Common Ulcerative Conditions of the

Mouth Relevant to the Internist

Alison J. Bruce, MBChB

Associate Professor of Dermatology
and Oral Medicine
Department of Dermatology
Mayo Clinic, Rochester
IV Curso Internacional de Actualizacin y Preparacin
del Board de Medicina Interna
November 7 12, 2011
Santiago, Chile CP985041-1
 Diagnostic Approach to Oral Ulcers

Oral ulcers

Acute Oral ulcers Chronic Oral ulcers

< 6 weeks duration > 6 weeks duration
History & Examination Special studies (biopsy)
 Acute Oral Ulcers
Single episode
Trauma
Drug reaction
Iatrogenic
Bacterial infection
Viral infection
 Acute Oral Ulcers
Single episode
Trauma
Drug reaction
Iatrogenic
Bacterial infection
Viral infection
Acute Oral Ulcers: Bacterial Infections
Primary syphilis
Painless round ulcer
with raised border and
indurated base
Chancre of tongue, lip,
or palate; usually single
 Acute Oral Ulcers
Single Episode

Bacterial infections
Acute necrotizing ulcerative
gingivostomatitis (ANUG)
 Acute Oral Ulcers
Varicella

Varicella-zoster virus
Scattered tiny papulovesicles
Posterior oral mucosa
Children > adults
Characteristic skin lesions
Chicken Pox
Hand-Foot-and-Mouth Disease
 Acute Oral Ulcers
Hand, Foot and Mouth Disease
Coxsackie A virus
Scattered tiny
papulovesicles

Posterior oral mucosa

Children > adults
Hand and foot lesions
Hand-Foot-and-
Mouth Disease
Acute Oral Ulcers: Single Episode
Bacterial infections
Acute necrotizing ulcerative
gingivostomatitis (ANUG)
Syphilis
Viral infections
Herpes zoster
 Acute Oral Ulcers
Herpes Zoster

Varicella-zoster
virus
Painful grouped
vesicles
Unilateral, nerve
root distribution
Adults > children
Skin lesions
Zoster
Zoster
Zoster
Herpes Simplex Virus Infection
Acute Herpetic Gingivostomatitis
 Acute Herpetic Gingivostomatitis

Herpes
simplex virus
Usually acquired in early childhood
Often sub clinical
Masticatory and
soft tissue mucosa
Children > adults
Fever, malaise, lymphadenopathy
Acute Herpetic Gingivostomatitis
Acute Herpetic Gingivostomatitis
Acute Herpetic Gingivostomatitis
 Approach
Approach to
to Diagnosis
Diagnosis
Single
Single Episode
Episode

Trauma
Trauma Drugs
Drugs Iatrogenic
Iatrogenic Infection
Infection

Chemotherapy
Chemotherapy Radiation
Radiation

Viral
Viral
Bacterial
Bacterial

HSV
HSV VZV
VZV Coxsackie
Coxsackie Rubeola
Rubeola EBV
EBV

HFMD
HFMD Herpangina
Herpangina
11
gingivostomatitis
gingivostomatitis

Zoster
Zoster Chickenpox
Chickenpox

ANUG
ANUG Syphilis
Syphilis Gonorrhea
Gonorrhea Tuberculosis
Tuberculosis Histoplasmosis
Histoplasmosis Rhinoscleroma
Rhinoscleroma

ANUG
ANUG == acute
acute necrotizing
necrotizing ulcerative
ulcerative gingivitis
gingivitis
HFMD = hand foot and mouth disease
HFMD = hand foot and mouth disease
EBV
EBV == Ebstein
Ebstein Barr
Barr virus
virus
HSV
HSV == herpes
herpes simplex
simplex virus
virus
VZV
VZV == varicella
varicella zoster
zoster virus
virus
Diagnostic Approach to Oral Ulcers

Oral ulcers

Acute Oral ulcers

< 6 weeks duration
History & Examination

Recurrent episodes

Canker sores Herpes simplex virus infection

Recurrent Aphthous Stomatitis
(Canker sores)
 Recurrent Aphthous Stomatitis

50-60%
Female
predominance
Recurrent bouts
of painful ulcers
at intervals of days to months
2 Patterns of behavior:
Simple or Complex
 Acute Oral Ulcers

Recurrent Recurrent
aphthous intra-oral
stomatitis herpes simplex
Anatomy of Mouth
LOCATION!

