The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. : I. Derivation of a minimum set of discriminators for atopic dermatitis

British Journal of Dermatology (1994) 131. 383-396.

WORKING PARTY REPORT

The U.K. Working Party's Diagnostic Criteria forAtopic Dermatitis.I. Derivation of a minimum set of discriminators foratopic dermatitis

H.C.WILLIAMS, P.G.J.BURNEY,* R.J,HAY, CB.ARCHER,! M.J.SHIPLEY,|J.J.A.HUNTER,§ E.A.BINGHAM,1 A.Y.FINLAY,** A.C.PEMBROKE,ff R.A.C.GRAHAM-BROWN.| | D.A.ATHERTON,§§ M.S.LEWIS-JONES,1[^ C.A.HOLDEN,*** J.I.HARPER,§§R.H.CHAMPION.ttt T.F.POYNER,Ht J.LAUNER§§§ AND T,J,DAVIDTOSt John's Institute of Dermatology and "Department of Public Health Medicine, UMDS, St Thomas' Hospital, London SEI 7EH,U.K.^University of Bristol, Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K.^Department of Epidemiology and Public Health, University College London Medical School, London WCIE 6EA, U.K.^Department of Dermatology, The Royal Infirmary, Edinburgh EH3 9YW, U.K.^Department of Dermatology, Royal Victoria Hospital, Belfast BT12 6BA, U.K."Department of Dermatology, University of Wales College of Medicine, Cardiff CF4 4XN, U.K.]-\Department of Dermatology. King's College Hospital, London SEI 7EH, U.K.ttLeicester Royal Infirmary, Leicester LEI 5WW, U.K.^^Department of Dermatology, Hospital for Sick Children, Great Ormond Street, London WCIN 3]H, U.K.nWrexham Maelor Hospital, Clwyd LL13 7TD, U.K.""St Helier Hospital, Carshalton, Surrey SM5 lAA, U.K.]]]Department of Dermatology, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.HtQueen's Park Medical Centre, Stockton-on-Tees TS18 2AW, U.K.§§§Tfie Health Centre, Edmonton, London N9 8RZ, U.K.

of Paediatrics, University of Manchester, Booth Hall Children's Hospital, Manchester M9 2AA, U.K.

Composition of the Atopic Dermatitis Diagnostic Criteria Working Party

Participating physiciansDermatologists: Dr C.Archer, Dr D.Atherton, Dr A.Bingham, Dr R.Champion, Dr. E.Cronin (St John's Institute ofDermatology, London), Dr A.Finlay, Dr R.Graham-Brown, Dr J.Harper, Prof. R.Hay, Dr C.Holden, Prof. J.Hunter,Dr S.Lewis-Jones and Dr A.Pembroke.General practitioners: Dr T.Poyner and Dr J.Launer.Paediatrician: Prof. T.David.

Coordinator: Dr H. Williams.Epidemiological and statistical support: Prof. P.Burney, Dr M.Shipley, Department of Medical Statistics, London School ofHygiene and Tropical Medicine (now at University College Hospital), and Dr D.Strachan, Department of Public HealthSciences, St George's Hospital Medical School.

Accepted for publication 17 March 1994

Summary A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled,with the aim of developing a minimum list of reliable discriminators for atopic dermatitis.

Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderateatopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examinedby two independent observers, who were blind to the clinical diagnosis and study aim. with regard to31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-fourpatients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosisas a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested.

Correspondence: Dr H.Williams, Department of Dermatology, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, U.K.

383

384 H.C.WILLIAMS etal

Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopicdermatitis was derived. These were: history of flexural involvement, history of a dry skin, onsetunder the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexuraldermatitis. Adjustment for age, sex. region, social class and ethnic group did not alter the choice offinal criteria. The discriminatory value of these criteria was also satisfactory when tested against afurther sample of 150 patients drawn from the community, who did not have skin disease.

Background

Atopic dermatitis (atopic eczema) is a common disease,with a lifetime prevalence of around 5-15% in childrenfrom industrialized countries, ~ Case definition isperhaps the most fundamental step of research intothe distribution and determinants of any disease. Theabsence of diagnostic criteria for atopic dermatitis (AD)prompted. Hanifin, Lobitz and Rajka to suggest majorand minor diagnostic criteria for AD.'^"' based onclinical features. These criteria represented a majorstep forward in ensuring some degree of uniformity ofAD subjects in subsequent hospital-based studies.

However, as Schultz-Larsen and others have pointedout,^""^^ these criteria are not suitable for population-based studies. Many of the criteria have no precisedefinition^'' (e.g. pityriasis alba), some are veryinfrequent (e,g, keratoconus^*" ), and others arenon-specific (e.g. white dermographism^*). They werederived from clinical experience with predominantlywhite, hospital-based cases of AD, and division intomajor and minor criteria was logical but empiricalMore importantly, the criteria have not been formallyvalidated against physician's diagnosis, or tested forrepeatability. The criteria contain invasive tests whichwe believe are not often used in routine clinical practice,and which may not be suitable for large studies withchildren.^'^^

Although these criteria continue to be useful inhospital clinical trials because of their probable highsensitivity, their complexity and lack of validation makethem less suitable for use in population-based studies oras a diagnostic aid to doctors in primary care.

A number of groups have examined the usefulness ofHanifin and Rajka's diagnostic criteria,^^''^""^* butinstead of addressing crucial issues such as validationagainst the physician's diagnosis or deciding whichshould be designated major and minor criteria, suchstudies have tended to focus on small differences in theapplication of the 30 minor criteria mentioned inHanifin and Rajka's original abstract.^ These minorfeatures may vary considerably following slight adjust-ments in their definition/interpretation. Eeatures such

as infraorbital folds, periorbital pigmentation, andhyperlinear palms are probably highly dependent onthe age, sex and ethnicity of the population under study,which may explain the large discrepancies betweenthese studies.^^"'̂ ^"'̂ * The cases of AD used in thesestudies were all from hospitals, which might explain thehigh frequency of signs such as anterior neck folds,Hertoghe's sign and hyperlinear palms, which areprobably more frequently seen in severe/chroniccases. The observers were not blinded to the diagnosticstatus of the patient in any of the studies, and repeat-ability (between and within observers) of the signs hasnot been assessed, A notable exception to these studiesis the work of Diepgen et al, who derived a scoringsystem of useful diagnostic features of AD based on xvalues.^ They compared established hospital-ascertained AD cases {n = 428) with normal youngadults from the community who did not have AD{n = 628), with respect to a number of Hanifin andRajka's diagnostic criteria. They used clinical evidenceof recurrent flexural itching or lichenified dermatitis asa gold standard for cases. This implied that it wasimpossible to assess the usefulness of flexural involve-ment (current or past) as a feature of AD as, bydefinition, this criterion had 100% sensitivity and100% specificity.

