ORAL MANIFESTATIONS IN BLOOD DYSCRASIAS
Many systemic hematological diseases have cutaneous findings as well as oral mucosal findings that are unique and can be the presenting clinical sign of the underlying disease. Awareness of the oral manifestations of these disorders is of paramount importance. Oral manifestations of blood dyscrasias can be seen in agranulocytosis, pernicious anemia, leukemia, polycythemia vera, and thrombotic thrombocytopenic purpura (TTP).
Clinical Findings: Agranulocytosis has been shown to produce oral ulcerations and erosions. Many different causes of agranulocytosis may result in these clinical findings. Medication-induced agranulocytosis is the most frequent cause of a decreased absolute neutrophil count of less than 500/µL. Many medications can cause this reaction, including dapsone, methotrexate, and a host of chemotherapeutic agents. A rare autosomal recessively inherited disease called infantile genetic agranulocytosis or Kostmann disease has been described. These patients present in the first months of life with recurrent oral ulcerations, multiple bacterial infections, and severely depressed absolute neutrophil counts. Death is the norm by 1 year of age unless the disease is correctly diagnosed and treated. Successful therapy is achieved with granulocyte colony-stimulating factor (G-CSF) or, in more advanced cases, with bone marrow transplantation. Even with successful G-CSF treatment, patients still develop oral ulcerations and severe periodontal disease. This is caused by the lack of an antimicrobial peptide, which allows certain bacteria to proliferate unabated. The species most frequently found is Actinobacillus actinomycetes comitans.
Pernicious anemia is caused by a deficiency of vitamin B12. This deficiency is most commonly seen in individuals with an inability to absorb vitamin B12 or in strict vegetarians. Pernicious anemia can manifest with a macrocytic anemia and neurological complications. Hunter’s glossitis is a form of atrophic glossitis that affects the tongue, leading to atrophy of the tongue filiform and fungiform papillae. The tongue takes on a beefy red appearance with a smooth surface. Varying amounts of glossodynia and decreased ability to taste are also found.
Gingival infiltration with leukemic cells may be the presenting sign of an acute leukemia, and gingival bleeding is the most frequent oral manifestation of leukemia. Oral ulcerations are commonly associated with the gingival leukemic hypertrophy. The gums appear red and swollen, with varying degrees of gingivitis. The gums may grossly enlarge to cover the majority of the teeth. This form of leukemic infiltration is seen almost exclusively in acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5). It is estimated to occur in two thirds of patients with M5 disease and in 20% of those with M4 disease. Other forms of leukemia have been implicated in causing gingival enlargement to a much lesser degree.
Polycythemia vera (previously termed polycythemia rubra vera) is caused by excessive production of red blood cells, which results in abnormally high hemoglobin and hematocrit values. The majority of cases are complicated by thrombosis. Most of these patients have a mutation in the JAK2 gene, which encodes a Janus family tyrosine kinase protein. The ability to test for these mutations has made diagnosis much easier. Oral manifestations are limited to the tongue and gingival mucosa. The tongue may become slightly enlarged, smooth, and hyperemic. Bleeding from the gingival mucosa can also be seen. The disease is manifested by many other systemic signs and symptoms.
TTP is a rare, life-threatening disease that can develop rapidly. It is manifested by the formation of microthrombi throughout the small vasculature. This causes multisystem organ failure and rapid death if not promptly treated. Most cases have been found to be caused by a hereditary defect in the ADAMTS13 gene or by decreased platelet levels caused by medications or autoimmunity. ADAMTS13 is a gene that encodes a plasma metalloprotease, which is important in regulating von Willebrand factor function. Oral manifestations of the disease include widespread petechiae and ecchymosis of the tongue, gingival, labial, and buccal mucosa. Petechial hemorrhages of the gums may appear later in the course of the disease.