Oral medicine — Update for the dental practitioner - Oral Cancer ...

IN BRIEF• Most mouth ulcers are inconsequential.• Cancer and some systemic diseases may present with ulceration.• Any single ulcer lasting three or more weeks should be regarded with suspicion.1Oral medicine — Update for the dental practitionerAphthous and other common ulcersC. Scully 1 and D. H. Felix 2This series provides an overview of current thinking in the more relevant areas of oral medicine for primary care practitioners,written by the authors while they were holding the Presidencies of the European Association for Oral Medicine and the BritishSociety for Oral Medicine, respectively. A book containing additional material will be published. The series gives the detailnecessary to assist the primary dental clinical team caring for patients with oral complaints that may be seen in general dentalpractice. Space precludes inclusion of illustrations of uncommon or rare disorders, or discussion of disorders affecting the hardtissues. Approaching the subject mainly by the symptomatic approach — as it largely relates to the presenting complaint — wasconsidered to be a more helpful approach for GDPs rather than taking a diagnostic category approach. The clinical aspects of therelevant disorders are discussed, including a brief overview of the aetiology, detail on the clinical features and how the diagnosisis made. Guidance on management and when to refer is also provided, along with relevant websites which offer further detail.ORAL MEDICINE1. Aphthous and othercommon ulcers2. Mouth ulcers of moreserious connotation3. Dry mouth and disordersof salivation4. Oral malodour5. Oral white patches6. Oral red andhyperpigmented patches7. Orofacial sensation andmovement8. Orofacial swellings andlumps9. Oral cancer10. Orofacial pain1 *Professor, Consultant, Dean, EastmanDental Institute for Oral Health CareSciences, 256 Gray’s Inn Road, UCL,University of London, London WC1X 8LD;2 Consultant, Senior Lecturer, GlasgowDental Hospital and School, 378Sauchiehall Street, Glasgow G2 3JZ /Associate Dean for Postgraduate DentalEducation, NHS Education for Scotland,2nd Floor, Hanover Buildings, 66 RoseStreet, Edinburgh EH2 2NN*Correspondence to: Professor CrispianScully CBEEmail: c.scully@eastman.ucl.ac.ukRefereed Paper© British Dental Journal 2005; 199:259–264Specialist referral may be indicated if the practitionerfeels:• the diagnosis is unclear• a serious diagnosis is possible• systemic disease may be present• unclear as to investigations indicated• complex investigations unavailable inprimary care are indicated• unclear as to treatment indicated• treatment is complex• treatment requires agents not readilyavailable• unclear as to the prognosis• the patient wishes this.ULCERATIONUlceration is a breach in the oral epithelium,which typically exposes nerve endings in theunderlying lamina propria, resulting in pain orsoreness, especially when eating spicy foods orFig. 1 A small erosioncitrus fruits. Patients vary enormously in thedegree to which they suffer and complain ofsoreness in relation to oral ulceration. It isalways important to exclude serious disorderssuch as oral cancer (Part 9) or other serious disease,but not all patients who complain of sorenesshave discernible organic disease. Conversely,some with serious disease have no pain. Even inthose with detectable lesions, the level of complaintcan vary enormously. Some patients withlarge ulcers complain little; others with minimalulceration complain bitterly of discomfort.Sometimes there is a psychogenic influence.TerminologyEpithelial thinning or breaches may be seen in:• mucosal atrophy or desquamation — termsoften used for thinning of the epithelium whichassumes a red appearance as the underlyinglamina propria containing blood vessels showsFig. 2 Minor aphthous ulcer, labial mucosaBRITISH DENTAL JOURNAL VOLUME 199 NO. 5 SEPT 10 2005 259

