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

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. Foreword 5 Contents 6 1: Introduction 10 References 11 2: Epidemiology 12 References 13 3: Aetiology 14 3.1 Factors of Exogenous Origin 14 3.1.1 Infectious Agents 14 3.1.2 Factors Causing Lichenoid Reactions 15 3.1.3 Habits and Trauma Factors 16 3.2 Factors of Endogenous Origin 17 3.2.1 Genetic Factors 17 3.2.2 Autoimmunity 18 3.2.3 Heat Shock Proteins (HSPs) 18 3.2.4 Psychological Disorders’ Correlation with OLP 18 3.2.5 Correlation with Other Systemic Diseases 19 References 20 4: Pathogenesis 24 4.1 Cells Involved in the Pathogenesis of OLP 26 4.1.1 Oral Keratinocytes 26 4.1.2 Antigen-Presenting Cells (APCs) and Humoral Immunity 28 4.1.3 T lymphocytes and Apoptosis 31 4.1.4 Natural Killer (NK) Lymphocytes 37 4.1.5 Mast Cells (MCs) 37 4.2 Pathogenic Hypotheses of the OLP 39 4.2.1 Sugerman’s Unifying Hypothesis 39 4.2.2 Modificate Hypothesis of Carrozzo 40 4.3 Soluble Factors Involved in the OLP Pathogenesis 40 4.3.1 Cytokine 41 4.3.2 Chemokine 63 4.3.3 Matrix Metalloprotease (MMP) 63 4.3.4 Role of OLP Immunopathogenesis in Response to Therapy 64 4.4 Other Factors Involved in the Pathogenesis of OLP 65 4.4.1 Micro-RNA (mi-RNA or miR) 65 4.4.2 Vitamin D (VIT.D) 66 4.4.3 Beta-Defensin 69 4.4.4 Histamine 71 4.4.5 Other Factors 75 4.5 Pathogenesis Related to the Malignant Transformation OF OLP, Prognosis, and Follow-Up 76 4.5.1 Epidemiology of Neoplastic Risk in OLP 76 4.5.2 Characteristics of Carcinoma Arising from the OLP Lesion 78 4.5.3 Pathogenetic Mechanisms of the Transformation Neoplastic OLP 79 4.5.4 Genetic Alterations Related to the Malignant Transformation of OLP 80 4.5.5 Prognosis and Follow-Up of OLP 81 References 81 5: Diagnosis 97 5.1 Clinical Classification of OLP Lesions 97 5.1.1 Papular OLP 100 5.1.2 Reticular OLP 100 5.1.3 Plaque OLP 100 5.1.4 Atrophic-Erythematous OLP 101 5.1.5 Erosive and Ulcer-Erosive OLP 101 5.1.6 Bullous OLP 103 5.1.7 Mixed and Atypical OLP 104 5.2 Histopathology of OLP Lesions 104 5.3 Diagnostic Criteria and Definitive OLP Diagnosis 107 5.3.1 WHO Criteria (1978) 108 5.3.2 van der Meij and van der Waal Modified Criteria (2003) 108 5.3.3 American Academy of Oral and Maxillofacial Pathology Criteria (2016) 110 5.3.4 Updated WHO Criteria (2020) 111 5.4 Additional Investigations in the Diagnosis of OLP 112 5.4.1 Direct Immunofluorescence (DIF) 112 5.4.2 Indirect Immunofluorescence (IIF) 113 5.4.3 Other Investigations and Biomarkers 114 5.5 Differential Diagnosis 116 5.5.1 Specific and Non-specific OLP Characteristics 116 5.5.2 Oral Lichenoid Contact Lesions (OLCLs or OLCHR) 117 5.5.3 Oral Lichenoid Drug Reactions (OLDRs) 119 5.5.4 OLL Related to Graft-Versus-Host Disease (OLL-GvHD) 120 5.5.5 Dental and Pharmacological Management of OLL/OLP 123 5.5.6 Pemphigus Vulgaris 124 5.5.7 Bullous Pemphigoid (BP) 131 5.5.8 Lichen Planus Pemphigoides (LPP) 135 5.5.9 Mucous Membrane Pemphigoid (MMP) 140 5.5.10 Lichen Planus-Like Variant of Paraneoplastic Pemphigus (PNP) 143 5.5.11 Chronic Ulcerative Stomatitis (CUS) 146 5.5.12 Erythema Multiforme (EM) 149 5.5.13 Discoid Lupus Erythematosus (DLE) 152 5.5.14 Systemic Lupus Erythematosus (SLE) 153 5.5.15 Leukoplakia and Erythroplakia (LK, ELK, EK, PVL) 160 5.5.16 Proliferative Verrucous Leukoplakia (PVL) 167 5.5.16.1 Lichenoid Dysplasia (LD) 169 5.5.16.2 Other Oral Lichenoid Lesions 171 5.5.16.3 Summary and Final Considerations 173 References 178 6: Therapy 195 6.1 Glucocorticoids 196 6.1.1 Systemic Glucocorticoids 197 6.1.2 Topical Glucocorticoids 198 6.2 Immunomodulating Agents 201 6.2.1 Calcineurin Inhibitors 201 6.2.2 Analogues of the Synthesis of Purine and Pyrimidine Bases 203 6.2.3 mTOR Inhibitors 205 6.2.4 NF-κB Inhibitors 206 6.2.5 Antibiotics 206 6.2.6 Antimicotics 207 6.2.7 Antiprotozoals 207 6.2.8 Anti-Welmintics 208 6.2.9 Other Immunomodulating Agents 208 6.3 Vitamin Complexes 209 6.3.1 Retinoids (Vitamin A) 209 6.3.2 Group B Vitamins 211 6.3.3 Vitamin D 211 6.3.4 Tocopherol (Vitamin E) 211 6.3.5 Flavonoids (Vitamin P) 212 6.4 Nutraceuticals 212 6.4.1 Oral Curcuminoids 212 6.4.2 Aloe Vera (AV) 213 6.4.3 Hyaluronic Acid (HA) 213 6.4.4 Green Tea 214 6.4.5 Propolis 214 6.4.6 Chamomile 214 6.4.7 Glycyrrhizin 215 6.4.8 Eiconol 215 6.4.9 Selenium 215 6.4.10 Ignatia 216 6.4.11 Portulaca Extract 216 6.4.12 Total Glucosides of Paeony (TGP) 216 6.4.13 Piperine 217 6.5 Monoclonal Antibodies 217 6.5.1 Anti-TNF-α 217 6.5.2 Anti-IL-2R 218 6.5.3 Anti-CD11a 218 6.5.4 Anti-CD2 218 6.5.5 Anti-CD20 219 6.5.6 Anti-VEGF 219 6.5.7 Other Monoclonal Antibodies 220 6.6 Non-pharmacological Therapy 220 6.6.1 Psychiatric Therapy 220 6.6.2 Bacillus Calmette-Guerin Polysaccharide Nucleic Acid (BCG-PSN) 220 6.6.3 Platelet-Rich Plasma (PRP) 221 6.6.4 Conventional Surgery 221 6.6.5 Cryotherapy 221 6.6.6 Phototherapy 222 6.6.7 Final Considerations 225 References 225