Recurrent aphthous stomatitis
Introduction
Recurrent
aphthous stomatitis is the most common inflammatory and ulcerative condition,
characterized by recurring episodes of oral ulcers, typically from childhood or
adolescence, each lasting from 1 to about 4 weeks before healing. Patients are
otherwise apparently healthy.
Recurrent aphthous ulcer (RAU) is a
T-cell-mediated immunological disorder and tumor necrosis factor (TNF)-α plays
an important role in its occurrence, resulting in immunologically
mediated damage to epithelial cells. This abnormal immune response may be triggered
or influenced by local trauma, hematinic (iron, folate or vitamin B12)
deficiencies, hormonal fluctuations, psychological stress, infectious agents,
hypersensitivities to food and sodium lauryl sulphate,
genetic factors, and HIV infection. A
positive family history is
found with about one‐third of patients and there is a
significant association with a number of HLA-haplotypes. Complex aphthosis, the
nearly constant presence of more than three oral aphthae or oral and genital
aphthae, requires the exclusion of Behçet disease, inflammatory bowel disease,
vitamin deficiencies (e.g. B12, folate) and
HIV infection.
Systemic and other factors that may occasionally underlie or be
associated with recurrent aphthous stomatitis (RAS):
|
|
Comments |
|
Autoinflammatory
disorders |
Association
of recurrent mouth ulcers with fevers and serositis |
|
Behçet
syndrome |
Association
of recurrent mouth ulcers with ocular lesions, genital ulcers and multisystem
disease |
|
Endocrine
factors |
In
some women, RAS is clearly related to a fall in progestogens in the luteal
phase of the menstrual cycle; hormone therapy may be beneficial |
|
Gastrointestinal
disease |
Malabsorption
states (pernicious anemia, coeliac disease and Crohn disease) may
precipitate RAS in a small minority |
|
Hematinic
deficiency |
In
some studies, 10–20% of patients with RAS have deficiencies of iron, folic
acid or vitamin B12 |
|
Immunodeficiency |
A
few patients have an immune defect such as HIV disease |
|
Environmental factors |
Exacerbations
with trauma, certain foods, stress and cessation of smoking |
Clinical
features
Idiopathic RAU occurs in 15%–20% of the
population beginning in the second decade of life and the disease generally
becomes less severe over the age of 50. Patients often report the sensation of
a small nodule beneath the epithelium before the ulcer appears. Aphthae typically are multiple round or ovoid ulcers with a
circumscribed margin, erythematous halo and a yellow – white floor.
Clinical
variants
There
are three main clinical types of simple aphthae. Most common are minor
recurrent aphthous stomatitis (MiRAS), which account for 80% of all recurrent
aphthous stomatitis. Some 10% of patients with recurrent aphthous stomatitis
have major aphthous ulcers, and a further 10% suffer from a herpetiform type of
ulceration.
Main
features of recurrent aphthous stomatitis
|
|
Minor aphthae |
Major aphthae |
Herpetiform ulcers |
|
Age
of onset |
10-19 |
10-19 |
20
-29 |
|
Ulcer
size |
<1cm |
>
1cm |
Initially
<1mm but ulcers coalesce |
|
Number
of ulcers |
Up
to about 6 |
Up
to about 6 |
10–100 |
|
Sites
affected |
Mainly
vestibule, labial, buccal mucosa and floor of mouth; rarely dorsum of tongue,
gingiva or palate |
Any
site |
Any
site but often on ventrum of tongue |
|
Duration
of each ulcer |
Up
to 10 days |
Up
to 1 month |
Up
to 1 month |
|
Other
comments |
Most
common type of aphthae |
May
heal with scarring |
Affects
females predominantly |
Systemic None Fever, odynophagia None
Features
Minor aphthous ulcers (synonym Mikulicz
ulcers)
MiRAS occur mainly in the 10–19‐year age group, and often cause minimal symptoms. It is the most common form and is
characterized by discrete, shallow, painful ulcers that are usually less than
1cm in diameter. Individual lesions are covered by a creamy-white
pseudomembrane and have a rather sharply defined border and an erythematous rim
and some edema. The ulcers are typically limited to the non-keratinized mobile oral mucosa, with common sites of involvement
including the labial and buccal mucosa, floor of the mouth, sulci or ventral surface of the tongue, soft palate and
oropharyngeal mucosa.
They are uncommon on the gingiva, palate or dorsum of the tongue. Only a few
ulcers (one to six) appear at a time. They are round to ovoid in shape, but are often more linear when in the buccal sulcus, a
common site. These lesions usually heal without scarring
within 1–2 weeks. Most patients experience infrequent recurrences, although
some may have almost continuous lesional activity.
