Clinical aspects and treatment of rosacea

CLINICAL SKILLS
Clinical aspects and
treatment of rosacea
Alison Layton
Approximately 10% of the UK population are affected by rosacea, an inflammatory skin condition that
primarily affects the face. The psychosocial impact of rosacea can be as disabling as the diverse signs and
symptoms. This article highlights the clinical aspects of rosacea and differential diagnoses. Therapeutic
options are considered and the gel formulation of azelaic acid is reviewed. Advice on maintenance of
remission and patient support is included.
KEY WORDS
Rosacea
Treatment
Patient support groups
Camouflage cosmetics
R
osacea is a chronic, progressive,
inflammatory skin condition, which
affects approximately 10% of the
UK population to a greater or lesser
degree (Berg and Linden, 1989). Because
rosacea affects the face — our first point
of visual social contact with those around
us — the emotional trauma can be just as
disabling as the physical impact of flushing,
rashes and acne-like spots associated
with the condition. In severe cases, fluid
build-up in the tissues (oedema) and eye
problems can occur.
Typically, rosacea patients show
a wide range of symptoms and signs
with alternating and variable periods
of remission and relapses, although the
frequency of attacks usually decreases
with time. It is more common in women
than men by a ratio of 3:1, but men
seem to be more severely affected. Fairskinned people are most likely to develop
Alison Layton is a Consultant Dermatologist
at Harrogate and District Foundation Trust
26
rosacea, but it may also be seen in the
Asian population. There is a tendency
for rosacea to run in families, so many
sufferers may think that they have simply
inherited their ‘rosy cheeks’ and do not
realise that their condition is treatable.
Alternatively, a flushed complexion or
the bulbous nose noted in some patients,
particularly males, can be wrongly
attributed to high alcohol intake. This
unjustified stigma can contribute further
to an already distressing condition.
Rosacea is most commonly seen in
people aged 40–60 years. It can coexist
with acne and seborrhoeic dermatitis. It
is important to be able to recognise such
concurrent disease and give appropriate
treatment to each condition.
Four subtypes of rosacea are
recognised:
Erythematotelangiectatic rosacea
This is characterised by flushing and
persistent redness (erythema) of the
central facial region, with or without
the dilation of superficial blood vessels
(telangiectasia). Patients often report
a burning or stinging sensation in the
affected area. Other forms of rosacea
may also be present.
Papulopustular rosacea
These patients also have central facial
erythema, but it is accompanied by
transient pustules and/or dome-shaped
papules. Stinging or burning sensations are
frequently reported, with patients being
particularly intolerant of topical therapies.
Other areas of the body can be affected,
such as the chest, ears and, in bald men,
the scalp. If these areas are affected,
response to treatment can be very slow.
Phymatous rosacea
This is caused by excessive growth
(hyperplasia) of sebaceous gland and
connective tissue and can be very
disfiguring. Typically, thickening of the
skin occurs on the nose: the so-called
‘boozer’s nose’. Other areas of the face
can also be involved, such as the chin,
forehead, ears and eyelids. There may
be no other features of rosacea present.
Phymatous rosacea is much more
common in males (10:1 ratio).
Ocular rosacea
Both eyes are usually affected and about
half of the cases are strongly linked
to flushing. The eye symptoms can
occur long before any skin problems.
The condition can present in many
ways, including watery or bloodshot
conjunctivae, foreign body sensation,
irritation, sensitivity to light and blurred
vision. More serious eye damage occurs
in about 5% of cases, usually in men.
Differential diagnoses
Some skin conditions can mimic rosacea,
so differential diagnoses are best tackled
by considering the possible alternative
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causes for similar symptoms to the basic
rosacea subtypes (Table 1).
Causes of rosacea
Despite its familiarity to dermatologists,
the underlying causes (pathogenesis)
of rosacea are currently poorly
understood. Pathogenic factors are a
mixture of genetic predisposition and
environmental/behavioural influences.
In 70% of cases, sun exposure will
aggravate the condition, with premature
skin ageing (elastotic degeneration)
visible in sun-exposed areas.
A number of trigger factors for
flushing have been identified (Table 2). It
is a good idea for the patient to keep a
detailed daily diary (see below), to look
for links between flushing episodes and
possible triggers, as these factors can vary
from person to person.
There are several theories that
hypothesise how rosacea begins and
develops (pathophysiology), but none
have been proven. Most experts believe
that blood vessels become damaged by
stimuli and are more prone to dilatation.
Eventually, the vessels remain dilated for
long periods, or even permanently, causing
the typical redness and flushing. However,
patients can be reassured that the
availability of new therapies, combined
with awareness of any likely trigger
factors, allow a long-term management
strategy to be developed.
or laser therapy. Nevertheless, laser and
other light therapies may help to reduce
telangiectasia and erythema. Application
of cool emollients or the use of cooling
fans can help reduce the burning sensation
often experienced by sufferers. For
phymatous rosacea, surgical reduction may
be necessary.
