Clinical Topic A-Z Clinical Speciality

Rosacea

Rosacea
D012393Rosacea
Skin and nail
2012-09-01Last revised in September 2012

Rosacea - Summary

Rosacea is a chronic relapsing disease of the facial skin, characterized by recurrent episodes of facial flushing, persistent erythema, telangiectasia, papules and pustules, and eye symptoms (ocular rosacea, usually bilateral, and often described as a foreign-body sensation). Typically, it first presents between the ages of 30–50 years in people who are fair-skinned. Although it is more common in women, it tends to be more severe in men.

Possible triggers include extremes of weather (in particular heat, and cold winds), sunlight, strenuous exercise, stressful situations, spicy food, alcohol, and hot drinks. These should be avoided where possible.

Management of rosacea is largely guided by the type and severity of symptoms:

Predominant symptoms should be assessed to rule out acne vulgaris (this usually affects younger people and areas other than the face; it features comedones, and does not feature erythema, telangiectasia, or flushing).

For symptoms of flushing, erythema (without inflammation), telangiectasia, and rhinophyma, there is no effective drug treatment in primary care. Management consists of lifestyle advice (e.g. frequent use of high-factor sunscreen, avoidance of triggers, and the use of emollients, if needed) for mild rosacea or referral. Drugs such as calcium-channel blockers can aggravate flushing and should be avoided where possible.

For mild or moderate papulopustular rosacea (limited number of papules and pustules, no plaques), treatment options include topical metronidazole and topical azelaic acid.

For moderate or severe papulopustular rosacea (extensive papules, pustules, or plaques), an oral tetracycline or erythromycin is recommended.

Eye symptoms (ocular rosacea) are usually treated with a combination of eyelid hygiene measures, ocular lubricants (for dry eye symptoms), and oral tetracyclines. People with ocular symptoms that are severe or resistant to maximal treatment in primary care should be referred to an ophthalmologist.

People with severe phymatous disease (e.g. prominent rhinophyma) should be referred to a plastic surgeon.

People with rosacea should be advised to return if the condition deteriorates despite lifestyle changes or drug treatment.

In people requiring treatment, a follow up appointment should be arranged after 12 weeks to assess effectiveness of the treatment and determine future management.

Have I got the right topic?

192months3060monthsBoth

This CKS topic covers the management of rosacea in primary care.

This CKS topic does not cover the management of rosacea in secondary care.

There are separate CKS topics on Acne vulgaris, Blepharitis, Dermatitis - contact, Eczema - atopic, and Seborrhoeic dermatitis.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

CKS gratefully acknowledges the contribution of the British Association of Dermatologists in the development of this topic.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in September 2012

September 2012 — reviewed. A literature search was conducted in September 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No changes to clinical recommendations have been made.

Previous changes

October 2009 — updated to include doxycycline 40 mg modified-release capsules, which have been recently licensed in the UK for the treatment of rosacea. Issued in October 2009.

May to August 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There are no major changes to the recommendations. Prescriptions for eye drugs have been removed; if these are required you are directed to the CKS topic on Blepharitis.

May 2007 — minor update. Topical azelaic acid 15% gel has recently been launched and is licensed for use in papulopustular rosacea. The prescription for topical azelaic acid 20% cream (unlicensed for this indication) has been substituted for azelaic acid 15% gel (licensed). Issued in May 2007.

October 2005 — minor technical update. Issued in November 2005.

March 2005 — written. Validated in June 2005 and issued in July 2005.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2012.

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2012.

Economic appraisals

No new economic appraisals relevant to England since 1 September 2012.

Systematic reviews and meta-analyses

No new systematic reviews since 1 September 2012.

Primary evidence

No new randomized controlled trials published in the major journals since 1 September 2012.

New policies

No new national policies or guidelines since 1 September 2012.

New safety alerts

No new safety alerts since 1 September 2012.

Changes in product availability

No changes in product availability since 1 September 2012.

