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212]

REVIEW ARTICLE

Atopic dermatitis and tacrolimus: Current perspectives

Tarang Goyal
Department of Dermatology, Venereology and Leprosy, Muzaffarnagar Medical College and Hospital, Muzaffarnagar,
Uttar Pradesh, India

ABSTRACT

The purpose of the following study is to convey the range of current understanding in relation to atopic dermatitis(AD) and
tacrolimus. A brief structured description is given starting with introducing the subject and continuing with the discussion
of the etiology of AD, a comparative evaluation of the diagnostic criteria, presents management algorithm, structure,
pharmacodynamics and pharmacokinetics of topical calcineurin inhibitors(TCI) and the comparative efficacy and safety
of available TCIs. Etiological hypothesis is still evolving. Until date, no single universally applicable diagnostic Criteria
or scoring system exists. Diagnostic Criteria and scoring system are to adopt according the design and population of any
study. TCIs provide a safe alternate to the present topical steroid dependent system of management of AD. This is not a
systemic review or metaanalysis. The studies cited were not compared statistically. Beneficial to practitioners of pediatric
dermatology to get an idea about the range of current understandings.

Key words: Atopic dermatitis, FK506, immunosuppressant drug, topical tacrolimus

INTRODUCTION multiple lesions with erythema, excoriation, erosions

accompanied by a serous exudate, accentuated

T he spectra of the prevalence of skin diseases

vary worldwide and from country to country.
Therefore, the information about the local
prevalence of diseases is very important in helping
the development of appropriate health improvement
policies for promotion of better management.[1]
Atopic dermatitis (AD) is the most common
chronic inflammatory skin disorder in children with
a worldwide 820% cumulative prevalence. The
number of AD patients is beyond the level that
can be dealt with at clinics and it is time to make
an effort to reduce the number of AD patients in
the community. Thus, caretakers and all persons
involved with AD management, including health care
providers, educators, technologists and medical policy
makers, should understand the development and the
management of AD.[2] AD has a chronic or chronically
relapsing course with remissions and exacerbations
of variable length. Typical clinical features include
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DOI:
10.4103/2319-7250.122163
skin markings(lichenification), fibrotic papules,
severely dry skin and a susceptibility to cutaneous
infections.[3] The main symptom is intense itching and
excessive scratching can cause further damage such
as excoriation, erosions and infections.[4] The lesions
have a typical agedependent distribution pattern. In
infants, nummular or seborrheic type eczema occurs
on the cheeks, chin and trunk. Among 14yearold
children, affected areas include extensor and
sometimes flexural sides of the extremities, the hands,
face and neck and perioral area. Among 416yearold
children, flexural eczema predominates, with face,
hands, feet and gluteal area affected.[5]
Topical calcineurin inhibitors(TCI) are a relatively
new class of drugs used in dermatology. There are
two drug forms availabletacrolimus 0.03% or 0.1%
ointment and 1.0% pimecrolimus cream. The drugs
act by inhibiting the synthesis of proinflammatory
cytokines [Figures 1 and 2]. The only approved
indication for using TCI is the treatment of AD.
The TCI may be used as an alternative therapy to
corticosteroids(CS). Tacrolimus is used to treat
moderatetosevere AD. TCI do not cause skin atrophy
ADDRESS FOR CORRESPONDENCE
Dr. Tarang Goyal,
Department of Dermatology, Venereology and Leprosy, Muzaffarnagar Medical
College and Hospital, Muzaffarnagar251203, Uttar Pradesh, India.
E-mail: tarang_derma@yahoo.co.in

54 Indian Journal of Paediatric Dermatology | Vol 14 | Issue 3 | September-December 2013

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Goyal: Current perspectives

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Figure1: Tacrolimus: Structural formula

