CASE REPORT/CLINICAL TECHNIQUES
Mo ^nica Soares de Albuquerque,
MD, Ariela Vilela Rizuto, PhD,

Aurea Fernanda de Arau jo Silva
Tavares, PhD,
Armiliana Soares Nascimento,
PhD, Pollyana Rodrigues de
Souza Arau jo, MD,
Eliane Alves de Lima, PhD, and
Rodivan Braz da Silva, PhD
SIGNIFICANCE
It is possible to treat an AIH
patient who is using
immunosuppressants and
bisphosphonates with an
acute apical abscess in a
conservative manner through
conventional endodontic
treatment, resulting in
periapical bone repair. The
result obtained will help in the
establishment of a treatment
protocol for these patients that
avoids postoperative
complications.
From the Faculty of Dentistry of
Pernambuco, Universidade de
Pernambuco, Camaragibe, Pernambuco,
Brazil
Address requests for reprints to Dr Ariela
Vilela Rizuto, General Nilton Cavalcanti
Avenue, 1650 Tabatinga, Camaragibe,
PE, Brazil 54753-220.
E-mail address: arizuto@hotmail.com
0099-2399/$ - see front matter
Copyright © 2019 American Association
of Endodontists.
https://doi.org/10.1016/
j.joen.2019.09.010
1550 de Albuquerque et al.
Treatment of an Acute Apical
Abscess in a Patient With
Autoimmune Hepatitis Taking
Alendronate: A Case Report
ABSTRACT
Introduction: The aim of this study was to report a patient’s clinical case who was diagnosed
with severe apical abscess and with autoimmune hepatitis (AIH) using immunosuppressive
drugs and bisphosphonate. Methods: A 32-year-old man of black African descent urgently
sought dental surgery because of an increase in volume in the right genic region and a
nuisance in the region of the lower right second premolar when chewing. After intraoral and
radiographic clinical examination, the patient was diagnosed with pulp necrosis and an acute
apical abscess. Because he had AIH and was taking corticosteroids and bisphosphonate
(alendronate), he was submitted to endodontic therapy as a minimally invasive treatment,
considering his systemic state. Results: After 3 years of follow-up treatment with periapical
and tomographic radiographic control, bone repair of the periapical region of the tooth was
observed. Conclusions: Through this report, we can infer that it is possible to reverse the
condition of a periapical lesion in a tooth with an acute apical abscess and necrotic pulp in an
AIH patient who is using alendronate without the need for more invasive procedures and that
would put at risk the patient’s general and oral condition in the postoperative period. (J Endod
2019;45:1550–1555.)
KEY WORDS
Acute apical abscess; autoimmune hepatitis; bisphosphonate; endodontic treatment
Autoimmune hepatitis (AIH) is an inflammatory, chronic, progressive, and rare liver disease that affects
all races and sexes, although women are more likely to develop it. It has been reported in several
regions of the world, and AIH can affect children and adults of all ages1–3. This pathology was first
described in 1950 by Waldenrtrom, who published a series of cases4. The etiology of AIH is still
unknown, but a higher susceptibility seems to be related to genetic and environmental factors3. In
general, the diagnosis of AIH is based on exclusion criteria for other pathologies and clinical, serologic,
biochemical, and histologic findings2. Various diseases such as viral hepatitis, metabolic liver disease
(alcoholic and nonalcoholic), drug-induced hepatitis, Wilson disease, alpha-1 antitrypsin deficiency, and
hereditary hemochromatosis present signs and symptoms similar to those of AIH, which makes the
differential diagnosis even more relevant2. AIH is characterized histologically by interface hepatitis and
lymphocytic infiltrate in the liver. Serologically, it is characterized by high levels of alanine
aminotransferase, aspartate aminotransferase, and immunoglobulin G and the presence of
autoantibodies3.
Prolonged immunosuppressive therapy with the use of prednisone and azathioprine has been
shown to be beneficial; the 10-year survival rate reaches 80% of cases. Therefore, it is the standard
treatment nowadays. However, a minority of patients progress to terminal liver disease and require liver
transplantation. Thus, continued administration of immunosuppressants is essential, and side effects and
possible complications may occur.
The various side effects caused by the prolonged use of medications for the treatment of AIH
include osteoporosis, susceptibility to infections, poor wound healing, and hypertension/fluid retention. In
order to promote the treatment or prevention of osteoporosis, the Food and Drug Administration
approved the use of bisphosphonate drugs, such as alendronate, which aims to improve mineral density
and bone strength2. However, continuous administration of bisphosphonates is an important risk factor
JOE  Volume 45, Number 12, December 2019
for the development of osteonecrosis of the
jaw5. Thus, special care and attention should
be given to patients with this disease who seek
dental care, given the potential risk of
postoperative complications.
