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Mucormycosis of the mandible after dental extractions in a patient with acute myelogenous leukemia
Mucormycosis of the mandible after dental extractions in a patient with acute myelogenous leukemia Paul Lee Salisbury, III, DDS, a Ron Caloss, Jr, DDS, b Julia M. Cruz, MD, c Bayard L. Powell, MD, c Roger Cole, MD, d and Robert I. Kohut, MD, e Winston-Salem, N. C. BOWMAN GRAY SCHOOL OF MEDICINE AND NORTH CAROLINA BAPTIST HOSPITAL
Mucormycosis is a fulminant fungal infection that occurs most often in diabetic and immunocompromised patients including those with hematologic malignancies. In this case, a patient with acute myelogenous leukemia developed mucormycosis in a recent mandibular extraction site. The successful management of this patient demonsrated that early diagnosis, aggressive surgical and medical treatment, and resolution of the underlying disease could improve the prognosis for survival. A case is made for the role of smoking as an initiator of mucormycosis, and treatment considerations for controlling periodontal and pulpal disease before chemotherapy are discussed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:340-4)
Infections produced by fungi of the class Zygomycetes, order Mucorales, have historically been known as mucormycosis (Table I). Ubiquitous in the environment and commonly found in bread molds and decaying vegetation, the Mucorales grow rapidly and constantly release spores into the atmosphere. Inhalation of spores rarely produces mucormycosis in healthy people. It is most often in the face of severe immunocompromising diseases, diabetes mellitus, tissue trauma, or burns that these saprophytic organisms become pathogenic. Even with one of these predisposing conditions, mucormycosis is quite uncommon. 1, 2 In the compromised host, mucormycosis results from diminished humoral and cellular defense mechanisms being overwhelmed by Mucorales organisms that proliferate rapidly and invade unchecked into deeper tissues. These fungi usually enter the body via the nasal mucosa, lungs, or skin. ! As in cutaneous mucormycosis, injured tissue in the oral cavity could be a suitable port of entry. For reasons that are unclear, the fungal hyphae preferentially invade the walls of blood vessels, producing thrombi and inaAssociate Professor, Department of Dentistry, Bowman Gray School of Medicine. bFormer Resident, Department of Dentistry, North Carolina Baptist Hospital. CAssociate Professor, Department of Internal Medicine -Hematology/Oncology, Bowman Gray School of Medicine. dFormer Resident, Division of Surgical Sciences-Otolaryngology, North Carolina Baptist Hospital. eprofessor, Division of Surgical Sciences-Otolaryngology, Bowm a n Gray School of Medicine. Received for publication Mar. 20, 1996; returned for revision May 1, 1996; accepted for publication Sept. 25, 1996. Copyright © 1997 by Mosby Year Book, Inc. 1079-2104/97/$5.00 + 0 7/13/78425
340
Table I. Classification of the agents of
mucormycosis 1. Zygomycotina--Phylum A. Zygomycetes--Class a. Mucorales--Order *1. Mucoraceae--Family i. Absidia--Genns ii. Mucor iii. Rhizomucor iv. Rhizopus *2. Cunningharnellacaeae 3-7. Other rare Mucorales organisms *Most common causes of mucormycosis. (Adapted with permission from Sugar AM, Agents of mucormycosis and related species, In: Principles and practice of infectious diseases, Chap. 239, New York: Churchill Livingstone, 1995.)
farctions. Progressive tissue ischemia and necrosis are the inevitable result. In leukemic patients with neutropenia, the disease occurs most commonly in pulmonary and rhinocerebral sites and can become widely disseminated to other organ systems 2. Neutrophils are known to play a crucial role in the protective host response to fungal colonization. In patients with leukemia, the bone marrow produces dysfunctional neutrophils, and remission-induction chemotherapy causes several weeks of myelosuppression and profound neutropenia. The combination of these two events puts the patient with leukemia at significant risk for several different opportunistic fungal infections. Prolonged treatment with broadspectrum antibacterial antibiotics increases the risk even more. Clinical evidence would indicate that restoration of adequate numbers of functional neutrophils must occur before mucormycosis can be resolved.l' 3 Mucormycosis has long been known for having a
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Fig. 1. Preoperative radiograph illustrates pathosis associated with second molar teeth.
