Rosacea
Salient
features
·
Rosacea
is a common facial skin disease in many countries.
·
Signs
and symptoms for rosacea include flushing, transient erythema, persistent
erythema, telangiectasia, papules, pustules, phymata, edema, pain, stinging or
burning, and (very rarely) pruritus.
·
The
pathophysiology of rosacea is poorly understood; however, a genetic
predisposition along with trigger factors activates a dysregulated
neurovascular, innate immune and adaptive immune system.
·
Taking
a thorough family and patient history and performing a clinical examination are
crucial to diagnose rosacea.
·
All
clinical features have to be considered with severity scores for a proper
treatment, combined with assessing patient’s quality of life.
·
Approved
topical or systemic drugs exist for various, but not all, features of rosacea
and should be used on the basis of pathophysiology and while considering
efficacy and side effect profiles.
·
Knowledge
about the beneficial use of physical therapies and their limitations is
important for best medical practice in patients with rosacea.
·
Education
about disease progress, general skin care, cosmetic usage and medication
effects and potential adverse events is mandatory; teaching of proper topical
use guarantees better treatment results.
·
Education
to prevent exacerbating “trigger factors” is critical for successful management
of patients with rosacea.
Introduction
It is a chronic disorder with partial
remission and relapse and predominantly affects middle aged fair‐skinned
individuals over the facial convexities. The
term “rosacea” encompasses a constellation of clinical
findings, with the key components being persistent facial erythema interspersed
by episodes of follicular
inflammation during which papules and pustules are evident. Additional features
are facial telangiectasias, a tendency for frequent facial flushing (sometimes
referred to as “pre-rosacea”), non-pitting facial oedema with erythema, ocular
inflammation, and phymatous changes. The latter predominantly affect the nose
and rarely the ears, forehead, chin, or eyelids. In 2002, rosacea was
classified into four clinical subtypes: (1) erythematotelangiectatic; (2)
papulopustular; (3) phymatous; and (4) ocular.
Many authorities have
expressed the view that vascular changes, particularly flushing, are the
initial and constant feature, followed by progression to inflammatory changes (papules
and pustules) and that the development of chronic lymphedema, thickening of
affected skin and rhinophyma are late complications.
A common feature in the majority of patients
with rosacea is the presence of persistent centrofacial erythema associated
with the following:
Facial vascular changes: subtype 1 (erythematotelangiectatic
rosacea).
Inflammatory lesions: subtype 2
(papulopustular rosacea).
Hypertrophic changes: subtype 3 (phymatous
rosacea).
Ocular involvement: subtype 4 (ocular
rosacea).
The cause of rosacea is unknown. It appears
that each of the different subtypes of rosacea has its own distinct
pathogenetic pathway that is responsible for its particular clinical
manifestations.
STAGING (PLEWIG AND KLIGMAN CLASSIFICATION)
The rosacea diathesis: episodic erythema,
"flushing and blushing."
Stage I: Persistent erythema with
telangiectases.
Stage II: Persistent erythema,
telangiectases, papules, and tiny pustules.
Stage III: Persistent deep erythema, dense
telangiectases, papules, pustules, and nodules; rarely persistent
"solid" edema on the central part of the face.
Note: Progression from one stage to another
does not always occur. Rosacea may start with stage II or III and stages may
overlap.
Epidemiology
Incidence
Relatively common disease and is one of the
most common dermatological conditions. Reported prevalence rates range from
0.09% - 22.00%. In about half of cases,
rosacea symptoms involve the eyes. Approximately 4% of rosacea patients are of
Asian descent.
Sex
Women are two to three times more likely to
be affected by rosacea than men. Women of menopausal age are at a greatest
risk.
Age
Rosacea usually has its onset during middle
age (30–50 years), with women being affected somewhat earlier than men. Although
women are said to be more frequently affected by rosacea than men, rhinophyma,
however, occurs primarily in men.
Ethnicity
Higher incidence of rosacea is seen in people
with fair skin.
Predisposing factors
Up to 25% of patients with rosacea have a
family history of the condition, indicating a significant genetic
predisposition in some individuals. These patients may develop rosacea at an
earlier age than those without a family history of the disorder. Patients with
the carcinoid syndrome who flush frequently are predisposed to developing
rosacea.
|
|
|
|
|
|
In rosacea, several different but
interrelated pathomechanisms have been proposed, with predominant pathways
reflecting clinical features. Both environmental triggers and genetic
predisposition play a role, with up to 20% of patients in some studies
reporting a family history of rosacea. Two of the major abnormalities are neurovascular dysregulation and an aberrant innate immune response, both of which can lead
to cutaneous inflammation.
