Diseases of the Oral Mucosa: Study Guide and Review

Foreword
Preface
Contents
About the Editor
1: Introduction
	1.1	 Introduction
	1.2	 Book Structure
	1.3	 Biopsy Sampling
	1.4	 Limitations
	References
2: Anatomy of the Oral Mucosa
	2.1	 Macroscopy of the Oral Cavity
	2.2	 Functions of the Oral Mucosa
	2.3	 Histology of the Oral Mucosa
		2.3.1	 Masticatory Mucosa
			2.3.1.1	 Epithelium of Masticatory Mucosa
		2.3.2	 Lining Mucosa
			2.3.2.1	 Epithelium of Lining Mucosa
		2.3.3	 Specialized Mucosa
		2.3.4	 Protein Expression of Oral Epithelium
			2.3.4.1	 Renewal of the Oral Epithelium
			2.3.4.2	 Aging
			2.3.4.3	 Cell-Cell- and Cell-Matrix-Contacts
			2.3.4.4	 Composition of the Epithelial Permeability Barrier
		2.3.5	 Non-Keratinozytes in Oral Epithelium
			2.3.5.1	 Melanocytes
			2.3.5.2	 Langerhans Cells
			2.3.5.3	 Merkel Cells
		2.3.6	 The Basement Membrane: Epithelial-Connective Tissue Interface
		2.3.7	 Lamina Propria
		2.3.8	 Submucosa
		2.3.9	 Organization of Blood and Nerve Supply in Oral Mucosa
	2.4	 The Immune System of the Oral Mucosa
	References
3: Medical History and Clinical Examination
	3.1	 Introduction
	3.2	 History Taking
	3.3	 Examination of the Oral Cavity
	3.4	 Examination of Extra Oral Sites
	References
4: Normal Variations
	4.1	 Linea Alba (White Line)
	4.2	 Morsicatio
	4.3	 Imprints
	4.4	 Fordyce Granules
	4.5	 Leukoedema
	4.6	 Pigmentation
		4.6.1	 Physiological Pigmentation
		4.6.2	 Melanotic Macule
	4.7	 Torus (Exostosis)
	4.8	 Retrocuspid Papilla
	4.9	 Reactive Fibroma
	4.10	 Papilla of the Parotid Duct
	4.11	 Leukoplakia
	4.12	 Aphthae
	4.13	 Variations of the Tongue
		4.13.1	 Lingual Tonsils
		4.13.2	 Foliate and Vallate Papillae
		4.13.3	 Varices
	References
5: Clinical Scores
	5.1	 Introduction
	5.2	 Clinician Reported Outcome Measures (CROM)
		5.2.1	 Methodologies for Use in Autoimmune Blistering Diseases
			5.2.1.1	 Generic
				Autoimmune Bullous Skin Disorder Intensity Score (ABSIS)
				Oral Disease Severity Score (ODSS) (Additionally Applicable to Oral Lichen Planus)
				Physician’s Global Assessment (PGA)
			5.2.1.2	 Disease specific clinical outcome measures
				Pemphigus Disease Area Index (PDAI)
				Mucous Membrane Pemphigoid Disease Area Index (MMPDAI)
