Topical corticosteroids

Bibliographic informationStudy type and evidence levelNumber of patientsPatient characteristicsIntervention and comparisonFollow-up and outcome measuresEffect sizeReviewer comments
Thomas KS;Armstrong S;Avery A;Po AL;O'Neill C;Young S;Williams HC;

2002 Mar 30

254
Study Type: RCT
Double-blind

Evidence level: 1+
207

Exclusions: severe eczema
Children with mild or moderate atopic eczema, 84% of children came from general practices, and 15% from a general hospital outpatient clinic (including 13 general practices and a teaching hospital).

Age 1–15 years, mean 5 years in the HC group vs 6 years in the betamethasone group
Intervention: Betamethasone valerate 0.1%
applied twice daily for 3 consecutive days, followed by a base emollient only (white soft paraffin) for 4 days (n=104

Comparison: Hydrocortisone ointment 1% applied twice daily for seven consecutive days (n=103)
Follow-up period: 18 weeks

Outcome Measures: 1) Number of scratch-free days (n evaluated 198; median with IQR)

2) Number of relapses (n=165)

3) Number of undisturbed nights (n=165)

4) Mean (SD) change in Children's Life Quality index (n=168)

5) Mean (SD) change in Dermatitis family impact (n=169)

6) Adverse effects

7) Withdrawals (dropped out or resorted to concurrent treatment)
1) Potent vs mild: 117.5 (99.3 to 125.0) vs 118.0 (99.8 to 124.0),
Difference: 0.5 (95% CI −3.0 to 2.0, day), p =0.68

2) 1.0 ( 0.0 to 3.0) vs 1.0 ( 0.0 to 3.0)
Difference:0, p = 0.66

3) 121.0 (101.3 to 126) vs 123.0 (109.5 to 126)
Difference: 2.0 (95% CI 0.0 to 2.0), p=0.53

4) −1.9 (3.0) vs −2.4 (4.0)
Difference: −0.5 (95% CI −1.52 to 0.62) p=0.41

5) −0.6 (2.2) vs −0.5 (2.4)
Difference: −0.1 (95% CI −0.60 to 0.80), p=0.78

6) Total 18 children reported adverse events (8.7%)

5% vs 9% worse symptoms
2% vs 0% spots/rashes
1% vs 0% hair growth
1% vs 0% viral encephalitis

Skin thickness was measured by ultrasound in 51%:
Baseline:
0.91 mm (mild arm), 0.99 (potent arm);
Mean change: −0.04 mm (SD 0.11mm) for mild arm, −0.05 mm (0.14) potent.

7) 25% vs 36%, mean difference 11%, 95% CI −3 to 25, p=0.19)
Funding: NHS R&D programme (Trent).

Most outcomes were evaluated for the community population only (n=165).

The total quantities of topical corticosteroids used during the trial were reported but only for 42% of the children.
Green C;Colquitt JL;Kirby J;Davidson P;Payne E;

2004

288
Study Type: Systematic review - meta- analysis HTA

Evidence level: 1++
10 RCTs (data for children from 3 RCTs; two published and one from a manufacturer' s submission to the NICE technology appraisal programme).

Refer to evidence tables for Richelli 1990287 for details of the first RCT

Data for RCTs 2 and 3 are reproduced from the HTA because data for children are not published elsewhere
RCT2
Children with at least moderately severe eczema (score of 6 or more from a maximum of 9 for erythema, pruritus and thickening).

RCT 3 (unpublished) Children with at least moderately severe eczema (score 7 or more but scale not described fully).
Age range 1–12 years (subgroup of RCT involving children and adults)
Intervention: RCT2:
Fluticasone propionate cream 0.05% applied once daily, n=63

RCT 3:
Fluticasone propionate ointment 0.005% applied once daily, n=63 of 123 were children

Comparison: RCT2:
Fluticasone propionate cream 0.05% applied twice daily, n=63

RCT 3
Fluticasone propionate ointment 0.005% applied twice daily, n=57 of 122 were children
Follow-up period: RCT 3
Duration of treatment, 4 weeks (or less if eczema cleared sooner)

Outcome Measures: RCT2

1) Global assessment, where success='cleared', 'excellent' or 'good'; and failure = 'fair', 'little' or 'worse'

2) Adverse events

RCT 3

1) Global assessment, where success='cleared', 'excellent' or 'good'; and failure = 'fair', 'little' or 'worse'

2) Patients' self- assessment of success:
success= totally, greatly, or moderately improved; failure = slightly improved, not changed, worsened or greatly worsened

3) Adverse events
RCT2

1) 86% once daily vs. 891% twice daily success, difference 3% (95% CI −15.5 to 9.6), p = 0.644

2) 37% vs 35% reported adverse events
24% vs 17% were possibly related to treatment, predominantly signs or symptoms relating to skin or their eczema

RCT 3

1) 77% once daily vs. 91% twice daily success, difference 13.5% (95% CI 0.6 to 26.4), p = 0.048

2) 72% vs. 91% success, difference 18.6% (95% CI 5.0 to 32.3), p=0.011

3) 49% vs 40% reported adverse events
8% vs 17% were possibly related to treatment, but no details of these adverse events were reported.
Funding of RCT2: Glaxo.

Funding of RCT3: not stated. Manufacturer (GlaxoSmithKline) assumed

Refer to evidence tables for Richelli 1990287 for details of RCT 1
Green C;Colquitt JL;Kirby J;Davidson P;Payne E;

2004

288
Study Type: Systematic review - meta- analysis
HTA

Evidence level: 1++
10 RCTs
(data for children from 3 RCTs; two published and one from a manufacturer' s submission to the NICE technology appraisal programme).

Refer to evidence tables for Richelli 1990287 for details of the first RCT

Data for RCTs 2 and 3 are reproduced from the HTA because data for children are not published elsewhere
RCT2
Children with at least moderately severe eczema (score of 6 or more from a maximum of 9 for erythema, pruritus and thickening).

RCT 3 (unpublished)

Children with at least moderately severe eczema (score 7 or more but scale not described fully).
Age range 1–12 years (subgroup of RCT involving children and adults)
Intervention: RCT2: Fluticasone propionate cream 0.05% applied once daily, n=63

RCT 3:
Fluticasone propionate ointment 0.005% applied once daily, n=63 of 123 were children

Comparison: RCT2:
Fluticasone propionate cream 0.05% applied twice daily, n=63

RCT 3
Fluticasone propionate ointment 0.005% applied twice daily, n=57 of 122 were children
Follow-up period: RCT 3
Duration of treatment, 4 weeks (or less if eczema cleared sooner)

Outcome Measures: RCT2

1) Global assessment, where success='cleared', 'excellent' or 'good'; and failure = 'fair', 'little' or 'worse'

2) Adverse events

RCT 3

1) Global assessment, where success='cleared', 'excellent' or 'good'; and failure = 'fair', 'little' or 'worse'

2) Patients' self- assessment of success:
success= totally, greatly, or moderately improved; failure = slightly improved, not changed, worsened or greatly worsened

3) Adverse events
RCT2

1) 86% once daily vs. 891% twice daily success, difference 3% (95% CI −15.5 to 9.6), p = 0.644

2) 37% vs 35% reported adverse events
24% vs 17% were possibly related to treatment, predominantly signs or symptoms relating to skin or their eczema

RCT 3

1) 77% once daily vs. 91% twice daily success, difference 13.5% (95% CI 0.6 to 26.4), p = 0.048

2) 72% vs. 91% success, difference 18.6% (95% CI 5.0 to 32.3), p=0.011

3) 49% vs 40% reported adverse events
8% vs 17% were possibly related to treatment, but no details of these adverse events were reported.
Funding of RCT2: Glaxo.

