Australian Dental Journal
The official journal of the Australian Dental Association
Australian Dental Journal 2015; 60:(1 Suppl): 44–53 doi: 10.1111/adj.12283
Oral medicine and the ageing population T Yap,* M McCullough* *Melbourne Dental School, The University of Melbourne, Victoria, Australia.
ABSTRACT The oral cavity is subject to age related processes such as cellular ageing and immunosenescence. The ageing population bears an increased burden of intraoral pathology. In oral medicine, the majority of presenting patients are in their fifth to seventh decade of life. In this review, we discuss the ageing population’s susceptibility to mucosal disorders and the increased prevalence of potentially malignant disorders and oral squamous cell carcinoma, as well as dermatoses including oral lichen planus and immunobullous conditions. We also address the ageing population’s susceptibility to oral discomfort and explore salivary secretion, ulceration and the symptoms of oral burning. Finally, we will describe orofacial pain conditions which are more likely encountered in an older population. This update highlights clinical presentations which are more likely to be encountered in the ageing population in a general practice setting and the importance of screening both new and long-term patients. Keywords: Ageing, mucosal, oral medicine. Abbreviations and acronyms: BMS = burning mouth syndrome; CLE = cutaneous lupus erythematosus; DAES = denture associated erythematous stomatitis; DLE = discoid lupus erythematosus; GCA = giant cell arteritis; LP = lichen planus; MMP = mucous membrane pemphigoid; MRG = median rhomboid glossitis; OLP = oral lichen planus; OSCC = oral squamous cell carcinoma; PMD = potentially malignant disorders; RAS = recurrent aphthous ulceration; TMD = temporomandibular disorders; TMJ = temporomandibular joint; TN = trigeminal neuralgia.
INTRODUCTION Human life expectancy has increased dramatically in the past century, particularly in developed countries. Fourteen per cent of the Australian population, or 3.22 million people, were over the age of 65 in 2012.1 As the number of older people continues to rise, oral health care must be tailored to address specific issues affecting the home, hospital and community dwelling elderly. Geriatricians refer to the subdivision of the over-65 age group as the ‘young-old’ (65–75 years), the ‘old’ (75–85 years), the ‘old-old’ (85–95 years), and the ‘extreme old’ (95+ years).2 The majority of patients presenting in the specialty of oral medicine are in their fifth to seventh decade of life.3
The ageing population’s susceptibility to mucosal disorders Well-established mechanisms of cellular ageing described in human and animal models include acquisition of genetic errors, oxidant damage, the presence of replicative ‘clocks’, and changes in 44
metabolic signal pathways involved in cellular growth and repair.2 It has been demonstrated that there are skin changes associated with age that are independent of solar damage.4,5 Analogous changes occur in the mouth, with epidermal turnover slowing due to decreased division of keratinocytes and longer migration from the basal layer to the surface.6 Fragility occurs due to atrophy of the epidermis and flattening of the dermoepidermal junction.7 Structural changes affect elasticity and superficial microvasculature and may be accompanied by impaired metabolic and reparative responses important in wound healing and immunity.7,8 Immunosenescence refers to the changes that occur in the immune system with increasing age, and cellular and molecular alterations affect both innate and adaptive immunity.9 Progressive age related decline of immune function cannot be understated in its contribution to the increased susceptibility of elderly persons to infectious disease, malignancies and autoimmune disorders.10 Elderly individuals are more likely to have comorbid conditions11 which can complicate the selection of therapies as well as the response to therapy and prognosis. © 2015 Australian Dental Association
Oral medicine and the ageing population Oral dermatoses The most common oral dermatoses have a peak incidence in the ageing population. Each may or may not present with associated cutaneous involvement. Orally, these conditions may also overlap in presentation with desquamative gingivitis (Fig. 1), ulceration and even the presence of intact vesicles and bullae (Fig. 2). Dermatoses on the gingivae may appear as areas of friable epithelium, ulceration and striae as well as a diffuse erythema extending from the marginal to the attached gingiva. These areas are likely to be associated with enhanced plaque accumulation due to discomfort when performing oral hygiene and can be misinterpreted as purely plaque related disease, especially when the gingivae are the only intraoral area involved (Fig. 3). The differentiating feature is that these areas will not completely resolve with traditional debridement and plaque control. These conditions differ in distinctive risks such as malignant potential, risk of ocular involvement and marked morbidity without prompt systemic treatment. Therefore, it is crucial to establish a diagnosis based on clinical and histological parameters as appropriate. Once the acute phase of the disease has been stabilized, it is important to continue general dental care. The retention of plaque due to rough restorative surfaces or inadequate oral hygiene and calculus can exacerbate oral dermatoses. Elimination of sharp cusps and correct oral hygiene instruction plays an important role in oral comfort for these patients. Oral lichen planus Lichen planus (LP) is a chronic mucocutaneous inflammatory disease which commonly affects the mucosa. Oral lichen planus (OLP) has a variety of clinical presentations which may or may not be accompanied by involvement of other sites. OLP is common and likely affects 1–2% of the general population.12 An average age of presentation of
Fig. 1 Desquamative gingivitis associated with an oral dermatosis. © 2015 Australian Dental Association
Fig. 2 Ulceration and intact bulla associated associated with an oral dermatosis.
