Case 28

A very painful mouth

Examination
Extraoral examination
The patient has enlarged cervical lymph nodes that are
slightly tender, mobile but soft or firm rather than hard.
Apart from this finding no abnormalities are found in a
routine examination of the head, neck and hands.

Intraoral examination
What do you see in Figure 28.1?
There are numerous ulcers on the labial mucosa which have
the following characteristics:

SUMMARY
A 20-year-old man presents to you in your general
dental practice, feeling ill and with a very sore
mouth.

Site

Labial mucosa and attached gingiva

Size

A few millimetres in diameter

Shape

Well defined, rounded, sometimes coalescing to

form larger irregular ulcers

Colour

Covered by a yellow-grey fibrin ulcer slough, no

well-defined rim of periulcer erythema

Background

The surrounding mucosa appears uniformly inflamed

In addition, one large ulcer lies at the commissure and there

are small bloodstained crusts around the lips.
If you were able to examine the patient you would discover
that more ulcers affect much of the oral mucosa, including
the gingivae, palate and tongue, and that they extend back
into the oropharynx.

Give a differential diagnosis on the basis of the information

you have so far.

Primary herpetic gingivostomatitis

Erythema multiforme.

Justify this differential diagnosis.

Fig. 28.1Appearance of the patients mouth.

History
Complaint
The patient complains of pain which is preventing eating
and hampering drinking. He also feels unwell.

History of complaint
He first noticed feeling unwell 4 days previously and
thought he had flu. He was slightly feverish and developed
a headache. His mouth was sore but it was not until about
1 day later that it became very painful. Because he felt
unable to take time off work, he took the remains of a course
of an unknown oral antibiotic which had been prescribed
for his brother who had an infected cut on his arm. This did
not appear to have led to any improvement. He has had no
similar attacks before.

Medical history
The patient is otherwise fit and well.

Primary herpetic gingivostomatitis and other oral viral

infections typically cause multiple round small ulcers of acute
onset, sometimes coalescing, on a background of inflamed
mucosa. The patient feels unwell and has enlarged tender
lymph nodes suggesting infection. Primary Herpes simplex
infection usually affects much of the mucosa and has a
predilection for the keratinized masticatory mucosa of the
gingiva. The patient is older than is normally expected for a
primary infection. However, the average age of patients with
this infection has increased over the last few decades because
improved living conditions have resulted in fewer individuals
coming into contact with the virus during their childhood.
Erythema multiforme (StevensJohnson syndrome) is
possible. The acute onset and bloody crusts on the lips
suggest this diagnosis and the age of the patient is
compatible. However, the distribution of ulcers is not
particularly suggestive of this condition. Erythema multiforme
affects primarily the lips and nonkeratinized lining mucosa of
the anterior mouth, and the ulcers have ragged margins,
whereas the irregular ulcers in the picture seem to be formed
by coalescence of small round ulcers. A trigger for erythema
multiforme is sometimes identified and antibiotics,
particularly sulphonamides, are sometimes the cause. This
patient has had recent antibiotics, but only after the
symptoms appeared. Erythema multiforme is typically

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A v e r y pa i n f u l m o u t h
recurrent and the history of previous attacks and their
periodicity is important in making the diagnosis. However, in
a first attack the features may be milder and, as in this case,
there is no history of similar attacks.

What diagnoses have you discounted and why?

Other oral viral infections do not produce a clinical picture of
this severity. Herpangina and hand, foot and mouth disease
are milder and usually affect the soft palate of children.
Varicella zoster would be expected to cause chicken pox in
this age group though children are the age group more
typically affected; oral zoster usually affects elderly patients
and is unilateral.
Herpetiform aphthous stomatitis should be considered but is
readily excluded. The ulcers may be numerous, small and
coalescing and may have an erythematous background.
However they are usually limited to the anterior or posterior
of the mouth, do not affect keratinized mucosa and are not
accompanied by systemic illness. Attacks are recurrent.
In a mild primary attack of Herpes simplex infection in an
adult, the ulcers may be limited to the gingiva, raising the
possibility of acute necrotizing ulcerative gingivitis. However,
in this case the ulceration is too extensive for necrotizing
gingivitis to be considered and in any case it is usually
clinically characteristic.

