Atopic Dermatitis

Alyson W. Smith, MD
Director of Pediatric Allergy
St. Barnabas Hospital

Atopic dermatitis (AD) is a chronic, highly pruritic,

eczematous skin disease that follows patients
from early childhood into puberty and sometimes
adulthood.

Also referred to as eczematous dermatitis, the

disease often has a remitting/flaring course, which
may be exacerbated by social, environmental, and
biological triggers.

Prevalence

Approximately 15% in the US and

Europe
This represents a profound increase
in recent years (from as low as 3% in
1960)

Natural History of Atopic

Dermatitis

60% of pts develop AD by 1 year of age.

85% of pts develop AD by age 5.
Earlier onset often indicates a more severe
course.
Many cases resolve by age 2, improvement by
puberty is common.
50%-60% of pts develop respiratory allergies
or asthma.
80% of occupational skin disease occur in
atopics.
It is rare to see AD after age 50.

The Atopic March

Bergmann (1998, Clin Exp Allergy)

Prospective birth cohort study, N 1314, 5yo
If AD at 3 mos and one parent/sibling atopic >50%
chance of asthma at age 5-6
Castro-Rodriquez (1999, AJRCCM)
Longitudinal, retrospective study, N 986
If AD and parental asthma; >75% chance of asthma
during school years.

Filaggrin

Filaggrins are filament-associated proteins

which bind to keratin fibers in epithelial cells
Individuals with truncation mutations in the gene
coding for filaggrin are strongly predisposed to a
severe form of dry skin, ichthyosis vulgaris,
and/or eczema
It has been shown that almost 50% of all severe
cases of eczema may have at least one mutated
filaggrin gene.

Ichythosis vulgaris

Infantile atopic
dermatitis

Infants less than one year old often have widely distributed
eczema. The skin is often dry, scaly and red with small scratch
marks made by sharp baby nails.
The cheeks of infants are often the first place to be affected by
eczema.
The diaper area is frequently spared due to the moisture retention
of diapers. Just like other babies, they can develop irritant diaper
dermatitis, if wet or soiled diapers are left on too long.

Toddlers and pre-schoolers

As children begin to move around, the eczema becomes

more localized and thickened. Toddlers scratch vigorously
and the eczema may look very raw and uncomfortable.
Eczema in this age group often affects the extensor (outer)
aspects of joints, particularly the wrists, elbows, ankles and
knees. It may also affect the genitals.
As the child becomes older the pattern frequently changes
to involve the flexor surfaces of the same joints (the creases)
with less extensor involvement. The affected skin often
becomes lichenified i.e. dry and thickened from constant
scratching and rubbing,
In some children the extensor pattern of eczema persists
into later childhood.

Atopic dermatitis in school-age

children

Older children tend to have the flexural pattern of eczema and it

most often affects the elbow and knee creases. Other susceptible
areas include the eyelids, earlobes, neck and scalp.
Many children develop a 'nummular' pattern of atopic dermatitis.
This refers to small coin-like areas of eczema scattered over the
body. These round patches of eczema are dry, red and itchy and
may be mistaken for ringworm (a fungal infection).
Mostly the eczema improves during school years and it may
completely clear up by the teens, although the barrier function of
the skin is never entirely normal.

Xerosis (dry skin)

Lichenification

Nummular Eczema

Keratosis pilaris

Palmar hyperlinearity

AD
(Juvenile Plantar Dermatosis)

Food Allergy and Atopic

Dermatitis

Children:
Moderate-Severe AD ( up to 33%) have
(transient) clinically significant food
allergy
Increasing severity of AD ~ increasing risk
of food allergy
Adults:
Low incidence (<2%)
Foods responsible (~85% of cases):
Outgrown: Milk, egg, soy, wheat
Persistent: Peanut, nuts, fish, shellfish