Funding of RCT3: not stated. Manufacturer (GlaxoSmithKline) assumed

Refer to evidence tables for Richelli 1990287 for details of RCT 1
Vernon HJ;Lane AT;Weston W;

1991 Apr

260
Study Type: RCT

Evidence level: 1+
48Children with more than 15% of body surface area involving atopic eczema, and a score of at least 8/15 for severity* and an erythema score of at least 2.

Age range: 6 months to 12 years
Intervention: Mometasone furoate 0.1% cream applied once daily (n=24)

Comparison: Hydrocortisone 1.0% cream applied twice daily (n=24)
Follow-up period: Up to 6 weeks treatment and follow-up; children whose condition had cleared by week 3, and those who had shown no improvement were withdrawn from the study. Outcome Measures: 1) Percentage improvement in severity* score from baseline

2) Change in % body surface area affected

3) Plasma cortisol levels

4) Adverse effects

5) Withdrawals
1) 95% mometasone vs 75% HC, p=0.01

2) −40% vs −26%, p=0.03

3) No numerical data. No significant differences were found in mean values, nor in any change in mean cortisol levels from baseline between groups.
One child treated with HC had a plasma cortisol level of 5 microg/dl (below normal range, although this range was not quoted) on day 8

4) 8% (n=2) vs 0% stinging on application
0 vs 4% molluscum contagiosum on area treated

5) 63% vs 63% due to clearance of the condition
0 vs 13% lack of response
0 vs 4% (n=1) flare of asthma requiring systemic corticosteroids
0 vs 4% lost to follow-up
4% vs 0 S. aureus infection of scalp
Funding: Schering-Plough

Double-blind study.

30 children (15 in each group) completed the study early (median duration 3 weeks).

Children who used antibiotics, antihistamines, or emollients were removed from the study.

Severity score: each of 5 signs/symptoms scored on a scale of 0–3 (none to severe).

The quantities of TCS used were not stated.
Wolkerstorfer A;Strobos MA;Glazenburg EJ;Mulder PG;Oranje AP;

1998 Aug

261
Study Type: RCT

Evidence level: 1+
22

Exclusions: use of systemic treatment for atopic eczema within 1 month
Children with moderately active atopic eczema. SCORAD scores 29 in the fluticasone group and 32 in the clobetasone group.

Aged from 3–8 years, mean
4.9 years (fluticasone) and 4.1 years (clobetasone)

Initial SCORAD: 29 (FP group); 32 (CB group)

Medication (emollient, hydrocortisone acetate 1%, antihistamines) not used in the week before the trial started
Intervention: Fluticasone propionate 0.05% cream applied once daily plus a vehicle cream once daily (n=12)

Comparison: Clobetasone butyrate 0.05% cream applied twice daily (n=10; 9 completed treatment)
Follow-up period: 6 weeks; up to 4 weeks treatment, or less if SCORAD score below 9 ('clinically healed'), and 2 weeks follow-up after treatment completed.

Outcome Measures: 1) SCORAD (mean score change from baseline to week 4)

2) SCORAD (mean score change from week 4 to week 6)

3) Urinary cortisol excretion (nmol/24 hours)
1) −19 (66%) vs −22 (69%), no statistically significant difference in groups

2) +13 (130%) vs +11 (110%)

3) No numerical data reported but it was noted that there were no significant differences between groups at baseline or weeks 4 or 6, p=0.8, and no signficant changes from baseline.

In one child levels fell from 162.8 at baseline to 67 nmol/24hr at week 4, but returned to the pre-treatmnet level by week 6.
Funding: none declared.

Basic skin care was used for all children.

Double-blind

One child in the clobetasone arm withdrew because of varicella.

The quantities of TCS used were not stated.
Wolkerstorfer A;Visser RL;De Waard van der Spek FB;Mulder PG;Oranje AP;

2000 Nov

328
Study Type: Cohort
Non-randomised controlled trial

Evidence level: 2−
31 children

Group 1: 50% dilution of fluticasone propionate (FP) 0.05%, n=18

Group 2: a side-to-side 10%, 25% and 50% dilution of FP 0.05% for one week, then 10% dilution for one week, n=5

Group 3: 0% (emollient), 5%, 10% or 25% dilution of FP 0.05%, n=8
Children with severe refractory atopic eczema aged 5 months to 13 years, mean age not reported.

SCORAD score >40 in 29 (94%)
Intervention: Group 1: 50% dilution of FP cream under wet wrap treatment for 2 weeks

Group 2: different dilution (10%, 25% and 50%) of FP cream under wet wraps treatment for body symmetrically eczema for 2 weeks

Group 3: different dilution (0% (emollient), 5%, 10% and 25%) of FP cream under wet wraps treatment for 2 children in each strength for 2 weeks

Comparison: The serum corticol levels before and after wet wrap treatment in different dilution of FP strength groups
Follow-up period: Duration of treatment: 2 weeks

Outcome Measures: 1) Mean serum cortisol levels (SD)
a) Group 1
b) Group 2
c) Group 3

2) Adverse effects
a) Group 1
b) Group 2
c) Group 3
1a) Overall, no significant decrease in cortisol levels at week 2, p=0.24. Levels were 'temporarily below the normal range' (0.2–0.8 micromol/l) in 3 (17%) children

1b) 0.45 (0.17) micromol/l at week 2 vs 0.42 (0.16) at baseline

1c) levels were below the normal range in 2/8 children (0.03 and 0.09 micromol/l).
Serum cortisol levels vs FP quantity per body surface area (microgram per m2) for each of the 8 patients:
0.28 vs 0
0.46 vs 0
0.55 vs 564
0.39 vs 728
0.36 vs 835
0.09 vs 957
0.03 vs 1129
0.33 vs 2071

2a) 30% (6/18) upper respiratory tract infection
30% (6/18) folliculitis
5.5% (1/18) herpes simplex infection
5.5% (1/18) diarrhoea
5.5% (1/18) itching

2b) 40% (2/5) upper respiratory infection
40% (2/5) folliculitis 20% (1/5) abdominal pain
20% (1/5) itching

2c) 63% (5/8) folliculitis
12.5% (1/8) balanitis
12.5% (1/8) furunculosis
Funding: none declared.

Tubifast was the bandage used.
The cream was applied to the whole body.
The bandage was rewetted every 2 hours with water using aspary bottle.

Cortisol was measured at 9 o'clock in the morning in groups 1 and 2, at baseline and after 2 weeks. In group 3 serum cortisol and urinary timed morning cortisol/creatinine ratio was measured daily at 6 o'clock in the morning for the first week of treatment.

