Actinomyces Orbital Osteomyelitis in the Setting of Multiple Myeloma and Bisphosphonate-Related Osteonecrosis

Actinomyces is a genus of filamentous, branching gram-positive bacteria that are commensal organisms in the oral cavity, although they may become invasive in both immunocompetent and immunocompromised patients (1). Infection may extend from cervicofacial foci along tissue planes, through the foramina or directly through bone, yet Actinomyces is a rare cause of orbital infection (2-4). We describe a patient with orbital osteomyelitis and vision loss in the setting of bisphosphonate-related osteonecrosis of the jaw (BRONJ), a poorly understood disease process that has been linked to Actinomyces osteomyelitis.

Clinical Correspondence Actinomyces Orbital Osteomyelitis in the Setting of Multiple Myeloma and Bisphosphonate-Related Osteonecrosis Katherine S. Hu, BA, Sangeeta Khanna, MD A ctinomyces is a genus of filamentous, branching grampositive bacteria that are commensal organisms in the oral cavity, although they may become invasive in both immunocompetent and immunocompromised patients (1). Infection may extend from cervicofacial foci along tissue planes, through the foramina or directly through bone, yet Actinomyces is a rare cause of orbital infection (2-4). We describe a patient with orbital osteomyelitis and vision loss in the setting of bisphosphonate-related osteonecrosis of the jaw (BRONJ), a poorly understood disease process that has been linked to Actinomyces osteomyelitis (5,6). A 69-year-old man with a history of multiple myeloma (IgA gammopathy, in remission) and glaucoma experienced persistent jaw pain, temporal headaches, and insidious onset of painless vision loss in his right eye over 4 months. Previous treatment of his multiple myeloma with zoledronic acid (infusion every 3 months for 4 years) was complicated by osteonecrosis of the jaw resulting in an oroantral fistula of the right maxilla, requiring 2 oral surgeries within the past 8 months. On referral to our neuro-ophthalmology service, visual acuity was no light perception, right eye, and 20/30, left eye. Fundus examination revealed asymmetrically cupped optic discs. There was 3 mm of right proptosis and mild limitation of abduction of the right eye. Imaging of the brain and orbits revealed extensive inflammatory changes in the right maxillary sinus, right ethmoid sinus, and right orbit extending posteriorly into the middle cranial fossa with osseous thickening and destruction (Fig. 1). The patient underwent endoscopic right-sided sinus surgery with decompression of the orbital apex and biopsies of bone and sinus mucosa. Histopathology showed osteonecrosis and acute osteomyelitis with abundant mixed bacteria without fungal or neoplastic elements. A gram stain was not performed. Biopsy cultures were unremarkable, but an anaerobic culture was not ordered. Flow cytometry on biopsied tissue was negative for a lymphoproliferative process and serum protein electrophoresis, and immunoglobulin levels did not show recurrence of multiple myeloma. FIG. 1. Neuroimaging studies: Computed tomography of facial bones in axial (A) and coronal (B) projections shows osseous thickening and destruction of the right maxillary sinus walls and skull base. There is complete loss of the bony floor of the right maxillary sinus (arrow). C. Postcontrast coronal T1 MRI reveals inflammatory changes in the right maxillary and ethmoid sinuses with abnormal enhancement within the right orbit. Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, Missouri. The authors report no conflicts of interest. Address correspondence to Sangeeta Khanna, MD, Department of Ophthalmology, Saint Louis University School of Medicine, 1755 S. Grand Boulevard, St. Louis, MO 63104; E-mail: [e-mail] 120 Review of previous operative reports revealed that a bone biopsy was obtained 4 months prior at the time of a layered closure of the oroantral fistula. This biopsy showed necrotic bone with filamentous, gram-positive organisms consistent with Actinomyces (Fig. 2). Despite the surgical pathology report of osteomyelitis, the patient had only