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 João N. A. R Ferreira
James Fricton
Nelson Rhodus
Editors

Orofacial Disorders

Current Therapies
in Orofacial Pain and
Oral Medicine

123
Orofacial Disorders
João N.A.R. Ferreira • James Fricton
Nelson Rhodus
Editors

Orofacial Disorders
Current Therapies in Orofacial Pain and
Oral Medicine
Editors
João N.A.R. Ferreira Nelson Rhodus
Faculty of Dentistry Diagnostic and Surgical Sciences
National University of Singapore University of Minnesota
Singapore Minneapolis, MN, USA

James Fricton
Diagnostic and Surgical Sciences
University of Minnesota
Edina, MN, USA

ISBN 978-3-319-51507-6    ISBN 978-3-319-51508-3 (eBook)

DOI 10.1007/978-3-319-51508-3

Library of Congress Control Number: 2017943711

© Springer International Publishing AG 2017

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recita-
tion, broadcasting, reproduction on microfilms or in any other physical way, and transmission or infor-
mation storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publica-
tion does not imply, even in the absence of a specific statement, that such names are exempt from the
relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, express or implied, with respect to the material contained herein or for any errors
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Printed on acid-free paper

This Springer imprint is published by Springer Nature

The registered company is Springer International Publishing AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
To our families,
this book is affectionately dedicated
Preface

Orofacial disorders are common in the general population causing chewing dys-
function, dental pain, intraoral pain, facial pain, jaw pain, earaches, and/or head-
ache. Orofacial disorders including oral cancer and lesions, oral candidiasis, salivary
gland dysfunctions, temporomandibular disorders, occlusal dysfunction and dyses-
thesia, orofacial pain disorders, oral neurosensory disturbances, malodor, orofacial
dystonias and dyskinesias, burning mouth syndrome, oral parafunctions, sleep
apnea and snoring disturbances, and others are very common in all dental and medi-
cal practices with a collective prevalence of over 40% of the population. Management
of these disorders differs from traditional dental practice because the dentist spends
significant clinic time providing medically based evaluation and treatment for these
patients. Services are usually reimbursed by time for consultation and procedures
through the patient’s medical insurance plans similar to physicians.
This guide is a quick reference for practicing clinicians. Its purpose is to provide
a concise evidence-based clinical summary of diagnosis, etiology, and management
of the most common orofacial disorders. Each chapter includes succinct bullet
points, tables, and illustrations that summarize important points in understanding
each orofacial disorder. In addition, interdisciplinary and multidisciplinary orofa-
cial pain management recommendations are presented to improve effectiveness
while providing patient care. Integrative therapies for pain management such as
biofeedback and hypnotherapy are also presented. The last section/chapter offers a
comprehensive strategy on how to conduct a structured history taking and physical
exam for orofacial disorders. The guide includes the following sections: Pearls of
Wisdom, Introduction and Diagnostic Subtypes, Clinical Presentation, Etiology,
Epidemiology, Pathophysiology and Mechanisms, Diagnosis and Diagnostic
Criteria, Rationale for Treatment, Treatment Options, Treatment Goals and
Sequencing of Care, and References.
We hope this guide is helpful to your daily care of patients with these disorders.

Sincerely,
João N.A.R. Ferreira Singapore, Singapore
James Fricton Edina, MN, USA
Nelson Rhodus Minneapolis, MN, USA

vii
In Memoriam

To Dr. Sol Silverman, Dr. Jonathan Ship, and Dr. Steven Graff-Radford our
­compassionate colleagues and enthusiastic educators.

ix
Contents

Part I Oral Cancer and Premalignant Lesions

1 Leukoplakia�������������������������������������������������������������������������������������������������� 3
Isaäc van der Waal
2 Oral Cancer�������������������������������������������������������������������������������������������������� 15
Douglas E. Peterson and Nelson L. Rhodus
3 Orofacial Pain in Cancer���������������������������������������������������������������������������� 21
Gary D. Klasser and Joel Epstein

