Acta Dermato-Venereologica Issue 8, 2017 97-8CompleteContent | Page 17

SHORT COMMUNICATION 957

Advances in dermatology and venereology Acta Dermato-Venereologica

Disrupted Skin Barrier is Associated with Burning Sensation after Topical Tacrolimus Application in Atopic Dermatitis

Seong Rak SEO , Seon Gu LEE , Hee Jung LEE , Moon Soo YOON and Dong Hyun KIM * Department of Dermatology , CHA University College of Medicine , Bundang CHA Medical Center , Yatap-ro 59 , Bundang-gu , Seongnam 13496 , Korea . * E-mail : terios92 @ cha . ac . kr Accepted May 16 , 2017 ; Epub ahead of print May 17 , 2017

Atopic dermatitis ( AD ) is strongly associated with skin barrier dysfunction , as indicated by a reduction in skin hydration and an increase in transepidermal water loss ( TEWL ) ( 1 ). Long-term use of topical corticosteroids poses a risk of developing adverse cutaneous effects , including skin atrophy and rebound flares . Topical calcineurin inhibitors , tacrolimus and pimecrolimus , were found to be as effective as moderately potent topical corticosteroids ( 2 ). However , the main obstacle to use of topical tacrolimus is its local side-effect , a burning sensation , which sometimes leads to discontinuation of treatment ( 3 ). Although the mechanism of the burning sensation after topical application of tacrolimus is thought to be associated with damaged skin barrier function , there has been no study to assess the association between TEWL and burning sensation following topical application of tacrolimus . This study evaluated the correlation between burning sensation following topical tacrolimus and skin barrier function in AD .

MATERIALS AND METHODS

This prospective study was performed in accordance with the ethics guidelines of the Declaration of Helsinki 1975 and approved by the institutional review board of Bundang CHA Medical Center , CHA University , Seongnam , Korea from April 2011 to April 2015 . All patients agreed to participate voluntarily and gave written informed consent . Patients aged ≥16 years with moderate to severe AD meeting the diagnostic criteria of Hanifin & Rajka , confirmed by the same dermatologists , were enrolled in the study . All patients were using topical tacrolimus ointment for the first time and had facial lesions . Patients were excluded from the study if they had any of the following conditions at the time of study entry : other concomitant dermatological disorders besides AD on the site to be treated ; known hypersensitivity to macrolides or other ointments ; tumour or a history of a tumour or systemic disease including HIV and chronic disease states where the patient is unstable or uncontrolled ; pregnant or lactating women . There was a 1 – 4-week wash-out period for previous AD therapies before the trial : 4 weeks for systemic corticosteroid or other immunosuppressive drugs and one week for topical corticosteroids , topical antibiotics or other topical immunomodulators .

To assess the skin barrier function of patients with AD , TEWL was measured using a Vapometer ® ( Delfin Technologies Ltd , Kuopio , Finland ) on the cheeks of patients with AD . Skin hydration was assessed with a Corneometer ® ( Courage & Khazaka electronic GmbH , Köln , Germany ) in the same areas as for TEWL . Three repeated measures were taken using each tool , and the mean value was calculated . A thin coat of 0.1 % tacrolimus ointment ( Protopic ; Astellas Pharma Korea Inc ., Seoul , Korea ) applied twice daily on the facial atopic lesion . At 2 weeks after the first visit , the occurrence of burning sensation was questioned . The definition of “ burning sensation ” in this study was a feeling of warmth or heat , including events such as pain , stinging and soreness at the application site ( 3 ).

Student ’ s t-test was used to compare the 2 groups of patients with / without burning sensation . The mean and standard deviation ( SD ) of the TEWL and skin hydration of the groups with or without a burning sensation after application of tacrolimus ointment were calculated and compared . SPSS ( version 24.0 , SPSS Inc . Chicago , IL , USA ) was used to analyse the data and p-values < 0.05 were considered significant .

RESULTS

A total of 60 patients ( age range 16 – 62 years , mean age 29.1 years ) completed the study ( Table I ). Among them , 30 patients ( 50 %) experienced a burning sensation . TEWL levels were statistically significantly higher in patients with a burning sensation than in those without ( 113.7 ± 78.4 g / m 2 h vs . 27.5 ± 23.2 g / m 2 h , p < 0.001 ). Skin hydration showed no statistically significant difference between patients with and without a burning sensation ( 51.8 ± 18.6 g / m 2 h vs . 53.6 ± 15.6 g / m 2 h , p = 0.673 ). Of the patients with a burning sensation , 11 had pruritus associated with tacrolimus , and 4 patients without a burning sensation had pruritus . Among 30 patients with a burning sensation , 13 ( 21.7 %) discontinued the use of topical tacrolimus , 17 gradually became tolerant to topical tacrolimus without discontinuation ( Table I ). There was no statistically significant difference between patients who discontinued ointment and those who did not ( 122.8 ± 78.5 g / m 2 h and 106.7 ± 80 g / m 2 h , p = 0.586 ). In the event of intolerable burning sensation , patients were recommended to apply topical tacrolimus ointment mixed with any commercially available moisturizers in a 1:1 ratio . Most of the discontinued patients ( 12 of 13 patients ) tolerated topical tacrolimus ointment when mixed with moisturizer .

Table I . Patients ’ characteristics

Burning sensation positive n = 30

Burning sensation negative n = 30

SD : standard deviation ; TEWL : transepidermal water loss .

This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2699 Acta Derm Venereol 2017 ; 97 : 957 – 958