and the drug absorption through the skin is minimal.
The TCI have been wellstudied, their efficacy was
evaluated in a number of vast, longterm studies.[6]
MULTIFACTORIAL PATHOGENESIS
OFAD
Genetic Factors
It is wellknown that genetic factors are involved in all
diseases and many genetic factors with allergic disease
have been reported [Figure 3]. Acohort study by Kim
etal.[7] has found out that when both parents had a
family history and showed sensitization to allergens
in a skin prick test, the cumulative prevalence of AD
up to 1year of age was 41.7%; when only the mother
showed sensitization the rate was 30.7%. However,
the rates of AD in children with only a sensitized
father were 22.2% only.
Hygiene Hypothesis
The prevalence of allergic diseases increases in a
community with a high socioeconomic level and was
inversely proportional to the prevalence of bacterial
infections such as tuberculosis and its incidence rate
was relatively low in a larger families or rural areas.
This hypothesis has been questioned with regard to
AD.[8,9]
Immaturity or Abnormality of Defense Mechanisms
Although the prevalence of AD has increased greatly
compared with the past, its tendency to occur most
frequently among infants aged 1year or less and to
reduce with increasing age has been maintained.
Therefore, while the incidence of AD is greatly affected
Figure2: Mechanism of action of tacrolimus
by changes in the environment, overall physical
immaturity is expected to be an important factor
influencing this incidence. In summary, immaturity
of skin barrier function, mucosal immunity, systemic
immunity and digestive enzymes are considered to
be factors that influence the development of AD
symptoms in infancy.
Environmental Factors
Environmental factors resulting from industrialization
have been studied as possible reasons why the
incidence of bronchial asthma, allergic rhinitis and
AD has skyrocketed since the 1980s. Air pollution
generated by cars, energy production and factories,
airconditioning and heating, indoor environmental
changes and dietary changes have been suggested as
factors in the development and aggravation of AD.[810]
The skin environment of the lesions plays a key role
in the incidence of AD. The skin of patients with
AD is mostly colonized by Staphylococcusaureus, a
toxinproducing organism.[11] The skin of AD patients
has been found to be deficient in antimicrobial
peptides, one of the components of the innate response
essential for host defense against bacteria, fungi and
viruses.[12,13]
AD: DIAGNOSTIC CRITERIA
The above major and minor criteria by Hanifin and
Rajka[14] exist as a guideline for arriving at a diagnosis

Indian Journal of Paediatric Dermatology | Vol 14 | Issue 3 | September-December 2013 55

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Goyal: Current perspectives

Figure3: Multifactorial pathogenesis of Atopic Dermatitis

of AD [Table 1]. Minor features vary with ethnicity Table1: The Hanifin and Rajka diagnostic
and genetic background and can be used to aid criteriaofAD
diagnosis. Major criteria(must Pruritus
have three or more of) Early age of onset
Typical morphology and distribution
Flexural lichenification and linearity in
EVALUATION OF MINOR CRITERIA: adults
AD IN CHILDREN Facial and extensor involvement during
infancy and childhood
Wahab etal.[15] [Figure 4] evaluated 20minor criteria Chronic or chronicallyrelapsing dermatitis
Personal or family history of atopy(asthma,
during their study in 201 patients of 112 years age
allergic rhino conjunctivitis, AD)
and found out that most common minor criteria Minor or less specific Xerosis
were cutaneous infection(80%), influence by an criteria(should have Ichthyosis, palmar hyperlinearity, keratosis
three or more of) pilaris
environmental factor(66.7%), high IgE level(60%),
Immediate(type1) skin test reactivity
intolerance of wool (50%), xerosis (43.8%), Raised serum IgE
infraorbital fold (39.5%), ichthyosis (34.3%), early Early age of onset
Susceptibility to cutaneous
age onset(31%), itch on sweating(26.7%), palmer infections(especially Staphylococcusaureus
hyperlinearity(24.8%), food hypersensitivity(19%), and herpes simplex) or impaired
keratosis pilaris(14.8%), pityriasis alba(14.3%), cellmediated immunity
Tendency toward nonspecific hand or foot
cheilitis (10.5%), hand eczema (9%), foot
dermatitis
eczema(7.6%), intolerance to lipid solvent(6.7%), Nipple eczema
scalp scaling(5.2%) infraauricular fissure(4.8%) and Cheilitis
Recurrent conjunctivitis
facial erythema(1.9%). These features were present Denniemorgan infraorbital fold
singly or in combination. The result evidenced that Keratoconus
minor criteria are many a times important for the Anterior subcapsular cataracts
Orbital darkening
diagnosis where major criteria are uncertain. Facial pallor or facial erythema
Pityriasis alba
Kanwar etal.[16,17] suggested diffuse scalp scaling and Anterior neck folds
Itch when sweating
infra auricular fissuring as more significant minor
Intolerance to wool and lipid solvents
indicators for diagnosis, which may be explained Perifollicular accentuation
by high colony counts of Pityrosporum producing Food intolerance
Course influenced by environmental or
subacute dermatitis. This study also noted an early
emotional factors
age of onset and put forward the logic of atopic White dermatographism or delayed blanch
facies. ADAtopic dermatitis