PRACTICEFig. 3 Chemical burn, rightmaxillary tuberosityFig. 4 Thermal burn, palatethrough. Most commonly this is seen in desquamativegingivitis (usually related to lichenplanus, or less commonly to pemphigoid) and ingeographic tongue (erythema migrans, benignmigratory glossitis). A similar process may alsobe seen in systemic disorders such as deficiencystates (of iron, folic acid or B vitamins).• mucosal inflammation (mucositis, stomatitis)which can cause soreness. Viral stomatitis,candidosis, radiation mucositis, chemotherapyrelatedmucositis and graft-versus-host-diseaseare examples.• erosion which is the term used for superficialbreaches of the epithelium. These often have ared appearance initially as there is little damageto the underlying lamina propria, but theytypically become covered by a fibrinous exudatewhich has a yellowish appearance (Fig.1). Erosions are common in vesiculobullousdisorders such as pemphigoid.• ulcer which is the term usually used wherethere is damage both to epithelium and laminapropria. An inflammatory halo, if present, alsohighlights the ulcer with a red halo around theyellow or grey ulcer (Fig. 2). Most ulcers aredue to local causes such as trauma or burns,but recurrent aphthous stomatitis and cancermust always be considered.Table 1 Main causes of oral ulcerationLocal causesAphthaeInfectionsDrugsMalignant diseaseSystemic diseasesTable 2 Main causes of mouth ulcersLocal causesTraumaAppliancesIatrogenicNon-accidental injurySelf-inflictedSharp teeth or restorationsBurnsChemicalColdElectricHeatRadiationRecurrent aphthaeInfectionsAcute necrotising gingivitisChickenpoxDeep mycosesHand, foot and mouth diseaseHerpanginaHerpetic stomatitisHIVInfectious mononucleosisSyphilisTuberculosisDrugsCytotoxic drugs,Nicorandil, NSAIDsMany othersMalignant neoplasmsOralEncroaching from antrumSystemic diseaseMucocutaneous diseaseBehcet's syndromeChronic ulcerative stomatitisEpidermolysis bullosaErythema multiformeLichen planusPemphigus vulgarisSub-epithelial immune blistering diseases(Pemphigoid and variants, dermatitisherpetiformis, linear IgA disease)Haematological disordersAnaemiaGammopathiesHaematinic deficienciesLeukaemia and myelodysplastic syndromeNeutropenia and other white cell dyscrasiasGastrointestinal diseaseCoeliac diseaseCrohn's diseaseUlcerative colitisMiscellaneous uncommon diseasesEosinophilic ulcerGiant cell arteritisHypereosinophilic syndromeLupus erythematosusNecrotising sialometaplasiaPeriarteritis nodosaReiters syndromeSweet's syndromeWegener's granulomatosis260 BRITISH DENTAL JOURNAL VOLUME 199 NO. 5 SEPT 10 2005

PRACTICECauses of oral ulcerationUlcers and erosions can also be the final commonmanifestation of a spectrum of conditions. Theserange from: epithelial damage resulting fromtrauma; an immunological attack as in lichenplanus, pemphigoid or pemphigus; damagebecause of an immune defect as in HIV diseaseand leukaemia; infections such as herpesviruses,tuberculosis and syphilis; cancer and nutritionaldefects such as vitamin deficiencies and somegastrointestinal diseases (Tables 1 and 2).Fig. 6 Minor aphthous ulcerationUlcers of local causesAt any age, there may be burns from chemicalsof various kinds (Fig. 3), heat (Fig. 4), cold, orionising radiation or factitious ulceration, especiallyof the maxillary gingivae or palate.Children may develop ulceration of the lowerlip by accidental biting following dental localanaesthesia. Ulceration of the upper labialfraenum, especially in a child with bruised andswollen lips, subluxed teeth or fractured jaw canrepresent non-accidental injury. At any age, trauma,hard foods, or appliances may also causeulceration. The lingual fraenum may be traumatisedby repeated rubbing over the lower incisorteeth in cunnilingus, in recurrent coughing as inwhooping cough, or in self-mutilating conditions.Most ulcers of local cause have an obviousaetiology, are acute, usually single ulcers, lastless than three weeks and heal spontaneously.Chronic trauma may produce an ulcer with akeratotic margin (Fig. 5).Fig. 5 Traumatic ulceration, lateral tongueRecurrent aphthous stomatitis (RAS; aphthae;canker sores)RAS is a very common condition which typicallystarts in childhood or adolescence and presentswith multiple recurrent small, round or ovoidulcers with circumscribed margins, erythematoushaloes, and yellow or grey floors (Fig. 6).RAS affects at least 20% of the population,with the highest prevalence in higher socio-economicclasses. Virtually all dentists will seepatients with aphthae.AetiopathogenesisImmune mechanisms appear at play in a personwith a genetic predisposition to oral ulceration. Agenetic predisposition is present, and there is apositive family history in about one third ofpatients with RAS. Immunological factors are alsoinvolved, with T helper cells predominating in theRAS lesions early on, along with some naturalkiller (NK) cells. Cytotoxic cells then appear in thelesions and there is evidence for