What You Should Have Read But...2010: Diagnosing Primary Immunodeficiencies

WHAT YOU SHOULD HAVE READ BUT….2010

 atopic dermatitis
Attilio Boner
University of
Verona, Italy

Diagnosis of primary immunodeficiency: Let your
eyes do the talking. Shah JACI 2009:124:1363
Every screening evaluation for
primary immunodeficiency must
include a physical examination of the
patient because the powers of
observation should direct the
evaluation for several types of
primary immunodeficiency.
For example, simple inspection of the
patient for growth, lymphoid tissue
(X-linked agammaglobulenemia), allow Lymph nodes are very small.
for proper direction toward making No cervical lymph nodes and no tonsills
the diagnosis of primary
immunodeficiency.


Every screening evaluation for primary
immunodeficiency must include a
physical examination of the patient
because the powers of observation
should direct the evaluation for several
types of primary immunodeficiency.
patient for telangiectasias
(ataxia-telangiectasia), allow for
proper direction toward making the
diagnosis of primary immunodeficiency.


include a physical examination of
the patient because the powers of
For example, simple inspection of
the patient for abnormal facies
(DiGeorge syndrome), allow for
proper direction toward making
the diagnosis of primary
immunodeficiency.
no thymus


patient for chronic eczema
(Wiskott-Aldrich syndrome,
Wiskott-Aldrich syndrome
hyper-IgE syndrome, and immune (WAS) is a condition with
dysregulation polyendocrinopathy variable expression, but
enteropathy X-linked syndrome), allow commonly includes IgM
deficiency and persistent
for proper direction toward making the thrombocytopenia


hyper-IgE syndrome, and immune
dysregulation polyendocrinopathy
enteropathy X-linked syndrome), allow
for proper direction toward making the

Every screening evaluation for primary a syndrome of variable autoimmune
immunodeficiency must include a features including eczema,
enteropathies, hemolytic anemia, and
physical examination of the patient endocrinopathies (diabetes mellitus
because the powers of observation and thyroid pathology), abnormal
should direct the evaluation for several responses to viral infections;
associated death in infancy or early
types of primary immunodeficiency. childhood
hyper-IgE syndrome, and immune
dysregulation polyendocrinopathy
enteropathy X-linked syndrome), allow
for proper direction toward making the


include a physical examination of the
patient because the powers of
For example, simple inspection of bone marrow
the patient for pale skin and smears show
photophobia "giant inclusion
bodies" in the
(Chediak-Higashi syndrome), allow cells
for proper direction toward making
the diagnosis of primary It is a disease with impaired bacteriolysis due
immunodeficiency. to failure of phagolysosome formation. so
phagocytosed bacteria are not destroyed


include a physical examination of
the patient because the powers of
For example, simple inspection of Leukocyte adhesion deficiency (LAD)
the patient for severe is a rare primary immunodeficiency.1
gingivostomatitis (leukocyte The clinical picture is characterized
by marked leukocytosis and localized
adhesion defect) allow for proper bacterial infections that are difficult
direction toward making the to detect until they have progressed
diagnosis of primary to an extensive level secondary to
lack of leukocyte recruitment at the
immunodeficiency. site of infection.


Every screening evaluation for Leukocyte adhesion deficiency type I
primary immunodeficiency must (LAD I) may be diagnosed prior to the
onset of infections when delayed
include a physical examination of umbilical cord separation (normal
the patient because the powers of separation is 3-45 d, with a mean of 10
observation should direct the d) is observed with a persistently high
WBC count (>20 X 109/L) in the absence
evaluation for several types of of infection. Patients with leukocyte
primary immunodeficiency. adhesion deficiency I typically
For example, simple inspection of experience from omphalitis, perirectal
and labial cellulitis, infections
the patient for severe classically seen in patients with
gingivostomatitis (leukocyte neutropenia, otitis media with minimal
adhesion defect) allow for proper inflammation, and other indolent
necrotic skin infections. Pus is not
direction toward making the present, but serosanguineous fluids
diagnosis of primary may be present.
immunodeficiency.

Global variations in prevalence of eczema symptoms
in children from ISAAC Phase Three
Odhiambo JACI 2009:124:1251

715,033 children from 154 centers in 56 countries.
For the age group 6 to 7 years the prevalence of
current eczema ranged from 0.9% in India to
22.5% in Ecuador.
For the age group 13 to 14 years prevalence values
ranging from 0.2% in China to 24.6% in Columbia.
Current eczema was lower for boys than girls
(odds ratio, 0.94 and 0.72 at ages 6 to 7 years
and 13 to 14 years.


World maps showing
prevalence of current
symptoms of eczema for
the age group 6 to 7 yrs.
Blue squares indicate
prevalence < 5%,
green circles indicate
prevalence of 5% to < 10%,
yellow diamonds indicate
red stars indicate
prevalence ≥ 15%

The prevalence of atopic dermatitis in Italy is 10% to 15%


World maps showing
prevalence of current
symptoms of eczema for the
age group 13 to 14 yrs.
Blue squares indicate
prevalence < 5%,
green circles indicate
yellow diamonds indicate
red stars indicate
prevalence ≥ 15%

The prevalence of atopic dermatitis in Italy is 5% to 10%

Infant-onset eczema in relation to mental health
problems at age 10 years: Results from a prospective
birth cohort study (German Infant Nutrition Intervention plus)
Schmitt JACI 2010;125:404

 A birth cohort (n=2916) In children with infant-onset
followed until age 10 eczema OR for
years. 2.0 –

 Association between 1.5 – 1.62
infant-onset eczema 1.49 1.31
(age 1-2 years) and 1.0 –
mental health problems
P=0.005 P<0.001 P=0.08
at age 10 years 0.5 –
according to the
Strengths and
0
Difficulties possible/probable emotional conduct
Questionnaire. mental health symptoms problems
problems

Infant-onset eczema in relation to mental health
problems at age 10 years: Results from a prospective
birth cohort study (German Infant Nutrition Intervention plus)
Schmitt JACI 2010;125:404

 A birth cohort (n=2916) In children with infant-onset
followed until age of
The strength 10 eczema OR for
years. 2.0 –
the association
between eczema
 Association between
and emotional 1.5 – 1.62
infant-onset at age
problems eczema 1.49 1.31
(age 1-2 years) and 1.0 –
10 years
mental health problems
increased with P=0.005 P<0.001 P=0.08
at age 10 years 0.5 –
increasing eczema
according to the
persistence.
Strengths and
0
Difficulties possible/probable emotional conduct
Questionnaire. mental health symptoms problems
problems

Increased risk of serious pneumococcal disease (SPD)
in patients with atopic conditions other than asthma
Jung JACI 2010:125:217

Background: We reported an increased risk of
serious pneumococcal disease (SPD) among patients with
asthma. It is not known whether this is true for
patients with other atopic conditions.
Objective: To determine the relationship between
atopic conditions other than asthma and SPD.

