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Treatment options for rosacea with concomitant conditions

Roebuck, Heather NP

doi: 10.1097/01.NPR.0000392794.17007.36
Feature: DERMATOLOGY CARE: CE Connection

Patients with rosacea frequently present with coexisting skin conditions, such as seborrheic dermatitis, acne, perioral dermatitis, and melasma, which may complicate diagnosis and treatment. This article discusses the presentation, pathophysiology, and management of rosacea with common concomitant skin disorders.

Patients with rosacea frequently present with coexisting skin conditions, such as seborrheic dermatitis, acne, perioral dermatitis, and melasma, which may complicate diagnosis and treatment. This article discusses the presentation, pathophysiology, and management of rosacea with common concomitant skin disorders.

Heather Roebuck is a nurse practitioner at The Dermatology Group, Waterford, Mich.

The author has disclosed she is a consultant for Amgen, Intendis, Ranbaxy, and OrthoNeutrogena and on the speaker's bureau for Amgen, Abbott, Intendis, and OrthoNeutrogena.

Rosacea is a common, chronic, persistent skin disorder that affects approximately 16 million individuals in the United States and 100 million people globally.1 Most prevalent in fair-skinned individuals, especially those of Celtic heritage (Fitzpatrick types I-III), rosacea has been reported in individuals with skin of Fitzpatrick types IV-VI as well.2(See Fitzpatrick skin types.) Onset of rosacea typically occurs between 30 and 50 years; however, it can develop at any age.2

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Although the exact pathophysiology of rosacea is unknown, the overexpression of cathelicidin antimicrobial peptides, which normally protect the host against infection, is thought to play a key role. Cathelicidins cause neutrophil recruitment, angiogenesis, and cytokine release, which may contribute to the inflammatory skin changes seen in patients with rosacea.3 Dysregulation of cathelicidins is observed in other skin diseases as well: these peptides are underexpressed in atopic dermatitis and other types of eczema.3–5

In addition to abnormal cathelicidin production and accumulation, Demodex folliculorum mites may be a factor in the pathophysiology of rosacea: increased numbers of this microorganism have been observed in some patients with rosacea. It is not known whether the increased levels of demodex are a result of rosacea or a cause, possibly by triggering a hypersensitivity reaction.6 Bacillus oleronius, a bacteria found within demodex mites, also has the ability to stimulate an inflammatory response among patients with rosacea.7 The exact cause of rosacea remains unknown.

More than half of patients with rosacea have concomitant skin disorders, according to a 2007 survey by the National Rosacea Foundation. Rosacea was accompanied by seborrheic dermatitis (SD) in 25%, acne in 20%, actinic keratosis in 16%, contact dermatitis in 14%, and psoriasis in 14% of patients.8 A survey of clinicians attending the Summer American Academy of Dermatology Meeting (N = 101) further supports these findings. SD was reported in 24% of rosacea patients and acne in 17%. Perioral dermatitis (PD) (11%) and melasma (8%) were also common conditions. Case studies presented in this article illustrate clinical approaches to the management of rosacea in patients with concomitant skin disorders.

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Rosacea with concomitant SD

Patients with both rosacea and SD have the erythema, papules and pustules, and other signs and symptoms of rosacea, as well as the flaking, scaly, usually oily, erythematous patches characteristic of SD. These patches may be pruritic.2 9 SD is thought to be caused by increased sebaceous and hormonal activity; the commensal yeasts Malassezia globosa and Malassezia furfur (Pityrosporum ovale) may also play a role.10 11 Yellowish scales typically develop on the scalp, hairline, and eyebrows with SD. When the honey-colored crusts and scales are noted along the eyelid margin, SD may be confused with ocular rosacea. Unlike rosacea, however, the greasy flakes or scales seen in SD are unaccompanied by flushing or inflammatory papules or pustules, except in severe cases, in which SD may be accompanied by yellowish-red scaling papules.9

Effective management of rosacea is based on skin type, rosacea classification and severity, concomitant diseases, and response to previous regimens.12 Financial ability and motivation to adhere to an individualized treatment plan must also be considered. Pharmacologic therapies include topical and oral therapeutic agents, used alone or in combination.2 13 Two first-line topical agents commonly used to treat rosacea are metronidazole gel 1% and azelaic acid gel 15%.2 14 The exact mechanism of action of metronidazole against rosacea is unknown; it may exert anti-inflammatory activity. Azelaic acid gel 15% is the only FDA-approved rosacea gel shown to reduce erythema in patients with papulopustular rosacea; it is thought to suppress rosacea through anti-inflammatory and antimicrobial mechanisms.15 Other FDA-approved topical treatments for rosacea are metronidazole cream, gel, and lotion 0.75% and 1% formulations and sulfacetamide 10%-sulfur 5% lotion, gel, pads, and foam.12 14 16

Oral antibiotics used to manage rosacea include tetracycline derivatives (such as tetracycline, doxycycline, and minocycline) and macrolides (such as erythromycin). However, the only FDA-approved oral antibiotic for the treatment of rosacea is doxycycline 40 mg.

