Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Periodontal disease in children: Associated systemic conditions

Martha Ann Keels, DDS, PhD
Dimitris N Tatakis, DDS, PhD
Section Editor
Ann Griffen, DDS, MS
Deputy Editor
Mary M Torchia, MD


Soft tissue lesions of the oral cavity are common in children, and distinguishing between findings that are normal and those that are indicative of gingivitis, periodontal disease, local or systemic infection, and potentially life-threatening systemic conditions is important. The loss of periodontal attachment in children, manifest by tooth mobility or premature loss, can be a symptom of neoplasia, immunodeficiency, or metabolic defects [1]. The early detection and treatment of these conditions can be life-saving.

Systemic conditions associated with childhood periodontitis will be reviewed here. Soft tissue lesions and periodontitis not associated with systemic conditions are discussed separately. (See "Soft tissue lesions of the oral cavity in children" and "Gingivitis and periodontitis in children and adolescents".)


Langerhans cell histiocytosis (previously known as histiocytosis X or eosinophilic granuloma) is a rare disorder that affects infants, children, and young adults and is characterized by histiocytic infiltration of the bones, skin, liver, or other organs [2]. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis".)

Langerhans cell histiocytosis (LCH) presents with single or multiple-site involvement. The skin, oral mucosa, bone, and lymph nodes are typical locations for single-site involvement. Multisite involvement occurs in the liver, spleen, lungs, bone marrow, and gastrointestinal and central nervous systems.

Between 10 and 20 percent of patients present with infiltration of the oral cavity, usually the posterior mandible [3]. The typical dental presentation of LCH is eruption of the primary molars at or soon after birth (picture 1). Additional oral manifestations include pain; ulceration; enlargement, inflammation, or recession of the gingiva; and mobility of teeth because of expansion of the alveolar bone [4,5]. Dental radiographs may show discreet, destructive bone lesions that make the teeth appear to be "floating on air" [2,5]. Periosteal new bone formation and slight root resorption also may be present [6]. Cases may present as aggressive periodontitis lesions that do not respond to routine periodontal therapy [7], despite the presence of periodontal flora typically associated with periodontitis [8].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 05, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Laskaris, G, Scully, C. Periodontal manifestations of local and systemic diseases: colour atlas and text. Springer, Berlin, New York 2003.
  2. Henry RJ, Sweeney EA. Langerhans' cell histiocytosis: case reports and literature review. Pediatr Dent 1996; 18:11.
  3. Hartman KS. Histiocytosis X: a review of 114 cases with oral involvement. Oral Surg Oral Med Oral Pathol 1980; 49:38.
  4. Ardekian L, Peled M, Rosen D, et al. Clinical and radiographic features of eosinophilic granuloma in the jaws: review of 41 lesions treated by surgery and low-dose radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 87:238.
  5. Guiglia R, Pizzo G, Aricò M, et al. Bifocal manifestation of eosinophilic granuloma in a pediatric patient. Med Sci Monit 2009; 15:CS95.
  6. Dagenais M, Pharoah MJ, Sikorski PA. The radiographic characteristics of histiocytosis X. A study of 29 cases that involve the jaws. Oral Surg Oral Med Oral Pathol 1992; 74:230.
  7. Silvestros SS, Mamalis AA, Sklavounou AD, et al. Eosinophilic granuloma masquerading as aggressive periodontitis. J Periodontol 2006; 77:917.
  8. Torrungruang K, Sittisomwong S, Rojanasomsith K, et al. Langerhans' cell histiocytosis in a 5-year-old girl: evidence of periodontal pathogens. J Periodontol 2006; 77:728.
  9. Klein F, Krigar D, Petzoldt D, Eickholz P. Periodontal manifestation of Langerhans' cell histiocytosis in a young man: case report with a 24-month follow-up. Quintessence Int 2006; 37:175.
  10. Delaney JE, Keels MA. Pediatric oral pathology. Soft tissue and periodontal conditions. Pediatr Clin North Am 2000; 47:1125.
  11. Weckx LL, Hidal LB, Marcucci G. Oral manifestations of leukemia. Ear Nose Throat J 1990; 69:341.
  12. Oral Pathology: Clinical-Pathologic Correlations, 2nd, Regezi JA, Sciubba J (Eds), WB Saunders, Philadelphia 1993. p.196.
  13. Peterson DE, D'Ambrosio JA. Nonsurgical management of head and neck cancer patients. Dent Clin North Am 1994; 38:425.
