Management of the thalassemia-induced skeletal facial deformity: Case reports and review of the literature

DREW

AND

J Oral Maxillofac 55:1331-1339,1997

1331

SACHS

Surg

Management of the Thalassemia-Induced Skeletal Facial Deformity: Case Reports STEPHANIE

and Review

J. DREW, DMD,*

The first reported cases of thalassemia are found in the literature in 1925.’ Cooley and Lee’ described patients with severe anemia occurring early in life associated with bone changes and splenomegaly. The genetic causes of this disease were not recognized until 20 years later. Researchers found that thalassemia was attributable to a partial autosomal dominant gene for which the homozygous state was termed thalassemia major and the heterozygous state, thalassemia minor. Thalassemia intermedia was a term used to describe disorders less severe than major forms but more severe than minor forms. Approximately 10% of patients with the homozygous trait have the clinical syndrome of intermediate severity.’ Thalassemia syndromes are part of a larger group of inherited hematologic disorders known as hemoglobinopathies. They are classified as either a problem with the structure of the globin chain, such as in sickle cell anemia, or a defect in the rate of synthesis of one or more globin chains, as in thalassemia. The latter leads to production of one type of globin chain more than the other, ineffective red blood cell production, hemolysis, and variable degrees of anemia. The thalassemias have been found in almost every ethnic group and geographic location; however, they are most common in the Mediterranean basin and equatorial regions of Asia and Africa. It is believed that the thalassemic patients living in these regions are protected against malaria. The malarial antigens are more efficiently exposed when a thalassemic cell is involved, making the parasites prone to ingestion by macrophages.zS3 As a group, the thalassemias are the most common single gene disorder known.’ Each of.the thalassemia Received from the New York Center for Orthognathic and Ma$llofacial Surgery, Lake Success, NY. *’ Private Practice, Lake Success, NY. t Private Practice, Lake Success, NY. Address correspondence and reprint requests to Dr Drew: The New York Center for Orthognathic and Maxillofacial Surgery, 2001 Marcus Ave. Suite N 10, Lake Success, NY 11042. 0 1997 American

Association

0278-2391/97/5511-0026$3.00/O

of Oral and Maxillofacial

Surgeons

of the Literature

AND STEPHEN

A. SACHS,

DDS-f

syndromes occurs as a result of a specific genetic mutation. These mutations are responsible for the decreased production of a specific globin. Often genes 11 and 16 may have either deletions, rearrangement of the loci, or point mutations leading to impaired transcription, processing, or translation of globin mRNA, and therefore, globin production.2,3 Many subdivisions and types of each category exist based on partial or total deficiency of each chain or the presence of other forms of globin, including HbF. Thus far, over 30 ol-haplotypes that produce cr-thalassemia have been identified.3 They are caused by deletion of either one to four of the a-gene loci; however, 1.5% to 20% are the result of a mutation. Many genetic mutations can cause abnormal a-hemoglobin synthesis. However, there are only four known phenotypic expressions of cw-thalassemia. The cr-Thal-2-trait represents one of the four alpha globin loci failing to function and is a silent carrier. The cu-Thal-l-trait stands for two of the four alpha globin loci not functioning. Both of these defects can produce a mild hemolytic anemia. Hemoglobin H disease is the term used to define the condition when three of the four alpha globin chains are not functioning, leading to accumulation of the p-4 tetrameres and severe hemolytic anemia. Hydrops fetalis, or Bart’s hemoglobin, is consistent with all four alpha chains not functioning, leading to accumulation of y-4 tetrameres and death in utero. Three phenotypic classes of ,kI-thalassemia have been defined: major, intermedia, and minor. Multiple complex genetic mutations are responsible for these three categories. More than 100 different varieties of mutations exist and are associated with the ,&thalassemia phenotypes.2.3 The clinical impact of these genetic mutations is only realized when the a’- or ,0-globin chains that are needed for HbA synthesis are affected. Formation of adult type of hemoglobin occurs within the first 6 months of life. The clinical picture of a patient with P-chain thalassemia does not become apparent until 6 months of age. However, a-chain abnormalities affect the fetus and are noted at birth. The impairment of embryonic chains is lethal and not clinically evident.2Z3

