The clinical manifestations of atopic dermatitis

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Anita Remitz and Sakari Reitamo

INTRODUCTION

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease related to other atopic symptoms like allergic rhinitis, allergic conjunctivitis, and asthma. AD usually starts before the age of 2 years and is the first of the atopic symptoms that shows clinical signs. Patients with AD have an increased risk of developing other atopic symptoms later in life. Both endogenous and exogenous factors interact in the development of clinical signs of the disease. Hereditary factors are important, but exogenous causes like the cold climate, stress and pollen are usually necessary to develop clinical symptoms.

The term atopic dermatitis was introduced by Wise and Sulzberger in 1933 as a skin disease characterized by dry skin, pruritus, and chronic relapsing erythematous lesions.1 The name 'atopy' comes from the Greek meaning 'wrongly placed'. Coca et al had introduced the term atopy to describe a hereditary disorder different from anaphylaxis which was clinically characterized by hay fever and bronchial asthma. The disorder was further characterised by a tendency different from normal subjects, i.e. to become sensitized to environmental factors.2 In 1967 Ishizaka et al3 and Johansson4 showed that IgE antibodies were characteristic of the atopic condition.

The diagnosis of AD is purely clinical; there is no specific clinical symptom or laboratory test. Itch is the main symptom of this disease and the localization of the eczema is often typical (face, jugular, bend of the elbow, hollow of the knee). However, the localization varies with age.

THE LOCALIZATION OF AD AT DIFFERENT AGES

Infancy (0 to 1 year)

The disease often starts around the third month of age and is located on the cheeks and scalp (Figure 1.1). The skin is pruritic and erythematous patches can be seen covered with crusts, which are often secondarily infected (Figure 1.2). Because the rash is scaly and crusted and resembles burnt milk the disease has also been called milk scale. The rash can also develop on the extensor surfaces of the extremities and on the trunk (Figure 1.3). Children with AD often have troubles with sleeping due to pruritus (Figure 1.4). Food allergies are rather common (Figure 1.5).

Childhood (1 to 4 years)

In young children from 1 to 4 years the eczema can still be located on the extensor sites of the extremities (Figure 1.6), but also on the flexural areas (Figure 1.7). It can also be located around the mouth, on the eyelids,

Atopic Dermatitis Children
Figure 1.1 AD in an infant.
Figure 1.2 Typical milkscale, also called prurigo Besnier.
Figure 1.3 AD of the extensor surfaces and trunk in a 1-year-old boy.
Acrodermatitis Flexures

Figure 1.4 Results of intensive pruritus and scratching in a 1-year-old infant. Figure 1.7 AD of the flexures.

Figure 1.5 AD exacerbated by insensitivity to milk and eggs in a 19-month-old-boy.
Atopicd Dermatitis Figure
Figure 1.6 AD on extensor surfaces of the lower extremities.

Figure 1.4 Results of intensive pruritus and scratching in a 1-year-old infant. Figure 1.7 AD of the flexures.

Symetric Erythematous Papules Child
Figure 1.8 Widespread AD with mild scales in a small child.

neck, and hands (Figure 1.8). The lips can be dry and scaly. The lesions are usually symmetric erythematous papules with excoriations, small crusts, and lichenifica-tion (Figure 1.9). Food allergies are less common than in infants.

Adolescents (4 to 16 years)

Children from 4 to 16 years usually develop symmetric eczema on the flexural areas (Figure 1.10), on the hands (Figure 1.11), and feet. The so-called horseback area on the back of the thighs can also be affected (Figures 1.12-13). During the winter months the children can develop eczema on their hands and feet (atopic winter feet) due to wet gloves or socks after playing outside. When the child comes closer to puberty eczema can also be seen on the upper body and face (Figures 1.14-15). Food allergies are unusual.

Adults (over 16 years)

In adults the eczema lesions are typically on the face (Figures 1.16-19), upper body (Figure 1.20), flexural areas (Figures 1.21-22), and hands (Figure 1.23). Sometimes the disease can develop into erythroder-mia (Figure 1.24). Stress and climate are important triggering factors.

Atopic Dermatitis Black Child Pictures
Figure 1.9 Nummular AD in a small child.
Atopic Dermatitis Elbow
Figure 1.10 Lichenified AD of the elbows in a child of African origin.

