Assessing Itch in ChildrenWith Atopic Dermatitis TreatedWith Tacrolimus: ObjectiveVersus Subjective Assessment

Kam-Lun Ellis Hon, FAAPMan-Ching Adrian Lam, MPhilTing-Fan Leung, FRCPCH, MDChung-Mo Chow, MRCPCHDepartment of Pediatrics

Eric Wong, MACentre for Epidemiology and BiostatisticsChinese University of Hong KongPrince of Wales HospitalShatin, Hong Kong SAR, China

Alexander K. C. Leung, MBBS, FRCPC, FRCP(UK & Irel), FRCPCHDepartment of PediatricsUniversity of CalgaryCalgary, Alberta, Canada

ABSTRACT

This study was undertaken to evaluate the clinical efficacy of tacrolimus for itchreduction in children with atopic dermatitis (AD). Seven children (3 boys and 4 girls) with AD were treated with topical tacrolimus for a consecutive 2-wkperiod after a 1-wk run-in. The clinical severity of AD was assessed with theSCORing Atopic Dermatitis (SCORAD) scale. Sleep disturbance, as reported bypatients, and nocturnal scratching documented by a wrist movement monitor(DigiTrac®), were evaluated at baseline and throughout treatment. The median(interquartile range) objective SCORAD scores before and after treatment were27.2 (24.8–36.7) and 23.9 (22.6–36.5), respectively (P=.248). Overall SCORADscores before and after treatment were 36.1 (32.8–45.7) and 29.4 (24.8–45.4),respectively (P=.05). Scores on the itch and sleep disturbance components ofthe SCORAD were reduced from 5.0 (5.0–6.5) and 4.0 (3.5–5.0) to 4.0 (2.0–5.0)and 3.0 (0.5–4.5), respectively. Total SCORAD was reduced in 6 patients (range,8%-36% reduction) and remained similar in 1 patient. No significant change in the area or intensity component of the SCORAD was detected 14 d aftertreatment began (P=.48 and P=.115, respectively). Scratching activity, as docu-mented by the DigiTrac movement recorder, was reduced from 115.0 g/min

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Advancesin Therapy®

Volume 24 No. 1January/February 2007

Address correspondence toDr. Kam-Lun Ellis HonDepartment of PediatricsChinese University of Hong Kong6/F, Clinical Sciences BuildingPrince of Wales HospitalShatin, Hong Kong SAR, ChinaEmail: ehon@cuhk.edu.hk

©2007 Health Communications IncTransmission and reproduction of this material in wholeor part without prior written approval are prohibited.

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(64.8–215.5) to 71.5 g/min (51.0–118.0) (P=.028) after 2 wk of treatment. Daily symptomscores (n=6 pairs) for sleep disturbance reported separately each day by patients and parentscorrelated strongly with each other (intraclass coefficient, 0.60–0.98). The findings of thisstudy show that tacrolimus is effective in relieving itch in children with AD. Investigators suggest that scratching movements, objectively measured with the use of DigiTrac, provide a reliable indicator of AD severity in children.

Keywords: atopic dermatitis; children; SCORAD; scratching; tacrolimus

INTRODUCTION

Atopic dermatitis (AD) is a common relapsing inflammatory skin disease thatoccurs in children, and it is associated with significant itching and sleep disturbance.1The degree of itch, as reported by patients or their caregivers, does not correlate wellwith the more objective scores of AD severity.2-7 In particular, no reliable method hasbeen devised to nonintrusively monitor itching and gauge therapeutic efficacy. In a recent study, investigators explored the use of the DigiTrac® wrist motion mon-itor (IM Systems, Baltimore, Md, USA) and showed that wrist activities, nonintru-sively measured with the DigiTrac monitor at home, were closely correlated withobjective clinical scores and levels of peripheral blood chemokine markers for ADseverity but not with reported symptoms of pruritus and sleep loss.2 Hence, it wasproposed that wrist activities at between 1 and 3 Hertz for the first 3 h are a goodindicator of AD severity in children; this criterion may substitute for the pruritusand sleep loss components of the SCORing Atopic Dermatitis (SCORAD) scale.

