Download superantigens in atopic dermatitis

Atopic Dermatitis
Dr.F.Iraji
Atopic Dermatitis
About 10 percent to 20 percent of all infants
have eczema; however, in nearly half of these
children, the disease will improve greatly by the
time they are between five and 15 years of age.
Others will have some form of the disease
throughout their lives.
interactions between environmental,
immunological, genetic and
pharmacological factors.
Atopic Dermatitis
A strong familial inheritance pattern seems to
exist for both AD and other atopic diseases, with
more than half of patients with AD reporting a
family history of respiratory atopy.
Researchers are continuing to examine the role
that chromosomal markers (chromosomal 11),
eosinophilia,
cell-mediated
immunity,
interleukins, and other inflammatory mediators
play in the pathophysiology of AD
Atopic Dermatitis
Immunological abnormalities associated
with
AD
include:
elevated
T-cell
activation; an imbalance in the Th1/Th2 Tcell subsets; increased production of
inflammatory cytokines; elevated IgE
levels (in the majority of cases); increased
numbers of dendritic cells and mast cells;
and increased numbers of eosinophils in
the peripheral circulation.
Cutaneous Immune response
The Langerhans cell, as well as T-cells,
and keratinocytes by production of
cytokines. T-cell cytokines can be divided
into Th-1 cytokines, the prototype being
gamma
interferon,
Th-2
cytokines
including Interleukins-4, 5, and 10.
Cutaneous diseases
primarily Th-1
mediated including psoriasis and allergic
contact dermatitis whereas the prototype
of the Th-2 mediated disease is atopic
dermatitis.
Atopic Dermatitis
the presentation of antigen by dendritic
cells mediated by IgE molecules bound to
FceRI receptors; intrinsic defects in
keratinocyte function; delayed eosinophil
apoptosis; disruption of prostaglandin
metabolism
and
the
effects
of
Staphylococcus aureus colonisation and
superantigen production.
Atopy and atopic
dermatitis (AD)
Worldwide increased incidence of Atopy
and AD, mainly in developed countries,
could be related to environmental as well
as psychosocial factors. Exposure to
infections very early in life and the use of
probiotics of Lactobacillus rhamnosus in
mothers might protect against the
development of AD.
superantigens in atopic
dermatitis
S. aureus exacerbates or maintains
skin inflammation in AD is by
secreting a group of toxins known to
act
as
superantigens.
These
molecules
stimulate
marked
activation of T cells and accessory
cells expressing HLA-DR.
superantigens in atopic
dermatitis
over half of AD patients have S.
aureus cultured from their skin that
secrete superantigens such as
enterotoxins A, B and toxic shock
syndrome toxin-1 (TSST-1).
superantigens in atopic
dermatitis
most AD patients make specific IgE
antibodies
directed
against
the
staphylococcal superantigens found on
their skin. These findings raise the
possibility that superantigens induce
specific IgE in AD patients and mast cell
degranulation
in
vivo
when
the
superantigens penetrate their disrupted
epidermal barrier.
superantigens in atopic
dermatitis
correlation has been found between
the presence of IgE to superantigens
and severity of AD. Patients with
superantigens on their skin generally
have increased IgE levels to specific
allergens.
superantigens in atopic
dermatitis
the combination of topical steroids
with antibiotics are much more
effective than either topical steroids
or antibiotic therapy alone. This
suggests that S. aureus secrete
products which interfere with the
action of steroids.
superantigens in atopic
dermatitis
superantigens can induce steroid
resistance. Therefore antibiotics may
enhance steroid action by reducing S.
aureus superantigens on the skin. These
data indicate that effective therapy in AD
requires a combination of therapies which
reduce skin inflammation and S. aureus
on the skin.
The atopic itch
The atopic itch is considered to be a
fundamental symptom of atopic dermatitis
(AD) to the extent that a non itching rash
excludes a diagnosis of AD. substance P
have been shown to modulate the function
of inflammatory cells and those of the
endothelium and epithelium through
effects on cell proliferation, cytokine
production and adhesion molecule
expression.
The chemical mediators of
itch
substances act on the sensory
receptors that respond to itch
stimuli. The result of this interaction
is the perception of itch at the site of
mediator release.