1332 A decline in globin chain production leads to a decrease in production of functioning hemoglobin tetrameres expressed as the clinical picture of hypochromia and microcytosis. The unbalanced synthesis of the a! or /? subunits leads to unpaired chains of (Y, @, or y globin that are insoluble and incapable of releasing oxygen normally. These unpaired chains accumulate, affect almost every organ system, and are the major sources of morbidity and mortality associated with untreated thalassemia. Systemic manifestations of thalassemia are easily understood once the pathophysiologic mechanism of this disease is defined. Untreated thalassemia patients have accumulation of unpaired globin chains that are not soluble in blood. These chains precipitate within red blood cell precursors and are recognized as inclusion bodies. Oxidative membrane damage occurs as a result of accumulation of these inclusion bodies, leading to death of the precursor cells within the bone marrow. A few inclusion-body-containing precursor cells survive to enter the circulation. These are quickly sequestered within the spleen. Hypersplenism, increased hemoglobin catabolism, and increased levels of bilirubin are the result of this event. Elevated levels of bilirubin subsequently lead to jaundice, gallstones, and potentially leg ulcers. Profound microcytic hypochromic anemia also exists. Hypochromia occurs because the amount of hemoglobin per cell is low. There is a massive decrease in mature red blood cell production. This is caused by hemolysis within the marrow and sequestration of these abnormal cells by the spleen. Tissue hypoxia secondary to the anemic state stimulates the kidneys to produce and release erythropoietin. Bone marrow expansion begins in response to the erythropoietin. However, erythropoiesis is ineffective in these patients, and a vicious cycle ensues causing the bone marrow to expand further. Disfiguring extramedullary hematopoiesis occurs primarily within the skull, maxilla, vertebrate, abdomen, pelvis, and chest. The gastrointestinal system responds to the demands of increased erythropoiesis by elevating the level of iron absorbed. There is a specific defect in iron transportation, and this causes iron levels to rise and accumulate. It is primarily deposited within the parenchyma of the liver and heart, leading to hemochromatosis. Cardiomyopathy, cirrhosis, and endocrine dysfunction are the end result of these processes. Skeletal changes resulting from this disease are striking. A multitude of functional and sometimes psychological consequences result from disfiguring marrow expansion. Growth of the marrow cavities causes skeletal deformities, thinning of the cortical portions of the bones (osteoporosis), and pathologic fractures.4 The first bones to be affected by this process are the metatarsals, metacarpals, and phalanges, which take

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on a rectangular shape.2.3,5,6 Premature fusion of the epiphysis of the long bones leads to shortening of the proximal humerus. Thus, many thalassemia patients are short. Cortical thinning may cause compression fractures of the vertebrate and subsequent neurologic defecits. The ribs are also affected and are abnormal in shape. On rare occasions, expansion of the rib into the spinal canal can result in cord compression.’ The facial appearance of the patient with thalassemia is characterized by a “rodentlike” resemblance (Fig 1). The frontal and parietal bones are prominent, the bridge of the nose is depressed, the zygomas appear to be protruding, and the eyes have a mongoloid cant. The maxilla is hypertrophied and procumbent. The dentition is secondarily displaced by the marrow expansion, and this leads to malocclusion and speech, swallowing, and eating difficulties. Radiographically, the skull appears thickened, with a hair-on-end pattern of the trabeculae within the diploe (Fig 2). The sinuses may become obliterated, and subsequent maxillary sinusitis can result.‘jZ7 Cephalometric evaluation of 60 thalassemic patients was done by Pusaksrikit et a1.8 Their study showed that the patient with thalassemia will usually have a Class II mal-

