DIFFERENTIAL DIAGNOSIS OF ACUTE AND CHRONIC SYMPTOMATIC ORAL ULCERATIONS

DIFFERENTIAL DIAGNOSIS OF ACUTE AND CHRONIC SYMPTOMATIC ORAL ULCERATIONS

DIFFERENTIAL DIAGNOSIS OF
ACUTE AND CHRONIC
SYMPTOMATIC ORAL ULCERATIONS
Acute and chronic ulcerations represent the most common symptomatic mucosal pathoses
encountered by oral health care practitioners. Every clinician should have an organized approach
to these problems which will be encountered frequently. The first step in all cases should be to
divide and conquer. The ulcerations can be classified as acute or chronic, and this will cut in half
the number of diseases in the differential diagnosis. Acute lesions arise rapidly (1 or 2 days),
normally heal in 10-14 days and may recur at varying intervals. In some cases, the lesions may
take longer than a month to heal, but this is not typical. Recurrences are highly variable. Some
may never recur, while others may recur before the first crop has healed.
On the other hand, chronic erosions tend to slowly evolve and become more problematic
over an extended period of time. Instead of crops of lesions interspersed with periods of
remission, the chronic erosions tend to persist with variable levels of intensity. Patients rarely
present to their health care professional when these lesions first arise; the vast majority of
chronic ulcerations have been present for months when the patients present for diagnosis and
treatment. Normally, the distinction between acute and chronic ulcerations is made easily; but
like everything else, there are gray areas.
Prior to the development of a differential diagnosis, the patient’s medical history should
be evaluated thoroughly. The presence of any extraoral lesions must be documented. A listing
of all utilized prescription and “over-the-counter” medications is mandatory. The following is a
list of common symptomatic oral ulcerations:
ACUTE
CHRONIC
Recurrent aphthous ulcerations
Herpangina
Hand, foot & mouth disease
Behçet's syndrome
Herpes simplex
Herpes zoster
Erythema multiforme
Necrotizing sialometaplasia
Erosive lichen planus
Mucous membrane pemphigoid
Pemphigus vulgaris
Lupus erythematosus
Drug reaction
Contact reaction
Graft-versus-host disease
Cinnamon reaction
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ACUTE ORAL ULCERATIONS
1.
Recurrent Aphthous Ulcerations
Recurrent aphthous ulcerations (RAUs) are the most common oral ulcerations
encountered by the health professional. Approximately 20 percent of the general population has
a positive history for these ulcerations. Prevalence as high as 55 percent has been reported in
populations under stress (professional school students).
Numerous studies have indicated an immunologic cause. Although the humoral system
is involved, the cell mediated immune response has received the most attention and is thought to
be responsible for the initiation of the ulceration. Early RAUs do show similarity to a delayed
hypersensitivity reaction. Investigators theorize RAUs are the result of bacterial toxins, foods,
and other substances acting as allergens or haptens which initiate an immune response. A variety
of allergens most likely is responsible. In addition, mucosal thickness and immunodysregulation
appears involved in many patients. Elimination of one allergenic source often resolves RAU in
some patients but not in others. Since discovery of the causative agent is most difficult, therapy
has been directed toward decreasing the immune reaction.
The prototypical and most common form is the minor aphthous ulceration (MiRAU).
These arise almost exclusively on nonkeratinized movable mucosa and exhibit yellow
fibrinopurulent membranes surrounded by erythematous halos. The ulcerations vary from
2-10 mm (majority approximately 5 mm) and usually heal without scarring within 10-14 days.
The recurrence rate is highly variable. The lesions may number from one to a hundred at a time.
Several systemic medical problems can result in lesions clinically identical to RAU and must be
ruled out in all cases which are severe or nonresponsive to therapy. A number of systemic
disorders such as blood dyscrasia (esp. leukopenia), nutritional deficiencies (low zinc, iron, B12
or folate), Behçet's syndrome, Crohn's disease, celiac sprue and AIDS are associated with an
increased prevalence of aphthous-like ulcerations. In addition, every one of the other acute
ulcerative conditions may resemble RAU and must be ruled out prior to therapy. Topical
steroids appear to be the most consistently efficacious; chemical cautery is contraindicated.
Most over-the-counter medications produce more problems than they solve. If clinical
contraindications to steroids exist (children, pregnancy, nursing, hypertension, diabetes,
granulomatous infectious disease, G.I. ulcerations, blood dyscrasia, previous malignancy, etc.),
permission for corticosteroid utilization must be obtained from the attending physician or utilize
antimicrobials such as tetracycline or chlorhexidine. In all severe cases and those resistant to
normal therapy, a systematic evaluation for the underlying trigger or any related systemic
disorders should be performed.
THERAPY
Localized
Diffuse
-Lidex gel (Sore Mouth Solutions [SMS] 1-1). Easy to apply but slightly
bitter
-Diprolene ointment (SMS 1-2). Thicker than gel but tasteless. Also available as
gel but slightly bitter. Often prescribed generically due to difficulty to obtain
15gram tube.
-Dexamethasone solution (SMS 1-6)
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Another type which exhibits significantly more morbidity is the major aphthous
ulceration (MaRAU). This variant also has been called periadenitis mucosa necrotica
recurrens or Sutton’s Disease. These ulcerations are similar to MiRAU but are significantly
larger, deeper, take longer to heal and result in scarring. The lesions are seen predominantly on
movable mucosa, vary in size from one to several centimeters and often take up to six weeks to
heal. It is not uncommon for a new lesion to arise before the current ulcer has healed. Long
periods of remission are difficult to obtain. The usual topical steroids normally are ineffective.
More potent local steroids (Kenacort® tablets, Kenalog 40® Injection, dexamethasone syrup) or
systemic prednisone often are required for temporary control. All MaRAU patients should be
thoroughly evaluated to rule out a systemic basis for their ulcerations.