After a search of the literature, the
authors failed to find any case reports of the
management of an acute apical abscess in a
patient with AIH who was taking
immunosuppressant or bisphosphonate
drugs. The aim of this study was to report the
clinical case of a patient with AIH who uses an
immunosuppressive drug (corticoid) and
bisphosphonate and attended an emergency
dental clinic with acute apical abscess.
CASE REPORT
A 32-year-old man of black African descent
attended the emergency clinic of the Faculty
of Dentistry of Pernambuco, Universidade de
Pernambuco, Camaragibe, Pernambuco,
Brazil (The Dentistry School of Pernambuco)
complaining of a growth of the right genian
region and pain in the region of the lower
right second premolar when chewing. During
the diagnostic process, he reported receiving
treatment for AIH since the age of 18 when
he was diagnosed with the disease. He
reported that when suffering any physical
trauma, he would have hematomas and
hemorrhages. Reinforcing the patient’s
report, the hepatologist who accompanied
the patient recommended that any procedure
to be performed should be based on the
requested blood tests. The blood tests
performed on the day he arrived at the clinic
showed the following results: hematocrit of
29.1%, platelets of 21,000, prothrombin time
of 17.5%, prothrombin activity of 44%, iron of
28mg/dL, and ferritin of 11 ng/mL, as well as
an international normalized ratio of 1.61 and
gamma-glutamyltransferase of 360 U/L,
which ratified the systemic contraindication
for surgical dental procedures. In addition,
the patient used to take the following
medications: prednisone 5 mg/d,
alendronate 70 mg/wk, tacrolimus 2 mg/d,
tamoxifen 10 mg, and hydroxychloroquine
400 mg/d.
The patient had no fever, and his blood
pressure was within normal limits. During the
extraoral examination, facial asymmetry was
observed because of a growth of the right
mandibular region (Fig. 1A and B). The intraoral
examination found the presence of an active
and extensive carious lesion. It reached the
pulpal chamber of the lower right second
premolar, which presented a negative
response to the cold pulpal sensitivity test. The
patient reported pain on palpation in the buccal
region corresponding to the previously
JOE  Volume 45, Number 12, December 2019
mentioned tooth; there was evidence of pulp
necrosis with an acute apical abscess and
vertical depressability (Fig. 2A). He also had
overall good oral hygiene, and the probing
depths were 3 mm. The periapical
radiographic examination revealed bone
rarefaction at the periapical level and loss of
alveolar crest bone at the distal of the dental
element as observed in the survey (Fig. 2B).
These clinical and radiographic signs and
symptoms led to the diagnosis of pulpal
necrosis with an acute apical abscess6.
Because it was an odontogenic infection, there
were 2 possible treatment options: endodontic
and/or surgical treatment. Because of the
systemic complications presented by the
patient, the most viable practice would be
endodontic treatment.
Before starting the case resolution,
alternatives for treatment and prognostic
uncertainties were discussed, and the
informed consent form was signed by the
patient. For urgent treatment, anesthesia was
performed by blocking the inferior and buccal
alveolar nerve with 2 tubes of 2% mepivacaine
with epinephrine 1:100,000 in the retromolar
trigone and vestibular fornix of the affected
region. After anesthesia, a rubber dam was
used. Access to the pulp chamber was
initiated after the removal of all carious tissue.
Chemical-mechanical preparation was
performed through the crown-down technique
using size 3 and 2 Gates-Glidden drills in the
cervical and middle third along with K-file–type
files ultimately finished with the apical
preparation using a stainless steel K-file #70k
(Dentsply Maillefer, Ballaigues, Switzerland)
accompanied by irrigation with 2.5% sodium
hypochlorite.
At the end of the preparation, irrigation
was performed with 17% EDTA and 2.5%
sodium hypochlorite. Calcium hydroxide–
based paste associated with p-chlorophenol
(Calen PMCC; SSWHITE, Sa ~o Cristova~o, RJ,
Brazil) was used as an intracanal medication
because of its effectiveness in teeth with pulp
necrosis and periapical lesions7,8.
Then, temporary filling was applied with
cement (Villevie, Dentalville do Brasil Ltda,
Joinville, SC, Brazil) and glass ionomer (Vitro
Fil; Nova DFL, Jacarepagua, Rio de Janeiro,
Brazil). Amoxicillin 500 mg was prescribed (1
capsule every 8 hours for 7 days). Fifteen days
after the urgent care in the clinic, before filling
the cavity, irrigation was done with 17% EDTA
for 3 minutes followed by irrigation with 2.5%
sodium hypochlorite. The canal was dried with
absorbent paper cones (Dentsply Maillefer)
and sealed by the lateral condensation
technique using cement sealer 26 (Dentsply
Maillefer) and gutta-percha cones (Dentsply
Maillefer).
Cavity sealing was performed with
temporary restorative cement (Villevie,
Dentalville do Brasil Ltda) and glass ionomer
