CHAPTER 1

INTRODUCTION

A definition of atopic dermatitis (AD) may be exceedingly simple: it is the

cutaneous manifestation of atopy. There is no doubt that the definition, this time,
is not at all easy or simple. Etymologically, "atopy" means "without" (a) "place"
(topos), that is, something that is out of place, something that is strange,
something that is unusual. The definition postulated by Coca and Cooke in 1923
has become classic: for these authors, atopy is "hypersensitivity to heterologous
proteins". And yet, atopy is beyond any doubt more than this, as –as will be
discussed later– an understanding of this condition is achieved not only through
immunological mechanisms but through many other non-immunological
phenomena that are involved, such as dryness of the skin, paradoxal skin
reactivity, microorganisms, etc., which play a significant role in its development.
From the point of view of terminology, the most adequate term for
defining the process is "dermatitis", as an inflammation of the skin is in truth the
underlying phenomenon of the disease. Furthermore, the adjective "atopic" should
be preferred to "constitutional", as the manifestations of the condition may first
appear in adult age and with no previous antecedents, even though it is quite true
that it may and usually does appear as a continuation of the infantile phase.
Atopic dermatitis (AD) - also known as atopic eczema - is a chronically
relapsing, highly pruritic, inflammatory skin disease that affects 2-5% of the
general population. AD has the largest impact on infants and children, affecting an
estimated 10-20% or more, but is also believed to affect 1-3% of adults. The
mechanisms underlying the pathogenesis of AD remain unclear, but numerous
studies have demonstrated the integral involvement of immunopathology, genetic
predisposition, and emotional and environmental stimuli in AD development and
progression.

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 Atopic dermatitis (AD) is a chronic itchy, inflammatory skin disease that
usually develops in early childhood and is commonly seen in individuals with a
personal or family history of similar skin disease or asthma. Persistence of AD has
been reported in 60% of adults who had the disease as children. It is notorious for
its recalcitrant and chronically recurrent nature. Along with the usual therapy of
topical steroids, general skin care, and topical antibiotics there are also systemic
methods of treating this disorder, which have already been well described.
Because effective medical treatments for this condition are limited in number,
many patients have turned to alternative therapies, including so-called natural
products, herbal products and OTC treatments, many of which remain unproven.

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 CHAPTER 2
CONTENT

DEFINITION
Atopic dermatitis is a difficult condition to define, because it lacks a
diagnostic test and shows variable clinical features. The following definition
seems to be in accord with most consensus groups. Atopic dermatitis (which is
synonymous with atopic eczema) is an itchy, chronic or chronically relapsing,
inflammatory skin condition. The rash is characterized by itchy papules
(occasionally vesicles in infants), which become excoriated and lichenified, and
typically have a flexural distribution. The eruption is frequently associated with
other atopic conditions in the individual or other family members.
Atopy
One of the difficulties in defining atopic dermatitis arises from the
impreciseness of its association with atopy and the nature of atopy itself. The
word ‘atopy’ was introduced by Coca in 1923 as a convenient collective term for
a group of diseases, chief among which are asthma and hay fever, which occur
spontaneously in individuals who have a family history of susceptibility. Later,
regain (IgE) antibodies were detected in these individuals, and could be
transferred to normal individuals by the Prausnitz–Küstner (PK) test. The atopic
diseases were once considered to be peculiar to humans, but it is now recognized
that several species are susceptible. Atopic dermatitis and disorders resulting from
anaphylaxis, for example those resulting from insect stings and food allergies,
were found to be associated with IgE antibodies and therefore grouped with the
atopic diseases. Such grouping is not completely acceptable, as 20–40% of
individuals with atopic dermatitis can have a normal total or specific IgE level,
and it is rarely attributable to a specific allergic reaction; the IgE antibodies
present in the blood often appear to be incidental to the condition.
Recently, it has been debated whether the group with dermatitis and
normal IgE levels can be distinguished clinically, immunologically and

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prognostically. This subgroup has been variably termed intrinsic, non-atopic
infantile eczema or atopiform dermatitis.