FIGURE 1. Typical treated thalassemia.

facial

characteristics

of a patient

with

un-

DREW

FIGURE pearance

AND

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SACHS

2. Cephalometric characteristics of the cranial bone (m-raw).

showing

hair-on-end

ap-

occlusion, especially males. This finding was attributed to the fact that the mandible grows slower in males and is being blocked by the excessive maxillary growth. The facial skeletal profile was found to correlate with the severity of the anemia. In a follow-up study of 88 patients with thalassemia, it was noted that the patients had a tendency toward a Class I malocclusion with anterior maxillary dentoalveolar protrusion.’ Some cases of Class II division I, with lip incompetence, also were noted. Posterior cross-bite and severe expansion of the alveolus in all dimensions were also described. In no patient studied did they find a Class III malocclusion. There have been several studies and case reports on the effect of marrow proliferation on the craniofacial skeleton. Logothetis et aI” studied 138 patients with thalassemia major. Their study determined that the patient’s age and duration of clinical symptoms, degree of anemia, timing of splenectomy, and the age at onset of transfusion therapy were important in determining the development of craniofacial deformities. The older the patient, the more likely he or she is to have craniofacial deformities. Decreasing hemoglobin levels were observed as the degree of craniofacial deformity became more pronounced. If the hemoglobin can be maintained above 10 g/dL, the skeletal changes may be controlled. When hypertransfusion therapy was instituted before age 4, it seemed to prevent the disfiguring skeletal changes. Splenectomy before age 4 also seemed to help in this regard. Karagiorga-Lagana et al5 studied 13 children with thalassemia intermedia undergoing transfusion therapy. The mean pretransfusion hematocrit was maintained at approximately 10 g/dL. They found that the skeletal manifestations of thalassemia reverted to normal with this transfusion regimen. If these patients had moderate craniofacial deformities, they found that the transfusions helped to decrease these deformities.

In another study, the dentition and skull were evaluated radiographically in thalassemic patients using periapical, occlusal, and lateral skull films.4 The most significant findings were blurring of the trabeculae, large bone marrow spaces, thin lamina dura and crypts, osteoporosis, prominent anterior maxilla, small paranasal sinuses, thin cortex at the posterior and inferior margin of the ramus, thickening of the calvarium primarily in the anterior region, fine granular pattern of bone, and condensed inner plate of the calvarium. A recent study from Thailand also confirmed these cephalometric changes in 60 thalassemic patients.7 Microradiographic studies of the dentition in thalassemic patients were done by Soni et al.” The dentin formed resembled osteodentin, with inclusion bodies in the lumens of the dentinal tubules. The bone was found to have an immature pattern, with irregular resorption cavities and few Haversian systems. Both of these findings are similar to those seen in dentinogenesis and osteogenesis imperfecta. Cementum was also found to be less mineralized, which was believed to be a compensatory change attributable to the bone and dentin changes. Diagnosis of any of the thalassemia syndromes begins with a careful family history, including racial characteristics. The age at onset of symptoms and development of the child are noted. Clinical examination may show anemic pallor, jaundice, splenomegaly, pigmentation, and skeletal manifestations. There has been a case reported of thalassemia intermedia diagnosed because of observed typical facial characteristics.12 Laboratory analysis, including a complete blood cell count, will show a microcytic hypochromic anemia, red blood cell inclusions in the marrow and blood, and precipitation of hemoglobin H. If these findings are detected, hemoglobin electrophoresis should be performed. This study will determine the presence of abnormal hemoglobin and specifically show hemoglobin H and Bart’s hemoglobin. Once detected, hemoglobin A2 and hemoglobin F estimations are done to confirm whether the patient has ,&thalassemia or another variant. The standard therapy for a patient with thalassemia is hypertransfusion of blood to maintain the level of hemoglobin between 10 and 14 g/dL. This therapy has helped these patients grow and develop normally without skeletal manifestations. Splenectomy is done in patients who develop hypersplenism. The transfusions are given every 6 to 8 weeks. Transfusions should begin when it is clear that the hemoglobin level is too low to be compatible with normal development.2Z3 Unfortunately, hypertransfusion therapy is not without complications,2X3 the most serious of which is the development of iron overload leading to siderosis, especially of the myocardium, and secondary heart failure. Endocrine disturbances such as diabetes mellitus

