Advertisement

Oral Signs of Hematologic Disease

  • Diana V. MessadiEmail author
  • Ginat W. Mirowski
Chapter

Abstract

The oral manifestations of hematologic disorders are variable and sometimes resemble other local or systemic conditions. In addition to the cutaneous and systemic findings, the mucous membranes, periodontal tissues, salivary glands, and perioral tissues are often impacted. The clinical constellation may include nonspecific findings such as hemorrhage; fungal, viral, and bacterial infections; ulcerations; and edema. When discussing hematologic disorders, white blood cell, red blood cell, and platelet dyscrasias must be considered.

Keywords

Blood dyscrasias Red blood cell disorders White blood cell disorders 

Notes

Acknowledgment

We would like to acknowledge Mr. Michael Gordon for his editorial support.

References

  1. 1.
    Schlosser BJ, Pirigyi M, Mirowski GW. Oral manifestations of hematologic and nutritional diseases. Otolaryngol Clin N Am. 2011;44(1):183–203., vii.  https://doi.org/10.1016/j.otc.2010.09.007.CrossRefGoogle Scholar
  2. 2.
    Burket LW, Greenberg MS, Glick M, Ship JA. Burket’s oral medicine. 11th ed. Hamilton: BC Decker; 2008.Google Scholar
  3. 3.
    Vogel VG, Fisher RE. Epidemiology and etiology of leukemia. Curr Opin Oncol. 1993;5(1):26–34.PubMedGoogle Scholar
  4. 4.
    Swerdlow SH, International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues, World Health Organization classification of tumours. 4th ed. Lyon: International Agency for Research on Cancer; 2008.Google Scholar
  5. 5.
    Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol. 2008;129(1):130–42.  https://doi.org/10.1309/WYACYWF6NGM3WBRT.CrossRefPubMedGoogle Scholar
  6. 6.
    Hou GL, Huang JS, Tsai CC. Analysis of oral manifestations of leukemia: a retrospective study. Oral Dis. 1997;3(1):31–8.CrossRefGoogle Scholar
  7. 7.
    Weckx LL, Hidal LB, Marcucci G. Oral manifestations of leukemia. Ear Nose Throat J. 1990;69(5):341–2.. 5–6PubMedGoogle Scholar
  8. 8.
    Hiraki A, Nakamura S, Abe K, Takenoshita Y, Horinouchi Y, Shinohara M, et al. Numb chin syndrome as an initial symptom of acute lymphocytic leukemia: report of three cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;83(5):555–61.CrossRefGoogle Scholar
  9. 9.
    Cooper CL, Loewen R, Shore T. Gingival hyperplasia complicating acute myelomonocytic leukemia. J Can Dent Assoc. 2000;66(2):78–9.PubMedGoogle Scholar
  10. 10.
    Neville BW, Damm DD, White DK. Color atlas of clinical oral pathology. 2nd ed. Baltimore: Williams & Wilkins; 1999.Google Scholar
  11. 11.
    Word ZH, Matasar MJ. Advances in the diagnosis and management of lymphoma. Blood Lymphat Cancer: Targets Ther. 2012;2012(2):29–55.  https://doi.org/10.2147/BLCTT.S15554.CrossRefGoogle Scholar
  12. 12.
    Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32.  https://doi.org/10.1182/blood-2011-01-293050.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Townsend W, Linch D. Hodgkin’s lymphoma in adults. Lancet. 2012;380(9844):836–47.  https://doi.org/10.1016/S0140-6736(12)60035-X.CrossRefPubMedGoogle Scholar
  14. 14.
    Molyneux EM, Rochford R, Griffin B, Newton R, Jackson G, Menon G, et al. Burkitt’s lymphoma. Lancet. 2012;379(9822):1234–44.  https://doi.org/10.1016/S0140-6736(11)61177-X.CrossRefPubMedGoogle Scholar
  15. 15.
    Bower M. Acquired immunodeficiency syndrome-related systemic non-Hodgkin’s lymphoma. Br J Haematol. 2001;112(4):863–73.CrossRefGoogle Scholar