Substance P
sensory nerve-derived neuropeptide
that demonstrates a number of
proinflammatory bioactivities and is
thought to play a role in
inflammatory skin disease
Substance P
The neurotransmitter responsible for
carrying sensations of pain between
the brain and the skin. It also
stimulates vasodilatation in the
arterioles and increased permeability
of capillaries in the epidermis.
Substance P
Stimulate mast-cell degranulation,
and thus, histamine release. When
injected into the skin, substance P
produces the wheal-and-flare
response typical of the effects of
histamine on the skin - redness,
swelling, and itch.
House dust mite and
the Atopy patch test
identification of allergens which may
be responsible for the exacerbation
of skin lesions in atopic dermatitis
(AD) are based on the identification
of specific IgE in the skin (prick
tests) or in the serum (RAST, etc).
patch test
Patch tests based on prolonged
exposure of the skin to inhalants or
food, aiming at the detection of
delayed reactions, represent a
testing modality reproducing skin
responses to allergens normally
occurring in AD.
patch test
Problems related to patch testing in
atopics mainly concern
standardization of patch test
modalities (exposure times and
reading) and of the allergenic
materials
patch test
delayed skin reactivity in healthy
subjects and other control
populations has been poorly
investigated and this hampers the
understanding and the interpretation
of skin responses to Atopy patch
tests in patients with AD and
respiratory Atopy
Major criteria (need 3 or more)
Pruritus
Typical morphology and distribution
Flexural lichenification in adults
Facial and extensor involvement in infants and
children
Dermatitis - Chronically or chronically relapsing
Personal or family history of atopy (asthma,
allergic rhinitis, atopic dermatitis
Minor
Minor criteria need 3 or more) )
Cataracts
Cheilitis
Conjunctivitis - Recurrent
Eczema - Perifollicular accentuation
Facial pallor or erythema
Food intolerance
Hand dermatitis – Non allergic
Ichthyosis
IgE- Elevated
Immediate (type I) skin test reactivity
Infections (cutaneous(
Minor
Dennie-Morgan infraorbital fold
Itching when sweating
Keratoconus
Keratosis pilaris
Nipple dermatitis
Orbital darkening
Palmar hyperlinearity
Pityriasis Alba
White dermographism
Wool intolerance
Xerosis
Physical
Acute lesions are erosions with serous exudate
or intensely itchy papules and vesicles on an
erythematous base.
Subacute lesions are characterized by scaling,
excoriated papules, or plaques over
erythematous skin.
In its chronic phase, skin shows lichenification
and pigmentary changes (increased or
decreased) with excoriated papules and
nodules.
Typical AD for Infants and Toddlers
Affects the cheeks, forehead, scalp, and extensor surfaces
Erythematous, illdefined plaques on
the cheeks with
overlying scale and
crusting
Erythematous, illdefined plaques on
the lateral lower leg
with overlying scale
33
More Examples of Atopic Dermatitis
Note the distribution of face and extensor surfaces
34
Typical AD for Older Children
Affects flexural areas of neck, elbows, knees, wrists, and ankles
Lichenified,
erythematous
plaques behind the
knees
Erythematous,
excoriated papules
with overlying crust
in the antecubital
fossa
35
Physical
The pattern of disease varies based on the
age of the patient.
Infants: Lesions typically develop during the
third month of life. Dry, red, scaly areas appear
on the cheeks but spare the perioral and
perinasal areas .
Physical
The lips may become affected as the child smacks
and licks the lips during winter months .
Usually, the diaper area is spared, although infants
may develop lesions and lichenification at easy to
reach crevices: directly below the diaper, extensor
surface of the forearm, or back of the hand .
If the scalp is involved, it may be very difficult to
distinguish AD from seborrheic dermatitis
Children:
– Atopic dermatitis appears in areas of repeated
flexion and extension (antecubital fossae,
neck wrists, and ankles). Areas of high
perspiration are most often affected,
especially when combined with form-fitting
clothing. Lesions are red, scaly, have sharply
demarcated borders, and develop
lichenification over time .
Adults
These patients develop generalized
eruptions. These are the patients
whose mood and behavior are most
affected by AD, especially as the
disease causes social embarrassment
and sleep disruption .
The disease may actually remit in
many of the pubescent patients.
Adults
Atopic dermatitis during adulthood most commonly
manifests as hand dermatitis, because adults are
exposed to irritating chemicals and they wash their
hands more frequently than children .