On the basis of their x^ results. Diepgen et al showedthat some features, such as a personal or family historyof atopy, which are considered as 'major' features inHanifin and Rajka's original criteria, are not as usefulas some previously designated 'minor' features suchas xerosis. They also showed that raised total serum IgE(> 150 U/ml) and a positive RAST for inhalantallergens were neither particularly sensitive norspecific for AD, the corresponding x^ values being lessthan most of the historical and cfinical features.Using their scoring system, Diepgen et al. demon-

strated good separation between cases and controls,although the scoring system was tested on the samedata set from which the criteria were derived, asopposed to an independent sample. It should also benoted that their scoring system refers to discriminationof hospital-based AD cases from community controls

U.K.-DERIVED CRITERIA FOR ATOPIC DERMATITIS 385

who do not have AD. and as such has not beensubjected to the more stringent test of discriminatingAD cases from subjects with other forms of dermatitisand inflammatory dermatoses. More importantly,repeatability of individual features has not been takeninto account.

Other groups have also proposed scoring systemsbased on various combinations of Hanifin and Rajka'scriteria, but the choice of factors and scoring weights isarbitrary and awaits further validation. ̂ °'^*

Atopic dermatitis is a difficult disease to define, as it isvariable in both place and time, and it lacks a specifictest which can serve as a reference standard.^"Although objective tests such as raised IgE and/orskin prick test positivity remain very important toolsfor research purposes, perhaps for examining definiteatopy, their inclusion as essential requirements for thediagnosis of AD in primary care is perhaps unwise.Studies comparing total IgE and specific aero-allergenIgE in AD subjects with those in normal individualshave found that neither is as helpful as the historicaland clinical features.^^ At an individual level, indeciding whether a child has AD or not, clinical criteriaalone are probably sufficient. Currently, our onlygold standard for atopic dermatitis is therefore a clinicalone.

The aim of this study was to develop a definition ofatopic dermatitis that is sensitive, specific, reproducible,non-invasive, applicable to a range of ethnic groups,and which is easy to perform in population-based andclinical studies.

Methodology

Outline of study

Using a study design similar to that used by theAmerican Rheumatism Council for deriving diagnosticcriteria for systemic lupus erythematosus,^^ a workingparty was assembled, composed of 16 physicians withan interest in atopic dermatitis. Each participatingphysician was asked to select 10 consecutivenew cases of typical mild to moderate AD and 10age-matched (within 10 years) controls with aninflammatory skin disease other than AD. Once thepatient had been seen by the physician and the clinicaldiagnosis and other demographic features such as age.sex, ethnic group and social class^^ had been noted,the patient was then examined by two observersindependently, using a list of 31 potentially usefuldiagnostic criteria shown in Appendix 1. Each observer

recorded a positive or negative response to each of thecriteria on a standard record form.

At the end of the study, sensitivity and specificity foreach criterion was calculated, using the physician'sdiagnosis as the standard. Regression techniques werethen used to derive a minimum set of criteria which bestdiscriminated between cases of AD and controlsrecruited in the hospital study. The criteria were alsotested against a group of patients selected from thecommunity who did not have skin disease, and againstpotential confounders such as age and sex.

The participating physicians

Thirteen of the key physicians were dermatologists witha special interest in AD (six of whom were paediatricdermatologists). Two family practitioners, and apaediatrician with a specific interest in AD, were alsoincluded. No attempt was made to define AD to thephysicians; they were asked to decide if theirpatients had AD in their usual clinical manner. Theobservers' response sheets were concealed fromthe physicians at all times. Observers were notpermitted to discuss their findings with the participat-ing physicians, and queries were referred back to thestudy organizers.

The observers

All of the observers taking part in the study were blindto the key physician's diagnosis. Although it wouldhave been naive to expect that the observers werecompletely unaware of the study's general aim, someblinding was achieved by telling the observers thatthe study's main aim was to examine AD in ethnicminorities.

Of the 32 observers taking part in the study, two wereclinical assistants, two were paediatric physicians, twowere nursing sisters specializing in dermatology,four were general practitioners (for the two familypractitioner key physicians), and the remaining 22were dermatology registrars and senior registrars.

Two observers were required to record the presenceor absence of a criterion for each patient, in order thatbetween-observer repeatabifity could be estimated.Although a combined response for each criterionmight have improved the precision of recordingof the criteria, this is impractical in normal practice.Instead, one of the pair of observer's responses wasrandomly selected as the 'correct' response for eachindividual.


Study population

Selection of cases. In order to provide a reasonable cross-section of AD cases, the factors listed below were takeninto account in selecting the sample.

1 Severity. In order to avoid an over-representationof severe or atypical cases which might occur inhospital-selected subjects, physicians were instructedto select only cases of unequivocal mild to moderateAD. Similarly, as it is perhaps more likely that follow-upcases might represent a more chronic/severe subset ofpatients, they were instructed to recruit only new cases.In order to compare the severity of hospital vs. com-munity-ascertained cases, eight of the assessors (bothgeneral practitioners, and a further six randomlychosen dermatologists) recorded the overall severity oftheir AD cases using the method suggested byRajka. '̂̂ This method, which incorporates an areaassessment (with suitable adjustment for smallchildren) with an assessment of intensity and courseof symptoms into an overall score, was chosen becauseof its simplicity, and because it could be performedrapidly on cases during one visit. In addition,information on the use and strength of topical steroidpreparations, oral steroids, phototherapy or photo-chemotherapy, and other immunosuppressive drugswas recorded.

2 Geography. England, Scotland, Northern Ireland andWales were all represented in the working party.Individual catchment areas included both rural andurban areas, with a wide distribution of social classand ethnic groups.

3 Age. All patients with AD aged 6 months to 50 yearswere eligible for inclusion in the study. Because mostpopulation-based studies on AD relate to children, itwas desirable that at least half of the cases werechildren. This aim was achieved, as seven of the 16key physicians drew cases solely from a paediatricsetting, and the majority of cases seen by generalpractitioners were children.

Selection of controls. For each case, the next age (within10 years)-matched patient with an inflammatorydermatosis was recruited, and tested with respect tothe 31 diagnostic criteria.

