ARTICLE
Auteur(s) :, Jean-Philippe Lacour
Questions put to the panel
Question 1:
What is the natural history of atopic dermatitis, what is its
epidemiology, what are the pathophysiological bases?
Question 2:
To what extent are complementary examinations useful in the
diagnosis and treatment of childhood atopic dermatitis?
Question 3:
How should flare-ups of atopic dermatitis in children be
treated?
Question 4:
What adjuvant measures are useful and how can flare-ups of
atopic dermatitis be prevented in children?
Question 5:
How should severe atopic dermatitis be managed in
children?
Introduction
Atopic dermatitis (AD) or atopic eczema is a chronic inflammatory
skin disease which is characterized by pruritic outbreaks of acute
eczema occurring on a background of permanent xerosis. It often
starts in infancy and mainly affects children but may persist into
adulthood. It is a common condition which is increasing in
frequency, particularly in the industrialised world, and is thus
becoming a public health preoccupation. Atopic dermatitis is of
concern to many health professionals and has also been the subject
of numerous scientific studies but it remains controversial. There
are several issues which divide practitioners in the management of
AD. These differences are sometimes between the approaches of
different specialities but can also often be found within a single
speciality. Examples of areas of disagreement include the role of
food allergies and the avoidance diets which are sometimes used as
a first approach; the preventive or curative advantages of breast
feeding; the need for allergological investigations; the use of
corticosteroids; the role of the new topical immunomodulators; the
benefits of topical or systemic antistaphylococcic treatment; the
true value of thermal cures or homeopathy; and the role of stress.
This lack of consensus, along with the chronic nature of AD,
results in many parents of atopic children trailing ‘nomadically’
through the medical world in search of treatment solutions which
they do not find. Fear of corticosteroids, insufficient use of
emollients, unsuitable avoidance diets and use of alternative
medicine are all attitudes which are detrimental to the treatment
of children and may even be dangerous for their health. Lastly,
this dermatosis is costly, both for the family and for the health
service, and has a major impact on the quality of life of both the
child and his parents.
The objective of the consensus conference was to provide for
both health care personnel and patients a critical analysis of
current management of childhood AD. The target population is the
child, infant to adolescent.
The aims are to improve management of the disease by the
simplifying and harmonising practices regardless of the discipline
concerned: dermatology, pediatry, allergology, general practice, to
which must be added the other persons concerned with the care of
the atopic child: nurses, child care assistants, pharmacists….
The participants
The groups participating in the consensus conference included
representatives of all the professionals concerned with childhood
AD.
An organising committee was set up with 8 members representing
the following disciplines: dermatology, pediatry, allergology,
immunology and general medicine.
A bibliographical group, consisting of six readers trained in
literature analysis, undertook a critical and objective study of
publications in the field of AD.
An expert group of 14 representatives of all the specialities
presented their points of view and experience in reply to the
questions put during the plenary session of the Conference on
Wednesday October 20 2004 at the Institut Pasteur in Paris.
A panel of 13 members was formed, maintaining a balance between
the specialities concerned, (dermatology, pediatry, allergology,
general medicine, immunology), private medical practice and
hospital doctors (research and non-research), and the geographical
location of the different teams.
For this sixth Consensus Conference, promoted by the Société
Française de Dermatologie, the methodology of the Agence Nationale
d’Accréditation et d’Évaluation en Santé (ANAES) was used.
Bibliographical search
An analysis and objective summary of the large amount of
information published in the literature on this subject was
undertaken by a group trained in the critical reading of medical
articles. The search was carried out electronically using data
found in Embase, Medline, Online journal sources, the Cochrane
Central Register of Controlled Trials and the Cochrane Database of
Systematic Reviews, within the following criteria: publication
dates – 01/01/1990 to 01/06/2004; Children aged 0-18 years; human;
French or English language. Articles were classed according to the
level of scientific proof, according to the criteria of the ANAES.
The level of proof of the articles was determined in the following
manner:
- – Level 1: large-scale randomised comparative trials or
meta-analyses of comparative randomised trials.
- – Level 2: small-scale randomised comparative trials, non
randomised, well-run studies, cohort studies.
- – Level 3: case -control studies.
- – Level 4: comparative studies containing important bias,
retrospective studies, case series, descriptive epidemiological
studies.
The experiences and expectations of patients were taken into
account during the review of the literature, in particular
concerning education and quality of life.
Recommendations
The recommendations of the panel were made in accordance with the
opinions of the experts and the information provided by the
bibliography group. Its task was to combine and classify
information from multiple and diverse sources. The benefits, side
effects and health risks were taken into consideration when forming
these recommendations. Unresolved questions were debated. Finally,
the consensus text defines the optimal medical strategy when faced
with childhood AD. The text was written using the scientific proofs
available, while noting that the absence of proof does not indicate
absence of efficacy; these recommendations clarify what is
appropriate and what is not, and what should be the object of
further studies.
The recommendations proposed by the panel have been graded A, B
or C, in function of the level of scientific proof provided in the
literature (table 1)( Table 1 ).
Level A: established scientific proof confirmed by studies at
level 1.
Level B: scientific assumption on the basis of level 2
studies.
Level C: low level of scientific proof (studies at levels 3 or
4).
In the absence of studies at a sufficiently high level, the
panel took into account normal professional practices while trying
to recommend common sense propositions.