Jung JACI 2010:125:217

2.5 –
OR FOR SPD

2.13
2.0 –

Between 1964 and 1983 1.5 –
174 serious P=0.04
1.0 –
pneumococcal disease
(SPD) cases. 0.5 –

0
ATOPIC CONDITIONS
OTHER THAN ASTHMA

Jung JACI 2010:125:217

2.5 –
OR FOR SPD
Like asthma, other atopic
2.13
2.0 –
conditions, particularly
Between 1964 and 1983
atopic dermatitis, 1.5 –
174 SPD cases. with an P=0.04
are associated 1.0 –
increased risk
of SPD. 0.5 –

0
ATOPIC CONDITIONS
OTHER THAN ASTHMA

Correlates of outcome for atopic dermatitis
Horwitz Ann Allergy Asthma Immunol 2009;103:146

% Patients with Persistent
AD at Age ≥ 5 Yrs
80 –

75.1%
70 –
 To identify significant
correlates of 60 –

persistent AD. 50 –

40 –
 177 patients with AD 30 –
(5-18 years.) 20 –

10 –

0


4.5 – OR for Persistant Atopic Dermatitis at ≥ 5 years
4.0 –

3.5 – 4.02
3.0 –

2.5 –

2.0 –
2.93 2.71
1.5 –

1.0 –

0.5 –

0
Peanut Egg Mite
ALLERGY TO


4.5 – OR for Persistant Atopic Dermatitis
4.0 –

3.5 – Egg, peanut, and dust mite4.02
3.0 – allergies are significant
2.5 –

2.0 –
2.93 correlates of AD persisting
2.71
beyond school age.
1.5 –

1.0 –

0.5 –

0
Peanut Egg Mite
ALLERGY TO

Early exposure to solid foods and the development
of eczema in children up to 4 years of age
Sariachvili Pediatr Allergy Immunol 2010:21:74

In Children with Early Introduction
 Birth cohort (within the First 4 Months) of Solid
Foods OR for
 252 children with 1.0 –
eczema (cases) and
305 children
without eczema
(controls).
0.5 –
0.69
0.49 0.35
 Timing of 0
introduction of ECZEMA UP TO ECZEMA IN ECZEMA IN
CHILDREN WITH CHILDREN WITH NO
solid foods. THE AGE 4 YRS
ALLERGIC PARENTS ALLERGIC PARENTS


 PIPO cohort (within the First 4 Months) of Solid
(Prospective Cohort
The current study Foods OR for
on doesInfluence of a 1.0 –
the not support
Perinatal Factors on
delayed introduction
the Occurrence offor
of solid foods
Asthmaprevention of 0.5 –
the and
Allergies). 0.69
eczema in
childhood.
0.49 0.35
 Timing of
introduction of 0
solid foods. ECZEMA UP TO
THE AGE 4 YRS
ECZEMA IN ECZEMA IN


 PIPO cohort
A possible (within the First 4 Months) of Solid
(Prospective Cohort
explanation for the Foods OR for
on the Influence of 1.0 –
'protective' effect
of early introduction
theof solids on the
Occurrence of
Asthma and
development of
Allergies).
0.5 –
0.69
eczema may be the
induction of oral
0.49 0.35
 Timing of
tolerance for foods. 0
introduction of
THE AGE 4 YRS
ECZEMA IN ECZEMA IN


 PIPO cohort (within the First 4 Months) of Solid
Continuation of
(Prospective Cohort Foods OR for
exposure of the 1.0 –
on the Influence of
immune system to
certain allergenic
the Occurrence of
food proteins once
Asthma and
responsible for 0.5 –
Allergies). 0.69
allergy, may help to 0.49
 Timing of tolerance
maintain 0.35
to this food.
introduction of 0
THE AGE 4 YRS
ECZEMA IN ECZEMA IN

• intestinal flora
• probiotics

Probiotics during weaning reduce the incidence of eczema
West Pediatr Allergy Immunol 2009:20:430

THE CUMULATIVE INCIDENCE
OF ECZEMA AT 13 MONTHS
25 –
 Lactobacillus F19 during
weaning.
22%
20 –

 Incidence of eczema and 15 – p<0.05
Th1/Th2 balance.
 Infants were fed cereals 10 –

with (n = 89) or without 05 –
11%
Lactobacillus F19 (n = 90)
from 4 to 13 months of age. 0
PROBIOTICS PLACEBO


THE CUMULATIVE INCIDENCE
OF ECZEMA AT 13 MONTHS
25 –
weaning.
22%
20 –
The number
 Incidence of eczema and p<0.05
needed to
Th1/Th2 balance.
15 –

treat was 9.
 Infants were fed cereals 10 –

with (n = 89) or without 05 –
11%
from 4 to 13 months of age. 0
PROBIOTICS PLACEBO


IFN-γ /IL4 mRNA ratio levels in
peripheral blood mononuclear cells of
13 months old infants

weaning.
 Incidence of eczema and
Th1/Th2 balance.
 Infants were fed cereals P<0.05
with (n = 89) or without
from 4 to 13 months of age.

The effects of selected probiotic strains on the
development of eczema (the PandA study)
Niers Allergy 2009:64:1349

 Double-blind, placebo- % children with eczema
controlled trial. at age 3 month
 A mixture of probiotic
bacteria (Bifidobacterium
bifidum, Bifidobacterium
lactis, and Lactococcus lactis; p=0.035
Ecologic® Panda).
p=0.021
 Prenatally administered to
mothers of high-risk
children and to their
offspring (n=156) for the
first 12 months of life.


 Double-blind, placebo-
controlled trial.

bifidum, Bifidobacterium P<0.05
lactis, and Lactococcus lactis;
Ecologic® Panda).



 Double-blind, placebo-
controlled trial.
This particular
combination of probiotic
bacteria shows a
preventive effect on the P<0.05
bifidum, Bifidobacterium
incidence of eczema in
lactis, and Lactococcus lactis;
high-risk children,
Ecologic® Panda).
which seems to be
sustained during the
first 2 years of life.


Real-time PCR quantification of Lactococcus lactis (A)
and Bifidobacterium spp (B) in stool samples


The number of
Lc. lactis is
significantly (P<0.0001)
higher in the probiotic
group during the first
year of life.