THERAPY
Accessible
Inaccessible
Kenacort tablets (SMS 1-9)
Compounded ultrapotent dexamethasone solution (SMS 1-10)
A relatively rare variant is the herpetiform aphthous ulceration (HeRAU). These
ulcerations appear similar to MiRAU but generally are smaller in size, more numerous and can
be found on movable or bound mucosa. The typical size is 2 mm or less, and it is not uncommon
for patients to exhibit more than 100 lesions at one time. The recurrences are spaced so closely
that the patients are seldom free of these very painful lesions and often have the ulcerations
continuously for several years. The lesions frequently cluster and superficially may resemble a
primary herpetic infection; the lack of a painful and intensely erythematous gingiva combined
with the recurrence history allows separation. Therapy with 2% tetracycline rinse has proved
efficacious but, on occasion, is not effective or becomes ineffective with time. Topical
corticosteroids is the treatment of choice.
2.
Herpangina
This is a specific viral infection which can be caused by any one of a number of strains of
enterovirus. It normally is seen in young children but may occur in older patients. Once
infected, permanent immunity to the infecting strain develops, but an individual can have the
disease several times from different strains. By adulthood, most individuals exhibit immunity to
several strains. Affected patients present with sore throat, low-grade fever, headache, sometimes
vomiting and abdominal pain. The lesions closely resemble RAU and most commonly occur on
the soft palate, pharyngeal wall and tonsillar pillars. They normally heal within a week.
THERAPY
OTC ibuprofen and maximum strength Sucrets®
3.
Hand, Foot & Mouth Disease
This is another clinical presentation of enterovirus infection which can be caused by one
of several strains. The majority of the cases arise in young children but can present in adulthood.
It is characterized by an erythematous maculopapular rash of the skin which most frequently
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involves the hands, feet, legs, arms and buttocks. Anorexia, low-grade fever, coryza, sometimes
lymphadenopathy, diarrhea, nausea and vomiting can occur. Oral lesions are invariably present
and are the principal symptoms in over 90% of the patients. The lesions resemble RAU and
occur primarily on the palate, tongue and buccal mucosa. The infection resolves within 10-14
days. Treat like herpangina.
4.
Behçet's Syndrome
This is a systemic abnormality which most likely is autoimmune and usually arises between the ages of 10 and 45. It is 5-10 times more common in males. Oral, genital, skin and
ocular lesions are seen. The oral lesions present as RAU, and the genital ulcers often are small
and occur on the scrotum, root of penis, labia majora or perianally. Ocular lesions range from
conjunctivitis to uveitis to hypopyon. The skin lesions usually present as pustules on the trunk,
limbs or genitalia. A number of other systemic complications may occur also. Classic triad: oral
ulcers, genital ulcers and ocular inflammation. If discovered, refer to an experienced
dermatologist.
5.
Herpes Simplex Infections
Classically, herpes simplex is divided into type I in which the infections arise above the
waist and type II which is seen below the waist. With the current changing sexual practices, a
widespread translocation of the two types has occurred. Type I infection is extremely common,
and 70-90% of the adult population has circulating antibodies against the virus. The following
comments will be limited to infections of the perioral areas and oral cavity.
When exposed to the virus, patients without circulating antibodies may luckily develop a
subclinical infection. Those not so blessed (<10%) develop the primary herpes infection, and
the most common pattern is acute herpetic gingivostomatitis. Primary herpes normally
develops only once, but it must be remembered that types I and II are different viruses with each
capable of producing its own primary infection.
These highly symptomatic cases typically begin with high fever and lymphadenopathy
which are followed in a few days by diffuse oral lesions. In all of the cases, the gingiva is
painful and demonstrates enlargement and an intense erythema. Ulcerations of the midfacial free
marginal gingiva are not uncommon. These ulcerations along with the pain help separate this
form of gingivitis from those which are plaque-related. Multiple fragile vesicles develop and
rapidly ulcerate; observation of an intact vesicle is rare. The lesions frequently cluster and
coalesce. The ulcerations vary in size from a few millimeters to a centimeter and may resemble
RAU closely, especially the herpetiform variety. The involvement of bound mucosa, especially
the gingival changes, is the clue to the diagnosis. The lesions can extend past the wetline and
involve the vermilion border of the lips. If the diagnosis is in question, a cytologic smear can be
beneficial if performed within the first 3-5 days. Intraoral culture is not worthwhile.
Therapeutic attempts most often are directed toward palliation. Benadryl elixir or
dyclonine can be utilized as a short-term anesthetic and can be complemented by a non-steroidal
anti-inflammatory medication such as Motrin®. Tetracaine lollipops work great in this situation.
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If the patient is diagnosed prior to day three of the ulcerations, liquid acyclovir has been shown
to be highly effective in reducing the severity of the infection. Without therapy, the ulcerations
normally heal in 10-14 days.
THERAPY
Acyclovir suspension (SMS 3-1), ibuprofen (SMS 3-8), tetracaine lollipops (SMS 3-6)
After the initial infection, the surviving virus is sheltered in the nerve ganglia which
innervate the area. The virus is contained in that location by the cell mediated immune response.
Any reduction of containment can result in reactivation of the virus and a recurrent infection
known as secondary herpes. Old age, pregnancy, allergy, trauma, respiratory illnesses,
menstruation, and underlying systemic disease or malignancy have been associated with an
increased frequency of the recurrent infection. Involvement of the lips and perioral skin is
common and known as herpes labialis.
The clinically evident portion of the infection frequently is preceded by prodromal
symptoms which include burning, stinging, soreness, paresthesia and/or redness of the affected
area. Shortly thereafter, vesicles appear. These vesicles are filled with clear fluid, subsequently
rupture and lead to formation of a brown crust. The vesicles are a few millimeters in diameter
but tend to cluster and coalesce. Significant edema and occasional secondary infections may
complicate the course. Most cases are unilateral, but bilateral examples are not rare. The fluid
within the vesicles is contagious and can cause spread of the lesions if allowed to contact other
open wounds. Patients with active lesions should be dismissed prior to dental therapy. In
addition, it must be remembered that the virus can survive up to five hours in a damp gauze; all
health care personnel must maintain barrier protection until all contaminated instruments and
disposable materials have been eliminated. The virus may infect any unprotected finger and
result in very painful recurrences to the affected digit (herpetic whitlow).
