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Guidelines on Management of Atopic Dermatitis in India- An Evidence-Based Review and an Expert Consensus

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Background: Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin condition that affects all age groups. There was a dearth of consensus document on AD for Indian practitioners. This article aims to provide an evidence‑based consensus statement for the management of AD with a special reference to the Indian context. This guideline includes updated definition, etiological factors, classification, and management of atopic dermatitis. Methodology: The preparation of guidelines was done in multiple phases. Indian Dermatology Expert Board Members (DEBM), recommended by the Skin Allergy Society of India, prepared 26 evidence‑based recommendations for AD. An extensive literature search was done in MEDLINE, Google scholar, Cochrane, and other resources. Articles published in the past 10 years were reviewed and recommendations were graded based on the quality of evidence as per GRADE. After forming the initial structure, DEBM met in Mumbai and gave their decisions on an agree and disagree scale with an Indian perspective. Finally, their suggestions were compiled for preparing the article. After DEBM finalized the draft, a treatment algorithm was formulated for the management of AD. Results: DEBM suggested a working definition for AD. The panel agreed that moisturizers should be used as mainstay of therapy and should be continued in all lines of therapy and in maintenance phase. Topical corticosteroids and topical calcineurin inhibitors should be considered as the first line of treatment. Among systemic therapies, cyclosporin should be considered first line, followed by azathioprine, methotrexate, and mycophenolate mofetil. Phototherapy can be an effecive alternative. Empirical food restriction was recommended against. Conclusion: These guidelines should form a reference for the management of patients with AD in an evidence‑based manner.
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Asian Academy Of Dermatology And Venereology
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Atopic dermatitis
· Indian guidelines
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Indian Journal of Dermatology • Volume 64 • Issue 3May-June 2019 • Pages 165-252
166 © 2019 Indian Journal of Dermatology | Published by Wolters Kluwer - Medknow
SPECIAL ARTICLE
Abstract
Background: Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin
condition that affects all age groups. There was a dearth of consensus document on AD for
Indian practitioners. This article aims to provide an evidence-based consensus statement for
the management of AD with a special reference to the Indian context. This guideline includes
updated definition, etiological factors, classification, and management of atopic dermatitis.
Methodology: The preparation of guidelines was done in multiple phases. Indian Dermatology
Expert Board Members (DEBM), recommended by the Skin Allergy Society of India, prepared 26
evidence-based recommendations for AD. An extensive literature search was done in MEDLINE,
Google scholar, Cochrane, and other resources. Articles published in the past 10 years were
reviewed and recommendations were graded based on the quality of evidence as per GRADE.
After forming the initial structure, DEBM met in Mumbai and gave their decisions on an agree
and disagree scale with an Indian perspective. Finally, their suggestions were compiled for
preparing the article. After DEBM finalized the draft, a treatment algorithm was formulated
for the management of AD. Results: DEBM suggested a working definition for AD. The panel
agreed that moisturizers should be used as mainstay of therapy and should be continued in
all lines of therapy and in maintenance phase. Topical corticosteroids and topical calcineurin
inhibitors should be considered as the first line of treatment. Among systemic therapies,
cyclosporin should be considered first line, followed by azathioprine, methotrexate, and
mycophenolate mofetil. Phototherapy can be an effecive alternative. Empirical food restriction
was recommended against. Conclusion: These guidelines should form a reference for the
management of patients with AD in an evidence-based manner.
kEy words: Atopic dermatitis, consensus, expert opinion, guidelines
Guidelines on Management of Atopic Dermatitis in India: An
Evidence-Based Review and an Expert Consensus
Murlidhar Rajagopalan, Abhishek De1, Kiran Godse2, D S Krupa Shankar3, Vijay Zawar4, Nidhi Sharma5,
Samipa Mukherjee6, Aarti Sarda7, Sandipan Dhar8
Access this article online
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DOI: 10.4103/ijd.IJD_683_18
Introduction
Nomenclature
Indian Dermatology Expert Board Members (DEBM), who
formulated the guidelines, agreed to use the term “atopic
dermatitis” (AD), which can be used as a synonym for
“atopic eczema” or “endogenous eczema.”
Why does India need a guiding tool for AD?
Globally, there are many guidelines established for
AD. All guidelines have their own region-specific
recommendations based on the ethnic, socioeconomic,
resource-based, and demographic characteristics of
AD. However, in India there is a paucity of published
data about the natural history, etiopathogenesis,
epidemiology, clinical patterns, and management of AD.
There is yet no guideline on AD from India, published in
any indexed journal. This article was developed by the
From the Department of
Dermatology, Apollo Hospital,
Chennai, Tamil Nadu,
1Department of Dermatology,
Calcutta National Medical College,
7Department of Dermatology,
Wizderm Specialty Skin and
Hair Clinic, 8Department of
Dermatology, Institute of Child
Health, Kolkata, West Bengal,
2Department of Dermatology,
D Y Patil Hospital, Navi Mumbai,
4Department of Dermatology,
Skin Diseases Center, Nashik,
Maharashtra, 3Department of
Dermatology, Mallige Hospital,
6Department of Dermatology,
Cloud Nine Hospitals, Bengaluru,
Karnataka, 5Department of
Dermatology, The Medicity,
Medanta Hospital, Gurugram,
Haryana, India
This is an open access journal, and articles are distributed under the terms of
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which allows others to remix, tweak, and build upon the work non‑commercially,
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For reprints contact: reprints@medknow.com
How to cite this article: Rajagopalan M, De A, Godse K, Krupa Shankar DS,
Zawar V, Sharma N, et al. Guidelines on management of atopic dermatitis
in India: An evidence‑based review and an expert consensus. Indian J
Dermatol 2019;64:166‑81.
Received: December, 2018. Accepted: February, 2019.
Address for correspondence:
Dr. Abhishek De,
Flat Number 3 A, Arcadia 1,
Dream Park, Sonarpur Station
Road Kolkata - 700 103,
West Bengal, India.
E-mail: dr_abhishek_de@yahoo.
co.in
Rajagopalan, et al.: Consensus on atopic dermatitis
Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019 167
Skin Allergy Research Society of India for an updated
evidence-based consensus statement for the management
of AD, with a special reference to the Indian context.
Scope of guidelines
This guideline addresses the management of pediatric and
adult AD of all severities. Other forms of dermatitis, such as
irritant dermatitis and allergic contact dermatitis, are outside
of the purview of this document. The recommendations were
prepared to cover an appraisal of all the relevant available
literature until May 2018. This guideline is intended
for specialists in dermatology, pediatric and adolescent
medicine, general medicine, and all groups of physicians
whose work includes the treatment of AD in India.
Methodology
The preparation of guidelines was projected in multiple
phases. An Indian DEBM, recommended by the Skin
Allergy Society of India, prepared 26 evidence-based
recommendations for AD. An extensive literature search
was done in MEDLINE, Google Scholar, Cochrane, and
other resources. Articles published in the past 10 years
were reviewed and recommendations were graded based
on the quality of evidence as per GRADE [Table 1]. After
forming the initial discussion proforma, DEBM met in
Mumbai. Their discussions were based on literature from
clinical research articles and also from their experience
and acumen. The members gave their independent
views on the preselected recommendations in agree
and disagree scale with an Indian perspective [Table 2].
Finally, their suggestions were complied for preparing
the article. After DEBM finalized the draft, a treatment
algorithm was formulated for the management of AD.
Atopic Dermatitis: General Aspects
Denition
AD, also known as atopic eczema, is a chronic,
inflammatory, relapsing skin disorder with usually an
early age of onset in infancy and early childhood.[1] It
follows a relapsing course with repeated exacerbation
and remission, which is characterized by dermatitis
with itch, and is often associated with elevated serum
immunoglobulin (IgE) levels. Natural history of AD often
involves typical progression including food allergy,
allergic rhinitis (hay fever), and asthma. This sequence
of events is referred to as the “atopic march.” It is
accompanied in a majority of patients with a personal or
family history of “atopic diathesis.”[1]
Definition of AD:
Consensus Statement-I
Atopic dermatitis is a chronic, recurrent inflammatory
skin disease, commonly having a childhood onset
and characterized by variably distributed pruritic
eczematous lesions with flexural predilection; mostly
exhibited by patients with personal or family history
of atopic diathesis.
Atopic diathesis: (i) Personal or family history of
bronchial asthma, allergic rhinitis and conjunctivitis,
and/or atopic dermatitis and/or (ii) predisposition to
overproduction of immunoglobulin E (IgE) antibodies.
Epidemiology
The cumulative incidence of AD varies between
11% and 21% depending on age and region.[2] In a
clinicoepidemiological study in a north Indian pediatric
population, the mean age at onset and mean duration
of the disease were 4.2 and 3.3 months, respectively,
in the “infantile AD” group, and in the “childhood AD”
group, the corresponding figures were 4.1 and 1.9 years,
respectively. Patients from urban areas significantly
outnumbered those from rural background.[3] Another
hospital-based north Indian study documented that AD
was the most common dermatosis in children registered
to a pediatric dermatology clinic with a prevalence
of 29.9% of the total patients. The male-to-female
ratio was 2.25:1, with a mean onset of 4.5 months.