SCORAD scores were also measured, but only selected numerical data were reported; results were mainly presented in graphs.

The proportions with mild, moderate and severe atopic eczema were also reported, but the method of classification was not described.
Lucky AW;Grote GD;Williams JL;Tuley MR;Czernielewski JM;Dolak TM;Herndon JH;Baker MD;

1997 Mar

285
Study Type: RCT

Evidence level: 3
20Children with atopic eczema affecting more than 20% of body surface area, (mean 38%).

Age range 11months to 11 years, mean 4.7 years desonide vs 2.6 years HC.

Baseline cortisol levels 2– 25 microg/ml
Intervention: Desonide ointment 0.05% applied twice daily (n=10)

Comparison: HC ointment 2.5% applied twice daily (n=10)
Follow-up period: Duration of treatment: 4 weeks

Outcome Measures: Change in cortisol levels in response to ACTH stimulation (measured at 30 minutes and 60 minutes after an intravenous dose)
% increase in stimulated 60 minute mean cortisol levels at day 28:
109% desonide vs 124% HC, p=0.69.

No clinically or statistically significant differences reported between treatment for changes in ACTH

Mean within-treatment change
−0.4 microg/ml (−1.3%), p>0.8
Funding: none declared

Mean quality of TCS applied was approximately 3g/day/child.
Patel L;Clayton PE;Addison GM;Price DA;David TJ;

1995

278
Study Type: Cross-sectional

Evidence level: 3
28

Exclusions: children receiving inhaled or systemic corticosteroid s in the preceding 6 months.
See intervention and comparisonsIntervention: Children aged 3.1–10.7 years, mean 7.2 years with atopic eczema affecting 16–90% (mean 58%) of body surface area and treated with HC ointment 1% since infancy for 3–10 years (mean 6.5 yrs) (n=14)

Quantity used: 48.7–223.2 mg/square metre (median 134.2) body surface area/day for 3–10 years.

64% had used moderately potent TCS intermittently

Comparison: Control group: children without atopic eczema being investigated for short stature, age 3.8–10.7 years, mean 7.8 years. Children had not received corticosteroids before the study, and had no endocrine abnormality or systemic disease (n=24)
Follow-up period: N/A; cross-sectional study

Outcome Measures: Plasma cortisol values (response to low-dose ACTH stimulation*); differences between medians in atopic eczema vs control groups, (95% CI)
Basal levels:
0.6 (95% CI −140 to 90 nmol/l)

Peak:
0.2 (95% CI −125 to 50 nmol/l)

Increment:
p=0.8 (95% CI −120 to 95 nmol/l)

Area-under-curve:
0.2 (95% CI −7725 to 1587, nmol/l)
Time to peak:

0.02 (95% CI −10 to 0, min)
Funding: none declared

*500ng/1.73 square metres body surface area
Lebwohl M; 1999 Aug256Study Type: RCT

Evidence level: 1−
219Children with moderate to severe atopic eczema who had failed to respond to at least 7 days consecutive treatment with a topical hydrocortisone preparation, the last application occurring within a week of enrolment in this study.

Age 2–12 years
Intervention: Mometasone furoate cream 0.1% cream once daily (n=109)

Comparison: Hydrocortisone valerate cream 0.2% twice daily (n=110)
Follow-up period: Duration of treatment, 3 weeks

Outcome Measures: 1) Mean percentage improvement in disease severity. (Severity signs and symptoms assessed on a scale of 0–3 (none to severe: erythema, induration/lichenification, scaling/crusting, excudation, excoriation and pruritus. A target area of at least 20cm2 was selected for evaluation of treatment effect).

2) Physician’s assessment of global clinical response vs baseline

3) Adverse effects

4) Withdrawals
1) Mometasone vs HC

87.2% vs 78.6% (p=0.01)

2) Global evaluation score at day 21
36.3 vs 19.6, p<0.01

3) 19.3% vs 17.3% reported adverse effects
3.7% vs 1.8% application-site reactions (other adverse effects ‘not considered to be treatment- related’ therefore no further details given)

4) Total withdrawals 19.6% Reasons:
16.5% vs 8% clearance of atopic eczema

2.7% vs 3.6% non-compliance

0 vs 1% treatment failure

2% vs 5% lost contact
Funding: Schering Plough Inc

Multicentre study (n=10).

No other therapies for atopic eczema were permitted.

Although described as a randomised controlled trial, no details of randomisation were given, nor any baseline data. Therefore it is not possible to know whether groups were similar other than in the intervention being given. Additionally, while treatment with a HC preparation had failed, it is assumed that this was a mild preparation, thereby not exposing the group receiving HC in this RCT to continued prior ineffective therapy.

The physician’s assessment of global clinical response compared to baseline at day 15 (p=0.009), day 22 (p=0.011), respectively.

The quantities of TCS used were not stated.
Andersen BL;Andersen KE;Nielsen R;Stahl D;Niordson A;Roders GA; 1988268Study Type: RCT Within patient left-right side comparison

Evidence level: 1−
96

Exclusions: primary bacterial or viral skin lesions; secondarily infected lesions, treatment with systemic corticosteroid s or potent TCS within 2 weeks
Children with dry bilateral symmetrical atopic eczema

Age range 2 months to 13 years, mean 4.9 years
Intervention: Hydrocortisone 1% lipocream (Mildison) applied twice daily

Comparison: Hydrocortisone 1% ointment (Uniderm) applied twice daily
Follow-up period: Duration of treatment, 4 weeks

Outcome Measures: 1) Change in global severity* of atopic eczema

2) Global improvement in skin lesions (% in each category):
a) clearance
b) considerable improvement
c) definite improvement
d) minimal improvement
e) no change
f) worse

3) Patients’ preference (based on cosmetic acceptability)

4) Adverse effects
1) −1.0 (59%) HC lipocream vs −0.9 (53%) HC ointment

2a) 37% vs 33%
2b) 11% vs 15%
2c) 26% vs 24%
2d) 16% vs 14%
2e) 4% vs 8%
2f) 5% vs 7%
p>0.05 between groups

3) 73% preferred lipocream vs 18% ointment, p<0.001

4) 0 vs 1% (n=1) pustules on target area
Funding: none declared

*Severity measured on a 5-point scale (0–4, none to severe)

One child from the hydrocortisone 1% ointment group was excluded from the analysis because of non- compliance

It is reported that analysis of baseline data was undertaken, but no baseline/demographic data were shown.
Olholm LP;Brandrup F;Roders GA; 1988269Study Type: RCT

Evidence level: 1−
60

Exclusions: primary bacterial or viral skin lesions; secondarily infected lesions; needing treatment with systemic corticosteroid s; use of potent corticosteroid s within two weeks
Children with dry bilateral symmetrical atopic eczema; 51 children were aged under 10 years, but the mean age was not reportedIntervention: Hydrocortisone 1% oil-in-water emulsion (Lipocream) applied twice daily

Comparison: Hydrocortisone 1% ointment (Uniderm) applied twice daily
Follow-up period: Duration of treatment, 4 weeks

Outcome Measures: 1) Global severity* of atopic eczema (% with none, slight, moderate, severe, very severe at endpoint)