Fig. 3 Diffuse gingival erythema associated with an oral dermatosis.
50–60 years has been suggested by large retrospective studies from the United States and Europe.13–16 Around 15% of those with OLP will have cutaneous LP17 and 20% of females with OLP have involvement in the genital mucosa.18 OLP may be divided into three clinical subtypes: reticular, erythematous (atrophic) and erosive (ulcerative), and more than one subtype may be present in an individual.19 Symptoms may range from unnoticed presence to pain impacting function and affecting quality of life. The course of the disease may be described as variably episodic with periods of remission and relapse. OLP remains aetiologically idiopathic. The concept of oral lichenoid reactions or lesions (OLR or OLL), eruptions in the oral cavity that have an identifiable aetiology and that clinically and histologically resemble OLP, is well recognized but controversial.20 There are several drugs which are suggested to be associated with a lichenoid reaction, and the strongest evidence is for beta blockers, methyldopa, penicillamine and non-steroidal anti-inflammatory agents.21 Additionally, the malignant potential of OLP continues to be debated, with research groups differing in proposed 45
T Yap and M McCullough approaches and interpretations.22 Given the uncertainty of the premalignant nature of OLP and the fact that early detection of oral cancer results in improved survival, it seems prudent to monitor all patients with OLP carefully and over the long term.20 Diagnosis is reached based upon clinical features and histopathological investigations, as necessary. Treatment aims may begin with identifying exacerbating factors such as sharp cusps and inadequate oral hygiene. The efficacy of topical steroids is well established. Escalation to intralesional steroids such as triamcinolone acetonide may be appropriate for isolated ulcerations.20 Systemic immunosuppression is reserved for recalcitrant disease and must be considered carefully with the patient’s health in a specialist environment. Vesiculobullous conditions Age related immune system dysfunction and the accumulation of autoantibodies lead to an ageing population with an increased incidence of immunobullous conditions.23 There is a great variability in the presentation and severity among patients with both localized and extensive involvement.24 Patients may present with concerns of bleeding or pain while eating or performing oral hygiene. Oral lesions usually involve the palate and gingival areas, and also the labial, tongue and buccal mucosa. Clinical presentation may include ulcerations and erythema, and in rarer cases intact vesicles and bullae.25 Differentiation between immunobullous diseases is based upon history and clinical presentation, which may include cutaneous lesions, and supporting histopathological investigations including direct and indirect immunofluorescence. Collaborative care with a dermatologist is indicated if there are also cutaneous lesions. In regards to cutaneous presentation, bullous pemphigoid is the most common of the immunobullous conditions, usually presenting with pruritus and urticated erythema affecting the limbs and central abdomen preceding or even in the absence of blisters.26 The mean reported age of incidence is between 68 to 82 years with an incidence rate of less than 14 per million.8 It rarely features mucosal involvement, but when it does, oral mucosa is the most common affected site.8 In contrast, mucous membrane pemphigoid (MMP), a heterogeneous group of chronic, autoimmune subepithelial blistering diseases, predominantly involves the mucous membranes and occasionally the skin. MMP mainly occurs in the elderly population, usually observed between 60 and 80 years of age. MMP can affect multiple mucosal sites, with skin involvement in around 25–30%.25 Oral involvement occurs in 85% of patients, the vast majority presenting with desquamative gingivitis, erosions and ulcerations but more rarely intact vesicles.24 Of significance, 65% of MMP patients may have ocular conjunctiva involve46
ment and the risk of scarring of any site underscores the importance of prompt referral to ophthalmology. Treatment for MMP may begin with topical corticosteroids and be escalated to systemic therapy, depending on severity and involvement. Pemphigus vulgaris has an average age of onset of 40–60 years27 with oral lesions found in two-thirds of patients.28 Pemphigus vulgaris was almost invariably fatal before the 1950s,29 owing to uncontrolled fluid and protein loss or opportunistic infection.28 However, since this time, with the advent of corticosteroids, life expectancy has increased significantly and now the mortality rate is approximately 6%, usually associated with the side effects of immunosuppressive therapy used to control the disease.30 Initial treatment for PV is prompt conventional immunosuppressive therapy in the form of high-dose tapering steroids with titrated adjunctive steroid sparing immunomodulatory drugs. Early treatment is thought to decrease the likelihood of disease extension and progression.31 Lupus erythematosus The onset of lupus erythematosus is typically younger, with the majority of onset occurring in the 20–40 year age bracket. It is more prevalent in females. It is mentioned here due to the chronicity of the disease and its association with the development of different malignancies.32 Oral lesions can be a feature of both systemic lupus erythematosus and subtypes limited to cutaneous involvement – cutaneous lupus erythematosus (CLE). The most common subtype of CLE is discoid lupus erythematosus (DLE). Patients with DLE have an approximately 10–15% risk of eventually