		5.2.2	 Methodologies Designed for Oral Lichen Planus (OLP)
			5.2.2.1	 Oral Disease Severity Score (ODSS)
			5.2.2.2	 Modified White-Erosive-Atrophic (WEA-MOD)
			5.2.2.3	 Reticular-Erythematous-Ulceration (REU)
		5.2.3	 Behçet Disease
		5.2.4	 Recurrent Aphthous Stomatitis
		5.2.5	 Orofacial Granulomatosis
		5.2.6	 Sjögren Syndrome
		5.2.7	 Summary of Clinician Reported Outcome Measures (CROM)
	5.3	 Patient-Reported Outcome Measures (PROM)
		5.3.1	 Generic-Oral
		5.3.2	 Discipline-Specific
		5.3.3	 Disease-Specific
		5.3.4	 Summary of Patient Reported Outcome Measures (PROM)
	5.4	 Clinical Pearls
	References
6: Histopathology of Oral Hyperplastic and Neoplastic Lesions
	6.1	 Introduction
	6.2	 Oral Squamous Cell Carcinoma
		6.2.1	 Verrucous Carcinoma [9] (Table 6.4)
		6.2.2	 Basaloid Squamous Carcinoma [10] (Table 6.5)
		6.2.3	 Leukoplakia [7, 11] (Tables 6.6 and 6.7)
		6.2.4	 Precancerous Leukoplakia [13]
		6.2.5	 Morsicatio
		6.2.6	 Frictional Keratosis
		6.2.7	 Smoker’s Palate
		6.2.8	 Viral Papillomas [8]
		6.2.9	 Multifocal Epithelial Hyperplasia (Heck Disease) [8]
		6.2.10	 Verruciform Xanthoma
		6.2.11	 Candidiasis
		6.2.12	 Lingua/Stomatitis Geographica
		6.2.13	 Lichen Planus Mucosae
		6.2.14	 White Sponge Nevus
		6.2.15	 Reactive Hyperplastic Lesions [18, 19]
			6.2.15.1	 Epulis
		6.2.16	 Pigmented Lesions [20, 21] (Table 6.9)
		6.2.17	 Exogenous Pigmentation
		6.2.18	 Amalgam Tattoo
		6.2.19	 Melanotic Macule
		6.2.20	 Melanocytic Nevi
		6.2.21	 Oral Mucosal Melanoma [22–24] (Table 6.10)
	References
7: Genodermatoses with Oral Manifestations
	7.1	 Introduction
	7.2	 Ehler-Danlos Syndrome
		7.2.1	 Clinical Features
			7.2.1.1	 Oral Cavity
			7.2.1.2	 Skin
			7.2.1.3	 Systemic Manifestations
		7.2.2	 Differential Diagnosis
		7.2.3	 Diagnosis
		7.2.4	 Management
	7.3	 Dyskeratosis Follicularis
		7.3.1	 Clinical Features
			7.3.1.1	 Oral Cavity
			7.3.1.2	 Skin
			7.3.1.3	 Systemic Manifestations
		7.3.2	 Differential Diagnosis
		7.3.3	 Diagnosis
		7.3.4	 Management
	7.4	 Nevoid Basal Cell Carcinoma Syndrome (Gorlin-Goltz Syndrome)
		7.4.1	 Clinical Features
			7.4.1.1	 Oral Cavity
			7.4.1.2	 Skin
			7.4.1.3	 Systemic Manifestations
		7.4.2	 Differential Diagnosis
		7.4.3	 Diagnosis
		7.4.4	 Management
	7.5	 Cowden Syndrome
		7.5.1	 Clinical Features
			7.5.1.1	 Mucocutaneous Manifestations
			7.5.1.2	 Systemic Manifestations
		7.5.2	 Differential Diagnosis
		7.5.3	 Diagnosis
		7.5.4	 Management
	7.6	 Hereditary Hemorrhagic Teleangiectasia
		7.6.1	 Clinical Features
			7.6.1.1	 Skin and Oral Cavity
			7.6.1.2	 Systemic Manifestations
		7.6.2	 Differential Diagnosis
		7.6.3	 Diagnosis
		7.6.4	 Management
	7.7	 Lipoid Proteinosis
		7.7.1	 Clinical Features
			7.7.1.1	 Oral Cavity
			7.7.1.2	 Skin
			7.7.1.3	 Systemic Manifestations
		7.7.2	 Differential Diagnosis
		7.7.3	 Diagnosis
		7.7.4	 Management
	7.8	 Hereditary Benign Intraepithelial Dyskeratosis
		7.8.1	 Clinical Features
		7.8.2	 Differential Diagnosis
		7.8.3	 Diagnosis
		7.8.4	 Management
	7.9	 White Sponge Nevus
		7.9.1	 Clinical Features
		7.9.2	 Differential Diagnosis
		7.9.3	 Diagnosis
		7.9.4	 Management
	7.10	 Hereditary Mucoepithelial Dysplasia
		7.10.1	 Clinical Features
		7.10.2	 Differential Diagnosis
		7.10.3	 Diagnosis
		7.10.4	 Management
	7.11	 Neurocutaneous Syndromes
	References
8: Oral Manifestations in Inherited Epidermolysis Bullosa
	8.1	 Introduction
	8.2	 Epidemiology
	8.3	 Genetics and Risk Factors
	8.4	 Pathophysiology
	8.5	 Diagnosis and Differential Diagnoses
	8.6	 Clinical Features
		8.6.1	 Oral Manifestations of EB
			8.6.1.1	 Pathophysiology of Oral Disease
			8.6.1.2	 Epidermolysis Bullosa Simplex
			8.6.1.3	 Junctional Epidermolysis Bullosa
			8.6.1.4	 Dystrophic Epidermolysis Bullosa
				Dominant Dystrophic EB
				Recessive Dystrophic EB
				Recessive Dystrophic EB Inversa
			8.6.1.5	 Kindler Epidermolysis Bullosa
		8.6.2	 Cutaneous Manifestations of EB
		8.6.3	 Gastrointestinal Manifestations
		8.6.4	 Genitourinary Manifestations
		8.6.5	 Respiratory Manifestations
		8.6.6	 Cardiac Manifestations
		8.6.7	 Systemic Manifestations of Severe EB
	8.7	 Management
		8.7.1	 General Management of EB
		8.7.2	 Management of Oral Disease in EB
			8.7.2.1	 Oral Blisters, Ulcers, and Erosions
			8.7.2.2	 Fibrotic Scarring Sequelae
				Microstomia
				Obliteration of the Oral Vestibule
	References
9: Dyskeratosis Congenita
	9.1	 Introduction
	9.2	 Epidemiology
	9.3	 Genetics
	9.4	 Clinical Features
		9.4.1	 Oral Manifestations
		9.4.2	 Cutaneous Manifestations
		9.4.3	 Systemic Manifestations
	9.5	 Differential Diagnoses
