what dermatological issue is linked to amiodarone use?
Med Sci Monit. 2014; 20: 2369–2372.
Cutaneous Adverse Reactions of Amiodarone
Krzysztof Jaworski
1Section of Cardiology and Hypertension, Key Clinical Hospital of the Ministry building of Interior, Warsaw, Poland
Irena Walecka
iiSection of Dermatology, Cardinal Clinical Hospital of the Ministry of Interior, Warsaw, Poland
Lidia Rudnicka
iiiSection of Dermatology, Medical University of Warsaw, Warsaw, Poland
Maciej Gnatowski
fourDepartment of Traumaorthopedic Surgery, Commune Hospital, Wołomin, Poland
Dariusz A. Kosior
aneSection of Cardiology and Hypertension, Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland
fiveMossakowski Medical Research Centre, Smooth University of Sciences, Warsaw, Poland
Received 2014 Apr xviii; Accepted 2014 May ix.
Abstract
Dermatological complications of amiodarone are ordinarily encountered problems in therapy. The incidence in the population of patients with prolonged employ of amiodarone reaches nigh 75% co-ordinate to various sources. All the same, they are ofttimes misdiagnosed or overlooked. The aim of this review is to present the current state of noesis about peel changes induced past amiodarone, including phototoxic and photoallergic reactions, too as hyperpigmentation. In most cases, the adverse effects are reversible and disappear after discontinuation of the drug. Although the dermatological complications usually exercise not influence the outcome of the therapy and rarely cause discontinuation of handling, they have a corking impact on patient quality of life.
MeSH Keywords: Amiodarone, Dermatology, Phototoxic Reactions, Hyperpigmentation
Background
Dermatology and cardiology at a first glance seem to be very distinct medical fields, only the relationship between them is shown by the adverse effects of amiodarone, the cardinal antiarrhythmic drug. Amiodarone has been used by physicians for over 50 years to treat supraventricular and ventricular cardiac arrhythmias, and it often provides the last treatment option due to its high efficacy. Nevertheless, prolonged amiodarone therapy unfortunately carries an extended chance of adverse effects, mainly involving the thyroid gland, liver, lungs, optics, and peel [1].
Dermatological complications of amiodarone are commonly encountered. The incidence in the population of patients with prolonged use of this drug reaches most 75% co-ordinate to various sources. The master skin changes induced by amiodarone are phototoxic and photoallergic reactions, as well every bit hyperpigmentation. In most cases the adverse effects are reversible and disappear later on drug withdrawal. Although the dermatological complications ordinarily do not influence the outcome of the therapy and rarely crusade the discontinuation of handling, they have peachy impact on patient quality of life.
Phototoxic and Photoallergic Reactions
Phototoxic reactions are the most common dermatological adverse outcome of amiodarone therapy, affecting 25–75% of patients on long-term treatment [2]. Photoallergy is considerably less likely to occur, but the take a chance also increases with prolongation of the therapy.
Amiodarone and its active metabolite, desethylamiodarone, cause decrease of MED (minimal erythema dose) in the range of ultraviolet radiation blazon A (UV-A 320–400 nm), which can attain up to 50% of the correct values. In individual cases there may likewise exist a reduction of MED for the ultraviolet type B radiations (UV-B 290–320 nm) [three]. The mechanism of the reaction seems to be continued with the creation of active metabolites due to radiation, such equally oxygen free radicals, which in plow leads to destruction of DNA particles, cell membranes, and oxygenation of lipids [four,five]. Ferguson et al. demonstrated phototoxic effects of amiodarone and desethylamiodarone past carrying out in vitro tests with the use of photohemolysis, DNA synthesis inhibition assay in PHA-stimulated lymphocytes, and the killing of macrophages obtained from mouse peritoneal fluid [half dozen].
Pare changes unremarkably occur after at least 4 months of therapy and with the minimal cumulative dose, which is 40 g [7]. They have the typical erythematous or eczematous appearance with accompanying pruritus in the parts exposed to sunlight, commonly on the hands, confront, and neck. The eruptions are less prominent on the chin, lower lip, and backside the ears [eight]. The symptoms brainstorm several minutes after exposure to the sunlight, continue upwardly to 24 hours and usually subside by around 48 hours, just in some cases they persist up to 72 hours. Phototoxic and photoallergic reactions might even occur a few months after the withdrawal of amiodarone due to its long emptying fourth dimension, which on boilerplate takes 35–xl days, and in obese patients can accept 100 days for complete excretion. In the literature there are as well descriptions of prolonged photosensitivity cases (upwards to fifteen years following the discontinuation of therapy) [9]. The extent of the reactions depends mostly on the private sensitivity of the pare to sunlight, but it is always proportional to the exposure time.
The basis of therapy is withdrawal of the medication and restoration of skin lipid layers. It too includes the apply of medium forcefulness topical glucocorticosteroid, oral non-steroidal anti-inflammatory drugs, and intensive sunscreen protection [viii].
Prevention of acute reactions caused past sunlight in patients treated with amiodarone should include avoidance of frequent lord's day exposure on the skin and the proper application of external sun protection products with high protection factors (SPF 50 or 50+), reapplied not less frequently than approximately every two hours. Sunscreen should provide the full spectrum of protection, including a UV-A radiations. Specially constructive are creams containing zinc oxide or titanium dioxide [10]. Glass commonly used in windows is permeable to UV-A radiation and does not provide protection to people in buildings and cars.