1334 and adrenal insufficiency also may develop. All patients on this therapy must be placed on iron chelation medications. The drug of choice at this time is deferoxamine, which is administered by a 12-hour overnight infusion in the subcutaneous tissues of the anterior abdominal wall. The quality and length of life have been prolonged subsequent to the initiation of chelation therapy in this patient population. Prognosis for the homozygous thalassemic patient at this time is fair despite transfusion and chelation therapy.253 These patients can typically survive into their third and maybe even fourth decade of life but eventually succumb to the effects of iron overload or, if untreated, die at a younger age of the effects of severe anemia. Because these patients now survive into adulthood, proper genetic counseling should be part of their treatment. The thalassemia intermedia patient has a better prognosis because transfusion therapy is not used in this population. These patients also develop iron overload and severe crippling bone disease, but not until the third or fourth decade of life. The role of gene manipulation therapy and replacement, and bone marrow transplantation, are exciting areas currently under investigation in the treatment of thalassemia. Bone marrow transplantation has the potential to cure the patient with this disease.2.3 Before 1969, management of the dentofacial deformities of thalassemic patients was primarily orthodontic. Adelman13 described orthodontic management in a 7-year-old patient with thalassemia major. This was accomplished with molar anchorage and extraoral headgear to retract the anterior maxillary arch and the dentition. Although he proved that orthodontic movement was possible in the thalassemic patient, the severe vertical and lateral maxillary bone deformity could not be corrected. Several case reports on the orthognathic surgical management of the patient with thalassemia can be found in the literature.14.15 In 1969, Jurkiewicz et all5 reported on a 6-year-old boy and his younger sister with ,&thalassemia trait. Both of these patients did not have transfusion therapy and showed severe maxillary hyperplasia with distortion of the occlusion. Their hemoglobin levels were reported to be between 7 and 10 g/dL. Their facial deformities resulted in speech, eating, and emotional difficulties. The preoperative management of the boy at age 14 consisted of packed cell transfusions at the time of surgery. They did not state the preoperative level of hemoglobin posttransfusion. The surgical technique consisted of removing approximately 1 cm of excess bone under the floor of the nose with rongeurs and chisels.15 An anterior segmental osteotomy was then created between the canine and premolar, allowing elevation and rotation of the segment into a more functional position. This anterior maxillary segment was stabilized by wiring it to the

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anterior nasal spine and with maxillomandibular fixation. The patient required two transfusions during surgery. Fixation was released 14 days postoperatively. Postoperatively, there was a step along the palate that interfered with eating. A second surgical recontouring was preformed 2 months later, this time by a palatal approach. The occlusion was reported to be stable with a 2-year follow-up. The younger sister was operated on at age 11 years. Her deformity was reported to be more severe than the brother’s secondary to excessive growth of the maxilla in the vertical and transverse dimensions. The same surgical technique was used involving removal of the first premolars, an anterior segmental osteotomy with vertical reduction, and maxillomandibular fixation in two stages, the first to elevate the segment and the second to recontour the excess bone. A surgical modification in treating this deformity was described in 1987 by Wee1 et al.‘” Their patient was a 14-year-old black boy with thalassemia major. His hemoglobin level was 5.8 g/dL preoperatively. They described preoperative ‘ ‘hematologic preparation,” but no details were provided. A two-step technique was performed, the first involving recontouring of the lateral maxilla and then a Le Fort I osteotomy that allowed vertical reduction and posterior repositioning of the maxilla. No preoperative orthodontics were performed. Fixation was maintained with skeletal suspension wires. Vacuum drains were placed into the wounds. The authors reported a significant amount of bleeding throughout the procedure, which required 2 units of blood. Postoperative complications included a hematoma that required evacuation, extraction of two teeth, and tuberosity reduction to achieve a more functional occlusion. Maxillomandibular fixation was maintained for 6 weeks. There was no long-term follow-up on this patient. Report

