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9 Diagnosis of Atopic Eczema S. Weidinger, J. Ring 9.1 Introduction The basic principles of diagnosing atopic eczema seem simple and are part of the daily routine work of any dermatologist. However, the combinations of poly- genic factors and modifications by individual expo- sures result in a wide spectrum of signs and symptoms from minimal manifestations via mild eczematous lesions to severe and chronic atopic eczema. The mor- phology of skin lesions may change with age, affected body area and environmental influence, giving rise to possible subpopulations of patients. In addition, there is a strong variability in disease course. Problems in diagnosing atopic eczema may also arise from the imprecision in the nomenclature, especially of the terms “eczema/dermatitis” and “atopy.” Eczema is a noncontagious inflammation of epider- mis and dermis with characteristic clinical (itch, ery- thema, papule, seropapule, vesicle, squames, crusts, lichenification, in the sense of a synchronous or metachronous polymorphy) and dermatopathological (spongiosis, acanthosis, parakeratosis, lymphocytic infiltrates, exocytosis) signs [1]. Since the introduction of the term “atopy” by Coca and Cooke in 1923 [2], its definition has been a matter of controversy. In the 1980s it was designated as “famil- ial tendency to develop certain diseases (asthma, rhi- noconjunctivitis, eczema) on the basis of a hypersensi- tivity of skin and mucous membranes against environ- mental substances, associated with increased IgE pro- duction and/or altered non-specific reactivity” [3]. Recently, a task force on nomenclature of the European Academy of Allergy and Clinical Immunology (EAACI) proposed the following definition: “Atopy is a personal or familial tendency to produce IgE antibodies in response to low doses of allergens, usually proteins, and to develop typical symptoms such as asthma, rhi- noconjunctivitis, or eczema/dermatitis” [4]. 9.2 Morphology of Skin Lesions Since there are no specific laboratory tests or histologic findings, the diagnosis “atopic eczema” is essentially clinical. In general, diagnosis is made on the basis of dermatologic examination of skin lesions under con- sideration of their age-specific morphology and distri- bution. Further cardinal symptoms leading to the diag- nosis of atopic eczema are the chronicity of the disor- der and its associated pruritus [5]. Depending on the severity of inflammation and dif- ferent stages of healing, chronic scratching and second- ary (super)infections, the morphology of skin lesions in atopic eczema is diverse. Acute lesions often consist of papules and vesicles on erythematous skin (Fig. 9.1). Fig. 9.1. Childhood atopic eczema, acute flexural lesions Chapter 9

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9 Diagnosis of Atopic EczemaS. Weidinger, J. Ring

9.1Introduction

The basic principles of diagnosing atopic eczema seemsimple and are part of the daily routine work of anydermatologist. However, the combinations of poly-genic factors and modifications by individual expo-sures result in a wide spectrum of signs and symptomsfrom minimal manifestations via mild eczematouslesions to severe and chronic atopic eczema. The mor-phology of skin lesions may change with age, affectedbody area and environmental influence, giving rise topossible subpopulations of patients. In addition, thereis a strong variability in disease course. Problems indiagnosing atopic eczema may also arise from theimprecision in the nomenclature, especially of theterms “eczema/dermatitis” and “atopy.”

Eczema is a noncontagious inflammation of epider-mis and dermis with characteristic clinical (itch, ery-thema, papule, seropapule, vesicle, squames, crusts,lichenification, in the sense of a synchronous ormetachronous polymorphy) and dermatopathological(spongiosis, acanthosis, parakeratosis, lymphocyticinfiltrates, exocytosis) signs [1].

Since the introduction of the term “atopy” by Cocaand Cooke in 1923 [2], its definition has been a matterof controversy. In the 1980s it was designated as “famil-ial tendency to develop certain diseases (asthma, rhi-noconjunctivitis, eczema) on the basis of a hypersensi-tivity of skin and mucous membranes against environ-mental substances, associated with increased IgE pro-duction and/or altered non-specific reactivity” [3].Recently, a task force on nomenclature of the EuropeanAcademy of Allergy and Clinical Immunology (EAACI)proposed the following definition: “Atopy is a personalor familial tendency to produce IgE antibodies inresponse to low doses of allergens, usually proteins,

and to develop typical symptoms such as asthma, rhi-noconjunctivitis, or eczema/dermatitis” [4].