Azelaic acid
A formulation of azelaic acid, Finacea®,
has been specially developed to treat
papulopustular rosacea. It has a hydrogel
formulation containing 15% azelaic acid
as very small particles (1–10nm), which
increases skin penetration and causes less
irritation, compared to the 20% azelaic
acid cream formulation, which is familiar
to nurses for the treatment of acne
(Draelos, 2006). Azelaic acid is a naturally
occurring dicarboxylic acid, found in
wheat, barley and some animals. There is
some evidence that it might have been
used as a skin treatment at least 1500
years ago, although its modern use for
rosacea dates from 1993.
In a randomised trial involving a total
of 251 patients given either Finacea or
metronidazole gel twice daily for 15
weeks (Elweski et al, 2003), Finacea was
shown to have a significant benefit over
metronidazole in reduction of the mean
nominal lesion count (minus 12.9 lesions
versus minus 10.7 lesions, respectively
Treatment of rosacea
Table 1
A recently published critical review of
treatments for rosacea (Van Zuuren et
al, 2007) considered the best evidence
available, using strict inclusion criteria,
with only the best randomised controlled
trials included. Of the 71 trials identified,
only 29 were of a suitable quality to be
included in the review, and just eight were
considered to be of good quality.The
authors concluded that there was good
evidence for the efficacy of the topical
treatments, metronidazole and azelaic
acid, and some evidence of efficacy for
the systemic treatments, oral tetracycline
and oral metronidazole.The authors
concluded that there was insufficient
evidence for the use of minocycline,
lymecycline, erythomycin, trimethoprim,
oral isotretinoin, topical retinoids, dapsone
Differential diagnoses of rosacea
Flushing
Telangiectatic
Papulopustular
rosacea
Rhinophyma
[P = 0.003]) and the mean percent
decrease in inflammatory lesions (minus
72.7% versus minus 55.8%, respectively
[P < 0.001]). A greater reduction in
erythema severity was also seen in
the Finacea patients (56% of Finacea
patients rated as improved, versus 42% of
patients who received metronidazole [P
= 0.02]). Moreover, the effectiveness of
metronidazole seemed to reach a plateau
after the first eight weeks of treatment,
whereas Finacea demonstrated a
progressive improvement thereafter.
How to use Finacea
As most, if not all, applications of Finacea
will be performed by the patient at
home, careful instructions need to
be given. Firstly, the skin should be
thoroughly cleaned with water and
dried. A mild skin-cleansing agent may
be used. Finacea gel should then be
applied sparingly to the affected skin
areas and gently massaged in. This should
be done twice a day (i.e. in the morning
and evening). Occlusive dressings or
wrappings should not be used, and
hands should be washed after applying
the gel. Care should be taken to avoid
contact with the eyes, mouth and other
mucous membranes. If accidental contact
occurs, the affected areas should be
washed with large amounts of water, and
patients should consult a physician if any
eye irritation persists.
Triggers: check for any link
Alternative reasons: carcinoid, phaeochromocytoma, mastocytosis
Actinic damage
Photosensitivity
Lupus erythematosus (butterfly rash)
Acne/acne agminata
Pyoderma faciale
Perioral dermatitis
Seborrhoeic eczema
Drugs: Steroid-induced dermatitis
Tacrolimus
Epidermal growth factor receptor (EGFR) inhibitors
Nasal sarcoidosis (lupus pernio): biopsy may be required
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Finacea can be used over an
extended period and may well be
required for several months. However,
if skin irritation occurs, the amount of
gel per application should be reduced or
the frequency of use cut down to once
per day. If required, treatment can be
temporarily stopped for a few days.
Contraindications
Finacea is contraindicated if the patient is
hypersensitive to azelaic acid or to any of
the components in the gel formulation,
in particular, to propylene glycol. The
full list of gel components are: lecithin;
triglycerides (medium chain); Polysorbate
80; propylene glycol; Carbomer 980;
sodium hydroxide; disodium edetate;
purified water; and benzoic acid (E210).
Other considerations
There have been no studies of
interaction between Finacea and other
drugs, and the gel composition gives no
indication of any undesired interactions
of the individual components that could
adversely affect safety. Also, no drugspecific interactions were noted during
any of the controlled clinical trials.
There are no adequate and
well-controlled studies of topically
administered azelaic acid in pregnant
women. The experience with azelaic
acid when used by pregnant women
is too limited to permit assessment of
the safety of its use during pregnancy,
therefore caution should be taken when
prescribing Finacea to pregnant women.
The passage of negligible quantities
of azelaic acid into maternal milk may
occur. These quantities are so low that
they should not cause any risk to the
infant; however, caution should be
exercised when Finacea is administered
to a nursing mother.
The only adverse events reported
during trials of 457 rosacea patients
treated with Finacea for up to 15 weeks
were skin-related, and symptoms were
mild or moderate in the great majority of
cases (Elweski et al, 2003; Thiboutot et al,
2003). Also, the frequency of cutaneous
adverse events gradually decreased
during the course of therapy. However,
patients should be warned that they may
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experience: a burning/stinging sensation
and/or pruritis (very common: ≥1 in 10
patients); dry skin, scaling and/or rash
(common: between 1 in 100 and 1 in 10
patients); or contact dermatitis and/or
facial oedema (between 1 in 100 and ≥1
in 1000 patients).
