ATOPIC DERMATITIS

Synonyms and related keywords: infantile eczema, Besnier's prurigo, intrinsic eczema, extrinsic eczema,
atopiform eczema, asthma, food allergy, peanut allergy, allergic reaction

Background

Atopic dermatitis (AD) is a pruritic disease of unknown origin that usually starts in early infancy and is typified
by pruritus, eczematous lesions, xerosis (dry skin), and lichenification on the skin (thickening of the skin and
increase in skin markings). AD is associated with other atopic diseases (eg, asthma, allergic rhinitis, urticaria,
acute allergic reactions to foods, increased immunoglobulin E [IgE] production) in many patients. It is a disease of
great morbidity, and the incidence appears to be increasing.

Pathophysiology

The pathophysiology of AD is poorly understood. Several cell types seem to be involved, including T
lymphocytes, eosinophils, Langerhans cells, and keratinocytes. Other factors, including cytokines and IgE, are
also implicated.

Laboratory findings suggest a number of different pathogenetic mechanisms. One invokes an immune defect
involving an abnormality of TH2 cells that interacts with Langerhans cells and results in increased production of
interleukin (IL)4, IL-5, IL-6, IL-10, and IL-13. This leads to increased IgE and decreased gamma interferon
levels. The imbalance of TH2 cells occurs in the acute process, with a swing toward TH1 cells in the chronic stages
of the disease. Another theory involves defective barrier function in the stratum corneum leading to the entry of
antigens, which results in the production of various inflammatory cytokines.

Frequency

The prevalence rate is as high as 18% and is rising, especially in developed countries. In China and Iran, the
prevalence rate is approximately 2-3%. The frequency is increased in patients who immigrate to developed
countries from underdeveloped countries.

Mortality/Morbidity

Incessant itch and work loss in adult life is a great financial burden. A number of studies have reported that the
financial burden to families and government is similar to that of asthma, arthritis, and diabetes mellitus. Mortality
due to AD is unusual.

With regard to bacterial infection (eg, with Staphylococcus aureus or Streptococcus pyogenes), note that
the skin of most patients with AD is colonized by S aureus. Clinical infection may occur and is worsened
by scratching and occlusion from medications. Eczematous and bullous lesions on the palms and soles are
often infected with beta-hemolytic group A Streptococcus.
Urticaria and acute anaphylactic reactions to food occur with increased frequency in patients with AD. The
food groups most commonly implicated include peanuts, eggs, milk, soya, fish, and seafood.
Latex allergy is more common in patients with AD than in the general population.
Of patients with AD, 30% develop asthma and 35% have nasal allergies.

Sex
The male-to-female ratio is 1:1.4.

Age

In 85% of cases, AD occurs in the first year of life; in 95% of cases, it occurs before age 5 years.

Disease is most prevalent in early infancy and childhood. The disease may have periods of complete
remission, particularly in adolescence, and may then recur in early adult life.
In the adult population, the rate of AD frequency diminishes to 0.9%. Rarely, onset may be delayed until
adulthood, when the disease is more difficult to control.

CLINICAL
History

Incessant pruritus is the only symptom. Although pruritus may be present in the first few weeks of life, parents
become more aware of the itch as the itch-scratch cycle matures when the patient is approximately age 3 months;
children then scratch themselves uncontrollably.

Physical

Primary findings include xerosis, lichenification, and eczematous lesions. The eczematous changes are seen in
different locations, and the morphology changes with age.

