IQoL-32: A new ichthyosis-specific measure of qualityof life

Isabelle Dreyfus, PharmD,a Charles Ta€ıeb, MD,b S�ebastien Barbarot, MD,c Aude Maza, MD,a

Isabelle Galera, MD,a Emmanuelle Bourrat, MD,d Christine Chiaverini, MD,e Khaled Ezzedine, MD, PhD,f

Anne Le Rhun, MD,g and Juliette Mazereeuw-Hautier, MD, PhDa

Toulouse, Lavaur, Nantes, Paris, Nice, and Bordeaux, France

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Background: Inherited ichthyoses are associated with impaired quality of life (QoL).

Objectives: The aim of this study was to create and validate a QoL questionnaire specifically dedicated topatients with ichthyosis.

Methods: A prequestionnaire was drawn after selecting items from a verbatim transcript. It was thensubjected to a cognitive debriefing. During the validation step, this questionnaire was sent to patients withthe Dermatology Life Quality Index, Short Form-12 health-related questionnaire, and severity scores (globalseverity: mild/moderate/severe/very severe; clinical severity evaluated by 6 visual analog scales). Ashortened version of the questionnaire was designed. The validity of the tool was confirmed: for itsstructure and 1-dimensional nature (Cronbach a), convergent (Spearman correlation) and discriminating(Tukey test) validity; a risk was fixed at 5%.

Results: The initial questionnaire included60 items.During the validationphase, 59 subjectswere tested. Theshortened version included 32 items (IQoL-32) and 7dimensions (Cronbacha: 0.94). Thehigher the score, themore impacted theQoL. IQoL-32was positively correlated toDermatology Life Quality Index (P\.0001) andnegatively to Short Form-12 health-related questionnaire (P\.0001). IQoL-32was highly correlated to clinicalseverity: overall analysis (Spearman ranking: 0.72; P\.0001) or analysis per dimension (highest correlations:discomfort, pain, interpersonal relations). IQoL-32 demonstrated a higher correlationwith visual analog scalecompared with Dermatology Life Quality Index and Short Form-12 health-related questionnaire. It alsoshowed a good discriminating power (P\.0001) according to overall severity levels.

Limitations: Only patients residing in France were included.

Conclusion: IQoL-32 is a specific and validated questionnaire for inherited ichthyosis. It will be very usefulfor patient care and research. ( J Am Acad Dermatol 2013;69:82-7.)

Key words: genodermatosis; ichthyosis; quality of life; questionnaire; score; tool.

Inherited ichthyoses are mendelian disorders ofcornification as a result of mutations in variousgenes involved in skin barrier function.1 The

clinical aspect and severity is variable but the generalaspect of the skin is always impaired with scales

the Reference Center for Rare Skin Diseases, Dermatology

epartment, Larrey Hospital, Centre Hospitalo-Universitaire

ulouse, Paul Sabatier Universitya; Public Health and Quality

Life Department, Pierre Fabre Dermo Cosm�etique, Les

auquillous, Lavaurb; Competence Center for Rare Skin Dis-

ses, Dermatology Department, Centre Hospitalo-Universitaire

antesc; Reference Center for Rare Skin Diseases, Dermatology

epartment, Saint-Louis Hospital, Assistance Publique -

opitaux de Paris, Parisd; Dermatology Department, Centre

ospitalo-Universitaire Nicee; Reference Center for Rare Skin

iseases, Dermatology Department, Centre Hospitalo-Universi-

ire Bordeauxf; and Pole d’Information M�edicale, d’Evaluation

de Sant�e Publique, Centre Hospitalo-Universitaire Nantes.g

all over the tegument and inconstant erythroderma.The skin is often uncomfortable, itchy, and painful.Other abnormalities may be associated, especiallyfor syndromic forms. The disease is chronic withperiods of exacerbation. No specific treatment is

Supported by the Association Athina Ichtyose Monaco.

Conflicts of interest: None declared.

Accepted for publication January 14, 2013.