EPIDEMIOLOGY
The data referring to the true incidence and prevalence of AD are quite
varied and even contradictory; this is partly due to the fact that the process may
possibly have an evident seasonal and geographic influence, or perhaps to the fact
that the series studied and reported by the various investigators have included very
diverse population groups, but first and foremost to the fact that the diagnostic
criteria lack a biochemical support that may provide a definitive diagnosis of the
disease. This implies that the inclusion criteria may be quite diverse. AD may
affect all races and ethnicities, as the studies performed do not reveal significant
differences between the various ethnic or racial groups. Thus, Jaafar and Petit
reviewed 14,342 cases seen in the Dermatology Clinics of the University of
Malaysia, a multiracial country, among which the incidence of AD was 3.7%, and
they did not find any significant differences between the various ethnic groups.
Atopic dermatitis is more common in females, with a 1.5:1 female to male
ratio. AD is possibly the earliest manifestation of atopy, as by the age of two years
50% of all atopic patients evidence AD, and 60% by age five, while in the same
age group only 40% have symptoms of asthma and only 25% have symptoms of
vasomotor rhinitis. Socially, the incidence of AD appears to be greater among the
higher classes. This, however, cannot be ascribed simply to a greater level of
information and/or greater or easier access to medical consultation in these elite
groups.

AETIOLOGY
Non-immunologic factors
Genetics. The genetic susceptibility to suffer respiratory atopy has been
linked to chromosome 11 (11q13). A number of studies have demonstrated the
presence of an autosomal dominant inheritance pattern. Uehara and Kimura
studied 270 adults with AD and found that 60% of their offspring were also
affected; the prevalence of the skin condition was 81% when both parents were

4
affected by AD, 59% when only one parent was affected by AD and the other one
had respiratory atopy, and 56% when only one of the parents was affected by AD.
In a Norwegian study12 of children with AD, the authors concluded that the risk
of evidencing the disease was 57% when the mother was affected and 46% when
the father was the affected parent; attempts have been made to correlate these
findings with modifications of the intra-utero immune response or with
breastfeeding.
Characteristics of the atopic patient’s skin. As will be commented in
greater detail when discussing the clinical features, the skin of the atopic patient,
and particularly that of the AD one is dry, pruriginous, irritable, and shows a
marked propensity to infection by viruses, bacteria and fungi. These peculiarities
are a consequence of the loss of the barrier function. In the causation of this
conditions the following are involved:
(a) Abnormalities in sweating. The atopic patient sweats badly, and this
dysfunction is determinant for the presence of pruritus. It is a frequent observation
in clinical practice that the AD patient reports pruritic crises in association to heat
and sweating. There have been many attempts to find a correlation between
sweating/dry skin/pruritus, without achieving any definitive conclusions. Greene
et al studied the sweating characteristics of atopic patients and concluded that they
evidence abnormal sweating patterns that are responsible for or associated to the
condition. These abnormalities appear to be due to an increased sweating response
to metacholine, so that it might be suggested that atopic patients evidence
hyperreactivity to cholinergic stimuli. The possibility may be postulated that when
the atopic individual sweats, and because of a deficiency in sebum production, the
sweat might be taken up into the stratum corneum; this would then cause an
occlusion of the sudoriparous gland pore (acrosyringia) and thus sweat retention,
and the latter would then condition small extravasations of the sweat fluid into the
dermis that would then stimulate pruritus receptors. This theory has not been
demonstrated, but the propensity of atopic patients to develop "miliaria" through
sweat retention is well known.
(b) Trans-epidermic water loss (TEWL). Baradesca and Maibach have studied this
factor in atopic patients; they found an increased trans-epidermal water loss and a