developing systemic involvement.33 Different studies of oral lesions in the course of lupus erythematosus have shown a frequency varying from 9% to 45% in systemic disease and 3% to 20% in localized cutaneous disease.34 It may be difficult to delineate oral lesions of different forms of lupus and clinical descriptions of oral lesions vary enormously in the different studies. The typical clinical picture is of a well demarcated, round or irregular red area that can be atrophic or ulcerated, with white radiating keratotic striae and telangiectases.34 They can resemble OLP or leukoplakia.35 Currently, the precancerous potential of the intraoral lesions of DLE is uncertain; however, patients with DLE require cautious and ongoing review of their oral and perioral tissues.36 Oral potentially malignant disorders – leukoplakia and erythroplakia The most common oral potentially malignant disorders (PMD) are leukoplakia and erythroplakia.37 Leukoplakia is defined as ‘a white plaque of questionable risk having excluded (other) known diseases or disorders © 2015 Australian Dental Association
Oral medicine and the ageing population that carry no increased risk for cancer’.38 The number of oral cancer cases attributable to PMDs most likely ranges between 17% and 35%.39 Virtually all studies emphasize the chronicity of the presence of these potentially malignant lesions. Some describe an increased tendency for malignant change in the first five years after which the rate exists but is decreased,37 proliferative verrucous leukoplakia being an exception with an ultimate course to verrucous carcinoma or squamous cell carcinoma over a 10- to 15-year period.37 PMDs can affect any age group but are found more frequently in the middle aged to elderly.37,40 Longitudinal studies have found the peak age of incidence of leukoplakia was in the sixth decade and most common prevalence between the fourth to seventh decades.40–44 There is no distinct gender preference,37,45 although some have found a male-to-female ratio of 3.1:1.41–44 Most authorities agree upon a prevalence rate of between 1% and 5%.46,47 Leukoplakia may be located on any part of the oral mucosa and may involve multiple sites.40 The most common location involves the buccal mucosa or commissure region.44 Although rarer, lesions on the lateral and ventral tongue, floor of mouth, retromolar area and soft palate appear much more likely to progress than regress, with oral squamous cell carcinoma (OSCC) more likely to develop in these locations than elsewhere.40 Clinical appearance is an important consideration with the vast majority of PMDs in which OSCC arises being non-homogenous in appearance, although 5% of homogenous PMD will also develop carcinoma. Of importance, the sole presence of a premalignant lesion may be a marker for increased aerodigestive tract cancer risk with 41% of new cancers developed in sites distinct from prior sites in patients with a history of cancer or leukoplakia.48 Diagnosis is based upon histopathology, but there are great limitations in identification of lesions at high risk for progression to malignancy. Presence, absence and level of dysplasia are not reliable prognostic indicators. Treatment modalities for PMDs include monitoring to surgery, laser therapy and chemotherapy. Hesitation for active treatment may be due to the likelihood of recurrence and unaltered progression to malignancy. Some studies show a positive impact on recurrence rates of active treatment when compared to vigilant monitoring. However, the ultimate malignant transformation rate of these lesions, irrespective of treatment, remains unaltered, supporting the notion of a pre-programmed mechanism at a molecular level.49–51 Oral squamous cell carcinoma Increasing age, particularly above 60 years, should be considered a risk factor for the development of OSCC. © 2015 Australian Dental Association
Cancer incidence and mortality markedly increases after age 65, levelling off around age 85 to 90.9 Ninetyfive per cent of oral and pharyngeal cancers occur after the age of 40 years.52 The majority of oral cancers are in the 60+ age group with males more commonly affected.53 It is difficult to establish the exact role of age related immune changes in carcinogenesis, which is a complex phenomenon. There are likely a myriad of contributors in the elderly, such as an increased mutational load, exposure to carcinogens, and diminished awareness and inadequate nutrition.53 Approximately 90% of all oral cancers are squamous cell carcinoma.54 Most oral cavity squamous cell carcinomas will present as a red patch, a white patch, an ulcer, or an easily traumatized outward growing mass with central ulceration. They are often non-tender.55 More than half of oral cavity cancers originate in the tongue or floor of mouth.54 There is a 50% incidence of spread to local/regional lymph nodes or metastases at the initial presentation. Over 80% of patients with stage 4 disease will not survive up to five years, contrasting with an 80% five-year survival rate of those with just localized disease.55 Five-year relative survival has also been shown to be lower for older and male patients with oral SCC.54 Dentists, dental specialists, oral health therapists, dental hygienists and dental prosthetists are in the best position to provide oral cancer surveillance during routine care. Examination of mucosal surfaces should be purposeful, systematic and thorough, and should begin with palpation of neck lymph nodes. In addition to age, the risk factors of smoking and alcohol and the combination of the two are well established. The joint effect between tobacco and alcohol use is greater than multiplicative in regards to head and neck