Oral and Maxillofacial Surgery

https://doi.org/10.1007/s10006-020-00896-x

CASE REPORT

Cervicofacial actinomycosis following third molar removal:

case-series and review
Cedric Vandeplas 1 & Constantinus Politis 2,3 & Johan Van Eldere 4,5 & Esther Hauben 6,7

Received: 22 May 2020 / Accepted: 11 August 2020

# Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract
Actinomycosis is an opportunistic infection caused by bacteria of the Actinomyces spp., commonly A. israelii. These are non-
pathogenic commensals in the mouth, gut, and female genital tract. An infection may arise following trauma or surgery, such as
tooth extraction. More than half of cases of actinomycosis occur in the perimandibular area and are termed cervicofacial
actinomycosis. Initially, the infection develops as a painful, rapidly progressive swelling. The lesion may then indurate and is
often painless while the overlying skin discolors red to purple-blue. Prolonged treatment with antibiotics and surgery are often
required for resolution, unless treatment is promptly started. However, diagnosis may be delayed or missed because of difficult
bacterial culturing and frequent confusion with malignancy and other infections. This case study describes six patients who
developed cervicofacial actinomycosis following third molar extraction. The purpose of this study is to inform clinicians on this
stubborn and deceitful disease entity and to highlight the importance of clinical recognition for quick resolution with minimal
morbidity.

Keywords Actinomycosis . Actinomyces . Cervicofacial actinomycosis . Third molar . Extraction . Infection

Introduction many other diseases, such as malignancy, tuberculosis, epi-

dermoid cyst, and various infections of bacterial and fungal
Actinomycosis is an odd and peculiar infection. It has fittingly origin. When first described in humans by Langenbeck in
been described as “a great pretender” and “the most 1845, it was in fact thought to be a fungal infection, owing
misdiagnosed disease” due to its clinical similarities with to the filamentous shape of the microbes that resemble fungal
hyphae. This is reflected in the term “actinomycosis” from the
Greek aktino and mykos, meaning “ray-fungus.” It is now
* Cedric Vandeplas known that the microbes of actinomycosis are in fact bacteria.
cedricvandeplas@gmail.com They are non-pathogenic inhabitants of mucous membranes
that may cause an opportunistic infection when the mucous
1
Faculty of Medicine, KU Leuven, Sint-Jansbergsesteenweg 3, box
membrane is disrupted, such as after surgery.
0201(D), 3001 Leuven, Belgium In this report, six patients are described who underwent
2
Department of Oral and Maxillofacial Surgery, University Hospitals
third molar extraction and consequently developed
Leuven, Leuven, Belgium cervicofacial actinomycosis. Common clinical features and
3
Department of Imaging and Pathology, Faculty of Medicine, KU
relevant diagnostic considerations are outlined.
Leuven, Leuven, Belgium
4
Department of Laboratory Medicine, University Hospitals Leuven,
Leuven, Belgium Presentation of cases
5
Department of Microbiology, Immunology and Transplantation,
Faculty of Medicine, KU Leuven, Leuven, Belgium Between January 2010 and December 2019, six patients
6
Department of Pathology, University Hospitals Leuven, were diagnosed with cervicofacial actinomycosis follow-
Leuven, Belgium ing third molar extraction at the Department of Oral and
7
Department of Imaging and Pathology, Translational Cell and Tissue Maxillofacial Surgery, University Hospitals Leuven,
Research, Faculty of Medicine, KU Leuven, Leuven, Belgium Leuven, Belgium.

