Original Article GCSMC J Med Sci Vol (II) No (II) July-December 2013 Clinical Study of Efficacy of Topical Tacrolimus in Various Dermatoses Jigna Padhiyar*, Krina B. Patel**, Nayan Patel***, Kishan Ninama****, Yogesh B. Shah***** Abstract : Introduction : Tacrolimus is a calcineurin inhibitor. Topical tacrolimus (0.03% and 0.1%) is currently approved for the treatment of atopic dermatitis. It has been found to be an effective treatment for oral erosive lichen planus, cutaneous lichen planus, psoriasis, vitiligo, few bullous and many other inflammatory dermatoses. Material and methods : Total 140 patients with clinically diagnosed dermatological conditions thought to be amenable to topical tacrolimus ointment attending our department were included in this study. Almost all children (except few who were given 0.1%) were given 0.03% topical tacrolimus. 0.03% topical tacrolimus was given on all mucosal lesions. Adults with skin lesions were either given 0.03 or 0.1% as per requirement. Results : Topical tacrolimus is very effective in treating atopic dermatitis, oral erosive lichen planus, vitiligo, genital lichen sclerosusatrophicus and post herpes labialis depigmentation. Its efficacy in other dermatoses like – granuloma annulare, twenty nail dystrophy, alopecia areata, hand eczema etc. - needs larger study to prove its usefulness as steroid sparing agent. Key Words: efficacy, topical tacrolimus, various dermatoses Introduction :
any component of ointment, children < 2 yr, active skininfection at the site to be treated, netherton syndrome
The macrolide immunomodulators in clinical use are-
aims of to assess the efficacy of topical tacrolimus in various
cyclosporine and sirolimus (rapamycin) .
dermatoses and to assess the adverse effect profile of the
tacrolimus - a calcineurin inhibitor produced by the soil
bacterium stretomycestsukubaensis was isolated in year1984, has strong immunosuppressive activity in vivo and
Material and methods :
prevents the activation of t-lymphocytes in response to
Patients with clinically diagnosed dermatological
conditions thought to be amenable to topical tacrolimus
tacrolimus is derived by taking the ‘t' for tsukuba, the name
ointment attending a tertiary teaching institute were
of mountain where the soil sample was extracted, ‘acrol'
included in this study. Biopsy was taken when necessary.
for macrolide and ‘imus' for immunosuppressant .
140 patients were included in the study after counselling for
Topical tacrolimus (0.03% and 0.1%) is currently
the compliance and side effect profile. Patients with
approved for the treatment of atopic dermatitis (>2year of
different dermatological disorders e.g. atopic dermatitis,
age). (1, 4) FDA has approved topical tacrolimus for
vitiligo, oral and genital erosive lichen planus, granuloma
continuous use of one year. Topical therapy with
annulare, genital lichen sclerosusatrophicus, alopecia
tacrolimus is safe and effective in paediatric and adult
areata, cicatricial alopecia, chronic eczema, hand eczema,
patient up to 4 years of continuous use. (5, 6) It has been
post herpetic depigmentation, twenty nail dystrophy were
found to be an effective treatment for oral erosive lichen
included in the study. Pregnant and lactating women were
planus, cutaneous lichen planus, psoriasis, vitiligo, few
excluded in the study. 41 patients were lost to follow up
bullous and many other inflammatory dermatoses. These
after 1st visit and were not included in the result.
extensive arrays of disorders treated successfully with
The details of history and examination findings were
topical tacrolimus warrants further study of this drug.
recorded. A detailed lesion assessment including number of
Contraindications include hypersensitivity to tacrolimus or
lesions (where necessary), sites of the lesions, size of the
lesions were carried out at visit-1(baseline), visit -2(15 days),
visit-3(30 days), visit-4(60 days), visit-5(90 days), visit-
***** Professor, Skin Department, GCS Medical College,
6(120 days) and visit-7(150days). Photographs were taken
Hospital & Research Centre, Ahmedabad, Gujarat, India
at each visit.All patients were observed for the recurrence
Associate Professor, Skin Department,GMERS Medical College-Sola, Gujarat, India
of the lesion or any other unusual local skin reaction after
Assistant Professor, Skin Department, SBKS Medical College
the last visit for 7 months. Almost all children (except few
and Research Centre, Vaghodia, Gujarat, India
who were given 0.1%) were given 0.03% topical
tacrolimus. 0.03% topical tacrolimus was given on all
Padhiyar J et al: Topical Tacrolimus
mucosal lesions. Adults with skin lesions were either given0.03 or 0.1% as per requirement. Response to treatmentwas graded as - no improvement (<25% improvement),mild improvement (25%-50% improvement), moderateimprovement (50%-75% improvement), excellentimprovement (75%-90% improvement), completeimprovement (90%-100% improvement). Adversereactions were graded as mild- did not significantlyinterfere with patient's functioning, moderate - interfere
Figure-3 : Oral erosive LP-
slightly with patient functioning and severe - interfere
(A) before treatment (B) after treatment-
significantly with patient functioning. excellent response Results :
Out of 140 patients 41 patients were lost to follow up. Sototal 99 (male-39 and female-60) were included in thestudy for results.