Goals and outcome measures

Goals

Assess the type, severity, and extent of rosacea

Prescribe appropriate treatment with topical drugs and/or oral antibiotics, and manage eye symptoms

Provide appropriate advice about managing symptoms and slowing disease progression

Follow-up of all people to assess the effectiveness of treatment and the need for referral

Background information

Definition

What is it?

Rosacea is a chronic relapsing disease of the facial skin, characterized by recurrent episodes of facial flushing, persistent erythema, telangiectasia, papules and pustules, and eye symptoms (ocular rosacea, usually bilateral, and often described as a foreign-body sensation). Typically, it first presents at the age of 30–50 years in people who are fair-skinned; although it is more common in women, it tends to be more severe in men [Powell, 2005].

Management

Management

Scenario: Rosacea : covers the management of rosacea in primary care.

Scenario: Rosacea

Scenario: Rosacea

192months3060monthsBoth

Treatment

How should I treat a person with rosacea?

Assess the predominant symptoms and rule out acne vulgaris (this usually affects younger people and areas other than the face; it features comedones, and does not feature erythema, telangiectasia, or flushing; see the CKS topic on Acne vulgaris).

Flushing, erythema (without inflammation), telangiectasia, and rhinophyma — there is no effective treatment for these symptoms in primary care, so management should consist of lifestyle advice (for mild rosacea) or referral. Some drugs can aggravate flushing (e.g. calcium-channel blockers), so avoid these where possible.

Mild or moderate papulopustular rosacea (i.e. limited number of papules and pustules, no plaques) — treat with a topical drug.

Metronidazole is usually preferred as it is well tolerated. Prescribe the gel (0.75%) or cream (1%) according to the person's preference (the cream may be more suitable for sensitive skin).

Azelaic acid is an alternative to metronidazole that may be more effective, especially in people who do not have sensitive skin. However, it may cause transient stinging.

Moderate or severe papulopustular rosacea (i.e. extensive papules, pustules, or plaques) — prescribe an oral tetracycline or erythromycin.

Tetracycline and oxytetracycline are both licensed for rosacea; they need to be taken twice a day on an empty stomach.

Doxycycline 100 mg and lymecycline are not licensed for rosacea; they need to be taken once a day (optionally with food).

A low-dose modified-release formulation of doxycycline 40 mg is now available. It is licensed for rosacea and is taken once a day.

Erythromycin is an option for pregnant or breastfeeding women, and other groups in whom tetracyclines are contraindicated.

Ocular rosacea — eye symptoms are usually treated with a combination of eyelid hygiene measures, ocular lubricants (for dry eye symptoms), and oral tetracyclines. For further information, see the CKS topic on Blepharitis.

Basis for recommendation

Basis for recommendation

CKS did not identify any authoritative, UK-based guidelines on the management of rosacea. Therefore, recommendations are based on evidence from randomized controlled trials (RCTs) where available [van Zuuren et al, 2011], and otherwise on the best available expert opinion described in narrative reviews [Powell, 2005; Diamantis and Waldorf, 2006; Berth-Jones, 2010].

A thorough assessment of rosacea is a pragmatic recommendation that reflects the need to rule out other diagnoses (especially acne vulgaris) and accurately determine the predominant subtype of rosacea in order to carry out optimal management. Vasodilatory drugs, such as calcium-channel blockers, should be avoided where possible, as they can exacerbate flushing [Powell, 2005].

Only papulopustular rosacea is receptive to treatments that are commonly used in primary care, with erythematotelangiectatic rosacea (i.e. persistent redness and flushing) being particularly difficult to treat [Baldwin, 2006]. In one RCT, people with poor outcomes were described as having 'redness rather than pustulation' as the predominant symptom of their rosacea [Pelle et al, 2004].

Topical treatments

Treatment of papulopustular rosacea is mainly symptomatic in nature, as there is a lack of evidence that treatment improves the underlying pathology or the long-term prognosis of the disorder [Berth-Jones, 2010]. However, treatment can lead to remission in the shorter term, and most drugs can be used intermittently or continuously to control symptoms (see Follow up).

Metronidazole is usually suitable as first-line treatment for mild-to-moderate papulopustular rosacea and for maintenance of more severe disease [Powell, 2005].