of Cases

Our group has had the opportunity to surgically manage three patients with severe thalassemic gnathopathy. The follow-up period has been from 2 (1994) to 19 years (1976). The first patient treated was initially seen at the age of 10 years. She was of Mediterranean descent and was diagnosed with P-thalassemia intermedia as an infant. Her family refused hypertransfusion therapy. At the age of 5 years, an elective splenectomy was performed. Because no transfusion regimen was used, the patient developed severe hypertrophy of the maxillary and frontal bones secondary to marrow hyperplasia (Figs l-3). The maxilla was procumbent and vertically excessive. A blue vascular pattern of the gingiva and flaring of the maxillary incisors were noted. Intraoral examination showed a skeletal Class II dental relationship with 100% overbite. This produced functional, esthetic, and severe secondary psychosocial problems. At initial presentation, this patient also had a II/VI systolic ejection murmur and hepatomegaly. Her laboratory examination showed a hemoglobin of 7.8 g/dL. The blood smear showed crenated

DREW AND SACHS

FIGU ;RE 3. Panoramic findings of the thalassemic deformity. Note the thin cortex and loose medullary spaces.

red blood cells, tear drops, Howell Jolly bodies, and bun cells. No major reconstructive surgery was attempted in 1976. Instead, the maxilla was recontoured to decrease the massive lateral expansion. Operative findings in this child were remarkable in that there was a total lack of cortex. The periosteum was elevated, and only honeycombed medullary bone was observed. Recontouring helped initially; however, maxillary hypertrophy continued especially in the vertical dimension. Three years later, in 1979, the patient’s dentofacial deformity was progressively getting worse. Therefore, an orthognathic surgical treatment plan was formulated. Cephalometric evaluation showed a diffuse opacity of the maxillary sinuses, prominent diploic spaces in the occipital region of the skull, relative retrognathia, maxillary asymmetry, and skeletal Class II relationship (Fig 4). Vertical excess of the maxilla exceeded 1.5 cm. Maxillary and mandibular facebow mounted models were used to predict the new functional position of the maxilla and fabricate an occlusal splint. The patient had preoperative orthodontic alignment of her dentition. The patient was started on exchange transfusion therapy in the preoperative period. The goal was to maintain her hemoglobin levels between 10 and 12 g/dL. The patient was also placed on iron chelation therapy. Six months after this

FIGURE 4. Preoperative lateral ecphalometric radiograph.

therapy was initiated, she showed considerable skeletal growth and developed secondary sexual characteristics. New radiographs showed evidence of a cortex forming on the maxilla. Because of the severity of her maxillary deformity and the effect it had on her psychological well-being, surgical treatment of her maxilla was done at the age of 13 years. A Le Fort I osteotomy was performed, with 15 mm of the maxilla resected above the apices of the permanent teeth to allow for superior and posterior repositioning (Fig 5). During the dissection, it was noted that the cortex of the maxilla had been reestablished. Stabilization was achieved with skeletal suspension and maxillomandibular fixation. No bleeding problems were encountered, and the patient tolerated the surgery well. Immediate improvement in function, esthetics, and emotional well-being followed. This patient has been compliant with medical management of her thalassemia, and follow-up over 19 years has shown a stable long-term result (Figs 6, 7). The second patient presented in 1991. He was a 12-yearold boy of Mediterranean descent diagnosed with /?-thalassemia major. He had maxillary hyperplasia, mandibular retrognathia, vertical and sagittal maxillary excess, gross lip incompetence, and speech difficulties (Fig 8A). He was be-

FIGURE 5. Intraoperative view of the section of the maxilla being removed. Note cortex formation secondary to hypertransfusion therapy.