A number of therapeutic medications have been utilized, most of which work well in
some patients but not in the majority. Idoxuridine, vidarabine, and lysine have demonstrated
limited usefulness in certain patients. Systemic antiviral capsules (acyclovir, valacyclovir,
famciclovir) have demonstrated clinical efficacy, but only valacyclovir has been studied
extensively in clinical trials. Although individual patients exhibit varying results, acyclovir
ointment has demonstrated no statistically significant clinical benefit for herpes labialis in the
immunocompetent patient. In contrast, penciclovir cream has demonstrated a measurable
reduction in the intensity and duration of the lesions. Although rare in immunocompetent
patients, viral resistance to acyclovir has been reported in immunocompromised patients and
should warn against over use. High-dose short-term systemic therapy with valacyclovir has been
proven to the highly effective in aborting or minimizing attacks.
THERAPY
During prodrome
After bubble appear
Prior to dental care
Valtrex (SMS 4-2)
Denavir (SMS 4-5)
Valtrex (SMS 4-3)
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Secondary herpes also can occur within the oral cavity and is known as recurrent
herpetic stomatitis. Once you have crossed over the wetline and entered the oral cavity,
recurrent herpes is seen in the immunocompetent patient only on keratinized mucosa which is
bound to bone. This is really nice, because it is exactly opposite from MiRAU which occurs
almost exclusively on movable mucosa. The lesions begin as small pin point areas of erythema
which, with time, develop central yellow zones of fibrin. Intact vesicles are rare. The lesions
tend to cluster and coalesce. Most areas are localized and unilateral. The majority of the cases
are associated with mild symptoms and do not require therapy. The ulcerations tend to heal in 57 days. These lesions are not unusual following dental procedures, even in patients who have not
had a history of primary herpes.
In the immunocompromised patient, recurrent herpes can appear very atypical clinically
(chronic or aggressive HSV infection). Many patients initially present with herpes labialis and
subsequently develop an intraoral ulceration with an elevated brownish cap (necrotic
epithelium). Instead of healing, the lesions spread laterally as superficial erosions which often
exhibit a raised white border. The lesions may occur on any mucosal surface. Treatment is to
resolve the cause for the immunocompromised status and treat with one of the effective systemic
antiviral medications. This unusual pattern has been seen in everything from asthma patients
using steroid inhalers to leukemia patients. If recurrent herpes is found on movable mucosa in a
“healthy patient” or becomes chronic and spreads laterally, immunosuppressive causes should be
investigated.
6.
Herpes Zoster
This viral infection is produced by the varicella-zoster virus and is much like recurrent
herpes in that it is a recurrence of a previously received infection: chickenpox. The virus resides
in sensory nerve ganglia and upon reactivation causes vesicular eruptions of the affected skin or
mucous membranes. The disease usually affects adults and presents with fever, malaise and pain
along the course of the involved nerves. The vesicles follow the nerves and usually are unilateral
and anatomic. Initially, intraoral lesions present as white, opaque vesicles that ultimately rupture
and form ulcerations that may resemble RAU. Many attacks begin for no apparent reason but
may be related to underlying trauma, tumor, malignancy or immunosuppression. Systemic
antivirals (acyclovir, valacyclovir, famciclovir) are efficacious, with topical capsaicin utilized for
residual neuritis.
THERAPY
Chickenpox
Zoster
7.
Acyclovir suspension (SMS 5-1)
Valtrex (SMS 5-3)
Erythema Multiforme
Erythema multiforme (EM) is an acute diffuse ulcerative condition of unknown cause
which can involve the skin and any mucosal surface. In about half the cases, a triggering event
can be found. A number of viral infections, the most common of which is herpes simplex,
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precedes the attack by one to three weeks. Other patients can trace the outbreak to an allergen
exposure, often one of a large number of possible medications. Rare cases have been associated
with underlying internal malignancies. The ulcerations may arise at any age but are most
commonly seen in young adult males.
The dermatologic manifestations characteristically present with erythematous macules,
papules and/or vesicles which are distributed on the extremities, face and neck. The classic
lesion is a macule which exhibits alternating rings of varying shades of erythema, the so-called
“bull’s eye” or “target” lesion. Oral lesions are common and occasionally can be seen in the
absence of other lesions. Out of all of the acute oral ulcerative conditions, primary herpes and
EM produce the most severe symptoms. It is not unusual for patients with oral EM to bring a
relative to speak for them.
The oral lesions present predominantly on movable mucosa but are not limited to that
location. The individual areas appear as a large zone of irregular epithelial necrosis. The
epithelium rapidly sloughs, leaving a large painful erosion. The lesions often are numerous and
diffuse. Involvement can extend past the wetline onto the vermilion border of the lips. On
occasion, the lesions can involve the skin and the mucosal surfaces of the eye, mouth and genital
areas and have been termed Stevens-Johnson Syndrome.
Because EM is self-limiting, some clinicians do not feel the necessity to treat the lesions.
In those patients receiving therapy, systemic steroids normally are utilized. Patients with
significant oral lesions should receive therapy. With appropriate therapy, the pain and duration
of their suffering can be diminished dramatically. Although systemic steroids are occasionally
required, those with only oral involvement often can be resolved with 0. 1 % dexamethasone
syrup or Prelone® syrup. Patients with diffuse dermatologic and oral involvement, which are
treated with systemic steroids, rarely exhibit failure of the oral lesions to resolve in a timely
fashion. This problem can be circumvented through use of Prelone® in a “swish and swallow”
pattern in the same dosages as that utilized with systemic prednisone. In patients with recurrent
EM limited to mucosal surfaces, prophylactic acyclovir should be prescribed to rule out a viral
trigger.
THERAPY
Restricted to mouth
Vermilion border
8.
Compounded ultrapotent dexamethasone solution (SMS 1-7)
Betamethasone gel or ointment (SMS 1-2)
Necrotizing Sialometaplasia
This entity is different from the other types of acute sore mouth because it most often is
confused with a salivary gland neoplasm and generally not included in a discussion of acute
ulcerations. The disorder may occur in serous or mucous glands of the oral, nasal or respiratory
areas but usually occurs in minor salivary glands of the palate. The changes mimic a
mucoepidermoid carcinoma both clinically and histologically, but the appropriate diagnosis can
be made by those with previous experience with these changes.
