Prescribing in practice
Oral ulceration: GP guide to
diagnosis and treatment
Stephen Flint MA, PhD, MB BS, BDS, FDSRCS, FFDRCSI, FICD
Figure 1. Nicorandil ulceration. The ulceration is persistent, painful, deep, punched
out, with little inflammatory halo and no induration. The ulceration may respond to
dose reduction, but usually cessation of the drug is required to allow healing to occur
lceration is one of the most
U common complaints of
patients who attend their GPs with
an oral problem and the differen-
tial diagnosis is extensive.
However, the artificial distinction
between medicine and dentistr y
has led to this important area of
disease presentation being over-
looked in medical training, and
many doctors therefore feel inad-
equately prepared to deal with oral
mucosal disease.
Although the cause of ulcera-
tion is often local, the oral mucosa
is an important site of manifesta-
tion of many systemic conditions
and oral ulceration may be the ini-
tial presentation in such cases. The
oral mucosa can be easily exam-
ined with a good light and a
wooden spatula, and a thorough
oral inspection should be part of
every clinical examination since it
32 Prescriber 5 March 2006
is such a readily accessible source
of diagnostic information.
Causes of oral ulceration range
from the relatively trivial, eg trau-
matic ulcers, to the serious, eg oral
cancer or pemphigus vulgaris (see
Table 1).
The key to appropriate therapy
is accurate diagnosis and this may
require liaison between general
and specialist medical and dental
practitioners.
Diagnosis of oral
ulceration
Ulcers of different causes may have
ver y similar clinical appearance
and a few important key questions
in the history provide useful diag-
nostic clues. Because of the rich
inner vation of the oral mucosa,
most ulcers are painful.
An important exception to this
rule is early squamous cell carci-
Simple mouth ulcers are
usually self-limiting and
rarely present in general
practice. However, severe,
recurrent or persistent oral
ulceration can be extremely
painful and may result from
an underlying systemic
pathology. Dr Flint describes
the different causes of oral
ulcers and discusses treat-
ment options.
noma (see Figure 2): this typically
presents as an ulcer with a rolled
everted edge and sloughing or
granular base. The exophytic form,
verrucous carcinoma, is uncom-
mon but has a better prognosis.
The ulcer is often painless
until it involves the periosteum,
bone or deep mucosal tissues and,
consequently, many patients pre-
sent late with extensive disease
and a poor prognosis. The key to
management of this disease is
early diagnosis and prompt surgi-
cal treatment.
Persistent, painless ulcers that
are found on routine examination,
particularly in the elderly, should
thus not be ignored, especially in
those who smoke or drink alcohol
regularly, or where there is evi-
dence of er ythroplakia or leu-
coplakia. The incidence of oral
cancer is increasing.
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Prescribing in practice

Primary ulcers sents with oral ulcers should prompt

the question of whether the oral
Recurrent aphthous stomatitis complaint is a manifestation of that
minor, major and herpetiform variants; associated with haematinic deficiencies, gastrointestinal disease or the drug therapy.
disease (Crohn’s disease, ulcerative colitis and coeliac disease), congenital and acquired immuno- A few pertinent questions
deficiency and blood dyscrasias; consider Behçet’s, MAGIC, and Sweet’s and PFAPA syndromes about the evolution and chronic-
ity of the ulceration may help the
Trauma clinician to arrive at the correct
usually accidental, or trauma from overextended dentures or sharp teeth; rarely, burns, stomatitis diagnosis. Ulcers may arise de novo
artefacta or trauma to exophytic lesion (primary ulcers) or secondary to
breakdown of vesicles or bullae
Dermatoses (secondar y ulcers) and may be
erosive and atrophic lichen planus, discoid and systemic lupus erythematosus, erythema multi- recurrent or persistent. A previous
forme, linear IgA disease history of trauma is usually offered
by the patient without direct ques-
Malignancy tioning. A systematic enquir y
squamous cell carcinoma usually presents as a persistent primary ulcer; exophytic lesions may be should also be undertaken.
traumatised and fungate Oral examination must be per-
formed with a good light source
Infections and taking a systematic approach
tuberculosis, syphilis, Reiter’s syndrome and acute necrotising ulcerative gingivitis; atypical or signs will be missed. It is essen-
lesions and ‘exotic’ infections in HIV disease, including deep mycoses tial to use an instrument such as a
wooden tongue depressor to exam-
Orofacial granulomatosis ine all the tissues. Wooden instru-
linear or serpiginous ulcers, particularly in the buccal sulci; associations with gastrointestinal ments should be wetted to avoid
diseases and allergies adherence to the oral tissues
which, in patients with extensive
Neutropenic ulcers ulceration, is very painful.
congenital and acquired immunodeficiencies; ulcers lack an inflammatory erythematous halo; may A basic management algorithm
be drug related; atypical viral fungal and bacterial lesions is shown in Figure 3.