Reprint requests: Isabelle Dreyfus, PharmD, Reference Center for

Rare Skin Diseases, Dermatology Department, Larrey Hospital,

Centre Hospitalo-Universitaire Toulouse, 24, Chemin de

Pouvourville, TSA 30030, Toulouse Cedex 9 31059, France.

E-mail: dreyfus.i@chu-toulouse.fr.

Published online March 13, 2013.

0190-9622/$36.00

� 2013 by the American Academy of Dermatology, Inc.

http://dx.doi.org/10.1016/j.jaad.2013.01.022

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VOLUME 69, NUMBER 1Dreyfus et al 83

available and symptoms are improved by emol-lients or systemic retinoids (acitretin). The impactof ichthyosis on quality of life (QoL) was previ-ously demonstrated.2-4 QoL is a dynamic processthat can be defined as an individual perception ofone’s position in life at a given time.5 This evalu-ation is a crucial step in the assessment of a patient

CAPSULE SUMMARY

d Impairment of quality of life (QoL) hasbeen demonstrated for inheritedichthyosis using nonspecifically designeddermatologic QoL assessment tools.

d To our knowledge, this is the firstquestionnaire specifically dedicated tothe evaluation of QoL in patients withichthyosis.

d This simple and easy-to-use tool will beuseful to specifically evaluate ichthyosisQoL in future clinical practice and trials.

with chronic disease such asichthyosis and could beconsidered as a better indi-cator of disease’s severitythan other clinical charac-teristics. Previous studies onichthyosis QoL were per-formed using DermatologyLife Quality Index (DLQI)or Short Form-12 health-related questionnaire (SF-12). These questionnairesare not specifically de-signed for ichthyosis andmay therefore not be spe-cific enough to preciselyexplore the particularities

of ichthyoses and measure changes in relatedQoL. To our knowledge, no specific medical toolis available for ichthyosis.

The aim of our studywas therefore to develop andvalidate a simple and easy-to-use ichthyosis-specificQoL scale for adult patients with inherited ichthyosis.

METHODSEach step of the construction of the preliminary

questionnaire and the elaboration of the final short-ened version were statistically validated, in accor-dance to standardized methodology used for QoLquestionnaire development.6

Questionnaire construction processPatient inputwas obtained after a qualitative phase

using focus groups. This first step was previouslyreported and included 25 adult patientswith inheritedichthyosis of various forms and severity.4 Based onthe verbatim transcripts, an exhaustive list of itemswas first elaborated by 2 researchers specialized inQoL of chronic diseases. From this exhaustive list ofitems, a working group including 10 experts (6 der-matologists, 1 pharmacist, 1 psychologist, and 2public health doctors) and 2 members of the patientsupport group, Association Nationale des Ichtyoses etPeaux S�eches pathologiques (ANIPS), identified apool of items after several meetings and discussions.Items were turned into questions to generate a pre-liminary questionnaire. The chosen format response(‘‘tremendously,’’ ‘‘a lot,’’ ‘‘a little,’’ ‘‘not at all,’’ ‘‘not

applicable’’) was in accordance with other recentlydeveloped disease-specific QoL instruments.7,8 Toavoid any confusion to QoL impairment related toother comorbidities or situations, each question wasassociated with the expression ‘‘because of myichthyosis.’’ Items were allocated to domains.

To explore the level of understanding of this

preliminary questionnaire,the selected itemswere testedby a panel of French nativeparticipants with various so-ciodemographic characteris-tics and trained in cognitivedebriefing (Lionbridge Co,Waltham, MA).