1336

MANAGEMENT

FIGURE 6. Postoperative view of the patient at 10 years old.

ing treated with monthly transfusions of 2 units of packed red blood cells and chelation 5 nights/week with 2 g of Desferal (Ciba-Gelgy Corp, Pharmaceuticals Division, Summit, NJ) subcutaneously. This maintained his hemoglobin level at least at 10 g/dL. He had not had a splenectomy. His viral serology, as well as his liver function and serum iron, were being monitored. Surgical treatment was delayed until age 14 years. Preoperative evaluation included a chest radiograph, electrocardiogram, hepatitis screen, prothrombin, and partial thromboplastin times, fibrinogen level, as well as a complete blood cell count, urinalysis, and blood chemistry. The patient was continued on his hypertransfusion therapy to maintain a preoperative hemoglobin level of at least 10 g/dL. No special antibiotic coverage was needed because the patient had not had a splenectomy. Postoperatively, the hypertransfusion protocol was maintained indefinitely to keep the hemoglobin above 10 g/dL and prevent extramedullary hematopoiesis and possible relapse of the dentofacial deformity. This hypertransfusion and chelation therapy will be maintained the rest of his life. The patient had preoperative orthodontic alignment of his dentition. A surgical treatment plan was developed that included a Le Fort I maxillary osteotomy to impact the maxilla

, FIGURE 7. Patient A, 13 and B, 19 years postsurgery showing good esthetic result,

OF THE THALASSEMIA-INDUCED

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9 mm and retrude it 6 mm. Rigid fixation was used to stabilize the maxilla. Bilateral sagittal split ramus osteotomies with 7 mm advancement was also performed. A genioplasty was done to position the chin 6 mm anteriorly. During this surgery, the patient had approximately 2,000 mL of blood loss. This was attributed to the persistant oozing from the hyperplastic marrow. The blood loss was treated with appropriate transfusions of packed red blood cells, fresh frozen plasma, and platelets. Overall he tolerated the procedure well. Three-year follow-up showed a stable result (Fig 8B, 9). The third patient was a 43-year-old woman diagnosed with /?-thalassemia minor seen in 1994. She gave a medical history of having significant anemia when pregnant and being given blood transfusions. She had maintained a hemoglobin of 10 g/dL throughout her life. Her orthodontist referred her for consultation regarding a skeletal Class II malocclusion with maxillary vertical excess and mandibular deficiency. The patient had lip incompetence, a long middle third of the face, excessive maxillary tooth exposure, and canting of the maxilla. She complained of intermittent pain in the right and left masseter and periodic jaw locking. No clinical evidence of internal derangement of the temporomandibular joint was found. Her surgical treatment plan included a maxillary Le Fort I osteotomy to impact the maxilla 4 mm, and extraction of the mandibular first premolars followed by an anterior mandibular segmental osteotomy to set back the anterior mandibular alveolar segment 5 mm. A hydroxylapatite chin implant was also to be placed. Preoperative evaluation included a chest radiograph, electrocardiogram, serum chemistry, urinalysis, and a complete blood cell count. Her hemoglobin was 10.4 g/dL, and hematocrit was 3 1.2%. Therefore, no transfusion therapy was recommended. Estimated blood loss during surgery was 700 mL. The immediate postoperative hemoglobin was 6.9 g! dL, and hematocrit was 21.5. Hematology consultation was obtained, and it was recommended that the patient receive folic acid and erythropoietin injections three times/week for 2 weeks. While in the hospital, she received 3,000 units of Epogen subcutaneously at 2 and 5 days postoperatively. She was discharged on the fifth postoperative day without incident. Her postoperative hemoglobin was 7.1 g/dL, and hematocrit was 22.2%. A 2-year follow-up showed a stable and functional occlusal result (Fig 10). Discussion Based on these surgical experiences, a protocol for the surgical management of the thalassemic dentofacial deformity can be established. A thorough hematology evaluation must be performed to establish a working baseline. Most of the patients that present for treatment today will have been diagnosed with thalassemia as a child. If they are from the United States, chances are that they will be on a hypertransfusion protocol with chelation therapy. Most of these patients do not form significant skeletal deformities.‘6 There are a group