Evaluation of Food Allergy in

AD
Laboratory studies
Specific IgE (Immunocap)-ONLY if
clinically
indicated!
Skin prick testing
Clinical evaluation:
Elimination diets
Oral food challenges
Physician supervised
Open, single blind, double-blind,
placebo controlled

Triggers

Irritants
Wool
Soaps/detergents
Disinfectants
Occupational
Tobacco smoke
Microbial agents
Staph aureus
Viral infection
?Dermatophytes

Heat/Sweating
Contactants
incl. Dust
mites
Psychological
Foods (IgEinduced) vasodilatory items
Aeroallergens
Hormones
Climate

Managing AD
(Preventative)

Prevent scratching or rubbing

a) apply cold compresses to itchy skin
Carefully eliminate all the triggers of
itch
a) environmental, occupational, and
temperature control
b) bathing soapless cleansers, Dove
c) LUBRICATION LUBRICATION
LUBRICATION

Managing AD
(Palliation)

Topical anti-inflammatory agents

a) corticosteroids
(ointments>creams)
more potent - when acute
least potent needed for chronic
b) Tacrolimus 0.1% ointment,
Pimecrolimus 1% Cream

Corticosteroids

These

are the cornerstones of therapy of

atopic dermatitis. The following principles
should be adhered to while instituting
topical steroid therapy:
High potency steroids are used for a short
period to rapidly reduce inflammation.
Maintenance therapy, if needed is best
done with mild steroids like
hydrocortisone.
On face and intertriginous areas, mild
steroids should be used, mid-potency
formulations are used for trunk and limbs.

Corticosteroids

Topical steroids are applied initially twice or three

times a day. After the symptoms are lessened,
frequency of application should be reduced.
Intermittent use if topical steroid may be alternated
with application of emollients.
Ointments are superior to creams or lotions.
The potential side-effects of topical steroids should
always be kept in mind.
Systemic steroids: a short course of systemic
steroids (prednisolone, triamcinolone) may
occasionally be needed to suppress acute flare-ups.
Intralesional steroids (triamcinolone acetonide)
may help resolve thickened plaques of eczema not
responding to topical agents

Calcineuron Inhibitors
Indications

Protopic (tacrolimus) Ointment, both 0.03% and 0.1% for adults;

0.03% for children aged 2-15 years
For short-term and intermittent long-term therapy in the
treatment of moderate to severe atopic dermatitis in patients
For whom the use of alternative, conventional therapies are
deemed inadvisable because of potential risks
or
Who are not adequately responsive to, or are intolerant of
alternative, conventional therapies.
Elidel (Pimecrolimus Cream 1%) for patients 2 years of age and
older
For short-term and intermittent long-term therapy in the
treatment of mild to moderate atopic dermatitis in nonimmunocompromised patients
For whom the use of alternative, conventional therapies are
deemed inadvisable because of potential risks
or
Who are not adequately responsive to, or are intolerant of
alternative, conventional therapies.

Calcineuron Inhibitors

Advantages
A Rx option to CS
No steroid atrophy
For adults and children >2yrs.
Sx improvement
within
1-3 weeks.
Long-term
intermittent
use

Limitations
Off-label for children
<2 yrs.
Burning, stinging,
itching, after application
often
minimal and
transient.
Black box warning

Basis for FDA

concern

Because of a perception by physicians and patients that topical

pimecrolimus and tacrolimus are safer than steroid preparations,
they had been increasingly been used as first-line therapy and off
label. There were almost 2 million prescriptions written of these
topical medications for children between June 2003 and May
2004 and approximately half a million were for those under 2
years of age.
Known toxicity of immunosuppressant doses of systemically
administered tacrolimus: lymphoproliferative disease,
photocarcinogenicity, and increased risk of nonmelanoma skin
cancers
Animal studies in mice, rats, and monkeys have found an
increased risk of lymphoma and skin cancers with topical and
oral exposure to calcineurin inhibitors (dose used 30x maximum
human dose in monkey study)
March 2010-46 cancer cases and 71 infection cases have been
reported in patients aged 16 and younger from 2004 to 2008
with Novartis' Elidel and Astellas' Protopic.