received Hu and Khanna: J Neuro-Ophthalmol 2019; 39: 120-121 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Pathology of right maxillary bone biopsy. A. Necrotic bone is present with inflammatory cells and paratrabecular neutrophils (hematoxylin & eosin, ·200). B. Filamentous, gram-positive organisms consistent with Actinomyces are present (gram stain, ·400). a ten-day course of amoxicillin/clavulanic acid. Following an infectious disease consultation, the patient was treated for Actinomyces with 6 weeks of ceftriaxone and oral metronidazole, and 6 months of oral penicillin. Vision in the right eye did not recover, but his headache and facial pain resolved and vision in the left eye remained stable. Computed tomography 6 months after completion of antibiotic therapy revealed resolution of orbital soft-tissue changes and lateral rectus muscle enlargement. Irregular sclerosis, fragmentation, and expansion of the walls of the right maxillary sinus, right sphenoid sinus, right greater sphenoid wing, and right pterygoid body remained unchanged. A repeat scan 1 year later showed an increase of reparative bone formation, and the patient has remained stable over 2 years of follow-up. Our patient developed an orbital infection with vision loss in the setting of BRONJ, a disorder in which increased virulence of Actinomyces may occur. Intravenous bisphosphonates frequently are used in patients with multiple myeloma and other cancers to decrease risk of lytic bone lesions. However, BRONJ may occur in 4%-10% of these patients (5). Although BRONJ most often affects the mandible (1,6), maxillary involvement, as seen in our patient, is a risk factor for orbital extension of Actinomyces osteomyelitis. Although the etiology of BRONJ remains uncertain, it has been proposed that bisphosphonate-related damage allows bone to become susceptible to colonizing Actinomyces from the oral cavity, resulting in osteomyelitis-associated lesions (5,6). Cultures are not always positive due to strict anaerobic and fastidious growth requirements. Diagnosis is often made on histopathology with detection of grampositive branching, filamentous bacilli. Prolonged jaw or facial pain, as well as any history of bisphosphonate treatment, BRONJ, or previous oral surgeries should raise suspicion and prompt imaging with gram stain of biopsy Hu and Khanna: J Neuro-Ophthalmol 2019; 39: 120-121 specimens. A multidisciplinary approach with oralmaxillofacial, oncology, and infectious disease specialists is needed to determine optimal treatment with appropriate antibiotics, surgery, or a combination of both (5,6). STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. Khanna and K. S. Hu; b. Acquisition of data: S. Khanna and K. S. Hu; c. Analysis and interpretation of data: S. Khanna and K. S. Hu; Category 2: a. Drafting the manuscript: S. Khanna and K. S. Hu; b. Revising it for intellectual content: S. Khanna and K. S. Hu; Category 3: a. Final approval of the completed manuscript: S. Khanna and K. S. Hu. ACKNOWLEDGMENTS The authors thank M. Drake Poeschl, MD, from Mercy Hospital, St. Louis, for aid in providing pathology slides for this case. REFERENCES 1. Kononen E, Wade W. Actinomyces and related organisms in human infections. Clin Microbiol Rev. 2015;28:419-442. 2. Sullivan TJ, Aylward GW, Wright JE. Actinomycosis of the orbit. Br J Ophthalmol. 1992;76:505-506. 3. Hegde V, Outhran N, Mahesha S, Anupama B. A rare and unusually delayed presentation of orbital actinomycosis following avulsion injury of the scalp. Indian J Ophthalmol. 2010;58:238-240. 4. Pagliani L, Campi L, Cavallini GM. Orbital actinomycosis associated with painful ophthalmoplegia. Ophthalmologica. 2006;220:201-205. 5. Rasmusson L, Abtahi J. Bisphosphonate associated osteonecrosis of the jaw: an update on pathophysiology, risk factors and treatment. Int J Dent. 2014;2014:471035. 6. Ceulaer D, Tacconelli E, Vandecasteele SJ. Actinomyces osteomyelitis in bisphosphonate-related osteonecrosis of the jaw (BRONJ): the missing link? Eur J Clin Microbiol Infect Dis. 2014;33:1873-1880. 121 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.