Transcript Atopic Dermatitis

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 (IgE-induced)
vaso-dilatory 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 non-immunocompromised 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, placebo-controlled 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 – Kaposi’s 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, ill-appearing 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 Dermatitis
Inflammation of the 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 solvent
exposures
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