	9.6	 Diagnosis
	9.7	 Pathophysiology
	9.8	 Management
	9.9	 Clinical Pearls
	References
10: Pachyonychia Congenita
	10.1	 Introduction
	10.2	 Epidemiology
	10.3	 Genetics
	10.4	 Clinical Features
		10.4.1	 Oral Manifestations
		10.4.2	 Extraoral Manifestations
	10.5	 Differential Diagnoses
	10.6	 Diagnosis
	10.7	 Pathophysiology
	10.8	 Management
	References
11: Oral Lichen Planus
	11.1	 Introduction
	11.2	 Epidemiology
	11.3	 Genetics and Risk Factors
		11.3.1	 Genetics
		11.3.2	 Autoimmune and Immune-Mediated Mechanisms
		11.3.3	 Drugs
		11.3.4	 Stress and Mood
		11.3.5	 Infection
	11.4	 Clinical Features
		11.4.1	 Reticular OLP
		11.4.2	 Atrophic
		11.4.3	 Plaque-Like
		11.4.4	 Erosive/Ulcerative
		11.4.5	 Papular
		11.4.6	 Bullous
		11.4.7	 Extra-Oral Manifestations of Lichen Planus
			11.4.7.1	 Skin
			11.4.7.2	 Nails
			11.4.7.3	 Scalp
			11.4.7.4	 Genital
	11.5	 Differential Diagnoses
		11.5.1	 Oral Lichenoid Reaction
		11.5.2	 Systemic Lupus Erythematosus
		11.5.3	 Discoid Lupus Erythematosus
		11.5.4	 Graft Versus Host Disease (GvHD)
	11.6	 Diagnosis
		11.6.1	 Histopathology
		11.6.2	 Immunofluorescence
		11.6.3	 Haematoserological Investigations
		11.6.4	 Patch Testing
	11.7	 Pathophysiology
	11.8	 Management
		11.8.1	 Asymptomatic Oral Lichen Planus: Non-Ulcerative
		11.8.2	 Non-ulcerative, Symptomatic Oral Lichen Planus
		11.8.3	 Ulcerative/Erosive/Atrophic Oral Lichen Planus
			11.8.3.1	 Intralesional Triamcinolone
		11.8.4	 Severe Ulcerative/Erosive/Atrophic Oral Lichen Planus
			11.8.4.1	 Systemic Corticosteroids
			11.8.4.2	 Hydroxychloroquine
			11.8.4.3	 Azathioprine
			11.8.4.4	 Mycophenolate Mofetil
			11.8.4.5	 Methotrexate
			11.8.4.6	 Systemic Retinoids
			11.8.4.7	 Biologics
			11.8.4.8	 Phototherapy
		11.8.5	 Non-pharmacological Treatment Modalities
			11.8.5.1	 Dental Hygiene Therapy
			11.8.5.2	 Dietary Avoidance
			11.8.5.3	 Laser Therapy
		11.8.6	 Malignant Potential
		11.8.7	 Monitoring of OLP
	References
12: Recurrent Aphthous Stomatitis
	12.1	 Introduction
	12.2	 Epidemiology
	12.3	 Genetics and Risk Factors
	12.4	 Clinical Features
	12.5	 Differential Diagnosis
	12.6	 Diagnosis
	12.7	 Pathophysiology
	12.8	 Management
	References
13: Behçet Disease
	13.1	 Introduction
	13.2	 Epidemiology
	13.3	 Genetics and Risk Factors
	13.4	 Clinical Features
		13.4.1	 Mucocutaneous Manifestations
			13.4.1.1	 Oral Ulcers
			13.4.1.2	 Genital Ulcers
			13.4.1.3	 Skin Lesions
			13.4.1.4	 Skin Pathergy Reaction
		13.4.2	 Musculoskeletal Involvement
		13.4.3	 Ocular Involvement
		13.4.4	 Neurologic Involvement
		13.4.5	 Vascular Involvement
			13.4.5.1	 Venous Involvement
			13.4.5.2	 Arterial Involvement
		13.4.6	 Gastrointestinal Involvement
	13.5	 Diagnosis
		13.5.1	 Diagnostic Criteria
		13.5.2	 Difficulties in Making Diagnosis
		13.5.3	 Diagnostic Process in Clinical Practice
	13.6	 Pathophysiology
	13.7	 Differential Diagnosis
	13.8	 Management
		13.8.1	 Mucocutaneous Involvement
		13.8.2	 Joint Involvement
		13.8.3	 Ocular Involvement
		13.8.4	 Neurologic Involvement
		13.8.5	 Venous Involvement
		13.8.6	 Arterial Involvement
		13.8.7	 Gastrointestinal Involvement
	References
14: Chronic Ulcerative Stomatitis
	14.1	 Introduction
	14.2	 Epidemiology
	14.3	 Genetics and Risk Factors
	14.4	 Clinical Features
		14.4.1	 Differential Diagnosis
	14.5	 Diagnosis
		14.5.1	 Histopathologic Features
		14.5.2	 Immunofluorescence Studies
		14.5.3	 Pathophysiology
		14.5.4	 Management
	References
15: Lichen Sclerosus of the Oral Mucosa
	15.1	 Introduction
	15.2	 Epidemiology
	15.3	 Genetics and Risk Factors
	15.4	 Clinical Features
	15.5	 Differential Diagnoses
	15.6	 Diagnosis
	15.7	 Pathophysiology
	15.8	 Management
	References
16: Cheilitis Granulomatosa and Melkersson Rosenthal Syndrome
	16.1	 Introduction
	16.2	 Epidemiology
	16.3	 Genetics and Risk Factors
	16.4	 Clinical Features
	16.5	 Differential Diagnosis
	16.6	 Diagnosis
	16.7	 Pathophysiology
	16.8	 Management
	References
17: Autoimmune Blistering Diseases: An Introduction
	17.1	 Introduction
	17.2	 Target Antigens
	17.3	 Diagnostic Principles
	17.4	 Oral Involvement
	17.5	 Pemphigoid Gestationis
	17.6	 Dermatitis Herpetiformis
	References
18: Pemphigus Vulgaris
	18.1	 Introduction
	18.2	 Epidemiology
	18.3	 Genetics and Risk Factors
	18.4	 Clinical Features
	18.5	 Differential Diagnosis
	18.6	 Diagnosis
	18.7	 Pathophysiology
	18.8	 Management
	References
19: Paraneoplastic Pemphigus
	19.1	 Introduction
	19.2	 Epidemiology
	19.3	 Genetics and Risk Factors
	19.4	 Clinical Features
	19.5	 Differential Diagnosis
	19.6	 Diagnosis
