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. 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).
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 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 References
basal-cell carcinoma. Clin Exp Dermatol. 1990;15(4): are not limited to, argyria, rosacea, and 1. Smith W, Members of CSANZ Cardiovascular Genetics 15. Maoz KB, Dvash S, Brenner S, Brenner S. Amiodarone- cutaneous lupus erythematosus. Argyria Working Group. Guidelines for the diagnosis and man- induced skin pigmentation and multiple basal-cell car- agement of arrhythmogenic right ventricular cardiomy- opathy. Heart Lung Circ. 2011;20(12):757-760.
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