Rosacea is a common chronic inflam-matory dermatitis characterised by

flushing and a spectrum of clinical signsincluding persistent central facial ery-thema, telangiectasia and an inflamma-tory papulopustular eruption. Thedisorder usually presents between theages of 30 and 50 years, although manypatients recall episodes of flushing yearsprior to presentation. Women are affectedmore commonly than men. It is most fre-quently observed in the fair-skinned butcan be seen in all skin types. The prominent visibility of the skin

changes can impact significantly on theindividual’s quality of life. Over 80 per centof patients with more severe rosaceareported that it impacted negatively on theirwork place interactions and over 50 percent missed work because of their skin con-dition.1 As well as the embarrassing appear-ance of the skin, patients often reportsensitive skin with symptoms ranging fromburning and itching to stinging and pain.

AetiologyThe cause of rosacea is unknown.Epidemiological studies indicate a geneticpredisposition but no specific rosaceagene has been identified.Environmental exposures are

reported to exacerbate rosacea. In a largesurvey conducted in the USA patientsreported several factors that triggered

their rosacea (see Table 1). Of these thetop ranked was sun exposure and 70 percent reported experiencing a flare-uprelated to emotional stress at least onceper month.1

Until recently there has been very lit-tle study of the disease. However, theapplication of current molecular biologytechniques is allowing the identificationof several different molecular inflamma-tory pathways in rosacea. An emerging hypothesis is that of an

exaggerated innate immune response.Patients with rosacea are found to haveincreased expression of Toll-like receptor 2(TLR2) in their skin.2 These are geneticallycoded detection systems that are triggeredby a number of different environmentalstimuli such as ultraviolet light, microbesand physical and chemical trauma. Once triggered they activate the

innate immune system producing anincrease in cathelicidins and other inflam-matory serum proteases producinginflammation with new vessel formationand telangiectasia.

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Treatment options in themanagement of rosaceaNoreen Cowley MRCP

Rosacea can be triggered bymany factors, and lifestyleadvice, trigger avoidanceand skin care should under-pin drug treatment. Here, theauthor discusses the clinicalsubtypes of rosacea and thetreatment options.

Figure 1. Erythematotelangiectatic rosacea is the most commonsubtype and the most difficult to treat; topical and oral antibioticsoffer limited benefit in treating background erythema

CPD questions available forthis article. See page 42

Clinical subtypesRosacea develops gradually. It typicallyaffects the central convexities of the face,nose, medial cheeks, forehead and chinwith a predilection for the nose in men.Skin may be rough or dry and may showevidence of solar damage. In April 2002 an expert committee

explicitly defined and classified rosacea

into four clinical subtypes based on specific clinical signs and symptoms(see Table 2).3 However, any one patientmay show features of more than onesubtype.

ErythematotelangiectaticErythematotelangiectatic rosacea (ETR)is the commonest type (see Figure 1).Patients report persistent erythema withprolonged episodes of flushing oftenaccompanied by a burning or stingingsensation. This group frequently reportsensitive skin that is intolerant of manyskin products. Examination reveals confluent ery-

thema affecting the forehead, cheek andnose with sparing of the chin. Closerexamination with magnified light revealstelangiectasia in these areas. To date,this clinical subtype has been the mostdifficult to treat.

Papulopustular rosacea Papulopustular rosacea (PPR) may looklike ETR with background redness but ischaracterised by inflammatory papulesand pustules on the cheeks and nose,and in some cases forehead and chin(see Figure 2). Many of these patientscome with a self-diagnosis of acne butthe classic comedones of acne areabsent. This subtype shows the best and

often dramatic clinical response to treat-ment that is gratifying for the patient anddoctor.

Phymatous rosacea Phymatous rosacea is characterised bythickening of skin with irregular surfacenodularities. It most often affects thenose (rhinophyma) but may also involveother areas such as the chin, foreheadand ears (see Figure 3).

Ocular rosaceaThe estimated risk of ocular rosaceavaries from less than 10 per cent to morethan 50 per cent in different studies.Most patients will have concomitant cuta-neous signs of rosacea, but in a smallnumber the ocular manifestations mayprecede the cutaneous changes. Severity of ocular rosacea is not pro-

portional to the severity of the facial

rosacea. It manifests as blepharitis, con-junctival hyperaemia, telangiectasia ofthe conjunctiva and lid margins, dry eyesand ocular discomfort. The patient oftengives a history of ‘styes’, irritability or intol-erance of contact lenses. The cause of ocular rosacea is

poorly understood and it is frequentlyundiagnosed. Patients are oftenunaware so it important that the clini-cian enquires specifically with regard toocular symptoms.

ManagementThe goal of treatment is to reduce mor-bidity and prevent complications. Currentmedical management is generallydirected at the subtype of rosacea andincludes both topical and systemicagents. However, because rosacea canhave a significant impact on quality of life,any treatment plan should also bedirected towards achieving improvementin general well-being. Typically, rosacea waxes and wanes.