2) Global improvement in skin disease

3) Patients’ preference (in relation to cosmetic acceptability)
1) 41% lipocream vs 38% ointment none
43% vs 45% slight
12% vs 14% moderate
3% vs 3% severe

No statistical analysis


2) 2% vs 2% worse
2% vs 2% no change
7% vs 5% minimal improvement
29% vs 33% definite improvement
20% vs 20% considerable improvement
40% vs 38% clearance

No statistical analysis

3) 26% preferred lipocream 25% found the lipocream was worse
49% no difference between products
Funding: none declared

*Severity measured on a 5-point rating scale (0–4, none to very severe)

No baseline data were given (other than severity scores). Two children withdrew from the study, and data were not included for some children for the outcomes cosmetic acceptability (n=1) and global improvement (n=3).
Veien NK;Hattel T;Justesen O;Norholm A;Verjans HL; 1984258Study Type:
RCT
Within-patient left-right side comparison

Evidence level: 1+
40Children with chronic symmetrical, bilateral atopic eczema. Mean severity score 2.6 (scale 0–4).

Age 10 months to 10 years, mean 4.1 years
Intervention: Hydrocortisone 17- butyrate 0.1% cream (Locoid), applied twice daily

Comparison: Hydrocortisone cream 1% (Uniderm), applied twice daily
Follow-up period: Duration of treatment, 4 clearance of lesions of the side involved, whichever was shorter)

Outcome Measures: 1) Global severity of atopic eczema (mean reduction in scores, on 5-point rating scale where 0=none, 1=slight, 2=moderate, 3=severe, 4=very severe)

2) Clearance rate

3) Investigator and patients/parents preference for HC-17- butyrate 0.1%, where moderate, good or excellent associated with score reductions of at least 1, 2, and 3 points on the rating scale. 4) Adverse events
1) HC-17-butyrate 0.1% vs HC 1%:

−2 (77%) vs −1.6 (62%), p<0.05

2) 60% vs 30%, p<0.01

3) Reported to be significantly in favour of HC-17-butyrate 0.1%; investigator’s preference p<0.01, patients/parents preference p<0.01

4) ‘No serious adverse events’
Funding: none declared

The quantities of TCS used were not stated.
Veien NK;Hattel T;Justesen O;Norholm A;Verjans HL; 1984258Study Type: RCT Within-patient left-right side comparison

Evidence level: 1+
40Children with chronic symmetrical, bilateral atopic eczema. Mean severity score 2.6 (scale 0–4).

Age 10 months to 10 years, mean 4.1 years
Intervention: Hydrocortisone 17− butyrate 0.1% cream (Locoid), applied twice daily

Comparison: Hydrocortisone cream 1% (Uniderm), applied twice daily
Follow-up period: Duration of treatment, 4 weeks (or until complete clearance of lesions of the side involved, whichever was shorter)

Outcome Measures: 1) Global severity of atopic eczema (mean reduction in scores, on 5-point rating scale where 0=none, 1=slight, 2=moderate, 3=severe, 4=very severe)

2) Clearance rate

3) Investigator and patients/parents preference for HC-17- butyrate 0.1%, where moderate, good or excellent associated with score reductions of at least 1, 2, and 3 points on the rating scale.

4) Adverse events
1) HC-17-butyrate 0.1% vs HC 1%:

−2 (77%) vs −1.6 (62%), p<0.05

2) 60% vs 30%, p<0.01

3) Reported to be significantly in favour of HC-17-butyrate 0.1%; investigator’s preference p<0.01, patients/parents preference p<0.01

4) ‘No serious adverse events’
Funding: none declared

The quantities of TCS used were not stated.
Munkvad M; 1989 Dec264Study Type: RCT Within-patient left-right side comparison

Evidence level: 1−
30Children with mild to moderate bilateral symmetrical atopic eczema

Mean age 11.8 years (range not reported)
Intervention: Clinitar (extract of crude coal tar) cream applied twice daily

Comparison: Hydrocortisone 1% cream applied twice daily
Follow-up period: Duration of treatment, up to 4 weeks

Outcome Measures: 1) Change in severity* scores of atopic eczema from baseline
a) infiltration
b) erythema
c) lichenification
d) scratch marks

e) dryness

2) Adverse effects
1a) −0.97 (75%) vs −0.97 (76%)

1b) −0.8 (71%) vs −0.87 (74%)

1c) −1.0 (70%) vs −1.13 (79%)

1d) −0.54 (70%) vs −0.6 (78%)

1e) −1.07 (78%) vs −1.0 (75%)

‘no significant differences between treatment’; p value not reported

2) Reported in 6 children (‘itching and soreness’); 5 in the coal tar group and 1 in the HC group.
Funding: Pharma medica a-s supplied the trials material. Smith & Nephew assisted in preparing the paper

No other medicines were permitted during the study period

Severity score used for infiltration, erythema, lichenification, excoriation and dryness, measured on a 5-point scale: 0–4 (none to severe)

No baseline/demographic data (other than severity scores) were reported for the two groups.
Smitt JHS;Winterberg DH;Oosting J; 1993257Study Type: RCT

Evidence level: 1+
40Children with atopic eczema, with a mean severity score of at least 4*, with at least two symptoms rated as moderate.

Eczema affected 44% of mean body surface area of the triamcinolone group and 53% of the alclometasone group

Age 1–15 years

Mean age, 5.1 years in the triamcinolone acetonide arm, and 3 years in the alclometasone diproprionate arm, p=0.046
Intervention: Triamcinolone acetonide cream 0.1% applied twice daily (n=20)

Comparison: Alclometasone diproprionate cream 0.05% applied twice daily (n=20)
Follow-up period: Duration of treatment, 3 weeks

Outcome Measures: 1) Severity of signs and symptoms, mean change from baseline to end of week 2 for:
a) erythema
b) lichenification
c) pruritus
d) exudation

(*4 point scale: 0=absent, 1=mild, 2=moderate, and 3=severe)

2) Serum cortisol levels (fasting, taken at 8.30am)
1a) 1.9 (−75%) triamcinolone vs 1.4 (−53%) alclometasone, p=0.047

1b) 1.6 (−65%) vs 0.6 (−25%), p=0.004

1c) 2.1 (−72%) vs 1.4 (−48%), p=0.005

1d) 1.7 (−94%) vs 0.7 (−45%), p=0.009

2) Results for 23 patients presented in the report, but no units nor normal ranges to know whether the levels were high, low, or normal. It was also reported that there were ‘no significant differences between groups’, meaning that there were no significant changes from baseline to weeks 2 or 3.
Funding: Essex (Nederland) BV, subsidiary of Schering Plough Corporation USA.

Use of bath oils, white petrolatum and antihistamines was continued for as long as necessary.

Baseline mean values for each parameter calculated from data reported in the paper - mean change was reported, but this did not clearly state that the changes were reductions.