Real-time PCR quantification of Lactococcus lactis (A)
and Bifidobacterium spp (B) in stool samples

Lactobacillus Reuteri Modulates Cytokines Production in
Exhaled Breath Condensate of Children With Atopic
Dermatitis Miniello J Ped Gast Nut 2010;in press

IL-4 and IFN-Υ concentration in children with nonatopic
(lined boxes) and atopic (empty boxes) eczema after
51 patients, treatment with Lactobacillus reuteri or placebo
4 to 10 years
referred due
to AD
L. reuteri
chewable tablets
or placebo for 8
weeks
Breath
condensate
IL-4 INF-Υ

Lactic acid bacteria differ in their ability to
induce functional regulatory T cells in humans
de Roock CEA 2010; 40:103

Background: Trials with probiotic lactic acid bacteria have
yielded different results, which may be due to the strains
used. Lactobacilli and bifidobacteria are known to be
potent modulators of the immune system.
The capacity of these bacteria used as probiotics to
influence both T helper type 1 (Th1)- and Th2-mediated
diseases has been shown before. However, the ability of
strains to induce forkhead box P3 (FOXP3+) expressing
regulatory T cells has not yet been investigated.


 Human PBMC were
co-cultured in vitro with
either
Bifidobacterium lactis W51,
Lactobacillus acidophilus
W55 or
Lactobacillus plantarum
W62 or an
Escherichia coli control
strain.

 Percentage of FOXP3+ cells Induction of CD25+forkhead box P3 (FOXP3+)
cells by bacteria in peripheral blood
mononuclear cells (PBMC).


 Human PBMC were
Some probiotic strains
co-cultured in vitro with
are potent inducers of
either
regulatory cells, while
Bifidobacterium lactis W51,
others are not. The clear
Lactobacillus acidophilus
differences between
W55 or
strains imply that an in
Lactobacillus plantarum
vitro characterization of
W62 or an
probiotic strains before
Escherichia coli control
application is
strain.
recommended.
 Percentage of FOXP3+ cells Induction of CD25+forkhead box P3 (FOXP3+)
cells by bacteria in peripheral blood
mononuclear cells (PBMC).

High circulating immunoglobulin A levels in infants are
associated with intestinal toxigenic Staphylococcus
aureus and a lower frequency of eczema
Lundell CEA 2009;39:662

 IgA in plasma from
infants at birth and
at 4 and 18 months.

 Colonization in the
first 8 weeks of life
by quantitative culture
of stool samples.

Plasma levels of IgA


 IgA in plasma from P<0.05
at 4 and 18 months.

of stool samples.

Intestinal colonization by toxigenic or non-toxigenic
Staphylococcus aureus and levels of IgA in plasma.


at 4 and 18 months.

of stool samples.


Early intestinal
infants at birth by
colonization and
toxigenic S. aureus
at 4 and 18 months.
strains seems to
promote systemic
IgA responses and
seem to correlate
negatively with
of allergy samples.
stool development.


infants Bacterialand
at birth
at 4 and 18 months.
colonization
trigger the
production
of T-reg cells.
of stool samples.

Antioxidant nutrient intakes and corresponding
biomarkers associated with the risk of atopic dermatitis
in young children. Oh SY, Eur J Clin Nutr. 2010;64:245.

180 AD children OR for Eczema in Children with the
(mean age 5.3 yrs) highest (vs lowest) quintile

1.0 –
242 non-AD
(mean age 5.2 yrs)
children.
0.5 –
Diet assessed
using a validated
0.44 0.33 0.37
semi-quantitative 0
food frequency
questionnaire Β-carotene Vitamin E Folic Acid

Gestational diabetes, atopic dermatitis, and
allergen sensitization in early childhood
Kumar JACI 2009;124:1031

% MOTHERS
5 –
 680 children
from the Boston
4 –
4.9%
Birth Cohort. 3 –

 Followed to a 2 –

mean age of 1 –
3.2 ± 2.3 years.
0
GESTATIONAL DIABETES (GDM)

Kumar JACI 2009;124:1031

OR in Term Children Born from
10 – Mothers with Gestational Diabetes
9 –
 680 children 8 –
from the Boston 7 – 8.3
6 – 7.7
Birth Cohort. 5 –
4 – 5.7
 Followed to a 3 –
mean age of 2 –
3.2 ± 2.3 years. 1 –
0
ATOPIC ALLERGEN FOOD
DERMATITIS SENSITIZATION SENSITIZATION

Kumar JACI 2009;124:1031

10 – Mothers with Gestational Diabetes
9 –
fromThe above
the Boston 7 – 8.3
6 – 7.7
Birth Cohort.were
associations
5 –
not observed in
4 – 5.7
 Followed to a
preterm births. 3 –
mean age of 2 –
3.2 ± 2.3 years. 1 –
0

Kumar JACI 2009;124:1031

These data 10 – Mothers with Gestational Diabetes
suggest that, at 9 –
 680least in term
children 8 –
fromThe above
infants, Boston
the prenatal 7 – 8.3
associations risk
metabolic 6 – 7.7
Birth Cohort.were 5 –
factors increase
not observed in
4 – 5.7
 Followed of allergic
the risk to a
preterm births. 3 –
disease and
mean age of 2 –
sensitization in
3.2 ± early life.
2.3 years. 1 –
0

Kumar JACI 2009;124:1031

Mothers with GDM have higher levels of TNF-α, leptin,
and visfatin, as well as lower levels of adiponectin.
Adiponectin attenuates allergic inflammation in murine
models. Thus it is possible that altered levels of
adipokines associated with GDM might have some effect
on immunologic development in infancy.
Krzyzanowska K. Clin Sci (Lond) 2006;110:605–609
Lewandowski KC. Diabetologia 2007;50:1033–1037
Gao XL. Chin Med J (Engl) 2008;121:701–705
Shore SA . J Allergy Clin Immunol 2008;121:1087–1095

Risk analysis of early childhood eczema
Bisgaard JACI 2009;123:1355

% INFANTS
 Copenhagen Study 45 –

on Asthma in 40 –

Childhood 35 – 43.5%
 A birth cohort 30 –

(411 children born 25 –

of mothers with 20 –

asthma). 15 –
10 –
 Follow-up 3 yrs 5 –
of life. 0
Developing Eczema


OR FOR ONSET OF ECZEMA
3.5 – IN CHILDREN
 Copenhagen Study 3.0 –
on Asthma in 3.2
Childhood 2.5 –
P=0.004 2.8
 A birth cohort 2.0 – P<0.0001
(411 children born
of mothers with
1.5 – 1.91
P=0.02
asthma). 1.0 –

