Intervention Review

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Topical anti-inflammatory agents for seborrhoeic dermatitis of the face or scalp

  1. Helena Kastarinen1,*,
  2. Tuija Oksanen1,
  3. Enembe O Okokon2,
  4. Vesa V Kiviniemi3,
  5. Kristiina Airola4,
  6. Johanna Jyrkkä1,
  7. Tuomas Oravilahti1,
  8. Piia K Rannanheimo1,
  9. Jos H Verbeek5

Editorial Group: Cochrane Skin Group

Published Online: 19 MAY 2014

DOI: 10.1002/14651858.CD009446.pub2


How to Cite

Kastarinen H, Oksanen T, Okokon EO, Kiviniemi VV, Airola K, Jyrkkä J, Oravilahti T, Rannanheimo PK, Verbeek JH. Topical anti-inflammatory agents for seborrhoeic dermatitis of the face or scalp. Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD009446. DOI: 10.1002/14651858.CD009446.pub2.

Author Information

  1. 1

    Finnish Medicines Agency Fimea, Assessment of Pharmacotherapies, Fimea, Finland

  2. 2

    University of Calabar Teaching Hospital, Department of Community Medicine, Calabar, Cross River State, Nigeria

  3. 3

    Finnish Medicines Agency, Assessment of Pharmacotherapies, Kuopio, Finland

  4. 4

    Finnish Medicines Agency Fimea, Assessment of Medicinal Products, Fimea, Finland

  5. 5

    Finnish Institute of Occupational Health, Cochrane Work Review Group, Kuopio, Finland

*Helena Kastarinen, Assessment of Pharmacotherapies, Finnish Medicines Agency Fimea, P.O. Box 55, Fimea, 00034, Finland. helena.kastarinen@fimnet.fi.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 MAY 2014

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Characteristics of included studies [ordered by study ID]

MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Other dermatological conditions of the scalp (e.g. psoriasis or secondary infected eczema)
  • Use of antimicrobial agents was not allowed for 2 weeks prior to the study


Number of randomised participants: 72 in the whole study. We only included participants in the hydrocortisone group (N = 23) and in the placebo group (N = 24) in this Cochrane review

Number of dropouts: 8 in the whole study (not reported separately in different intervention groups)

Sex: 49 male, 23 female

Mean age (range): 35 (14 to 79) years

Country: Finland


InterventionsTreatment

  • Hydrocortisone 1% liniment, applied on the scalp once daily for 4 weeks


Comparator/s

  • Placebo (propylene glycol 30% liniment), applied on the scalp once daily for 4 weeks
  • Clotrimazole 1% and hydrocortisone 1% liniment, applied on the scalp once daily for 4 weeks


Outcomes
  1. Severity of scaling, erythema, itching, exudation, stinging, and papule formation (none - mild - moderate - severe)
  2. Global assessment (completely healed - clearly better - no change - deteriorated)
  3. Area of affected skin (completely cured - good response - somewhat better - no response)
  4. Overall efficacy of the treatment evaluated by participants and investigators (excellent - good - some help - poor)


NotesStandard deviations were not given


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Patients were randomly allocated"

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Unclear riskQuote: "There were no significant differences between the treatment groups"

Differences in the severity of symptoms was not reported

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDropout rate was not reported separately for the intervention groups

Selective reporting (reporting bias)Low riskPredefined outcomes as stated in the article were reported

Other biasUnclear risk2 authors were affiliated to the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: not reported

Intention-to-treat analysis used: not reported


ParticipantsInclusion criteria of the trial

  • Not reported, but all had seborrhoeic dermatitis of the scalp clinically characterised by erythema, scaling, and itching


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 60 in total (betamethasone N = 30, calcipotriol N = 30)

Number of dropouts: 7, all from 1 treatment arm (23%)

Sex: not reported

Age: not reported

Country: Turkey


InterventionsTreatment

  • Calcipotriol solution 50 μg/ml, applied on the scalp twice daily for 28 days


Comparator/s

  • Betamethasone 17-valerate 1 mg/ml, applied on the scalp twice daily for 28 days


If there was only slight improvement at the end of 4 weeks, treatment was continued for another 4-week period After cessation of treatment, participants entered a follow-up period for 4 weeks

Before the start of treatment, there was a 1-week wash-out period, during which only a mild non-medicated shampoo was used


Outcomes
  1. Severity of erythema, scaling, and itching of the scalp rated on a 4-point scale (0 to 3)
  2. Total clearance
  3. Total score (the sum of the individual scores)
  4. Adverse events
  5. Routine biochemical analysis including serum total calcium levels


NotesResults were reported mainly at 4 weeks. The dropout rate was unbalanced and considerable


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "randomly assigned"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Unclear riskThis was not reported in sufficient detail

Blinding of participants (performance bias)High riskThere was no mention of blinding in the report

Blinding of care providers (performance bias)High riskThere was no mention of blinding in the report

Blinding of outcome assessment (detection bias)
All outcomes
High riskThere was no mention of blinding in the report

Incomplete outcome data (attrition bias)
All outcomes
High riskMore than 20% of participants withdrew from the calcipotriol arm

Selective reporting (reporting bias)Unclear riskNot all results related to predefined outcomes were reported in sufficient detail

Other biasUnclear riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported sufficiently

Blinding: not reported

Intention-to-treat analysis used: not fully


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis (facial)


Exclusion criteria of the trial

  • Psoriasis, acne rosacea, acne vulgaris, and other dermatoses of the face
  • Topical treatments (corticosteroids, antifungals, antibiotics, zinc pyrithione, selenium, salicylates, retinoids, benzoyl peroxide, or α-hydroxy acids) during the 15 days before inclusion in the protocol
  • Oral treatment with lithium, antifungals, inhaled corticosteroids, or systemic corticosteroids during the 6 months prior to entry
  • Pregnancy or lactation
  • HIV-positive people were excluded


Number of randomised participants: 64 in total (pimecrolimus N = 21, methylprednisolone N = 22, metronidazole N = 21)

Number of dropouts: 4 (6%)

Sex: 32 males, 32 females

Mean age (range): pimecrolimus arm = 31.6 (19 to 56) years, methylprednisolone arm = 34.2 (17 to 65) years, metronidazole arm = 30.7 (17 to 44) years

Country: Turkey


InterventionsTreatment

  • Pimecrolimus 1% cream, applied to the face twice daily for 8 weeks


Comparator/s

  • Methylprednisolone aceponate 0.1% cream, applied to the face twice daily for 8 weeks
  • Metronidazole 0.75% gel, applied to the face twice daily for 8 weeks


