BJD

B A D G UID EL IN ES British Journal of Dermatology

British Association of Dermatologists guidelines for the

management of people with rosacea 2021*
P.J. Hampton iD ,1 J. Berth-Jones iD ,2,3 C.E. Duarte Williamson,4 R. Hay iD ,5 T.A. Leslie,6 I. Porter,3 S. Rauz
7,8,9
iD , D. Seukeran,10 R.T. Winn,1 M. Hashme,11 L.S. Exton iD ,11 M.F. Mohd Mustapa iD ,11 and L. Manounah
iD 11
on behalf of the British Association of Dermatologists’ Clinical Standards Unit
1
Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK
2
Department of Dermatology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK
3
Patient representative
4
King’s College Hospital NHS Foundation Trust, London, SE5 9RS, UK
5
St John’s Institute of Dermatology, Kings College London, London, SE1 9RT, UK
6
Royal Free Hospital, London, NW3 2QG, UK
7
University of Birmingham, Birmingham, B15 2TT, UK
8
Birmingham & Midland Eye Centre, Sandwell and West Birmingham NHS Trust, Birmingham, B18 7QH, UK
9
Royal College of Ophthalmologists, NW1 2HD, UK
10
South Tees Hospitals NHS Foundation Trust, Middlesbrough, TS4 3BW, UK
11
British Association of Dermatologists, Willan House, 4 Fitzroy Square, London, W1T 5HQ, UK
Linked Comment: J.S.S. Ho and Y. Asai. Br J Dermatol 2021;
Correspondence 185:689–690.
Philip J. Hampton
Email: philip.hampton@nhs.net; guidelines@bad.org.uk
1.0 Purpose and scope
Accepted for publication
13 May 2021 The overall objective of the guideline is to provide up-to-date,
evidence-based recommendations for the management of rosa-
Funding sources cea. The document aims to: (i) offer an appraisal of all rele-
None. vant literature up to February 2020 focusing on any key
developments; (ii) address important, practical clinical ques-
Conflicts of interest tions relating to the primary guideline objective; and (iii) pro-
P.J.H. has received educational and travel grants (nonspecific); and research funding
vide guideline recommendations and, if appropriate, research
from LEO Pharma, Janssen, UCB Pharma and Eli Lilly (nonspecific). J.B.-J. ran a
recommendations.
clinical trials unit with an interest in rosacea until 2014 (specific). C.E.D.W. has
been an invited speaker for AbbVie, Galderma and Janssen (specific); and has accepted
The guideline is presented as a detailed review with high-
invitations to attend congresses and meetings related to psoriasis/biologics (nonspecific). lighted recommendations for practical use in primary care and
T.A.L. has been on advisory boards for Galderma, La Roche-Posay and Novartis (speci-in the clinic, in addition to an updated Patient Information
fic); and has been an invited speaker for Novartis (specific). D.S. received travel and Leaflet [available on the British Association of Dermatologists’
conference sponsorship for the 2018 European Academy of Dermatology and Venereology(BAD) website: www.skinhealthinfo.org.uk/a-z-conditions-
spring conference from Galderma (specific). treatments/].

This is a guideline prepared for the British Association of Dermatologists (BAD) Clini-
cal Standards Unit, which includes the Therapy & Guidelines Subcommittee. Members 1.1. Exclusions
of the Clinical Standards Unit that have been involved are: N.J. Levell, B. McDonald, This guideline does not cover the diagnosis of rosacea. The
P. Laws, S.L. Chua, A. Daunton, H. Frow, I. Nasr, M. Hashme (Information Scien-
evidence supporting the recommendations does not include
tist), L.S. Exton (Senior BAD Guideline Research Fellow), L. Manounah (BAD Guide-
evidence that is specific to children.
line Research Fellow) and M.F. Mohd Mustapa (Director of Clinical Standards).

2.0 Methodology
NICE has accredited the process used by the British Association of Dermatologists to produce
clinical guidelines. The renewed accreditation is valid until 31 May 2021 and applies to
guidance produced using the process described in Updated guidance for writing a British
Association of Dermatologists clinical guidance – the adoption of the GRADE methodology This set of guidelines has been developed using the BAD’s rec-
2016. The original accreditation term began on 12 May 2010. Accreditation renewal in
progress at time of publication. More information on accreditation can be viewed at ommended methodology,1 with reference to the Appraisal of
www.nice.org.uk/accreditation
Guidelines Research and Evaluation (AGREE II) instrument
DOI 10.1111/bjd.20485 (www.agreetrust.org)2 and Grading of Recommendations
Assessment, Development and Evaluation [GRADE; Appendix L
*Plain language summary available online (see Supporting Information)].3 Recommendations were