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Following local ischemia of undetermined origin, coagulative necrosis develops within
the affected gland. Intraorally, the most common site is the palate, and the presentation is so
distinctive that the diagnosis often can be made secondary to the unique clinical pattern. The
affected area begins as an enlarged, tender and erythematous zone which arises over a couple of
days. Subsequently, the overlying mucosa breaks down with the formation of a wellcircumscribed and deep ulceration. Bilateral lesions can occur. Pain often is mild considering
the size of the defect, which may be large with healing taking as long as 10 weeks. Biopsy often
is utilized to confirm the clinical impression.
CHRONIC ORAL ULCERATIONS
1.
Oral Lichen Planus
Lichen planus (LP) is a very common chronic disorder which may affect skin or mucosal
surfaces. The cause is idiopathic, but the cell mediated immune response is known to attack the
basal cell layer of the affected epithelium. As in aphthous ulcerations, the primary event could
be a delayed hypersensitivity reaction to an as yet unknown antigen(s). The inciting antigen
could vary from patient to patient, thereby making the final discovery more difficult. Chronic
drug reactions can produce a mucosal reaction which can mimic lichen planus and should be
ruled out thoroughly. Dental restorative materials have been implicated as a source of the
antigens for LP, but only a minority of those studied exhibit a reaction to the dental materials.
Removal of the dental restorative materials also has failed to resolve the lesions. In spite of this,
amalgam is known to produce a mucosal reaction which is similar to, but not, LP (see later
section).
The clinical presentations of the early lesions can be described best utilizing the “3 Ps”.
On skin, the early lesions can be described as purple polygonal plaques. The involved skin is
sharply demarcated and often intensely pruritic. The early oral lesions can be described as
porcelain pinhead papules (papular pattern). These small papules can become confluent and
form striae (reticular pattern). Beware of any isolated and nonmigratory plaque diagnosed as
“plaque-type of lichen planus”; most of these represent epithelial dysplasia with a lichenoid
immune reaction. With progression, areas of painful erythema (atrophic pattern) or ulceration
(bullous or erosive patterns) may develop.
Any mucosal surface may be involved, but the gingiva and buccal mucosa are affected
most frequently. In the majority of the cases, patients with oral LP do not present with skin
lesions. If skin lesions are present or develop in the future, they should be investigated to rule
out the possibility of lupus erythematosus. Oral lupus erythematosus can resemble closely LP
clinically and histopathologically, and this separation is best made via immunofluorescence.
The possibility of LP representing a premalignant condition remains an area of hot
debate. Patients with LP are not immune to development of squamous cell carcinoma; the
question is whether they are disposed to its development. In investigations of LP in which more
than 100 patients were studied, the rate of cancer arising in LP varied from 0.0% to 5.3%.
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The classification of generic oral LP as a premalignant lesion does not seem justified for
several reasons. There is significant disagreement as to the frequency of malignant
transformation among the authors of the numerous studies. This is not surprising because of the
clinical and histopathologic similarities between dysplasia and LP. Many reports of LP
developing into carcinoma actually may represent dysplasia with a lichenoid mucositis, not true
LP. A literature review of 223 reported cases of cancer arising in LP revealed only 15 with
sufficient evidence. The patients included in these studies are most frequently those with
symptomatic LP who are not representative of LP as typically seen in the general population. In
one of the larger studies, 75% of those included had complaints of pain and/or ulceration.
In conclusion, cancer occasionally develops in patients with LP, but the true occurrence
of carcinomatous development in the general LP population currently is not known. Patients
with asymptomatic reticular lichen planus should be followed like any other dental patients
receiving routine care. In contrast, patients with chronic, severe atrophic lichen planus should be
followed closely with biopsy of any unusual areas. Long-term atrophy of the oral cavity should
be considered premalignant, whether it is occurring in a process such as Plummer-Vinson
syndrome or poorly controlled lichen planus. This is most challenging due to the clinical
similarities between atrophic LP and erythroplakic dysplasia. Beware of a histopathologic
diagnosis of LP in a patient with an isolated white or red patch. Beware of an LP patient who
develops an atypical erythematous area which is resistant to normal interventions. NEVER let
patients with atrophic lichen planus smolder; control of the disease process is mandatory.
Asymptomatic LP requires no therapy. Symptomatic, atrophic and erosive LP is best
treated with topical corticosteroids. When widespread, the lesions may be treated with topical
corticosteroids in a liquid or gel formulation. Difficult cases may resolve with 0.1%
dexamethasone or Prelone® syrup; but on occasion, systemic steroids (swallow Prelone®) are
required to obtain control. The patients should be told this is not a cure and should expect the
lesions to recur and require future treatment. Secondary candidiasis is not rare and can be
controlled with Nizoral®, Mycelex® or Mycostatin® or by mixing clotrimazole or nystatin into
the topical corticosteroid gel.
THERAPY
First line
Second line
Third line
Fourth line
Fifth line
Tacrolimus aqueous oral rinse (SMS 1-15)
Temovate gel (SMS 1-3). For gingival involvement use trays as occlusive
dressings.
Protopic ointment (SMS 1-11)
Systemic prednisolone (SMS 1-14)
Pray. Repeat after me. I HATE LICHEN PLANUS. I HATE LICHEN
PLANUS.
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10
Oral Pemphigoid
Pemphigoid is a chronic epithelial vesiculoerosive process secondary to autoimmune
destruction of a portion of basement membrane zone (BMZ) with the formation of a subepithelial
separation from the underlying connective tissue. This disease presents in two different patterns:
bullous pemphigoid (BP) and cicatricial mucosal pemphigoid (CP). In the past, the two types
have been thought to be variations of the same disease, but recent work suggests the autoimmune
destruction may be occurring at different sites within the BMZ. At least eight different clinical
variants have been documented.
Pemphigoid is diagnosed from an incisional biopsy which includes an area of separation
in addition to a portion of the adjacent normal epithelium. Rubbing the affected area prior to
surgery is recommended as in aid in biopsy site selection. The initial histopathologic diagnosis
should be confirmed with immunofluorescence (IF). Direct IF almost always is positive and
demonstrates IgG and/or C3 in a linear band along the BMZ. Indirect IF is not highly beneficial,
since the titers do not correlate to the severity and there is a significant number of false
negatives. As with any chronic vesiculoerosive process, prior to definitive therapy, all patient
medications should be screened for a possible relationship.