Part II Oral Mucosal Diseases

4 Herpes Simplex�������������������������������������������������������������������������������������������� 35
Andres Pinto
5 Oral Vesiculobullous Diseases �������������������������������������������������������������������� 41
Francina Lozada-Nur and Chelsia Sim
6 Oral Candidiasis������������������������������������������������������������������������������������������ 53
Scott S. De Rossi and Katharine Ciarrocca

Part III Oral Diseases of the Senses

7 Chemosensory Disorders���������������������������������������������������������������������������� 63
Joseph A. D’Ambrosio
8 Oral Malodor������������������������������������������������������������������������������������������������ 71
Patricia Lenton

Part IV Salivary Gland Dysfunctions

9 Salivary Gland Dysfunction and Xerostomia�������������������������������������������� 89
Mahvash Navazesh
10 Gene Therapy for Radiation-Induced Salivary Hypofunction���������������� 95
Bruce J. Baum

xi
xii Contents

11 Salivary Hypofunction in Aging Adults �������������������������������������������������� 105

Catherine Hong and João N.A.R. Ferreira

Part V Oral Parafunctions and Sleep Disorders

12 Oral Parafunctional Behaviors ���������������������������������������������������������������� 115
Alan G. Glaros and James Fricton
13 Obstructive Sleep Apnea and Snoring ���������������������������������������������������� 127
Antonio G. Romero and João N.A.R. Ferreira

Part VI Temporomandibular Disorders and Occlusal Dysfunction

14 Temporomandibular Joint Disorders������������������������������������������������������ 145
Jeffrey P. Okeson, Cristina Perez, and James R. Fricton
15 Temporomandibular Muscle Disorders �������������������������������������������������� 159
Edward F. Wright
16 Orofacial Dystonias and Dyskinesias ������������������������������������������������������ 171
Gary M. Heir and José L. de la Hoz
17 Occlusal Dysesthesia and Dysfunction ���������������������������������������������������� 189
Somsak Mitrirattanakul, Tan Hee Hon, and João N.A.R. Ferreira

Part VII Orofacial Pain Disorders

18 Non-odontogenic “Tooth” Pain���������������������������������������������������������������� 197
Flavia P. Kapos and Donald R. Nixdorf
19 Trigeminal Neuropathic Pain and Orofacial Neuralgias������������������������ 213
David A. Sirois and Teekayu P. Jorns
20 Burning Mouth Syndrome������������������������������������������������������������������������ 223
Miriam Grushka and Nan Su

Part VIII Headaches

21 Chronic Daily Headache���������������������������������������������������������������������������� 235
Roger K. Cady and Kathleen Farmer
22 Migraine������������������������������������������������������������������������������������������������������ 245
Steven B. Graff-Radford
23 Cluster and Facial Headache�������������������������������������������������������������������� 257
Robert G. Kaniecki
24 Migraine Variants�������������������������������������������������������������������������������������� 269
Robert L. Merrill
Contents xiii

Part IX Health Care Approaches in Orofacial and Widespread Pains

25 Interdisciplinary and Multidisciplinary Approaches
to Orofacial Pain Care ������������������������������������������������������������������������������ 283
Shawn McMahon
26 Transformative Care for Orofacial Disorders ���������������������������������������� 301
James R. Fricton
27 Integrative Approaches to Orofacial Pain: Role of Biofeedback
and Hypnosis���������������������������������������������������������������������������������������������� 317
Gabriel Tan, Alan Glaros, Richard Sherman, and Chin Yi Wong

Part X A Comprehensive Approach to Orofacial Disorders

28 History Taking and Physical Examination for
Orofacial Disorders������������������������������������������������������������������������������������ 327
David Ojeda Díaz and Thomas P. Sollecito
 Part I
Oral Cancer and Premalignant Lesions
Leukoplakia
1
Isaäc van der Waal