British Journal of Dermatology (2021) 185, pp725–735 725

© 2021 British Association of Dermatologists
726 BAD guidelines for the management of people with rosacea 2021, P.J. Hampton et al.
Information)], GRADE evidence profiles indicating the cer-
tainty of evidence (Appendix D; see Supporting Information),
developed for implementation in the UK National Health Ser-
summary of included studies (Appendix E see Supporting
vice (NHS).
Information), narrative findings from comparative without
The guideline development group (GDG), which consisted of
data in an extractable format (Appendix F; see Supporting
consultant dermatologists, a consultant ophthalmologist, patient
Information), narrative findings from within-patient studies
representatives and a technical team (consisting of a guideline
(Appendix G; see Supporting Information), narrative findings
research fellow and project manager who provided method-
from non-comparative studies (Appendix H; see Supporting
ological and technical support), established several clinical ques-
Information), critical appraisal of the included systematic
tions pertinent to the scope of the guideline and a set of
reviews (Appendix I; see Supporting Information), PRISMA
outcome measures of importance to patients, ranked by the
flow diagram (Appendix J; see Supporting Information) and
patient representatives according to the GRADE methodology
list of excluded studies (Appendix K; see Supporting Informa-
[section 2.1 and Appendix A (see Supporting Information)].
tion) are detailed in the Supporting Information. The strength
A systematic literature search of PubMed, MEDLINE, Embase
of recommendation is expressed by the wording and symbols
and the Cochrane databases was conducted to identify key
shown in Table 1.
articles on rosacea up to February 2020; search terms and
strategies are detailed in the supporting information
(Appendix M; see Supporting Information). Additional refer-2.1. Clinical questions and outcomes
ences relevant to the topic were also isolated from citations in
The GDG established several clinical questions pertinent to
reviewed literature. Data extraction and critical appraisal, data
the scope of the guideline. See Appendix A (Supporting
synthesis, evidence summaries, lists of excluded studies and
Information) for the full review protocol. The GDG also
the Preferred Reporting Items for Systematic Reviews
established two sets of outcome measures of importance to
(PRISMA) diagram were prepared by the technical team. Evi-
patients: one set for topical and systemic treatments; and one
dence from included studies was graded according to the
for procedural therapies [light, laser and intense pulsed light
GRADE system (high, moderate, low or very-low certainty).
(IPL)], which were agreed and ranked by the patient repre-
Recommendations are based on evidence drawn from system-
sentatives according to the GRADE methodology.4 Outcomes
atic reviews of the literature pertaining to the clinical ques-
ranked 7, 8 and 9 are critical for decision-making; those
tions identified, following discussions with the entire GDG,
ranked 4, 5 and 6 are important but not critical for decision-
and factoring in all items that would affect the strength of the
making; and those ranked 3, 2 and 1 are least important for
evidence according to the GRADE approach (i.e. balance
decision-making.
between desirable and undesirable effects, certainty of evi-
dence, patient values and preference, and resource allocation).
Systematic review question 1: topical therapies
All GDG members contributed towards drafting and/reviewing
In people with rosacea what is the clinical effectiveness and
the narratives and supporting information.
safety of topical therapies, compared to each other or pla-
The summary of findings with forest plots (Appendix B; see
cebo?
Supporting Information), tables Linking the Evidence To the
Recommendations [LETR; Appendix C (see Supporting

Table 1 Strength of recommendation ratings

Strength Wording Symbols Definition

Strong recommendation for ‘Offer’ (or similar, e.g. ‘use’, ↑↑ Benefits of the intervention outweigh the risks; most patients
the use of an ‘provide’, ‘take’, would choose the intervention, while only a small proportion
intervention ‘investigate’, etc.) would not; for clinicians, most of their patients would receive the
intervention; for policy makers, it would be a useful performance
indicator
Weak recommendation for ‘Consider’ ↑ Risks and benefits of the intervention are finely balanced; most
the use of an patients would choose the intervention but many would not;
intervention clinicians would need to consider the pros and cons for the
patient in the context of the evidence; for policy makers it would
be a poor performance indicator where variability in practice is
expected
No recommendation Θ Insufficient evidence to support any recommendation
Strong recommendation ‘Do not offer’ ↓↓ Risks of the intervention outweigh the benefits; most patients
against the use of an would not choose the intervention, while only a small proportion
intervention would; for clinicians, most of their patients would not receive the
intervention

