LEADING ARTICLE

Rosacea: New and Emerging Treatments

Farah A. Moustafa • Laura F. Sandoval •

Steven R. Feldman

Published online: 26 August 2014

� Springer International Publishing Switzerland 2014

Abstract Rosacea is a chronic inflammatory skin condi-

tion that negatively impacts patients’ quality of life. We

sought to review important aspects of the pathogenesis of

rosacea and the role of new treatment options in its man-

agement. New, emerging treatments show promise; how-

ever, quality randomized controlled trials for many of these

drugs are lacking. Brimonidine tartrate is an effective

newly approved treatment for erythematotelangiectatic

rosacea. Topical oxymetazoline has potential for the

treatment of erythematotelangiectatic rosacea, with effi-

cacy described in case reports and randomized controlled

trials currently underway. Both oral and topical ivermectin

have been studied for the treatment of papulopustular

rosacea, both showing benefit; however, only topical

ivermectin 1 % cream has been studied in randomized

controlled trials. As our understanding of the etiology of

rosacea continues to evolve, so will our options for thera-

peutic interventions. Further studies need to be performed

to assess the long-term safety and efficacy of these

treatments.

Key Points

Rosacea is a chronic inflammatory skin condition

that remains difficult to treat.

New, emerging treatments such as brimonidine

tartrate, oxymetazoline, and ivermectin have been

studied and show promise; however, evidence is

limited at this time.

Further studies are needed to assess the long-term

safety and efficacy of these treatments.

1 Introduction

Rosacea is a chronic inflammatory skin disease and is one

of the most common conditions that dermatologists treat.

The reported prevalence of rosacea is between 1 and 22 %

[1]. This wide discrepancy in data largely stems from

various methodologies used to capture prevalence and

therefore cannot be reliably compared. The National

Rosacea Society recently reported that rosacea now affects

16 million Americans [2]. There are four well-known

manifestations of disease: erythematotelangiectatic (ET),

papulopustular (PP), phymatous (PH), and ocular [3]. It is

more common in middle-age individuals, women, Cauca-

sians, and those with Fitzpatrick skin type I and II. Because

it typically localizes on the central face, and can be dis-

figuring in some cases, many patients experience a

decreased quality of life [4]. The pathogenesis of this

disease is complex and poorly understood. Many theories

have been proposed and include dysregulation of innate

immunity, dysregulation of the neurovascular system, and

overgrowth of commensal organisms (e.g., Demodex).

F. A. Moustafa � L. F. Sandoval � S. R. Feldman (&)

Department of Dermatology, Center for Dermatology Research,

Wake Forest School of Medicine, Medical Center Boulevard,

Winston-Salem, NC 27157-1071, USA

e-mail: sfeldman@wfubmc.edu; sfeldman@wakehealth.edu

S. R. Feldman

Department of Pathology, Wake Forest School of Medicine,

Winston-Salem, NC, USA

S. R. Feldman

Department of Public Health Sciences, Wake Forest School

of Medicine, Winston-Salem, NC, USA

Drugs (2014) 74:1457–1465

DOI 10.1007/s40265-014-0281-x

Treatment recommendations vary based on subtype of

rosacea or on the signs and symptom present; however,

effective treatment can prove difficult [5]. Therapies pri-

marily focus on symptom suppression, in general targeting

inflammation. A better understanding of the pathogenesis

of rosacea is necessary to ensure better treatment outcomes.

In this paper, we review the recent developments in the

pathogenesis of rosacea and discuss the role of new treat-

ments and their relationship to the pathophysiology of

rosacea.

2 Pathogenesis of Rosacea

The pathogenesis of rosacea is complex and thought to

involve dysregulation of the immune, vascular, and ner-

vous systems. While not caused by microorganisms,

another evolving theory of the pathophysiology of rosacea

is the involvement of overgrowth of commensal mites on

the skin (Demodex folliculorum and Demodex brevis) in

some patients with rosacea. Evolving theories on the

pathophysiology of rosacea appreciate the complex inter-

play of dysregulation from these systems culminating in

the clinical picture of rosacea [6]. There is also a strong

suggestion of a genetic component, as transcriptome ana-

lysis has verified distinct gene profiles of rosacea subtypes

[7].