		19.6.1	 Histopathology
		19.6.2	 Direct Immunofluorescence Microscopy
		19.6.3	 Indirect Immunofluorescence Microscopy
		19.6.4	 Other Serological Assays
		19.6.5	 Diagnostic Criteria
	19.7	 Pathophysiology
	19.8	 Management
	19.9	 Prognosis
	References
20: Mucous Membrane Pemphigoid
	20.1	 Introduction
	20.2	 Epidemiology
	20.3	 Clinical Features
		20.3.1	 Oral Involvement
		20.3.2	 Ocular Involvement
		20.3.3	 Laryngeal Involvement
		20.3.4	 Esophageal Involvement
		20.3.5	 Genital Involvement
	20.4	 MMP Subtypes Related to Target Antigens
		20.4.1	 Anti-Laminin 332 MMP
		20.4.2	 Anti-Type VII Collagen MMP
	20.5	 Diagnosis
		20.5.1	 Histopathology
		20.5.2	 Direct Immunofluorescence Microscopy
		20.5.3	 Serration Pattern Analysis
		20.5.4	 Serological Tests
			20.5.4.1	 Target Antigens
			20.5.4.2	 Indirect Immunofluorescence
			20.5.4.3	 ELISA and Immunoblot
	20.6	 Outcome Measurements
		20.6.1	 Patient Reported Outcome Measurements
	20.7	 Therapy
		20.7.1	 Mild to Moderate MMP
		20.7.2	 Severe MMP
	References
21: Bullous Pemphigoid
	21.1	 Introduction
	21.2	 Epidemiology
	21.3	 Genetics and Risk Factors
		21.3.1	 Medications
	21.4	 Clinical Features
		21.4.1	 Initial Prodrome of BP and Non-bullous Presentations
		21.4.2	 Bullous Stage
		21.4.3	 Mucosal Involvement in Bullous Pemphigoid
		21.4.4	 Atypical Variants
		21.4.5	 Pediatric Bullous Pemphigoid
		21.4.6	 Neurological and Psychiatric Comorbidities
		21.4.7	 Other Comorbidities
	21.5	 Differential Diagnosis
	21.6	 Diagnosis
		21.6.1	 Histopathology
		21.6.2	 Direct Immunofluorescence Microscopy
		21.6.3	 Indirect Immunofluorescence Microscopy
		21.6.4	 Enzyme-linked Immunosorbent Assay
		21.6.5	 Other Diagnostic Modalities
	21.7	 Pathophysiology
		21.7.1	 Blister Formation
		21.7.2	 T Cells
		21.7.3	 Inflammatory Cells
		21.7.4	 Proteolytic Enzymes
	21.8	 Management
		21.8.1	 Mucosal Disease
		21.8.2	 Wound Care
		21.8.3	 Other Treatments and Clinical Trials
	References
22: Anti-p200 Pemphigoid
	22.1	 Introduction
	22.2	 Epidemiology
	22.3	 Genetics and Risk Factors
	22.4	 Clinical Features
	22.5	 Differential Diagnosis
	22.6	 Diagnosis
	22.7	 Pathophysiology
	22.8	 Management
	References
23: Linear IgA Disease
	23.1	 Introduction
	23.2	 Epidemiology
	23.3	 Genetics and Risk Factors
	23.4	 Clinical Features
	23.5	 Differential Diagnosis
	23.6	 Diagnosis
	23.7	 Pathophysiology
	23.8	 Management
	References
24: Epidermolysis Bullosa Acquisita
	24.1	 Introduction
	24.2	 Epidemiology
	24.3	 Genetics and Risk Factors
	24.4	 Clinical Features
	24.5	 Differential Diagnosis
	24.6	 Diagnosis
	24.7	 Pathophysiology
		24.7.1	 Type VII Collagen is the Autoantigen in EBA
		24.7.2	 Loss of Tolerance and Autoantibody Production
		24.7.3	 Autoantibody-Induced Tissue Damage
		24.7.4	 Resolution
	24.8	 Management
	References
25: Oral Lupus Erythematosus
	25.1	 Introduction
	25.2	 Epidemiology
	25.3	 Genetics and Risk Factors
	25.4	 Clinical Features
	25.5	 Differential Diagnosis
	25.6	 Diagnosis
	25.7	 Pathophysiology
	25.8	 Management
	References
26: Systemic Sclerosis
	26.1	 Epidemiology
	26.2	 Genetics and Risk Factors
	26.3	 Clinical Features
		26.3.1	 Extraoral Manifestations
		26.3.2	 Oral and Perioral Manifestations
		26.3.3	 Radiological Findings
	26.4	 Differential Diagnosis
	26.5	 Diagnosis
	26.6	 Pathophysiology
	26.7	 Management
	References
27: ANCA-Associated Vasculitis
	27.1	 Introduction
	27.2	 Granulomatosis with Polyangiitis
		27.2.1	 Epidemiology
		27.2.2	 Clinical Features of Systemic Involvement
		27.2.3	 Mucocutaneous Features
		27.2.4	 Histopathological Features
		27.2.5	 Direct Immunofluorescence Studies on Lesional Skin and/or Mucosa
	27.3	 Eosinophilic Granulomatosis with Polyangiitis
		27.3.1	 Epidemiology
		27.3.2	 Clinical Features of Systemic Involvement
		27.3.3	 Mucocutaneous Features
		27.3.4	 Histopathological Features
	27.4	 Microscopic Polyangiitis
		27.4.1	 Epidemiology
		27.4.2	 Clinical Features of Systemic Involvement
		27.4.3	 Mucocutaneous Features
		27.4.4	 Histopathological Features
		27.4.5	 Direct Immunofluorescence Studies on Lesional Skin and/or Mucosa
	27.5	 Diagnosis and Differential Diagnosis
	27.6	 Management
	References
28: Viral Infections
	28.1	 Introduction
	28.2	 Herpes Virus Family
	28.3	 Herpes Simplex Virus Type 1
		28.3.1 Epidemiology
		28.3.2 Transmission and Replication
		28.3.3 Primary Herpetic Gingivostomatitis
		28.3.4 Herpes Recidivans
	28.4	 Herpes Simplex Virus Type 2
	28.5	 Varicella Zoster Virus
		28.5.1 Varicella
		28.5.2 Herpes Zoster
	28.6	 Epstein-Barr Virus
		28.6.1 Infectious Mononucleosis
