-
Recurrent aphthous stomatitis (RAS) and recurrent intraoral
herpes (RIH) are the two most commonlypresenting oral lesions in
the dental setting. It is critical that the oral health
professional be able toaccurately discriminate between these
disorders. To facilitate the differential diagnosis between RASand
RIH, important components of assessment are discussed. These
include: prodromal signs andsymptoms, lesion location, and
appearance of the initial and mature lesion. The comparative
etiology,prevalence, pathogenesis, and treatment considerations for
these lesions are presented. A familialcase report is provided.
Keywords: Herpes, lesion, primary herpetic gingivostomatitis,
aphthous stomatitis, RIH, RAS, recur-rent intraoral herpes,
recurrent aphthous stomatitis, ulcer, canker sore, cold sore, fever
blister.
Citation: Tilliss TSI, McDowell JD. "Differential Diagnosis: Is
It Herpes or Aphthous?" J ContempDent Pract 2002 Feb;(3)1:
001-015.
1
Abstract
“Differential Diagnosis: Is It Herpes or Aphthous?”
The Journal of Contemporary Dental Practice, Volume 3, No. 1,
February 15, 2002
Volume 3 Number 1 February 15, 2002
© Seer Publishing
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2The Journal of Contemporary Dental Practice, Volume 3, No. 1,
February 15, 2002
IntroductionRecurrent aphthous stomatitis (RAS) and recur-rent
intraoral herpetic (RIH) lesions are commonoral disorders that are
often mistaken for oneanother. The confusion associated with
develop-ing an accurate diagnosis is somewhat under-standable since
these two very different lesionsshare some common characteristics.
However,since they do differ in a variety of parameters,
thewell-informed clinician should be able to differenti-ate between
these distinctly separate conditions.
The patient history, the physical examination, andthe results of
any indicated tests are important tothe diagnostic process. A
complete and accuratepatient history is a critical component of
develop-ing a working diagnosis. Information regarding
initiating factors, frequency of lesions, relievingfactors
(including any previously prescribed orover-the-counter
medications), and aggravatingfactors provides historically
important data. It hasoften been said that if you listen to the
patient, heor she will give you the diagnosis.
If the patient history is accurate and the physicalexamination
allows the clinician to see thelesion(s), other tests may not be
necessary. Inmost cases, the clinician should be able to
differ-entiate herpetic lesions from aphthous ulcers.
Lesion Identification: How Accurate Are You?Review the following
images of mucosal lesions toassess your skills at differentiating
between apht-hous ulcers and RIH lesions. (Figures 1 A-D)
Figure 1a Figure 1b
Figure 1c
Figure 1d
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3The Journal of Contemporary Dental Practice, Volume 3, No. 1,
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The high prevalence and often-painful presenta-tion of these
lesions suggests that patients willfrequently seek out the oral
health professional fordiagnosis and treatment. Since the lesions
arealmost always self-limiting, one might questionthe importance of
being able to distinguish onefrom the other. What then is the
rationale for thedifferential diagnosis?
Table 1 summarizes some of the features of RIHand RAS.
Rationale for Differential DiagnosisDeveloping an accurate
diagnosis for herpes andaphthous is critical to the treatment plan
becausethe recommended treatment approaches are verydifferent for
herpetic lesions and aphthous ulcera-tions. Treating a herpetic
lesion with topicalsteroids (as appropriate for an aphthous
ulcer)can have serious sequelae. Telling a patient withan active
herpes infection that he or she has anaphthous ulcer and that it is
not potentially conta-gious is simply bad healthcare. Additionally,
the
accompanying peace of mind that occurs withproviding a name and
treatment for what mayhave been a long-standing condition can
havepsychological advantages for the patient.
Prodromal SymptomologyBoth herpetic and aphthous lesions often
presentwith prodromal symptoms which can provideimportant clues to
the development of a diagnosis.However, the indications of an
impending herpeticlesion are generally more descriptive than for
adeveloping aphthous ulcer.
Awareness of the initiation of the aphthous lesionis generally
indicated by local discomfort at thelesion site. The degree of pain
can vary fromslight to severe and is frequently described as outof
proportion to the size of the lesion.
The prodromal symptomology for herpes mayseem confounding to the
patient at initial occur-rence, but for those experiencing frequent
out-breaks of herpetic lesions, the symptoms areoften recognizable.