The following data were collected from the patient files:
age, sex, symptoms, diagnosis, treatment, resolution, and clin-
ical photographs. These data are detailed in Table 1.
All patients were female. Ages ranged between 14 and 30
years (mean 20.7 years). Three patients (cases 1, 5, and 6)
underwent prophylactic third molar removal; the other three
patients (cases 2, 3, and 4) had their third molars removed due
to pericoronitis. All cases involved extraction of a mandibular
third molar. None involved the maxilla.
The onset of symptoms ranged from several days to 3
months after extraction.
The most common symptoms were swelling in the
perimandibular area, pus formation, induration of the lesion,
migratory abscess, and skin discoloration (100%; present in
all cases). Four patients had pain (66.7%), three had devel-
oped fistulas (50%), and in one patient the abscess pus
contained sulfur granules (16.7%). Trismus, cachexia, and
pyrexia were either not present or not reported. Five patients
had radiographs in their records, but none demonstrated de-
struction of bone (indicative of actinomycotic osteomyelitis).
All diagnoses were based on characteristic clinical signs.
Additionally, five patients had pus samples taken, of which
two were positive for actinomyces in culture and three were
negative. One patient had an excisional biopsy taken and also
tested positive in culture. Diagnoses were made between 10
Table 1 Tabulation of case details. FNAC fine needle aspiration cytology. : positive/present; : negative/not present; ?: not specified
Oral Maxillofac Surg
weeks and 10 months after onset of symptoms (mean 7.6
months). The most delayed diagnosis (10 months after symp-
tom onset) was delayed because of incorrect diagnosis as id-
iopathic lymphadenopathy (case 4). As demonstrated by these
cases, diagnosis is often missed or delayed in the early stages
of disease. Reasons for these delays and ways to avoid these
scenarios will be discussed below.
Of the six patients, four had received routine courses of
low-dose penicillin or tetracycline antibiotics which were un-
successful before final diagnosis was confirmed. After diag-
nosis, all patients were treated with various doses of penicillin:
either clometocillin (cloxacillin), benzylpenicillin (long-act-
ing), or amoxicillin, with or without addition of clavulanic
acid. Except for two patients, every patient received either a
different drug or different daily dose. The duration of antibi-
otic therapy (not including previous unsuccessful treatment)
ranged between 4 and 18 months (mean 10.7 months) (Fig. 1).
Three patients underwent additional surgical drainage due to
poor response to initial antibiotic treatment (cases 2 and 4, also
see Fig. 2) or extensive infection (case 6). Resolution of the
lesion was reached in all patients, from 6 to 21 months after
the onset of symptoms (mean 16.3 months). At the time of
resolution, the three patients who previously had fistulas now
had a visible skin scar. The other three patients who did not
previously develop fistulas only had palpable subcutaneous
Oral Maxillofac Surg
Fig. 1 Visualization of individual treatment courses. The lengths of the
bar segments are representative of the time between each stage of
treatment as described in Table 1. A: third molar extraction; B: onset of
symptoms; C: diagnosis and treatment; D: resolution
scarring with no visible skin scar. These records were in ac-
cordance with comparable previous reports, apart from the
male to female ratio, however. This is most likely coincidental
given the small sample size.
Discussion
Pathogenesis
Actinomycosis is a bacterial infection. As the name suggests,
Actinomyces exhibit clinical and microscopic characteristics
that resemble fungi. That is to say, the bacteria are filamentous
and resemble fungal hyphae. Furthermore, the disease spreads
by direct extension through the surrounding tissues, which is
quite atypical for a bacterial infection [1–3]. It is caused by
bacteria of the Actinomyces spp., most commonly A. israelii
Fig. 2 Clinical photographs of case 1. Left: at the start of treatment; middle: after 13 months of treatment; right: after 18 months of treatment. Note the
anterior position of the skin swelling in relation to the third molar extraction socket
and A. gerencseriae in humans. These are anaerobic, Gram-
positive, bacteria that are part of the commensal flora of the
mucous membranes in the gastrointestinal tract, female genital
tract, and oropharynx [2, 4–6]. These bacteria are normally
non-pathogenic but may cause an opportunistic infection
when the mucous membrane is breached by local trauma,
typically following tooth extraction or jaw surgery. Over half
of cases arise in the perimandibular area and are termed
cervicofacial actinomycosis. Dental extractions, especially
mandibular molar extractions, are considered the leading
cause of cervicofacial actinomycosis and even actinomycosis
as a whole [4, 7–12].
The occurrence of actinomycosis correlates with poor oral
hygiene, diabetes, immunosuppression, radiotherapy,
bisphosphonates, smoking, and alcoholism [1, 2, 7, 9].
It has been postulated that Actinomyces cannot cause an
infection by itself but requires co-pathogens to inhibit host
defenses and create an anaerobic environment in which
Actinomyces can proliferate. This theory is supported by ad-
ditional virulence and resistance of Actinomyces in the pres-
ence of Streptococcus spp., and by the difficulty of culturing
Actinomyces alone [13, 14].
Prevalence
The prevalence was estimated at 1/100,000 in Germany and
the Netherlands in the 1960s and approximately 1/300,000 in
Cleveland during the 1970s. More recent studies on the prev-
alence of actinomycosis are lacking, but the prevalence is
thought to be declining due to better oral hygiene and wide-
spread use of antibiotics [1, 3].
Symptoms and diagnosis
Because actinomycosis is preceded by trauma or surgery, the
source-lesion should be quite easily identifiable, though one
should be aware that symptoms may sometimes only present