Infancy
o AD may be noticed soon after birth. Xerosis also occurs in the neonatal period. Xerosis involves
the whole body but usually spares the diaper area.
o The earliest lesions are often evident in the creases (ie, antecubital and popliteal fossae), where the
lesions consist of erythema with exudation. Over the following few weeks, lesions localize to the
cheeks and forehead and extensors of the lower legs, but they may occur in any location on the
body, often sparing the diaper area. Lesions are xerotic, erythematous, and scaly (eczematous) ill-
defined patches and plaques.
o The scalp is frequently involved with a pruritic scaly dermatitis.
o Lichenification is seldom seen in infancy.
Childhood
o Xerosis is often generalized. The skin is flaky and rough.
o Lichenification is characteristic of childhood AD. It signifies repeated rubbing of the skin and is
seen mostly over the folds and bony protuberances.
o Lesions are eczematous and exudative. Pallor of the face is common; erythema and scaling occur
around the eyes. Dennie-Morgan folds (increased folds below the eye) are often seen. Flexural
creases, particularly the antecubital and popliteal fossae, and buttock-thigh creases are often
affected.
o Excoriations and crusting are common.
Adulthood
o Lesions become more diffuse with an underlying background of erythema. The face is commonly
involved and has a dry, scaling appearance.
o Xerosis is prominent.
o Lichenification is present.
o A brown macular ring around the neck is typical but not always present.
Hanifin diagnostic criteria: In 1980, Hanifin and Rajka1 developed criteria for the diagnosis of AD. They
 developed main criteria and numerous minor criteria. Many articles have questioned the validity of the
minor criteria, and the original criteria have been modified on numerous occasions. Following are the
criteria for 2001.
o Essential features: These features must be present and, if complete, are sufficient for diagnosis.
Pruritus
Eczematous changes
Typical and age-specific changes: Patterns include facial, neck, and extensor
involvement in infants and children, current or prior flexural lesions in adults or
persons of any age, and sparing of the groin and axillary regions.
Chronic and relapsing course
o Important features (seen in most cases): These features are seen in most cases and add support to
the diagnosis
Early age of onset
Atopy (IgE reactivity)
Xerosis
o Associated features (clinical associations): These changes help in suggesting the diagnosis of AD
but are too nonspecific to be used for defining or detecting AD for research and epidemiologic
studies.
Keratosis pilaris/ichthyosis/palmar hyperlinearity
Atypical vascular responses
Perifollicular changes
Ocular/periorbital changes
Perioral/periauricular lesions
o Exclusions: Note that a firm diagnosis of AD depends on excluding conditions such as scabies,
allergic contact dermatitis, seborrheic dermatitis (SD), cutaneous lymphoma, ichthyosis, psoriasis,
and other primary disease entities.
Williams diagnostic criteria: According to the criteria of Williams et al, proposed diagnostic guidelines
include the following:
o Patients must have an itchy skin condition (or parental report of scratching or rubbing in children).
o Patients also must have 3 or more of the following:
History of involvement of the skin creases, such as folds of the elbows, behind the knees,
fronts of the ankles, or neck
Personal history of asthma or hay fever or a history of atopic disease in a first-degree
relative in patients younger than 4 years
History of generally dry skin in the last year
Visible flexural dermatitis or dermatitis involving the cheeks or forehead and outer limbs in
children younger than 4 years
Onset younger than age 2 years (not used if child is <4 y)

Causes

A genetic abnormality is possibly related to bands 11q13 or 5q31.2 These findings have yet to be
corroborated; a family history of AD is common.
The skin of patients with AD is colonized by S aureus. Lesions flare following infection by S aureus, but
they may occur with any type of skin or systemic infection. S aureus has been proposed as a cause of AD
by acting as a superantigen.
AD flares occur in extremes of climate. Heat is poorly tolerated, as is extreme cold. A dry atmosphere
increases xerosis. Sun exposure improves lesions, but sweating increases pruritus. All these external
factors may act as antigens, ultimately setting up an inflammatory cascade.
The role of food antigens in the pathogenesis of AD is controversial, both in the prevention of AD and by
their effect with withdrawal of certain foods in persons with established AD. Most reported research has
 methodologic flaws. One article showed improvement at 1 year with continued breastfeeding. At 4 years,
no difference was noted in the incidence of AD between the group that had not been exclusively breastfed
and the group that had.
A role for aeroallergens and house dust mites has been proposed, but this awaits further corroboration.