< FIGURE tographs.

8.

A, Preoperative

and B, postoperative

lateral facial pho-

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of patients, however, that do not ordinarily receive transfusion therapy, the thalassemia intermedia patients. These patients are chronically anemic and many develop compensatory bone marrow hyperplasia. Preoperative preparation should be coordinated with the hematologist. The anesthesiologist also should be consulted preoperatively. A thorough history and physical examination, including evaluation of cardiac and liver function, should be done. Genetic counseling should be recommended. Chest radiographs and electrocardiograms are necessary for a proper cardiac evaluation. The multiple systemic manifestations of thalassemia and its treatment require analysis of the blood cell count, serum chemistries, coagulation profile, iron profile, fibrinogen level, hepatitis screen, and urine analysis. If the patient had undergone previous splenectomy, preoperative prophylactic antibiotic therapy may be needed. Ideally, the hematologists should always try to maintain the patient’s hemoglobin level above 10 g/dL with transfusion therapy. This will prevent the extramedullary hematopoiesis and increase the oxygen-carrying capacity of the blood. In our first patient, we observed that even if not on transfusion therapy previously, once started it begins to stop the marrow hyperplasia and allows the bone to reestablish a cortical plate.

FIGURE 10. ative (dotted)

FIGURE 9. Superimposition tive (dotted) cephalometric

of preoperative tracings.

(solid)

and postopera-

Superimposition of preoperative cephalometric tracings.

(solid)

and postoper-

The thalassemic dentofacial deformity is primarily a maxillary problem; hence, the Le Fort osteotomy and bone recontouring will be the procedures used most frequently to treat these patients. It is well known that significant hemorrhage can result from the Le Fort osteotomy. The anesthesiologist should therefore use hypotensive as well as hemodilution techniques to help control blood loss. The chronic anemic state of the thalassemic patient generally prohibits these patients from donating their own blood. Erythropoietin therapy and folic acid supplementation were used in our thalassemia minor patient postoperatively. The hematologists believed that her anemic state could be tolerated without the use of blood transfusions because she was asymptomatic. They decided to let the patient reestablish her baseline hemoglobin by stimulating hematopoiesis with the Epogen. Perhaps use of erythropoietin therapy preoperatively should be considered in the future to increase the hemoglobin in all thalassemia patients. The severe dentofacial deformities resulting from the thalassemia syndromes have been declining sec-

OGATA,

OKINAKA,

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ondary to treatment with hypertransfusion and chelation therapy. However, there is still a population of these patients that may not be treated and may present to the oral and maxillofacial surgeon with dentofacial deformities. Thorough knowledge of the multiple systemic manifestations, therapy, and prognosis of this syndrome is necessary to formulate a safe, comprehensive surgical plan for these patients.