2.1 Dysregulation of the Innate Immune System

Dysregulation of the innate immune system may contribute

to chronic inflammation and vascular abnormalities in

patients with rosacea [8]. One pathway that may be relevant

involves Toll receptor activation. Initially, Toll-like recep-

tor 2 (TLR2) (a component of the innate system) is trig-

gered by inciting factors. Numerous environmental stimuli

can trigger TLR2, such as physical or chemical trauma, UV

light, and microorganisms. This results in release of a

processing enzyme, Kallikrein 5 (KLK5), from epidermal

keratinocytes. This enzyme is responsible for processing the

antimicrobial peptide cathelicidin into active its active

form, LL-37. In rosacea-prone skin, the proteolytically

processed forms of cathelicidin peptides are also different

from normal individuals and are more pro-inflammatory. It

is unclear how the abnormal form of cathelicidin is devel-

oped, but it is hypothesized to be the result of post-trans-

lational processing abnormalities associated with an

increase in KLK5, also known as stratum corneum tryptic

enzyme (SCTE), in the epidermis [8]. There is also higher

expression of TLR2 in keratinocytes of rosacea skin [9].

Increased levels of cathelicidin and KLK5 present in skin

from rosacea patients support the hypothesis of their role in

pathogenesis [8]. Downstream effects of these proteins

result in increased inflammatory cytokine release and

angiogenesis, contributing to the clinical picture of rosacea

Fig. 1 The role of innate

immune system dysregulation in

rosacea pathogenesis.

CAP18 cathelicidin-related

antimicrobial peptide 18, KLK5

kallikrein-related peptidase 5,

TLR2 Toll-like receptor 2, UV

ultraviolet

1458 F. A. Moustafa et al.

(Fig. 1). Mouse studies involving the injection of cathelic-

idin peptides from patients with rosacea led to inflammation

and vascular dilation, further supporting the role of cath-

elicidin in rosacea pathogenesis [8].

2.2 Dysregulation of the Vascular and Neurovascular

System

Facial erythema is a central component of rosacea and is

required for diagnosis. Worsening of disease is associated

with persistence and intensity of facial erythema. Skin

blood flow is increased in some patients, raising questions

regarding the role of vascular dysregulation in the patho-

genesis of rosacea and a potential factor to facial erythema

in rosacea patients [10–14]. Facial erythema in rosacea can

be divided into two major groups with different etiologies:

(1) central facial erythema; and (2) perilesional erythema

(surrounding papules and pustules in PP rosacea) [3, 15,

16]. Distinguishing between these types of erythema is

important for treatment selection.

Persistant facial erythema is a result of abnormal vas-

culature that results from chronic inflammation present in

rosacea-prone skin. This is a multifactorial process, but one

component involves LL-37 (the active form of cathelicidin)

promotion of inflammation and angiogenesis through its

downstream effects on endothelial growth factor receptors

(EGFRs) in keratinocytes [9]. Chronic inflammation also

leads to the associated telangiectasias found in rosacea

[15]. Increases in vascular endothelial growth factor

(VEGF) and endothelial nitric oxide (eNO) leading to

increased vascularization and vasodilation, respectively,

are also implicated in the chronic facial erythema present

in rosacea [8, 9].

Neurovascular dysregulation or increased ‘vasoactivity’

is also thought to play an important role [17]. The super-

ficial cutaneous system is largely regulated by the sympa-

thetic nervous system through action on adrenoreceptors.

While their role in rosacea pathophysiology is currently

poorly understood, they do seem to play an important role

as evidenced by the ability of new medications targeting

these adrenoreceptors to reduce erythema [14, 18].