In atopic dermatitis group (n=19), 9(47.37%) showedexcellent and 10(52.63%) showed complete response. (Figure-1, 2)
Figure-4: Alopecia areata-
In oral LP (lichen planus) group (n=21), 1(4.76%) showed
(A) before treatment (B) after treatment-
no response, 2(9.52%) showed mild response, 7(33.33%)
showed moderate response, 11(52.38%) showedexcellent response (figure-3) and complete response wasnot seen in any patient.
In alopecia areata group (n=4) 1(25%) showed completeresponse 3(75%) (figure-4) showed mild response. Figure-5: Post-herpes labialis depigmentation- (A) before treatment (B) after treatment- complete response followed by new lesions. Figure-1: Atopic dermatitis in child- (A) before treatment (B) after treatment- complete response Figure-6: Pompholyx- (A) before treatment (B) after treatment- complete response. Figure-2: Atopic dermatitis in adult-
In twenty nail dystrophy (n=2) both showed noimprovement. None of the patient of GA (granuloma
(A) before treatment (B) after treatment-
annulare) group (n=2) showed response in this study during
excellent response GCSMC J Med Sci Vol (II) No (II) July-December 2013
study period. In genital lichen sclerosus atrophicus (LSA)
topical tacrolimus (n=27), 4(14.81%) showed no,
group (n=3), 2(66.66%) showed moderate and 1(33.33%)
8(29.62%) showed mild, 5(18.51%) showed moderate,
showed excellent response. In post herpes labialis
5(18.51%) showed excellent and 5(18.51%) showed
depigmentation group (n=3), 1(33.33%) showed mild,
complete response. In vitiligo group who did not showed
1(33.33%) showed excellent and 1(33.33%) showed
any response to topical tacrolimus alone were additionally
given topical steroids after study period (n=6), 1(16.66%)
eczema group (n=3) 1(33.33%) showed complete
showed no, 3(50%) showed mild and b2(33.33%) showed
response (figure-6) and 2(66.66%) showed moderate
response. In eczema other than hand eczema group (n=2)
Only 4 (3.74%) out of total 99 patients reported mild
transient adverse events. In scarring alopecia group (n=7),
In scaring alopecia group (n=7) no showed improvement,
2(28.57%) showed adverse effect- one patient showed mild
but one patient was having associated depigmentation and
itching and other one showed pyoderma. In lichen
depigmentation improved moderately but not scarring
sclerosus atrophicus group (n=3), 1(33.33%) showed mild
alopecia. In vitiligo group (n=33) who were only given
erythema. In vitiligo group (n=33), 1(3.03%) showedacneform eruption. Table 1: Efficacy and Safety Analysis for various Dermatoses Moderate Excellent Complete response response response response response reaction Table 2 : Efficacy and Safety Analysis for various Dermatoses (continued.) Moderate Excellent Complete response response response response response reaction Padhiyar J et al: Topical Tacrolimus Discussion :
having scarring alopecia due to DLE but did not improve
Hanifin JM et al (7) showed that there is >90%
with 0.1% at 5 month. This again can be due to once/d
improvement in 36.8 %( 0.1% ointment) and in 27.5 %(
application of medicine and shorter duration of treatment.
0.03% ointment) with twice/day application for atopicdermatitis patients. My study showed >75% improvement
in all patient. So, once/day application may be as effective
Lin AN. Topical calcineurin inhibitors. In: Wolverton SE, editors.
as twice/day; though larger sample size is required to have
Comprehensive dermatologic drug therapy, 2 ed. China: Elsevier;2007.p.671-89.
Similarly Schammeret (8) al showed >90%
Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara
improvement in 51% of patient with 0.03% ointment
M, Kohsaka M, Aoki H, Imanaka H. "FK-506, a novel
twice/d application. My study showed > 90%
immunosuppressant isolated from a Streptomyces. I. Fermentation,
improvement in 57.14 %( 0.03% ointment) and 50 %(
isolation, and physio-chemical and biological characteristics."JAntibiot (Tokyo) 1987; 40(9):1249–55.