  16. 16.
    Kolokotronis A, Konstantinou N, Christakis I, Papadimitriou P, Matiakis A, Zaraboukas T, et al. Localized B-cell non-Hodgkin’s lymphoma of oral cavity and maxillofacial region: a clinical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99(3):303–10.  https://doi.org/10.1016/j.tripleo.2004.03.028.CrossRefPubMedGoogle Scholar
  17. 17.
    Gabarre J, Raphael M, Lepage E, Martin A, Oksenhendler E, Xerri L, et al. Human immunodeficiency virus-related lymphoma: relation between clinical features and histologic subtypes. Am J Med. 2001;111(9):704–11.CrossRefGoogle Scholar
  18. 18.
    Canellos GP, Rosenberg SA, Friedberg JW, Lister TA, Devita VT. Treatment of Hodgkin lymphoma: a 50-year perspective. J Clin Oncol. 2014;32(3):163–8.  https://doi.org/10.1200/JCO.2013.53.1194.CrossRefPubMedGoogle Scholar
  19. 19.
    Berliner N, Horwitz M, Loughran TP Jr. Congenital and acquired neutropenia. Hematol/Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2004:63–79.  https://doi.org/10.1182/asheducation-2004.1.63.
  20. 20.
    Dale DC, Bolyard AA, Aprikyan A. Cyclic neutropenia. Semin Hematol. 2002;39(2):89–94.CrossRefGoogle Scholar
  21. 21.
    Bellanne-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, et al. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood. 2004;103(11):4119–25.  https://doi.org/10.1182/blood-2003-10-3518.CrossRefPubMedGoogle Scholar
  22. 22.
    Dale DC. ELANE-related neutropenia. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT et al., editors. GeneReviews (R). Seattle (WA): University of Washington; 1993.Google Scholar
  23. 23.
    Horwitz MS, Duan Z, Korkmaz B, Lee HH, Mealiffe ME, Salipante SJ. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood. 2007;109(5):1817–24.  https://doi.org/10.1182/blood-2006-08-019166.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cohen DW, Morris AL. Periodontal manifestations of cyclic neutropenia. J Periodontol. 1961;32(2):159–68.CrossRefGoogle Scholar
  25. 25.
    Hammond WP 4th, Price TH, Souza LM, Dale DC. Treatment of cyclic neutropenia with granulocyte colony-stimulating factor. N Engl J Med. 1989;320(20):1306–11.  https://doi.org/10.1056/NEJM198905183202003.
  26. 26.
    Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337(13):898–909.  https://doi.org/10.1056/NEJM199709253371306.CrossRefPubMedGoogle Scholar
  27. 27.
    Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349(6):583–96.  https://doi.org/10.1056/NEJMra023144.CrossRefPubMedGoogle Scholar
  28. 28.
    Biewend ML, Menke DM, Calamia KT. The spectrum of localized amyloidosis: a case series of 20 patients and review of the literature. Amyloid. 2006;13(3):135–42.  https://doi.org/10.1080/13506120600876773.CrossRefPubMedGoogle Scholar
  29. 29.
    Stoopler ET, Sollecito TP, Chen SY. Amyloid deposition in the oral cavity: a retrospective study and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95(6):674–80.  https://doi.org/10.1067/moe.2003.136.CrossRefPubMedGoogle Scholar
  30. 30.
    Mardinger O, Rotenberg L, Chaushu G, Taicher S. Surgical management of macroglossia due to primary amyloidosis. Int J Oral Maxillofac Surg. 1999;28(2):129–31.CrossRefGoogle Scholar
  31. 31.
    Aono J, Yamagata K, Yoshida H. Local amyloidosis in the hard palate: a case report. Oral Maxillofac Surg. 2009;13(2):119–22.  https://doi.org/10.1007/s10006-009-0158-4.CrossRefPubMedGoogle Scholar
  32. 32.
