| Back 2001256 | Ketoconazole (oral) (200 mg/day) taken as one dose per
day for 3 months | Placebo taken as one dose per day for 3 months | | There are no details on the composition of the placebo; only
stated that it was taken in ‘capsule’ form | Sweden | 32 | Adults with atopic eczema diagnosed according to the Hanifin and
Rajka8 criteria
and with specific serum IgE antibodies to M.
furfur/P. orbiculare
(> 3.5 kU/l) and elevated serum IgE
(> 400 kU/l) | Clinical improvement measured by SCORAD index at baseline, 1
month and 3 months
Change in total IgE at baseline, 1
month and 3 months
Change in specific IgE at baseline, 1
month and 3 months
Quantity of betamethasone
used
Participant-assessed evaluation of improvement | The outcomes did not appear to be prestated | The improvement in clinical score (SCORAD) for the ketoconazole
group did not differ significantly from that for the placebo
group; however, the improvements in the second and third months
correlated to the amount of betamethasone used in the placebo
group (r = 0.66,
p = 0.013), but not in the
ketoconazole group (r = 0.15,
p = 0.61). There was a
decrease in total serum IgE levels and specific IgE levels to
M. furfur/P. orbiculare
and C. albicans. These decreases were not
significant at the end of month 1 but were highly significant at
the end of the study (month 3) for specific IgE to M.
furfur/P. orbiculare. The
decreases in total IgE and specific IgE to C.
albicans were close to significance levels | The exact process of generating the randomisation sequence was
not stated. Allocation concealment was described as the
‘code’ being kept secret by the pharmacy until
all participants had completed the final clinical examination
and the case report forms were handed in. The data were not
analysed according to the intention-to-treat principle |
| Breneman 2010253 | Antibacterial soap containing 1.5% triclosan
(Safeguard®; Procter & Gamble). The
whole body was washed at least once a day for 63 days (42
days = treatment period, 21
days = regression period) | Placebo soap bar (not antibacterial). The whole body was washed
at least once a day for 63 days (42
days = treatment period, 21
days = regression period) | | For the standardisation period (14 days) and for the entire
length of the trial all participants used a non-medicated
cleansing bar and a non-medicated moisturising cream and could
not use systemic/topical antibiotics or
antimicrobial/antibacterial soap, lotion, cream and shampoo.
Participants were also given 0.025% triamcinolone acetonide in
place of all other topical corticosteroids. In the treatment
period the participants were allowed to use 0.025% triamcinolone
acetonide as needed. Regression period – no topical
corticosteroid allowed, but study treatment continued | Not stated | 50 participants; group allocations not stated | Atopic eczema according to Hanifin and Rajka8 criteria; moderate
severity according to Rajka and Langeland228 scale; Fitzpatrick skin types
I–IV; active lesions (presence of combinations of
erythema, scales, lichenification, crusting and
excoriation) | Severity of eczema (SASSAD score) including itching assessment
and body surface area assessment (7-point scale, with
0 = 0% affected,
6 = 90–100% affected)
Total
aerobic micro-organisms
Reductions in S.
aureus
Dermatologist-assessed change in
global eczema severity (–5 = severe
worsening, 0 = no change,
5 = total clearing)
Amount of topical
corticosteroid used (weight of tubes) | | Antimicrobial soap resulted in a significantly better
improvement in the extent and severity of eczema skin lesions
compared with placebo soap. There were reductions in S.
aureus for those with S. aureus at
baseline and total aerobic micro-organisms correlated with the
improvement in eczema | Method of randomisation and allocation concealment not stated.
