteroids). This article reviews the purine synthesis inhibitors (azathioprine and mycophenolate), which are currently the most commonly used systemically immunosuppressive agents in the management of orofacial mucocutaneous diseases. Subsequent articles discuss other corticosteroid‐sparing agents used in the management of orofacial disease, such as calcineurin inhibitors, and the cytotoxic and other immunomodulatory agents.     

Orofacial adverse effects of biological agents

Biological agents (BA) are increasingly used effectively in the treatment of a range of disorders, but to date, their application in diseases affecting the orofacial region has been fairly limited. Several orofacial adverse effects related to BA have been recently reported. However, the evidence for such adverse reactions is not always strong, and some of the adverse effects of BA have only been reported in case reports or case series. Most reactions to BA reported thus far have been in association with antitumor necrosis factor‐α agents, which is not surprising, as these are the most widely‐used BA. In the present study, the orofacial adverse effects are reported with various BA in order to sensitize clinicians to the possibilities. In addition, we briefly summarize the mode of action and indications of these BA. As the use and range of BA increases, the number and diversity of adverse effects might well increase. Despite the adverse effects of biological agents, these may often be less serious than the adverse effects of the more traditional immunosuppressive agents.     

Role of oral medicine in the teaching of temporomandibular disorders and orofacial pain

This paper discusses the role of oral medicine in the teaching of temporomandibular disorders (TMD) and orofacial pain. Education in orofacial pain and TMD has traditionally been managed in academic dental settings as 2 distinct processes separate from the teaching of diagnosis and management as applied to systemic diseases and oral conditions. The rationale for such a segmented approach appears to have been driven by the concept that orofacial pain usually reflects a localized disease rather than arising as a component of more generalized systemic disease or modulated in intensity or morbidity by systemic pathology, generalized neurobiological, or behavioral contributors. Conversely, oral disease and head and neck manifestations of systemic disease often provoke pain as a major symptom. Management of such conditions should include acute and long-term pain management strategies when the underlying condition has no definitive cure and the pain is disabling. An argument is made for integrating the teaching of oral medicine and orofacial pain to enhance a broad-based approach to the assessment and management of primary pain disorders and to assure appropriate management of pain that is associated with mucosal disease and other forms of regional or systemic pathology including behavioral disorders that present as somatic and painful complaints.     

Ancillary factors in the treatment of orofacial pain: A topical narrative review

Ancillary factors, not directly related to treatment, often play a significant role by affecting therapeutic outcome. A search of the literature was conducted including words related to the placebo phenomenon and orofacial diseases. Therefore, critical factors have been grouped into three major categories: (a) the natural course of the diseases; (b) the regression of the symptoms to their mean intensity; and (c) placebo response. This topical narrative review describes the elements mentioned above, provides an up‐to‐date overview of the hot topics and gaps in the field and indicates developing and future research direction of the orofacial pain field. Such a knowledge might be positively used during daily clinical practice to optimise the management of orofacial pain diseases, as well as in conducting future clinical trials for validating new interventions.     

Topical review-connective tissue diseases: orofacial manifestations including pain

This topical review presents an overview of orofacial manifestations associated with the more common connective tissue diseases affecting multiple organs. The orofacial manifestations associated with these autoimmune disorders include oral mucosa alterations, salivary gland pathosis, sensory neuropathies, headaches, and temporomandibular disorders. Since many of these orofacial manifestations may be painful, the practitioner managing pain patients should be familiar with them. An understanding of the orofacial manifestations associated with these systemic diseases will enable the pain practitioner to establish an appropriate diagnosis within the context of the underlying systemic disease. This will allow the practitioner the opportunity to contribute and collaborate as a member of a multidisciplinary health-care team in the management of these systemic autoimmune diseases.     

Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice

BACKGROUND: In recent years, dental practitioners have relied on ibuprofen and other nonsteroidal anti-inflammatory drugs, or NSAIDs--such as naproxen, diflunisal and ketoprofen--to manage acute and chronic orofacial pain. Two NSAIDs that recently came on the market, celecoxib and rofecoxib, have been developed to limit the adverse effects seen after chronic use of NSAIDs. LITERATURE REVIEWED: The authors have summarized all available publications describing the human pharmacokinetics, clinical pharmacology and known adverse effects of these new specific cyclooxygenase-2, or COX-2, inhibitors. CONCLUSIONS: Although peripherally acting analgesics are remarkably effective, chronic administration of nonselective COX inhibitors has been associated with gastrointestinal ulceration and prolonged bleeding. The authors present the distinctive mechanism of action for these new COX-2 inhibitors, compare their relative anti-inflammatory and analgesic properties and describe their safety profile. They also summarize indications, contraindications and dosing recommendations. CLINICAL IMPLICATIONS: Celecoxib and rofecoxib are valuable dental therapeutic agents for the management of inflammatory joint disorders and associated chronic orofacial pain. Additionally, rofecoxib, with its more rapid onset, may be useful in treating selected cases of acute postsurgical pain.     

Orofacial diseases in solid organ and hematopoietic stem cell transplant recipients

Oral Diseases (2012) 19 , 18–36 Objective: Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at risk of several diseases, principally attributable to immunosuppression. This global overview of SOT/HSCT‐associated orofacial diseases is aimed at providing a practical instrument for the oral healthcare management of SOT/HSCT recipients. Methods: Literature search was made through MEDLINE. The associations between orofacial diseases and SOT/HSCT were assessed using observational studies and case series and were classified into ‘association’, ‘no association’, and ‘unclear association’. Results: Lip/oral cancers, drug‐induced gingival overgrowth (DIGO), infections, including hairy leukoplakia and, less frequently, post‐transplantation lymphoproliferative disorders (PTLDs) and oral lichenoid lesions of graft‐versus‐host disease (GVHD), were associated with SOT. Lip/oral cancers, GVHD, mucositis, DIGO, infections and, less frequently, PTLDs were associated with HSCT. Associations of orofacial granulomatosis‐like lesions and oral mucosa‐associated lymphoid tissue‐type lymphoma with SOT, and of pyogenic granuloma and hairy leukoplakia with HSCT were unclear. Periodontal disease and dental caries were not associated with SOT/HSCT. For none of the local treatments was there a strong evidence of effectiveness. Conclusions: Solid organ transplant/HSCT recipients are at risk of orofacial diseases. Adequate management of these patients alleviates local symptoms responsible for impaired eating, helps prevent systemic and lethal complications, and helps where dental healthcare has been neglected.     

Effects of long‐term use of HAART on oral health status of HIV‐infected subjects

J Oral Pathol Med (2010) 39 : 397–406 Background: The aim of this study was to determine the effects of long‐term use of highly active antiretroviral therapy (HAART) on oral health status of HIV‐infected subjects. Methods: Oral examination and measurement of saliva flow rate of both unstimulated and wax‐stimulated whole saliva were performed in HIV‐infected subjects with and without HAART, and in non‐HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long‐term use of HAART on oral health status of HIV‐infected subjects. Results: One hundred and fifty‐seven HIV‐infected subjects – 99 on HAART (age range 23–57 years, mean 39 years) and 58 not on HAART (age range 20–59 years, mean 34 years) – and 50 non‐HIV controls (age range 19–59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV‐infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short‐term HAART (P < 0.01). The subjects with long‐term HAART were found to have a greater risk of having oral lesions than those with short‐term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). Conclusion: We conclude that long‐term HAART has adverse effects on oral health status of HIV‐infected subjects.     