    Hachulla E, Janin A, Flipo RM, Saile R, Facon T, Bataille D, et al. Labial salivary gland biopsy is a reliable test for the diagnosis of primary and secondary amyloidosis. A prospective clinical and immunohistologic study in 59 patients. Arthritis Rheum. 1993;36(5):691–7.CrossRefGoogle Scholar
  33. 33.
    Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60.  https://doi.org/10.1056/NEJMra1011442.CrossRefPubMedGoogle Scholar
  34. 34.
    Vela-Ojeda J, Garcia-Ruiz Esparza MA, Padilla-Gonzalez Y, Sanchez- Cortes E, Garcia-Chavez J, Montiel-Cervantes L, et al. Multiple myeloma- associated amyloidosis is an independent high-risk prognostic factor. Ann Hematol. 2009;88(1):59–66.  https://doi.org/10.1007/s00277-008-0554-0.CrossRefPubMedGoogle Scholar
  35. 35.
    Rajkumar SV, Merlini G, San Miguel JF. Haematological cancer: redefining myeloma. Nat Rev Clin Oncol. 2012;9(9):494–6.  https://doi.org/10.1038/nrclinonc.2012.128.CrossRefPubMedGoogle Scholar
  36. 36.
    Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–e48.  https://doi.org/10.1016/S1470-2045(14)70442-5.CrossRefPubMedGoogle Scholar
  37. 37.
    Cardoso RC, Gerngross PJ, Hofstede TM, Weber DM, Chambers MS. The multiple oral presentations of multiple myeloma. Support Care Cancer. 2014;22(1):259–67.  https://doi.org/10.1007/s00520-013-1960-y.CrossRefPubMedGoogle Scholar
  38. 38.
    Chou T. Multiple myeloma: recent progress in diagnosis and treatment. J Clin Exp Hematopathol. 2012;52(3):149–59.CrossRefGoogle Scholar
  39. 39.
    Allen CE, Li L, Peters TL, Leung HC, Yu A, Man TK, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol. 2010;184(8):4557–67.  https://doi.org/10.4049/jimmunol.0902336.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Caldemeyer KS, Parks ET, Mirowski GW. Langerhans cell histiocytosis. J Am Acad Dermatol. 2001;44(3):509–11.  https://doi.org/10.1067/mjd.2001.109304.CrossRefPubMedGoogle Scholar
  41. 41.
    Kilborn TN, Teh J, Goodman TR. Paediatric manifestations of Langerhans cell histiocytosis: a review of the clinical and radiological findings. Clin Radiol. 2003;58(4):269–78.CrossRefGoogle Scholar
  42. 42.
    Hoover K, Rosenthal D, Mankin H. Langerhans cell histiocytosis. Skelet Radiol. 2007;36(2):95–104.  https://doi.org/10.1007/s00256-006-0193-2.CrossRefGoogle Scholar
  43. 43.
    Stull MA, Kransdorf MJ, Devaney KO. Langerhans cell histiocytosis of bone. Radiographics. 1992;12(4):801–23.CrossRefGoogle Scholar
  44. 44.
    Windebank K, Nanduri V. Langerhans cell histiocytosis. Arch Dis Child. 2009;94(11):904–8.  https://doi.org/10.1136/adc.2007.125872.CrossRefPubMedGoogle Scholar
  45. 45.
    Milian MA, Bagan JV, Jimenez Y, Perez A, Scully C, Antoniades D. Langerhans’ cell histiocytosis restricted to the oral mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(1):76–9.  https://doi.org/10.1067/moe.2001.110031.CrossRefPubMedGoogle Scholar
  46. 46.
    Hicks J, Flaitz CM. Langerhans cell histiocytosis: current insights in a molecular age with emphasis on clinical oral and maxillofacial pathology practice. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(2 Suppl):S42–66.  https://doi.org/10.1016/j.tripleo.2005.06.016.CrossRefPubMedGoogle Scholar
  47. 47.
    Götz G, Fichter J. Langerhans’-cell histiocytosis in 58 adults. Eur J Med Res. 2004;9(11):510–4.PubMedGoogle Scholar
  48. 48.
    Annibali S, Cristalli MP, Solidani M, Ciavarella D, La Monaca G, Suriano MM, et al. Langerhans cell histiocytosis: oral/periodontal involvement in adult patients. Oral Dis. 2009;15(8):596–601.  https://doi.org/10.1111/j.1601-0825.2009.01601.x.CrossRefPubMedGoogle Scholar