(Vitro Fil R, Nova DFL) (Fig. 3A). After the
endodontic treatment was completed, the
tooth was restored with composite resin.
Shortly after the restorative procedure, the
coronary part of the tooth fractured, and there
was invasion of the biological space; due to
the patient’s systemic condition and because
he took a corticosteroid and bisphosphonate,
the treatment for the clinical crown
augmentation or dental exodontia was
contraindicated.
After that, the exposed glass ionomer
was removed and added over the buffer of
the temporary restorative cement and
composite resin Filtek Z250 (3M ESPE, St.
Paul, MN), thus sealing the cervical third. The
follow-up of the case has been done with
control radiographic and tomographic
imaging. After 3 years of preservation, it was
possible to observe repair of the periapical
lesion where there was bone resorption
because of the infectious inflammatory
process (Figs. 3B and 4). The tooth was
asymptomatic, with absence of a periodontal
pocket and mobility.
DISCUSSION
The prevalence of liver disease is rapidly
advancing, and its etiologic factors include the
use of drugs, alcohol, or some systemic
conditions, such as an autoimmune disease9.
AIH is a chronicle hepatocellular disease
probably caused by a loss of tolerance of
T lymphocytes to specific hepatocytes10.
There are 3 main arguments that indicate that
AIH is a disease mediated by T cells:
(1) the strong connections that exist
between the genes of the human
leukocyte antigens from class II,
(2) the lack of pathogenicity of the
autoantibodies, and
(3) the characterization of the inflammatory
infiltrate found in liver biopsies11.
The diagnosis of AIH depends largely on
biopsy findings, and all guidelines recommend
that the diagnosis should not be made without
a liver biopsy11. In the near future, it is
expected that AIH will have a detailed and
updated characterization of its intrahepatic
composition so that the main effective cell
types of human AIH can be reduced and
possible new therapeutic targets can be
identified12.
The characteristics of AIH include
predilection for females, elevation of
aminotransferases, nonspecific autoantibodies
or organ-specific autoantibodies,
Treatment of an Acute Apical Abscess 1551
FIGURE 1 – Unilateral volume growth causing facial asymmetry. (A ) The side view and (B ) front view.
immunoglobulin G levels, and interface
hepatitis in liver biopsy13. Although women are
affected by this pathology 3 times more often
than men14, this case report describes an
urgent endodontic treatment performed in a
male patient. The absence of treatment for AIH
is associated with an 80% mortality risk14.
Prednisolone monotherapy or a combination
of azathioprine and azathioprine are the
therapeutic options on this pathology. The
association of both drugs should be the
prevalent treatment15. However, prednisolone
causes side effects to patients. The impact of
steroid-induced adverse events, such as
metabolic syndrome or psychiatric reactions
on compliance and prognosis, also need to be
evaluated. In addition, findings on the
pathogenesis should be intensified. This will
pave the way for more accurate diagnostic
tests as well as less toxic immunologic
therapies11.
Individuals affected by this pathology
should be assisted in a multidisciplinary way,
and the dental surgeon should be prepared to
attend to those patients considering the
particularities of this systemic condition and its
implications in the formation of the treatment
plan. The patient in the study had
osteoporosis, corroborating the studies
performed by the previously mentioned
FIGURE 2 – (A ) Growth of the alveolar mucosa corresponding to the region of the lower right second premolar, which presents temporary fractured restoration. (B ) A periapical
radiograph of the lower right second premolar showing a carious process in communication with the pulp chamber and the area of bone.
1552 de Albuquerque et al.
authors. In order to treat this bone pathology,
he used oral alendronate, which is a
bisphosphonate belonging to the group of
synthetic inorganic analogs of pyrophosphate,
an endogenous regulator of bone
mineralization that suppresses the proliferation
and action of osteoclasts16,17.
The endodontic literature reports a
positive correlation between the performance
of intraoral surgery with bone involvement,
such as exodontia and a clinical crown
increase with osteotomies, and the risk of
osteonecrosis of the jaw induced by the
continuous use of this medicine18. According
to Miniello et al19, the main causes of
osteonecrosis of the jaw associated with
bisphosphonates follow a decreasing order,
beginning with dental extractions followed by
tumor resection or reconstruction, periodontal
disease, periapical lesions, dental implants,
prosthesis trauma, cingulate enucleation, and
gingival biopsy. Bisphosphonate-related
maxillary osteonecrosis (ONJ) was first
described by Marx20, who reported cases of
extensive osteolytic lesions in the jaw similar to