Intention-to-treat analysis not reported |
| Canpolat 2012248 | Hydrocortisone acetate applied by parents as a thin coating to
affected areas twice daily at least 2 hours before bathing for
up to 7 days | Hydrocortisone plus mupirocin ointment applied by parents as a
thin coating to affected areas twice daily at least 2 hours
before bathing for up to 7 days. Hydrocortisone was applied
morning and evening whereas mupirocin was applied at noon and at
night | Emollient – no further details given | Before all medication, swab cultures were obtained from lesions
for S. aureus colonisation. Non-steroidal
immunosuppressants (pimecrolimus), other investigational drugs,
systemic corticosteroids and UV light therapy as well as
concomitant topical medications (including other topical
corticosteroids, topical H1 and H2 antihistamines and other
topical antimicrobials) were not allowed during the treatment
period. Use of sunscreen was allowed and application of
non-medicated emollients was permitted on non-treatment areas.
Use of cosmetics on treatment sites was not allowed. It appears
from the trial report that the use of oral antihistamines was
not allowed during the trial; however, the information in the
report is unclear | Not stated | 83 (n = 30 control emollient
only, n = 26 steroid,
n = 27 steroid plus
mupirocin) | Infants aged between 6 months and 2 years; diagnosis of mild to
moderate (Rajka and Langeland228 severity scale) atopic
dermatitis based on the Hanifin and Rajka8 criteria involving 2–30% of
the body surface area | SCORAD index [including an assessment by a physician of
objective signs (extent and intensity) and subjective symptoms
(pruritus and sleep disturbance) compiled on an analogue scale
by parents]
EASI score including assessment of disease
extent and percentage involved body surface
area
Treatment success (defined as > 50%
recovery of the lesions or > 50% decrease in
EASI or SCORAD scores) | | 65% (17/26) of patients were treated successfully with
hydrocortisone based on SCORAD and EASI scores. There was a
significant improvement in patients using hydrocortisone plus
mupirocin ointment [74% (20/27)]. The improvement from baseline
in EASI score was significantly greater in the hydrocortisone
group and the combined hydrocortisone/mupirocin group than in
the emollient treated patients (36%)
(p = 0.0187 and
p = 0.012
respectively) | Randomisation not clearly described. No description of
allocation concealment. Authors state that the study was double
blind but parents were unblinded. No description of
intention-to-treat population although number analysed appears
to be the number randomised |
| Gong 2006247 | Mupirocin ointment (Bactroban) and hydrocortisone butyrate
ointment. Mupirocin applied once every morning at
0800–0900 and then hydrocortisone butyrate applied
between 1000 and 1100 | Base ointment and hydrocortisone butyrate ointment. Base
ointment applied once every morning at 0800–0900 and
then hydrocortisone butyrate applied between 1000 and 1100 | | The order of the ointments could not be changed and there had to
be 2–3 hours between applications of the two ointments,
but the timings were flexible | China | 119 participants (n = 5
mupirocin group, n = 61 control
group) | Participants diagnosed using the Hanifin and Rajka8 criteria; age
2–65 | Severity (EASI score)
Global therapeutic effect (4-point
scale)
Colonisation rates
Colonisation
density | | At the end of treatment there was no significant difference
(p > 0.05) in
global therapeutic effect between the two groups. In the
participants with eczema with a clinical score of
> 7, the therapeutic effect in the mupirocin
group was significantly greater than that in the control group
(p < 0.05) on the
seventh day of treatment | Method of generation of the randomisation sequence was not
described. Allocation concealment was unclear. Blinding is well
described and the numbers of participants are given for all the
outcomes. Clear reporting of means and SDs allows the analyses
to be accurately interpreted. There are a few possibly post hoc
subgroup analyses |
| Hung 2007150 | Fluticasone propionate 0.05% cream either with fusidic acid 2%
cream (group I) or without (group II) applied to all effective
areas, twice daily (morning and evening), for 8 weeks | Tacrolimus 0.03% ointment either with fusidic acid 2% cream
(group III) or without (group IV) applied to all affected areas,
twice daily (morning and evening), for 8 weeks | | The use of medicated soaps and detergents was not permitted
during the study. The only topical treatments that were allowed
were the participants’ own moisturisers, which they were
told to apply immediately after bathing. Oral antihistamines
were given to all participants | Taiwan | 60 participants (n = 15
fluticasone, n = 15 tacrolimus,
n = 15 fluticasone and
fusidic acid, n = 15 tacrolimus
and fusidic acid) | Atopic eczema diagnosed according to the criteria of Hanifin and
Rajka;8 use of
topical or systemic corticosteroids in the 4 weeks before entry
to the study; use of topical or systemic antibiotics in the 4
weeks before entry to the study; overt secondary infection that
required oral antibiotic therapy; moderate to severe eczema
according to the Rajka and Langeland228 severity scale at entry | Overall clinical severity (SCORAD index; max. score
103)
Local severity (modified local SCORAD index
– score of 0–3, with 0 = absent,
3 = severe, for each of erythema/darkening,
oedema/papulation, oozing/crusts, excoriation,
lichenification/prurigo, local dryness; max. score
18)
Colonisation rate of S.