an antibodydependent cellular cytotoxicity (ADCC) reaction. Itnow seems likely therefore that a minor degree ofimmunological dysregulation underlies aphthae.RAS may be a group of disorders of differentpathogeneses. Cross-reacting antigens betweenthe oral mucosa and microorganisms may be theinitiators, but attempts to implicate a variety ofbacteria or viruses have failed.Predisposing factorsMost people who suffer RAS are otherwiseapparently completely well. In a few, predisposingfactors may be identifiable, or suspected.These include:1. Stress: underlies RAS in many cases. RAS aretypically worse at examination times.2. Trauma: biting the mucosa, and dentalappliances may lead to some aphthae.3. Haematinic deficiency (deficiencies of iron,folic acid (folate) or vitamin B 12) in up to 20%of patients.4. Sodium lauryl sulphate (SLS), a detergent insome oral healthcare products may produceoral ulceration.5. Cessation of smoking: may precipitate oraggravate RAS.6. Gastrointestinal disorders particularly coeliacdisease (gluten-sensitive enteropathy) andCrohn’s disease in about 3% of patients.7. Endocrine factors in some women whose RASare clearly related to the fall in progestogenlevel in the luteal phase of their menstrual cycle.8. Immune deficiency: ulcers similar to RAS maybe seen in HIV and other immune defects.9. Food allergies: underlie RAS rarely.Drugs may produce aphthous-like lesions (seebelow).Key points for dentists: aphthous ulcers• They are so common that all dentists willsee them• It is important to rule out predisposingcauses (sodium lauryl sulphate, certainfoods/drinks, stopping smoking or vitaminor other deficiencies) or conditions such asBehcet’s syndrome• Enquire about eye, genital, gastrointestinalor skin lesions• Topical corticosteroids are the maintreatmentBRITISH DENTAL JOURNAL VOLUME 199 NO. 5 SEPT 10 2005 261

PRACTICEClinical featuresThere are three main clinical types of RAS,though the significance of these distinctions isunclear and it is conceivable that they may representthree different diseases:1. Minor aphthous ulcers (MiAU; Mikulicz Ulcer)occur mainly in the 10 to 40-year-old agegroup, often cause minimal symptoms, and aresmall round or ovoid ulcers 2-4 mm indiameter. The ulcer floor is initially yellowishbut assumes a greyish hue as healing andepithelialisation proceeds. They are surroundedby an erythematous halo and some oedema,and are found mainly on the non-keratinisedmobile mucosa of the lips, cheeks, floor of themouth, sulci or ventrum of the tongue. Theyare only uncommonly seen on the keratinisedmucosa of the palate or dorsum of the tongueand occur in groups of only a few ulcers (oneto six) at a time. They heal in seven to 10 days,and recur at intervals of one to four monthsleaving little or no evidence of scarring (Fig. 7).are found on any area of the oral mucosa,including the keratinised dorsum of thetongue or palate, occur in groups of only a fewulcers (one to six) at one time and heal slowlyover 10 to 40 days. They recur extremely frequentlymay heal with scarring and are occasionallyfound with a raised erythrocyte sedimentationrate or plasma viscosity.3. Herpetiform Ulceration (HU) is found in aslightly older age group than the other formsof RAS and are found mainly in females. Theybegin with vesiculation which passes rapidlyinto multiple minute pinhead-sized discreteulcers (Fig. 10), which involve any oral siteincluding the keratinised mucosa. Theyincrease in size and coalesce to leave largeround ragged ulcers, which heal in 10 days orlonger, are often extremely painful and recurso frequently that ulceration may be virtuallycontinuous.Fig. 7 Minor aphthaeFig. 10 Herpetiform aphthae2. Major aphthous ulcers (MjAU; Sutton’s Ulcers;periadenitis mucosa necrotica recurrens(PMNR)) (Figs 8 and 9) are larger, of longerduration, of more frequent recurrence, andoften more painful than minor ulcers. MjAUare round or ovoid like minor ulcers, but theyare larger and associated with surroundingoedema and can reach a large size, usuallyabout 1 cm in diameter or even larger. TheyDiagnosisSpecific tests are unavailable, so the diagnosismust be made on history and clinical featuresalone. However, to exclude the systemic disordersdiscussed above, it is often useful to undertakethe investigations shown in Table 3. Biopsyis rarely indicated, and only when a differentdiagnosis is suspected.Table 3 Investigation of aphthaeFull blood countHaematinicsFerritinFolateVitamin B 12Screen for coeliac diseaseFig. 