Dr George Moncrieff, Chair of the Dermatology Council for England, provides his personal view of the recent PCDS rosacea treatment pathway

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Read this article to learn more about:

  • the different types of rosacea, and what treatments are best suited for each type
  • common triggers that can aggravate rosacea symptoms
  • pharmacological alternatives to antibiotics.

Key points

GP commissioning messages

W ith an overall prevalence of around 10%,1 rosacea is commonly encountered in general practice; however, very often the problem is not raised because of embarrassment or a perception that little can be done. Rosacea predominantly affects the face, so inevitably it can have a serious impact on an individual’s self-confidence, and even their career opportunities. It is important therefore, that practitioners do not dismiss rosacea as either trivial or simply a 'cosmetic issue'.

In May 2016, the Primary Care Dermatology Society (PCDS) released Rosacea—primary care treatment pathway.2 The PCDS recognised that patients with rosacea will often remain on antibiotics for many years; however, a number of very effective non-antibiotic alternatives are now available. In an era of increasing concern regarding antibiotic stewardship (see section below), the PCDS is keen to share its views on where these new therapies should be positioned.

Note: Some of the medicines discussed in this article currently (December 2016) do not have UK marketing authorisation for the indications mentioned. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices3 for further information.

What is rosacea?

Rosacea is a chronic skin condition of the face. Middle-aged (30–60 years) and fair-skinned people are most affected (though it can occur in all skin types).2,4 It is more common in women, but is more severe and peaks a little later in men.1

The hallmark of rosacea is permanent erythema of the face—notably the cheeks, nose, and forehead areas. Typically, the skin around the eyes is spared, although the eyelids are often affected (see Figure 1, below). Rosacea rarely affects the scalp, chest, or elsewhere. Patients presenting with rosacea will usually describe an exaggerated tendency to flush, which can be prolonged and uncomfortable; some may also describe a stinging or burning sensation in the skin.4 These episodes are often triggered by:

  • embarrassment
  • temperature changes
  • sunlight
  • hot or spicy foods
  • alcohol
  • exercise
  • emotional stimuli.

Areas of the face commonly affected by rosacea

Figure 1: Areas of the face commonly affected by rosacea

Over time, this vasomotor instability can result in the development of permanent telangiectasia in the affected areas—so-called 'erythrotelangiectatic rosacea'.2

Some people develop a more inflammatory pattern, with papules and pustules—this is known as papulo-pustular rosacea (PPR). People with PPR may have fewer problems with flushing. The affected skin often feels rough and scaly. Unlike in acne vulgaris, open comedones (blackheads) are not a feature of any type of rosacea,2 although they may be present incidentally.

Around one-half of all people with rosacea have some involvement of the eyelids or eyeball (called 'ocular rosacea'), and this can be a useful marker for the diagnosis. Problems include: blepharitis, dry 'gritty' eyes, styes, and keratitis.2

Rhinophyma (the thickening of the nasal skin) is a related but separate condition and is not covered in this article.

Differential diagnosis

Practitioners should be aware of the following differential diagnoses.2

Acne vulgaris

Acne vulgaris usually affects a younger age group, although it is not uncommon to see acne in people aged over 30 years.5 Distinguishing features of acne include a lack of background erythema, a general greasiness of the skin, and the presence of comedones. Involvement of the chest and back is also often present in acne.

Seborrhoeic dermatitis

Most patients with seborrhoeic dermatitis will have a history of dandruff. There is usually some dryness and scaliness of the nasolabial folds. Other areas that are commonly affected include the eyebrows, ears, sternal area, and axillae.

Periorificial dermatitis

Periorificial dermatitis can present with a spectrum of skin changes from acneiform lesions to ones that look more eczematous. Patients will almost invariably have a history of exposure to a topical steroid, but no history of flushing.6 The papules and pustules are typically smaller than in rosacea.

Antibiotic stewardship

Prolonged courses of antibiotics, both topical and systemic, have been the mainstay of managing rosacea for many years. Most prescriptions for an antibiotic in primary care are for short courses (for example, to treat a chest or urinary tract infection). It is estimated that roughly 8% of all antibiotics prescribed in the UK are for dermatological indications.7

When antibiotics are used to treat conditions such as acne or rosacea, the course typically lasts many years and consequently has an exaggerated impact on the human microbiome and antibiotic resistance;8 hence the need to explore non-antibiotic therapies (see below).