The COX-2 inhibitors: new analgesic and anti-inflammatory drugs

Selective COX-2 inhibitors offer a therapeutic alternative to the conventional nonselective NSAIDs. Rofecoxib has been demonstrated to be a valuable therapeutic agent in the management of acute orofacial pain. Selective COX-2 inhibitors are also indicated in patients who are likely to undergo surgery or invasive procedures in the near future because these drugs do not prolong the bleeding time. The efficacy of these drugs in the management of chronic orofacial pain is yet to be evaluated. The pharmacoeconomic impact of COX-2 inhibitors must also be considered, as the cost of selective COX-2 inhibitors is considerably higher than the other commonly used NSAIDs. Although it is clear that COX-2 inhibitors offer some advantages over the nonselective NSAIDs in terms of a lower risk of GI toxicity with long-term use, the effects following short-term use are still unclear. Until more data are available, COX-2 inhibitors should be avoided or used with the same caution as for conventional NSAIDs in patients with compromised renal and cardiac function.     

Biologics in oral medicine: ulcerative disorders

Oral Diseases (2012) 19 , 37–45 Inflammatory ulcerative diseases of the oral mucosa are wide ranging but include especially aphthous and aphthous‐like ulceration, vesiculobullous disorders and erosive lichen planus (LP). While most patients with these conditions respond to conventional topical and/or systemic immunosuppressive agents, treatment‐resistant cases remain challenging. In these, the use of biologics such as tumour necrosis factor alpha (TNF‐α) inhibitors or rituximab may be of benefit. This article reviews the use of biologics in ulcerative oral conditions, highlighting potential benefits, adverse effects and principles of use and future developments. TNF‐α inhibitors such as infliximab can be effective in inducing resolution in oral aphthous and aphthous‐like ulcers and may be an appropriate therapy in those patients in which disease is severe and refractory to, or patients are intolerant of, traditional immunomodulatory regimens. There would also seem support and rationale for use of biologics (mainly rituximab) in pemphigus but not in oral LP or other oral ulcerative conditions.     

Vesiculo-erosive oral mucosal disease--management with topical corticosteroids: (1) Fundamental principles and specific agents available

Vesiculo-erosive diseases of the oral mucosa pose a major challenge in oral medicine, because they are chronic, painful, and interfere with the daily activities and quality of life of the patients, including disturbing eating, drinking, talking, and personal relationships. Many are autoimmune diseases, and corticosteroid therapy is currently central to their treatment. These diseases present with inflammation and alterations to epithelial integrity, through cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets. Until recently, despite their serious adverse effects, it was necessary to prescribe systemic corticosteroids to control severe erosive oral diseases. Now, however, many of these diseases can be controlled by high-potency topical corticosteroids, which have proved to be highly efficacious and to cause fewer adverse effects compared with systemic corticosteroids. Nevertheless, although topical corticosteroids are still the most widely used drugs in the practice of oral medicine, the scientific body of evidence for their use in the oral cavity is virtually non-existent, and therefore many of the protocols followed are, of necessity, drawn from experience of their use in a dermatological setting. This review aims to set out the key aspects of the use of topical corticosteroids in oral medicine. The issues covered include the indications and basic rules for their use, the types of corticosteroids, the drug selection, and the specific formulations.     

An uncommon presentation of an inflammatory gingival enlargement--responding to non-surgical periodontal therapy

To cite this article:
Int J Dent Hygiene 9 , 2011; 303–307 DOI: 10.1111/j.1601‐5037.2010.00497.x
Agrawal N, Agrawal K, Mhaske S. An uncommon presentation of an inflammatory gingival enlargement – responding to non‐surgical periodontal therapy. Abstract: Background: The various clinical manifestations of inflammatory gingival enlargement reported are more or less similar regardless of the underlying aetiological factors. Unusual presentation and unknown aetiology pose a diagnostic challenge for a periodontist. Methods: A 34‐year‐old Indian woman presented with the complaint of gum swelling that was sessile, lobulated, soft in consistency and bluish red in colour with ulcerated surface in some region, which was covered by the necrotic slough. This type of enlargement was unusual and some underlying systemic pathology was suspected. But a written consultation from her physician confirmed her systemic health, which was based on clinical, radiological and haematological investigations. Histopathological examination confirmed the diagnosis of inflammatory gingival enlargement. Patient was treated with oral hygiene instructions, scaling and root planning. Result: Within a month of conventional periodontal therapy, gum enlargement reduced markedly and patient was put on oral hygiene maintenance programme. Conclusion: Periodontal therapy is diagnosis‐driven and, to the extent possible, should address all the possible factors that impact development and progression of diseases that may affect periodontal tissue. In plaque‐induced periodontal diseases, non‐surgical periodontal therapy is still a gold standard among all the therapies available.     