		28.6.2 Oral Hairy Leukoplakia
		28.6.3 EBV-Positive Mucocutaneous Ulcer
	28.7	 Cytomegalovirus
		28.7.1 Mucocutaneous CMV Ulcer
	28.8	 Kaposi Sarcoma Herpesvirus
	28.9	 Human Papilloma Virus
		28.9.1 Virus Characteristics
		28.9.2 Transmission and Epidemiology
		28.9.3 Oral Potentially Malignant Disorders
		28.9.4 Oral Epithelial Dysplasia and Oral Intraepithelial Neoplasia
		28.9.5 High-Risk HPV-Associated Oral Epithelial Dysplasia
		28.9.6 Verruca Vulgaris
		28.9.7 Condyloma Acuminatum
		28.9.8 Immunodeficiency-Associated Oral Papillomatosis
		28.9.9 Focal Epithelial Hyperplasia
	28.10	 Enteroviruses
		28.10.1 Herpangina Zahorsky
		28.10.2 Hand-Foot-Mouth Disease
	28.11	 Rubeola (Measles)
		28.11.1 Clinical Features
		28.11.2 Treatment and Prevention
	28.12	 Rubella (German Measles)
		28.12.1 Forchheimer Spots
	28.13	 Arthropod-Born Viruses
		28.13.1 Dengue
		28.13.2 Chikungunya
		28.13.3 Zika
		28.13.4 West Nile Virus
	28.14	 SARS-CoV-2
	References
29: Bacterial Infections of the Oral Mucosa
	29.1	 Introduction
	29.2	 Dental Caries
		29.2.1 Introduction
		29.2.2 Epidemiology
		29.2.3 Clinical Features
		29.2.4 Diagnosis and Pathophysiology
		29.2.5 Management
	29.3	 Actinomycosis
		29.3.1 Introduction
		29.3.2 Epidemiology
		29.3.3 Clinical Features
		29.3.4 Diagnosis and Pathophysiology
		29.3.5 Management
	29.4	 Tuberculosis
		29.4.1 Introduction
		29.4.2 Epidemiology
		29.4.3 Clinical Features
		29.4.4 Diagnosis and Pathophysiology
		29.4.5 Management
	29.5	 Leprosy
		29.5.1 Introduction
		29.5.2 Epidemiology
		29.5.3 Clinical Features
			29.5.3.1	 Oral Manifestations
			29.5.3.2	 Extraoral Manifestations
			29.5.3.3	 Leprosy Reactions
		29.5.4 Diagnosis and Pathophysiology
		29.5.5 Management
	29.6	 Other Bacterial Infections
		29.6.1 Gram Positive Bacteria
		29.6.2 Gram Negative Bacteria
	29.7	 Sexually Transmitted Infections (STI)
		29.7.1 Syphilis
			29.7.1.1	 Introduction
			29.7.1.2	 Epidemiology
			29.7.1.3	 Clinical Features
				Primary Stage
				Secondary Stage
				Latency
				Tertiary Stage
				Congenital Syphilis
			29.7.1.4	 Diagnosis
			29.7.1.5	 Pathophysiology
			29.7.1.6	 Management
		29.7.2 Neisseria Gonorrhoea and Other Neisseria spp.
		29.7.3 Chlamydia spp.
		29.7.4 Mycoplasma spp.
	References
30: Fungal Diseases of Oral Cavity
	30.1	 Introduction
	30.2	 Oral candidosis
		30.2.1	 Epidemiology
		30.2.2	 Genetics and Risk Factors
		30.2.3	 Pathophysiology
		30.2.4	 Clinical Features
			30.2.4.1	 Pseudomembranous Candidosis
			30.2.4.2	 Erythematous Candidosis
			30.2.4.3	 Hyperplastic Candidosis
			30.2.4.4	 Median Rhomboid Glossitis
			30.2.4.5	 Angular Cheilitis
			30.2.4.6	 Denture Stomatitis
			30.2.4.7	 Linear Gingival Erythema
			30.2.4.8	 Chronic Mucocutaneous Candidosis
		30.2.5	 Differential Diagnosis
		30.2.6	 Diagnosis
			30.2.6.1	 Direct Examination of Smears
			30.2.6.2	 Culture
			30.2.6.3	 Histological Examination
		30.2.7	 Management
	30.3	 Aspergillosis
		30.3.1	 Epidemiology
		30.3.2	 Genetics and Risk Factors
		30.3.3	 Pathophysiology
		30.3.4	 Clinical Features
		30.3.5	 Differential Diagnosis
		30.3.6	 Diagnosis
		30.3.7	 Management
	30.4	 Mucormycosis
		30.4.1	 Epidemiology
		30.4.2	 Genetics and Risk Factors
		30.4.3	 Pathophysiology
		30.4.4	 Clinical Features
		30.4.5	 Differential Diagnosis
		30.4.6	 Diagnosis
		30.4.7	 Management
	30.5	 Cryptococcosis
		30.5.1	 Epidemiology
		30.5.2	 Genetics and Risk Factors
		30.5.3	 Pathophysiology
		30.5.4	 Clinical Features
		30.5.5	 Differential Diagnosis
		30.5.6	 Diagnosis
		30.5.7	 Management
	30.6	 Histoplasmosis
		30.6.1	 Epidemiology
		30.6.2	 Genetics and Risk Factors
		30.6.3	 Pathophysiology
		30.6.4	 Clinical Features
		30.6.5	 Differential Diagnosis
		30.6.6	 Diagnosis
		30.6.7	 Management
	30.7	 Paracoccidioidomycosis
		30.7.1	 Epidemiology
		30.7.2	 Genetics and Risk Factors
		30.7.3	 Pathophysiology
		30.7.4	 Clinical Features
		30.7.5	 Differential Diagnosis
		30.7.6	 Diagnosis
		30.7.7	 Management
	30.8	 Geotrichosis
		30.8.1	 Epidemiology
		30.8.2	 Genetics and Risk Factors
		30.8.3	 Pathophysiology
		30.8.4	 Clinical Features
		30.8.5	 Differential Diagnosis
		30.8.6	 Diagnosis
		30.8.7	 Management
	30.9	 Conclusion
	References
31: Benign Tumors and Hyperpigmentations of Oral Mucosa
	31.1	 Introduction
	31.2	 Lipomatous Tumor
		31.2.1	 Lipoma
	31.3	 Vascular Tumors
		31.3.1	 Pyogenic Granuloma
		31.3.2	 Hemangioma
		31.3.3	 Epithelioid Hemangioma and Kimura Disease
		31.3.4	 Bacillary Angiomatosis
		31.3.5	 Lymphangioma
	31.4	 Tumors of Nerve Sheet Origin
		31.4.1	 Neurofibroma