aureus
Colonisation density of S.
aureus
Levels of staphylococcal enterotoxin
A-specific IgE
Levels of staphylococcal enterotoxin
B-specific IgE | It is not clear whether any of these outcomes were prespecified
from the structure of the trial report | Topical tacrolimus was comparable to fluticasone for reduction
of SCORAD scores; however, tacrolimus was slower to eradicate
S. aureus. Complementary treatment with
fusidic acid did not result in any additional benefit over
tacrolimus and fluticasone alone. Two participants developed
fusidic acid-resistant S. aureus during the
study after 8 weeks of fusidic acid treatment | Method of randomisation not described. Allocation concealment
not reported. Intention-to-treat population used for the
analyses |
| Huang 2009205 | Half a cup of 0.005% bleach in a bath twice weekly for
5–10 minutes and mupirocin ointment applied twice daily
for 5 consecutive days per month | Half a cup of water in the bath twice weekly for 5–10
minutes and Vaseline applied twice daily for 5 consecutive days
per month (placebo) | | All household members had to use the mupirocin/Vaseline
treatment. The participants were allowed to bathe in addition to
the treatment baths as much as desired throughout the trial. All
participants used a stable treatment regimen using topical
corticosteroids and emollients for the duration of the
study | Not stated | 31 participants (n = 15
treatment, n = 16 placebo) | Age 6 months to 17 years; moderate to severe eczema (IGA
determined); bacterial skin infection as characterised by
weeping, oozing and/or pustules | (Primary) EASI score [validated composite score, with
0 = clear, 72 (max.
score) = very severe]. Calculated from the
percentage body surface area affected and physician assessment
of individual signs score
IGA (0 = clear,
1 = almost clear, 2 = mild,
3 = moderate, 4 = severe,
5 = very severe)
Antibiotic sensitivity
of bacteria from the nares and worst infected skin lesion
(antibiotics tested = amoxicillin,
amoxicillin–clavulanate, oxacillin, cephalexin,
trimethoprim–sulfamethoxazole, erythromycin, clindamycin
and mupirocin)
Adverse events | Participants were removed from the study if they developed an
allergic reaction | Prevalence of community-acquired MRSA: skin 7.4%, nares 4%
(lower than hospital centre population at 75–85%).
