C A S E R E P O R T Open Access
Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report
Miller H Smith1, Paul W Harms2, Duane W Newton3, Bill Lebar3, Sean P Edwards1and David M Aronoff4,5*
Abstract
Background: Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon.
Case Presentation: We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment.
A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible.
Conclusions: Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis.
Background
Actinomycosis is a slowly-progressive infection caused by filamentous, gram-positive, anaerobic (or facultatively anaerobic) bacilli of the Actinomyces genus [1]. Such infections are characterized by suppurative and granulo- matous inflammation with abscesses, tissue fibrosis, and the presence of draining sinus tracts or fistulae [2]. Acti- nomycosis usually spreads contiguously, ignoring tissue planes, and extruding bacteria-laden “sulfur granules”
from erupting sinus tracts [3]. Cervicofacial infections are the most common manifestation of actinomycosis, although this is generally limited to the soft tissues with- out spreading to involve neighboring bone [1,2]. An odontogenic origin is typical for cervicofacial actinomy- cosis, which evolves as a chronic (or subacute) soft
tissue swelling of the submandibular or paramandibular region [3].
The diagnosis of actinomycosis is easily missed because it mimics more common problems such as neo- plasia [4]. In addition, actinomycetes are very sensitive to many common antimicrobials, so even a relatively few doses can render cultures negative [5]. However, it is important to make the diagnosis because actinomyco- sis can be disfiguring or even fatal, if vital structures (such as major arteries and airways) are involved [5].
And while antimicrobial therapy is effective against the actinomycetes, the treatment duration is remarkably long (6-12 months) [3]. Thus, the diagnostic and thera- peutic challenges of actinomycosis underscore the need for an improved understanding of risk factors for infec- tion and new information about clinical circumstances associated with this condition.
Florid cemento-osseous dysplasia (FCOD) is a disease with multiple bilateral and often symmetrically extensive lesions throughout the maxillofacial region (predomi- nantly in the mandible) demonstrating a predilection for
* Correspondence: daronoff@umich.edu
4Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA
Full list of author information is available at the end of the article
© 2011 Smith et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
middle-aged African-American females [6,7]. Lesions are often asymptomatic and indolent in nature and may present as incidental findings on radiographs [6,8].
Occasionally patients present with dull pain or drainage from a prior extraction socket, or from a chronic irrita- tion beneath a denture base, while some infrequently appear with expansion of the native bone [9,10]. Radio- graphically, the lesions present a mixed radiolucent and radiopaque “cotton wool” appearance with ill-defined borders with densely sclerotic irregularly shaped masses.
Though they may occasionally look very similar in appearance to fibrous dysplasia, there is often a distinct sclerotic component with surrounding radiolucency [6,10,11].
Histopathologically, the lesions of FCOD demonstrate mature lamellar bone being replaced with thickened woven bone with curvilinear branching bony trabeculae, and separate masses closely resembling dental remnants such as cementum [7,9]. There is a high preponderance of fibrous tissue and osteoclasts but rarely inflammation unless secondary contamination results [7,9]. Chronic inflammation and infection may develop within the dys- plastic densely mineralized tissue, which possesses a less robust blood supply, thereby resulting in sequestrum formation [6,8]. Given a preponderance of inflammation on pathology, some authors in the past have incorrectly characterized the lesions as diffuse sclerosing osteitis or chronic diffuse sclerosing osteomyelitis (CDSO) [9,12-17]. This characterization is incorrect as the multi- focal bilateral lesions of FCOD represent a distinct dif- fuse pathologic spectrum despite occasional areas of inflammation, while CDSO lesions are unilateral and often contained within the mandible with universal inflammation [8].
Herein we report, possibly for the first time, the first association between these two chronic, disfiguring dis- eases, in a patient who presented with mandibular osteomyelitis caused by Actinomyces in the setting of underlying FCOD. We speculate that the infection was initiated when bacteria contaminated a denture-related ulceration of the soft tissues overlying the involved area.
Clinicians should be aware of the pathogenesis of acti- nomycosis and the importance of bone biopsy and cul- ture in making a timely diagnosis.
Case presentation
A 53 year-old, edentulous, African-American woman with longstanding FCOD presented to her dentist with a 1 month history of swelling, pain, and purulent dis- charge involving the region of the left lower mandible.