More controlled studies are needed

on the use of TCI, especially in
patients less than two
years.
Long term effects not known.
Should only be used as a second line
agent.

Emollients
Atopic dermatitis patients frequently have dry skin
which is aggravated during winter months.
Xerosis (dryness) breaks the barrier function of the
skin and promotes infection and inflammation.
Ointments are preferred over lotions or creams.
Emollients should be applied immediately after a
soaking bath to retain the moisture.
Emollients containing urea or alpha-hydroxy acids
often cause stinging or burning sensations.

Antihistamines

Antihistamines give variable results in controlling

pruritus of atopic dermatitis since histamine is
not the only mediator of itching in atopic patients.
Any of the non-sedating antihistamines like
cetirizine, loratadine or fexofenadine may be
used.
The conventional antihistamines like
diphenhydramine or hydroxyzine may give better
results for their additional actions as a sedative
or anxiolytic.
Topical antihistamines should be avoided for their
sensitizing potential.

Antimicrobials
Infections and colonization with Staphylococcus
aureus may aggravate or complicate AD.
Antibiotics like erythromycin, cephalosporins, or
cloxacillin are usually prescribed.
Dermatophytosis or Pityrosporum infections are
treated with antifungals.
Acyclovir or other appropriate antiviral agents
should be promptly advised for treatment of
herpes simplex infections.

Oral immunomodulators

Cyclosporine:
By virtue of its immunomodulating action,
cyclosporine has a limited role in controlling
atopic dermatitis in recalcitrant adult cases.
The potential side effects should always be
kept in mind.
Azathioprine:
This immunosuppressive agent has also been
used in severe adult cases. Again, potential
side effects limit its role in selected cases.

Other Therapies

Tar
may be useful, particularly for the scalp, over the counter, smelly,
stained clothes
Phototherapy
Ultraviolet B (UVB) alone, or in combinations with UVA may be
beneficial in selected patients.
Probiotics
The rationale for their use is that bacterial products may induce
an immune response of the TH 1 series instead of TH 2 and
could therefore inhibit the development of allergic IgE antibody
production.
Chinese herbal medicine
Some Chinese herbal preparations contain prescription
medications, including prednisone, and have been associated
with cardiac and liver problems.
Bleach baths-A randomized, investigator-blinded, placebocontrolled trial including 31 patients showed that intranasal
mupirocin ointment and diluted bleach (sodium hypochlorite)
baths improved atopic dermatitis symptoms in patients with
clinical signs of secondary bacterial infection.

Complications of AD

Secondary Infection
a) bacterial
impetiginization
super-antigenicity
b) viral
localized verruca, molluscum, herpes
systemic Kaposis herpetiform eruption
c) mycotic
Dermatophyte
Candidal

Staphylococcus aureus &

Skin

S. aureus a saprophytic bacteria detected in 5%

to 30% of healthy persons skin and in 20% of
their nares.
S. aureus carriage rate in AD is 76% for
uninvolved skin, 93% for lesional skin and 79%
for the anterior nares.
S. aureus colonization has potential to modify
dermatologic diseases, in particular, S. aureus
enterotoxins A-E can act as superantigens.
Superantigens bind as intact proteins to T-cell
receptors and MHC class II molecules.