5
decreased water-retaining capacity of the stratum corneum, contributing to a
deficiency in the epidermal barrier function.
(c) Changes in the cutaneous lipids. The atopic patient’s skin is dry because of the
water loss, and changes in the lipid composition of the cutaneous lipid layer.
Rajka showed, using absorption techniques, that in the atopic skin there are
decreased levels of the glandular lipids (waxy esters, triglycerides and squalene),
while those of epidermal origin are increased.
One of the more interesting findings in atopic patient is that of a serum
deficiency of the enzyme Δ-6 desaturase, which under normal conditions allows
the conversion of linoleic acid into γ-linolenic and dihydro-γ-linolenic acids; the
latter is then converted through the action of the enzyme Δ-5 desaturase into
arachidonic acid. Because of this, linoleic acid-rich diets increase
the concentration of this acid but not those of its metabolites (γ-linolenic, dihydro-
γ-linolenic and arachidonic acids). This metabolic abnormality would have an
effect in the production of PGE1, which is an important factor in T-cell
maturation after birth, with the consequent immunologic imbalance.
(d) Lowering of the pruritus threshold. Atopic patients more readily experience
pruritus, and a pruritic stimulus leads in them to a longer-lasting pruritus
sensation.

Genetic factors
The importance of genetic factors in determining the expression of the
atopic phenotype is reflected in data from twin studies. Thus, monozygotic twins
have a concordance rate of 0.72, whereas dizygotic twins have a concordance rate
of only 0.23. Recently, studies of genetic linkage have identified a number of
genes related to the expression of different atopic syndromes, IgE levels, and
cytokines relevant to the regulation of IgE levels. However, no gene of causal
significance has yet been identified for atopic eczema.
A gene predisposing to atopy, as defined by hyper-IgE responsiveness,
was found on chromosome 11q13, and it may encode the β chain of the high-
affinity IgE receptor FCεR1β. However, there appears to be no linkage of atopic
eczema to this gene. Genes on chromosome 5q encoding the interleukin-4 (IL-4)

6
gene cluster have been linked to atopic mucosal syndromes, but this linkage has
also not been confirmed. A gene at 16p11.2–12 encoding the α chain of the IL-4
receptor has been linked to atopy. The gene encoding mast cell chymase has been
linked to atopic eczema, but this association has not been confirmed. Variants in
the RANTES gene promoter-region have been reported to be associated with
atopic eczema.

Environmental factors
The rate of increase in the prevalence of atopic eczema is too rapid to be
accounted for by changes in population genetics. Therefore, environmental factors
are the most likely modulating influences. The two principal aspects that have
attracted attention are ‘pollution’ and microbes.
The fall of the Berlin Wall separating East and West Germany provided an
opportunity to examine the role of industrial pollution by comparing the ‘dirty’
East with the ‘clean’ West. Cohorts of preschool children from comparable cities
in the East (Halle) and West (Duisburg) and a rural area (Borken), were recruited
in one study. Questionnaires assessed the personal and family history of atopic
disease, as well as many of the relevant factors such as socio-economic status. All
of the children were examined by dermatologists. The levels of airborne pollutants
were compared, and sulphur dioxide was fourfold higher in Halle, whereas dust
and nitrogen oxides were comparable between the cities. The prevalence of atopic
eczema was 17.5% in Halle, but only 5.7–7.3% in Duisburg. However, conflicting
findings emerged in a study comparing the prevalence of atopic disease in Leipzig
(East Germany) and Munich (West Germany). A slightly lower prevalence was
observed in Leipzig compared with Munich. The identification of relevant
pollutants that might contribute to the expression of the atopic phenotype is still
confused. Indoor pollution levels from cigarette smoke or nitrogen oxides in the
gas exhaust from cookers and heaters are difficult to quantify.