Selection of community controls. Although we were mainlyinterested in deriving criteria which best separated AD

from other conditions which could be confused with AD,such as other forms of dermatitis, psoriasis, scabies, etc.,it was also important to ensure that the criteria per-formed equally well in discriminating AD cases fromindividuals who did not have skin disease. To addressthis issue, 10 British general practitioners wereapproached to provide 20 controls each. These werecomposed of randomly selected individuals whoattended because of complaints other than skin disease.In order to ensure age comparability with the hospitalcases, the sample was stratified so that half the patientswere aged under 16 and half were aged 16 or over.Subjects who were known to have AD or other skindiseases were excluded. The practitioners conducting thispart of the study were also blind to the study hypothesis.These community controls were then tested against thehospital cases, using the same criteria.

Selection of criteria to test

It was impractical to test every criterion which has everbeen studied with respect to its diagnostic significance forAD without compromising data quality. All of the majorcriteria proposed by Hanifin and Rajka were thereforetested, as were all minor criteria with a sensitivity of atleast 30%, as indicated by three studies which haveexamined the usefulness of the minor criteria.^^"'̂ '̂̂ ^Invasive investigations such as skin prick tests, serumIgE, RAST tests, testing for white dermographism, eosi-nophilia, and skin swabs were also excluded, as this wasa study requirement, although they were noted ifperformed. This left us with 31 criteria, 13 of whichwere historical, and the remainder were physical signs(Appendix 1). The precise wording ofthe questions usedin the study is shown in Appendix 2. An additional threecompound questions (which might be used in futureepidemiological studies), were also asked at the end oftheinterview, and are shown in Appendix 2.

In order to minimize the subjective component inassessing the signs, precise definitions were provided forthe observers to follow strictly, as shown in Appendix 3.Terms open to misinterpretation, such as 'pityriasisalba' were replaced, and defined by terms such as'hypopigmented patches'. One additional sign, that offine hair, was also tested in this study as a possiblemarker of the atopic state (C.Rowland-Payne, pers.comm., 1989).

Development of the questionnaire

Question stemming and structure were piloted on


dermatology out-patients. In addition, the opinion of anindependent expert was sought (C.E.M.V.). The ques-tions were administered by the trained observer.

Statistics

Data entry. Data were coded, entered twice on to adatabase, and verified. Range checks, and a random10% check against original records, were also carriedout. All equivocal or unclear responses wereadjudicated by independent personnel, and if a cleardecision could not be made, the data were enteredunder a missing value code.

Crude sensitivity and specificity of each criterion werecalculated, and 2 x 2 analysis of the associationbetween a positive feature and active disease wascarried out using the x^ statistic (with Yates' cor-rection where appropriate), using the Epi-Infosoftware statistical package.^* In addition to sensitivityand specificity, an overall measure of usefulness orrelative value was employed (Youden's / statistic'^').This is derived by adding the sensitivity and specificitytogether and subtracting 100, and has a maximumvalue of 100. Along with the magnitude ofthe x^ value,it provides a simple guide of the overall discriminantusefulness of individual criteria.

Unconditional logistic regression was chosen inpreference to other discriminant techniques so thatlinear variables such as age could be modelled along-side binary variables such as the presence or absence ofa cutaneous sign. Regression was carried out using theEgret software package,^° using a combination of astep-up and step-down approach. Variables wereretained in the model if their retention significantlyimproved the fit of that model at the 5% level ofstatistical significance, or if they were deemed to beessential on clinical grounds.

Ethics

Overall ethical approval was granted by the Chairman ofWest Lambeth Health Authority (Professor Smith), andby the appropriate authorities in each centre, as required.

Results

1 Patient characteristics

Control diagnoses

Two hundred and twenty-four subjects (120 cases and

104 controls) were eventually recruited into the studyin the 6 months allocated for this purpose. Although nosubjects refused to participate in the study, difficultywas encountered in finding suitable control patients, asmany individuals with an inflammatory dermatosis(especially in childhood) had AD. Although all of theAD patients were new, consecutive follow-up controlpatients were also accepted into the study at the half-way stage because of the slow accrual of new controlcases.

Diagnoses of the 102 control patients used inthe study are shown in Fig. 1. Of the 39 'otherdermatitis', 12 were allergic contact dermatitis, ninewere cases of discoid eczema, six were primary irritantdermatitis, six were unclassified hand and foot eczema,three were seborrhoeic dermatitis, and there wasone each of lichen simplex, stasis dermatitis andpsoriasiform dermatitis.

Of the 33 'other inflammatory dermatoses', sixwere cases of acne vulgaris, three were lichen planus,two were Henoch-Schonlein purpura, two wereurticaria, two were pityriasis rosea, two were toxicerythemas due to drugs, and there was one caseeach of scabies, tinea corporis, post-streptococcalerythema, pityriasis Uchenoides chronica, viralwarts, keratoderma, keratosis pilaris, inflammatorynodules on the legs, pigmented purpuric eruption,impetigo contagiosa, generalized granuloma annulare,perioral dermatitis, morphoea, molluscum con-tagiosum, aphthous ulceration, and discoid lupuserythematosus.

Demographic characteristics

These are summarized in Table 1. Cases were

Other dermatitis38%

Psoriasis29%

Other inflammatory dermatoses32%

Figure 1. Diagnoses of control subjects {n = 102).


Table 1. Differences in demographic variables between cases andcontrols. Cases were significantly younger than controls (P < 0-01)and non-whites were significantly under-represented in controls(P = 0-01)

Age-groupUnder 1010-19-920-29-930-39-9Over 40

Ethnic groupWhite CaucasianIndian subcontinentAfro-CaribbeanOrientalOther

SexMaleFemaleNot recorded

Social classHigher professionalManagerialNon-manual skilledManual skilledSemiskilledUnskilledNot recorded

Cases (%)( n = 120)

63 (52-5)16 (13-3)26 (21-7)11 (9-2)4 (3-3)

90 (75-0)9 (7-5)

15(12-5)4 (3-3)2 (1-7)

56 (46-7)60 (50-0)

4 (3-3)

15(12-5)42 (35-0)15 (12-5)21 (17-5)12 (10-0)10 (8-3)

5 (4-2)

Controls (%)(n = 102)

16 (15-7)21 (20-6)27(26-5)19 (18-6)19 (18-6)

91 (89-2)3 (2-9)5 (4-9)3 (2-9)0 (0-0)

46(45-1)55 (53-9)

1 (1-0)

7 (6-9)27 (26-5)15 (14-7)27(26-5)11 (10-8)-

6 (5-9)9 (8-8)

significantly younger than controls. The median ageof cases and controls (interquartile range) was8 (3-22-5) and 26-5 (15-37) respectively, a sig-nificant difference (Wilcoxon text P < 001) .Non-whites were significantly under-representedamong the control population. These potentialconfounders have been examined further in theregression analysis. There were no significantdifferences in the sex or social class distributionbetween cases and controls, although both wereconsidered as potential confounders in the regressionanalysis.

