Biologics in oral medicine: ulcerative disorders.

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.

Biologics in oral medicine: Sjogren syndrome.

Oral Diseases (2012) doi:10.1111/j.1601-0825.2012.01932.x Biologic therapy has a potential to benefit patients with orofacial manifestations of Sjogren syndrome (SS). The most appropriate use of biologics would appear to be in patients with severe or multisystem features of SS, but their use early in the pathogenesis has the potential to prevent disease progression. Tumour necrosis factor-alpha blockade has not proven effective in SS. B-cell depletion using rituximab has been of benefit, mainly in relation to extraglandular features, and to some extent in relation to hyposalivation where there is still residual salivary function. Rituximab is also effective in the treatment of SS-associated (extrasalivary) lymphomas, although the therapeutic response in salivary lymphoma is poorer. Rituximab is given as a single or periodic intravenous infusion. Potential adverse effects exist, notably infusion reactions and infection, and so a full risk/benefit analysis is indicated for prospective patients. This and clinical use is best performed and monitored in conjunction with rheumatologists with appropriate training and experience in biologic therapies. Further studies of rituximab in SS are ongoing, and newer agents under trial include belimumab.

Biologics in oral medicine: oral Crohn's disease and orofacial granulomatosis.

Antitumour necrosis factor (TNF-α) therapy has a potential to benefit patients with oral lesions of Crohn's disease (CD) and patients with orofacial granulomatosis (OFG). The most appropriate use would appear to be in patients with severe or multisystem features, where other available agents have failed or have been associated with adverse effects. TNF-α antagonists (infliximab in particular) have a role in the management of orofacial CD and OFG, but potential adverse effects of TNF-α antagonists include acute infusion reactions, infection and increased risk of malignancy. Thus, a full risk-benefit analysis is indicated, with patient selection, use and subsequent monitoring coordinated with gastroenterologists with appropriate training and experience in biological therapies.

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.

Efficacy of tumour necrosis factor-α antagonists in aphthous ulceration: review of published individual patient data.

BACKGROUND: Severe aphthous ulceration may require systemic immunosuppressive or immunomodulatory therapy, but a small subset of patients remains resistant to or intolerant of these agents. Although use of TNF-α antagonists in aphthous ulceration is increasingly reported, the current evidence base for use is weak and evaluation of individual cases may provide the best available data to support such use. OBJECTIVES: The aim of this study was to review all published data on the use of TNF-α antagonists in patients with severe aphthous ulceration refractory to systemic agents and discusses this in the context of any possible benefits that may guide any future use. METHODS: A comprehensive search on MEDLINE and EMBASE from 1995 to 2010 was performed using pre-defined search terms, with articles included if they met specific criteria. RESULTS: Sixteen cases from individual case reports or small case-series in which use of TNF-α antagonists in aphthous ulceration were identified in which details of previous systemic therapy and use of subsequent adjunctive therapy were available. Agents with reported success in resolving active ulceration and reducing ulcer recurrence were infliximab, etanercept and adalimumab. CONCLUSIONS: Evidence for efficacy of TNF-α antagonists in aphthous ulceration infection is limited. Such data suggest that in patients with severe aphthous ulceration TNF-α antagonists have some efficacy in inducing ulcer resolution and reducing recurrence. These agents may represent an option in severe refractory aphthosis, although in the absence of controlled studies, caution is advocated if use is to be considered.

Odontogenic myxoma in an adolescent with tuberous sclerosis.

Tuberous sclerosis is a hamartoneoplastic syndrome characterised by early onset of convulsive seizures with mental retardation. Oral abnormalities, including enamel hypoplasia and mucosal fibromas, have been previously reported. We report here a 17-year-old girl with this disorder who had received repeated dental trauma. She presented with a swelling associated with a traumatised maxillary central incisor that suggested a diagnosis other than the odontogenic myxoma found at operation. Odontogenic myxoma has not previously been reported in this condition; it may represent an unusual phenotypic expression of the genetic defect understood to determine tuberous sclerosis, or it may be an unrelated coincidental finding.