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Goyal: Current perspectives

AD: ASSOCIATIONS SCORING SYSTEM IN AD

The term atopic diathesis refers to the presence of Presently, four tools are used to assess AD severity.
allergic rhinitis, bronchial asthma or AD.[18] AD(AD, They are the scoring atopic dermatitis (SCORAD)
atopic eczema and eczema) occurs in families with index, the objective SCORAD, the eczema area and
atopic diseases(AD, bronchial asthma and/or allergic severity index and the threeitem severity (TIS)
rhinoconjunctivitis) [Figure 5].[19] Surveys from score. Each of these assessment tools has its own
advantages and disadvantages. The SCORAD
Western countries have shown that these features, in
and objective SCORAD indices were developed
particular the minor features, vary with ethnicity and
by the European task force on AD [Table 2]. The
genetic background and can be used to aid diagnosis.
SCORAD index is based on three parameters: The
disease extent, intensity and some subjective items.
RELATIONSHIP OF AD AND AGE
Table2: Grading of AD(eczema) as mild, moderate
Hadiuzzaman etal.[1] evaluated 1753 children in and severe
the age group up to 14 years and found that 355 Eczema grading Mild Moderate Severe

children(20%) in various age groups were suffering Objective SCORAD <15 1540 >40
TIS score <3 36 6
from AD [Figure 6]. About 60% of children presented
SCORAD Scoring atopic dermatitis; TIS Threeitem severity; AD Atopic
with AD in age groups of 15years and 1114years. dermatitis






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Figure6: Relation of age group with number of atopic dermatitis cases Age
Figure5: Atopic dermatitis and its associations Group 1-14 years (n=355)

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Goyal: Current perspectives

To measure the extent of AD, the rule of nines is
applied in a fronttoback drawing of the patients
inflammatory lesions. The extent can be graded
0100. The intensity scoring consists of six items:
Erythema, edema, excoriations, lichenification,
oozing or crusting and dryness. Each item is graded
on a scale of 03. The subjective items include daily
pruritus and sleeplessness and both items can be
graded on a 10cm visual analog scale.
In the objective SCORAD, the two subjective items
are omitted and only the extent and intensity items are
considered. The formula for the objective SCORAD is
A/5+7B/2, where A is the extent(0100) and B is the
intensity (018).
The maximum objective SCORAD score is 83(plus an
additional 10 points for severe disfiguring eczema on
the face and hands). The TIS score is a simple scoring
system that uses three of the intensity items of the
SCORAD index, i.e., intensity of erythema, edema
and excoriations (scratches). Each of the three items
is graded on a 03 scale. Therefore TIS scores range
from 0 to 9. The objective SCORAD should be used
in clinical trials, whereas the TIS score is preferred in
epidemiological studies and in daily practice. The TIS
has a great advantage because it is simple, quick and
easy to perform in routine settings and is shorter to
complete.[20]
STEPWISE MANAGEMENT OF AD
GUIDELINE IN CHILDREN
The above atopic dermatitis organizer guideline
[Table 3] is written with the concept of AD as:
A multifactorial disease,
One of the most common chronic childhood diseases
predominantly found in infants and young children,
A disease that tends to wax and wane over time, and
A disease that disappears with increasing age
and/or progresses to bronchial asthma or allergic
rhinitis.
TACROLIMUS, ITS MECHANISM OF
ACTION AND PHARMACOKINETICS IN
PEDIATRIC PATIENTS
Tacrolimus ointment contains tacrolimus, a macrolide
immunosuppressant produced by Streptomyces
tsukubaensis. It is for topical dermatologic use
only. Chemically, tacrolimus is designated as
[3S[3R*[E (1S*, 3S*, 4S*)], 4S*, 5R*, 8S*, 9E,
12R*, 14R*, 15S*, 16R*, 18S*, 19S*, 26aR*]]5,
6, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, 24,
25, 26, 26ahexadecahydro5, 19dihydroxy3
[2(4hydroxy3methoxycyclohexyl)1
methylethenyl] 14, 16dimethoxy4, 10,12,
18tetramethyl 8(2propenyl)15, 19epoxy3H
pyrido[2, 1c] [1, 4] oxaazacyclotricosine 1, 7, 20, 21
(4H, 23H)tetrone, monohydrate.
Tacrolimus ointment, 0.03% for children aged
215years, is indicated as secondline therapy for the
shortterm and noncontinuous chronic treatment of
moderate to severe AD in nonimmunocompromised
children who have failed to respond adequately to
other topical prescription treatments for AD, or when
those treatments are not advisable.
MECHANISM OF ACTION
Pharmacokinetics in Pediatrics Patients
In a pharmacokinetic study of 14 pediatric AD
patients, between the ages of 2 and 5years, peak blood
concentrations of tacrolimus ranged from undetectable
to 14.8ng/mL after single or multiple doses of 0.03%
tacrolimus ointment, with 86% of patients having
peak blood concentrations below 2ng/mL throughout
the study.
In a similar pharmacokinetic study with 61 enrolled
pediatric patients (ages 612 years) with AD, peak
tacrolimus blood concentrations ranged from
undetectable to 5.3ng/mL after single or multiple doses
of 0.1% tacrolimus ointment, with 91% of evaluable
patients having peak blood concentrations below 2ng/
mL throughout the study period. In clinical studies

