Mandibular Actinomyces osteomyelitis mimicking osteosarcoma

Received 1 October 2016 Accepted 23 November 2016 Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Department of Internal Medicine, Jazan University, Jazan, Saudi Arabia Department of Internal Medicine, Section of Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada


Introduction
Actinomyces are filamentous Gram-positive microaerophilic bacilli that are commensal organisms of the oropharynx, gastrointestinal tract and urogenital tract.These organisms are well known to cause odontogenic and cervicofacial infections, including gingivitis, periapical abscesses, periodontitis and surrounding soft tissue infection, but occasionally they are also the causative organism in pneumonia, empyema, abscesses, osteomyelitis and pericarditis.
Osteomyelitis of the mandible is a rare complication of odontogenic infections that frequently develops from contiguous spread of a chronic dental infection with Actinomyces.It presents as an indolent course with swelling of the surrounding soft tissue that may or may not be painful.Diagnosis is particularly challenging, as Actinomyces osteomyelitis closely resembles other infectious and noninfectious aetiologies, both clinically and radiographically.Diagnosis is confirmed by demonstration of actinomycotic granules in necrotic bone tissue and growth on anaerobic culture obtained from surgical biopsy.
We describe a case of mandibular Actinomyces osteomyelitis that posed a diagnostic challenge.

Case report
A 26-year-old woman from Northern Manitoba in her second trimester of pregnancy presented to the emergency department with a 2-month history of progressive pain and swelling of her right mandible.About 1 month prior, she had presented to her dentist with similar symptoms.She was prescribed a short course of amoxicillin without demonstrable improvement in her symptoms.On initial examination, she had extensive dental caries with several missing teeth and significant swelling over the angle of the mandible extending to the temporomandibular joint.Submandibular lymph nodes were noted without tenderness on palpation.There were no fistulizing tracts observed.

Investigations
A panoramic radiograph of her mandible showed osseous and cortical erosion on the right ramus (Fig. 1).A computed tomography scan of her facial bones showed a lytic lesion involving the angle and ramus of the mandible extending to the right mandibular condyle with extension of the lesion into the adjacent masseter and pterygoid muscles (Fig. 2).The deep cervical and submandibular lymph nodes were not enlarged on imaging.
Maxillofacial surgery was primarily considered because of suspected osteosarcoma of the mandible, and the patient was taken into the operating room for an extensive surgical procedure.During this procedure, significant granulation tissue was seen on the anterior border of the ramus with a lytic loculated lesion seen underneath the periosteum from which frank purulent discharge was expressed.Several areas of significantly decorticated and rough osteomyelitic bone were debrided.

Diagnosis
Intraoperative culture of the mandible revealed Actinomyces odontolyticus, which was sensitive to penicillin.Intraoperative pathology specimens of the affected bone revealed intense acute and chronic inflammation.Special stains (including Gomori's methenamine silver stain) showed no micro-organisms.

Treatment
Three weeks after the mandibular debridement, a hemimandibulectomy with mandibular and temporomandibular joint reconstruction was performed.The patient was treated with piperacillin-tazobactam for 6 weeks and then stepped down to amoxicillin-clavulanate for a further 6 months.

Outcome and follow-up
Subsequent computed tomography imaging confirmed interval regression of the extent of osteomyelitis.She subsequently underwent routine total replacement of the temporomandibular joint and has continued to remain well on serial follow-up visits.