Drugs Common causes of oral

aspirin and other caustic burns; cytotoxic drugs often cause mucositis and ulceration; fixed and ulceration
lichenoid drug eruptions, nicorandil and bisphosphonate ulceration The four most common presenta-
tions are trauma, recurrent aph-
Secondary ulcers
thous stomatitis, herpes virus group
Viral diseases infections and dermatoses,
mostly herpes virus group and enterovirus group enanthemata although the differential diagnosis
is extensive (see Table 1). The rarer
Dermatoses disorders should probably be man-
pemphigus (and variants), pemphigoid (and variants), congenital and acquired epidermolysis aged by a team approach through
bullosa, dermatitis herpetiformis and bullous lichen planus specialist centres. Some drugs may
also be the direct cause of oral
Angina bullosa haemorrhagica ulceration.
idiopathic blood blisters, usually on the soft palate
Traumatic ulceration
Table 1. Due to the similar clinical appearance of many oral ulcers, the differential diagnosis is extensive
Traumatic ulceration is usually
Although there are many con- tions may cause or be associated with caused by denture trauma, sharp,
genital or hereditary causes of oral oral ulceration. Further, drug ther- broken teeth or accidents and will
ulceration, they are all very rare. apy for systemic conditions may also resolve within two weeks following
Disorders of the gastrointestinal, cause or worsen oral ulceration. Any dental treatment. Persistence of a
haematological, immunological and patient with a known systemic dis- lesion after removal of the pre-
dermatological systems or viral infec- ease or taking medication who pre- sumed cause, particularly in the

34 Prescriber 5 March 2006 www.escriber.com

Prescribing in practice

elderly, raises the possibility of an

underlying tumour or foreign
body and exploration or biopsy is
indicated. The healing power of
the mouth is remarkable and most
traumatic ulcers resolve unevent-
fully, but occasionally superinfec-
tion occurs.
If the ulcer is infected and the
patient toxic, the antibiotics of
choice in this situation are phe-
noxymethylpenicillin, amoxicillin
or metronidazole. Useful adjuncts
are antimicrobial mouthwashes –
chlorhexidine, povidone-iodine
(Betadine) or benzydamine
(Difflam) – which may also be used
prophylactically.
Figure 2. Squamous cell carcinoma of the tongue. This is the commonest site for oral Artefactual stomatitis is rare
squamous cell carcinoma; the ulcer is persistent, often relatively painless, with raised, and is a difficult diagnosis. Most
rolled edges, necrotic base and indurated on palpation continued on page 40

36 Prescriber 5 March 2006 www.escriber.com

Prescribing in practice

oral ulceration

pre-existing systemic previously healthy

disease, drug therapy

arises de novo vesicles, bullae

oral manifestation?
drug reaction?