DIAGNOSTIC CRITERIA OF AD

Although the diagnosis of AD is purely clinical, it is not always easy to define the disease and therefore several authors have suggested guidelines to help in making the diagnosis. The diagnosis is based on medical history (personal and/or family history) and typical signs and symptoms. However, none of these clinical features is diagnostic for AD. Hanifin et al5 based their

Atopic Dermatitis Hands
Figure 1.11 Lichenified AD of the hand in a child of African origin.
Figure 1.12 AD in the horse-back area in a white young female.
Figure 1.13 AD in the horse-back area in a black young female.
Figure 1.14 AD of the face with scales in a girl of Japanese origin.

Figure 1.15 Severe AD of the face in a white girl.

Asian Severe Eczema
Figure 1.16 AD with widespread erythema in a 25-year-old man.
Bad Hair Styles For Men
Figure 1.17 Severe AD with oedema but little erythema of the face in a 19-year-old female.
Figure 1.18 Severe AD with profound oedema and erythema of the face in a 56-year-old man.
Eczema Scars
Figure 1.20 Nummular eczema with scars from scratching in a 18-year-old female.
Eczema One Year Old
Figure 1.21 Lichenified eczema of the wrist with signs of intense scratching in a 16-year-old female.

Figure 1.19 Retroauricular eczema in a 20-year-old Figure 1.22 Severe lichenified eczema of the knees in woman with AD. a 17-year-old male.

Figure 1.23 Typical irritant eczema of the hands in AD in a 22-year-old female.

Figure 1.24 Severe erythrodermia in a 51-year-old male with long-standing AD resistant to therapy.

diagnosis on 4 major criteria and several minor criteria (Table 1.1). Williams et al6 applied and simplified Hanifin and Rajka's criteria and suggested that the patient must have itchy skin (obligatory) and then at least three of the additional features (Table 1.2).

Several investigators have looked at the prevalence of the minor criteria of Hanifin et al in atopic patients. Böhme et al7 studied 221 children 24 months of age or younger, who were re-examined after 2 years. A control group of 99 children of the same age, with no history of eczema were examined in the same way. They found 7 minor criteria that were met more in atopic children: namely, xerosis (100%), course influenced by environmental factors (87%), facial erythema (54%), skin reactions provoked by ingested food (39%), itch when sweating (34%), positive skin prick tests (29%),

Table 1.1 Hanifin et al: diagnostic criteria.The patient must have at least 3 of the major characteristics and 3 of the minor characteristics to have AD. (Hanifin JM, Rajka G. Diagnostic features of atopic dermititis. Acta Derm Venereol Suppl (Stockh) 1980; 92: 44-7.)

Major characteristics

Pruritus (excoriations can often be seen, Figure 1.25)

Lichenification (flexural lichenification in adults and older children, facial and extensor involvement in infants, Figure 1.26) Chronic or chronically relapsing course Personal or family history of atopy (asthma, allergic rhinoconjunctivitis, atopic dermatitis, contact urticaria Figure 1.27)

Minor characteristics

Xerosis (dryness of skin)

Ichthyosis (especially with palmar hyperlinearity or keratosis pilaris, Figure 1.28) Immediate type I reactions to skin test allergens

(positive prick test reactions, Figure 1.29) Elevated serum IgE (about 20% of atopic patients have normal IgE levels) Early age of onset

Cutaneous infections by Staphylococus aureus (Figure 1.30), herpes simplex (Figure 1.31) and other viral infections, warts (Figures 1.32-33), or molluscum contagiosum (Figure 1.34) Non-specific hand (and/or foot) dermatitis

(Figure 1.35) Nipple eczema (Figure 1.36) Cheilitis (Figure 1.37) Recurrent conjunctivitis (Figure 1.38) Dennie-Morgan infraorbital fold (Figures 1.39-40) Keratoconus

Anterior subcapsular cataracts

Orbital darkening (Figure 1.41)

Facial pallor/erythema (Figures 1.42-43)

Anterior neck folds

Itch when sweating

Food intolerance

Course influenced by environmental or emotional factors

Intolerance to wool and lipid solvents or any course fabric or non-absorptive occlusive garment, and wet working conditions Perifollicular accentuation White dermographism/delayed blanch (Figures 1.44-45)

and hand eczema (28%). Early age of onset was an inclusion criteria for the study. Approximately half of

Table 1.2 Williams et al: diagnostic criteria. Williams et al suggested that the patients must have itchy skin and then at least 3 of the additional features. (Williams HC, Burney PG, Pembroke AC. Br J Dermatol 1994; 131: 406-16.)

Basic feature (obligatory)

Itchy skin

Additional features (at least 3 of the following)

Skin symptoms in flexural regions such as knee and elbow flexures, in front of the wrists and neck (in cheeks in children under 10 years)

Asthma or allergic rhinitis (or atopic diseases in close relatives in children under 4 years)

Dry skin during the last year

Visible eczema in flexural areas (or on cheeks and/or forehead in children under 4 years)

Eczema starting before the age of 2

Dermatite Lac
Figure 1.25 Lower extremities with signs of chronic scratching due to intense pruritus in a 16-year-old female patient with AD.

