Oral medicine-Aphthous and other common ulcers-Diagnosis and Management

Ulceration
Ulceration  is  a  breach  in  the  oral epithelium,  which  typically  exposes  nerve endings in  the underlying  lamina  propria,  resulting in  pain  or  soreness,  especially when  eating spicy  foods  or  citrus  fruits.  Patients vary  enormously  in  the  degree  to which they  suffer  and  complain  of soreness  in   relation   to   oral  ulceration.   It   is always  important to  exclude  serious  disorders  such as oral cancer(Part 9) or other serious disease, but not all patients who complain of soreness have discernible organic disease. Conversely,  some with seriousdisease have no pain. Even in  those  with detectable  lesions, the  level  of  complaint can vary enormously. Somepatients with large ulcers complain little; others with minimal ulceration    complain    bitterly   of  discomfort.  Sometimes there is a psychogenicinfluence.

Terminology
Epithelial thinning or breaches may be seen in:  mucosal  atrophy   or   desquamation  — terms often used for thinning of the epithelium which  assumes  a red  appearance  as the  underlying  laminapropria containing blood vessels shows  through. Most commonly this isseen in desqua-  mative   gingivitis   (usually  related   to   lichen  planus, or lesscommonly to pemphigoid) and in  geographic  tongue  (erythema migrans,  benign migratory glossitis). A similar process mayalso  be seen in systemic disorders such as deficiency  states (ofiron, folic acid or B vitamins). 

Small Erosions and Minor aptheous ulcers

Chemical Burn-Above and Thermal burn-Below

Mucosal inflammation (mucositis, stomatitis)  which  can cause  soreness.  Viral stomatitis,  candidosis,radiation mucositis, chemotherapy-  related  mucositis  and graft-versus-host-disease are examples.  erosion which is the termused for superficial  breaches of the epithelium. These often have a redappearance initially as there is little damage to the underlying laminapropria, but they  typically become covered by a fibrinous exudatewhich  has  a  yellowish  appearance.  Erosions  are  common  in vesiculobullousdisorders such as pemphigoid.  ulcer  which  is  the term  usually  used  where  there is damage both toepithelium and lamina  propria. An inflammatory halo, if present, also highlightsthe ulcer with a red halo around the  yellow  or  grey ulcer.  Most ulcers  are  due to  local  causes  such  as  trauma  or burns, but  recurrent  aphthous stomatitis  and cancer  must  always be considered.

Main causes of oral ulceration

Local causes

• Aphthae
• Infections
• Drugs
• Malignant disease
• Systemic diseases
• Chemical burn, right
• maxillary tuberosity  
• Thermal burn, palate

Main causes of mouth ulcers
Local causes
Trauma

• Appliances
• Iatrogenic
• Non-accidental injury
• Self-inflicted
• Sharp teeth or restorations

Burns

• Chemical
• Cold
• Electric
• Heat
• Radiation

Recurrent aphthae

Infections

• Acute necrotising gingivitis
• Chickenpox
• Deep mycoses
• Hand, foot and mouth disease
• Herpangina
• Herpetic stomatitis
• HIV
• Infectious mononucleosis
• Syphilis
• Tuberculosis

Drugs

• Cytotoxic drugs,
• Nicorandil, NSAIDs
• Many others

Malignant neoplasms

• Oral
• Encroaching from antrum

Systemic disease

• Mucocutaneous disease
• Behcet's syndrome
• Chronic ulcerative stomatitis
• Epidermolysis bullosa
• Erythema multiforme
• Lichen planus
• Pemphigus vulgaris
• Sub-epithelial immune blistering diseases (Pemphigoid and variants, dermatitis  herpetiformis, linear IgA disease)

Haematological disorders

• Anaemia
• Gammopathies
• Haematinic deficiencies
• Leukaemia and myelodysplastic syndrome
• Neutropenia and other white cell dyscrasias