The drainage was described as white, thick, and malo- dorous. Radiographs revealed multifocal diffuse bony changes consistent with FCOD and a new radiolucency in the bone of the mandible underlying the swollen and
draining soft tissues. She was treated with a chlorhexi- dine gluconate oral rinse and a two-week course of oral levofloxacin but did not improve. A biopsy performed approximately two months after the onset of symptoms revealed dead bone but no specific diagnosis. Two months after this biopsy the patient noted what appeared to be a bone fragment erupting from the same pus-draining ulcer. The ulceration and drainage contin- ued and seven months after the onset of symptoms the patient was referred to our institution for further man- agement. She denied fevers, chills, night sweats or other constitutional symptoms. Her dental history was signifi- cant for FCOD, a condition shared with her mother.
The diagnosis of FCOD was established twenty five years prior to her presentation to the University of Michigan by biopsy coincident with the extraction of her remaining teeth. Her present dentures were more than 10 years old. Her medical history was significant for multiple sclerosis treated with interferon 1b and a venous thromboembolic disorder managed with oral warfarin.
On physical examination the patient’s poorly-fitting mandibular denture was removed and the alveolar tis- sues revealed slight swelling along the anterior border of the ramus with an area of exposed bone measuring approximately 1 cm along the external oblique ridge lat- erally. There was soft tissue edema and congestion in this area. Her neck was otherwise supple without lym- phadenopathy. She had no other oral lesions. Panoramic radiographs revealed bilateral lesions consistent with FCOD involving both the maxilla and mandible (Figure 1A). A maxillofacial computed tomography (CT) scan revealed midface, and mandibular findings consistent with FCOD (Figures 1B and 1C). On the patient’s left, there was bony sequestrum within a radiolucent capsule to the anterior border of the ascending ramus (Figures 1B and 1C).
Because of concern for chronic infection, the patient underwent debridement with bone biopsy and cultures of the diseased left mandibular ramus. The ulcerated soft tissues were repaired with a simple advancement flap. Purulence and necrotic bone were observed during this procedure. Histopathological examination of the biopsied bone revealed irregular trabeculae and bosse- lated cementum droplets in a fibrous stroma, typical of cemento-osseous dysplasia (Figure 2A). Changes consis- tent with osteomyelitis were also observed (Figure 2B).
A Brown-Hopps tissue Gram stain revealed abundant gram-positive filamentous organisms consistent with Actinomyces (Figure 2C), which also stained positively with GMS silver stain (Figure 2D). Operative cultures yielded numerous (in quantity) Actinomyces species (not further identified to the species level) along with a mix- ture of oral anaerobic bacteria (table 1). Coagulase-
negative Staphylococcus was the only aerobic bacterium isolated from the bone biopsy. Cultures for acid fast bacteria, fungi, and Nocardia were negative.
The patient was initially treated for one week with oral amoxicillin combined with clavulinic acid 875 mg twice daily. However, because of the complicated poly- microbial nature of the infection, including bone invol- vement, therapy was changed to intravenous ertapenem one gram daily and the patient was treated for eight weeks. An additional 10 months of oral therapy were instituted with amoxicillin/clavulanic acid 875 mg twice daily. The patient responded well to antimicrobial treat- ment with complete healing of her operative site, and to date denies any further pain, swelling, or drainage.
This case newly demonstrates an association between two chronic, destructive and disfiguring conditions of the mandible, FCOD and Actinomyces osteomyelitis. It also emphasizes the utility of performing biopsies with appropriate aerobic and anaerobic cultures to establish a diagnosis in complicated cases such as this one. Initially our patient was felt to be suffering only from a progres- sion of her FCOD coupled with ulceration caused by her poorly-fitting dentures. This led to a delay in her diagnosis. However, the eruption of purulent fluid from the ulcer and the eventual radiographic demonstration of an enlarged radiolucent ring surrounding more poorly-defined lesional tissue/sequestrum suggested that a superimposed osteomyelitis was present. While radio- graphs did not show a progressive osteolysis of the bone
as might be expected typical osteomyelitis, the diagnosis was confirmed histopathologically. We speculate that our patient developed Actinomyces osteomyelitis follow- ing the mandibular ulceration.