British Journal of Dermatology (2021) 185, pp725–735 © 2021 British Association of Dermatologists
 (*), are based on available evidence, as well as consensus
within the GDG and specialist experience. Good practice point
Critical
(GPP) recommendations are derived from informal consensus.
Objective response to treatment scoring systems
• Reduction in lesion counts 8
• Reduction in erythema 8 General recommendations
• Improvement in quality of life (QoL) 7 R1 (GPP) Advise people with rosacea to limit exposure to
• Adverse events and tolerability 7 known aggravating factors such as alcohol, sun exposure, hot
Important drinks and spicy food.
• Physician Global Assessment (PGA) 6
R2 (GPP) Provide a patient information leaflet (www.skin-
• Relapse/recurrence 6
healthinfo.org.uk/a-z-conditions-treatments/) to people with
• Patient global assessment 6
• Reduction in flushing 6 rosacea.
R3 (GPP) When characterizing the clinical subtypes and
symptoms of rosacea, classify the patient according to the phe-
notypes identified by Gallo et al.5 This approach encompasses
Systematic review question 2: systemic therapies
the objective clinical signs and the subjective symptoms expe-
In people with rosacea what is the clinical effectiveness and
rienced by the patient with rosacea. Diagnostic phenotypes
safety of systemic therapies, compared to topicals, each other
include characteristic fixed centrofacial erythema or phymatous
or placebo?
changes. Other features include flushing, papules or pustules,
telangiectasia, ocular changes, burning or stinging sensations,
Critical oedema and dryness.
Objective response to treatment scoring systems R4 (GPP) Take into account the older classification system for
• Reduction in lesion counts 8
rosacea, which was based on clinical signs: erythematotelang-
• Reduction in erythema 8
• Improvement in QoL 7 iectatic, papulopustular, phymatous or ocular. Characterize the
• Adverse events and tolerability 7 clinical subtypes and symptoms of rosacea affecting the person
Important according to these clinical signs.
• PGA 6 R5 (GPP) Whenever possible, avoid long-term use of oral
• Relapse/recurrence 6 antibiotics in people with rosacea (i.e. antibiotic stewardship).
• Patient global assessment 6 The optimal duration of antibiotic therapy is not known. In
• Reduction in flushing 6
acne, a lack of response after 2–3 months of antibiotic therapy
is usually regarded as treatment failure, and a similar duration
to establish benefit may be appropriate in rosacea. When
Systematic review question 3: procedural therapies antibiotics are working, the pros and cons of longer-term
In people with rosacea what is the clinical effectiveness andtreatment need to be evaluated carefully.
safety of light, laser and IPL treatments? R6 (GPP) Advise that some people with rosacea find it benefi-
cial to wash their skin with emollients, moisturize regularly
Critical and use appropriate sun protection. Soaps and washing prod-
Objective response to treatment scoring systems ucts that contain detergent are irritant in some people and
• Reduction in erythema 8 should be avoided if they worsen the symptoms.
• Reduction in telangiectasia 8 R7 (GPP) Consider skin camouflage in people with rosacea
• Improvement in QoL 7
‘whose main clinical feature is’ OR who are ‘presenting with’
• Adverse events and tolerability 7
intractable erythema.
Important
• PGA 6 R8 (GPP) Consider the need for psychological support or psy-
• Patient global assessment 6 chiatric interventions in people with rosacea who experience
• Relapse/recurrence 6 anxiety or depression. Initial assessment in primary care is
• Reduction in flushing 6 often appropriate.

Topical therapies
3.0 Summary of recommendations R9 (↑↑) Offer either ivermectin, metronidazole or azelaic acid as
first-line topical treatment options to people with papulopustular
The following recommendations and ratings were agreed
rosacea. Discuss the potential for irritancy of different products
upon unanimously by the core members of the GDG and
and formulations prior to prescribing the topical agent.
patient representatives. For further information on the word-
R10 (↑) Consider topical minocycline foam in people with
ing used for recommendations and strength of recommenda-
papulopustular rosacea (minocycline foam is currently not
tion ratings, see section 2.0. The GDG is aware of the lack of
available in the UK).
high-certainty evidence for some of these recommendations,
R11 (↑) Consider topical brimonidine in people with rosacea
therefore strong recommendations, marked with an asterisk
where the main presenting feature is facial erythema. Warn

© 2021 British Association of Dermatologists

British Journal of Dermatology (2021) 185, pp725–735
 728 BAD guidelines for the management of people with rosacea 2021, P.J. Hampton et al.

