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Atopic Dermatitis.
Jonathan I. Silverberg, M.D., Ph.D., M.P.H.
Assistant Professor, Departments of Dermatology,
Preventive Medicine and Medical Social Sciences
Director, Northwestern Multidisciplinary Eczema Center
Northwestern University, Feinberg School of Medicine
Chicago, IL USA

No relevant financial disclosures or conflicts
of interest

At times, I will use the term eczema and
atopic dermatitis. These are not actually the
same thing.

We will touch upon a number of important
topics in eczema, but there is so much more
that we wont have time to address.

What does eczema look like?

How common is eczema?

What are some common risk factors for
eczema?

What are some common treatment
approaches for eczema?

What health problems occur in patients with
eczema?

Ill-defined
Hard to delineate
where the lesions
start and stop

Erythematous
Ranges from light pink
to flaming red

Patches or
Plaques
Ranges from flat to
very thick plaques

asdsad
Spongiosis

Fluid between cells

Perivascular
infiltrate
Inflammation around
the blood vessels

Early or acute eczema
Eosinophils

asdsad
Parakeratosis

Scale

Acanthosis
Thickening of the
epidermis
Chronic eczema

asdsad
Eczema is a morphological pattern either
visually or microscopically.

There are several types of eczema:

 Atopic dermatitis (AD)
 Contact dermatitis
▪ Irritant contact dermatitis (ICD)
▪ Allergic contact dermatitis (ACD)
 Drug-induced dermatitis
Age related changes of distribution:




Infancy:
Facial and scalp dermatitis
Toddler:
Extensor dermatitis
Older children and adults:
Flexural distribution
Adults:
More head & neck and hand lesions.
Flexural distribution
Lichenification
Antecubital and popliteal fossa,
anterior neck, wrists, ankles
Accentuation of skin lines
Secondary to rubbing and
scratching
Pathomnomonic
Occurs in chronic lesions
Erythema may appear more
purple or brown than red in skin
of color

Head and neck
distribution
More common in adults
 Eyelids
Usually accompanied by other
signs and symptoms of AD.
Case reports of AD presenting
exclusively on the eyelids.
 Hands
Often only finding in adults with
AD.
Katsarou A, Armenaka M. Atopic
dermatitis in older patients:
particular points. Journal of the
European Academy of
Dermatology and Venereology :
JEADV. 2011;25(1):12-18.

1-year prevalence of eczema in US adults is
10.2%
Silverberg JI, Hanifin J. Adult eczema prevalence and associations with asthma and other
variables: A US population-based study. Journal of Allergy and Clinical Immunology. 2013
Nov;132(5):1132-8.

Remarkably similar to the 10.7% prevalence
of eczema found in US children.
Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States:
data from the 2003 National Survey of Children's Health. J Invest Dermatol. 2011
Jan;131(1):67-73.

Most common inflammatory skin disease.
Silverberg JI. Unpublished data.
Statewide prevalence
of eczema was divided
into tertiles. Data are
presented as the
percent (95% CI) of
subjects who
endorsed having
eczema in the past 12
months.

2012 National Health Interview Survey
Children: 12.0% (11.3-12.7%)
Adults: 7.2% (6.9-7.6%)
US ECZEMA PREVALENCE (%)
16
14
12
10
8
6
4
2
0
Silverberg JI. Unpublished data.
AGE (YR)
Silverberg JI and Simpson EL.
Pediatric Allergy and Immunology. 2013.
 Higher prevalence in African American children and
adolescents.
Variable
Race/ethnicity – no. (%)
African-American
Hispanic
White
Other/mixed
No eczema
Eczema
6495 (80.3)
8582 (89.7)
46777 (87.9)
6186 (86.1)
1618 (19.7)
1215 (10.3)
6326 (12.1)
1079 (13.9)
P-value
< 0.0001
* Rao-Scott Chi square test
Silverberg JI, Hanifin J, Simpson EL. Climatic factors are associated with childhood
eczema prevalence in US. Journal of Investigative Dermatology. July 2013.
Similar results observed in: Shaw T, Currie GP, Koudelka CW, Simpson EL: Eczema
prevalence in the United States: Data from the 2003 National Survey of Children’s Health.
J Invest Dermatol 131:67-73, 2011.
Inside US
Percent
(95% CI)
13.3
10133
(12.7 – 13.8)
Eczema prevalence
Freq
Freq
8731
Freq
7004
Freq
174
Percent
Freq
(95% CI)
13.2
1076
(13.5 – 14.8)
Percent
(95% CI)
13.0
(12.3 – 13.7)
Freq
894
Outside US
Child’s birthplace
Percent
OR
P-value
(95% CI)
(95% CI)
6.1
0.43
<0.0001
(4.1 – 8.1) (0.30 – 0.61)
Mother’s birthplace
Percent
OR
P-value
(95% CI)
(95% CI)
9.2
0.62
<0.0001
(8.0 – 10.5) (0.53 – 0.72)
Father’s birthplace
Percent
OR
P-value
(95% CI)
(95% CI)
9.5
0.70
<0.0001
(8.2 – 10.8) (0.59 – 0.82)
aOR
(95% CI)
0.45
(0.30 – 0.69)
aOR
(95% CI)
0.58
(0.48 – 0.71)
aOR
(95% CI)
0.68
(0.54 – 0.85)
P-value
0.0003
P-value
<0.0001
P-value
0.0009
Silverberg JI, Simpson EL, Durkin HG, Joks R. Prevalence of allergic disease is lower in foreignborn American children, but increases with prolonged US residence. JAMA Pediatrics. 2013.
Duration of residence in the US (yr)
> 10
0–2
3 – 10
Percent
Percent
aOR
Percent
aOR
Freq
Freq
P-value Freq
P-value
(95% CI)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
5.1
6.5
1.96
35
6.8
4.93
0.029
44
94
0.15
(2.7 – 7.5)
(3.4 – 9.7) (0.79 – 4.85)
(1.9 – 11.7) (1.18 – 20.62)
Silverberg JI, Simpson EL, Durkin HG, Joks R. Prevalence of allergic disease is lower in foreignborn American children, but increases with prolonged US residence. JAMA Pediatrics. 2013.

