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231 Oral Manifestations of Inflammatory Bowel View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio istituzionale della ricerca - Università di Palermo JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS Vol. 31, no. 3, xx-xx (2017) LETTER TO THE EDITOR ORAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE I. MORTADA1, A. LEONE2, A. GERGES GEAGEA1, R. MORTADA3, C. MATAR1, M. RIZZO4, I. HAJJ HUSSEIN5, L. MASSAAD-MASSADE6 and A. JURJUS1 1Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut (AUB), Beirut, Lebanon; 2Department of Experimental Biomedicine and Clinical Neuroscience, Section of Histology, (BIONEC), University of Palermo, Italy; 3School of Dentistry, Lebanese University, Hadath, Lebanon; 4Internal Medicine, University of Palermo, Palermo, Italy; 5Oakland University William Beaumont School of Medicine, Rochester, MI, United States of America; 6Laboratoire de vectorologie et Trasfert de genes, Gustave Roussy, Villejuif Cedex, France Received July 5, 2017 – Accepted August 2, 2017 Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, have important extraintestinal manifestations, notably in the oral cavity. These oral manifestations can constitute important clinical clues in the diagnosis and management of IBD, and include changes at the immune and bacterial levels. Aphthous ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their presentations vary considerably and might be well diagnosed and distinguished from other oral lesions. Infections, drug side effects, deficiencies in some nutrients and many other diseases involved with oral manifestations should also be taken into account. This article discusses the most recent findings on the oral manifestations of IBD with a focus on bacterial modulations and immune changes. It also includes an overview on options for management of the oral lesions of IBD. To the Editor, diseases, the inflammation persists and becomes Extra intestinal manifestations (EIM) of chronic, thus leading to functional and anatomical inflammatory bowel disease (IBD) have been alterations. The inflammatory bowel diseases, reported to affect several systems including those including Crohn’s disease (CD) and ulcerative cardiovascular, skin and skeletal. These manifestations colitis (UC), are examples of chronic relapsing also involve the oral cavity, with inflammation being inflammatory disorders of the gastrointestinal a common denomination. Inflammation, in a well- tract. IBD has wide and non-pathognomonic controlled immune system, is a normally exhibited clinical characteristics which can usually mislead physiological reaction in intestinal mucosa as a the clinician. Therefore, in addition to the clinical response to microbial antigens. Gastrointestinal presentation, histological and radiological findings microbiota is, however, very complex and rich as well as endoscopic, serological and anatomo- inPROOF antigenic determinants. Once these offending pathologic evaluations constitute important elements agents are eliminated, the inflammation disappears. for establishing an accurate diagnosis. Recently, However, in the case of abnormal conditions and stool markers were detected and seemed helpful for Key words: Crohn’s disease, dysbiosis, IBD, Inflammation, ulcerative colitis Mailing address: Prof. Angelo Leone, 0393-974X (2017) BioNec Section of Histology and Embryology, Copyright © by BIOLIFE, s.a.s. School Of Medicine and Surgery, This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. University of Palermo, Palermo, Italy Unauthorized reproduction may result in financial and other penalties Tel.: +39 0916553581 231 DISCLOSURE: ALL AUTHORS REPORT NO CONFLICTS OF e-mail: [email protected] INTEREST RELEVANT TO THIS ARTICLE. 232 I. MORTADA ET AL. diagnosis (1). On the other hand, the oral cavity is and environmental factors such as smoking, diet, a large reservoir of bacteria profoundly relevant to use of antibiotics or nonsteroidal anti-inflammatory host health and disease. Current studies highlighted drugs and the presence of enteric infections (2). various oral symptoms such as aphthous stomatitis, It is well documented that the most widely lip swelling, oral ulcer and pyostomatitis vegetans accepted mechanism of IBD pathogenesis includes (PV) that are frequently seen in IBD patients inflammation due to altered host immune response (2). These oral findings are manifestations of the in association with continuous stimulation from the underlying disease process. Since saliva-producing resident gut microbiota and consequent secretions cells are part of the digestive system, the assessment of an array of proinflammatory entities and reactive of this