Bleach bath and mupirocin group had a significantly greater mean
reduction in EASI score from baseline than the placebo group at
1 month and 3 months. Head and neck area (not treated by the
baths): no difference between groups. Body and extremities
(treated by baths): decreased at 1 and 3 months in the bleach
bath and mupirocin group compared with the placebo group | The method of randomisation was described. Allocation
concealment was unclear. Intention-to-treat principle was used
for the analyses and a definition was given |
| Larsen 2007102 | Fucicort [fusidic acid (20 mg/g) and betamethasone
17-valerate (1 mg/g)] lipid cream applied to all
eczematous areas except the face, twice a day for 2 weeks | Fucicort [fusidic acid (20 mg/g) and betamethasone
17-valerate (1 mg/g)] applied to all eczematous areas
except the face, twice a day for 2 weeks | Lipid cream vehicle applied to all eczematous areas except the
face, twice a day for 2 weeks | For treatment of the face, group I topical corticosteroid were
used if needed. For non-treatment areas, emollient cream was
used (Locobase®) | Six European counties | 629 participants (n = 275
Fucicort lipid group, n = 264
Fucicort group, n = 90
vehicle) | Age ≥ 6 years; clinical diagnosis of infected
eczema; diagnosis of atopic eczema according to the Hanifin and
Rajka8
criteria; target lesion at least
4 × 4 cm; target lesion must
have a minimum score of 1 for each of erythema,
oedema/papulation, oozing/crusting, excoriation; negative
pregnancy test and agreement to use an adequate method of
contraception during the study (women of childbearing age) | TSS (4-point scale from ‘absent’ to
‘severe involvement’ for each of erythema,
oedema/papulation, oozing/crusting, excoriation; max. score
12)
Participant-assessed overall treatment efficacy for
the whole treatment area (excluding face) relative to baseline
(6-point scale)
Investigator-assessed overall treatment
efficacy for the whole treatment area (excluding face) relative
to baseline (6-point scale)
Participant-assessed cosmetic
acceptability (4-point scale)
Compliance (weight of
returned study treatment)
Bacterial susceptibility to
antibiotics
Successful bacterial response | | TSS at the end of treatment: Fucicort lipid cream group 82.9%,
Fucicort cream group 82.7%, vehicle group 33.0%. Successful
bacteriological response: Fucicort lipid cream group 89.7%,
Fucicort cream group 89.6%, vehicle group 25.0%. Fucicort lipid
cream of similar efficacy to Fucicort cream and superior to
vehicle | Method of randomisation described. Allocation concealment not
described. Intention-to-treat population used for some of the
analyses but not defined |
| Lintu 2001255 | Ketoconazole tablets (Nizoral®)
(200 mg) taken once daily for 30 days | Placebo taken once daily for 30 days | | Topical treatment with emollients or 1% hydrocortisone was
allowed provided that the same brand was used throughout the
30-day treatment period | Finland | 80 participants (40 in each group) | Age ≥ 18 years with previous skin-prick test or
positive RAST to Pityrosporum ovale, C.
albicans or S. cerevisiae and
current atopic eczema diagnosed using the Hanifin and Rajka8 criteria | Severity (SCORAD index): extent estimated as the percentage of
the body surface area affected with adult measures (A);
erythema, papulation, excoriation, dryness, crusts and
lichenification assessed on a scale of 0–3 (none, mild,
moderate and severe) (B); and pruritus and sleep disturbances
assessed on a scale from 0 (none) to 10 (severe) (C). Calculated
as A/5 + 7B/2 + C (max. score
103)
Total serum IgE
Specific IgE to P.
orbiculare, C. albicans and
S. cerevisiae
Presence of P.
orbiculare, C. albicans and
S. cerevisiae (culture)
Allergy to
P. orbiculare, C. albicans
and S. cerevisiae (skin-prick test –
positive reaction was regarded as at least 50% of the diameter
of the histamine wheal, which had to be at least
3 mm) | | A significant improvement in the SCORAD values was seen in the
ketoconazole group at the second visit (treatment end) compared
with the first visit (before treatment)
(p < 0.0005,
n = 36), but not in the
placebo group. Of the individual determinants of the SCORAD
index, itching
(p < 0.05), the extent
of dermatitis (area percentage), excoriation, lichenification
(p < 0.01),
erythema, papulation and dryness
(p < 0.05) improved
significantly in the ketoconazole group. In the placebo group
only the extent of dermatitis (area percentage) decreased
significantly
(p < 0.05). In the
ketoconazole group the number of positive P.