DIFFERENTIALS
Other Problems to be Considered

AD occasionally is indistinguishable from other causes of dermatitis. In infancy, the most common difficulty is
distinguishing it from SD. This entity is not seen with the same frequency as a decade ago. Both AD and SD are
associated with cradle cap (a scale found on the vertex of the scalp), which is greasy and yellow in individuals
with SD and dry and crusted in individuals with AD. Other areas of involvement in SD are the intertriginous
areas, where marked erythema and a greasy scale can be seen over the eyebrows and the sides of the nose. In AD,
xerosis of the skin and severe pruritus are seen, which are not usually features of SD. Both conditions should be
distinguished from psoriasis.

Scabies manifests in infancy or childhood as a pruritic eruption. Other members of the family may be itchy, and
the primary sites of involvement are moist warm areas. The eruption is polymorphic with a dermatitis, nodules,
urticaria, and 6-10 burrows. Pustules on the hands and feet are common in infancy. Facial involvement is rare, and
xerosis does not occur.

Other causes of dermatitis, particularly contact dermatitis from nickel in infants, are sometimes difficult to
distinguish from AD. A central area of dermatitis (from nickel snaps in undershirts or snaps in jeans) is helpful for
making the diagnosis, although a dermatitic eruption may occur as an Id reaction in other areas, particularly the
antecubital fossae. Xerosis and facial involvement are absent. AD usually starts earlier than contact dermatitis.

Children with a severe itch and generalized dermatitis in the setting of recurrent infections should be investigated
for evidence of an immunodeficiency. Failure to thrive and repeated infections help distinguish the eruption from
AD.

Tinea corporis usually manifests as a single lesion, but inappropriate treatment with steroids may cause a
widespread dermatitis. Facial involvement, the presence of xerosis, the age of appearance, and an early onset (in
AD) help distinguish between the 2 conditions.

Lab Studies

Laboratory testing is seldom necessary.

Allergy and radioallergosorbent testing is of little value.
A platelet count for thrombocytopenia helps exclude Wiskott-Aldrich syndrome, and testing to rule out
other immunodeficiencies may be helpful.
Scraping to exclude tinea corporis is occasionally helpful.

TREATMENT
Medical Care

Patients with AD do not usually require emergency therapy, but they may visit the emergency department for
treatment of acute flares caused by eczema herpeticum and bacterial infections.