What further questions would you ask and what further

examinations would you perform and why?
Do you suffer from cold sores? If the patient has had
recurrent Herpes simplex infection, usually in the form of
herpes labialis, then the present ulcers cannot be due to a
primary herpetic infection. Recurrent herpetic infection is
sometimes a trigger for attacks of erythema multiforme
and a cold sore 12 weeks before onset would raise this
possibility.
In answer to this question, the patient indicates that he does
not suffer from cold sores.
Have you been in contact with anyone with cold sores?
Identification of a possible source of Herpes simplex 12
weeks before the ulcers would give further credibility to this
diagnosis. Contact with Herpes zoster is not significant in this
case but in less clear-cut cases it would be prudent to ask
about both chicken pox and shingles contacts.
The patient has no known contact with any viral disease.
Did you notice small blisters in your mouth before the
ulcers appeared? This would suggest herpes virus infection,
each ulcer being preceded by a small round vesicle. Larger
vesicles and blisters are also found in erythema multiforme
but these are irregular and usually limited to the vermilion
border of the lips and floor of mouth.
Have you taken any drugs or medicines in the last 3
weeks? This will clarify the possibility that medication has
triggered an attack of erythema multiforme.
The patient has taken no medication apart from the antibiotic noted in the history.
Have you any rash anywhere on your body? Erythema
multiforme is associated with a variety of rashes (hence its

name) and the patient should have a skin examination. The

presence of typical target lesions indicates erythema
multiforme but other less characteristic rashes should also be
noted, together with their time of onset.
No rash is present.
Take the patients temperature. This simple investigation is
easily forgotten, but often valuable. A raised temperature in
the early stages indicates infection. The temperature is not
raised in erythema multiforme even when severe (unless
there is infection of skin lesions).
His temperature is 38C.

Diagnosis
This differential diagnosis sometimes poses problems. If
the patient has erythema multiforme he should be treated
with a moderately high dose of systemic steroids, but this
should be avoided if he has a viral infection. A period of
time must elapse before the results of investigations will
be available.

Can you make a diagnosis and commence treatment?

Yes. In this case there is sufficient evidence to make a working
diagnosis of primary Herpes simplex infection. Investigations
should be performed to confirm the diagnosis but need not
delay treatment. Investigations are probably only available to
those in hospital practice. Practitioners confident in the
diagnosis may well instigate treatment without confirmatory
tests.

Investigations
What investigations might you consider, and what are their
advantages and disadvantages?
See Table 28.1.
In the current case, a smear for light microscopy and viral
antibody titre against Herpes simplex were requested.

Treatment
What treatment would you provide?
The patient should be reassured that he has a common viral
infection which, while unpleasant, has no significant
implications. It will run its course in a further 10 days or so
but it is unlikely to worsen significantly now that it is in its
fifth day. Some adult patients may confuse this diagnosis with
genital herpes and require some additional explanation.
While unwell the patient should rest and maintain a good
fluid intake. This is especially important in children who refuse
fluids and become dehydrated rapidly. A sedative
antihistamine such as promethazine is sometimes suggested
for very small and fractious children who cannot sleep during
the acute phase. It also has the advantage of drying the reflex
salivation.
The patient should be warned about infectivity. The virus is
transmitted only by close contact but while there are vesicles
or ulcers in the mouth, the saliva is infectious. Care should be
taken to avoid close contact with other individuals, especially

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Table 28.1Investigations to be considered

Test

Advantages and disadvantages

Smear for light microscopy

Simple and rapid. Characteristic viral changes may indicate herpes virus infection provided epithelial cells from the ulcer
margin are present in the smear. Most hospitals should be able to give an urgent result the same day. However, a smear
will only be positive for the first few days of ulceration. As a result, a positive smear indicates infection but a negative
smear cannot exclude it in all cases.

Swab for viral culture

Simple but takes several days. In general terms this test has the advantage that it detects a wide range of viruses but in
this differential diagnosis the broad specificity is not particularly helpful.

Swab for viral antigen screen

Simple and moderately fast. A small number of viruses may be identified from their antigens in a swab using ELISA
(enzyme-linked immunosorbent assay). Results from this test may be available in 24 hours but it is only available in some
centres.

Swab for polymerase chain reaction (PCR)-based viral detection

Obtaining the smear is simple but the laboratory procedure is complex. Highly specific and moderately fast. Results should
be available in 2448 hours. The test is only available in specialized centres.

Smear for electron microscopy

Very specific and relatively simple but again only available in specialized centres. The result is usually available the same
day.

