Oral manifestation in hematologic diseases and related problem

1. Oral manifestation in hematologic diseases and related problem Friday 7 January 2554 01.00-04.00 PM

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3. References Greenberg MS, Glick M, Ship JA, Diabetes mellitus and endocrine diseases. Burket�s Oral Medicine, 11th ed. Hamilton: BC Decker Inc. 2008. Scully C, Cawson RA. Medical problems in dentistry. 5th ed. Edinburgh: Elsevier. Churchill Livingstone; 2005.

4. IDENTIFICATION OF THE DENTALPATIENT WITH A BLEEDINGDISORDER review of the medical history a family history A patient�s past history of bleeding current medication with hemostatic effect Active medical conditions may predispose to bleeding problems a history of heavy alcohol intake is a risk factor for bleeding consequences

5. Drug for hematological diseases Ifosfamide ????????? non-Hodgkin�s lymphoma ???? relapse ???? refractory ?????????????????????????????????? Idarubicin hydrochloride ????????????? acute myelogenous leukemia Mitoxantrone hydrochloride ??????????????????????????????? acute myelogenous leukemia Thioguanine ????????? chronic myeloid leukemia, acute lymphocytic leukemia, acute non-lymphocytic leukemia Hydroxyurea (hydroxycarbamide) ?????????????????????? myeloproliferative disorder, chronic myeloid leukemia

6. anticoagulants Warfarin sodium Heparin sodium Enoxaparin sodium Nadroparin calcium ????????? venous stroke ??? intracranial embolism ??????????????????????????????????????????????????? heaparin sodium ????????

7. Important causes of drug-induced leucopenia Analgesics Antibacterial agents Phenothiazines Antithyroids Cytotoxics Carbamazepine

8. Some causes of folate and vitamin B12 deficeincy folate deficiency dietary alcoholism malabsorption states pregnancy drugs anticonvulsants cytotoxic vitamin B12 deficiency rarely dietary pernicious anemia other malabsorption states surgery to GI tract Pernicious anemia give positive Schilling testPernicious anemia give positive Schilling test

9. Symptoms of hemorrhagic diatheses frequent epistaxis excessive menstrual flow hematuria easy bruising, prolonged bleeding from superficial cuts spontaneous gingival or oral mucosal bleeding Diathesis=??????????????????????Diathesis=??????????????????????

10. Oral manifestations of blood dyscrasia Petechiae, ecchymoses Spontaneous gingival hemorrhage Prolong bleeding following oral surgery Gingival enlargement Mucosal ulcers Dyscrasia=???????????Dyscrasia=???????????

12. Extensive Ecchymosis A 71-year-old man was evaluated for severe anemia (hemoglobin level, 7.1 g per deciliter; mean corpuscular volume, 106 �m3), extensive ecchymosis of the lower limbs (Panel A), gingivitis, and hemorrhages of the oral cavity (Panel B, arrows). There was no history of recent trauma. What is the diagnosis?

13. Smooth, Shiny tongue A 77-year-old woman presented with an insidious onset of fatigue and a burning sensation of the tongue on swallowing food. Six years earlier, she had undergone a total gastrectomy for early gastric cancer, which was curative. On physical examination, she was pale and had a depapillated, smooth, shiny red tongue with some central fissuring, findings that were consistent with a beefy red tongue (Panel A

14. Laboratory testing cytopenia (white-cell count, 3400 per cubic millimeter; hemoglobin level, 6.4 g per deciliter; and platelet count, 154,000 per cubic millimeter) with macrocytosis (mean corpuscular volume, 132 fl [normal range, 80 to 100]; red-cell distribution width, 18.6%; and reticulocyte count, 2.8%) and hypersegmented neutrophils (Panel B, Wright's stain).