  14. Otsubo H, Yokoe H, Miya T, et al. Gingival squamous cell carcinoma in a patient with chronic graft-versus-host disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 84:171.
  15. Ponce-Torres E, Ruíz-Rodríguez Mdel S, Alejo-González F, et al. Oral manifestations in pediatric patients receiving chemotherapy for acute lymphoblastic leukemia. J Clin Pediatr Dent 2010; 34:275.
  16. de Oliveira Lula EC, de Oliveira Lula CE, Alves CM, et al. Chemotherapy-induced oral complications in leukemic patients. Int J Pediatr Otorhinolaryngol 2007; 71:1681.
  17. Consensus statement: oral complications of cancer therapies. National Institutes of Health Consensus Development Panel. NCI Monogr 1990; :3.
  18. Childers NK, Stinnett EA, Wheeler P, et al. Oral complications in children with cancer. Oral Surg Oral Med Oral Pathol 1993; 75:41.
  19. Sonis S, Kunz A. Impact of improved dental services on the frequency of oral complications of cancer therapy for patients with non-head-and-neck malignancies. Oral Surg Oral Med Oral Pathol 1988; 65:19.
  20. da Fonseca MA. Pediatric bone marrow transplantation: oral complications and recommendations for care. Pediatr Dent 1998; 20:386.
  21. Moutsopoulos NM, Konkel J, Sarmadi M, et al. Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med 2014; 6:229ra40.
  22. Watanabe K. Prepubertal periodontitis: a review of diagnostic criteria, pathogenesis, and differential diagnosis. J Periodontal Res 1990; 25:31.
  23. Roberts MW, Atkinson JC. Oral manifestations associated with leukocyte adhesion deficiency: a five-year case study. Pediatr Dent 1990; 12:107.
  24. Berrocal T, Simón MJ, al-Assir I, et al. Shwachman-Diamond syndrome: clinical, radiological and sonographic findings. Pediatr Radiol 1995; 25:356.
  25. Ye Y, Carlsson G, Wondimu B, et al. Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia. J Clin Immunol 2011; 31:936.
  26. Duplomb L, Duvet S, Picot D, et al. Cohen syndrome is associated with major glycosylation defects. Hum Mol Genet 2014; 23:2391.
  27. Alaluusua S, Kivitie-Kallio S, Wolf J, et al. Periodontal findings in Cohen syndrome with chronic neutropenia. J Periodontol 1997; 68:473.
  28. Logue GL, Shimm DS. Autoimmune granulocytopenia. Annu Rev Med 1980; 31:191.
  29. Bux J, Behrens G, Jaeger G, Welte K. Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. Blood 1998; 91:181.
  30. Lalezari P, Khorshidi M, Petrosova M. Autoimmune neutropenia of infancy. J Pediatr 1986; 109:764.
  31. Bux J, Kissel K, Nowak K, et al. Autoimmune neutropenia: clinical and laboratory studies in 143 patients. Ann Hematol 1991; 63:249.
  32. Neglia JP, Watterson J, Clay M, et al. Autoimmune neutropenia of infancy and early childhood. Pediatr Hematol Oncol 1993; 10:369.
  33. Wright DG, Dale DC, Fauci AS, Wolff SM. Human cyclic neutropenia: clinical review and long-term follow-up of patients. Medicine (Baltimore) 1981; 60:1.
  34. Haurie C, Dale DC, Mackey MC. Cyclical neutropenia and other periodic hematological disorders: a review of mechanisms and mathematical models. Blood 1998; 92:2629.
  35. Dale DC, Hammond WP 4th. Cyclic neutropenia: a clinical review. Blood Rev 1988; 2:178.
  36. Lange RD, Jones JB. Cyclic neutropenia. Review of clinical manifestations and management. Am J Pediatr Hematol Oncol 1981; 3:363.
  37. Palmer SE, Stephens K, Dale DC. Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis. Am J Med Genet 1996; 66:413.
  38. Delaney JE, Kornman KS. Microbiology of subgingival plaque from children with localized prepubertal periodontitis. Oral Microbiol Immunol 1987; 2:71.
  39. Carlsson G, Wahlin YB, Johansson A, et al. Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. J Periodontol 2006; 77:744.
  40. Buduneli N, Baylas H, Aksu G, Kütükçüler N. Prepubertal periodontitis associated with chronic granulomatous disease. J Clin Periodontol 2001; 28:589.
  41. Cohen MS, Leong PA, Simpson DM. Phagocytic cells in periodontal defense. Periodontal status of patients with chronic granulomatous disease of childhood. J Periodontol 1985; 56:611.