Fig. 2. Lesion at time of biopsy, mandibular left second molar extraction site.
v e r y p o o r p r o g n o s i s , however, with a g g r e s s i v e m e d ical and surgical m a n a g e m e n t , survival rates are n o w thought to e x c e e d 80%. 2 E a r l y detection has been correlated with less tissue destruction and a better overall outcome. The antifungal agent a m p h o t e r i c i n B and surgical d e b r i d e m e n t o f necrotic tissue are c o m m o n l y used interventions that attempt to contain the infection until the patient with l e u k e m i a can achieve b o n e m a r r o w r e c o v e r y and r e m i s s i o n o f the u n d e r l y i n g disease. E v e n with successful treatment,
M u c o r a l e s can b e c o m e d o r m a n t and r e a p p e a r during future courses o f c h e m o t h e r a p y and neutropenia. N o p r e v e n t i v e m e a s u r e s are k n o w n to be effective, i n c l u d i n g p r o p h y l a x i s with the n e w e r azole drugs such as f l u c o n a z o l e and itraconazole. 1' 3, 4 CASE REPORT A 60-year-old white man was referred to the hematology/oncology service with pancytopenia and admission laboratory values as follows: white blood cell count = 1200/~tl,
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Fig. 3. Biopsy specimen with silver stain reveals fungal organisms in submucosa. Note broad nonseptate hyphae characteristic of Mucorales.
absolute neutrophil count = 200/laL hemoglobin = 8.6/gm/ dl, hematocrit = 24.5%, platelets = 15,000/pL. He was afebrile but complained of dizziness. His medical history included prostate cancer, hypertension, and heavy use of alcohol and tobacco. A bone marrow biopsy diagnosed acute myelogenous leukemia. A dental consultation was performed the day of admission. The dental history included no regular care and recent pain and swelling associated with the mandibular right second molar. Radiographs showed deep vertical bone defects involving the second molars and a periapical radiolucency of the mandibular right second molar (Fig. 1). In addition, the mandibular left second molar had previous endodontic treatment and a falling restoration but no periapical radiolucency. Periodontal probings up to 7 mm were associated with all four of these teeth. After consultation with the oncologists, the decision was made to extract the four second molars. Before this procedure the patient empirically received broad-spectrum antibacterial agents intravenously grid transfusions of red blood cells and platelets. No prophylactic antifungal medication was given. The four teeth were routinely extracted in the clinic with no apparent complications. Although the patient smoked postoperatively in spite of our warnings, his initial course was uneventful, and myelosuppressive chemotherapy was begun 3 days after the extractions. At 16 days postextraction, during the period of profound neutropenia, the mandibular left extraction site was encompassed by white necrotic-appearing tissue (not black crusts as is often described2' 5) (Fig. 2). Swell-
ing was noted in the adjacent buccal vestibule. A biopsy of the necrotic lesion showed fungal hyphae consistent with Mucorales invading the submucosal connective tissue and vasculature (Fig. 3). The biopsy confirmed the diagnosis of mucormycosis, and tissue cultures were also positive for Mucorales. Amphotericin B was immediately begun, and the patient was taken to the operating room for excision of the necrotic lesion. The resection included removal of the adjacent tooth, underlying bone, and a wide margin of normal appearing soft tissue. The neurovascular bundle was not disrupted, and the wound was closed primarily. Postoperative management included ongoing cellular support, including white blood cell transfusions, and granulocyte-macrophage colony-stimulating factor to promote earlier production of neutrophils. A soft diet was maintained and wound care included hydrogen peroxide irrigation of the surgical area and chlorhexidine rinses. With aggressive medical management the patient held a steady course, and a week after the resection his neutropenia had resolved. Antibiotics were gradually tapered as clinical conditions improved. He was discharged from the hospital 8 weeks after admission with leukemia in remission and no clinical evidence of mucormycosis. One month after discharge, the oral cavity showed no tissue breakdown in the area of previous infection (Fig. 4). Even though intensificationchemotherapy was deferred for fear of reactivating mucormycosis, remission of his leukemia lasted for 1 year at which time he relapsed and required additional treatment. There has not been any reappearance of mucormycosis.
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Fig. 4. Left posterior mandible area of resection shows well-healed mucosal tissue without evidence of recurrent mucormycosis.