Occur on soft, mobile, non-

keratinized mucosa

CP984118-4
Recurrent Aphthosis
Recurrent Aphthous Stomatitis
 RAS: Simple Aphthosis

Episodic, short-lived flares

Few lesions, lasting 4-10 days,
recurring 3-6 a year
Initially painful, then aching as
healing occurs
Affects the soft oral tissues
 RAS: Complex aphthosis

Episodic or continuous flares of

aphthosis
Few to many lesions, small to large
in size

Slow healing, greater pain and

disability

Short remissions, long exacerbations

May have genital ulcers
International Criteria for Behcets Disease
Oral ulceration RAS > 3 attacks / year
PLUS 2 of:
Genital ulcers
Eye inflammation Ant. uveitis (hypopyon)
Post. uveitis
Retinal vasculitis

Skin lesions E. nodosum

Pseudo-folliculitis
Papulo-pustular acne
nodules

Pathergy test 2mm erythema 24 48

hours after #25 needle
pricked to depth of 5mm
 Diagnostic Difficulty
Modified ODuffy criteria:

Oral ulcers
PLUS 2
Genital ulcers
Posterior uveitis
Synovitis
Cutaneous pustular vasculitis
Meningoencephalitis

exclude IBD
 Recurrent Aphthous Stomatitis
Associated diseases
Inflammatory
bowel disease
Gluten sensitive
enteropathy
Behcets disease
Vitamin
deficiencies
HIV
 RAS Evaluation
Identify a cause if possible
Review of systems
Oral ulceration associated
with systemic disease
require referral
Screen for vitamin deficiency
CP984118-21
 Work-up of RAS
CBC & diff

Hematinic screen
Fe studies, ferritin
Folate
Zinc GI eval
B12
Ophthalm
Endomysial antibody, tissue Rheum
transglutaminase

LFTs, chem, ESR, G6PD

Cytology (Tzanck)
Culture
 Recurrent Aphthous Stomatitis
Management
Reduce trauma
Correct dental
defects
Careful oral hygiene
Avoid sharp-
surfaced foods
Avoid talking while
chewing CP984118-22
 RAS Management: Simple steps

Toothpaste
Elimination of sodium
lauryl sulfate
containing dentrifice
(SLS - a detergent)

Triclosan (Colgate
Total)
Recurrent Aphthous Stomatitis
Palliative Topical Therapy

Mixture of Diphenhydramine
HCl 12.5mg/ml 1:1 with Maalox
Viscous lidocaine HCl 2%
Rinse with 1 teaspoon every 2
to 4 hours and expectorate
CP984118-25
 Anti-Infammatory Therapies
Topical corticosteroids Intra-lesional corticosteroids
ointments, gels, (Kenalog-40 =
pastes, adhesive Triamcinolone)
vehicles and rinses
Inject 0.3 ml in different sites
of varying
potencies
Fluocinonide gel
(Lidex)
Systemic corticosteroids
Topical tetracycline (pulse therapy with
(sumycin suspension Prednisone)
125mg/5ml)
 RAS
Management of Severe Disease
Systemic therapy
Colchicine
Dapsone
Tetracycline / niacinamide
Pentoxifylline
Corticosteroids
Azathioprine
Thalidomide CP984118-27
 Herpes Simplex Virus
Recurrent

Recurrent intra-oral herpes simplex

stomatitis
 Recurrent HSV

Recurrent intra-oral herpes simplex stomatitis

Rare
Usually immunocompromised
Grouped lesions
Early intense pain,
then aching before
healing
Masticatory mucosa
affected (keratinized)
Positive Tzanck preparation and culture
Recurrent Intraoral HSV Infection
What is your diagnosis?
 Approach
Approach to
to Diagnosis
Diagnosis
?? inciting
inciting Recurrent
Recurrent episodes
episodes
stimulus
stimulus

No
No systemic
systemic Systemic
Systemic CBC
CBC
Traumatic
Traumatic EMA
symptoms
symptoms symptoms
symptoms EMA
GI/rheum/ophthal
GI/rheum/ophthal eval
eval
Location
Location
IBD
IBD Sprue
Sprue

Keratinized
Keratinized Cyclic
Cyclic Behcets
Behcets
Culture
Culture neutropenia
neutropenia

HIV
HIV
+ Non-keratinized
Non-keratinized

Hematinic FAPA
FAPA
HSV Atypical
Atypical RAS
RAS Hematinic screen
screen
HSV
HIV
HIV
Cyclic
Cyclic neutropenia
neutropenia MAGIC
MAGIC
RAS
RAS