In genetically predisposed
individuals (e.g. HLA-DRB1*03:01, HLA-DQA1*05:01, HLA-DQB1*02:01, SNP
rs763035), environmental factors can trigger neurovascular dysregulation and an
aberrant innate immune response, both of which can lead to cutaneous inflammation,
including the clinical manifestations of rosacea.
Vascular changes
Several clinical features of
rosacea, including transient erythema, persistent centrofacial erythema,
telangiectasias and flushing, point to the important role the vascular system
plays in its pathogenesis. An increase in blood flow within skin lesions of
rosacea has been demonstrated, and patients with rosacea flush more readily in
response to heat. Histopathologic studies of lesional skin found an elevated
expression of vascular endothelial growth factor (VEGF), CD31, and the
lymphatic endothelial marker D2-40 (podoplanin), implying increased stimulation
of vascular and lymphatic endothelial cells.
Neurogenic
inflammation
In patients with rosacea, including ETTR, sensations of stinging
or burning of the skin are commonly reported and affected individuals also
exhibit lower heat pain thresholds, as compared to controls. Stimulation of
cutaneous nerve endings expressing transient receptor potential vanilloid
(TRPV) cation channels by trigger factors (e.g. spicy food, heat, alcohol) can
lead to dysesthesia, flushing, and erythema. Heightened TRPV activity within
the skin of patients with rosacea is associated with neurogenic inflammation,
an inflammatory response induced by sensory nerves in which neuromediators are
released at the site of inflammation. The latter can result in vasodilation of arterioles and capillaries, extravasation of plasma
proteins and recruitment of inflammatory cells.
Aberrant
innate immune system
An aberrant innate immune response also plays a role in the
pathogenesis of rosacea. The
innate immune response protects against microbial infection without requiring
specific recognition of the pathogenic stimulus. Activation of innate immunity
leads to release of antimicrobial peptide such as the cathelicidin
LL-37 via enhanced processing of cathelicidin by the trypsin-like serine
protease kallikrein 5. These
cathelicidin peptides and their associated enzymes induced pro-inflammatory and
angiogenic activity features which may be of greater relevance to
papulopustular rosacea. In histopathologic studies of
PPR, inflammatory changes are noted to be most pronounced near the bulge region
of the pilosebaceous follicle, the site of stem cells whose expression profile
overlaps with that of the innate immune system.
Ultraviolet radiation (UVR)
Based upon a higher prevalence in
those with skin phototypes I and II, ultraviolet light has
been proposed as an additional contributing factor to the pathogenesis of
rosacea. Exposure to UVB can induce angiogenesis and it increases the secretion
of angiogenic factors (e.g. VEGF) from keratinocytes. UVR also induces
production of reactive oxygen species, which then upregulate matrix
metalloproteinases that lead to vascular and dermal matrix damage.
Epidermal
barrier dysfunction
Several clinical features of
rosacea imply skin barrier dysfunction. Rosacea
patients often report facial dryness, and studies have confirmed a lowered
threshold for skin irritancy. Both ETTR and PPR patients have increased
transepidermal water loss, a marker of epidermal barrier dysfunction, and it
has been suggested that disruption or abnormality of the stratum corneum allows
penetration of sensory irritants. In addition, patients with PPR have an
abnormal skin surface fatty acid profile as well as reduced epidermal hydration
levels; the latter were noted to improve following treatment with minocycline
and resolution of inflammatory lesions.
Microbes
Demodex mites
(folliculorum and brevis) are normally
present on the face as commensal microbes, are found in greater numbers within the pilosebaceous
follicles of rosacea patients and follicular infestation with multiple mites is
associated with an intense perifollicular infiltrate of predominantly CD4+
helper T cells. Antigenic proteins from a bacterium (Bacillus oleronius) isolated from Demodex mites can stimulate inflammation in
patients with PPR. It has been suggested that Demodex
mites and their associated bacteria upregulate local cutaneous proteases, thereby potentiating
the dysregulation of the local innate immune response. These patho-mechanisms
are probably most relevant for the papulopustular subtype of rosacea.