DISCUSSION This case typifies the kind of treatment planning decisions frequently made by hospital dentists involved in the care of cancer patients. Management of chronic dental infections in patients with hematologic malignancies ideally should be based on data that correlates examination findings with outcomes of treatment. 6 There are, however, no controlled studies that identify when conservative or more aggressive treatment strategies should be used. As a result, clinicians must rely on case reports, personal experience, and clinical judgment. The quandary centers around whether to retain chronically diseased teeth in myelosuppressed patients, or whether such teeth should be extracted to eliminate the potential for acute odontogenic infection. The latter strategy presumably incurs some risk of infection, bleeding, and prolonged wound healing resulting from invasive surgical procedures. In a report of 119 extractions in 28 patients with acute myelogenous leukemia, Overholser et al. 7 showed no serious postoperative infections or other adverse sequelae, even in the subgroup of 15 patients with a mean granulocyte count of 750 pl at the time of surgery. The indications used for extraction included severe periodontal disease with pocket depths exceeding 6 m m or pulpal necrosis with periapical pathosis. A second study published by Williford et al. s reported on 26 patients with hematologic malig-
nancies that underwent 142 extractions. Over half of these extractions were done during severe neutropenia, and only minor complications were encountered in seven patients. 8 No invasive fungal infections were reported in either study. These are the only reports that give any substantial clinical experience with prechemotherapy dental extractions in patients with leukemia. There is considerable support in the literature for the periodontium as a nidus of infection in neutropenic patients with chronic preexistent periodontal disease. 9 Reduction in host defenses, especially in patients with leukemia, has been associated with acute periodontal infections from pathogenic organisms as well as increased numbers of indigenous oral bacteria. A thorough dental scaling before chemotherapy has been shown to lower the infection profile as well as the incidence of such acute exacerbations. 9 Pulpal and periapical infections are less frequently encountered, and there are no studies that describe the potential for acute infections from necrotic teeth in this population. An empiric regimen for endodontic care in patients scheduled to receive myelosuppressive chemotherapy has been published by Peterson et al. 9 A recent article addresses the issue of postendodontic periapical radiolucencies in bone marrow transplant (BMT) candidates. 6 In this retrospective review, 23 patients had dental screenings before myelosuppressive chemotherapy for BMT. Each patient
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had one asymptomatic tooth with a postendodontic periapical radiolucency. Because there were no differences in outcome between the group receiving no dental intervention versus the group receiving endodontic therapy, apicoectomy, or extraction, the authors concluded that treatment, of teeth with asymptomatic postendodontic periapical lesions was unnecessary in B M T patients. 6 The issue of smoking by patients with leukemia during and after induction chemotherapy has been untouched in the literature. The patient in our case report continued to smoke heavily after dental extractions and throughout the period of neutropenia. Although not studied, it could reasonably be assumed that tobacco, like other decaying vegetative matter, should contain Mucorales and other fungal organisms. Smoking could bring increased concentrations of fungi into the oral cavity and into contact with injured tissue after dental extractions. Smoking itself has long been known for adversely affecting neutrophil function and wound healing in the oral cavity. 10 Consequently, we believe that this patient's disregard for our warnings against smoking put him at increased risk for mucormycosis. More recently, another patient with leukemia who continued to smoke after prechemotherapy dental extractions developed aspergillosis in two extraction sites (unpublished). As a result, we are very reluctant to use dental extractions as a means of controlling chronic asymptomatic periodontal and pulpal disease in patients with leukemia who will not stop smoking. I n this circumstance, asymptomatic teeth having periapical radiolucencies, with or without previous endodontic treatment, can probably be left alone until remission. Symptomatic necrotic teeth, however, must still be considered for extraction. Periodontal disease can be initially managed with thorough dental scaling before chemotherapy, followed by improved oral hygiene on the ward. The management of oral mucormycosis in our case followed recommendations found elsewhere in the literature. 1'2 Several points should be emphasized. There are no serologic tests that can help with the diagnosis of mucormycosis. 4 Deep invasion of fungal organisms must be demonstrated histologically, and the biopsy needs to be done as soon as a necrotic lesion is recognized. Complete resection of the lesion with margins in bleeding tissue, medical management including appropriate cellular support, and aggressive amphotericin B therapy are the most accepted approaches to treating mucormycosis. In patients with leukemia, the prognosis depends in large part on the functional status of the bone marrow after chemotherapy.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY March 1997