Figure 1.26 Flexural lichenification in a 20-year-old female with AD.

Lower Extremities Keratosis Images
Figure 1.27 AD in a mother and baby.
Severe Keratosis Pilaris
Figure 1.28 Keratosis pilaris is a sign not restricted to AD.
Figure 1.29 Positive prick test reactions to milk and egg-white in a 17-month-old child with food allergy.
Figure 1.30 Folliculitis caused by Staphylococcus aureus in a 54-year-old male with severe AD.

Figure 1.32 Long-standing viral warts in a 36-year-old male with severe AD.

Figure 1.32 Long-standing viral warts in a 36-year-old male with severe AD.

Herpes Simplex DermatitisNipple Dermatitis Eczema
Figure 1.31 Herpes simplex infection at an unusual site in a 15-year-old female with AD.

Figure 1.33 Viral warts of the face in the same male as in Figure 1.33.

Figure 1.34 Molluscae in a 4-year-old girl.
Figure 1.35 Irritant hand eczema in a 25-year-old female with AD.
Nipple Eczema
Figure 1.36 Nipple eczema in 24-year-old female with AD.
Figure 1.37 Cheilitis in a 17-year-old female with AD.

Figure 1.38 Chronic conjunctivitis in a 41-year-old male with severe AD.

Dennie Morgan Fold Picture
Figure 1.39 Dennie-Morgan infraorbital fold in a young girl.
Dennie Morgan Fold
Figure 1.40 Dennie-Morgan fold in a young woman.
Dennie Morgan

Figure 1.41 Orbital darkening in a 20-year-old female with mild AD.

Figure 1.38 Chronic conjunctivitis in a 41-year-old male with severe AD.

Figure 1.41 Orbital darkening in a 20-year-old female with mild AD.

Dennie Morgan Infraorbital Fold
Figure 1.42 Facial pallor in a 20-year-old female with AD.
Figure 1.44 White dermographism caused by scratching in 22-year-old female with AD.
Figure 1.45 Delayed blanch in a 17-year-old male with widespread AD.

the criteria occurred in 3% or fewer of the studied patients and may be of minimal use in this age group.

In addition to age the clinical condition of the patient seems to be of importance on several minor characteristics. Therefore, effective treatment will have an effect on the expression of several signs. The occurrence of the Dennie-Morgan infraorbital fold was low in the infant study by Böhme, but when Diepgen et al8 studied the age group of 10 to 55 years, it had a prevalence of 69%. As with many symptoms and signs of AD, the Dennie-Morgan sign is clearly dependent on the clinical condition of the patients (Figure 1.46). This applies also to the anterior neck folds (Figure 1.47). The infra-auricular fissure has often been proposed to be a diagnostic feature of AD. Kim et al9 showed a prevalence of 55% and Tada et al10 of 82% in atopic patients up to 52 years.

As a conclusion, there are no specific criteria that would occur only in atopic patients. They can, however, help in the diagnosis of AD. The age of the atopic patients seems to be of great importance in the occurrence of the different minor criteria, and racial differences can also be seen. Pruritus seems to be a symptom which is quite resistant to treatment, and can also be provoked by other diseases in patients with AD (Figure 1.48).

Firooz et al11 studied the frequency of the main criteria (Table 1.3). The most common symptoms were itch, which was seen in 70%, and history of dry skin in 40% of patients.

Dennie Morgan Fold
Figure 1.46 Dennie-Morgan infraorbital fold before (a) and after (b) treatment with topical tacrolimus ointment.
Anterior Neck Fold

Figure 1.47 Anterior neck folds before (a) and after (b) treatment with topical tacrolimus ointment.

Figure 1.47 Anterior neck folds before (a) and after (b) treatment with topical tacrolimus ointment.

Infraorbital Dermatitis Treatment

Figure 1.48 Scars caused by intense pruritus and scratching scratching during varicella infection.

Table 1.3 Frequency of the proposed diagnostic criteria for AD in patients and controls. (Firooz A, Davoudi SM, Farahmand AN et al. Validation of the diagnostic criteria for atopic dermititis. Arch Dermatol 1999; 135: 514-16.)

Table 1.3 Frequency of the proposed diagnostic criteria for AD in patients and controls. (Firooz A, Davoudi SM, Farahmand AN et al. Validation of the diagnostic criteria for atopic dermititis. Arch Dermatol 1999; 135: 514-16.)