  49. 49.
    Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: current concepts and treatments. Cancer Treat Rev. 2010;36(4):354–9.  https://doi.org/10.1016/j.ctrv.2010.02.012.CrossRefPubMedGoogle Scholar
  50. 50.
    Gadner H, Grois N, Potschger U, Minkov M, Arico M, Braier J, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008;111(5):2556–62.  https://doi.org/10.1182/blood-2007-08-106211.CrossRefPubMedGoogle Scholar
  51. 51.
    Sekhon SS, Roy V. Thrombocytopenia in adults: a practical approach to evaluation and management. South Med J. 2006;99(5):491–8.CrossRefGoogle Scholar
  52. 52.
    Priziola JL, Smythe MA, Dager WE. Drug-induced thrombocytopenia in critically ill patients. Crit Care Med. 2010;38(Suppl):S145–54.CrossRefGoogle Scholar
  53. 53.
    Aster RH, Boughie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357:580–7.CrossRefGoogle Scholar
  54. 54.
    Israels S, Schwetz N, Boyar R, McNicol A. Bleeding disorders: characterization, dental considerations and management. J Can Dent Assoc. 2006;72(9):827.PubMedGoogle Scholar
  55. 55.
    Fillmore WJ, Leavitt BD, Arce K. Dental extractions in the thrombocytopenic patient. Oral Surg Oral Med Oral Pathol Oral Radiol. 117(4):e300.Google Scholar
  56. 56.
    Rund D, RachmiIewitz E. β-Thalassemia. N Engl J Med. 2005;353:1135–46.CrossRefGoogle Scholar
  57. 57.
    Perisano C, Marzetti E, Spinelli MS, Calla C, Graci C, Maccauro G. PhysiopathoIogy of bone modifications in β -thalassemia. Hindawi Publishing Corporation Anemia Volume 2012, Article ID 320737, 5 p.Google Scholar
  58. 58.
    Vogiatzi MG, Macklin EA, Fung EB, Cheung AM, Vichinsky E, Olivieri N, et al. Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res. 2009;24(3):543–57.CrossRefGoogle Scholar
  59. 59.
    Javid B, Said-Al-Naief N. Craniofacial manifestations of β-thalassemia major. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119(1):e33–40.CrossRefGoogle Scholar
  60. 60.
    Azam M, Bhatti N. Hair on end appearance. Arch Dis Child. 2006;91(9):735.CrossRefGoogle Scholar
  61. 61.
    Stover PJ. Vitamin B12 and older adults. Curr Opin Clin Nutr Metab Care. 2010;13:24–7.CrossRefGoogle Scholar
  62. 62.
    Koybasi S, Parlak AH, Serin E, Yilmaz F, Serin D. Recurrent aphthous stomatitis: investigation of possible etiologic factors. Am J Otolaryngol. 2006;27(4):229–32.CrossRefGoogle Scholar
  63. 63.
    Piskin S, Sayan C, Durukan N, Senol M. Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol. 2002;16(1):66–7.CrossRefGoogle Scholar
  64. 64.
    Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003;134(2):200–7.CrossRefGoogle Scholar
  65. 65.
    Patton LL, Brahim JS, Travis WD. Mandibular osteomyelitis in a patient with sickle cell anemia: report of case. J Am Dent Assoc. 1990;121(5):602–4.CrossRefGoogle Scholar
  66. 66.
    Bizarro N. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014;13:565–8.CrossRefGoogle Scholar
  67. 67.
    Stabler SP. Vitamin B12 Deficiency. New Engl J Med. 2013;368:149–60.CrossRefGoogle Scholar
  68. 68.
    Macleod RI, Hamilton PJ, Soames JV. Quantitative exfoliative oral cytology in iron-deficiency and megaloblastic anemia. Anal Quant Cytol Histol. 1988;10(3):176–80.PubMedGoogle Scholar
  69. 69.
    Lee HJ, Jo DY. Images in clinical medicine. A smooth, shiny tongue. N Engl J Med. 2009;360(6):e8.CrossRefGoogle Scholar