SUMMARY This case demonstrated a rare occurrence of mucormycosis in the mandible after dental extractions. Preexistent periodontal disease and symptomatic periapic pathologic conditions led us to extract four molar teeth 3 days before the onset of induction chemotherapy in a patient with acute myelogenous leukemia. Necrotic tissue associated with one of the extraction sites was diagnosed by biopsy as mucormycosis. Even though the patient continued to smoke, he recovered from this infection with minimal morbidity. Factors related to a favorable outcome included early diagnosis, rapid surgical and medical management, and recovery of normal bone marrow function. This patient' s outcome was also enhanced by having close coordination between the dental, medical, and surgical services involved. REFERENCES 1. Sugar AM. Agents of mucormycosis and related species. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Vol 2. 4th ed. New York: Churchill Livingstone, 1995:2311-21. 2. Sugar AM. Mucormycosis. Clin Infect Dis 1992;14(suppl 1):S126-9. 3. St.-Germain G, Robert A, Ishak M, Tremblay C, Claveau S. Infection due to Rhizomucor pusillus: report of four cases in patients with leukemia and review. Clin Infect Dis 1993; 16:640-5. 4. Boelaert JR. Mucormycosis (zygomycosis): is there news for the clinician? J Infect 1994;28(supl 1):1-6. 5. Rosenberg SW, Lepley JB. Mucormycosis in leukemia. Oral Surg Oral Med Oral Pathol 1982;54:26-32. 6. Peters E, Monopoli M, Woo SB, Sonis S. Assessment of the need for treatment of postendodonfic asymptomatic periapical radiolucencies in bone marrow transplant recipients. Oral Surg Oral Med Oral Pathol 1993;76:45-8. 7. Overholser CD, Peterson DE, Bergman SA, Williams LT. Dental extractions in patients with acute nonlymphocytic leukemia. J Oral Maxillofac Surg 1982;40:296-8. 8. Williford SK, Salisbury PL, Peacock JE, Cruz JM, Powell BL, Lyerly ES, et al. The safety of dental extractions in patients with hematologic malignancies. J Clin Oncol 1989;7:798802. 9. Peterson DE. Pretreatment strategies for infection prevention in chemotherapy patients. Natl Cancer Inst Monogr 1990;9: 61 71. 10. Christen AG, McDonald JL, Christen JA. The impact of tobacco use and cessation on nonmalignant and precancerous oral and dental diseases and conditions. Indianapolis: Indiana University School of Dentistry, 1991:32-3.
Reprint requests: Lee Salisbury, DDS Department of Dentistry Bowman Gray School of Medicine Medical Center Blvd. Winstom-Salem, NC 27157
Mucormycosis is a fulminant fungal infection that occurs most often in diabetic and immunocompromised patients including those with hematologic malignancies. In this case, a patient with acute myelogenous leukemia developed mucormycosis in a recent mandibular extraction site. The successful management of this patient demonsrated that early diagnosis, aggressive surgical and medical treatment, and resolution of the underlying disease could improve the prognosis for survival. A case is made for the role of smoking as an initiator of mucormycosis, and treatment considerations for controlling periodontal and pulpal disease before chemotherapy are discussed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:340-4)
Infections produced by fungi of the class Zygomycetes, order Mucorales, have historically been known as mucormycosis (Table I). Ubiquitous in the environment and commonly found in bread molds and decaying vegetation, the Mucorales grow rapidly and constantly release spores into the atmosphere. Inhalation of spores rarely produces mucormycosis in healthy people. It is most often in the face of severe immunocompromising diseases, diabetes mellitus, tissue trauma, or burns that these saprophytic organisms become pathogenic. Even with one of these predisposing conditions, mucormycosis is quite uncommon. 1, 2 In the compromised host, mucormycosis results from diminished humoral and cellular defense mechanisms being overwhelmed by Mucorales organisms that proliferate rapidly and invade unchecked into deeper tissues. These fungi usually enter the body via the nasal mucosa, lungs, or skin. ! As in cutaneous mucormycosis, injured tissue in the oral cavity could be a suitable port of entry. For reasons that are unclear, the fungal hyphae preferentially invade the walls of blood vessels, producing thrombi and inaAssociate Professor, Department of Dentistry, Bowman Gray School of Medicine. bFormer Resident, Department of Dentistry, North Carolina Baptist Hospital. CAssociate Professor, Department of Internal Medicine -Hematology/Oncology, Bowman Gray School of Medicine. dFormer Resident, Division of Surgical Sciences-Otolaryngology, North Carolina Baptist Hospital. eprofessor, Division of Surgical Sciences-Otolaryngology, Bowm a n Gray School of Medicine. Received for publication Mar. 20, 1996; returned for revision May 1, 1996; accepted for publication Sept. 25, 1996. Copyright © 1997 by Mosby Year Book, Inc. 1079-2104/97/$5.00 + 0 7/13/78425
340
Table I. Classification of the agents of
mucormycosis 1. Zygomycotina--Phylum A. Zygomycetes--Class a. Mucorales--Order *1. Mucoraceae--Family i. Absidia--Genns ii. Mucor iii. Rhizomucor iv. Rhizopus *2. Cunningharnellacaeae 3-7. Other rare Mucorales organisms *Most common causes of mucormycosis. (Adapted with permission from Sugar AM, Agents of mucormycosis and related species, In: Principles and practice of infectious diseases, Chap. 239, New York: Churchill Livingstone, 1995.)