Gastrointestinal disease

• Coeliac disease
• Crohn's disease
• Ulcerative colitis

Miscellaneous uncommon diseases

• Eosinophilic ulcer
• Giant cell arteritis
• Hypereosinophilic syndrome
• Lupus erythematosus
• Necrotising sialometaplasia
• Periarteritis nodosa
• Reiters syndrome
• Sweet's syndrome
• Wegener's granulomatosis

Causes of oral ulceration
Ulcers and erosions can also be the final common  manifestation of aspectrum of conditions. These  range  from:  epithelial  damage resulting  from  trauma;  an immunological attack  as  in  lichen planus,    pemphigoid    or   pemphigus;    damage because  of an  immune  defect  as  in HIV  disease and leukaemia; infections such as herpesviruses,  tuberculosis andsyphilis; cancer and nutritional  defects  such  as vitamin  deficiencies  and  some  gastrointestinaldiseases.

Ulcers of local causes
At any age, there may be burns from chemicals  of  various kinds,  heat ,  cold,  orionising radiation or factitious ulceration, especially of the maxillarygingivae or palate. Children may develop ulceration of the lower lip  by  accidental biting  following  dentallocal  anaesthesia.    Ulceration   of    the    upper   labial fraenum,  especially  in  achild with  bruised  and  swollen lips, subluxedteeth or fractured jaw can  represent non-accidental injury. At any age,trauma,  hard  foods,  or appliances  may  also cause ulceration. The lingual fraenum may be trauma-  tised by repeated  rubbing  over  the lower incisor  teeth in cunnilingus, in recurrent coughing as in whooping cough, or in self-mutilating conditions.  Most  ulcers of  local  cause  have an  obvious aetiology,  are acute,  usually  single  ulcers, last  less  than  three  weeks and  heal spontaneously. Chronic  trauma  may  produce an  ulcer  with  a  keratotic margin.

 

Minor aphthous ulceration

RAS  lesions  early  on,  along  with  some natural  killer (NK) cells. Cytotoxic cells then appear in the lesions  and  there  is  evidence  for  an antibody  dependent cellular cytotoxicity (ADCC) reaction. It now seems likely therefore that a minor degree of immunologicaldysregulation underlies aphthae. RAS may be a group of disorders of different pathogeneses.  Cross-reacting  antigens  between  theoral mucosa and microorganisms may be the  initiators, but attempts toimplicate a variety of  bacteria or viruses have failed.

Predisposing factors
Most   people   who   suffer   RAS  are   otherwise  apparently completely well. In afew, predisposing  factors  may  be  identifiable,  or suspected.
These include:
1. Stress: underlies RAS in many cases. RAS are typically worse at examinationtimes.
2. Trauma: biting the mucosa, and dental appliances may lead to some aphthae.
3. Haematinic deficiency (deficiencies of iron, folic acid (folate) or vitaminB  12) in up to 20% of patients.
4. Sodium lauryl sulphate (SLS), a detergent in some oral healthcare productsmay produce oral ulceration.
5. Cessation of smoking: may precipitate or aggravate RAS.
6. Gastrointestinal disorders particularly coeliac disease (gluten-sensitiveenteropathy) and Crohn's disease in about 3% of patients.
7. Endocrine factors in some women whose RAS are clearly related to the fall inprogestogen level in the luteal phase of their menstrual cycle.
8. Immune deficiency: ulcers similar to RAS may be seen in HIV and other immunedefects.
9. Food allergies: underlie RAS rarely.

Drugs may produce aphthous-like lesions.

Key points for dentists: 

Aphthous ulcers They are so common that all dentistswill see them
It is important to rule out predisposing causes (sodium lauryl sulphate,certain foods/drinks, stopping smoking or vitamin or other deficiencies) orconditions such as

Behcet's syndrome
Enquire about eye, genital, gastrointestinal or skin lesions
Topical corticosteroids are the main treatment

Traumatic ulceration, lateral tongue Recurrent aphthous stomatitis(RAS; aphthae; canker sores)

RAS is a very common condition which typically starts  in  childhood or  adolescence  and presents with  multiple recurrent  small,  round  or  ovoid ulcers withcircumscribed margins, erythematous haloes, and yellow or grey floors.RAS  affects  at  least 20%  of the population, with the highest prevalence in higher socio-economic   classes. Virtually  all   dentists   will  see patients with aphthae.