9.2Morphology of Skin Lesions

Since there are no specific laboratory tests or histologicfindings, the diagnosis “atopic eczema” is essentiallyclinical. In general, diagnosis is made on the basis ofdermatologic examination of skin lesions under con-sideration of their age-specific morphology and distri-bution. Further cardinal symptoms leading to the diag-nosis of atopic eczema are the chronicity of the disor-der and its associated pruritus [5].

Depending on the severity of inflammation and dif-ferent stages of healing, chronic scratching and second-ary (super)infections, the morphology of skin lesionsin atopic eczema is diverse. Acute lesions often consistof papules and vesicles on erythematous skin (Fig. 9.1).

Fig. 9.1. Childhood atopic eczema, acute flexural lesions

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Fig. 9.2. Subacute eczematous lesions with scales and lichenifi-cation

Fig. 9.3. Chronic wrist eczema

Subacute lesions may develop scales and lichenifi-cation (Fig. 9.2). Chronically involved areas appear dry,thick and fibrotic and sometimes show nodules(Fig. 9.3). Resolved lesions often leave postinflamma-tory hypopigmentation or hyperpigmentation [6].

The distribution of skin lesions can be highly vari-able but is generally age-related [7].

9.2.1Infantile Phase (0–2 Years)

The earliest clinical features are dryness and roughnessof the skin. Distinct eczematous lesions usually do notappear before 2 months of age. In infants, the dermati-tis commonly affects face and scalp and spreads toinvolve the neck and trunk (Fig. 9.4). Typically, lesionsare erythematous and have highly pruritic, moist, ooz-

ing papulovesicles that may crust and scale. Secondaryimpetiginization may occur. The nasolabial and nap-kin areas are often spared. In children 1–2 years of age,the distribution of lesions moves from the face to theantecubital and popliteal fossae, neck, wrists, ankles,and retroauricular folds. Due to the developing abilityto scratch, the primary lesions are altered and a morevariable clinical picture develops with papules, poorlydemarcated scaly patches, excoriations and haemor-rhagic crusts. While the truncal lesions are often dif-fuse, on the extremities localized patches prevail thattend to involve both extensor and flexor aspects andcommonly the wrists and ankles [8, 9].

Fig. 9.4. Infantile eczema affecting face and trunk

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9.2.2Childhood Phase (2–12 Years)

During childhood, polymorphous manifestations withdifferent types of skin lesions at different locations arecommon. At sites of chronic involvement, thickenedplaques with excoriation and mild lichenificationdevelop. During phases of exacerbation, acute erythe-ma, plaque-like infiltrations and weeping or erosiveskin lesions may occur. Other morphological variantsof the childhood phase are nummular, papulovesicularor lichenoid lesions. Flexures and buttocks become thepredominant predilection sites (Fig. 9.5). The nailsmay become shiny and buffed from constant rubbingand long-lasting eczema of the periungual skin (“ecze-ma nails”) [5, 8, 9].

9.2.3Adolescent Phase (12–18 Years) and Adulthood

The main clinical picture of atopic eczema in ado-lescents are flexural lichenified and often excoriatedskin lesions [10]. In addition, wrists, ankles and eye-lids are frequently affected [11]. In more widespreaddisease, the upper trunk, shoulders and scalp may beaffected.

Atopic eczema spontaneously clears in about 40% ofchildren before or during adolescence but may remainquiescent in others until adulthood, when it most com-monly shows facial and extensor involvement, licheni-fications in the flexural areas, and involvement ofwrists, hands, ankles, feet, fingers and toes. It may also

Fig. 9.5. Atopic eczema in childhood (nummular variant),involvement of buttocks

reappear as hand eczema. A small subgroup of patientsexhibits the first symptoms not before adulthood [5].In patients who do not outgrow atopic eczema by ado-lescence, the disease typically worsens with the skinbecoming thicker and drier and lichenified eczemabeing the predominant lesion type.