Table 1 Recommended grading system for clinical
studies
|
Level of scientific proof found in the literature
|
Recommended grade
|
- Level 1
- – large-scale randomised comparative trials
- – meta-analyses of comparative randomised trials
- – analysis of decisions based on well run studies
|
A) Established scientific proof
|
- Level 2
- – small-scale randomised comparative trials
- – non randomised, well-run studies
- – cohort studies
|
B) Scientific assumption
|
- Level 3
- – case-control studies
|
C) Low level of scientific proof
|
- Level 4
- – comparative studies containing important bias
- – restrospective studies
- – case series
- – descriptive epidemiological studies (transversal,
longitudinal)
|
|
Presentation
The short text contains the key recommendations which correspond to
the main clinical questions. The long text provides detailed
information on the scientific proof on which the recommendations
are based. These recommendations reflect current knowledge; an
update procedure is envisaged, along with a post-recommendation
survey of practices, reviewing items chosen during the preliminary
survey. This has been programmed for 2006. Publication of the
updates will be in the main scientific journals in the specialities
concerned, the journals of the co-organising Societies and on the
website of the Société Française de Dermatologie
(www.sfdermato.org).
Editorial independence
The organisation of the association “Conférence de Consensus en
Dermatologie” is financed by the Société Française de Dermatologie
and by the inscriptions to the main conference. The conclusions and
recommendations presented in this document have been drawn up by
the panel independently and without financial support from any
interested organisation. All the panel members have declared that
they personally had no conflict of interest.
Question 1: What is the natural history of atopic dermatitis,
what is its epidemiology, what are the pathophysiological
bases?
Definition
Atopic dermatitis (AD), or atopic eczema, is an inflammatory skin
disease which mainly concerns infants. Atopy includes AD, asthma
and allergic rhinoconjuntivitis. The diagnosis of AD is clinical
and is validated by the criteria of the United Kingdom Working
Party as a chronic relapsing pruritic dermatosis mainly affecting
the flexural folds.
The clinical aspect varies according to age
AD starts from the first weeks of life with a symmetrical
appearance, predominantly on the convex areas of the face and
limbs. Dryness of the skin (xerosis) is common. Pruritus is
constant from the age of 3 months, often associated with sleep
disturbance. The appearance of the lesions varies according to
whether they are in acute phase or remission at the time
examination.
Children over the age of 2
Lesions are usually located on the folds (neck, elbows, knees) and
extremities (hands, wrists, ankles). Lichenification (thickening of
the skin) is a frequent symptom and indicates a chronic local
pruritis.
Adolescents
AD generally disappears during childhood. When AD persists into
adolescence, lichenification and xerosis are frequent. In addition,
the face and neck are characteristically affected by erythema.
Other atopic manifestions may be associated with eczema
Food allergy, most commonly before the age of 3, asthma in 1/3 of
cases, and allergic rhinitis may occur in these children. The risk
of these occurrences depends on the age at which AD began and
varies according to different studies.
Complications may arise
- – Staphylococcus aureus colonises both healthy skin and
lesions in AD. Secondary infection can be difficult to recognise,
particulary in exudative forms. The presence of unusual pustular or
crusted lesions suggests this complication.
- – Herpes can be responsible for serious secondary
infection by viral diffusion on the eczema areas. A rapid change in
the appearance of the lesions and/or the presence of umbilicated
vesicules and pustules are danger signs for this infection.
Association with fever or a general malaise suggests eczema
herpeticum (Kaposi-Juliusberg disease) which requires urgent
treatment.
- – Allergic contact dermatitis: this is more common in
children with AD and should be suspected where there is an unusual
location and/or persistence, even worsening, of the condition
despite good compliance with treatment.
- – Delayed growth may be associated with severe AD. This is
rectified when the AD is treated effectively.
How should the severity of AD be measured?
Severity scores
There are several clinical scores for evaluating the severity of
AD. These scores have the advantage of enabling comparison from one
consultation to another. SCORAD (Scoring of Atopic Dermatitis) is
one of the most used scores in clinical studies. It takes into
account the intensity of the clinical symptoms, the extent of the
dermatosis and the severity of the functional signs: pruritus and
loss of sleep. SCORAD can be used during each clinical consultation
for severe AD. It evaluates the condition of the patient’s skin at
a particular moment in time, enabling the precise objectives of the
treatment to be defined and offering a possible comparison from one
consultation to the next, while remaining reproducible from one
doctor to another (professional agreement). However, SCORAD does
not take into consideration the overall severity of the disease nor
of its evolution.
Quality of life measurements
The Quality of life (QOL) score depends on the adaptation of the
patient to his disease. Knowing it is of value in assessment of the
disease as it adds a qualitative score from the point of view of
the patient himself. The QOL is not systematically correlated to
clinical severity. There are QOL scales specific for AD for the
infant and child but also for those living with him. These scales
were developed in Britain and have been translated into French but
have not been subjected to transcultural validation. These QOL
scores are useful for prospective studies but are little used in
daily practice.
Epidemiology of AD
Few epidemiological studies have been undertaken in France. In the
ISAAC investigation by questionnaire in 1999, the prevalence of AD
in France was 8.8% in children of 6-7 years of age and 10.0% in
13-14 year olds. In other studies by questionnaire in Europe the
prevalence varied from 7% to 28%; in studies including a medical
examination they varied from 6% to 16%. The authors emphasise the
increase in the prevalence of the disease in the past 20 years and
its variable distribution in different social classes. The increase
in the prevalence of AD in higher social classes has been linked to
a reduction in exposure to infectious agents. This observation is
behind the hygiene hypothesis which believes that a reduction in
infections is responsible for changes in the innate immune system.