primary ulcer secondary ulcer

recurrent persistent febrile: afebrile

constitutional
upset?
longstanding?
skin lesions?
typical not aphthous local cause no local cause
aphthous stomatitis
probable
stomatitis probably viral
dermatosis

investigate or
treat refer? remove cause biopsy symptomatic
refer for
treatment
specialist
investigation
refractory or
change in resolution no resolution resolution no resolution
disease pattern

investigate biopsy refer

predisposing
disease or refer

Figure 3. Recommended management of oral ulceration

patients will deny self-injury and
the underlying psychopathology
requires attention. Treatment of
oral lesions is symptomatic.
Recurrent aphthous stomatitis
Recurrent aphthous stomatitis is
common and may affect 10 per
cent of the population at some
time during their lives. One in 15
patients have an underlying cause
in some series which, if treated,
will ameliorate or cure the condi-
tion. One in three patients has a
family history and the onset is usu-
ally in the young. Most are non-
smokers and otherwise healthy.
The diagnosis is clinical and
three variants – minor (see Figure
4), major and herpetiform – are
described. The pathogenesis is
immunologically mediated but
poorly understood.
In most patients outbreaks are
infrequent and respond to simple
treatments such as topical steroids,
eg 0.1 per cent triamcinolone ace-
tonide in carboxymethylcellulose
paste (Adcortyl in Orabase), and
antimicrobial mouthwashes, eg
chlorhexidine, povidone-iodine or
benzydamine.
For maximum benefit treat-
ment is best initiated in the ‘pro-
dromal’ phase or as soon as the
ulcer begins to form. It is impor-
tant that the oral mucosa is dried
before applying carboxymethyl-
cellulose preparations so that the

40 Prescriber 5 March 2006 www.escriber.com

 Prescribing in practice

paste will adhere to the mucosa

and cover the ulcer. Some patients
appear to be sensitive to sodium
laur yl sulphate (SLS), and may
respond to an SLS-free toothpaste.
In adults, herpetiform aphthous
stomatitis usually responds to tetra-
cycline mouthrinse and swallow
(but this is contraindicated in chil-
dren due to the problem of dis-
coloration of the developing
teeth).
Patients whose ulcers prove
unresponsive to these therapies
may respond to one of the many
other suggested systemic therapies
(see Table 2). However, there is a Figure 4. Recurrent aphthous ulceration (minor type). These ulcers are common,
dearth of evidence for most of painful, with a yellow-white sloughing base and inflammatory erythematous halo; the
these treatments and many are of ulcers are not indurated and heal spontaneously within two weeks
questionable efficacy, or are unli-
censed in this indication. with interstitial chondritis) may presentation and there may be a
Some over-the-counter med- be a forme fruste (incomplete geographical distribution.
ications may offer some sympto- presentation). PFAPA syndrome Haematinic deficiencies (of iron,
matic relief for patients with (periodic fever, aphthous ulcera- vitamin B12 or folic acid), even in
occasional ulcers, since the disease tion, phar yngitis and adenopa- the absence of frank anaemia,
is self-limiting. More aggressive thy) has a distinct clinical predispose to aphthous stomatitis
prescription-only therapy is indi-
cated in patients with continuous Topical
ulcers and those whose quality of
life is severely affected. However, chlorhexidine beclometazone
accurate diagnosis is paramount benzydamine betamethasone
before embarking on this course. carbenoxolone sucralfate
Recalcitrant major aphthous betadine tetracyclines
ulcers, which may be seen in HIV hydrocortisone HC sodium lauryl sulphate avoidance
disease, may be successfully treated triamcinolone bioadhesives
with triamcinolone acetonide fluocinolone lasers
intralesional injections or thalido-
mide. However, before treatment Systemic
it is important to exclude an levamisole ciclosporin
opportunistic infectious cause, transfer factor amlexanon
such as a deep mycosis. colchicine 5-ASA
Patients with severe aphthosis gammaglobulins zinc sulphate
who are rarely ulcer free, have a azathioprine MAOIs
change in disease pattern or are dapsone contraceptive pill
unresponsive to treatment should thalidomide H2-antagonists
be investigated for an underlying pentoxifylline cromoglicate
cause. Behçet’s syndrome, a triad prednisolone liquorice
of orogenital ulceration with azelastine etretinate
uveitis and variable dermatologi- alfa interferon diclofenac
cal, musculoskeletal and neuro- LongoVital aspirin
logical manifestations, should be prostaglandin E2
excluded. MAGIC syndrome
(mouth and genital ulceration Table 2. Reported treatments for aphthous ulceration

