Monitoring growth

Bibliographic informationStudy type and evidence levelNumber of patientsPatient characteristicsIntervention and comparisonFollow-up and outcome measuresEffect sizeStudy summaryReviewer comments
Kristmundsdottir F;David TJ; 1987 Jan510Study Type: Case series

Evidence Level: 3
n=89 childrenChildren with atopic eczema of duration of at least 1 year who had at least 5% of skin surface affected and who had been referred to a paediatrician or dermatologist because of the severity of their condition. 55 boys (mean age 5.35, range 1.3–16.95 years. 34 girls (mean age 5.2, range 1.66–10.85 years)Intervention: None

Comparison: None
Height SD
Sitting height SD
Subischial leg length SD
Weight
Triceps and subscapular skinfold tests
Head circumference SD
Skeletal maturation using the TW2 method SD
10% of the 89 children had a standing height below the third centile (7 were boys and 2 were girls).
n=6 were >2SD below mean
n=3 were more than 2.5SD below mean
Mean height was less than the general population although the overall distribution was not statistically significantly different

Male −0.31 SD1.22
Female −0.37 SD1.11

Both boys and girls had statistically significantly reduced sitting height (p<0.001)
Subischial leg length was not different from normal standards.
The difference between sitting height and subischial leg length was disproportionally shorter than normal standards (mean values, boys 0.55SD, girls 0.88SD

The centile distributions for weight and skinfold tests were not different from the normal population

The mean head circumference was significantly greater than for the general population for both boys (p<0.01) and girls (p<0.02).

Skeletal maturity SDS was more delayed in the girls (p<0.001) than the boys (p<0.05)

Using parental heights (n=69), there was a small but statistically significant excess of boys over girls with a corrected height centile below the 10th centile (10 vs. 5).
There were consistent trends of disease severity, TCS strength and asthma score with decreasing height centile.
This study suggests that impaired linear growth is a feature of atopic eczema and that caution in the use of potent TCS in children should be applied.This study includes a highly selected population with severe atopic eczema.
The funding of this study is undeclared
Pike MG; 1989509Study Type: Cohort

Evidence level: 2−
n= 128 parents of children with atopic eczema

n=117 parents of healthy control children
Children with atopic eczema who had been seen by a hospital consultant (no details of severity)
Mean age 6.9 years (range 1.2–16.2 years) 50% were boys

Control children mean age 7.0 years (range 1.1–16.5 years). 52% were boys
Intervention: None

Comparison: Growth between children with atopic eczema and unaffected children
Follow-up period: None

Outcome Measures: Postal questionnaire:

Envelope contained two envelopes. One contained a questionnaire concerning the child with eczema.
The second, a questionnaire for a healthy similarly aged child known to the family.
The questionnaire included questions on:
Paternal employment
presence or absence of asthma
date of birth and height of both parent and child
(instructions were given as to height measurement)

If there was no response a second letter was sent
245/296 replies were received (83%)
128 cases and 117 controls
Not all questionnaires were complete

There were no significant differences in ages, paternal employment (measure of social class) and parental height of both sexes between the two groups.

The mean SD score of the children with eczema (−0.4505 SE 0.119) was significantly less than the controls (−0.0595 SE 0.097) even after controlling for parental height (p<0.005)

n=12 were more than 2SD below the mean, n=4 were more than 3SD below the mean (12 of these very short children had asthma)

57% of the children reported no asthma or use of antihistamine or steroid treatment. When compared to the control group who also answered negatively, the height SD was significantly different (p<0.01) even after correction for age and parental height.

There was also a significant difference even when children under 5 years were excluded (the rationale that the onset of asthma is later; p<0.005)
The findings of this study suggest that children who have atopic eczema but not asthma are shorter than genetically expected from parental height.The study was funded jointly by the National Eczema Society and the Glaxo group Research Ltd.
Massarano AA;

1993512
Study Type: Case series

Evidence Level: 3
Intervention: None

Comparison: None
n=68 childrenChildren aged 2.3– 11.9 years (mean 6.2) years with atopic eczema diagnosed by the Hannifin and Rajka criteria who attended a university department of child health. The median surface area affected by eczema was 30% (46 boys and girls)Height SD of parents and children

Maximum figure ever recorded for surface area of skin affected by eczema

TCS and SCS use

Exclusion diets were noted

Bone age was measured in children above 6 years

Presence of asthma was reported and graded
Highly significant correlation (Spearman coefficient) between height SD score and surface area of eczema rs=0.42, p=0.03

The children were then divided into two groups for analysis:
I) less than 50% skin involved n=41
II) more than 50% skin involved n=27
age and sex ratios were similar
group II had higher treatment (p<0.01) and diet (p<0.0001) score but were similar for asthma

The height SD of group I children was comparable to their parents. Only n=2 were below the third centile (of these ?missing number eczema lesions were inflamed)

The height SD of the group II children was significantly different from their parents (p=0.001) and the children in group I (p=0.0007)
n=8 were below the third centile. 4/8 were receiving a elemental diet and 1/8 had received systemic steroids