Validation processingPatients and study de-

sign. The local ethics com-mittee of Toulouse UniversityHospital and CommissionNationale Informatique etLibert�es both approved thisstudy. The preliminary ques-

tionnaire was mailed to patients aged 15 years andolder with inherited ichthyosis of various clinicalforms and degrees of severity. Patients were en-rolled from 3 French dermatologic centers expert inichthyosis and the patient support group ANIPS.Patients had to be able to read and understandFrench language. The mailing included a patientinformation sheet, an evaluation of disease severity,the preliminary questionnaire, and 2 other QoLassessment tools: DLQI and SF-12. DLQI is a 10-itemskin diseaseespecific QoL instrument that rangesfrom 0 to 30 (the higher the score, the poorer theQoL).7 SF-12 is an abridged version of the medicaloutcomes study Short Form-36 health questionnaire(SF-36) that consists of 2 components: physicalcomponent summary and mental health compo-nent summary, with scores ranging from 0 to 100(the lower the score, the poorer the QoL).8

Ichthyosis severity was self-assessed by the patientsin 2 ways: global severity (4 grades of severity: mild,moderate, severe, or very severe disease) and clin-ical severity using 6 visual analog scales evaluatingthe intensity of erythema, scales, pruritus, cutane-ous pain, eye pain, and daily life disability. Thesevisual analog scales were scored from 0 to 10 andtotal score was obtained by summing the 6 scores(range 0-60). We previously demonstrated on asample of 29 patients that evaluation made by thepatients or by physicians was not statistically dif-ferent (Mann Whitney test, P [ .05) (personalunpublished data).

Table I. Characteristics of 59 patients whoresponded to IQoL questionnaire

Patient characteristics Values

Sex, n (%)Female 31 (53)Male 28 (47)

Age (y), mean 6 SD (range) 36.2 6 17.6 (17-70)Global severity, n (%) Mild: 11 (18.6)

Moderate: 20 (33.9)Severe: 19 (32.2)Very severe: 9 (15.3)

Clinical severity/60, mean 6 SD(range)

25 6 13.7 (0-55.05)

Intensity of scales 5.2 6 2.4Intensity of erythema 3.8 6 2.6Intensity of pruritus 4.7 6 2.7Intensity of cutaneous pain 4.4 6 2.9Intensity of eye pain 4.5 6 3Intensity of disability 3.2 6 3

Abbreviations used:

ANIPS: Association Nationale des Ichtyoses etPeaux S�eches pathologiques

DLQI: Dermatology Life Quality IndexQoL: quality of lifeSF-12: Short Form-12 health-related

questionnaire

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Statistical analyses. Internal consistency of thequestionnaire was assessed by calculating Cronbacha (statistical index ranging from 0-1, which measuresthe homogeneity of an assessment tool, composed ofa set of items that together should contribute to acommon understanding entity, ie, the impact ofichthyosis on QoL; a value\0.8 indicates that indi-vidual items are providing an inadequate contribu-tion to the overall scale). The validity of thequestionnaire with both severity scores (global andclinical) and other QoL questionnaires (DLQI and SF-12) was analyzed using linear regression andSpearman correlation coefficient (convergent capac-ity) and Tukey test (discriminating capacity).Spearman correlation coefficient (r) had to be 0.7or greater, with a lower limit of 95% confidenceinterval of 0.65 or greater. All tests were 2-sided andarisk was set at 5% for the whole study.

Shortened version of the questionnaireTo obtain the shortest and easiest-to-use ques-

tionnaire, we suppressed items that were redundantor nonrelevant (items for which answers were ‘‘notconcerned’’ for a majority of patients and items witha low impact in terms of disability in QoL, ie, deletionof such items did not affect the reliability of thequestionnaire). Internal consistency and reliability ofthis shortened version was evaluated using the samestatistical analyses. Each item of the questionnairewas scored using a 5-point Likert scale (‘‘tremen-dously’’ = 4, ‘‘a lot’’ = 3, ‘‘a little’’ = 2, ‘‘not at all’’ = 1,‘‘not applicable’’ = 0). Finally, an English version wasdeveloped after cultural and linguistic validation.

RESULTSPatients’ characteristics

The initial questionnaire, which included 60items, was sent to 130 patients (125 from hospitaldepartments and 5 from ANIPS). A total of 62 werereturned, including 59 assessable questionnaires forwhich responder characteristics are shown in Table I.The study population comprised amajority of femalepatients. All ages and grades of ichthyosis severitywere represented in the study population, the mostcommon being moderate and severe ichthyosis.