www.escriber.com Prescriber 5 March 2006 41

 Prescribing in practice

as do coeliac disease, Crohn’s dis-

ease and ulcerative colitis, which
may be co-existent or occult. It is
important to ascertain the cause
of, as well to treat, haematinic
deficiencies.
Further predisposing factors
include congenital and acquired
immunodeficiency states, blood
dyscrasias and food allergy.
Occasionally female patients report
premenstrual aphthous ulcers that
have been found to respond to hor-
monal manipulation.

Herpes virus and enteroviral

infections Figure 5. Lichenoid eruption (to a beta-blocker). There is central ulceration, but
Primary herpetic gingivostomatitis peripherally reticular (strial) white lesions are present; the ulceration is persistent and
is caused by the herpes simplex painful, but will resolve completely with cessation of the offending drug
virus (HSV) type I or II and usually
affects children and young adults; varicella zoster virus infection. The enterovirus group infec-
however, it is occasionally seen in High-dose systemic aciclovir treat- tions, such as hand, foot and
older patients, and causes consti- ment is indicated in shingles, par- mouth disease and herpangina
tutional upset with fever and may ticularly if the ophthalmic tend to be seasonal and occur in
be more florid than in the young. division is involved, and may epidemics. Treatment is sympto-
The treatment of this self-limiting decrease the incidence of pos- matic and supportive.
disease is supportive with attention therpetic neuralgia. Oral ulcera-
to rehydration and antipyretic tion may also be seen in infections Dermatoses
analgesia, avoiding aspirin in chil- with Epstein-Barr virus and A number of dermatological con-
dren. Antimicrobial mouth rinses cytomegalovirus infection in the ditions have ulcerative oral mani-
are useful – in those old enough to immunocompromised. festations. Definitive diagnosis of
use them – and may reduce super-
infection and accelerate healing of
the ulcers. Benzydamine mouth-
wash, if held in the mouth for a
period of time, may have a tempo-
rar y numbing effect, which may
make eating easier during the
acute period.
Recurrent herpes labialis may
be treated with idoxuridine in
dimethyl sulfoxide (Herpid) solu-
tion or aciclovir cream applied early
to the lesions, although penciclovir
cream (Vectavir) may have greater
efficacy. Caution should be exer-
cised, however, since HSV strains
that encode for an aciclovir-resis-
tant thymidine kinase have been
reported. The drug may be life-sav- Figure 6. Erythema multiforme. Although there is usually skin involvement (Stevens-
ing in herpetic encephalomyelitis. Johnson syndrome), an isolated oral variant of erythema multiforme can occur. The
Intraoral ulceration is a fea- ulceration is of acute onset, painful, superficial and irregular; often the entire oral
ture of primar y and secondar y mucosa is involved and there is bloody crusting of the lips