		31.4.2	 Schwannoma
		31.4.3	 Neuroma
	31.5	 Granular Cell Tumor
	31.6	 Reactive Fibroblastic Tumors
		31.6.1	 Peripheral Giant Cell Granuloma
		31.6.2	 Focal Fibrous Hyperplasia
		31.6.3	 Peripheral Ossifying Fibroma
	31.7	 Fibroblastic and Myoblastic Tumors
		31.7.1	 True Fibroma
		31.7.2	 Solitary Fibrous Tumor
		31.7.3	 Rhabdomyoma
	31.8	 Genetic Diseases with Benign Oral Tumors
	31.9	 Pigmented Lesions
		31.9.1	 Focal Lesions
			31.9.1.1	 Oral Melanotic Macules
			31.9.1.2	 Laugier-Hunziker Syndrome
			31.9.1.3	 Melanocytic Nevi
			31.9.1.4	 Oral Melanoacanthoma
			31.9.1.5	 Foreign Body Pigmentation
				Amalgam, Graphite, and Carbon
		31.9.2	 Diffuse or multifocal lesions
			31.9.2.1	 Physiologic Pigmentation
			31.9.2.2	 Drug Induced Pigmentation
			31.9.2.3	 Smoker’s Melanosis
			31.9.2.4	 Heavy Metal Pigmentation
			31.9.2.5	 Post-Inflammatory Pigmentation
			31.9.2.6	 In Systemic Diseases
	References
32: Leukoplakia and Squamous Cell Carcinoma
	32.1	 Introduction
	32.2	 Oral Premalignant Disorders and Oral Epithelial Dysplasia
		32.2.1	 Epidemiology
		32.2.2	 Clinical Features
		32.2.3	 Diagnosis
		32.2.4	 Histological Criteria
			32.2.4.1	 Cellular Changes in OPMD
			32.2.4.2	 Architectural Changes in OPMD
		32.2.5	 Differential Diagnosis
		32.2.6	 Pathophysiology and Risk Factors
		32.2.7	 Management
	32.3	 Squamous Cell Carcinoma of the Oral Mucosa
		32.3.1	 Epidemiology
		32.3.2	 Genetics and Risk Factors
		32.3.3	 Clinical Features
		32.3.4	 Differential Diagnosis
		32.3.5	 Histopathologic Diagnosis
		32.3.6	 Management
			32.3.6.1	 Staging
			32.3.6.2	 Radiology
			32.3.6.3	 Surgery
			32.3.6.4	 Postoperative Treatment
			32.3.6.5	 Alternative Treatment
	References
33: Oral Submucous Fibrosis
	33.1	 Introduction
		33.1.1	 Definitions
	33.2	 Epidemiology
	33.3	 Etiology, Etiopathogenesis, and Malignant Transformation
	33.4	 Clinical Features
		33.4.1	 Clinical Presentation (Fig. 33.3)
		33.4.2	 Radiographic Presentation
		33.4.3	 Laboratory Findings
		33.4.4	 Histopathological Presentation
	33.5	 Diagnosis
	33.6	 Management
		33.6.1	 Management of Stage 1 OSMF
		33.6.2	 Management of Stage 2 OSMF
		33.6.3	 Management of Stage 3 OSMF
		33.6.4	 Management of Stage 4A OSMF
		33.6.5	 Management of stage 4B OSMF
	33.7	 Clinical Pearls
	References
34: Melanoma of the Oral Cavity
	34.1	 Introduction
	34.2	 Epidemiology
	34.3	 Genetics and Risk Factors
	34.4	 Clinical Features
	34.5	 Differential Diagnosis
	34.6	 Diagnosis
	34.7	 Pathophysiology
	34.8	 Management
		34.8.1	 Immunotherapy
	References
35: Lymphoma, Hematological Neoplasia, and Metastases of the Oral Cavity
	35.1	 Lymphoma
		35.1.1	 Non-Hodgkin Lymphoma
			35.1.1.1	 Epidemiology
			35.1.1.2	 Common Variants
			35.1.1.3	 Oral Lesions
			35.1.1.4	 Primary Cutaneous Lymphomas
			35.1.1.5	 EBV-Positive Mucocutaneous Ulcer
			35.1.1.6	 Diffuse Large B Cell Lymphoma
			35.1.1.7	 Diagnosis and Management
		35.1.2	 Hodgkin Lymphoma
	35.2	 Hematological Neoplasia
		35.2.1	 Leukemia
		35.2.2	 Langerhans Cell Histiocytosis
	35.3	 Sarcomas
		35.3.1	 Extramedullary Myeloid Sarcoma
		35.3.2	 Other Sarcomas
	35.4	 Metastatic Tumours
	References
36: Oral Mucositis Following Cancer Therapy
	36.1	 Introduction
	36.2	 Epidemiology
		36.2.1	 Chemotherapy
		36.2.2	 Hematopoietic Stem Cell Transplantation
		36.2.3	 Head and Neck Radiation Therapy
		36.2.4	 Targeted Anti-cancer Therapy and Immunotherapy
	36.3	 Genetics and Risk Factors
		36.3.1	 Demographic/Lifestyle Factors
		36.3.2	 Genetic Factors
		36.3.3	 Systemic Factors
		36.3.4	 Tumor-related Variables
	36.4	 Pathobiology
		36.4.1	 The Five-stage Model
		36.4.2	 Oral Toxicity Associated with Targeted Therapies and Immunotherapy
	36.5	 Clinical Features
		36.5.1	 Oral Mucositis Induced by Chemotherapy- and Radiotherapy
		36.5.2	 Long-term Post-radiation Oral Mucosal Changes
		36.5.3	 Targeted Therapy-induced Oral Toxicity
	36.6	 Outcome Assessment Measures
		36.6.1	 Clinician Reported Outcome Measures
		36.6.2	 Patient Reported Outcome Measures
	36.7	 Outcomes and Economic Impact
	36.8	 Management
		36.8.1	 Preventive Measures
		36.8.2	 Therapeutic Measures
		36.8.3	 Nutritional Support
	References
37: Erythema Multiforme
	37.1	 Introduction
	37.2	 Epidemiology
	37.3	 Pathogenesis, Genetics and Risk Factors
		37.3.1	 Herpes Simplex Virus Infection-related EM
		37.3.2	 Drug-related EM
	37.4	 Clinical Features
	37.5	 Differential Diagnosis
	37.6	 Diagnosis
		37.6.1	 Histopathology
	37.7	 Management
	References
38: Epithelial Necrolysis
	38.1	 Introduction
	38.2	 Epidemiology
	38.3	 Genetics and Risk Factors