15. The serum vitamin B12 level was 75 pmol per liter (55 pg per milliliter) (normal range, 160 to 970 [118 to 716]), and the serum folate level was normal. The patient received a diagnosis of megaloblastic anemia due to vitamin B12 deficiency. She was treated with intramuscular vitamin B12 and had a complete recovery after approximately 5 months. A smooth, thickened, depapillated tongue may be associated with a variety of systemic disorders, including nutritional deficiency The patient received a diagnosis of megaloblastic anemia due to vitamin B12 deficiency. She was treated with intramuscular vitamin B12 and had a complete recovery after approximately 5 months. A smooth, thickened, depapillated tongue may be associated with a variety of systemic disorders, including nutritional deficiency

16. Graells J et al, 2009 Pernicious anemiaPernicious anemia

17. Gingival hyperthrophy 46-year-old woman who was not taking any medications presented with anemia and gingival hypertrophy that had been progressing over a period of 3 months. She was otherwise healthy.

18. Histopathological evaluation a gingival-biopsy specimen revealed a myeloblastoma.

19. CBC findings The white-cell count was 10,300 per cubic millimeter, the hematocrit was 26%, and the platelet count was 81,000 per cubic millimeter.

20. Acute myeloid leukemia (AML) was suspected, and AML subtype M4 (according to the French�American�British classification) was finally confirmed by a repeated bone marrow biopsy 3 months later. She did not have a t(8;21) abnormality. A previous bone marrow biopsy had shown no excess of myeloblasts. Myeloblastoma is an extramedullary collection of immature myeloid cells that can occur in any tissue and that is often confused with an active infection. Myeloblastomas may precede the development of AML and are typically associated with its monocytic variants. This patient was treated with induction chemotherapy, which resulted in a complete histologic remission in the bone marrow after one course and in the gingiva after two courses. Because of the high risk of disease recurrence, the patient underwent allogeneic stem-cell transplantation, and she remains in remission 3 years later. She did not have a t(8;21) abnormality. A previous bone marrow biopsy had shown no excess of myeloblasts. Myeloblastoma is an extramedullary collection of immature myeloid cells that can occur in any tissue and that is often confused with an active infection. Myeloblastomas may precede the development of AML and are typically associated with its monocytic variants. This patient was treated with induction chemotherapy, which resulted in a complete histologic remission in the bone marrow after one course and in the gingiva after two courses. Because of the high risk of disease recurrence, the patient underwent allogeneic stem-cell transplantation, and she remains in remission 3 years later.

21. Aplastic anemia Diffuse gingival hyperplasia with sulcular hemorrhage

22. hemophilia The risk of bleeding are greatest on the day of operation and again from 4-10 days postoperatively

23. Laboratory investigations

24. A high or a low white blood cell count could also be a sign of underlying cancer such as leukemia or lymphoma. A high platelet count may also be suggestive of an inflammation or blood malignancy, such as leukemia and lymphoma. A low platelet count (thrombocytopenia) may also be detected in the complete blood count.A low red blood cell or hemoglobin count typically indicates anemia (low blood).Hodgkin's lymphoma is stage III, IV  Having a high white blood cell count (15,000 or higher).  Having a low lymphocyte count (below 600 or less than 8% of the white blood cell count). 

25. Thalassemia, first described in 1925 by Cooley and Lee, is a group of diseases related to an inherited abnormality of globin production and not to a structural abnormality in the globin chain as is present with SCA.Thalassemia, first described in 1925 by Cooley and Lee, is a group of diseases related to an inherited abnormality of globin production and not to a structural abnormality in the globin chain as is present with SCA.

26. A hair-on-end skull A 24-year-old man with thalassemia major was seen for joint pain without swelling in both ankles and hands. He had received a total of 37 transfusions. He had a fetal hemoglobin value of 94 percent and an A2 hemoglobin value of 1 percent; his father had a high percentage of A2 hemoglobin, and his mother a high percentage of fetal hemoglobin and a normal A2 hemoglobin value. A lateral film of the skull (Panel A) showed generalized osteopenia, widening of the diploetic space (arrows), and thinning of the outer table. The characteristic "hair-on-end" appearance of the outer table spares the inferior aspect of the occiput. A sagittal view of a T1-weighted magnetic resonance image of the skull (Panel B) shows expansion of the diploetic portion of the cranium (arrows) and the clivus and obliteration of the air space of the sphenoidal sinus. A radiograph of the tibia and fibula (Panel C) shows coarse osteopenia, cortical thinning, small cystic lesions, and a widened marrow cavity. All these features are compatible with the presence of massive hyperplasia of the bone marrow.