Table3: Basic framework of the stepwise management in ADO guideline[2]

Step Medication for skin inflammation Medications for itching Basic management
CS Other antiinflammatory treatment and and complication
investigational therapy
1 None None None Skin care
2 Topical CS Topical calcineurin inhibitor Antihistamine Dietary management
3 Systemic CS Cyclosporin A, interferon gamma injection, azathioprine, Antibiotics Indoor environmental control
phototherapy, investigational therapy(IVG, omalizumab, Topical keratolytic agent Psychological support
allergen desensitization, herb medicine)
IVG Intravenous immunoglobulin; ADO Atopic dermatitis organiser; CS Corticosteroid

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Goyal: Current perspectives

with periodic blood sampling, a similar distribution of
tacrolimus blood levels was also observed, with 98%
of pediatric patients having a blood concentration
below 2ng/mL.
Renal Insufficiency
The effect of renal insufficiency on the
pharmacokinetics of topically administered tacrolimus
has not been evaluated. The mean clearance of
intravenous administered tacrolimus in patients with
renal disease was similar to that of normal volunteers.
On the basis of this information doseadjustment is
not expected to be needed.
Hepatic Insufficiency
The effect of hepatic insufficiency on the
pharmacokinetics of topically administered tacrolimus
has not been evaluated but doseadjustment is not
expected to be needed.[6,21]
EFFICACY AND SAFETY OF TACROLIMUS
OINTMENT IN AD
Difficult to control AD presents a therapeutic challenge
and often requires combinations of topical and
systemic treatment. Antiinflammatory treatment of
severe AD most commonly includes topical CS and
topical calcineurin antagonists used for exacerbation
management and more recently for proactive therapy in
selected cases. Topical CS remains the mainstay of therapy,
the TCI tacrolimus and pimecrolimus are preferred in
certain locations. Systemic antiinflammatory treatment
is an option for severe refractory cases. Microbial
colonization and superinfection contribute to disease
exacerbation and thus justify additional antimicrobial/
antiseptic treatment. Pruritis caused by AD is not always
controlled by topical CS therapy, but use of tacrolimus
often helps to soothe such intractable pruritis in clinical
settings.
Takeuchi etal.[22] evaluated relief from pruritis with
tacrolimus monotherapy group versus emollient group
and found out the efficacy rate in controlling pruritis
with tacrolimus monotherapy was 76.2% compared
with 0% with emollient group. This difference was
statistically significant [Figure 7].
Cumulative itch recurrence in the tacrolimus
monotherapy maintenance group and emollient
maintenance group at day 28 was 23.8% and 100%
respectively in maintenance treatment.
Hon etal.[23] evaluated the clinical efficacy of topical
tacrolimus for reducing the sensation of pruritis in
children with AD. Nocturnal scratching activity measured
using a DigiTrac movement recorder was reduced from
115 g/minto 71.5 g/min after 2weeks of treatment.
Healy etal.[24] evaluated children with moderate and
severe AD, twiceweekly maintenance treatment with
tacrolimus ointment and tacrolimus was found to
be more effective and less costly treatment than the
standard treatment regimen.
Kirsner etal.[25] evaluated patients with AD previously
treated with CS and then given tacrolimus or
pimecrolimus [Figures 8-11]. Majority of the patients
in mild, moderate or severe AD were evaluated for
the efficacy of tacrolimus ointment v/s pimecrolimus
cream [Table 4].
Dhar and Banerjee[26] evaluated 15 children with
moderate to severe AD after treatment with
topical tacrolimus(0.1%) ointment. There was a
significant reduction in severity when compared to
sunflower oil application in all 15 children. Topical
tacrolimus(0.1%) was found to be safe and effective
in moderate to severe AD in children.