KLK5,
an enzyme in the cathelicidin pathway, is increased in facial skin of rosacea
patients. Individuals who have higher levels
of KLK5 respond best to treatment with azelaic acid and doxycycline. Patients
can be separated into those with high and low levels of KLK5 for better
treatment outcomes.
Pathology
The pathological findings in skin biopsies
taken from patients with different subtypes of rosacea can differ
significantly. A common finding is the histological evidence of chronic actinic
damage, as might be expected in a predominantly sun‐sensitive
middle‐aged population.
In ETR, a sparse, perivascular
lymphohistiocytic infiltrate with frequent plasma cells is accompanied by mild
oedema and ectatic capillaries, venules
and lymphatics in the upper part of the dermis. Similar features are found in
the PPR, but a dense lymphohistiocytic infiltrate with numerous neutrophils,
plasma cells and less commonly eosinophils also surrounds hair follicles and
sebaceous glands.
Sebaceous gland hyperplasia
is marked in severe rhinophyma. The sebaceous ducts become dilated and filled
with keratin and sebum. There is marked dermal thickening with sclerotic
collagen bundles and large amount of mucin and a variable degree of
perivascular lymphocytic/neutrophilic infiltration are the histological
findings of PR.
The histological findings of OR are non‐specific.
Blepharitis in rosacea mainly involves the posterior meibomian glands
(posterior blepharitis). There is an inflammatory infiltrate
(lymphocytic/histiocytic/neutrophilic) that varies according to the severity of
the condition.
Folliculorum mites may be found in all types
of rosacea within the follicular infundibula and sebaceous ducts.
In the granulomatous form of rosacea,
non-caseating epithelioid granulomas are seen around disrupted hair follicles
within the dermis. Multinucleated giant cells of foreign-body type may
aggregate around follicular contents spilled from a ruptured follicle.
Triggering factors
Triggers of rosacea may include environmental
factors (extreme temperature, sunlight, and wind), intense exercise, dietary
factors (ingesting hot liquids, caffeinated beverages, spicy foods, large
meals, and alcohol especially red wine), emotions, cosmetic products with fragrance, alcohols,
abrasives or other irritating ingredients, topical irritants, menopausal
flushing, and medications that promote flushing. These elements may exacerbate
a flushing tendency (predominantly in ETTR) but do not worsen the inflammatory
lesions of PPR or the phymatous or ocular changes of PR and OR, respectively.
Clinical features
Rosacea is a
polymorphic disease. The cardinal features are erythema and oedema, papules and
pustules, and telangiectasia. The areas characteristically affected are the central
convex areas of the face (nose, forehead, cheeks and chin). Occasionally, the
scalp, retroauricular region, side of the neck and upper chest and back.
The natural course of
the disease is slow progression. Rosacea is classified clinically into four
subtypes; but there is some overlap amongst the subtypes and patient can have
more than one subtype.
Erythematotelangiectatic
rosacea (subtype
1; ETR)
The onset is most
often marked by vascular changes, notably episodic flushing (transient
erythema) lasting > 10 minutes, usually unaccompanied by sweating, of the
mid-face triggered by environmental and dietary stimuli as mentioned (anything
that reddens the face). The flushing is combined with a background of
persistent facial erythema, telangiectasias and transient central face oedema
with burning and stinging sensation, especially in reaction to make up,
sunscreen and other facial creams. Mild, moderate, and severe grades are
recognized.
Papulopustular rosacea (subtype 2; PPR)
Is characterized by persistent
centrofacial erythema with eruption of multiple, small (<3 mm), dome-shaped,
erythematous papules, some of which are surmounted by a tiny area of pustulation
at the apex. Characteristically, the papules and pustules are in varying stages
of evoluation. These lesions can appear singly or in crops, but all lesions are
relatively superficial and comedones, nodules and cysts are not a feature of
PPR. Again, mild, moderate, and severe grades are recognized.