Treatment

General measures and advice

Where possible, patients should be encouraged to avoid triggers that cause flushing. Clearly that is not always possible, but avoiding any recognised triggers (e.g. spicy foods, alcohol, or a hot sauna) would be sensible. Some patients benefit from using a high-factor sunblock (sun protection factor 30+) all year round. Most foundation creams will already contain sunblock, but men in particular may need advice. A green-tinted cream can help to camouflage the background erythema.2

Because the skin barrier is disturbed in rosacea, I encourage patients to use leave-on emollients and to avoid detergents.

At first, patients may require a combination of topical and systemic treatments; however, in the longer term, topical treatments are preferable.

If no significant improvement is seen after 2 months of treatment, review the diagnosis and the patient's adherence to advice, and consider referring the patient to specialist services (see Box 1, below).2

Box 1: When to refer2

Refer if:

  • there is doubt about the diagnosis
  • there is severe psychological distress
  • there is no response to treatment
  • the patient may benefit from IPL or PDL therapy.

IPL=intense pulsed light; PDL=pulsed dye laser

Adapted from Primary Care Dermatology Society. Rosacea—primary care treatment pathway. PCDS, 2016. Available at: www.pcds.org.uk/ee/images/uploads/general/Rosacea-Guidelines-FINAL.pdf

Topical steroids may temporarily improve some of the inflammatory elements of rosacea, but they are notorious for aggravating rosacea and should be avoided.2 I have even seen rosacea caused by inadvertent exposure to steroids from a steroid nasal spray, or after inadequately washing a topical steroid off the hands (having used it elsewhere on the body) and touching the face. I suspect that the problem with topical steroids is through the damaging effect they have on the skin barrier. Clearly, careful avoidance of any exposure to a topical steroid is crucial.

Treatment options are directed by the predominant type of rosacea affecting the patient (see Table 1, below);2 the following sections discuss the most suitable treatments for each type.

ProductFlushing and fixed erythemaInflammatory papules and pustulesOcularProtocol and comments*
Table 1: Treatment options for rosacea subsets2
Ivermectin cream 1%   +++   Well tolerated, once daily, greater efficacy than metronidazole and no concerns with antibiotic resistance
Azelaic acid gel   ++   Effective twice daily, may cause irritation and no concerns with antibiotic resistance
Metronidazole gel or cream 0.75%   +   Twice daily, less effective than ivermectin
Brimonidine gel 0.33% ++     Effective and fast-acting vasoconstrictor, patients should be warned about the possibility of rebound flush, which can limit usage
Eye lubricants     +++ Lid hygiene and warm eye compresses also important
Doxycycline MR 40 mg   +++   Once daily. Fewer side-effects and equivalent efficacy as full dose (100 mg). Sub-microbial dose reduces risk of antibiotic resistance compared with other antibiotics
Doxycycline 100 mg and 

 

Lymecycline 408 mg capules

  ++ ++ Less expensive, more side-effects.

 

Well tolerated, once daily

Oxytetracycline 250–500 mg   + + Twice daily, avoid taking with meals
Erythromycin/clarithromycin 250–500 mg   +   Twice daily, useful in pregnancy
Isotretinoin   ++   Useful in secondary care for resistant cases
Intense pulsed light (IPL) +++     Limited NHS availability
Pulsed dye laser (PDL) ++     Limited NHS availability and causes significant bruising
Clonidine 25–50 µg ++     Up to three times daily, improves flushing in some patients
Propranolol 10–40 mg +     Up to three times daily
Carvedilol 3.125–6.25 mg +     Up to three times daily
+++ = strong recommendation; ++  = moderate recommendation;  = low recommendation.

* These comments are the opinions of the contributors, reviewed by the PCDS Executive Committee and do not consider NHS costs and local prescribing restrictions, if any.

Primary Care Dermatology Society.Rosacea—primary care treatment pathway. PCDS, 2016. Available at: www.pcds.org.uk/ee/images/uploads/general/Rosacea-Guidelines-FINAL.pdf Reproduced with permission.

Erythrotelangiectatic rosacea

Clinical features: flushing, persistent erythema and/or telangiectasia

There are few options here. In my experience, antibiotics have virtually no benefit, whether used topically or systemically.

A novel product, brimonidine gel,9 has become available. Brimonidine is an alpha-adrenergic receptor agonist, and has been used as an eye drop to treat glaucoma for decades. Topical application of brimonidine gel to the skin results in rapid vasoconstriction, and thus, control of any background erythema or flushing for up to about 12 hours. Some patients complain of rebound vasodilatation, and very rarely the product can cause contact dermatitis, so it is not universally acceptable. Practitioners should warn patients of these adverse effects.2,10 Nevertheless, brimonidine gel is an exciting new and logical remedy and it will be interesting to see if controlling vasomotor instability in this way may prevent progression of the disease to a more inflammatory state.