The bone age of children over 6 years was mildly retarded in both groups but the difference was not statistically significant (U=225 p=0.09)

Predicted heights of group 2 children were not significantly below those of mid-parental height (p=0.08) but were below those of Group I despite having taller parents (U=111, p=0.18)

Regression analysis showed that the height SD scores were best explained by parental target height (r2=0.24)
Surface area of eczema r2=0.13
Combination of above explained 36% of variation in height
Further combination with treatment and diet only had a marginal effect (r2=0.03, r2=0.0 respectively)
Asthma and duration of disease had no effect.
This study suggests that children with atopic eczema which affects less than 50% of their skin surface area have normal height. Those with more extensive disease may have impaired growth for which the mechanism is unknown.The funding of this study is undeclared.

Growth of children is related to surface area of skin affected as opposed to severity
Morava E; 1994513Study Type: Case series

Evidence Level: 3
Intervention: None

Comparison: None
n=92 of which n=72 had atopic eczema, n=12 had atopic eczema and asthma and n=8 had urticarian=92 children (51 boys and 41 girls) age range 0.51– 10.5 years for boys, 0.51–9.5 for girls
Allergic status was confirmed by IgE levels and a detailed medical history concerning their atopic status was taken.
Somatometric measurements:

Skinfold thickness (Tanner- Whitehouse)

BMI (French)

Relative body weight 120% =obese

Height SD score >2.0=obese
Children were divided into 2 age groups: Group 1 age 0–2.99 years n=36, Group 2: age 3 years upwards n=56

Group 1(&2):
Children were tall and heavy for age
16/36 (25/56) were above the 75th weight centile
11/36 (20/56) were above the 90th weight centile.
14/36 (21/56) were above the 90th height centile

skinfold tests:
3/36(20/56) had tricep folds above the 90th centile
6/36 (20/56)had subscapular skinfold thickness above the 90th centile
but 6/36 (N/A) were also under the 10th centile for both these measures

BMI:
4/36 (16/56) were above the 90th centile
10/36 (N/A) were below the 10th centile

Relative weight:
above 120% in 4/36 (17/56)cases
7/36 (20/56) were above 90th centile for weight for height

Mean SD score was 0.43+/−0.15 (N/A)
5/36 (N/A) had an SD of >2.

Sub group analysis for group 2 in which 8/56 had urticaria and 12/56 had atopic eczema and asthma showed these above measurements were similar in all three groups
The study shows that in this population of atopic children, there is a special pattern of somatic development characterised by high stature and a high ratio of obesity in the prepubertal groupThe funding of the study is undeclared.

Population is Hungarian children for whom obesity patterns may be different from UK children. Hungarian centile charts were not available for some of the measures
Patel L;

1998508
Study Type: Cohort

Evidence level: 2−
n=77 children with atopic eczema

n= 71 children acting as controls
Children with atopic eczema (mean age 4.8 years, range 2.0–10.5 years) attending a university department referred by paediatricians or dermatologists because of the severity or intractable nature of the atopic eczema. Children had mild to severe atopic eczema involving 8–95% (median 47%) of the body surface areaIntervention: None

Comparison: Linear growth between prepubertal children with atopic eczema and those whom were unaffected
Follow-up period: 2 years

Outcome Measures: For children with atopic eczema:
Age of onset
Percentage body surface affected
Potency of TCS
Asthma scores
For both groups:
Height velocity at year 1 and 2
Weight (BMI)
SDS were calculated of the above triceps and subscapular skinfold
Bone age by wrist radiographs
Height and height velocity SDS did not differ between patients and controls and were not influenced by body surface area affected by atopic eczema, TCS potency or coexisting asthma.

Height SDS (r =−0.37), and height velocity SDS (r=−0.31) correlated inversely to age in patients but not in controls. A greater proportion (z=2.84) of patients than controls had year 2 height velocity SDS of less than −1.96. Patients had a mean delay in bone age of 0.22 years and 0.41 years at year 1 and year 2 of the study respectively. The delay in bone age correlated positively with age (r=0.39) and duration of atopic eczema (r=0.39)and negatively with height SDS (r=−0.5) and height velocity SDS (r=−0.38)
This study shows that prepubertal children with atopic dermatitis are not as tall as controls. However, as they approach puberty, their height velocity decreases, the proportion of children with extremely low height velocity increases and the delay in bone age increases. These features are consistent with a pattern of growth seen in people with constitutional growth delay.The funding of this study is undeclared
Patel L;Clayton PE;Jenney ME;Ferguson JE;David TJ;

1997 Jun511
Study Type: Cross sectional

Evidence level: 3
n=35 adult patients with atopic eczema

n=35 control patients with contact dermatitis or psoriasis
Adult patients (mean age 26.3 years, range 18–50 years) 15 men and 20 women with a history of childhood onset eczema before the age of 5 years, continuing throughout childhood and requiring attendance at a hospital dermatology clinic.