R23 (↑↑) Refer* people with ocular rosacea to an ophthalmolo-

patients that there are reports that redness may flare after dis-
gist if they are (i) experiencing eye discomfort, sticky eye dis-
continuation of treatment.
charge persisting for > 12 months despite frequent (> 6 times
R12 (↑) Consider topical oxymetazoline in people with rosa-
daily) topical lubricant use and adequate lid hygiene; or (ii)
cea where the main presenting feature is facial erythema.
experiencing symptoms such as reduced vision, pain on eye
Warn patients that there are reports that redness may flare
movement and pain that keeps the patient awake at night.
after discontinuation of treatment (oxymetazoline is currently
not available in the UK).
Summary of future research recommendations
The following list outlines future research recommendations
Systemic therapies
(FRRs).
R13 (↑↑) Offer* an oral antibiotic as a first-line treatment
FRR1 A prospective randomized controlled trial (RCT) investi-
option for more severe papulopustular rosacea. Options (in
gating the effect of topical ivermectin on ocular rosacea.
alphabetical order) include azithromycin, clarithromycin, doxy-
FRR2 A prospective RCT investigating various interventions
cycline 40 mg (modified release) daily, doxycycline 100 mg
(topical/systemic/procedural) for transient erythema (flushing).
daily, erythromycin, lymecycline and oxytetracycline. These
FRR3 A study investigating the psychological impact of rhino-
antibiotics (especially tetracyclines) are considered safe and have
phyma, the effect of treatment and the optimal choice of sur-
been prescribed for rosacea for decades. There is insufficient evi-
gical or laser treatments.
dence to establish the superiority of one over another, especially
FRR4 A study investigating other acaricidal drugs currently
in the absence of head-to-head trials or a network meta-analysis.
used in veterinary practice, such as moxidectin and afoxolaner
Currently, only the modified-release formulation of doxycycline
against Demodex.
is licensed specifically for papulopustular rosacea in the UK.
FRR5 A cost-effectiveness analysis of treatments for people
R14 (↑↑) Avoid minocycline in people with rosacea due to
with rosacea within a UK setting.
potential side-effects, unless there are no other treatment
FRR6 Investigations of the aetiology, pathophysiology and psy-
options.
chological issues of rosacea, and treatment of the sensory symp-
R15 (↑) Consider intermittent courses of low-dose isotretinoin
toms of rosacea, sometimes referred to as neurogenic rosacea.
(e.g. 0!25 mg kg–1) in people with persistent and severe rosa-
cea. Discuss the potential side-effects and teratogenicity.
R16 (↑) Consider oral propranolol in people with rosacea4.0 Algorithm
where the main presenting feature is transient facial erythema
The recommendations, discussions in the LETR (Appendix C;
(flushing).
see supporting information) and consensus specialist experience
were used to inform the algorithm/pathway of care (Figure 1).
Procedural therapies
R17 (↑) Consider pulsed dye laser, neodymium-doped
yttrium aluminium garnet (Nd:YAG) laser or intense pulsed5.0 Background
light in people with rosacea where the main presenting feature
is persistent facial erythema. An appropriately qualified laser5.1. Definition
practitioner should be consulted to ensure safe and high-qual-
Rosacea is a chronic disorder that predominantly affects the
ity practice.
central areas of the face (nose, forehead, cheeks and chin). It
R18 (↑) Consider nasal debulking by laser ablation or surgical
is characterized by frequent flushing, persistent erythema and
intervention (dependent on local expertise) in people with
telangiectasia, and episodes of inflammation during which
significant rhinophyma.
swelling, papules and pustules are evident. These symptoms
are frequently accompanied by periocular inflammation and
Ocular therapies
are sometimes associated with the later development of cuta-
R19 (↑↑) Advise* people with ocular rosacea to minimize expo-
neous swellings known as phymas.
sure to aggravating factors such as air conditioning, excessive
central heating, smoky atmospheres and periocular cosmetics.
R20 (↑↑) Identify* and modify/eliminate systemic medica-5.2. Classification
tions that could be triggering eye dryness in people with ocu-
Rosacea is a clinical diagnosis and can be classified according to
lar rosacea (e.g. antidepressants and anxiolytics).
the predominant clinical features. In this guideline, we have
R21 (↑↑) Offer* warm compresses using proprietary lid-
continued to use the traditional approach to the classification of
warming devices and lid hygiene with homemade bicarbonate
rosacea, which maps very well to most clinical trials. Some
solution or commercially available lid wipes.
authors have suggested that a phenotype approach to the classifi-
R22 (↑↑) Offer* over-the-counter ocular lubricants or liposo-
cation of rosacea could have some advantages, and it will
mal sprays to alleviate symptoms in people with ocular rosa-
become clear over time which system is more useful.5 It is not
cea, ensuring preservative-free preparations are used if using >
clear to what degree the clinical classification of rosacea corre-
6 times daily. Increasing humidity using humidifiers can help
sponds to any underlying difference in aetiology and
to reduce tear evaporation.
© 2021 British Association of Dermatologists
British Journal of Dermatology (2021) 185, pp725–735
Figure 1 Management pathway for people with rosacea. Nd:YAG, neodymium-doped yttrium aluminium garnet; OTC, over-the-counter.