		38.3.1	 Risk Factors
		38.3.2	 Genetics
	38.4	 Clinical Features
	38.5	 Differential Diagnosis
	38.6	 Pathophysiology
	38.7	 Diagnosis
	38.8	 Management
		38.8.1	 Identification and Withdrawal of Potential Causes
		38.8.2	 Supportive Care and Topical Treatment
		38.8.3	 Immunomodulating Therapy
	References
39: Allergic Contact Stomatitis
	39.1	 Introduction
	39.2	 Epidemiology
	39.3	 Genetics and Risk Factors
	39.4	 Clinical Features
		39.4.1	 Contact Urticaria and Oral Allergy Syndrome
		39.4.2	 Plasma Cell Gingivitis
	39.5	 Differential Diagnosis
	39.6	 Diagnosis
	39.7	 Pathophysiology
	39.8	 Management
	References
40: Oral Allergy Syndrome
	40.1	 Introduction
	40.2	 Epidemiology
	40.3	 Genetics and Risk Factors
	40.4	 Clinical Features
		40.4.1	 Potential Symptoms Due to Bet v 1-associated IgE-cross-reactivity to Plant Foods [1]
			40.4.1.1	 Symptom Complex (Organ/Localization)
	40.5	 Differential Diagnosis
	40.6	 Diagnosis
	40.7	 Pathophysiology
		40.7.1	 Allergens: Single Allergenic Molecules
		40.7.2	 Allergen Nomenclature
		40.7.3	 Allergen Structure and its Effect on Function
			40.7.3.1	 Bet v 1-homologues
			40.7.3.2	 Profilins: Panallergens
			40.7.3.3	 Lipid Transfer Proteins
	40.8	 Management
		40.8.1	 Pharmaceutical Intervention
		40.8.2	 Allergen-specific Immunotherapy
	References
41: Gingivitis and Periodontitis
	41.1	 Gingivitis
		41.1.1	 Plaque-induced Gingivitis
			41.1.1.1	 Epidemiology
			41.1.1.2	 Genetics and Risk Factors
			41.1.1.3	 Clinical Features
			41.1.1.4	 Differential Diagnosis
			41.1.1.5	 Diagnosis
			41.1.1.6	 Pathophysiology
			41.1.1.7	 Management
		41.1.2	 Non-plaque-induced Gingivitis
	41.2	 Periodontitis
		41.2.1	 Introduction
		41.2.2	 Periodontitis
			41.2.2.1	 Epidemiology
			41.2.2.2	 Genetics and Risk Factors
			41.2.2.3	 Clinical Features
			41.2.2.4	 Differential Diagnosis
			41.2.2.5	 Diagnosis
			41.2.2.6	 Pathophysiology
			41.2.2.7	 Management
		41.2.3	 Periodontitis as a Direct Manifestation of Systematic Diseases
		41.2.4	 Necrotizing Periodontitis
			41.2.4.1	 Introduction
			41.2.4.2	 Epidemiology
			41.2.4.3	 Genetics and Risk Factors
			41.2.4.4	 Clinical Features
			41.2.4.5	 Differential Diagnosis
			41.2.4.6	 Diagnosis
			41.2.4.7	 Pathophysiology
			41.2.4.8	 Management
	References
42: Gingival Overgrowth
	42.1	 Introduction
	42.2	 Inflammatory Enlargement
	42.3	 Drug-induced Gingival Overgrowth
	42.4	 Gingival Enlargement Associated with Systemic Diseases
		42.4.1	 Leukemia
		42.4.2	 Crohn’s Disease
	42.5	 Idiopathic Gingival Enlargement
	42.6	 Gingival Enlargement Associated with Benign Tumours
	References
43: Diseases of the Tongue
	43.1	 Introduction
	43.2	 Fissured Tongue
		43.2.1 Clinical Features and Epidemiology
		43.2.2 Diagnosis
		43.2.3 Pathophysiology
		43.2.4 Management
	43.3	 Median Rhomboid Glossitis
		43.3.1 Clinical Features and Epidemiology
		43.3.2 Diagnosis
		43.3.3 Pathophysiology
		43.3.4 Management
	43.4	 Geographic Tongue
		43.4.1 Clinical Features and Epidemiology
		43.4.2 Diagnosis
		43.4.3 Pathophysiology
		43.4.4 Management
	43.5	 Black Hairy Tongue (Lingua Villosa Nigra)
		43.5.1 Clinical Features and Epidemiology
		43.5.2 Diagnosis
		43.5.3 Pathophysiology
		43.5.4 Management
	43.6	 Macroglossia
		43.6.1 Clinical Features and Epidemiology
		43.6.2 Diagnosis
		43.6.3 Pathophysiology
			43.6.3.1 Congenital macroglossia
			43.6.3.2 Acquired macroglossia
		43.6.4 Management
	43.7	 Vascular Malformation
		43.7.1 Clinical Features and Epidemiology
		43.7.2 Diagnosis
		43.7.3 Pathophysiology
		43.7.4 Management
	43.8	 Sublingual Varices
		43.8.1 Clinical Features and Epidemiology
		43.8.2 Diagnosis
		43.8.3 Pathophysiology
		43.8.4 Management
	43.9	 Amyloidosis
		43.9.1 Clinical Features and Epidemiology
		43.9.2 Diagnosis
		43.9.3 Pathophysiology
		43.9.4 Management
	43.10	 Hunter Glossitis (Atrophic Glossitis)
		43.10.1 Clinical Features and Epidemiology
		43.10.2 Diagnosis
		43.10.3 Pathophysiology
		43.10.4 Management
	43.11	 Strawberry Tongue
		43.11.1 Clinical Features and Epidemiology
		43.11.2 Diagnosis
		43.11.3 Pathophysiology
		43.11.4 Management
	43.12	 Cowden Disease
		43.12.1 Clinical Features and Epidemiology
	43.13	 Acanthosis Nigricans
		43.13.1 Clinical Features and Epidemiology
		43.13.2 Diagnosis
		43.13.3 Pathophysiology
		43.13.4 Management
	43.14	 Eosinophilic Granulomatosis with Polyangiitis
		43.14.1 Clinical Features and Epidemiology
	References
44: Diseases of the Oral Mucosa in Infants, Children and Adolescents
	44.1	 Introduction
	44.2	 Aphthous Disorders
		44.2.1	 Recurrent Aphthous Stomatitis