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Immune dysregulation
The defining characteristic of the atopic immune system is the capacity to
generate IgE antibodies in response to allergens. The key disturbance to immune
regulation that results in this IgE production appears to be the differentiation
pathway followed by CD4+ helper T lymphocytes. Naive precursor Th0 cells are
induced to differentiate into Th2 cells, characterized by the production of
interleukins (IL) -4, -5 and -13. Th2 cells ‘help’ or control the type of
immunoglobulin (Ig) that B lymphocytes make, inducing synthesis of IgE.

Cellular mechanisms
The regulatory mechanisms that underlie the preferential development of
Th2 cells appear to involve the interaction between dendritic antigen-presenting
cells and CD4+ helper T lymphocytes. The question arises of whether there is
something different about the dendritic cells
(DCs) of atopic individuals and the signals they give to T cells, or whether there is
a defect in the T cells themselves.
Dendritic cells. Much work has gone into examining the mechanisms by which
DCs regulate the differentiation of Th cells, and there is accumulating evidence
that DCs may also subdivide into DC1, preferentially inducing Th1 cells, and
DC2, inducing Th2 cells. The critical stimulus, ‘signal 1’, is given during the
presentation of antigenic peptides held in the groove of major histocompatibility
complex (MHC) class II molecules. Secondary signals (‘signal 2’) come via
interactions of ‘co-stimulatory’ surface molecules such as CD80 and 86 on the
DCs with their counter receptors CD28 and CTLA4 on the T cells. In murine
systems, signalling via CD80 can preferentially induce Th1 differentiation, and
CD86 can induce Th2 differentiation.
There is evidence that signalling through CD28 gives a positive activation
signal, whereas signaling through CTLA4 may either give an inhibitory signal or
activate T-regulatory cells which have inhibitory (suppressor) activities. In
addition, binding of CD40 ligand on T cells interacting with CD40 on the DC is
one of the strongest signals for the T cell to produce interferon-γ (IFN-γ) and to
differentiate towards a Th1 phenotype. Cytokines released from the DCs give

8
‘signal 3’, which is also important in determining the final differentiation into Th1
or Th2 cells. IL-12 drives a Th1 response and IL-4 drives a Th2 response.
There is little direct evidence that DC function is altered in atopic
individuals. However, it has been observed that monocytes from atopic donors
produce greater quantities of prostaglandin E2 (PGE2) and IL-10 than cells from
nonatopic individuals. PGE2 can suppress production of IFN-γ, a cytokine which
is not only produced by Th1 lymphocytes but which also favours the
differentiation of naive Th0 cells towards the Th1 phenotype. Similarly,
IL-10 is both a suppressive/regulatory cytokine and also drives Th0 cells towards
a Th2 phenotype. DCs from atopic individuals have yet to be shown to behave
similarly.

PATHOGENESIS OF ECZEMA—THE ROLE OF ALLERGY

There are many factors, including allergies, infections, emotional, climatic
and other environmental influences that contribute to the causation of atopic
dermatitis. In early life, atopic infants develop eczema as the first of the possible
atopic syndromes, which include eczema, asthma and rhinitis. There is evidence
that immune sensitization occurs to food-derived allergens as well as

9
aeroallergens. The infantile intestine shows increased permeability to
macromolecules and this is greater in atopic infants. This may be due to inherent
‘leakiness’ and also, because of the transient deficiency of IgA, the IgAmediated
clearance mechanisms are less effective, allowing greater entry of food-derived
macromolecules into the systemic circulation, where they may induce
immunological sensitization. It is completely unclear why circulating T cells
reactive with food antigens should home to the skin and generate an eczematous
process rather than producing a gut-centred pathology. It may be hypothesized
either that food-derived antigens somehow activate immature T cells to become
skin-homing, or that skinhoming lymphocytes are stimulated as a result of their
target antigens reaching the skin via the circulation.