www.escriber.com Prescriber 5 March 2006 43

Prescribing in practice
Antimalarials where ulceration is a feature).
chloroquine, pyrimethamine Extraoral lesions are not invariable
and areas of non-ulcerated mucosa
Antihypertensives usually show some signs of the dis-
beta-blockers, methyldopa ease. Oral lichen planus is
reported to carr y a low risk of
Antimicrobials malignant change.
azoles, tetracycline The aims of treatment are to
convert the ulcerated regions into
NSAIDs asymptomatic forms by the use of
aspirin, phenylbutazone, naproxen immunomodulator y drugs and
then to maintain the status quo by
Oral hypoglycaemics regular monitoring and prompt
tolbutamide, chlorpropamide treatment of relapses. Relapses of
lichen planus are common and,
Other unlike the dermatological variant,
penicillamine, allopurinol, carbamazepine, levamisole, the disease may be present for
lithium, lorazepam many decades.
The mainstays of treatment are
Table 3. Drugs causing lichenoid reactions (after McCartan steroid drugs given topically,
and McCreary) intralesionally or, on occasions, sys-
these conditions usually involves temically. Maintenance of good
conventional histopathology sup- oral hygiene and dental health is
ported by direct and indirect also important. Other therapeutic
immunofluorescence. strategies, such as dapsone, grise-
Lichen planus Lichen planus is ofulvin, retinoids, topical
a common oral disease and is ciclosporin, tacrolimus and pime-
either asymptomatic (hyper- crolimus, sulfasalazine, pentoxi-
trophic, reticular and papular fylline and levamisole have also
forms) or symptomatic (erosive, been tried with varying degrees of
atrophic and bullous variants, success.
Figure 7. Aspirin burn. This patient had a toothache in the lower first molar tooth and
allowed the aspirin tablet to dissolve over the tooth, causing an acid burn with
sloughing of the surrounding mucosa; although not present in this case, central ulcer-
ation often occurs
44 Prescriber 5 March 2006
Discoid and systemic lupus ery-
thematosus and graft versus host
disease have a very similar clinical
appearance to lichen planus when
affecting the mucosa, as do
lichenoid reactions (see Figure 5)
to a wide range of commonly pre-
scribed drugs (see Table 3). The
diagnosis is established by history,
biopsy and serology and patients
with drug-associated lichenoid
lesions usually respond to a change
of medication.
Er ythema multiforme Erythema
multiforme (see Figure 6) and
Stevens-Johnson syndrome may
have a very florid oral presentation
and often ‘target lesions’ on the
skin give the clinical diagnosis.
Occasional triggers include
Mycoplasma infection or herpes
virus reactivation, but often the
cause is cryptic. Erythema multi-
forme may be drug induced from
a wide range of medications.
Those with a well-defined herpetic
trigger may respond to low-dose,
continuous prophylactic aciclovir.
Treatment regimens range
from simple supportive therapy to
systemic steroid therapy.
Avoidance of any known drug trig-
gers is obvious.
The blistering dermatoses Pem-
phigus, pemphigoid, linear IgA
disease (a pemphigoid variant),
epidermolysis bullosa acquisita
and dermatitis herpetiformis have
a well-defined immunopathogen-
esis and diagnosis is by immuno-
fluorescent histopathology and
serology.
Clinically, the bullae of pem-
phigus are fragile and are rarely
seen intraorally. Over half of
patients in their first episode of
pemphigus vulgaris have intraoral
lesions that precede the skin
lesions. The bullae of benign
mucous membrane pemphigoid
and epidermolysis bullosa
acquisita are more robust and are
often blood-filled when seen
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Prescribing in practice

Figure 8. Bisphosphonate ulceration. A long-standing, nonhealing ulcer of the

attached mucosa of the jaws is present, with exposure of the underlying
hypermineralised, hypovascularised bone; these ulcers pose a very significant
management problem, since surgical removal of any sequestra appears to make
the ulceration worse

intact. Linear IgA disease has sim- be usefully monitored by pem-

ilar features. Intraoral dermatitis
herpetiformis is rarely seen in iso-
lation and skin lesions are typical.
Pemphigus vulgaris is treated
with high-dose systemic steroids
with the addition of azathioprine
for a steroid-sparing effect. More
recently, the use of tacrolimus or
mycophenolate mofetil is being
explored, since they are less toxic
than azathioprine and may be use-
ful for patients with TPMT (thio-
purine S-methyltransferase)
deficiency. Patients have to be
monitored intensively for any
steroid side-effects or excessive
immunosuppression during this
phase of their treatment.
Once the lesions have healed,
the steroid treatment and aza-
thioprine dosage are reduced to a
maintenance level. Treatment can
phigus autoantibody titre mea-
surements.
Mucous membrane pem-
phigoid, epidermolysis bullosa
acquisita and linear IgA disease
may respond to topical steroid
preparations, but occasionally the
patient requires a short course of
systemic steroids for a full response
to treatment. Linear IgA disease
may be steroid unresponsive, when
sulphur drugs are the treatment of
choice.
There is an association with
coeliac disease and oral lesions
respond to a gluten-free diet or
dapsone.
Angina bullosa haemorrhagica
presents with blood-filled bullae
that arise rapidly, often on the soft
palate, following minimal trauma
such as eating. Patients become