The mechanism of action of topical metronidazole in rosacea is not fully understood, but it may act as an anti-inflammatory and antioxidant, rather than as an antibiotic [Nally and Berson, 2006].

There is relatively good evidence from RCTs showing that topical metronidazole is more effective than placebo and equally as effective as oral tetracyclines; it causes fewer adverse effects than azelaic acid [van Zuuren et al, 2011].

Azelaic acid is an alternative that may be more effective than metronidazole, but is more likely to cause adverse effects [Pelle et al, 2004].

The mechanism of azelaic acid is likely to be similar to that of metronidazole. Azelaic acid has been shown to be superior to placebo. There is limited evidence from two head-to-head RCTs that azelaic acid is more effective than metronidazole, although further studies are required to confirm if this is clinically relevant [van Zuuren et al, 2011].

Azelaic acid may cause burning, stinging, itching, scaling, and dry skin in 26–38% of people, although these effects are transient and do not usually affect compliance [Gupta and Gover, 2007].

Oral treatments

Systemic treatment is recommended when there is moderate-to-severe papulopustular rosacea covering extensive areas that would be difficult to treat topically [Powell, 2005].

Tetracyclines are effective at a dose that is subtherapeutic to their antibiotic effect; this is thought to be an anti-inflammatory effect [Baldwin, 2006].

There is limited evidence from RCTs that tetracyclines are more effective than placebo, and as effective as both topical and oral metronidazole [van Zuuren et al, 2011]. The drugs used in these studies were tetracycline and oxytetracycline, which is reflected in their product licenses [BNF 64, 2012].

Low-dose doxycycline has recently been reported, in two RCTs, to be effective in the treatment of rosacea [Del Rosso et al, 2007], and lymecycline is also likely to be effective. Lymecycline is not licensed for this use in the UK, however, doxycycline 40 mg modified-release capsules have recently been licensed in the UK for rosacea. Both drugs are more convenient to take than the older tetracyclines, an important consideration for a drug that is be used in the long term.

Erythromycin is an alternative if tetracyclines are contraindicated (e.g. pregnancy, reactions to sunlight), and is recommended on the basis of clinical experience rather than controlled studies [Baldwin, 2006]. However, its effectiveness can be extrapolated from another macrolide, clarithromycin, which has been reported to be more effective, and better tolerated, than doxycycline in one RCT (n = 40) [Pelle et al, 2004].

Ocular rosacea

Ocular rosacea is the usual cause of posterior blepharitis (Meibomian gland dysfunction), which is discussed fully in the CKS topic on Blepharitis.

The eye is affected in about half of people with rosacea [Berth-Jones, 2010], and requires treatment to relieve symptoms and prevent deterioration.

Evidence for the effectiveness of treatment for blepharitis is, in general, lacking. However, CKS identified one RCT (n = 35) that found that oxytetracycline was associated with more remissions than placebo [Bartholomew et al, 1982].

Self-care advice

What self-care advice should I give about rosacea?

Reassure the person about the benign nature of rosacea and that progression to severe disease, such as rhinophyma, is uncommon (especially in women).

Recommend the frequent application of high-factor sunscreen (minimum sun-protection factor 30) to the face whenever the person is going to be exposed to sunlight. In addition:

If flushing is problematic, advise the avoidance of trigger factors (where practical). Possible triggers include extremes of weather (in particular heat, and cold winds), sunlight, strenuous exercise, stressful situations, spicy food, alcohol, and hot drinks.

If the skin is dry, advise the use of skin-care products as required (e.g. hypoallergenic and non-comedogenic emollient creams). The use of abrasive products or topical corticosteroids on the face should be avoided (even if they appear to help in the short term).

Basis for recommendation

Basis for recommendation

There is a lack of evidence from controlled trials to support lifestyle changes, as they are generally not suitable interventions for this type of study. Recommendations are therefore based on physiological and pharmacological principles, pragmatism, and clinical experience, as described in narrative reviews [Powell, 2005; Diamantis and Waldorf, 2006; Berth-Jones, 2010].