0.5 –
 Follow-up 3 yrs
of life. 0
FILLAGRIN MOTHER FATHER WITH
MUTATIONS WITH ALLERGIC
ECZEMA RHINITIS


OR FOR ONSET OF ECZEMA
3.5 – IN CHILDREN
 Copenhagen Study
Risk of eczema 3.0 –
on Asthma in
was significantly 3.2
Childhood by birth
reduced 2.5 –
P=0.004 2.8
 A birthlength
cohort 2.0 – P<0.0001
(411 (OR per born
children cm
ofincrease, with
mothers 0.87;
1.5 – 1.91
P=0.02
P = 0.02)
asthma). and dog 1.0 –
living in the home 0.5 –
 Follow-up 3 yrs
(OR, 0.44;
of life. = 0.02)
P 0
FILLAGRIN MOTHER FATHER WITH
MUTATIONS WITH ALLERGIC
ECZEMA RHINITIS


 The mechanism by which exposure to dogs around
birth protects against eczema is unknown.

 We speculate that the particular microbiology
carried by pets may be mediating their effect on
disease expression. Alternatively, having dog is a
surrogate measure of other particular lifestyle
factors, which needs to be explored in future
studies.


 Length at birth exhibited an inverse association to
risk of eczema after confounder adjustment.

 Our observation suggests an association between
intrauterine growth and eczema, and lends support
to the theory of intrauterine programming as a
determinant of the risk of eczema.

Filaggrin mutations in the onset of eczema, sensitization,
asthma, hay fever and the interaction with cat exposure.
Schuttelaar Allergy 2009:64:1758

OR IN FLG MUTATIONS

4.0 –
 FLG mutations R501X,
3.7
3.5 –
2282del4 and R2447X. 3.0 –

 Prevention and Incidence 2.5 –

of Asthma and Mite Allergy 2.0 –
birth cohort (n = 934). 1.5 –

1.0 –
2.0
 For up to 8 years
0.5 –

0
ECZEMA ASTHMA

Filaggrin mutations in the onset of
eczema, sensitization, asthma, hay fever and the
interaction with cat exposure. Schuttelaar Allergy
2009:64:1758
10 – OR IN FLG MUTATIONS
9 –
8 –
 FLG mutations R501X,
2282del4 and R2447X. 7 – 8.2
6 –
5 –
 Prevention and Incidence
of Asthma and Mite Allergy 4 – 5.4
3 –
birth cohort (n = 934).
2 –
1 –
 For up to 8 years
0
ECZEMA AT ECZEMA AT
AGE 1 YR AGE 8 YRS

IN CAT EXPOSED SUBJECTS

Meta-analysis of filaggrin polymorphisms in eczema
and asthma: Robust risk factors in atopic disease
Rodríguez JACI 2009;123:1361

 24 studies on FLG OR FOR ECZEMA
3.5 –
mutations and
3.12
3.0 –
eczema involving.
2.5 –
 5,791 cases, 26,454
2.0 –
control subjects.
1.5 –
 17 studies on asthma
1.0 –
involving 3,138 cases,
17,164 control 0.5 –

subjects 0
IN FLG HAPLOINSUFFICIENCY


 24 studies on FLG OR FOR ASTHMA
2.0 –
mutations and
eczema involving.
1.5 –
 5,791 cases, 26,454
control subjects. 1.0 –
1.48
involving 3,138 cases, 0.5 –

17,164 control
subjects 0


 24 studies on FLG OR FOR ECZEMA
3.5 – & ASTHMA
mutations and
3.29
3.0 –
eczema involving.
2.5 –
 5,791 cases, 26,454
2.0 –
control subjects.
1.5 –
1.0 –
involving 3,138 cases,
17,164 control 0.5 –

subjects 0

Maternal Asthma, its Control and Severity in Pregnancy
and the Incidence of Atopic Dermatitis and Allergic
Rhinitis in the Offspring M Martel, J Ped 2009;155:707

HR in children

2 –
atopic
dermatitis allergic
 26.265 singletons rhinitis
born to mothers with 1 –
and without asthma 1.11 1.04
0
Maternal asthma during
pregnancy


HR in children
Maternal AR and
intranasal 2 –
corticosteroid atopic
dermatitis allergic
 26.265during
use singletons
rhinitis
pregnancy
born to mothers with 1 –
increased the
risk of childhood
AR by 70% and
45% 0
pregnancy


Children of HR in children
mothers with
asthma or AR 2 –
atopic
during pregnancy allergic
 26.265 singletons dermatitis
should be closely rhinitis
bornmonitored to with
to mothers 1 –
diagnose
and treat AD and
AR as early as
0
possible
pregnancy

Maternal meat and fat consumption during pregnancy and
suspected atopic eczema in Japanese infants aged
3–4 months: The Osaka Maternal and Child Health Study
Saito Pediatr Allergy Immunol 2010:21:38

% Infants With Atopic
Dermatitis at 3-4
771 mother–child pairs. 10 – Months
9 –
Maternal dietary intake 8 –
during pregnancy.
Questionnaire
7
6
–
–
8.4%
5 –
completed by mothers
4 –
3–4 months postpartum. 3 –
2 –
1 –
0

OR for Doctor Diagnosis of
4.0 – Atopic Eczema in Infants
771 mother–child pairs. 3.5 –

Maternal dietary intake
3.0 –
2.5 –
3.53
during pregnancy. 2.0 – p=0.02
Questionnaire 1.5 –
completed by mothers 1.0 –

3–4 months postpartum. 0.5 –
0

HIGHEST VS LOWEST QUARTILE OF MEAT
CONSUMPTION DURING PREGNANCY

771 mother–child pairs.
Certain components of 3.5 –

meat may affect
3.0 – 3.53
foetal immune 2.5 –
during pregnancy.
responses. 2.0 – p=0.02
Questionnaireprimary
Meat is a 1.5 –
completed of saturated
source by mothers 1.0 –

3–4 months postpartum.
fatty acids. 0.5 –
0


771 mother–child pairs.
The formation of 3.5 –

heterocyclic amines
3.0 – 3.53
during cooking and 2.5 –
during pregnancy. in
nitroso compounds 2.0 – p=0.02
Questionnaire
processed meat are 1.5 –
indicated as plausible
completed by mothers 1.0 –
mechanisms.
3–4 months postpartum. 0.5 –
0


Prevalence and risk factors of wheeze and eczema in
1-year-old children: the Butajira birth cohort, Ethiopia
Belyhun CEA 2010; 40:619