Hyperpigmentation
Skin hyperpigmentation is another important adverse result, affecting four–9% of patients taking amiodarone [ii]. In dissimilarity to the phototoxic reactions, which do not depend on the skin type, hyperpigmentation usually occurs in patients with skin type I phototype [7]. In these patients, long-term therapy with amiodarone leads to characteristic blueish-gray discolorations, located mostly on the face, ears, and palms of the easily (Figure 1). The mechanism past which these changes occur is not precisely understood. Histopathological examination of the skin shows yellow-dark-brown deposits of lipofuscin aggregates inside macrophages, mast cells, endothelial cells, smooth musculus cells, keratinocytes, and fibroblasts [11]. Pathologically accumulated phospholipids appear under electron microscopy as irregular or oval structures. Some authors report that the hyperpigmentation is likely due to the amiodarone deposits instead of lipofuscin [12,thirteen]. Amiodarone binds to phospholipids and creates insoluble compounds that do not follow the regular degradation pathways, which leads to their accumulation in cellular lysosomes. The discovery of increased amounts of iodine or drug metabolites in granules proves that amiodarone or desethylamiodarone are present in the affected skin [12]. In improver to the deposits of lipofuscin, histopathological examination revealed the presence of inflammatory cells around the microvessels [7]. The full explanation of the mechanisms involved in the mentioned processes requires further investigation.
Amiodarone-induced blue-grey facial pigmentation associated with diffuse erythema in 81-year-old patient treated with amiodarone 200 mg daily for fifteen years due to paroxysmal atrial fibrillation. The clinical manifestation is indicative of a phototoxic reaction. The surface area shaded from the UV-exposure by a hat remained unaffected.
Hyperpigmentation ordinarily occurs 20 months into amiodarone treatment regime and sometimes after longer periods of fourth dimension [6]. The doses of the drug used are higher in patients with hyperpigmentation (400–800 mg per day) compared to patients with only phototoxic reactions. The minimal cumulative dose is around 160 g [vii]. The changes accept bluish-grey discoloration, but in x% of patients information technology takes on xanthous-brown pigmentation. Discontinuation of the drug usually causes gradual reduction of the symptoms [14]. Full remission is commonly achieved afterwards a few months to several years, which is the outcome of deadening emptying of amiodarone and its metabolites from tissues. Unfortunately, even after drug withdrawal for a few years, some changes may persist. Prophylaxis includes avoidance of directly excessive sunlight exposure to the skin and utilize of sunscreen products with high protection factors (SPF 50 or higher) confronting UV-A and UV-B radiation. Switching from amiodarone to another antiarrhythmic drug could also be very beneficial. Targeted treatments usually do not give satisfactory results. There have been individual reports on the efficacy of vitamin B6 at 300 mg per day. Local depigmentation treatment using hydroquinone and monobenzone does not improve the skin status. In contrast, in that location are reports of spectacular efficacy of cosmetic laser application, which could possibly be very beneficial in patients with likewise many cardiovascular complications to allow amiodarone withdrawal [xv–17]. In that location are accounts of very successful therapy with UV-B rays, leading to higher tolerance to sunlight and prolongation of possible exposure times without adverse furnishings [18].
Pseudoporphyria
Amiodarone is considered to be a cause of pseudoporphyria, which is a disease with clinical picture similar to this of porphyria cutanea tarda, merely without any identified biochemical changes in the metabolism of porphyrins. Pseudoporphyria is commonly manifested by tense bullae, erosions, scars, postinflammatory hyperpigmentation, and increased pare fragility, especially in the sun-exposed regions.
Linear IgA Bullous Dermatosis
A very rare adverse reaction to amiodarone treatment is linear IgA bullous dermatosis, and information technology is thought that amiodarone tin exacerbate the course of this disease. Characteristic changes include the presence of well-differentiated blisters located either on healthy pare or on erythematous and edematous areas. Location of the changes does not represent to the sun-exposed parts of the skin.
Effects of Amiodarone Therapy on Other Cutaneous Diseases
The amiodarone molecule contains a large corporeality of inorganic iodine, which may exacerbate certain pare diseases, such equally dermatitis herpetiformis and psoriasis. Moreover, there have been reports of post-amiodarone pseudo-purulent changes, such as acne or blister-purulent lesions characteristic of iodism [19,20]. This should be considered when choosing the optimal antiarrhythmic therapy.
Other Agin Effects
Less common dermatological complications of amiodarone include hives, pruritus, erythema nodosum, purpura, and the most astringent variant of erythema multiforme – toxic epidermal necrolysis [21,22]. The acute complication of handling with intravenous amiodarone administration can take on the grade of necrosis of the skin and soft tissue due to venous extravasation. The gamble is related to depression pH (three.five–four.v) of the solution and the content of solvents, such as benzyl alcohol and polysorbates [23].
There are some reports indicating the possible carcinogenic furnishings of amiodarone. A few cases of basal cell carcinoma associated with chronic use of this drug take been reported. Most of the changes were observed on the site of a preexisting astute phototoxic reaction [24,25].
Conclusions
Complications of chronic amiodarone therapy hogtie the prescribing physician to inform the patient near all possible adverse reactions, methods of fugitive them, and the need for specialist communication if symptoms occur. Any doctor approached by a patient with pare lesions secondary to amiodarone must be aware of the risks of stopping treatment, considering information technology can exacerbate the severity of arrhythmias and fifty-fifty lead to sudden cardiac death. Cooperation between cardiologists and dermatologists will undoubtedly facilitate hazard stratification and ensure that optimal decisions will be fabricated to provide maximum safety of the patient, while at the same time reducing the adverse effects.
Footnotes
Source of support: Cocky financing
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