Detection of halitosis in breath: Between the past,present, and future

To develop a new generation of diagnostics for halitosis, replacing the subjective organoleptic assessment, a series of exhaled breath analyzers has been developed and assessed. All three devices rely on the assessment of exhaled volatile sulfuric compounds (VSCs), which are mainly generated in and emitted from the oral cavity, contributing to the malodor. Portable, on‐site and easy to use, these devices have potential for non‐invasive diagnosis of halitosis. However, global assessment of exhaled VSCs alone has two main drawbacks: (i) the absence of VSCs does not rule out halitosis; (ii) non‐sulfuric volatile compounds that could be biomarkers of systemic diseases, found in up to 15% of halitosis cases, are neglected. In this article, we review and discuss progress to date in the field of oral/exhaled volatile compounds as potential non‐invasive diagnostics for halitosis. We will briefly describe the generation of these compounds both from local (oral) and distal (extra‐oral) sources. In addition, we debate the different analytical approaches in use and discuss the potential value of bio‐inspired artificially intelligent olfaction in diagnosing and classifying oral and systemic diseases by analyzing exhaled breath.     

Position paper: appropriate use of pharmacotherapeutic agents by the orofacial pain dentist

Orofacial Pain Dentistry is concerned with the prevention, evaluation, diagnosis, treatment, and management of persistent and recurrent orofacial pain disorders. The American Dental Association, through the Commission on Dental Accreditation (CODA), now recognizes Orofacial Pain as an area of advanced education in Dentistry. It is mandated by CODA that postgraduate orofacial pain programs be designed to provide advanced knowledge and skills beyond those of the standard curriculum leading to the DDS or DMD degrees. Postgraduate programs in orofacial pain must include specific curricular content to comply with CODA standards. The intent of CODA standards is to assure that training programs develop specific educational goals and objectives that describe the student/resident’s expected knowledge and skills upon successful completion of the program. A standardized core curriculum, required for accreditation of dental orofacial pain training programs, has now been adopted.Among the various topics mandated in the curriculum are pharmacology and, specifically, pharmacotherapeutics. The American Academy of Orofacial Pain (AAOP) recommends, and the American Board of Orofacial Pain (ABOP) requires, that the minimally competent orofacial pain dentist* be knowledgeable in the management of orofacial pain conditions using medications when indicated. Basic knowledge of the appropriate use of pharmacotherapeutics is essential for the orofacial pain dentist and, therefore, constitutes part of the examination specifications of the ABOP. The minimally competent orofacial pain clinician must demonstrate knowledge, diagnostic skills, and treatment expertise in many areas, such as musculoskeletal, neurovascular, and neuropathic pain syndromes; sleep disorders related to orofacial pain; orofacial dystonias; and intraoral, intracranial, extracranial, and systemic disorders that cause orofacial pain or dysfunction. The orofacial pain dentist has the responsibility to diagnose and treat patients in pain that is often chronic, multifactorial, and complex. Failure to understand pain mechanisms can lead to inaccurate diagnoses and ineffective, delayed, or harmful treatment. It is the responsibility of the orofacial pain dentist to accurately diagnose the cause(s) of the pain and decide if treatment should be dentally, medically, or psychologically oriented, or if optimal management requires a combination of all three treatment approaches. Management may consist of a number of interdisciplinary modalities including, eg, physical medicine, behavioral medicine, and pharmacology or, in rare instances, surgical interventions. Among the essential armamentarium is the knowledge and proper use of pharmacologic agents.     