The infants had more of facial involvement and acute
eczema, whereas children had nonspecific distribution
and chronic eczema, with overall mild to moderate AD
being more prevalent. Winter exacerbation was noted in
a majority of the population (62%).[4] A lower prevalence
0.42% in the eastern part of the country was reported
among dermatology outpatient department attendees.[5]
Table 1: Level of evidence and strength of the
recommendations
Strength of
recommendation
Level of evidence
A 1 a Systematic review of RCTs, meta-analysis
1 b Individual RCTs
B 2 a Systematic review of cohort studies
2 b Individual cohort study (including
low-quality RCT)
3 a Systematic review of case-control studies
3 b Individual case-control study
C 4 Case series (and poor-quality cohort and
case-control studies)
D 5 Expert opinion
RCT: Randomized controlled trial
Table 2: Recommendation levels
Recommendation type Recommendation strength
Positive Recommended
Can be recommended
Can be considered
Negative Must not be done
Is not recommended
Rajagopalan, et al.: Consensus on atopic dermatitis
168 Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019
Etiology and pathogenesis
Genetic factors
The causes of AD are varied. Both a genetic predisposition
and numerous trigger factors play an important role
in the first manifestation and in exacerbations of the
disease. Major candidate genes reported to date include
CTLA4, interleukin (IL)-18, TLR9, CD14, CARD4, PHF11,
TLR2, SCCE, MCC, IL-4R, GM-CSF, TIM1, CARD15, GSTT1,
SPINK5, eotaxin, TGFb1, IL-13, RANTES, IL-4, and Fc
3RIb.[6]
Immunological mechanism
In the acute stage, the dominant mechanisms of AD are
governed by Th2 cell–related cytokines, such as, IL-4
and IL-13, and chemokines, such as, TARC (thymus and
activation-regulated chemokine) and eotaxin.[7] Later,
Th1 cells producing interferon (IFN)-γ and IL-12 perform
a dominant role in the chronic stage.[8] Langerhans
cells and mast cells are also involved in the disease
pathogenesis as they express a high-affinity IgE
receptor (FcεRI) that causes antigen-presenting cells and
mast cells to release histamine, cytokines, and so on.
IL-4 and IL-13 stimulate fibroblasts to produce periostin,
causing keratinocytes to produce thymic stromal
lymphopoietin, which in turn induces TARC/CCL17
production by dendritic cells. In an eczematous lesion of
AD, antimicrobial peptides (defensins, cathelicidins, etc.)
are inhibited from being expressed by keratinocytes.[9]
Barrier dysfunction
Expression of ceramide and filagrin decreases in skin
with AD and is considered as a primary cause of
barrier dysfunction. It is also considered as a secondary
phenomenon associated with inflammation and as a
cause of AD.[6]
Exacerbating factors
Environmental factors responsible for exacerbation of AD
vary and include climatic changes, sweating, physical
irritation (including scratching), microbes/fungi, contact
allergens, stress, and foods.
Atopic dermatitis and vaccinations
It is recommended that children, adolescents, and
adults with AD are vaccinated regularly according to the
standard national vaccine program recommendation. In
an acute exacerbation, postponement of the vaccination
until the skin condition has stabilized is recommended.
Course
AD dermatitis has a variable course, and informing
patients/parents of the chronic and/or recurrent course
is recommended. Spontaneous cure or remission is
possible at any time, but about 30% of the children who
suffer from the disease may have episodes in adulthood.
Complications
Infections can be frequent complications of AD and
include secondary infections with bacteria, virus, and
fungi. AD can rarely be complicated with eye diseases
(glaucoma, keratoconus, retinal detachment, blindness),
alopecia areata, and growth delay. AD can be associated
with concomitant ichthyosis vulgaris.
Diagnosis
General aspects
The diagnosis of AD is made clinically and is based on
historical features, morphology and distribution of skin
lesions, and associated clinical signs. Formal sets of
criteria have been developed by various groups to aid in
classification.
Diagnostics criteria for atopic dermatitis
Diagnostic criteria proposed by Hanin and Rajka
One of the earliest and most recognized sets of
diagnostic criteria is the 1980 Hanifin and Rajka criteria,
which requires 3 of the 4 major criteria and 3 of the
23 minor criteria to be met.[10]
Diagnostic criteria proposed by the United Kingdom
Working Party
These consist of one mandatory and five major criteria,
it is easy to use and do not require any laboratory
testing. The original UK criteria cannot be applied to
very young children, but revisions to include infants
have since been proposed [Tables 2 and 3]. The Hanifin
and Rajka diagnostic criteria were used in 44% of the
trials and the UK diagnostic criteria in 12%.[11]
Diagnostic criteria proposed by American Academy
of Dermatology
A 2003 consensus conference spearheaded by the
American Academy of Dermatology suggested revised
Table 3: Diagnostic criteria proposed by the United Kingdom Working Party
Mandatory criterion (must be positive) An itchy skin lesion or parental report of scratching or rubbing of skin
Major criteria (at least three of the
five should be positive)
Onset below 2 years of age (not used if the child is less than 4 years of old)
History of skin crease involvement (including cheeks in children under 10 years)
History of generally dry skin
Personal history of other atopic disease (or history of any atopic disease in a first-degree
relative of children under 4 years)
Visible flexural dermatitis (or dermatitis of cheeks, forehead, or outer limbs in children below 4 years)
Rajagopalan, et al.: Consensus on atopic dermatitis
Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019 169
Hanifin and Rajka criteria that are more streamlined
and additionally applicable to the full range of ages
affected[12] [Tables 3 and 4].
Disease severity scales for atopic dermatitis
For the measurement of disease severity, more than 28
different scales were identified, with none of them being
the gold standard. The most commonly used severity
criteria for AD are the SCORAD index, the Eczema Area and
Severity Index (EASI), Patient Oriented Eczema Measure,
and the Six Area, Six Sign Atopic Dermatitis severity score.
SCORAD
SCORAD is an international severity criterion that has
been most popularly adopted in the English written
literature at present. SCORAD incorporates both objective
physician estimates of extent and severity and subjective
patient assessment of itch and sleep loss.[13]
EASI
EASI uses only objective physician estimates of disease
extent and severity.
Laboratory investigations for diagnosis
The diagnosis of AD remains clinical, because there is
currently no reliable biomarker available to confirm the
diagnosis.
Serum total IgE level
A high serum total IgE level is observed in approximately
80% of patients with AD, but is not present in about
20% of the affected individuals. AD was classified into
“extrinsic” and “intrinsic” groups based on the presence
or absence of IgE elevation; however, this delineation
remains controversial. In many, elevation of IgE may be
a secondary phenomenon, developed due to epicutaneous
sensitization because of impaired skin barrier.
Allergen‑specic IgE levels
Although patients with AD are known to produce IgE
antibodies in response to various allergens such as mites,
foods, and pets, these elevations are also nonspecific,
because they are found in about 55% of the general
population.[7]
Increases in tissue mast cells and peripheral
eosinophil counts
They have inconsistent association with disease severity.
Others
Various studies have shown that serum levels of CD30,
macrophage-derived chemoattractant, IL-12, IL-16, IL-18,
and IL-31, and TARC may correlate with disease severity
scores, but to date none has shown reliable sensitivity
or specificity for AD to support general clinical use for
diagnosis or monitoring.[14]
Recommendation for the use of laboratory
investigations for diagnosis and assessment
of disease severity
There are no specific biomarkers available for AD
that can be recommended for diagnosis and/or
assessment of disease severity. Monitoring of IgE levels
is not recommended. Routine allergy testing is not
recommended as the results show many false positives
and less reproducibility. Even with the Phadiatop or the
enzyme-linked immunospot (ELISpot) assays, a negative
value has a better predictive value rather than a positive
value.
Histopathology
A skin biopsy taken from a site with acute atopic eczema
is characterised by spongiosis, perivascular infiltrates
primarily of lymphocytes, and parakeratosis. Chronic
eczema is dominated by hyperkeratosis and acanthosis,
but sparse lymphocytic infiltrates. Routine skin biopsy is
NOT recommended.
Atopic patch tests
Skin tests with protein allergens (known as atopy patch
test) are not recommended in routine diagnostics.
Controlling Factors Responsible for
Exacerbation of AD
Food allergens
There are conflicting evidences available for
associations of specific food with AD. Werfel et al.
concluded a prevalence of food allergy from eight
studies proven by double-blind placebo-controlled food
challenge studies to be 33%–63%.[15] The common food
allergens identified for triggering AD are milk and
milk products, peanuts, eggs, soy, wheat, seafood,
and shellfish. The DEBM recommended against dietary
exclusion for management of AD in patients not having
confirmed food allergy (milk or egg). To diagnose a
food allergy, clinical symptoms or signs after suspected
food allergen intake or exposure must be reproducible,
as broad-panel allergy testing unrelated to a clinical
Table 4: Diagnostic criteria proposed by the American
Academy of Dermatology
Essential
features
Itch
Eczema with typical morphology and age-specific
pattern
Important
features
Early age of onset
Atopy (personal or family history)
Dry skin
Associated
features
Atypical vascular response (i.e., facial pallor, white
dermographism)
Keratosis pilaris, palmar hyperlinearity, ichthyosis
Ocular and periorbital changes
Other regional findings (e.g., perioral and
periauricular lesions)
Perifollicular accentuation, lichenification, and
excoriations
Rajagopalan, et al.: Consensus on atopic dermatitis
170 Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019
history of a reaction to certain foods should be
avoided.
Recommendation for specific-food-free diet in patients
of AD
•Levelof Evidence(GRADE):2b
Consensus Statement-II
Food allergens may contribute to eczema. However,
empirical food restriction is NOT recommended in
patients of atopic dermatitis. The food should be
restricted based only on clinical experience and
food diagnosis procedures. A specific-food-free diet
(especially for infants or toddlers) should only be
considered when allergy to the specific food trigger
is identified based on proper procedures, including a
food diary and allergy test by a specialist.
Clothing
Coarse and irritating fabrics causing skin irritation
are preferably avoided. Occlusive clothing that can
induce heat sensation is not appropriate. Some
studies suggest silver-coated textiles can significantly
reduce the numbers of Staphylococcus aureus and
improve the symptoms of AD.[16] Another fabric,
derma silk, is also suggested due to its sericin-free
composition and nonirritating with antibacterial
properties.[17] However, keeping in mind the Indian
context, the members suggested use of nonirritant
cotton cloths.