cancer risk.56 At this point in time, the presence of P16 positivity of the tumour does not impact treatment selection and prognosis of intraoral lesions (in contrast to oropharyngeal tumours).57 Diagnosis of OSCC is established upon clinical presentation and histopathology. These patients require prompt referral to a multidisciplinary head and neck tumour team. Patients with resectable tumours are considered for surgery and postoperative radiotherapy. The ageing population’s susceptibility to oral discomfort Salivary secretion It is accepted that the output of the major salivary glands do not undergo clinically significant reduction in healthy ageing individuals.58–61 There is a loss of acinar cells with ageing; however, salivary production in healthy older adults has been shown to remain stable, suggesting the existence of a secretory reserve.59 Other 47
T Yap and M McCullough studies, however, have found that elderly people do have significantly reduced and altered salivary secretion. Despite this, severe salivary hypofunction is not necessarily perceived by the healthy elderly as subjective dry mouth (xerostomia). In contrast, over 80% of patients on medications reported xerostomia or a disturbed sense of taste or burning mouth sensitivity.62 These individuals make up the majority of the 50% of elderly patients who report such complaints with no accompanying pathological attribution, such as Sj€ ogren’s syndrome or previous radiotherapy. A chronically dry mouth can affect quality of life, impacting speech, ingestion of foods and adaptation to dentures.63 Intraoral issues of low salivary flow extend beyond the symptom of discomfort from a dry mouth with a loss of the protectant qualities of saliva, resulting in stagnation of plaque, lower resting pH and subsequent increased susceptibility to caries, erosion and Candida overgrowth. Causes of dry mouth include medication side effects, autoimmune disease (Sj€ ogren’s syndrome), radiotherapy, hormone disorders (diabetes) and infections.64
salivary hypofunction.67 Regardless of the cause of dry mouth, it is important to assess caries risk and continue preventive dental care with the aim for longterm function and adequate nutrition. Augmentation of existing secretory reserve in the form of adequate fluid intake and limiting caffeine consumption should be implemented early. Goals of outcome communicated to the patient should be aimed at functional ability to eat the foods they enjoy rather than improvement in the subjectiveness of the dry mouth throughout the day. Low cost interventions should be considered such as a sodium bicarbonate mouthwash. Escalation to novel salivary replacements should be reserved as a last resort due to the continuous expense and effects of the low pH (20%) among elderly people and can be subtle in presentation. Causes included malabsorption problems, such as pernicious anaemia, but also insufficient dietary intake. The haematological screening for a patient with symptoms of oral burning or other signs of anaemia should include a full blood examination, random glucose, iron studies, folate and B12 levels.85 Deficiency of iron, folate and B12 can occur without anaemia. Communication with the patients’ overseeing medical practitioner is necessary for further investigation and appropriate management which may include supplementation where appropriate.
Burning mouth syndrome Primary burning mouth syndrome is defined as an ‘intraoral burning for which no medical or dental cause was found’. It is a diagnosis of exclusion and the aetiology is unknown.79,80 It is seen predominantly in peri- and postmenopausal patients with a suggested prevalence of 18–33% in this group.78 The prominent feature is the symptom of burning pain which can be localized just to the tongue and/or lips but can be more widespread and involve the whole of the oral cavity.81 Levels of psychiatric dysfunction in patients with BMS are high, just as they are in other groups of patients with chronic pain conditions.82 Only a small number of patients resolve completely; however, moderate improvement is common and reassurance that it will not worsen and that it is not associated with disease may play a crucial role in patient coping.83 Therapy begins with reassurance and education. No single treatment is universally effective for all BMS patients.82 There may be a role for the use of cognitive behavioural therapy.78 Topical therapies may include topical analgesics, capsaicin or clonazepam.80 Systemic medications include the use of the antioxidant alpha lipoic acid, antidepressants such as tricyclics and anticonvulsant drugs such as clonazepam,84 gabapentin and pregabalin. If BMS is suspected, the patient should be referred to an oral medicine specialist as this condition, if left unmanaged, can have a profound impact on the patient’s quality of life.
Malnutrition Elderly patients frequently have suboptimal nutritional status, particularly for institutionalized patients, but this is also seen in nursing home and community settings.87 Adequate nutrition is necessary for healthy ageing. Contributing reasons include difficulty in eating due to problems with the dentition and swallowing. Dysphagia is present in approximately 7% to 10% of the older adult population.88 Additionally, issues with loss of smell or taste sensations, digestion or absorption associated with chronic illnesses or medications, cognitive impairments and economic barriers predispose the elderly to malnutrition.89 Malnutrition has also been shown to be associated with increased morbidity and mortality.90 A primary role of the dentist is to ensure maximum function so that the dentition will not be a hindrance to adequate nutrition.