Major aphthous ulcers (synonym Sutton ulcers)
Major
recurrent aphthous stomatitis (MaRAS) are characterized by larger
ulcerations, typically >1 cm and sometimes approaching 3 cm. They recur more
frequently less than a month, last longer and are more painful than MiRAS. MaRAS are found on any area of the oral
mucosa, including the dorsum of the tongue or palate. Usually only a few ulcers
(one to six) occur at one time. Lesions are usually deeper, persist for 4-6
weeks, and may heal with white, depressed scarring. Major aphthae are
associated with considerable oral pain, and are sometimes accompanied by fever,
malaise and raised ESR. These are more common in patients with HIV disease.
Herpetiform ulceration
Herpetiform
aphthae are uncommon and found in a slightly older age
group with a female predominance. They are often extremely painful and recur so
frequently that ulceration may be virtually continuous. Herpetiform ulceration
begins with vesiculation, which passes rapidly into multiple, minute (<1mm),
clustered ulcers,
typically confined to non-keratinized mobile mucosa and are recurrent,
features that help distinguish the condition from primary HSV infection. Up to
100 ulcers are possible at one time. The ulcers increase in size and coalesce to leave large
ragged ulcers that heal in 10 –30 days. Their similarity to herpetic
stomatitis gives herpetiform ulcers their name, but there is no evidence that
herpes simplex virus (HSV) is involved.
Differential diagnosis
Recurrent erosions and ulcerations due to:
- An inflammatory disorder, e.g. erythema multiforme, fixed drug eruption, contact stomatitis – less pain at onset, less peripheral erythema
- Recurrent herpes simplex – only involves mucosa overlying bone (hard palate, attached gingiva) in immunocompetent hosts
- Trauma – less pain at onset, less peripheral erythema, more ragged edges
Diagnosis
Diagnosis of recurrent aphthous stomatitis is based on the
history and clinical features and histopathology analysis; no specific tests
are available. Biopsy is indicated only where some other cause of ulceration is
suspected. To exclude relevant systemic predisposing factors it is often useful
to perform:
·
Full
blood count
·
Iron
studies.
·
Red
cell folate level.
·
Serum
vitamin B12 measurements.
·
Serum
antiendomysial antibodies and IgA anti tissue transglutaminase antibodies.
Management
Recurrent
aphthous stomatitis in most patients resolves or abates spontaneously with age.
An underlying, identifiable predisposing cause is particularly likely where
ulceration commences or worsens in adult life and these patients are better
classified as suffering aphthous‐like
ulcers.
The primary goals of therapy are promotion of
healing, management of pain and nutrition, and prevention of recurrence. Predisposing factors should be corrected. Ensure that
patients brush atraumatically (e.g. with a small-headed, soft toothbrush) and
avoid eating particularly hard or sharp foods (e.g. toast, potato crisps), and
avoid other trauma to the oral mucosa. Avoid acidic foods and change
toothpaste to one that does not contain sodium lauryl sulfate. Good oral hygiene should be maintained: chlorhexidine or
triclosan mouthwashes help to achieve this and may help reduce ulcer duration.
Topical minocycline and tetracycline mouth rinses may be of benefit.
A doxycycline capsule
of 100 mg in 10 mL of water administered as a mouth rinse for 3
minutes.
Topical
corticosteroids are the primary therapeutic agents used. Application
of a thin film of a super potent topical corticosteroid gel used at least four times daily, as early as
possible in the course of an outbreak will typically reduce significantly the
pain and time to healing. Topical anesthetics, in particular benzydamine
hydrochloride mouth wash can produce transient relief of pain. While it is not
possible to prevent recurrences, the frequency of episodes is often reduced
following topical corticosteroid therapy. Anti-inflammatory agent such as amlexanox 5% paste
and sucralfate may be useful. Patients with complex aphthosis may require therapy with
oral colchicine, dapsone or combination of these two.
Dissolve one tablet of 0.5 mg betamethasone
soluble tablet in 10-20 ml of water (two to four teaspoons) to make up a
mouthwash. Swirl the mouthwash around your mouth for 5 minutes before spitting
out. Do not swallow the contents. Use up to a maximum of 4 times per day,
ideally after mealtimes and after you have brushed your teeth last thing at
night. Do not eat or drink for at least
30 minutes after use.
Systemic therapy with prednisone for a few
weeks and maintenance with pentoxifylline may
reduce the number, duration and size of ulcers, and reduce the number of
episodes.
Topical
tacrolimus may be effective but randomized trials are awaited.