The first indication of a
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4The Journal of Contemporary Dental Practice, Volume 3, No. 1,
February 15, 2002
recurrent herpetic outbreak may be an unusualsensation of the
affected tissue that may manifestas a lack of tactile or sensory
perception. Thismay progress to a tingling, burning, or
throbbingsensation. The development of vesicles (smallblisters)
within 24-48 hours will help to validatethe occurence of a
recurrent herpes outbreak.
Lesion LocationThe site of the initial lesion can provide
importantclues concerning the presenting condition.Recurrent
aphthous ulcerations are usuallydescribed as occurring on
non-keratinized, orgland-bearing tissues. Common sites for
recur-rent aphthous ulcers include labial and buccalmucosa, floor
of the mouth, oropharynx, vestibule,and lateral tongue. With the
exception of sites offrequent trauma, there appears to be no
predilec-tion for aphthous ulcers to recur at a
previouslocation.
In contrast, RIH generally appears on keratinizedtissues such as
the vermillion borders of the lips,hard palate, attached gingivae,
and alveolarridges. The initial lesion can be at any of
theselocations with subsequent outbreaks often mani-festing at or
very near the original site.
Appearance of LesionsThe clinician is not always able to view a
lesion atthe initial stage when most easily diagnosed.Therefore,
eliciting a detailed description of thecourse of the eruption
becomes essential. Inmost cases the combination of the history of
thelesion and viewing the current stage can allow fora working
(presumptive) diagnosis.
The aphthous ulcer does not transition throughspecific
discernable stages as does the herpeticlesion. It may, however,
increase in size from firstdetection to maturity. Aphthous ulcers
are usuallydivided into two general categories: aphthousmajor and
minor. Amore uncommon form,herpetiform aphthousstomatitis, mimics
her-petic lesions in appear-ance but is found in thesame areas as
theother forms of aphthousstomatitis.
In the aphthous minor form of aphthous stomati-tis, the ulcer is
shallow and 0.5-2 cm in size. Itusually appears as a single lesion,
although 1-5ulcers may be present. The initial lesion maybegin as
an erythematous macule, but it quicklyprogresses to an ulcer
characterized by a white toyellow or gray center of necrosis
surrounded by asmooth, symmetrical, round or elliptically
shapederythematous perimeter often described as a "redhalo." Within
10-14 days of the initial presentation,the aphthous ulcer should
usually be fully healed.
Major aphthae typically are larger, last longerthan aphthous
minor, and may heal with scarring.Clinicians should remember that
HIV/AIDSpatients can present with ulcers demonstrating aclinical
appearance similar to or indistinguishablefrom major aphthae due to
their immunocompro-mised health status.
Following the characteristic prodromal stage pre-viously
described, the herpetic lesion manifestsas a cluster of small grey
to white vesicles thatrupture to form small punctate ulcers that
areusually 1 mm or less in diameter. These ulcersmay coalesce into
one larger ulcer up to 1.5 cmin size. A red halo effect may be
visible, but willappear scalloped in contrast to the smooth
haloseen in aphthous ulceration. The next stage is'crusting,' which
precedes the healing process.From prodrome to crusting takes up to
96 hourswith pain resolution over 96-120 hours and complete healing
by 8-10 days. Since "crusting"does not occur intraorally, this
feature is noted primarily in labial or cutaneous lesions.
Comparing the two lesions, it is apparent thatboth become
ulcerative, but the progression tothe ulcer stage differs widely,
as does the appear-ance of the mature lesions associated with
herpes and aphthous.Thus, the history, loca-tion, and appearance
ofthe lesions should allowthe knowledgeable clini-cian to establish
a pre-sumptive diagnosis.Regarding transmissibili-ty, it is
important to notethat while the aphthous ulcer is not
contagious,the herpetic lesion is transmissible to a suscepti-ble
host. Herpes is communicable throughout thecourse of the outbreak,
particularly during thevesicle and ulceration phases.
