SPECIAL REPORT
`
`Standard classification of rosacea: Report of the
`National Rosacea Society Expert Committee on
`the Classification and Staging of Rosacea
`
`Committee members; Jonathan Wilkin, MD, Chairman,a Mark Dahl, MD,I) Michael Detmar, MD,C
`Lynn Drake, MD,c Alvan Feinstein, MD," Richard Odom, MD,e and Frank Powell, MD 1
`Rockville, Maryland; Scottsdale, Arizona; Boston, Massachusetts; New Haven, Connecticut;
`San Francisco, California; and Dublin, Ireland
`
`R usacea is well recognized as a chro (cid:9)
`
`-
`nouns disorder primarily of the convexities of
`the central fitce (cheeks, chin, nose, and cen-
`tral tbrehead), often characterized by remissions and
`exacerbations. Based on present knowledge, it is
`considered a syndrome, or typolog%. encompassing
`VariOLIS combinations of such cutaneous signs as
`flushing, erythema, telangiectasia, edema, papules,
`pustules, ocular lesions, and rhinophyma. 1 In most
`cases, some rather than all of these stigmata appear
`n any given patient.
`Rosacea appears to he quite common, and in an
`cpidemiologic study in Sweden its prevalence was
`.10%. 2 It has been most frequently observed in
`patients with fair skin, but has also been diagnosed
`in Asians and African Americans. Rosacea occurs in
`hoth men and women and, although it may occur at
`any age, the onset typically begins at any time after
`age 30. 3
`Despite its apparent high incidence, the nosology
`of rosacea is not well established, and the term
`"rosacea" has been applied to patients and research
`subjects with a diverse set of clinical findings that
`may or may not be an i ltegral part of this disorder.
`
`From the Division of Dermatologic and Dental Drug Products, Food
`and Drug Administration, Rockville; the Department of
`Dermatology, Mayo Clinic Scottsdaleb; the Department of
`Dermatology,Harvard Medical School, Boston'; the Departments
`of Medicine and Epidemiology and Public Health,Yale University,
`New Havend; the Department of Dermatology, University of
`California San Franciscoe; and the Regional Centre of
`Dermatology, Mater Misericordiae Hospital, Dublin.f
`The opinions set forth in this report are those of the committee mem-
`bers and do not represent the Food and Drug Administration in
`any way.
`Reprint requests: The National Rosacea Society, 800 S Northwest
`Highway, Suite 200, Barrington, IL 60010.
`J Am Acad Dermatol 2002;46:584-7.
`16/1/120625
`doi:10.1067/mjd.2002.120625
`
`584
`
`In addition to the diversity of clinical manifestations,,
`the etiology and pathogenesis of rosacea are
`unknown, and there are no histologic or serologic
`markers.
`'I'hereb ire, the National Rosacea Society assem-
`bled a committee to develop a standard classification
`system that can serve as a diagnostic instrument to
`invest :he manifestations and relationships of
`the se\ eral subtypes and potential variants of
`rosacea. Standard criteria for diagnosis and classifica-
`tion of patients are essential to perform research,
`analyze results and compare data from different
`sources, and may further serve as a diagnostic refer-
`ence in clinical practice. The standard terminology
`will also facilitate clear communication among a
`hroad range of basic, clinical, and other researchers;
`practicing dermatologists, prinlary care physicians,
`ophthalmologists and other specialists; health and
`insurance administrators; and patients and the gen-
`eral public.
`The committee based the standard classification
`system on present scientific knowledge and mor-
`phologic characteristics. This avoids assumptions on
`pathogenesis and progression, and provides a frame-
`work that can be readily updated and expanded as
`new discoveries are made. As knowledge increases,
`it is hoped that the definition of rosacea may ulti-
`mately he based on causality, rather than on mor-
`phology alone.
`The following provisional classification system
`describes the primary features of rosacea and
`defines 4 subtypes and 1 variant. Evolution from
`one subtype to another may or may not occur, and
`research to investigate this process may provide
`important insight into the pathogenesis of rosacea.
`Regardless of subtype, however, each individual
`characteristic may progress from mild to moderate
`to severe. Early diagnosis and treatment are there-
`fore recommended.
`
`1
`
`Galderma Laboratories, Inc. Ex 2007
`Dr. Reddy's Labs v. Galderma Labs., Inc.
`IPR2015-01777
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`

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`DIAGNOSTIC CRITERIA
`Primary features
`
`BOtiacea
`re of the fol-
`-ice of
`central (cid:9)
`lova c; signs With a t entral hoe C
`On is indica-
`' (cid:9)
`sient,
`• 51.,!115 .ire COIM1101
`(it t . (cid:9)
`lents
`Ntin
`illay
` diaenostic
`rnai. present with mill c rh.ai ,-, ne of these
`features.