several weeks after extraction, even as late as 12 weeks, as
demonstrated by Stenhouse et al. [8]. Accordingly, in the
present study the time between the onset of symptoms and
the third molar extraction ranged from several days to 3
months (see Table 1).
The initial acute phase is predominated by a painful and
fluctuant swelling in the perimandibular region that will rap-
idly indurate and discolor to red or blue-purple as the pain
subsides. It may be noted that its position is relatively anterior
to the culprit-tooth, often in the region of the first molar and
premolars. This is a characteristic feature caused by abscess
migration to the anterior border of the masseter muscle (see
Figs. 2 and 3). When left to run its course, the infection will
progress into a chronic lesion with multiple draining fistulas.
These fistulas may close spontaneously and erupt elsewhere
on the skin [1, 2, 4].
Yellow flecks called sulfur granules are present in the
drained pus in 60 to 75% of cases. These granules are strongly
suggestive, though not conclusive of actinomycosis, as they
may be present in other pathologies, such as nocardiosis and
various fungal infections [3, 15–17].
The lesion will indurate and the overlying skin often dis-
colors red or purple-blue. In the chronic stage, the lesion is
frequently painless and is might be mistaken for a neoplasm or
epidermoid cyst. Most often, lymphatic structures remain un-
affected. Lymphadenopathy is therefore rare and might only
be present if lymphatic structures are in the direct pathway of
the extension of the disease [15]. In rare instances the infection
has been observed to disseminate to contiguous structures,
such as the trachea, carotid artery, orbital cavity, and cranium
[18–22]. In these cases, the infection can indeed become life
threatening.
Clinical diagnosis should be complemented by microbio-
logic or histological tests. The diagnostic method of choice is
microbiological isolation (i.e., culture) of Actinomyces from a
specimen of pus or affected tissue. However, this method may
have limited success because of specimen contamination,
Fig. 3 Clinical photographs of case 2. Left: at the start of unsuccessful treatment; middle: at the start of successful treatment; right: after 4 months of
treatment
Oral Maxillofac Surg
inappropriate culture conditions, or overgrowth of co-patho-
gens. In patients who received antibiotic therapy prior to test-
ing, isolation has an even higher failure rate of over 50%.
Alternatively, histological examination through Gram staining
can be performed (Fig. 4). Samples are preferably retrieved
with fine-needle aspiration, rather than swabs because swab
specimens produce less accurate samples when analyzed un-
der the microscope and bear a higher risk of being contami-
nated [1, 2, 4, 6, 9, 15]. Clinicians should request the labora-
tory to specifically test for Actinomyces to ensure that the
appropriate media conditions are selected.
As mentioned earlier, Actinomyces are part of the normal
oral flora [5]. This implies that their microbiological identifi-
cation without sufficient clinical evidence is of no signifi-
cance. In fact, because of the limited success and time-
consuming nature of microbiologic testing (commonly 2
weeks), diagnosis often relies solely on clinical recognition
to minimize time lost before starting treatment. It is therefore
crucial that the aforementioned clinical pictures should
promptly be recognized.
Differential diagnosis should include staphylococcal infec-
tion, nocardiosis, fungal infections (such as sporotrichosis),
malignancy, (infected) epidermoid cyst, foreign body infec-
tion, lymphoproliferative disorders, tuberculosis, and other
chronic granulomatous infections [3, 6, 9, 23].
Treatment
Actinomycosis responds well to high doses of penicillin such
as benzylpenicillin and amoxicillin (Table 2). Daily doses of
20 million IU are not uncommon for IV or IM
benzylpenicillin. When treating with oral amoxicillin, recom-
mended doses are 2 to 4 g daily. Patients should be treated for
at least 3 months, and treatment is preferably prolonged 2 to 3
weeks after all symptoms have subsided [4, 6, 9, 24].
The addition of β-lactamase inhibitors (e.g., clavulanic ac-
id) is useful. The Actinomyces themselves are not affected by
Oral Maxillofac Surg

Fig. 4 Histologic image of the

Gram staining of a pus sample
(magnification × 40). The blue
arrow indicates a sulfur granule
consisting of a colony of
Actinomyces with radiating
filaments. The red arrow indicates
an inflammatory infiltrate
composed largely of neutrophils