  70. 70.
    Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123(5):615.CrossRefGoogle Scholar
  71. 71.
    Love AL, Billett HH. Obesity, bariatric surgery and iron deficiency: true, true true and related. Am J Hematol. 2008;83:403–9.CrossRefGoogle Scholar
  72. 72.
    Eisen D, Lynch DP. Oral manifestations of systemic diseases. The mouth: diagnosis and treatment. St. Louis: Mosby; 1998. p. 212–36.Google Scholar
  73. 73.
    Cawson RA, Odell EW. Cawson’s essentials of oral pathology and oral medicine. 8th ed. Edinburgh: Churchill Livingstone/Elsevier; 2008.Google Scholar
  74. 74.
    Deloughery TG. Microcytic anemia. N Engl J Med. 2014;371(14):1324–31.. 2010CrossRefGoogle Scholar
  75. 75.
    Tefferi AB, Suman VJ, Sobell JL, Codd MB, Silverstein MN, Melton LJ 3rd. Trends in the incidence of polycythemia vera among Olmsted Coutny, Minnesota resident, 1935–1989. Am J Hematol. 1994:4789–93.Google Scholar
  76. 76.
    Najean Y, Rain JD, Billotey C. Epidemiological data in polycythaemia vera: a study of 842 cases. Hematol Cell Ther. 1998;40:159–65.PubMedGoogle Scholar
  77. 77.
    Lele MV. Oral manifestations of polycythaemia rubra vera. J All India Dent Assoc. 1965;37(11):345–8.PubMedGoogle Scholar
  78. 78.
    Ruparella PB, Ruparella KP, Shirolkar R, Tipathy A. Chronic myeloproliferative disorders: a rarest case with oral manifestations and dental management. J Indian Aca Oral Med Radio. 2012;24(2):155–7.CrossRefGoogle Scholar
  79. 79.
    Creary M, Williamson W, Kulkarni R. Sickle cell disease: current activities, health implications, and future directions. J Women’s Health (Larchmt). 2007;16:575–82.CrossRefGoogle Scholar
  80. 80.
    Laurence B, George D, Woods D, Shosanya A, Katz RV, Lanzkron S, et al. The association between sickle cell disease and dental caries in African Americans. Spec Care Dentist. 2006;26:95–100.CrossRefGoogle Scholar
  81. 81.
    Luna AC, Rodrigues MJ, Menezes VA, Marques KM, Santos FA. Caries prevalence and socioeconomic factors in children with sickle cell anemia. Braz Oral Res. 2012;26:43–9.CrossRefGoogle Scholar
  82. 82.
    Javed F, Correa FO, Nooh N, Almas K, Romanos GE, Al-Hezaimi K. Orofacial manifestations in patients with sickle cell disease. Am J Med Sci. 2013;345(3):234–7.CrossRefGoogle Scholar
  83. 83.
    Shroyer JV 3rd, Lew D, Abreo F, Unhold GP. Osteomyelitis of the mandible as a result of sickle cell disease. Report and literature review. Oral Surg Oral Med Oral Pathol. 1991;72(1):25–8.CrossRefGoogle Scholar
  84. 84.
    Friedlander AH, Genser L, Swerdloff M. Mental nerve neuropathy: a complication of sickle-cell crisis. Oral Surg Oral Med Oral Pathol. 1980;49(1):15–7.CrossRefGoogle Scholar
  85. 85.
    Gregory G, Olujohungbe A. Mandibular nerve neuropathy in sickle cell disease. Local factors. Oral Surg Oral Med Oral Pathol. 1994;77(1):66–9.CrossRefGoogle Scholar
  86. 86.
    Kelleher M, Bishop K, Briggs P. Oral complications associated with sickle cell anemia: a review and case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82(2):225–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Section of Oral Medicine and Orofacial Pain, Division of Oral Biology and MedicineUCLA School of DentistryLos AngelesUSA
  2. 2.Department of Oral Pathology Medicine, RadiologyIndiana University School of DentistryIndianapolisUSA
  3. 3.Department of DermatologyIndiana University School of MedicineIndianapolisUSA

Personalised recommendations