Moisturization
o Depending on the climate, patients may benefit from short, cool showers or baths followed by the
application of a moisturizer such as white petrolatum. Another regimen includes "soaking and
greasing." Frequent baths with oil (1 capful of emulsifying oil added to lukewarm bath water) for
5-10 minutes comprise this regimen. In infants, 3 times a day is not a great burden; in adults, once
or twice a day is usually all that can be achieved. Leave the body wet after bathing. Oil and water
are kept in solution by an emulsifier in the oil, thus preventing evaporation of water to the outside
environment.
o Advise patients to apply an emollient such as petrolatum all over the body while wet, to seal in
moisture and allow water to be absorbed through the stratum corneum. The ointment spreads well
on wet skin.
Topical steroids
o Topical steroids are currently the mainstay of treatment. In association with moisturization,
responses to this regimen are excellent.
o Ointment bases are preferred, particularly in dry environments.
o Patients with AD may develop a contact allergy to topical medications and moisturizers. The
allergy may be to a preservative or the active ingredient. Allergy to hydrocortisone is recognized
with increasing frequency. Preservatives are less commonly present in ointments.
o Initial therapy consists of hydrocortisone 1% powder in an ointment base applied 3 times daily to
lesions on the face and in the folds.
o A midstrength steroid ointment (desonide for milder areas or higher-strength steroids such as
triamcinolone or betamethasone valerate for more severe areas) is applied daily to lesions on the
trunk until the eczematous lesions clear.
o Steroids are discontinued when lesions disappear and are resumed when new patches arise.
o Flares may be associated with seasonal changes, stress, activity, staphylococcal infection, or
contact allergy.
Immunomodulators
o Tacrolimus (topical FK506) is an immunomodulator and acts as a calcineurin inhibitor. Studies
have shown excellent results compared with placebo and hydrocortisone 1%. Little absorption
occurs. A stinging sensation may occur following application, but this can be minimized by
applying the medication only when the skin is very dry. The burning usually disappears within 2-3
days. Tacrolimus is available in 2 strengths, 0.1% for adults and 0.03% for children, although some
authorities routinely use the 0.1% preparation in children. Tacrolimus is an ointment and is
indicated for moderate-to-severe AD. The latter is indicated for children older than 2 years.
o Pimecrolimus 1% is also an immunomodulator and calcineurin inhibitor. It is more effective than
placebo. Pimecrolimus is produced in a cream base for use twice a day; it is indicated for mild AD
in persons older than 2 years.
o A recent black box warning has been issued in the United States based on research that has shown
an increase in malignancy in associated with the calcineurin inhibitors. While these claims are
being investigated further, the medication should likely only be used as indicated (ie, for AD in
persons older than 2 y and only when first-line therapy had failed).
Other treatments, effective and ineffective
o Probiotics have recently been explored as a therapeutic option for the treatment of AD. The
rationale for their use is that bacterial products may induce an immune response of the TH1 series
instead of TH2 and could therefore inhibit the development of allergic IgE antibody production.
This research, although garnering fairly convincing support, has yet to be proven.
o UV-A, UV-B, a combination of both, psoralen plus UV-A (PUVA), or UV-B1 (narrow band UV-B)
therapy may be used. Long-term adverse effects of skin malignancies in fair-skinned individuals
 should be weighed against the benefits.
o In patients with eczema herpeticum, acyclovir is effective.
o In patients with severe disease, and particularly in adults, phototherapy, methotrexate (MTX),
azathioprine, and cyclosporine have been used with success.
o Both hydroxyzine and diphenhydramine hydrochloride provide a certain degree of relief from
itching but are not effective without other treatments.
o Ketotifen (a calcium channel blocker) may be effective.
o Oil of evening primrose was believed to be effective, but in a randomized controlled study, it
showed no benefit in children and little improvement in adults.
o Results with many other medications, such as thymopentin, gamma interferon, and Chinese herbs,
have been disappointing. Many medications are not practical to use, and they can be expensive.
Some Chinese herbal preparations contain prescription medications, including prednisone.
o Antibiotics are used for the treatment of clinical infection caused by S aureus or flares of disease.
They have no effect on stable disease in the absence of infection. Laboratory evidence of S aureus
is not evidence of clinical infection because staphylococcal organisms commonly colonize the skin
of patients with AD.
Nonmedical efforts
o Clothing should be soft next to the skin. Cotton 100% is comfortable and can be layered in the
winter.
o Cool temperatures, particularly at night, are better because sweating causes irritation and itch.
o A humidifier (cool mist) prevents excess drying and should be used in both winter, when the
heating dries the atmosphere, and in the summer, when the air conditioning absorbs the moisture
from the air.
o Clothes should be washed in a mild detergent with no bleach or fabric softener.

Diet

Avoid foods that provoke acute allergic reactions (hives, anaphylaxis). Most frequently, allergic reactions
occur to peanuts (peanut butter), eggs, fish and seafood, milk, soya, and chocolate.
Advise patients to apply a barrier of petroleum jelly around the mouth prior to eating to prevent irritation
from tomatoes, oranges, and other irritating foods.

Activity

Advise patients to avoid activities that cause excessive sweating.

Swimming in an outdoor pool (or wading pool for babies) in summer provides therapeutic benefit by
exposing the person to the sun but avoiding the heat.

MEDICATION
The basis of treatment is to provide moisturization for dryness, allay pruritus, and manage inflammation of the
eczematous lesions.

Complications

If topical corticosteroids are used inappropriately or if superpotent steroids are used in teenagers during
rapid growth, striae may occur. Skin thinning can result if steroids are used inappropriately in older
patients.
Whether verrucae vulgaris and mollusca contagiosa are more frequent is difficult to assess, but certainly,
they can be more widespread and difficult to eliminate.
 Tachyphylaxis to topical steroids occurs if they are not used on a stop-start basis.

Prognosis

Most patients improve; this can occur at any age. While the frequency of AD is as high as 20% in
childhood, it is 0.9% in adults.
One third of patients develop allergic rhinitis.
One third of patients develop asthma.