Severity of cases

Score. As anticipated, the 65 hospital cases of AD inwhom severity was evaluated scored slightly higherthan the 11 community-ascertained cases of AD.Using a system whereby an individual can score from0 to 9 points,'^'' the median severity score for hospitalAD cases was 7 (interquartile range 6-8) compared

with a median score of 5 (interquartile range 3-6)for the general practitioner cases ( P < 0 - 0 1 ,Kruskal-Wallis statistic 13-8).

2 Crude sensitivity and specificity of each criterion

In view of the difficulty in finding sufficient suitablecontrol subjects, and because the age-matchingillustrated in Table 1 was very crude, it was consideredinefficient to analyse the data as a matched data set.Matching was therefore broken, and the data set wastreated as an unmatched case-control study.

The sensitivity and specificity of the 31 individualcriteria tested in this study are shown in Table 2.Sensitivity refers to the proportion of true casescorrectly identified, and specificity denotes theproportion of true negatives correctly identified. Onsetunder the age of 2 years was used as the cut-off point forthe criterion of early onset, as it appeared to bemore discriminating than onset under the age of 3or 5. Similarly, family history of atopic disease in theimmediate family was more discriminating than apositive family history in any family member.

As seen in Table 2, relative values (RV) weregenerally slightly higher for questions than forsigns. The five most useful criteria, as judged from theranking of the RV or x^ scores, are early onset,history of fiexural involvement, history of dry skin,visible fiexural dermatitis and xerosis. All of the criteriaare significantly associated with AD, with the exceptionof keratosis pilaris. The sensitivity and specificity of theadditional compound questions are also shown inTable 2.

3 Regression to determine the minimum list of gooddiscriminators. Steps in trimming the number ofvariables entered into the regression model

Because it was desirable to keep the ratio of the numberof parameters to number of subjects in the regressionmodel as low as possible, and also to minimize potentialproblems with missing values, rather than enter all 31potential criteria into the regression model, two pruningstages were employed.1 All criteria, which on inspection of the crude analysisdata would have been very unlikely candidates aspowerful discriminators. All those criteria (seven intotal) with a x^ value of < 10 were therefore omitted.These were: duration of > 6 months, blocked nose, itchworse in winter, perifollicular accentuation, fine hair.


Table 2. Sensitivity and specificity of 31 diagnostic criteria for atopic dermatitis for patients with a dermatosis. Responses to four additionalquestions are shown at the bottom of the Table. RV denotes relative value (Youden's / statistic'''), and is derived by adding the sensitivity andspecificity, and subtracting 100. All y^ value over 3-84 are significant at the 5% level, and values exceeding 6-63 are significant at the 1% level

SymptomsItchy skinWool intoleranceItch when sweatingDuration > 6 monthsOnset under age 2 yearsRash affected skin creasesPersonal history asthmaPersonal history hay feverBlocked noseFamily history ecz./asth./hay.Suffer from dry skinDoes soap make skin worse?Worse in winter

SignsVisible dermatitisVisible flexural dermatitisVisible extensor dermatitisHand/foot dermatitisFacial dermatitisTruncal dermatitisVisible dry skinHypopigmented patchesPerifollicular accentuationFine hairInfraorbital creasePeriorbital dermatitisPeriorbital pigmentationPeriaural dermatitisInfra-auricular fissureCheilitisHyperlinear palmsKeratosis pilaris

Additional questionsItchy rashItchy rash coming and going for 6 monthsItchy rash coming and going for 6 months.and affecting the skin creasesDo you have eczema?

Sensitivity (%)

94-274-582-387-280-390-050-840-329-284-095-080-747-4

99-275-262-459-053-866-477-422-031-534-253-441-024-143-229-723-943-6

8-8

94-989-073.1

97-5

Specificity (%)

42-264-964-527-091-874-592-288-286-152-461-465-670-3

31-484-172-371-3378-268-374-095-886-579-277-493-197-088-197-094-177-095-9

35-351-087-3

82-0

x'

39-631-143-3

6-1108-6

93-245-621-2

6-631-479-244-1

6-3

37.674-224-818-922-124-653-512-1

8-23-9

20-532-018-124-624-612-0

9-30-3

30-737-077-1

141-2

RV

36-439-446-814-272-164-543-028-515-336-456-446-317-7

30-659-334-730-332-034-751-417-818-013-430-834-121-131-326-718-020-6

4-7

30-240-060-4

79-5

keratosis piiaris, and paimar hyperlinearity. These werere-examined, however, at the end of the regressionanalysis.2 Ali criteria with unsatisfactory between-observerrepeatability, defined as a K value of < 0-4. Thesevalues were derived from a specially designed con-sultant repeatability study (Paper 11^ )̂, and by com-paring responses of the two observers in this study. ̂ ^Twelve criteria failed to reach this standard, three ofwhich (marked with an asterisk) were already omitted

in stage 1 above. These were visible dermatitis at anysite (K = 0 -17 ) , extensor dermatitis (K = 0-34),truncal dermatitis («; = 0-39), xerosis (K = 0-07),perifollicular accentuation* (K = 0 - 2 7 ) , fine hair*(K = 0-03), prominent infraorbital folds (K = 0-38),orbital pigmentation (K = 0-12), periaural dermatitis(K = 0-29), cheilitis (K = 0-34) and keratosis pilaris*(K = 0-08). This left 16 criteria (shown in Table 3),which were then entered for analysis into the regressionmodel for AD cases and controls from the hospital study.


Table 3. Steps taken in the regression of the 16 most useful diagnostic criteria. The figures represent likelihood ratio statistic values, and can beconsidered as x' values with 1 degree of freedom. Missing values signify that the criterion has been dropped from that model, and the symbol=> implies that this criterion has been accounted for in the base of the model

Deviance of base model

Degrees of freedom

Number of observations

CriterionItchyWoolSweatOnset < 2History of flexural dermatitisAsthmaHay feverAtopy in familyDry skinSoap worseVisible flexural dermatitisHypopigmented patchesOrbital dermatitisAuricular fissureHand/footFacial

Step 1

212-0

152

153

56-636-836-883-294-844-819-926-183-337-667-3

8-337-027-915-327-2

Step 2

117-3

151

153

35-08-6

10-855-4

25-310-617-537-114-519-0

3-917-6

9-51-8

11-9

Step 3

67-5

164

167

18-55-23-8

=^=>13-7

6-88-7

11-29-3

11-3

13-80-4

10-9

Step 4

83-7

182

186

0-7

8-14-56-05-96-37-5

6-7

5-4

Step 5

79-5

190

195

= > •

3-23-96-13-85-5

2-7

1-9

Step 6

87-8

205

211

4-1

The main regression analysis

The results of the multiple logistic regression modellingare shown in Table 3. The likelihood ratio statisticvalues shown in this Table can be considered as x^values with 1 degree of freedom, and represent thechange in deviance in the model with the factor addedwhen compared with the base model, the deviance ofwhich is shown in the top row. Large likelihood ratiostatistics imply powerful discriminators. The deviance ofthe final model, a measure of the goodness of fit of theregression model to the data, was 83-7 on 204 degreesof freedom.