9.3Morphological Variants

9.3.1Follicular Variant

The follicular type of atopic eczema, which is com-mon in Japanese and black patients, is characterizedby skin-coloured, whitish or red-brown, denselyaggregated follicular papules (Fig. 9.6). Predilectionsites are the lateral parts of the trunk, the neck and theextensor surfaces. The course is usually cyclic withexacerbations in winter and improvements duringsummer [9].

9.3.2Papular Lichenoid Variant

Skin lesions typical for the lichenoid variant of atopiceczema are skin-coloured, flat, polygonal or roundpapules symmetrically affecting the extensor surfaces(Fig. 9.7). The papules may be disseminated or aggre-gated, sometimes show desquamation, and tend toappear in spring or summer [9].

Fig. 9.6. Atopic eczema, follicular variant

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Fig. 9.7. Atopic eczema, papular lichenoid variant

9.3.3Prurigo Type

This variant is rare in children, but may sometimes beseen in adolescents. Erythematous, often excoriatedpapules and hyper- or hypopigmented residual macu-lopapular lesions and sometimes indurated nodulesare seen primarily on the extensor surfaces of theextremities (Fig. 9.8) [8, 9].

9.3.4Nummular or Discoid Variant

The nummular type of atopic eczema is characterizedby sharply demarcated, coin-sized patches of inflamedskin. Lesions are reddish in color, dry, often infiltrated,and may ooze and become crusty (Fig. 9.9). The legs

Fig. 9.8. Prurigo type of atopic eczema

Fig. 9.9. Nummular atopic eczema

are most commonly affected, but trunk and arms,especially the backs of the hands, may also be affected.In adults, it commonly occurs as a distinct entity with-out association with atopy. Exacerbation often occursduring the winter [9, 12].

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9.4Manifestations of Atopic Eczemaat Special Body Areas9.4.1Fingertip Eczema and Atopic Hand Eczema

In patients with chronic hand eczema, including dys-hidrosis (or pompholyx), an increased prevalence ofatopy between 47% and 64% has been reported. Pal-mar/plantar dermatitis has been reported to occur in70% of children with atopic eczema [13, 14]. Fingertipeczema and/or palmar dermatitis may be localized“minimal variants” of atopic eczema. Clinically, thepalmar surface of the finger tips shows dry, nonpruriticplaques, recurrent hyperkeratosis and fissuring (pulpi-tis sicca). The palmar skin may appear slightly ery-thematous and scaly or appear thickened, dry andleathery (Fig. 9.10). Nonspecific irritants play a majorrole, since the atopic skin is susceptible to all irritants(e.g., cleansers, solvents, wet work). The dorsum of the

Fig. 9.10. Dyshidrotic and hyperkeratotic rhagadiform atopichand eczema

hand may be similarly involved, but if eczema is pre-sent, allergic or irritant contact dermatitis must beconsidered.

9.4.2Atopic Winter Feet

There is no consensus regarding the relation betweenthe “atopic winter feet” and juvenile plantar dermatosis.The clinical picture is similar. A glittering erythemaappearing like lacquered skin with scaling and fissuringof the plantar forefeet and toes is typical. The non-weight-bearing areas of the sole are spared. The condi-tion usually starts at school age, shows a chronicallyrelapsing course with worsening in winter, and healsabout the age of 14 years in the majority of patients[15–17]. Misdiagnosis and treatment as athlete’s foot orallergic contact dermatitis are frequent [18].

9.4.3Eyelid Eczema

Involvement of the eyelids is frequent in patients withatopic eczema. In some atopic patients, it may be thepredominant dermatologic finding. The clinical pic-ture reaches from soft scaly erythema to hyperpig-mented lichenifications with excoriations (Fig. 9.11).Eyelid eczema often relapses due to the vulnerability ofthe thin skin of the eyelids, which is constantly exposedto contact irritants and allergens, and due to its easyaccessibility to being rubbed. Contact irritant andallergic dermatitis should be ruled out [18].

