Actinomycosis in the maxilla of a young asymptomatic patient: unusual case report

ABSTRACT The aim of this study is to report an unusual case of actinomycosis in the maxilla region of an asymptomatic patient. A 21-year-old white man was referred for the analysis of panoramic radiography and cone beam computed tomography, where it was observed the presence of a hypodense lesion on the left side of the maxilla, which extended from the maxillary left central incisor to the region of the maxillary left second premolar. During intraoral examination, a depression was observed in the hard palate mucosa, as well as a fistula in the alveolar mucosa close to maxillary left central incisor, which had pulp vitality confirmed by thermal tests. A fistulography was performed, with periapical radiography, where it was found that the fistulous path did not originate from the tooth mentioned above. An incisional biopsy was performed for diagnostic purposes. However, given the inconclusive microscopic findings, four months later, a new biopsy was performed. The histopathological examination revealed the presence of a colony of microoganisms with filamentous pattern of radiated rosette, surrounded by polymorphonuclear inflammatory cells. Based on the morphological characteristics, the diagnosis of actinomycosis was established. The treatment was based on antibiotic therapy. Six months after treatment of the infection, no signs of recurrence were observed, and the patient remains in follow-up. Actinomycosis in the maxilla is an uncommon infection with a predilection for males between the ages of 20 and 60, whose treatment is antibiotic therapy associated or not with surgical excision.


INTRODUCTION
Actinomycosis is a subacute to chronic infection caused by filamentous Gram-positive bacteria, anaerobic [1,2], non-acidic [1,2] and without spores.This disease has, clinically, four types: thoracic, abdominopelvic, cerebral and cervicofacial [2].The latter usually affects the body of the jaw, followed by the mental region and angle of the jaw, but rarely affects the maxilla or the temporomandibular joint [3].
Actinomycosis in the maxilla accounts for only 0.5% to 9% of all head and neck cases [4], with periapical actinomycosis being one of the rarest forms of actinomycosis occurring in the maxillofacial region [5].The pathogenesis of cervicofacial actinomycosis is not exactly known, however, dental caries and trauma seem to be favorable factors to the development of the disease [4,6].Loss of mucosal integrity caused by tooth extractions, periodontal disease [4,6], local anesthesia, bone or dental fractures, tooth eruption, pulp exposure or even endodontic treatment [6] and non-vital teeth can function as a gateway for these bacteria, and thus, start the infection [4].
The most common clinical presentation of actinomycosis is soft tissue abscess and drainage of cervical fistulas [4,7].The skin that covers the abscess is red to purplish and hardened on palpation [7].The discovery of "holes" or large defects of the jaw bone within the oral cavity is a relatively unusual presentation of cervicofacial actinomycosis, when it results in osteomyelitis [3,4].
Actinomycosis is termed "masker" in the head and neck region due to its unusual presentations [4], because it often mimics a malignant lesion or a granulomatous lesion [8].Therefore, the final diagnosis is usually reached only after surgical removal of the lesion and the histopathological examination of the sample.Long-term high-dose penicillin is needed for treatment [4,6], which can vary from four weeks to one year, based on the severity of the disease.
Given the above, the objective of the present study is to report an unusual case of actinomycosis in the maxilla region of an asymptomatic young patient.