The six most useful features which emerged from theregression analysis are shown in Table 4.

The final regression equation for the log odds of AD isas follows:

Log odds of AD = - 5 - 6 + 2-4 history flexuraldermatitis +3-7 onset under 2 + 1-2 presence itchyrash +1-9 personal history of asthma +1-3 history ofa dry skin +1-3 visible fiexural dermatitis.Equation 1. The regression equation for the entire dataset.

Although history of an itchy skin became insignifi-

cant when visible fiexural dermatitis was added to thefinal model, it was retained, as pruritus was felt to be anessential feature of AD.

Identical results were obtained when the regressionanalysis shown in Table 3 was repeated using twodifi'erent paths (by adding either age of onset or historyof dry skin into the base model of step 1). In order toensure that none of the criteria discarded in the initialtrimming down stages was potentially useful, each ofthese was added in turn to the final regression model.

Of the 15 discarded criteria, only visible dermatitis(any site) and visible xerosis further improved the fit ofthe model, but were rejected on the grounds of poorrepeatability. 31

Table 4. The six most useful diagnostic criteria for atopic dermatitisderived from the logistic regression analysis

History of flexural dermatitisOnset under the age of 2 yearsPresence of an itchy rashPersonal history of asthmaHistory of a dry skinVisible flexural dermatitis


Potential confounders

In order to see if the final choice of criteria wasinfluenced by potential confounders such as age andsex, these were entered individually and in combinationinto the final model. There was no evidence to suggestthat the final choice of criteria was confounded by age,sex, ethnic group, hospital, whether a new or follow-uppatient, or social class.

Interaction

There was no evidence of interaction between the fiveterms included in the final model, nor was there anyevidence of interaction between the terms and a dummyvariable (age < 16).

Regression of the paediatric data

Criteria for the 102 individuals (70 cases and 32controls) under the age of 16 were examinedseparately. The only difference from the model usingall individuals was that a history of a dry skin andasthma no longer remained significant when a historyof fiexural involvement, onset under the age of 2, visiblefiexural dermatitis, and itchy skin, were taken intoaccount.

The regression equation for the paediatric data whenanalysed separately was:

Log odds AD = - 4 - 3 6 + 1 - 8 4 history fiexuraldermatitis +3-46 onset before 2 + 2-09 visible fiexuraldermatitis +1-71 presence of an itchy rash.Equation 2. The regression equation for 102 paediatricsubjects.

4 Discriminatory value of features against a sample ofthe normal population

The sensitivity and specificity of the 31 criteria whenhospital cases are contrasted with community controlswho did not have overt skin disease is shown in Table 5.Generally, the discriminant values (as shown by the x^values) are better than those compared with hospitalcontrols. The specificity of all the questions increased,with the exception of asthma and hay fever. Similarly,all of the signs increased in specificity, with theexception of orbital dermatitis and cheilitis. It wasimpossible to assess the usefulness of early age ofonset, duration of itch, and history of fiexural involve-ment as, by definition, community controls did not haveskin disease.

5 Invasive tests

Invasive tests were rarely performed in the diagnosis ofAD cases. With the exception of skin swabs for micro-biology (which were not used to assist in establishingthe diagnosis of AD), all other investigations such asIgE, RAST tests or skin prick tests were performed in< 10% of cases.

Discussion

This study suggests that good separation of atopicdermatitis cases from controls with other infiam-matory dermatoses can be achieved by just six fea-tures: (i) history of fiexural involvement, (ii) onsetunder the age of 2, (iii) history of an itchy rash, (iv)personal history of asthma, (v) history of a dry skin, and(vi) visible fiexural dermatitis.

The addition of other criteria does not improve thisdiscrimination, and is likely to have an adverse effect, byintroducing additional variability. Although cases weregenerally younger, and included more white Caucasiansubjects, when compared with the controls (both ofwhich might confound the validity of criteria such asage of onset and infraorbital crease), controlling forthese factors made no difierence to the final choice ofcriteria.

It was reassuring that the same criteria were derivedwhen three separate regression paths were used, andthat the same six criteria (with the exception of asthma)were also shown to be the best discriminators for thechildren under 16 years old.

The historical features, which many physicians mayeschew in favour of more 'objective' physical signs,appear to be better discriminators. Only one of thephysical signs, that of visible fiexural dermatitis,survived as a useful additional discriminator whenhistorical features were taken into account, and eventhen it accounted for only a small amount of the totalvariation between cases and controls (LRS of 4-1,P = 0.04). This may be because the history of ADpatients may be more crucial than physical signs, orbecause the signs of AD are so variable in morphology,distribution and time that they are too difficult tostandardize precisely, in spite of attempts at cleardefinitions. This observation is welcome news to thoseconducting large epidemiological surveys, as it impliesthat the prevalence of AD in any given population canbe reasonably estimated on the basis of questions alone.

It is also noteworthy that of the four major criteriasuggested by Hanifin and Rajka, i.e. pruritus, typical

392 H.C.WILLIAMS et al

Table 5. Sensitivity and specificity of criteria of hospital cases of AD compared with 150 community controls without skin disease. Data aremissing for questions 4 to 6 as, by deflnition, these community controls did not have any skin disease

Question Sensitivity (%) Specificity (%) RV

1 Itchy skin2 Wool intolerance3 Itch when sweating4 Duration > 6 months5 Onset under age 2 years6 Rash affected skin creases7 Personal history asthma8 Personal history hay fever9 Blocked nose

10 Family history ecz./asth./hay.11 Suffer from dry skin12 Does soap make skin worse?13 Worse in winter

SignVisible dermatitisVisible fiexural dermatitisVisible extensor dermatitisHand/foot dermatitisFacial dermatitisTruncal dermatitisVisible dry skinHypopigmented patchesPerifollicular accentuationFine hair

Infraorbital creasePeriorbital dermatitisPeriorbital pigmentationPeriaural dermatitisInfra-auricular flssureCheilitisHyperlinear palmsKeratosis pilaris

Additional questionsItchy rashItchy rash coming and going for 6 monthsItchy rash coming and going for 6 months,and affecting the skin creasesDo you have eczema?