2.3 Overgrowth of Commensal Organisms

D. brevis and D. folliculorum are two commensal mite

species that colonize the pilosebaceous follicle of human

skin. The role of the Demodex overgrowth in the patho-

genesis of rosacea has been controversial. Because the

presence of these mites on human skin is ubiquitous,

developing a causal relationship is difficult. The presence

of Demodex does not indicate rosacea; however, Demodex

infestation (defined as C5 mites/cm2) is higher in some

patients with ETR and PPR rosacea [17, 19].

Key components of Demodex overgrowth on the skin

and their interaction with an aberrant immune system

makes it an important consideration to better understand

the etiology of rosacea as well as therapeutic options.

Demodicosis (Demodex infestation) closely resembles

rosacea clinically; patients often experience erythema, tel-

angiectasias, and itching [20–22]. It is difficult to differentiate

patients as having Demodex infestation resembling rosacea or

rosacea with greater than average density of Demodex.

Perhaps it is not simply a Demodex infestation that

triggers rosacea, but the interaction of Demodex mite pro-

ducts interacting with the already aberrant and sensitive

innate immune system in rosacea-prone skin. As mentioned

above, TLR2 is over-expressed and more sensitive to acti-

vation in rosacea prone skin. Recently, Bacillus oleronius

bacterium has been cultured from Demodex mites and its

role in the pathogenesis of rosacea is under investigation

[23]. Antigens on the mite as well as the bacteria may could

potentially be recognized by TLR2 and result in its acti-

vation and downstream inflammatory effects in the skin.

In cases in which patients are found to have high Demodex

counts, it may be worth considering anti-parasitic agents

(ivermectin, permethrin) for the treatment of their rosacea.

3 Overview of Treatment

3.1 Current Treatment

In general, adjunct measures including high-factor sunsc-

reens, cosmetic camouflage, cooling, and avoidance of

irritants and triggers (extremes of temperatures, sunlight,

diet, alcohol, exercise, acute psychological stressors,

medications, menopausal hot flashes) are recommended for

all patients with rosacea [5]. The use of photoprotection is

particularly important in that it may prevent a flare trig-

gered by UV exposure, as well as help avert photodamage

skin changes such as erythema and telangiectasias that only

contribute to vascular changes of rosacea [24].

When conservative measures fail to control disease,

patients may benefit from medical interventions, including

pharmacologic and light-based therapies (Table 1). A

treatment algorithm based on signs and symptoms, with

consideration to severity, has been proposed by the Rosa-

cea International Expert Group [5]. For episodic erythema

or flushing, only experimental treatments are suggested

such as oxymetazoline, nadolol, and clonidine. In patients

with persistent erythema, topical treatment with azelaic

acid or sulfacetamide should be considered. However,

since the publication of guidelines, brimonidine tartrate

(BT) has recently been approved in the USA specifically

for treatment of persistent facial erythema. Oxymetazoline,

which works by a similar mechanism as brimonidine,

Rosacea: New and Emerging Treatments 1459

stimulating a-adrenergic receptors resulting in vasocon-

striction, could potentially also fall under the category for

treatment of persistent erythema. When topical therapies

fail to control disease or the rosacea is more severe, short-

term oral antibacterials including tetracyclines and mac-

rolides can be added. Topical agents, including brimoni-

dine, do not target telangiectasias; however, electrosurgery

can be used to treat these small vessels and laser can be

used to treat both telangiectasias and PH changes. Support

for the use of lasers is limited, but a Cochrane review by

van Zuuren et al. [25] did find some evidence for the use of

pulsed dye laser (PDL) and intense pulse light (IPL) ther-

apy for reducing erythema and telangiectasias. The

American Acne and Rosacea Society current consensus

recommendations for the use of physical modalities for the

treatment of rosacea include the use of IPL, PDL, and

neodymium-doped yttrium aluminium garnet (Nd:YAG)

lasers to target telangiectasias [26]. The recommendations

encourage appropriate patient selection and setting of

patient expectations; while improvement of 50–75 % in

telangiectasias over one to two sessions can be achieved,

improvement is of a much lesser extent in persistent ery-

thema, and complete resolution should not be anticipated.

