paper yudhistira

8/7/2019 PAPER YUDHISTIRA

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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 heterologousproteins". 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 PrausnitzKstner (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 2040% ofindividuals 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 significantdifferences 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


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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 patients 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 thisconditions 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 alstudied 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


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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 patients 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 -6 desaturase, which under normal conditions allows

the conversion of linoleic acid into -linolenic and dihydro--linolenic acids; the

latter is then converted through the action of the enzyme -5 desaturase into

arachidonic acid. Because of this, linoleic acid-rich diets increasethe concentration of this acid but not those of its metabolites (-linolenic, dihydro-

-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 chain of the high-

affinity IgE receptor FCR1. However, there appears to be no linkage of atopic

eczema to this gene. Genes on chromosome 5q encoding the interleukin-4 (IL-4)


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gene cluster have been linked to atopic mucosal syndromes, but this linkage has

also not been confirmed. A gene at 16p11.212 encoding the 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 5.77.3% 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-presentingcells 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- (IFN-) and to

differentiate towards a Th1 phenotype. Cytokines released from the DCs give


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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-, 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 ECZEMATHE 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


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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


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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 g/g of Der p1, and that even 2 g/g confers a significant risk. Itappears 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


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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 ageof 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 diseases 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


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over the whole body giving rise to erythrodermic forms (Hills 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.


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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


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- 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 Kaposis 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 beexcessively 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 diseases 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 Hanifins 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


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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 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 18C 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.


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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


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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 -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 -interferon at adose of 5 g/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 patients own personality traits and

the psychology of the patients 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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