BJD
PERSPECTIVES
Shortcomings in rosacea diagnosis and classification
DOI: 10.1111/bjd.14819
In 2002, the National Rosacea Society (NRS) proposed a pro-
visional classification for rosacea based on the clinical knowl-
edge of that time and on morphological features.1 Explicit was
the intent that this was a framework that could be readily
updated and expanded as new discoveries were made.1 That
scheme posited primary and secondary criteria for diagnosis
and division into four subtypes, representing common clinical
patterns of presentation, and one variant.1 It also helped to
increase recognition of rosacea as a disease and to guide
research.
Subsequent incorporation of this paradigm in epidemiologi-
cal, pathophysiological and translational research has provided
for greater standardization in rosacea reporting. Now, after
more than a decade of using this scheme in research and clini-
cal practice, it should be re-evaluated to incorporate current
scientific knowledge and address shortcomings in guiding
diagnosis and classification of rosacea.
Unequivocal diagnoses can be challenging in the absence of
an absolute gold standard (histology in malignancy; reduced
ejection fraction in congestive heart failure; positive bacterial
blood cultures in sepsis). Accuracy of a diagnostic test is based
on the proportion of true results of the test (true positive, or
sensitivity; and true negative, or specificity) in a population.
In rosacea, where there are multiple potential symptoms
and signs which may be present in varying permutations in
individual patients, the crux of diagnostic criterion determina-
tion must address two issues: which feature(s) is/are essential
(without which the condition cannot be present) and is this
finding unique to the condition? In assessing diagnostic crite-
ria, the goal is to seek those with a high true-positive rate
(that is, a high proportion of those with the criterion truly
have the disease referring to sensitivity) and true-negative
rate (a high proportion of those who do not have the criterion
do not have the disease referring to specificity).2 In the clin-
ical paradigm, diagnosis is optimized by excluding other con-
ditions that can present similarly, the differential diagnosis.
The NRS classification requires reappraisal based on these
considerations. The presence of one or more of the following
four primary features in a centrofacial distribution was defined
by the NRS as indicative of rosacea: flushing (transient ery-
thema), nontransient erythema, inflammatory papules and
pustules and telangiectasia.1 Thus, each should be evaluated as
a critical criterion.
Is flushing independently diagnostic of rosacea in the absence
of other features? Can it be accurately distinguished from emo-
tional blushing, cancerous (neuroendocrine tumours) or post-
menopausal flushing? While some authors aver to
2017 British Association of Dermatologists
British Journal of Dermatology
distinguishing these variations of blushing, the accuracy of
these assertions is unknown.
Using inflammatory papules and pustules as a primary fea-
ture implies that their sole presence indicates rosacea. If so,
the counterargument is that they are also the feature of many
other conditions, the most relevant in the age context of rosa-
cea being adult acne, folliculitis, pityriasis folliculorum
(demodicosis) and perioral/periorificial dermatitis.3 Is the sole
presence of centrofacial inflammatory papules/pustules
diagnostic of rosacea?
Centrofacial telangiectasia are ubiquitous in adults as exami-
nation for telangiectasia at alar creases will readily demon-
strate. Using the current classification, almost all adults would
have rosacea based on telangiectasia.
Of the primary features, we concur that centrofacial ery-
thema may be the sole requisite criteria for rosacea. Neverthe-
less, diagnosis using this feature should depend on the
severity. Lesser degrees of centrofacial erythema may not be
adequately diagnostic in certain societal contexts. This may
also be an inappropriate diagnostic criterion for very dark skin
where erythema or redness is not readily visible. Adjunctive
features may be more appropriate in this cohort, although epi-
demiology and acceptance for rosacea in skin of colour con-
tinues to be debated. Could this be one reason for the
reported paucity of rosacea from regions with dark popula-
tions? The primacy of clinical criteria for case finding was
demonstrated by a recent histological and molecular analysis
demonstrating differences between erythematotelangiectatic
rosacea (ETR) and telangiectatic photoageing. This study relied
solely on clinical criteria for differentiation: those for the latter
included telangiectasia and prominent feature(s) of photodam-
age (atrophy, premalignant or malignant neoplasms, facial
wrinkling, dyspigmentation and/or poikiloderma), while
those for the former were transient erythema (flushing), non-
transient erythema and/or facial telangiectasia.4
We are uncertain why phyma should be considered a sec-
ondary feature of rosacea, implying that it is nondiagnostic of
rosacea. There is no stated rationale for these very distinct
changes not being a primary feature.1 Phyma has few mimics
(lymphoma, rhinoscleroma, blastomycosis, nonmelanoma skin
cancer, sarcoidosis), but none are completely identical with
phymata, even clinically.1 The latter can be distinguished by
clinical evaluation and biopsy, as required.
Ocular rosacea is a collection of signs and symptoms with-
out a sense of diagnostic prioritization.1 Similar to the diag-
nostic hallmarks of cutaneous rosacea, what are the essential
clinical criteria for diagnosis of ocular rosacea? Along this line,
why is ocular rosacea included as a subtype but not granulo-
matous rosacea or rosacea conglobata?