osteomyelitis caused by the prolonged use of
bisphosphonates. Another study21 shows that
besides the maxilla and the mandible,
osteonecrosis induced by bisphosphonates
also affects the maxillary sinus. In addition,
these patients are occasionally observed with
pathologies such as osteoporosis, Paget
disease, or metastatic cancer22, which
corroborates the results of Aljohani et al5; they
reported that patients who undergo treatment
with corticosteroids or immunosuppressants
appear to be at even greater risk of developing
osteonecrosis, even patients who have used
those drugs for ,4 years.
Miniello et al19 reported that it was not
possible to measure the effects of
bisphosphonates on mandibular
osteonecrosis, although patients with a history
of having used bisphosphonates reported a
shortened average time to develop ONJ,
which is in agreement with the study by Nabil
and Samman23. Thus, because there was no
scientific consensus on the subject, intraoral
surgery was contraindicated to the patient, not
only because of the AIH itself but also because
of the possible side effects caused by the
drugs that he had been using continuously. On
the other hand, although drainage of the
abscess through a mucosal incision could also
have been indicated as a form of treatment, the
clinical decision made was not to perform the
invasive surgical procedure because of
coagulopathy, which is frequently associated
with AIH. The other reason considered was
that because the mental foramen is in the
JOE  Volume 45, Number 12, December 2019
FIGURE 3 – (A ) Periapical radiography immediately after canal obturation. (B ) Bone repair was noted within a 3-year period of follow-up.
region of the lower premolars, severe
dangerous bleeding may occur because of any
mental artery wound. These factors could
bring more risks than benefits to the patient,
given his systemic state. Some authors20,24
have recommended endodontic treatment as
an alternative to dental surgeries in order to
minimize the risk of developing osteonecrosis,
although damage may occur to gingival tissue
during the use of a rubber dam clamp25 and
the extravasation of microorganisms during
intraradicular instrumentation.
However, a cohort study on 1621
patients found that tooth extraction and
denture use were triggering factors for ONJ.
Endodontic treatment and periodontitis were
not associated with an increased probability of
developing this pathology26. Thus, the
FIGURE 4 – A cone-beam computed tomographic scan was performed for monitoring and prognostic verification. A
sagittal cut of the region.
JOE  Volume 45, Number 12, December 2019
importance of endodontic treatment and
periodic dental follow-up is highlighted. In the
present case, semiannual periapical
radiographs were taken, and conical beam
tomographic imaging was performed 3 years
after the endodontic treatment. It was also
noted that the periapical lesion, which was
evident before treatment, underwent repair. It
contradicts the study by Russell et al27, who
argue that bone remodeling in the jaws is more
difficult to achieve in patients who use
bisphosphonates.
Also, according to this study, patients
medicated with bisphosphonates show some
healing disorder after dental procedures, such
as dental extraction and endodontic treatment.
However, the results of the present case report
seem aligned with the findings of Xiong et al28,
who performed a laboratory investigation in
rats in which alveolar bone resorption
associated with periapical lesion was inhibited
even with the administration of alendronate.
The results of the present clinical case also
corroborate with Hsiao et al29, who reported
that patients using chronic bisphosphonates
can present periradicular healing after
endodontic treatment.
It also seems important to demonstrate
in this case report the prolonged activity of
prothrombin (44%). This is because
prothrombin, also known as coagulation factor
II, is 1 of the major proteins in the liver’s blood
coagulation system30. According to
Yamamoto et al31, approximately 50% of
patients who exhibit prothrombin activity
corresponding to 40% or an international
normalized ratio equal to or greater than 1.5
achieve fatal outcomes, and evaluation of this
activity is a useful prognostic factor.
The patient in this case report has
successfully performed standard treatment for
AIH for years. However, a few months after the
endodontic treatment was completed, the
patient’s systemic condition worsened, and a
liver transplant was performed. Thus, the
choice of endodontic therapy in similar cases
rather than more invasive dental procedures
seems to be assertive.
CONCLUSIONS
Therefore, it is possible to achieve long-term
success in endodontic treatment in patients
with AIH. However, further reports and
scientific studies are needed to correlate the
management of patients with autoimmune liver
disease and endodontic treatment.
ACKNOWLEDGMENTS
The authors deny any conflicts of interest
related to this study.
Treatment of an Acute Apical Abscess 1553
REFERENCES