ovale cultures decreased from 60% to 31%
(n = 35) whereas the
corresponding figures in the placebo group, were a decrease from
64% to 56% (n = 39). The
clinical response was most significant in female participants
with positive yeast cultures | No information was given on the method of randomisation,
blinding or whether the intention-to-treat principle was used
for the analyses |
| Ravenscroft 2003246 | Fusidic acid 2%/betamethasone 0.1% cream applied to all affected
areas twice daily for 2 weeks | Topical mupirocin ointment and betamethasone 0.1% cream applied
to all affected areas twice daily for 2 weeks | | All participants also given a standardised emollient
(Diprobase® cream; Schering-Plough) | UK | 46 participants (n = 28 fusidic
acid group, n = 18 mupirocin
group) | Atopic eczema that on examination by a dermatologist appeared to
warrant the use of a potent topical steroid for 2 weeks | Dermatitis severity (modified version of Costa and
colleagues’ simple scoring method249): sum of scores of 0–6
for the worst affected area of each of the following: erythema,
oedema, vesicles, exudation, crusts, excoriation, scale and
lichenification); pruritus and sleep loss each assessed on a
0–10 scale; and distribution assessed on a 0–3
scale for each of 10 areas (max. score 98 – 70% for
worst area and symptoms and 30% for
distribution)
Participant-assessed global severity (scale
0–10, with 0 = no eczema,
10 = worst eczema imaginable)
Prevalence
of carriage of fusidic acid-resistant S. aureus
at eczema sites
Prevalence of carriage of fusidic
acid-sensitive and -resistant S. aureus at
eczema sites
Prevalence of carriage in the nares of
fusidic acid-resistant S.
aureus
Prevalence of carriage in the nares of
fusidic acid-sensitive and -resistant S.
aureus | | Both groups showed similar clinical improvement after 1 and 2
weeks. Overall median clinical improvement was paralleled by
reduction in prevalence and population density of fusidic
acid-sensitive and -resistant S. aureus | The method of randomisation is described; however, the method is
open to potential bias. Allocation concealment not described.
Intention to treat is not mentioned; however, no participants
withdrew |
| Schuttelaar 2008250 | TT (0.1%, 3%) ointment applied twice daily all over the body for
2 weeks | T 0.1% ointment applied twice daily all over the body for 2
weeks | | All participants used 0.1% T for 6 weeks after the 2-week RCT
period to assess maintenance treatment | The Netherlands | 44 participants (n = 22 TT
ointment, n = 22 T
ointment) | Diagnosis of atopic eczema according to Hanifin and Rajka8 criteria; moderate
to severe eczema (≥ 25 objective SCORAD
score) | (Primary) Objective SCORAD score at week 2
(Primary)
SASSAD score at week 2
(Secondary) Objective SCORAD score
at weeks 4 and 8
(Secondary) Bacterial load
(‘successful’ efficacy defined as pretreatment
pathogen eradicated) | | Eczema severity: no significant difference between the two
treatments. Clinically relevant improvements in both groups
compared with baseline at week 2. Bacterial colonisation: TT
group improvement 14/22 (63.6%), T group improvement 5/22
(22.7%) | Method of randomisation and allocation concealment both
described and adequate. Intention-to-treat analysis not stated
but dropouts in the maintenance phase were not included in the
analyses |
| Svejgaard 2004258 | Itraconazole 200 mg daily Two capsules (itraconazole,
placebo) were taken in the morning and two (itraconazole,
placebo) in the evening with a meal, every day for 7 days | Itraconazole 400 mg daily (100-mg capsules). Two
capsules (itraconazole , itraconazole) were taken in the morning
and two (itraconazole, itraconazole) in the evening with a meal,
every day for 7 days | Placebo (100-mg capsules). Two capsules (placebo, placebo) were
taken in the morning and two (placebo, placebo) in the evening
with a meal, every day for 7 days | | Not stated | 53 participants (n = 18
itraconazole 200 mg,
n = 17 itraconazole
400 mg, n = 18
placebo) | Age between 18 and 50 years; atopic eczema involving the head
and neck; diagnosis of atopic eczema according to Hanifin and
Rajka8
criteria; at least four clinical signs out of erythema,
oedema/papulation, oozing/crusting, excoriation, lichenification
and/or dryness; head and neck area total intensity score greater
than total intensity score of remaining body surface area;
generally good health; negative urine pregnancy test for
women | (Primary) SCORAD index (head, neck and upper thorax to a line
through the nipples)
(Primary) SCORAD index (body except
head and neck region)
Participant-assessed global
evaluation (whole body) (1 = cured,
2 = markedly improved,
3 = moderately improved, 4 = no
change,
5 = deterioration)
Investigator-assessed
global evaluation (whole body) (1 = cured,
2 = markedly improved,
3 = moderately improved, 4 = no
change,
5 = deterioration)
Hypersensitivity to
Malassezia
Cross-reactivity between
fungi (Malassezia and C.