It is not clear exactly how azelaic acid
acts against rosacea, but studies have
indicated that azelaic acid may exert an
anti-inflammatory effect by reducing the
formation of pro-inflammatory reactive
oxygen species.
Finacea comes in standard aluminium
tubes of 30g, with screw caps of highdensity polyethylene. There are no
special precautions for storage and it has
a shelf life of three years.
patient support groups, including:
8 Outlook (www.nbt.nhs.uk/services/
surgery/outlook)
8 Changing Faces (www.changingfaces.
co.uk)
8 In April, Valeant Pharmaceuticals
Ltd launched a website to provide
information about rosacea to
patients (www.myrosacea.co.uk).
Just as important as effective
treatment is advice on how to remain in
remission from flare-ups (Table 3).
Table 2
Trigger factors for rosacea
Patient information leaflets and diaries
In conjunction with Alison Bowser,
former chief executive of the patient
support group for rosacea sufferers, the
manufacturers (Valeant Pharmaceuticals
Ltd) have developed a simple patient
information leaflet and a useful skin
diary, which can help to identify possible
trigger factors. Each day, patients can
record what they have eaten, any
medication taken, skin products used,
the weather, activities undertaken and
their general mood, and compare this
with a score of how their skin looks.
By keeping this diary over a few weeks
patterns may emerge that link certain
foods or events with a worsening of
symptoms.
Environmental
Diet
Drugs
Temperature extremes
Wind
Sun exposure
Hot baths
Hot, spicy food
Alcohol
Hot drinks
Vasodilators
Emotional factors
Physical exertion
Hormonal factors
Skin care products
Final thoughts
As stated earlier, rosacea can be as
emotionally scarring to the patient,
or even more so, than the physical
symptoms. Flare-ups can cause the
sufferer to avoid social contact and miss
work or educational commitments.
However, there are a number of ‘skin
camouflage’ cosmetic ranges available,
which are safe and effective to use,
and will help the patient literally to feel
able to ‘face the world’ again. Cognitive
behavioural therapy (CBT) techniques,
which aim to make patients more
socially confident, can also be taught.
Advice on camouflage cosmetics
and CBT can be obtained from several
Table 3
Maintaining remission
8 Wash with body temperature/
cool water
8 Use very gentle non-alcoholbased cleansers
8 Blot dry, do not rub
8 Apply topical agents 30 minutes
after cleansing
8 Try to avoid known trigger factors for
rosacea (see Table 2)
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Key points
8 Rosacea is a chronic, progressive
skin condition affecting up to
10% of the UK population.
8 There are a number of
possible trigger factors but
the pathophysiology is poorly
understood.
8 A recent critical review suggests
that metronidazole and azelaic
acid 15% gel are the only two
topical rosacea treatments with
reasonable evidence of efficacy.
1a
1b
Figures 1a and 1b: Treatment of erythema with azelaic acid 15% gel: a) at baseline; b) after four
weeks of treatment.
8 An azelaic acid gel has been shown
to be affective in the treatment of
rosacea.
8 Nurses should be aware of the
impact of the condition and the
resources available for supporting
patients.
The author of this article was provided
with an unrestricted educational grant by
Valeant Pharmaceuticals Ltd.
References
Berg M, Linden S (1989) An epidemiological
study of rosacea. Acta Derm Venereol 69(5):
419–23
Draelos Z (2006) The rationale for advancing
the formulation of azelaic acid vehicles. Cutis
77(Suppl 2): 7–11
2a
2b
Figures 2a and 2b: Treatment of papules and pustules with azelaic acid 15% gel: a) at baseline;
b) after four weeks of treatment.
Finally, it is important not to
forget the dangers of ocular rosacea.
Approximately half of all rosacea
patients have ocular manifestations,
which may occur long before any facial
changes appear. Therefore, nurses
should pay attention to symptoms
such as dry eyes, redness, crusting,
recurrent styes or infections and patient
reports of itchy or burning sensations
in the eyes. Ocular rosacea is a serious
condition that can lead to blepharitis,
corneal clouding, neovascularisation and
eventual blindness. DN
Elewski BE, Fleischer AB Jr, Pariser DM, et
al (2003) A Comparison of 15% azelaic acid
and 0.75% metronidazole gel in the topical
treatment of papulopustular rosacea: results
of a randomised trial. Arch Dermatol 139:
1444–50
Thiboutot D, Thieroff-Ekerdt R, Graupe
K (2003) Efficacy and safety of azelaic
acid (15%) gel as a new treatment for
papulopustular rosacea: results from two
vehicle-controlled, randomized phase III
studies. J Am Acad Dermatol 48(6): 836–45
Van Zuuren E, Gupta A, Gover M, et
al (2007) Systematic review of rosacea
treatments. J Am Acad Dermatol 56: 107–15
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