1. Lowe D, John S. Autoimmune hepatitis: appraisal of current treatment guidelines. World J

Hepatol 2018;10:911–23.

2. Janmohamed A, Hirschfield GM. Autoimmune hepatitis and complexities in management.

Frontline Gastroenterol 2019;10:77–87.
3. nez P, Secchi MF, et al. Etiopathogenesis of autoimmune hepatitis. J
Floreani A, Restrepo-Jime
Autoimmun 2018;95:133–43.

4. Mackay IR. Historical reflections on autoimmune hepatitis. World J Gastroenterol 2008;14:3292–

300.

5. Aljohani S, Fliefel R, Ihbe J, et al. What is the effect of antiresorptive drugs (ARDs) on the
development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: a
systematic review. J Craniomaxillofac Surg 2017;45:1493–502.

6. Glickman GN. AAE Consensus conference recommended diagnostic terminology. J Endod

2009;35:1619–20.
7. Lana PE, Scelza MF, Silva LE, et al. Antimicrobial activity of calcium hydroxide pastes on
Enterococcus faecalis cultivated in root canal systems. Braz Dent J 2009;20:32–6.

8. -Mun
Prada I, Mico ~oz P, Giner-Lluesma T, et al. Update of the therapeutic planning of irrigation
and intracanal medication in root canal treatment. A literature reviews. J Clin Exp Dent
2019;11:e185–93.