Outcomes
  1. Mean severity score (consisting of erythema and scaling scores with scales of 0 to 3)
  2. Participants' self-assessed pruritus (scale 0 to 3)
  3. Furthermore, erythema, scaling and pruritus scores (0 to 3) as side-effects


NotesErythema and pruritus were used to assess both efficacy and side-effects. It was not reported how the judgement between a lack of efficacy and a side-effect was done. Erythema, scaling, and pruritus scores were not reported separately but as part of mean clinical severity score


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The patients were divided into three randomized groups"

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Low riskDifferences were not statistically significant

Blinding of participants (performance bias)High riskNo information was provided

Blinding of care providers (performance bias)High riskNo information was provided

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo information was provided

Incomplete outcome data (attrition bias)
All outcomes
High riskDropout rate was 20% in 1 group only and reported to be due to side-effects; these participants were excluded from the study. The side-effect rate was reported for the remaining participants only

Selective reporting (reporting bias)Low riskNo selective reporting bias was identified

Other biasHigh riskErythema and pruritus were used both as efficacy and adverse effect elements. How the judgement between efficacy effect and adverse effect classification was conducted was not reported


MethodsStudy type: RCT of body parts

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis


Exclusion criteria of the trial

  • Pregnant women
  • People with known allergies to any component of the test medications
  • People who had used topical or systemic corticosteroid or other treatment for SeD during the month preceding the study
  • People with clinical evidence of skin atrophy, those requiring topical or systemic medication that would affect the course of the dermatologic disease, or people requiring more than 90 gm (45 gm per side) of study medication applied bi-weekly


Number of randomised participants: 51 in total

Number of dropouts: 6 (12%)

Sex: 23 males, 28 females

Age (range): 19 to 82 years

Country: USA


InterventionsTreatment

  • Alclometasone 0.05% ointment, applied to the scalp, face, and trunk twice daily for 6 weeks


Comparator/s

  • Hydrocortisone 1.0% ointment, applied to the scalp, face, and trunk twice daily for 6 weeks


Outcomes
  1. Changes in telangiectasia
  2. Overall severity of the dermatoses (scaling, erythema, and crusting, scale 0 to 3)
  3. Total clearance


NotesThe location of seborrhoeic dermatitis lesions was not mentioned as inclusion criteria. However, the outcomes were evaluated on the face/neck, retroauricular areas, and scalp. The primary objective of the study was to compare atrophogenic potential of the products, but their efficacy was also evaluated. This is 1 of 2 included studies that compared 2 mild steroids with each other. The results concerning side-effects are controversial. Score data can not be used because standard deviations and P values are lacking


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Study was a randomized"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskPretreatment symptom scores were identical between groups

Blinding of participants (performance bias)Low riskDouble-blind: Colour-coded side-labelled tubes were used

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNone were identified

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: computer-generated randomisation

Blinding: blinded

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Known intolerance of or hypersensitivity to topical corticosteroids
  • Previous non-responsiveness to topical corticosteroids
  • Pregnancy or lactation
  • Concurrent illness that would contraindicate corticosteroid therapy
  • A need for concomitant therapies that would confound the results


Number of randomised participants: 54 in total (amcinonide N = 26, betamethasone N = 28)

Number of dropouts: 0

Sex: 30 males, 24 females

Mean age (range): amcinonide arm = 42 (26 to 81), betamethasone arm = 45 (23 to 73) years

Country: USA


InterventionsTreatment

  • Amcinonide 0.1% lotion, applied to scalp twice daily for 3 weeks


Comparator/s

  • Betamethasone valerate 0.1% lotion, applied to the scalp twice daily for 3 weeks


Outcomes
  1. Erythema, excoriation, crusting/scales, and pruritus (scale 0, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0)
  2. Overall therapeutic efficacy (evaluated by investigators and participants, scale 1 to 7)
  3. Adverse effects


NotesThis was the only included study comparing 2 strong steroids with each other. Necessary data were calculated from other statistics


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer-generated randomisation list was used

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Low riskThere were no statistically significant differences between groups

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was small

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: RCT of body parts

Randomisation method: computerised randomisation

Blinding: double-blind

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Pregnant and nursing women
  • People with known hypersensitivities to any of the products or their ingredients
  • People with evidence of atrophy


Number of randomised participants: 30 in total

Number of dropouts: 1 (3%)

Sex: 14 males, 16 females

Age (mean): 37.7 years

Country: USA


InterventionsTreatment

  • Desonide 0.05% cream, applied to the scalp twice daily for 8 weeks


Comparator/s

  • Hydrocortisone 1.0% cream, applied to the scalp twice daily for 8 weeks


Outcomes
  1. Total number of telangiectasia


Notes1 of 2 included studies comparing mild steroids with each other. The adverse events rate was calculated from a table


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputerised randomisation was used

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Unclear riskBilateral disease severity was not reported separately

Blinding of participants (performance bias)Low riskColour-coded side-labelled tubes were used

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe number of dropouts was small

Selective reporting (reporting bias)Low riskNo selective reporting bias was identified

Other biasUnclear riskThe pharmaceutical industry supported the study, and the corresponding author was affiliated with the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: included all randomised participants who had at least 1 efficacy evaluation after baseline


ParticipantsInclusion criteria of the trial

  • Facial seborrhoeic dermatitis


Exclusion criteria of the trial

  • Cutaneous diseases requiring a specific topical treatment of the face (e.g. atopic dermatitis, psoriasis), general or local lithium therapy, facial topical or oral immediate-release corticosteroids in less than 2 weeks and slow-release corticosteroids in less than 2 months


Number of randomised participants: 129 in total (lithium N = 66, placebo N = 63; however, there were follow-up data available only for 63 participants in the lithium group and 61 participants in the placebo group, and 1 participant was left out of the analyses as he did not fulfil the inclusion criteria)

Number of dropouts: 22 (17%)

Sex: 85 males, 44 females

Mean age (range): lithium arm = 38.6 (19 to 69) years, placebo arm = 40.2 (19 to 73) years

Country: France


InterventionsTreatment

  • Lithium gluconate 8% ointment, applied to the face twice daily for 8 weeks


Comparator/s

  • Placebo (vehicle only) twice daily for 8 weeks


Outcomes
  1. Complete remission
  2. An overall remission rate (complete and partial)
  3. Improvement of erythema, desquamation, burning, pruritus, stretching, and skin oiliness
  4. Adverse events


NotesFor symptoms scores (erythema and desquamation), results were presented only in figures without numerical data. Results concerning burning, pruritus, and stretching, as well as skin oiliness, were mentioned very briefly in the text without numerical or visual data given. For this reason, these data could not be used in the meta-analysis in this review


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly allocated"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskThere were no statistically significant differences between groups

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskIt is unclear whether the percentages were calculated using ITT or per-protocol analysis

