Abstract

Background: Actinomycosis is a rare infection, frequently misdiagnosed as a neoplasia. This chronic and granulomatous disease is caused by Actinomyces israelii species. Cervicofacial actinomycosis occurs in 60% of cases and the diagnosis is commonly made by histopathology study.

Case Description: We report a case of fronto-orbital osteomyelitis initially misdiagnosed as a cranial bone meningioma, but later proved to be a case of actinomycosis. ^99mTechnetium (^99mTc) three-phase bone single-photon emission computed tomography/computed tomography (SPECT/CT) and ^99mTc-ubiquicidin (UBI) 29-41 bone SPECT/CT scans were performed to corroborate the control of the infection.

Conclusion: Craniofacial actinomycosis is the most common presentation of actinomycosis. However, it continues to be a rare and difficult disease to diagnose and is often confused with a neoplastic process. The ^99mTc-UBI 29-41 bone SPECT/CT scan could be an auxiliary noninvasive diagnostic alternative and a follow-up method for these patients.

Keywords: Actinomyces, Craniofacial, Osteomyelitis

INTRODUCTION

Actinomycosis is a rare invasive bacterial disease that causes a chronic, suppurative, granulomatous infection. Actinomyces israelii are Gram-positive, anaerobic, filamentous bacilli that have low pathogenicity and normally colonize the mouth and gastrointestinal tract.[ 4 ] This disease can affect multiple anatomical sites, being the cervicofacial presentation (60%) the most frequent[ 17 , 22 , 25 ] followed by the thoracic pulmonary (30%) and abdominopelvic (20%). Central nervous system (CNS) involvement is less common.[ 10 , 11 , 20 ] This disease can mimic neoplastic processes, tuberculosis, nocardiosis,[ 22 , 25 ] and even fibrous dysplasia.[ 11 ] In consequence, the diagnosis of actinomycosis is challenging and the disease is frequently overlooked.

Given that actinomycosis is a purulent bacterial infection, radiotracers which detect bacteria colonization have diagnosis potential. Recent reports have showed that ^99mtechnetium-ubiquicidin (^99mTc-UBI) 29-41 bone single-photon emission computed tomography/computed tomography (SPECT/CT) scan can be a useful diagnostic study for pyogenic vertebral osteomyelitis.[ 9 , 15 ] This radiotracer can differentiate inflammatory from infectious processes.[ 7 ]

The diagnosis of actinomycosis is made by a positive culture or the visualization of necrosis with sulfur granules and Gram-positive filamentous bacteria in the histopathology study.[ 24 ] Therapy consists in high doses of penicillin’s G or amoxicillin for long periods of time (6–12 months).[ 24 ]

CASE DESCRIPTION

A 57-year-old woman from Torreon Coahuila was referred in November 2015 for sudden increase in volume of the right fronto-orbital region. The patient reported a contusion in the right frontal region 1 month before and was underwent treatment with metronidazole but not improvement was observed [ Figure 1a - c ].

Figure 1:

(a) Presurgical images, significant bilateral fronto-orbital defect, predominantly right side. (b and c) control 3 years after surgery, significant remission of bone deformity.

Relevant antecedents included cardiothoracic surgery at 4 years old to treat an unspecified cyanotic heart condition and in 1992 plastic surgery established the diagnosis of “craniofacial dysostosis” and a fronto-orbital advancement, including osteotomies and bone cranial remodeling with methyl methacrylate.

In January 2016, a magnetic resonance imaging study reported heterogeneous enhancement mass in the bilateral fronto-orbital region [ Figure 2a - c ] Pre-surgical MRI and [ Figure 2d - f ] post-surgical CT scan, control 6 months after surgery, causing significant craniofacial deformation a malignant neoplastic process was suspected. Bone meningioma (an atypical location) [ Table 1 ], bone metastasis, and monostotic fibrous neoplasm were considered into the differential diagnoses. During screening for a primary tumor, a thoracic abdominal CT scan was performed. In May 2016, a highly vascularized hyperostotic lesion was partially resected. This procedure was aborted as consequence of an important intraoperative hemorrhage. Pathology reported fibroconnective tissue with hemorrhage, fibrin, and unspecified polymorphonuclear inflammatory infiltrate. As the craniofacial bone deformity worsened with bilateral ocular extension, a second partial resection was performed in September 2016. Histopathological findings included a multifocal foreign body-type granulomatous lesion and granulation tissue [ Figure 3 ].

Figure 2:

(a-c) (Upper quadrants) Presurgical gadolinium-enhanced T1-weighted magnetic resonance imaging showing heterogeneous enhancement mass in the bilateral fronto-orbital region predominantly on the right side, we can see a hypodensity in relation to methyl methacrylate. (d-f) (Lower quadrants) Computed tomography scan control 6 months after the medical treatment with resolution of the deformity.

Figure 3:

Hematoxylin and eosin staining. Basophilic structure, granular, and peripheral-pseudopalisading, hemorrhagic background, and peripheral lymphocytic and polymorphonuclear infiltrate.