Fig. 9.11. Adolescent phase, bilateral atopic eyelid eczema

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9.4.4Nipple Eczema

Nipple eczema occurs in 12%–23% of patients[19–21]. If present, it is a quite reliable criterion foratopic eczema [22]. In the areolar area, a symmetric,oozing, papulovesicular erythema is seen that mayextend onto the surrounding breast skin.

9.4.5Cheilitis

Cheilitis often starts in childhood as dry and scalyupper and lower lips. Eczematization of the lips mayproceed to fissuring, angular cheilitis and perioraleczema (Fig. 9.12). Besides the habitual lip-licking toease the dryness and nibbling of adherent scales, thelips are constantly exposed to noxious fluids from foodand drinks.

9.4.6Pityriasis Alba

In areas of previous eczema, especially in the face,neck, and upper trunk, finely scaling and diffuselydemarcated hypopigmented patches sometimesresembling tinea corporis or vitiligo may develop. Thecondition is most prominent after prolonged sun expo-sure and represents postinflammatory hypopigmenta-tion. Pityriasis alba has been reported to occur in35%–44% of eczema patients [20, 21].

Fig. 9.12. Exfoliative cheilitis with perleche

9.5Stigmata of Atopy

Stigmata of atopy are minor skin signs not represent-ing actual “disease” that are characteristic but not spe-cific for atopic individuals. They are significantly morecommon in patients with atopic eczema than in healthyindividuals. They appear to be constitutional markersof the atopic state, since most of them are also found inatopic respiratory diseases [23]. Stigmata may be valu-able clues to the diagnosis of atopic eczema. For furtherdetails see Chap. 7.

9.5.1Dry Skin (Xerosis)

Xerosis is the most common skin finding in patientswith atopic eczema. It is characterized as slightly scal-ing, noninflamed skin involving large areas of the body.Usually it persists throughout the patient’s life, but mayshow seasonal variations [24, 25]. Atopic skin appearsrough and dry, which is the result of the atopic kerati-nocytes’ decreased ability to bind water and anincreased transepidermal water loss [26, 27].

Xerosis is one of the triggers of pruritus and con-tributes to the abnormal protective barrier layer inatopic eczema. It sometimes causes fissures that mayserve as a portal of entry for infectious agents.

9.5.2Hyperlinearity of the Palms/Soles

Hyperlinearity of the palms or the soles is noted moreoften in atopic patients than in nonatopic patients andhas been found in up to 88% of atopic eczema patients.It is regarded as increased expression of palmar and/orplantar creases and lines [28].

9.5.3Infraorbital Fold (Dennie-Morgan Lines)

Dennie-Morgan lines are symmetric, striking single ordouble folds beneath the lower eyelids first reported byDennie as mentioned by Morgan [29]. They may beseen in 50%–60% of atopic patients with a possibleethnic variation [23, 30].

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9.5.4White Dermographism

In nonatopic individuals, firm stroking of the skincauses a red line with a reflex erythema. In contrast, themajority of eczema patients shows a delayed white line,which replaces the initial erythematous reaction after1 min [31]. It has been noted to be age-dependent andto develop within the 1st year of life [32].

9.5.5Facial Pallor

Atopic persons frequently have paleness of the face.Like white dermographism, it is believed to be causedby the atopic patient’s altered vascular reactivity.

9.5.6(Peri-)Orbital Darkening

Many eczema patients exhibit a blue-grey hue aroundthe eyes with accentuation of the suborbital area. Thiscondition is more frequent in the young [19] and isoften seen in other atopic family members.

9.5.7Herthoge’s Sign

This sign refers to the thinning or absence of the lateralportion of the eyebrows. A prevalence of 39% has beenreported in eczema patients compared to 1% in con-trols [21].

9.5.8Keratosis Pilaris

Keratosis pilaris is a disorder of keratinization of the(xerotic) hair follicles characterized by tiny roughbumps on the skin (like “chicken skin”). Primarily, itappears on the back and outer sides of the upper arms,but can also occur on thighs and buttocks or any bodypart except palms or soles. It is frequently associatedwith atopic eczema but can also be seen in otherinflammatory dermatoses or occur in individuals with-out other skin lesions. It most often appears in child-hood, reaches its peak incidence in adolescence, andbecomes less apparent during adulthood [33].