Selective reporting (reporting bias)Unclear riskMost results were not reported in sufficient detail

Other biasUnclear riskThe pharmaceutical industry supported the study


MethodsStudy type: individual RCT

Randomisation method: computer-generated

Blinding: Investigators were blinded until the first follow-up visit (not reported for participant or care provider)

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Facial seborrhoeic dermatitis


Exclusion criteria of the trial

  • Scalp seborrhoeic dermatitis requiring antifungal, selenium sulphide, or corticosteroid therapy
  • Any other cutaneous disease of the face requiring a specific topical treatment during the previous 15 days; oral treatment with tetracyclines, lithium, antifungals, or inhaled corticosteroids during the previous month; and systemic corticosteroids and retinoids during the previous 2 months
  • SeD associated with Parkinson's disease; HI-virus; or ears, nose, and throat carcinoma
  • Severe concomitant disease
  • Allergy to any of the tested treatment components


Number of randomised participants: 288 in total (lithium N = 152, ketoconazole N = 136)

Number of dropouts: 34 withdrawn and 19 excluded from analyses because of major protocol deviation (18%)

Sex: 183 males, 105 females

Age (mean): lithium arm = 29.2 years, ketoconazole arm = 41.3 years

Country: France


InterventionsTreatment

  • Lithium gluconate 8% ointment, applied to the face twice daily for 8 weeks


Comparator/s

  • Ketoconazole 2%, applied to the face twice weekly for 4 weeks and then once weekly for 4 weeks


Outcomes
  1. Complete remission without any premature withdrawal for inefficacy or safety
  2. Rate of participants with complete remission
  3. Rate of participants with partial remission
  4. Spontaneously reported adverse events


NotesThis was the only included study comparing lithium with azole


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation was computer-generated

Allocation concealment (selection bias)Low riskThis was probably low risk

Quote: "computer-generated blocks and the randomisation code was concealed in sealed envelopes"

Similarity of the study groups (selection bias)Low riskThere were no statistically significant differences between groups

Blinding of participants (performance bias)High riskParticipants were not blinded

Blinding of care providers (performance bias)Unclear riskThis was not reported in detail

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskThis was not reported in detail. The investigators were blinded at the allocation period

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe percentage of dropouts was less than 20% and comparable between groups

Selective reporting (reporting bias)Low riskNo selective reporting bias was identified

Other biasUnclear riskThe pharmaceutical industry organised and sponsored the study


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: investigator-blinded

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Facial seborrhoeic dermatitis


Exclusion criteria of the trial

  • Unwilling to stop treatment for dandruff or SeD on the scalp
  • Presented with severe (score = 4) SeD on the face as assessed by the investigator
  • Use of any topical antiseborrhoeic dermatitis or antidandruff product in the 14 days before baseline or systemic medication 30 days before baseline
  • Chronic or active liver disease, renal impairment, severe facial acne, rosacea, or any other disease that would interfere with the study or place the person under undue risk
  • Known hypersensitivity to the ingredients of the products


Number of randomised participants: 77 in total (desonide N = 39, Promiseb® N = 38)

Number of dropouts: 5 (7%)

Sex: 56 males, 21 females

Mean age (range): 51.9 (21.1 to 84.5) years

Country: USA


InterventionsTreatment

  • Desonide 0.05% cream, applied to the face twice daily for 2 and 4 weeks


Comparator/s

  • Non-steroidal cream (Promiseb®), applied to the face twice daily for 2 and 4 weeks


Outcomes
  1. Proportion of participants with IGA (Investigator Global Assessment)-rated (score 0 to 4) success at either day 14 or day 28
  2. Erythema (score 0 to 4), scaling (score 0 to 4), pruritus (score 0 to 4), and mean total IGA scores at days 14 and 28
  3. Proportion of participants who were cleared at day 14 that were still clear at day 28
  4. Safety score (scale 0 to 3)
  5. Spontaneous reported adverse events


NotesNo standard deviations were given for symptom scores. Additional data were requested (results in numerical form with standard deviations and P values), but could not be received. This was the only included study comparing steroid with Promiseb® topical cream


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomized"

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Unclear riskThis was not reported sufficiently

Blinding of participants (performance bias)High riskThe study was "investigator blind"

Blinding of care providers (performance bias)Unclear riskThe study was "investigator blind". It was not clear whether the care providers were investigators

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe investigator was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe number of dropouts was small

Selective reporting (reporting bias)Low riskNo selective reporting bias was identified

Other biasUnclear riskThe pharmaceutical industry supported the study, and the author was affiliated to the pharmaceutical industry. The pharmaceutical industry provided the comparator treatment


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: not reported


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • No topical or systemic treatment with antifungal agents or corticosteroids for 3 weeks prior to the start of the study


Number of randomised participants: 70 participants in the whole study. In this review, we only considered the participants in the hydrocortisone (N = 24) and miconazole (N = 23) arms

Number of dropouts: 3 (5%)

Sex: 36 males, 34 females

Mean age (range): 38 (21 to 69) years

Country: Sweden


InterventionsTreatment

  • Hydrocortisone 1% solution, applied to the scalp once daily for 3 weeks


Comparator/s

  • Miconazole 2%
  • Miconazole 2% and hydrocortisone 1% solution, applied to the scalp once daily for 3 weeks


Outcomes
  1. Number of cured participants and treatment failures
  2. Relapse rate
  3. Efficacy of prophylaxis


NotesThe combination treatment arm of the trial was not included in this review. Adverse events were not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly allocated"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Unclear riskBaseline data were not reported

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe number of dropouts was small

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskThe pharmaceutical industry provided the intervention solutions


MethodsStudy type: individual RCT

Randomisation method: computer-generated randomisation list

Blinding: investigator-blind

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Facial seborrhoeic dermatitis


Exclusion criteria of the trial

  • Malignant or active viral lesions on the face
  • People who had used antibiotics, immunosuppressive drugs, or phototherapy 1 month before treatment, and any topical therapy suspected to affect facial SeD during the 1 week before the beginning of the study


Number of randomised participants: 40 in total (pimecrolimus N = 20, hydrocortisone N = 20)

Number of dropouts: 3 (8%)

Sex: 28 males, 12 females

Age (mean): pimecrolimus arm = 28.65 years, hydrocortisone arm = 37.45 years

Country: Iran


InterventionsTreatment

  • Pimecrolimus 1% cream, applied to the face twice daily for 2 weeks


Comparator/s

  • Hydrocortisone 1% cream, applied to the face twice daily for 2 weeks


Outcomes
  1. Complete disappearance of disease
  2. Severity of pruritus, erythema, and scaling (scales 0 to 3)
  3. Adverse events
  4. Relapses