British Journal of Dermatology (2017) 176, pp197199 197
198 Shortcomings in rosacea diagnosis and classification, J. Tan et al.
While rosacea subtyping was intended to designate com-
mon combinations of clinical presentation, it has led to inade-
quate determination of phenotypic presentations of rosacea in
epidemiological research. While there are some distinctive his-
tological, immunohistochemical features and selective differ-
ences at the transcriptome level for the three cutaneous
subtypes of rosacea [ETR, papulopustular rosacea (PPR) and
phymatous rosacea (PhR)], there is also significant overlap.58
These include innate immune activation involving mast cells
in ETR and PPR (mast cells are a key source of cathelicidin
LL-37 the antimicrobial peptide pivotal in rosacea pathogen-
esis), macrophages (PPR > PhR > ETR) and neutrophils (PPR
and PhR)6,7; adaptive immune activation with a T-helper (Th)
1/Th17-polarized response (PPR > PhR > ETR);5 and distinc-
tive gene array profiles with overlap of certain genes.8 There
is limited information on molecular markers responsible for
the initiation and perpetuation of the different cutaneous fea-
tures of rosacea. Some mediators appear to be important in all
subtypes [S-100 proteins, tumour necrosis factor-a, inter-
feron-c, interleukin (IL)-17], while other mediators show
significant differences among subtypes such as matrix metallo-
proteinases, antibody-producing genes, kallikreins, neuropep-
tides and IL-26, for example.4,5,8 The only clear connection
thus far between mediators and symptoms is the association
between neutrophil-attracting chemokines like IL-8 and devel-
opment of pustules.5
Further, grouping into subtypes provides no details on the
frequency of those presenting with flushing alone, erythema
alone (both are required for diagnosis of ETR); papules/pus-
tules without erythema (both are required for PPR diagno-
sis), phyma with or without papules/pustules or with or
without erythema. There is no subtype category for those
presenting solely with centrofacial erythema without flushing
and vice versa; nor centrofacial erythema without inflamma-
tory papules and vice versa. If each are indeed primary fea-
tures, the absence of a means to categorize their
presentation independently inadequately details the variable
expression of rosacea. Evaluation for rosacea phenotype pro-
gression is hindered, not aided, by the use of subtypes.
Assessment of interventions is also confused with this termi-
nology. In studies of inflammatory papules/pustules in rosa-
cea, use of the term PPR confers two diagnostic dimensions:
centrofacial erythema and inflammatory papules/pustules.
This has led to development of scales that measure both fea-
tures together, implying that they rise and fall in parallel.
This is an unproven hypothesis and largely contrary to
clinical opinion. This issue has practical importance a
treatment solely directed at one dimension of PPR and not
the other may be deemed a failure if both dimensions do
not respond.
Assessment of severity is critical to diseases under investiga-
tion to discriminate varying levels of the disease and to evalu-
ate for change longitudinally, either by natural progression or
due to intervention. Severity can be evaluated from either the
clinician or patient perspective. The former, termed clinician-
reported outcomes, are typically external observer measures;
British Journal of Dermatology (2017) 176, pp197199
the latter, patient-reported outcomes, are based on patient
responses. While the NRS proposed scales designating mild,
moderate and severe9 for clinician-reported outcomes, no fur-
ther detail on the components of these scales was provided.
Practical scales are required that discriminate between severity
categories and that demonstrate clinically relevant responsivity
and reproducibility. Dimensions within each of the phenotypic
features of rosacea need to be defined and then incorporated
into scale development. For clinically reported outcomes, clin-
icians specifically, dermatologists should be involved in
the development. From prior use in studies, such scales are
available for persistent facial erythema (Clinicians Erythema
Scale)10 and inflammatory papules/pustules. A validated scale
for flushing to evaluate the effect of niacin treatment has been
developed and may be applied to flushing in rosacea.11 No
validated scales presently exist for phyma, telangiectasia or
ocular rosacea. We suggest that these scales should be devel-
oped a priori in anticipation of use in interventional studies to
accurately establish efficacy or lack thereof. Potentially the
individual scales could be merged to provide an overall clini-
cal score measuring disease severity and changes with treat-
ment.
Almost a decade and a half has elapsed since the initial
proposition of criteria for rosacea diagnosis and grouping
into common presentations or subtypes. Reappraisal of these
items suggests shortcomings in case-finding and diagnostic
accuracy that require revision to facilitate rather than under-
mine future investigation. Subtyping of rosacea, a post-hoc
means of grouping more common presentations, can be and
has been subverted inappropriately to imply strict categories
without adequate consideration of the varying phenotypic
presentation of individuals and the potential for temporal
variation. Scales for rosacea severity are also confounded by
similar multidimensional aspects represented in subtyping. In
clinical investigation, this can interfere with study of the
course of singular features of rosacea and their measurement.
Redefinition of primary criteria for rosacea diagnosis and
development of single-dimensional scales for clinically impor-
tant aspects of rosacea should be undertaken as a research
priority. Beyond inclusion of solely European and North
American experts, global representation in achieving consen-
sus on rosacea diagnostic criteria and severity dimensions
based on critical analysis of prior efforts and current research
should be undertaken to guide future investigations into this
enigmatic condition.
Funding sources
Funding for writing services provided by Galderma Interna-
tional.
Conflicts of interest
The authors have served as consultants to Galderma Interna-
tional, a company that manufactures prescription treatments
for rosacea.
2017 British Association of Dermatologists
 Shortcomings in rosacea diagnosis and classification, J. Tan et al. 199

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2017 British Association of Dermatologists British Journal of Dermatology (2017) 176, pp197199