9.6Diagnostic Criteria for Atopic Eczema

Numerous lists of diagnostic criteria have been devel-oped in order to establish a definition for atopic ecze-ma with known validity and reproducibility using reli-able discriminators. Most widely accepted are the crite-ria of Hanifin and Rajka [34]; other criteria includethose of Diepgen et al. [35], the United Kingdom Work-ing Party’s Diagnostic Criteria for Atopic Dermatitis[36], the Millennium Criteria for the Diagnosis ofAtopic Dermatitis [37], and Ring’s criteria [38].

The Hanifin and Rajka consensus criteria estab-lished in 1980 are based on traditional clinical majorand minor features and are often used in clinical andepidemiological studies. Diepgen et al. constructedscoring systems for these criteria using 110 atopic der-matitis patients and 527 controls. Their top five criteriaturned out to be “itch when sweating”, “intolerance towool”, xerosis, white dermographism, and Hertoghe’ssign.

The UK Working Party’s Diagnostic Criteria forAtopic Dermatitis have been established preferential-ly for epidemiological studies by nondermatologists.These criteria are relatively simple, requiring re-sponses by the patient or parent to five questions and aclinical examination.

In 1982, Ring’s criteria were set up based on clinical,history and laboratory findings.

9.6.1Diagnostic Criteria According to Hanifin and Rajka

In 1980, Hanifin and Raika [34] proposed criteria fordiagnosis of atopic eczema based on the presence of atleast three major and three additional minor criteria(Table 9.1). These criteria represented an importantmilestone in describing the clinical aspects of atopiceczema and established some degree of comparabilityin subsequent hospital-based studies. They have beenevaluated by a number of investigators, and their reli-ability has been fully validated [19]. However, due totheir partly unknown validity, their complexity andheterogeneity, and since some of the criteria are notprecisely defined, very rare, or unspecific, their use inpopulation-based epidemiological studies is limited[39–41].

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Table 9.1. Diagnostic criteria for atopic eczema according to Hanifin and Rajka

At least three major criteria: Plus three or more minor features:

Pruritus XerosisTypical morphology and distribution: Ichthyosis/ palmar hyperlinearity/ keratosis pilaris

Flexural lichenification or linearity in adults Immediate (type I) skin test reactivityFacial and extensor involvement in infants and children Elevated serum IgEChronic or chronically relapsing dermatitis Early age at onsetPersonal or family history of atopy (asthma, allergic

rhinitis, atopic dermatitis)Tendency toward cutaneous infections (especially Staphylococcus

aureus and Herpes simplex)/impaired cell-mediated immunityTendency toward nonspecific hand or foot dermatitisNipple eczemaCheilitisRecurrent conjunctivitisDenny-Morgan infraorbital foldKeratoconusAnterior subcapsular cataractsOrbital darkeningFacial pallor/ facial erythemaPityriasis albaAnterior neck foldsItch when sweatingIntolerance to wool and lipid solventsPerifollicular accentuationFood intoleranceCourse influenced by environmental/emotional factorsWhite dermographism/delayed blanch

9.6.2The UK Working Party’s Diagnostic Criteriafor Atopic Dermatitis

In 1994, a minimum list of discriminators for the diag-nosis of atopic eczema was established and validated ina hospital setting with sensitivity and specificity ofroughly 90% [36, 42]. The criteria have also been vali-dated in Germany [43]. The diagnosis of atopic eczemacan be made if an itchy skin condition plus three ormore of the following criteria are present:

) History of involvement of skin creases (the folds ofthe elbows, the fronts of the ankles, around theneck, or the cheeks in children less than 4 yearsold)) History of asthma or hay fever in the patient, or of

atopic disease in a first-degree relative (i.e. mother,father, brother or sister) if the child is less than4 years old) History of general dry skin in the past year) Visible flexural eczema (or eczema involving the

cheeks/forehead and outer limbs in children under4 years)) Onset during the first 2 years of life (not used for

children less than 4 years old).