Perhaps because the epidermal permeability barrier is disrupted by the

eczema, allowing penetration of environmental aeroallergens, during the first few
years of life there is progressive development of immune reactivity to
aeroallergens, reflected by the presence of specific IgE and
T-cell responses.
The role of airborne environmental allergens both in the initial
sensitization of atopic individuals and the subsequent elicitation of the clinical
features is becoming clear. Environmental allergen levels are probably the major
determinant of whether sensitization of genetically predisposed individuals
occurs. Thus, children born just before the birch pollen season in Scandinavia

10
have a higher risk of sensitization to birch pollen than those born after the season.
Babies born in autumn, when housedust mite (HDM) numbers are highest, have a
greater risk of sensitization by HDM [6], and avoidance of exposure to HDM and
food allergens for the first year of life was associated with significant diminution
in the proportions of clinically detectable eczema and asthma. A recent Japanese
study showed that if atopic babies (with detectable IgE antibodies to various foods
but not HDM) were protected from contact with HDM by encasing their bedding
in dust-proof bags, there was significantly less sensitization to HDM, reflected by
IgE and prick test response. However, it was not followed through to see whether
there was a reduction in associated clinical problems. It has been proposed that the
risk of becoming sensitized to HDM is greatly increased by exposure to dust
containing 10 μg/g of Der p1, and that even 2 μg/g confers a significant risk. It
appears that, in some individuals, priming of immune responses to a range of
allergens may happen during intrauterine development. In others, the induction of
sensitization appears to occur postnatally and during childhood. The sensitization
is reflected by the presence of antigen-specific helper T lymphocytes and specific
antibodies of IgE class.
The crucial question is whether allergic reactions induced by any allergen
or food are of pathogenic importance in the causation of lesions of atopic eczema.
The strongest evidence that this can be the case derives from studies of the effects
of avoidance of house-dust allergens in the domestic environment. A
placebocontrolled, double-blind study by Tan et al. examined a combination of
dust-mite eradication measures (sealed containment bags for the mattress, pillows
and bedding top covers, a high-power vacuum cleaner and a spray containing
agents to kill mites and denature their allergens).

CLINICAL FEATURES
Atopic dermatitis is an inflammatory dermatosis that causes pruritus. Its
clinical features therefore will be those of a cutaneous inflammation with well-
defined chronology and topography in association to secondary lesions induced by
scratching (excoriations, lichenification, auto-eczematisation, secondary
infections, etc.). The lesions may range from simple erythema, through the

11
presence of papules, vesicles, exsudation, scabbing and desquamation, to the
presence of lichenified lesions.
Classically, AD is clinically divided into two stages: early AD,
manifesting in early infancy and thus also known as infantile AD, and late AD,
which appears during late childhood and encompasses this period (up to the age of
12 years), adolescence (up to the age of 23 years), and adulthood. Late AD may
be, but not always is, a continuation of the early form. Thus, the cutaneous
manifestations of AD may first appear at any age, without having been
foreshadowed
by any previous manifestations.
Early atopic dermatitis
The onset of this form was classically understood to occur beyond the age
of three months, and it is still usual to read or hear the lapidary sentence
"dermatitis at an age before three months is seborrhoeic, beyond the age of three
months it is atopic". We now know that early AD may have its onset at any age,
and seborrhoeic dermatitis may indeed represent an initial form of AD. The age at
onset is variable and does not correlate with genetic predisposition or with the
severity of the disease. About 75% of the cases have their onset within the first six
months of life, and especially between the 6th and 12th weeks.
Three findings help in establishing the differential diagnosis between the
two conditions: the presence of a family history of atopy, the presence of pruritus,
and thetypical sites of occurrence of the disease. A family history is quite
frequent, and not only in the purely cutaneous form (AD), as it may also exist in
other forms of atopy such as rhinitis, conjunctivitis or asthma. Pruritus is severe
and incoercible; children with AD begin scratching quite early and scratch
themselves continuously, mainly when they are undressed and even during sleep,
causing distress to their parents and relatives. Scratching is the fundamental cause
of the disease’s complications. In this first stage the lesions are located in the face,
particularly on the cheeks, and show a centrifugal distribution affecting the malar
region, the forehead, the scalp, the chin and the ears while sparing the central
areas (nose, paranasal creases). In severe cases the condition progresses and
spreads and may affect the trunk, the limbs and the flexures, and may even spread

12
over the whole body giving rise to erythrodermic forms (Hill’s atopic
erythrodermia).