		44.2.2	 Bednar Aphthae in Neonates and Infants
	44.3	 Infections
		44.3.1	 Candida Infections
		44.3.2	 Gingivostomatitis Herpetica
		44.3.3	 Oral Lesions in Classical Exanthems, Other Viral Exanthems and Paraviral Exanthematous Diseases
		44.3.4	 Mucocutaneous Lesions in Coxsackieviruses
		44.3.5	 Papular Purpuric Gloves and Socks Syndrome
		44.3.6	 Focal Epithelial Hyperplasia
	44.4	 Immnune-mediated Reactions
		44.4.1	 Kawasaki Disease
		44.4.2	 Erythema Multiforme
		44.4.3	 Reactive Infectious Mucocutaneous Eruption
	44.5	 Genodermatoses
		44.5.1	 Down Syndrome
		44.5.2	 Cathepsin C Coding Gene-related Disorders
			44.5.2.1	 Papillon-Lefèvre Syndrome
			44.5.2.2	 Haim-Munk Syndrome
			44.5.2.3	 Prepubertal Periodontitis
		44.5.3	 Peutz-Jeghers Syndrome
	References
45: Diseases of the Oral Mucosa in East Africa
	45.1	 Syphilis
		45.1.1 Epidemiology
		45.1.2 Clinical Features
		45.1.3 Diagnosis
		45.1.4 Management
	45.2	 Oral Candidiasis
		45.2.1 Epidemiology
		45.2.2 Clinical Features
		45.2.3 Diagnosis
		45.2.4 Management
	45.3	 Herpes Simplex Virus Infection
		45.3.1 Clinical Features
		45.3.2 Diagnosis
		45.3.3 Management
	45.4	 Herpes Zoster
		45.4.1 Epidemiology
		45.4.2 Clinical Features
		45.4.3 Diagnosis
		45.4.4 Pathophysiology
		45.4.5 Management
	45.5	 Erythema Multiforme
		45.5.1 Clinical Features
		45.5.2 Diagnosis
		45.5.3 Management
	45.6	 Recurrent Aphthous Stomatitis
		45.6.1 Clinical Features
		45.6.2 Diagnosis
		45.6.3 Management
	45.7	 Pemphigus Vegetans
		45.7.1 Clinical Features
		45.7.2 Diagnosis
		45.7.3 Management
	45.8	 Oral Lichen Planus
		45.8.1 Clinical Features
		45.8.2 Diagnosis
		45.8.3 Management
	45.9	 Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
		45.9.1 Epidemiology and Etiology
		45.9.2 Clinical Features
		45.9.3 Diagnosis
		45.9.4 Management
	45.10	 Oral Hairy Leukoplakia
		45.10.1 Etiology and Clinical Presentation
		45.10.2 Differential Diagnosis
		45.10.3 Diagnosis
		45.10.4 Management
	45.11	 Kaposi Sarcoma
		45.11.1 Epidemiology
		45.11.2 Clinical Features
		45.11.3 Differential Diagnosis
		45.11.4 Diagnosis
		45.11.5 Pathophysiology
		45.11.6 Management
	45.12	 Other Sarcomas
	45.13	 Oral Malignant Melanoma
		45.13.1 Epidemiology
		45.13.2 Clinical Features
		45.13.3 Diagnosis
		45.13.4 Management
	45.14	 Impact of HIV Infection on Oral Disease
	References
46: Nutrition-related Disorders
	46.1	 Introduction
	46.2	 Malnutrition and Undernutrition
	46.3	 Chronic Disease-related Malnutrition with Inflammation/Cachexia
	46.4	 Protein-energy Malnutrition
	46.5	 Noma
	46.6	 Malassimilation
	46.7	 Hematinic Nutrients
	46.8	 Vitamins
	46.9	 Minerals
	46.10	 Overnutrition and Oral Mucosa
	46.11	 Metabolic Syndrome
	46.12	 Conclusion
	References
47: Xerostomia
	47.1	 Introduction
	47.2	 Epidemiology
	47.3	 Etiology
	47.4	 Clinical Features
		47.4.1	 Xerostomia Caused by Systemic Diseases
			47.4.1.1	 Sjögren Syndrome
			47.4.1.2	 Systemic Lupus Erythematosus
			47.4.1.3	 Rheumatoid Arthritis
			47.4.1.4	 Systemic Sclerosis
			47.4.1.5	 Diabetes Mellitus
			47.4.1.6	 Thyroid Diseases
			47.4.1.7	 Infectious Diseases
			47.4.1.8	 Graft-versus-host Disease
			47.4.1.9	 Other Systemic Diseases
		47.4.2	 Xerostomia Caused by Local or Alternative Factors
			47.4.2.1	 Medications
			47.4.2.2	 Head and Neck Radiation
			47.4.2.3	 Life Style
			47.4.2.4	 Aging
	47.5	 Diagnosis
	47.6	 Management
		47.6.1	 Topical Agents
		47.6.2	 Systemic Agents
	References
48: Miscellaneous Disorders with Oral Manifestations
	48.1	 Introduction
	48.2	 Effect of Tobacco Usage
	48.3	 Salivary Gland Disorders
		48.3.1 Mucocele and Ranula
		48.3.2 Necrotizing Sialometaplasia
	48.4	 Gastrointestinal Disorders
		48.4.1 Crohn’s Disease
		48.4.2 Ulcerative Colitis
		48.4.3 Coeliac Disease
	48.5	 Pyoderma Gangrenosum
	48.6	 Sarcoidosis
	48.7	 Reactive Arthritis
		48.7.1 Oral Mucosa
		48.7.2 Skin
		48.7.3 Arthritis
		48.7.4 Ocular Symptoms
		48.7.5 Urogenital Symptoms
		48.7.6 Gastrointestinal Symptoms
	48.8	 Immunosuppression-associated Oral Manifestations
	48.9	 Transplantation-related Oral Lesions
		48.9.1 Mucositis
		48.9.2 Infections
		48.9.3 Graft-versus-host Disease
		48.9.4 Squamous Cell Carcinoma
		48.9.5 Neutropenic Ulcer
		48.9.6 Ohers
	48.10	 Drug-induced Oral Lesions
		48.10.1 Drug-induced Oral Lesions Detailed in Other Chapters
		48.10.2 Lichenoid Lesions
		48.10.3 Drugs Inducing Oral Ulcers
		48.10.4 Fixed-drug Eruption
		48.10.5 Angioedema
	48.11	 Burning Mouth Syndrome
	48.12	 Trauma
		48.12.1 Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE)
	References
Index