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It also introduces a framework for categorizing these diseases according to their principal pathological pathways and their periodontal effects. Periodontitis arises from a disruption of host\u2013microbe homeostasis, which leads to a dysbiotic microbiota, chronic inflammation, and subsequent periodontal tissue loss. Complex systemic diseases, particularly those causing systemic inflammation or having an autoimmune component (e.g., diabetes mellitus, osteoporosis, arthritis, and inflammatory bowel disease), can exacerbate pre\u2010existing periodontal inflammation and cause further tissue loss. As their inflammatory and pathological pathways are intertwined with periodontitis, their periodontal manifestations are not considered distinct forms of the disease. In contrast, other systemic diseases disrupt host\u2013microbe homeostasis by causing specific defects in the immune response, whereas others impair tissue metabolism or disrupt the physiology and integrity of epithelial and connective tissues. These diseases can lead to significant periodontal destruction and are considered distinct forms of periodontitis. Examples include Down syndrome, leukocyte adhesion deficiency syndromes, Papillon\u2013Lef\u00e8vre syndrome, Haim\u2013Munk syndrome, Chediak\u2013Higashi syndrome, neutropenia, primary immunodeficiency diseases, Cohen syndrome, glycogen storage diseases, Gaucher disease, hypophosphatasia, hypophosphatemic rickets, Hajdu\u2013Cheney syndrome, epidermolysis bullosa, hypoplasminogenemia, and Ehlers\u2013Danlos syndrome. A third category encompasses diseases that induce periodontal tissue loss through mechanisms independent of periodontitis. Examples of this group include Langerhans cell histiocytosis, hyperparathyroidism, and giant cell granulomas. In conclusion, systemic diseases contribute to periodontal tissue loss through overlapping inflammatory pathways, immune dysfunction, or other independent mechanisms. Grouping these diseases by their primary pathological pathways offers a clearer understanding of their effect on periodontal health. This framework may also help direct research toward uncovering shared and unique mechanisms of systemic disease\u2010related periodontal pathology, potentially leading to more targeted therapies and improved disease management.<\/jats:p>","DOI":"10.1111\/jre.70034","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T12:15:52Z","timestamp":1758024952000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Periodontal Manifestations of Systemic Diseases"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-908X","authenticated-orcid":false,"given":"Cristiano","family":"Susin","sequence":"first","affiliation":[{"name":"Department of Periodontology, Endodontics, and Dental Hygiene, Adams School of Dentistry University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Finger","family":"Stadler","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Endodontics, and Dental Hygiene, Adams School of Dentistry University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Haas","sequence":"additional","affiliation":[{"name":"Periodontology, Faculty of Dentistry Federal University of Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-3811","authenticated-orcid":false,"given":"Jasim M.","family":"Albandar","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Implantology, Kornberg School of Dentistry Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0006"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12945"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13337"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1999.70.1.13"},{"issue":"83","key":"e_1_2_13_6_1","first-page":"26","article-title":"The Role of Inflammation and Genetics in Periodontal Disease","volume":"2020","author":"Loos B. 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