15 – % Children at 1 Year with

 1065 pregnant 10 –
11.5%
women. 8.6%
05 –
 At 1 year of age,
data on wheeze
and eczema in 0

the children. Wheeze Eczema

OR for Eczema
4.0 –

3.68
3.5 –

3.0 –

 1065 pregnant 2.5 –

women. 2.0 –
2.6
1.5 –
 At 1 year of age, 1.0 –
data on wheeze 0.5 –
and eczema in 0
the children. Maternal allergic Paracetamol use
history by the child

OR for Wheeze OR for Eczema
11 –
10 – 11.0 4.0 –

3.68
9 – 3.5 –
8 – 3.0 –
7 –
2.5 –
6 –
5 – 2.0 –
2.6
4 – 1.5 –
3 –
2 – 3.0 1.0 –

0.5 –
1 –
0 0
Maternal allergic Paracetamol use Maternal allergic Paracetamol use
history by the child history by the child


OR for Eczema
1.5 –

1.48
1.0 –
 1065 pregnant 1.0
women.
0.5 –

 At 1 year of age, 0.42
data on wheeze 0
and eczema in Bed Floor Grass Matting
the children.
Child’s Sleeping Place

Swimming pool attendance and risk of allergic
symptoms in children
Font-Ribera ERJ 2009:34:1304

OR for eczema in those
 3,223 9–12-yr-old children attending swimming pool
in Sabadell (Spain). >5 yrs versus 0 yrs
2 –
 Questionnaire on
lifetime frequency of pool
attendance and symptoms 1.71
in the last 12 months
1 –
(wheezing, asthma
medication, rhinitis and
allergic rhinitis).
 eczema
0

Swimming pool attendance and risk of allergic
symptoms in children
Font-Ribera ERJ 2009:34:1304

OR for eczema in those
 3,223 9–12-yr-old children attending swimming pool
An increased >5 yrs versus 0 yrs
in Sabadell (Spain).
prevalence of eczema 2 –
 Questionnaire on with
was associated
duration of lifetime
lifetime frequency of pool
pool attendance
attendance and symptoms 1.71
in(OR 1.71, for >5 yrs
the last 12 months
versus 0 yrs). 1 –
(wheezing, asthma
medication, rhinitis and
allergic rhinitis).
 eczema
0

• batteri
• funghi
• virus

Expression patterns of atopic eczema (AE) and
respiratory illnesses in a high-risk birth cohort
Singh JACI 2010;125:491

70 – % children
 Natural history of AE
60 –
in children (n=287) 62%
enrolled in the 50 –
Childhood Origin of
40 –
ASThma (COAST)
study, a high-risk 30 –

birth cohort composed 20 –
of children with 24%
parental histories of 10 –
14%
asthma and/or 0
allergies never had AE or had
a transient course
little or no disease in the
first 3 years of life, and
early and persistent
skin manifestations
then developed AE in years throughout the period
4 to 6 (late-onset AE) of observation.

Expression patterns of atopic eczema (AE) and
respiratory illnesses in a high-risk birth cohort
Singh JACI 2010;125:491

70 – % children
 Natural history of AE
Contrary
60 –
in childrenhygiene
to the (n=287)
62%
hypothesis children
enrolled in the 50 –
with early/recurrent
Childhood Origin of
AE had more
ASThma (COAST)
40 –

moderate-to severe
study, a high-risk 30 –
viral respiratory
birth cohort composed
illnesses in the first 20 –
year of life with
of children compared 24%
parental histories of
with the healthy/
10 –
14%
asthma and/or
transient group 0
allergies .02)
(P=0
never had AE or had
a transient course
little or no disease in the
first 3 years of life, and
early and persistent
skin manifestations
then developed AE in years throughout the period
4 to 6 (late-onset AE) of observation.

ROLE OF STAPHYLOCOCCUS AUREUS NASAL
COLONIZATION IN ATOPIC DERMATITIS IN INFANTS
Lebon Arch Ped Adoles Med 2009;163:745

In children colonized with S.Aureus
at 6 mo OR for Atopic Dermatitis
3 –
 1079 children
 Nasal swabs for 2 –
2.88
S. aureus
cultivation were 2.13
taken at ages 1.5, 1 –
6, and 14 months

0
1st year 2nd year
of life


OR for Atopic dermatitis during
5 – the second year
 Nasal swabs for
S. aureus
3 – 4.29
cultivation were 2 –
taken at ages 1.5,
6, and 14 months 1 –

0
in children with frequent
colonization in the first year
of life (≥2 times)


OR for Atopic dermatitis during
5 – the second year
Nasal colonization –
 1079 children 4
of S Aureus is a
 Nasal swabs for
S. aureus factor
risk
3
that
– 4.29
cultivation were
precedes 2 –
taken at ages 1.5,
6, Atopic Dermatitis –
and 14 months 1
in infants
0
in children with frequent
colonization in the first year
of life (≥2 times)

Infected atopic dermatitis lesions contain pharmacologic
amounts of lipoteichoic acid. Travers JACI 2010:125:146

Background: Bacterial infection with
Staphylococcus aureus is a known trigger for
worsening of atopic dermatitis (AD); the exact
mechanisms by which bacterial infection worsens
dermatitis are unknown.

Objective: We sought to characterize the amounts
of the biologically active bacterial lipoprotein
lipoteichoic acid (LTA) in infected AD lesions.


 89 children with
impetiginized AD
were enrolled in
this study.

 Eczema Area and
Severity Index
(EASI).
Typical subject with clinically impetiginized
 Wash fluid obtained AD lesion at first visit, and second visit
from the lesion. 2 weeks later after treatment with topical
corticosteroid and oral antibiotic.


 89 children with
impetiginized AD
were enrolled in
this study.

 Eczema Area and
Severity Index
(EASI).

 Wash fluid obtained
from the lesion.


r=0.27 p=0.01
 89 children with r=0.28 p=0.01
impetiginized AD
were enrolled in
this study.

 Eczema Area and
Severity Index
(EASI).

 Wash fluid obtained
from the lesion.

Wash fluid obtained at first visits (red circle)
and follow-up visits (blue triangle)


r=0.27 p=0.01
 89 children with r=0.28 p=0.01
Approximately
impetiginized AD
30% of clinically
were enrolled in
this impetiginized AD
study.
lesions contained
 Eczema Area and 1
greater than
Severity Index
μg/mL LTA,
(EASI).amounts that
 Wash fluideffects on
exert obtained
from the lesion. types
various cell
in vitro.
Wash fluid obtained at first visits (red circle)
and follow-up visits (blue triangle)

Secreted virulence factor comparison between methicillin-
resistant and methicillin-sensitive Staphylococcus aureus,
and its relevance to atopic dermatitis
Schlievert JACI 2010:125:39
 Staphylococcus aureus is a
gram-positive bacterium that
produces a remarkable array
of cell-surface and secreted
virulence factors to facilitate
disease causation, and rapidly
develops antimicrobial
resistance almost as quickly as
new therapeutic agents are
developed.