Eyelid inflammation is common in adults with AD
and causes patients to rub excessively at their
eyes. This may cause atopic pleats (DennieMorgan infraorbital fold), an extra line on the lower
eyelid that, although common in patients with AD,
is also seen in patients without the disease
Other associations
Dry skin and xerosis: A hallmark of AD,
patients have rashes and severely dry skin
that itches. Even infants with AD have
excessively dry skin, especially in the
winter months. Continued moisturized and
mild soaps help with this.
Other associations
– Ichthyosis vulgaris can be observed in
patients with atopic dermatitis. Characterizing
features are dry, rectangular scales on the
extensor surfaces of the arms and legs. This
condition is treated with 1% ammonium
lactate lotion and often improves with age.
– Hand and foot dermatitis may be the only
manifestation in adults and adolescents.
Fissuring of the palms, soles, and fingers
often occurs.
Other associations
– Keratosis pilaris is an asymptomatic condition
where horny follicular papules on the extensor
surfaces of the upper arms, buttocks, and
anterior thighs (sparing the palms and soles).
Lesions may also appear on the face and may
be confused with acne, especially in the
adolescent patient. Treatment may be with
topical steroids or ammonium lactate cream.
– Hyperlinear palmar creases may be seen in
patients with AD often associated with
continued itching and scratching.
Other associations
– Keratoconus is an elongation and protrusion of the
corneal surface, which is seen in a few patients with
AD. Its appearance is not associated with cataracts.
– Patients with AD do have a higher likelihood of
cataracts; however, most of these are asymptomatic.
The appearance of cataracts may be related to the
use of systemic steroids throughout the lifetime of the
patient with AD.
– Pityriasis alba (asymptomatic, hypopigmented scaling
plaques on the face and arms) may also be seen in
patients with AD. No acute treatment is indicated.
Causes
Exact etiology is unknown, but several triggers
have been identified. Anything that could dry the
skin may exacerbate atopic dermatitis. Potential
triggers include excessive bathing, swimming,
hand washing, and lip licking.
Contact with solvents, detergents, deodorants,
cosmetics, and soaps can exacerbate the
disease. Cigarette smoke has also provoked
inflammation.
Causes
Patients are extremely sensitive to temperature changes.
They should avoid clothing that traps heat or causes
sweating. They will also see increased flare-ups during
times of low humidity, as dry air exacerbates the
disease. Commercial humidifiers may help with the
symptoms.
Although no direct correlation has ever been
documented, most AD show increased sensitivity to
aeroallergens like dust mites. Some researchers believe
these allergens can trigger exacerbations of AD, but this
has not been proven.
Other Problems to be
Considered
Lichen simplex chronicus
Seborrheic dermatitis
Nummular eczema
Xerotic eczema
Dyshidrotic eczema
Prelymphomatous
Drug reactions
Hyperimmunoglobulin E syndrome
Photosensitivity rashes
Wiskott-Aldrich syndrome
Lab Studies
The diagnosis of AD is based on history and
physical examination. Laboratory tests are not
helpful for diagnosing atopic dermatitis;
however, they may be used to exclude other
disorders.
Serum immunoglobulin E (IgE) levels usually are
elevated. This may be useful for treating
refractory AD with anti-IgE antibodies
(omalizumab). This medication is not currently
approved for AD treatment.
Procedures
Biopsy: Pathologic findings include
spongiosis with a severely damaged
stratum corneum, with hyperproliferation in
advanced case
Before prescribing a treatment plan
a dermatologist considers the type of eczema,
extent and severity of the eczema, patient’s
medical history, and a number of other factors.
Medication and other therapies will be
prescribed as needed to:
Control itching
Reduce skin inflammation
Clear infection
Loosen and remove scaly lesions
Reduce new lesions
Atopic Dermatitis: Treatment
4 Major Components
Anti-inflammatory
Anti-pruritic
Antibacterial
Moisturizer
54
Care
Many patients with AD present to a clinic
during acute exacerbation. Therapy is
targeted toward alleviation of pruritus and
prevention of scratching. ED physicians
must also look for signs and symptoms of
bacterial superinfection and treat
accordingly.
Skin care
– In the acute setting patients should be
instructed to bathe once-to-twice daily using
mild soaps (eg, Dove). There is no preference
over showers or baths, whichever makes the
patient most comfortable.
– The patient should dry quickly and
immediately (within 3 min) lubricate the skin.