Figure7: Changes in visual analogue scale (VAS)-itch score and disease severity after add-on tacrolimus therapy. (a) There was a significant decrease in
VAS-itch score in responders after the add-on therapy. (b) Scoring atopic dermatitis score reduced after the add-on topical tacrolimus therapy

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Goyal: Current perspectives

  


   
  

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Figure8: Efficacy of Tacrolimus ointment v/s Pimecrolimus cream in all Figure9: Efficacy of Tacrolimus ointment v/s Pimecrolimus cream in
patient of atopic dermatitis (at baseline) at the end of day 43/end of study severe/very severe patients of atopic dermatitis (at baseline) at the end of
(n=171, n=176) day 43/end of study (n=19, n=32)


 



 
 
 

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Figure10: Efficacy of Tacrolimus ointment v/s Pimecrolimus cream in Figure11: Efficacy of Tacrolimus ointment v/s Pimecrolimus cream in
moderate disease (at baseline) of AD at the end of day 43/end of study mild disease (at baseline) of AD at the end of day 43/end of study (n=87,
(n=65, n=51) n=93)

Table4: Most common adverse events reported with CONCLUSIONS

tacrolimus were
Adverse event Tacrolimus ointment(n=171) % The first line therapy of topical CS for treatment
Applicationsite reactions of AD patients has continued for a long time. The
Burning 9.9 chronic use of topical CS, particularly to sensitive
Pruritus 7.0
Pain 4.1
and widely extensive areas, is an important
Warmth 1.2 concern for patients and health care providers.
Alcohol intolerance* 1.2 Noncompliance or under treatment issues may
Erythema 1.8
Temperature intolerance 1.8 arise from patients fears about the safety of topical
Folliculitis 0.01 CS(steroid phobia) and can result in reduction
Skin infection 0.01 of disease control.
*Localized facial flushing, erythema or heat sensation after ingestion of alcoholic
beverages
Results from the International Study of Life with
The improvements in Investigator Global Atopic Atopic Eczema reported that while the majority
Dermatitis Assessment status are depicted in of patients with AD received topical CS, 49% of
Figures 811 showing that tacrolimus ointment is respondents were concerned about their use, 39%
better than pimecrolimus cream in the management of respondents applied them less frequently or for
of mild, moderate and severe AD. shorter time periods than prescribed and 74% of
60 Indian Journal of Paediatric Dermatology | Vol 14 | Issue 3 | September-December 2013
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Goyal: Current perspectives
respondents would prefer to apply a nonsteroid
treatment.
The management of AD with tacrolimus and pimecrolimus
may overcome some of the limitationsassociated with
topical CS use and may be used aspart of an integrative
or multipletherapy approach forimproving the overall
management of AD.
Comparison of tacrolimus and pimecrolimus in
various studies has shown that tacrolimus is better
than pimecrolimus with a safer adverse event profile
compared with pimecrolimus.
REFERENCES
1. Hadiuzzaman M, Hasibur MR, Nahida I, Islam MS,
Sabrina AM, Bhuyan MK. Prevalence of dermatoses in rural
paediatric population. Community Based Medical Journal
2013:02:914.
2. Lee SI, Kim J, Han Y, Ahn K. A proposal: Atopic Dermatitis
Organizer (ADO) guideline for children. Asia Pac Allergy
2011;1:5363.
3. Reitamo S, Wollenberg A, Schpf E, Perrot JL, Marks R,
RuzickaT, etal. Safety and efficacy of 1year of tacrolimus
ointment monotherapy in adults with atopic dermatitis. The
European Tacrolimus Ointment Study Group. Arch Dermatol
2000;136:9991006.
4. LeungDY. Atopic dermatitis: New insights and opportunities
for therapeutic intervention. J Allergy Clin Immunol
2000;105:86076.
5. Bhme M, Svensson A, Kull I, Nordvall SL, Wahlgren CF.
Clinical features of atopic dermatitis at two years of age:
Aprospective, populationbased casecontrol study. Acta Derm
Venereol 2001;81:1937.