Aetiopathogenesis
Immune  mechanisms  appear  at  play  in  a person with a genetic predisposition to oral ulceration. A genetic predisposition  is  present,  and  there  is a positive   family  history  in  about   one   third   of
patients with RAS. Immunological factors are also involved, with T helper cellspredominating in the


Clinical features
There   are   three   main   clinical  types   of   RAS, though  the significance  of  these distinctions  is
unclear and it is conceivable that they may rep- resent three differentdiseases:

1. Minor aphthous ulcers (MiAU; Mikulicz Ulcer) occur  mainly  in the  10  to 40-year-old age group, often cause minimal symptoms, and are small   round  or   ovoid   ulcers   2-4 mm  in diameter. The ulcer floor is initially yellowishbut  assumes  a  greyish  hue  as healingand epithelialisation proceeds. They are surrounded by  an erythematous  halo and some  oedema, and  are found  mainly  on  the  non-keratinised mobile mucosaof the lips, cheeks, floor of the mouth,  sulci  or  ventrum of  the tongue.  They are only uncommonly seen on thekeratinised mucosa of the palate or dorsum of the tongue and occur in groups ofonly a few ulcers (one to six) at a time. They heal in seven to 10 days, and recur at  intervals  of  one  to  four months leaving little or no evidence of scarring. are found  on  any  area  of  the  oral mucosa, including    the    keratinised   dorsum of   the tongue orpalate, occur in groups of only a few ulcers (one to six) at one time and healslowly over 10 to 40 days. They recur extremely frequently may heal withscarring and are occasionally found with a raised erythrocyte sedimentation rate or plasma viscosity.

3. Herpetiform  Ulceration  (HU)  is  found  in a slightly older age group than the other forms of RAS and are foundmainly in females. They begin with vesiculation which passes rapidly into multiple  minute  pinhead-sized  discrete ulcers (Fig.  10),  which involve  any  oral site including    the    keratinised   mucosa.    They increase  in  sizeand  coalesce  to  leave  large round ragged ulcers,which heal in 10 days or longer, are often extremely painful and recur sofrequently that ulceration may be virtually continuous.

2. Major aphthous ulcers (MjAU; Sutton's Ulcers; periadenitis    mucosa     necroticarecurrens (PMNR))  (Figs  8  and 9)  are  larger,  of  longer duration,  of more  frequent recurrence,  and often  more painful  than  minor  ulcers.  MjAU are round orovoid like minor ulcers, but they are  larger  and  associated with  surrounding oedema  and  can reach  a large  size,  usually about  1  cm  in diameter  or  even  larger.  They

Major Aptheous Ulceration

Diagnosis
Specific  tests  are  unavailable,  so  the diagnosis must  be  made  on  history  and clinical  features alone.  However,  to  exclude  the  systemic disorders discussed above, it is often useful to undertake theinvestigations shown in Table 3. Biopsy is  rarely indicated, and  only  when  a  different diagnosis is suspected.

Investigation of aphthae

1. Full blood count
2. Haematinics
3. Ferritin
4. Folate
5. Vitamin B12
6. Screen for coeliac disease

Management
Other  similar  disorders  such  as  Behcet's syndrome must be ruled out (see below). Predisposing factors should thenbe corrected. Fortunately, the natural history of RAS is one of eventualremission  in  most  cases.  However,  few patients do  not  have spontaneous  remission for  several years   and  although  there is  no  curative treatment, measures should be taken torelieve symptoms,  correct  reversible  causes(haematological disorder, trauma) and reduce ulcer duration.

Maintain good oral hygiene Chlorhexidine or triclosan mouthwashes may help.