94-274-582-3

50-840-329-284-095-080-747-4

99-275-262-459-053-866-477-422-031-534-253-441-024-143-229-723-943-6

94-989-0

73-197-5

84-758-784-7

86-081-781-242-276-764-273-1

85-098-697-397-993-997-384-298-295-687-486-698-293-096-5

100-093-889-598-2

91-494-3

97-1100

162-626-6

162-6

41-114-9

3-420-1

135-649-411-0

182-6154-9109-4103-6

72-4120-3

82-420-326-013-439-150-211-548-837-512-530-2

4-4

103-985-1

51-7129-2

78-933-267-0

36-822-010-426-271-744-920-5

84-273-859-756-947-763-761-620-227-121-640-039-217-139-729-717-733-1

7-0

morphology and distribution, personal or family historyof atopy, and chronicity, three are included in the sixfeatures derived from this study (or four out of flve in amore recent revision ).

Crude validity of criteria

It should be emphasized that it is the sensitivity andspeciflcity, and overall discriminatory function (assessedby the x^ statistic and Youden's / statistic^^), that areimportant in assessing the validity of individual criteria,and not statistical signiflcance.'^^'^^'^* All ofthe criteria

should, by deflnition, be significantly associated withAD, although features with a low prevalence in cases ofAD, such as keratosis pilaris, may not have achievedsigniflcance because of lack of statistical power. Thelack of statistical signiflcance for keratosis pilariscould also be due to misclassiflcation from an uncleardeflnition, although we endeavoured to provide as stricta deflnition as possible (Appendix 3).

The fact that 5% of AD cases gave a negative answerto itchy skin, a cardinal feature of AD, might seemworrying. However, all of the individuals in whom theanswer to this question was negative were young


children with mild AD, and we believe that the wordingof the question 'does he/she scratch the skin at leastonce a day on most days of the year?' was perhaps toodaunting for some parents.

General practitioner data

Most of the criteria performed better when comparedwith controls without skin disease selected from thecommunity, although it was impossible to assess thevalue of early onset and history of flexural involvement,as the responses to these questions are dependent on thepresence of a rash. As might be anticipated, featureswhich refer to skin disease, such as 'itchy skin' or'visible dermatitis' are more speciflc when comparedwith the hospital study, although asthma and hay feverbecame slightly less speciflc, perhaps because atopy wasunder-represented in hospital controls.

Regression analysis

Some authors have pointed out that regressiontechniques may not be the ideal solution for developingdiagnostic criteria as, to some extent, they depend onthe characteristics of the sample,^^ and representativesamples may vary. To minimize these problems ofexternal validity, we have taken a number of steps toensure that we have as representative a sample of casesas possible, and a reasonable cross-section of suitablecontrols.

The presence of an itchy skin was retained in themodel, despite borderline statistical signiflcance,because we deemed it clinically essential for thediagnosis of AD. Otherwise, we were careful tominimize the number of parameters entered into themodel by two pruning stages. It is reassuring that theemergent criteria appear to have good face validity, anddo not contain obscure or implausible criteria. Each ofthe criteria appears to explain different elements whichbest encapsulate the concept of AD, i.e. itch, atopy,flexural involvement, dry skin, early onset and visibledermatitis, all of which are features which other keyworkers have considered to be important.^*'^^ This doesnot imply that the minor criteria discarded in this studyare not useful in the diagnosis of individual hospitalcases if they are present, but simply that when given theresponses to the six minimum criteria derived from theregression analysis, addition of these minor criteria doesnot contribute to further discrimination between casesand controls. It is also worth emphasizing that the mainaim of our study was to develop AD diagnostic criteria

for use in epidemiological studies. Highly speciflccriteria such as nipple dermatitis, if present, may bevery helpful in the diagnosis of individual difficult cases,but are of little help in epidemiological studies becauseof their low ^^^*

Paediatric regression model

Although the paediatric regression model was limited to102 individuals aged 16 and under, the results suggestthat the criteria for children are not necessarily verydifferent from those derived in the main model using allavailable data. There was no evidence to support aninteraction between being aged less than 16 with the sixterms derived using the entire data set.

Continuous or binary definition

It is likely that most clinicians and workers conductingresearch into disease distribution will require a simplebinary disease deflnition, i.e. atopic dermatitis yes/no.Such a deflnition will be derived from the six featuresemerging from this study in Paper III. It might alsobe desirable in aetiological studies to estimate theprobability of AD for each individual by employing ascoring system derived from the regression equation.Such a prediction score is relevant only to thosewith a dermatosis,- as values may be different whendiscriminating cases of AD from community cases whodo not necessarily have any skin lesions.

Compound questions

It is encouraging to note that just one sentence, i.e.'Have you had an itchy rash that has been coming andgoing for at least 6 months, which at some time hasaffected the skin creases?' has a sensitivity of 73-1% andspeciflcity of 87-3%, and as such may prove to be veryuseful in simple large prevalence surveys where thenumber of questions permitted is at a premium.Although the question 'Do you have eczema?' hasthe highest relative value, it is unlikely to perform sowell in the community as, by deflnition, nearly all oftheAD cases referred to a hospital have seen their owndoctor and have already been told that they have'eczema'.

General application of findings

Although the median severity score for hospitalcases was higher than that for community-ascertained


cases, none of the cases was using very potent topicalsteroids at the time ofthe study, and we believe that thecases used to derive the criteria in this study were notatypical or unduly severe. The study population wasalso deliberately selected to provide a sample which wasrepresentative in terms of age, ethnic group, geographyand social class of that of the rest of the U.K. We believethat the flnal selection of control diagnoses providesa good test of the discriminatory potential of thecriteria.