farctions. Progressive tissue ischemia and necrosis are the inevitable result. In leukemic patients with neutropenia, the disease occurs most commonly in pulmonary and rhinocerebral sites and can become widely disseminated to other organ systems 2. Neutrophils are known to play a crucial role in the protective host response to fungal colonization. In patients with leukemia, the bone marrow produces dysfunctional neutrophils, and remission-induction chemotherapy causes several weeks of myelosuppression and profound neutropenia. The combination of these two events puts the patient with leukemia at significant risk for several different opportunistic fungal infections. Prolonged treatment with broadspectrum antibacterial antibiotics increases the risk even more. Clinical evidence would indicate that restoration of adequate numbers of functional neutrophils must occur before mucormycosis can be resolved.l' 3 Mucormycosis has long been known for having a
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Fig. 1. Preoperative radiograph illustrates pathosis associated with second molar teeth.
Fig. 2. Lesion at time of biopsy, mandibular left second molar extraction site.
v e r y p o o r p r o g n o s i s , however, with a g g r e s s i v e m e d ical and surgical m a n a g e m e n t , survival rates are n o w thought to e x c e e d 80%. 2 E a r l y detection has been correlated with less tissue destruction and a better overall outcome. The antifungal agent a m p h o t e r i c i n B and surgical d e b r i d e m e n t o f necrotic tissue are c o m m o n l y used interventions that attempt to contain the infection until the patient with l e u k e m i a can achieve b o n e m a r r o w r e c o v e r y and r e m i s s i o n o f the u n d e r l y i n g disease. E v e n with successful treatment,
M u c o r a l e s can b e c o m e d o r m a n t and r e a p p e a r during future courses o f c h e m o t h e r a p y and neutropenia. N o p r e v e n t i v e m e a s u r e s are k n o w n to be effective, i n c l u d i n g p r o p h y l a x i s with the n e w e r azole drugs such as f l u c o n a z o l e and itraconazole. 1' 3, 4 CASE REPORT A 60-year-old white man was referred to the hematology/oncology service with pancytopenia and admission laboratory values as follows: white blood cell count = 1200/~tl,
342
Salisbury et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
March 1997
Fig. 3. Biopsy specimen with silver stain reveals fungal organisms in submucosa. Note broad nonseptate hyphae characteristic of Mucorales.