Additionally, sometimes controversial, non–FDA-approved treatments for rosacea include short-term courses of topical corticosteroids (such as desonide or hydrocortisone); systemic corticosteroids; topical and oral antifungals; benzoyl peroxide; isotretinoin; the alpha-adrenergic agonist, clonidine and the beta-adrenergic blocker, propranolol; and antihistamines.2 14 Effective treatments for rosacea also include the avoidance of triggers (see Most common triggers of rosacea flares). The impaired skin barrier and vascular hyperreactivity characteristic of rosacea make the use of non-irritating skin care products essential.17

Daily use of a therapeutic moisturizer, gentle cleanser, and sunblock improve the signs and symptoms of rosacea,17–19 and may enhance the efficacy of therapeutic agents in patients with SD.10 Patients with lesional sites on the scalp may also benefit from the use of pyrithione-zinc containing shampoos, which significantly reduce flaking.20 Thus, education and direction on appropriate skin care are critical in managing patients with both rosacea and SD.

First-line, FDA-approved therapy for SD includes antifungal agents such as ketoconazole gel 2%.10 Anti-inflammatory therapies, including glucocorticosteroids, reduce the inflammation and erythema, and keratolytic agents such as over-the-counter (OTC) salicylic acid soften the scales associated with SD. Immunomodulators such as the topical calcineurin inhibitors, although not FDA-approved for SD, are sometimes prescribed to treat this condition.10 Sulfacetamide-sulfur and azelaic acid are also used for the management of SD.10 For patients with rosacea and SD, some topical treatments with anti-inflammatory properties may be effective against both skin disorders. Use of multitasking products can simplify the patient's treatment regimen, and may also reduce costs by minimizing the number of treatments needed.

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Case 1: A patient with rosacea and SD

Mr. J is a 43-year-old White man who presented with rosacea and SD (see Example of rosacea and SD). Mr. J has combination skin of Fitzpatrick type III and had been using OTC antibiotic ointment and protective ointment to treat his symptoms. He was prescribed azelaic acid gel 15% to be applied to the affected areas twice daily and oral doxycycline 40 mg once daily. In this case, azelaic acid gel 15% provides multiple mechanisms of action to reduce the signs and symptoms of both rosacea and SD, whereas the low dose of doxycycline provides anti-inflammatory action, which is beneficial for both conditions. Azelaic acid can effectively treat both SD and rosacea through its anti-inflammatory, antikeratinizing, antimicrobial, and antifungal activity. Azelaic acid acts specifically against Malassezia, which may further contribute to its efficacy in treating SD.10 15

Mr. J was initiated on a skin care regimen of a hydrating cleanser, sunblock with SPF 70, and moisturizing lotion. At a follow-up visit 2 weeks later, marked improvement in Mr. J's condition was noted, and doxycycline was discontinued. At a subsequent visit, the patient reported that his dentist had requested he take doxycycline 20 mg twice daily for periodontal disease. He verbalized being inconsistent with the twice-daily dosing and was switched to doxycycline 40 mg once daily. He was also referred to an ophthalmologist for ocular rosacea.

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Rosacea with concomitant acne

Clinical presentation, particularly the facial redness and inflammation of the skin, can be similar in acne and rosacea. Unlike acne, rosacea involves telangiectases and never presents with comedones. In addition, the redness seen in rosacea predominantly affects the central part of the face.14

Inflammation plays a key role in the pathogenesis of both acne and rosacea, although its causes are better characterized in acne. In acne, sebaceous hyperplasia with seborrhea, alteration of the follicular milieu, and colonization of the follicle with Propionibacterium acnes, result in inflammation and immune response.21 Acne is classified as comedonal or inflammatory, and mild, moderate, or severe.22