Alternatively, off-licence oral clonidine can be prescribed (25–50 micrograms, up to three times a day), but I have had little experience of this, as it is quite 'old-fashioned' and not free of side-effects. Oral beta blockers can be used, but their effect is usually marginal. If the condition is severe, referral for intense pulsed light (IPL) or pulsed dye laser (PDL) therapy are options; however, both IPL and PDL have limited availability on the NHS, so referral is usually private. It is also worth noting that PDL therapy can cause significant bruising.2

Papulo-pustular rosacea

Clinical features: presence of papules and pustules

In the past I would have prescribed a topical or oral antibiotic first-line for PPR, but for the reasons discussed above regarding antibiotic stewardship, it is best to avoid that practice.

Anti-mite treatments such as topical permethrin or oral ivermectin have been used for years, off-licence, to treat resistant rosacea. I believe the demodex folliculorum mite and the bacterium, bacillus oleronius, which lives in its gut, have a central role in the pathogenesis of PPR.11 A topical formulation of ivermectin12,13 was licensed in 2015 and this has now become my first-line choice for PPR. I have been impressed with the results (see Figure 2, below), with most patients achieving full or almost complete control of their symptoms within a couple of months. I warn patients that the product might initially cause some stinging or even worsening of their rosacea (I believe this is likely to be due to the release of inflammatory elements when the mites are killed), but usually within a week they see signs of improvement. Ivermectin cream is more expensive than many of the alternative antibiotic creams per gram, but these often require application twice a day, whereas topical ivermectin only needs to be applied once a day. Consequently, the cost is very similar, it is more convenient for patients, the effect is superior, and of course, it is not an antibiotic.2,13,14

Figure 2: Treatment progress of rosacea on a patient’s forehead using ivermectin
T=0 (baseline)T=4T=8
ivermectin rosacea treatment progress A ivermectin rosacea treatment progress B ivermectin rosacea treatment progress C
T=time (weeks)
Click images to view full size.
Photographs by Dr George Moncrieff.

A second-line option, azelaic acid gel, has a relatively mild but useful effect and can control mild PPR. It can cause some stinging (especially on initial use);2 however, this can be helped by keeping the gel in the fridge and applying it cold. Tolerance to this side-effect usually develops with ongoing use.

I would now only consider using metronidazole 0.75% cream or gel as a third-line option.

More severe or resistant disease may require systemic treatment. Although I remain keen to avoid using antibiotics, lymecycline (off-licence) is a reasonable and inexpensive option. Personally, I prefer low-dose doxycycline (40 mg modified-release) as at this dose it has negligible antibacterial activity or effect on the microbiome.15 It is, however, more expensive so it is not always available on local formularies. If a systemic treatment were needed during pregnancy or breastfeeding, clarithromycin could be considered.2

Low-dose isotretinoin, again off-licence, can be remarkably effective for resistant PPR. The dose needed is usually around a quarter of that used to treat acne, so most side-effects are minimal, but the course often needs to continue for many months or longer. Prescription in the UK, however, is still limited to secondary care, and meticulous attention to the Pregnancy Prevention Programme can mean that this is not a realistic option for any woman of child-bearing potential.2

Ocular rosacea

Clinical features: eye symptoms, including blepharitis, dry 'gritty' eyes, styes, and keratitis

Ocular rosacea can be tricky. Clearly, sensible advice such as simple eyelid hygiene (e.g. washing regularly with hot saline and using eye lubricants and warm eye compresses) can be helpful.2 It is critical to avoid topical steroids. In more severe cases, an oral antibiotic (either doxycycline or lymecycline) may be required. Oral isotretinoin is contraindicated as this usually renders the eye too dry, and is liable to aggravate the skin. Referral to an eye specialist may be necessary.

Follow up

Patients with rosacea should expect to see a significant improvement within a few weeks of commencing treatment. I would therefore recommend a review between 6 and 8 weeks after a new treatment has been started. Although the Dermatology Life Quality Index16 was originally designed for people with psoriasis, it is perfectly reasonable to use it for those with rosacea. It can be completed by the patient within a couple of minutes and can provide an extraordinary insight into the impact of the disease on their life. Increasingly, I also suggest that patients take a 'selfie' (a self-portrait photograph) on their smartphone, if they have one. This allows for a more objective assessment to be made of any skin improvement.

A patient information leaflet developed by the British Association of Dermatologists explaining what rosacea is, what causes it, what can be done, and where to find more information may be a useful handout.17

Summary

Rosacea is a chronic condition that usually lasts for several decades. There are now some outstanding, non-antibiotic treatments, which I believe should be first-line options in primary care. I commend the PCDS guideline to you and I hope you will find it is a clear, easily accessible resource in primary care. It should help direct practitioners to some of the newer, highly-effective treatment options and encourage more responsible use of antibiotics.