absolute neutrophil count = 200/laL hemoglobin = 8.6/gm/ dl, hematocrit = 24.5%, platelets = 15,000/pL. He was afebrile but complained of dizziness. His medical history included prostate cancer, hypertension, and heavy use of alcohol and tobacco. A bone marrow biopsy diagnosed acute myelogenous leukemia. A dental consultation was performed the day of admission. The dental history included no regular care and recent pain and swelling associated with the mandibular right second molar. Radiographs showed deep vertical bone defects involving the second molars and a periapical radiolucency of the mandibular right second molar (Fig. 1). In addition, the mandibular left second molar had previous endodontic treatment and a falling restoration but no periapical radiolucency. Periodontal probings up to 7 mm were associated with all four of these teeth. After consultation with the oncologists, the decision was made to extract the four second molars. Before this procedure the patient empirically received broad-spectrum antibacterial agents intravenously grid transfusions of red blood cells and platelets. No prophylactic antifungal medication was given. The four teeth were routinely extracted in the clinic with no apparent complications. Although the patient smoked postoperatively in spite of our warnings, his initial course was uneventful, and myelosuppressive chemotherapy was begun 3 days after the extractions. At 16 days postextraction, during the period of profound neutropenia, the mandibular left extraction site was encompassed by white necrotic-appearing tissue (not black crusts as is often described2' 5) (Fig. 2). Swell-
ing was noted in the adjacent buccal vestibule. A biopsy of the necrotic lesion showed fungal hyphae consistent with Mucorales invading the submucosal connective tissue and vasculature (Fig. 3). The biopsy confirmed the diagnosis of mucormycosis, and tissue cultures were also positive for Mucorales. Amphotericin B was immediately begun, and the patient was taken to the operating room for excision of the necrotic lesion. The resection included removal of the adjacent tooth, underlying bone, and a wide margin of normal appearing soft tissue. The neurovascular bundle was not disrupted, and the wound was closed primarily. Postoperative management included ongoing cellular support, including white blood cell transfusions, and granulocyte-macrophage colony-stimulating factor to promote earlier production of neutrophils. A soft diet was maintained and wound care included hydrogen peroxide irrigation of the surgical area and chlorhexidine rinses. With aggressive medical management the patient held a steady course, and a week after the resection his neutropenia had resolved. Antibiotics were gradually tapered as clinical conditions improved. He was discharged from the hospital 8 weeks after admission with leukemia in remission and no clinical evidence of mucormycosis. One month after discharge, the oral cavity showed no tissue breakdown in the area of previous infection (Fig. 4). Even though intensificationchemotherapy was deferred for fear of reactivating mucormycosis, remission of his leukemia lasted for 1 year at which time he relapsed and required additional treatment. There has not been any reappearance of mucormycosis.
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Fig. 4. Left posterior mandible area of resection shows well-healed mucosal tissue without evidence of recurrent mucormycosis.
DISCUSSION This case typifies the kind of treatment planning decisions frequently made by hospital dentists involved in the care of cancer patients. Management of chronic dental infections in patients with hematologic malignancies ideally should be based on data that correlates examination findings with outcomes of treatment. 6 There are, however, no controlled studies that identify when conservative or more aggressive treatment strategies should be used. As a result, clinicians must rely on case reports, personal experience, and clinical judgment. The quandary centers around whether to retain chronically diseased teeth in myelosuppressed patients, or whether such teeth should be extracted to eliminate the potential for acute odontogenic infection. The latter strategy presumably incurs some risk of infection, bleeding, and prolonged wound healing resulting from invasive surgical procedures. In a report of 119 extractions in 28 patients with acute myelogenous leukemia, Overholser et al. 7 showed no serious postoperative infections or other adverse sequelae, even in the subgroup of 15 patients with a mean granulocyte count of 750 pl at the time of surgery. The indications used for extraction included severe periodontal disease with pocket depths exceeding 6 m m or pulpal necrosis with periapical pathosis. A second study published by Williford et al. s reported on 26 patients with hematologic malig-
nancies that underwent 142 extractions. Over half of these extractions were done during severe neutropenia, and only minor complications were encountered in seven patients. 8 No invasive fungal infections were reported in either study. These are the only reports that give any substantial clinical experience with prechemotherapy dental extractions in patients with leukemia. There is considerable support in the literature for the periodontium as a nidus of infection in neutropenic patients with chronic preexistent periodontal disease. 9 Reduction in host defenses, especially in patients with leukemia, has been associated with acute periodontal infections from pathogenic organisms as well as increased numbers of indigenous oral bacteria. A thorough dental scaling before chemotherapy has been shown to lower the infection profile as well as the incidence of such acute exacerbations. 9 Pulpal and periapical infections are less frequently encountered, and there are no studies that describe the potential for acute infections from necrotic teeth in this population. An empiric regimen for endodontic care in patients scheduled to receive myelosuppressive chemotherapy has been published by Peterson et al. 9 A recent article addresses the issue of postendodontic periapical radiolucencies in bone marrow transplant (BMT) candidates. 6 In this retrospective review, 23 patients had dental screenings before myelosuppressive chemotherapy for BMT. Each patient