Explaining the natural history of the disease will usually reassure the person. Although the categorization of rosacea implies a progressive disorder, this is not necessarily the case. For instance, many people with facial flushing do not develop other symptoms; this has led some experts to believe the term 'pre-rosacea' (that is sometimes used) is inappropriate [Powell, 2005]. Where severe disease does develop (e.g. rhinophyma), the person can usually be treated by surgery or laser treatment in secondary care [Berth-Jones, 2010].

Solar radiation has been implicated in the pathogenesis of rosacea, and areas of exposed fair skin are most affected [Diamantis and Waldorf, 2006]. The use of sunscreens should limit further skin damage from sunlight, although this has not been verified by controlled studies.

The possible trigger factors (temperature, exercise, stress, alcohol, foodstuffs) all have the potential to physically irritate skin or dilate cutaneous blood vessels and elicit blushing [Powell, 2005]. It is therefore reasonable to advise the person to avoid them, at least on a trial basis.

Dry skin is a common complaint of rosacea, therefore CKS recommends an emollient should be used as appropriate. However:

People with rosacea tend to have sensitive skin [Jappe et al, 2008], so products with potential irritants (e.g. perfumes) should be avoided.

Topical corticosteroids (e.g. hydrocortisone) should not be used, except for severe inflammatory rosacea (under expert supervision) [Nally and Berson, 2006], as they can trigger, worsen, or mimic, the condition [Powell, 2005].

Follow up

How should I follow up a person with rosacea?

Advise the person to return if the condition deteriorates despite lifestyle changes or drug treatment.

Arrange to follow up after 12 weeks in people requiring treatment, to assess effectiveness and determine future management.

If treatment has been effective, it may be stopped. However, advise the person that their rosacea may relapse, requiring restarting the same treatment. Options include:

Maintenance treatment. This may be continuous (e.g. a reduced dose of oral treatment for 2–6 months followed by a 'drug holiday') or intermittent (e.g. using a topical treatment on alternate days or twice a week).

'Stepping down' from oral to topical treatment.

If treatment has not been satisfactory:

For people receiving topical treatment, consider switching to a different topical treatment, or prescribing an oral antibiotic.

For people receiving an oral antibiotic, consider adding a topical treatment, or seek specialist advice. Switching to an alternative oral antibiotic is unlikely to be of benefit.

Basis for recommendation

Basis for recommendation

CKS did not identify any authoritative, UK-based, guidelines on the management of rosacea. Recommendations on follow up and subsequent maintenance of rosacea are based on expert opinion described in narrative reviews [Powell, 2005; Diamantis and Waldorf, 2006; Berth-Jones, 2010].

CKS recommends people should be followed up after 12 weeks, as this reflects a reasonable individual trial period to assess whether treatment has been effective.

Most randomized controlled trials (RCTs) of interventions for rosacea have assessed response at 4–15 weeks, but mainly at the higher end of this range [van Zuuren et al, 2011].

The effect of treatment for rosacea often has a gradual onset, and some experts believe there is little point in discontinuing treatment before 3 months [Berth-Jones, 2010]. However, prescribing longer courses of treatment without monitoring is not recommended, especially for systemic drugs, as they may cause adverse effects without significant benefit [Powell, 2005].

Rosacea is a chronic, relapsing condition, which in general does not spontaneously resolve. However, RCTs studying the disorder have generally been performed over the short term, so recommendations on maintenance are based mainly on clinical experience and pragmatism [Powell, 2005].

Most people will benefit from maintenance or intermittent treatment, as rosacea often relapses after a successful course of treatment. For example, two studies found that the rate of relapse after stopping a course of tetracycline was 25% after 1 month, 50–60% after 6 months, and 70% after 1–4 years [Baldwin, 2006].

One longer-term RCT randomized people who had been successfully treated with oral tetracycline and topical metronidazole (n = 88) to receive maintenance treatment with metronidazole gel or placebo (gel vehicle). After 6 months, metronidazole gel significantly reduced the likelihood of relapse and the number of residual lesions compared with placebo [Dahl et al, 1998].