Pathophysiology
AD corresponds to the development of an inflammatory immune
response, occurring on a predisposed genetic background,
accompanied by anomalies in the skin barrier function. The
pathophysiological mechanisms at the origin of AD have not yet been
clarified but they consist of three elements.
Genetic factors
50% to 70% of patients with AD have a first degree relative
suffering from AD, asthma or allergic rhinitis. The transmission
mode of atopy is unknown but atopy is probably polygenic.
Immunological factors
Several recent discoveries have improved our knowledge of the
pathophysiology of atopic eczema:
- – the discovery of IgE molecules which bind to the surface
of antigen presenting cells in the skin;
- – the identification of allergen specific T cells in the
skin of AD patients;
- – the observation of eczema at the contact site during
atopy patch tests to environmental allergens.
Thus, eczema in AD represents a form of delayed hypersensitivity
reaction which involves lymphocytes and antigen presenting cells.
The development of a specific, protein-antigen, Th2-type,
inflammatory immune response is at the origin of eczema lesions in
AD. An immunological heterogeneity is found among AD patients. Two
principal immunological profiles have been identified: one consists
of hyper IgE blood level and high specific IgE levels. The first
group is readily associated with other atopic manifestations
(asthma, rhinitis and conjunctivitis): it is known as extrinsic or
allergic AD. The second group does not have a hyper IgE level and
has a minimal risk of asthma: this is referred to as intrinsic or
non-allergic AD.
Innate or induced anomalies of the epidermal barrier
Increase in the epidermal water loss and anomalies in the skin
lipids characterise the anomalies in the skin barrier which are
observed in AD patients.
Question 2: To what extent are complementary examinations
useful in the diagnosis and treatment of childhood atopic
dermatitis?
The diagnosis of AD is clinical. It is not necessary to carry out
complementary tests in order to treat an AD patient (professional
agreement). On the other hand, the possible role of allergens as
factors perpetuating certain ADs in children may lead to allergy
testing in specific cases (professional agreement).
Which allergy tests?
A positive allergy test only indicates that the child is sensitized
to an allergen, without proof that exposure to the allergen
triggers or maintains the symptoms. Whatever the results of allergy
tests, they should always be compared with the clinical history.
The tests used include:
- 1) Prick tests. There is no clearly defined limit
indicating positivity. The allergens tested are selected in
function of the age, the clinical history (detailed by questioning
the parents), the environment and diet of the child. They are
usually adequate to confirm sensitisation to an allergen.
- 2) The levels of specific IgE in the blood, screening
tests without identification of the allergen (Phadiatop and
Trophatop), and the total IgE levels in the blood do not confirm
the presence of an allergy with certainty. However, certain levels
of some specific IgE allergens in the blood can make further oral
provocation testing unnecessary.
- 3) Patch tests. The standard European series tests for
the main contact allergens. Testing an atopic child is of no
interest unless an additional contact allergy is suspected. The
atopy patch tests which were first developed for pneumallergens and
more recently for some dietary allergens (cow’s milk, wheat flour,
eggs) have not been standardised and are still being evaluated. The
usefulness of ready-made atopy patch tests is still to be
assessed.
- 4) An avoidance diet for diagnostic purposes should not
be started without a prior allergological investigation,
particularly for cow’s milk proteins, in infants. The avoidance
diet should be strictly based on the findings of the investigation.
In the absence of an improvement of the AD after one month, the
diet should be discontinued.
- 5) Food challenge tests (FC) aim to prove the
responsibility of a food allergy. The double-blind,
placebo-controlled FC is the gold standard, which is only possible
in a few centres in France. In practice open FC tests are mainly
used in services equipped to deal with an anaphylactic shock
reaction.
Which children should be tested?
1) Three situations were considered suitable (professional
agreement)
a) Serious AD, defined as a failure of appropriate treatment
with good compliance, even in infants fed exclusively on maternal
milk (maternal milk contains most of the alimentary proteins
consumed by the mother and can thus be a vector of sensitization by
proxy).
b) In an atopic child with a slowing-down or break in the
weight/height growth curve.
c) In a child with atopy associated with the following signs and
symptoms:
- – signs suggesting a food allergy after eating or having
contact with a food: oral syndrome, skin (urticaria, angioedema),
respiratory (asthma, rhinitis) or digestive (vomiting, diarrhoea)
manifestations, even anaphylaxis;
- – signs suggesting a respiratory allergy: asthma, rhinitis
or rhino-conjunctivitis;
- – signs suggesting a contact allergy: eczema localised in
an unusual place, the buttocks, palms and soles of the feet); AD
which does not respond to or is aggravated by the usual
treatment.
2) Other situations are still under discussion due to bias in
study enrolment and low levels of proof in the studies published.
They did not allow for consensus.
a) The presence of mild digestive symptoms (gastro-oesophageal
refluxes, crying, and digestive symptoms not controlled by the
usual treatment), symptoms so common that they have no diagnostic
value in infants.
b) A family history of severe atopy.
c) A very early appearance of cutaneous symptoms, before the age
of 3 months (the panel expressed reservations about the possibility
of confirming AD before the age of 3 months).