Actinomycosis of the head and neck is an indolent infection that generally presents as a soft tissue swelling, mass, abscess, or ulceration of the oral-cervical region [1].“Lumpy jaw” is caused when an actinomycete resi- dent of the mouth (or other mucosal site) invades the underlying tissues through a loss of mucosal integrity [1]. The most common region for lesions to occur is the perimandibular area, but involvement of the bone is rare [1]. Anaerobic cultures are necessary to isolate the bac- terium from pathological specimens, but culture-inde- pendent means of establishing the presence of these bacteria, such as PCR, are increasingly utilized [18].
Gram stains are more sensitive than cultures, perhaps because a lack of strict anaerobic processing or previous antibiotic use can render the cultures negative [1]. In cases of perimandibular infections, actinomycetes are often present in the setting of multiple other species of bacteria [1]. Although it is not always known how much the other bacteria are participating in the pathogenesis of infection, antimicrobial therapy is generally broad enough to cover these microbes. Although biopsy clearly demonstrated invasive actinomycosis, our patient had malodorous, purulent drainage from her mandible, sug- gesting that anaerobes or pyogenic bacteria were also present, which was confirmed by culture (table 1). It is
Figure 1 Radiographic evidence ofActinomyces osteomyelitis complicating florid cemento-osseous dysplasia (FCOD). (A) Panoramic radiograph demonstrating mixed radiolucent and radiopaque lesions in the mandible with“cotton wool” appearance. Lesions are well
demarcated with a radiolucent ring in all four quadrants though they are more subtle in the maxilla (B) Axial CT scan image showing hypertrophic, sclerotic and heterogeneous changes of FCOD within the mandible (open arrow). There is a large lytic lesion in the body of the left mandible with loss of bone at its lateral aspect and central sclerosis consistent with infection (solid arrow). (C) 3-dimensional CT image of generalized bony changes with expansion to maxilla and mandible consistent with FCOD (open arrow, corresponding to same location in panel A). There is focal erosion of left mandible in area of Actinomyces infection (solid arrow). CT images were reformatted with OsiriX imaging software (OsiriX Foundation).
likely that her infection was driven by this polymicrobial collection of pathogens and was not simply due to acti- nomycosis alone.
As evidenced in the present case, the treatment of cer- vicofacial actinomycosis requires attention to other iden- tified pathogens, since these infections can be polymicrobial [3]. However, in many cases co-pathogens (such as oral anaerobic bacteria) are susceptible to the
agents targeting the actinomycete. In cases where Acti- nomyces is the only identified pathogen then targeted therapy is warranted. Fortunately, actinomycetes remain exquisitely susceptible to beta lactam drugs and intrave- nous penicillin G remains a first-line agent [3]. For patients with intolerance to beta lactam agents, tetracy- cline agents can be substituted [2,3]. As detailed in a recent review [2], parenteral penicillin G, 10 to 20
Figure 2 Histopathological changes ofActinomyces osteomyelitis complicating florid cemento-osseous dysplasia (FCOD). (A) Excised mandibular bone revealed FCOD with irregular cementum droplets and rounded forms in a fibrovascular stroma (hematoxylin and eosin (H&E), magnification 200 ×). (B) Neutrophilic infiltrate (arrowheads) with adjacent necrotic bone (arrows) (H&E, magnification 400 ×). (C) Gram-positive filamentous organisms in marrow space (arrowheads) (Brown-Hopps stain). (D) Colonies of filamentous organisms in marrow (GMS).
million units daily divided every 6 hours for 4 to 6 weeks can be used for complicated cases, followed by oral penicillin V, 2 to 4 g/d divided four times daily for 6 to 12 months to prevent relapse [3]. The ultimate length of treatment depends upon clinical and patholo- gic response [2]. A number of alternatives to penicillin are available and include macrolides, tetracyclines, clin- damycin, and carbapenem agents [2]. Importantly, many commonly used antimicrobials are not active against Actinomyces species and these include metronidazole, aminoglycosides, aztreonam, trimethoprim-sulfamethox- azole, penicillinase-resistant penicillins (e.g., nafcillin and oxacillin) and cephalexin [2,3]. In the present case ertapenem was used for the parenteral therapy because of the polymicrobial nature of the osteomyelitis and the convenience of once daily dosing.