Pearls of Wisdom
• Oral leukoplakia is the most common premalignant lesion or disorder of
the oral mucosa.
• The expert clinician is occasionally surprised by the presence of epithelial
dysplasia or even invasive squamous cell carcinoma in a leukoplakia
lesion, irrespective of its clinical presentation.
• The annual malignant transformation rate amounts approximately 1–2%.
Of the many predictors of future cancer development, including a vast
number of genetic and molecular biomarkers, the presence and degree of
epithelial dysplasia is still the most important one.
• Dysplastic leukoplakias in non-smokers carry a higher risk of cancer
development.
• Malignant transformation may also occur in non-dysplastic leukoplakias.
• Spontaneous regression is rather rare. In small lesions, e.g., less than
2–3 cm, the taking of an excisional biopsy is recommended.
• Leukoplakias persisting for more than 3 months should be biopsied at least
once, and, if left untreated, a biopsy should be performed thereafter if clin-
ical changes occur.
• Symptomatic leukoplakias should always be biopsied as soon as possible.
• In case of larger or multiple lesions, surgical removal may be limited to the
clinically most suspicious area, if any, and may be combined with CO2
laser evaporation.

I. van der Waal, DDS, PhD

VU University Medical Centre/ACTA, Department of Oral and Maxillofacial
Surgery/Pathology, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
e-mail: [Link]@[Link]

© Springer International Publishing AG 2017 3

J.N.A.R. Ferreira et al. (eds.), Orofacial Disorders,
DOI 10.1007/978-3-319-51508-3_1
4 I. van der Waal

• Because of the lack of prospective randomized trials, it is questionable

whether removal of leukoplakias does truly eliminate or reduce the risk of
future development of oral cancer.
• All patients with leukoplakias, being actively treated or not, should be
­followed up with intervals of 3–6 months, depending on the histopatho-
logical findings.

1.1 Introduction

Leukoplakia is primarily a clinical term for a predominantly white lesion that can-
not be wiped off and that cannot be characterized as any other definable white lesion
of the oral mucosa. It is the most common premalignant lesion of the oral mucosa.
A premalignant or potentially malignant lesion is a lesion that carries a signifi-
cantly increased risk of transforming into cancer. Some prefer to refer to leukopla-
kia as a disorder instead of a lesion since cancer development may not only occur in
or adjacent to the leukoplakic area but also elsewhere in the oral cavity or the head-­
and-­neck region.

1.2 Clinical Presentation

• Oral leukoplakias are clinically classified into homogeneous and nonhomoge-

neous leukoplakias.
• Homogeneous leukoplakias are consistently white and flat and usually do not
cause symptoms (Fig. 1.1).
• Nonhomogeneous leukoplakias comprise lesions with a mixture of white and
red changes (erythroleukoplakias) and nodular or speckled leukoplakias

Fig. 1.1 Homogeneous

(flat and thin) leukoplakia
1 Leukoplakia 5

Fig. 1.2 Nonhomogeneous

(erythematous) leukoplakia
(“erythroleukoplakia”)

Fig. 1.3 Nonhomogeneous

(nodular) leukoplakia

(Figs. 1.2 and 1.3); these nonhomogeneous leukoplakias usually cause some
discomfort. Another type of nonhomogeneous leukoplakia is the verrucous
leukoplakia in which there is a somewhat exophytic, verrucous texture
(Fig. 1.4). Verrucous leukoplakias are usually asymptomatic. A rare subtype of
verrucous leukoplakia is proliferative verrucous leukoplakia (PVL), character-
ized by widespread occurrence and resistance to treatment. Recurrences of
PVL are, indeed, common and malignant transformation may be inevitable in
many if not all patients [1].
• When redness is the predominant color of a lesion that cannot be recognized as
any other definable red lesion or disorder of the oral mucosa, the term erythro-
plakia is applied (Fig. 1.5). Erythroplakias are usually symptomatic with a local-
ized burning pain. Erythroplakias are less common than leukoplakias, but the
risk of malignant transformation is much higher than in leukoplakias.
6 I. van der Waal

Fig. 1.4 Nonhomogeneous

(verrucous) leukoplakia

Fig. 1.5 Erythroplakia of

the palate

1.3 Etiology and Epidemiology

• Oral leukoplakias occur much more often in smokers than in non-smokers.