Many creams and lotions are available, and
the optimal one is the greasiest the patient
can tolerate.
Skin care
– Creams (eg, Eucerin, Cetaphil) are preferred
over lotions, as they have lower or no water
content and will not evaporate off of the skin
during the day. Parents may use petroleum
jelly on infants, but most children and adults
will not tolerate the texture
Topical steroids
Acute attacks should be treated by midhigh strength topical steroids for up to 2
weeks. Medium-to-high potency topical
steroids should not be used on the face or
neck area because of the potential
adverse effects. These are preferred over
low-mid strength medications, as they
better control exacerbations. Patients
should apply the ointment within 5 minutes
of twice-daily bathing.
Antihistamines:
Physicians have been prescribing
antihistamines for years to control the
pruritus associated with acute AD. Little
evidence exists that antihistamines help
with the itching in an awake patient;
however, the use of sedating
antihistamines is supported to control
scratching while the patient is asleep.
Systemic steroids
The use of systemic steroids in the treatment of
acute exacerbation of AD is controversial. Most
authors reserve oral prednisone (at least 20
mg/d for 7 d) for the most severe cases,
although it seems the disease quickly relapses
once the medication is discontinued. Patients
also tend to discontinue topical steroid creams
and other treatment as they feel better, which
contributes to the relapse after oral steroids are
done .
Advances in the treatment
of AD
Topical immunosuppressive drugs
(tacrolimus and pimecrolimus) and
leukotriene receptor antagonists, the
preventive role of systemic antistaphylococcal antibiotics, and
topical moisturizers.
Topical Immunomodulators
Immunosuppressive macrolides are
synthesized by fungus-like bacteria of
various Streptomyces strains. Of these
macrolides, tacrolimus (FK506, Prograf®,
Protopic®) and sirolimus (rapamycin,
Rapamune®) are natural products,
whereas pimecrolimus (ASM 981, Elidel®)
is semi synthetic
Topical Immunomodulators
Topical Immunomodulators (TIMs)
represent a new class of therapeutic
agents, which specifically target T-cell
activation through a mode of action
completely distinct from that of
corticosteroids. Tacrolimus (Protopic®) is
the first in this new class of topical
immunomodulatory agents.
Topical Immunomodulators
Topical agents that can down regulate an
immune response can include Tacrolimus,
which acts by inhibiting early cell cycle
stages of T-cell activation by blocking
nuclear factor of activated T- cells in the
nucleus (NFAT). Pimecrolimus also inhibits
T-cell activation and both agents have
demonstrated efficacy in atopic dermatitis.
Topical Immunomodulators
As a consequence, the activation of
T-cells is inhibited at an early stage,
including the expression of
inflammatory T-cell cytokines such
as interleukin (IL-2, IL-3, IL-4, IL-5),
granulocyte-macrophage colonystimulating factor, interferon-g and
tumor necrosis factor a.
Topical Immunomodulators
The effect of TIMs has also been studied
on antigen-presenting cells, as well as
their impact on the release of pre-formed
inflammatory mediators from mast cells
and basophils and it seems that their
immunomodulatory properties have a
positive effect on the overall immune
mechanisms underlying AD.
Topical Immunomodulators
TIMs bind to the same receptor within Tlymphocytes, an immunophilin referred to
as the FK-binding protein (FKBP). The
TIM-FKBP complex binds calcineurin,
inhibiting its dephosphorylating action and
thereby the nuclear factor of activated Tcells is prevented from translocating to
the nucleus.
Tacrolimus (Protopic®)
The first in this new class of topical
immunomodulatory agents, effective
for chronic actinic dermatosis, special
types of psoriasis and seborrheic
dermatitis etc.
Tacrolimus ointment
Highly effective treatment of AD and is
known to be a potent inhibitor of T-cell
activation in the skin. It has recently been
demonstrated that epidermal dendritic
cells (DCs) isolated from untreated
lesional skin of AD patients highly
stimulate autologous T-cells. This activity
was greatly diminished concurrent with
clinical improvement during application of
tacrolimus.
Tacrolimus Ointment
(0.03%-0.1%BID)
immunomodulatory effects of topical
tacrolimus extend beyond its pronounced
effect on T-cells located in the skin, by
also positively affecting other cellular
players involved in the pathogenesis of
AD.