Control group adult patients (mean age 31.6 years, range 18–46 years) 15 men and 20 women attending dermatology clinic with no history of atopy.
Intervention: None

Comparison: None
Follow-up period: None

Outcome Measures:
Age of onset of atopic eczema
Age when TCS started and the potency of the TCS
Duration of treatment
Surface area affected
History and treatment of asthma

Standing and sitting height
Parental height if known Weight

SD values were calculated for the above as well as the BMI
There were no significant difference of standing height, mid parental height, sitting height and subischial leg length SD values and BMI between the atopic eczema and control group or any sub analysis thereof: surface skin affected, potency of TCS, with or without asthmaThis study shows that short stature was not a feature of this group of adult patients who had childhood onset atopic eczema continuing into adulthood, severe enough to require specialist care.

This suggests that if growth impairment occurs in childhood atopic eczema, it is likely to be temporary and reversible.


The funding of this study is undeclared
Ellison JA;514Study Type: Case series

Evidence Level: 3
Intervention: None

Comparison: None
n=70 male and 40 female patients with atopic eczemaPatients had developed atopic eczema in early childhood (median age of onset 0.7 years, range 0.01–5.0 years) and had the condition throughout growth measurement period. 92/110 also had a history of asthma which was mild in 85 of casesHeight
Weight
BMI
expressed as SDS
Regression analysis showed that the trends in height, weight and BMI SDS for atopic eczema patients were significantly different from zero and also different between males and females.

Both sexes were short and relatively overweight from early childhood and the trend was more pronounced in males than females.

At 5 years (school entry) the 50th centile BMI of male but not female was 0.44kgm-2 higher than the reference population but height and weight were lower. The age at adiposity rebound in atopic eczema males and females were 0.8 years and 0.7 years later than in the UK population (5.4 years, 5.3 years, and 6.2 years respectively). Children with atopic eczema attained peak height velocity later than the 1990 UK population (males 16.0 years vs. 13.5 years, p=0.0002; females 13.4 years vs.11.0 years p=0.008). In addition males had a greater mean gain in height during late adolescence (12.2 vs. 8.8 cm, p=0.03) and were shorter as young adults (170.9 vs.177.6 cm, p=0.0005).
This study showed that patients with childhood onset atopic eczema were relatively overweight very early but had a later adiposity rebound, were short in childhood and had a delayed adolescent growth spurt. The authors suggest that serial growth measurements should be done on all children with troublesome atopic eczema and can be helpful in counselling about the growth prognosisThe funding of the study is undeclared
Carrington LJ;

2006515
Study Type: Case series

Evidence Level: 3
Intervention: None

Comparison: None
n=256 7-year old children7-year old children registered with 2 GP practices in Northampton UKHistorical and current growth data obtained through a structured interview either at surgery or home.

3 part questionnaire collecting demographic data, history of illness and growth measurement both current and historical.
Demographic data: occupation (used for social class), number of people in house, pets, smoking and immunisation history.

History of illness: data on wheezing and eczema were collected on questions based on the International
Study of Asthma and Allergies in Childhood (ISAAC) criteria

Growth data: were obtained from PCRB plus current measurements by health visitor.
Atopic eczema at 7 years was not related to any anthropometric indices at birth or during infancy.

A smaller head circumference at 10–15 days of age was noted in children with current wheeze at age 7 years (p=0.018) regardless of confounding factors. Comparison of children with a head circumference over 36.5 cm at 10–15 days with those under 36.5 cm showed reduced odds for wheeze at 7 years (odds ratio 0.12, 95% CI 0.03–0.44, p trend=0.009)
Atopic eczema at 7 years of age is not related to any growth data from birth or during infancy.The study was funded by the Northampton NHS Primary Care Trust
Fergusson DM;Crane J;Beasley R;Horwood LJ;
1997 Dec 516
Study Type: Case series

Evidence Level: 3
Intervention: None

Comparison: None
n=891 children who had complete data on patterns of atopic illness up to the age of 16 years (original cohort n=1265 children)A birth cohort of 1265 New Zealand childrenPerinatal measures:
Birth weight gestational age head circumference length at birth
Measures of atopic illness up to 16 years by structured interview and hospital, GP and parents records including eczema and asthma

Two categories of atopic eczema were used
i) any eczema: whether the child had made any medical consultation for eczema by the age of 16 years: 36.6% of the sample met this criterion,

ii) Recurrent eczema: whether the child had made at least three medical consultation for eczema by the age of 16 years: 13.6% of the sample met this criterion
There was no association of eczema or any other atopic status other than asthma with perinatal measures as shown by Chi square tests.

Exception to this was a small non- significant association between birth weight and other atopic status as defined using the criterion of at least one medical attendance (p<0.05)

There were significant associations between head circumference and risks of asthma (Any diagnosis of asthma p<0.1, 5+ medical consultations for asthma p<0.0001). A head circumference of greater than 37 cm had greater risks of asthma.

