Received: 9 March 2017 Revised: 4 September 2017 Accepted: 13 September 2017 DOI: 10.1002/JPER.17-0163 2017 WORLD WORKSHOP Non–plaque-induced gingival diseases Palle Holmstrup1 Jacqueline Plemons2 Joerg Meyle3 1 Section of Periodontology, Department of Abstract Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, While plaque-induced gingivitis is one of the most common human inflammatory Copenhagen, Denmark diseases, several non–plaque-induced gingival diseases are less common but often 2Department of Periodontics, Texas A&M of major significance for patients. The non–plaque-induced gingival lesions are University College of Dentistry, Dallas, TX, USA often manifestations of systemic conditions, but they may also represent pathologic 3Department of Periodontology, University changes limited to gingival tissues. A classification is proposed, based on the etiol- of Giessen, Giessen, Germany ogy of the lesions and includes: Genetic/Developmental disorders; Specific infections; Correspondence Inflammatory and immune conditions and lesions; Reactive processes; Neoplasms; Prof. Palle Holmstrup, Section of Periodon- Endocrine, Nutritional and metabolic diseases; Traumatic lesions; and Gingival tology, Department of Odontology, Faculty of Health and Medical Sciences, University pigmentation. of Copenhagen, 20 Noerre Allé, DK-2200 Copenhagen, Denmark. KEYWORDS Email: [email protected] classification, diagnosis oral, epulis, gingiva, gingival diseases, immunological, inflammation, mouth The proceedings of the workshop were mucosa, oral manifestations, oral medicine, periodontal disease, rare diseases jointly and simultaneously published in the Journal of Periodontology and Journal of Clinical Periodontology. Human gingiva as well as other oral tissues may exhibit sev- cuss briefly the more common of these. The major difference eral non–plaque-induced pathologic lesions, which may in between the present classification proposal and that of the some instances be manifestations of a systemic condition 1999 workshop is creation of a more comprehensive nomen- or a medical disorder. They may also represent pathologic clature and inclusion of ICD-10 diagnostic codes. Because changes limited to gingival tissues. Although these lesions some of the conditions seldom manifest in the oral cavity are not directly caused by plaque, their clinical course may and some even more seldom present gingival manifestations, be impacted by plaque accumulation and subsequent gingi- detailed appraisal is included within Table 2. val inflammation. Dentists are the key healthcare providers in establishing diagnoses and formulating treatment plans for DESCRIPTION OF SELECTED patients affected by such lesions. Specialists in periodontol- DISEASE ENTITIES: ogy should be familiar with and be able to diagnose, treat, or refer for treatment any such lesion. 1 GENETIC/DEVELOPMENTAL A review of non–plaque-induced gingival lesions was pre- ABNORMALITIES sented at the 1999 International Workshop for a Classifica- 1 tion of Periodontal Diseases and Conditions, and the present 1.1 Hereditary gingival fibromatosis (HGF) review aims to add available additional literature as well as diseases and conditions which were not included in the for- Clinically, gingival fibromatosis may present gingival over- mer review. Several of the diseases and their treatment have growth in various degrees. Compared to drug-related gingi- been reviewed recently.2–4 The purpose of the current review val overgrowth, hereditary gingival fibromatosis is a rare dis- is not to repeat the details of such texts, but to present a ease which may occur as an isolated disease or as part of a contemporary classification of the most relevant non–plaque- syndrome. It has a genetic basis in mutations of the Son of induced gingival diseases and conditions (Table 1) and to dis- Sevenless gene5 (see Table 2). © 2018 American Academy of Periodontology and European Federation of Periodontology S28 wileyonlinelibrary.com/journal/jper J Periodontol. 2018;89(Suppl 1):S28–S45. HOLMSTRUP ET AL. S29 TABLE 1 Classification table summary: non–plaque-induced gin- TABLE 1 (Continued) gival diseases and conditions 6 Endocrine, nutritional, and metabolic diseases 1 Genetic/developmental disorders 6.1 Vitamin deficiencies 1.1 Hereditary gingival fibromatosis (HGF) Vitamin C deficiency (scurvy) 2 Specific infections 7 Traumatic lesions 2.1 Bacterial origin 7.1 Physical/mechanical insults Necrotizing periodontal diseases (Treponema spp., Frictional keratosis Selenomonas spp., Fusobacterium spp., Prevotella Toothbrushing-induced gingival ulceration intermedia, and others) Factitious injury (self-harm) Neisseria gonorrhoeae (gonorrhea) 7.2 Chemical (toxic) insults Treponema pallidum (syphilis) Etching Mycobacterium tuberculosis (tuberculosis) Chlorhexidine Streptococcal gingivitis (strains of streptococcus) Acetylsalicylic acid 2.2 Viral origin Cocaine Coxsackie virus (hand-foot-and-mouth disease) Hydrogen peroxide Herpes simplex 1/2 (primary or recurrent) Dentifrice detergents Varicella-zoster virus (chicken pox or shingles affecting V Paraformaldehyde or calcium hydroxide nerve) 7.3 Thermal insults Molluscum contagiosum virus Burns of mucosa Human papilloma virus (squamous cell papilloma, condyloma acuminatum, verrucca vulgaris, and focal 8 Gingival pigmentation epithelial hyperplasia) Gingival pigmentation/melanoplakia Smoker's melanosis 2.3 Fungal Drug-induced pigmentation (antimalarials; minocycline) Candidosis Amalgam tattoo Other mycoses (e.g., histoplasmosis, aspergillosis) 3 Inflammatory and immune conditions and lesions 3.1 Hypersensitivity reactions Contact allergy SPECIFIC INFECTIONS Plasma cell gingivitis 2 Erythema multiforme 3.2 Autoimmune diseases of skin and mucous membranes 2.1 Bacterial origin Pemphigus vulgaris Necrotizing periodontal disease Pemphigoid Lichen planus Necrotizing gingivitis (NG), necrotizing periodontitis (NP), Lupus erythematosus and necrotizing stomatitis (NS) are severe inflammatory peri- 3.3. Granulomatous inflammatory conditions (orofacial odontal diseases caused by bacterial infection in patients with granulomatosis) specific underlying risk factors (poor oral hygiene, smok- Crohn's disease ing, stress, poor nutrition, compromised immune status [e.g., Sarcoidosis HIV]). 4 Reactive processes Although the necrotizing diseases often run an acute, 4.1 Epulides rapidly destructive course, the term acute has not been Fibrous epulis included in the diagnoses since 1999. Since superficial necro- Calcifying fibroblastic granuloma sis always involves an ulcer, it is requested to delete the term Pyogenic granuloma (vascular epulis) “ulcerative.” The term “gingivitis” is used for lesions only Peripheral giant cell granuloma (or central) involving gingival tissue and characterized by no loss of peri- 5 Neoplasms odontal attachment.6 Central necrosis of the papillae may 5.1 Premalignant result in considerable tissue destruction with formation of a Leukoplakia crater. If loss of attachment is established, the diagnosis con- 7 Erythroplakia sequently becomes NP. For lesions with ulceration extending > 5.2 Malignant 1.0 cm from the gingival margin, including tissue beyond 8 Squamous cell carcinoma the mucogingival junction, the term NS has been used. Leukemia The three necrotizing diseases appear to represent various Lymphoma stages of the same disease process,9 and a distinction between (Continues) the different manifestations has not always been made in S30 TABLE 2 Features of the more common non–plaque-induced gingival lesions and conditions ICD-10 Subheading and diagnosis code Clinical presentation Etiology Associated conditions Diagnostic investigations 1. Genetic/developmental disorders 1.1. Hereditary gingival K06.1 Generalized fibrous gingival enlargement Mutation localized to 2p21-p22 N/A Excisional biopsy for fibromatosis of tuberosities, anterior free/attached (HGF1) & 5q13-q22 histopathology gingiva and retro-molar pads (HGF2)Mutations of “Son of Sevenless” genes (SOS 1, SOS2)119 2. Specific infections 2.1. Bacterial origin Necrotizing periodontal A69.0 Ulceration with central necrosis of the Treponema spp., Selenomonas Poor oral hygiene, smoking, Characteristic clinical features diseases papillae may result in considerable spp., Fusobacterium spp., stress, poor nutrition, tissue destruction with formation of a and Prevotella intermedia immune compromise e.g. crater7,8 and others10,11 HIV Gonorrhea A54.8 Unspecific lesions with ulcers or fiery red Neisseria gonorrhoeae May be associated with painful Microbiological identification of mucosa and white pseudomembrane pharyngitis and pathogen with or without symptoms120 lymphadenopathy. Genital infection of sexual partner. Syphilis A51.2 Fiery red, edematous and often painful Treponema pallidum Clinical features combined with ulcerations, asymptomatic chancres or dark-field examination of mucous patches, or atypical smear. Serologic reactions are non-ulcerated, inflamed gingivitis present after few weeks. Tuberculosis A18.8 Nodular or papillary proliferation of Mycobacterium tuberculosis Most often combined with Biopsy demonstrating inflamed gingival tissues19 pulmonary infection granulomas with multinucleated giant cells Streptococcal gingivitis K05.01 Acute gingivitis not associated with Strains of streptococcus Sometimes preceded by upper Biopsy combined with plaque respiratory infection microbiologic examination 2.2. Viral origin Hand-foot-and-mouth disease Small vesicles that after rupture leave Coxsackie virus A 6, A 10 and Similar skin lesions of hands Clinical