Discussion
Although cervicofacial Actinomyces osteomyelitis is uncommon in an immunocompetent host, it should be in the differential diagnosis when there is a suspicion of contiguous odontogenic soft tissue infection.The most common inciting events are dental caries, dental manipulation and oromaxillofacial trauma facilitating mucosal breakdown and spread of infection (Volante et al., 2005).Other risk factors for acquiring Actinomyces infections include poor oral hygiene, diabetes mellitus, steroid and bisphosphonate therapy, leukaemia with chemotherapy, human immunodeficiency virus co-infection, prior transplant with immunosuppression and heavy alcohol intake (Wong et al., 2011).
Several features in the presentation of this case were suggestive of Actinomyces infection.The chronicity of presentation was characteristic: a painless, fluctuant mass progressively enlarging over the course of months (Wong et al., 2011).The incomplete response to a short course of empiric antibiotics may have represented temporary improvement with inevitable relapse (Russo, 2015).Actinomycosis is known to spread contiguously, crossing tissue planes, progressing from periodontitis to myofasciitis and osteomyelitis as observed here.It sometimes also involves the pharynx, larynx, tonsils and paranasal sinuses.Although not seen in this patient, sinus tracts within the mass may develop and then heal over time (Russo, 2015).Unlike in most cervicofacial  infections, regional lymphadenopathy is uncommon (Gannepalli et al., 2015).Submandibular involvement is the most common presentation of cervicofacial actinomycosis; less frequently, the temporomandibular joint maybe involved among other locations.The diagnosis is particularly challenging as Actinomyces osteomyelitis mimics several infectious and noninfectious pathologies.The differential diagnosis includes osteosarcoma, metastases, lymphoma, and diseases involving granuloma formation such as Langerhans cell histiocytosis, sarcoidosis and tuberculosis.Computed tomography and magnetic resonance imaging are useful in determining the extent of infection and for preoperative planning.The challenge is to suspect and treat Actinomyces infection in order to avoid unnecessary surgery (Russo, 2015;Bartkowski et al., 1998).
In light of this, direct specimen culture is the cornerstone for diagnosis of Actinomyces.The ideal specimen contains pus or tissue and is obtained prior to the initiation of antibiotics.Swab specimens should be avoided.Specimens are cultured on selective anaerobic culture medium and may take up to 3 weeks to grow (Russo, 2015;Wong et al., 2011).Histopathological findings suggestive of Actinomyces infection are Gram-positive filamentous rods and sulfur granules, which are collections of inflammatory cells surrounded by hyphae, degenerated bacteria and proliferating fibroblasts.It is important to note that sulfur granules are commonly missed, which may have occurred in this case (Russo, 2015;Kubo & Osada, 1980).Gram, Gomori methenamine silver and Giemsa stains are helpful for visualization of these features (Brook, 2008).
The management of cervicofacial actinomycosis includes antibiotics with or without surgical debridement as even in extensive infection antibiotics alone may be sufficient (Russo, 2015).A recent retrospective review of resistance patterns in Actinomyces species shows near complete susceptibility to b-lactam antibiotics with and without a blactamase inhibitor, carbapenems, tetracyclines and vancomycin.In contrast, isolates were almost completely resistant to metronidazole (Steininger & Willinger, 2015).As odontogenic infections are often polymicrobial, the initial antibiotic choice should be appropriately broad with 4-6 weeks of intravenous antibiotics and followed by step down to broad oral antibiotics.A first line regimen may consist of piperacillin-tazobactam to cover both aerobes and oral anaerobes and b-lactamase producers with step down to an oral antibiotic with similar coverage such as amoxicillinclavulanate.
Historically, surgical debridement has played a role where there are areas of necrotic tissue, fistulizing sinus tracts and cases in whom malignancy is difficult to exclude such as in this case (Wong et al., 2011).Evidence from several case reports of actinomycosis suggests that medical therapy alone may be sufficient for cure of even severe infections (Fu & Tsai, 2010;Colmegna et al., 2003;Hawnaur et al., 1999).While the traditional approach is to treat with antibiotics for up to 12 months, this prolonged duration may not be necessary.Treatment regimens should be individualized based on individual clinical presentation.Factors that affect duration of treatment include initial burden of disease, the site of infection, extent of surgical debridement and the clinical and radiological response to therapy.Close followup is essential in determining the trajectory of the treatment course and the need for surgical revision, especially, in patients where compromised immunity or socio-economic factors have contributed to the burden of disease.

Fig. 2 .
Fig. 2. Computed tomography showing lytic osseous lesions of the ramus of the right mandible, in transverse view.