Bullous pemphigoid typically presents with large tense bullae most commonly
seen in the groins, axillae and forearms. The disease usually arises in elderly adults but
has been seen in all ages. Oral involvement is not a prominent part of the process but has
been reported in 11-45 % of the cases. In healthy patients, the disease usually runs a
benign course and subsides after months or years. Low dose systemic prednisone with or
without azathioprine is the first line therapy. On occasion, LP and BP may occur
concurrently and has been termed lichen planus pemphigoides.
Cicatricial pemphigoid also is known as mucous membrane pemphigoid and is a more
unremitting chronic disorder which may involve any mucosal surface. Oral involvement is very
common and the percentage of involvement varies according to practitioner type. Multiple oral
sites may be involved, but the vast majority demonstrate gingival involvement. The term
“desquamative gingivitis” (DG) has been applied to the diffuse vesiculoerosive changes that may
be seen in pemphigoid. It must be emphasized that DG is a clinical diagnosis and must be
investigated. Although many cases do represent CP, similar lesions have been seen in lichen
planus, pemphigus and several other less common vesiculoerosive processes. Palatal, labial and
buccal mucosae also are affected frequently. Oral lesions present as areas of painful erythema,
scattered intact vesicles and/or superficial erosions. Typically, scarring is not seen.
CP may remain isolated to the oral cavity, but management of this disease requires a
multidisciplinary approach. Nasal, vaginal, genital, anal, laryngeal, esophageal and ocular
involvement is seen. Any patient presenting with oral lesions diagnostic of CP should be
thoroughly evaluated for involvement of these sites. In addition, thorough dermatologic
evaluation also is mandatory. Lesions located in the larynx, esophagus and ocular mucosa do
frequently exhibit significant scarring which can result in serious debilitation and rarely death.
Every patient is different; and the type, amount and duration of medication required to obtain
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satisfactory control is variable. The patients require long-term follow-up to maintain control of
discovered lesions and to provide surveillance for additional sites of involvement.
THERAPY
Oral only
Treat similar to lichen planus (SMS 1-3, 1-11, 1-14). Often beneficial to combine
topical steroid therapy with systemic tetracycline and niacinamide (SMS 1-12,
requires medical supervision, please contact me for additional handout)
Extraoral
Refer to experienced dermatologist
3.
Oral Pemphigus Vulgaris
Pemphigus is another chronic immunologic mucocutaneous vesiculoerosive disorder.
Most cases arise after the age of 30, but occurrence in children is reported. Four patterns may be
seen: vulgaris, vegetans, foliaceous and erythematosus. Pemphigus vulgaris (PV) is the most
common type and the only variant to exhibit common oral involvement. Pemphigus is an
antibody mediated destruction of the intercellular cement which results in intraepithelial
acantholysis. The diagnosis is obtained secondary to histopathologic examination and IF. The
biopsy should include an area of erosion with a margin of normal uninvolved epithelium. Direct
IF demonstrates IgG and often C3 in the intercellular spaces. Indirect IF is worthwhile and
positive in approximately 90% of the cases. In addition, the titers correlate well to the severity
of the disease. Sequential indirect titers have been used to assess the clinical activity but have
not always been consistent. On skin, PV is characterized by rapid development of numerous
vesicles or bullae which may cover large areas of the surface. The lesions rupture and result in a
denuded surface after loss of the remaining detached surface epithelium.
PV is relatively rare. In an active oral pathology service, LP usually is diagnosed at least
once a day, CP four times every month and PV about once every 2-3 months. The initial lesions
usually occur on skin, but oral involvement normally is present at some time during the course of
the disease. Occasionally, the oral lesions may be seen initially; and rarely, the oral mucosa may
be the only site of involvement. As in LP and CP, the patient's medication history should be
reviewed thoroughly. In addition, a significant percentage of PV has been associated with food
hypersensitivity. Due to the intense therapy required for this disease, it is mandatory to
investigate a medication or food-related trigger prior to initiation of treatment.
The oral lesions develop on any mucosal surface with an average time of seven months
between the onset and diagnosis. The vesicles tend to rupture as soon as they form, and most
patients present with areas of superficial erosion which are very tender and often bleed upon
manipulation. The lesions tend to enlarge peripherally, and often the surface epithelium can be
dislodged with manipulation (+Nikolsky’s sign).
If untreated, PV is progressive and can result in widespread infection, electrolyte imbalance, cachexia, toxemia and death. Topical steroids often are not effective. Treatment
usually consists of high dose systemic steroids, often combined with azathioprine, methotrexate,
cyclophosphamide, levamisole, Dapsone or gold.
THERAPY
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All patients should be referred to experienced dermatologist. The possibility of a chronic food or
drug reaction should be ruled out prior initiation of therapy.
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A rare form termed paraneoplastic pemphigus is seen in association with systemic
disease, usually lymphoma or leukemia. These lesions often demonstrate a rapid onset and
clinically resemble erythema multiforme. Upon biopsy, histopathologic features of lichen
planus, pemphigoid and pemphigus are noted. Direct immunofluorescence reveals IgG in the
basement membrane zone and the intercellular areas. Although the antibodies present in typical
pemphigus react only with stratified squamous epithelium, those in the paraneoplastic variety are
broad spectrum and also react with transitional epithelium (such as bladder epithelium). Therapy
in these patients is problematic, and the prognosis is poor.
4.
Lupus Erythematosus
Lupus erythematosus is a chronic autoimmune disorder which typically affects the skin
and involves the oral mucosa in 10-40% of the cases. Two different variants of lupus are seen.
Discoid lupus erythematosus (DLE) affects primarily the skin while systemic lupus
erythematosus (SLE) also involves multiple tissues and organs. The skin lesions present as
elevated erythematous plaques with a surface scale. The affected areas usually are sun-exposed,
and a butterfly rash over the bridge of the nose and malar areas is classic.