Combining oral and topical treatment has not been studied in controlled trials, but is a reasonable practice for people with severe disease.

Referral criteria

When should I refer a person with rosacea?

Refer routinely to dermatology those people with:

Flushing, persistent erythema, telangiectasia, or phymatous rosacea that is causing psychological or social distress.

Papulopustular rosacea that has not responded to 12 weeks of oral plus topical treatment.

An uncertain diagnosis.

Refer routinely to a plastic surgeon those people with severe phymatous disease (e.g. prominent rhinophyma).

Refer to an ophthalmologist:

Urgently, if keratitis is suspected (eye pain, blurred vision, sensitivity to light). See Referral criteria in the CKS topic on Blepharitis.

Routinely, if ocular symptoms are severe or resistant to maximal treatment in primary care.

Basis for recommendation

Basis for recommendation

CKS did not identify any national referral criteria or guidelines for rosacea. In the absence of established policy, these recommendations are based on pragmatism and what is accepted in the UK as good clinical practice.

A dermatologist is in a position to offer several pharmacological treatments that are not suitable for the treatment of rosacea in primary care. In general, there is a lack of evidence from controlled trials to support these treatments, rather than evidence of no effect. Therefore, an expert may trial them on an individual basis. These include [Pelle et al, 2004; Powell, 2005; Baldwin, 2006]:

Other topical treatments, such as benzoyl peroxide, topical antibiotics (other than metronidazole), tacrolimus, or retinoids (e.g. tretinoin).

Other oral antibiotics, such as clarithromycin, azithromycin (useful if erythromycin is poorly tolerated), or minocycline.

The combined oral contraceptive pill (if a hormonal cause is suspected in a woman).

Oral isotretinoin or clonidine (for flushing).

Cardiovascular drugs to prevent flushing (e.g. beta-blockers or spironolactone).

Some forms of rosacea are resistant to pharmacological treatment. Referral to secondary care allows for other options to be considered:

Persistent erythema is often mistakenly attributed to heavy drinking, and this can cause considerable stigma [Powell, 2005; Baldwin, 2006]. Erythema can be masked with camouflage makeup; the dermatology department should be able to provide the person with the relevant local contact information (see www.timewarp.demon.co.uk/redcross.html for details of the Red Cross Beauty Care and Cosmetic Camouflage Service).

Treatment options for telangiectasia and phymatous disease in secondary care include laser treatment and corrective electrosurgery [Pelle et al, 2004; Powell, 2005]. However, these are not generally available on the NHS.

Evidence

Evidence

Supporting evidence

Effectiveness of lifestyle changes

Evidence on the effectiveness of lifestyle changes

Lifestyle modifications are recommended on the basis of known physiological principles, epidemiological factors, and clinical experience, rather than data from controlled trials. One randomized controlled trial (RCT) reported that the use of sunscreen combined with metronidazole was more effective than placebo, but this does not provide evidence for the use of sunscreen alone.

A Cochrane review (search date: February 2005) identified a double-blind RCT (n = 120) that randomized people with rosacea to receive either a topical cream consisting of metronidazole (1%) combined with sunscreen (sun-protection factor 15), or placebo, for 4 weeks [van Zuuren et al, 2011].

More people in the treatment group than the placebo group reported improvement (p = 0.02).

There was a significant reduction in the number of lesions in the treatment group compared with placebo (13.6 compared with 4.6, p = 0.006).

However, this RCT does not support the use of sunscreen alone in the treatment of rosacea, as the benefit might have been solely due to topical metronidazole, which has been shown to be effective on its own. For more information, see Effectiveness of topical treatments.

Effectiveness of topical treatments

Evidence on the effectiveness of topical treatments (metronidazole and azelaic acid)

There is some evidence from randomized controlled trials (RCTs), identified by a Cochrane review, to support the use of topical treatments for rosacea. Topical metronidazole and azelaic acid have both been found to be more effective than placebo. Head-to-head trials have suggested that azelaic acid may be slightly more effective than metronidazole, but it may also cause more adverse effects.