Recommendation for Clothing:
•Levelof Evidence:5
Consensus Statement-III
Smooth clothing and avoidance of irritating fabrics
and fibers and loose-fitting garments are recommended
in patients with AD. Use of woolen, acrylic and nylon
fabric should be avoided. Cotton is recommended as
best fabric.
Sweating
Sweating is an important exacerbating factor for AD,
hence washing away sweat by bathing and showering
will lead to the improvement of symptoms. Avoiding
occupational or recreational exposure to high
temperature and humidity can help in controlling
exacerbation.
Environmental factors
Allergens such as mites, house dust, pollens, and organic
solvents such as formaldehyde and toluene can become
problematic. Being sensitized to mites in infancy is
reportedly a marker for the development of asthma.[18]
Periocular pathological changes are often observed during
airborne pollen seasons.
Occupational dermatology aspects
It is recommended to investigate potential occupational
trigger factors of AD in working patients. It is also
recommended to reduce potential occupational trigger
factors of AD and/or implement skin preventive measures.
If hand eczema has already occurred in adolescence in
the context of AD, adoption of wet occupations is not
recommended.
Perinatal prevention
A randomized comparative study revealed that
consumption of an elimination diet free of highly
sensitized food antigens such as egg and cow milk by
pregnant or lactating mothers has NO protective effect
on newborns from developing sensitization to food
allergens or AD.[19] A meta-analysis provided evidence
in support of a moderate role of probiotics in the
prevention of AD and IgE-associated AD in infants. The
favorable effect was similar regardless of the time of
probiotic use (pregnancy or early life) or the subject(s)
receiving probiotics (mother, child, or both).[20]
General Care
Bathing
Bathing and showering are important not only for
washing away the components of perspiration but also
for washing away allergens, such as, dust and pollens,
and microbes on the skin surface. Bathing also allows
removal of dirt and debris from the skin and thereby
reduces the chance of infection. Swimming should be
avoided in acute flares as the amount of free residual
chlorine may impact the skin barrier and contribute to
AD exacerbation.[21]
Recommendation for Bathing
•Levelof Evidence:3b
Consensus Statement-IV
Once daily bathing with lukewarm water
(27 degree Celsius to 30 degree Celsius), which is not
too hot and not too cold, for a short period of time
(e.g., 5 to 10 min), is recommended preferably during
day time
Cleansing
The skin must be cleansed thoroughly, but gently and
carefully to get rid of crusts and bacterial contaminants
in case of bacterial superinfection. Strong scrubbing or
rubbing immediately after bath should be avoided. Skin
should be dried using soft towels.
Rajagopalan, et al.: Consensus on atopic dermatitis
Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019 171
Recommendation for use of Syndet cleansers
•Levelof Evidence(GRADE):4
Consensus Statement-V
Use of non-soap cleansers (e.g., Syndet) that are
neutral to low pH, hypoallergenic, non-irritant and
fragrance free is recommended for AD.
Avoidance of perfumes, personal hygiene and
cosmetic products
Fragrances, formaldehyde, lanolin, nickel, neomycin,
preservatives, such as, parabens, and rubber chemicals are
the common contact allergens which should be avoided
in products manufactured for use by patients with AD.
Recommendation for avoidance of perfumes and
personal hygiene and cosmetic products
•Levelof Evidence:5
Consensus Statement-VI
The avoidance of perfumes, personal hygiene and
cosmetic products containing solvents such as
formaldehyde, and preservatives such as paraben
can be recommended particular to the individuals.
Perfumed soaps and other toiletries should be avoided.
Education (patients and parents)
Patient and parent education is effective in the
management of AD[22] and should aim to provide
information about the clinical characteristics of AD
(etiology, clinical manifestations, and disease course in
common person language), aggravating and relieving
factors, self-management and improving coping skills.
Recommendation for education of the patient or
caregiver for better management of AD
•Levelof Evidence:2b
Consensus Statement-VII
Education of patient or caregiver is highly
recommended at each consultation in the management
of AD and should encompass: a. appropriate
treatment doses and application frequency; b. how
to step up or step down treatment; c. skin care and
bathing; d. management of infection. This leads to
more effective management of AD and should be
reinforced at every consultation.
Psychological factors and psychosomatic
interventions
Patients with AD often complain aggravation due to
stress. Minimizing stress may be helpful in controlling
the disease.[23] Psychotherapeutic approaches and
behavior therapy can be considered to manage individual
emotional factors that trigger AD, such as, vicious
itch-scratch cycles, comorbidity with anxiety and
depression, and low quality of life (QOL).
Recommendation for recognition of psychological
factors and inclusion of psychosomatic interventions
in the management of AD
•Levelof Evidence:1a
Consensus Statement-VIII
Psychological and psychosomatic interventions are
helpful and recommended (if available) for the
management of AD.
Stepladder treatment in atopic dermatitis
Depending on the severity of the AD, topical treatment
methods and/or systemic treatments are recommended.
It is recommended to implement stepladder treatment
appropriate to the clinical severity. Once remission is
achieved, it is advisable to shift to proactive maintenance
therapy to reduce the number of subsequent flare ups.
Oral antihistamines
Their usefulness is controversial and debated.[24] Published
data from randomized controlled trials (RCTs) are available
for both sedating and nonsedating antihistamines; the
results of these trials generally suggest a limited role for
antihistamines in the treatment of AD. Panel members
suggested that a subset of patients with AD with allergic
rhinitis and bronchial asthma benefit maximum from
antihistamines. Sedating antihistamines (cetirizine)
may be used short-term, under supervision where
itch of eczema causes sleep disturbance especially in
children under age of 2 years.[25] Cetirizine also shows
steroid-sparing effect. Addressing itch in young atopics
is of primary importance. The nocturnal itch that
accompanies AD leads to a fall in QOL indices. The active
scratching can further disturb the skin barrier function.
This will worsen the atopic state. Hydroxyzine and
cetirizine will have an ameliorative effect by producing
the required sedation and pruritus relief.
Recommendation of use of antihistamines in AD
Level of Evidence: 1a
Consensus Statement-IX
The use of antihistamines is recommended to control
pruritus in AD, although their role is limited.
Use of systemic and topical antibiotic
therapy
In the pathogenesis of AD, there is a significant
role of microbial pathogens such as staphylococcus,
streptococcus, herpes simplex, molluscum contagiosum,
Rajagopalan, et al.: Consensus on atopic dermatitis
172 Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019
human papillomavirus, and Malassezia furfur infection.
There is a lack of quality trials to support the use of
antimicrobial and antiseptic preparations to treat AD and
there were no reports available on the benefit of topical
antibiotics/antiseptics, antibacterial soaps, or antibacterial
bath additives in clinically uninfected AD.[26] The DEBM
recommends against the indiscriminate use of topical or
oral antibiotics and also against the use of combinations
of creams of steroids and antibiotics. Secondary infection
should be suspected in patients with moderate-to-severe
eczema who have weeping dermatitis, folliculitis and overt
clinical signs of infection, or who are not responding to
first-line topical therapy. Topical antibiotic therapy may
be appropriate for localized areas of infection. Systemic
antibiotics should be used according to clinical condition.
Recommendation of use of topical and oral antibiotics
in AD
•Levelof Evidence:2b
Consensus Statement-X
Preventive use of topical antibiotic is not recommended.
Short courses of topical and systemic antibiotics should
be used only with clinical evidence of overt infection.
Long-term use of systemic and topical antibiotic
therapy should be avoided to reduce the risk of
bacterial resistance and sensitization.
Wet wrap therapy
Wet wrap therapy (WWT) can be helpful to quickly reduce
AD severity, and it is often useful for acute flares and/
or recalcitrant disease. A recent RCT demonstrated that
a 4-week proactive schedule of WWT with diluted topical
corticosteroids (TCSs) was superior to WWT with moisturizer
in children with severe AD.[27] The first step of WWT is to
apply topical agents to the lesion. Next, the skin is covered
with a wet inner layer of tubular bandage followed by a
dry outer layer. Gauze or a cotton suit can be used as an
alternative. The WWT can be maintained from several hours
to a day at a time.
The panel members suggested that its use might not be
feasible in every region of India due to varied climatic
conditions. However, wherever suitable, it can be used in
severe or resistant patients older than 6 months of age,
but if used with TCSs it may be associated with the risk
of systemic absorption.
Recommendation of wet wrap therapy in AD
•Levelof Evidence:2b
Consensus Statement-XI
Wet wrap theory with diluted corticosteroids or
emollient with moderate to severe AD without risk of
infection can be used for the quick reduction of AD
severity.
First Line of Therapy
Moisturizers/emollients
Patients with AD suffer from dry skin and defective skin
barrier function. Regular use of moisturizer constitutes
the core of the management of AD. A moisturizer repairs
the skin barrier, maintains skin integrity and appearance,
reduces transepidermal water loss, and restores the
lipid barrier’s ability to attract, hold, and redistribute
water[28] [Table 5]. Data from RCTs show that moisturizers
have a long- and short-term steroid-sparing effect in
mild to moderate AD and in preventing AD flares.[29]
Table 5: Classification of moisturizers
Class Mechanism of action Mimics natural skin components Examples
Occlusive Moisturizers influence the skin barrier
function of normal skin to reduce TEWL and
susceptibility to irritants.
Intercellular lipid bilayers
Ceramide
Cholesterol
Free fatty acids
Beewax
Lanolin
Mineral oils
Paraffin
Petrolatum
Propylene glycol
Silicones
Squalene
Humectants Humectants are low-molecular-weight
substances with water-attracting properties.