Having established the validity of a minimumnumber of good discriminators for AD, it is equallyimportant to test the repeatability of these criteria.This will be the purpose of.the next study (Paper 11^ )̂.Regression equations and scoring systems, althoughattractive in that they purport to present diseaseon a continuum, are perhaps too complex formost studies which require a binary deflnition ofatopic dermatitis, yes/no. It is therefore important topropose an arrangement of the criteria that willgenerate such a binary deflnition, i.e. which areessential, and the number of criteria which need tobe fulflUed in order to qualify as a 'case'. Derivingthis format, and validation of the flnal proposedcriteria on independent samples, will be addressedsubsequently (Paper III).36

AcJcnowledgments

We wish to express our sincere thanks to thefollowing people: Professor Jon Hanifln, Oregon, U.S.A.,Professor Georg Rajka, Oslo, Norway, Dr FinnSchultz-Larsen, Fredericia, Denmark. Additional adviceregarding study design: Dr David Strachan, Departmentof Public Health Sciences, St George's Hospital, and thelate Professor Geoffrey Rose, Emeritus Professor ofEpidemiology, London School of Hygiene and TropicalMedicine, Drs Myfanwy Morgan, Charles Wolfe andNick Taub from The Department of Public HealthMedicine, UMDS, St Thomas' Hospital, and ProfessorChris Vickers, retired Professor of Dermatology,Liverpool.

Family practitioners participating in this study were:Dr Bryan Scaife, Dr Michael Elder, Dr Kevin Hall, DrDavid Hazelton, Dr Sarah Peacock and Dr Sally Basti-man from Queens Park Medical Centre, Stockton-on-Tees, Dr Jonathan Luckett, Kingston, Surrey, and DrAnthony Stimmler, Dr Raj Murthi, Dr Richard Penny,Dr Nan Doble, and Dr Claire Osmond, SE London.

Our thanks also go to Dr Elizabeth Higgins, Dr IanWhite, Dr Richard Rycroft, Dr Cathy Stephens, and all

the registrar (resident) observers and patients partici-pating in the study. We are indebted to Stiefel UK forsponsoring the flrst meeting of the working party.Hywel Williams was supported by a fellowship fromthe Wellcome Trust.

References1 Golding J. Peters TJ. The epidemiology of childhood eczema. Paed

Perinatal Epidemiol 1987; 1: 67-9.2 Schultz-Larsen F. Holm NV. Henningsen K. Atopic dermatitis. A

genetic-epidemiological study in a population-based twin sample./ Am Acad Dermatol 1986; 15: 487-94.

3 Diepgen TL. Fartasch M. Recent epidemiological and geneticstudies in atopic dermatitis. Acta Derm Venereol (Stockh) 1992;(Suppl. 176); 13-18.

4 Rajka G. Essential Aspects of Atopic Dermatitis. Berlin; Springer-Verlag. 1989; 5.

5 Kjellman N-IM. Atopic disease in seven-year-old children. ActaPaediatr Scand 1977; 66; 465 -71 .

6 Neame RL, Berth-Jones J. Graham-Brown RAC. A populationbased prevalence study of atopic dermatitis in the U.K. / InvestDermatot 1993; 100: 543.

7 Rajka G. The clinical aspects of atopic dermatitis. In; AtopicDermatitis. London; WB Saunders 1975; 4.

8 Hanifin JM. Lobitz WC Jr. Newer concepts of atopic dermatitis.Arch Dermatol 1977; 113: 663-70.

9 Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. ActaDerm Venereol (Stockh) 1980; (Suppl. 92); 44-7 .

10 Schultz-Larsen F. Hanifln JM. Secular change in the occurrence ofatopic dermatitis. Acta Derm Venereol (Stockh) 1992; (Suppl. 176);7-12.

11 Schultz-Larsen F. The epidemiology of atopic dermatitis. In;Epidemiology of Clinical Allergy (Burr M. ed.). Basel; Karger,1993; 9-28.

12 Seymour JL, Keswick BH. Hanifin JM et al. Clinical effects of diapertypes on the skin of normal infants and infants with atopicdermatitis. / Am Acad Dermatol 1987; 17: 988-97.

13 Arshad SH. Matthews S. Gant C. Hide DW. Effect of allergenavoidance on development of allergic disorders in infancy. Lancet1992; 339: 1493-7.

14 Svensson A. Edman B, Moller H. A diagnostic tool for atopicdermatitis based on clinical criteria. Acta Derm Venereol (Stockh)1985; (Suppl. 114); 33-40.

15 Visscher MO, Hanifln JM. Bowman WJ. Reed BR. Atopic dermatitisand atopy in non-clinical populations. Acta Derm Venereol (Stockh)1989; (Suppl. 144); 34-40.

16 Diepgen TL, Fartasch M. Stigmata and signs of atopic eczema. In;New Trends in Allergy III (Ring J. Pryzbilla B, eds). Berlin; Springer-Verlag, 1991; 222-9.

17 Hanifin JM. Clinical and basic aspects of atopic dermatitis. SemDermatol 1983; 2: 5-19.

18 Kennedy RH, Boume WM. Dyer JA. A 48-year clinical andepidemiologic study of keratoconus. Am ] Ophthalmol 1986;101: 267-73.

19 Gelmetti C. Extracutaneous manifestations of atopic dermatitis.Pediatr Dermatol 1992; 9: 380-2.

20 Mevorah B, Frenk E, Wietlisbach V, Carrel CF. Minor clincialfeatures of atopic dermatitis. Dermatologica 1988; 177: 360-4.

21 Diepgen TL. Fartasch M, Hornstein OP. Evaluation and relevanceof atopic basic and minor features in patients with atopic


dermatitis and in the general population. Acta Derm Venereol(Stockh) 1989; (Suppl. 144); 50-4.

22 Kang K. Tian R. Atopic dermatitis. An evaluation of clinical andlaboratory findings. Int ] Dermatol 1987; 26: 27-32.

23 Kanwar AJ, Dhar S. Kaur S. Evaluation of minor clinical featuresof atopic dermatitis. Pediatr Dermatol 1991; 8; 114-16.

24 Kim KH. Chung JH, Park KC. Clinical evaluation of minor clinicalfeatures of atopic dermatitis. Ann Dermatol 1993; 5: 9-12.

25 Tan EM. Cohen AS. Fries JF et al. The 1982 revised criteria for theclassification of systemic lupus erythematosus. Arthritis Rheum1982; 25: 1271-7.

26 Leete R. Fox AJ. Registrar General's social classes; origins anduses. Population Trends 1977; 9: 1-7.

2 7 Rajka G. Langeland T. Grading of the severity of atopic dermatitis.Acta Derm Venereol (Stockh) 1989; (Suppl. 144); 13-14.

28 Dean AD, Dean JA. Burton JH. Dicker RC. Epi Info, Version 5: aWord Processing, Database and Statistics Program for Epidemiology onMicrocomputers. Centres for Disease Control, Atlanta. Georgia.U.S.A.. 1990.

29 Youden WJ. Index for rating diagnostic tests. Cancer 1950; 3: 3 2 -5.

30 Epidemiological Graphics, Estimation and Testing Package. Statisticsand Epidemiology Research Corporation. Seattle. U.S.A.; 1988.