Children born outside the US have significantly lower
prevalence of eczema (and other allergic disorders).

Duration of residence in the US is a previously unrecognized
factor in the epidemiology of AD.
Silverberg JI, Hanifin J, Simpson EL. Journal of Investigative Dermatology. 2013.


Recent meta-analysis of 30 studies from across the medical literature.
Obesity was associated with higher rates of eczema in children and
adults in North America and Asia.
Zhang A and Silverberg JI. Journal of the American Academy of Dermatology. In Press.

Topical agents
 Corticosteroids, e.g. hydrocortisone
 Calcineurin inhibitors, e.g. tacrolimus.

Systemic agents
 Corticosteroids
 Cyclosporine
 Mycophenolate mofetil
 Tacrolimus
 Methotrexate
 Azathioprine

Light therapy and lasers
 NBUVB, Excimer, PUVA




Oral: prednisone, methylprednisolone, etc.
IV: methylprednisolone
Intralesional and intramuscular: Triamcinolone
Rapid onset, dramatic improvement of
disease.
Horrific adverse effect profile:


Weight gain, Cushingoid habitus, diabetes, hypertension,
gastroesophageal reflux, osteoporosis with prolonged use,
osteonecrosis even with a single dose, adrenal insufficiency,
increased risk of mild and serious infections and malignancy,
neurocognitive events including depression and psychosis,
fluid overload secondary to mineralcorticoid activity, etc.

More appropriate for contact dermatitis with brief or
limited exposures, e.g. poison ivy.

Should be avoided for chronic persistent atopic
dermatitis.
Best evidence for shutting down active disease and
preventing flares
Typically works as fast as prednisone, but has longer
lasting benefit.
Adverse effect profile not perfect, but better than
prednisone:






Hypertension, kidney injury/disease, hyperkalemia, hypomagnesemia,
gingival hypertrophy, hypertrichosis, dizziness, GI upset, increased risk
of infection, increased risk of solid organ and hematological malignancy
especially with prolonged use.
Can only use for limited period of time (6-24 months).
Must monitor blood pressure regularly and check
bloodwork periodically.

Efficacy also established in well-designed trials
Easier dosing: once weekly
Slower onset of action than CsA. Can be used for
extended periods.
May not be as effective as CsA at standard doses

Adverse effects:






Anemia/pancytopenia, elevated transaminases and liver
fibrosis/failure, GI upset, heavy menstrual bleeding, increased
risk of infection and malignancy
Must monitor bloodwork periodically.
Should be given with folic acid 1mg daily

Efficacy demonstrated in well-designed trials;
however, allowed the most breakthrough flares
requiring add-on tx with prednisone

My personal experience: not as effective as CsA or
MTX


Generally, better tolerated than other systemics.
Adverse effects:

Anemia, pancytopenia, gastrointestinal discomfort and
diarrhea, genitourinary complaints, swelling, increased risk of
infection and malignancy, case-report of PMLE.




Multiple RCT demonstrated efficacy in AD.
Used commonly in Europe. Not as much in US.
Check bloodwork at baseline and periodically.
Can monitor therapeutic levels with blood test.

Adverse effects:

Hypersensitivity with rash, GI upset, increased risk of
infections and malignancy, bone marrow suppression.
Fully human anti- interleukin 4 receptor alpha
antibody
Blocking antibody  downregulation of IL4 and
IL13 pathways, i.e. Th2 immune responses.






Th2 responses are found in acute and chronic AD skin lesions,
asthma, hay fever and food allergies.
Represents first “targeted therapy” for AD
Initial benefit demonstrated in asthma with
eosinophilia (NEJM, 2013).
Currently in phase 2B recruitment.

The toxicity of the abovementioned systemic
agents lies in their blanket immunosuppression.