pathogenesis, or indeed whether the clinical variants represent

overlap, it is possible, and clinically convenient, to classify most
separate but associated entities. The diverse clinical features,
cases of rosacea into the following four groups in accordance
which often occur in combination, may also occur in isolation,
with the clinical presentation. The clinical value of this classifica-
suggesting that these may be different clinical entities that com-
tion is that it is broadly reflected in different approaches to treat-
monly coexist. Notwithstanding the considerable clinical
ment, although there is, again, considerable overlap.
© 2021 British Association of Dermatologists British Journal of Dermatology (2021) 185, pp725–735
 It has been proposed that damage to dermal connective tis-
1. Erythematotelangiectatic rosacea (vascular rosacea) In
sue, often caused by solar irradiation, may be the initiating
these cases, the predominant features are vascular (flushing,
event.14 This may result in dysfunction of the unsupported
erythema and telangiectasia). Flushing is often noticed first
facial blood vessels with consequent endothelial damage, leak-
and progresses gradually to persisting erythema and increas-
age, oedema and inflammation. Others have argued for a cen-
ingly prominent telangiectasia. Factors that trigger flushing
tral role of abnormal vascular reactivity.15
include emotion and stress,6 hot drinks,7 alcohol and other
It has also been proposed that lowered neural thresholds for
vasodilating drugs,8 and spicy food. The flushing and ery-
reaction to noxious stimuli may result in neurogenic inflamma-
thema are often accompanied by a burning sensation.9
tion.9 Sensitivity to noxious stimuli, including heat, is increased
2. Papulopustular rosacea (inflammatory rosacea) In these
in involved skin, regardless of whether vascular or inflamma-
cases, the predominant features are inflammatory lesions
tory features predominate.9 This may explain the burning sen-
(eruptions of papules and pustules). In contrast to acne, the
sation frequently reported by patients with rosacea.
lesions are usually painless, not consistently associated with
Changes in redox status, with reduced levels of superoxide
hair follicles and not accompanied by comedones.
dismutase have been observed in the skin in cases of inflam-
3. Ocular rosacea The predominant features of ocular rosacea
matory rosacea.16
include blepharitis, episcleritis, meibomian gland dysfunc-
Abnormally high levels of the endogenous antimicrobial
tion, conjunctival scarring and corneal vascularization. Ini-
peptide cathelicidin have been demonstrated in the facial skin
tially, there is a sensation of grittiness, burning or irritability
of patients with rosacea.17Cathelicidin and related peptides
of the eyes, accompanied by visible reddening of the eyelid
trigger inflammation by promoting leucocyte chemotaxis and
margins and conjunctiva. The blepharoconjunctivitis is asso-
angiogenesis. Elevated levels of cathelicidin may be a sec-
ciated with a predominantly evaporative dry eye accompa-
ondary phenomenon, perhaps related to the presence of Demo-
nied by aqueous deficiency, which results in an unstable tear
dex spp. or microorganisms in the skin. Upregulation of
film and a static or slowly progressive cicatrising conjunctivi-
various elements of the innate skin immune system such as
tis.10,11 Ocular rosacea may be seen in isolation or occur
Toll-like receptor 2 (TLR2) and the NOD-, LRR- and pyrin
before the onset of cutaneous features, especially in chil-
domain-containing protein 3 (NLRP3), which is an intracellu-
dren.12 The condition may be unilateral or asymmetrical.12
lar sensor that detects a broad range of microbial motifs,
4. Phymatous rosacea (mainly rhinophyma) This most fre-
endogenous danger signals and environmental irritants, have
quently manifests as rhinophyma, a bulbous, rugose, soft-
been reported.18 Transient vanilloid receptor potential ion
tissue swelling of the nose, although similar lesions occur
channel 1 (TRVP1) has a key role in temperature perception
less often in other facial locations including the ears (oto-
and is significantly overexpressed in erythematotelangiectatic
phyma), forehead (metophyma) and chin (gnathophyma).
rosacea.19
Because there is usually no associated sweating, it has been
5.3. Epidemiology argued that flushing in rosacea is mediated by released vasoac-
tive substances rather than by a neural mechanism.20 Numer-
Rosacea is a very common disease. It is predominantly a dis-
ous possible vasoactive mediators have been proposed, but
ease of young-to-middle-aged adults but is seen in patients of
none has yet been firmly and consistently linked to the patho-
all ages, including, occasionally, in children. Estimates of
genesis of rosacea.
prevalence vary considerably, but this is certainly a very com-
Rosacea has often been linked with gastrointestinal symp-
mon skin disease, estimated in 2018 to affect 5!5% of the glo-
tomatology, although there is no conclusive evidence to sup-
bal adult population.13 Women are more commonly affected
port this. A possible role for Helicobacter pylori, infection of the
than men, especially within the age range of 36–50 years. It
gastric mucosa has been the subject of particular controversy,
is considered more common in individuals with less deeply
but in controlled studies prevalence rates have sometimes been
pigmented skin (Fitzpatrick skin types I–III) than in those with
similar to controls.21–24 The infection may be more prevalent
more deeply pigmented skin (Fitzpatrick skin types IV–VI),
in patients with papulopustular rosacea than those with ery-
although it does occur in all skin types. The development of
thematotelangiectatic disease.25 Certain chemicals found in
rhinophyma is more common in men. Symptoms of ocular
common foods have been shown to stimulate sensory nerves.
rosacea are also common, although these are also often
These include capsaicin (chilli) and resveratrol (a phenol
encountered in patients without other features of the disease,
found in red wine).26
and as the symptoms in these cases are indistinguishable from
A potential role has often been proposed for the follicle
those of ‘ocular rosacea’, it is probably impossible to ascertain
mites Demodex folliculorum and Demodex brevis in the pathogenesis
the prevalence of the latter as a distinct entity.
of rosacea. Infestation with these mites is extremely common
in the general population, reaching up to 100% of patients in
5.4. Aetiology and pathogenesis some studies.25 Eruptions strongly resembling rosacea and
associated with the presence of large numbers of D. folliculorum
The cause, or causes, of rosacea remain uncertain, and both
have been reported under the title of ‘rosacea-like demodico-
aetiology and pathogenesis seem likely to differ between the
sis’. These cases have improved following treatment to
various categories.

British Journal of Dermatology (2021) 185, pp725–735 © 2021 British Association of Dermatologists
 BAD guidelines for the management of people with rosacea 2021, P.J. Hampton et al. 731