Criteria

with AD

Controls

Itch

42 (70.0)

128 (36.0)

History of

involvement of

skin diseases

20 (33.3)

40 (11.2)

History of asthma

or hay fever

11 (18.3)

51 (13.3)

History of general

dry skin

24 (40.0)

35 (9.8)

Visible flexural

eczema

8 (13.3)

9 (2.5)

Onset < 2 years

3 (5.0)

0

Figure 1.48 Scars caused by intense pruritus and scratching scratching during varicella infection.

DIFFERENTIAL DIAGNOSIS

In infancy AD can be mixed with seborrhoeic dermatitis, which also can occur on the face and scalp. These infants often suffer from diaper dermatitis and do not have a family history of atopic diseases. Seborrhoeic disease also subsides after a few weeks when the stimulatory effect of maternal hormones disappears. Ichthyosis vulgaris can be suspected in children with very dry skin and with positive family history of ichthyosis. The typical scaling is seen especially on the extensor surfaces of the extremities after 2 months of age. Scabies can be seen with severe itch and dermatitis. Usually other family members also have symptoms, and the finding of burrows, usually on the hands, and the isolation of mites provide the diagnosis. Psoriasis also sometimes starts in infancy although it is rare. Then the lesions are more defined and can be present with the typical white scale.

In childhood and adolescence the localization of AD is usually on flexural areas and the disease has usually started earlier in infancy. However, the atopic winter foot can sometimes be misdiagnosed to tinea pedis. Impetigo of the face can also sometimes be misdiagnosed as AD. Psoriasis can also start in childhood, usually after streptococcal infections in the form of psoriasis guttata. Pityriasis rosea usually starts with

Table 1.4 Diseases associated with AD

Elevated IgE

Hyper-IgE syndrome

Immunodeficiency

Wiskott-Aldrich syndrome

Ataxia-telangiectasia

Selective IgA deficiency

Genodermatoses

Phenylketonuria

Hypohidrotic ectodermal dysplasia

Biotin deficiency

Hartnup disease

Acrodermatitis enteropathica

Langerhans cell histiocytosis

Netherton Syndrome Atopic Diathesis

Figure 1.49 A girl with Netherton syndrome a larger primary lesion which is followed by smaller scaly lesions on the trunk. The lesions subside in approximately 6 weeks.

In adults hand eczema can be a sign of AD, but possible contact allergies have to be excluded if the eczema continues for several months in spite of treatment.

There are also rare conditions where AD has been described as a feature. However, the dermatitis which has been described in these patients rarely fulfils the criteria for AD. AD is also a common disease, so it is possible that these patients have two diseases. The diseases are listed in Table 4. The rare Netherton syndrome is also associated with AD (Figure 1.49).

REFERENCES

1. Wise F, Sulzberger MB. Footnote on problem of eczema, neurodermatitis and lichenification. In: Wise F, Sulzberger MB, eds. Year Book of Dermatology and Syphilogy. Chicago: Year Book Publishers, 1933: 38-9.

2. Coca AF, Cooke RA. On the classification on the phenomenon of hypersensitivities. J Immunol 1923; 8: 163-82.

3. Ishizaka K, Ishizaka T. Identification of xE antibodies as carrier of reaginic activity. J Immunol 1967; 99: 1187-98.

4. Johansson SGO. Raised levels of of a new immunoglobulin (IgND) in asthma. Lancet 1967; 2: 951-53.

5. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1980; 92: 44-7.

6. Williams HC, Burney PG, Pembroke AC. The UK working parties & diagnostic criteria for atopic dermatitis III. Br J Dermatol 1994; 131: 406-16.

7. Böhme M, Svensson A, Kull I, Wahlgren C-F. Hanifin's and Rajka's minor criteria for atopic dermatitis: Which do 2-year-olds exhibit? J Am Acad Dermatol 2000; 43: 785-92.

8. Diepgen TL, Sauerbrei W, Fartasch M. Development and validation of diagnostic scores for atopic dermatitis incorporating criteria of data quality and practical usefulness. J Clin Epidemiol 1996: 1031-8.

9. Kim KH, Chung JH, Park KC. Clinical evaluation of minor clinical features of atopic dermatitis. Ann Dermatol 1993; 5: 9-12.

10. Tada J, Toi Y, Akiyama H, Arata J. Infra-auricular fissures in atopic dermatitis. Acta Derm Venereol 1994; 74: 129-31.

11. Firooz A, Davoudi SM, Farahmand AN et al. Validation of the diagnostic criteria for atopic dermatitis. Arch Dermatol 1999; 135: 514-16.

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