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation was computer-generated

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskThere were no statistically significant differences between groups

Blinding of participants (performance bias)High riskOnly investigators were blinded

Blinding of care providers (performance bias)Unclear riskQuote: "investigator blind"

This probably refers to outcome assessment

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe investigator was blinded. We assume this refers to outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe number of dropouts was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskThe pharmaceutical industry provided - free of charge - the intervention creams


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: not clearly reported; at least the participants were blinded

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 64 in total (betamethasone N = 32, hydrocortisone N = 32)

Number of dropouts: 2 (3%)

Sex: 35 males, 27 females

Age (range): 15 to 61 years

Country: Sweden


InterventionsTreatment

  • Betamethasone valerate 0.1% lotion, applied to the scalp for 4 weeks


Comparator/s

  • Hydrocortisone 17-butyrate 0.1% lotion, applied to the scalp for 4 weeks


Outcomes
  1. Erythema, infiltration, peeling, crust, and itching scores (5-point scale)
  2. Freedom of symptoms (percentage of participants)


NotesDosing frequency was not reported. Adverse events were not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly allocated"

Allocation concealment (selection bias)Unclear riskThis was not reported in detail

Similarity of the study groups (selection bias)Unclear riskNo information was provided

Blinding of participants (performance bias)Low riskQuote: "Patients...received the lotion in identical, coded bottles"

Blinding of care providers (performance bias)Unclear riskQuote: "Patients...received the lotion in identical, coded bottles"

This was not reported in sufficient detail

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "Patients...received the lotion in identical, coded bottles"

This was not reported in sufficient detail

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskThere were limitations in reporting, but results were displayed for all predefined outcomes

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis without secondary infection


Exclusion criteria of the trial

  • Not reported (secondary infection)


Number of randomised participants: 55 in total (hydrocortisone 17-butyrate N = 28, betamethasone N = 28)

Number of dropouts: 1 (2%)

Sex: 33 males, 22 females

Mean age (range): 40.4 (15 to 75) years

Country: United Kingdom


InterventionsTreatment

  • Hydrocortisone 17-butyrate for 3 weeks


Comparator/s

  • Betamethasone valerate (probably 0.1%) for 3 weeks


Outcomes
  1. Pruritus, erythema, scaling, crusting, and ulceration with a 4-point scale (0 to 3)
  2. Side-effects
  3. Total severity scores in participants with an occupation involving possible contact with irritants


NotesDosing frequency was not reported. The location of the SeD lesions was not mentioned as inclusion criteria. It was however reported that the outcomes were evaluated in the head and neck


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "in a random manner"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Unclear riskQuote: "The two groups matched one another in relation to these various factors, except that there was a higher proportion of male patients in the Betnovate group and minor differences in relation to age, duration and treatment given during the previous two weeks...with the exception of the eyelids, which were relatively more severely involved in the Locoid group than in the Betnovate group"

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was small

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: probably yes, as there were no dropouts


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 35 in total (betamethasone N = 17, hydrocortisone 17-butyrate N = 18)

Number of dropouts: 0

Sex: 17 males, 18 females

Age (mean): betamethasone arm = 49.9 years, hydrocortisone arm = 46.8 years

Country: Sweden


InterventionsTreatment

  • Betamethasone 17-valerate 0.1% lotion, applied to the scalp twice daily for 4 weeks


Comparator/s

  • Hydrocortisone 17-butyrate 0.1% lotion, applied to the scalp twice daily for 4 weeks


Outcomes
  1. Itching, erythema, scaling, and crusting scores (scale 1 to 5)
  2. Adverse events


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly allocated"

The randomisation method was not reported

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Low riskBaseline characteristics were comparable

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts were reported

Selective reporting (reporting bias)Low riskPredefined outcomes were reported in sufficient detail

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 391 in total (initial assignment numbers were not reported; at 2 weeks, 140 participants were using betamethasone, and 163 participants were using placebo)

Number of dropouts: 88 (23%)

Sex: 171 males, 132 females

Age: not reported

Country: USA


InterventionsTreatment

  • Betamethasone valerate 0.1% lotion, applied twice daily for 2 weeks


Comparator/s

  • Placebo (vehicle only) lotion, applied twice daily for 2 weeks


Outcomes
  1. Total clearance
  2. Lichenification, excoriation, inflammation, crusting, scaling, vesiculation, exudation, fissures, maceration, pruritus, burning, pain, secondary bacterial infection (score 1 to 4)


NotesResponse was regarded as excellent with clearance of 75% or more. This is less than in other included studies, and therefore we excluded the results from the meta-analysis. For scores, no standard deviations or exact P values were given. The actual number of participants randomised to each group was unknown


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly assigned"

Allocation concealment (selection bias)Unclear riskQuote: "The test preparations were supplied...in identical packages, code labelled for blind randomized assignment to patients...Master codes for each study were maintained separately from the investigators..."

Similarity of the study groups (selection bias)Unclear riskNo information was provided

Blinding of participants (performance bias)Low riskQuote: "double-blind"

Quote: "Neither patient nor physician was aware of which of the two was being used"

Blinding of care providers (performance bias)Low riskQuote: "double-blind"

Quote: "Neither patient nor physician was aware of which of the two was being used"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "double-blind"

The codes were kept separately from the investigators

Incomplete outcome data (attrition bias)
All outcomes
High riskThe dropout rate was 23%. The actual number of participants randomised to each group was not reported. There is considerable uncertainty in the reporting of the therapeutic response

Quote: "Patients who did not return due to a successful response were included in the excellent group and patients who did not return because of treatment failure were included in the poor group"

Selective reporting (reporting bias)Unclear riskPredefined outcomes were reported, but not in sufficient detail. For example, the standard deviations were not given

Other biasUnclear riskThe author was affiliated to a pharmaceutical company


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Known hypersensitivity to any of the components of the test medication
  • Need for other medication that might affect the disease (e.g. systemic corticosteroids or systemic antimycotics)
  • Use of topical remedies for SeD during the 7 days before enrolment or any investigated drug within 1 month before enrolment


Number of randomised participants: 54 in total (the initial assignment numbers were not reported by treatment group; at 4 weeks, 27 participants were treated with mometasone, and 22 participants were treated with ketoconazole)

Number of dropouts: 5 (9%)

Sex: 40 males, 14 females

Mean age (range): 58 (22 to 85) years

Country: Sweden


InterventionsTreatment

  • Mometasone furoate 0.1% solution, applied to the scalp once daily for 4 weeks


Comparator/s

  • Ketoconazole 2% shampoo, applied twice a week for 4 weeks


Outcomes
  1. Erythema, scaling, and pruritus (scale 0 to 3)
  2. Total clearance