Burning and stinging
of the facial skin may occur in PPR, but occurs less commonly compared with
ETR. Flushing is less severe in PPR than ETR. In both types, erythema spares
the periorbital areas. Oedema can be mild or severe. Severe oedema may take on
the plaque morphology of solid facial oedema and present as persistent, asymptomatic, non-pitting swelling of the
central upper face that is associated with fixed facial erythema. This
occurs most often on the forehead and glabella and less commonly affects the
eyelids and upper cheeks.Areas of
greatest involvement can acquire a “peaud'orange” appearance. A halo of
erythema may surround the larger inflammatory lesions and tiny telangiectatic
blood vessels may be visible within this rim. Individual papules or pustules last about 2
weeks and are then replaced by blotchy post inflammatory erythema which
gradually fades over 10 days. Residual scarring is not a feature of PRP. As
some lesions fade, others appear. Occasionally, when
there is more severe disease, scaling or superficial crusting may be seen and
this has been referred to as “rosacea dermatitis”. Rarely, the lesions
spread from the typical mid-facial involvement to other areas such as scalp,
neck and upper parts of the trunk. Lastly, some
patients will have some degree of persistent erythema of the cheeks that may
represent a combination of post inflammatory erythema, telangiectasias, and
vasodilation.
Phymatous rosacea
(subtype 3; PR)
The phymas are
localized swellings of facial soft tissues due to combinations of fibrosis, marked
sebaceous hyperplasia and lymphedema causing disfigurement of the nose, forehead,
eyelids, ears, and chin.
Rhinophyma
(the commonest form of PR are seen typically in male patients), may appear de
novo (without preceding inflammatory changes) or occur in a patient with pre‐existing
PPR. Involvement of other anatomic sites has been
reported, but it is rare. Here also, mild, moderate, and severe grades
are distinguished.
The earliest clinical
sign of rhinophyma is the appearance of dilated pores (patulous follicles) with
tortuous, telangiectatic vessels on
the distal aspect of the nose that contribute to its hyperemic appearance; this hyperemia may
predispose to the subsequent hypertrophic changes of rhinophyma. In severe
cases of rhinophyma, there is hypertrophy of sebaceous glands with nasal
distortion as soft, fleshy, nodular growths that increase in size. Women with
rosacea do no develop phyma, perhaps for hormonal reasons. There is no
associated pain or discomfort with these progressive nasal skin changes but the
patient may note an unpleasant oiliness of the skin surface of the nose and
malodorous greasy material may be discharged on squeezing the skin of the nose.
Very marked lobular
sebaceous hyperplasia (glandular type) and/or marked increase/hypertrophy in
connective tissue (fibrous type) with large ecstatic veins (fibroangiomatous
type).
|
TYPES OF PHYMATOUS
ROSACEA |
|
|
Phyma |
Clinical features |
|
Rhinophyma |
Apparent initially as dilated patulous
follicles at the distal end of the nose |
|
Gnathophyma |
asymmetrical swelling of central chin |
|
Otophyma |
Usually affects the lower half of the
helices and lobes of the ears with cauliflower-like swelling |
|
Mentophyma |
Cushion-like, firm swelling of central
forehead |
|
Blepharophyma |
Swelling
of the eyelids |
Ocular rosacea (subtype 4; OR)
This entity may or may not be accompanied by cutaneous changes of rosacea.
Ocular
rosacea may develop before cutaneous symptoms in up to 20% of affected
individuals (in which case the diagnosis is difficult to make with certainty).
In half of patients, ocular symptoms develop after skin symptoms. In a
minority, skin and eye symptoms present simultaneously. OR may be seen in
patients with any of the other subtypes of rosacea but those with ETR and PPR
appear to be particularly vulnerable to the development of ocular inflammation.
Symptoms are nonspecific and include dryness, a gritty sensation,
and an inability to wear contact lenses, tearing, crusting of the eyelid
margins, frequent styes (hordeola), and sometimes pruritus. Patients usually do
not associate these ocular symptoms with their rosacea and may not volunteer such
information unless specifically asked. The clinical signs of ocular rosacea are
diverse- there
may be tiny concretions at the bases of the cilia (conical dandruff), or mild
scaling of the eyelid margins (scurf). More active disease manifests as
blepharitis, often with eyelid swelling and conjunctival injection; the overall
appearance is that of a “red eye”. Cysts arising from the meibomian glands
(chalazia) present as firm non-tender swellings of the cutaneous tarsal
surface, while hordeola are similar, but are tender and often painful swellings.
Patients often refer hordeolum as “styes”. Severe ocular disease (keratitis,
uveitis, scleritis or iritis) is fortunately rarely seen in patients with
rosacea. Patients who complain of pain or photophobia require specialist
attention.