eradicate the mite. Papulopustular rosacea has also been5.7. Differential diagnosis
demonstrated to respond to this therapeutic approach.27 It is
Acne vulgaris and rosacea are quite distinct diseases, although
well established that there are increased numbers of D. folliculo-
there are occasional patients in whom the distinction is diffi-
rum in the facial skin of patients with rosacea relative to con-
cult and, as both conditions are very common, it is to be
trols.28–34 Demodex mites have also been histologically
expected that, by chance, both will often occur in the same
demonstrated in the dermis associated with an inflammatory
patient. Acne vulgaris affects a younger age group and often
response and undergoing phagocytosis by multinucleate giant
has an extensive distribution over the face, neck and trunk,
cells. This phenomenon has been observed both in localized
whereas extrafacial rosacea is rare. Typical acne vulgaris lacks
and more widespread facial eruptions resembling rosacea.35,36
the redness, telangiectasia and flushing of rosacea, while rosa-
Furthermore, D. brevis is often present in the eyelid in hair fol-
cea lacks the comedones and seborrhoea characteristic of acne
licles, eyelash follicles and meibomian glands,37,38and is often
vulgaris.
reported in association with periocular pathology, including
Seborrhoeic dermatitis is often observed in association with
blepharitis and meibomianitis.39–41 These observations would
rosacea and is therefore a potential cause of confusion, espe-
suggest that the presence of Demodex mites might also play a
cially when the features of one disease predominate at one
role in some of the ophthalmic features of rosacea. The mites
consultation and features of the other at the next. However,
are associated with bacteria, which may also provoke an
the typical pattern of seborrhoeic dermatitis differs markedly
inflammatory response.
from rosacea. The former, but not the latter, characteristically
involves the scalp, the retroauricular area, the eyelids and the
5.5. Impact on quality of life nasolabial folds. Scaling is not normally a feature of rosacea
but is the rule in seborrhoeic dermatitis.
Rosacea is a facial dermatosis and therefore easily visible. It
Lupus erythematosus is an occasional cause of concern. Dis-
can cause significant embarrassment and handicap to those
coid lupus typically causes scarring, scaling and follicular
who suffer from it. This impact has been quantified in a
plugging, which are not features of rosacea. However,
limited and heterogeneous range of studies. A 2014 review
patients are often referred to the dermatology clinic with a
identified 12 studies in which the effect of rosacea on QoL
‘butterfly’ erythema and a tentative diagnosis of systemic
was evaluated using validated instruments. The Dermatology
lupus. The latter is not pustular and is usually associated with
Life Quality Index (DLQI) was the most frequently used
systemic symptoms. In some cases, lupus serology and a skin
instrument (in seven of the studies identified). DLQI scores
biopsy for histological and immunofluorescent examination
ranged from 4!1 to 17!3, depending substantially on the
may be necessary.
population studied, with the highest scores being recorded
Carcinoid syndrome is another cause of flushing often diag-
in a study examining only severe cases.42 Another review
nosed after a significant delay from the onset of symptoms,
that year found a similarly wide range of reported severity
and may initially be mistaken for rosacea. Atypical (pro-
of impairment, with DLQI scores in rosacea ranging from 2
longed, generalized or severe) flushing, or the presence of
to 17!7.43 In a 2019 study of the impact of facial ery-
additional symptoms (sweating, bronchospasm, abdominal
thema, the mean (SD) DLQI score was 5!2 (6!0), and the
pain, diarrhoea) should prompt measurement of urinary 5-
impairment in QoL was strongly correlated with the severity
hydroxyindoleacetic acid and further investigation if suspi-
of the centrofacial erythema.44 When compared with viti-
cion persists.
ligo, the mean DLQI score was 4!3 in patients with rosacea,
Nasal sarcoidosis (lupus pernio) superficially resembles rhino-
and 7 in those with vitiligo. Severe QoL impairments (DLQI
phyma. However, sarcoidosis often affects the nasal septum
> 10), were less frequent (11!0%) than in vitiligo
(causing nasal obstruction). The surface of the thickened nose
(24!6%).45
in lupus pernio, although telangiectatic, is generally smooth,
lacking the rugose peau d’orange surface that characterizes rhino-
5.6. Natural history phyma. Patients with lupus pernio almost invariably have evi-
dence of multisystem disease.
Rosacea usually follows a fluctuating course. The eventual dura-
tion and outcomes are variable, and there is a paucity of pub-
lished data. In a survey of 92 patients ≥ 10 years after a diagnosis5.8. Complications
of rosacea, 48 responded and 25 still had active disease, while 23
Lymphoedema is a relatively rare complication of rosacea that
had cleared.46 In patients in whom the rosacea had resolved, the
can develop over the face and ears. In time, this may
duration of the disease had ranged from 1 to 25 years.
develop into a coarsening of the features known as leonine
Treatment of rosacea can effectively suppress the symptoms
facies. A characteristic pattern of lymphoedema of the upper
and signs of the disease, but there is no evidence that this is
half of the face developing as a complication of chronic
curative. In a follow-up study of 70 patients after 6 months of
rosacea has been termed chronic upper facial erythematous
treatment with tetracycline, two-thirds had relapsed after a
oedema or Morbihan disease. The orbital skin is often
mean follow-up period of 2!6 years.47