They increase water absorption from the
deeper epidermis and dermis to the stratum
corneum
Natural moisturizing factors in
stratum corneum
Alpha hydroxyl acids
Glycerin
Hyaluronic acid
Propylene glycol
Urea
Emollients They have the ability to instill small droplet
of oil into the cracks between desquamating
corneocytes in dry skin and consequently to
improve the appearance of the skin in terms
of softness, flexibility and smoothness.
Natural lipids Lauric acid
Linoleic acid
Linolenic acid
Oleic acid
Stearic acid
TEWL: Transepidermal water loss
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Although no clinical trials have studied the proper amount
or frequency of moisturizer use in patients with AD,
moisturizer should be used at least twice daily and more
frequently during acute flare-ups. Adult patients with AD
should use approximately more than 250 g of moisturizer
per week.[30] It is recommended to use moisturizer within
3 min after taking a bath while the skin is still moist.
DEBM advised that moisturizers should be used in
continuation, even when the AD is clear. It should be
part of all treatment phases; mild, moderate, and severe.
Prescription emollient devices (PEDs) are a newer class
of topical agents designed to target specific defects in
skin barrier function observed in AD. There is limited
evidence to suggest that PEDs lessen symptoms and
signs of AD, including xerosis and inflammation. The
results of few head to head trials of PED versus over-
the-counter base moisturizers have shown no statistically
significant differences.[31] DEBM discussed the role of
PEDs, which are expensive in comparison to moisturizers
but can be helpful in selected scenario.
Moisturizers contain ingredients with anti-inflammatory
properties that may reduce or substitute the use of TCS,
thus minimizing their side effects.[32] An RCT between
aloe vera in olive oil cream versus 0.1% betamethasone
cream in the treatment of chronic skin lesions following
sulfur mustard exposure showed that aloe vera in olive
oil cream was at least as effective as betamethasone
0.1% after 6 weeks of applications.[33]
In acute inflammatory models, virgin coconut oil
showed moderate anti-inflammatory effects on ethyl
phenylpropiolate–induced ear edema in rats.[34] The main
nonglyceride constituents of shea butter have been reported
to be triterpene alcohols. With regard to the emollient effect,
in vivo and in vitro studies have shown that the biological
activities of triterpene acetate and cinnamate esters include
antiinflammatory and anti-tumor properties.[35]
Thus, the most constructive way to spare steroids and
avoid steroid-related side effects is through consequent
baseline emollient skin care combined with early
anti-inflammatory intervention to stabilize the disease
and prevent treatment-intensive flares.
Where the literature is (long-term randomized,
controlled trials in patients) lacking regarding use of
moisturizer and bathing habits
• Optimalfrequencyor duration ofbathing.
• Efcacyof thesoak andsmeartechnique.
• Optimalcleansercomposition.
• Efcacy of bath additives (eg, oatmeal, Epsom
salts, vinegar, or essential oils).
• Efcacyof watersofteners
• Comparison of soap versus synthetic detergents
(Syndets).
Recommendation for use of moisturizer in AD
• Level of Evidence: 1b (steroid sparing action of
moisturizer)
• Level of Evidence: 5 (ideal frequency of use of
moisturizer)
Consensus Statement-XII
The regular use of moisturizer has short and long term
steroid-sparing effects and reduces the frequency of
acute episodes.
Moisturizer should be used at least twice a day and
should be more frequently used during acute flares.
Topical corticosteroids
Topical corticosteroids (TCSs) are important
anti-inflammatory drugs for managing AD, especially
during acute stage. TCSs are first-line treatment for
patients with AD who have failed good skin care,
including moisturizer use.
Efficacy: RCTs have demonstrated safety and continued
efficacy of repeated courses of low- to mid-potency TCS
on active AD skin until clearance for up to 5 years in
children and up to 1 year in adults.[36]
Long-term proactive TCS: The proactive approach of
applying low–mid potency TCS twice weekly for the
prevention of flares in stabilized AD has been shown
to be effective in both adults and children.[37] Proactive
treatment (along with reactive) was found to be superior
to reactive only management in a year-long RCT in
pediatric patients.[38]
Classification: As per British National Formulary
Classification, TCSs are classified as very potent, potent,
moderate, and mild [Table 6].[39] A variety of factors
should be considered when choosing a particular TCS
for the treatment of AD, including patient age, areas of
the body to which the medication will be applied, and
other patient factors such as degree of xerosis, patient
preference, and cost of medication.
Long-term TCS adverse effects: When used cautiously,
long-term use of low to mid potency TCS is reasonably
safe. However, the long term use of TCS, especially if
high potency, may cause local side effects, such as,
striae rubrae, skin atrophy, telangiectasia, skin burning,
erythema and acneiform eruptions. In rare cases,
systemic effects may occur including hypothalamic–
pituitary–adrenal axis suppression, more frequently in
children due to the high ratio of total body surface
area to body mass, which is about 2.5 to 3 times higher
than for adults.[40] The use of twice-weekly proactive
treatment has not been shown to cause skin atrophy.[37]
Dosage: No universal standard exists for quantity
of application, although suggested methods include
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174 Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019
use of the adult fingertip unit (the amount from
the distal interphalangeal joint to the fingertip,
or approximately 0.5 g, being applied over an area
equal to two adult palms), following the rule of 9’s
that measures the percent of affected area and use
of charts that propose amounts based on patient age
and body site.
Frequency of application: Twice daily application of TCSs
is generally recommended for the treatment of AD;
however, evidence suggests that once-daily application
of some TCSs may be sufficient. Proactive, intermittent
use of TCSs as maintenance therapy (one to two times
per week) on areas that commonly flare is recommended
to help prevent relapses and is more effective than use
of emollients alone.
Recommendation for use of TCS in AD
• Levelof Evidence:1a
Consensus Statement-XIII
• TCSscan effectivelyrelieveADpruritus
• TCSs have a signicant effect in the short term
and long term treatment of AD
• TCSs are used as rst-line therapy along with
appropriate use of moisturizing agents
• Duringmaintenancetreatment,TCSscanbeapplied
weekly twice (weekend therapy) to “hotspots” as a
proactive management during maintenance
• Adequate and suitable quantities of TCS to be
used, should be discussed with the patient
attendant/care giver. They should be counseled
regarding finger-tip unit.
Topical calcineurin inhibitors
Topical calcineurin inhibitors (TCIs) (pimecrolimus
and tacrolimus) have been approved since 2002 for
anti-inflammatory therapy in AD.
Efficacy: RCTs have demonstrated that TCIs are
safe and effective when used twice daily for the
intermittent treatment of AD flares in children and
infants (3 months) for up to 5 years and in adults
for up to 1 year.[41] A meta-analysis of 25 RCTs found
tacrolimus 0.1% to be as effective as the mid-potency
TCS hydrocortisone butyrate 0.1%, whereas tacrolimus
0.03% is less effective than hydrocortisone butyrate
0.1% but more effective than the low-potency TCS
hydrocortisone acetate 1%.[42]
Strength: There are two available TCIs, tacrolimus
ointment and pimecrolimus cream. Both agents
have been shown to be more effective than vehicle
in short-term (3–12 weeks) and long-term (up to
12 months) studies in adults and children with active
disease.
Topical calcineurin inhibitors are approved for the
following ages
Pimecrolimus 1% cream: 2 years
Tacrolimus 0.03% ointment: 2 years
Tacrolimus 0.1% ointment: 16 years
The DEBM suggests that tacrolimus ointment 0.1% usage
should not be restricted to above 12 years. It can safely
be used for younger children.
Long-term proactive TCI: The proactive use of tacrolimus
has been shown to be effective and safe for up to 1 year
in both children and adults.
Long-term safety and adverse events of TCI: TCIs are
very safe, the most common side effect being skin
burning, which resolves in 80% of patients after
1 week. TCIs do not increase the risk of bacterial
infections, but the risk of viral infections such as
herpes simplex virus is slightly elevated.[43] There
was a boxed warning based on a theoretical risk of
malignancy against TCI since 2006. However, there is
no convincing evidence, either from controlled studies
with follow-up of patients or from studies of patient
databases that TCIs can induce malignant disease. The
largest and longest trial looking at infants treated
with pimecrolimus found no evidence of increased
malignancy risk.[44]
What the literature is lacking for TCS and TCI
• RCTsinvestigatingtheuseofbothTCIsandTCSon
the same site
• Comparison trials with the proactive use of TCIs
versus TCS.
Table 6: BNF classification of topical corticosteroids
Class Potency Generic name and strength
Class I Very potent Clobetasol propionate 0.05%
Class II Potent Beclometasone dipropionate 0.025%
Betamethasone valerate 0.1%
Betamethasone dipropionate 0.05%
Diflucortolone valerate 0.1%
Fluocinolone acetonide 0.025%
Hydrocortisone butyrate 0.1%
Mometasone furoate 0.1%
Triamcinolone acetonide 0.1%
Class III Moderate Alclometasone dipropionate 0.05%
Betamethasone valerate 0.025%
Clobetasone butyrate 0.05%
Fluocinolone acetonide 0.00625%
Fluocortolone 0.25%
Class IV Mild Hydrocortisone 0.1%-2.5%
Fluocinolone acetonide 0.0025%
BNF: British National Formulary
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Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019 175
Recommendation for use of TCIs in AD
• Levelof Evidence:1b
Consensus Statement-XIV
• TCIs have a signicant effect in the short-term
and long-term treatment of AD.
• TCIs can  be considered as rst-linetherapy along
with appropriate use of moisturizing agents
• Duringmaintenancetreatment,TCI canbe applied
weekly twice (weekend therapy) to “hotspots” as a
proactive management during maintenance.