Patients may have significant periods offreedom from lesions, though in practicemany have two to three attacks per year.As it is a chronic disease rosacea requireslong-term treatment and it is importantthat patients are made aware of this fromthe outset. In all forms of rosacea it is important

to identify and limit exacerbating stimuliand council avoidance. In most patientssun exposure is a trigger.

Basic skin careIt is important to discuss basic skin care,especially in patients with ETR. The useof daily sunscreen is recommended forall patients. A sunscreen that protectsagainst UVA and B should be selected(sun protection factor >15). Physical sun-screens that contain titanium dioxide andzinc oxide are better tolerated.The patient should be encouraged

to use nonirritating formulations wher-ever possible. For skin cleansing a mildagent should be used and the patientadvised to avoid astringents, toners,waterproof cosmetics requiring solventsfor removal or products containingsodium lauryl sulphate. The use of moisturisers should be

encouraged both to improve barrier

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Table 2. Clinical subtypes of rosacea

erythematotelangiectatic rosacea (ETR)papulopustular rosacea (PPR)phymatous rosacea ocular rosacea

Figure 2. Papulopustular rosacea is characterised by inflammatory papules and pustules; topical metronidazoleand azelaic acid are beneficial, as are oral tetracyclines

Table 1. The commonest triggers of rosaceaaccording to a survey conducted by the USNational Rosacea Society

sun exposureemotional stresshot weatherwindheavy exercisealcohol consumptionhot bathscold weatherspicy foods

SPL

function of the skin and enhance toler-ability of topical medications. Soothingmoisturizers with a high water contentcan be helpful for symptomatic burningand flushing. Patients should also beadvised that cosmetic camouflageadvice is available.4

Patients with ocular rosacea shouldbe advised on lid hygiene. Warm soaksand compresses are recommended alongwith twice-daily cleaning of the base ofthe lashes with baby shampoo or propri-etary lid cleansers along with the removalof any crust. Artificial tears are advisedfor patients with dry eyes. Ocular symp-toms will often improve with oral antibi-otics. One study showed benefit fromtopical ciclosporin5 but this is an unli-censed use. Facial redness is the commonest fea-

ture of rosacea and the most difficultaspect to treat. Topical and oral antibi-otics offer limited benefit in treating thebackground erythema. Recently, however,

the US Food and Drug Administration(FDA) has approved a topical alpha-2adrenergic agent for the treatment of red-ness in rosacea and other similar agentsare in development.6

Topical agentsAlthough there are numerous treatmentsavailable for rosacea there have beenvery few well-designed clinical trials. A Cochrane review evaluated 58 ran-

domised controlled trials of rosacea ther-apies. The two most commonly usedtopical agents metronidazole and aze-laic acid (Finacea) were better thanplacebo in 6633 patients with moder-ately severe rosacea.7 In studies compar-ing the two there was no significantdifference between the treatmentgroups in terms of patient-assessed out-comes.8

Both agents have been shown toreduce inflammatory lesions and peri -lesional erythema and possibly a reduc-tion in background erythema. They aremost beneficial in PPR.

Metronidazole 0.75 per cent cream or gel Topical metronidazole has been used fordecades to treat rosacea. Its mechanismof action is thought to be anti-inflamma-tory by reducing the release of reactiveoxygen species from neutrophils. It isapplied once to twice daily for 8 to 16weeks. Topical metronidazole has alsobeen shown to be effective in maintainingremission.9

Azelaic acid 15 per cent gel Azelaic acid possesses anti-inflammatoryactions that are believed to stem fromsuppressing neutrophil-derived reactiveoxygen species. Azelaic gel applied oncedaily has been demonstrated to be aseffective as twice daily, which is the gen-erally recommended dosing schedule.10

Other topical therapiesOther topical antibiotics such as erythro-mycin and clindamycin, along with calcineurin inhibitors (tacrolimus, pime-crolimus), are sometimes used as sec-ond-line treatments but there are littledata to support their use.Brimonidine 0.33 per cent gel,

recently approved by the FDA, is the first

agent developed specifically to target theredness of rosacea. Clinical trials haveshown significantly greater improvementin facial redness compared with the vehi-cle gel control. It is not yet available inthe UK.

Oral agentsTetracycline antibiotics have been usedand been effective for decades in thetreatment of PPR. Their benefit in rosaceais via an anti-inflammatory mechanism.Tetracyclines are known to have a host ofanti-inflammatory properties and havebeen shown to indirectly inhibit catheli-cidins by directly inhibiting matrix metal-loproteinases (MMPs).11

Nonmicrobial doses of slow-releasedoxycycline 40mg (Efracea) have beenshown to be as effective as 100mg (unli-censed indication) antimicrobial doses,supporting a primary anti-inflammatoryrather than antimicrobial effect inrosacea.12 Lower-dose doxycycline hasthe advantage of avoiding the develop-ment of resistance as well as the photo-toxicity seen at higher doses. Other tetracyclines such as lymecy-

cline 408mg daily and minocycline100mg daily have the advantage over tra-ditional oxytetracycline 500mg twice dailyof a once-daily dosage and lower potentialfor interaction with dietary calcium. Oral therapy is generally continued

until inflammatory lesions clear or 12weeks of therapy. As with topical therapyoral antibiotics are most effective in thepapulopustular form of rosacea. It is common practice to use both a

topical preparation such as metronida-zole or azelaic acid in combination withan antibiotic such as doxycycline to bringan acute flare under control. Once theinflammatory component responds thepatient can be continued on topicaltreatment.