In the absence of sufficient proof and in view of their
differing opinions, the panel recommended that further prospective
studies should be carried out to evaluate these indications.
Why test?
In theory the complementary explorations in AD are first of all to
achieve a short-term improvement in the dermatosis but also to try
to determine the factors affecting the prognosis so that long term
preventive measures can be put in place.
Can AD be improved?
If an allergy is confirmed, avoidance is certainly recommended,
however, the effects on the AD are not always obvious and vary
considerably in function of the clinical context and the type of
allergen.
- – Contact allergy: it was agreed that avoiding the
allergen responsible improves allergic contact dermatitis
(professional agreement).
- – Dietary allergy: the results of avoiding alimentary
allergies on the course of AD remain debated (grade B). The panel
recommends that further ethical and methodologically acceptable
studies should be carried out.
- – Sensitization to pneumallergens: contradictory studies
at level 2 do not allow conclusions to be drawn about the efficacy
of avoidance of environmental factors, in particular the control of
house dust mite in bedding with special covers.
Is it possible to define prognostic markers for the evolution
of the disease?
- – Studies at various levels of scientific proof have
demonstrated a relationship between sensitization to eggs and the
severity of eczema. However, carrying out allergological tests to
establish an individual prognosis is not appropriate (grade
C).
- – Apart from the clinical severity of AD in an infant,
there are no prognostic factors which enable the risk of asthma
occurring during childhood to be assessed.
- – The level of total IgE has no value for early detection
of infants at risk of developing a chronic or severe AD.
Question 3: How should flare-ups of atopic dermatitis in
children be treated?
The treatment of AD is symptomatic. The objectives are to treat
flare-ups and prevent relapses with long-term treatment. A survey
of practices which was undertaken on a national scale showed a
great diversity in the therapies used by different practitioners,
particularly concerning topical treatments.
Topical corticosteroids
Topical corticosteroids have long been the only efficacious
treatment for this condition. They remain the reference for all new
products tested. They have a triple action, anti-inflammatory,
immunosuppressive and antimitotic. Their mechanisms of action are
not fully known.
Which are the available molecules?
There are several commercially available forms: creams, ointments,
lotions and gels. Topical corticosteroids are classed according to
the strength of their action. In contrast to the international
classification, French classification ranks anti-inflammatory
activity in a descending order. For reasons of consistency, the
panel recommends adopting the international classification of
topical corticosteroids: very strong (class or level IV), strong
(class or level III), moderate (class or level II), and weak (class
or level I). This has been used in the following text.
Which topical corticosteroid should be chosen?
The choice is made in function of the age of the patient, the
severity of the AD, the site and the area to be treated. Thus, very
strong topical corticosteroids (class IV) are contra-indicated in
infants and young children, on the face, the body folds and the
buttocks. Strong corticosteroids (class III) are reserved for short
term use in very inflamed or very lichenified forms on the limbs.
Moderate corticosteroids (class II) are used on the face, the
body folds and genital areas and for infants. Weak topical steroids
are of little therapeutic value. Not all these professional
practices are supported by studies at level 1.
Are topical corticosteroids effective?
- – In the acute stage: comparisons of topical
corticosteroids (limited trials, small numbers, imperfect
methodology) found that strong corticosteroids were effective more
quickly, but that those of a lower strength were just as effective
over a period of a few weeks.
- – In the prevention of relapses: one single study (level
1) showed the value of a maintenance therapy for the prevention of
relapses. It does not justify changing the usual practices in the
use of corticosteroids for the moment.
Are there side effects with the use of corticosteroids?
Side effects are directly linked to the strength of the molecule,
to the length of treatment, to occlusion, to the surface area
treated, to the integrity of the skin and to the age of the child.
- – Local side effects are uncommon. Few studies have
objectively measured in detail the side effects of topical
corticosteroids in children. Although they are often mentioned, in
practice they are rarely seen. The theoretical worries about side
effects should not limit the prescription of topical
corticosteroids (professional agreement).Care should be taken when
using them on the eyelids (class I or II corticosteroids and short
treatment) (professional agreement).
- – Systemic secondary effects.
The theoretical potential systemic adverse effects are linked to
a slowing down of the hypothalamo-hypophyso-adrenal axis: they do
not warrant systematic endocrinological investigations
(professional agreement).
These effects are exceptional and may appear clinically as a
delay in growth, sometimes related to the underlying severity of
the eczema. In the event of a chronic affection in a child, the
growth curve must be carefully monitored.
How should corticosteroids be used?
- – Which pharmaceutical preparation should be
preferred?Creams are preferable for oozing lesions and folds;
ointments for dry and lichenified lesions. Topical corticosteroids
should not be diluted.
- – Should topical corticosteroids be applied once
or twice daily?Once daily is just as effective and has the
advantage of being easier to apply, thus assuring a better
compliance and reducing the risk of secondary effects and the cost
(professional agreement).
- – What is the maximum quantity of topical steroids which
should be used?No information is given in the literature allowing
for the maximum quantity of topical corticosteroids/weight of a
child to be stated. Observation of the clinical effectiveness is
more useful than defining a theoretical dosage.