Shortened version of the questionnaireThe shortened version contained 32 items named

‘‘Ichthyosis Quality of Life- 32 items’’ questionnaire(IQoL-32) (Fig 1), each item scored from 0 to 4 for atotal score that may therefore vary between 0 and128. The 32 items were classified into 7 dimensions(Table II). Cronbach a coefficient was 0.94, whichindicates excellent internal consistency. Half of theitems were related to discomfort and interpersonalrelations. Mean IQoL-32 score (6SD) was 74.5 621.1 (range: 21-118). Significant differences werefound according to gender, with mean IQoL scoresbeing significantly higher for female (81.1 6 19.4)than male (66.2 6 20.2) patients (P = .0074). Incontrast, there were no significant differencesaccording to age.

With regard to global severity, IQoL-32 presentedan adequate convergent capacity because the higherthe global severity, the higher the IQoL score and thegreater the QoL impairment. Moreover, it presentedgood discriminating capacity with significant differ-ences observed in mean IQoL scores according toglobal severity (analysis of variance, P \ .0001).Mean IQoL-32 scores were significantly higher forthe group of patients with severe and very severedisease compared with the group of patients witheither mild (P # .0001) or moderate (P # .001)disease, respectively (Fig 2).

With regard to clinical severity, we observed ahighly significant positive linear correlation withIQoL score (Spearman correlation coefficient 0.72[P \ .0001]). The higher the clinical severity,the higher the IQoL-32 score. This linear correlationwas also noted when analyzed dimension by

Table II. Characteristics of 59 patients whoresponded to IQoL questionnaire

Dimensions Items

Discomfort 10 items: I11 I21 I31 I41 I61I71 I81 I91 I131 I14

Relation to others 4 items: I221 I231 I241 I25Pain 3 items: I51 I121 I16Social aspects 1 item: I15Work 5 items: I271 I281 I291 I311 I32Physical health care 2 items: I261 I30Interpersonalrelations

7 items: I101 I111 I171 I181I191 I201 I21

Fig 2. Comparison of mean IQoL scores in patients withvarious grades of global severity (comparison betweensevere and very severe grades vs mild grade: **P\ .0001;comparison between severe and very severe grades vsmoderate grade: *P # .001).

Table III. Correlation between clinical severity(visual analog scales score) and IQoL score (analysisdimension by dimension)

Dimensions

Spearman correlation coefficient

r (P value)

Discomfort 0.83 (\.0001)Pain 0.74 (\.0001)Social aspects 0.60 (\.0001)Work 0.53 (\.0001)Interpersonal relations 0.48 (.0001)Relation to others 0.45 (.0004)Physical health care 0.30 (.0221)

Fig 1. IQoL-32.

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dimension, the strongest correlations beingidentified for discomfort, pain, and social aspects(Table III).

Finally, during the validation process, IQoL-32 wascompared with SF-12 and DLQI scores (Table IV).Mean SF-12 score was 46.66 11.1 and 36.66 10.9 forphysical and mental health component summaries,respectively. Mean DLQI score was 12.86 7. IQoL-32score was significantly positively correlated to DLQIscore (r = 0.68, P\ .0001). A moderate and negativesignificant correlationwas foundbetween IQoL-32andSF-12 scores (physical component summary: r=�0.49,P = .0002; mental health component summary:r = �0.57, P\ .0001). QoL evaluation using IQoL-32

Table IV. Variations in IQoL-32, Short Form-12 health-related questionnaire (physical and mental healthcomponent summaries), and Dermatology Life Quality Index scores according to global severity

Patient subgroups IQoL-32 score DLQI score SF-12 score

Global severity n Mean 6 SD n Mean 6 SD n PCS mean 6 SD MCS mean 6 SD

Mild 11 56.09 6 18.73 11 10.09 6 6.89 10 52.08 6 7.82 37.80 6 11.75Moderate 20 65.20 6 16.04 20 8.75 6 3.96 18 51.63 6 9.06 41.82 6 10.45Severe 19 86.95 6 17.01*y 15 16.33 6 5.92zx 17 44.69 6 10.77 30.63 6 8.09x

Very severe 9 91.56 6 11.62*y 8 20.25 6 6.32z// 8 32.49 6 4.76{//# 36.01 6 11.62

DLQI, Dermatology Life Quality Index; MCS, mental health component summary; PCS, physical component summary; SF-12, Short Form-12

health-related questionnaire.