Examples of readily available topical corticosteroids
Steroid                                         Dosage every six hours
Low potency
Hydrocortisone
hemisuccinate pellets                             2.5 mg pellet dissolved in mouth close to ulcers

Medium potency
Triamcinolone acetonide 0.1% in           Apply paste to dried lesions
carmellosegelatinpaste
Betamethasone
phosphate tablets

High potency
Beclometasone                              0.5 mg; use as mouthwash Becotide 100 1 puff to lesions (100micrograms)

(Beclomethasone)
dipropionate spray

Topical corticosteroids can usually control symptoms
There is a spectrum of topical anti-inflammatory agents  that  may help  in  the management  of RAS.  Common preparations  used  include  the following, four timesdaily:
•  Weak potency corticosteroids topical hydrocortisone hemisuccinatepellets (Corlan), 2.5mg
or
Medium potency steroids - topical triamcinolone acetonide in carboxymethylcellulose paste (Adcortyl in orabase), or betamethasone
or
Higher   potency   topical   corticosteroids  (eg beclometasone).

The  major  concern  is  adrenal  suppression with  long-term   and/or   repeated application, but  there  is  evidence  that 0.05%  fluocinonide in    adhesive   paste    and  betamethasone-17-valerate mouthrinse do not cause this problem. Topical   tetracycline (eg   doxycycline),   or tetracycline  plus nicotinamide   may   provide relief andreduce ulcer duration, but should be avoided in children under 12 who mightingest the tetracycline  and  develop  tooth staining.  If RAS  fails  to  respond  to these  measures, systemic   immunomodulators  may   be   required, under specialistsupervision.

Key points for patients: aphthous ulcers These are common
They are not thought to be infectious Children may inherit ulcers from parentsThe cause is not known but some follow use of toothpaste with sodium laurylsulphate, certain foods/drinks, or stopping smoking
Some vitamin or other deficiencies or conditions may predispose to ulcers
Ulcers can be controlled but rarely cured No long-term consequences are known

Infections
Infections  that  cause  mouth  ulcers  are mainly viral,  especially  the  herpesviruses,Coxsackie, ECHO   and   HIV   viruses.  Bacterial   causes   of mouth  ulcers,   apart  from   acute  necrotising ulcerative gingivitis, are less common. Syphilis andtuberculosis are uncommon but increasing, especially   in  people   with   HIV/AIDS.   Fungaland protozoal causes of ulcers are also uncommon but increasingly seen inimmunocompromised persons, and travellers from the developing world.

Herpes simplex virus (HSV)
The term 'herpes' is often used loosely to refer to infections with herpessimplex virus (HSV). This is a ubiquitous virus which commonly produces lesions in  the  mouth  and oropharynx.  HSV  iscontracted  by  close  contact  with  infected individuals from infected saliva or other body fluids after an incubationperiod of approximately four to seven days. Primary    infection   is    often    subclinicalbetween the ages of 2-4 years but may present with   stomatitis  (gingivostomatitis).   This   is usually caused  by HSV-1  and  is  commonly attributedto 'teething' particularly if there is a fever. In teenagers or older people,this may be due  to  HSV-2  transmitted  sexually. Generally speaking,  HSV  infections  above  the belt  (oral or  oropharyngeal)  are  caused  byHSV-1  but below  the  belt  (genital  or anal)  are  caused  by HSV-2.
The  mouth  or  oropharynx  is  sore  (herpeticstomatitis or gingivostomatitis): there is a single   episode  of   oral   vesicles   which  may   be widespread,  and  which  breakdown to  leave oral ulcers that are initially pin-point butfuse to  produce  irregular painful ulcers.Gingival oedema,  erythema  and  ulceration  are prominent,    the   cervical  lymph  nodes    may   be enlarged  and  tender,  and  there is  sometimes fever  and/or malaise. Patients with  immune defects  are  liable  to  severe and/or protracted infections.
HSV  is  neuroinvasive  and  neurotoxic  and infects neurones  of  the  dorsal  root  andautonomic ganglia. HSV remains latent thereafter in those  ganglia, usually  the trigeminal  ganglion, but   can  be   reactivated   to   result  in   clinical recrudescence (see below).