31 Williams HC, Burney PGJ. Strachan D. Hay RJ. The U.K. WorkingParty's Diagnostic Criteria for Atopic Dermatitis. IT; Observervariation of clinical diagnosis and signs of atopic dermatitis. Br ]Dermatol 1994; 131: 397-405.

32 Hanifin JM. Atopic dermatitis. In; Dermatology (Moschella SL.Hurley HJ. eds). 3rd edn. Philadelphia; W.B. Saunders. 1992;441-64.

33 Wells CK. Feinstein AR, Walter SD. A comparison of mathematicalmultivariate models for predicting survival—III. Accuracy ofpredictors in generating and challenge sets. / Clin Epidemiol1990; 43: 361-72.

34 Rajka G. On deflnition and framework of atopic dermatitis. ActaDerm Venereol (Stockh) 1989; (Suppl. 144); 10-12.

35 Archer CB. Hanifin JM. Recognising atopic dermatitis. Diagnosis1987; 3: 91-6 .

36 Williams HC. Burney PGJ, Strachan D, Hay RJ. The U.K. WorkingParty's Diagnostic Criteria for Atopic Dermatitis. Ill; Independenthospital validation. Br] Dermatol 1994; 131: 406-16.

Appendix 1. The 31 criteria tested in this study. Theprecise wording of the questions and definitions ofthe physical signs are given in Appendices 2 and 3,respectivelyThirteen historical featuresA Itch

Presence/absenceWool intoleranceSweat-induced

B ChronicityDurationAge of onset

C Atopic backgroundPersonal history of diagnosed asthmaPersonal history of hay feverBlocked nose in absence of coldsFamily history of atopy

D Distribution/generalHistory of fiexural involvementHistory of a dry skinSoap intoleranceWorsening of skin in winter

Eighteen clinical signsVisible dermatitis at any siteElexural dermatitisExtensor dermatitisHand/foot dermatitisFacial dermatitisTruncal dermatitisXerosisHypopigmented patchesPerifollicular accentuationFine hairInfraorbital creasePeriorbital dermatitisPeriorbital pigmentationPeriauricular dermatitisInfra-auricular fissureCheilitisPalmar hyperlinearityKeratosis pilaris

Appendix 2. Exact questions used in the questionnaire(or parental response for subjects under 10 years ofage). All questions were answered in a yes/no fashion,with the exception of itch when sweating, age at onset,and durationItchy skin: Do you sufi'er from an itchy skin.' (or toparent, 'Does he/she scratch at least once a day on mostdays of the year.'')Wool intolerance: 'Can you wear wool next to theskin with comfort?'Itch when sweating: 'Does your skin itch when yousweat.'' (don't know refers to those in whom thissymptom is very difficult to assess, e.g. small infants)Duration > 6 months: 'For how long have you hadyour rash on and off.'' (continuous dermatitis treated asthe same)Onset under age 2: 'When did your skin problemsbegin?'Rash affected skin creases: 'Has your rash everafi'ected the skin creases in the past, i.e. folds ofelbows, behind the knees, fronts of ankles, under thebuttocks, around the neck, ears or eyes?'Personal history asthma: 'Do you sufi'er or have youever suffered from asthma (bouts of wheezing andcoughing)?'


Personal history hay fever: 'Do you sufi'er or have youever suffered from hay fever?' (bouts of sneezing, with arunny nose and/or itchy eyes in the summer)Blocked nose: 'Do you sufi'er from a blocked nose mostdays of the year?'Family history ecz./asth./hay: 'Does anyone in yourfamily sufi'er from eczema/asthma/hay fever?' (Theafi'ected person was specified, and only immediatefamily members were included)Dry skin: 'Do you sufier from a dry skin?'Does soap make skin worse: 'If you use ordinary soap,does it make your skin worse?' (worse can mean aworsening of dermatitis or dryness)Worse in winter: 'Does your skin get worse in winter?'(again, worse refers to dermatitis or dryness)

Additional compound questions testedDo you have an itchy rash?Do you have an itchy rash that has been coming andgoing for at least 6 months?Do you have an itchy rash that has been comingand going for at least 6 months that at times hassettled in the fronts of the elbows or behind theknees?

Appendix 3. Definitions of physical signs used in thestudyVisible dermatitis: poorly defined erythema withsurface change. Surface change denotes any ofthe following: fine scaling, vesicles, fissures,lichenification, oozing or crusting.Flexural dermatitis: one or more patches of dermatitisafiecting popliteal fossae/antecubital fossae/infraglutealclefts/front or sides of neck/fronts of ankles/periorbitalor periauricular areas.Extensor dermatitis: two or more dermatitis patchesafi'ecting knees/elbows/outer aspects of upper or lowerlimbs.Hand/foot dermatitis: dermatitis afiecting one or bothhands/feet, which does not show features of an obviouscontact dermatitis.

Cheeks/forehead dermatitis: dermatitis present on oneor both cheeks, or forehead.Truncal dermatitis: any dermatitis present on trunk.Dry skin: a lustreless skin with fine white scaling, inthe absence of visible dermatitis involving one areagreater than the size of the patient's palm. Ignorechanges localized to lower shins.Hypopigmented patches: two or more hypopigmentedareas greater than 2 cm in diameter (e.g. a 20p piece),in the absence of clinically apparent dermatitis.Perifollicular accentuation: dermatitis (includinglichenification) or hypopigmentation enhancedaround hair follicles in two or more areas > 2 cmdiameter.Fine hair: hair that appears fine on inspection andpalpation, and returns rapidly to its original positionwhen lifted (allowing for age).Infraorbital crease: single or double prominentinfraorbital skin fold afi'ecting one or both eyes, extend-ing beyond the midline of the pupil when the gaze isdirected anteriorly.Periorbital dermatitis: any area of dermatitis withinthe confines of the orbital cavity, afiecting one or botheyes.Periorbital pigmentation: a subtle symmetricalhyperpigmentation of the periorbital skin involvingboth eyelids.Periauricular dermatitis: any dermatitis around oneor both ears.Infra-auricular fissure: a skin crack under the earlobe,which may be present in the absence of dermatitis.Cheilitis: erythema and scaling of lips, with blurring ofvermilion border of one or both lips, regardless ofwhether it is felt to be secondary to lip licking.Hyperlinear palms: more than five prominent fineslonger than 2 cm running horizontally across thethenar eminence.Keratosis pilaris: more than 20 horny follicularpapules involving posterolateral aspects of upperarms, thighs or buttocks.

Documents

The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. : I. Derivation of a minimum set of discriminators for atopic dermatitis