Aphthous Ulcer
Herpetic Lesion
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Etiology, Prevalence, and Pathogenesis
Aphthous StomatitisThe term 'aphthous' originated with
Hippocratesas far back as 460-370 BC in reference to disor-ders of
the mouth.1 In general usage, the word'aphthae' refers to the
presence of an otherwiseundefined ulcer.2 Despite the fact that
aphthousstomatitis is the most common human oralmucosal disease,
the cause is poorly understood.Although symptomatic treatment is
available, aphthous is not preventable.3 Since the etiologyof
aphthous ulcers is indeterminate, research hasfocused upon a
variety of potentiating factors.Until the etiology is clarified,
the focus has shiftedtoward the notion of 'precipitating
factors.'Studies of these are not conclusive, but precipitat-ing
factors that have been identified include:stress, nutritional
deficiencies, trauma, hormonalchanges, diet, and immunologic
disorders. Othercontributors that have received attention
are:foods, allergies, progesterone levels, psychologicfactors, and
a familial history. Despite extensiveresearch, no conclusive
etiology has been deter-mined. For some time it was thought that
aphthous ulcerations were due to an L-form ofStreptococcus since
this organism was often isolated from the lesions. A more common
beliefis that the lesions may become secondarily infected with
streptococci. Since the lesions areoften suppressed by steroid
therapy, which affectsthe immune response, it is more likely that
thelesions are a manifestation of the immuneresponse, perhaps a
hypersensitivity to strepto-cocci or another oral phenomenon.4 RAS
is currently characterized as an idiopathic disorderwhose
fundamental etiology is unclear. It is, how-ever, widely recognized
as immunologically mediated.
RAS is a common oral disorder. The prevalenceamong differing
populations has been document-ed as 5-66%3 and 50%.4 World-wide,
approxi-mately 15-20% are afflicted with RAS.5 It is especially
common in North America.3,5 RAS also occurs in association with
some systemicdisorders that are associated with chronic
gas-trointestinal malabsorption disturbances such asCrohn's disease
and celiac disease. Another systemic disorder associated with
aphthous ulcer-ation is Behcet syndrome that is characterized
byrecurrent attacks of genital and oral ulcers.
Aphthous stomatitis is divided into three clinicalpresentations.
It is unclear whether these presentations are manifestations of one
diseaseor represent other oral disorders characterized byrecurrent
ulcers. The three designations are apthous minor, apthous major and
herpetiformulcers.
Etiology, Prevalence, and PathogenesisAphthous minor is the most
common varietyaccounting for 80%1 to 95%5 of all RAS lesions.The
lay term for this lesion is canker sore.
During an attack of minor aphthous, lesions mayoccur singly or
up to five or more concurrentulcers. Each lesion typically lasts
10-14 days.Lesions may continually appear and heal sponta-neously
during a 3-4 week period.
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Aphthous major, which accounts for about 10% ofcases of aphthous
stomatitis1,5 is characterizedby large lesions which vary from 5-20
mm ormore in size. Usually only 1-2 lesions occur at atime and
primarily in two locations, lip mucosaand posterior palate/anterior
fauces area.
The lesions are much more severe than that ofminor aphthae and
are associated with severepain. The lesions are crateriform and
deep,involving much tissue necrosis, often resulting inscarring
upon healing. Aphthous major can last 6 weeks or more and can
become secondarilyinfected with bacterial and fungal
organisms.Lesions of aphthous major can become intra-ctable in
those with immunodeficiency disorderssuch as HIV and AIDS,
resulting in weight lossdue to painful deglutition.
Herpetiform aphthous is the least common varietycomprising about
10% of occurrences. The nameis misleading since it suggests a
herpetic infec-tion. Rather it is the similar appearance of
theulcers that can mimic the appearance of primaryherpetic
gingivostomatitis. Additionally, althoughmost commonly occurring on
non-keratinized surfaces, herpetiform aphthae can
infrequentlyappear on keratinized mucosa as can primaryherpetic
gingivostomatits.
Herpetiform aphthous is characterized by multiplerecurrent crops
of 10 or more small crateriformulcers of variable size. The
episodes may lastseveral weeks or months with individual
ulcershealing after 1-2 weeks. The lesions are shallow,like
aphthous minor, and heal without scarring.
The age of onset of herpetiform aphthous is laterthan with the
other types, with the initial episodeusually presenting in the
second or third decadeof life.