Diagnosis
Diagnosis  is  largely  clinical.  Viral  studies are used occasionally and can include: culture; this takes days to give aresult electron microscopy; this is not always available
polymerase chain reaction (PCR) detection of HSV-DNA; this is sensitive butexpensive
immunodetection; detection of HSV antigens is of some value.
Management
Although  patients  have  spontaneous  healing within 10-14  days,  treatment  is indicated particularly to reduce fever and control pain. Adequate  fluid intake  is important,  especially  in children, and antipyretics/analgesics  such  asparacetamol/acetoaminophen    elixir    help.   A soft  bland  diet  may be  needed, as  the mouth can be very sore. Aciclovir orally orparenterally is    useful    mainly   in   immunocompromised patients or in theotherwise apparently healthy patient if seen early in the course of the disease but  does  not  reduce  the  frequency  of subsequent recurrences.

Recurrent HSV infections
Up  to  15%  of  the  population  have recurrent HSV-1  infections,  typically  on  the lips (herpes labialis:  cold  sores)  from reactivation  of  HSV latent  in  the trigeminal ganglion.  The  virus  is shed  into   saliva,   and   there  may   be   clinical recrudescence.   Reactivating    factors   include fever  such  as  caused  by upper respiratory  tract infection  (hence  herpes labialis  is  often  termed 'cold' sores), sunlight,menstruation, trauma and immunosuppression.
Lip  lesions  at  the  mucocutaneous  junction may be  preceded  by  pain,  burning, tingling or itching.  Lesions  begin  as  macules  that rapidly become  papular,  then vesicular  for about  48 hours, then pustular, and finally scab within 72- 96 hoursand heal without scarring (Fig. 11). treatment  is  indicated. Antivirals  will  achieve maximum benefit only if given earlyin the disease but may be indicated in patients who have severe, widespread  or  persistent  lesions  and  inimmunocompromised   persons.  Lip   lesions  in healthy patients may be minimised with penciclovir  1% cream  or aciclovir  5%  cream  applied in   the    prodrome.    In   immunocompromised patients, systemic  aciclovir or  other  antivirals such   as  valaciclovir   (the   precursor   of penciclovir) may be needed.

Key points for patients: cold sores
These are common
They are caused by a virus (Herpes simplex) which lives in nerves forever Theyare infectious and the virus can be transmitted 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 on

Drug-induced ulceration
Drugs   may   induce   ulcers   by  producing   a local  burn,  or  by  a variety  of mechanisms such   as   the  induction   of   lichenoid   lesions.  Cytotoxic  drugs (eg  methotrexate)commonly  produce  ulcers,  but  non-steroidalanti-inflammatory   drugs    (NSAIDs),   alendronate   (a   bisphosphonate),  nicorandil   (a cardiac drug) and a range of other drugsmay also cause ulcers.

Herpes labialis

Recurrent   intraoral   herpes   in  apparently healthy  patients  tends  to  affect the hard  palate or gingivae  with  a  small crop  of  ulcers  which heals within one to two weeks.Lesions are usually over the greater palatine foramen, following a palatallocal anaesthetic injection, presumably because of the trauma. Recurrent intraoral  herpes  in immunocompromised patients mayappear as chronic, often dendritic, ulcers, often on the tongue.

Diagnosis
Diagnosis  is  largely  clinical;  viral  studies are used occasionally.

Management
Most  patients  will  have  spontaneous  remissionwithin one week to 10 days but the condition is both   uncomfortable  and   unsightly,   and   thus

Lichenoid reaction to propranolol

A  drug  history  is  important  to  elicit such uncommon  reactions,  and  then  the offending drug should be avoided. Patients to refer:

• Severe aphthae
• Malignancy
• HIV-related ulceration
• TB or syphilis
• Drug-related ulceration
• Systemic disease
• Mucocutaneous disorders.