344
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had one asymptomatic tooth with a postendodontic periapical radiolucency. Because there were no differences in outcome between the group receiving no dental intervention versus the group receiving endodontic therapy, apicoectomy, or extraction, the authors concluded that treatment, of teeth with asymptomatic postendodontic periapical lesions was unnecessary in B M T patients. 6 The issue of smoking by patients with leukemia during and after induction chemotherapy has been untouched in the literature. The patient in our case report continued to smoke heavily after dental extractions and throughout the period of neutropenia. Although not studied, it could reasonably be assumed that tobacco, like other decaying vegetative matter, should contain Mucorales and other fungal organisms. Smoking could bring increased concentrations of fungi into the oral cavity and into contact with injured tissue after dental extractions. Smoking itself has long been known for adversely affecting neutrophil function and wound healing in the oral cavity. 10 Consequently, we believe that this patient's disregard for our warnings against smoking put him at increased risk for mucormycosis. More recently, another patient with leukemia who continued to smoke after prechemotherapy dental extractions developed aspergillosis in two extraction sites (unpublished). As a result, we are very reluctant to use dental extractions as a means of controlling chronic asymptomatic periodontal and pulpal disease in patients with leukemia who will not stop smoking. I n this circumstance, asymptomatic teeth having periapical radiolucencies, with or without previous endodontic treatment, can probably be left alone until remission. Symptomatic necrotic teeth, however, must still be considered for extraction. Periodontal disease can be initially managed with thorough dental scaling before chemotherapy, followed by improved oral hygiene on the ward. The management of oral mucormycosis in our case followed recommendations found elsewhere in the literature. 1'2 Several points should be emphasized. There are no serologic tests that can help with the diagnosis of mucormycosis. 4 Deep invasion of fungal organisms must be demonstrated histologically, and the biopsy needs to be done as soon as a necrotic lesion is recognized. Complete resection of the lesion with margins in bleeding tissue, medical management including appropriate cellular support, and aggressive amphotericin B therapy are the most accepted approaches to treating mucormycosis. In patients with leukemia, the prognosis depends in large part on the functional status of the bone marrow after chemotherapy.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY March 1997
SUMMARY This case demonstrated a rare occurrence of mucormycosis in the mandible after dental extractions. Preexistent periodontal disease and symptomatic periapic pathologic conditions led us to extract four molar teeth 3 days before the onset of induction chemotherapy in a patient with acute myelogenous leukemia. Necrotic tissue associated with one of the extraction sites was diagnosed by biopsy as mucormycosis. Even though the patient continued to smoke, he recovered from this infection with minimal morbidity. Factors related to a favorable outcome included early diagnosis, rapid surgical and medical management, and recovery of normal bone marrow function. This patient' s outcome was also enhanced by having close coordination between the dental, medical, and surgical services involved. REFERENCES 1. Sugar AM. Agents of mucormycosis and related species. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Vol 2. 4th ed. New York: Churchill Livingstone, 1995:2311-21. 2. Sugar AM. Mucormycosis. Clin Infect Dis 1992;14(suppl 1):S126-9. 3. St.-Germain G, Robert A, Ishak M, Tremblay C, Claveau S. Infection due to Rhizomucor pusillus: report of four cases in patients with leukemia and review. Clin Infect Dis 1993; 16:640-5. 4. Boelaert JR. Mucormycosis (zygomycosis): is there news for the clinician? J Infect 1994;28(supl 1):1-6. 5. Rosenberg SW, Lepley JB. Mucormycosis in leukemia. Oral Surg Oral Med Oral Pathol 1982;54:26-32. 6. Peters E, Monopoli M, Woo SB, Sonis S. Assessment of the need for treatment of postendodonfic asymptomatic periapical radiolucencies in bone marrow transplant recipients. Oral Surg Oral Med Oral Pathol 1993;76:45-8. 7. Overholser CD, Peterson DE, Bergman SA, Williams LT. Dental extractions in patients with acute nonlymphocytic leukemia. J Oral Maxillofac Surg 1982;40:296-8. 8. Williford SK, Salisbury PL, Peacock JE, Cruz JM, Powell BL, Lyerly ES, et al. The safety of dental extractions in patients with hematologic malignancies. J Clin Oncol 1989;7:798802. 9. Peterson DE. Pretreatment strategies for infection prevention in chemotherapy patients. Natl Cancer Inst Monogr 1990;9: 61 71. 10. Christen AG, McDonald JL, Christen JA. The impact of tobacco use and cessation on nonmalignant and precancerous oral and dental diseases and conditions. Indianapolis: Indiana University School of Dentistry, 1991:32-3.
Reprint requests: Lee Salisbury, DDS Department of Dentistry Bowman Gray School of Medicine Medical Center Blvd. Winstom-Salem, NC 27157