• Other possible etiologies for oral leukoplakia include Candida albicans and cer-
tain human papillomaviruses.
• Limited information is available on the epidemiology of oral leukoplakia. The
reported prevalence rates vary between 1.0% and 2.7% [2].
• Most affected patients are in the fourth decade of life or above.
• The male-female ratio varies in different parts of the world. In the Western world,
there is no distinct gender predilection.
1 Leukoplakia 7

1.4 Pathophysiology and Mechanisms

• In patients who smoke, the epithelial changes that result in the development of
leukoplakia are thought to be brought about by the carcinogens of tobacco
products.
• In non-smokers with oral leukoplakia, the pathophysiology is currently unknown.
• The possible role of Candida albicans in the development or the malignant trans-
formation of leukoplakia is poorly understood.
• Suggested determinants contributing to malignant potential include advanced
age, female gender, size exceeding 200 mm2, nonhomogeneous clinical type, and
higher grades of epithelial dysplasia [3]. In many of the reported studies, location
on the tongue is another risk factor.
• Apparently, dysplastic leukoplakias in non-smokers carry a higher risk of cancer
development than in smokers [4].
• Of the numerous suggested genetic and molecular biomarkers that may be predic-
tive of future malignant transformation, loss of heterozygosity at 9p and mutated
p53 in biopsies of oral leukoplakias are at present the most promising ones [5, 6].

1.5 Diagnosis and Diagnostic Criteria

• The diagnosis of oral leukoplakia is in most cases primarily based on clinical

aspects.
• White lesions that may be caused by friction, such as vigorously toothbrushing, may
be diagnosed as frictional lesions but only so if the lesions have disappeared after
changing the brushing habits. Otherwise, the term leukoplakia should be applied.
• Occasionally, it may be difficult to distinguish leukoplakia from other white
lesions and disorders (Table 1.1); this particularly applies to the plaque type or
erosive, erythematous type of lichen planus.
• Whitish or reddish changes of the oral mucosa may also be the result of direct
contact with large dental restorations, particularly amalgam, being referred to as
“contact lesions.”
• For diagnostic purposes there is hardly a role for exfoliative cytology, brush
cytology, or vital staining, such as by toluidine blue, except in case of erythroleu-
koplakia or erythroplakia. Nevertheless, the use of toluidine blue staining may
aid in determining the site of the biopsy [7]. Preference is given to one or more
incisional biopsies or, in case of a lesion less than a few centimeters in diameter,
by an excisional biopsy.
• The biopsy should be taken at the site of induration, redness, or symptoms, if
present. In multiple or large leukoplakias, the taking of multiple biopsies should
be considered. The pathologist should be provided with proper clinical informa-
tion, among others with regard to the site where the biopsy has been taken.
8 I. van der Waal