The quantities of TCS used were not stated.
Chunharas A;Wisuthsarewong W;Wananukul S;Viravan S; 2002 Apr342Study Type: Cohort

Evidence level: 2+
50 (48 analysed)

Mometasone furoate 0.1% cream plus loratadine syrup, n=24

Mometasone furoate 0.1% cream plus placebo syrup, n=24
Children with atopic eczema who an affected are at least 4cm2, and severity scores (SCORAD) of at least 10 out of 18 (mean was 12); pruritus of the target area present, with a minimum score of 2.5 (scale 0–3), mean was ~2.7

Age 2–11.2 years, mean 6.2 years

Exclusions: history of hypersensitivity to either drug, or nonresponsvie to mometasone before the study. If antibiotics or antihistamine were used or severe illness and side effects were noted, the patient was withdrawn from the study.
Intervention: Loratadine syrup once daily (5ml if weight up to 30kg, 10mls if over 30kg) in addition to mometasone furoate 0.1% cream, applied once daily after a bath in the evening

Comparison: Placebo syrup once daily (5ml if weight up to 30kg, 10mls if over 30kg) in addition to mometasone furoate 0.1% cream, applied once daily after a bath in the evening
Follow-up period: Duration of treatment, 15 days

Outcome Measures: 1. Severity of the disease (% change in SCORAD score from baseline)

2. Physician global assessment

Cleared=100% improvement
Marked=75–100% improvement
Moderate=50–75% improvement
Slight=<50% improvement
No change
Exacerbation

3. Pruritus score (0= none to 3=severe; % change from baseline)

4. Adverse effects
1. −84% loratadine vs −85% placebo, p=0.883 (actual score change 12.4 to 1.94 vs 12.21 to 1.83)

2. 75% vs 91.6% had 75–100% improvement, p=0.245
8.3% vs 8.3% had 50–75% improvement, p=1.0
17% vs 0% had <50% improvement, p=0.109

3. −90% vs −97% (from 2.77 to 0.29 vs 2.63 to 0.09), p=0.097

4. No reports of drowsiness or difficulty awakening

1 child in each group reported dizziness
1 vs 0 nausea
0 vs 1 anorexia
Funding: none declared.

The study is described as a double-blinding, multicentre trial, however, the methods of blinding are unclear.

Two children from the loratadine group withdrew (1 due to impetigo, 1 because rash ‘very much improved’)

Although the volume (and not strength) was reported in the paper, it is assumed that the only available proprietary preparation of loratadine was used (5mg/5ml).
Kirkup ME;Birchall NM;Weinberg EG;Helm K;Kennedy CT; 2003 Sep255Study Type: RCT

Evidence level: 1+
Two multicentre RCTs in one report

Exclusions: signs of skin infection; severe atopic eczema requiring hospital admission; treatment with very potent or systemic corticosteroids in the previous 3 weeks; history of adverse response to corticosteroids
Children experiencing a flare of moderate to severe atopic eczema (total atopic eczema score of 6 or more*), treated at outpatient clinics.

Age 2–14 years, mean age 8 years

Mean number of body areas affected, 67% (8 out of a possible 12)
Intervention: Study
A: Fluticasone propionate 0.05% cream (n=70)

Study B: Fluticasone propionate 0.05% cream (n=66)

Acute phase - twice daily for 2–4 weeks until atopic eczema stabilised

Maintenance phase - intermittently up to twice daily as required for 12 weeks
plus emollients as required

Comparison: Study A: Hydrocortisone cream 1% (n=67)

Study B: Hydrocortisone 17− butyrate cream 0.1% (n=62)

Acute phase - twice daily for 2–4 weeks until atopic eczema stabilised

Maintenance phase - intermittently up to twice daily as required for 12 weeks plus emollients as required
Follow-up period: Duration of treatment, acute phase (2–4 weeks) and maintenance phase (up to 12 weeks)

Outcome Measures: Study A

1) Total atopic eczema score* (reduction in scores, and mean difference between groups)

2) Patient’s diary at end of acute phase (change in score vs baseline; difference in scores at endpoint. Score used was 1–7, worse than ever to better than ever)
a) rash
b) itch
c) sleep disturbance

3) Physician’s assessments:
Improved=better than
ever, or better than usual,
Not improved= same, worse than ever, or worse than usual

4) Median time to recurrence during the maintenance phase (days)

5) Adverse effects

6) Withdrawals

7) Quantity of TCS used

Study B

1) Total atopic eczema score* (reduction in scores, and mean difference between groups)

2) Patient’s diary at end of acute phase (change in score vs baseline; difference in scores at endpoint. Score used was 1–7, worse than ever to better than ever)
a) rash
b) itch
c) sleep disturbance

3) Physici
Study A (fluticasone vs HC 1%)

1a) At the end of the acute phase: −4.91 (41%) vs −2.37 (20%), difference −2.39, 95% CI −3.47 to −1.31, p<0.001

1b) At the end of the maintenance phase: −6.87 (57%) vs −4.84 (41%), difference −1.88, 95% CI −3.20 to −0.56 p=0.006

2a) +31% vs +8%, difference 0.81, 95% CI 0.45 to 1.16, p<0.001

2b) +29% vs +9%, difference 0.70, 95% CI 0.33 to 1.07, p<0.001

2c) +26% vs +12%, difference 0.46, 95% CI 0.08 to 0.84, p=0.019

3) 94% vs 85% improved, p=NS

4) 62 (range 7–118) vs 36 (7–114)

5) 29% vs 31% reported an adverse event
7% vs 10% general symptoms
8.5% vs 6% influenza
8.5% vs 8.5% ‘miscellaneous events related to the skin

Possibly related to treatment:
1% vs 0% folliculitis and ringworm
0 vs 1% severe flare with secondary infection

6) 26% vs 20% reasons:
2.9% vs 12% treatment failure
10% vs 3% non- compliance/personal
4.2% vs 1.5% early cure
0% vs 1.5% adverse event
11.4% vs 3% protocol violation/no reason

7) median 57g (range 10–259) vs 60g (15–252)

Study B (fluticasone vs HC-17- butyrate 0.1%)

1a) At the end of the acute phase: −4.37 (41%) vs −4.52 (37%) difference −1.25, 95% CI −2.46 to −0.05, p=0.042

1b) At the end of the maintenance phase: −6.76 (63%) vs −6.78 (56%) difference −1.39, 95% CI −2.72 to −0.05 p=0.042

2a) +11% vs +10%, difference 0.38 95% CI −0.01 to 0.77, p=0.056

2b) +11% vs +12%, difference 0.50 95% CI 0.09 to 0.92 p=0.017

2c) +7% vs +7%, difference 0.48 95% CI 0.11 to 0.85, p=0.011

3) 98% vs 84% improved, p=0.024

4) 51 (range 7–121) vs 57 (9–123)

5) 42% vs 35% reported an adverse event
12% vs 8% upper respiratory tract infection
11% vs 2% cough
8% vs 15% ‘miscellaneous events related to the skin

Possibly related to treatment:
1.5% (n=1) vs 0% red papules/boil
0 vs 3.2% (n=2) itchy skin after applying cream
0 vs 1.6% minor skin infections and pustules
0 vs 1.6% impetigo on the face

6) 11% vs 18%
reasons:
0% vs 8% treatment failure
3% vs 4.8% non- compliance/personal
1.5% vs 4.8% adverse event
6% vs 9.7% protocol violation/no reason

7) Median 62g (17–201) vs 59g (16–126)
Funding: Glaxo Wellcome R&D UK.

