Oral Medicine, Oral Diagnosis, Oral Pathology Facial pigmentation associated with amiodarone Wilfredo Alejandro Gonzalez-Arriagada, DDS, MSc n Alan Roger Santos Silva, DDS, PhD n Pablo Agustin Vargas, DDS, PhD
Oslei Paes de Almeida, DDS, PhD n Marcio Ajudarte Lopes, DDS, PhD
Amiodarone is one of the most commonly used drugs for treatment
is to increase clinicians’ awareness about the potential adverse
of cardiac arrhythmia. Several undesirable effects are associated with
its long-term use. This report describes the case of a 71-year-old
female patient, with a diagnosis of cardiac arrhythmia, who presented
with a stigmatizing blue-gray facial pigmentation and altered serum values of thyroid hormones associated with the intake of amiodarone.
Key words: amiodarone, skin pigmentation,
The patient was referred to her cardiologist. The aim of this report
photosensitivity, hyperpigmentation, arrhythmia
Amiodarone is a drug taken for the Brazil, with the chief complaint of a nodule the hard palate, which presented a super-
on the hard palate that had been present
ficial area of bluish pigmentation (Fig. 2).
cardiac arrhythmia.1,2 However, sev- for approximately 7 years. The patient had
Discreet areas of denture-related stomatitis
eral adverse effects have been reported in
patients taking amiodarone.3,4 Two of the and cardiac arrhythmia, which had been
collateral effects of amiodarone—which
hepatic and thyroid functions, with abnor-
years. The patient recounted that she took
mal values for aminotransferase, T4, and
elderly patients—are skin photosensitiv-
400 mg daily in the first 15 months, and
TSH: AST/TGO = 38 U/L (ref. <31 U/L);
ity and blue-gray facial pigmentation.3,4
T4 = 2.66 ng/dL (ref. 0.75 to 1.80 ng/dL);
physical examination revealed a distinct
the nose, zygomatic, and frontal regions
visional diagnosis of facial pigmentation
(Fig. 1). According to the patient, this had
associated with amiodarone, a skin biopsy
had been noticeable for the last 18 months; was performed on the zygomatic region.
process, as well as to the differential diag-
when asked about the facial pigmentation,
H & E stain revealed an orthokeratinized
noses of this drug-related complication.
the patient reported that she was diagnosed stratified epithelium covering the dermis
with evident signals of solar elastosis. A
Case report
treated her with tetracycline and sunblock
was observed inside histiocytes along the
Oral Diagnosis Clinic, Piracicaba Dental
months without improvement. Intraorally,
dermis, close to the blood vessels (Fig. 3).
Fig. 1. Extraoral photograph showing a blue-gray facial skin discoloration, affecting the upper and middle
Fig. 2. Intraoral view showing a fibrous hyperplasia
in the palate with a posterior pigmentation.
www.agd.org General Dentistry July 2013 e15
Oral Medicine, Oral Diagnosis, Oral Pathology Facial pigmentation associated with amiodarone
were negative, excluding the possibility
of fibrous hyperplasia. The pigmentation
scattered in the connective tissue. Perls
stain was positive, being compatible with
hemosiderine (Fig. 6). Finally, the patient
was referred to her cardiologist with the
Fig. 3. Light microscopy photograph of the
Fig. 4. Skin biopsy showing pigmentation in the
diagnosis of facial skin pigmentation asso- biopsy taken from the facial pigmented skin
connective tissue negative for Fontana-Masson
showing intracytoplasmatic pigmented granules in
stain. Note the internal positive control in
macrophages mainly around the vessels and solar
melanocytes in the basal epithelial layer (400X). Discussion
monly used drugs available for treatment
of cardiac arrhythmia.1-3,5 It has a high
lipophilicity and a long plasma half-life.
nel block and nonselective β-adrenergic
inhibition.5 It has a variable (20%–80%)
ethylamiodarone. The peak serum level of
amiodarone, after oral dosage, is achieved
Fig. 5. Skin biopsy showing pigmented granules in
Fig. 6. Fibrous hyperplasia excisional biopsy
several adverse effects, such as corneal
the connective tissue negative for Perls stain (400X).