9.6.3Ring’s Criteria

In 1982, Ring established a list of diagnostic criteria foratopic eczema [38]. The diagnosis of atopic eczema canbe made if at least four of the following six criteria arepresent:

) Age-specific morphology) Pruritus) Age-specific distribution of skin lesions) Stigmata of atopic eczema (“typus neurodermiti-

cus”)) Personal or family history of atopy) IgE-mediated sensitization

9.6.4Assessment of Disease Severity: the SCORAD System

The heterogeneity in expression, severity and extent ofatopic eczema has led to the establishment of parame-ters or criteria for assessing the severity of the disease.The most common and universally accepted systemused for assessment of disease severity was developedby the European Task Force on Atopic Dermatitis(ETFA) as the Scoring Index of Atopic Dermatitis(SCORAD) [44]. The SCORAD consists of an objective

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score that quantifies extent and intensity of skin lesionsand a subjective score that quantifies daytime pruritusand sleep loss. The extent is measured as the percent-age of affected skin surface area, and the intensityreflects different qualities of skin morphology and is

Fig. 9.13. SCORADevaluation form [44]

scored in terms of erythema, edema/papulation, ooz-ing/crusting, excoriation, lichenification, and xerosis.Subjective complaints are scored on a visual scale of0–10. This scoring index is particularly useful in clini-cal trials (Figs. 9.13–9.15).

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Fig. 9.14. Clinical examples illustrating the Scoring Index ofAtopic Dermatitis (SCORAD): Classification of erythema [44]

Fig. 9.15. Clinical examples illustrating the Scoring Index ofAtopic Dermatitis (SCORAD): Classification of edema/papula-tion [44]

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Fig. 9.16. Clinical examples illustrating the Scoring Index ofAtopic Dermatitis (SCORAD): Classification of oozing/crust-ing [44]

Fig. 9.17. Clinical examples illustrating the Scoring Index ofAtopic Dermatitis (SCORAD): Classification of excoriation[44]

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Fig. 9.18. Clinical examples illustrating the Scoring Index ofAtopic Dermatitis (SCORAD): Classification of lichenification[44]

9.7Differential Diagnosis of Atopic Eczema

9.7.1Seborrheic Dermatitis

In infants, seborrheic dermatitis is the most commondifferential diagnosis of atopic eczema. A clear-cut dif-ferentiation may be difficult at first presentation, asimportant clues to the diagnosis (e.g., course) are notavailable. Pruritus, age of onset and family history ofatopy can not reliably discriminate the two entities.Lesions on forearms and shins as well as specific IgE toegg white and milk point towards atopic eczema.Smooth, nonscaling, sharply marginated, brightly ery-thematous dermatitis in the axillae or initially onlyaffecting the napkin area and heavy yellow scales onthe cheeks, trunk, and limbs favour the diagnosis seb-orrheic dermatitis [45, 46].

9.7.2Scabies

Scabies may be very difficult to distinguish from atopiceczema if secondary eczematization has occurred. Ahistory of acute itchy conditions within the family, thepresence of relatively large papules on the upper backand in the genital and axillary areas, vesicles on thepalms and soles in infants, and sparing of the face aresigns favouring scabies. Mites or ova can be easily dem-onstrated in scrapings of the vesicles [47].

9.7.3Psoriasis

Early-onset psoriasis with extensive involvement mayalso be confused with atopic eczema. It is rare in infan-cy. Usually, pruritus is not present. Sharply demarcatedfawn-colored scaly lesions and psoriasis in one or morefamily members are helpful in distinguishing this dis-ease from atopic eczema.

In older children, contact dermatitis (irritant orallergic), tinea, eczematous pityriasis rosea and rarelydrug eruption have to be differentiated from atopiceczema.