Anaemia in the elderly – iron, B12, folate deﬁciency Anaemia, in particular iron, B12 or folate deficiency anaemia, may be suspected in the elderly who
Candida Fifty per cent of the population are likely to have a positive culture of Candida as an oral commensal
© 2015 Australian Dental Association
T Yap and M McCullough with the most common strain being C. albicans.91 There are a number of factors that predispose the elderly to Candida and Candida-associated conditions. One is the increased likelihood of co-morbidities, such as diabetes mellitus, and associated medications. Medication which may contribute to Candida overgrowth include broad spectrum antibiotics, drugs that cause changes to the immune system by their therapeutic action or side effects, as well as the many drugs which have dry mouth as a side effect. Due to the effectiveness of antibiotics or immunomodulatory therapy, alterations in the balance of commensal oral microflora may lead to overgrowth of Candida.92 Reduction of salivary flow volume and salivary constituents means a loss of innate antifungal defence and buffering capacity, facilitating Candida overgrowth.93,94 There may also be contribution from protein-energy malnutrition and deficiencies in vitamins and minerals, in particular iron, folate, B12 and vitamin C, all of which are necessary for a healthy immune system.94 Candidosis and Candida-related conditions are often asymptomatic but should be considered in the patient presenting with the sensation of oral burning. There are three primary oral manifestations of candidosis. The first is pseudomembranous candidosis, in which there is a removable mesh of fungal hyphae containing entangled desquamated epithelial cells, fibrin, keratin, necrotic tissue and bacteria95 overlying erythematous mucosa. Secondly, erythematous candidosis which presents as localized erythema with no pseudomembrane, the most common sites being the tongue and palate. Finally, hyperplastic candidosis presents as a well demarcated, slightly elevated, adherent white lesion of the oral mucosa ranging from small translucent lesions to large, dense opaque plaques.96,97 Diagnosis of hyperplastic candidosis can be complicated by the presence of dysplasia. Correlation with epithelial dysplasia and presence of Candida exists98 but it is so far unclear what role Candida plays in the progression of epithelial dysplasia and carcinogenesis. Candida-associated conditions include dentureassociated erythematous stomatitis (DAES), papillary hyperplasia, angular cheilitis, median rhomboid glossitis (MRG) and linear gingival erythema. Patients may present with more than one type of candidosis or Candida-associated conditions. The distinction between candidosis and Candida-associated conditions is made in order to promote the consideration for contributory factors such as poor denture hygiene, nocturnal denture wear, loss of vertical dimension or incorrect use of steroid inhalers. Thus, an emphasis should be placed on conservative treatment such as improved oral and denture hygiene before the prescription of antifungal agents. 50
Orofacial pain conditions in the ageing population Temporomandibular disorders Temporomandibular disorders (TMD) can affect any age group; it is known to have a female predilection and some studies have found a higher prevalence in the elderly.100 The distribution of severity is similar to other groups with the minority presenting with severe signs and symptoms. Increasing age is associated with an increased risk of radiographic degenerative changes in the temporomandibular joint (TMJ). However, such radiographic findings do not necessarily translate into pain.99 Similarly, the association between the presence of reported joint noises and the finding of sensitivity to TMJ palpation (arthralgia) was not found to be significant.100 TMD related symptoms may decrease after age 80 and the female predominance may become less prominent.101 The number and presence of teeth is not predictive of TMD-related symptoms, with general health co-morbidities playing a more associative role.101 Trigeminal neuralgia Trigeminal neuralgia (TN) is a rare, episodic facial pain that is unilateral, electric shock-like, and provoked by light touch.102 The peak incidence of TN is in the 50–60 year age group and increases with age.103 The male-to-female ratio is approximately 2:3. Lifetime prevalence has been suggested to be 0.3%.104 Classic TN includes the most common cause: neurovascular compression of the trigeminal nerve root, as well as idiopathic cases. Rarely, TN is symptomatic of other conditions such as multiple sclerosis or central lesions.80 This disease is rare and will not be seen by the majority of dental practitioners. However, there is importance in correct diagnosis in order to avoid inappropriate dental treatment which may be well intentioned to help a distressed patient in obvious pain. Untreated or poorly controlled TN could result in weight loss and depression, and even suicide.102 Prompt referral to neurology via the patient’s general practitioner or pain specialist is warranted. Temporal (giant cell) arteritis The differential diagnosis of temporal arteritis should be considered in the patient over the age of 50 with pain in the temporal region, until confidently eliminated. Giant cell arteritis (GCA) involves the major branches of the aorta, in particular, the extracranial branches of the carotid artery which include the temporal artery. It is a condition that increases in incidence with age and almost exclusively occurs above © 2015 Australian Dental Association
Oral medicine and the ageing population the age of 50. GCA is more common among people of North European decent than among Mediterranean people, and is rare among African Americans, Native Americans and Asians.105 Females are 2–3 times more commonly affected. The arteritis can mimic TMD with 70–85% of patients presenting with facial pain and headache, and up to 40% presenting with pain or weakness upon movements of the mandible. It is usually unilateral and develops over a period of several weeks, although it can also be abrupt in onset.105 Differentiating characteristics include systemic signs such as fever, malaise, fatigue, anorexia, weight loss, prominent or tender temporal arteries, scalp tenderness or visual changes although these may not all be present in every patient.106 GCA requires prompt referral and must be treated rapidly with systemic corticosteroids due to the risk of blindness.80 CONCLUSIONS General dental practitioners should be aware of the dynamic nature of the oral cavity environment with subtle age related changes, accumulation of comorbidities and accompanying therapies in their ageing patient population. There should be an appreciation for the increased likelihood of onset of common and less common mucosal conditions, as well as pain presentations. In addition, an understanding of the chronicity of these conditions and the possibility of sinister progression is crucial in caring for this particular population. DISCLOSURE The authors have no conflicts of interest to declare. REFERENCES 1. Australian Bureau of Statistics. Population by Age and Sex, Regions of Australia, 2012. URL: ‘http:/www.abs.gov.au’. Accessed November 2013. 