`• Flushing dran ent erythem
`quent blushing or fluslng is
`• Nontransient cry ema. Persistent redness of the
`facial skin is the (cid:9)
`in sign of rosacea.
`• Papules and pustules. Dome-shaped red papules
`I or without accompanying pustules, often in
`crops, are typical. Nodules may also occur.
`Although patients with coneomitant acne may
`,
`r -ics should he con-
`exhibit comedones, conie
`sidcred part of an Si tO
`ros;iccii.
`• Telan.,:jectasia. (cid:9)
`not necessary for a rosacea iliagnosis
`
`mon but
`
`Secondary features
`The following signs and symptoms oftei appear
`with one or more of the primary features of i sa
`hut in some patients can occur indepenc
`nsa-
`• Burning or stinging. Burning or stin,, (cid:9)
`tions with or without scaling or derma itis may
`occur, especially on malar skinH
`
`• Plaque. Elevated red plaques without epiderm aJ
`changes in the surrounding skin may occur.
`• Dry appearance. Central facial skin may be rough
`and scaling so as to resemble dry skin and suggest
`an eczematous dermatitis, and may often include
`the coesistellce of sehorrheic dermatitis. This
`"dryness" may he associated with burning or
`stinging sensations, and may be caused by irrita-
`tion rather than the disease process.
`• Edema. Edema inay accompany or follow pro-
`longed facial erythema or flushing. Sometimes
`soft edema may last for days or be aggravated by
`inflammatory changes. Solid facial edema (per-
`sisting hard, nonpitting edema) can occur with
`rosacea, usually as a sequel of the papulopustular
`type, and also independently of redness, papules
`and pustules, or phymatous changes.
`• Ocular manifestathms. Ocular manifestant ins are
`common, and range from symptoms of burning
`or itching to signs of conjunctival hyperemia and
`lid inflammation. Styes, chalazia, and corneal
`damage may occur in many patients with rosacea
`in addition to cutaneous stigmata. The severity of
`ocular manifestations may not be proportional to
`those of the skin.
`
`Table I. Guidelines for the diagnosis of rosacea
`
`Presence of one or more of the following primary features:
`Flushing (transient erythema)
`Nontransient erythema
`Papules and pustules
`Telangiectasia
`May include one or more of the following secondary
`features:
`Burning or stinging
`Plaque
`Dry appearance
`Edema
`Ocular manifestations
`Peripheral location
`Phymatous changes
`
`• Peripheral location. Rosacea has been reported to
`occur in other locations, 5 but the frequency and
`occurrence of this are. ill-defined. Rosacea in
`peripheral lo( xiinP, may or may nor he accompa-
`nwd (cid:9)
`facial manifestations.
`• Phiduittotis cl:angcs. These can include patulons
`follicles, skin thii kcning or fibrosis, and a bulbous
`appearance. Rhinophyma is the most common
`form, hut other phymas may occur (Table H.
`
`SUBTYPES
`The primary and secondary rosacea features
`described above often occur together. The most
`common patterns or groupings of signs are provi-
`illy designated as specific subtypes of rosacea
`and are described here (Table II). Each subtype
`includes the fewest signs sufficient to make a diag-
`nosis of the subtype (though not necessarily limited
`to these), and patients may have characteristics of
`more than one rosacea subtype at the same time.
`
`Subtype 1: Erythematotelangiectatic rosacea
`Erythematotelangiectatic rosacea is mainly charac-
`qJ by flushing and persistent central facial ery-
`thema. The appearance of telangiectases is common
`but not essential for a diagnosis of this subtype.
`Central facial edema, stinging and burning sensations,
`and roughness or scaling may also be reported. A his-
`tory of flushing alone is common among patients pre-
`senting with eiythematotelangiectatic rosacea.
`
`Subtype 2: Papulopustular rosacea
`Papillopustular rosacea is characterized by persist-
`em central facial erythema with transient papules or
`pustules or hoth in a central facial distribution,
`However, papules and pustules also may occur per--
`orificially (that is, they may occur in the perioral,
`pednasal, or periocular areas). The papulopustular
`
`2
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`Galderma Laboratories, Inc. Ex 2007
`Dr. Reddy's Labs v. Galderma Labs., Inc.
`IPR2015-01777
`
`(cid:9)
`

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`586 IV/llkia (cid:9)
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`al
`
`AM A c,s11)
`A PIZ I L 2002
`
`Table H. Subtypes and variants of rosacea and their characteristics
`
`Characteristi
`
`Subtype
`Erythematotelangiectatic
`Papulopustular
`Phymatous
`
`Ocular
`
`Variant
`Granulomatous (cid:9)
`
`Flushing and persistent central facial erythema with or without telangiectasia.
`Persistent central facial erythema with transient, central facial papules or pustules or both.
`Thickening skin, irregular surface nodularities and enlargement. May occur on the nose,
`chin, forehead, cheeks, or ears.
