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Drug-Induced Rosacea-Like Dermatitis View metadata, citation and similar papers at core.ac.uk brought to you by CORE Acta Dermatovenerol Croat 2016;24(1):49-54 REVIEW Drug-Induced Rosacea-like Dermatitis Saida Rezaković1, Zrinka Bukvić Mokos2, Zrinjka Paštar3 1“Sunce” Polyclinic – Polyclinic for Internal Medicine, Neurology, Urology, Physical Medicine, Occupational Medicine, Orthopedics, Psychiatry, Gynecology, Ophthal- mology, Dermatovenerology, Otorhinolaryngology, Cytology, and Radiology, Zagreb, Croatia; 2Department of Dermatovenerology, University Hospital Center Zagreb and School of Medicine University of Zagreb, Zagreb, Croatia; 3Health Department, Ministry of Defence Republic of Croatia, Zagreb, Croatia Corresponding author: ABSTracT Rosacea is a common, chronic cutaneous disorder Saida Rezaković, MD with a prevalence of 0.5-10%, predominantly affecting women. The disease presents with a heterogeneous clinical picture char- “Sunce” Polyclinic - Polyclinic for Internal Medicine, acterized by transient flushing, persistent facial redness, telangi- Neurology, Urology, Physical Medicine, Occupational ectasias, and, in more severe clinical forms, the presence of in- Medicine, Orthopedics, Psychiatry, Gynecology, flammatory papules and pustules in the central third of the face. Ophthalmology, Dermatovenerology, Although its pathophysiology is complex and still remains un- known, factors that exacerbate the disease are well defined. They Otorhinolaryngology, Cytology and Radiology include genetic predisposition as well as external factors such as Trnjanska cesta 108 exposure to UV light, high temperature, and diet. Besides these 10 000 Zagreb well-known factors, recent studies suggest that drugs and vita- mins could also be possible factors inducing rosacea-like derma- Croatia titis or aggravating pre-existing rosacea. Although these are less [email protected] common possible triggering factors, the aim of this article is to present the current knowledge on the association between use of certain drugs or vitamins and rosacea. Received: July 8, 2014 Accepted: January 19, 2016 KEY WOrdS: drugs, rosacea-like dermatitis INTRODUCTION Rosacea is a chronic skin inflammatory condition contributing factors for rosacea, recent studies show affecting the blood vessels and pilosebaceous units. emerging evidence that some drugs and vitamins Although it has many different clinical presentations, aggravate rosacea or induce rosacea-like symptoms. in the majority of cases it presents with centrofacial These agents include topical corticosteroids, topi- erythema and the presence of telangiectasia, occur- cal immunomodulators, oral parabens, epidermal ring more frequently in persons with fair complexion growth factor receptor inhibitors (erlotinib, geftinib, and light eyes (1). Although numerous studies have cetuximab), calcium channel blockers, selective phos- identified possible risk and triggering factors that in- phodiesterase inhibitors, and vitamin B complex (5-9). duce or exacerbate rosacea, the pathophysiology of Although the exact mechanism of how each of these rosacea still remains unknown (2). The contributing agents contributes to the development of rosacea is factors include family history of the disease, very light not yet fully understood, some studies suggest that skin phototype, exposure to sun and high tempera- drug induced rosacea-like dermatitis occurs primarily ture, and diet (3,4). Apart from well identified possible in genetically predisposed individuals (6,10). ACTA DERMATOVENEROLOGICA CROATICA 49 Rezaković et al. Acta Dermatovenerol Croat Drug-induced rosacea-like dermatitis 2016;24(1):49-54 TOPICAL CORTICOSTEROIDS tions associated with topical use of immunomodula- The regular and excessive use of topical cortico- tors (16,19-21,23). Possible pathological mechanism steroids is identified as a potential risk factor that can responsible for the immunomodulator-induced ro- aggravate or induce rosacea (11-13). Patients usually sacea-like dermatitis could include different factors, start using this topical therapy for the treatment of such as vasoactive properties of topical immuno- common dermatoses such as seborrheic dermatitis, modulator therapy, proliferation of Demodex follicu- acne, or melasma, usually as a result of recommen- lorum due to local immunosuppression, and an oc- dations from nonmedical personnel or through self- clusive effect which is more pronounced with use of prescribing (12). Young women are the most affected tacrolimus ointment than with pimecrolimus cream population by this problem (12). After diminishing (16,20-23). Although clinical presentation is similar to signs of the primary dermatitis due to the vasocon- rosacea caused by topical corticosteroids, it is impor- strictive and anti-inflammatory