Oral Lichen Planus and Lichenoid Lesions: Etiopathogenesis, Diagnosis and Treatment

Description:

This book is an extensive, evidence-based, in-depth review of all aspects of the frequent oral potentially malignant disorder Oral Lichen Planus, from the complex pathogenesis and differential diagnosis to therapeutic management. It highlights the main discoveries and the limits of current knowledge in the epidemiology, pathogenesis, and therapy of this oral disorder, projecting clinicians to the best possible therapeutic management and researchers to the main research fields potentially interesting for the understanding of etiopathogenesis and the establishment of a universally recognized diagnostic criteria. Detailed orientation is provided on oral lichen planus and on the main oral disorders clinically and histologically very similar to it. This work is aimed at clinicians, who are often faced with oral lesions that are not always easily diagnosed, and researchers who are interested in dentistry, oral medicine, and the partly mysterious disease Oral Lichen Planus.

Introduction

The mouth can be regarded as the window of the body: it can reflect, even at an early stage, a systemic disease state. The oral mucosa, primarily, is derived embryologically from the invagination of the ectoderm, and, therefore, it is not surprising that it may be involved in disorders primarily associated with the skin.

Lichen planus (LP) is a chronic mucocutaneous disorder of stratified squamous epithelium that may affect the oral, esophageal, laryngeal, nasal, conjunctival, anal, and genital mucous membranes, skin, nails, and scalp (causing alopecia) [1–3]. OLP (oral lichen planus) is considered to be a chronic inflammatory clinical condition, of noninfective origin, affecting the stratified squamous epithelium of the oral cavity and the underlying lamina propria [4]—derived from the Greek word “leichen” meaning tree moss and from the Latin word “planus” meaning flat. The term “lichen” was applied to the disease because of the common presentation of the flat lesions that suggested a resemblance to lichens [1].

Ferdinand von Hebra (1816–1880), professor at the Viennese school of dermatology and leader of modern dermatology, was the first to provide, in 1860, a scientific description of certain chronic inflammatory lesions of the skin, confluent with each other and characterized by papular eruptions, itchy eruptions, hence the name “lichen ruber” (from the Latin ruber meaning red) which was later referred to as “lichen planus” for the not particularly noticeable redness and the characteristic flatness of the lesions, which would better describe the pathognomonic nature of the lesion.

Significant contributions to the description of the disease were made by the famous British surgeon and British dermatologist Erasmus Wilson (1809–1884) who redefined in 1866 the “lichen ruber” of Hebra and called it “lichen planus” (LP). He described several clinical cases of lichen planus, in which he treated with an iron-arsenical mixture, Fowler’s solution (1% solution of potassium arsenate biacid), and a mercury bichloride lotion, all substances used in the past as medicines for various ailments, now considered toxic and dangerous [5].

In 1895, the French pathologist Louis Frédéric Wickham (1861–1913) observed the characteristic hyperkeratotic striae, whitish and arborescent skin striae on the surface of papules, known today as “Wickham’s striae” [6].

LP was therefore mainly diagnosed on the basis of objective and clinical-morphological aspects of the lesions until in 1906, when William Dubreuilh (1857–1935) and Ferdinand-Jean Darier (1856–1938), universally recognized as the father of French dermatology, described the histopathological changes [7].

Despite the first description of LP dating back to the second half of the nineteenth century, thanks to the studies of Erasmus Wilson, the pathogenic mechanisms that cause LP are still not fully clarified.

Table of contents :