A Cochrane review (search date: February 2005) identified a total of 29 RCTs that investigated a variety of interventions for the treatment of rosacea [van Zuuren et al, 2011]. Although the authors excluded trials that were of low methodological quality, they found flaws in the included trials, mainly in the reporting of outcome data. This limited the number of meta-analyses that could be performed.

Topical metronidazole (mostly 0.75%, applied twice a day) was compared with placebo in nine trials:

Self-assessed outcomes: two RCTs that used self-assessed improvement as the outcome were combined in a meta-analysis (n = 174), which found metronidazole to be more effective than placebo (OR 6.0, 95% CI 3.0 to 12.1). This result concurred with another study using subjects as their own controls, which found the metronidazole-treated side of the face improved compared with the placebo-treated side (OR 7.0, 95% CI 2.5 to 20.0).

Physician-assessed outcomes: pooled data from three RCTs (n = 303) found that metronidazole was superior to placebo in terms of global assessment (OR 7.0, 95% CI 3.6 to 13.8). Several trials used outcomes with a continuous scale (e.g. number of lesions), but these could not be combined due to poor reporting (e.g. the standard deviation was omitted). However, the authors of the review reported that in general the data from individual trials supported the effectiveness of metronidazole.

Topical metronidazole was compared with oral tetracyclines (oxytetracycline and tetracycline) in two RCTs (n = 126). Neither study showed any significant difference between the treatments in terms of effectiveness, and adverse effects were similar.

Topical azelaic acid (15% or 20%, twice a day) was compared with placebo in four RCTs.

Self-assessed outcomes: data from three studies were pooled (n = 778) that used the person's own assessment of their improvement. Azelaic acid was found to be significantly more effective than placebo, with around 70–80% of people reporting improvement (OR 2.4, 95% CI 1.8 to 3.3). The superiority of azelaic acid was also reflected in a study using subjects as their own controls, where nearly half the participants reported benefit, compared with 3% for placebo.

Physician-assessed outcomes: the assessing physicians of three RCTs rated azelaic acid as being more effective than placebo, with a global improvement rate of 60–80%. However, 40–60% of people were assessed as having improved with placebo, meaning that, on average, five people would need to be treated with azelaic acid for one person to benefit (NNT 5, 95% CI 4 to 7). Nearly all participants were reported as benefiting from azelaic acid in a study using subjects as their own controls, compared with 33% for placebo.

There was a non-significant increase in drop-out rate and adverse effects in people receiving azelaic acid, compared with placebo. However, adverse effects, when present, were described as mild.

Head-to-head trials — two head-to-head RCTs directly investigated the relative effectiveness of topical metronidazole and azelaic acid.

One trial randomized people with rosacea (n = 251) to receive metronidazole (0.75%) or azelaic acid (15%) for 15 weeks. There was a trend towards azelaic acid being more effective in terms of global improvement, but this was not significant when rated by the person (OR 1.3, 95% CI 0.8 to 2.2) or the physician (OR 1.8, 95% CI 1.1 to 3.1). However, there was a significant reduction in lesions and erythema with azelaic acid, although it also caused more adverse effects (OR 4.6, 95% CI 2.1 to 10.0).

One study using subjects as their own controls (n = 40) compared metronidazole 0.75% cream with azelaic acid 20% cream. Azelaic acid significantly reduced disease severity according to the treating physician, and was preferred by 92% of recipients compared with 66% for metronidazole (p < 0.02).

Effectiveness of oral treatments

Evidence on the effectiveness of oral treatments (tetracyclines)

There is some evidence from randomized controlled trials (RCTs), identified by a Cochrane review, to support the use of oral tetracyclines to treat rosacea. Tetracycline and oxytetracycline have been found to be more effective than placebo, when assessed by the physician. Head-to-head trials have suggested that tetracyclines are as effective as topical and oral metronidazole, and more effective than oral ampicillin.

A Cochrane review (search date: February 2005) identified seven RCTs that investigated oral tetracyclines for the treatment of rosacea [van Zuuren et al, 2011].

Three studies (n = 152) were identified that compared oral tetracyclines (tetracycline or oxytetracycline) with placebo.