Granulomatous rosacea
Granulomas can sometimes be found
histologically in all four common subtypes of rosacea. There is, however, an
uncommon variant in which firm, non‐tender,
skin-coloured to red-brown papules and nodules
arise on otherwise normal‐appearing
skin. The lesions are more persistent than lesions of PRP and favour central
face, particularly on the cheeks and periorificial facial skin- around the
mouth and eyes. The appearance of the skin lesions is monomorphic in each
individual. Upon diascopy, these
papules and nodules reveal apple jelly like change in colour similar to
sarcoidosis or lupus vulgaris. This variant
occurs in both children and adults and it may resolve spontaneously a few years
after lesions first appear and not recur. When they resolve there may be
significant scarring.
Rosacea conglabata
It
is rare rosacea like eruption that has a gradual onset, affecting mainly in
young women and is characterised by marked facial erythema with abscesses and
indurated haemorrhagic plaques that can result insignificant scarring. Unlike
acne conglabata, comedones are not a feature and the trunk is spared.
Rosacea fulminans
It
is a severe variant of rosacea conglobate. It may arise de novo or may develop
in patients with pre-existing rosacea. Inflammatory haemorrhagic plaques
studded with pustules erupt abruptly superimposed on a
background of facial erythema, usually occurring in young women (20-30 years)
and sometimes during pregnancy. It can result in significant scarring. It can
be complicated by acute OR with conjunctivitis and severe keratitis.
Diagnostic, major and minor features of rosacea
Diagnostic features
1. Persistent
centrofacial erythema associated with periodic intensification by potential
trigger factors
2. Phymatous
changes
Major features
1. Flushing/transient
centrofacial erythema
2. Inflammatory
papules and pustules
3. Telangiectasia
4. Ocular
manifestations
·
Lid margin telangiectasia
·
Blepharitis
·
Keratitis/ conjunctivitis/
sclerokeratitis
Minor features
1. Burning
sensation of the skin
2. Stinging
sensation of the skin
3. Oedema
4. Dry
sensation of the skin
|
Classification, clinical features and management of subtypes of rosacea
1.
Persistent
centrofacial erythema 2.
Flushing 3.
Telangiectasias 4.
Skin
sensitivity
Management: 1. General recommendations for
facial skin care 2. Reduce flushing 3. Minimize irritation 4. Topical treatments used in
papulopustular rosacea may cause irritation 5.
Laser
therapy of prominent blood vessels in grades 2 and 3 disease Papulopustular(PPR) 1.
Persistent
centrofacial erythema 2.
Papules 3.
Pustules/papulopustules 4.
Overlap
with other subtypes may occur Grade 1.Few papules and/or papulopustules; mild persistent centrofacial erythema Grade 2.Several
papules and/or papulopustules; moderate persistent centrofacial erythema Grade 3.Extensive
papules and/or papulopustules; pronounced persistent centrofacial erythema;
inflammatory plaques or edema may be present Management:
1.
Thickened,
nodular skin 2.
Prominent
pores 3.
Can
affect nose (rhinophyma), chin (gnathophyma), forehead (metophyma), ears
(otophyma), eyelids (blepharophyma) 4.
May
be associated with other features of rosacea or occur in isolation Grade 1. Puffiness; mildly patulous
follicles; no clinically apparent hypertrophy of connective tissue or
sebaceous glands; no change in contour Grade 2. Moderate swelling;
moderately dilated patulous follicles; clinically, mild hypertrophy of the
sebaceous glands or connective tissue; change in nasal contour without
nodular component Grade 3. Marked
swelling; large dilated follicles; distortion of contour due to hypertrophy
of the sebaceous glands and/or connective tissue, with a nodular component Management: 1.
Surgical
or laser therapy for grades 2 and 3 rhinophyma 2.
Other
phymas are more difficult to treat but may improve with systemic treatments,
if an inflammatory component is present Ocular (OR) 1.
Dry,
gritty sensation 2.
Blepharitis 3.
Conjunctivitis 4.
Chalazia
and hordeola 5.
Keratitis,
episcleritis, scleritis, iritis (rare) Grade 1.Mild
itch, dryness or grittiness; fine scaling of eyelid margins; telangiectasia
of eyelid margins; mild conjunctival injection Grade 2.Burning
or stinging; crusting, erythema
and/or edema of eyelid margins; definite conjunctival injection; chalazion
or hordeolum Grade 3.Pain,
photosensitivity, blurred vision; severe eyelid changes with loss of lashes,
severe conjunctival inflammation; corneal changes, with potential loss of
vision; episcleritis, scleritis; iritis Management: 1.