- – Which treatment schedule is recommended?There is a great
diversity of professional practices, both for starting and ending
treatment. This lack of agreement leads patients to worry,
encourages a certain degree of mistrust, even a phobia against
cortisone treatment, and it is one of the factors that sends
patients wandering ‘nomadically’ from one type of therapy to
another.Currently, most of the experts prefer to use the following
method:
- – use of strong corticosteroids over short periods of
time followed by a break using only emollients until the next
relapse
- – continuation of daily application on persistant
lesions until they disappear. In the absence of clinical trials
evaluating the optimal conditions for the use of topical
corticosteroids, it seems necessary to harmonise our practices,
based on comparative trials which need to be further
developed.
- – What sort of follow up is necessary?
In mild to moderate forms of AD the effect of topical
corticosteroid treatment is spectacular, with the disappearance of
pruritis in a few days and improvement of the lesions within a
week. Regular follow up is necessary to ensure that this favourable
evolution is maintained, that the patient is complying with the
treatment by measuring the quantity of corticosteroids used, and to
modify the treatment if needed.
Calcineurin inhibitors
The recent development of topical calcineurin inhibitors (CI) for
the treatment of AD in children is an important breakthrough. These
macrolide molecules have an immunosuppressive action through the
inhibition of calcineurin, a molecule necessary for the activation
of Th2 T cells.
The molecules available
Two molecules have been studied for several years: tacrolimus and
pimecrolimus (the latter is not yet available in France).
How effective are CIs?
- – For the treatment of outbreaks.The short term clinical
efficacity of tacrolimus has been demonstrated in studies comparing
it with placebo or with low to moderate level corticosteroids.
These studies have shown that topical tacrolimus quickly and
effectively reduces the signs and symptoms of moderate to severe
AD, from the first week of treatment (level 1).Pimecrolimus is also
rapidly active in mild to moderate AD, with all the clinical
parameters significantly improved compared to the excipient. In a
level 1 study, it was less effective than betamethasone valerate
(high potency).
- – For the prevention of relapses.
The effectiveness of tacrolimus is maintained during the year of
treatment, if it is continued. Longer term studies are not
currently available.
For pimecrolimus, a level 1 study has shown that 1%
pimecrolimus, applied twice daily from the appearance of the first
lesions, was more effective than the excipient.
Do CIs have adverse side effects?
- – Local side effects.For tacrolimus and
pimecrolimus the most common local side effects are a burning
sensation and itching at the application site, this is usually mild
and transitory (a few days). There is no risk of atrophy. The risk
of bacterial infection is not increased. This also applies to viral
infections apart from herpes, against which precautions are
necessary (information about the risks of transmission, clinical
monitoring and stopping of treatment in the event of a herpes
infection).
- – Systemic side effects.
Short term
- – In most of the short term studies, no biological
anomalies have been noted.
- – With tacrolimus, plasma levels are lower one month after
the start of treatment than they are with therapeutic
immunosuppression.
Long term
These are products with immunosuppressive properties, thus they
could be carcinogenic over the long term. In vitro, they have not
been found to be carcinogenic in the majority of tests, except with
albino mice. The risk of skin cancer in man remains hypothetical
but cannot be discounted until there has been a much longer use of
these products.
How should CIs be used with children?
- – Only 0.03% tacrolimus is currently approved for moderate
to severe AD in children over 2 years of age. The entire surface of
the lesions should be treated twice daily until they disappear. It
may be used as a short term treatment or intermittently over a
longer term. The prescription is made on a special form and can
only be given by a dermatologist or paediatrician.
- – The current regulations for tacrolimus are
unsatisfactory as they do not accord with the inclusion criteria
for patients in published studies and they limit its usage by
giving it the status of a restricted drug which can only be
prescribed by certain groups of practitioners.Within the framework
of a revision of the regulations, data from on-going studies into
long term effects should be integrated, as well as those evaluating
the prevention of relapses.
- – The use of pimecrolimus should also be made
available.
What precautions are necessary for a good use of CIs?
- – In the event of skin infections, antibiotic treatment is
necessary before the start of CIs.
- – In view of the potential photocarcinogenic risk,
association with phototherapy or sun exposure is not
recommended.
- – The presence of developing herpes infection is a
temporary contra-indication for the use of CIs. Precautions should
be taken where the patient has a history of recurrent herpes
infection.
- – Vaccines are not contra-indicated during treatment with
CIs.
Emollients
(This subject is further developed in question 4).
Emollients can be used in the acute stage on areas of xerosis.
On damaged skin, local intolerance reactions are possible.
H1-antihistamines- (H1-A)
Few studies have been carried out in children on the clinical
effectiveness of HI-A. The clinical results obtained with
non-sedative H1-As by mouth are comparable with sedative H1-As.
Oral antihistamines are not systematically prescribed during the
acute phase. They can be considered in the event of serious
pruritis and for short periods of time (grade A). Local
antihistamines have no role in the treatment of AD.
Antiseptics
Children with AD are carriers of Staphylococcus aureus on the skin
lesions and on healthy skin. It is necessary to distinguish between
being a normal carrier and true secondary infection (indicated by
crusts, blisters, pustules, increase in weeping, greater area of
lesions, increase in pruritis). Studies have shown that topical
corticosteroids reduce the density of S. aureus with a
corresponding clinical improvement. On the other hand, topical or
oral antibiotics and antiseptics reduce the load of S. aureus but
do not alter the clinical parameters.
Except in the case of an evident bacterial infection, there is
no reason to use either local or systemic antibiotics, or
antiseptics (professional agreement).