 The cell-surface MSCRAMMs
(matrix molecules) typically are
produced during exponential
phase of growth. Virulence factor production by S aureus

Phenotype of atopic dermatitis subjects with
a history of eczema herpeticum
Beck JACI 2009;124:260

Background:
A subset of subjects
with atopic dermatitis
(AD) are susceptible to
serious infections with
herpes simplex virus,
called eczema
herpeticum, or vaccina
virus, called eczema
vaccinatum.

Beck JACI 2009;124:260

p<0.001

 Subjects with AD with
and without a history
of eczema herpeticum
[ADEH+ (134) and
ADEH− (419)] and
healthy control (348).
 Eczema Area and
Severity Index (EASI)

Beck JACI 2009;124:260

p<0.001

 Subjects with AD with
and without a history
of eczema herpeticum
ADEH+ subjects
[ADEH+ (134) and
had more
ADEH− (419)] and
severe disease.
healthy control (348).
 Eczema Area and
Severity Index (EASI)

Beck JACI 2009;124:260

p<0.001
p<0.001

Beck JACI 2009;124:260
Subjects with AD in whom eczema herpeticum develops have more severe
TH2-polarized disease with greater allergen sensitization and more
commonly have a history of food allergy, asthma, or both.

p<0.001
p<0.001

Beck JACI 2009;124:260

Percentage of subjects with AD or caregivers who self-report a
history of, or current food allergy (A) or asthma (B).

Beck JACI 2009;124:260

Percentage of subjects
(ADEH+, ADEH-, and
CTL subjects) who
self-report a history
of ocular infections
with HSV (A), or skin
infections with S aureus
(B), human papilloma
virus (HPV) (C), or
molluscum contagiosum
virus (MCV) (D).

Exploring the repertoire of IgE-binding
self-antigens associated with atopic eczema
Zeller JACI 2009;124:278

Background: Atopic eczema (AE) is the most
common chronic inflammatory skin disease.
Recent data demonstrate the presence of
autoreactive serum IgE antibodies correlating with
the severity of the disease.

Exploring the repertoire of IgE-binding
self-antigens associated with atopic eczema
Zeller JACI 2009;124:278

 140 sequences encoding
 Phage surface–displayed potential IgE-binding
human cDNA libraries self-antigens associated
were enriched for clones with AE were identified.
binding to serum IgE
 By binding IgE antibodies
from patients with AE
or activating specific
and screened by using
T cells, they might
high-throughput
promote, perpetuate,
technology.
or both existing skin
inflammation.

High sensitization rate to food allergens in
breastfed infants with atopic dermatitis
Han Ann Allergy Asthma Immunol 2009;103:332
Total IgE Ku/L
 143 infants with AD 110 – p=0.004
who younger than 100 –
107
6 months. 90 –
80 –
p=0.07
 3 groups : 70 –
60 – 69
- breastfed, 50 –
- mixed feeding, and 40 –

- formula fed. 30 –
20 –
10 –
25
 All infants had never 0
been fed egg or soy. BF MF FF
Groups


 143 infants with AD Specific IgE to Cow’s Milk Ku/L
who younger than 3.0 – ns
6 months.
2.5 – 2.75
 3 groups : 2.0 –
- breastfed, 1.5 – ns
- mixed feeding, and 1.34
1.0 –
- formula fed.
0.5 –
0.57
 All infants had never 0
Groups


 143 infants with AD sIgE to Egg withe Ku/L
10 –
p=0.002
6 months. 8 – 8.43 p=0.0002
7 –
 3 groups : 6 – 7.97
- breastfed, 5 –

- mixed feeding, and 4 –
3 –
1 –
 All infants had never 0 0.09
Groups


 143 infants with AD sIgE to Egg withe Ku/L
10 –
p=0.002
6 months.
Our results suggest 8 – 8.43 p=0.0002
that breastfeeding 7 –
 3 groups not always be
might : 6 – 7.97
- breastfed, in allergy
beneficial 5 –

- mixed feeding,some
prevention in and 4 –
high-risk infants. 3 –
1 –
 All infants had never 0 0.09
Groups


 One limitation of our study is that the FF group was smaller
than the other groups.
 In the present study, the 3 groups (BF, MF, and FF) were not
randomly divided but were determined according to parental
preferences.
 The number of infants in the FF group was small.
 In conclusion, our results showed that BF patients with AD had
a higher rate of sensitization to egg white during early infancy,
which suggests that BF might not always be beneficial in allergy
prevention in some high-risk infants (ie, maternal AD).

Temperature modulated histamine-itch in lesional
and nonlesional skin in atopic eczema – a combined
psychophysical and neuroimaging study.
Pfab Allergy 2010:65:84

 10 patients with AD. VAS Itch Intensity
 9 healthy controls. | | | | | | | |
0 10 20 30 40 50 60 70 80 90 100
| | |

 Thermal modulation
from 32°C (warm) COLD 55.2
to 25°C (cold).
 VAS itch intensity. p<0.0001
WARM 36.0

Temperature modulated histamine-itch in lesional
and nonlesional skin in atopic eczema – a combined
psychophysical and neuroimaging study.
Pfab Allergy 2010:65:84

 10 patients with AD. VAS Itch Intensity
Mean VAS itch
 9 healthy controls.
intensity was
| | | | | | | |
0 10 20 30 40 50 60 70 80 90 100
| | |

 Thermal modulation
significantly
from 32°C (warm)
(P < 0.0001) higher COLD 55.2
to 25°C (cold).
during the relative
VAS itch intensity.
cold [55.2 ± 8.3% p<0.0001
WARM 36.0
(LS); 48.6 ± 8.2%
(NLS)] compared to
the relative warm
blocks

Epidermal Barrier Dysfunction in Atopic Dermatitis
M J. Cork J Invest Dermatol 2009;129:1892

The structure of the epidermal
barrier located in the lower part
of the stratum corneum (SC).
Highly differentiated flattened
keratinocytes, referred to as
corneocytes (beige rectangles), are
the building blocks of the epidermal
barrier. They contain natural
moisturizing factor (NMF), derived
from pro-filaggrin, a mix of
hygroscopic compounds, which help
maintain skin hydration.
A water resistant layer of lipid
lamellae (pink) encases the
corneocytes preventing water loss and
impeding barrier permeability.
The corneocytes are held together by
corneodesmosomes (purple spheres),
the integrity of which is dependent on
a cocktail of proteases and protease
inhibitors.