graphs used in dentistry. Oral Surg Oral Med Oral Path01 25564, 1968 Karagiorga-Lagana M, Vosakaki E: Sbyrakis S, et al: Blood transfusions for the prevention of bone deformities in thalassemia intermedia. Birth Defects: Original Article Series 23(5A):435, 1988 Razmus TF, Fotos PG: Oral medicine in clinical dentistry: Hematologic disorders. Compendium 8214, 1987 Wisetsin S: Cephalography in thalassemic patients. J Dent Assoc Thailand 40:260, 1990 (Abstract in English only) Pusaksrikit S, Hathirat P, Isarangkura P: Cephalometric radiography in thalassemic patients. Birth Defects: Original Article Series 23(5A):421, 1988 Pusaksrikit S, Isarangkura P, Hathirat P: Occlusion of the teeth in thalassemic patients. Birth Defects: Original Article Series 23(5A):429, 1988 Logothetis J, Economidou J, Constanttoulakis M, et al: Cephalofacial deformities in thalassemia major (Cooley’s anemia): A correlative study among 138 cases. Am J Dis Child 121:300, 1971 Soni NN, Barbee FE, Ferguson AD: Microradiographic study of odontologic tissues in Cooley’s anemia. J Dent Res 45:281, 1966 Ficarra G, Hansen LS, Beckstead JH, et al: Thalassemia diagnosed through facial distortion. Br J Oral Maxillofac Surg 16:227, 1987 Adelman AB: Cooley’s anemia from an orthodontic viewpoint. NY State Dent J 31:405, 1965 Wee1 F, Jackson IT, Crookendale WA, et al: A case of thalassemia major with gross dental and jaw deformities. Br J Oral Maxillofac Surg 25:348, 1987 Jurkiewicz MJ, Pearson HA, Furlow LT: Reconstruction of the maxilla in thalassemia. Ann NY Acad Sci 165:437, 1969 Scutellari PN, Orziocolo C, Andraghetti D, et al: Anomalies of the masticatory apparatus in beta-thalassemia: The present status after transfusion and iron-chelating therapy. Radio1 Med Torin 87:389, 1994 (Abstract in English only)

5.

6. 7. 8.

9.

Acknowledgment The authors thank the following doctors who had helped in the management of these patients: Michael Schwartz, Michael Kleinman: Kristin Lyons, Janet Stoess, Richard Pasternack, and Kenneth Zipkin.

10.

11.

References

12.

1. Cooley TB, Lee P: A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr Sot 37:29, 1925 2. Schwartz E, Benz EJ, Forget BG: Thalassemia syndromes, irz Hoffman R, Benz EJ, Shattil SJ, et al (eds): Hematology Basic Principles and Practice. New York, NY, Churchill Livingstone, 1995 3. Weatherall DJ: The thalassemias, in Beutler E, Lichtman MA, Coller BS, et al (eds): Williams Hematology (ed 5). New York, NY, McGraw-Hill, 1995 4. Poyton HG, Davey KW: Thalassemia: Changes visible in radio-

13. 14.

15. 16.

J Oral Maxillofac Surg 55:1339-1341, 1997

An trolith Associated With Aspergillosis of the Maxillary Sinus: Report of a Case YOICHI

OGATA, MD,* YOSHIHIKO OKINAKA, AND MASAHIRO TAKAHASHI, MD+-

Since aspergillosis of the paranasal sinuses was first recognized in the late 19th century, there have been an increased number of cases reported.‘-” The radiologic appearance of aspergillosis of the paranasal sinuses From the Department of Otolaryngology, Yamaguchi University School of Medicine, Yamaguchi. Japan. :/: Senior instructor. t Associate Professor. $ Professor and Chairman. Address correspondence and reprint requests to Dr Ogata: Department of Otolaryngology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755, Japan.

is generally characterized by metallic-dense shadows resembling foreign bodies.’ An x-ray fluorescence analysis has shown that this phenomenon is due to local deposition of calcium phosphate in the center of the fungal masses.’ We report a case of an antrolith accompanied by aspergillosis of the maxillary sinus and discuss its radiologic characteristics. Report A %-year-old

0 1997 American 027%2391/97/551

Association i-0027$3.00/0

of Oral and Maxillofacial

Surgeons

MD,t

man

suffered

of Case from

recurrent

purulent

dis-

charge from a gingival fistula in the left superior maxilla after

he underwent

extraction

of a molar

tooth

a year

before.