Other treatments
There are few indications for phototherapy during the acute phase
and it is poorly tolerated. This is further dealt with in question
5.
Corticosteroids by mouth or injection have no role in the
treatment of flare-ups of AD.
Question 4: What adjuvant measures are useful and how can
flare-ups of atopic dermatitis be prevented in children?
AD is a chronic disease where several factors come into play. It is
therefore necessary to take a multidimensional (medical,
psychological and environmental) approach.
Patient education
Associated with curative and other treatments, therapeutic
education places the patient at the centre of the management of his
disease. AD changes the quality of life of both children and their
families. Therapeutic education is a new approach in AD. Its main
objective is to improve the cooperation between the health
professionals, the patient and those around him to ensure the best
possible management of the condition. Several studies (level 3)
have shown that therapeutic education increases the effectiveness
of the treatment of pruritus and of sleep problems. Therapeutic
education in childhood AD seems to be beneficial for understanding
the disease and its management. Therapeutic education is
principally concerned with moderate to severe forms of AD. It
should not be reserved for specialised centres but should form part
of normal professional practices.
Adjuvant measures
AD is sometimes worsened by aggravating factors (dietary factors,
environmental factors, contact factors or psychological stress…).
Adjuvant and preventive measures have therefore been developed.
They have been classed in two categories, those which have been
validated (scientific studies or professional agreement) and the
others.
Validated therapies
- – Emollients.Xerosis of the skin alters the barrier
function of the epidermis. Emollients are used with the aim of
re-establishing this function of the skin. The efficacity of
emollients on xerosis have been demonstrated (level 2). Tolerance
is usually good. Sometimes sensations of burning, itching and
redness on application have been reported: these side effects
justify changing the emollient.Sensitisation to one of the
components (lanolin, fragrance…) should be suspected if the
inflammation is exacerbated after application of an emollient.
Information in the literature does not indicate that any particular
emollient is preferable, nor whether a short or long usage is
better, nor whether application should be once daily or more
frequently. The panel would like to see several commercially
available products provided free by the French Health Service or at
a cheap rate for these patients.
- – Hygiene practices.Hygiene advice relies on custom and
has not been validated. A short daily bath or shower with luke-warm
water and using non-soap bars or gels is recommended (professional
agreement). There is no reason at present to recommend additives to
the water (oils).
- – Clothing.It is preferable to wear cotton or other
well-tolerated materials like silk or fine fibre polyesters (grade
B). Wool, which is irritating, should be avoided. Where soap
powders and softeners have no impact on adult atopy, there is no
need for restrictions of their usage (professional agreement).
- – Psychological management.Interactions between AD,
emotions and psychological problems exist. Severe AD changes the
quality of life and can change the personality of the patient or
induce psychological problems.Stress has been put forward as a
triggering factor in flare-ups of AD, but the mechanism is unclear:
it is probably an important factor for some people and negligible
for others. Families who are suffering need to be identified so
that a specific treatment can be proposed.
Non validated therapies
- – Antihistamines.There is no level 1 or 2 study
demonstrating the preventive efficacity of H1-antihistamines during
flare-ups of AD.
- – Thermal cures.Thermal cures are popular in France,
where numerous cure centres exist. Thermal waters are very
different in their chemical and physical properties. There is no
scientific reason to recommend them in the absence of a conclusive
study.
- – Complementary medicine.Many parents try complementary
medicines because they consider that conventional treatments are
ineffective or they fear side effects.The rare studies of the
efficacity of homeopathy in AD are contradictory. No scientific
proof leads to the recommendation of its use.The panel was against
the use of acupuncture with children in the absence of scientific
proof, in view of its painful nature and potential complications
(professional agreement).
- – Probiotics. Probiotics have been proposed in the
prevention and treatment of childhood AD on the basis of the
‘hygiene theory’, which is based on an inverse relationship between
the degree of exposure to microbes and the risk of developing an
allergy pathology.
- – Does the administration of probiotics to children at
risk prevent the appearance of AD? Only one single-centred study
(level 1) suggested that giving Lactobacillus rhamnosus to the
mother one month before birth and to children at risk of atopy
three or six months after birth, could be useful to prevent the
occurrence of AD. In the absence of further studies it is premature
to recommend administering probiotics for preventive reasons to
pregnant women or to infants at risk of atopy.
- – Is the administration of probiotics useful in treating
flare-ups of childhood AD?Two studies, of doubtful methology, have
evaluated the interest of probiotics in the treatment of outbreaks
of AD. They do not come out in favour of the curative use of
probiotics in AD.
- – Chinese herbal medicine.Secondary effects reported go
from simple nausea to the most serious complications (acute
hepatitis, severe nephropathy, Stevens-Johnson syndrome, dilated
cardiomyopathy …). These facts suggest that this treatment should
not be recommended.
- – Essential fatty acids (EFA).Different oils rich in EFA
omega 6 (borage oil, evening primrose oil…) or EFA omega 3 (fish
oils) have been used in AD. A study of the literature leads to the
conclusion that treatment with essential fatty acids is
ineffective, regardless of the origin and the dosage, in childhood
AD (grade A).
Practices currently debated: restrictions
- – Vaccination of an atopic child. Flare-ups of AD are
frequently reported as clinical observations in infants. There is
no scientific proof in the literature confirming the role of
vaccines in triggering or aggravating AD. In the event of an
associated egg allergy, only vaccinations against flu and yellow
fever, which are cultivated on embryonic eggs, require expert
advice. The vaccination programme in AD children should be the same
as for non-atopic children. It is wise, however, to temporarily
delay vaccinations during a severe flare-up of AD (professional
agreement).