After 4–6 weeks, 56 of 73 participants receiving tetracyclines improved according to the treating physician, compared with 28 of 79 people who received placebo. The effectiveness of tetracyclines was significant (OR 6.1, 95% CI 3.0 to 12.4).

One trial followed up the participants for 6 months, and found that most people relapsed after 2–3 weeks without continuous treatment.

Two studies were identified which compared a tetracycline with another oral antibiotic (neither oral metronidazole nor ampicillin are used to treat rosacea in the UK).

One study (n = 40) compared oral metronidazole with oral oxytetracycline (12 weeks of treatment). There were no significant differences in terms of effectiveness or adverse effects.

One small RCT (n = 20) found oral tetracycline was more effective than oral ampicillin, as assessed by the treating physician (OR 5.0, 95% CI 1.1 to 23.8).

Oral tetracyclines (oxytetracycline and tetracycline) have been compared with topical metronidazole in two head-to-head RCTs (n = 126). Neither study showed any significant difference between the treatments in terms of effectiveness or adverse effects.

Two North American RCTs published subsequent to the Cochrane review (n = 537) investigated the longer-term use (16 weeks) of low-dose doxycyline (40 mg controlled-release doxycyline once a day; this formulation is now available in the UK) in people with inflammatory rosacea [Del Rosso et al, 2007].

Both trials found that the drug significantly improved lesion count compared with placebo.

The authors commented that there was evidence that the treatment effect had not plateaued at this time, and that the most effective treatment for inflammatory rosacea may take months or years to manifest its full effects.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Rosacea.

Search dates

April 2008 - September 2012

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Rosacea/, rosacea.tw, ocular rosacea.tw

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

References

Baldwin, H.E. (2006) Oral therapy for rosacea. Journal of Drugs in Dermatology 5(1), 16-21. [Abstract]

Bartholomew, R.S., Reid, B.J., Cheesbrough, M.J. et al. (1982) Oxytetracycline in the treatment of ocular rosacea: a double blind trial. British Journal of Ophthalmology 66(6), 386-388. [Abstract] [Free Full-text]

Berth-Jones, J. (2010a) Rosacea, perioral dermatitis and similar dermatoses, flushing and flushing syndromes. In: Burns, T., Breathnach, S., Cox, N. and Griffiths, C. (Eds.) Rook's textbook of dermatology. 8th edn. Oxford: Blackwell Publishing. 43.1-43.20.

BNF 64 (2012) British National Formulary. 64th edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.

Dahl, M.V., Katz, I., Krueger, G.G. et al. (1998) Topical metronidazole maintains remissions of rosacea. Archives of Dermatology 134(6), 679-683. [Abstract] [Free Full-text]

Del Rosso, J.Q., Webster, G.F., Jackson, M. et al. (2007) Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. Journal of the American Academy of Dermatology 56(5), 791-802. [Abstract]

Diamantis, S. and Waldorf, H.A. (2006) Rosacea: clinical presentation and pathophysiology. Journal of Drugs in Dermatology 5(1), 8-12. [Abstract]

Gupta, A.K. and Gover, M.D. (2007) Azelaic acid (15% gel) in the treatment of acne rosacea. International Journal of Dermatology 46(5), 533-538. [Abstract]

Jappe, U., Schäfer, T., Schnuch, A. and Uter, W. (2008) Contact allergy in patients with rosacea: a clinic-based, prospective epidemiological study. Journal of the European Academy of Dermatology and Venereology 22(10), 1208-1214. [Abstract]

Nally, J.B. and Berson, D.S. (2006) Topical therapies for rosacea. Journal of Drugs in Dermatology 5(1), 23-26. [Abstract]

Pelle, M.T., Crawford, G.H. and James, W.D. (2004) Rosacea: II. Therapy. Journal of the American Academy of Dermatology 51(4), 499-512. [Abstract]

Powell, F.C. (2005) Clinical practice. Rosacea. New England Journal of Medicine 352(8), 793-803. [Free Full-text]

van Zuuren, E.J., Kramer, S., Carter, B. et al. (2011b) Interventions for rosacea (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]