Multicentre RCT. The two studies were identical in design.

*Total atopic eczema score (Max, 21) = Number of body areas affected (out of possible 12 body areas) + sum of three signs (erythema, excoriation and lichenification) graded as 0–3 for target area (max 9)

Recurrence of atopic eczema was defined as an increase of 1.0 in either the number of body areas affected or in the sum of scores for the target area.

Use of regular inhaled or intranasal corticosteroids was permitted
Sefton J;Galen WK;Nesbitt LT;Landow RK; 1983283Study Type: RCT

Evidence level: 1−
66Children/young people with atopic eczema, bilaterally symmetrical lesions in a chronic stable state.

Age 4 months to 22.8 years (mean 5.3 years).

[EL=1−] only completers analysed (n=54, 82%). Reasons for withdrawal: 10 lost to follow-up, 2 intercurrent medical conditions
Intervention: Triamcinolone acetonide cream 0.1% applied twice daily (n=66)

Comparison: HC valerate cream 0.2% applied twice daily (n=66)
Follow-up period: Duration of treatment, 2 weeks

Outcome Measures: 1) Severity

2) Global evaluation

3) Adverse effects
1) No numerical data. Results shown in graphs only

2) 74% vs 74% experienced ‘clearance’ or an ‘excellent response’

3) 3% triamcinolone vs 3% HC transient stinging on application
Funding: none declared

Double-blind
Ellison JA, Patel L et al 2000279Study Type: Cross-sectional

Evidence level: 3
46See interventions and comparisonsIntervention: Children/adolescen ts with atopic eczem, attending a tertiary referral clinic. Age 0.7–18.7 years, median 9.3 years. Had been using TCS, applied twice daily since infancy, median 6.9 years (0.5–17.7) (n=35)

7 had used HC 1%

17 used moderately potent TCS

4 used potent TCS

Comparison: Children being investigated for short stature, age 3.8–17.3 years, median 10.3 years. Never treated with corticosteroids (n=14)
Follow-up period: N/A

Outcome Measures: 1) Serum cortisol levels in response to low-dose ACTH*; differences between children with atopic eczema and controls

2) Correlation between plasma cortisol response to the test and severity of atopic eczema and its treatment (variables considered by multiple linear regression; treatment and severity scores, age, prepubertal status, treatment duration)
1) No significant differences in basal, peak, incremanet, or time to peak cortisol values between children treated with mild or moderately potent TCS and controls.

All children treated with potent TCS failed the ACTH test.
Peak, increment and area- under-curve cortisol responses were significantly lower in the atopic eczema group, with no significant difference between groups in baseline or time to peak cortisol values.

3) Severity score was the only significant variable influencing peak (r2=24%, p=0.0016) and increment (r2=25%, p=0.014) cortisol response.
Funding: none declared

*500ng/1.73 square metre body surface area, after discontinuing TCS treatment for 24 hours (normal response: peak plasma cortisol 500nmol/l or more, increment 200nmol/l or more)

Subggroup analysis of 7 children with severe eczema ws also reported, although this was confounded by other treatments (inhaled and/or systemic corticosteroids).
Stalder JF;Fleury M;Sourisse M;Rostin M;Pheline F;Litoux P; 1994 Oct270Study Type: RCT

Evidence level: 1+
40

n=19 desonide applied once daily

n=21 vehicle applied once daily
Children aged 4.5 months - 15 years (mean 40 months) with atopic eczema.

Exclusions: clinical infection requiring antibiotic therapy
Intervention: Desonide

Comparison: Vehicle
Follow-up period: 7 days

Outcome Measures: 1) Change in clinical score
1) 66.7% vs 15.8% showed ‘improvement or resolution), p<0.001This was a DB RCT.

All other treatments for atopic eczema were excluded during the study.

The effects of treatment on Staph aureus denisty was also reported - data not reproduced here.
Prado de Oliveira ZN;Cuce LC;Arnone M; 2002284Study Type: RCT

Evidence level: 3
25Children with atopic eczema, with minimum total severity score* of 8 (and 2 for erythema)

Age range 2–12 years, mean 7.2 years mometasone vs 4.8 years desonide
Intervention: Mometasone furoate 0.1% once daily (n=13)

Comparison: Desonide 0.05% once daily (n=12)
Follow-up period: Duration of treatment: 42 days

Outcome Measures: 1) Atrophy (on scale of 0–3, absent to intense)

2) Other adverse effects
1) ‘evidence of atrophy’ in 17% desonide vs 31% mometasone (mean scores between 0.2 and 0.4 according to graph)

2) n=1 vs 0 pneumonia
1 vs 3 ardor (burning)
0 vs 1 appearance of laguna (fine hair)
Funding: none declared

*Severity of erythema, lichenification, desquamation, excoriation, pruritus on a scale of 0–3 (none to severe).

Use of emollients was permitted.

Severity and global improvement were also evaluated but data not reproduced here.

Atrophy was assessed by measuring the following signs on a four-point scale (thinning of the skin, striae, shiny skin, telangectasia, loss of elasticity, loss of normal lines on the cutaneous surface).
Rafanelli Aea; 1993

259
Study Type:
RCT

Evidence level: 1+
60Children with atopic eczema, showing three signs/symptoms (erythema, induration, pruritus)in the area to be observed durig the study.

Total severity score at entry at least 6; each sign/symptom scored on a scale of 0–3 (none to severe)

Mean age about 7 years.

Duration of disease significantly longer in the mometasone group (26.7 vs 16.4 with clobetasone), p<0.05.
Intervention: Mometasone furoate 0.1% applied once daily (n=30)

Comparison: Clobetasone 0.05% applied twice daily (n=30)
Follow-up period: Duration of treatment, up to 3 weeks.

Outcome Measures: 1) Reduction in mean disease severity score from baseline

2) Response to treatment
a) cleared (100% improvement)
b) marked improvement (>75%)
c) moderate improvement (50–75%)
d) slight improvement (<50%)
e) no change

3) Adverse events
1) −6.7 (85%) vs −4.8 (66%), p<0.01

2a) 50% vs 6.7%
2b) 30% vs 36.6%
2c) 20% vs 50%
2d) 0 vs 6.7%

3) No 'drug-induced' skin alterations nor atrophy.

No adverse events were reported
Funding: none declared

The quantities of TCS used were not stated.
Lassus A;

1984 Oct

263
Study Type: RCT

Evidence level: 1−
43Children aged 5–11 years with atopic eczema, stable or worsening for more than 1 week. Three signs/symptoms of eczema (erythema, induration, pruritus) with a total severity score* of 6 or more (baseline score was about 8)Intervention:
Alclometasone dipropionate cream 0.05% applied twice daily (n=22)

Comparison:
Clobetasone butyrate cream 0.05% applied twice daily (n=21)
Follow-up period:
Duration of treatment, 2 weeks

Outcome Measures: 1) Severity score (mean change from baseline)

2) Investigator's global evaluation
a) no. children with at least 75% improvement
b) no. children with 100% improvement

3) Adverse effects
1) −7.0 (85%) vs −7.14 (86%), p >0.10

2a) 64% vs 75%
2b) 41% vs 48%

3) 10% (n=2) vs 0 stinging
Funding: none declared

Double-blind study

*Severity score used: 0=absent, 1=mild, 2=moderate, 3=severe

Lesions on the face, neck, trunk, and upper and lower extremities were included as study areas

It was not stated whether an emollient was also used.