Tacrolimus (Protopic®; Fujisawa, Staines, UK) is a calcineurin inhibitor that hasproved useful in the treatment of patients with AD. Extensive clinical trials haveshown that tacrolimus is effective in reducing various clinical scores (such as itch)for AD.8 Itch is a very distressing cardinal symptom, however, and it has been diffi-cult to document objectively in clinical trials. The purpose of this pilot study was toevaluate whether there is a correlation between scratching movements, objectivelymeasured with DigiTrac, and a subjective sense of itch and sleep disturbance in chil-dren treated with tacrolimus.

MATERIALS AND METHODS

This study was conducted in the Pediatrics Department of a university hospitalin Hong Kong. Ethical approval from the Clinical Research Ethics Committee of theUniversity and parental written informed consent for use of the DigiTrac duringtreatment were obtained. Patients with AD, aged 2 to 18 y, were recruited from theoutpatient clinic. AD was diagnosed according to criteria proposed by Hanifin andRajka.9 The clinical severity of AD was evaluated according to the SCORAD scale.10

All patients had a SCORAD ≥15 (ie, moderate to severe AD) at entry into this study.Patients were excluded if they had active concurrent disease (except allergic dis-eases, such as asthma and allergic rhinitis) or a history of sensitivity to calcineurininhibitors, or if they had received psoralen ultraviolet (UV)A treatment within 8 wkbefore the study began.

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Study participants underwent a 1-wk run-in period, during which data on base-line dietary intake, emollient and drug use, and severity of AD were collected.Medications (such as the usual topical corticosteroid or oral antihistamine) were notpermitted, but regular emollients were continued during the run-in and treatmentperiods. Patients were then started on topical tacrolimus applied to affected areastwice daily. The clinical severity of AD was assessed with the SCORAD at run-in(day 1), before treatment (day 7), and at 2 wk after treatment (day 21). Sleep distur-bance (scores ranged from 0–10, recorded daily by patients and parents) and noc-turnal scratching (documented with DigiTrac on days 8, 9, 10, 22, 23, and 24) wereevaluated during the 2-wk treatment period.

Adherence to the study regimen was examined by weighing the amount oftacrolimus that remained in drug tubes and reviewing the information recorded bypatients in their eczema diaries regarding drug use and sleep disturbance. Paireddata on SCORAD before and after tacrolimus were analyzed through Wilcoxon’s 2-tailed signed rank test. P<.05 was considered statistically significant.

RESULTS

Three boys and 4 girls, with a median age of 11.8 y (range, 5.3–18.4 y), participat-ed in the current study. The average amount of tacrolimus used over the 2-wk coursewas 19.5 g. Median (interquartile range) objective SCORAD scores before and aftertreatment were 27.2 (24.8–36.7) and 23.9 (22.6–36.5), respectively (P=.248). OverallSCORAD scores before and after treatment were 36.1 (32.8–45.7) and 29.4 (24.8–45.4),respectively (P=.059; Fig 1). Total SCORAD was reduced in 6 patients (range, 8%–36%reduction) and remained similar in 1 patient. No significant change in the area orintensity component of the SCORAD was detected 14 d after treatment began (P=.48and P=.115, respectively). Median scores (interquartile range) of the pruritus andsleep disturbance components of the SCORAD were reduced from 5.0 (5.0–6.5) and4.0 (3.5–5.0) to 4.0 (2.0–5.0) and 3.0 (0.5–4.5) (P=.033 and P=.268, respectively). Medianscratching activity during the first 3 h of sleep, as documented by the DigiTrac move-ment recorder, was reduced from 115.0 g/min (64.8–215.5) average acceleration at baseline (day 8) to 67.6 g/min (47.8–152.0) (P=.052) on day 10, and 71.5 g/min(51.0–118.0) (P=.028 by Wilcoxon’s signed rank test) at 2 wk (day 22) (Fig 2). Onepatient reported an itch sensation with topical application of tacrolimus.Compliance with treatment was good, and no oral antihistamine or topical cortico-steroid usage was reported during the study period for any patient. Daily symptomscores for sleep disturbance (n=6 pairs) reported separately each day by patients andparents correlated strongly with each other (intraclass coefficient, 0.60–0.98). Thesescores were significantly reduced 2 d after treatment started (Fig 3; P=.03 andP=.013, respectively). Only 6 pairs of data were obtained for daily scores because 1 girl was unable to provide reliable scores for her symptom of sleep disturbance.