TreatmentOnce a diagnosis of aphthous is reached, the clinician
must decide whether to provide morethan palliative care. As part of
informed consent,the patient should receive instruction about
thecondition, treatment options, and the expectedoutcome from each
of the various treatment plansoffered. Patients with frequent or
severe out-breaks of aphthae should be counseled regardingthe
advisability of a medical screening for dia-betes, various forms of
anemia, gastrointestinaldisease, food "allergies," and other
diseases
potentially affecting the immune system. It maymay also be wise
to rule out Behcet's diseasethrough questioning about the presence
of lesionsof the genital mucosa. Suggested supportivecare includes
rest, increased fluid intake, ade-quate nutritional intake,
multi-vitamin and mineraltherapy, and reassurance that aphthae are
notcommunicable.
When conservative, palliative care such as elimi-nating trauma
(where possible), avoiding expo-sure to identified causative
factors, and stressreduction are not enough, steroids of
varioustypes can be utilized. Aphthae that are localizedor in small
numbers can often be effectively treated with a topical steroid.
For single (or few)shallow lesions, a mild steroid ointment or gel
isusually adequate. Kenalog (triamicinalone acetonide 0.1%) in
Orabase can be used onmany mild aphthae cases. Larger lesions,
whenaccessible, can be treated with a more potentsteroid like Lidex
(0.05%) or Temovate (0.05%)gels or ointments. When the lesions are
more diffuse, difficult to access (i.e., orophaynx), or inlarger
numbers, a steroid rinse is more helpfulthan a topical ointment or
gel. Decadron (dexam-ethasone) elixir 0.5 mg/5 ml can be
consideredwhen treating these lesions. If the lesion(s) arelarge
and accessible, combining dexamethasonewith a topical ointment or
gel can reduce thesigns and symptoms.
Although topical steroids used appropriately on alimited basis
rarely cause untoward effects,patients should be counseled
regarding thepotential for candidal overgrowth when steroidrinses
are used for extended periods. The morepotent steroids (i.e.,
Temovate) when appliedmore than twice per day for more than two
weekscan lead to mucosal thinning and erosions.
Aphthae are expected to respond quickly tosteroid therapy. It
must be emphasized that whenan intraoral ulcer does not heal after
potentialcauses have been addressed and/or after steroidtherapy,
the lesion should be re-assessed andbiopsied. Oral malignancy and
other diseaseprocesses should be considered as part of
thedifferential diagnosis for lesions that do notrespond to
conservative therapy. Other immune-mediated disease may also mimic
aphthae andrequire an accurate diagnosis before an
adequatetreatment plan can be developed.
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Herpes Etiology,Prevalence, Pathogenesis The herpes infection
has ahistory dating back to ancientGreece. The word 'herpes'was
used by Hippocrates todescribe lesions that 'creep' or'crawl.'
Although previouslywell characterized, it was notuntil 1893 that
the transmissi-bility was recognized.6
The herpes family of viruses currently is thoughtto consist of
herpes simplex 1 (HSV-1), herpessimplex 2 (HSV-2),
varicella-zoster, Epstein-Barr,cytomegalovirus, and human herpes
virus VI, VII,and VIII.5 All are capable of entering and
replicat-ing in epithelial cells, while some of the herpesfamily is
neurotropic and others are lymphotropic.HSV-1 and HSV-2 are
neurotropic, infecting sen-sory nerve fibers and have been
demonstrated toreproduce in epithelial cells. HSV-1 and HSV-2are
lytic to human epithelial cells and latent inneural tissue at the
site of regional ganglions.Usually the virus initially enters the
body througha break in the mucous membrane integrity,although there
is evidence that it may penetrateintact skin. In either case,
transmission resultsfrom mucocutaneous contact with infected
secre-tions and aerosols. When reactivated, the virustravels along
the nerve axon to the surfaceepithelial cells and can cause a
recurrent epithe-lial outbreak.
Often the initial herpes infection goes undetected.However, in a
small percentage of cases, the ini-tial oral infection with HSV-1
or HSV-2 is acutelysymptomatic causing many signs and
symptomsdetected by the patient. When the patient demonstrates
systemic signs, symptoms, and hasperioral and intraoral vesicular
lesions, it isreferred to as primary herpetic
gingivostomatitis.Although the condition most often occurs in
chil-dren, it can also affect adolescents and adults.Fever and
lymphadenopathy may occur, lastingfrom 2-10 days. Pharyngitis,
malaise, myalgia,fiery red gingival, and mucosal tissues
associatedwith painful swallowing are hallmarks of the pri-mary
infection. Intraorally, many small punctateulcers may form on
keratinized and nonkera-tinized mucosa as well as at the
nasopharynx.Perioral tissues can also be affected.