I am looking forward to seeing whether good control of the flushing can help to curtail progression to more inflammatory changes; this would certainly support early, aggressive treatment.

Key points

  • Rosacea is a common condition characterised by redness of the facial skin, and can have a significant impact on an individual’s psychological wellbeing
  • It predominantly affects middle-aged (30–60 years) people with fair skin, but can occur at any age and in all skin types
  • Treatment is often required because avoiding triggers can be difficult for patients
  • Several different subtypes of rosacea exist; it is important to choose the right treatment for the type of rosacea present
    • Treatment options are directed by the predominant type of rosacea present
  • The PCDS Rosacea—primary care treatment pathway has been developed in response to the growing concerns about antibiotic resistance
  • If possible, long-term use of antibiotics should be avoided.

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GP commissioning messages

written by Dr David Jenner, GP, Cullompton, Devon

  • Rosacea is a complex condition to treat due to the various types that can present, with each type requiring different treatments
  • Commissioners should agree a treatment pathway with dermatologists and include it in local formularies and referral guidelines
  • Local formularies should identify the acquisition cost of treatments and their licensed indications, and provide reasons for advising the use of any agent off-licence
  • These formularies could also include patient information sheets that can be printed off and handed to patients
  • In most cases, rosacea can be managed in primary care, but the local pathway should identify trigger points for referral to specialists.

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Read the Guidelines summary of the PCDS Rosacea—primary care treatment pathway for more recommendations on the management of rosacea

References

  1. Spoendlin J, Voegel J, Jick S, Meier C. A study on the epidemiology of rosacea in the U.K. Br J Dermatol 2012; 167 (3): 598–605.
  2. Primary Care Dermatology Society. Rosacea—primary care treatment pathway. PCDS, 2016. Available at: www.pcds.org.uk/ee/images/uploads/general/Rosacea-Guidelines-FINAL.pdf
  3. General Medical Council. Good practice in prescribing and managing medicines and devices. GMC, 2013. Available at: www.gmc-uk.org/Prescribing_guidance.pdf_59055247.pdf
  4. Primary Care Dermatology Society. Rosacea. PCDS, 2016. Available at: www.pcds.org.uk/clinical-guidance/rosacea
  5. Collier C, Haper J, Cantrell W et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol, 2008; 58 (1): 56–59.
  6. Dermnetz. Periorificial dermatitis. www.dermnetnz.org/topics/periorificial-dermatitis (accessed 30 November 2016).
  7. Walsh T, Efthimiou J, Dréno B. Systematic review of antibiotic resistance in acne: an increasing topical and oral threat. Lancet Infect Dis 2016; 16 (3): e23–33.
  8. Nagler A, Milam E, Orlow, S. The use of oral antibiotics before isotretinoin therapy in patients with acne. J Am Acad Dermatol 2016; 74 (2): 273–279.
  9. Electronic Medicines Compendium. Miravaso 3mg/g gel. Summary of product characteristics. www.medicines.org.uk/emc/medicine/28682 (accessed 30 November 2016).
  10. NICE. Facial erythema of rosacea: brimonidine tartrate gel. NICE, 2014. Available at: www.nice.org.uk/advice/esnm43/chapter/key-points-from-the-evidence
  11. Erdemir A, Gurel M, Aksu A. Demodex mites in acne rosacea: reflectance confocal microscopic study. Australas J Dermatol 2016; doi: 10.1111/ajd.12452
  12. Electronic Medicines Compendium. Soolantra 10mg/g cream. Summary of product characteristics. www.medicines.org.uk/emc/medicine/30353 (accessed 30 November 2016).
  13. NICE. Inflammatory lesions of papulopustular rosacea: ivermectin 10 mg/g cream. NICE, 2016. Available at: www.nice.org.uk/advice/esnm68/chapter/key-points-from-the-evidence
  14. Taieb A, Ortonne J, Ruzicka T et al. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol 2015; 172 (4): 1103–1110.
  15. Preshaw P, Novak M, Mellonig J et al. Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease. J Periodontol 2008; 79 (3): 440–452.
  16. Cardiff University Department of Dermatology. Dermatology quality of life index (DLQI). Available at: www.cardiff.ac.uk/dermatology/quality-of-life/ (accessed 11 November 2016).
  17. British Association of Dermatologists. Rosacea. BAD, 2004 (updated 2014). Available at: www.bad.org.uk/shared/get-file.ashx?id=229&itemtype=documentG