Ceramide biosynthesis in keratinocyte and its role in
skin function Y Mizutani Biochimie 2009;91:784


The structure of the epidermal
barrier located in the lower part
of the stratum corneum (SC).
The balance between the
expression and activity of
proteases, such as KLK7 (SCCE), and
protease inhibitors, such as LEKTI and
cystatin A, determines the rate of
desquamation (corneocytes shedding)
and thereby the thickness of the
barrier. Under normal conditions, the
barrier is only degraded in the upper
layers of the SC providing a
resilient permeability barrier that
prevents the penetration of allergens.


A defective epidermal barrier
is a poor permeability
barrier, which permits the
entry of allergens and the
loss of moisture.
Changes in the FLG gene encoding
pro-filaggrin result in reduced, or
absent, expression of filaggrin
thereby adversely affecting the
structure of the corneocytes
(beige)—the ‗‗bricks‘‘.
The levels of natural moisturizing
factor (NMF), derived from
filaggrin, are also adversely
affected, resulting in a decreased
ability of the corneocytes to hold
water and a concomitant elevation
of pH.


A defective epidermal barrier
is a poor permeability
barrier, which permits the
entry of allergens and the
loss of moisture.
Elevated pH favors serine protease
activity and inhibits enzymes
involved in the synthesis of lipid
lamellae (pink)—the ‗‗mortar‘‘.
Genetic changes in the genes
encoding SCCE (KLK7), LEKTI
(SPINK5), and cystatin A (CSTA)
all lead to elevated protease
activity involved in desquamation—
cleavage of the corneodesmosome
junctions (purple spheres) between
the corneocytes analogous to
‗‗rusting‘‘ of the ‗‗iron rods‘‘.


There is a defective epidermal
barrier in individuals with atopic
dermatitis.
The epidermal barrier is found in the
lower layers of the stratum corneum,
and is composed of differentiated
keratinocytes, termed corneocytes
(beige rectangles), held together with
corneodesmosomes (purple spheres).
The hyperactivity of degradatory
proteases (red hexagons) found
within the epidermis, and contributed
to by exogenous proteases (red
hexagons), from house dust mites and
Staphylococcus aureus, for example,
facilitate the cleavage of the
corneodesmosome junctions.


dermatitis.
The epidermal barrier is found in the
lower layers of the stratum corneum,
and is composed of differentiated
keratinocytes, termed corneocytes
(beige rectangles), held together with
corneodesmosomes (purple spheres).
The hyperactivity of degradatory
proteases (red hexagons) found
within the epidermis, and contributed
to by exogenous proteases (red
hexagons), from house dust mites and
Staphylococcus aureus, for example,
facilitate the cleavage of the
corneodesmosome junctions.
.


dermatitis.
This is just one event in the
breakdown of the epidermal barrier
that permits the penetration of
allergens. Dendritic cells (DC) (green)
found in the dermis take up and
present these allergens (red stars) to
helper T (TH) cells and recruit
CD4þ T cells (blue). Activated DC and
IL-4, expressed by CD4þ T cells,
promote TH1 to TH2
switching with the subsequent release
of pro-inflammatory cytokines and
elevation of IgE levels
The clinical outcome of this
type of response is atopy and
asthma.

Broad defects in epidermal cornification in atopic
dermatitis identified through genomic analysis
Guttman-Yassky JACI 2009:124:1235

 Both psoriasis and AD skin
 Cutaneous biopsy. lesions displayed
regenerative epidermal
 Genomic profiling of hyperplasia.
mRNA in chronic
psoriasis (n = 15)
 In AD, we found selective
defects in expression of
and AD (n = 18)
multiple genes encoding the
skin lesions compared
cornified envelope, with the
with normal human
largest alteration in loricrin
skin (n = 15)
(expressed at 2% of the
level of normal skin).

Broad defects in epidermal cornification in atopic
dermatitis identified through genomic analysis
Guttman-Yassky JACI 2009:124:1235

Real-time PCR
analysis showing
significant
downregulation
of
LCE1, LCE2, CDS
N, and SPRR2C in
AD;.

Mite serine protease activates protease-activated receptor-2
and induces cytokine release in human keratinocytes
Kato Allergy 2009:64:1366

Serine protease-rich extract
of whole mite culture

Release of IL-8 and
granulocyte-macrophage
colony-stimulating factor.
HUMAN KERATINOCYTES
Stimulated intracellular
Ca2+ mobilization.

Mite serine protease activates protease-activated receptor-2
and induces cytokine release in human keratinocytes
Kato Allergy 2009:64:1366

Serine protease-rich extract
Mite-derived of whole mite culture
serine protease
activity may
contribute to
the pathogenesis
of atopic Release of IL-8 and
dermatitis by granulocyte-macrophage
activating colony-stimulating factor.
HUMAN KERATINOCYTES
keratinocytes.
Stimulated intracellular
Ca2+ mobilization.

Filaggrin deficiency confers a paracellular barrier abnormality
that reduces inflammatory thresholds to irritants and haptens
Scharschmidt JACI 2009;124:496

Topical irritants and aptens

• Reduced inflammatory
thresholds when exposed
repeatedly to topical haptens
at doses that produce no
inflammation in wild-type mice,
• FLG deficient mice experience
a severe AD-like dermatosis
with a further deterioration in
FLG deficient barrier function and features
mouse of a TH2 immunophenotype

Filaggrin mutations that confer risk of atopic
dermatitis confer greater risk for eczema herpeticum
Pei-Song Gao JACI 2009;124:507

Background
Loss-of-function null mutations R501X and 2282del4 in
the skin barrier gene, filaggrin (FLG), represent the
most replicated genetic risk factors for atopic
dermatitis (AD). Atopic dermatitis eczema herpeticum
(ADEH) is a rare but serious complication of AD
resulting from disseminated cutaneous herpes simplex
virus infections.