Even after allowing for confounding factors e.g. Maternal smoking, maternal drinking, gender, birth order etc children with a head circumference at birth of 37 cm or greater had odds of asthma that were 1.8 (p<0.01) to 3.0 (p<0.0001) times higher than the these with head circumference of 37 cm.
Large head circumference at birth may be associated with the development of asthma but no other atopic condition.The study was funded by the
Health
Research Council of New Zealand, the
National Child
Health
Research
Foundation and the Canterbury Medical research
Foundation.
Eichenfield L; Ellis C; Fivensen D; Herbert A; Dromgoole S; Piacquadio D. 2007517Study Type: Case series

Evidence Level: 2−
n=21‘Healthy’ boy and girls in equal numbers with ‘stable atopic eczema’ mean age 9+/−2.5 (range 5–12) years.

No systematic or topical treatments exclusive of emollients were allowed for 2 weeks prior to study.
Intervention: Lipid- rich moisturising formulation of hydrocortisone butyrate 0.1% three times over a minimum body surface area of 25% daily for up to 4 weeks.

In children noted to be ‘clear’ at 3 weeks, treatment was discontinued early.

Comparison: none
Evaluations were made at days 1, 8, 15, 22 and 29.

PGA for overall disease severity (0=clear to 6=extreme)

Four point scoring system for severity of individual symptoms (0=none to 4=severe)

Pruritus severity scores were defined by interference with daily activities

% BSA

Cosyntropin® stimulation test (CST) was used to challenge the responsiveness of the adrenal gland with a 30 min post injection assessment at day 1 and end of treatment.
20/21 children completed the study.

2/22 children were clear at 22 days and 18/22 were treated for the 4 weeks.

PGA scores, pruritus scores, % BSA and individual symptoms severity was improved significantly over the period of treatment. 48% of children were ‘clear’ or ‘almost cleared’ at 22 weeks.

None of the children were found to have adrenal suppression

Mean cortisol conc (μg/dL +/−SD)

Day 0:
pre stimulation 15.8 (7.0) post stimulation 28.3 (5.5)
Final day: pre stimulation 13.0 (4.6), post stimulation 27.8 (4.5).

A normal adrenal response was defined as greater than 18ug/dL

The treatment was well tolerated and no changes in biochemical tests were noted.

2 AE’s reported, mild transient burning on 1st day of application and a tinea corporis infection.
Overall a 4 week period with maximal treatment of hydrocortisone butyrate 1% there were no signs of adrenal suppression in 20 healthy children with ‘stable atopic eczemaSmall uncontrolled study [EL=2−]

This study was funded by a grant from Ferndale laboratories, Inc.
Turpeinen M; 518Study Type: Case series

Evidence Level: 3
Intervention: Application of hydrocortisone cream 1% followed by skin absorption tests. (n=14)

ACTH test at 2 hours to evaluate the effect of previous treatment with TCS. (n=10)
n=18 children of which n=14 had atopic eczema18 children, (14 with atopic eczema)
Aged 6 weeks to 14.4 years with chronic skin disease and who had been admitted to hospital due to the exacerbation of their skin disorder
Serum cortisol determination at 1, 2, 3,4,5,6,8,12,18 and 24 hours after application of hydrocortisone cream

Serum cortisol was measured 2 hrs after administration of ACTH bolus,
Endogenous secretion of cortisol was suppressed by dexamethasone. A 24 hour absorption test was performed on 9 children of which 6 showed percutaneous absorption of hydrocortisone cream. The highest serum cortisol level was recorded within the first 6 hours.

A 4 hour test was performed on 9 children showed 8 of them had absorbed hydrocortisone. The rise of serum cortisol ranged from 98–2669 nmol/L

The 2 hour ACTH was performed on 10/14 children with atopic eczema and 3 of these tested had suppressed adrencortical function. This effect was associated with post application of serum cortisol levels following hydrocortisone cream. This occurred more often in infants with severe skin condition than mild or moderate.
The study concluded that this skin absorption test at 4 hours, in addition to the monitoring of adrenocortical function and growth should be recommended for infants with chronic severe skin disorders requiring long term treatment with TCS.The finding of this study was the Allergy Research Foundation of Finland
McGowan R;Tucker P;Joseph D;Wallace AM;Hughes I;Burrows NP;Ahmed SF;

2003 Sep 331
Case series EL=3Intervention: Wet wrap dressings with emollient (n=1) or beclomethasone dipropionate, strength not stated, diluted to 10% (n=6) or 25% (n=1) applied under tubular bandages.