these inhibitors (as they do not produce β-lactamase); howev-
er, actinomycosis is generally considered a polymicrobial in-
fection and may contain co-pathogens that are susceptible to
β-lactamase inhibitors [6, 10, 15–17, 25–29]. In patients with
penicillin allergy, clindamycin and erythromycin are excellent
alternatives. These may also serve as an addition to the peni-
cillin regimens described above [27–30]. Metronidazole and
aminoglycosides are ineffective [6].
Chronic actinomycosis has a strong tendency to form dense
fibrous tissue around the lesion, which helps create a favorable
anoxic environment for proliferation by limiting blood flow
but thereby also limiting penetration of antibiotics [26, 31].
For this reason, clinicians have been advised to treat with β-
lactam antibiotics for 6 to 15 months [1, 4, 11, 16, 25, 32, 33].
However, this prolonged therapy could be shortened to
approx. 3 months if clinical diagnosis is made early and
Table 2 Key points of cervicofacial actinomycosis of importance to the
clinician
Cervicofacial actinomycosis – Key points
Cause Actinomyces bacteria (most commonly A. israelii, A. gerencseriae)
Pathogenesis Local trauma, tooth extraction, jaw surgery
Aggrevated by
Poor oral hygiene, diabetes, immune suppression, radiotherapy,
bisphosphonates, smoking, alcoholism
Pain, swelling, induration, pus, sulfur granules, fistulae, skin discoloration,
Symptoms
migratory abscess
Diagnosis
Clinical recognition, fine needle aspiration sampling, culture, microscopic
examination
High-dosed penicillin for ~3 months or until 2-3 weeks after symptoms
Treatment
subside, abscess drainage and debridement in severe cases
empirical antibiotic treatment is started immediately, as acti-
nomycosis is most responsive to treatment in its early stages
[17, 24, 26, 34]. In severe cases or when response to antibiotic
treatment is not adequate, additional surgical debridement and
curettage can be beneficial due to disrupting the protective
fibrous compartmentalization, thereby increasing the effec-
tiveness of antibiotics.
In the present patient group, initial treatment with
flucloxacillin and doxycycline proved unsuccessful in cases
4 and 5 respectively (see Table 1). As pointed out by Smith
et al., the MIC50 (minimum inhibitory concentration) of
doxycycline is over 20 times higher than that of penicillin G
for A. israelii (0.047 mg/L versus 0.002 mg/L respectively)
[28]. Flucloxacillin, as prescribed for case 4, is mostly used
against β-lactamase-producing staphylococci and quite inef-
fective against Actinomyces. Because of these unsuccessful
treatments, there was an avoidable delay before adequate an-
tibiotic therapy was initiated, which arguably is the cause of
why such long treatment with penicillin was required (9
months for case 4, 12 months for case 5). This was further
complicated in case 4 by an incorrect diagnosis as lymphade-
nopathy, which further delayed the initiation of treatment for
this patient. This is also demonstrated by comparing case 4
and case 2. Similar to case 4, case 2 was initially unsuccess-
fully treated for 2 months with inadequately dosed penicillin
(see Fig. 3 middle). However, case 2 only required 4 months
of high-dose amoxicillin, compared with 9 months for case 4.
The main difference between these patients was the time to
diagnosis after onset of symptoms: 2 months for case 2 versus
14 months for case 4.

Case 1 was treated with the same penicillin as case 4 (long-
acting benzylpenicillin, dosed at 1,200,000 IU once a month)
for 6 months, but was concurrently administered amoxicillin
and clavulanic acid orally for the first 6 months.
Benzylpenicillin was then continued by itself for another 6
months when symptoms subsided. This patient responded
well to initial treatment. This contrast in initial treatment re-
sponse between case 1 and case 2 not only demonstrates the
effectiveness of amoxicillin but also highlights the importance
of using adequately high dosages (see Fig. 2) and that surgical
drainage can be avoided when diagnosis is made early and
correct treatment is started promptly.
Conclusion
Cervicofacial actinomycosis is a stubborn disease that responds
poorly to traditional short courses of antibiotics. Misdiagnosis
is common due to the limited success of microbiological testing
and similarities with other more common diseases. For this
reason, diagnosis often relies solely on clinical recognition.
Thus, clinicians should be well aware of characteristic signs
that should provoke suspicion for this disease. These are an
acute and painful swelling arising in the perimandibular area
following dental manipulation or jaw surgery, the relatively
anterior positioning of the swelling to the suspected source of
infection, the red to purple-blue discoloration of overlying skin,
the formation of pus draining fistulas as the infection establishes
chronicity, the possible presence of sulfur granules in this pus;
and a relapse of disease after a conventional short course of
antibiotics. A treatment with β-lactam antibiotics of sufficient
dosage and duration is recommended.
Authors’ contributions All of the authors have substantially contributed
to the writing of this manuscript, have approved of its contents, and have
agreed to submission policies of Oral and Maxillofacial Surgery.
Data availability In consideration of Oral and Maxillofacial Surgery tak-
ing action in reviewing and editing our submission, the authors hereby
convey all copyright ownership to the Oral and Maxillofacial Surgery in
the event that such work is published in the Journal. The authors under-
stand that when the manuscript is accepted, the Editors reserve the right to
determine whether it will be published in the print edition or solely in the
online edition of the Journal.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethics approval This retrospective study involving human participants
was in accordance with the 1964 Helsinki Declaration and its later
amendments or comparable ethical standards. This study was approved
by an independent ethical committee (Ethics Committee Research UZ/
KU Leuven) on March 11, 2020 (file number S63785).
Oral Maxillofac Surg
Consent for participation and publication All included patients signed
an informed consent, granting permission for their clinical records and
photographs to be used by the authors for the purposes of this publication.
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