S. aureus & Skin

HSV- ezcema herpeticum

Clusters of multiple, uniform, 2-3mm crusted

papules and vesicles develop in untreated or
poorly controlled atopic dermatitis. The initial
infection may be accompanied by fever,
malaise, and lymphadenopathy.
Complications: keratoconjunctivitis and
viremia (multiple organ involvement with
meningitis and encephalitis)
Tx: acyclovir (PO for mild, localized
symptoms), hospitalization for febrile, illappearing or young infants, No steroids or
calcineurin inhibitors

Differential Diagnosis of
Atopic Dermatitis

Dermatitis
-Contact
-Seborrheic
Immunodeficiencies
Metabolic Diseases
Neoplastic Diseases
Infection and Infestation
-Candida
-Herpes simplex
-Scabies
Psoriasis

Seborrheic dermatitis

Flaky,white to yellowish scales form on oily areas

Involvement of the top of the scalp (cradle cap),
axilla, and diaper area

Allergic Contact
Inflammation of the Dermatitis
skin caused by direct contact with an irritating
substance
Skin lesion or rash at the site of exposure
Lesions of any type: redness, rash, papules (pimple-like),
vesicles, and bullae (blisters)
May involve oozing, draining, or crusting
May become scaly, raw, or thickened
Dx: patch testing
Tx: avoidance, topical steroids

Uroshiol
Uroshiol

Nickel

Textile dye

Patch testing

Irritant Contact
Dermatitis
Irritant contact dermatitis
occurs when chemicals or physical
agents damage the surface of the skin faster than the skin is able
to repair the damage.
Irritants include such everyday things as water, detergents,
solvents, acids, alkalis, adhesives, metalworking fluids and friction.

47-year-old
housekeeper was the
result of chronic hand
washing combined with
surfactant and other

Immunodeficiencies

Wiskott-Aldrich syndrome
-X-linked recessive disease
-Eczema, thrombocytopenia, and
immunodeficiency
DiGeorge syndrome
Hyper-IgE syndrome
Severe combined immune deficiency

Hyper IgE (Job

Syndrome)

Characterized by recurrent skin abscesses, pneumonia with

pneumatocele development, and high serum levels of IgE.
Facial, dental, and skeletal features are also associated with
this syndrome.

Job Syndrome

Metabolic disease

Phenylketonuria
Tyrosinemia
Histinemia
Multiple carboxylase deficiency
Essential fatty acid deficiency

Neoplastic Diseases

Cutaneous T-cell lymphoma

Histiocytosis X
Sezary syndrome

**Skin lesions that do not heal with

normal medications!

Histiocytosis

Langerhans cell histiocytosis often produces a seborrheic

dermatitis-like eruption that involves the axilla or diaper
area. Lesions are erythematous or red-brown papules that

may become eroded. Petechiae often are present

Scabies
Sites of predilection include the interdigital folds on the
hands and feet, the anterior axillary folds, the areolae
of the breasts and the peri-umbilical region.
The pathognomonic lesions of scabies are comma-shaped
or irregularly convoluted burrows.
At the end of each burrow, the mite is just discernible
with the naked eye as a dark point.

Psoriasis
Psoriasis is a chronic autoimmune disease that appears on the
skin. It commonly causes red, scaly patches to appear on the
skin, although some patients have no dermatological symptoms.
The scaly patches commonly caused by psoriasis, called
psoriatic plaques, are areas of inflammation and excessive skin
production.

When to Refer.

When the diagnosis is uncertain

When patients have failed to respond to
appropriate therapy
If treatment of atopic dermatitis of the
face or skin folds with high potency topical
corticosteroids is being contemplated
If treatment with systemic
immunosuppressive agents is being
considered

Prevention?

There is evidence that for infants at high risk of

developing atopy, breastfeeding for at least 4
months or breastfeeding with supplements of
hydrolyzed infant formula decreases the risk of
atopic dermatitis and cow milk allergy in the first
2 years of life.
There is modest evidence that the onset of atopic
disease may be delayed or prevented by the use of
hydrolyzed formulas compared with formula made
with intact cow milk protein, particularly for
atopic dermatitis.

Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and
Children: The Role of Maternal Dietary Restriction, Breastfeeding, Timing of Introduction
of Complementary Foods, and Hydrolyzed Formulas PEDIATRICS Volume 121, Number 1,
January 2008