showing positivity for Perls stain, compatible with
gastrointestinal, myopathic, or neurologi-
cal complications.3,4,6-8 Drug interactions
reported to cause diverse collateral effects.9 find any significant difference between
The majority of these effects are related to
the 2 groups.3 There are 2 types of skin
been reported, but the patient in this case
dosage. Intraorally, hypersalivation, blue
sitivity, which is characterized by pruritis brown or brown pigmented granules in
and erythema; the second is a slate-grey
macrophages of the dermis.7,13 Studies have
of patients, and is associated with a pro-
a predilection for males.3,7,12 The current
longed use of the drug (generally >1 year), case presents an asymptomatic facial pig-
a dosage of 200-800 mg daily, and/or sun mentation with a clinical appearance sim- phages, and tend to concentrate in areas
ilar to other reports in the literature.4,12,13
of highly sun-exposed skin.3,7 In addition,
it causes skin pigmentation is still con-
ultraviolet light induces amiodarone and
troversial, but several theories have been
its metabolites to bind to the blood vessel
walls and the perivascular tissue, triggering
dosis, photosensitivity reaction to ultravi-
it may persist for long periods, even after
an associated vasodilatation that increases
olet light, or leucocytoclastic vasculitis.11
the diffusion of these metabolites, resulting
in chronic accumulation in the tissues.7
The incisional skin biopsy of the current
its metabolites in patients with and with-
drug.4,12 Corneal microdeposits, with no
features to the previous published cases.
e16 July 2013 General Dentistry www.agd.org
Published with permission by the Academy of General Dentistry. Copyright 2013
by the Academy of General Dentistry. All rights reserved. For printed and electronic
reprints of this article for distribution,please contact [email protected].
The pigmentation of the oral fibrous hyper- the intake of drugs or other substances
2. Van Herendael H, Dorian P. Amiodarone for the treat-
containing silver. Rosacea is a chronic
ment and prevention of ventricular fibrillation and ven-
pigmentation, and represented a reactive
skin condition with predominantly facial
tricular tachycardia. Vasc Health Risk Manag. 2010;
manifestations, and is characterized by ery-
3. Harris L, McKenna WJ, Rowland E, Holt DW, Storey GC,
thema, flushing, pustules, and telangecta-
Krikler DM. Side effects of long-term amiodarone ther-
the chronic trauma on the palate with the
sias. Cutaneous lupus erythematosus affects
the face and other parts of the body and
4. Ioannides MA, Moutiris JA, Zambartas C. A case of
its diagnosis depends on a combination of
pseudocyanotic coloring of skin after prolonged use of
amiodarone. Int J Cardiol. 2003;90(2-3):345-346.
5. Sohns C, Zabel M. Current role of amiodarone in anti-
darone inhibits the reversion of T4 into
arrhythmic therapy. [article in German] Herzschrittm-
Conclusion
acherther Elektrophysiol. 2010;21(4):239-243.
levels, and decreased T3 levels, in long-
6. Itoh K, Kato R, Hotta N. A case report of myolysis dur-
term users. Our patient presented normal
sensitivity, thyroid dysfunction, or other
ing high-dose amiodarone therapy for uncontrolled
ventricular tachycardia. Jpn Circ J. 1998;62(4):305-308.
T3 serum values, increased levels of T4,
alterations associated with the use of amio-
7. Bahadir S, Apaydin R, Cobanoilu U, et al. Amiodarone
and decreased levels of TSH. The levels of
pigmentation, eye and thyroid alterations. J Eur Acad
cians, geriatrists, dermatologists, dentists,
Dermatol Venereol. 2000;14(3):194-195.
8. Raptis L, Papathanasiou H, Pappas G, Akritidis N. It’s all
in the face: amiodarone-induced myxedema and skin
levels were normal). Similar to complica-
see patients that receive this drug, in order
pigmentation. Eur J Dermatol. 2006;16(5):590-591.
9. Pawar PS, Woo DA. Extrapyramidal symptoms with
laboratory results indicate that the thyroid
concomitant use of amitriptyline and amiodarone in
and hepatic function were altered due to
Author information
an elderly patient. Am J Geriatr Pharmacother. 2010;
10. Scully C, Bagan JV. Adverse drug reactions in the oro-
these adverse effects, it has been suggested
facial region. Crit Rev Oral Biol Med. 2004;15(4):221-
Semiology and Oral Pathology, Piracicaba
determined individually, according to the
11. Wiper A, Roberts DH, Schmitt M. Amiodarone-induced
results of the patient’s follow-up.6 The
skin pigmentation: Q-switched laser therapy, an effec-
tive treatment option. Heart. 2007;93(1):15.
patient returned once after the diagnosis,
12. Enseleit F, Wyss CA, Duru F, Noll G, Rischitzka F. Im-
ages in cardiovascular medicine. The blue man: amiod-
mones levels, because the medication was
Dr. Gonzalez-Arriagada is also a professor,
arone-induced skin discoloration. Circulation. 2006;
not discontinued by the cardiologist.
Oral Diagnosis and Pathology, Facultad de
13. Nikolidakis S, Kyriakides ZS, Barbatis C. Images in car-
diology. Blue-grey cutaneous discolouration secondary
to amiodarone treatment. Heart. 2006;92(4):436.
basal cell carcinomas has been reported.14,15
14. Monk B. Amiodarone-induced photosensitivity and
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www.agd.org General Dentistry July 2013 e17
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