The oral lesions may present as areas of erythema or leukoplakia but often exhibit a
strong similarity to lichen planus. The classic intraoral lesions of lupus appear as an area of
speckled erythroplakia with a peripheral border of perpendicular radiating white striae and
telangiectasia. Histopathologically, classic lupus can be diagnosed on an oral biopsy, but the
specimens often closely resemble lichen planus. In addition, occasional lichen planus biopsies
may exhibit features of lupus. If skin lesions are present, the distinction between these two
disorders is best made on skin. Immunofluorescence is beneficial in separating the two diseases
when only oral lesions can be found. Lupus should be considered anytime there are skin lesions
present in addition to oral lichenoid changes. In addition, lupus should be ruled out anytime the
oral lesions demonstrate the classic pattern of peripheral radiating striae and telangiectasia.
One of the most common drug reactions is lupus-like, mandating investigation of this
possibility prior to initiation of therapy. The treatment of lupus varies with the severity and
usually consists of antimalarials (lowers circulating ANAs), topical or systemic steroids. The
prognosis of DLE usually is excellent with good response to topical steroids; about 5% progress
to SLE. Although most cases of SLE can be controlled with proper medication, death can result
from severe renal or CNS involvement.
THERAPY
All patients should be referred to an experienced rheumatologist or dermatologist.
Damm Sore Mouth
5.
14
Chronic Drug Reactions
Chronic oral vesiculoerosive lesions related to drug ingestion are second in frequency of
occurrence, with lichen planus being the most frequent. The lesions most commonly present on
the lateral border of the tongue and/or posterior buccal mucosa and frequently are bilateral. The
classic lesion presents as a zone of chronic ulceration which frequently demonstrates radiating
white striae. The offending drugs are too numerous to mention and may be either prescription or
over-the-counter. All patients with a chronic vesiculoerosive process should be closely
questioned concerning all currently used medications. Most offending medications will have a
previous history of producing a lichen planus, pemphigoid, pemphigus, lupus-like or nonspecific chronic vesiculobullous reaction. Medications can mimic any of the chronic
vesiculoerosive disorders with identical clinical, histopathologic and immunofluorescence
findings. Treatment includes discontinuation of the medication with a course of topical steroids
to insure resolution. If the lesions return after steroids and cessation of the medication, the drug
was not the inciting cause.
The PDR is insufficient for investigation. One of the best pharmaceutical guides is Drug
Facts and Comparisons. This resource describes all OTC and prescriptions medications legally
available in the US. This references is offered in several formats, is not cheap and is available
from JB Lippincott (1-800-223-0554). Another useful drug reference system is Clinical
Pharmacology (www.clinicalpharmacology.com; 1-800-375-0943; for demo: [email protected] ).
This program has the ability to quickly and easily produce an adverse reaction or drug interaction
report from a long list of patient utilized medications. My personal favorite (DRUGDEX) is
more difficult to use than Clinical Pharmacology (must investigate each drug one at a time) but
provides all of the well known adverse reactions along with individual case reports from the
literature (www.micromedex.com; 1-(877) 843-6796). A different kind of useful item is the IDENTA-DRUG Handbook offered by the Therapeutic Research Center (1-209-931-2923).
Three other problems, xerostomia, dysgeusia and osteonecrosis are not rare and
frequently associated with medications. Discussion of bisphosphonate osteonecrosis requires an
extended presentation and is a topic for another day.
Some degree of xerostomia occurs with aging, but a large number are due to medications.
In many instances, an association with medications is ignored; and the patients are evaluated for
Sjögren Syndrome. Xerostomia is very common and associated with an increased prevalence of
cervical caries, candidiasis and orolingual paresthesia.
Dysgeusia is a persistent abnormal taste that is much less common than loss of smell or
loss of taste. The pathosis is not well tolerated and often leads to dental consultation. Many
cases are related to an underlying systemic disorder or previous radiation therapy to the head and
neck. Xerostomia often is associated with a metallic taste. In these patients, hydration and/or
oral moisturizers may prove effective. Since 75% of flavor is derived from smell, many
perceptions of dysgeusia are not secondary to an alteration of taste. The “jelly bean” test is used
by many but is not definitive in many cases. Orange and yellow (lemon) jelly beans taste
identical but have different smells.
Damm Sore Mouth
15
Appropriate diagnosis is difficult and often involves formal taste/smell testing combined
with electrical and chemical analysis of taste bud function. Such an evaluation often is outside
the scope of most general practices and mandates a referral to a Taste and Smell Center. Prior to
this referral, three possibilities should be investigated: oral foci of infection, asymptomatic postnasal drip and an adverse drug reaction.
6.
Lichenoid Reaction to Amalgam
Amalgam has been blamed for almost every physical and social ailment known to man,
but no scientifically sound investigation has ever proven any significant problems associated
with its use. It has withstood the passage of time and remains an excellent dental restorative
material. In spite of this, one oral pathologic condition has been proven to be related to dental
amalgams (and less frequently other metallic restorative materials) in susceptible patients.
Rarely, patients may present with areas of leukoplakia which are in direct contact with
large amalgams. The lesions most frequently are present on the lateral border of the tongue or
posterior buccal mucosa. The white lesions often have radiating peripheral striae and may
closely resemble lichen planus. Biopsy of the lesions presents a pattern very similar to lichen
planus. Unlike lichen planus, the lesions do not migrate and remain stationary and adjacent to
the amalgam. Periodic atrophy and ulceration may occur and require topical steroid application.
Replacement of the adjacent amalgam with resin results in rapid resolution.
7.
Oral Mucosal Chronic Graft-Versus-Host Reaction
Patients who have received a bone marrow transplant and subsequently develop graftversus-host-disease not infrequently demonstrate chronic vesiculoerosive lesions which closely
resemble lichen planus. Diffuse erosion and ulceration may occur. Well-developed striae often
are seen, and the pattern may become very closely meshed. The vermilion of the lower lip often
is affected frequently, in addition to diffuse oral involvement.
8.
Oral Mucosal Reactions to Cinnamon-flavored Products
In 1981, Allen and Blozis described several patients with chronic oral mucosal lesions
associated with the use of cinnamon-flavored gum. This reaction is not a rare occurrence; but
because of lack of suspicion, the diagnosis is made infrequently. The clinical presentation is
rather distinctive; and once a clinician has seen one case, then many usually are found. Biopsy
presents a pattern of mucositis which is not totally diagnostic but can lead to the final answer if a
good clinicopathologic correlation is present. The changes most often present bilaterally on the
buccal mucosa and/or lateral borders of the tongue. The affected mucosa is erythematous and
often exhibits an overlying shaggy hyperkeratosis. The excess keratin presents in a pattern very
similar to cheek biting. Cinnamon reactions will present with discomfort and surrounding
erythema, while morsicatio buccarum will not. Cinnamon-flavored floss presently is available
and may be associated with chronic gingival lesions.