Angular Cheilitis
Introduction
Angular
cheilitis is an acute or chronic inflammation of the skin and contiguous labial
mucous membrane at the angles of the mouth.
In most cases, this represents a form of candidiasis
often with concomitant S. aureus infection. The prevalence is
approximately 1% in the general adult population and 28% in denture wearers. Drooping of the corners of the mouth with
drooling and retention of saliva in the creases leading to candidiasis often
associated with wearing of full dentures that do not provide adequate soft
tissue support is a major predisposing factor. Permanent cure can be achieved only by eliminating the Candida
beneath the upper denture.
Patients with
hematinic deficiencies or who are immunocompromised are also prone to
developing this condition.
Predisposing
factors
- Infective agents are the major cause.
- Immune deficiency, such as diabetes and HIV
infection, may present with angular stomatitis.
- Mechanical
factors in
edentulous patients who do not wear a denture or who have inadequate
dentures, and also as a normal consequence of the ageing process, produce
an oblique curved fold and keep the small area of skin constantly
macerated.
- Nutritional
deficiencies,
particularly deficiencies of riboflavin, folate, iron and general protein
malnutrition, may produce smooth shiny red lips associated with angular
stomatitis, a combination called cheilosis.
- Hyposalivation, such as after drug therapy
such as chemotherapy or anticholinergic drugs, irradiation or in Sjögren
syndrome may predispose.
Clinical
features
Angular cheilitis presents as a roughly triangular area of
erythema and edema at one or more commonly both, angles of the mouth. Linear
furrows or fissures radiating from the angle of the mouth (rhagades) are seen
in the more severe forms, especially in denture wearers. Lesions
may heal and recur within days or weeks.
Treatment
Antifungal creams with topical steroid therapy are particularly useful in the treatment of this condition. If lesions only partially resolve, S. aureus infection should be suspected and treatment with topical antibiotic fusidic acid cream at least four times daily usually resolves the residual lesion.
Dentures should be removed from the mouth at night and
stored in a candidacidal solution such as hypochlorite. Denture‐related stomatitis should be treated with an antifungal.
Miconazole may be preferable treatment for candidosis (cream applied locally,
together with the oral gel) as it has some Gram‐positive bacteriostatic action. New dentures that restore
facial contour may help.
If there is a hematinic deficiency, repletion should be
undertaken.
Oral Sub mucous fibrosis (OSMF)
Introduction
Oral sub mucous fibrosis
is a chronic disease of the oral mucosa that appears to be caused by exposure
to constituents of the Areca nut, characterized by inflammation
and progressive fibrosis followed by stiffening of otherwise yielding mucosa
resulting in difficulty in opening the mouth.
Epidemiology
Incidence
and prevalence
The rate varies from 0.2
to 2.3% in males and 1.2 to 4.57% in females in Indian communities.
Age
Any.
Sex
Females are more commonly
affected than males.
Ethnicity
It is found virtually
exclusively in persons from the Indian subcontinent; most of those affected
chew Areca nut with tobacco, betel leaf and lime and may be
related to copper, possibly through dietary copper or copper sulphate, a
constituent of Bordeaux mixture, the fungicide sprayed on Areca plantations
in monsoon regions.
Pathophysiology
It is generally
accepted today that areca nut quid plays a major role in the etiology. The
pathogenesis of the disease is not well established, but the cause of OSMF is
believed to be multifactorial. Ingestion of chilies, genetic susceptibility,
nutritional deficiencies, and autoimmunity and collagen disorders may be
involved in the pathogenesis of this condition.
It is strongly associated with chewing areca nut, a habit
practiced by patients of sub continental Indian, Southeast Asian, and Taiwanese
descent. The areca nut may be prepared in a variety of ways, but is often
wrapped in betel leaf together with slaked lime, spices, and other ingredients,
and the mixture is chewed for its stimulatory effects.
Commercially freeze‐dried products such as
pan masala (a commercially manufactured powdered version of betel quid without
tobacco), gutka (a manufactured version of betel quid with tobacco sold as a
single‐use sachet) and mawa (a
combination of Areca nut, tobacco and lime.) have higher
concentrations of Areca nut per chew and appear to cause oral sub
mucous fibrosis more rapidly than self‐prepared conventional betel quid.
Arecoline, an active alkaloid in betel nuts,
stimulates fibroblasts to increase collagen production, while flavanoid,
catechin and tannin cause collagen fibers to cross‐link.