Other oral antibiotics Although not commonly used, other oralantibiotics that have been used includeerythromycin 250–500mg twice daily,amoxicillin 250–500 three times dailyand metronidazole 200mg three timesdaily. Azithromycin 250mg three timesweekly is also effective and has beenused in refractory disease.

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Figure 3. Isotretinoin has been shown to reduce earlyrhinophyma and is useful for nodular inflamed disease

Figure 4. Ocular symptoms will often improve with oralantibiotics and lid hygiene should be advised

IsotretinoinIsotretinoin is used in the treatment ofsevere and phymatous rosacea (unli-censed indications). It has been shown to reduce early rhinophyma and is useful for nodular inflamed disease. It is used in lower doses than to treat acne.Unfortunately rosacea tends to relapseonce the treatment is stopped.

Laser and light therapies Laser treatment is effective at reducingthe redness and telangiectasia ofrosacea. It is probably the most usefulmodality for treating ETR. Studies com-pared pulsed-dye laser to intense pulsedlight and found both therapies to beeffective, with no difference between thetwo.13 Telangiectasia can recur aftersome time. The ablative CO2 laser or erbium YAG

laser can be used to treat rhinophyma/phymatous disease.

Surgical careSurgical care is indicated for establishedrhinophyma. Surgeons use excision, the

CO2 laser, the cauterising scalpel or acombination of these.

ConclusionManagement strategies in rosacea needto address the multifactorial aetiologyand varied clinical picture of the disease.Increased understanding of the aetiol-ogy and inflammatory mechanismsinvolved in rosacea should allow thedevelopment of more targeted therapyin the future. It is important that patients are made

aware from the outset of the chronicrelapsing- remitting nature of rosacea andhave realistic expectations of the out-come of treatment. Advice on lifestyle,trigger avoidance and appropriate skincare should underpin pharmacologicaltherapy.

References1. National Rosacea Society. Rosacea triggerssurvey. www.rosacea.org/patients/materials/triggersgraph.php.2. Yamasaki K, et al. J Invest Dermatol SympProc 2011:15;12–15.

3. Wilkin J, et al. J Am Acad Dermatol2002;46:584–7.4. Changing Faces. Find out about the skincamouflage service. www.changingfaces.org.uk/Skin-Camouflage/Find-out.5. Schechter BA, et al. Adv Ther 2009;26:651–9.6. Fowler J, et al. Br J Dermatol 2012;166:633–41.7. Van Zuuren EJ, et al. Brit J Dermatol 2011;165(4):760–81.8 .Elewski BE, et al. Arch Dermatol 2003;139(11):1444–50.9. Dahl MV, et al. Arch Dermatol 1998;134:679–83.10. Thiboutot DM, et al. J Drugs Dermatol2008;7(6):541–6.11. Kanada KN, et al. J Invest Dermatol2012;132:1435–42.12. Del Rosso JQ, et al. J Drugs Dermatol2008;7:573–6.13. Neuhaus IM, et al. Dermatol Surg 2009;35:920–8

Declaration of interestsNone to declare.

Dr Cowley is consultant in dermatologyat St Helier Hospital, Carshalton

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For each section, one of the statements is false – which is it?

1. Rosacea is a common chronic inflammatory dermatitis that:

a. may affect people of all skin types

b. may be worsened by sun exposure

c. is associated with increased expression of Toll-like receptor 2in the skin

d. usually presents before the age of 30

2. Rosacea is classified into four clinical subtypes, of which:

a. PPR is the most common

b. ETR is the most difficult to treat

c. phymatous rosacea is characterised by thickening of skinwith irregular surface nodularities

d. ocular rosacea may be associated with intolerance of contactlenses

3. In the management of rosacea:

a. all patients should use sunscreen

b. metronidazole gel is not effective in patients with moderatelysevere rosacea

c. azelaic gel applied once daily is as effective as twice daily

d. moisturisers enhance the tolerability of topical medication

4. In the treatment of rosacea:

a. azithromycin 250mg three times weekly has been used inrefractory disease

b. slow-release doxycycline 40mg is less effective than doxycy-cline 100mg

c. isotretinoin is useful for nodular inflamed disease

d. laser therapy is probably the most useful modality for treat-ing ETR

CPD: Management of rosaceaAnswer these questions online at Prescriber.co.uk and receive a certificate of completion for your CPD portfolio. Utilise the Learning into Practice form to record how your learning has contributed to your professional development.