Topical
medications for grade 1 2.
Systemic
medications for grade 2 3.
Refer
to ophthalmologist for persistent grade 1 or 2 disease or suspected grade 3
disease | |||||||||||||||||||||
Treatment
Rosacea is not curable but can be managed
with proper treatment. The approach to the management of rosacea differs
according to the principal subtype manifest in each patient. Categorizing rosacea into subtypes and grading each subtype
into mild, moderate and severe (grades 1–3) assist in guiding initial
therapeutic interventions and in monitoring the clinical response. At the
initial consultation, the patient should be made aware of the chronic relapsing
nature of rosacea and the need for maintenance therapy even when in remission.
However, some aspects of skin care are common to the management of all forms of
rosacea. Because most patients with rosacea are fair‐skinned
(skin types 1 or 2) they should be advised to avoid undue sun exposure and use
sun‐protective measures (apply daily sun block
cream all year round and wear a hat) as chronic UV damage will contribute to
facial erythema, especially in patients with ETTR. Physical sunscreens based on
zinc or titanium is best tolerated. Wind and cold exposure, which contribute to
the development of facial telangiectasia and vascular instability, should also
be avoided when possible.
Many patients with rosacea have dry, easily
irritated skin. Use soap‐free
cleansers and apply a non‐scented,
colour‐free moisturizing cream
daily. Cosmetic cover (with light liquid
foundation preparations) and particular focus on the masking of erythema should
be advised to lessen the social impact of the disorder. Avoidance of potential
irritants (abrasive soaps, astringents, perfumes, aftershave lotions and skin‐peeling
agents) is important as they tend to aggravate the facial erythema and the
burning or stinging sensation, especially in patients with ETTR.
Factors which trigger
flushing (mainly those with ETTR) include emotion and stress, hot drinks,
alcohol, spicy food and vasodilating drugs. Despite traditional beliefs to the
contrary it is the heat, not the caffeine content of hot drinks, which causes
flushing. Patients should avoid these triggers.
The use of topical corticosteroids should be
avoided on the face of patients with rosacea except in particular
circumstances.
Erythematotelangiectatic rosacea
Patients with grade 1 ETR have mild fixed facial erythema and
intermittent flushing. Frequent flushing with the presence of multiple
telangiectasias characterizes grades 2 and 3 disease. Therapy is directed at
diminishing the facial erythema, removing the telangiectasias via vascular
laser therapy, and addressing the flushing tendency; the latter includes
avoidance of precipitating factors and the use of specific medications. Topical
application of adrenergic agonists, such as brimonidine (selective α2) or
oxymetazoline (selective α1A and partial α2), may help to diminish the erythema in individuals
with ETR. These
agents appear to be effective in diminishing the facial erythema temporarily,
but have to be used repeatedly for sustained effect. However,
some patients find the alabaster white colour unappealing and there can be
rebound erythema. Topical and systemic antibiotics used to treat PPR are ineffective
in the treatment of ETR and topical agents may actually irritate the skin.
Avoidance of sun exposure, diligent use of a high SPF sunscreen, and cosmetic
care of the skin are also part of the management strategy for this subtype of
rosacea.
Laser therapy (using pulse dye, intense
pulsed light, 532 nm green light or combination devices, e.g. 595 nm
neodymium:yttrium‐aluminium‐garnet
(Nd:YAG) lasers) can eliminate malar telangiectatic vessels and reduce facial
erythema significantly. This also tends to stabilize facial vascular reactivity
in these patients. Improvement can persist for years but relapse eventually
occurs. Laser treatment does not appear to have any effect on the subsequent
development of papules and pustules.
Low‐dose
β‐blocking medications (propranolol, nadolol,
carvedilol) should be considered for those patients who are troubled by a
persistent flushing tendency. Carvedilol, a nonselective beta-adrenergic
blocker (3.125 to 6.25 mg, two to three times a day) is started and the daily
dose is titrated gradually up to 31.25 mg. Significant improvement occurs
within 3 weeks.