Bandages left on for 24 hours a day for up to 2 weeks, reducing to overnight use for 1 week, then as required for the remaining 12 week

Comparison: N/A
8Children with atopic eczema aged 3.3–8.8 years, median 5.1 years1) Lower leg length velocity (knemometry); millimetres per week

2) Urinary deoxypyridinoline crosslink excretion (UDPD); median rate, nmol/l
1) 0.42 (vs 0.43 during the pretreatment period), p value not reported

2) 26.3 (vs 25.9 in pretreatment period), p value not reported
This study found no change in growth rates (lower leg velocity) or in urinary excretion of deoxypyridinoline crosslink, a marker of bone turnover, in children treated with wet wrap dressings for a median duration of 12 weeks.Funding: Addenbrookes Charities Committee, the Marmaduke Shiled Fund, Serono Pharmaceutical s Ltd, and Mason Medical Research Foundation.
Heuck C; 519Study Type: Case series

Evidence Level: 3
Intervention: In period one (run- in of 2 weeks) emollient (Locobase) was given twice daily In period 2 (2 weeks) budesonide cream 0.025% (Preferid) and emollient were applied with an interval of 5 mins morning and night

In period three (run-out of 2 weeks) emollient (Locobase ) was given twice daily

Comparison: None
n=14 children (n=12 completed study)7 girls and 7 boys with atopic eczema mean age 9.5 years, range 5.8 to 12.5 years were recruited from a secondary centre. There was no treatment 2 weeks prior to study with exogenous glucocorticoidsAt time 0, 2 an 4 weeks severity of atopic eczema was scored as to its extent (1–4) and its activity (1–4)

Knemometry of the right lower leg was performed twice a week and lower leg growth rates were calculated
Severity of Eczema

period 1: 4.33 (2.21)
period 2: 2.78 (1.46)p<0.05 vs.period1
period 3: 2.79 (1.45)p<0.05 vs.period1

Lower Leg Growth

period 1: 0.25 (SD 0.43)
period 2: 0.14 (SD 0.37) p<0.05 vs.period3
period 3: 0.54 (SD 0.35) p<0.05 vs.period1
The authors suggest that knemometry may be useful for comparing different TCS and treatment regimes in children with atopic eczemaThe study is short in duration and small in numbers of participants. The growth measures do not include height and weight (normal growth parameters) The funding of this study is undeclared
Wolthers OD;Heuck C;Ternowitz T;Heickendorff L;Nielsen HK;Frystyk J; 1996

520
Study Type: Case series

Evidence Level: 3
Intervention: In period one (run in of 2 weeks) emollient (Locobase) was given twice daily In period 2 (2 weeks) budesonide cream 0.025% (Preferid) and emollient were applied with an interval of 5 mins morning and night

Comparison: None
n=13 children6 girls and 7 boys with atopic eczema recruited from a secondary referral centre. Mean age 9.5 years, range 5.8–12.5 years).
Mean body surface area affected 1.1m2, range 0.7–1.3
No treatment with exogenous glucocorticosteroids in the past year
At time 0, 2 and 4 weeks severity of atopic eczema was scored as to its extent (1–4) and its activity (1–4)

Serum analysis of IGF-I, IGFBP-3, osteocalcin, PICP, ICTP and PHINP at 2 and 4 weeks
Severity of atopic eczema:
(Period 1) 1 4.1 SD 2.0
(Period 2) 1.9 SD 1.1 p<0.002

No statistically significant effects were seen on serum levels of IGF-1, IGFFBP-3, osteocalcin or ICTP.
The mean (1SD) serum concentrations of PICP and PHINP were reduced between period 1 and 2
PICP 398 (132) and 7.6(1.8) ug/l (p=0.03)
PHINP 355(132) and 6.4 (1.4) ug/l (p=0.01)
Type I and II collagen turnover may be suppressed during short term topical budesonide use in children with atopic eczemaThe number of the participants was small and the outcome measures of growth were biochemical tests as opposed to clinical measures
Aylett SE;

1992521
Study Type: Case series

Evidence Level: 3
Intervention: Beclomethasone dipropionate (BDP) mean dose 1800ug/day in 3 divided doses, range 800–1800. If therapeutic response was judged to be favourable after 4 weeks, the dose of BDP was the gradually reduced over 6 weeks to an maintenance dose for each child

Comparison: None
n=15 children of which n=10 provided data for the studyChildren with persistent, extensive, non- exudative atopic eczema whose
a) condition was not controlled
b) age was 2–10 years for girls, 2–11 years for boys
c) height above above the 10th centile

d) treatment had not included oral, inhaled or nasal corticosteroids in the past year.

Mean age of 5.7 years, range 1.8–10.9 years) The median total Ig E was 19,954 kU/I (79–68,300)
At 24 hours and 6 months

Plasma cortisol profile and free urinary cortisol

Atopic eczema was assessed throughout using standard scores (Pike et al 1989)

Weight and height at 0 and 6 months from which height SDS were calculated and were compared to normal values for height (Tanner et al 1966)
14/15 derived benefit from BDP treatment 10/14 were able to reduce to a maintenance dose (mean 1000ug, range 800–1800ug)

Of these 10 children:

3/10 continued to grow normally in the 6 months of treatment according to growth charts 7/10 showed some sign of growth impairment (numerical data reported for n=6 only)

For this group of n=6: pre treatment median height SDS was +0.285 (95% CI −0.295 to +1.055)
Post treatment −0.390(95% CI −0.94 to +0.465)
This difference was statistically significant (Wilcoxon Signed Rank Test 0.3–1.03)

There was no significant difference in plasma cortisol levels or urinary cortisol excretion although the latter was reduced throughout the study 32.5 ( 95% CI 26.5–40.00) to 25nmo/24 hour (95% CI 25.0 to 31.5) (95% CI for the difference −3.75–15.0)
Oral BDP is useful in controlling childhood atopic eczema but growth should be monitored regularly through its use.The data are of use but in the study is small in numbers of children and relatively short term.