27. anaemia Haemolytic anaemias Sickle cell disease thalassemias Aplastic aneamia and leucopenia Agranulocytosis Leucopenia Drug-induced leucopenia cyclic neutropenia Dyshaemopoietic anaemias

28. Most common oral changes in Dyshaemopoietic anaemias Angular cheilitis Apthous stomatitis Glossitits, Depapillation of tongue Lowered resistance to infection Plummer Vinson syndrome (Paterson-Brown-Kelly syndrome) associated between iron deficiency, dysphagia, and postcricoid esophageal stricture with ensuring malignant change in the postcricoid area affect in woman, Nothern Europeans, particularly Scandinavians ????? oral candidosis, ????????????????? osteomyelitis ?? severe anemia????? oral candidosis, ????????????????? osteomyelitis ?? severe anemia

29. Oral manifestation of iron, folate and B12 deficiency anemia mouth ulcers atrophic glossitis Candidosis Angular cheilitis

30. Oral manifestation of other blood disorders Sickle cell anemia Osteomyelitis, particularly the mandible Pale or yellowish Pain which is indintinguishable from tooth ache

31. Oral manifestation of other blood disorders Agranulocytosis Leucopenia Drug-induced leucopenia cyclic neutropenia Ulceration at gingivae and pharyx No symptoms until it becomes so severe Stopping drug is the immediate management Oral ulceration and periodontal breakdown Agranulocytosis=severe neutropenia, fever, prostration (?????????????) Agranulocytosis=severe neutropenia, fever, prostration (?????????????)

32. Pernicious anemia The dorsal tongue shows erythema and atrophy Pernicious anemia causes fatigue, depression, nausea, heartburn, and weight loss. Other symptoms include low blood pressure, muscle weakness, shortness of breath, neuropathic pain and diarrhea. When the red blood cells are too large, they cannot carry a sufficient amount of oxygen through the body. Therefore, those who suffer from pernicious anemia are often tired and weak. Pernicious anemia causes fatigue, depression, nausea, heartburn, and weight loss. Other symptoms include low blood pressure, muscle weakness, shortness of breath, neuropathic pain and diarrhea. When the red blood cells are too large, they cannot carry a sufficient amount of oxygen through the body. Therefore, those who suffer from pernicious anemia are often tired and weak.

33. Etiology Vit B12 deficinecy (erythrocyte maturing factor or extrinsic factor) Clinical features generalized redness of tongue due to atrophy of the papillae clinical signs of anemia more severe case�..CNS&GI manifestation If this disease continues over time, it can cause heart, brain, and nerve damage. This disease can also cause stomach cancer. If this disease continues over time, it can cause heart, brain, and nerve damage. This disease can also cause stomach cancer.

34. Iron deficiency anemia Etiology iron deficiency due to��. Clinical features generalized redness of tongue due to atrophy of the papillae angular cheilitis brittle nails and hair and koilonychia (spoon-shaped nails) Plummer-Vinson syndrome mucosal atrophy, dysphagia, predisposition for oral cancer

35. Folic acid deficinecy Megaloblastic anemia Complication of poor diet, alcoholism, Crohn�s disease, or pregnancy Positive Schilling test Result from treatment with phenytoin Cause severe apthae

36. Leukemia Neoplastic proliferation of white blood cells acute leukemia acute lymphoblastic leukemia acute myeloblastic leukemia chronic leukemia chronic lymphocytic leukemia chronic myeloid leukemia Acute leukemia: release primitive blast cells into the peripheral blood Chronic leukemia: most of apparent cells is normal white blood cellsAcute leukemia: release primitive blast cells into the peripheral blood Chronic leukemia: most of apparent cells is normal white blood cells

37. Oral manifestation of hemophilias Gingival bleeding Mucosal purpura in von Willebrand disease

38. Early stage Hyperplastic gingivitis Spontaneous gingival hemorrhage Persistent acute ulcerative gingivitis Oral ulceration Late stage Severe hemorrage Hypertrophic gingivitis