Systemic corticostroids
Although systemic corticosteroids (CSs) improve the
clinical symptoms of AD, their administration should
generally be avoided because of adverse effects and
the rebound phenomenon. Their use should be limited
to short courses as a transition to a more sustainable
treatment. There are no long-term RCTs evaluating
efficacy and safety of systemic corticosteroids in AD.
There are two RCTs which studied the efficacy of systemic
CS in children. Both the trials were of low quality and
none of them studied methylprednisolone, which is the
most widely prescribed CS in clinical practice.[45,46] The
Practical Allergy (PRACTALL) Consensus Group guidelines
published in 2006 suggested that patients with acute
flares may benefit from a short course of systemic CSs,
but their long-term use, especially in children, should be
avoided.[47] A slow taper is advisable to decrease the risk
of rebound. There is no consensus on the duration of the
taper, but it should overlap with a steroid-sparing agent.
Special consideration should be made with pediatric
patients because of concerns with delayed or reduced
bone growth.
Recommendation for use of systemic corticosteroids in AD
• Levelof Evidence:5
Consensus Statement-XV
• Systemic corticosteroids have a largely
unfavourable risk/benefit ratio in AD treatment,
but may be an option in acute flare treatment.
• An initial dose of 0.5 mg prednisolone equivalent
/kg/day is recommended followed by a slow taper
to decrease the risk of rebound.
Second Line of Therapy
Cyclosporine
Cyclosporine (CsA) is an oral calcineurin inhibitor that
suppresses the activation of the T-cell transcription
factor, nuclear factor of activated T cells, inhibiting the
transcription of a number of cytokines, including IL-2.
It is approved for the treatment of adults with AD in
European countries, Australia and Japan.
Efficacy: Studies in both adults and children have
confirmed that cyclosporin is effective in the short-term
management of severe AD, at doses of 3–5 mg/kg/day.
RCT with 64 proven patients who received CsA had a
decrease both in the surface area of involvement and in
the degree of inflammation of the remaining dermatitis
at the 6 week time mark. Based on seven long-term RCTs,
CsA can be recommended as an effective second-line
agent for AD for up to 1–2 years in both adults and
children 2 years and older.[48]
Dosage and scheduling: CsA is applicable to patients
16 years of age or older with failure/resistance to
first-line therapies. The drug should be administered
twice a day at a daily dose of 3–5 mg/kg/day. CsA
has been shown to be effective and relatively safe
in four long-term RCTs in adults who received up
to 1 year of continuous treatment.[48] Low starting
doses (3 mg/kg/day) and high starting doses (5 mg/
kg/day) were found to be equally effective (EASI/body
surface area improvement) after 2 weeks.[49]
Adverse effects and monitoring: Irreversible
nephrotoxicity, infection, hypertension, electrolyte
disturbances, dyslipidemia, tremor, hypertrichosis,
headache, gingival hyperplasia, and nonmelanoma skin
cancer are the major serious side effects of CsA. Two
or more months with serum creatinine more than 30%
above baseline may predict irreversible nephrotoxicity.[50]
These adverse effects may occur regardless of daily
dosage used, but high dose and low dose groups have
only been compared and measured over short periods of
time (up to 12 weeks).[51]
Pediatric considerations: CsA is an effective treatment for
AD in the pediatric population, similar to adults. Both
continuous long-term (up to 1 year) and intermittent
short-term dosing schedules (3- to 6-month courses)
are efficacious. CsA can be used in children older than
2 years of age. Long-term safety in children has not yet
been established and caution should be exercised.
Recommendation for use of Cyclosporine in AD
• Levelof Evidence:1a
Consensus Statement-XVI
• Cyclosporine is the first choice among systemic
immunomodulators in moderate to severe AD
patients who are unresponsive to conventional
topical treatment methods.
Third Line of Therapy
Phototherapy
Morison et al. first attempted to treat refractory AD
with oral psoralen and ultraviolet (UV) light, with
success.[52] Phototherapy can be used as monotherapy
or in combination with emollients and topical
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176 Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019
steroids. Few clinical studies suggest that UV-B and
UV-A1 are efficacious in the management of AD.[53,54]
The use of light therapy may decrease the need for
topical steroid and topical immunomodulator use.
The common adverse effects include actinic damage,
local erythema and tenderness, pruritus, burning, and
stinging. Rarer side efffects include nonmelanoma
skin cancer, melanoma (mostly with PUVA), lentigines,
photosensitive eruptions, folliculitis, photo-onycholysis,
HSV reactivation, and facial hypertrichosis.[52-54]
There is still no standard protocol for the optimal
dose, duration, and frequency of narrowband (NB)-UVB
treatment [Table 7]. The optimal treatment dose of
UVA1 has not been determined yet. Considering the
low accessibility of UVA1 devices compared with other
modalities of phototherapy, NB-UVB offers the most
efficacious and cost-effective evidence based treatment
for patients with chronic AD.
Studies document the safe and effective use of both UVA
and UVB phototherapy in children and adolescents.[55]
However, there is an increased risk of nonmelanoma skin
cancer in children receiving PUVA treatment.[56]
Recommendation for use of Phototherapy in AD
• Levelof Evidence:2a
Consensus Statement-XVII
• UV therapy can be one of useful treatment
modalities for moderate to severe AD.
• UVA1 (acute phase) and NB-UVB (chronic phase)
are the most suitable phototherapy modalities for
AD treatment.
• NB-UVBisthemostpreferredphototherapyoption
because of better availability
Azathioprine
Off-label use of azathioprine (AZA) can be considered
in adult patients unresponsive to, contraindicated to,
or experiencing adverse effect with CsA. Double-blind
placebo-controlled studies demonstrate that AZA improves
both QOL and signs and symptoms of the disease when
used in patients with AD as monotherapy.[57,58]
Measurement of the enzyme thiopurine
methyltransferase (TPMT) is recommended before the
initiation of treatment. A dose of 1–3 mg/kg/day is
recommended depending on TPMT activity.
Nausea, vomiting and other gastrointestinal (GI)
symptoms are common while on AZA. The other side
effects include headache, hypersensitivity reactions,
elevated liver enzymes and leukopenia. There is literature
to support the use of AZA to treat AD in the pediatric
population, but the dosage and optimal duration of
therapy still needs to be defined.[59,60]
Recommendation for use of Azathioprine in AD
• Levelof Evidence:1a
Consensus Statement-XVIII
• Azathioprine should be considered as a second-
line choice among systemic immunomodulators
in adult patients unresponsive to or experiencing
side effects with cyclosporine.
Mycophenolate mofetil
A long-term RCT investigating mycophenolic acid showed
similar efficacy to CsA (3 mg/kg/day) in adults after
the 10th week of therapy, but a delayed onset of action
in the mycophenolic acid group.[61] Insufficient data
exist to make recommendations regarding the optimal
mycophenolate mofetil (MMF) dosing or duration of
therapy for patients with AD.
Recommendation for use of Mycophenolate mofetil in AD
• Levelof Evidence:1b
Consensus Statement-XIX
• Mycophenolate mofetil, administered at a dose of
1.5 g/day or less, has long term safety and can
be considered as an alternative immunomodulator
in adult patients unresponsive to or experiencing
side effects with cyclosporine.
Dosing ranges from 0.5 to 3 g/day. MMF is generally well
tolerated, with GI symptoms being the most commonly
encountered. Hematologic (anemia, leukopenia,
thrombocytopenia) and genitourinary (urgency,
frequency, dysuria) symptoms were rarely reported.
Methotrexate
The true efficacy of methotrexate (MTX) in the treatment
of refractory AD is unknown, because of inadequate
data. In an RCT comparing MTX (10–22 mg/week) with
AZA (1.5–2.5 mg/kg/day) in adults with severe AD, both
treatments were found to have similar effects on disease
severity.[62] Based on only two small long-term RCTs,
MTX seems to be a well-tolerated and effective third-line
Table 7: Guidelines for narrowband UVB according to
skin type
Skin
type
Initial UVB
dose
Dose increment
after each treatment
Maximum
dose
I 130 mJ/cm215 mJ/cm22000 mJ/cm2
II 220 mJ/cm225 mJ/cm22000 mJ/cm2
III 260 mJ/cm240 mJ/cm23000 mJ/cm2
IV 330 mJ/cm245 mJ/cm23000 mJ/cm2
V 350 mJ/cm260 mJ/cm25000 mJ/cm2
VI 400 mJ/cm265 mJ/cm25000 mJ/cm2
UV: Ultraviolet
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Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019 177
option for the long-term treatment of moderate-to-severe
AD in both children (above 8 years) and adults.
Recommendation for use of Methotrexate in AD
• Levelof Evidence:2b
Consensus Statement-XX
• Methotrexate can be considered as a second-line choice
among systemic immunomodulators after cyclosporine.
Fourth Line of Therapy: Biologics and
Emerging Therapies
Crisaborole
Crisaborole is a topical phosphodiesterase-4 inhibitor that
reduces the production of proinflammatory cytokines.
In two short-term (28 days), identically designed,
multicenter, phase III studies in this patient population,
topical therapy with crisaborole ointment 2% reduced
disease severity and pruritus severity compared with
vehicle, with the effect established early and sustained
over the course of treatment.[63]
Dupilumab
Dupilumab is a fully human monoclonal antibody directed
against the IL-4a receptor a-subunit, which blocks the
signaling of both IL-4 and IL-13, the two key drivers
of type 2 immune response.[64] In 2017, dupilumab was
approved by the US Food and Drug Administration (FDA)
for treatment of moderate to severe AD in patients 18 years
of age and older. A systematic review and meta-analysis of
efficacy and safety of dupilumab treatment in moderate
to severe AD provided evidence that dupilumab had an
acceptable safety profile and resulted in clinically relevant
improvements in signs and symptoms of AD.[65]
Omalizumab
Limited data exist to determine the efficacy of
omalizumab in the treatment of AD. One double-blind,
placebo-controlled study did not show clinical
improvement in AD with its use despite reducing free
serum IgE levels.[66] In general, treatment of AD with
omalizumab is not recommended.