The treatment of acne rosacea with papules and pustules

involves the use of topical agents for mild disease and

combination topical and oral therapy for more severe dis-

ease. Topical treatments including the topical antibacterials

metronidazole, clindamycin, and sulfacetamide-sulfur as

well as topical azelaic acid and retinoids are recommended.

A Cochrane systematic review of rosacea therapies pro-

vided support for the use of topical metronidazole and

azelaic acid, which were both more effective than placebo

[25]. There was some evidence that azelaic acid was more

effective than metronidazole in the treatment of PP rosa-

cea, but metronidazole may be better tolerated. When oral

therapy is warranted, low-dose doxycycline (40 mg/day) is

recommended for less severe disease, and for severe dis-

ease, high-dose antibacterials or low-dose oral isotretinoin

(10 mg/day) should be considered [5]. The anti-inflam-

matory properties of the tetracyclines, rather than their

antibacterial properties, are a primary rationale for their use

in rosacea [27, 28]. It is noteworthy that in a comparison

study doxycycline 40 and 100 mg/day were equally

effective, with the lower-dose regimen having few adverse

effects, specifically gastrointestinal symptoms [29]. In

addition, of all the systemic drugs used for rosacea, only

the modified-release doxycycline 40 mg/day formulation is

US Food and Drug Administration (FDA) approved. This

specific formulation was designed to exert anti-inflamma-

tory properties, with no antibacterial effects [30]. In rosa-

cea with nodules and plaques, systemic treatment with

high-dose tetracyclines and macrolides or isotretinoin

(0.5–1 mg/kg/day) is recommended, combined with topical

therapy. The use of isotretinoin is considered off-label for

the treatment for rosacea; however, studies support its use

in recalcitrant PP rosacea [31]. Unlike in the treatment of

acne, the use of isotretinoin is not likely to result in

remission of rosacea.

3.2 New and Emerging Treatments

3.2.1 Brimonidine Tartrate

Brimonidine 0.33 % gel (which contains 0.5 % BT salt)

was approved by the FDA in August 2013 for treatment of

persistent facial erythema. BT is an a2-adrenergic receptor

agonist, with vasoconstriction its primary mechanism of

action. To a lesser degree, it may also exert anti-inflam-

matory effects [32]. It has historically been used in the

treatment of open-angle glaucoma.

Phase II Clinical Trial (Table 2) The phase II clinical

trial consisted of two studies [33]. In Study A, BT gel was

effective in a dose-dependent fashion in reduction of ery-

thema for up to 12 h after a single application. The per-

centage of subjects who achieved a one-grade

improvement in Clinician’s Erythema Assessment (CEA)

Table 1 Current and emerging treatment options for rosacea

Rosacea presentation Current and emerging drug treatment options

Episodic erythema or

flushing

Topicals (oxymetazoline)

Oral (nadolol and clonidine)

Persistent erythema Topical a-adrenoreceptor agonists (brimonidine tartrate and oxymetazoline)

Topical azelaic acid or sulfacetamide

Papulopustular Mild: topical antimicrobials (metronidazole, clindamycin, and sulfacetamide-sulfur, and ivermectin),

azelaic acid, or retinoids

Moderate: topicals plus oral antimicrobials [tetracyclines (low-dose doxycycline 40 mg/day), macrolides,

or ivermectin]

Severe: topicals plus high-dose tetracyclines or low-dose isotretinoin

Recommendations based on the Rosacea International Expert Group, the Consensus Recommendations from the American Acne and Rosacea

Society on the management of rosacea, and the current literature [5, 14, 18, 20, 21, 33, 34, 41–43, 46, 47]

1460 F. A. Moustafa et al.

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Rosacea: New and Emerging Treatments 1461

and the Patient’s Self-Assessment (PSA) was 84, 81, 75,

and 28 % (BT 0.5, 0.18, 0.07 %, and vehicle, respectively).