2. Hall KE, Proctor DD, Fisher L, Rose S. American gastroenterological association future trends committee report: effects of aging of the population on gastroenterology practice, education, and research. Gastroenterology 2005;129:1305– 1338. 3. Farah CS, Simanovic B, Savage NW. Scope of practice, referral patterns and lesion occurrence of an oral medicine service in Australia. Oral Dis 2008;14:367–375. 4. Fisher GJ, Kang S, Varani J, et al. Mechanisms of photoaging and chronological skin aging. Arch Dermatol 2002;138:1462– 1470. 5. Suwabe H, Serizawa A, Kajiwara H, Ohkido M, Tsutsumi Y. Degenerative processes of elastic fibers in sun-protected and sun-exposed skin: immunoelectron microscopic observation of elastin, fibrillin-1, amyloid P component, lysozyme and alpha1-antitrypsin. Pathol Int 1999;49:391–402. 6. Ashcroft GS, Mills SJ, Ashworth JJ. Ageing and wound healing. Biogerontology 2002;3:337–345. © 2015 Australian Dental Association
7. Moragas A, Castells C, Sans M. Mathematical morphologic analysis of aging-related epidermal changes. Anal Quant Cytol Histol 1993;15:75–82. 8. Parker SR, MacKelfresh J. Autoimmune blistering diseases in the elderly. Clin Dermatol 2011;29:69–79. 9. Malaguarnera L, Cristaldi E, Malaguarnera M. The role of immunity in elderly cancer. Crit Rev Oncol Hematol 2010;74:40–60. 10. Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transplant Int 2009;22:1041– 1050. 11. Hall WH, Ramachandran R, Narayan S, Jani AB, Vijayakumar S. An electronic application for rapidly calculating Charlson comorbidity score. BMC Cancer 2004;4:94. 12. McCartan BE, Healy CM. The reported prevalence of oral lichen planus: a review and critique. J Oral Pathol Med 2008;37:447–453. 13. Eisen D. The clinical features, malignant potential, and systemic associations of oral lichen planus: a study of 723 patients. J Am Acad Dermatol 2002;46:207–214. 14. Carbone M, Arduino PG, Carrozzo M, et al. Course of oral lichen planus: a retrospective study of 808 northern Italian patients. Oral Dis 2009;15:235–243. 15. Bermejo-Fenoll A, Sanchez-Siles M, Lopez-Jornet P, Camacho-Alonso F, Salazar-Sanchez N. A retrospective clinicopathological study of 550 patients with oral lichen planus in south-eastern Spain. J Oral Pathol Med 2010;39:491–496. 16. Banoczy J, Rigo O. Prevalence study of oral precancerous lesions within a complex screening system in Hungary. Community Dent Oral Epidemiol 1991;19:265–267. 17. Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:431–436. 18. Rogers RS 3rd, Eisen D. Erosive oral lichen planus with genital lesions: the vulvovaginal-gingival syndrome and the penogingival syndrome. Dermatol Clin 2003;21:91–98, vi–vii. 19. Eisen D. The clinical manifestations and treatment of oral lichen planus. Dermatol Clin 2003;21:79–89. 20. Eisen D, Carrozzo M, Bagan Sebastian JV, Thongprasom K. Number V Oral lichen planus: clinical features and management. Oral Dis 2005;11:338–349. 21. Thompson DF, Skaehill PA. Drug-induced lichen planus. Pharmacotherapy 1994;14:561–571. 22. Gonzalez-Moles MA, Scully C, Gil-Montoya JA. Oral lichen planus: controversies surrounding malignant transformation. Oral Dis 2008;14:229–243. 23. Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin 2011;29:427–438, viii-ix. 24. Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol 2002;138:370–379. 25. Xu HH, Werth VP, Parisi E, Sollecito TP. Mucous membrane pemphigoid. Dent Clin North Am 2013;57:611–630. 26. Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Immunol Allergy Clin North Am 2012;32:217–232, v. 27. Joly P, Litrowski N. Pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis). Clin Dermatol 2011;29: 432–436. 28. Baroni A, Lanza A, Cirillo N, Brunetti G, Ruocco E, Ruocco V. Vesicular and bullous disorders: pemphigus. Dermatol Clin 2007;25:597–603, ix.
T Yap and M McCullough 29. Bystryn JC. Adjuvant therapy of pemphigus. Arch Dermatol 1984;120:941–951.
52. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106–130.
30. Bystryn JC, Steinman NM. The adjuvant therapy of pemphigus. An update. Arch Dermatol 1996;132:203–212.
53. Sugerman PB, Savage NW. Oral cancer in Australia: 1983– 1996. Aust Dent J 2002;47:45–56.
31. Mignogna MD, Fortuna G, Leuci S, Ruoppo E. Oropharyngeal pemphigus vulgaris and clinical remission: a long-term, longitudinal study. Am J Clin Dermatol 2010;11:137–145.
54. Funk GF, Karnell LH, Robinson RA, Zhen WK, Trask DK, Hoffman HT. Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report. Head Neck 2002;24:165–180.
32. Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum 2005;52:1481–1490. 33. Durosaro O, Davis MD, Reed KB, Rohlinger AL. Incidence of cutaneous lupus erythematosus, 1965–2005: a populationbased study. Arch Dermatol 2009;145:249–253. 34. Nico M, Vilela M, Rivitti EA, Lourencßo SV. Oral lesions in lupus erythematosus: correlation with cutaneous lesions. Eur J Dermatol 2008;18:376–381. 35. L opez-Labady J, Villarroel-Dorrego M, Gonzalez N, Perez R, Mata de Henning M. Oral manifestations of systemic and cutaneous lupus erythematosus in a Venezuelan population. J Oral Pathol Med 2007;36:524–527. 36. Savage NW, Boras VV, Zaini ZM. Oral squamous cell carcinoma with discoid lupus erythematosus. Oral Oncology Extra 2006;42:32–35. 37. van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa: terminology, classification and present concepts of management. Oral Oncol 2009;45:317–323. 38. Warnakulasuriya S, Johnson NW, Van Der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007;36:575–580. 39. van der Waal I, Schepman KP, van der Meij EH, Smeele LE. Oral leukoplakia: a clinicopathological review. Oral Oncol 1997;33:291–301. 40. Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med 2008;37:1–10. 41. B an oczy J, Sug ar L. Longitudinal studies in oral leukoplakias. J Oral Pathol Med 1972;1:265–272. 42. B an oczy J. Follow-up studies in oral leukoplakia. J Maxillofac Surg 1977;5:69–75. Occurrence of epithelial dysplasia in oral 43. B an oczy J, Csiba A. leukoplakia: analysis and follow-up study of 12 cases. Oral Surg Oral Med Oral Pathol 1976;42:766–774.