Serum for viral antibody level

Serum for antibody to herpes and other viruses is simple to obtain and provides a result in about 48 hours. A high titre of
anti-viral lgM indicates acute infection (though it may take a day or two to rise to a detectable level) and a low stable titre
of lgG denotes a previous infection. In the absence of raised lgM, two samples several days apart to demonstrate an
increasing lgG level are required for confident diagnosis of primary infection. This test is widely available and frequently
used.

Biopsy of ulcer

Relatively readily performed but almost never necessary in Herpes simplex infection (except for the unusual chronic
infections found in the immunosuppressed). Will give the diagnosis of herpetic infection in almost all cases. Also diagnostic
in most cases of erythema multiforme.

children. In the nonimmune patient (by definition anyone

with a primary infection) other sites may also become
infected and particular care should be taken not to spread
saliva to the eye.
Antiviral treatment with aciclovir should be considered.
Aciclovir is only effective in the earliest stage of the infection
when the virus is replicating. It must be taken in the first 48
hours for best effect, while vesicles rather than ulcers are
present. Aciclovir is not indicated in this case because of the
delay in presentation (though it might be considered in an
immunosuppressed patient). A dose of 200mg five times
daily is recommended for immunocompetent patients.
Related drugs giving higher levels in the blood, such as
valaciclovir, are usually reserved for Varicella zoster infection.
Preparations for symptomatic relief of the oral ulceration are
indicated. Tetracycline mouthwash (250mg capsule of a
soluble preparation dissolved in water, used four times daily)
is very useful in reducing discomfort and would be an
appropriate choice in this patient who has presented too late
to benefit from aciclovir. Antiseptic mouthwashes such as
chlorhexidine are also effective. These presumably reduce oral
discomfort by preventing bacterial infection of the ulcers.
Chlorhexidine would also compensate for difficulty in carrying
out oral hygiene procedures. Analgesic mouthwashes such as
benzydamine are an alternative.

Prognosis
What is the risk that this patient will suffer from cold sores
in the future?
Between 15 and 30% of individuals who come into contact
with the virus develop recurrent infection. It is not clear
whether those who suffer a symptomatic primary infection
such as gingivostomatitis have an increased risk. Although

this percentage seems high, many patients with recurrent

herpes infection suffer only very occasional lesions.

What are the mechanisms and significance of recurrent

infection?
During infection, H. simplex is transported back along axons of
sensory nerves to their nuclei. There, neurones are infected
but do not die and the virus becomes latent, that is, virus
persists but no infectious virions are produced.
A viral latency gene and the cell mediated immune response
contribute to a balance between latency and reactivation. If
infection reactivates, virus travels down the nerve to cause a
localised recurrent infection of the mucosa or skin, a cold
sore. Because the virus is intracellular for most of this life
cycle, antibodies of the humoral immune response are not
effective in preventing recurrences. Environmental triggers for
cold sores include ultraviolet light, illness and stress.
Latent infection has important consequences. Subclinical
reactivation may result in infectious virus being shed from the
mucosa without the individual realising they have an active
infection. This may be a mechanism of spread in the
population. Latent infection in the geniculate ganglion is one
cause of Bells palsy and very occasionally virus may spread
along nerves to the brain causing herpetic encephalitis.
Labial recurrences are painful and unpleasant but relatively
readily treated because there is often a characteristic
prodromal sensation of burning or itching and vesicles are
easily seen. Early treatment is therefore possible and antiviral
drugs can be very effective. Topical preparations of 5%
aciclovir are available without prescription.

When would you ask the patient to return?

The patient should return in about 1 week to check that
healing is progressing, but earlier if symptoms worsen or new
signs develop.

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At some stage during treatment or follow up the patient
should be warned not to take medications prescribed for
others. The antibiotic prescribed for the patients brother was
apparently a harmless but inappropriate drug. Those who
take others drugs run the risk of hypersensitivity, drug
interaction or other unwanted reaction. The importance of
completing the prescribed dose should be emphasized to all
patients receiving antibiotics, both to ensure effective
treatment and because this is critically important in
preventing the emergence of resistant strains in the
community.

Final outcome
The next day a report on the smear for microscopy shows
no evidence of viral infection (possibly because the ulcers
have been present for several days), but on the following
day the serum antibody result by complement fixation test
shows an anti-Herpes simplex type 1 antibody titre of 160
(normal <10). The diagnosis of herpetic gingivostomatitis is
confirmed.