Other biologicals
On the basis of positive case reports, there is limited
experience for the use of ustekinumab, rituximab,
tocilizumab, and alefacept in AD. Current evidence does
not allow use of these biologicals in AD, except for some
exceptional situation.
Apremilast
Apremilast, an oral phosphodiesterase-4 inhibitor, was
FDA-approved in September 2014 for the treatment
of moderate-to-severe plaque psoriasis. However, its
upstream anti-inflammatory effects, ease of use as
an oral agent, and mild side effect profile make it an
interesting treatment option for AD as well. Multiple
open-labeled trials of apremilast in moderate-to-severe
AD produce conflicting reports on efficacy, some showing
fair and other showing limited efficacy.[67,68]
Interferon gamma
There are a few studies on IFN-γ that demonstrate its
efficacy in the treatment of AD.
High‑dose intravenous immunoglobulin
A review of literature showed improvement was observed
in 61% of patients with AD treated with high-dose
intravenous immunoglobulin (hdIvIg). Adults appeared
less likely to respond (48%) than children (90%), and
the duration of response was also more prolonged in
children. Adjunctive therapy in adults was more effective
than monotherapy (59% vs. 0%), whereas monotherapy
was effective in 90% of children. HdIVIg may offer a safe
potential therapeutic avenue for resistant cases of AD,
particularly in children, but should be further assessed
using double-blind placebo-controlled trials.[69]
Recommendation for use of Biologics and Apremilast in AD
• Levelof Evidence:5
Consensus Statement-XXI
• In patients with recalcitrant atopic
dermatitis, biologics especially dupilumab or
phosphodiesterase-4 inhibitor like apremilast
can be used as off-label therapy. However, the
costeffectiveness should be seriously considered.
Maintenance Therapy
The proactive use of topical anti-inflammatory therapy to
address subclinical inflammation is an effective, contemporary
clinical strategy for the management of AD. Systematic
review of RCTs reporting efficacy of TCSs and/or TCIs for
flare prevention in AD reveals efficacy of proactive treatment
with TCS and TCI to prevent AD flares. The trials, however,
do not allow firm conclusions about long-term safety beyond
1 year.[69] Indirect evidence from vehicle-controlled trials
suggests that twice-weekly application of the potent TCS
may be more efficacious to prevent AD flares than tacrolimus
ointment.
Recommendation for proactive treatment with
intermittent TCS or TCI in AD
• Levelof Evidence:1a(TCS)
• Levelof Evidence:1b(TCI)
Consensus Statement-XXII
• Proactive treatment with intermittent TCS therapy
during long-term follow-up is helpful to reduce
acute flares.
• Proactive therapy with tacrolimus ointment is
effective to reduce the occurrence of flares.
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Adjunctive Treatment
Alitretinoin
Alitretinoin, also known as 9-cis-retinoic acid, is a
recently developed retinoid derivative. Alitretinoin is
useful for the treatment of chronic hyperkeratotic atopic
hand eczema.
Probiotics/prebiotics
Probiotics (Lactobacillus alone or Lactobacillus with
Bifidobacterium) appeared to play a protective role in AD
prevention upon administration in the pre- and postnatal
periods. However, there is no evidence to support the
benefit of probiotics in infants.[70]
Essential fatty acids
Diet supplementation with evening primrose oil or an
omega-3 fatty acid (docosahexaenoic acid) is safe and
may be helpful in AD, but there are still insufficient
RCT data assessing clinical efficacy for this method to be
recommended.
Vitamin D
RCTs have reported contradictory results for the
therapeutic value of vitamin D supplementation in
AD. One meta-analysis showed that serum vitamin D
level was lower in the patients with AD, and vitamin
D supplementation could be a new therapeutic option
for AD. Vitamin D has a potentially significant role for
improving the symptoms of AD. The results from this
study suggest that vitamin D supplementation may help
ameliorate the severity of AD and can be considered as a
safe and tolerable therapy.[71]
Conclusion
AD has a profound impact on the physical, mental, and
social well-being of the patients and the parents. These
guidelines suggest a treatment algorithm for patients
with AD. However, to achieve high treatment efficacy,
compliance, and patient satisfaction, treatment decisions
should be made jointly by the treating physician and
the patient or parents. It is of paramount importance
to consider disease severity, socioeconomic factors,
psychological status, and the patient’s desire for
treatment, before choosing an appropriate treatment for
individual patient with AD.
Acknowledgements
The authors acknowledge Knowledge Isotopes Pvt. Ltd.
(http://www.knowledgeisotopes.com) for the medical
resources. Wockhardt Ltd., Mumbai, provided the
Treatment Algorithm for Atopic Dermatitis
Rajagopalan, et al.: Consensus on atopic dermatitis
Indian Journal of Dermatology | Volume 64 | Issue 3 | May-June 2019 179
scientific and financial support for the conduct of expert
group meetings.
Disclaimer
This guideline reflects the best available evidence at
the time of preparation. Adherence to these guidelines
may not ensure successful treatment in every situation.
The treating physician must make the ultimate judgment
regarding the choice of any specific therapy in the
context of circumstances for individual case scenarios.
Financial support and sponsorship
Wockhardt Ltd., Mumbai, provided the scientific and
financial support for the conduct of expert group
meetings.
Conicts of interest
There are no conflicts of interest.
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... Dermatol Ther (Heidelb) The management practice of AD varies across Asian countries and territories (Table S1), including Hong Kong, India, Indonesia, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam. When managing patients with moderate-to-severe AD, countries tend to follow their own national guidelines [6,[13][14][15][16][17][18][19]. In geographically diverse India, hospitals across the country even developed individualized guidelines in response to the different setting-specific management approaches used. ...
... In geographically diverse India, hospitals across the country even developed individualized guidelines in response to the different setting-specific management approaches used. However, existing national AD guidelines, along with previously developed regional consensus, have largely excluded recommendations on advanced novel treatments such as biologics and Janus kinase (JAK) inhibitors, as they were authored prior to the availability of these newer treatment options in the region [6,[13][14][15][16][17]20]. Consequently, physicians in these Asian countries may over-rely on nonregion specific disease management recommendations (such as those described in the 2022 EuroGuiDerm AD guidelines) to manage patients with AD, even though, ideally, treatment choices should take into consideration the barriers and limitations faced by patients in these countries [21,22]. ...
... When used for acute AD, the use of UVA1 has been shown to reduce SCORAD scores after 3 weeks of treatment, with results being evident after the first week of treatment [94,95]. Meanwhile, narrowband UVB (NB-UVB) was found to reduce total disease activity, extent of dermatitis, Dermatol Ther (Heidelb) Adults • Short-term treatment for acute flares [15,16] • To bridge treatments [15,75] • The next treatment option after failure with topical treatments [14,20] • An adjunct therapy to control itch [22] • For people with comorbidities and are not suitable for conventional DMARDs • A third-line treatment option [14,15], starting with the following priorities: CsA > AZA or MTX > MMF [15][16][17] CsA is recommended in young and fit patients [15][16][17]. In case of contraindications or treatment failure, physicians should then consider azathioprine or methotrexate, followed by MMF [15][16][17] c Owing to cost considerations d Baricitinib may be considered in patients with noncontraindicated comorbidities owing to its lower efficacy rates in clinical trials [82][83][84] e This practice is common in Singapore. ...
Article
Full-text available
Rapid progress made in the management of atopic dermatitis (AD) in recent years and the differences in patient journey between Asian and non-Asian populations call for a review of current atopic dermatitis landscape in Asia. A roundtable meeting with nine regional dermatological experts was held in June 2023 to discuss the optimal management approaches for moderate-to-severe AD, focusing on the use of advanced therapies. Disease burden on patients’ quality of life, treatment adherence, and financial constraints were identified as major concerns when managing patients with moderate-to-severe AD in parts of Asia. It was agreed that the Hanifin and Rajka’s criteria or the UK Working Party’s Diagnostic Criteria for Atopic Dermatitis can be used to guide the clinical diagnosis of AD. Meanwhile, patient-reported outcome scales including the Dermatology Life Quality Index and Atopic Dermatitis Control Tool can be used alongside depression monitoring scales to monitor treatment outcomes in patients with AD, allowing a better understanding for individualized treatment. When managing moderate-to-severe AD, phototherapy should be attempted after failure with topical treatments, followed by conventional disease-modifying antirheumatic drugs and, subsequently, biologics or Janus kinase inhibitors. Systemic corticosteroids can be used as short-term therapy for acute flares. Although these advanced treatments are known to be effective, physicians have to take into consideration safety concerns and limitations when prescribing these treatments. Treatments in AD have evolved and its management varies country by country. Unique challenges across Asian countries necessitate a different management approach in Asian patients with AD.
... 1 It is characterized by recurrent eczematous lesions 1 , and intense itch 1 and is often associated with elevated serum immunoglobulin E (IgE) levels. 2 It affects up to approximately 2.4% of the population worldwide 3 and can also appear in adults. 1 Onset of AD usually presents by the age of five years, but timely diagnosis and treatment will avoid future complications and improve patients' quality of life. 4 As per the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence of atopic dermatitis in India is 2.7% (age 6-7 years) and 3.6% (age 13-14 years). ...