albicans)
Participant-assessed sleep loss
and itching (0–100-mm VAS) | SCORAD index – number of participants with
> 50% reduction in scores | At 7 and 14 days: significant improvement in head and neck
region SCORAD index for 400 mg of itraconazole
(p = 0.0385 and
p = 0.0134, respectively)
and 200 mg of itraconazole
(p = 0.0140 and
p = 0.0006, respectively).
Placebo group improved slightly
(p = 0.0785). At day 14 there
was a significant difference in favour of 200 mg of
itraconazole compared with placebo
(p = 0.0318) | Method of randomisation and allocation concealment not stated.
Intention-to-treat analysis carried out on all participants
receiving treatment; however, exact numbers in the
intention-to-treat population were unclear |
| Tan 2010252 | 1% Triclosan-containing leave-on emollient cream applied to the
whole body twice daily for 41 days | Vehicle cream applied to the whole body twice daily for 41
days | | Both groups applied 0.025% betamethasone valerate cream in a
thin layer over the eczematous areas once a day for the first 27
days, before application of study treatment | Singapore | 60 participants (n = 30
triclosan-containing emollient,
n = 30 vehicle cream) | Age between 12 and 40 years; atopic eczema according to the
Hanifin and Rajka8
criteria; mild to moderate eczema according to the SCORAD
index | (Primary) SCORAD response on day 27 (response defined as a
reduction of ≥ 20 points from
baseline)
(Secondary) Change in SCORAD index from
baseline
(Secondary) Use of topical corticosteroids | | Day 14: significant decrease in SCORAD index from baseline for
the triclosan-containing emollient compared with vehicle
(p < 0.05). Day 27:
improved mean reduction, but no longer significant
(p > 0.05). Mean
amount of topical corticosteroid applied was significantly lower
for the emollient group than for the control group
(p = 0.40). Day 27: overall
benefit of triclosan-containing emollient not significant | Method of randomisation described and adequate. Allocation
concealment not reported. Intention-to-treat principle used for
data analysis, but not defined |
| Wong 2008115 | Hydrocortisone 1% cream plus miconazole cream twice daily to the
affected areas, approximately 12 hours apart, for 2 weeks | Hydrocortisone 1% cream twice daily to the affected areas,
approximately 12 hours apart, for 2 weeks | | No concomitant medication allowed. Only usual moisturisers and
cleansers allowed | Hong Kong, China | 30 participants | Diagnosis of atopic eczema according to the UK Working Party
criteria;9 age
between 5 and 14 years (criterion not stated); active eczema
equally affecting the knees or elbows; asked whether the
participant had used an antimycotic in the 3 months before the
trial | Participant-assessed relief of symptoms at 2
weeks
Dermatologist-assessed change in clinical signs
(from photographs) after 2 weeks
Number of topical
corticosteroid-free days (6-week follow-up period) | | The addition of an antimycotic did not provide any enhanced
benefit compared with standard treatment as shown by all three
study outcomes | Method of randomisation and allocation concealment not reported.
Intention-to-treat analysis not reported |