Botulinum
toxin injections have been reported to be helpful for some patients with
recalcitrant flushing reactions. Consider highly selective sympathectomy only
in disabling cases because of the risk of serious side effects.
|
Papulopustular rosacea Sun avoidance, sun protection, moisturizing
and cosmetic cover should be undertaken as for ETR. In
general, patients with PPR are treated with topical and/or systemic
antibiotics. For active inflammatory lesions select topical agent such
as metronidazole 0.75% gel or cream, azelaic acid 15% gel or ivermectin 1%
cream. Ivermectin 1% cream has better tolerability profile and safety, no
tachyphylaxis, superior efficacy, and a longer time to relapse in comparison
to metronidazole 0.75% cream twice a day. Azelaic acid 15% foam received FDA
approval in 2015 with a statistically significant reduction in inflammatory
lesions and is well tolerated. Cream preparations are generally better
tolerated if the skin is acutely inflamed. In the initial clearing phase, the
selected preparation should be applied before use of a moisturizer twice
daily for 6–8 weeks. As inflammatory lesions clear, once‐daily application (usually preferred by
patients in the evening) may be sufficient. If the skin remains clear after
3–4 months, treatment can be discontinued and replaced by regular daily use
of a moisturizer. If flares occur the patient should be instructed to
recommence topical treatment twice daily. Topical α1‐receptor agonists such as brimonidine and
oxymetazoline may reduce perilesional erythema in patients with PPR but do
not appear to have an effect on papule and pustule formation. Traditionally,
systemic antibiotic therapy ( doxycycline, azithromycin, minocycline) given
in full dosage (as for patients with acne vulgaris) but for a shorter period
(6–8 weeks as opposed to 4 to 6 months), either prescribed alone or in
combination with one of the topical agents mentioned above, have been used
and appear to be effective in clearing even florid PPR. The facial erythema
associated with florid PPR often subsides significantly when the inflammatory
lesions clear but may persist in a lesser form for some weeks. Patients with
PPR respond to doxycycline (100 to 200 mg/day), minocycline (50 to 100 mg
twice each day) or sustained action formula (1 mg/kg) daily for 6–12 weeks.
Dosage schedules of azithromycin 500 mg on Monday, Wednesday, and Saturday in
the first month; 250 mg on Monday, Wednesday, and Saturday in the second
month; and 250 mg on Tuesday and Saturday in the third month are as effective
as doxycycline. Sometimes, successful treatment of the inflammatory lesions
of PPR reveals background telangiectasias (the PERT phenomenon – “post-erythema-revealed
telangiectasias”) which then need to be addressed.
It is useful to warn patients of this possibility, as otherwise they might
attribute the appearance of these telangiectasias to the prescribed
treatment. Following successful clearance of inflammatory lesions,
individuals with PPR should continue with maintenance therapy (usually
topical as mentioned above); otherwise, relapse is likely 3 to 6 months after
discontinuation of treatment. Many patients with moderate to severe (grades 2
and 3) PPR require repeated courses of systemic antibiotic therapy, but subsequent courses can often be shorter in duration,
i.e. 3 to 4 weeks. Some patients may remain clear of inflammatory lesions
even when a single dose of an oral antibiotic is taken every other day and
then relapse if the drug is discontinued. In PPR patients resistant to conventional
antibiotic therapy consider oral metronidazole 200 mg twice daily for 4–6
weeks or isotretinoin low‐dose
therapy (10–20 mg daily) taken over a period of 2–6 months to gain control of
the disorder. Careful monitoring for side effects is mandatory. Inflammation
will tend to recur when these therapies are discontinued, so an alternative
longer term treatment will need to be introduced when control is achieved. When high levels of Demodex exacerbate
rosacea, or in cases refractory to tetracyclines, oral ivermectin
may be a useful adjunctive therapy. It can be given as a single 12mg dose
repeated once weekly or once monthly as needed for symptom control. Phymatous rosacea Treat accompanying inflammatory lesions, if
present, as for PPR. Rhinophyma is the type of
phymatous rosacea most amenable to treatment. Mild disease may be responsive
to low-dose isotretinoin (10–20 mg daily) taken over a period of 2–6
months has been reported to reduce the nasal volume and halt the progression
of rhinophyma. However, the effect may not be prolonged and the nasal
enlargement may increase when the medication is discontinued. Appropriate patient
monitoring is required. Consider nasal application of a skin‐peeling agent if there are large occluded
follicles (sometimes due to trichostasis) and oily skin. Ablate perinasal telangiectatic
vessels with electrocautery or laser. More severe (grades 2 and 3)
disease responds best to physical modalities such as CO2 laser therapy, electrosurgery, or surgical
excision. Rhinophymatous tissue is ablated with
carbon dioxide laser or surgical electrosection of excessive nasal tissue
with remodelling of the shape of the nose. Results are often excellent and
sustained in the long term. Longitudinal evaluation
of patients treated with CO2 laser
therapy suggests that improvement persists long-term. Other sites of
phymatous rosacea are very rare and there are no established therapeutic
interventions. Ocular rosacea Ocular rosacea is a common
entity that is commonly underdiagnosed. Patients with mild ocular rosacea
(grade 1 disease) often respond to daily lid hygiene.