... 6 Emollients remain the mainstay treatment for atopic dermatitis as they improve the epidermal barrier function, maintain skin integrity and appearance, reduce trans epidermal water loss, and restore the lipid barrier's ability to attract, hold, and redistribute water. 2 The Indian guidelines also recommend the use of Moisturizers & Emollients as a firstline treatment for AD. 2 Emollients contain a humectant or moisturizer (promoting stratum corneum hydration) and an occludent (reducing evaporation such as lipids or petrolatum). Emollients containing moisturizers are better compared to those without, for reducing investigator-reported severity and leading to fewer flares and reduced usage of topical corticosteroids (TCS). ...
... 6 Emollients remain the mainstay treatment for atopic dermatitis as they improve the epidermal barrier function, maintain skin integrity and appearance, reduce trans epidermal water loss, and restore the lipid barrier's ability to attract, hold, and redistribute water. 2 The Indian guidelines also recommend the use of Moisturizers & Emollients as a firstline treatment for AD. 2 Emollients contain a humectant or moisturizer (promoting stratum corneum hydration) and an occludent (reducing evaporation such as lipids or petrolatum). Emollients containing moisturizers are better compared to those without, for reducing investigator-reported severity and leading to fewer flares and reduced usage of topical corticosteroids (TCS). ...
Article
Full-text available
The prevalence of atopic dermatitis (AD) in India is 2.7% (age 6–7 years) and 3.6% (age 13–14 years). Emollients remain mainstay treatment for atopic dermatitis. The present review article focuses on the role of active ingredients in emollients towards the management of AD. Article were selected by searching in database like Google Scholar and PubMed and were reviewed by the authors. Daily use of emollients from birth may significantly reduce the incidence of AD in a high-risk population. Emollients with a variety of active ingredients to target AD pathophysiology have been developed which contain active ingredients like liquorice extract (anti-inflammatory and anti-pruritic), niacinamide (restoration of barrier function), sterols (restoration of barrier function), laureth-9-polydocanol (anti-pruritic), xylitol (microbiome maintenance) and galacto-oligosaccharide (GOS) (microbiome maintenance). Emollient plus may be a useful adjunct to pharmacological therapy in AD and as maintenance therapy, providing rapid and significant improvements in skin moisture, epidermal barrier function, and signs and symptoms of AD.
... [4] Emollients, topical corticosteroids, topical calcineurin inhibitors, and phototherapy are the mainstays of treatment for AD; however, moderate to severe AD is frequently resistant to these treatments. [5] Although immunomodulatory drugs (such as cyclosporine, methotrexate, and azathioprine) had been tried in refractory AD with varying degrees of effectiveness, a better understanding of the pathogenesis has opened the door to the prospect of the novel, targeted therapies. [6] In various inflammatory skin conditions, including AD, the JAK inhibitors have been explored and proven to be beneficial. ...
... Cyclosporine, azathioprine, and methotrexate are some of the other systemic treatments that have been suggested in the Indian context. [5] The US FDA has approved dupilumab as the first targeted biologic medication for the treatment of adults with moderate to severe AD. The authors have published the first reports from India, where dupilumab was successfully used to treat 25 adult patients with AD. [6] However, due to its high price and limited availability, the use of dupilumab in patients with refractory AD in India has remained out of reach for most patients who actually need it. ...
Article
Full-text available
Background Atopic dermatitis (AD) has a complex etiology that includes Th2 polarization, which is accompanied by the cytokines IL4, IL-5, IL-13, and IL-31, as well as Th17 and Th22, and in chronic lesions, Th1 cells. Tofacitinib inhibits Th1-, Th2-, and Th17-associated cytokines by selectively blocking JAK1 and JAK3 receptors. We conducted a multicentric, retrospective chart analysis to study the efficacy and safety of tofacitinib in patients with moderate to severe refractory AD. Materials and Methods We included 16 adult patients (aged >18 years) with moderate to severe AD who had previously undergone systemic therapy with inadequate response. In the baseline, demographic data, previous treatment history, severity scores (eczema area and severity index [EASI] and SCORing Atopic Dermatitis [SCORAD]), and quality of life score (Dermatology Life Quality Index [DLQI]) were noted. Baseline blood investigations, including complete blood count, liver function test, renal function test, lipid profile, and interferon gamma release assay for tuberculosis, were done. Patients were followed up every month for 6 months that included documentation of severity scores, blood investigations, and DLQI. Any adverse events, if reported, were noted. Result All 16 patients completed the 6-month trial. Our patients were previously treated with cyclosporine (n = 10), methotrexate (n = 3), or both (n = 3). The mean EASI scores improved from 23.38 ± 9.56 at baseline to 8.50 ± 7.57 at the end of 6 months. The mean SCORAD score improved from 41.25 ± 8.69 at baseline to 14.93 ± 7.82 at the end of 6 months. Quality of life also improved as the mean DLQI improved from 15.18 ± 2.73 at baseline to 5.31 ± 4.11 at the end of the study period. No severe adverse reactions were noted, but 3 patients experienced dyslipidemia and 2 patients had altered bleeding time. Conclusion Tofacitinib is a safe and effective treatment option for recalcitrant moderate to severe adult AD.
... [19] Topical corticosteroids may cause skin atrophy, telangiectasia, rosacea, and acne [2] whereas topical calcineurin inhibitors may be associated with burning and stinging and theoretical risk of malignancy. [2] In patients not responding to topical treatment, systemic agents [22] and phototherapy [18,23] are the options. Examples of systemic agents include immunosuppressive therapies including cyclosporine, methotrexate, mycophenolate mofetil, corticosteroids, and other newer agents. ...
... [22] Moisturizers/emollients, topical corticosteroids, and topical calcineurin inhibitors are among the first-line treatment options, whereas cyclosporine and phototherapy are recommended as second-line and third-line options, respectively. [23] Despite several available options, differences in efficacy and suboptimal patient satisfaction due to poor compliance and very high expectations from the patients demand newer agents for the management. ...
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Atopic dermatitis is a chronic inflammatory dermatological condition associated with intense pruritus seen in all age groups and ethnic diversities. It can have a significant impact on the quality of life. The options for treatment include skincare, topical therapies, systemic therapies, and phototherapy. Treatment of atopic dermatitis may be associated with several challenges including suboptimal efficacy, risk of adverse events, and limited patient satisfaction. A better understanding of the pathophysiology of atopic dermatitis has resulted in the evaluation of many treatment options. Phosphodiesterase 4 plays a role in the pathogenesis of atopic dermatitis and hence can be a target for treatment. Crisaborole 2% ointment is a phosphodiesterase 4 enzyme inhibitor approved for the treatment of mild‑to‑moderate atopic dermatitis in patients above 2 years of age by the USFDA. Currently, it is not approved for use in Indian patients. In this article, the role and potential place of crisaborole in the management of atopic dermatitis in Indian patients based on global experience and evidence is discussed.
... It is based on the Indian and European guidelines. [81][82][83] ...
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Atopic dermatitis (AD) a chronically relapsing dermatosis characterized by pruritus and a significant impact on the quality of life. Emollient and moisturizers are an integral part of its management and those containing natural moisturizing factors (NMF) and pseudoceramides are known to be efficacious barrier repair agents. Conventionally topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) are considered as the mainstay of treatment. Systemic medications such as azathioprine, cyclosporine and methotrexate may be associated with substantial side effects, with long-term usage. Novel therapeutic agents such as Janus kinase (JAK) inhibitors, subcutaneous monoclonal antibodies and topical PDE4 inhibitors targeting the complex pathophysiology have been recently developed. Dupilumab is a subcutaneous monoclonal antibody and is FDA approved. Amongst the newer topicals, Crisaborole ointment is found to be potentially effective and is FDA approved. Only dupilumab and crisaborole have been successfully marketed for patients <18 years of age.
... 4 Atopic dermatitis is a potential contributor to cause debilitating symptoms, and it significantly reduces the patient's quality of life. 5,6 Due to the heterogeneity in age, ethnicity, and lifestyle factors of patients, the etiology of atopic dermatitis has not been fully clarified. 7---9 Currently, topical application of emollients and anti-inflammation agents is still the basic strategy for treating atopic dermatitis. ...
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Background The treatment for atopic dermatitis (AD) has been the focus of clinical research, and behavioral intervention is considered an indispensable treatment method. To our knowledge, no relevant meta-analysis has evaluated the effects of behavioral interventions on atopic dermatitis. Objectives To evaluate the effects of behavioral interventions on atopic dermatitis. Methods The authors searched PubMed, EMBASE, and Cochrane CENTRAL to retrieve relevant RCTs (up to Feb 2022). The search strategy involved a combination of related keywords. The Cochrane Q and I² statistics were used to assess heterogeneity. Results Six RCTs involving seven reports with 246 patients were included. The results suggested that behavioral interventions could relieve eczema severity (correlation coefficient [r = −0.39]; p < 0.001) and scratching severity significantly (r = −0.19; p = 0.017), while not affect itching intensity (r = −0.02; p = 0.840). A sensitivity analysis confirmed the robustness of the results. Study limitations An important limitation of this study was the insufficient number of RCTs and the limited sample size. In addition, the study lacked a control group receiving a type of intervention other than the experimental protocol. Another limitation was the short duration of follow-up. Conclusions This study suggests that behavioral interventions could be effective in treating atopic dermatitis by reducing eczema and scratching severity. Additionally, habit-reversal behavioral therapy may be more effective for treating atopic dermatitis.
... ,21 . U Hrvatskoj nisu dostupni TKS I. i IV. kategorije, dok dostupni betametazon, prednizolon i metilprednizolon pripadaju u jake, a mometazon i alklometazon u umjereno jake. ...