Mild acne is generally treated with topical retinoids, such as tretinoin 0.025% to 0.1%, which have anti-inflammatory activity and reverse the abnormal keratinization seen in acne.21 23 Azelaic acid's antikeratinizing, anti-inflammatory, and antibacterial (against P. acnes) activities make it useful for the treatment of mild acne as well as rosacea. Its ability to diminish postinflammatory hyperpigmentation is particularly helpful for patients with darker skin tones who have acne.15 21

Mild-to-moderate acne is generally treated with topical retinoids, antimicrobials, and benzoyl peroxide agents. Oral antibiotics such as tetracycline, minocycline, doxycycline, clindamycin, and erythromycin are usually added for moderate cases with papules, pustules, or nodules.21 23 Antibiotics also have anti-inflammatory activity, which contributes to their effect in acne.21 Benzoyl peroxide, a topical antimicrobial agent, also kills P. acnes, and unlike antibiotics is not associated with bacterial resistance. Benzoyl peroxide is available OTC and by prescription in gels, creams, foams, pads, and washes.21 23 Benzoyl peroxide products, however, may worsen inflammation in some patients with rosacea, and thus are not first-line for patients with both rosacea and acne. Oral contraceptives such as ethinyl estradiol plus drospirenone are also indicated for the treatment of acne, and are generally used for moderate cases of acne in women who desire an oral contraceptive for birth control.22

For appropriately selected and managed patients with severe acne, oral isotretinoin may be prescribed. Isotretinoin is also used off-label to treat rosacea in severe cases that have proved resistant to antibiotics.2 14 21 Because isotretinoin has been shown to cause birth defects, its use is contradicted in women who are, or who may become, pregnant. All patients prescribed this medication must be willing to comply with regulations set forth by the iPLEDGE program.

Patients with acne should be educated on the importance of gentle cleansing routines. Too-vigorous scrubbing can exacerbate the inflammatory phase of acne,21 just as it can rosacea. In addition, patients with acne and rosacea should be encouraged to use cleansers, moisturizers, and cosmetic products that are gentle and noncomedogenic.

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Case 2: Patient with rosacea and acne

Ms. R is a 30-year-old White woman with skin of Fitzpatrick type II who presented with rosacea subtype II and acne (see Rosacea subtype II and acne). Ms. R took oral tetracycline 500 mg once daily to treat her skin condition. Her skin care regimen consisted of an eczema care body wash, moisturizing lotion, and sunscreen with SPF 30. She continued her current skin care regimen and tetracycline 500 mg once daily. Azelaic acid gel 15% was prescribed to be applied to the affected areas of her face twice daily. Azelaic acid provides efficacy against both the patient's rosacea and acne. At a follow-up visit 1 week later, an increased number of papules were noted on Ms. R's skin. Ms. R also reported feeling "tightness" about her cheeks. The frequency of application of azelaic acid gel 15% was reduced to once daily. Two months later, the patient reported that the feelings of tightness had improved, and a visible reduction in Ms. R's facial erythema was noted. Ms. R stated that she did not utilize her medication consistently, and was counseled again regarding the chronic nature of her condition. Tools to improve adherence to her treatment plan were also shared.

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Case 3: Patient with rosacea and acne

Ms. M is a 53-year-old White woman who presented with rosacea subtype II and acne (see Rosacea and severe acne). Ms. M has Fitzpatrick type II skin. She had previously used metronidazole gel 0.75% twice daily and minocycline hydrochloride 100 mg once daily with limited success. Because of the severe nature of her acne, she had previously taken isotretinoin 40 mg twice daily. This had been discontinued after 3 months because of pyogenic granulomas around several of her fingernails. She had later been prescribed various topical retinoids with limited success. At the current visit, she was prescribed azelaic acid gel 15% once daily to alleviate both her acne and rosacea symptoms. She was also initiated on a skin care regimen with a hydrating cleanser, moisturizing lotion, and sunscreen with SPF 30. At 1-month follow-up, the patient was tolerating and remained on her oral and topical medications. Ms. M has experienced fewer flares of acne and rosacea with this combination regimen, and commented that she really likes the way her face feels.

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Rosacea with concomitant PD

PD presents as symmetrically grouped, discrete, erythematous papules, pustules, or vesicles grouped periorally and on the chin (see Typical presentation of PD in a 28-year-old woman). This condition, such as rosacea, is more frequently diagnosed in women, although PD tends to be more prevalent in young women while rosacea is most common in older women.24 At first glance, PD papules and pustules may appear similar to those associated with the patient's rosacea, but the distribution of papules and pustules in rosacea and PD is often different. PD, as its name suggests, appears in a perioral and sometimes perinasal or periocular distribution,24 whereas rosacea typically affects the central third of the face.