In this period the differential diagnosis to seborrhoeic dermatitis is

obligate. This may sometimes be utterly impossible (the lesions are quite often
only transitional forms or situations in which both conditions overlap). Data that
may help in establishing the diagnosis of seborrhoeic dermatitis are the early onset
(neonatal), the absence of a family history of atopy, the absence of pruritus and
the location of the lesions: retroauricular, diaper area, scalp (milk scab) or
flexures.
Late atopic dermatitis
This form may represent a continuation of the early one or debut in the
absence of foregoing dermatosis. The clinical features resemble those of the early
stage, although lichenification predominates: hardened, dry skin with markedly
evident creases and scratching stigmata. The sites of the lesions also change,
leaving the face and appearing mainly in the flexures (the antecubital and
popliteal ones are most frequently involved. However, extensive forms may also
occur with involvement of other skin structures, as well as, of course, generalized
erythrodermic forms.

13
 Atopic dermatitis is a chronic disease with a "flare and subsidence"
evolutionary course, affecting mainly the young and the adolescents but also
many adults. For the patients it may be a stressing situation to be told that the
have a "for life" disease; this affects their psychological development and causes a
number of peculiarities, to be discussed later.

DIAGNOSIS
As no biochemical criteria exist that may firmly establish the certainty
diagnosis of atopic dermatitis, clinical criteria must be reverted to. The universally
accepted criteria are those postulated in 1983 by Hanifin and Rajka. These criteria
have been examined by a number of investigators, and their reliability has been
fully validated.
Diagnostic criteria for Atopic Dermatitis
MAJOR CRITERIA
- Pruritus
- Characteristic morphology and distribution
- Flexure lichenification in adults

14
- Involvement of face, flexures and extensor surfaces in children and adolescents
- Combination of the two patterns in children and adults
- Chronic and recurrent character
- Personal or familial history of atopy
MINOR CRITERIA
- Xerosis
- Ichthyosis / exaggerated palmar creases / keratosis pilaris
- Immediate (Type I) skin reactivity on skin testing
- Increased serum IgE levels
- Early onset age
- Tendency to skin infections and cell-mediated immunity deficiency
- Tendency to non-specific hand and foot dermatitides
- Nipple eczema
- Cheilitis
- Recurrent conjunctivitis
- Infraorbitary (Dennie-Morgan) skin fold
- Keratoconus
- Anterior subcapsular cataract
- Eye rings ("shiners"), periocular darkening of the skin
- Facial pallor or erythema
- Pityriasis alba
- Skin folds on the anterior aspect of the throat
- Pruritus induced by sweating
- Intolerance to wool and to fat solvents
- Perifollicular enhancement
- Intolerance to some foods
- Course influenced by environmental and emotional factors
- White dermographism
Three or more major and three or more minor criteria must be met for diagnosis.

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COMPLICATIONS
In the large majority of the cases, the complications of atopic dermatitis
are consequences of the pruritus and of the proneness to bacterial
(impetiginisation, folliculitis) or viral (herpetic eczema or Kaposi’s varicelliform
erup-tion) infection. Some particular clinical events, e. g. sudden death, are more
frequent among atopics than in the general population. A relation has been
suggested to anaphylactic shock, but, fortunately, it is a rather infrequent
observation.
A wide variety of disease processes are associated to AD; some of them
are also associated to other manifestations of atopy or are a consequence of the
fact that this is an immune disease, while others represent only associations with
as yet no established linkage. A discussion of all these conditions would be
excessively detailed and burdensome.