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Psorijaza je imunološki posredovana kronična upalna bolest kože i zglobova. Najčešći oblik psorijaze jest vulgarna ili kronična stacionarna psorijaza, a očituje se pojavom eritematoznih plakova prekrivenih srebrnkastim ljuskama, praćenih svrbežom. Rjeđi oblici psorijaze jesu kapljičasta, eritrodermijska i pustulozna psorijaza te psorijaza praćena psorijatičnim artritisom. Procjena težine bolesti vrši se pomoću kliničkih bodovnih sustava, a važna je zbog odabira prikladne terapije. Prvu liniju liječenja blage do srednje teške psorijaze čini lokalna terapija, dok je kod težih oblika bolesti te pacijenata koji nemaju adekvatan odgovor na lokalnu terapiju ili fototerapiju, indicirana sustavna terapija. Postoji mogućnost kombiniranja lokalne i sustavne terapije, a u određenim slučajevima i fototerapije. U skladu sa smjernicama Hrvatskog dermatovenerološkog društva prva linija lokalnog liječenja psorijaze jest fiksna kombinacija kalcipotriola i betametazon propionata jednom dnevno uz mogućnost proaktivnog liječenja dva puta tjedno. U terapiji održavanja prvenstveno se preporučuje fiksna kombinacija kalcipotriola i betametazon propionata jednom ili dva puta tjedno. U slučaju psorijaze lica i intertriginoznih regija preporučuje se započeti liječenje lokalnim kortikosteroidima, a potom nastaviti s lokalnim inhibitorima kalcineurina. Lokalni pripravci u liječenju psorijaze neizostavan su dio liječenja blage do srednje teške psorijaze, ali i potpora liječenju težih oblika psorijaze uz sustavnu terapiju.
... Hence, it needs increased patient education. [3] Phosphodiesterase 4 (PDE4) regulates inflammatory cytokine production in AD by degrading cyclic adenosine monophosphate (cAMP). Inflammatory cells in AD patients have higher PDE4 *Corresponding author: Abhishek De, Department of Dermatology, Calcutta National Medical College, Kolkata, West Bengal, India. ...
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Objectives Managing mild-to-moderate atopic dermatitis (AD) often necessitates topical therapies, and one such recently introduced option is crisaborole ointment. This study sets out to assess the efficacy and safety of crisaborole ointment in pediatric cases of AD over four weeks. Material and Methods Nineteen children between 2 and 16 years old with mild-to-moderate AD were enrolled and treated with crisaborole ointment twice daily in affected areas for 30 days. The primary objective was to appraise the shift in the investigator’s static global assessment (ISGA) scores (0–4) every week for the four-week follow-up. The severity of pruritus score (SPS) was another secondary objective. Furthermore, individual indicators of clinical signs that included erythema, exudation, excoriation, induration/papulation, and lichenification, were examined with subjective scores (0–3). Children’s dermatology quality of life index (CDLQI) was employed to study the quality of life. Results Following four weeks of crisaborole ointment treatment, the average ISGA score declined from 2.58 ± 0.61 to 0.95 ± 0.78, signifying a substantial reduction in AD severity ( P < 0.001). The SPS score also decreased from a mean of 2.32 ± 0.478 to 0.84 ± 0.60 ( P < 0.001), underscoring a significant reduction in itching. Moreover, individual markers for clinical signs of AD, including erythema, exudation, excoriation, induration/papulation, and lichenification, all exhibited statistically significant improvement. Crisaborole ointment was well tolerated. Only 6 of the 19 patients reported a localized burning sensation, which was manageable. No patient needed to be withdrawn during the study period. The CDLQI showed a substantial drop in scores, decreasing from an average of 13.79 ± 3.57 at the commencement to 6.74 ± 1.97 ( P < 0.001). Furthermore, 14 out of 19 patients met the study’s primary goal, achieving at least a 2-point reduction in ISGA along with the attainment of clear or nearly clear skin (ISGA 0–1). Conclusion Our study found crisaborole ointment significantly improved pediatric AD symptoms and was well-tolerated. The only adverse event was localized burning in a few patients. Further, research is needed for validation.
... Pityriasis alba was the third most common among the eczemas in our study, whereas it was <2% in the studies done in Iraq and Ethiopia. This might be because pityriasis alba [43] is common in higher skin phototypes (Indian) with prolonged sun exposure and dry skin as additional risk factors in desert regions. ...
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Background While phototherapy is a well-established treatment for many dermatoses, data from the literature regarding its use in elderly patients are quite limited. Objective In this study, we aimed to determine the phototherapy indications in geriatric patients and to evaluate the effectiveness and reliability of phototherapy in this group. Methods This study included 95 patients of 65 years of age and older who were treated in our phototherapy unit between 2006 and 2015. The data for this study were collected retrospectively from patient follow-up forms in the phototherapy unit. Results Phototherapy was administered to 28 (29.5%) patients for mycosis fungoides, 25 (26.3%) patients foplaque type psoriasis, 12 (12.6%) patients for palmoplantar psoriasis, 12 (12.6%) patients for generalized pruritus, and 18 (19%) for other dermatoses. Of the patients, 64.2% had received a narrowband UVB (NB-UVB), 21.1% oral psoralen UVA (PUVA), and 14.7% local PUVA treatment. A complete response was achieved in 76.9-85.7% of the mycosis fungoides and in 73.71-100% of the psoriasis vulgaris patients treated with NB-UVB and PUVA, respectively. All the patients with generalized pruritus were treated with NB-UVB, and 80% of these patients achieved significant improvement. The erythema rate was found to be 0.43% per session for NB-UVB treatment and 0.46% per session for PUVA treatment as a side effect. Study limitations The limitations of our study are that it was retrospective and the remission durations of the patients are not known. Conclusion This study showed that phototherapy is effective and reliable in the elderly population with proper dose increases and close follow-up.
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Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is an inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level. The basics of treatment discussed in this guideline are based on the ?Guidelines for the Treatment of Atopic Dermatitis 2008? prepared by the Health and Labour Sciences Research and the ?Guidelines for the Management of Atopic Dermatitis 2015 (ADGL2015)? prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the ?Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2016? together with those for other allergic diseases.
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Background: Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks. Objective: We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792). Methods: Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus. Results: More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity. Limitations: Short study duration was a limitation. Conclusions: Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
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Background Many clinicians have concerns about the safety of atopic dermatitis (AD) treatments, particularly in children requiring long-term daily maintenance therapy. Topical corticosteroids (TCS) have been widely used for >5 decades. Long-term TCS monotherapy has been associated with adverse cutaneous effects including atrophy, rebound flares, and increased percutaneous absorption with potential for adverse systemic effects. Topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, available for 1–2 decades, are not associated with atrophy or increased percutaneous absorption after prolonged use and have much lower potential for systemic effects. However, since 2006 TCIs have carried a controversial Boxed Warning based on a theoretical risk of malignancy (eg, skin and lymphoma) that has limited TCI use for standard-of-care maintenance therapy. Methods A comparative systematic search of PubMed was done for long-term (≥12 week) clinical trials of TCS or TCI treatment in patients <12 years with AD. Citations were reviewed for inclusion based on MeSH terms, abstracts, and relevant article text. Studies were excluded if they did not encompass subjects <12 years, or were <12 weeks’ duration, retrospective, meta-analyses, or limited to anecdotal case reports. Results Of 27 trials meeting criteria, 21 included 5825 pediatric patients treated with TCIs, and 6 included 1999 patients treated with TCS. TCS studies were limited to low- to mid-potency products, and all but one study lacked a vehicle control. Eight TCI studies were vehicle-controlled, and safety data were well reported, with ≤5 % of patients reporting discontinuation due to adverse effects (DAEs). Cutaneous and systemic adverse events (AEs) were similar in TCI and vehicle groups, with no reports of lymphoma. Safety data in TCS trials were less well reported. DAE incidence was addressed in just 2 trials, and systemic and cutaneous AEs were mostly unreported. Conclusions Data supporting long-term use of TCIs are robust, documenting safety and efficacy, while data supporting long-term TCS use are limited to low- to mid-potency products. Our review identifies a lack of information on the safety of commonly prescribed, long-term monotherapy with mid- to high-potency TCS in pediatric AD, and supports standard-of-care maintenance therapy with TCIs and intermittent use of low- to mid-potency TCS for flares.
Article
Background: Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD). Objective: We aimed to assess the overall efficacy and safety of dupilumab treatment in AD. Methods: PubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively). Results: Six trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = -0.89, 95% CI: -1.0 to -0.78), percentage of body surface area (BSA) (SMD = -0.83, 95% CI: -0.90 to -0.75), pruritus numeric rating scale (NRS) scores (SMD = -0.81, 95% CI: -0.96 to -0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = -0.78, 95% CI: -0.89 to -0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04). Conclusions: Our analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.
Article
The optimal method and dosage for topical application of moisturizers (Hirudoid®Soft and Hirudoid®Lotion) were investigated. To this end, we examined the Finger-tip unit(FTU), moisturizing effects for artificial dry skin at varying dosages, moisturizing effects at varying frequencies of application, and the relationship of moisturizing effects to the timing of topical application after bathing. The results suggest that FTU serves as a convenient and reliable indicator of the optimal dosage of moisturizers, and that higher moisturizing effects may be obtained if the moisturizers are applied at dosages slightly higher than the seemingly appropriate dosage, at frequencies higher than usual and soon after bathing.
Article
Many patients with mild to moderate atopic dermatitis (AD) are managed by identifying and avoiding allergens and irritants, ensuring skin moisturization, and graded use of topical corticosteroids and/or calcineurin inhibitors. There is little consensus on the next step. Most systemic therapies are "off label" in the United States and include phototherapy, cyclosporine, mycophenolic acid precursors, azathioprine, and methotrexate. The decision to use these therapies should be based on efficacy and safety readouts from well designed, long-term trials. This article reviews the long-term randomized, controlled trials examining safety and/or efficacy of interventions recommended for patients with mild to severe AD.
Article
Atopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www. awmf. org).