NotesParticipants and investigators evaluated reduction of pruritus, scaling, and erythema scores, but numerical information of these was not reported. We approximated the numbers from figures. The actual number of participants randomised to each group was unknown


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, but not reported in sufficient detail

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Unclear riskNo information was provided

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe actual number of participants randomised to each group was unknown. The dropout rate was 10%, but the study did not report if this was balanced between groups

Selective reporting (reporting bias)Unclear riskThe primary outcomes were not prespecified in detail, yet the outcomes reported were those that are usually used in such studies

Other biasUnclear riskThe pharmaceutical industry supported the study


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 50 in total (hydrocortisone N = 26, ketoconazole N = 24)

Number of dropouts: 0

Sex: not reported

Age: not reported

Country: Greece


InterventionsTreatment

  • Hydrocortisone 1% cream, applied to the scalp, face, sternum, and ears twice daily for 4 weeks


Comparator/s

  • Ketoconazole 2% cream, applied to the scalp, face, sternum, and ears twice daily for 4 weeks


Outcomes
  1. Combined erythema, scaling, papules, and pruritus score, global evaluation (total improvement, good, fair, poor)
  2. Growth ofPityrosporum ovale


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomized fashion"

Allocation concealment (selection bias)Unclear riskQuote: "randomized fashion"

There was no mention of the allocation concealment

Similarity of the study groups (selection bias)Unclear riskThis was not reported

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were no dropouts

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear risk1 author was affiliated to the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: participants were randomised according to a random digit table

Blinding: no (open-label)

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis


Exclusion criteria of the trial

  • Coexistent other dermatoses involving the face or other affected area (e.g. psoriasis, rosacea, and acne vulgaris)
  • Allergy to medications
  • Use of any topical or systematic treatments in the previous month
  • Participants who had severe SeD requiring systemic treatment


Number of randomised participants: 48 in total (pimecrolimus N = 23, ketoconazole N = 25)

Number of dropouts: 10 (21%)

Sex: 34 males, 4 females

Mean age (range): pimecrolimus arm = 32.3 (21 to 50), ketoconazole arm = 29.8 (20 to 47)

Country: Turkey


InterventionsTreatment

  • Pimecrolimus 1% cream, applied twice daily for 6 weeks


Comparator/s

  • Ketoconazole 2% cream, applied twice daily for 6 weeks


The total follow-up time was 12 weeks


Outcomes
  1. Total clinical severity scores (including erythema, scaling, and infiltration with scale 0 to 3)
  2. Adverse events


NotesWe received additional data from the first author

The affected area or site of SeD lesions as inclusion criteria were not reported. However, coexistent dermatoses involving the face or other affected areas were mentioned as exclusion criteria, suggesting that facial SeD was an inclusion criterion


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "random digits table"

Allocation concealment (selection bias)Unclear riskQuote: "random digits table"

Similarity of the study groups (selection bias)Low riskQuote: "The treatment groups were not statistically significantly different at baseline"

Blinding of participants (performance bias)High riskThis was an open-label study

Blinding of care providers (performance bias)High riskThis was an open-label study

Blinding of outcome assessment (detection bias)
All outcomes
High riskThis was an open-label study

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe dropout rate over was 20%; reasons were not given in detail. There was discrepancy between text and figure 1 with regard to distribution of dropouts

Selective reporting (reporting bias)Low riskPredefined outcomes as stated in the article were reported

Other biasLow riskNote: The affected area was not reported


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: not reported


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 40 in total (hydrocortisone N = 20, ketoconazole N = 20)

Number of dropouts: 1 (3%)

Sex: 21 males, 19 females

Age (mean): 33.7 years

Country: Greece


InterventionsTreatment

  • Hydrocortisone 1% cream, applied to the affected areas once daily for 4 weeks


Comparator/s

  • Ketoconazole 2% cream, applied to the affected areas once daily for 4 weeks


Outcomes
  1. Erythema score (scale 0 to 9), scaling score (scale 0 to 10), pruritus score (scale 0 to 6), decrease in the number of Pityrosporum ovale colonies, and global evaluation (total improvement, good, fair, poor)
  2. Adverse events


NotesNo standard deviations nor exact P values were given in the report. We have approximated the actual numbers from figures


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "They were randomized"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskQuote: "At the start of treatment, erythema, scaling, and pruritus were present in all patients of both groups without any statistically significant difference in the mean scores"

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was small

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear risk2 authors were affiliated to the pharmaceutical industry


MethodsStudy type: RCT of body parts

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: not used


ParticipantsInclusion criteria of the trial

  • Advanced AIDS and facial seborrhoeic dermatitis


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 12 in total

Number of dropouts: 6 participants (50%) by 2 weeks; 7 participants by end of study at 8 weeks

Sex: only male participants

Age: not reported

Country: UK


InterventionsTreatment

  • Lithium succinate 8% ointment, applied to the face twice daily for 8 weeks


Comparator/s

  • Placebo (ointment base), applied to the face twice daily for 8 weeks


Outcomes
  1. Redness, greasiness, scaling, and overall severity scores (100 mm analogue line)


Notes50% of participants had dropped out by 2 weeks, and only 5 participants out of 12 completed the study. However, the last visit occurred at 47 +/- 15 days (standard deviation) giving a wide variation there. We decided to use the results obtained at 2 weeks. It was not reported whether the paired t-test was used, and the available data did not allow recalculations. Therefore, the results have been presented qualitatively. The trial included only men with HIV as participants


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Each was randomly assigned to be applied"

Allocation concealment (selection bias)Unclear riskNo information was provided

Similarity of the study groups (selection bias)Unclear riskBilateral disease severity was not reported in detail

Blinding of participants (performance bias)Low riskQuote: "Both doctor and patient were blinded"

Blinding of care providers (performance bias)Low riskQuote: "Both doctor and patient were blinded"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Both doctor and patient were blinded"

Incomplete outcome data (attrition bias)
All outcomes
High riskThe dropout rate was 50% by 2 weeks and 58% by the end of the study at 8 weeks

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskThe pharmaceutical industry supported the study. 2 authors were affiliated to the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: computer-based randomisation

Blinding: double-blind

Intention-to-treat analysis used: not used


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 30 in total (betamethasone N = 15, hydrocortisone N = 15, but 1 of the participants in the latter group proved to be too young to be included, and the results were not used)

Number of dropouts: 1 participant was excluded after randomisation because of their young age (not considered a dropout); 1 participant was lost to follow up (considered a dropout, 3%)