The funding of this study is undeclared
Woo WK;

2003

522
Study Type: other

Evidence Level: 3
Intervention: None

Comparison: None
n=1Case report of 5 year old boy with long standing severe atopic eczema since 6 months

TCS such as betamethasone valerate (0.1%) had been applied continuously at up to 30g per week and clobetasol propionate 0.05% had been applied intermittently over the last year
He had asthma from the age of 12 months with moderate severity requiring hospitalisation about twice a year for which he used a beclometasone dipropionate inhaler twice daily
At presentation the boy was small for age (height and weight on the 9th centile). Unclear as to whether this was normal for him (mid- parental height 165cm). He was 103 cm.

Full biochemical analysis was carried out: Serum IgE 3850 kU/l (range 0–70)

Serum cortisol 277 nmol/l (range 300–700)
ACTH stimulation showed results at baseline: 8nmol/l (normal >120)
30 mins: 112nmol/l (normal >570)
60 mins: 150nmol/l (normal >570)

No steroid skin effects were noted
Adrenal gland suppression should be suspected in any patient who has regularly been using potent TCS and is small for his or her ageThis case report is EL=3 as it is an n=1 study
Bode HH

1980523
Study Type: case report

Evidence Level: 3
Intervention: None

Comparison: None
n=1A case report of a 13 year old boy who was referred to a paediatric unit due to his short stature.

He was born full term with normal birth weight, length and early development.

He developed atopic eczema at 18 months which covered most of his body. This was treated with a TCS cream (betamethasone ointment 2%) for 6 years and this improved his atopic eczema and relieved his discomfort. The quantity of TCS used weekly was 45g.

At 13 years, he had a height of 131.7cm (mean for age 155 cm) and he weighed 30kg. His head circumference was 53.3cm, span 128.3cm and upper to lower body segment ratio 0.95. His skin was dry, red, thin and transparent. His face appeared slightly cushingoid and there was hirsutism on both shoulders, arms and forehead.
At age 13 years

Serum cortisol was 0.1ug/dL

Plasma ACTH was <10pg/ml

Normal thyroid function

Bone age was that of a 9 year old boy

Therapy was changed to an emulsion ointment base (Eucerin cream) and the use of beclomethasone was limited to wrists and ankles where eczema was still present.

9 days after his first visit, an ACTH stimulation test was performed and the basal ACTH level was unmeasurable, the serum cortisol level was 0.9ug/dL and the latter rose to only 1.5ug/dL 60 min after ACTH stimulation

7 weeks later (after treatment change)

Serum ACTH 57pg/ml Serum cortisol 7.8ug/dL which rose to 22ug/dL after ACTH stimulation.

Over the next year, TCS ointment was only used intermittently. In that time the boy grew 7.9cm and showed further advancement of puberty.

Bone ages of 11 and 12.5 years were found at 6 and 12 months after change in treatment The eczema was controlled with non-steroidal preparations and the severe pruritus was suppressed with hydroxyzine chloride
This case report is EL=3 as it is a n=1 study
Caffarelli C;524Study Type: Cohort

Evidence level: 2−
n=65 children with atopic eczema

N=65 children unaffected by atopic eczema
Children (40 boys and 25 girls) with a mean age of 3.55, range 6 months-14 years. Atopic eczema was diagnosed by Hanifin and Rajka criteria.

Control children had a mean age 3.65 range 6mths–14 years
Intervention: None

Comparison: None
Follow-up period: None

Outcome Measures: Questionnaire completed by parents regarding their children’s gastrointestinal symptoms including questions on eczema for the affected children’s group.

Children’s skin was examined

Weight, height and abdominal circumference

Skin prick tests (for affected children’s group)
Gastrointestinal (GI) symptoms:

Diarrhoea (31% vs. 0%, p<0.001), vomiting (18% vs. 3% p<0.01) and regurgitation (38% vs. 17% p<0.001) occurred with greater frequency in the eczema group compared to the controls.

Frequency of abdominal pain, distension, eructation and flatulence was also greater in the eczema group compared to controls but not statistically so.

In 67% of the eczema children GI symptoms preceded the onset of eczema. No association of severity of eczema and GI symptoms were observed.