`Foreign body sensation in the eye, burning or stinging, dryness, itching, ocular photosen-
`sitivity, blurred vision, telangiectasia of the sclera or other parts of the eye, or periorbital
`edema.
`
`Noninflammatory; hard; brown, yellow, or red cutaneous papules; or nodules of uniform
`size.
`
`subtype resemhles acne vui Igaris, except dint come-
`clones are absent. Rosacea and acne may occur con-
`comitantly, and such patients may have comedones
`as well as the papules and pustules of rosacca.
`Burni ng and stinging sensations 11
`he reported by
`patients with papulopustular n tsa,
`This suhtype has often been seta i tif)er or in COM-
`hination with subtype I, including the presence of
`telangiectases. The telangiectases may he obscured
`by persistent erythema, papules, or pustules, and
`tend to become more visible after successful treat-
`ment of these masking components.
`
`Subtype 3: Phymatous rosacea
`Phymatous rosacea includes thickening skin,
`ce nodularities, and enlargement,
`irregular
`Rhinophyma is the most common presentation, hut
`phymatous rosacea may occur in other locations,
`including the chin, forehead, cheeks, and ears.
`Patients with this subtype also ialay have patulous,
`expressive follicles in the phyrnatous area, and
`telangiectases may he present.
`This subtype has frequently been observed after
`or in combination with subtypes -1 or 2, including
`persistent erythema, telangiectases, papules, and
`pustules. In the case of rhinophyma, these addition-
`al stigmata may be especially pronounced in the
`nasal area.
`
`Subtype 4: Ocular rosacea
`The diagnosis of ocular rosacea should he consid-
`ered when a patient's eyes have one or more of the
`following signs and symptoms: watery or bloodshot
`appearance (interpalpebral conjunctival hyperernia),
`foreign body sensation, burning or stinging, dryness,
`itching, light sensitivity, blurred vision, telangiectases
`of the conjunctiva and lid margin, or lid and pet -jocu-
`lar elythema. Blepharitis, conjunctivitis, and irregular-
`ity of the eyelid margins also may occur: 6 Meibomian
`
`g:and dysfunction presenting as chala (cid:9)
`onic
`aphylococcal infection as manifested by hordeolum
`(sitter are common signs of rosacea-related ocular dis-
`ease. Si tme patients may have decreased visual acuity
`caused by cortical complications (punctate keratitis,
`corneal infiltrates/ulcers, or marginal keratitis). 7
`Treatment of cutaneous rosacea alone may be inade-
`quate in terms of lessening the risk of vision loss
`resulting from ocular rosacea, and an ophthalmologic
`appmach may he neecled.K
`Ocular rosacea is most frequently diagnosed
`when cutaneous signs and symptoms of rosacea are
`also present. However, skin signs and symptoms are
`not prerequisite to the diagnosis, and limited studies
`suggest that ocular signs and symptoms may occur
`before cutaneous manifestations in up to 20% of
`patients with ocular rosacea. Approximately half of
`these patients experience skin lesions first, and a
`minority have both manifestations simultaneousle
`
`VARIANTS
`Variants of rosacea, which do not represent mor-
`phologic patterns or combinations as seen in
`rosacea subtypes, may occur, lb date, the committee
`has recognized one such variant.
`
`Granulomatous rosacea
`Granulomatous rosacea is characterized by hard,
`yellow, brown, or red cutaneous papules or nodules
`that may he severe and lead to scarring. These
`lesit ins tend to he less inflammatory than papules
`and pustules and sit upftn relatively normal-appear-
`. skin. They can vary in size among patients but are
`monomorphic in each individual patient, and typi-
`cally appear on the cheeks and periorificial areas.
`Granulomatous rosacea may occur in locations other
`than those in which thc phyrnas are observed. The
`presence of other rosacea signs is not needed for a
`diagnosis of the granulomatous rosacea variant.
`
`3
`
`Galderma Laboratories, Inc. Ex 2007
`Dr. Reddy's Labs v. Galderma Labs., Inc.
`IPR2015-01777
`
`(cid:9)
`

`
`I AM ACAI) DEItMARA. (cid:9)
`VOI.I.IMF 40, N 11M1IFIZ 4
`
`11''Ylkirt et ol 587
`
`EXCLUSIONS
`The COMIIIIIICY ni)ted tI j (cid:9)
`ii CIL '1(.1vis HIJV
`haVe been prema 1 urely LII (cid:9)
`itc (cid:9)
`with
`i :is (cid:9)
`aritv
`rosacea or as a variant of Ft CA, and ior
`should he recognized at this time as separate enti-
`ties, There is insufficient 1 , :i•is at present to include
`the following conditioi is as :‘ pes of rosticeta.
`
`Rosacca fulminans
`Popularly known as pyodernia laciale, the group-
`orC !pC of I-Lis:WC:I is premature.