effects of the steroids, tant to emphasize the absence of skin atrophy during persistent use of these agents leads to epidermal at- persistent use of topical immunomodulator therapy, rophy, degeneration of dermal structure, and deterio- unlike under corticosteroid therapy (16,24). ration of collagen, consequently leading to the skin disorder resembling rosacea (11,12,14). Skin atrophy VITAMIN B can be observed on the centrofacial area, together As far as vitamin B inducing rosacea is concerned, with erythema, telangiectasia and possible papulo- few studies have been conducted so far (10,25,26). Vi- pustular eruptions, photosensitivity, and vulnerabil- tamin B3 (niacin) has been associated with skin flush- ity to bacterial, viral, and fungal infections (11,13,15). ing, while vitamins B2 (riboflavin), B6 (pyridoxine), Furthermore, the immunosuppressive effects of and B12 (cyanocobalamin) have shown association corticosteroids facilitate an overgrowth of bacteria, with outbreak of acneiform lesions (5,10,25-29). There which may act as superantigens, inducing formation have also been reports of rosacea fulminans follow- of follicular granulomatous lesions (16). This relatively ing the administration of vitamin B derivatives; how- new dermatosis was given various names by different ever, the reactions were associated with daily intake authors, such as perioral dermatitis, rosacea-like der- of vitamin B6 that exceeded the recommended daily matitis, steroid rosacea, steroid dermatitis resembling allowance (5,10). Regarding treatment modalities for rosacea, and steroid-induced rosacea-like dermatitis vitamin B--triggered rosacea, clinical symptoms tend (13-15,17). Pathological mechanisms that are thought to improve rapidly after discontinuation of the agent, to be responsible for development of rosacea-like while other standard therapy for rosacea does not symptoms include dilatation of blood vessels, release achieve optimal therapeutic response (10,27). This of proinflammatory cytokines, and accumulation of type of cutaneous side effect of vitamin B appears nitric oxide (12,18). Although some researchers sug- to be more common in women than in men (10). Al- gest that the minimum duration needed to develop though the pathological mechanism of vitamin B in rosacea-like symptoms was 3 months of continuous development of rosacea-like dermatitis is not yet fully use, the average duration of persistent use of topical corticosteroids required to produce these adverse ef- understood, the potential factor could be an irritation fects is in most cases 6 months or more (11,12). This of the follicular epithelium, leading subsequently to variability is largely conditioned by individual genetic an inflammatory reaction (5,10). In conclusion, vita- predisposition as well as the potency of the local cor- min B-triggered rosacea-like dermatitis is rare and ticosteroid used (11,13,15). Consequently, high-po- usually associated with the intake of large doses of tency topical corticosteroids such as clobetasol pro- vitamins over a shorter period of time, with early pre- pionate, betamethasone, fluticasone, and mometa- sentation of clinical symptoms. sone are more likely to induce this condition (11). VASOACTIVE DRUGS TOPICAL IMMUNOMODULATORS Vasoactive drugs, primarily vasodilators, could Local immunomodulator therapy is used for vari- be possible triggers that can induce or exacerbate ous skin diseases including atopic dermatitis, sebor- rosacea (30,31). Among this group of drugs, calcium rheic dermatitis, asteatotic eczema, contact dermati- channel blockers are most often associated with skin tis, or psoriasis localized in sensitive areas such as the disorders, affecting dominantly the facial area. These face (19-22). Although these agents have a good safe- agents are powerful peripheral arterial vasodilators ty profile and adverse effects are generally rare, there and are frequently used in the treatment of ischemic have been case reports of rosacea-like dermatitis, heart disease or arterial hypertension (32). Although rosacea-like demodicosis, and granulomatous erup- calcium channel blockers are in general rarely associ- 50 ACTA DERMATOVENEROLOGICA CROATICA Rezaković et al. Acta Dermatovenerol Croat Drug-induced rosacea-like dermatitis 2016;24(1):49-54 ated with adverse skin reactions, flushing is a com- (8,45,46). The earliest and most common skin side mon adverse effect of these drugs experienced by effect is an acneiform or papulopustular skin rash 5% of patients, with greater incidence in women than which is found in up to two thirds of patients receiv- in men (30,33). Side effects such as the appearance ing any of these agents (8,45-49). Clinical presenta- of subclinical rosacea as well as the exacerbation tion is usually mild or moderate and
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