GI symptoms were more common in children with diffuse (100%) than localised eczema (70%) p<0.05 (95% 0.187 to 0.433)

Mean age of onset of GI symptoms

Eczema children: 11.2 months (15 days-74 months)
Control children: 4.12 months (15 days to 74 months) p<0.05

60% of the children with eczema had at least one positive skin prick test and 54% had a positive skin prick test to one food antigen. whole egg 37% egg yolk 34% egg white 28% whole cows milk 22% etc

There was no statistically significant difference in age, height, weight and eleventh-rib circumference between the atopic eczema and control group
An increased frequency of GI disorders appears to be associated with the presence of atopic eczema in children and may be critical in some children’s failure to thrive.Interesting data but there may be many confounding factors and the number of children involved is relatively small. The funding of the study is undeclared
Agostoni C;

2006525
Study Type: Cohort

Evidence level: 2−
n=55 children with atopic eczema of which n=36 breastfed and n=19 nonbreastfed

n=114 healthy infants of which n=58 breastfed and n=56 nonbreastfed
55 (24 females and 31 males) children born in the maternity unit and subsequently admitted to an allergy clinic at the hospital for symptomatic atopic eczema diagnosed by the Hanifin criteria.

The control group were recruited from the maternity unit.
Intervention: None

Comparison: None
Follow-up period: None

Outcome measures: Body weight and length of atopic eczema children was evaluated retrospectively at diagnosis and then prospectively through the first 12 months of life.

The control group were followed up from birth.

Measurements were made at age 1, 2, 3, 4, 6, 9 and 12 months.

Z scores for weight (WA)and length were (LA) calculated from these

In addition the following data were recorded:
infants birth date
mother’s age, height, prepregnancy body weight and education level.
Familial social status
gestational age and parity

Severity of atopic eczema (SCORAD), elimination diets and presence of asthma
Atopic eczema and control children were comparable for the baseline characteristics e.g. gestational age, birth weight and length.

Mean (SD) age at atopic eczema onset was 3.0 (1.6) months in BF children, 2.4 (1.2) months in non-BF children (p=0.12)

Presence of asthma:
13 atopic eczema patients (9BF, 4 non BF)
No cases in the control group

Patients affected by atopic eczema showed progressive impairment of growth in both WA and LA z scores (p<0.001).

Weight

After onset mean difference −0.27; 95% CI, − 0.41 to −0.14
Length
After onset mean difference −0.17; 95%CI −0.3 to −0.03

Before the onset of atopic eczema the LA z score was already significantly negative (−0.22; 95% CI: −19 to −0.6)

Differences between children with atopic eczema and control children were significant after the second month and more markedly so at 6 months even after adjustment for confounders and type of early feeding (BF vs non-BF).

At 12 months the adjusted mean difference was −0.69 (95% CI −1.00 to −0.38) for WA z score and −0.67 (95%CI −0.98 to −0.36 for LA z score

In the atopic eczema group an impairment of growth (height and weight) occurred in both the breastfed (p<0.001) and the non-breast fed (p<0.001) infants

Analysis to determine any possible association of growth with age of onset, severity of disease, elimination diet or presence of asthma showed that severity of disease was associated with increased WA growth impairment in the second 6 months of life (p<0.05) even after adjusting for confounding factors.
This study showed that in the first year of life, infants with atopic eczema showed a progressive impairment in growth irrespective of the type of early feeding (BF vs non-BF) and that disease severity of the disease may be an independent factor negatively affecting growth.Despite small numbers it provides interesting data on dietary influences in the first year of life of infants with atopic eczema. The funding of the study is undeclared.
Isolauri E; 526Study Type: Cohort

Evidence level: 2−
n=100 children with suspected cow milk allergy
n=60 healthy age-matched control children
Children aged 1 to 17 months (mean 7 months) who had been referred to hospital on the basis of suspected cow’s milk allergy by a positive open or double-blind, placebo-controlled cow’s milk challenge. Their atopic eczema was diagnosed by the Hannifin criteria.

Control children were recruited from a well-baby clinic.
Intervention: Cow’s milk elimination diet with either an extensively hydrolysed casein or whey formulation (n=44) or a soya formula (n=45) or in older patients with a calcium supplement

Comparison: None
Follow-up period: 24 months

Outcome Measures: Length and weight during the first 24 months of life

Length for age and weight for length SDS were calculated
The diagnosis of cow’s milk allergy was made at 7 months (6–8 months)

The reactions involved pruritus, urticaria, morbilliform exanthema or reactions of an eczematous type.

The relative length of children decreased compared to the healthy control group (p<0001). The fall in length coincided with the onset of symptoms of allergy, and the start of the elimination diet. (Patients were divided into two groups)
Early onset group (3–6 months)p=0.003
Later onset group (6–10 months)p=0.009

No catch up was seen at 24 months. The relative weight in patients continued to fall compared with that in the control group p=0.03

The delay on growth was more pronounced in a subgroup of patients with early onset than in late onset patients (p<0.0001).