In Study B, the outcome measure was defined as a two-

grade improvement in the CEA and PSA scores over 12 h

[33]. The percentage of subjects using BT 0.5 % gel who

had a two-grade improvement on CEA and PSA scores on

day 29 at hours 3, 6, 9, and 12 after application was 30, 28,

32, and 19 %, respectively, compared with 4, 7, 4, and 4 %

for vehicle once daily (p \ 0.001).

Phase III Clinical Trial (Table 2) The phase III clinical

trial comprised of two identical studies, with a total of 537

subjects randomized in a 1:1 fashion to apply BT gel 0.5 %

or vehicle daily for 4 weeks, followed by a 4-week follow-

up phase [34]. CEA and PSA were assessed during the

treatment phase before drug application as well as 30 min,

3, 6, 9, and 12 h after study drug application. The primary

outcome measure or defined ‘treatment success’ was a two-

grade improvement on both CEA and PSA scores over

12 h. In Study A, the percentage of subjects using BT gel

0.5 % who had a two-grade improvement on CEA and PSA

scores on day 29 at hours 3, 6, 9, and 12 after application

was 31.5, 30.7, 26.0, and 22.8 %, respectively (vs. 10.9,

9.4, 10.2, and 8.6 % for vehicle once daily; p \ 0.05). In

Study B, the percentage of subjects using BT gel 0.5 %

who had a two-grade improvement on CEA and PSA

scores on day 29 at hours 3,6, 9, and 12 after application

was 25.4, 25.4, 17.6, and 21.1 %, respectively (vs. 9.2, 9.2,

10.6, and 9.9 % for vehicle once daily; p \ 0.05).

One-grade improvement was a secondary outcome

measure in phase II and III clinical trials. Although there

were modest two-grade improvements in CEA and PSA in

these studies, one-grade improvements were significant

(Table 2) and represented clinically relevant effects.

All doses of topical BT gel were safe and well-tolerated

during the studies. The majority of related adverse events

were dermatological (skin irritation, erythema, skin burn-

ing sensation, dry skin, and pruritus). Most of these cases

were transient and mild. In B10 % of cases, the following

adverse effects occur: flushing, skin burning sensation, and

contact dermatitis. No clinically significant rebound

(worsening of erythema compared with baseline after

stopping treatment) was observed. In practice, however,

rebound has been an issue for select patients. A case report

describes rebound erythema in three patients using an

FDA-approved dosage of brimonidine gel 0.33 % for

treatment of rosacea [35]. All three patients reported

reduced erythema from baseline 1–6 h after application,

followed by severe erythema and burning sensation lasting

for approximately 12 h. Signs of hypersensitivity such as

urticaria and edema were not present. In our clinical

practice, we have seen a handful of patients who cannot

tolerate the medication due to rebound erythema. It is also

important to remind patients to avoid trigger factors while

using brimonidine, as the use of brimonidine does not

override flares as a result of exposure to a trigger.

An open-label study assessing the long-term safety and

efficacy of once-daily topical BT 0.5 % gel for 1 year

reported that efficacy of BT gel was maintained over the

time period with no observed tachyphylaxis (mean CEA

score prior to application of BT gel reduced gradually from

3.1 on day 1 to 2.4 at month 3 and remained stable until

month 12) [36]. PSA results were similarly maintained.

Drug-related adverse events were highest during the first

90 days of the study, and decreased after continued use.

The most frequently observed adverse events were flushing

(9.1 %), worsening of erythema (6.5 %), worsening of

rosacea (3.6 %), skin burning sensation (3.3 %), skin irri-

tation (3.1 %), contact dermatitis (2.2 %), and pruritus

(2.0 %).

The efficacy of brimonidine on PP lesions of rosacea has

not been studied. It appears not to aggravate inflammatory

lesions of rosacea in randomized trials evaluating its effi-

cacy for facial erythema, including when patients used

concomitant topical medications for PP rosacea [36].

However, due to the vasoconstrictive effects of the drug

and reduction of erythema, PP lesions may be more

noticeable. Brimonidine does not have effects on fixed

changes such as telangiectasia, and these lesions too may

become more visible when erythema is reduced. Patients

should be educated on expectations of treatment with

brimonidine prior to use.