© 2021 British Association of Dermatologists British Journal of Dermatology (2021) 185, pp725–735
 males and females approximately equally, argue against this
affected, resulting in severe eyelid swelling and sometimes
being a form of rosacea. It can be difficult to distinguish from
ectropion.
micropapular sarcoidosis.
Malignancy, most frequently basal cell carcinoma, may be
Granulomatous perioral dermatitis in children (facial Afro-Caribbean
seen as a complication of rhinophyma. This can be difficult to
childhood eruption [FACE], Gianotti-type perioral dermatitis, granulo-
diagnose owing to the phymatous distortion of normal skin
matous periorificial dermatitis and sarcoid-like granulomatous dermati-
contours, so it is important to be alert to this risk.
tis) is seen in prepubertal children and may represent a
juvenile form of perioral dermatitis or of acne agminata. It is
5.9. Facial dermatoses possibly related to rosacea considered relatively common in Afro-Caribbean children.52
This is a papular eruption generally confined to the face, with
Perioral dermatitis (periorificial dermatitis) is sometimes regarded as
lesions clustering around the mouth, eyes, nose and ears.53,54 In
a variant of rosacea. It presents as a persistent erythematous
contrast to perioral dermatitis it does not spare the narrow zone
eruption of tiny papules and papulopustules that appears
bordering the lips, and pustules are not seen. The histology has
abruptly in the nasolabial areas and spreads rapidly to the
been variously described as showing nonspecific inflammation
perioral zone, sparing the lip margins. Occasionally, it may
with hyperkeratosis or, more often, as granulomatous, with the
spread to the forehead, eyelids and glabella. Pruritus, burning
inflammatory changes often, but not invariably, being perifollic-
and soreness are prominent symptoms. The lesions consist of
ular. Blepharitis has occasionally been present.
monomorphic small papules and pustules occurring against a
Complete resolution usually occurs after a few months –
background of redness and variable scaling. The papules may
either spontaneously or in response to treatment. In some
occur in recurrent crops and are usually less substantial than
cases, small, pitted scars have been reported.
those of rosacea. A similar eruption involving the eyelids and
Pyoderma faciale (rosacea conglobata, rosacea fulminans) is a florid
periorbital skin has been termed periocular dermatitis. It
eruption of pustules and cystic swellings that may be intercon-
almost entirely affects young adult females, the age range
nected by sinuses, confined to the face, with an absence of
tending to be somewhat younger than that of rosacea, and
comedones.55,56The latter two features distinguish this entity
occurrence in childhood more frequent. Topical corticosteroid
from acne conglobata. However, it remains possible that this
therapy is known to be an important aetiological factor. Occa-
is an unusual variant of acne vulgaris. This is a distressing dis-
sionally, this can result from inadvertent transfer during topi-
ease, often followed by severe scarring. Pyoderma faciale
cal corticosteroid treatment to other regions such as the
mainly affects adults, and most frequently females (in contrast
hands. The use of inhaled corticosteroids for treating asthma,
to acne conglobata). There is often no preceding history of
particularly from nebulizers, may also cause perioral dermati-
acne or rosacea. It is usually a fulminant eruption (rosacea ful-
tis. Periocular dermatitis may be caused by corticosteroid eye
minans). Marked erythema and oedema are usually present.
ointment.48 A variety of primary irritant and allergic contact
Some cases have developed during pregnancy, suggesting that
factors and cosmetic products have been proposed to play a
hormonal factors may play a role. Occasional cases may arise
role, but this has not been substantiated.49 A high prevalence
as a side-effect of medication. Culture of the purulent dis-
of atopy has been reported in patients with perioral dermati-
charge or needle aspiration may be sterile or may yield a
tis.50 Perioral dermatitis tends to resolve if exposure to topical
growth of commensal organisms, including Staphylococcus epider-
corticosteroid stops, although this may take some weeks or
midis and Propionibacterium acnes. This investigation can be helpful
months. Less often, the condition may persist, continuously or
in excluding Gram-negative infection. Significant scarring
intermittently.
develops in many cases.
Acne agminata (lupus miliaris disseminatus faciei, acnitis and facial
Steroid rosacea is the term used for the induction of symp-
idiopathic granulomas with regressive evolution [FIGURE]) is seen
toms closely resembling erythematotelangiectatic rosacea
mainly in adolescents and young adults of either sex. It pre-
and/or inflammatory rosacea by the application of topical
sents as multiple, monomorphic, symmetrical, reddish-brown
corticosteroids.57 This is usually associated with the use of
papules on the chin, forehead, cheeks and eyelids.51 The
potent and very potent corticosteroids, although less potent
lesions may cluster around the mouth or on the eyelids or
compounds can occasionally cause similar problems. This
eyebrows so that the term ‘agminata’ is appropriate, although
entity is clearly associated with the use of topical corticos-
– paradoxically – in many cases, the lesions are widely dis-
teroids, and it is not clear whether there are mechanisms in
seminated around the face and the term ‘disseminatus’ seems
the pathogenesis shared with rosacea. Topical corticosteroids
more applicable. Diascopy of larger lesions often reveals an
may also induce features of acne vulgaris, and these may
apple jelly nodule-like appearance, indicating their granuloma-
coexist in the same patients.
tous histology. This eruption tends to be self-limiting, resolv-
Facial dysaesthesia is a clinical presentation in which sensory
ing completely over a few months or up to 2 years. In some
disturbance predominates and is often out of proportion to
cases, there is scarring. The clinical picture in classical cases is
any visible abnormality.58 The most common complaint is a
distinctive and does not closely resemble rosacea.
severe facial burning sensation, usually occurring intermit-
The aetiology remains unknown. It has been considered by
tently, and sometimes triggered by contact, temperature
some to be a variant of rosacea. While the distribution of
changes or particular foods. Facial hypersensitivity is often a
lesions is similar, the natural history and the tendency to affect