BMP-1= Bone morphogenic protein
HIF= Hypoxia-inducible factor
OSCC = Oral squamous cell carcinoma
Clinical Findings
The buccal mucosa is the
most commonly involved site, but any part of the mouth can be involved, and the
pharynx. Oral sub mucous fibrosis develops insidiously, often initially
presenting with oral dysesthesia (burning sensation).
Oral sub mucous fibrosis
appears to be restricted to the mouth, although many patients are also anemic.
Later there may be symmetrical
fibrosis of the cheeks, lips or palate, which may be symptomless. Patients
may report that they cannot open their mouths wide. It is better palpated than
seen and the teeth show rust-colored staining. Palpation reveals dense
fibrosis and rigidity of the tissues and often “piano wire-like” bands running through the mucosa. This can, however, become so
severe that the affected site becomes white and firm, with severely restricted
opening of the mouth.
Disease
course and prognosis
Oral sub-mucous fibrosis
may predispose to the development of leukoplakia, and oral carcinoma, which
occurs in 2–10% of patients over a period of 10 years.
Differential Diagnosis
and Laboratory Studies
Patients
who develop sclerosis such as those with progressive systemic sclerosis may
have a similar fibrotic appearance, but there is no history of areca nut use.
The diagnosis can be
confirmed by biopsy. The
biopsy shows a sub epithelial
chronic inflammatory reaction with marked fibrosis extending to the sub mucosa and muscle.
The surface epithelium is usually atrophic and must be evaluated
for dysplasia.
Treatment
Treatment is difficult. Cessation of the habit
will not reverse this condition but may stop its progress. Intralesional corticosteroids and jaw exercises may be
useful in the early stages, but surgery may be needed to relieve the fibrosis.
Pentoxifylline, spirulina, salvianolic acid B, aloe vera, isoxsuprine and
lycopene have each been used with some effect.
Pemphigus
The oral cavity may be involved
by pemphigus vulgaris and paraneoplastic pemphigus. The antigen is desmoglein
3.
Clinical Findings
Pemphigus vulgaris is an
uncommon condition, most often seen in adults. Patients may present with
lesions in the mouth before developing skin lesions. Lesions may present as
desquamative gingivitis, but almost invariably, other mucosae are involved, in
particular the hard and soft palate. Oral lesions are denuded and erythematous,
painful, and slightly depressed. Remnants of the bullae or necrotic debris may
overlie the erosion, or be heaped up at the edges. Some patients have lesions
limited to the oral cavity and never develop skin lesions.
In
addition to the erosions and ulcers present intraorally, patients with
paraneoplastic pemphigus (also known as paraneoplastic autoimmune multiorgan
syndrome) present with hemorrhagic crusting of the lips. It is usually
associated with a lymphoid malignancy.
Differential Diagnosis
and Laboratory Findings
Large ulcers of Behçet disease
and recurrent aphthae major may look similar to pemphigus vulgaris.
Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis may
resemble lesions of paraneoplastic pemphigus.
The
biopsy for pemphigus vulgaris shows suprabasilar acantholysis and direct immunofluorescence
studies show intercellular deposition of IgG. Paraneoplastic pemphigus shows
deposition of IgG and C3 both intercellularly and at the basement membrane
zone. Patients with only oral lesions of pemphigus usually do not exhibit
elevated serum IgG.
Treatment
Treatment for pemphigus
vulgaris is with topical steroids in mild cases with the use of a stent for
gingival lesions.
More severe cases can be successfully treated with prednisone and mycophenolate
mofetil in conjunction with topical steroids.
Exfoliative Cheilitis
This is a rare inflammatory
condition of the lip and some cases are associated with factitial injury and
lip licking or picking, sometimes associated with psychological distress;
however, many cases are of unknown etiology. It is seen in approximately 25%
of patients with HIV infection.
The lip is covered by fine or
thick scales and crusts that can be peeled away, leaving an erythematous, raw
area. Patients will report that within a few hours, a new scale or crust forms.
The lips may also appear
cracked, fissured, and chapped. Some patients admit picking at the lesions
while others deny this. Cultures in patients with HIV disease yield Candida
in 50% of cases.
Differential Diagnosis
and Laboratory Studies
Actinic keratosis is an
important consideration and this also causes scaly plaques but these do not
tend to peel and recur as quickly. Plasma cell cheilitis should be considered
although this presents as an erythematous rather than scaly lesion.,
A biopsy shows parakeratosis,
acanthosis, and chronic inflammation, either somewhat consistent with factitial
injury or nonspecific in nature.
Some
patients have been at least partially successfully treated with
antidepressants, suggesting that factitial injury associated with psychological
distress plays a role. Other
treatment modalities include mupirocin and tacrolimus.