Sex: 17 males, 12 females

Mean age (range): 49.9 (19 to 82) years

Country: Denmark


InterventionsTreatment

  • Betamethasone 0.05% lotion, applied to the scalp twice daily for 3 weeks


Comparator/s

  • Hydrocortisone 0.1%, applied to the scalp twice daily for 3 weeks


Outcomes
  1. Erythema, scaling, follicular papule formation, crusting, itching, and burning/local irritation scores (scale 0 to 3)
  2. Total clearance evaluated by participants and clinician
  3. Adverse events


NotesParticipants used drugs for 3 weeks or until complete healing. Outcomes were assessed at 3 weeks. Scores were calculated only for those who had the symptom


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "A computer programme was used to give the randomization code, which was stratified into blocks of 10 with a restriction against more than three successive patients receiving the same therapy"

Allocation concealment (selection bias)Unclear riskQuote: "randomization code, which was stratified into blocks of 10 with a restriction against more than three successive patients receiving the same therapy"

Similarity of the study groups (selection bias)Low riskQuote: "No statistically significant difference in patient classification of mean age, sex distribution and initial symptom score distribution was found between the two treatment groups but there was a numerically lower mean age in the HCB-treated group"

44 years versus 56 years

Blinding of participants (performance bias)Unclear riskThe study was "double-blind"; this was not reported in detail. The participants were given Locoid® or Diproderm®, and it was not reported if the packages were blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was small

Selective reporting (reporting bias)Unclear riskPredefined outcomes were reported, but they were assessed as scores only for those who had the symptom

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: computer-based randomisation

Blinding: double-blind

Intention-to-treat analysis used: not used


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp and other hairy areas


Exclusion criteria of the trial

  • Allergies to tested products
  • Pregnant or lactating women
  • Acute systemic illness (including convalescence)
  • Active cutaneous infections
  • Participants who required concomitant systemic medications and therapies with potential for healing or relief during the course of the trial (e.g. antihistamines, topical or systemic corticosteroids, antimetabolites, psoralen with ultraviolet A), or other specific treatment for a dermatologic condition


Number of randomised participants: 168 in total (amcinonide N = 86, placebo N = 82)

Number of dropouts: 10 (6%)

Sex: 121 males, 47 females

Mean age (range): amcinonide arm = 51.2 (20 to 88) years, placebo arm = 50.9 (18 to 87) years

Country: USA


InterventionsTreatment

  • Amcinonide 0.1% lotion, applied to the scalp or other selected lesions twice daily for 3 weeks


Comparator/s

  • Placebo, applied twice daily for 3 weeks


Outcomes
  1. Erythema, crusting/scales, excoriation and pruritus scores (scale 0.0 - 0.5 - 1.0 - 1.5 - 2.0 - 2.5 - 3.0)
  2. Overall therapeutic efficacy (scale 1 to 7)


NotesFinal evaluations were performed as soon as the participant had cleared completely if this occurred before week 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "a computer-generated randomization list designed to produce approximately equal numbers of patients in each study arm"

Allocation concealment (selection bias)Unclear riskThis was not reported in detail

Similarity of the study groups (selection bias)Low riskQuote: "There were no statistically significant differences between the two treatment groups for any of the demographic variables...for severity of the objective signs of erythema and scaling and the subjective symptom of pruritus"

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: "third-party-blind"; it is not specified who was blinded

Intention-to-treat analysis used: not reported, but probably was; no dropouts during the treatment phase


ParticipantsInclusion criteria of the trial

  • Not reported. All participants were 13 to 70 years of age and had a clear diagnosis of seborrhoeic dermatitis with facial involvement present for 7 to 8 years


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 117 in total (mometasone N = 59, hydrocortisone N = 58)

Number of dropouts: no dropouts during the treatment phase

Sex: 68 males, 49 females

Mean age (range): mometasone arm = 45 (15 to 70) years, hydrocortisone arm = 43 (13 to 70) years

Country: not reported, probably USA


InterventionsTreatment

  • Mometasone furoate cream 0.1%, applied once daily on the face for 6 weeks


Comparator/s

  • Hydrocortisone cream 1%, applied twice daily on face for 6 weeks


All antiseborrhoeic agents were prohibited for at least 2 weeks prior to the initiation of treatment, and systemic corticosteroids were prohibited for at least 4 weeks


Outcomes
  1. Global clearance evaluation, individual and total disease sign/symptom severity scores (sum of individual scores for erythema, scaling, and pruritus/burning, scale 0 to 3 in each) in target area lesions
  2. Participants' own evaluation of the response to treatment (excellent, good, fair, poor)
  3. Side-effects


NotesAny medications that might have affected the course of the disease were not allowed during the course of the study. The last evaluation was made at 2 weeks post-treatment. 1 area on the face of each participant was selected for evaluation of treatment effectiveness


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "randomly assigned"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskQuote: "The two treatment groups were comparable for all comparisons"

Blinding of participants (performance bias)High riskQuote: "Third-party-blind" - obviously not referring to the participant

Blinding of care providers (performance bias)High riskQuote: "Third-party-blind" - obviously not referring to the care-giver

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "Third-party-blind" - possibly referring to the outcome assessor

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were no dropouts

Selective reporting (reporting bias)Low riskResults concerning predefined outcomes were reported, with the exception of participants' own assessment where the results were not given in a numerical form

Other biasUnclear riskAt least 4 out of 8 authors were affiliated to the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: "a single blind"

Intention-to-treat analysis used: not used


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis (scalp associated with other locations)


Exclusion criteria of the trial

  • Pregnant or nursing women
  • HIV-positive people
  • People with pityriasis capitis
  • People with psoriasis vulgaris


Number of randomised participants: 62 in total (betamethasone N = 31, ketoconazole N = 31)

Number of dropouts: 9 (15%)

Sex: 39 males, 23 females

Mean age (range): betamethasone arm = 41 (23 to 68) years, ketoconazole arm = 35 (18 to 65) years

Country: France


InterventionsTreatment

  • Betamethasone dipropionate 0.05% lotion, applied to affected areas


Phase 1: once daily for the first week, every other day in the second week, twice weekly until the end of the first month of treatment

Phase 2: once weekly for 3 months

Comparator/s

  • Ketoconazole 2% foaming gel, applied to affected areas


Phase 1: twice weekly for 1 month

Phase 2: once weekly for 3 months

Phase 3: This was a wash-out phase for both treatment arms (1 month)


Outcomes
  1. Severity of erythema, scaling, and itching of the scalp (scale 0 to 3)
  2. Mycological evaluation (scale 0 to 3)
  3. Global evaluation of improvement by investigator and participant (excellent, good, moderate, poor)
  4. Participants' evaluation of the treatment's efficacy
  5. Relapse rate


NotesTotal clearance is not evaluated in the report


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "randomized fashion"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskQuote: "The treatment groups were comparable for all the patient characteristics, as well as for all symptoms and localizations"