8 Major aphthous ulceration,soft palate complexFig. 9 Major aphthous ulcerationManagementOther similar disorders such as Behcet’s syndromemust be ruled out (see below). Predisposingfactors should then be corrected. Fortunately,the natural history of RAS is one of eventualremission in most cases. However, few patientsdo not have spontaneous remission for severalyears and although there is no curative treatment,measures should be taken to relieve symptoms,correct reversible causes (haematologicaldisorder, trauma) and reduce ulcer duration.Maintain good oral hygieneChlorhexidine or triclosan mouthwashes mayhelp.262 BRITISH DENTAL JOURNAL VOLUME 199 NO. 5 SEPT 10 2005

PRACTICETable 4 Examples of readily available topicalcorticosteroidsSteroid UK trade name Dosage everysix hoursLow potencyHydrocortisone Corlan 2.5 mg pellethemisuccinate pelletsdissolved inmouth close toulcersMedium potencyTriamcinolone Adcortyl in Apply paste toacetonide 0.1% in Orabase dried lesionscarmellose gelatin pasteBetamethasone Betnesol 0.5 mg; use asphosphate tabletsmouthwashHigh potencyBeclometasone Becotide 100 1 puff(Beclomethasone)(100 micrograms)dipropionate sprayto lesionsTopical corticosteroids can usually controlsymptomsThere is a spectrum of topical anti-inflammatoryagents that may help in the management ofRAS. Common preparations used include thefollowing, four times daily:• Weak potency corticosteroids topical hydrocortisonehemisuccinate pellets (Corlan), 2.5 mgor• Medium potency steroids - topical triamcinoloneacetonide in carboxymethyl cellulosepaste (Adcortyl in orabase), or betamethasoneor• Higher potency topical corticosteroids (egbeclometasone) (Table 4).The major concern is adrenal suppressionwith long-term and/or repeated application,but there is evidence that 0.05% fluocinonidein adhesive paste and betamethasone-17-valerate mouthrinse do not cause this problem.Topical tetracycline (eg doxycycline), ortetracycline plus nicotinamide may providerelief and reduce ulcer duration, but should beavoided in children under 12 who might ingestthe tetracycline and develop tooth staining. IfRAS fails to respond to these measures, systemicimmunomodulators may be required,under specialist supervision.Key points for patients: aphthous ulcers• These are common• They are not thought to be infectious• Children may inherit ulcers from parents• The cause is not known but some followuse of toothpaste with sodium lauryl sulphate,certain foods/drinks, or stoppingsmoking• Some vitamin or other deficiencies orconditions may predispose to ulcers• Ulcers can be controlled but rarely cured• No long-term consequences are knownWebsites and patient informationhttp://www.usc.edu/hsc/dental/opath/Cards/AphthousStomatitis.htmlhttp://openseason.com/annex/library/cic/X0033_fever.txt.htmlInfectionsInfections that cause mouth ulcers are mainlyviral, especially the herpesviruses, Coxsackie,ECHO and HIV viruses. Bacterial causes ofmouth ulcers, apart from acute necrotisingulcerative gingivitis, are less common. Syphilisand tuberculosis are uncommon but increasing,especially in people with HIV/AIDS. Fungaland protozoal causes of ulcers are also uncommonbut increasingly seen in immunocompromisedpersons, and travellers from the developingworld.Herpes simplex virus (HSV)The term ‘herpes’ is often used loosely to refer toinfections with herpes simplex virus (HSV). Thisis a ubiquitous virus which commonly produceslesions in the mouth and oropharynx. HSV iscontracted by close contact with infected individualsfrom infected saliva or other body fluidsafter an incubation period of approximately fourto seven days.Primary infection is often subclinicalbetween the ages of 2-4 years but may presentwith stomatitis (gingivostomatitis). This isusually caused by HSV-1 and is commonlyattributed to ‘teething’ particularly if there is afever. In teenagers or older people, this may bedue to HSV-2 transmitted sexually. Generallyspeaking, HSV infections above the belt (oralor oropharyngeal) are caused by HSV-1 butbelow the belt (genital or anal) are caused byHSV-2.The mouth or oropharynx is sore (herpeticstomatitis or gingivostomatitis): there is a singleepisode of oral vesicles which may bewidespread, and which break down to leaveoral ulcers that are initially pin-point but fuseto produce irregular painful ulcers. Gingivaloedema, erythema and ulceration are