MANAGEMENT
There is at present no curative therapy for atopic dermatitis. Nevertheless,
a number of measures are available that help palliate the disease’s manifestations
and will help the patients lead a normal life. Atopic dermatitis remains as one of
the therapeutic challenges facing the Dermatologist, the Allergologist or the
Paediatrician in his everyday clinical practise. Current therapies aimed at
controlling the disease are not as effective as we would wish, and particularly so
in the severe forms that still represent a considerable therapeutic problem. In most
cases, the actual management must be based on a number of measures.
General hygienic measures
Bathing. The question whether the AD patient may bathe, and how, is obligate.
According to Hanifin’s recommendations and depending on the severity of the
disease, bathing should be preferred, in the severe and pruriginous forms, to
showering, the latter being reserved for those cases in which the skin has
improved as to erythema, pruritus and desquamation. The patient should remain
immersed in the bath for 20 minutes (until the fingertips become creased and
prune-like); adding to the water emollient substances that mitigate pruritus and
soften the skin is quite adequate. The most widely used emollients are oat-derived

16
colloids, but some tar preparations (at present highly controversial) or mineral or
vegetable oils may also be useful. The soap used should maintain an acidic pH
and be devoid of irritant and sensitising substances; for these reasons, the so-
called "syndets" (soapless soaps) are the most adequate ones. Soaps that have an
antiseptic action help in preventing Staphylococcus aureus overpopulation, so that
chlorhexidine soaps or preparations may be useful.
The sponge or terrycloth used should be soft and cause no irritation of the
skin. After bathing, the skin should be dried carefully using always soft towels.
Rubbing or hot air dryers should not be used, as they will further dehydrate the
skin. An emollient cream should be applied after bathing, not immediately but
some minutes later. A large variety of such products are commercially available;
the most useful ones are perhaps those containing ω fatty acids (primrose oil,
linoleic and/or linolenic acid) or ceramides.
General measures. Clothing should be recommended that does not increase the
itching sensation; the garments used should therefore be light and not tight fitting,
and whenever possible should contain neither wool nor synthetic textile fibres;
cotton and linen should be recommended.
Care should be taken to remove the labels stitched to the clothing, which
have a strongly irritant action on the atopic skin. Atopic patients do not tolerate
heat, as they sweat abnormally and the itching sensation increases. They should
therefore be advised to be moderate regarding physical exercise and exertion and
to avoid warm and excessively dry environments. The adequate environmental
conditions for these patients are 18ºC temperature and 50% relative humidity.
Atopic patients should avoid contact with irritant and/or sensitising
substances; this must be borne in mind when considering possible topical
therapies, and this possibility should be considered whenever a patient
experiences an exacerbation while under local topical therapy. Substances that
should be avoided in topical preparations are mainly the antihistamines,
neomycin, sulfamides and perfumes, and one should always remember that some
topical corticosteroids, as well as some preservants and stabilisers, may trigger
local intolerance.

17
Topical therapy
Corticosteroids. The use of topical corticosteroids is absolutely recommended in
AD. Their use requires experience as a choice must be made, depending on the
clinical manifestations, the location of the lesions and the type of skin, between
the more and the less potent ones, considering both the potential benefits and the
side effects, so as to achieve a balance between them. In selecting the most
adequate corticosteroid it must be remembered that their use will be required over
long periods of time; those with less side effects should therefore be preferred.
The new-generation steroids provide good results, acceptable potency and a low
transcutaneous absorption. The combined use of corticosteroids and antibiotics,
and particularly mupirocine and fusidic acid, may be useful in those cases where
secondary infection is suspected, and always during short periods of time.
Classical antipruritic therapies (camphor and menthol lotions). These may help
in palliating and controlling the itching sensation and can be beneficial for the
evolution of the disease. As already stated, topical antihistamines should not be
used because of their sensitising ability. However, a number of studies have
demonstrated the usefulness of 5% doxepine because of its marked antipruritic
effect; nevertheless, with the passage of time a certain degree of sensitising ability
has been demonstrated also for this substance, so that it should be used cautiously,
if at all. A number of topical therapies such as 10% disodium cromoglycate or 10-
30% anhydrous caffeine were the target of considerable interest in the past
decade. Interest regarding these substances has waned, however, as they have
been demonstrated not to be more effective than placebo.
Systemic therapy
Antihistamines. These are by themselves insufficient for the management of AD,
but they can be useful as a complementary therapy. Their efficacy is derived from
both their antihistamine and their sedative effects; for these reasons, the most
useful ones in this context are still hydroxyzine hydrochloride and ciproheptadine
hydrochloride. Among the new-generation antihistamines, loratadine, terfenadine,
acrivastine and cetirizine have been shown to be more effective. The combination
of these drugs to membrane-stabilising agents such as ketotifen, when a