Biologics in oral medicine: principles of use and practical considerations

Oral Diseases (2012) 18, 525-536 Biologic therapies are relatively innovative treatments aimed at modulating lymphocytes or cytokines. There are currently three broad classes of biologic therapies, tumour necrosis factor-alpha inhibitors, lymphocyte modulators and interleukin inhibitors; all are increasingly used in the treatment of inflammatory immune-mediated conditions, and several have potential applications in oral medicine. Guidelines for their use in licensed indications (e.g. rheumatoid arthritis, psoriasis, inflammatory bowel disease) include recommendations and guidance for patient selection and subsequent monitoring with discussion of potential adverse effects. An understanding of these is important when managing patients receiving biologic therapy for systemic disease, and compliance is essential in any use in oral medicine. Key aspects of current guidance are presented with particular emphasis on their relevance to clinicians working within oral and maxillofacial medicine/pathology/surgery and in specialist practice.     

Orofacial and dental trauma of young children in Dunedin,New Zealand

Abstract – Aim: The aims were to identify the predominant causes and types of orofacial injury in young children attending clinics at a University Dental School in Dunedin, New Zealand. Material and methods: A retrospective analysis of data from the records of all children aged 0–10 years who had been seen for orofacial trauma in 1999 and 2000 was undertaken. Results and conclusions: Three hundred traumatic incidents in 288 children were analysed; 86.6% had causes noted. In very young children, most injuries were because of falls, while collisions, falling and sports were responsible for more injuries in school‐aged children. Playground equipment and ride‐on vehicles played a role particularly in the older children. There were no incidents of trauma as a result of road traffic accidents. Ten injuries were caused by animals, mainly dogs. Location was recorded for two‐thirds of accidents: the predominant place was at home, followed by school. No seasonal variation was apparent. There were 228 non‐dental injuries, of which the majority were to the lips. The predominant dental injuries in both dentitions were concussions and subluxations with a significantly higher occurrence of both in the primary dentition (P < 0.001). Upper central incisors were most often involved. The age distribution for boys and girls was similar. In conclusion, the causes and types of orofacial trauma in this group of young New Zealand school children attending a university dental school were similar to other studies, except for the high proportion of concussions recorded in both dentitions. While the injuries were well described, not all records noted the cause or location. This has resulted in changes to the standard recording form to provide consistency in data capture. Information from this study will also be used to support child injury prevention strategies in New Zealand.     

Mouse mandible contains distinctive mesenchymal stem cells

Although human orofacial bone-marrow-derived mesenchymal stem cells showed differentiation traits distinctly different from those of mesenchymal stem cells (MSCs) derived from long bone marrow (BMMSCs), mouse MSCs derived from orofacial bone have not been isolated due to technical difficulties, which in turn precludes the use of mouse models to study and cure orofacial diseases. In this study, we developed techniques to isolate and expand mouse orofacial bone/bone-marrow-derived MSCs (OMSCs) from mandibles and verified their MSC characteristics by single-colony formation, multi-lineage differentiation, and in vivo tissue regeneration. Activated T-lymphocytes impaired OMSCs via the Fas/Fas ligand pathway, as occurs in BMMSCs. Furthermore, we found that OMSCs are distinct from BMMSCs with respect to regulating T-lymphocyte survival and proliferation. Analysis of our data suggests that OMSCs are a unique population of MSCs and play an important role in systemic immunity. Abbreviations: BMMSC, bone marrow mesenchymal stem cell; HA/TCP, hydroxyapatite/tricalcium phosphate; OMSC, orofacial mesenchymal stem cell; OVX, ovariectomized.