Several types of immunodeficiency syndromes arefrequently associated with atopic eczema, e.g. Wiskott-Aldrich syndrome [48], selective IgA deficiency [49]and hyper-immunoglobulin E syndrome [50, 51]. In avariety of other primary immunodeficiencies, occa-

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sional associations with atopic eczema have beendescribed [48]. They can be distinguished by the pres-ence of additional symptoms such as recurrent infec-tions, generalized lymphadenopathies, chronic diar-rhoea, haematological abnormalities or failure tothrive [52]. Metabolic disorders also predispose toatopic eczema. (See also chapter 10.)

9.8Allergy Diagnosis in Atopic Eczema

9.8.1Skin Prick Testing

Skin prick testing to common allergens will identifyspecific IgE-mediated sensitizations. However, positivetest results do not necessarily indicate clinical relevance.Skin prick tests only indicate that the patient has beensensitized to the particular antigens. To be informative,the skin prick tests must be related to the clinical contextof the patient’s history and the physical examination.The selection of the antigens and the administration oftests require experience and knowledge [53]. A skin testmay be positive both before the allergy is clinicallyapparent and years after cessation of symptoms.

9.8.2Total Serum-IgE

Among atopic diseases, the highest serum IgE levels arefound in atopic eczema (AE) [54], and total serum IgElevels are elevated in the majority of AE patients.Although total serum IgE is one of the parameters usedto discriminate intrinsic and extrinsic forms of AE, theclinical applications and interpretation of total serumIgE concentrations are of modest value, and elevatedlevels cannot be considered pathognomic signs of ato-py or allergy. A normal IgE level does not exclude aller-gy, while highly elevated levels may be seen in nonato-pic people. In addition, total IgE is elevated in a varietyof disease syndromes such as allergic bronchopulmo-nary aspergillosis, hyper-IgE syndrome, certain stagesof HIV infection, lymphoproliferative diseases, drug-induced interstitial nephritis, graft-versus-host dis-ease, several parasitic diseases, and several immunedeficiency diseases, as well as idiopathically [51]. TotalIgE is not of predictive value for the course of the dis-ease or long-term prognosis.

9.8.3Specific IgE

Specific IgE antibodies are most commonly detected bythe readioallergosorbent test (RAST) or related tech-niques measuring the amount of IgE directed to a spe-cific allergen [55–58].

Skin tests are generally considered to be more sensi-tive than IgE assays, but patients may be skin test-nega-tive and RAST-positive or vice versa. Thus, RAST maybe particularly useful in patients with severe skin dis-ease who cannot be skin tested. Quantitative specificIgE tests have a high reliability and sensitivity (approx-imately 90%).

9.8.4Atopy Patch Test

The role of allergy in atopic eczema has been debatedrigorously in the past, partly due to the limited speci-ficity of skin prick test and RAST with regard to theclinical course. The flare-up of eczematous lesions aftercontact with aeroallergens, a predictive lesional pat-tern affecting air-exposed skin, and a seasonal fluctu-ating course of the disease are well-known clinical fea-tures in many patients with atopic eczema. In 1982, itwas demonstrated that epicutaneous application ofseveral allergens on the uninvolved, abraded skin ofpatients with severe AE could induce eczematouslesions only in patients who also showed a positiveimmediate skin reaction to the same allergen [59].Based on these observations, an epicutaneous patchtest with allergens known to elicit IgE-mediated reac-tions used to evaluate the occurrence of eczematousskin lesions was named the atopy patch test [60] andfurther developed. Several groups have used this so-called atopy patch test (APT) as a model to study therole of aeroallergens in atopic eczema [61–67].

The APT reaction has been shown to be specific foreczema patients, and does not occur in healthy volun-teers or in patients suffering from asthma or rhinitis[68, 69]. The APT seems to act as a marker of exposureand may be viewed as a kind of provocation test for thedermoepidermal unit in patients with atopic eczema[64]. However, due to differences in patient selectionand in methodology, the results of atopy patch testingmay show large variations [69, 70]. Thus, the atopypatch test is widely accepted as an useful model forstudying inflammatory reactions and the effect of topi-

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cal treatment in atopic eczema [71]. Although the diag-nostic value of this test in clinical practice is still con-troversial [72], it is a helpful tool for identification ofthe patient group suffering from aeroallergen-inducedeczema flare-ups [73].

References

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