Kamis, 08 Desember 2011

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

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 sore ness have discernible organic disease. Conversely,  some with serious disease have no pain. Even in  those  with detectable  lesions,  the  level  of  complaint can vary enormously. Some patients with large ulcers complain little; others with minimal  ulceration    complain    bitterly    of  discomfort.  Sometimes there is a psychogenic influence.

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  lamina propria containing blood vessels shows  through. Most commonly this is seen in desqua-  mative   gingivitis   (usually   related   to   lichen  planus, or less commonly to pemphigoid) and in  geographic  tongue  (erythema  migrans,  benign migratory glossitis). A similar process may also  be seen in systemic disorders such as deficiency  states (of iron, 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 term used for superficial  breaches of the epithelium. These often have a red appearance initially as there is little damage to the underlying lamina propria, but they  typically become covered by a fibrinous exudate which  has  a  yellowish  appearance.  Erosions  are  common  in vesiculobullous disorders such as pemphigoid.  ulcer  which  is  the  term  usually  used  where  there is damage both to epithelium and lamina  propria. An inflammatory halo, if present, also highlights the 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
  • Appliances
  • Iatrogenic
  • Non-accidental injury
  • Self-inflicted
  • Sharp teeth or restorations
  • Chemical
  • Cold
  • Electric
  • Heat
  • Radiation
Recurrent aphthae
  • Acute necrotising gingivitis
  • Chickenpox
  • Deep mycoses
  • Hand, foot and mouth disease
  • Herpangina
  • Herpetic stomatitis
  • HIV
  • Infectious mononucleosis
  • Syphilis
  • Tuberculosis
  • 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 a spectrum 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 and syphilis; cancer and nutritional  defects  such  as  vitamin  deficiencies  and  some  gastrointestinal diseases.

Ulcers of local causes
At any age, there may be burns from chemicals  of  various  kinds,  heat ,  cold,  or ionising radiation or factitious ulceration, especially of the maxillary gingivae or palate. Children may develop ulceration of the lower  lip  by  accidental biting  following  dental local  anaesthesia.    Ulceration    of    the    upper    labial fraenum,  especially  in  a child with  bruised  and  swollen lips, subluxed teeth 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 immunological dysregulation underlies aphthae. RAS may be a group of disorders of different  pathogeneses.  Cross-reacting  antigens  between  the oral mucosa and microorganisms may be the  initiators, but attempts to implicate a variety of  bacteria or viruses have failed.

Predisposing factors
Most   people   who   suffer   RAS   are   otherwise  apparently completely well. In a few, predisposing  factors  may  be  identifiable,  or  suspected.
These include:
1. Stress: underlies RAS in many cases. RAS are typically worse at examination times.
2. Trauma: biting the mucosa, and dental appliances 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 in some oral healthcare products may produce oral ulceration.
5. Cessation of smoking: may precipitate or aggravate RAS.
6. Gastrointestinal disorders particularly coeliac disease (gluten-sensitive enteropathy) and Crohn's disease in about 3% of patients.
7. Endocrine factors in some women whose RAS are clearly related to the fall in progestogen level in the luteal phase of their menstrual cycle.
8. Immune deficiency: ulcers similar to RAS may be seen in HIV and other immune defects.
9. Food allergies: underlie RAS rarely.

Drugs may produce aphthous-like lesions.

Key points for dentists: 

Aphthous ulcers They are so common that all dentists will see them
It is important to rule out predisposing causes (sodium lauryl sulphate, certain foods/drinks, stopping smoking or vitamin or other deficiencies) or conditions 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 with circumscribed 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.

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 cells predominating 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 different diseases:

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 yellowish but  assumes  a  greyish  hue  as healing and epithelialisation proceeds. They are surrounded by  an  erythematous  halo and some  oedema, and  are  found  mainly  on  the  non-keratinised mobile mucosa of the lips, cheeks, floor of the mouth,  sulci  or  ventrum  of  the tongue.  They are only uncommonly seen on the keratinised mucosa of the palate or dorsum of the tongue and occur in groups of only 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 or palate, occur in groups of only a few ulcers (one to six) at one time and heal slowly over 10 to 40 days. They recur extremely frequently may heal with scarring 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 found mainly 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  size and  coalesce  to  leave  large round ragged ulcers, which heal in 10 days or longer, are often extremely painful and recur so frequently that ulceration may be virtually continuous.