AD and food allergy: can AD be improved with an avoidance diet
or a change of milk?
The responsibility of food allergies in AD remains controversial
and is evoked too often. The systematic prescription of an
avoidance diet can in certain cases lead to dietary
insufficiencies.
The prevention of AD can be discussed at several levels:
- – primary prevention: avoidance of risk factors before the
appearance of the disease;
- – secondary prevention: avoidance of risk factors with
known disease;
- – third level prevention: avoidance of risk factors to
guard against relapses and complications.
Primary prevention in pregnant women
Avoidance diets in pregnant women with the aim of preventing AD in
the child are difficult to follow and the results have not been
proved.
There is no particular diet for pregnant women which will
prevent the appearance of AD.
Primary prevention in the new-born at risk of AD
The definition of ‘new-born at risk’ is not universally agreed and
the idea of direct family history is not sufficient in itself for
this label. Exclusive breast feeding for at least three months
reduces the risk of AD in at-risks infants (level 1). Maternal
feeding, with no particular diet for the mother, is recommended
(grade A).
If the breast feeding is not exclusive (mixed feeding), the risk
of AD is not changed. Soya milks have no value for primary
prevention (grade B).
Secondary prevention in infants who have AD
Apart from the classic avoidance situations in populations at risk
(see chapter 2) there is currently no valid study or meta-analysis
showing any systematic impact of changes in milk on AD.
In the absence of studies with a sufficient level of proof and
in view of the great variety of practices, there is no professional
agreement.
Secondary or tertiary prevention after weaning
The foodstuffs most implicated in food allergies in infants are
milk, eggs, peanuts, soya, fish, leguminous plants and wheat. Level
3 studies have shown that a multiple allergy syndrome (at least two
allergens responsible) may correlate with severe AD. Avoidance of
the allergen is only justified if its role in provoking an allergic
reaction is proved.
AD and environmental allergens
Although sensitization to acarians is often found in AD, it is
difficult to be certain what the role of inhaled allergens is in
the genesis of AD, or in triggering flare-ups. Added to which,
avoidance methods do not show any convincing clinical effects.
The low level of proof and the discordant results of the studies
at our disposal lead us to draw no conclusions about the
responsibility of domestic animals in the appearance of AD in
children. Where AD exists, the panel suggests avoiding domestic
animals (in particular, cats).
Published studies do not confirm that primary prevention of AD
is possible. The effect on AD outbreaks of avoiding pneumallergens
is not clear, which makes secondary and tertiary prevention
superfluous.
Question 5: How should severe atopic dermatitis be managed in
children?
The answers proposed to this question are based on professional
agreement rather than on studies with a high level of proof, due to
the small number of patients involved.
Definition of severe AD
The severity depends on a number of parameters: objective ones (the
number and seriousness of the flare-ups), but also subjective ones
(the psychological repercussions, the quality of life of the
patient and his family). There is no validated scale which takes
into account all these elements and enables a threshold value for
the diagnosis of severe AD to be given. Before considering if it is
in fact a case of severe AD, it is essential to ensure that
management is optimal: the treatment prescribed has been understood
and correctly applied, an allergy investigation has been carried
out and possible avoidance measures have been taken.
If the treatment does not seem to be effective, training in care
techniques should be given by the doctor himself or a nurse,
therapeutic education or psychological help should be offered.
Hospitalisation in a dermato-pediatric structure might be useful.
If the treatment is being correctly managed, either from the start
or after the failure of all these measures, it is a true case of
severe AD. For each case specialised advice is necessary to decide
on difficult therapeutic measures, often not included in the
approved list of treatments, but which are justified by the
seriousness of the rare cases of failure of local therapy.
Alternative treatments to be considered with severe AD
Phototherapy
There are few studies concerning the use of phototherapy in
childhood AD and they are of a poor level of scientific proof. The
phototherapies recommended are UVA-UVB, narrow band UVB (known as
UVB TL01) and UVA1. They are efficient and well tolerated in the
short term; the long term risks are unknown. UVA-UVB and narrow
band UVB phototherapies may be used in the treatment of severe AD
in children from the age of 8-10 (professional agreement).
In practice, the limits of this treatment are the need for 2 or
3 sessions per week added to the lack of cabins equipped with UVB
or narrow band UVB lamps, their unequal availability in different
parts of France and the distance from the patient’s home.
Antileucotrienes
Antileucotrienes are not a treatment for severe AD. Their possible
role as an additional treatment in moderate AD remains to be
determined.
Systemic steroids
The use of systemic corticoids, either by injection or by mouth,
should be avoided (professional agreement).
Cyclosporine
Cyclosporine is an approved therapy for this condition in adults.
The initial prescription is only permitted in a hospital setting
and by a practitioner with experience of using this molecule.
Cyclosporine is not approved for AD in children. Three studies in
children (levels 3 and 4) show good results with short term
treatment (6 to 12 weeks), frequent early relapses and few cases of
prolonged remission after 6 months.
Oral cyclosporine, at an initial dose of 5 mg/kg/d, enables a
difficult phase to be passed but it is limited to 6 months or a
maximum of 1 year, due to the risks of renal damage and arterial
hypertension (grade C). The panel proposes that a group of experts
should determine the value of the systematic dosage of
cyclosporinemia, in view of the different opinions found among
prescribers.