39. Oral manifestation of leukemia Gingival swelling and hemorrhage Mucosal purpura Mucosal pallor Fungal and viral infections Oral ulceration Lymphadenopathy Cytotoxic therapy can provoke oral ulceration and mucositis Busalfan can produce brown pigmentation of the oral mucosa

40. Oral and perioral effects of acute leukemia Mucosal ulceration Herpetic infections and candidosis Bleeding; Purpura Anaemic, mucosal pallor Cervical lymphadenopathy Gingival swelling leukopenia, anemia, and hrombocytopenia Leukemic infiltration of the gums Purpura can appear as excessive gingival bleeding, purplish mucosal patchs, blood blisters, or prolonged bleeding after surgeryPurpura can appear as excessive gingival bleeding, purplish mucosal patchs, blood blisters, or prolonged bleeding after surgery

41. Additional tests panoramic X-ray of the jaw showed no evidence of periodontal resorption. Differential diagnosis necrotizing acute gingivitis opportunistic infection caused by AIDS or extramedullary leukemic infiltrate diffuse and hypercellular infiltrate of monocytoid cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm diffuse and hypercellular infiltrate of monocytoid cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm

42. the oral cavity may be the primary site of onset of leukemia, so physicians and dentists should be aware of these changes.

43. Immunohistochemistry reactions were positive for antibodies antimyeloperoxidase, antiterminal deoxynucleotidyl transferase, and antilysozyme.

44. Acute lymphocytic leukemia age of 2-5 years Oral complications Clinical course of the tumor itself or may be a side effect of antineoplastic therapy Treatment methotrexate

45. Acute monocytic leukemia

46. Generalized gingival enlargement Gingival swelling as a result of low-grade infection at the gingivaal margins but lack of effective white cellsGingival swelling as a result of low-grade infection at the gingivaal margins but lack of effective white cells

47. Infiltrates may be seen in bone, causing lucencies with pain and paresthesia

48. Typical oral, head and neck manifestations of acute myelogenous leukemia Spontaneous gingival bleeding or oozing Petechiae formation Oral soft tissue or gingival infection Pharyngitis lymphodenopathy Plt count < 20,000 spontanoeus gingival oozingPlt count < 20,000 spontanoeus gingival oozing

50. lymphoma Hodgkin�s lymphoma Non-Hodgkin�s lymphoma Oropharyngeal involvement is rare Persistent enlarged superficial neck lymph nodes not painful, discrete, firm and rubbery in texture, not tnder Lymphoma should always be considered in the differential disgnosis of neck swellings. Hodgkin�s lymphoma rarely involves the oral cavity and is excluded from this discussion.Lymphoma should always be considered in the differential disgnosis of neck swellings. Hodgkin�s lymphoma rarely involves the oral cavity and is excluded from this discussion.

51. Oral lymphomas may present before, concomitantly with, or after lymph node expression.

52. thrombocytopenia Early stage Petechial hemorrhage Blood-filled bullae form on the mucosa Important Differential diagnosis from mucosal telangiectasia If this level decreases to below 30,000 (called thrombocytopenia) then abnormal bleeding can occur.Counts below 5,000 are life threatening.If this level decreases to below 30,000 (called thrombocytopenia) then abnormal bleeding can occur.Counts below 5,000 are life threatening.

53. Schilling test The Schilling test is named for Robert F. Schilling, a doctor known for researching vitamin B12 and using urine to test for its absorption. Compose of four-stages medical examination

54. Schilling test In the first stage, the patient is given two doses of vitamin B12. The administrators then collect the patient�s urine and check its vitamin B12 levels. If the first stage is abnormal, then the patient will move on to Stage 2. In the second stage, the patient is given radioactive B12 with a protein from the stomach lining. The patient�s intestines should absorb the vitamin B12; if not, then the patient will proceed to the third stage. During the third stage, the administrators will give the patient antibiotics for two weeks. The patient will return, and the subsequent test will reveal whether the patient has abnormal bacterial activity, which can cause low vitamin B12 levels. In the fourth stage, the patient will be given pancreatic enzymes for three days. If this stage of the Schilling test returns a positive result, then the pancreas is the cause of the low vitamin B12.

55. Blanching test (compression test) Blanching of hemangioma following application of pressure under glass slide or transparent splatula