It is interesting that our patient developed actinomy- cosis while on an immunomodulatory agent, interferon 1b, which was used to treat her multiple sclerosis. We were unable to identify previous reports of osteomyelitis associated with this medication. Infectious complications of interferon 1b are uncommon [19]. Although neutro- penia can be a complication of therapy, our patient did not have any record of this while on therapy (data not shown).
FCOD is a benign lesion that can be disfiguring and lead to tooth loss, jaw fractures, and chronic infections.
Although the etiology and pathogenesis of FCOD are unknown, the disease represents a disturbance in bone metabolism where normal bone becomes replaced by a connective tissue matrix that gradually develops cemento-osseous tissue [20]. As in our patient, the dis- ease is more common in persons of African ancestry and can be familial [21]. FCOD is typically diagnosed through incidental findings on routine radiographic eva- luation and biopsy often avoided to avoid the risk of chronically infected, non-healing wounds. The lesions are characteristic of a diffuse bilateral involvement of the maxillary and mandibular bones. Pathologic evalua- tion is often free of inflammation, however superinfec- tion can occur and progress to osteomyelitis due to the limited blood supply of the dense bone [6,8,10]. Trau- matic extractions and pressure ulceration caused by poorly fitting prosthetics can cause bone exposure
which is susceptible to inflammation and infection of various organisms. Prior to the characterization of FCOD by Melrose in 1976 [9] these lesions were believed to represent CDSO [12-17]. Due to the dysplas- tic anatomy of the lesions, surgical intervention is often necessary for treatment of chronic infections combined with prolonged antibiotic therapy [8,10,11].
As observed in this case report, FCOD is characterized by fibrovascular stroma with a“ginger-root” pattern of irregular curvilinear trabeculae, as well as droplets of cementum ("cementicles”) that fuse to form bosselated structures [22-24]. Coexisting bone cysts with fibrovas- cular lining may also be present [22,23], although these were not observed in the present case. Early-stage lesions of FCOD display fewer trabeculae and more pro- minent fibrovascular stroma, often with hemorrhage [22]. In the case presented here, these typical findings of FCOD were seen in conjunction with key features of Actinomyces osteomyelitis including filamentous gram- positive organisms, acute inflammation, and necrotic bone [25,26].
Conclusions
In summary, we present a complicated association of two uncommon and destructive diseases of bone, FCOD and actinomycosis. The existing FCOD possibly contrib- uted to a delay in establishing the diagnosis of actino- mycosis because the deforming and destructive changes to the mandible produced by the infection were assumed to be due to progressing FCOD. Healthcare providers should be aware that actinomycosis can be an opportunistic pathogen of the mandible that can estab- lish deforming and severe infections when a break in the integrity of the oral mucosa occurs. Proper cultures performed under anaerobic conditions are helpful and antimicrobial management should take into considera- tion the frequent polymicrobial nature of these infections.
Informed consent
After approval by the Institutional Review Board of the University of Michigan Health System, written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Edi- tor-in-Chief of this journal.
Abbreviations
FCOD: florid cement-osseous dysplasia.
Author details
1Department of Oral and Maxillofacial Surgery, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA.
2Department of Pathology, University of Michigan Medical School, 1150 W.
Medical Center Drive, Ann Arbor, MI, 48109, USA.3Clinical Microbiology Table 1 Bacteria cultured from mandibular biopsy
Aerobic bacteria Anaerobic bacteria
Coagulase-negative Staphylococcus Numerous Actinomyces spp.
Lactobacillus spp.
a-hemolytic Streptococcus Leptotrichia buccalis Capnocytophaga spp.
Prevotella spp.
Laboratories, Department of Pathology, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA.4Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA.5Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA.
Authors’ contributions
All authors read and approved the final manuscript. MHS provided clinical care for the patient and wrote the manuscript. PWH provided expertise in the interpretation of tissue biopsies and assisted in writing the manuscript.
DWN and BL conducted laboratory studies of the bacterial cultures isolated from the patient and provided expertise on the microbiology of
Actinomyces. SPE provided clinical care for the patient and contributed to writing the manuscript. DMA provided clinical care for the patient, coordinated all aspects of this report, and wrote the manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 9 April 2011 Accepted: 21 July 2011 Published: 21 July 2011
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Cite this article as: Smith et al.: MandibularActinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report. BMC Oral Health 2011 11:21.
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