3.2.2 Oxymetazoline

Oxymetazoline, a derivative of xylometazoline, is a

selective adrenoreceptor agonist (a1 and partial a2) and is

present in over-the-counter decongestants. It is also indi-

cated for the treatment of epistaxis, allergic rhinitis, and

conjunctivitis [37]. Although there is a much more com-

plex action than previously understood, topical application

reduces erythema through vasoconstrictive effects on the

a1-adrenoreceptors on smooth muscle surrounding blood

vessels that maintain vascular tone. Because of its action

on the a-receptors present on smooth muscle of larger

blood vessels, it has no effect on smaller blood vessels,

capillaries, and telangiectasias that are not surrounded by

smooth muscle (and are therefore not regulated by the

sympathetic nervous system). Activation of a-receptors has

also demonstrated anti-inflammatory effects [32, 38].

Oxymetazoline and xylometazoline have been shown to

inhibit neutrophilic phagocytosis and to decrease the gen-

eration of proinflammatory cytokines, which could con-

tribute to the inflammation in rosacea [38]. Oxymetazoline

and xylometazoline work through a similar mechanism as

BT (a2-agonist), and therefore have potential indications

for the treatment of persistent facial erythema. Compared

1462 F. A. Moustafa et al.

to brimonidine, oxymetazoline was a less potent vasocon-

strictor of the small subcutaneous vessels (less than

200 lm in diameter) that are thought to be the most

important in rosacea [32]. Concerns regarding long-term

use of these medications include tachyphylaxis and

rebound phenomenon.

Several case reports have described the off-label topical

use of oxymetazoline and xylometazoline in rosacea. In

two patients with recalcitrant ETR, once-daily application

of OTC nasal decongestant containing oxymetazoline hy-

drocholoride 0.05 % resulted in significant improvement of

facial erythema after application [18]. At long-term follow-

up (8 and 17 months), both patients reported continued

satisfaction with their treatment and had discontinued all

other medications for rosacea control except for the oxy-

metazoline nasal spray, with no reported tachyphylaxis or

rebound erythema. One patient with ETR treated topically

with xylometazoline 0.05 % solution experienced

improvement in erythema as well as in subjective symp-

toms (flushing, itching). Improvement in symptoms lasted

hours after application and long-term follow-up (8 months)

showed that daily topical application of the solution con-

trolled facial erythema with no reported adverse effects

[14].

Erythema is universal in patients with rosacea, yet it

remains the most difficult feature to treat. Given the

reported efficacy and safety of oxymetazoline and xylo-

metazoline in the treatment of persistent erythema, formal

randomized control trials are underway to assess its long-

term safety and efficacy [39].

3.2.3 Ivermectin

Both oral and topical ivermectin have been used to treat

rosacea and rosacea-like dermatitides. Ivermectin is a

macrocyclic lactone disaccharide antiparasitic agent typi-

cally used to treat parasitic infestations such as onchocer-

ciasis, strongyloidiasis, and filariasis, among others. In

dermatology, it is also used for the treatment of scabies, an

ectoparasitic infection. Ivermectin also targets the over-

growth of Demodex mites. As support for the role of

D. folliculorum and D. brevis in the pathophysiology

of rosacea grows, more interest is taken in investigation of

anti-parasitic agents that can control overpopulation of

these commensal mites on the skin. Ivermectin also has

anti-inflammatory properties that may contribute to miti-

gating rosacea symptoms. Ivermectin exerts its anti-

inflammatory effect by down-regulating the nuclear tran-

scription factor jB activation pathway that leads to

downstream production of pro-inflammatory cytokines

such as tumor necrosis factor (TNF)-a [40].

Two case reports of immunocompetent patients

describe the use of single doses of oral ivermectin (200

and 250 lg/kg) and topical permethrin resulting in com-

plete resolution of rosacea-like demodicidosis [20, 21].

Both patients had many Demodex mites on biopsy.