body fluid was conducted in many studies. oxygen species (ROS) (1). IL-6 seems to have an For instance, elevated interleukin-6 (IL-6) was found important role in the regulation of IBD chronic in saliva of patients with IBD, indicating that the inflammatory process. The overproduction of IL-6 general involvement of the gastrointestinal tract is by immunocompetent cells is thought to contribute extending to the oral cavity. Therefore, measuring to the development of the inflammatory condition. IL-6 can be a convenient tool to monitor disease Patients with CD and UC have higher concentrations activity and progression. This minireview sheds the of IL-6 in the saliva compared to plasma. This could light on the oral manifestations of IBD. Relevant be expected and may indicate that the inflammatory findings in the literature for the past 15 years or so process in the bowel causes a higher release of on bacterial modulations and immune changes were IL-6 in the saliva since the saliva-producing cells evaluated. Management of the oral lesions of IBD is are greatly involved with the functions of the also covered. digestive tract, the inflamed organ. Further analysis of immunological biomarkers in the saliva of IBD Prevalence of oral manifestations in IBD patients showed higher levels of many inflammatory Oral lesions have been reported to occur in up to cytokines, immunoglobulin A, IL-1β and IL-8 as well 50% of IBD patients. They are more prevalent in CD as a lower lysozyme level (8). Additionally, saliva patients and are more likely to occur in males and in contains a variety of components such as cytokines, children (3). The prevalence of oral lesions in CD immunoglobulins, hormones and antimicrobial reportedly ranges from 20% to 50% (2). However, proteins involved in host defense mechanisms for a recent systematic review on pediatric CD revealed maintaining oral and systemic health. Levels of many that the prevalence of oral manifestations ranged salivary cytokines and IgA were significantly higher between 10% and 80%, based on 28 papers published in both CD and UC patients than those observed in between 2000 and 2015 (4). On the other hand, oral healthy patients, documenting that inflammatory lesions have been also reported to occur in only 8% responses are triggered in the oral cavity of the of UC patients (5). Some studies, however, noted no patients (8). As mentioned above, increased salivary statistically significant differences between the two IL-1β, and tumor necrosis factor-α (TNF-α) levels in diseases (6). CD patients and an elevated IL-8 level in the saliva PROOF PROOFof patients with bowel disease were also reported Immune changes in the oral cavity (9). On the other hand, IBD patients demonstrate The exact pathogenesis of IBD has not been autoimmune changes affecting the minor salivary clearly elucidated, however, it is thought to be glands, leading to dry mouth (5). This results in caused by a dysregulated immunity (7). Generally, significantly reduced salivary lysozyme levels it is assumed that IBD is a multifactorial disease as compared with those of healthy controls (8). involving the immune system (abnormal self- Lysozyme is an antimicrobial protein expressed by recognition and autoantibodies against organ-specific various cells including epithelial cells, neutrophils cellular antigens shared by the gastrointestinal tract and macrophages. It plays a major role in the host and other organ systems) (7), genetic susceptibility, constitutive defense mechanisms and is abundant Journal of Biological Regulators & Homeostatic Agents 233 in saliva. Salivary lysozyme was reported to be not directly associated with the activity of intestinal significantly lower in patients with gingivitis and IBD (25). Mucosal tags are indurated, polypoid, periodontitis as compared with healthy subjects (10). tag-like lesions that are mainly seen in the labial and buccal mucosa as well as in retromolar regions. Bacterial changes in the oral cavity Mucogingivitis lesions are characterized by gingival Alterations in the oral microbiota were described redness, swelling and easy bleeding in addition to among IBD patients. Analysis of salivary microbiota having a hyperplastic and edematous appearance (2). of IBD patients as compared to healthy controls In a prospective 3-year study conducted by Harty et revealed that Bacteroidetes were significantly al., up to 60% of CD patients had mucogingivitis increased with a concurrent decrease in Proteobacteria. (12). Furthermore, patients usually complain of The dominant genera, including Streptococcus, swelling of the face and the lips. These lesions may Prevotella, Neisseria,
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