Table 1.1 Definable white lesions and disorders that may have a leukoplakic appearance
Lesion Main diagnostic criteria
Alveolar ridge “keratosis” Primarily a clinical diagnosis of a flat, white change of the
mucosa of an edentulous part of the alveolar ridge; may
overlap frictional lesion (“keratosis”)
Aspirin burn History of prolonged local application of aspirin tablets
(paracetamol may cause similar changes)
Candidiasis, pseudomembranous, Clinical aspect (pseudomembranous, often symmetrical pattern)
hyperplastic Somewhat questionable entity; some refer to this lesion as
candida-associated leukoplakia
Darier-White diseases Associated with lesions of the skin and the nails; rather typical
histopathology
Frictional “keratosis” Disappearance of the lesion within an arbitrarily chosen period
of 6–12 weeks after elimination of the suspected mechanical
irritation (e.g., habit of vigorous toothbrushing); therefore, it is
a retrospective diagnosis only
Geographic tongue Primarily a clinical diagnosis; characterized by a wandering
pattern in time
Glassblower lesion Occurs only in glassblowers; disappears within a few weeks
after cessation of glassblowing
Hairy leukoplakia Clinical aspect (bilateral localization on the borders of the
tongue); histopathology (including EBV immunohistochemical
stain)
Lesion caused by a dental Disappearance of the anatomically closely related (amalgam)
restoration (often amalgam) restoration within an arbitrarily chosen period of 6–12 weeks
after its replacement; therefore, it is a retrospective diagnosis
only
Leukoedema Clinical diagnosis (including symmetrical pattern) of a
veil-like aspect of the buccal mucosa
Lichen planus, reticular type and Primarily a clinical diagnosis (including symmetrical pattern);
erythematous type histopathology is not diagnostic by its own
Linea alba Clinical aspect (located on the line of occlusion in the cheek
mucosa; almost always bilateral)
Lupus erythematosus Primarily a clinical diagnosis (including symmetrical pattern);
almost always cutaneous involvement as well. Histopathology
is not diagnostic by its own
Morsicatio (habitual chewing or History of habitual chewing or biting; clinical aspects
biting of the cheek, tongue, lips)
Papilloma and allied lesions, e.g., Clinical aspect; medical history; HPV typing of a biopsy may
condyloma acuminatum, multifocal be helpful
epithelial hyperplasia, squamous
papilloma, verruca vulgaris
Skin graft, e.g., after a History of a previous skin graft
vestibuloplasty
Smokers’ lesion Disappearance of the lesion within an arbitrarily chosen period
of 6–12 weeks after cessation of the tobacco habits; therefore,
it is a retrospective diagnosis only
Smokers’ palate (“stomatitis Clinical aspect; history of smoking
nicotinica”)
Syphilis, secondary (“mucous Clinical aspect; demonstration of T. pallidum; serology
patches”)
Verrucous hyperplasia and Clinicopathological entities
verrucous carcinoma
White sponge nevus Family history; clinical aspect (often symmetrical pattern)
1 Leukoplakia 9

Fig. 1.6 Mild

a
hyperkeratosis; no
epithelial dysplasia (a);
moderate epithelial
dysplasia (b)

• The pathologist report should include a statement on the absence or presence of

epithelial dysplasia and, if present, its degree. Usually three such grades are rec-
ognized, being mild, moderate, and severe (Fig. 1.6a, b). The difficulties encoun-
tered in establishing a reproducible way of dysplasia grading are well discussed
in a study by Speight et al. [8].
• In rare cases, particularly in erythroplakias, carcinoma in situ or invasive squa-
mous cell carcinoma is seen in a biopsy of a leukoplakic lesion. In such instances
the diagnosis of leukoplakia is replaced by the histopathological diagnosis. In all
other cases a final diagnosis of dysplastic or non-dysplastic leukoplakia remains.
10 I. van der Waal

Fig. 1.7 Leukoplakia of

a
the floor of the mouth; no
treatment instituted (a);
squamous cell carcinoma
developing 4 years later (b)

1.6 Rationale for Treatment

Treatment is directed at removal of symptoms, if any, but above all at prevention of

malignant transformation. Unfortunately, such removal may actually not entirely
eliminate or reduce the risk of future development of oral cancer [9–11]. This also
applies to all other surgical and nonsurgical treatment modalities.
If untreated, transformation into a squamous cell carcinoma occurs at an annual
rate of approximately 1–2%. The absence or presence of epithelial dysplasia, and, if
present, the degree of dysplasia as assessed by histopathological examination of a
biopsy, is at present still the most reliable predictive factor of malignant transforma-
tion. Nevertheless, malignant transformation may occasionally occur in non-­
dysplastic leukoplakias, while some dysplastic leukoplakias may remain unchanged
or regress (Fig. 1.7a, b) [12].