55. Sciubba JJ. Oral cancer. The importance of early diagnosis and treatment. Am J Clin Dermatol 2001;2:239–251. 56. Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 2009;18:541–550. 57. Campisi G, Giovannelli L. Controversies surrounding human papilloma virus infection, head and neck vs oral cancer, implications for prophylaxis and treatment. Head Neck Oncol 2009;1:8. 58. Ship JA, Pillemer SR, Baum BJ. Xerostomia and the geriatric patient. J Am Geriatr Soc 2002;50:535–543. 59. Ghezzi EM, Ship JA. Aging and secretory reserve capacity of major salivary glands. J Dent Res 2003;82:844–848. 60. Baum BJ. Evaluation of stimulated parotid saliva flow rate in different age groups. J Dent Res 1981;60:1292–1296. 61. Tylenda CA, Ship JA, Fox PC, Baum BJ. Evaluation of submandibular salivary flow rate in different age groups. J Dent Res 1988;67:1225–1228. 62. Nagler RM, Hershkovich O. Age-related changes in unstimulated salivary function and composition and its relations to medications and oral sensorial complaints. Aging Clin Exp Res 2005;17:358–366. 63. Thomson WM, Chalmers JM, Spencer AJ, Slade GD, Carter KD. A longitudinal study of medication exposure and xerostomia among older people. Gerodontology 2006;23:205– 213. 64. Scully C, Felix DH. Oral medicine – update for the dental practitioner: dry mouth and disorders of salivation. Br Dent J 2005;199:423–427. 65. Gonzalez S, Sung H, Sepulveda D, Gonzalez M, Molina C. ogren’s synOral manifestations and their treatment in Sj€ drome. Oral Dis 2014;20:153–161.
44. B an oczy J, Sug ar L. Progressive and regressive changes in Hungarian oral leukoplakias in the course of longitudinal studies. Community Dent Oral Epidemiol 1975;3:194–197.
66. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sj€ ogren’s syndrome. Arch Intern Med 2004;164:1275–1284.
45. Waldron CA, Shafer WG. Leukoplakia revisited. A clinicopathologic study 3256 oral leukoplakias. Cancer 1975;36:1386–1392.
67. Furness S, Worthington HV, Bryan G, Birchenough S, McMillan R. Interventions for the management of dry mouth: topical therapies. Cochrane Database Syst Rev 2011: CD008934.
46. Kleinman DV, Swango PA, Pindborg JJ, Gupta P. Toward assessing trends in oral mucosal lesions: lessons learned from oral cancer. Adv Dent Res 1993;7:32–41. 47. Bouquot JE. Oral leukoplakia and erythroplakia: a review and update. Pract Periodontics Aesthet Dent 1994;6:9–17. 48. Lee JJ, Hong WK, Hittelman WN, et al. Predicting cancer development in oral leukoplakia: ten years of translational research. Clin Cancer Res 2000;6:1702–1710. 49. Lim B, Smith A, Chandu A. Treatment of oral leukoplakia with carbon dioxide and potassium-titanyl-phosphate lasers: a comparison. J Oral Maxillofac Surg 2010;68:597–601. 50. Lo J, McNaughtan J, Rani V, et al. An immunohistochemical analysis of cell cycle markers in oral mucosal dysplastic lesions treated by laser therapy. A pilot study. J Maxillofac Oral Surg 2011;10:190–194. 51. Holmstrup P, Vedtofte P, Reibel J, Stoltze K. Long-term treatment outcome of oral premalignant lesions. Oral Oncol 2006;42:461–474. 52
68. Aframian DJ, Helcer M, Livni D, Robinson SD, Markitziu A, Nadler C. Pilocarpine treatment in a mixed cohort of xerostomic patients. Oral Dis 2007;13:88–92. 69. von Bultzingslowen I, Sollecito TP, Fox PC, et al. Salivary dysfunction associated with systemic diseases: systematic review and clinical management recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103 Suppl: S57.e51–15. 70. Nakamura N, Sasano N, Yamashita H, et al. Oral pilocarpine (5 mg t.i.d.) used for xerostomia causes adverse effects in Japanese. Auris Nasus Larynx 2009;36:310–313. 71. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997;16:278–283. 72. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc 2003;134:200–207. © 2015 Australian Dental Association