CASE REPORT
A 21-year-old white man was referred by an orthodontist for the analysis of cone-beam computed tomography, in which significant imaging alterations were observed.During the anamnesis, the patient reported that there had been no previous use of bone modifying agents.The extraoral physical examination did not reveal any changes.On intraoral physical examination, a soft and resilient depression was observed in the mucosa of the hard palate, in addition to a parulis in the alveolar mucosa at the height of the maxillary left central incisor, which had pulp vitality confirmed by thermal tests.A fistulography was performed, with periapical radiography, where it was found that the fistulous path did not originate from the tooth mentioned above.
In cone beam computed tomography, a hypodense image was observed, extending from the region of the maxillary left central incisor to the region of maxillary left second premolar, with regular margins and well-defined limits.
In addition, it was also possible to observe the withdrawal of the roots of maxillary left central incisor, maxillary left lateral incisor and maxillary left canine, in absence of root resorption (figure 1A); compression of the anterior wall of the maxillary sinus (figure 1B) and expansion and rupture of the vestibular and palatal cortex of the incisive canal (figure 1C).Under the diagnostic hypothesis of a cyst of odontogenic nature, an intraosseous incisional biopsy was chosen to be performed, with access through the palatal region.In view of the inconclusive microscopic findings, monitoring of the patient for four months was recommended, to then perform a new biopsy, which was performed after evaluation of a tomographic examination, which revealed the stagnation of the lesion, without increasing the extent of bone destruction.In the second biopsy, a partial resection of the lesion was performed.At this time, a Partsch type incision was made in the alveolar mucosa, vestibule background, followed by a bone window in the left hemimaxila, to access the lesion (figures 2A and 2B).Then, the bone cavity was curetted, and fragments of the lesion were removed followed by the overlying mucosa suture (figures 2C and 2D).
Histopathological analysis of soft tissue fragments showed the presence of connective tissue which varied in density, with collagen fibers randomly arranged, permeated by fusiform and ovoid fibroblasts, in addition to inflammatory infiltrate, predominantly lymphoplasmacytic, and blood vessels, of various calibers and congested by red blood cells, with hemorrhagic areas.In the focal area, there was a microorganism colony with a filamentous pattern of radiated rosette, whose central portions were basophilic and the peripheral ones, eosinophilic, surrounded predominantly by polymorphonuclear cells (figure 3A).
Regarding the analysis of the histological sections of the bone pieces, it was possible to verify, on the periphery of the specimen, trabrecular bone with normal aspect.In addition, there was an intense presence of foamy macrophages,  endothelial cells, and few multinucleated giant cells.In these areas, cells with altered morphology and some mitosis figures were observed (figures 3B and 3C).In order to rule out the possibility of being a neoplastic lesion, the immunohistochemical marker CD68 was used, which demonstrated immunopositivity for foamy macrophages (figure 3D).
The diagnosis of actinomycosis was established, and the chosen treatment was antibiotic therapy with Amoxicillin (875mg) associated with Clavulanic Acid (125mg) (Generic Medication Law No. 9,787, 1999), for 30 days, one tablet every 12 hours.The antibiotic time was reduced as a result of the surgical intervention performed previously.After finishing the drug therapy, a panoramic radiography was performed, indicating slight regression of the lesion.Therefore, the patient was instructed to attend periodically.Upon patient's return, four months later, it was observed that the maxillary left central incisor had extensive provisional restoration and compromised marginal sealing, as well as the maxillary left lateral incisor, which presented unsatisfactory restoration.Sensitivity tests were performed to evaluate the pulp vitality of both teeth, and both showed a negative response to the tests.Periapical radiography was performed, and the lesion was located at the root apex of these two teeth.In view of this, endodontic treatment of both teeth was requested, and, after the endodontic treatments were completed, total lesion regression was observed (figure 4).Six months after the infection treatment, no clinical or radiographic signs of recurrence were observed, and the patient remains in follow-up.