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Treatment commenced on day 8 after a 1-wk run-in and was completed on day 21.

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Fig 2. Average wrist activity (g/min) during the first 3 h of sleep with tacrolimustreatment.

DISCUSSION

Tacrolimus appears to have a faster effect on subjective rather than objectivesymptoms. Scratching activity objectively measured with the DigiTrac is a reliableindicator. Therefore, DigiTrac monitors should be used along with conventionalmethods in assessing the therapeutic response of patients during treatment for AD.Battery life span (usually 7 d) is not a limiting factor for serial scratching measure-ments, but the memory capacity of DigiTrac (10 h overnight recording) is an impor-tant consideration. If the serial effects of a tested medication are to be monitored,data must be downloaded each day.

The present study shows that tacrolimus is effective in relieving itch in childrenwith AD, as evidenced by a significant reduction in median scratching activity dur-ing the first 3 h of sleep; this was documented by the DigiTrac movement recorder.Measurement of subjective symptoms is notoriously unreliable,2-7 especially withthe small sample size used here. The clinical efficacy of tacrolimus described in thisopen-label study should be confirmed through a double-blind, randomized, con-trolled trial that uses the dual approach described in the present study to combineobjective and subjective tools.7 The authors propose that all novel topical and sys-temic therapy for AD should be evaluated through such a combined approach.7

DISCLAIMER

Tacrolimus was freely supplied for this study by Fujisawa Healthcare.

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Fig 3. Subjective daily scores of sleep disturbance reported by parents andpatients.

REFERENCES

1. Leung AK, Barber KA. Managing childhood atopic dermatitis. Adv Ther. 2003;20:129-137.

2. Hon KL, Lam MC, Leung TF, et al. Nocturnal wrist movements are correlated with objectiveclinical scores and plasma chemokine levels in children with atopic dermatitis. Br J Dermatol.2006;154:629-635.

3. Hon KL, Ma KC, Wong E, et al. Validation of a self-administered questionnaire in Chinese in the assessment of eczema severity. Pediatr Dermatol. 2003;20:465-469.

4. Hon KL, Leung TF, Wong Y, et al. Lesson from performing SCORADs in children with atopicdermatitis: subjective symptoms do not correlate well with disease extent or intensity. Int JDermatol. 2006;45:728-730.

5. Hon EKL, Leung TF, Fok TF. Measuring eczema in children: what actually are we measuring?HK Dermatol Venereol Bull. 2004;12:6-11.

6. Hon KL, Leung TF, Ma KC, et al. Urinary leukotriene E4 correlates with severity of atopic dermatitis in children. Clin Exp Dermatol. 2004;29:277-281.

7. Hon KL, Kam WYC, Lam MCA, et al. CDLQI, SCORAD and NESS: are they correlated? QualLife Res. 2006;15:1551-1558.

8. Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topicalpimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomisedcontrolled trials. BMJ. 2005;330:516-522.

9. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh).1980;2:44-47.

10. Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the EuropeanTask Force on Atopic Dermatitis. Dermatology. 1993;186:23-31.

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