2. Major aphthous ulcers (MjAU; Sutton's Ulcers; periadenitis     mucosa     necrotica recurrens (PMNR))  (Figs  8  and  9)  are  larger,  of  longer duration,  of  more  frequent recurrence,  and often  more  painful  than  minor  ulcers.  MjAU are round or ovoid 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

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 the investigations 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

Other  similar  disorders  such  as  Behcet's  syndrome must be ruled out (see below). Predisposing factors should then be corrected. Fortunately, the natural history of RAS is one of eventual remission  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 to relieve 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
hemisuccinate pellets                             2.5 mg pellet dissolved in mouth close to ulcers
Medium potency
Triamcinolone acetonide 0.1% in           Apply paste to dried lesions
phosphate tablets

High potency
Beclometasone                             0.5 mg; use as mouthwash Becotide 100 1 puff to lesions (100micrograms)
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 times daily:
•  Weak potency corticosteroids topical hydrocortisone hemisuccinate pellets (Corlan), 2.5mg
Medium potency steroids - topical triamcinolone acetonide in carboxymethyl cellulose paste (Adcortyl in orabase), or betamethasone
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 and reduce ulcer duration, but should be avoided in children under 12 who might ingest the tetracycline  and  develop  tooth  staining.  If RAS  fails  to  respond  to  these  measures, systemic   immunomodulators   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 follow use of toothpaste with sodium lauryl sulphate, 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  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 and tuberculosis are uncommon but increasing, especially   in   people   with   HIV/AIDS.   Fungal and protozoal causes of ulcers are also uncommon but increasingly seen in immunocompromised persons, and travellers from the developing world.

Herpes simplex virus (HSV)
The term 'herpes' is often used loosely to refer to infections with herpes simplex virus (HSV). This is a ubiquitous virus which commonly produces lesions  in  the  mouth  and oropharynx.  HSV  is contracted  by  close  contact  with  infected  individuals from infected saliva or other body fluids after an incubation period of approximately four to seven days. Primary    infection    is    often    subclinical between the ages of 2-4 years but may present with   stomatitis   (gingivostomatitis).   This   is usually  caused  by HSV-1  and  is  commonly attributed to '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  by HSV-1  but below  the  belt  (genital  or  anal)  are  caused  by HSV-2.
The  mouth  or  oropharynx  is  sore  (herpetic stomatitis or gingivostomatitis): there is a single   episode   of   oral   vesicles   which   may   be widespread,  and  which  break down to  leave oral ulcers that are initially pin-point but fuse 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  and autonomic ganglia. HSV remains latent thereafter in those  ganglia,  usually  the trigeminal  ganglion, but   can   be   reactivated   to   result   in   clinical recrudescence (see below).

Diagnosis  is  largely  clinical.  Viral  studies  are used occasionally and can include: culture; this takes days to give a result electron microscopy; this is not always available
polymerase chain reaction (PCR) detection of HSV-DNA; this is sensitive but expensive
immunodetection; detection of HSV antigens is of some value.
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  as paracetamol/acetoaminophen    elixir    help.    A soft  bland  diet  may be  needed,  as  the mouth can be very sore. Aciclovir orally or parenterally is    useful    mainly    in   immunocompromised patients or in the otherwise 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 hours and heal without scarring (Fig. 11). treatment  is  indicated.  Antivirals  will  achieve maximum benefit only if given early in the disease but may be indicated in patients who have severe,  widespread  or  persistent  lesions  and  in immunocompromised   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 They are 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 creams or 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-steroidal anti-inflammatory   drugs    (NSAIDs),    alendronate   (a   bisphosphonate),   nicorandil   (a cardiac drug) and a range of other drugs may 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 palatal local anaesthetic injection, presumably because of the trauma. Recurrent  intraoral  herpes  in immunocompromised patients may appear as chronic, often dendritic, ulcers, often on the tongue.

Diagnosis  is  largely  clinical;  viral  studies  are used occasionally.

Most  patients  will  have  spontaneous  remission within 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.

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