The quantities of TCS used were not stated.
Lassus A;

1983

262
Study Type: RCT

Evidence level: 1+
40Children with atopic eczema, stable or worsening for more than 1 week. Three signs or symptoms (erythema, induration, pruritus) with a severity score* of 6 or more (score 7.70 and 8.05 in alclometasone and HC groups respectively)

Age 5–11 years, mean about 8 years.
Intervention:
Alclometasone dipropionate cream 0.05%, applied twice daily (n=20)

Comparison:
Hydrocortisone butyrate cream 0.1%, applied twice daily (n=20)
Follow-up period:
Duration of treatment, 2 weeks

Outcome Measures: 1) Severity score (mean change from baseline)

2) Investigator's rating of improvement
a) 100%
b) >75%

c) 51–75%
d) 26–50%
e) 1–25%
f) 0

3) Adverse effects
1) −5.85 (76%) vs−5.55 (69%), p>0.10

2a) 10% vs 15%

2b) 30% vs 20%
2c) 55% vs 45%
2d) 5% vs 15%
2e) 0 vs 0

2f) 0 vs 5%

3) 10% vs 5% stinging
Funding: none declared

Double-blind study.

*Severity score used: 0=absent, 1=mild, 2=moderate, 3=severe.

Areas treated were the face, neck, trunk, and upper and lower extremities.

The quantities of TCS used were not stated.
Bleehen SS;Chu
AC;Hamann
I;Holden C;Hunter
JA;Marks R;


1995 Oct

286
Study Type:
RCT

Evidence level:
Intervention:

Comparison:
Follow-up period:

Outcome Measures:
1)
Richelli C;Piacentini
GL;Sette
L;Bonizzato
MC;Andreoli
A;Boner AL;

1990

287
Study Type:
RCT

Evidence level:
1−
30

Once daily, n=9

Twice daily at 8am and 3pm, n=13


Twice daily at 3pm and 8pm, n=8
Children with atopic eczema who had not used TCS within 2 weeks. Mean age ranged from 4–5.5 years across groups.Intervention:
Clobetasone 17-butyrate 0.05% lotion applied once daily

Comparison:
Clobetasone 17-butyrate 0.05% lotion applied twice daily (at 8am and 3pm)

Clobetasone 17-butyrate 0.05% lotion applied twice daily (at 3pm and 8pm)
Follow-up period:
Duration of treatment, 1 week

Outcome Measures: 1) Severity of signs and symptoms

2) Serum cortisol and ACTH levels
No numerical data for 1) or 2).

Data shown in graphs only, showing reduction in severity of signs and symptoms in all groups. It was reported that there were 'no differences' between groups.
Funding: none declared
Bibliographic informationStudy type and evidence levelAim of studyNumber of patients and patient characteristicsPopulation characteristicsOutcome measuresResults and commentsReviewer comment
Devillers ACA;de Waard-van der Spek FB;Mulder PGH;Oranje AP;

2002 329
El=3Intervention: Application of fluticasone propionate (FP) 0.05% wet wraps once daily to whole body for one week.

Thereafter, application of FP to affected areas, and emollient to unaffected areas for days 1–4 of the week, followed by emollient only for days 5–7 of the week.

Wet wrap dressings worn for a minimum of 12 hours per day.

5% dilution was used on the face

A side-to-side left-right treatment comparison was made using 5% and 10% dilutions.

Comparison: N/A
14 children and 12 adultsAdults and children with refractory atopic eczema who visited paediatric outpatient department between March 1999 and 2000, unsuccessfully treated with topical corticosteroids and emollients.

Age range of children 6 months to 10 years, mean 3 years.

Mean SCORAD score in children 39.09.
1) SCORAD (mean change form baseline to day 9)

2) Serum cortisol levels (nmol/ml), at day 7
1) −28 (71%), 95% CI 20.87 to 34.40, p<0.0005

2) No values <200nmol/ml (although temporary drop to <200ml seen in 3 children mid week).

Baseline minimum 28, maximum 890, median 585; Day 7 minimum 206, maximum 549, median 410, p<0.016
Funding: none declared

Serum cortisol measured at 6 a.m.; reference value for lower limit 200 nmol/l.

One child did not use/need a facial mask. Three used an additional mild to moderate topical corticosteroids to treat facial or scalp lesions.
McGowan R;Tucker P;Joseph D;Wallace AM;Hughes I;Burrows NP;Ahmed SF;

2003 Sep 331
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
Funding: Addenbrookes Charities Committee, the Marmaduke Shiled Fund, Serono Pharmaceuticals Ltd, and Mason Medical Research Foundation.
Boner AL;Richelli C;De SG;Valletta EA;Ferrari S;Mengoni M;

1985 Feb 274
El=3Intervention:
Clobetasone butyrate cream 0.05% applied twice daily for 7 days (n=17)

Comparison:
Clobetasone butyrate cream 0.05% applied twice daily for 14 days (n=12)
29

Exclusions: children
treated with topical corticosteroids within 2 weeks
Children with chronic atopic eczema

Mean age 5 years and 7 months in the one-week arm and 1 year 8 months in the two-week arm
1) Plasma cortisol concentrations (micromol/l; before vs after)

2) ACTH concentrations (pg/ml; before vs after)
1a) Group receiving 7 days' treatment

At 0800hrs: 0.4 vs 0.4, p<0.5
At 2000hrs: 0.29 vs 0.30, p<0.5

Group receiving 14 days' treatment

At 0800hrs: 0.44 vs 0.39, p<0.3
At 2000hrs: 0.27 vs 0.28, p<0.3

2) Group receiving 7 days' treatment

At 0800hrs: 41 vs 36, p<0.3
At 2000hrs: 38 vs 34, p<0.4

Group receiving 14 days' treatment

At 0800hrs: 31 vs 37, p<0.5
At 2000hrs: 31 vs 34, p<0.3
Funding: none declared Children were reported to have been randomised to one or two weeks treatment; but for the outcome measured, the evidence level is considered to be a before and after study [EL=3]
Furue M;Terao H;Rikihisa W;Urabe K;Kinukawa N;Nose Y;Koga T;

2003 Jan 280
El=3Intervention: Adverse effects to TCS

Comparison: N/A
6661271 people with atopic eczema who had been followed fro 6 months in Japanese outpatient clinics (666 [52%] infants or children; up to 12 years). All were treated with TCS and emollients.