9. Daniyal M, Akram M, Zainab R, et al. Prevalence and current therapy in chronic liver disorders.
Inflammopharmacology 2019;27:213–31.

10. Sahebjam F, Vierling JM. Autoimmune hepatitis. Front Med 2015;9:187–219.

11. Sebode M, Hartl J, Vergani D, et al. Autoimmune hepatitis: from current knowledge and clinical
practice to future research agenda. Liver Int 2018;38:15–22.

12. Oo YH, Weston CJ, Lalor PF, et al. Distinct roles for CCR4 and CXCR3 in the recruitment and
positioning of regulatory T cells in the inflamed human liver. J Immunol 2010;184:2886–98.
13. Gatselis NK, Zachou K, Koukoulis GK, et al. Autoimmune hepatitis, one disease with many faces:
etiopathogenetic, clinico laboratory and histological characteristics. World J Gastroenterol
2015;21:60–83.
14. Lohse AW, Mieli-Vergani G. Autoimmune hepatitis. J Hepatol 2011;55:171–82.

15. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis.
Hepatology 2010;51:2193–213.
16. Kim MS, Jung SY, Kang JH, et al. Effects of bisphosphonate on the endochondral bone
formation of the mandibular condyle. Anat Histol Embryol 2009;38:321–6.
17. Yi JW, Lee WS, Kim SB, et al. Effect of zoledronate on the expression of vascular endothelial
growth factor-A by articular chondrocytes and synovial cells: an in vitro study. J Bone Metab
2014;21:249–55.

18. Aslam-Pervez N, Lubek JE. Most cited publications in oral and maxillofacial surgery: a
bibliometric analysis. Oral Maxillofac Surg 2018;22:25–37.

19. jo JP, Silva ML, et al. Influence of bisphosphonates on clinical features of
Miniello TG, Arau
osteoradionecrosis of the maxilla and mandible. Oral Dis 2019;25:1344–51.
20. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the
jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115–7.

21. Wasserzug O, Kaffe I, Lazarovici TS, et al. Involvement of the maxillary sinus in bisphosphonate-
related osteonecrosis of the jaw: radiologic aspects. Am J Rhinol Allergy 2017;31:36–9.

22. Kyrgidis A, Barbas A. Osteonecrosis of the jaw among bisphosphonate users. Am J Med
2008;121:e21.
23. Nabil S, Samman N. Risk factors for osteoradionecrosis after head and neck radiation: a
systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:54–69.
24. Moinzadeh AT, Shemesh H, Neirynck NA, et al. Bisphosphonates and their clinical implications in
endodontic therapy. Int Endod J 2013;46:391–8.

25. Gallego L, Junquera L, Pelaz A, et al. Rubber dam clamp trauma during endodontic treatment: a
risk factor of bisphosphonate-related osteonecrosis of the jaw? J Oral Maxillofac Surg
2011;69:e93–5.

1554 de Albuquerque et al. JOE  Volume 45, Number 12, December 2019
 26. Vahtsevanos K, Kyrgidis A, Verrou E, et al. Longitudinal cohort study of risk factors in cancer
patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 2009;27:5356–62.

27. Russell RG, Watts NB, Ebetino FH, et al. Mechanisms of action of bisphosphonates: similarities
and differences and their potential influence on clinical efficacy. Osteoporos Int 2008;19:733–59.
28. Xiong H, Peng B, Wei L, et al. Effect of an estrogen-deficient state and alendronate therapy on
bone loss resulting from experimental periapical lesions in rats. J Endod 2007;33:1304–8.
29. Hsiao A, Glickman G, He J. A retrospective clinical and radiographic study on healing of
periradicular lesions in patients taking oral bisphosphonates. J Endod 2009;35:1525–8.

30. Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev 2007;21:131–42.
31. Yamamoto K, Miyake Y, Ohira H, et al. Prognosis of autoimmune hepatitis showing acute
presentation. Hepatol Res 2013;43:630–8.

JOE  Volume 45, Number 12, December 2019 Treatment of an Acute Apical Abscess 1555