  42. Rezende KM, Canela AH, Ortega AO, et al. Chediak-Higashi syndrome and premature exfoliation of primary teeth. Braz Dent J 2013; 24:667.
  43. Bailleul-Forestier I, Monod-Broca J, Benkerrou M, et al. Generalized periodontitis associated with Chédiak-Higashi syndrome. J Periodontol 2008; 79:1263.
  44. Shibutani T, Gen K, Shibata M, et al. Long-term follow-up of periodontitis in a patient with Chédiak-Higashi syndrome. A case report. J Periodontol 2000; 71:1024.
  45. Iughetti L, Marino R, Bertolani MF, Bernasconi S. Oral health in children and adolescents with IDDM--a review. J Pediatr Endocrinol Metab 1999; 12:603.
  46. Grossi SG, Genco RJ, Machtei EE, et al. Assessment of risk for periodontal disease. II. Risk indicators for alveolar bone loss. J Periodontol 1995; 66:23.
  47. Taylor GW, Burt BA, Becker MP, et al. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. J Periodontol 1998; 69:76.
  48. Lalla E, Cheng B, Lal S, et al. Periodontal changes in children and adolescents with diabetes: a case-control study. Diabetes Care 2006; 29:295.
  49. Merchant AT, Jethwani M, Choi YH, et al. Associations between periodontal disease and selected risk factors of early complications among youth with type 1 and type 2 diabetes: a pilot study. Pediatr Diabetes 2011; 12:529.
  50. Lalla E, Cheng B, Lal S, et al. Diabetes-related parameters and periodontal conditions in children. J Periodontal Res 2007; 42:345.
  51. Merchant AT, Oranbandid S, Jethwani M, et al. Oral care practices and A1c among youth with type 1 and type 2 diabetes. J Periodontol 2012; 83:856.
  52. Harrison R, Bowen WH. Periodontal health, dental caries, and metabolic control in insulin-dependent diabetic children and adolescents. Pediatr Dent 1987; 9:283.
  53. de Pommereau V, Dargent-Paré C, Robert JJ, Brion M. Periodontal status in insulin-dependent diabetic adolescents. J Clin Periodontol 1992; 19:628.
  54. Lundgren T, Westphal O, Bolme P, et al. Retrospective study of children with hypophosphatasia with reference to dental changes. Scand J Dent Res 1991; 99:357.
  55. Karjalainen KM, Knuuttila ML. The onset of diabetes and poor metabolic control increases gingival bleeding in children and adolescents with insulin-dependent diabetes mellitus. J Clin Periodontol 1996; 23:1060.
  56. Lakschevitz F, Aboodi G, Tenenbaum H, Glogauer M. Diabetes and periodontal diseases: interplay and links. Curr Diabetes Rev 2011; 7:433.
  57. Hu CC, King DL, Thomas HF, Simmer JP. A clinical and research protocol for characterizing patients with hypophosphatasia. Pediatr Dent 1996; 18:17.
  58. Chapple IL. Hypophosphatasia: dental aspects and mode of inheritance. J Clin Periodontol 1993; 20:615.
  59. Whyte MP, Teitelbaum SL, Murphy WA, et al. Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature. Medicine (Baltimore) 1979; 58:329.
  60. Fallon MD, Teitelbaum SL, Weinstein RS, et al. Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. Medicine (Baltimore) 1984; 63:12.
  61. Silve C. Hereditary hypophosphatasia and hyperphosphatasia. Curr Opin Rheumatol 1994; 6:336.
  62. Moore CA, Curry CJ, Henthorn PS, et al. Mild autosomal dominant hypophosphatasia: in utero presentation in two families. Am J Med Genet 1999; 86:410.
  63. Deeb AA, Bruce SN, Morris AA, Cheetham TD. Infantile hypophosphatasia: disappointing results of treatment. Acta Paediatr 2000; 89:730.
  64. Taillandier A, Lia-Baldini AS, Mouchard M, et al. Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia. Hum Mutat 2001; 18:83.
  65. Wappner, RS. Inborn errors associated with faulty bone mineralization. In: Oski's Pediatrics. Principles and Practice, 4th ed, McMillan, JA, Feigin, RD, DeAngelis, C, Jones, MD (Eds), Lippincott, Williams & Wilkins, Philadelphia 2006. p.2238.
  66. Fedde KN, Blair L, Silverstein J, et al. Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 1999; 14:2015.
  67. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with hypophosphatasia. Arch Dis Child 1990; 65:130.