British Journal of Dermatology (2021) 185, pp725–735 © 2021 British Association of Dermatologists
 BAD guidelines for the management of people with rosacea 2021, P.J. Hampton et al. 733

feature of rosacea, but in some cases appears to occur with

minimal or no other features of that disease. These symptoms
9.0 Plans for guideline revision
are sometimes referred to as neurogenic rosacea. The proposed revision date for this set of recommendations is
scheduled for 2026; where necessary, important interim
changes will be updated on the BAD website.
6.0 Recommended audit points
In the last 20 consecutive people with rosacea, is there clear
documentation of:
Acknowledgments
We are very grateful to patient representatives Mr Ian Porter
1. A trial of topical ivermectin in those on long-term antibi-
and Dr John Berth-Jones for their input in formulating the
otics?
clinical questions, ranking of the outcomes, reviewing of the
2. Advice to avoid aggravating factors such as alcohol, sun
evidence and subsequent draft guideline. We are also very
exposure, hot drinks or spicy food?
grateful to Drs Edward Seaton and Iaisha Ali, and Professors
3. Discussion of the pros and cons of intermittent low-dose
Alison Layton, Frank Powell and Malcolm Greaves (consultant
isotretinoin as an alternative to long-term antibiotics, in
dermatologists), and Mr Jeremy Prydal (consultant ophthal-
whom there is no contraindication?
mologist) for their involvement during the early stages of the
4. Offering of propranolol in those with symptomatic flushing,
guideline development process, and to Miss Alina Constantin
in whom there is no contraindication?
(BAD Guideline Research Fellow) for assisting with the final
The audit recommendation of 20 cases per department is to stages, as well as all those who commented on the draft dur-
reduce variation in the results due to a single patient and ing the consultation period.
allow benchmarking between different units. However,
departments unable to achieve this recommendation may
choose to audit all cases seen in the preceding 12 months References
(Appendix N; see Supporting Information). 1 Mohd Mustapa MF, Exton LS, Bell HK et al. Updated guidance for
Supporting Information
7.0 Stakeholder involvement and peer review Additional Supporting Information may be found in the online
The draft document and supporting information was madeversion of this article at the publisher’s website:
available to the BAD membership, British Dermatological
Nursing Group, Primary Care Dermatological Society, British Appendix A Review protocol.
Society for Medical Dermatology, British Society for Dermato- Appendix B Forest plots.
logical Surgery and the Royal College of Ophthalmologists for Appendix C Linking the Evidence to the Recommendations
comments, which were actively considered by the GDG. Fol-(LETR).
lowing further review, the finalized version was sent for peer Appendix D Grading of Recommendations Assessment,
review by the Clinical Standards Unit of the BAD (made up ofDevelopment and Evaluation (GRADE) evidence tables.
the Therapy & Guidelines Subcommittee) prior to submission Appendix E Summary of included studies.
for publication. Appendix F Comparative studies with no extractable data.
Appendix G Narrative findings from within-patient studies.
Appendix H Narrative findings from noncomparative stud-
8.0 Limitations of the guideline
Appendix I Critical appraisal of included systematic
This document has been prepared on behalf of the BAD and is reviews: AMSTAR 2.
based on the best data available when the document was pre- Appendix J Preferred Reporting Items for Systematic
pared. It is recognized that under certain conditions it may be Reviews and Meta-Analyses (PRISMA) diagram: study selec-
necessary to deviate from the guidelines and that the results of tion.
future studies may require some of the recommendations Appendix K Papers excluded from quantitative analysis.
herein to be changed. Additionally, it is acknowledged that Appendix L Methodology.
limited cost-effectiveness data in the context of the UK health- Appendix M Search strategy.
care setting may affect the availability of a given therapy Appendix N Audit standards, data items and data collection
within the NHS, despite evidence of efficacy. Failure to adhere methodology.
to these guidelines should not necessarily be considered negli-
gent, nor should adherence to these recommendations consti-
tute a defence against a claim of negligence. Limiting the
systematic review to English language references was a prag-
matic decision, but the authors recognize that this may
exclude some important information published in other lan-
guages.

© 2021 British Association of Dermatologists

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Supporting Information
Additional Supporting Information may be found in the online
version of this article at the publisher’s website:
Appendix A Review protocol.
© 2021 British Association of Dermatologists
 BAD guidelines for the management of people with rosacea 2021, P.J. Hampton et al. 735

Appendix B Forest plots. Appendix I Critical appraisal of included systematic

Appendix C Linking the Evidence to the Recommendations reviews: AMSTAR 2.
(LETR). Appendix J Preferred Reporting Items for Systematic
Appendix D Grading of Recommendations Assessment, Reviews and Meta-Analyses (PRISMA) diagram: study selec-
Development and Evaluation (GRADE) evidence tables. tion.
Appendix E Summary of included studies. Appendix K Papers excluded from quantitative analysis.
Appendix F Comparative studies with no extractable data. Appendix L Methodology.
Appendix G Narrative findings from within-patient studies. Appendix M Search strategy.
Appendix H Narrative findings from noncomparative stud- Appendix N Audit standards, data items and data collection
ies. methodology.

© 2021 British Association of Dermatologists British Journal of Dermatology (2021) 185, pp725–735