6. Gutfreund K, Bienias W, Szewczyk A, Kaszuba A. Topical
calcineurin inhibitors in dermatology. PartI: Properties,
method and effectiveness of drug use. Postep Dermatol Alergol
2013;30:1659.
7. Kim HY, Jang EY, Sim JH, Kim JH, Chung Y, Park SH,
etal. Effects of family history on the occurrence of atopic
dermatitis in infants. Pediatr Allergy Respir Dis (Korea)
2009;19:10614.
8. WilliamsH, FlohrC. How epidemiology has challenged 3
prevailing concepts about atopic dermatitis. J Allergy Clin
Immunol 2006;118:20913.
9. Zutavern A, Hirsch T, Leupold W, Weiland S, Keil U, von
MutiusE. Atopic dermatitis, extrinsic atopic dermatitis and the
hygiene hypothesis: Results from a crosssectional study. Clin
Exp Allergy 2005;35:13018.
10. IbargoyenRotetaN, AguinagaOntosoI, FernandezBenitezM,
MarinFernandez B, GuillenGrima F, SerranoMonzo I,
etal. Role of the home environment in rhinoconjunctivitis
and eczema in schoolchildren in Pamplona, Spain. JInvestig
Allergol Clin Immunol 2007;17:13744.
Indian Journal of Paediatric Dermatology | Vol 14 | Issue 3 | September-December 2013
11. Leung DY. Infection in atopic dermatitis. Curr Opin Pediatr
2003;15:399404.
12. NomuraI, GolevaE, HowellMD, HamidQA, OngPY, HallCF,
etal. Cytokine milieu of atopic dermatitis, as compared to
psoriasis, skin prevents induction of innate immune response
genes. JImmunol 2003;171:32629.
13. Suh L, Coffin S, Leckerman KH, Gelfand JM, Honig PJ,
YanAC. Methicillinresistant staphylococcusaureus colonization
in children with atopic dermatitis. Pediatr Dermatol
2008;25:52834.
14. HanifinJM, RajkaG. Diagnostic features of atopic dermatitis.
Acta Derm Venereol Suppl(Stockh) 1980;92:447.
15. WahabMA, RahmanMH, KhondkerL, HawladerAR, AliA,
HafizMA, etal. Minor criteria for atopic dermatitis in children.
Mymensingh Med J 2011;20:41924.
16. Kanwar AJ, Dhar S, Kaur S. Evaluation of minor clinical
features of atopic dermatitis. Pediatr Dermatol 1991;8:1146.
17. KanwarAJ, DharS. Frequency and significance of major and
minor clinical features of atopic dermatitis. Dermatology
1995;190:317.
18. DharS, BanerjeeR. Atopic dermatitis in infants and children
in India. Indian J Dermatol Venereol Leprol 2010;76:50413.
19. Ring J, Przybilla B, Ruzicka T, editors. Handbook of Atopic
Eczema. 2nded. Heidelberg: Springer; 2006.
20. 20.OranjeAP, GlazenburgEJ, WolkerstorferA, de Waardvan
der SpekFB. Practical issues on interpretation of scoring atopic
dermatitis: The SCORAD index, objective SCORAD and the
threeitem severity score. Br J Dermatol 2007;157:6458.
21. Available from: http://www.rxlist.com/protopic. [Last accessed
on 2013Aug31].
22. Takeuchi S, Saeki H, Tokunaga S, Sugaya M, Ohmatsu H,
TsunemiY, etal. Arandomized, openlabel, multicenter trial of
topical tacrolimus for the treatment of pruritis in patients with
atopic dermatitis. Ann Dermatol 2012;24:14450.
23. HonKL, LamMC, LeungTF, ChowCM, WongE, LeungAK.
Assessing itch in children with atopic dermatitis treated with
tacrolimus: Objective versus subjective assessment. Adv Ther
2007;24:238.
24. HealyE, BentleyA, FidlerC, ChambersC. Costeffectiveness of
tacrolimus ointment in adults and children with moderate and
severe atopic dermatitis: Twiceweekly maintenance treatment
vs. standard twicedaily reactive treatment of exacerbations
from a third party payer(U.K. National Health Service)
perspective. Br J Dermatol 2011;164:38795.
25. Kirsner RS, Heffernan MP, Antaya R. Safety and efficacy
of tacrolimus ointment versus pimecrolimus cream in the
treatment of patients with atopic dermatitis previously treated
with corticosteroids. Acta Derm Venereol 2010;90:5864.
26. DharS, BanerjeeR. Topical tacrolimus in aopic dermatitis:
Aplacebo controlled study with 15 children. Indian J Dermatol
2004;49:224.
How to cite this article:Goyal T. Atopic dermatitis and tacrolimus: Current
perspectives. Indian J Paediatr Dermatol 2013;14:54-61.
Source of Support: Nil, Conflict of Interest: Nil
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