Damm Sore Mouth
16
SORE MOUTH SOLUTIONS
RAU, ERYTHEMA MULTIFORME, LICHEN PLANUS, LOCALIZED PEMPHIGOID
1-1.
Lidex Gel (0.05% Fluocinonide): Apply thin film to affected area three times a day.
1-2.
Augmented betamethasone dipropionate ointment 0.05% (Diprolene): Apply thin film to
the affected area three times a day.
1-3.
Temovate Gel (0.05% Clobetasol Propionate): Apply thin film to the affected area 3
times a day. POTENT. Treatment should be limited to 14 days and amounts greater than
50 grams a week should not be used (unlikely).
1-4.
Clobetasol 0.05% and Clotrimazole 0.1% 10 grams compounded in an oral powder
puffer. Use up to five times daily. This custom formulation is used for patients who are
having problems with secondary candidiasis.
1-5.
Clobetasol 0.05% and Clotrimazole 0.1% compounded in 3% methocel gel. Dispense 30
gram tube and apply thin film to affected area 4-5 times daily. This custom formulation
is used for patients who are having problems with secondary candidiasis.
1-6.
Dexamethasone Solution {0.5mg/5ml (0.01%)}: Rinse and hold for two minutes, then
expectorate. Use 1-2 tsp. four times a day.
1-7.
Dexamethasone Solution {5mg/5ml (0.1%)}: Rinse and hold for two minutes, then
expectorate. Use 1-2 tsp. four times a day. Very potent; must expectorate; use with
caution. Must be compounded upon request.
1-8.
Prelone Syrup (Prednisolone 15mg/5ml): Rinse and hold for two minutes, then
expectorate. Use 1-2 tsp. four times a day. In addition, Prelone utilized as “swish and
swallow” is an excellent method for local coverage and systemic administration selected
cases (erythema multiforme, pemphigus, etc).
1-9.
Kenacort Tablets (8mg Triamcinolone): Dissolve one tablet TID for 3 days; one tablet
BID for 3 days and one tablet once a day for three days.
1-10. Kenalog 40 Injection (5cc vials, 40mg/ml Triamcinolone): Inject one cc around border of
large ulcers.
1-11. Protopic (topical tacrolimus ointment, 0.1 or 0.03%): Apply thin film to the affected area
2-3 times daily. More potent than cyclosporine. The medication should be used only as a
second line therapy in patients who have failed corticosteroid use.
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1-12. Tetracycline (500mg QID) and Niacinamide (500mg QID): Use for resistant pemphigoid.
Improvement usually seen in 2-6 weeks. After six months, attempt to taper if disease is
well controlled. Patients on niacinamide can experience flushing which normally
resolves if reduced to 1.5 gms/day.
1-13. Dapsone: Use for resistant cases of pemphigoid. Doses ranging from 25-200 mg/day are
used. Referral to experienced dermatologist often wise due to significant side effects.
1-14. Systemic Prelone Syrup (Prednisolone 15mg/5ml): Instruct patient to rinse entire daily
amount first thing in the morning. Rinse and hold +/-2tsp at a time for AT LEAST two
minutes then swallow. First four days: 5tsp. Days 5-8: 4 tsp. Days 9-11: 3 tsp. Days 1213: 1.5tsp. Day 14: 1tsp. Patient should be instructed to call at the end of day three. If
improving, continue on schedule. If not improving, continue at 5tsp for three more days
then call again. If this fails, refer to MD and suggest systemic steroids at
1.5-2mg/kg/day until the lesions clear. Use of Prelone formulation will improve
response.
1-15
Tacrolimus aqueous oral rinse: Mix 1mg Prograf capsule in 1000ml of purified water.
Dispense 1000ml. Rinse tsp (10ml) of solution for at least two minutes, then expectorate.
Repeat four times daily. Store refrigerated. Shelf-life is one month.
CANDIDIASIS
2-1.
Mycostatin Oral Suspension (100,000 units of Nystatin per ml): Rinse and hold for two
minutes. Use one tsp. four times a day. This is not my favorite due to high sucrose
content and expense.
2-2.
Mycelex Troches (10mg Clotrimazole): Dissolve one troche five times a day for 14 days.
Liver function tests required for course longer than 14 days. Excellent choice but
expensive.
2-3.
Nizoral Tablets (200mg Ketoconazole): Take one tablet a day for 14 days. Liver function
tests required for a course over 14 days. Generic ketoconazole now available and makes
this a good choice.
2-4.
Diflucan (200mg Fluconazole): Take one tablet a day for 14 days.
2-5.
Clotrimazole 1% cream: This represents the first line therapy against angular cheilitis.
This medication is OTC and surprisingly is effective in cases due to candida and bacteria.
2-6.
Mycolog II Ointment (100,000 units of Nystatin and l mg of Triamcinolone per gram):
Apply thin film to the affected area four times a day. Works well for angular cheilitis in
many patients. Will not be beneficial in cases of angular cheilitis due to strep or staph.
Difficult to find, but generic equivalent can be obtained.
Damm Sore Mouth
18
2-7.
Hydrocortisone 1% / Iodoquinol 1% Cream (Generic or Dermazene): Dispense 1 oz
(28.4 gram) tube. Apply thin film to the affected area four times a day. This has antiinflammatory, antibacterial and antifungal actions. Works well for angular cheilitis but
tastes like death (helps stops chronic lip lickers). Also available in gel > Alcortin A gel:
aloe polysaccharide 1%, hydrocortisone acetate 2%, iodoquinol 1% in 2 gram packets.
Packets come individually or in box of 24.
2-8.
Peridex (0.12% Chlorhexidine Gluconate): For prevention, rinse capful (1/2 ounce) twice
a day. Sold in 16 ounce containers. Avoid in pregnancy and nursing females. May
cause staining of teeth, increased supragingival calculus and altered taste.