  68. Lepe X, Rothwell BR, Banich S, Page RC. Absence of adult dental anomalies in familial hypophosphatasia. J Periodontal Res 1997; 32:375.
  69. Barcia JP, Strife CF, Langman CB. Infantile hypophosphatasia: treatment options to control hypercalcemia, hypercalciuria, and chronic bone demineralization. J Pediatr 1997; 130:825.
  70. van den Bos T, Handoko G, Niehof A, et al. Cementum and dentin in hypophosphatasia. J Dent Res 2005; 84:1021.
  71. Valenza G, Burgemeister S, Girschick H, et al. Analysis of the periodontal microbiota in childhood-type hypophosphatasia. Int J Med Microbiol 2006; 296:493.
  72. Liu H, Li J, Lei H, et al. Genetic etiology and dental pulp cell deficiency of hypophosphatasia. J Dent Res 2010; 89:1373.
  73. US Food and Drug Administration. FDA approves new treatment for rare metabolic disorder. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468836.htm (Accessed on October 28, 2015).
  74. Whyte MP, Madson KL, Phillips D, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight 2016; :e85971.
  75. Gasque KC, Foster BL, Kuss P, et al. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl-/- mice by administration of soluble (non-targeted) chimeric alkaline phosphatase. Bone 2015; 72:137.
  76. Whyte MP, Rockman-Greenberg C, Ozono K, et al. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab 2016; 101:334.
  77. Reuland-Bosma W, van Dijk J. Periodontal disease in Down's syndrome: a review. J Clin Periodontol 1986; 13:64.
  78. Amaral Loureiro AC, Oliveira Costa F, Eustáquio da Costa J. The impact of periodontal disease on the quality of life of individuals with Down syndrome. Downs Syndr Res Pract 2007; 12:50.
  79. Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol 2009; 156:189.
  80. Tanaka MH, Rodrigues TO, Finoti LS, et al. The effect of conventional mechanical periodontal treatment on red complex microorganisms and clinical parameters in Down syndrome periodontitis patients: a pilot study. Eur J Clin Microbiol Infect Dis 2015; 34:601.
  81. Papillon-Lefèvre syndrome. In: Mendelian Inheritance in Man. Johns Hopkins University. Available at www.ncbi.nlm.nih.gov:80/entrez/dispomim.cgi?id=245000. (Accessed on February 2, 2008).
  82. Ghaffer KA, Zahran FM, Fahmy HM, Brown RS. Papillon-Lefèvre syndrome: neutrophil function in 15 cases fron 4 families in Egypt. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 88:320.
  83. Firatli E, Tüzün B, Efeoğlu A. Papillon-Lefèvre syndrome. Analysis of neutrophil chemotaxis. J Periodontol 1996; 67:617.
  84. Hamon Y, Legowska M, Fergelot P, et al. Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome. FEBS J 2016; 283:498.
  85. Ishikawa I, Umeda M, Laosrisin N. Clinical, bacteriological, and immunological examinations and the treatment process of two Papillon-Lefèvre syndrome patients. J Periodontol 1994; 65:364.
  86. Lundgren T, Parhar RS, Renvert S, Tatakis DN. Impaired cytotoxicity in Papillon-Lefèvre syndrome. J Dent Res 2005; 84:414.
  87. de Haar SF, Hiemstra PS, van Steenbergen MT, et al. Role of polymorphonuclear leukocyte-derived serine proteinases in defense against Actinobacillus actinomycetemcomitans. Infect Immun 2006; 74:5284.
  88. Eick S, Puklo M, Adamowicz K, et al. Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis. Orphanet J Rare Dis 2014; 9:148.
  89. Preus H, Gjermo P. Clinical management of prepubertal periodontitis in 2 siblings with Papillon-Lefèvre syndrome. J Clin Periodontol 1987; 14:156.
  90. Wiebe CB, Häkkinen L, Putnins EE, et al. Successful periodontal maintenance of a case with Papillon-Lefèvre syndrome: 12-year follow-up and review of the literature. J Periodontol 2001; 72:824.
  91. Tinanoff N, Tempro P, Maderazo EG. Dental treatment of Papillon-Lefèvre syndrome: 15-year follow-up. J Clin Periodontol 1995; 22:609.
  92. Kressin S, Herforth A, Preis S, et al. Papillon-Lefèvre syndrome--successful treatment with a combination of retinoid and concurrent systematic periodontal therapy: case reports. Quintessence Int 1995; 26:795.