`It is characterized by the sudden appearance of
`impules, pustules, turd nodules, along with fluctuat-
`I draining SHILISCS that may be interconnect-
`Tondition appears primarily in women ir
`and intense redness and edema also may
`
`he pron
`
`Steroid -induced acnciform eruption
`Steroid-induced acneiform eruption is not a vari-
`ant of rosacett and can occur as an inflammatory
`response in an n paiitalt during or after chronic corn-
`costeroid use. The saine inflammatory response may
`also, of course, oci lir in patients with rosacea.
`
`Perioral dermatitis
`Although rosacea papules may appear it
`oral area, as noted earlier, perioral derma
`out rosacea symptoms cannot be classified tiS a vari-
`ant of rosacea. Perioral dermatitis is characterized hv
`such stigmata as microvcsicles, scaling, and peeling.
`
`FUTURE
`This investigational instrument is intended to set
`the stage for a better understandin rosacea and
`its subtypes among researchers and practitioners by
`fostering communication and facilitating the des cl-
`opment of a research-based classification system. AS
`tt provisional standarcl classification system, it is like-
`-equire modification in the future as the patho-
`genesis and subtypes of rosacea become clearer, and
`as its relevance and applicability are tested by invres-
`tigators and clinicians. The committee s n elcomes
`reports on the usefulness and limitations of these
`criteria.
`
`II (cid:9) Comm (cid:9)
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`coiiuiuhiuted to
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`III: , (cid:9)
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`idllaIS 55110
`Dr Joel
`\ Lir\ - "Duluth
`
`i I i•
`ts Iserg. De lii (cid:9)
`Cling Dr (cid:9)
`Hospital, (cid:9) Eskilsiuna, (cid:9)
`Dr Albert (cid:9) Kliginan,
`ermau (cid:9)
`of Pennsylvania: Dr
`f P (cid:9)
`k NIancus, Dep;iruuieiut (cid:9)
`i.iltttol a. University of
`C.ilifornia-Davis; (cid:9) Dr (cid:9) Ronald (cid:9)
`ic::.irtinent (cid:9)
`I/crrnatolngy, t [irs ersits ol (cid:9)
`Cemer, Cardiff,
`Drs Gerd Plewig .111d Claudia F3n1:•11i, Dc.dartment
`if
`13ermatology, Ludwig.Ma infilitins University, :Munich,
`Gctmany; Dr Alfredo Ne1 , ora. Department of Dermatology,
`UMversity of Genoa, Ital'n : Dr Diane Illiboutot, Department
`nf Dermatology, Pennsylvania State University; ;ind Dr Guy
`clnror, Deparmient of Dermatology, Thomas Jefferson
`L. nn.er4ty The final document does not necessarily reflect
`[iii 5 leWs of :my single individual, and lint all comments
`were I f 1COrpOrated.
`
`iii
`
`mc)(3) Hot
`The mtinir.,I (cid:9)
`whir,. mission is to support rnsacea
`01:hiding !lie awarding of research grants, and to
`, vide ed cational information on rosticen to physicians,
`patients, and the public. Reports trr inquiries should be
`directed to the National Rosacea Society, SOO S Northwest
`Hwy, Suite 200, liarrintnn, IL 00010; telephone 847//'382-
`897 ; E-mnil: rostg
`
`REFERENCES
`1. Wilkin JK. Rosacea: pathophys ology and treatment. Arch
`Dermatol 1994;130:359-62.
`2. Berg M, Liden S. An epidemiological study of rosacea. Acta
`Derm Venereal 1989;69:419-23.
`3. Drake L. Survey maps typical progression from rosacea's first
`appearance.Rosacea Review 1995;winter2.
`4. Lonne-Rahm S-B, Fischer 1, Berg M. Stinging and rosacea. Acta
`Derm Venereol 1999;79:460-1.
`5. Jansen T, Plewig G.Rosacea:classificat on and treatment.J R Soc
`Med 1997;90:144-50.
`6. Macsai MS, Mannis MJ, Huntley AC. Acne rosacea. In: Eye and
`skin disease. Philadelphia: Lippincott-Raven; 1996. p.335-41.
`7. Chen DM, Crosby DL.Periorbital edema as an initial presenta-
`tion of rosacea.l Am Acad Dermatol 1997;37:346-8.
`8. Akpek EK, Merchant A, Pinar V, Foster CS.Ocular rosacea: patient
`characteristics and follow-up. Ophthalmology 1997;104:
`1863-7.
`9. Browning DJ, Praia AD.Ocular rosacea. Sun./ Ophthalmol 1986;
`31:145-58.
`
`4
`
`Galderma Laboratories, Inc. Ex 2007
`Dr. Reddy's Labs v. Galderma Labs., Inc.
`IPR2015-01777
`
`(cid:9)