HSV
HSV == herpes
herpes simplex
simplex virus
virus
RAS
RAS == recurrent
recurrent aphthous
aphthous stomatitis
stomatitis
IBD
IBD == inflammatory
inflammatory bowel
bowel disease
disease
Idiopathic
Idiopathic RAS 22oo to
RAS to FAPA
FAPA == fever,
fever, aphthosis,
aphthosis, pharyngitis,
pharyngitis, adenitis
adenitis
RAS
RAS nutritional
nutritional deficiency
deficiency MAGIC
MAGIC = mouth & genital ulcers
= mouth & genital ulcers &
&
inflamed
inflamed cartilage
cartilage
Diagnostic Approach to Oral Ulcers

Oral ulcers

Chronic Oral ulcers

> 6 weeks duration
Special investigations

Biopsy
Culture
Histopathology
Immunofluorescence
 Lichen Planus
Common inflammatory
disorder (all the Ps)

T-cell mediated disorder in

genetically susceptible
individuals

Activated T-lymphocytes
cytokine production tissue
destruction
 Oral lichen planus

CP985041-10
 Clinical Appearance
3 types of lesions:

Reticular
White lace-like

Asymptomatic

CP985041-14
 Clinical Appearance
Atrophic or erythematous

Red, eroded
plaques on
the mucosa

CP985041-14
 Clinical Appearance

Erosive

Ulcerated, eroded
areas
Symptomatic

CP985041-14
Clinical Appearance
 Clinical Appearance
Disease frequent in extra-oral sites
vulva & vagina (VVG) in 25%
scalp, ears, nails, eyes, esophagus less
common
Clinical appearance
How is it Diagnosed?
 Diagnosis
Direct immunofluorescence
Associations: Gold allergy?
CP1156367-96
 Stepwise Approach to Treatment:
Choice of therapy depends on severity

Mild disease:
Topical corticosteroids (ointments, gels,
mouthwashes)
Fluocinonide gel 4X day
Topical tretinoin (Retin-A)
Only with primarily gingival disease
Stepwise Approach to Treatment:

Moderate disease:
Topical tacrolimus
Protopic 0.03% or 0.1%
Apply 3X day with Q-tip for 30 secs
No PO intake for 30 min thereafter
Systemic hydrochloroquine (Plaquenil)
Topical cyclosporin
5 ml swished in mouth for 5 min, then
discarded, 3X day
Prohibitive cost
Topical Tacrolimus
 Chronic Oral Ulcer:
Mucous membrane pemphigoid

Oral mucosa:
erythema, blisters
and slow healing
erosions

Heterogeneoous
disorder of
autoantibodies
against various BMZ
antigens
 Mucous membrane pemphigoid
Immunofluorescence

Subepithelial blister Linear band of IgG

with and C3 at BMZ
modest dermal
inflammation
 Indirect Immunofluorescence

Salt-split skin demonstrates deposition on

blister roof
 Chronic Oral Ulcers:
Connective Tissue Disease
Systemic Lupus
Erythematosus
Lupus erythematosus
 Chronic Oral Ulcer:
Malignancy

Lymphoma
Biopsy essential
H&E
Special stains
Culture

Post transplant
lymphoproliferative disorder
Diagnostic Approach to Oral Ulcers

Oral ulcers

Acute Oral ulcers Chronic Oral ulcers

< 6 weeks duration > 6 weeks duration
History & Examination Special studies (biopsy)
Help with Differentiating Look-a-likes

Age

Pattern (chronicity)

Behavior

Anatomic location

Apppearance
Lichen
Lichen Planus
Planus Canker
Canker sores
sores HSV-initial
HSV-initial HSV-Recurrent
HSV-Recurrent
intra-oral
intra-oral

Middle-age
Middle-age Any
Any Childhood
Childhood Young
Young adulthood
adulthood

Chronic
Chronic Intermittent,
Intermittent, short-
short- Single
Single Recurrent
Recurrent
lived
lived episodes
episodes episode
episode episodes
episodes (rare)
(rare)

Asymptomatic
Asymptomatic Intense
Intense pain
pain Painful
Painful with
with Some
Some pain
pain
painful
painful erosions
erosions constitutional
constitutional
symptoms
symptoms

Any
Any Soft
Soft Mucosa
Mucosa Soft
Soft and
and Masticatory
Masticatory
masticatory
masticatory mucosa
mucosa (keratinized)
(keratinized)
mucosa
mucosa

Lace-like
Lace-like Red
Red halo,
halo, yellow
yellow Necrotic
Necrotic Clustered,
Clustered, ruptured
ruptured
slough
slough vesicles
vesicles

Biopsy
Biopsy Dermatologist!!
Dermatologist!! Tzanck,
Tzanck, Tzanck,
Tzanck, culture,
culture, PCR
PCR
culture,
culture, PCR
PCR
Thank you!