Azathioprin
Azathioprin has been little used in AD in adults, due to the risk
of myelosuppression. Only one retrospective study has evaluated the
use of azathioprin in severe childhood AD. These data were
insufficient to recommend its use in children in the absence of
further studies (grade C).
Other immunosuppressors
Mycophenolate mofetil has been used successfully in a few cases of
adult AD.
No studies on the use of methotrexate and cyclophosphamide in
childhood AD have been published.
Polyvalent immunoglobulins
Despite several encouraging results in children, this treatment
cannot be recommended in view of the cost, the risks and the need
for repeated hospitalisation (grade C).
Interferon gamma
Two studies at level 1 and 2 and two at level 4 have been carried
out, mainly with adults, showing moderate efficiacy but with
frequent side effects. This treatment is not recommended in
children (grade A).
Conclusion
In the present state of knowledge, UVA-UVB or narrow band UV
phototherapy and cyclosporine are the two treatments which can be
used for the rare cases of severe AD. The child and his parents
should be informed orally and in writing of the risks of these
treatments. In the absence of comparative studies, the relative
place of the two treatments is difficult to define. The choice
should be made on the basis of feasibility (age, associated
pathologies, access to a UVB cabin…) and as a result of discussions
with the child and his parents. The other therapies cannot be
recommended.
This consensus conference was made possible with the aid of
grants from the following laboratories:
3M Santé, Fujisawa, Galderma International, GlaxoSmithKline, LEO
Pharma, Novartis Pharma, Pierre Fabre Dermatologie,
Schering-Plough, UCB Pharma.
Co-promotors
Association des Enseignants d’Immunologie des Universités de
Langue Française,
Association Française de Pédiatrie Ambulatoire,
Association Nationale de Formation Continue en Allergologie;
Collège National des Enseignants de Dermatologie et
Vénéréologie;
Collège National des Généralistes Enseignants;
Fédération Française de Formation Continue en
Dermato-Vénéréologie;
Groupe d’Etude et de Recherche en Dermato-Allergologie;
Société Française d’Allergologie et d’Immunologie Clinique;
Société Française d’Immunologie;
Société Française de Dermatologie Pédiatrique;
Société Française de Pédiatrie
Organising committee
Jean-Philippe LACOUR, President. Dermatologist, Nice; Béatrice
CRICKX, Dermatologist, Paris; Christophe DUPONT, Pediatrician,
Paris
Jean-François FONTAINE, Allergist, Reims; Yvon LEBRANCHU,
Immunologist, Tours; Ludovic MARTIN, Dermatologist, Orléans; Michel
NAVEL, Pediatrician, Ancenis; Jean-Baptiste SAUTRON, General
Practitioner, Bagnols-en-Forêt; Jean-François STALDER,
Dermatologist, Nantes
With the participation of the
Association Consensus en Dermatologie;
Conférence de consensus organisée selon la méthodologie de
l’ANAES
Panel
Jean-François STALDER, President. Dermatologist, Nantes; Pierre
ARMINGAUD, Dermatologist, Orléans; Sylvie AULANIER, General
Practitioner, Le Havre; Thierry BOURRIER, Pediatrician, Allergist,
Nice; Jérôme CASTANET, Dermatologist, Monaco; Philippe CÉLERIER,
Dermatologist, Le Mans; Marie Sylvie DOUTRE, Immunologist,
Dermatologist, Bordeaux.; Marie Françoise FARDEAU, Allergist, Les
Milles; Nicolas KALACH. Pediatrician, Lille; Christine LABREZE.
Dermatologist, Bordeaux; Pierre LE MAUFF. General Practitioner, La
Roche-sur-Yon; Sylvie MONPOINT. Dermatologist, Montpellier;
Françoise REMBERT-SAGOT, Pediatrician, Allergist, Dunkerque; Lyonel
ROSSANT, Pediatrician, Nice
Experts
Sébastien BARBAROT, Dermatologist, Nantes; Christine BODEMER,
Dermatologist, Paris; Delphine de BOISSIEU, Pediatrician,
Paris;
Franck BORALEVI, Dermatologist, Bordeaux; Frédéric CAMBAZARD,
Dermatologist, Saint-Etienne; Jean-Marc CHAVIGNY, Dermatologist,
Allergist, Nantes; Gisèle KANNY, Internist, Allergist, Nancy;
Laurent MISERY, Dermatologist, Brest; Jean-François NICOLAS,
Immunologist, Dermatologist, Lyon; Patrice PLANTIN, Dermatologist,
Quimper; Yves DE PROST, Dermatologist, Paris; Fabienne RANCÉ,
Pediatrician, Allergist, Toulouse; Pierre SCHEINMANN, Pediatrician,
Allergist, Paris; Alain TAÏEB, Dermatologist, Bordeaux
Bibliographical group
Frédéric BÉRARD, Immunologist, Lyon; Claire BERNIER,
Dermatologist, Nantes; Christine CHIAVERINI, Dermatologist, Nice;
Mathilde KEMULA, Dermatologist, Paris; Emmanuel MAHÉ,
Dermatologist, Paris; Brigitte NICOLIE, Allergist, Angers; Nhan
Pham THI, Pediatrician, Paris
We are indebted to Jenny Messenger for translating this
article.
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