*Comparison vs mild, P\ .0001.yComparison vs moderate, P\ .001.zComparison vs mild, P\ .05.xComparison vs moderate, P\ .05.//Comparison vs moderate, P\ .0001.{Comparison vs mild, P\ .001.#Comparison vs severe, P\ .05.

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was therefore convergent with those performed withDLQIandSF-12. Inaddition, IQoL-32wasasefficient asDLQI and more efficient than SF-12 to discriminatebetween different grades of severity. Mean IQoL-32and DLQI scores were significantly higher for patientswith severe and very severe disease compared withpatients with mild or moderate disease.

DISCUSSIONTo our knowledge, this is the first ichthyosis-

specific QoL assessment tool. It is available in 2languages (French and English). If necessary it couldbe translated in other languages after cultural andlinguistic validations.

IQoL-32 is a short and easy-to-use questionnairecontaining 32 questions and organized in 7 domains.The questions are specifically dedicated to ichthyosisand explore all disease particularities such as skinpain/discomfort, ear- and eye-related problems, heatintolerance, skin odor, scalp involvement, restric-tions related to thedisease (dressings, sports, leisure),expenses, psychological aspects, and consequencesof the treatment: time for skin care, oily skin orclothes, and side effects. Items related to the nature ofthe treatment (local or systemic) were part of the firstversion of the questionnaire but were deleted fromthe final shortened version because they had a lowimpact in terms of disability in QoL and their deletiondid not affect the reliability of the questionnaire.

Because the study population is representative ofthe entire ichthyosis patient population (variousclinical aspects and grades of severity, both followedup in hospital or members of ANIPS), this QoLassessment tool is designed to and can be used forany patient with ichthyosis. One limitation could bethe exclusive inclusion of patients residing in France.

Based on our experience, we decided to validateour QoL questionnaire using classic methodologyrather than Rasch analysis. Some authors used bothmethodologies (classic and Rasch) and found com-parable results.9 Rasch analysis may be used in afuture step, with the aim to further document andvalidate the measurement of each item of ourquestionnaire.

During the validation process we correlated QoLscores with disease severity at the time of theevaluation. This severity is indeed influenced bytreatments but this information was not collected.This could be a limitation of the study. Nevertheless itdoes not influence the validity of our QoL question-naire. By comparison with SF-12 and DLQI, validityof IQoL-32 was demonstrated for its structure and1-dimensional nature (Cronbach a), convergent(Spearman correlation) and discriminating (Tukeytest) validity. As expected, IQoL-32 was more dis-criminant with regard to global severity than SF-12,which is not specific to skin diseases. IQoL-32 wasdemonstrated to be as discriminant as DLQI. Asguidelines recommend the use of a combination of 2different QoL questionnaires (specific/nonspecific),future studies on ichthyosis will ideally be performedusing both IQoL-32 and DLQI. Because IQol-32includes questions specifically related to ichthyosis,it is expected to better assess the impact on ichthy-osis QoL during experimental studies, ie, sensitivityto changes.

Future studies should be performed to demon-strate the responsiveness of IQoL-32 measures tochange in QoL, arising for example from therapeuticinterventions.

In conclusion, in dermatology there is a need foraccurate tools to measure disease-specific QoL im-pairment. Indeed, IQoL-32 may help to better

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evaluate changes of QoL in patients with ichthyosisbefore and after treatment and may thus become awidely used tool in further therapeutic interventions.

We thank patients and the patient support group ANIPSfor their important contribution to this work.

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