Foreword
Contents
1: Introduction
References
2: Epidemiology
References
3: Aetiology
3.1 Factors of Exogenous Origin
3.1.1 Infectious Agents
3.1.2 Factors Causing Lichenoid Reactions
3.1.3 Habits and Trauma Factors
3.2 Factors of Endogenous Origin
3.2.1 Genetic Factors
3.2.2 Autoimmunity
3.2.3 Heat Shock Proteins (HSPs)
3.2.4 Psychological Disorders’ Correlation with OLP
3.2.5 Correlation with Other Systemic Diseases
References
4: Pathogenesis
4.1 Cells Involved in the Pathogenesis of OLP
4.1.1 Oral Keratinocytes
4.1.2 Antigen-Presenting Cells (APCs) and Humoral Immunity
4.1.3 T lymphocytes and Apoptosis
4.1.4 Natural Killer (NK) Lymphocytes
4.1.5 Mast Cells (MCs)
4.2 Pathogenic Hypotheses of the OLP
4.2.1 Sugerman’s Unifying Hypothesis
4.2.2 Modificate Hypothesis of Carrozzo
4.3 Soluble Factors Involved in the OLP Pathogenesis
4.3.1 Cytokine
4.3.2 Chemokine
4.3.3 Matrix Metalloprotease (MMP)
4.3.4 Role of OLP Immunopathogenesis in Response to Therapy
4.4 Other Factors Involved in the Pathogenesis of OLP
4.4.1 Micro-RNA (mi-RNA or miR)
4.4.2 Vitamin D (VIT.D)
4.4.3 Beta-Defensin
4.4.4 Histamine
4.4.5 Other Factors
4.5 Pathogenesis Related to the Malignant Transformation OF OLP, Prognosis, and Follow-Up
4.5.1 Epidemiology of Neoplastic Risk in OLP
4.5.2 Characteristics of Carcinoma Arising from the OLP Lesion
4.5.3 Pathogenetic Mechanisms of the Transformation Neoplastic OLP
4.5.4 Genetic Alterations Related to the Malignant Transformation of OLP
4.5.5 Prognosis and Follow-Up of OLP
References
5: Diagnosis
5.1 Clinical Classification of OLP Lesions
5.1.1 Papular OLP
5.1.2 Reticular OLP
5.1.3 Plaque OLP
5.1.4 Atrophic-Erythematous OLP
5.1.5 Erosive and Ulcer-Erosive OLP
5.1.6 Bullous OLP
5.1.7 Mixed and Atypical OLP
5.2 Histopathology of OLP Lesions
5.3 Diagnostic Criteria and Definitive OLP Diagnosis
5.3.1 WHO Criteria (1978)
5.3.2 van der Meij and van der Waal Modified Criteria (2003)
5.3.3 American Academy of Oral and Maxillofacial Pathology Criteria (2016)
5.3.4 Updated WHO Criteria (2020)
5.4 Additional Investigations in the Diagnosis of OLP
5.4.1 Direct Immunofluorescence (DIF)
5.4.2 Indirect Immunofluorescence (IIF)
5.4.3 Other Investigations and Biomarkers
5.5 Differential Diagnosis
5.5.1 Specific and Non-specific OLP Characteristics
5.5.2 Oral Lichenoid Contact Lesions (OLCLs or OLCHR)
5.5.3 Oral Lichenoid Drug Reactions (OLDRs)
5.5.4 OLL Related to Graft-Versus-Host Disease (OLL-GvHD)
5.5.5 Dental and Pharmacological Management of OLL/OLP
5.5.6 Pemphigus Vulgaris
5.5.7 Bullous Pemphigoid (BP)
5.5.8 Lichen Planus Pemphigoides (LPP)
5.5.9 Mucous Membrane Pemphigoid (MMP)
5.5.10 Lichen Planus-Like Variant of Paraneoplastic Pemphigus (PNP)
5.5.11 Chronic Ulcerative Stomatitis (CUS)
5.5.12 Erythema Multiforme (EM)
5.5.13 Discoid Lupus Erythematosus (DLE)
5.5.14 Systemic Lupus Erythematosus (SLE)
5.5.15 Leukoplakia and Erythroplakia (LK, ELK, EK, PVL)
5.5.16 Proliferative Verrucous Leukoplakia (PVL)
5.5.16.1 Lichenoid Dysplasia (LD)
5.5.16.2 Other Oral Lichenoid Lesions
5.5.16.3 Summary and Final Considerations
References
6: Therapy
6.1 Glucocorticoids
6.1.1 Systemic Glucocorticoids
6.1.2 Topical Glucocorticoids
6.2 Immunomodulating Agents
6.2.1 Calcineurin Inhibitors
6.2.2 Analogues of the Synthesis of Purine and Pyrimidine Bases
6.2.3 mTOR Inhibitors
6.2.4 NF-κB Inhibitors
6.2.5 Antibiotics
6.2.6 Antimicotics
6.2.7 Antiprotozoals
6.2.8 Anti-Welmintics
6.2.9 Other Immunomodulating Agents
6.3 Vitamin Complexes
6.3.1 Retinoids (Vitamin A)
6.3.2 Group B Vitamins
6.3.3 Vitamin D
6.3.4 Tocopherol (Vitamin E)
6.3.5 Flavonoids (Vitamin P)
6.4 Nutraceuticals
6.4.1 Oral Curcuminoids
6.4.2 Aloe Vera (AV)
6.4.3 Hyaluronic Acid (HA)
6.4.4 Green Tea
6.4.5 Propolis
6.4.6 Chamomile
6.4.7 Glycyrrhizin
6.4.8 Eiconol
6.4.9 Selenium
6.4.10 Ignatia
6.4.11 Portulaca Extract
6.4.12 Total Glucosides of Paeony (TGP)
6.4.13 Piperine
6.5 Monoclonal Antibodies
6.5.1 Anti-TNF-α
6.5.2 Anti-IL-2R
6.5.3 Anti-CD11a
6.5.4 Anti-CD2
6.5.5 Anti-CD20
6.5.6 Anti-VEGF
6.5.7 Other Monoclonal Antibodies
6.6 Non-pharmacological Therapy
6.6.1 Psychiatric Therapy
6.6.2 Bacillus Calmette-Guerin Polysaccharide Nucleic Acid (BCG-PSN)
6.6.3 Platelet-Rich Plasma (PRP)
6.6.4 Conventional Surgery
6.6.5 Cryotherapy
6.6.6 Phototherapy
6.6.7 Final Considerations
References