More targeted therapy may:




Improve efficacy
Eliminate toxicity beyond the immune system
Minimize immunological sequelae with decreased
risk of infection and malignancy.
In turn, these open the door for ongoing
maintenance therapy for months or even years.

Phase 2 study of a monoclonal anti-IL31
antibody for AD (Chugai).

Phase 1 study of a monoclonal anti-IL31
antibody for AD (Bristol-Myers Squibb).

Both with promising results as treatments for
itch in AD and well tolerated.

Intravenous immunoglobulin, omalizumab –
evidence does not support efficacy in AD.
 AD is a Th2 mediated, but not an IgE mediated
disease.

Anti-interleukin 5 antibodies – only modest
effects.
 Higher out of pocket (OOP) costs
overall.
 $32,875,382,250 annual OOP costs in
eczema patients.
 $502/ year additional OOP cost per
patient.
Silverberg JI. JAMA Dermatology. In Press.
 5,898,289 lost workdays for eczema per se
 221,607,545 days in bed for adults with eczema
 More doctor visits and ER visits for adults with
eczema.
 1 in 4 adults with eczema did not see a doctor for
their eczema.
Silverberg JI. JAMA Dermatology. In Press.
 One third of adults with eczema reported having
regular fatigue, daytime sleepiness and
insomnia.
 Sleep disturbance and fatigue are major players
in the poor quality of life, number of sick days
and doctor visits in patients with eczema.
Silverberg JI, et al. Journal of Investigative Dermatology. 2014.
Silverberg JI and Simpson EL. Pediatric Allergy and Immunology. 2014.
Silverberg JI and Simpson EL. Pediatric Allergy and Immunology. 2014.
 Children with eczema have lower bone mineral
density.
Silverberg JI. Pediatric Allergy
and Immunology. In Press.
 Adults with eczema have:
 Lower bone mineral density overall.
 Higher rates of osteoporosis.
 Higher rates of fractures.
Garg NK and Silverberg JI.
Journal of Allergy and Clinical
Immunology. In Press.
 Children with eczema have higher rates of
serious injuries requiring medical attention.
Garg NK and Silverberg JI. Annals of
Allergy, Asthma and Immunology. 2014.
Garg NK and Silverberg JI.
JAMA Dermatology. 2014.
Not an allergy per se.
Infrequent exposure to strong irritants or frequent
exposure to milder irritants.
 Often occurs in atopic dermatitis due to impaired
barrier and lower irritant threshold.


Nassif A, Chan SC, Storrs FJ, Hanifin JM. Abnormal skin irritancy in atopic dermatitis and
in atopy without dermatitis. Archives of dermatology. 1994;130(11):1402-1407.

Common exposures include:
 Frequent hand washing
 Hand sanitizers
 Harsh soaps, e.g. antibacterial.
 Heavily fragrant skin care products.


Skin allergy.
May become allergic after infrequent
exposure to strong allergens or frequent
exposure to milder allergens.

Once an allergy develops, even minimal
exposures can be provocative.

Delayed reactions that take takes, sometimes
weeks, to develop.

Monday: Patches applied to back
with adhesive tape.

Wednesday: Patches removed and
placemarker grid is drawn with
marker.
 Thursday: Final
reading.

Sometimes: Monday,
Thursday, Monday
sequence

Rationale
 15.7% of adults with eczema have active hay fever
 21.1% of adults with eczema have a history of asthma, of
which 40.8% had an asthma attack in past year.
Silverberg JI, Hanifin J. Adult eczema prevalence and associations with asthma and other variables: A US population-based
study. Journal of Allergy and Clinical Immunology. 2013 Nov;132(5):1132-8.
 One third of adults with eczema have sleep disturbances
that cause poor quality of life.
Silverberg JI, Garg NK, Paller AS, Fishbein A, Zee PC. Sleep disturbances in adults with eczema are associated with impaired
overall health: A US population-based study. Journal of Investigative Dermatology. 31 July 2014; doi: 10.1038/jid.2014.325.
 Eczema is associated with significant psychological
comorbidities and behavioral problems, including
depression, anxiety and attention deficit (hyperactivity)
disorder.
Gark NK, Silverberg JI. Association between childhood allergic disease, psychological comorbidity and injury requiring medical
attention. Annals of Allergy, Asthma and Immunology. 2014 Jun. 112(6): 525-32.
Monthly clinic
Providers from Dermatology (Silverberg), AllergyImmunology (Peters and Grammer) and Neurology-Sleep
Medicine (Attarian).
 Psychiatry will be joining soon (Franks).


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Services provided include:
 Consultation and treatment.
 Patch testing for allergic contact dermatitis.
 Skin prick testing for seasonal and food allergies.
 Spirometry for asthma assessment.
 Actigraphy for assessment of sleep disturbances.

History
 First session in May, 2014
 Seen >70 patients from 6 states to-date.
 Provided unique insight into the comorbidities of
atopic dermatitis, resulting in two research grant
submissions.
Thank you.
Questions??