% SUBJECTS WITH
R501X MUTATION
 Loss-of-function
25 –
mutations plus 9 FLG
polymorphisms . 20 – 25%
15 – OR=3.4 P=0002
 278 patients with AD,
of whom 112 had Atopic 10 –
Dermatitis Eczema
Herpeticum (ADEH), 5 – 9%
and 157 nonatopic
0
controls.
ADEH AD


% SUBJECTS WITH
R501X MUTATION
 Loss-of-function
25 –
mutations plus 9 FLG
R501X mutation in
polymorphisms .
the gene encoding
20 – 25%
OR=3.4 P=0002
 278 patients confers
filaggrin, 15 –
with AD,
an even greater
of whom 112 had Atopic 10 –
risk for ADEH.
Dermatitis Eczema
Herpeticum (ADEH), 5 – 9%
and 157 nonatopic
0
controls.
ADEH AD

UV-B–triggered induction of vitamin D3 metabolism
differentially affects antimicrobial peptide expression
in keratinocytes Peric JACI 2010;125:746

 Human keratinocytes possess the
enzymatic machinery to produce
calcitriol from the precursor
7 dehydrocholesterol (7-DHC)
under the influence of UV-B
irradiation.
 UV-B irradiation (290-315 nm)
rapidly generates previtamin D3
from 7-DHC in these cells, and
thermal isomerization subsequently
generates vitamin D3, which is
sequentially hydroxylated to yield
calcidiol and finally calcitriol.


 Keratinocytes
were treated
with 7-DHC
and/or inhibitor
ketoconazole and
irradiated with
UV-B.


 Keratinocytes of
Hydroxylation
were treated to
vitamin D3
formactive calcitriol
with 7-DHC
was
and/or inhibitor
blocked by the CYP
ketoconazole and
inhibitor
irradiated with
ketoconazole.
UV-B.

• Treatment
general consideration

Bathing and cleansing in newborns from day 1 to first
year of life: recommendations from a European round
table meeting Blume-Peytavi JEADV 2009,23,751/759

: routine bathing of infants

: safety while bathing infants


: procedures after bathing

•Bathing can be a fun experience for the infant, providing
tactile stimulation and bonding with parents and other
caregivers,
•Bathing can be a calming, soothing experience for the
infant.


: use of liquid cleansers in bathing

• Treatment
exclusion diet

Skin barrier breakdown: a renaissance in emollient
therapy. Cork MJ, Br J Nurs. 2009;18:872
Within the corneocytes, in a normal skin barrier, are high levels of
a substance called natural moisturising factor (NMF). NMF is a
humectant, which means that it attracts water to itself

It is important that the actions of proteases are held in check by protease
inhibitors, such as LEKTI. It is important to prevent excessive protease
activity because this will lead to a thinning of the stratum corneum, causing
it to become vulnerable to the penetration of irritants and allergens.

Breakdown of the skin barrier, producing dry, itchy skin, is an extremely
common problem in babies and children. Up to 25% of babies and children
are affected by atopic eczema. As we grow older we will all develop drier
skin, particularly on our legs and arms, which can be manifest as asteatotic
eczema.

Breakdown of the skin barrier is commonest at the extremes of age.

As a result of these decreased NMF levels, the amount of water
that can be held within the corneocytes is reduced. The lipid
lamellae are also defective in eczematous skin – this is analogous
tobroken, crumbly mortar in an old brick wall.

Breakdown of the skin barrier is commonest at the extremes of age.

Effects of a genetic predisposition to atopic eczema.

Effects of a genetic predisposition plus environmental
factors on the skin barrier.

Complete emollient therapy
The most important treatment for all dry skin diseases,
including atopic eczema, asteatotic eczema and irritant 1
contact dermatitis, is complete emollient therapy
Complete emollient therapy consists of:
2
1) Emollient bath products
2) Emollient wash products
3) Emollient creams or ointments
3
Everything that goes on to the skin should be emollient based.
All soap and detergents should be replaced with
emollient wash, bath and shower products

In their simplest form, emollient products provide an occlusive layer
of oil (such as petrolatum) over the surface of the stratum corneum

However, such ‘heavy’ emollient ointments are extremely
greasy and therefore are cosmetically unacceptable to the
majority of patients

The most important determinant in choosing an emollient is
cosmetic acceptability

Emollient formulations containing low concentrations of
humectants are therefore much more likely to be
cosmetically acceptable to patients


•If a patient likes a particular emollient formulation,
they will use it regularly and it will be effective.

•If a patient does not like an emollient formulation,
they will not use it; therefore it can have no effect.

•It is important to use sufficient quantities of emollients to
achieve the optimum repair of the skin barrier.

•For a leave-on emollient cream for a child with atopic eczema, this
should be between 250 and 500 grams per week.

•In order to produce the optimum repair of the skin barrier in AD
a complete emollient therapy regimen should be used


•Emollient regimens can be complex and
their combination with treatments for
flares such as topical corticosteroids
and topical calcineurin inhibitors even
more complicated.

•It is essential that all topical
treatments are demonstrated and
explained in detail to patients to ensure
they are effective.
Cork MJ, Br J Dermatol 2003;149:582–9
Staab D, Br Med J 2006;332: 933–8

Empiric Antimicrobial Therapy for Pediatric Skin and
Soft-Tissue Infections in the Era of Methicillin-Resistant
Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959

 Effectiveness of monotherapy
with β-lactams, clindamycin, or 10 –
trimethoprim-sulfamethoxazole 9 –
in the outpatient management % of children with
8 –
of nondrained noncultured skin and treatment failure
soft-tissue infections (SSTIs), 7 –
7.7%
in a methicillin-resistant 6 –
Staphylococcus aureus 5 –
(MRSA)-endemic region.
5.0%
4 –
 Treatment failure 3 –
(a drainage procedure, hospitalization, 2 –
change in antibiotic, or second 1 –
antibiotic prescription within 28 days).
0
 2096 children


Compared with
with β-lactams, clindamycin, or 10 –
trimethoprim-sulfamethoxazole
β-lactam therapy,
in the outpatient management
9 –
% of children with
clindamycin was
of nondrained noncultured skin and 8 –
treatment failure
equally effective but
7.7%
trimethoprim-
Staphylococcus aureus 5 –
sulfamethoxazole
5.0%
4 –
was associated
 Treatment failure with 3 –

an increased risk
change in antibiotic, or second
of failure.
1 –
0
 2096 children


with β-lactams,regions with
Even in clindamycin, or 10 –
trimethoprim-sulfamethoxazole
endemic 9 –
% of children with
in the outpatient management
community-acquired
of nondrained noncultured skin and 8 –
treatment failure
MRSA, β-lactams
7.7%
may still be
Staphylococcus aureus
appropriate, 5 –
5.0%
first-line, 4 –
empiric therapy for
 Treatment failure 3 –
children presenting
change in antibiotic, or second
with these infections. 1 –
0
 2096 children

What You Should Have Read But...2010: Diagnosing Primary Immunodeficiencies

What You Should Have Read But...2010: Diagnosing Primary Immunodeficiencies

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