Blinding of participants (performance bias)High riskThis was a single-blind study; it did not specify which party was blinded

Blinding of care providers (performance bias)High riskThis was a single-blind study; it did not specify who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
High riskThis was a single-blind study; it did not specify who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: "central computed randomization list, block-size of 4"

Blinding: "blinded investigators"

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Adults (18 years or more) with moderate or severe scalp seborrhoeic dermatitis


Exclusion criteria of the trial

  • Pregnancy or lactating state
  • Women planning pregnancy
  • HIV positivity


Number of randomised participants: 326 in the whole study; we used only the results of the clobetasol group (N = 82) and the ketoconazole group (N = 80)

Number of dropouts: 12 (7%) at "end of study"

Sex: 88 males, 74 females

Age (mean): clobetasol arm = 44.9 years, ketoconazole arm = 44.7 years

Country: Belgium, France, Germany, Mexico, South Korea


InterventionsTreatment

  • Treatment phase: clobetasol propionate shampoo 0.05%, applied for 15 minutes on dry scalp twice weekly for 28 days


Comparator/s

  • Treatment phase: ketoconazole shampoo 2%, applied for 5 minutes on wet scalp twice weekly for 28 days. (In both arms followed by maintenance phase: ketoconazole once weekly; and follow-up phase: no active treatment, only mild non-medicated shampoo). (The study had 2 other arms: clobetasol and ketoconazole alternating or clobetasol four times weekly alternating with ketoconazole)


Outcomes
  1. Total severity score (mean change from baseline)
  2. Erythema, scaling, and pruritus severity scores (0 to 3 each, expressed as change from baseline and not in exact numbers)
  3. Extent index (extent of scalp involved (0 = less than 10% to 4 = more than 70%)


NotesOnly the results for the clobetasol propionate only, and the ketoconazole only, and for the treatment phase are used in the analyses

The results for the outcomes were expressed in a way not relevant for the review; therefore, we could use only information for adverse events


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "randomized in a 1:1:1:1 ratio by a designated statistician (using a central computed randomization list that generated treatment numbers in a block-size of 4)"

Allocation concealment (selection bias)Unclear riskThis was not reported clearly

Similarity of the study groups (selection bias)Low riskQuote: "The demographic and baseline disease characteristics were similar among the four groups"

Blinding of participants (performance bias)High riskThe participants were not blinded

Blinding of care providers (performance bias)High riskThe care providers were not blinded

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe investigator was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear risk4 out of 8 authors were affiliated to the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: "The primary investigator was blinded to treatment"

Intention-to-treat analysis used: Only those who completed at least 4 weeks of treatment were included in the efficacy analyses on an intent-to-treat basis


ParticipantsInclusion criteria of the trial

  • Age 18 years or older, with seborrhoeic dermatitis on the face, an erythema score of 1 or greater, and an area index of 5% or greater


Exclusion criteria of the trial

  • Clinically significant medical conditions that were not well controlled
  • Any condition interfering with the ability to evaluate facial seborrhoeic dermatitis
  • Any known or suspected hypersensitivity to any constituent of study medication
  • Untreated or uncontrolled infection involving the face
  • Untreated cutaneous malignancies on the face at the baseline visit
  • Women who was pregnant, breastfeeding, or planning on becoming pregnant during the course of the study period


Number of randomised participants: 30 in total (tacrolimus N = 16, hydrocortisone N = 14)

Number of dropouts: 1 (3%)

Sex: 24 males, 6 females

Mean age (range): tacrolimus arm = 52.8 (25 to 70) years, hydrocortisone arm = 52.9 (20 to 80) years

Country: Canada


InterventionsTreatment

  • Tacrolimus ointment 0.1%, applied on the face twice daily for 84 days


Comparator/s

  • Hydrocortisone ointment 1%, applied on the face twice daily for 84 days


Outcomes
  1. Seborrhea Area and Severity Index-Face (SASI-F)
  2. Physician Static Global Assessment-Face
  3. Participants' self-assessment of seborrhoea (11-point scale)
  4. Safety and tolerability


NotesThe only outcomes relevant for this review were adverse effects


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly assigned"

This was not reported in sufficient detail

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskQuote: "The two treatment groups were well balanced for baseline demographics"

Blinding of participants (performance bias)High riskFor participants, the study was open-label

Blinding of care providers (performance bias)High riskOnly the primary investigator was blinded to treatment

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskThe primary investigator was blinded to treatment, but the participant was not. Therefore, outcomes evaluated and reported by the participant or a care provider other than the primary investigator were subject to detection bias

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskQuote: "This study was an investigator-initiated research project funded by Astellas Pharma Canada Inc"

1 author was financially supported by Astellas Pharma Canada Inc. The primary investigator reported receiving grants and honoraria from Astellas Pharma Canada Inc


MethodsStudy type: individual RCT

Randomisation method: "stratified blocked random method"

Blinding: double-blind

Intention-to-treat analysis used: at least partly


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the face and trunk


Exclusion criteria of the trial

  • People on chlorpromazine, cimetidine, alpha-methyldopa, INAH (isonicotinic acid hydrazide), or steroids
  • Infants
  • People with Parkinsonism or AIDS


Number of randomised participants: 36 in total (clobetasol N = 19, ketoconazole N = 17)

Number of dropouts: 5 (14%)

Sex: not reported

Age: not reported

Country: India


InterventionsTreatment

  • Clobetasol 17-butyrate 0.05% cream, applied to the affected areas (except scalp) twice daily for 4 weeks


Comparator/s

  • Ketoconazole 2% cream, applied to the affected areas (except scalp) twice daily for 4 weeks


Outcomes
  1. Severity score (severity combined with erythema, scaling, and papules)
  2. Itching (scale not reported)
  3. Remission rate
  4. Relapse rate (at the end of 3 months)
  5. Side-effect profile


NotesResults were not reported separately for face and trunk. Adverse events were not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "A stratified blocked random method was used to allocate the recruited patients into two groups according to severity"

Allocation concealment (selection bias)Unclear riskThis was not reported in detail

Similarity of the study groups (selection bias)Unclear riskThis was not reported in detail

Blinding of participants (performance bias)Low riskQuote: "Neither the doctor nor the patient knew"

Blinding of care providers (performance bias)Low riskQuote: "Neither the doctor nor the patient knew"

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskThe study did not report whether the outcome was assessed by a third party

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)High riskThe predefined outcomes included side-effects, but they were not reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis with desquamation or dandruff


Exclusion criteria of the trial

  • SeD without desquamation
  • Pregnant women
  • Unco-operative or used concomitantly other antidandruff agents