DISCUSSION
Actinomycosis is a rare granulomatous suppurative disease caused by Actinomyces spp [3,4], originated from the Greek word "Aktino", which means radiant appearance of sulfur granules, and "Mykos", which labels the condition as mycotic disease [1,3].However, actinomycetes are now grouped as bacteria, due to their composition in the cell wall, lack of nuclear membrane and lack of growth inhibition by antifungal agents [4].Like fungi, these bacteria form a mycelial network of branched filaments, but like bacteria, they are thin, have cell walls containing muramic acid and are susceptible to antibiotics [3].
Typically, these bacteria have low potential for pathogenicity or invasion [1], but they become pathological when gaining access to subcutaneous tissues.In addition, the infection is polymicrobial, with up to five to 10 other bacterial species present [10], like Staphylococcus and Streptococcus [4].These associated bacteria seem to increase the low pathogenic potential of actinomycetes [4], working synergistically to form a specific ecosystem with low oxidation reduction potential favorable to anaerobic growth [11].
In cases of actinomycosis in the apical region, the source of infection can be intraradicular biofilm or extraradicular bacterial aggregations, such as sulfur granules [9].In addition to local risk factors for the development of infections, diabetes mellitus, alcohol use disorders, malnutrition, malignancies, HIV+ patients, transplantation of solid organs such as lungs and kidneys, biological agents such as infliximab and acute lymphoblastic leukemia treated with chemotherapy are other known risk factors [10].In the case reported here, the patient did not have any systemic factors that could trigger an infection, and one of the teeth associated with the lesion, confirmed with fistulography, showed positive response to pulp sensitivity tests.In addition, the patient had no history of trauma or soft tissue lesion.
Cervicofacial actinomycosis is a relatively rare condition worldwide, without any predilection for age, race [6] and sex.In the study by Pulverer et al. [12], aiming to evaluate microbiological and clinical data from 1997 cases of human cervicofacial actinomycosis, a predisposition of male patients was observed, which varied with age and it seemed to be especially pronounced in patients aged from 20 to 60 years, with a higher incidence found in female patients aged from 11 to 40 years and in male patients aged from 21 to 50 years old.This infection usually involves tissues around the maxilla or mandible, including the mandible itself in approximately 50% of cases, buccal mucosa (15%), mentum (15%) and branch and angle of the mandible (10%) [6].Few cases in the literature report maxillary involvement [1,11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] (table 1).In the present case, the patient was male, 21 years old and the lesion was present in the anterior region of the maxilla.Although the patient in the present case was quite young, two cases of 16-year-old patients have already been reported [13,14].Clinically, cervical actinomycosis presents as a significant increase in volume associated with external drainage ulcers, fistulas and, occasionally, sulfur granules [10].In addition, it is asymptomatic, hardened on palpation and may present a reddish to purplish color, which evolves to multiple abscesses [10].When located in the maxilla region, the authors report, in their cases, as ulcerated areas involving bone destruction [11,22], which may be associated with areas of multiple bone sequestrations exposed in the oral cavity [19].In its occurrence, when symptomatic, in the periapical form, it presents as a persistent and recurrent drainage fistula in the periapical region [5].In the present case, the patient did not present painful symptoms or any increase in volume, despite the extent of the lesion.On the other hand, a parulis was observed in the region above maxillary left central incisor, which was vital by pulp sensitivity tests.
The imaging findings are nonspecific and do not contribute to the diagnosis of the disease but will help to assess the degree of involvement of soft tissues and bones.Periapical radiographs are useful in assessing apical abscesses [10].In the case reported here, panoramic radiography and cone beam computed tomography were performed for orthodontic purposes, being the lesion discovered accidentally.A fistulography was performed, with periapical radiography, where it was found that the fistulous path did not originate from the tooth mentioned above.The other imaging exams were essential for knowing the extent of the lesion and planning the surgery.
The diagnosis of infection is made based on clinical manifestations, associated with microbiological and histopathological findings [30].In the case reported here, clinical, imaging, and histopathological findings were used to close the diagnosis due to the initial diagnostic hypotheses.A fact also to be considered is the difficulty of conducting the cultivation of bacterial species in an anaerobic environment for subsequent microbiological analysis.
Microscopically, it is possible to observe a zone of granulation tissue that consists of collagen fibers around central purulent loculations containing abundant neutrophils [4,22].In the central part, bacterial colonies are observed, with small basophilic heads called conidiophores towards the center and thin eosinophilic hyphae radiating outwards towards the periphery [4].In the present case, this characteristic pattern was observed and to discard the hypothesis of neoplastic lesion, the immunohistochemical marker CD68 was used, which was positive for foamy macrophages.
For the treatment of actinomycosis, antibiotic therapy with 6 to 12 million IU penicillin is recommended, which can vary from four weeks to one year, based on the severity of the disease [8].In addition, drainage of abscesses, debridement and surgical excision of the sinus tract is recommended to increase the penetration of antibiotics [4].Surgical treatment without antibiotic therapy is associated with recurrence.Although good responses have been reported with combined surgical treatment and short-term antibiotic therapy for cervicofacial actinomycosis, surgical treatment is associated with morbidity, especially with extensive lesions [8], therefore, the need for surgical treatment associated with antibiotic therapy must be carefully considered.In the present case, curettage of the lesion associated with the prescription of 30 days of amoxicillin (875 mg) associated with clavulanic acid (125 mg) was performed.After this period, no signs of recurrence were observed, and the patient remains in follow-up.However, even though surgery was effective in the treatment and essential to reduce the time of antibiotic therapy, probably led to necrosis of the involved teeth.
It is concluded that the present case was of a young patient with actinomycosis in the maxilla without clear evidence of infection, whose treatment of choice was surgery associated with antibiotic therapy.Surgical treatment favored a reduction in the time of antibiotic use and this association promoted an excellent recovery.Despite this, the surgery led to necrosis of the involved teeth and endodontic treatments were performed.

Collaborators
TJ Silva Filho and DQC Gomes, conception and design of the case report.JLSH Pereira, RCV Souza, TJ Silva Filho and DQC Gomes, clinical management of the patient.DFB Silva and TJ Silva Filho, analysis and interpretation of radiographic and histopathological data.JLSH Pereira, DFB Silva and IJ Dias, article writing.TJ Silva Filho, RCV Souza and DQC Gomes, critical revision of the text.

Figure 1 .
Figure 1.A: Cone beam computed tomography in panoramic reconstruction.To observe hypodense image in the maxilla, on the left side, of teeth 21 to 25. B: Cone beam computed tomography, in axial section, showing the extent of the lesion.C: Axial section on a cone beam computed tomography showing a rupture of the incisive canal cortex.

Figure 2 .
Figure 2. A: Incision in the mucosa.B: Opening the bone window.C: Access to the injury.D: Suture (3-0 silk thread).

Figure 4 .
Figure 4. Panoramic radiograph showing total regression of the lesions that were at the apexes of teeth 21 and 22.

Table 1 .
Cases of actinomycosis involving the maxilla reported in the literature.

Table 1 .
Cases of actinomycosis involving the maxilla reported in the literature.

Table 1 .
Cases of actinomycosis involving the maxilla reported in the literature.