18
participation of airborne allergens is suspected, or disodium cromoglycate in the
case of suspected food allergy, may enhance their effects.
Corticosteroids. Systemic corticosteroids are not the therapy of first choice in AD,
but they should be used in definite situations when other measures are ineffective.
The administration of systemic corticosteroids over short periods of time may
help reduce the severity of the disease and facilitate the institution of less
aggressive measures.
Interferon. The altered balance between the Th-1 and Th-2 lymphocyte
subpopulations, with predominance of the latter, causes the AD patients to
evidence a deficient γ-interferon production; it thus appears to be reasonable to
consider that the systemic administration of this substance may be beneficial in
this disease. Several studies have demonstrated that therapy with γ-interferon at a
dose of 5 μg/m2 per day for three months achieves good results with scarce side
effects.
Other therapies
Hypnosis. Some reports have commented on its usefulness. Logically, there are no
studies of extensive series in support of its application.

PROGNOSIS
The variety in the expression, severity and extent of involvement in atopic
dermatitis has led to the establishment of parameters or criteria for assessing the
severity of the disease. The currently and universally accepted criterion is the
Scoring Index of Atopic Dermatitis, or SCORAD67, which considers a number of
variables: extent of the lesions, objective symptoms and subjective symptoms.
This scoring index is particularly useful in clinical trials. The evolution of the
disease is unpredictable, but in most cases it shows a trend towards resolution or
improvement with the passage of time. There have been a number of attempts to
establish criteria that may help predict the course of the disease; the first work in
this context was the one by Vickers68. Based on the follow-up of 2000 atopic
dermatitis patients, he underscored the following aspects: (1) Adverse factors: late
onset (after the age of 15 months), inverted pattern, discoid-like eczema and social

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problems and disagreements between the parents; (2) Favourable factors: early
onset, seborrhoeic pattern, and appropriate use of appropriate medication.
Rystedt, in 1985, proposed the following signs of adverse prognosis:
occurrence of severe episodes during childhood, positive family history (the
natural history of the disease in relatives may be informative regarding the course
of the disease in the index case), presence of other manifestations of atopy, female
gender, young age (persistence after the age of 15-20 years is a sign of
chronicity), persistent dry skin in the adult, the patient’s own personality traits and
the psychology of the patient’s parents.
We should always bear in mind that all these data are only orientative, and
that there is no single criterion or set of criteria that may reliably establish the
future course of the disease in the particular AD patient sitting in front of us.

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 CHAPTER 3
CONCLUSIONS

Atopic dermatitis (which is synonymous with atopic eczema) is an itchy,

chronic or chronically relapsing, inflammatory skin condition. The rash is
characterized by itchy papules (occasionally vesicles in infants), which become
excoriated and lichenified, and typically have a flexural distribution. The eruption
is frequently associated with other atopic conditions in the individual or other
family members.
There are so many factors that played in AD. It is important not only know
about the factors but also know how to avoid them. We need patience enough to
deal with AD, we should care in manage them. Actually there is no definitive
treatment that can eradicate AD from patient, but since we can control the factors
AD will be disappear and can not be happen.

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