Infants' mean age 1.1 year, children mean 5.6 years
1) Cumulative incidence of adverse effects (infants vs children)

2) Effects of TCS (and other variables) on three major adverse effects, analysed using stepwise logistic regression analysis

a) telangiectasia on cheek

b) skin atrophy of antecubital fossae

c) skin atrophy of popliteal fossae
1) 0.5% vs 1% hyperspertirchosis
0 vs 2.3% telangiectasia on cheek

1.5 vs 5.2% skin atrophy of antecubital fossae

1.9% vs 4.1% skin atrophy of popliteal fossae

0 vs 0 striae atrophica

0 vs 1.3% acne and folliculitis

1.4% vs 2.1% bacterial infection
1.9% vs 0.6% fungal infection
0 vs 0.4% steroid-induced dermatitis
0 vs 0.4% contact dermatitis

2a) duration: OR 1.77 (95% CI 1.41 to 2.22) p=0.0000
age: OR 3.61 (1.84 to 7.1), p=0.000
duration 6 years: OR 0.534 (0.396 to 0.72), p=0.000
doses of TCS to face (20g 'changing point'): OR 1.37 (1.14 to 1.65), p=0.0013

2b) age: OR 2.8 (95% CI 1.75 to 4.47) p=0.0000
duration: OR 1.24 (1.12 to 1.38), p=0.000
duration 9 years: OR 0.626 (0.464 to 0.845), p=0.0022
doses of TCS to truck and extremities (500g 'changing-point'): OR 3.82 (1.07 to 13.6), p=0.0465

2c) duration: OR 1.35 (95% CI 1.19 to 1.52) p=0.0000
age: OR 2.08 (1.21 to 3.56), p=0.0063
duration 9 years ('changing point'): OR 0.492 (0.345 to 0.7), p=0.0001
Funding: Japanese Ministry of Education, Culture, Sports, Science and Technology.

TCS were classified as 'strongest, very strong, strong, mild, weak'. It is unknown which products the classification relates to.

Quantity of TCS used (median, infants and children)
face 1g vs 15g
scalp 0 vs 0
trunk 21g vs 45g extremities 25g vs 45g

Type used (n, infants vs children)
Face:
strongest 0 vs 0
very strong 1 vs 5
strong 1 vs 17
mild 94 vs 71
weak 4 vs 7

Scalp:
strongest 0 vs 0 very strong 1 vs 5
strong 1 vs 17
mild 94 vs 71
weak 4 vs 7

Trunk and extremities
strongest 1 vs 1
very strong 17 vs 27
strong 34 vs 37
mild 46 vs 35
weak 2 vs 0


'changing point' believed to be threshold at which comparison was made
Queille C;Pommarede R;Saurat JH;

1984 Jan 277
EL=3Intervention: A topical corticosteroid preparation, applied once daily. One of: betamethasone dipropionate (n=5), difluorocortolone valerianate (n=4), halcinonide (n=4), clobetasone butyrate (n=5), desonide (n=5), fluocortine butylester (n=3

Comparison: N/A
26Children with severe atopic eczema requiring hospitalisation. Children had not been treated with TCS for at least 2 weeks, and never with systemic corticosteroids.

Mean cortisol levels at baseline 10.96 (SD 3.46 microg/100ml).

Age 5 months to 12 years.
Plasma cortisol levels (mean, microg/100ml, before vs after treatment)Betamethasone dipropionate
10.46 vs 4.14 (−61%)

Difluorocortolone valerianate
12.35 vs 3.4 (−72%)

Halcinonide
12.53 vs 7.76 (−38%)

Clobetasone butyrate

12.22 vs 9.67 (−21%)

Desonide
9.53 vs 9.67 (+1%)

Fluocortine butylester
8.2 vs 9.43 (+15%)
Funding: none declared

No statistical analysis.

No normal range given for serum cortisol, and no analysis vs baseline

Quantity of TCS used (g/day/square metre):
5.9 betamethasone
9 difluorocortolone
3.98 halcinonide
5.3 clobetasone
9.9 desonide
13 fluocortine
Friedlander SF;Hebert AA;Allen DB;Fluticasone
Pediatrics
Safety Study
Group.;

2002 Mar 276
EL=3Intervention: Fluticasone propionate cream 0.05% applied twice daily to all lesions, including facial areas but not nappy areas, eyelids, perioral area, nostrils, or areas of atrophy

Comparison: N/A
51

Exclusions: acute self limiting eczema; use or anticipated use of topical or inhaled corticosteroids within 1 week, or continuous therapies including ciclosporin, ultraviolet light and topical products within 4 weeks
Children with moderate to severe atopic eczema affecting more than 35% of the body surface area (mean body surface area 64%).

Age range 3 months to 5 years (63% aged 3 months to 2 years, and 37% aged 3 to 5 years)
1) Serum cortisol levels in response to stimulation with cosyntropin (mean difference in pre-and post-stimulation values)

2) Adverse events
1) Prestimulation −1.78 microg/dl, p=0.1734

Poststimulation −2.49 microg/dl, p=0.719

Two children (4.7%, 2/43) had serum cortisol values below 18 microg/dl following stimulation at treatment end. They had been treated for 4 and 5 weeks.

2) 50% reported 39 adverse events, 'most frequently' fever and cold symptoms.

Drug-related adverse events:
1 burning
1 urticaria
1 erythematous rash
3 telangiectasia
Funding: Glaxo Wellcome Inc

17% withdrew from the study (10% in older group, 7% in younger group)

'normal adrenal response' defined as a poststimulation cortisol peak value of more than 18.0 microg/dl measured by fluorescence-polarisation immunoassay
Boner AL;Richelli C;De SG;Antolini I;Aprili F;Mengoni M;

1985 275
EL=3Intervention: Clobetasone butyrate cream 0.05% applied three time a day for 1 week, then twice daily for 3 weeks

Comparison: N/A
12

Exclusions: children receiving oral corticosteroids during the study period or in the previous 3 months
Children with chronic atopic eczema, with pruritus, persistent scratching, excoriations, crusting and thickening or lichenification

Age range 2–13 years, mean 8.2 years
Cortisol level measured following administration of tetracosactrin at 8a.m. (dose given: 0.25mg/square metre by intramuscular injection)

Mean levels before vs after
At 0800hrs: 12.8 vs 15.5 microg/ml
At 0830hrs: 32.4 vs 28.7 microg/ml
At 0900hrs: 42.3 vs 37.5 microg/ml

At 1800hrs: 12.7 vs 10.9 microg/ml

p>0.1 for all comparisons
Funding: none declared.

Mean quantity of clobetasone used during the study period was 82.5g

The significance of any changes in cortisol levels in individual children was not considered in the trial report
Hebert AA;

2006 Sep

543
Study Type: Other
Open-label study with no comparator group

Evidence Level: 3
Intervention: 0.05% Fluticasone propionate lotion

Comparison: Serum cortisol levels measured before and after treatment
n=44Children aged 3 months to 6 years with moderate to severe AE affecting >35% of body surface areaSerum cortisol levelsBaseline serum cortisol:
pre-cosyntropin stimulation test
13.2 micrograms/dL (sd=6.1)
post-cosyntropin stimulation test
35.3 micrograms/dL (sd=6.02)

End of treatment serum cortisol:
pre-cosyntropin stimulation test
12.4 micrograms/dL (sd=6.3)
post-cosyntropin stimulation test
33.3 micrograms/dL (sd=8.1)

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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