The culture was reported negative, but tissue staining with hematoxylin and eosin revealed bacilli compatible with A.israelii was isolated in the tumor tissue by histopathological study by staining for hematoxylin and eosin [ Figure 3 ]. Amoxicillin-clavulanic acid 3 times a day was initially indicated and followed by intramuscular benzathine penicillin’s every 2 weeks for 6 months. At the end of the treatment, infectious remission had been achieved. In 2017, the supraorbital methyl methacrylate bar was surgically removed [ Figure 4a and b ]. No recurrence of the deformity was identified in the follow-up visits. In February 2020, ^99mTc three-phase bone SPECT/CT scan and ^99mTc-UBI 29-41 bone SPECT/CT scan was performed, and a negative infection result was reported [ Figure 4c and d ].

Figure 4:

(a and b) 3D computed tomography (CT) scan showing silicone implants in the chin and zygomatic bone, a supraorbital methyl methacrylate bar and plates in the bilateral parietal region (upper quadrants). (c and d) (Lower quadrants): ^99mtechnetiumUbiquicidin (29–41)/three-phase bone single-photon emission computed tomography/CT scan control 3 years after the last surgical intervention showing diffuse uptake of the radiotracer, suggestive of an inflammatory process, an active infectious process is ruled out.

DISCUSSION

Cervicofacial[ 5 , 19 , 21 , 26 ] or craniofacial[ 1 , 16 , 18 , 23 ] Actinomyces is the most common presentation of actinomycosis, accounting for 60% of cases [ Tables 1 and 2 ].[ 17 , 22 , 25 ] Brain abscesses are the rarest and most serious presentation of the infection by A.israelii.[ 3 , 10 , 11 ] Bonnefond et al.[ 4 ] reported a series of 28 patients with A.israelii, including five cases with orocervicofacial presentation (17%) and one patient with intracranial involvement. In 92% of cases, the diagnosis was not suspected at admission. This infection frequently misdiagnosed with neoplastic processes, such as meningioma,[ 6 , 8 , 12 , 13 ] granulomas, and osteomyelitis secondary to tuberculosis or nocardiosis.[ 22 , 25 ] In the present case, we did not consider actinomycosis in the initial differential diagnosis. However, it is important to suspect this entity in cases with recurrent craniofacial deformations and a history of dental extractions with alveolar abscesses,[ 16 , 26 ] ontological surgeries, and reconstructive surgeries with prosthetics as methyl methacrylate.

Table 1:

Published cases of craniofacial Actinomyces with misdiagnosis of meningioma.

Table 2:

Cases reported with craniofacial and CNS Actinomyces israelii.

A positive uptake with ¹⁸F-fluorodeoxyglucose positron emission tomography/CT,[ 14 ] tecnetium-99mmethoxyisobutylisonitrile and Thalio-201[ 2 ] has been reported in cases of actinomycosis infection with a previous misdiagnosis of neoplastic disease. However, UBI 29-41 is an antimicrobial peptide with greater effectiveness against bacterial diseases.[ 23 ] ^99mTc-UBI 29-41 bone SPECT/CT scan is an useful radiotracer in the diagnosis of pyogenic vertebral osteomyelitis[ 9 , 15 ] with a high sensitivity and specificity (96.3% and 94.1%, respectively).[ 7 ] Diagnostic accuracy for osteomyelitis is 100% in studies with ^99mTc-UBI 29-41 bone SPECT/CT scan versus 90% reported in ^99mTc three-phase bone SPECT/CT scan.[ 7 ] We performed ^99mTc three-phase bone SPECT/CT and ^99mTc-UBI 29-41 bone SPECT/CT scans as part of the follow-up protocol in this patient, to screen for sings of active infection. Nevertheless, no reports have been found in literature about the use of radiopharmaceuticals in cranial osteomyelitis diagnosis. However, we consider that they could be a promising auxiliary diagnostic and follow-up method in patients with confirmed craniofacial actinomycosis although more studies are required.

A positive actinomycosis culture occurs in 50% of cases. Therefore, diagnosis is generally made by histology.[ 24 ] Bonnefond et al.[ 4 ] reported a series with 50% of cultures positive for A.israelii. In contrast, only 42% of histopathological studies were positive, even though 71% of the patients underwent a biopsy. However, most of the cases had an abdominopelvic presentation (9/28) and only five patients had a craniofacial disease. A positive culture in cases with craniofacial or CNS presentation was uncommon[ 3 , 21 , 23 ] and the diagnosis was made by histopathology sand immunohistochemistry[ 10 ] or PCR[ 16 ] for A.israelii.

Patients with actinomycosis require high doses of penicillin’s G or amoxicillin for long periods of time (6–12 months), but the duration of antimicrobial therapy could be reduced to 3 months in patients with total surgical resection.[ 24 ] In Bonnefond et al.[ 4 ] study, a treatment with amoxicillin for approximately 120 days (range 60–180) was indicated. Metronidazole has not demonstrated effectiveness in craniofacial A.israelii[ 24 ] and therefore should not be used. In the case here presented, penicillin’s treatment of 100–200 mg/kg per doses was maintained for 6 months. This patient progression was controlled and resolution was achieved only after targeted antibiotic treatment was established.

CONCLUSION

Craniofacial actinomycosis is the most common presentation of actinomycosis. However, it continues to be a rare and difficult disease to diagnose and is often confused with a neoplastic process.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgments

None.

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