Oral medicine and the ageing population 73. Rennie JS, Reade PC, Hay KD, Scully C. Recurrent aphthous stomatitis. Br Dent J 1985;159:361–367. 74. Oxman MN. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology 1995;45:S41–46. 75. Benoliel R, Eliav E. Neuropathic orofacial pain. Oral Maxillofac Surg Clin North Am 2008;20:237–254, vii. 76. Ragozzino MW, Melton LJ 3rd, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine (Baltimore) 1982;61:310–316. 77. Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med 2000;9:863–869. 78. Buchanan JA, Zakrzewska JM. Burning mouth syndrome. Clin Evid (Online) 2010 Jul 19;2010. pii: 1301. 79. Ducasse D, Courtet P, Olie E. Burning mouth syndrome: current clinical, physiopathologic, and therapeutic data. Reg Anesth Pain Med 2013;38:380–390. 80. Zakrzewska JM. Differential diagnosis of facial pain and guidelines for management. Br J Anaesth 2013;111:95–104. 81. Dutt P, Chaudhary S, Kumar P. Oral health and menopause: a comprehensive review on current knowledge and associated dental management. Ann Med Health Sci Res 2013;3:320–323. 82. Torgerson RR. Burning mouth syndrome. Dermatol Ther 2010;23:291–298. 83. Sardella A, Lodi G, Demarosi F, Bez C, Cassano S, Carrassi A. Burning mouth syndrome: a retrospective study investigating spontaneous remission and response to treatments. Oral Dis 2006;12:152–155. 84. Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T. A double-blind study on clonazepam in patients with burning mouth syndrome. Laryngoscope 2012;122:813–816. 85. Lu SY, Wu HC. Initial diagnosis of anemia from sore mouth and improved classification of anemias by MCV and RDW in 30 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98:679–685. 86. Patel KV. Epidemiology of anemia in older adults. Semin Hematol 2008;45:210–217. 87. Guigoz Y, Lauque S, Vellas BJ. Identifying the elderly at risk for malnutrition. The Mini Nutritional Assessment. Clin Geriatr Med 2002;18:737–757. 88. Achem SR, Devault KR. Dysphagia in aging. J Clin Gastroenterol 2005;39:357–371. 89. Volkert D, Saeglitz C, Gueldenzoph H, Sieber CC, Stehle P. Undiagnosed malnutrition and nutrition-related problems in geriatric patients. J Nutr Health Aging 2010;14:387–392. 90. Chandra RK. Nutrition and the immune system from birth to old age. Eur J Clin Nutr 2002;56 Suppl 3:S73–76. 91. Borromeo GL, McCullough MJ, Reade PC. Quantitation and morphotyping of Candida albicans from healthy mouths and from mouths affected by erythematous candidosis. J Med Vet Mycol 1992;30:477–480. 92. Soysa NS, Samaranayake LP, Ellepola AN. Antimicrobials as a contributory factor in oral candidosis–a brief overview. Oral Dis 2008;14:138–143.
© 2015 Australian Dental Association
93. Leung KC, McMillan AS, Cheung BP, Leung WK. Sjogren’s syndrome sufferers have increased oral yeast levels despite regular dental care. Oral Dis 2008;14:163–173. 94. Figueiral MH, Azul A, Pinto E, Fonseca PA, Branco FM, Scully C. Denture-related stomatitis: identification of aetiological and predisposing factors – a large cohort. J Oral Rehabil 2007;34:448–455. 95. McIntyre GT. Oral candidosis. Dent Update 2001;28:132– 139. 96. Ellepola AN, Samaranayake LP. Oral candidal infections and antimycotics. Crit Rev Oral Biol Med 2000;11:172– 198. 97. McCullough MJ, Savage NW. Oral candidosis and the therapeutic use of antifungal agents in dentistry. Aust Dent J 2005;50:S36–39. 98. McCullough M, Jaber M, Barrett AW, Bain L, Speight PM, Porter SR. Oral yeast carriage correlates with presence of oral epithelial dysplasia. Oral Oncol 2002;38:391–393. 99. Wiese M, Svensson P, Bakke M, et al. Association between temporomandibular joint symptoms, signs, and clinical diagnosis using the RDC/TMD and radiographic findings in temporomandibular joint tomograms. J Orofac Pain 2008;22:239–251. 100. Camacho JG, Oltramari-Navarro PV, Navarro Rde L, et al. Signs and symptoms of temporomandibular disorders in the elderly. CoDAS 2014;26:76–80. 101. Carlsson GE, Ekback G, Johansson A, Ordell S, Unell L. Is there a trend of decreasing prevalence of TMD-related symptoms with ageing among the elderly? Acta Odontol Scand 2014;72:714–720. 102. Zakrzewska JM, Linskey ME. Trigeminal neuralgia. BMJ 2014;348:g474. 103. MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 2000;123(Pt 4):665–676. 104. Mueller D, Obermann M, Yoon MS, et al. Prevalence of trigeminal neuralgia and persistent idiopathic facial pain: a population-based study. Cephalalgia 2011;31:1542–1548. 105. Nesher G. The diagnosis and classification of giant cell arteritis. J Autoimmun 2014;48–49:73–75. 106. Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology 2010;49:1594–1597.
Address for correspondence: Professor Michael McCullough Department of Oral Anatomy, Medicine and Surgery Melbourne Dental School The University of Melbourne 720 Swanston Street Melbourne VIC 3010 Email: [email protected]