Instruct patients to dilute several drops of baby shampoo in warm water in an
eggcup and apply the solution to the lid margins with a cotton bud (lid
scrubs). Warm compresses used before the scrubs help to liquefy the
solidifying secretion from the meibomian glands and facilitate its removal.
Oily tear substitute, lubricating eye drops/aqueous gels are important for
all stages of OR and should be prescribed as first line therapy. Consider careful lid massage to express the
contents of blocked meibomian glands in addition to warm compresses and lid
scrubs as described above. Burning or stinging of the eyes with crusting of
the eyelid margins or the formation of chalazia or hordeola are
manifestations of moderate (grade 2) disease and patients require either
topical antibiotics (such as metronidazole gel or fucidic acid) or systemic
antibiotic therapy as outlined for PPR. The use of topical corticosteroids in
blepharitis is controversial and is best avoided. Symptoms
such as pain and photophobia as well as visual disturbances are features of
severe (grade 3) disease. Such symptoms or if symptoms persist in spite of
the above recommendations, the patient should be referred to an
ophthalmologist. |
Granulomatous
rosacea is difficult to treat. Therapeutic options include dapsone,
minocycline, isotretinoin, hydroxychloroquine, and the 1450-nm diode laser.
While
some authors consider rosacea fulminans (pyodermafaciale) and rosacea
conglobata to be within the rosacea spectrum, others view them as variants of
acne vulgaris. Nonetheless, systemic corticosteroids are required to control
the aggressive inflammation observed in both of these disorders and this is
often followed by the use of oral isotretinoin. Scarring can be a sequela
despite these interventions.
Therapeutic ladder
ETR
First line
Sun avoidance and protection
Non‐scented,
colour‐free moisturizer
Soap‐free
cleansers
Cosmetic cover
Avoid factors that provoke flushing
Topical α‐receptor
agonists such as brimonidine or oxymetazoline
Second line
Laser therapy for facial erythema and
telangiectasia
Low‐dose
β‐blocking medications (propranolol, nadolol,
carvedilol)
Third line
Botulinum toxin
Highly selective sympathectomy in disabling
cases
PPR
First line
Sun avoidance, sun protection, moisturizing
and cosmetic covers as for ETR
Topical metronidazole, azelaic acid,
ivermectin for active inflammatory lesions
Topical α‐receptor
agonists such as brimonidine and oxymetazoline for perilesional erythema
Second line
Systemic antibiotic therapy with
tetracyclines (doxycycline, minocycline) and azithromycin
Third line
Systemic metronidazole
Isotretinoin low‐dose
therapy
Topical acaricide (ivermectin, crotamiton,
permethrin) if Demodex proliferation is relevant
PR
First line
As for PPR for accompanying inflammatory
lesions
Topical skin‐peeling
agent if there are large occluded follicles
Electrocautery or laser for telangiectases
Second line
Low‐dose
isotretinoin therapy
Third line
Ablation of phymatous tissue with carbon
dioxide laser
Surgical remodelling of nose
OR
First line
Daily lid hygiene
Oily tear‐substitute
lubricating eye drops or aqueous gels
Second line
Careful lid massage
Topical metronidazole
Fusidic acid ophthalmic ointment if secondary
bacterial infection is suspected
Third line
Systemic tetracyclines
Referral to ophthalmologist for specialist
care
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MEDICAL AND SURGICAL THERAPIES FOR ROSACEA |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
If moderate to severe flushing persists despite avoidance of
triggers, beta-blockers (e.g. carvedilol, nadolol) can be tried.
* FDA-approved treatments for rosacea
(evidence-based support = 1). † In a Cochrane review of randomized
controlled trials conducted for moderate to severe rosacea, these were the
treatments shown to be effective. ** In a 16-week trial, minocycline 100 mg
daily was noninferior to doxycycline 40 mg daily. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