prominent,the cervical lymph nodes may beenlarged and tender, and there is sometimesfever and/or malaise. Patients with immunedefects are liable to severe and/or protractedinfections.HSV is neuroinvasive and neurotoxic andinfects neurones of the dorsal root and autonomicganglia. HSV remains latent thereafter inthose ganglia, usually the trigeminal ganglion,but can be reactivated to result in clinicalrecrudescence (see below).DiagnosisDiagnosis is largely clinical. Viral studies areused occasionally and can include:• culture; this takes days to give a result• electron microscopy; this is not alwaysavailable• polymerase chain reaction (PCR) detectionof HSV-DNA; this is sensitive butexpensive• immunodetection; detection of HSV antigensis of some value.BRITISH DENTAL JOURNAL VOLUME 199 NO. 5 SEPT 10 2005 263

PRACTICEManagementAlthough patients have spontaneous healingwithin 10-14 days, treatment is indicated particularlyto reduce fever and control pain. Adequatefluid intake is important, especially inchildren, and antipyretics/analgesics such asparacetamol/acetoaminophen elixir help. Asoft bland diet may be needed, as the mouthcan be very sore. Aciclovir orally or parenterallyis useful mainly in immunocompromisedpatients or in the otherwise apparently healthypatient if seen early in the course of the diseasebut does not reduce the frequency of subsequentrecurrences.Recurrent HSV infectionsUp to 15% of the population have recurrentHSV-1 infections, typically on the lips (herpeslabialis: cold sores) from reactivation of HSVlatent in the trigeminal ganglion. The virus isshed into saliva, and there may be clinicalrecrudescence. Reactivating factors includefever such as caused by upper respiratory tractinfection (hence herpes labialis is often termed‘cold’ sores), sunlight, menstruation, trauma andimmunosuppression.Lip lesions at the mucocutaneous junctionmay be preceded by pain, burning, tingling oritching. Lesions begin as macules that rapidlybecome papular, then vesicular for about 48hours, then pustular, and finally scab within 72-96 hours and heal without scarring (Fig. 11).treatment is indicated. Antivirals will achievemaximum benefit only if given early in the diseasebut may be indicated in patients who havesevere, widespread or persistent lesions and inimmunocompromised persons. Lip lesions inhealthy patients may be minimised with penciclovir1% cream or aciclovir 5% cream appliedin the prodrome. In immunocompromisedpatients, systemic aciclovir or other antiviralssuch as valaciclovir (the precursor of penciclovir)may be needed.Websites and patient informationhttp://openseason.com/annex/library/cic/X0033_fever.txt.htmlKey points for patients: cold sores• These are common• They are caused by a virus (Herpes simplex)which lives in nerves forever• They are infectious and the virus can betransmitted by kissing• They may be precipitated by sun-exposure,stress, injury or immune problems• They have no long-term consequences• They may be controlled by antiviral creamsor tablets, best used early onDrug-induced ulcerationDrugs may induce ulcers by producing alocal burn, or by a variety of mechanismssuch as the induction of lichenoid lesions(Fig. 12). Cytotoxic drugs (eg methotrexate)commonly produce ulcers, but non-steroidalanti-inflammatory drugs (NSAIDs), alendronate(a bisphosphonate), nicorandil (acardiac drug) and a range of other drugs mayalso cause ulcers.Fig. 11 Herpes labialisRecurrent intraoral herpes in apparentlyhealthy patients tends to affect the hard palateor gingivae with a small crop of ulcers whichheals within one to two weeks. Lesions are usuallyover the greater palatine foramen, followinga palatal local anaesthetic injection, presumablybecause of the trauma.Recurrent intraoral herpes in immunocompromisedpatients may appear as chronic, oftendendritic, ulcers, often on the tongue.DiagnosisDiagnosis is largely clinical; viral studies areused occasionally.ManagementMost patients will have spontaneous remissionwithin one week to 10 days but the condition isboth uncomfortable and unsightly, and thusFig. 12 Lichenoid reaction to propranololA drug history is important to elicit suchuncommon reactions, and then the offendingdrug should be avoided.Patients to refer:• Severe aphthae• Malignancy• HIV-related ulceration• TB or syphilis• Drug-related ulceration• Systemic disease• Mucocutaneous disorders.264 BRITISH DENTAL JOURNAL VOLUME 199 NO. 5 SEPT 10 2005