1.7 Treatment Options

• Spontaneous regression of oral leukoplakia is rare.

• Possible mechanical and chemical etiologic factors should be eliminated, par-
ticularly any tobacco habits, cheek and mucosal biting, sharp and irritating teeth,
alcohol, and others.
1 Leukoplakia 11

• In lesions that are in close contact with large amalgam restorations, replace-
ment of such restorations, e.g., by composite type of material or porcelain,
should be considered; no reliable tests are available to predict the result of such
replacement.
• Lesions smaller than a few centimeters may be excised or vaporized by CO2 laser
(but only after the taking of a biopsy), although recurrence rates may vary from
10% to 30%; in larger lesions or in case of multiple occurrences, the morbidity
of treatment should be weighted against the relative low risk of malignant
transformation.
• In widespread lesions, surgical intervention (including laser-based) may have to
be limited to the clinically most suspicious part of the leukoplakia.

1.8 Treatment Goals and Sequencing of Care

A flowchart for the sequence of care of oral leukoplakia is showed in Table 1.2.
Nevertheless, the following goals and recommendations should be taken into con-
sideration while managing these lesions:

• Goals of treatment include a healthy mouth and a minimal risk of developing oral
cancer.
• Initial treatment is aimed at cessation of tobacco habits, if any, excessive
intake of alcohol, and reduction of oral habits such as cheek or mucosal
biting.

Table 1.2 Flowchart with the sequence of care for the management of oral leukoplakia
Management of oral leukoplakia
(Provisional clinical diagnosis)

In case of symptoms consider the taking of a biopsy

Elimination of possible cause(s), incl. tobacco habits No possible cause(s)
(No more than 6-12 weeks observation) (Definitive clinical diagnosis)

Good response No response Biopsy

(Definable lesion; (Definitive clinical diagnosis)
e.q. frictional lesion)
· Management accordingly

No epithelial dysplasia Epithelial dysplasia Definable lesion;

(Nondysplastic leukoplakia) (Dysplastic leukoplakia) e.g. lichen planus
· Management accordingly

Treatment, if feasible Treatment indicated

Follow-up at intervals Follow-up at intervals
of six months; lifelong (?) of three months; lifelong (?)
12 I. van der Waal

• Possible other etiologic factors should be eliminated, such as sharp edges of

teeth or large amalgam restorations that are in close contact with the lesion. In
symptomatic cases, it is a safe practice to first perform a biopsy.
• In the absence of etiologic factors or in persisting lesions of more than 3-month dura-
tion, performing one or more biopsies should be considered in an early stage in order
to be informed about the presence and, if so, of the degree of epithelial dysplasia.
• Although removal of leukoplakia may actually not eliminate or reduce the risk of
future development of oral cancer, a wait-and-see policy is for most patients,
particularly in case of a small lesion, not an acceptable strategy. Such strategy
may be more acceptable in non-dysplastic lesions that are too large for simple
excision or (CO2) laser treatment.
• In a few studies, wide surgical excision has resulted in a lower rate of recurrence
and progression to malignancy in comparison to lesions that have been excised
in a more conservative way [13, 14].
• Surgical removal is preferable above laser evaporation because of the availability
of a surgical specimen that allows additional histopathological examination of
the entire leukoplakic lesion.
• Cessation of smoking habits may reduce the risk of unfavorable events after sur-
gical removal of leukoplakias in smokers [15].
• Intervals of follow-up in treated and untreated patients are largely dependent on
the degree of epithelial dysplasia; in the absence of dysplasia, intervals of
6 months seem to be justified, while in case of untreated dysplastic lesions, inter-
vals of 3 months are recommended.
• Follow-up visits are aimed at early detection of recurrences or, in untreated leu-
koplakias, at changes in size, color, or texture of the leukoplakia or the presence
of symptoms.
• No strict rules can be provided for the length of follow-up; in patients in whom
complete removal has been obtained of a non-dysplastic leukoplakia, follow-up
may be completed after 3 years.

References
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