2-9.
Clorox: Dilute 1:5 with water and use as denture soak. Will discolor metallic
frameworks.
PRIMARY HERPES
3-1.
Zovirax Suspension {200mg/5ml (tsp) Acyclovir}: Rinse and swallow required amount
five times a day for five days. For children too young to swallow capsules or in patients
with primary herpetic gingivostomatitis. The dosage is 5mg/kg, not to exceed the adult
dose.
Weight (KG=2.2 lbs)
Required amount
5-10
11-15
16-20
21-25
26-30
31-35
>35
1/4
3/8
1/2
5/8
3/4
7/8
1
KG
KG
KG
KG
KG
KG
KG
TSP
TSP
TSP
TSP
TSP
TSP
TSP (adult dose)
3-2.
Zovirax Capsules (200mg Acyclovir): Take one capsule five times a day for five days.
Avoid in pregnancy and ages 0-12.
3-3.
Valtrex (1g Valacyclovir hydrochloride): Take one caplet twice daily for ten days.
Therapy is most effective if initiated within 48 hours of initial signs and symptoms.
3-4.
Famvir (125mg Famciclovir): Take one tablet twice daily for five days.
Damm Sore Mouth
19
3-5.
Dyclonine HCL, 0.5%: The brand name Dyclone has been discontinued by
manufacturer due to low profits. This active ingredient can be obtained easily by
compounder and custom formulated as desired. Rinse, spray or swab on affected areas
PRN for pain. Supplied in 1 oz bottles. Also available in 1% strength for severe cases
which fail to respond to 0.5%. Excellent topical anesthetic.
3-6.
Tetracaine 0.5% lollipops (compound medication): Swab in mouth for 8-10 minutes per
hour. Don’t chew and be careful of hot/cold food or drink.
3-7.
Sucrets maximum strength oral anesthetic lozenges. These are over-the-counter and
contain dyclonine.
3-8.
Benylin Cough Syrup (12.5mg/5ml diphenhydramine hydrochloride): Rinse and hold for
two minutes. Use one tbsp. four times a day. Can be used as an inexpensive but not
strong topical anesthetic.
3-9.
Motrin (400-600mg Ibuprofen): Take one tablet every four hours.
3-10. Tylenol (325mg acetaminophen): Take two caplets every 4-6 hours.
SECONDARY HERPES
4-1.
Zovirax Capsules (200mg Acyclovir): Take one capsule five times a day for five days,
beginning in the prodrome or prior to known trigger. Avoid in pregnancy and ages 0-12.
For maintenance in severe cases, take three capsules a day. Temporarily discontinue
every six months to monitor activity of the virus. Therapy often breaks the back of the
virus within a couple of years. Females must be sterile or practicing excellent
contraception.
4-2.
Valtrex (1g Valacyclovir hydrochloride): take two caplets (total of 2 grams) twice daily
for 1 day taken about 12 hours apart. Therapy should be initiated at the earliest symptom
(tingling, itching, burning, etc.). For suppressive therapy, take 1 caplet daily.
4-3.
Valtrex (1g Valacyclovir hydrochloride) for prevention of recurrence associated with
dental therapy: take two caplets (total of 2 grams) twice daily for 1 day taken about 12
hours apart, followed by one caplet twice daily for one additional day.
4-4.
Famvir (125mg Famciclovir): Take one tablet twice daily for five days.
4-5.
Denavir Cream (1% Penciclovir): Dispense 1.5mg tube. Beginning in the prodrome,
apply thin film to the affected area every two hours during waking hours for a period of
four days. Works best if initiated prior to appearance of vesicles.
Damm Sore Mouth
20
4-6.
Zovirax Cream (5% Acyclovir): Beginning in the prodrome, apply thin film to the
affected area six times a day for seven days. Superior absorption when compared to
ointment formulation.
4-7.
Zovirax Ointment (5% Acyclovir): Beginning in the prodrome, apply thin film to the
affected area six times a day for seven days. Does not penetrate skin well and is of
limited usefulness, although some patients respond well.
4-8.
Abreva Cream (OTC; 10% topical docosanol): Few published studies. In the early
stages of the recurrence, apply sufficient quantity to cover all lesions; rub in gently and
completely; repeat five times a day until the lesions are healed.
4-9.
Viroxyn Swab (Sold through participating DDS/DMD & MD offices, 0.13%
alkylbenzyldimethylammonium chlorides): Single-application treatment system with
little available information. Break glass vial and saturate swab. Vigorously rub swab
against lesion until are ingredients are dispensed. Do not use soap or other cleansers for
24 hours in the affected area.
4-10. Lysine Tablets (OTC): Beginning in the prodrome, take at least 2000mg per day for
seven days; for maintenance, utilize 1000mg per day. This is effective in up to 40% of
affected patients.
4-11. Peridex (0.12% Chlorhexidine gluconate): Rinse and hold one capful for two minutes
then expectorate. Repeat twice daily. Good choice for mild recurrent herpetic stomatitis.
VARICELLA & HERPES ZOSTER
5-1.
Zovirax Suspension (200mg/5ml Acyclovir): Dispense required amount five times a day
for five days. For children with varicella. The dosage is 20mg/kg, not to exceed the
adult dose.
Weight (KG = 2.2 lb)
5-10
11-15
16-20
21-25
26-30
31-35
>35
5-2.
KG
KG
KG
KG
KG
KG
KG
Required amount
1
1.5
2
2.5
3
3.5
4
TSP (5ml)
TSP
TSP
TSP
TSP
TSP
TSP (Adult dose)
Famvir (500mg Famciclovir): Take one tablet three times a day for seven days. Appears
to decrease time to resolution of pain when compared to acyclovir. In addition, prompt
utilization appears to reduce the duration of postherpetic neuralgia.
Damm Sore Mouth
5-3.
Valtrex (1g Valacyclovir hydrochloride): Take one caplet three times daily for seven
days. Appears to decrease time to resolution of pain when compared to acyclovir. Due
to lower cost, Valtrex appears to be a better choice than Famvir.
5-4.
Zovirax Capsules (800mg Acyclovir): Take one capsule five times a day for five days.
21