Low serum albumin was present in 6% of children
24% had abnormal urea concentration
8%had a low serum phospholipid docosaheaenoic acid

The duration of breast feeding correlated positively with the sum of n-3 polyunsaturated fatty acids (p=0.001) and with the relative amount of docosahexaenoic acid (p=0.002)
It was concluded that co-ordinated dietetic and paediatric evaluation is needed for evaluation of allergies so as to avoid unnecessary elimination diets and encourage compliance to the individually tailored elimination diets.The eczematous status of the children is unclear and no details of the eczema are given in the results of the study.
The funding of this study is undeclared.
Laitinen K; 527Study Type: other

Evidence level: 3
n=159 childrenChildren with a family history of atopic eczema (mother, father and/or older sibling) and who had previously participated in a prenatal probiotic study.Intervention: Supplementation with Lactobacillus rhamnosus Strain GG; ATCC 53 103 was administered to the children postnatally for 6 months

Comparison: None
Follow-up period: 48 months

Outcome Measures: Children were followed for 4 years with study visits at 3 weeks, and at 3,6,12,18, 24 and 48 months at which the following were measured

Weight
Height at 48 months
Biceps, triceps and suprailiac skinfold thickness
mid upper arm thickness

SDS scores and weight for height % were calculated using Finnish reference values.

Diagnosis of eczema was by Hanifin and cow’s milk allergy was diagnosed by a double blind, placebo controlled challenge.

Dietary intake was recorded at 6,12 and 48 months with 4 day diaries
Atopic eczema was diagnosed in 29% (46/159) at 6 months, 46% (65/140) at 12 months, 35% (46/132) at 24 months and 36% (39/107) at 48 months.
Cow’s milk allergy was diagnosed in 14% in 18 children at 12 months

Logistic regression analysis showed that increased intakes of retinol, calcium and zinc (i.e. taking the probiotic diet) reduced the risk of atopic eczema whilst an increase of ascorbic acid increased the chances of atopic eczema.

Probiotic administration was not associated with any detrimental effect on growth overall at 48 months

Height mean difference 0.04 SDS 95% CI −0.33 to 0.4, p=0.852)
Weight for height (mean difference −3.35 (95% CI−7.07,0.37)%, p=0.077)

The effect of atopic eczema was significant with respect to weight −5.1 SDS 95%CI −8.9 to − 1.2, p=0.001) but not height −0.05 SDS 95% CI −0.42 to 0.33, p=0.815) although mean weight for height in children with atopic eczema was − 5.1% 95% CI −8.9−1.2% lower compared with control children (p=0.01)

Mid upper arm muscle circumference and proportion of body fat were lower in children with atopic eczema at 48 months (p=0.041 and p=0.007, respectively).
Administration of a perinatal supplement with probiotics had no detrimental effect on growth but may have some effect on the incidence of atopic eczema. The presence of atopic eczema appeared to have an effect on the growth of children up to the age of 48 monthsThis is a complex study with detailed analysis. The results are interesting but more evidence is needed before a probiotioc supplement could be advocated. Importantly the supplement appears safe and has no effect detrimental effect on growth The funding of this study is undeclared.
Estrada-Reyes E; 528Study Type: Other

Evidence Level: 3
Intervention: Extensively hydrolysed milk formula for 1 year adminstered according to weight and age.

Comparison: None
n=45 infants and toddlersChildren 6 (1.0 to 27) months with a positive history of cow’s milk allergy confirmed by a positive skin prick test and high IgE levels for either alpha-lactalbumin, beta-lactoglbulin or casein and positive single-blind food challengeSex normalised percentiles of heights and weights of infants and toddlers before enrolment and after study (1 year).Results for all children (atopic eczema and bronchitis)
Percentile weights (CI 95% −3.1 to −2.3) and heights (CI 95% −5.2 to 8.1) at baseline were similar to those at 1 year of follow up.

Correlation coefficients at baseline and year one:
Weight 0.85 (95% CI, 0.74 to 0.92, p<0.001)
Height 0.87 (95% CI 0.76 to 0.92, p<0.001)
Between weight and height at baseline 0.93 (95% CI, 0.88 to 0.96; p<0.0001) and year one 0.95 (95% 0.92 to 0.97; p<0.001)

Multivariate analysis showed that sex, breastfeeding, early bottlefeeding, ingestion of adapted or special milk formulas, atopic eczema were not correlated with either the children’s weight or height at diagnosis of allergy or at 1 year of follow up (p>.10)

Atopic eczema was reported in 18 (40%) of patients at the beginning of study and 13 (28.9%) at the end.

Weights (95% CI −0.6 to 2.6) and heights (95% CI −1.5 to 9.5) were not different between toddlers who had atopic eczema during the study period and those who did not (p>0.05).
Growth of infants and toddlers with cow’s milk allergy was not affected by the intake of extensively hydrolysed milk for one year. The presence of atopic eczema in this population did not appear to have any deleterious effect on these children’s growth.It was a small study and many other confounding factors e.g. other illness, social class need to be considered. Children with atopic eczema formed aa small (n=13) proportion of the study population and therefore the effect on growth in the atopic eczema population as a whole is difficult to extrapolate. The funding of this study is undeclared

From: Evidence tables

Cover of Atopic Eczema in Children
Atopic Eczema in Children: Management of Atopic Eczema in Children from Birth up to the Age of 12 Years.
NICE Clinical Guidelines, No. 57.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2007 Dec.
Copyright © 2007, National Collaborating Centre for Women’s and Children’s Health.

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