Tacrolimus ointment
Furthermore, there was a
concomitant decrease in the
expression of FceRI in LCs and
inflammatory dendritic epidermal
cells (IDECs). Decrease in the IDEC
population within the pool of
epidermal DCs suggesting a
reduction in local inflammation.
Pimecrolimus Cream
Pimecrolimus (Elidel, ASM981) cream 1%,
a selective inhibitor of inflammatory
cytokine release, was found to be safe and
effective in the management of adult
patients and children with atopic
dermatitis. A significant improvement of
eczema and relief of pruritus was
observed within the first week.
pimecrolimus 1% cream
safe and effective therapy in children
as well as infants being able to
prevent the progression and
recurrence of the disease and thus
offering an excellent therapeutical
approach for the long-term
management of atopic dermatitis.
Pimecrolimus 1% cream
effectively improve eczema even in
severe cases, to prevent the
occurrence of eczema and to
significantly reduce the incidence of
recurrences as well as the use of
corticosteroids in children as well as
infants.
Indications of Tacrolimus
It is effective in a variety of
inflammatory dermatoses, specially
those responsive to cyclosporin. Its
main indication, however, is atopic
eczema.
Efficacy Tacrolimus in
atopic eczema
Long term studies performed up to 12
months showed the absence of severe
systemic side effects and very low or
unmeasurable serum concentrations.
Thus, Tacrolimus represents the first nonsteroidal anti-inflammatory drug for the
use in atopic eczema since the
introduction of glucocorticosteroids in the
1950.
Tacrolimus: clinical
results in Atopy
The era of immunosuppressive drugs in
dermatology has been heralded by the
introduction of cyclosporin. This drug is
useful particularly for severe inflammatory
skin diseases, but is ineffective on topical
application. Tacrolimus is the prototype of
topically active immunosuppressive
macrolides. , Tacrolimus is effective in
psoriasis only under occclusion ,skin ulcers
.
Topical calcineurin inhibitors:
are available for patients older than 2 years.
These medications may be used all over skin
surfaces (including face, neck, and hairline)
because they do not have the side effects seen
with topical steroids. Evidence supports the
twice-daily use of these creams during acute
exacerbation of AD, and some evidence exists
to support use up to 4 years. The long-term side
effects (including the possibility of increased risk
for malignancy) have not fully been elucidated.
Side effects of tacrolimus include burning and
stinging on broken skin .
Oral immunosuppressive agents:
Patients with refractory AD may benefit
from oral immunosuppressive agents,
such as cyclosporine A. This medication is
effective in treating severe AD in the acute
setting. It is not recommended for longterm use.
Light treatment (phototherapy)
is another option for unresponsive and severe eczema.
People with eczema often comment that sunshine
improves their skin, and light treatment is sometimes
offered in hospital dermatological centres. UVB light
therapy can be extremely beneficial, as can PUVA,
which involves a combination of a drug called psoralen
taken by mouth, followed two hours later by UVA light
treatment. Short-term side effects of light treatment
include sunburn-like reactions, and potential long-term
side effects include premature skin ageing and skin
cancer.
Alternative treatments
Gamolenic acid (evening primrose extract) is an
alternative remedy sometimes used to treat
eczema. It is thought that it might work by
increasing the levels of the essential fatty acid
that may be deficient in, and perhaps responsible
for the symptoms of, atopic eczema. Two
products containing gamolenic acid,. Evening
primrose oil is still available as a dietary
supplement from health food shops for those who
wish to try it, but it is no longer a licensed
medicine for the treatment of eczema. A three
month trial should be long enough to produce
benefits.
Traditional Chinese herbal
medicines
are another alternative treatment for eczema, though at
present it is unclear whether they do more harm than
good. Results from several studies have suggested that
patients with atopic eczema benefit from these therapies,
but there is also concern about the side effects of some
of the herbs on the liver and heart. Cases of
corticosteroids being illegally added to Chinese herbal
creams have also been reported, and this is hard to
monitor as the production of such herbal products is not
standardised or regulated. For these reasons it is
recommended that Chinese herbal remedies should only
be
used
under
specialist
supervision.
:Further Inpatient Care
Few patients with AD will require hospitalization.
Patients with cellulitis or severe secondary
infection may require IV antibiotics and sedation.