Both PD and rosacea are characterized by impaired skin barrier function, although the impairment is more pronounced in PD.25 Based on these findings, patients with both rosacea and PD would be expected to benefit from treatments shown to improve the epithelial barrier.

Among patients currently on topical corticosteroids and experiencing outbreaks of PD, the first step toward treatment is transition to a lower-potency corticosteroid and then off of corticosteroids altogether. Long-term corticosteroid use is not helpful for rosacea either; thus, removal of corticosteroid therapy from patients with rosacea and PD may ultimately help both sets of symptoms. The use of a step-down approach reduces the risk of a rebound flare of PD as the patient is transitioned off of topical corticosteroids.26

PD and rosacea are frequently treated with selections from the same group of agents, which may simplify treatment for those patients who have both skin disorders. Both rosacea and PD are commonly treated topically with metronidazole gel, sulfacetamide, erythromycin solution, tetracycline, and clindamycin.14 26 Azelaic acid, known to be effective in rosacea, may also be effective in the treatment of PD.27 Oral therapies for PD include tetracyclines and macrolides such as erythromycin.26

Paraffin, petrolatum, and other occlusives in cosmetics and moisturizers may aggravate PD. Therefore, products containing these ingredients should be avoided when choosing a skin care regimen for patients with PD and rosacea.27

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Rosacea with concomitant melasma

Melasma presents as an irregular gray or brown facial hypermelanosis, and is more common in women, particularly those with darker complexions (see A 43-year-old woman with melasma).28 Although the exact pathogenesis of melasma is unknown, it is hypothesized that, following UV light exposure (or another inducer), hyperfunctional melanocytes within involved skin produce increased amounts of melanin.11 Melasma can also occur in pregnancy due to changes in hormones; this is known as chloasma. Although melasma is more common in darker skin types and rosacea is more common in lighter skin types, cases of concomitant rosacea and melasma are not infrequent.

Traditionally, lightening agents such as FDA-approved hydroquinone are used to treat melasma, although recent questions regarding its safety have generated interest in other agents.29 Kojic acid, tretinoin, and azelaic acid also selectively inhibit cells with active tyrosinase activity, preventing the synthesis of melanin, and may be of use.28

In a trial evaluating the efficacy of azelaic acid cream 20% in treating melasma, the majority of patients showed significant improvement.30 This was likely mediated through azelaic acid's antityrosinase activity and antioxidant properties.15 Azelaic acid is one of the few agents with activity against both melasma and rosacea, making it a natural choice for patients with both conditions.

Laser treatments and chemical peels are also used to treat melasma; their mechanisms of action may be through selective thermal damage and removal of melanin, respectively. The most popular chemical peel for melasma is the glycolic acid peel.28 Discontinuation of oral contraceptives, scented cosmetic products (both in makeup and as facial cleansers), and phototoxic drugs is also recommended. Use of sunscreen is vital for the management of melasma, as it is for the management of rosacea, and should be emphasized in patients presenting with both conditions.28 31

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Patients with rosacea frequently present with other skin disorders, such as acne, SD, PD, and melasma. For patients with multiple concomitant skin disorders32—a group that includes more than half of all patients with rosacea—quality of life can be negatively affected, as the challenges of coping with multiple conditions may create additional frustration. Patients with rosacea demonstrate increased sensitivity to skin care products, which may pose a challenge to the management of concomitant skin conditions, as products used to treat the coexisting condition may exacerbate the rosacea symptoms, and vice versa.19

An individualized skin care regimen includes counseling about appropriate skin care and the pharmacologic therapies prescribed. Instructing patients on how to best use cosmetics to cover blemishes as needed can also significantly improve the patient's quality of life.17 33 34 Challenges in assembling a treatment regimen that fits the patient's needs include complexity—with overly complex regimens increasing the likelihood of nonadherence—and cost. In many cases, agents can be selected that are effective for more than one of a patient's skin conditions. Although combination therapy may often be necessary, in many cases a single agent with multiple mechanisms of action can treat more than one condition in the same patient. This parsimony of treatment can significantly benefit the patient, resulting in fewer co-pays and simplified treatment regimens. Educating patients about potential lifestyle modifications, appropriate skin care, and suitable pharmacotherapeutic agents can improve outcomes in patients with rosacea and concomitant skin conditions.

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rosacea management; seborrheic dermatitis; rosacea and concomitant skin disorders

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