46 Prescriber 5 March 2006 www.escriber.com

Prescribing in practice
very alarmed with a choking sen-
sation. Rupture of the bulla leads
to ulceration. There is no demon-
strable immunopathogenesis; how-
ever, there are some reports that
show an association with the use of
steroid inhalers and poor inhaler
technique, leading to deposition
of high doses of steroid on the soft
palate leading to mucosal atrophy
and capillar y fragility. Such
patients should be instructed on
inhaler technique and asked to
gargle after inhaler use.
Oral ulceration caused by drugs
Drugs themselves can cause oral
ulceration in a number of ways.
They can have a direct effect, be
associated with fixed drug or
lichenoid eruption, allergy, er y-
thema multiforme or be chemi-
cally caustic and cause a burn if
administered or taken inappro-
priately.
Oral mucosal burns are seen if
bisphosphonates are allowed to
dissolve in the mouth rather than
swallowed whole, with copious
amounts of water, sitting upright.
Classically, patients with toothache
may place an aspirin over the
affected tooth and cause an acid
burn to the mucosa (see Figure 7).
Cytotoxic drugs by their ver y
nature affect rapidly dividing cells
and cause bone marrow suppres-
sion, hair loss and oral (and other)
mucositis and, in sufficient dose,
ulceration.
48 Prescriber 5 March 2006
Key points
• the most common causes of oral
ulceration are trauma and recur-
rent aphthous stomatitis
• any ulcer that does not heal within
two weeks of the removal of the
suspected cause should be biop-
sied
• some ulcers are manifestations of
systemic disease or drug therapy
for that disease
• some drugs themselves can
cause oral ulceration
• immunofluorescent histopathol-
ogy is an important diagnostic
procedure for blistering disorders
• serious diseases such as pemphi-
gus or malignancy may present as
oral ulceration
• appropriate therapy depends on
accurate diagnosis
The list of drugs causing
lichenoid eruptions is presented in
Table 3. Although some of the
drugs are rarely used nowadays,
since the classes of drugs causing
lichenoid eruptions are so disparate
it is likely that these types of lesion
are generally under-reported and
under-recognised, and the full list
may include many new drugs. The
importance of this diagnosis is that
the ulceration will resolve with with-
drawal of the drug, or changing the
drug to a different class of drug to
treat a particular condition.
Some drugs may cause oral
ulceration directly. Oral mucosal
ulceration is associated with nico-
randil (Ikorel) therapy (see Figure
1) and there appears to be a dose
response. The ulceration is long-
standing and will not heal unless
the drug is withdrawn or at least
the dose reduced.
The widespread use of the bis-
phosphonates in a number of
indications is now becoming
recognised as a serious cause of
osteonecrosis of the jaws, pre-
senting as ulceration of the
attached oral mucosa and dead,
infected bone exposure (see
Figure 8), which is proving to be a
serious and ver y difficult man-
agement issue.
Further reading
Oral and maxillofacial diseases. Scully C,
Flint SR, Porter SR, et al. London:
Taylor Francis, 2004.
Oral lichenoid drug eruptions.
McCartan BE, McCrear y CE. Oral
Diseases 1997;(3):58-63.
Oral medicine in practice. Lamey P-J,
Lewis MAO. London: British Dental
Journal Publications, 1992.
Osteonecrosis of the jaw and bisphos-
phonates. Maerevoet M, Martin C,
Duck L. N Engl J Med 2005;7(353):
99-102.
Persitent nicorandil-induced oral
ulceration. Healy CM, Smyth Y, Flint
SR. Heart 2004; 90(7):e38-41.
Dr Flint is a consultant and senior
lecturer at the Dublin Dental School
and Hospital and Trinity College,
Dublin
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