Deterrence/Prevention:
The mainstay of treatment for AD is prevention
of outbreaks. Patients should continue to take
short showers/baths followed by immediate
hydration of skin with emollients even during
rash-free times.
They should also continue to avoid any triggers
that my exacerbate AD.
Complications
Because of frequent scratching and fissuring of
the skin, secondary infection is not uncommon.
Suspect infection in persons with fever,
surrounding erythema, or yellow crusting of the
lesions. In severe exacerbations, it may be
difficult to identify signs of secondary infection;
empirical treatment for infection may be
warranted.
Eczema herpeticum
(Kaposi varicelliform eruption) can be a
life-threatening complication of atopic
dermatitis. Most commonly seen during an
initial infection with HSV in a child whose
AD has recently healed, the vesicular
eruption can progress from mild to fatal
quickly.
Eczema herpeticum
This disease should be suspected in any child with a
remote history of AD, high fever, lymphadenopathy, and
vesicular eruption, especially of the face. Affected patient
should be treated with acyclovir (dose appropriate for
age) and monitored closely.
Atrophy or striae occur if fluorinated corticosteroids are
used on the face or in skin folds.
Systemic absorption of steroids may occur if large areas
of skin are treated, particularly if high-potency
medications and occlusion are combined.
Prognosis
About 90% of patients with AD have
spontaneous resolution by puberty .Adults
who continue to have the disease usually
have localized dermatitis (eg, chronic hand
or foot dermatitis, eyelid dermatitis, lichen
simplex chronicus.)
Prognosis
Unfavorable prognostic factors for AD (in
order of relative importance) include the
following:
– Persistent dry or itchy skin in adult life
– Widespread dermatitis in childhood
– Family history of AD
– Associated bronchial asthma
– Early age at onset
– Female gender
Prognosis
The objective when treating a patient for
AD is control of exacerbations, not
elimination of the disease. Using the
above treatment modalities, patients and
their families can hope to minimize the
frequency and severity of outbreaks.
Patient Education
Instruct patients about proper skin
care. Patients should bathe
appropriately, keep skin well
lubricated, use mild soaps, and
avoid known triggers.
The goal is control, not cure.
Special Concerns
Given the chronic nature of this disease
and patients' concerns about appearance,
emotional support and psychological
counseling may be helpful. Physicians
need to be sensitive to the needs of
patients and their families
Dupilumab
is a fully human monoclonal antibody that
binds to the alpha subunit of the IL-4
receptor. Through blockade of this
receptor, dupilumab inhibits downstream
signaling of IL-4 and IL-13, cytokines of
type 2 helper T lymphocytes (Th2) that are
believed to play a key role in atopic
diseases, including asthma and atopic
dermatitis.
Dupilumab
Dupilumab was evaluated in four small,
industry-sponsored randomized trials in adult
patients with moderate to severe atopic
dermatitis. In the largest study, 109 patients
were randomly assigned to receive weekly
subcutaneous dupilumab at a dose of 300 mg
(55 patients) or placebo (54 patients). At 12
weeks, 85 percent patients in the active
treatment group had a 50 percent or greater
reduction in the Eczema Area and Severity
Score versus 35 percent in the placebo
group.
dupilumab
The results of these trials indicate that
dupilumab may be an alternative systemic
therapy for long-standing atopic dermatitis in
adults, despite the relatively low proportion of
patients achieving complete or near-complete
clearance after 16 weeks of treatment. The
results of two ongoing maintenance and
open-label extension trials are expected to
provide additional information on the longterm efficacy and safety of dupilumab for the
treatment of atopic dermatitis.
Crisaborole
Crisaborole is a small-molecule, topical
phosphodiesterase-4 inhibitor in clinical
development for the treatment of mild to
moderate atopic dermatitis. Preliminary
studies in adolescents and adults
indicated that crisaborole 2% ointment
may improve the clinical signs of atopic
dermatitis, including erythema, excoriation,
exudation, lichenification, and, in
particular, pruritus.
Crisaborole
Adverse effects of topical crisaborole were
mild and mainly limited to application site
reactions (pain, paresthesia). Systemic
exposure to crisaborole appears to be
limited even after maximal use (3 mg/cm2
Crisaborole
crisaborole
appears
a
promising
nonsteroidal topical treatment for mild to
moderate atopic dermatitis. However,
studies of longer duration than four weeks
are needed to evaluate its long-term
efficacy and safety
Thank you for your attention