Another patient with recalcitrant PP rosacea with many

Demodex organisms on histologic examination was treated

with oral ivermectin (3 mg daily for a total dose of

24 mg) with complete resolution [41]. Oral ivermectin

was also safe and effective in three cases of demodicidosis

in patients with HIV infection [42]. Although there are no

formal randomized control trials to date that assess oral

ivermectin for treatment of rosacea, these cases suggest

that it can be a valuable treatment consideration in

patients who have recalcitrant rosacea and are found to

have excess Demodex infestation.

The efficacy and safety of topical ivermectin 1 % cream

has recently been investigated in PP rosacea with promis-

ing results. Two phase III multicenter, randomized, dou-

ble-blinded, parallel-group, vehicle-controlled trials of

identical design assessed use of ivermectin 1 % cream or

vehicle daily in patients to moderate to severe PP rosacea

[43]. At 12 weeks, significantly more patients in the iver-

mectin 1 % group achieved ‘clear’ or ‘almost clear’ on the

Investigator’s Global Assessment of Rosacea Severity in

both Study 1 (38.4 %) and Study 2 (40.1 %) compared

with vehicle (11.6 and 18.8 %, respectively). Inflammatory

lesion counts were also reduced with a mean difference of

-8.13 lesions (Study 1) and -8.22 (Study 2) between

ivermectin 1 % and vehicle (p \ 0.001 for both studies).

No serious related adverse effects were reported and the

ivermectin group reported less related adverse effects than

the vehicle group in both studies (4.2 and 2.6 % vs. 7.8 and

6.5 %, respectively). In a related extension study, patients

used vehicle used azaleic acid 15 % twice daily for

40 weeks instead of vehicle, with less treatment-related

adverse effects in the ivermectin group than in azaleic acid

group: 1.3 vs. 5.3 %, respectively [44]. A 16-week study

comparing the efficacy and safety of ivermectin 1 % cream

and metronidazole 0.75 % cream has also been completed

with results yet to be published.

3.2.4 Other Antiparasitics

Other scabicidal treatments such as permethrin and cro-

tamatin cream have been used for treatment of Demodex

dermatitis [20, 41, 45]. A retrospective chart review of 63

patients with resistant rosacea-like dermatitis treated twice

daily with topical crotamatin showed that 90.6 % of

patients experienced C50 % reduction in erythema, dry-

ness, scaling, roughness, and/or papules/pustules at the first

follow-up visit (range 13–55 days) compared with baseline

[45]. Improvements in symptoms were sustained over the

second follow-up visit (13–59 days after the first follow-

up).

Rosacea: New and Emerging Treatments 1463

4 Conclusion

As our understanding of the etiology of rosacea continues to

evolve, so will our options for therapeutic interventions. The

emergence of BT and oxymetazoline/xylometazoline for ET

rosacea, as well as ivermectin for PP rosacea show promise

for the future of rosacea treatment and more targeted ther-

apy. These drugs need further investigations assessing long-

term safety and efficacy in the treatment of rosacea. Rosacea

is a common skin condition that affects many people, and

can negatively impact quality of life. Interventions aimed at

controlling this chronic inflammatory condition and delay-

ing disease progression can positively affect the quality of

life of the many people affected by rosacea.

Acknowledgments The Center for Dermatology Research is sup-

ported by an unrestricted educational grant from Galderma Labora-

tories, L.P. Dr. Feldman is a consultant and speaker for Galderma,

Connetics, Abbott Labs, Warner Chilcott, Centocor, Amgen, Pho-

tomedex, Genentech, BiogenIdec, and Bristol Myers Squibb. Dr.

Feldman has received grants from Galderma, Connetics, Astellas,

Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex,

Genentech, BiogenIdec, Coria, Pharmaderm, Ortho Pharmaceuticals,

Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol Myers

Squibb, Stiefel, GlaxoSmithKline, and Novartis and has received

stock options from Photomedex. Farah Moustafa and Dr. Sandoval

have no conflicts to disclose.

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Rosacea: New and Emerging Treatments 1465

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