Another manifestation of acuteprimary herpetic stomatitis is
anacute inflammation of the mar-ginal and attached gingiva with-out
accompanying vesicularlesions. It has been reportedthat only 12% of
those with RIHremember an initial infection.7,8
After the initial infection, thevirus will remain dormant
untilactivated. The frequency of
reactivation with clinical recurrence has beenreported as
occurring in 40%9 and 10-15%4 ofthose with the latent virus.
Reactivation can occur as a result of several fac-tors that
suppress the immune system. Theseinclude but are not limited to
emotional stress,trauma, cold, sunlight, extreme fatigue, fever,
andmenstrual cycle.
The recurrent vesicular/ulcerative lesions havebecome known as
'cold sores' or 'fever blisters'because people may notice
activation following anillness such as upper respiratory infection.
Somepatients may report an outbreak following animmunosuppressive
experience.
The incubation period between infection or reacti-vation and the
appearance of vesicles is about 7-8 days but may range from 1-26
days. Duringthis pre-emergence period and during the vesicu-lar
stage, secretions are highly contagious.6
Additionally, there is evidence that those withrecurrent HSV-1
shed the virus in the saliva even when asymptomatic. People with
genitalHSV-2 shed the virus about 10% of the dayswhen they are
asymptomatic, although thisdeclines over time.9
HSV-1 and HSV-2 are both different and alike.HSV-1 generally is
described as occurring abovethe waist, with HSV-2 occurring below
the waist.In reality, either variety can reside at either
loca-tion. HSV-1 usually establishes latency in thetrigeminal or
other ganglion. HSV-2 is usuallylatent at the sacral ganglion at
the base of thespine. Usually at its alternate site, the virus
caus-es milder infection as well as less asymptomaticshedding. It
is much more common for HSV-1 tospread genitally than for HSV-2 to
occur orally.Overall 80%-90% of the adult human populationhave been
infected with HSV.
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8The Journal of Contemporary Dental Practice, Volume 3, No. 1,
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Treatment for RecurrentIntraoral HerpesAs with aphthae, an
accuratediagnosis of RIH must bedeveloped prior to
initiatingdefinitive treatment for theviral lesions. Patients
shouldbe informed that there ispotential for self-inoculationand
transmission of the virusto other susceptible hosts.Patients or
their caregiversshould be warned aboutpotentially transmitting the
virus to the eye, geni-tals, or hands through direct contact with
saliva orvesicular fluid containing the virus.
Topical steroids applied to intraoral herpeticlesions must be
avoided as steroid use allows thevirus to spread. As with aphthae,
adequatehydration and nutrition are essential to the
healingprocess. Palliative rinses combining equal partsby volume of
a topical anesthetic (Lidocaine 2%or Dyclonine 1%), an
antihistamine (diphenhyr-damine 12.5 mg/ml), and a coating agent
thatbinds to the lesion's surface (Maalox orKaopectate) can relieve
the symptoms associatedwith the herpetic lesions. Clinicians might
con-sider discussing the mixing of such palliative rins-es with a
pharmacist. When using a topical anes-thetic that can potentially
affect the swallowingprocess, patients should be counseled to
usecaution when drinking and eating. Depending onthe degree of
patient discomfort, acetaminophenwith or without a narcotic can
also be given forrelief of pain.
Systemic medications interfer-ing with viral DNA synthesiscan be
helpful but are not routinely used for mild RIH inthe
immunocompetent patient.In the less common case ofan
immunocompromised orimmunosuppressed adultpatient, antivirals can
be pre-scribed. Sample prescriptionsare listed below for three
ofthe more commonly usedantivirals. Dosages may needto be adjusted
up or downbased on the size and sys-temic health (especially in
the
presence of renal disease) ofthe patient.
Rx: Acyclovir (Zovirax) 200mg capsulesDisp: 50 (fifty)
capsulesSig: Take by mouth one capsule five times per dayduring the
waking hours forten days.