0.1% ointment) of patients. So we can say that once/d
Sehgal VN, Srivastava G, Dogra S. Tacrolimus in dermatology-
application may be as effective as twice/day.
pharmacokinetics, mechanism of action, drug interactions, dosages,and side effects: part-I. Skinmed.2008; 7:27-30.
As compare to study by Jain S. Et al (9) my study did not
show any response in GA, may be due to application used
Macrolactumimmunomodulators for topical treatment of
inflammatory skin diseases. J Am AcadDermatol 2001; 45:736-43.
Gupta AK, Adamiak A, Chow M. Tacrolimus: a review of its use for
Though number of patient was few in my study, results
the management of dermatoses. J Eur Acad Dermatol Venereol
were comparable to study by Schilieman et al (10) for hand
Hanifin JM et al. Tacrolimus in atopic dermatitis: long term efficacy
and safety. J AM Acad Dermatol. 2005; 53(2 suppl2):S186-94.
Total response rate and duration for response in present
Hanifin JM, Ling MR, Langley R, Breneman D, Rafal E. Tacrolimus
study for vitiligo group were comparable to study by XuAE
ointment for the treatment of atopic dermatitis in adults patients:Part I, efficacy. J Am AcadDermatol 2001; 44(1 Suppl):S28-38.
et al (11). My study also showed greater response in lesions
Schachner LA, Lamerson C, Sheehan MP et al. Tacrolimus ointment
on head and neck as in Xu AE et al. Response rate in
0.03% is safe and effective for the treatment of mild to moderate
atopic dermatitis in pediatric patients: results from randomized,
double-blind, vehicle controlled study. Paediatrics 2005; 116:e334-e342.
acrofacialis group was less in my study compared to same.
Jain S, Stephens CJ. Successful treatment of disseminated
As compare to Hodgson TA et al(13) and Vente C. et al(14) my
granuloma annulare with topical tacrolimus. Br J Dermatol 2004;150:1042-3.
study did not showed complete improvement in any
10. Schliemann S, Kelterer D, Bauer A, et al. Tacrolimus ointment in the
patient of oral erosive LP group, may be because, in
treatment of occupationally induced chronic hand dermatitis.
present study only 0.03% topical tacrolimus was used and
Contact Dermatitis 2008; 58(5):299-306.
that also only once/day. Even mean duration of partial
11. Xu AE, Zhang DM, Wei XD, Huang B, Lu LJ. Efficacy and safety of
tarcrolimus cream 0.1% in the treatment of vitiligo. Int J Dermatol.
response was also higher in my study. Relapse rate was
comparable to study by Vente C et al.
12. Udompataikul M, Boonsupthip P, Siriwattanagate R.Effectiveness of
0.1% topical tacrolimus in adult and children patients with vitiligo. J
As compare to other study by BöhmM Et al (n=6)
13. Hodgson TA, Sahani N, Kaliakatsou F et al. Long –term efficacy and
group no patient showed complete response, may be
safety of topical tacrolimus in the management of ulcerative/erosive
because, in present study 0.03% once daily was used and
oral lichen planus. Eur J Dermatol. 2003; 13(5):466-70.
14. Vente C, Reich K, Rupprecht R, Neumann C. Erosive mucosal lichen
that also for lesser duration. Further study with larger
planus: response to topical treatment with tacrolimus. Br J Dermatol
15. Böhm M, Frieling U, Luger TA, Bonsmann G. Successful treatment
Anecdotal reports of efficacy of topical tacrolimus in lichen
of anogenital lichen sclerosus with topical tacrolimus. Arch
planopilaris by Blazek C et al (17) is there. In my study two
patient of scarring alopecia were diagnosed as LPP (lichen
16. Luesley DM, Downey GP. Topical tacrolimus in the management of
planopilaris). Both of them did not showed any response
lichen sclerosus. BJOG 2006; 113:832-834.
17. Blazek C, Megahed M. Lichen planopilaris. Successful treatment
with tacrolimus. Hautarzt. 2008; 59(11):874-7.
Anecdotal reports of efficacy of topical tacrolimus in
18. Lampropoulos CE, Sangle S, Harrison P et al.topicaltacrolimus
therapy of resistant cutaneous lesions in lupus eryhtematosus: a
possible alternative. Rheumatology (Oxford) 2004; 43(11):1383-5.
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