Rx: Valacyclovir (Valtrex)500 mg tablets
Disp: 21 (twenty one) tabletsSig: Take by mouth one tablet three
times per day for seven days
Rx: Famciclovir (Famvir) 250 mg tabletsDisp: 21 (twenty one)
tabletsSig: Take by mouth one tablet three times per day for seven
days
Case ReportTwo days prior to embarking upon a planned
out-of-town trip, a 33-year old woman became awareof vague symptoms
of illness in her two children,ages 2 and 5. Symptoms included
irritability,anorexia, painful deglutition, and pharyngitis.
Thiscombination of symptoms did not appear pathog-nomonic for any
particular disorder and were sug-gestive of a non-descript viral
disorder, possiblyan upper respiratory infection. The day of
depar-ture, upon examining the mouths of the children,a generalized
acute inflammation of the gingivaewas apparent. This sign combined
with the previ-ous signs and symptoms allowed for a presump-tive
diagnosis of primary herpetic stomatitis.
Once this designation wasdetermined, the self-limitingnature of
the disorder allowedfor the children to be left with acaretaker and
the parents con-tinued with vacation plans. Aspredicted, the
children's illnessran its course within 3-5 days.
Approximately 2-3 weeks laterthe maternal parent begin
toexperience similar symptoms.The malaise and discomfortwere so
severe that she wasbedridden for 3 days. With ahistory of being
quite healthy,
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9The Journal of Contemporary Dental Practice, Volume 3, No. 1,
February 15, 2002
she had no prior recollection of being ill enoughto 'stay in
bed'.3 Her gingivae were so severelyinflamed and painful that it
was impossible to fol-low her usual oral hygiene regimen. Full
recuper-ation ensued within 5-7 days.
Subsequently, the paternal parent, age 35, devel-oped the same
disorder. In his case, the palataltissue was so affected that it
became denuded tothe bone. Painful deglutition resulted in a
weightloss of 15 pounds over a 7-10 day period of time.Full
recuperation ensued. Both parents hadexperienced primary herpetic
gingivostomatitis,presumably infected by the children who mayhave
been exposed in child-care settings.
The oral pathologist who examined the familymembers commented
that it was extremely rareto find 2 adults in the same household
who hadnot previously experienced the primary episodeearly in
life.
At current age 16, the youngest child had not hadsecondary
herpes eruptions, while the older, now19, has had several episodes
of recurrent herpeslabialis.
The mother has had recurring bouts of non-vesic-ular herpetic
gingival inflammation, usually asso-ciated with precipitating
factors of stress and/orfatigue and unrelated to any changes in
local fac-tors/oral hygiene regimen. The father has had
norecurrences.
ConclusionThe oral health professional is viewed as the'expert'
when an individual develops mouth sores.These peri-oral or
intraoral lesions can be verydisconcerting to the affected
individual both dueto pain and fear/confusion about the meaning
ofsuch lesions.
Along with performing a thorough and skilledintraoral and
extraoral examination at every dentalvisit, the oral health
professional must be knowl-edgeable in differentiating between RIH
and RAS.
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10The Journal of Contemporary Dental Practice, Volume 3, No. 1,
February 15, 2002
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2. Vincent SD, Lilly GE. Clinical, historic, and therapeutic
features of aphthous stomatitis. Literaturereview and open clinical
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3. Scully C, Porter SR. Recurrent aphthous stomatitis: current
concepts of etiology, pathogenesis and management. J Oral Pathol
Med. 1989 Jan;18(1):21-7. Review.
4. Baughman RA. Recurrent aphthous stomatitis vs. recurrent
herpes: do you know the difference? J Ala Dent Assoc. 1996
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5. Sapp JP, Eversole LR, Wysocki, GP. Contemporary Oral and
Maxillofacial Pathology. Mosby: St.Louis, 1997, pp. 245.
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CID 1998 26:541-553.7. Langlais RP, Miller CS. Color Atlas of
Common Oral Diseases. Lippincott Williams and Wilkins:
Philadelphia. pp. 128.8. Juretic M. Natural history of herpetic
infection. Helv Paediatr Acta. 1966 Sep;21(4):356-68.
No abstract available.9. (On-line journal)
http://www.herpes.com/hsv1-2.html.
About the Authors