Number of randomised participants: 101 in total (hydrocortisone N = 50, ketoconazole N = 51)

Number of dropouts: 4 (4%)

Sex: 38 males, 63 females

Age (mean): 52.9 years

Country: Finland


InterventionsTreatment

  • Hydrocortisone 1% liniment, applied to the scalp once daily for 4 weeks


Comparator/s

  • Ketoconazole 2% shampoo, applied twice weekly for 4 weeks


Outcomes
  1. Erythema, desquamation, and pruritus scores (scale 0 to 3)
  2. Global assessment evaluated by participant and investigator (scale: normalised - markedly improved - slightly improved - unchanged - deteriorated)
  3. Safety assessment


NotesThe participants were diagnosed with either SeD or dandruff. The proportion of participants with dandruff was 37%. Location of SeD lesions was not mentioned as inclusion criteria, but the interventions were used on the skin of the scalp. Necessary data were calculated from other statistics


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "This randomized...study"

This was not reported in sufficient detail

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskQuote: "There were no significant differences between the treatment groups"

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskThe first author was affiliated to the pharmaceutical industry, and the pharmaceutical industry provided medication


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: not reported


ParticipantsInclusion criteria of the trial

  • Established diagnosis of seborrhoeic dermatitis of the scalp with lesions suitable for evaluation of the response to the test agent
  • Age of at least 12 years


Exclusion criteria of the trial

  • Pregnant or nursing women
  • Hypersensitivity to any of the components of the test material
  • Under systemic corticosteroid medication within the previous month or topical corticosteroid therapy within the previous week
  • If the scalp showed signs of atrophy


Number of randomised participants: 100 in total (fluocinolone N = 50, vehicle N = 50)

Number of dropouts: 2 (2%)

Sex: 75 males, 25 females

Age (range): 16 to 83 years

Country: USA


InterventionsTreatment

  • Fluocinolone acetonide shampoo 0.01%, applied on the scalp once a day for 5 minutes for 14 days


Comparator/s

  • Vehicle alone, applied on the scalp once a day for 5 minutes for 14 days


After 2 weeks, the participants were asked to discontinue use of the test product and were re-evaluated 7 days post-treatment


Outcomes
  1. Target areas on the scalp were designated and recorded on a dermograph
  2. Global assessments (erythema, scaling, and pruritus), using an 8-point scale (0 to 3.5)
  3. Improvement
  4. Adverse effects


NotesNon-medicated shampoo to be used when necessary


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "The patients...were each assigned a number and randomly allocated...according to a schedule known only to the sponsor"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Unclear riskThis was not reported. According to information in Table 1 of the report, there were no significant differences between the groups in erythema, scaling, and pruritus scores

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskThe first author was affiliated to industry, and the sponsor provided non-medicated shampoos


MethodsStudy type: individual RCT

Randomisation method: computer-based randomisation

Blinding: investigator-blinded

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Total severity score less than 2


Number of randomised participants: 55 in total (11 participants in each group)

Number of dropouts: 4 (7%)

Sex: 30 males, 25 females

Mean age (range): 36.9 (18 to 64) years

Country: France


InterventionsTreatment

  • Clobetasol 0.05%, applied to the scalp twice weekly for 4 weeks (applied for 2.5, 5, or 10 minutes)


Comparator/s

  • Ketoconazole 2% foaming gel, applied to the scalp twice weekly for 4 weeks (for 5 minutes)
  • Placebo (vehicle), applied to the scalp twice weekly for 4 weeks (for 10 minutes)


Outcomes
  1. Erythema and desquamation (7-point scale from 0 to 3), itching (100 mm analogue scale), and global improvement assessed by the investigator (7-point scale: -1 = worse than baseline to +5 = clear)
  2. Safety evaluations (burning, 7-point scale from 0 to 3) and adverse events


NotesThe design of this trial was different from any other included study. The treatments were applied for different times: clobetasol propionate shampoo 0.05% for 2.5, 5, or 10 minutes; clobetasol propionate vehicle for 10 minutes; or ketoconazole foaming gel 2% for 5 minutes. After that, they were to be rinsed off. These kind of application methods were not used in any other included studies; therefore, we did not use the results in the meta-analysis. Results were not obtainable for all groups from the printed article. The actual symptom scores relevant for this review were not given in the text. Itching scores were given in a figure, but the figure displays only the results for the placebo (vehicle) and the azole group, which was irrelevant for this review. Only the results for complete clearance were given in the text


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "were randomized according to a computerized randomization schedule"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskAccording to the report, there were no significant differences between the treatment groups for any of the symptoms, race, age, and gender distribution

Blinding of participants (performance bias)High riskQuote: "investigator blinded"

Blinding of care providers (performance bias)High riskQuote: "investigator blinded"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "investigator-blinded"

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe overall dropout rate was acceptable, but varied between 0%, 9%, and 18% in different treatment arms

Selective reporting (reporting bias)Low riskAll predefined outcomes were reported

Other biasUnclear riskSome authors were affiliated to a pharmaceutical company


MethodsStudy type: individual RCT

Randomisation method: computer-based randomisation

Blinding: no (open-label)

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis


Exclusion criteria of the trial

  • Other dermatoses of face
  • Topical treatments during the 6 months prior to entry in the study
  • Pregnancy or lactation


Number of randomised participants: 20 in total (pimecrolimus N = 11, betamethasone N = 9)

Number of dropouts: 0

Sex: 16 males, 4 females

Mean age (range): pimecrolimus arm = 36.4 (24 to 45) years, betamethasone arm = 37.2 (24 to 47) years

Country: Greece


InterventionsTreatment

  • Pimecrolimus 1% cream, applied to the face twice daily until symptoms were absent


Comparator/s

  • Betamethasone 0.1% cream, applied to the face twice daily until symptoms were absent


Outcomes
  1. Erythema, pruritus, and scaling scores (scale 0 to 3)
  2. Clearance and relapse rate


NotesThe participants were instructed to discontinue use of the medicine as soon as symptoms were absent. All participants stopped treatment by day 9 because symptoms had disappeared

We could not use erythema, pruritus, and scaling scores in the meta-analysis because standard deviations or exact P values were not given in the report

The location of SeD lesions were not mentioned as inclusion criteria, but other dermatoses of the face were reported as exclusion criteria suggesting that the skin of the face was a site of interest in the trial


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomly assigned to treatment...using a program that allocated every consecutive group of two patients to one patient in each group. The random numbers were generated by a computer and were assigned to the patients by the investigator's assistant"

Allocation concealment (selection bias)Unclear riskThe randomisation and allocation program allocated every consecutive group of 2 participants to 1 participant in each group, so the assistant would have known the latter participant's group in advance. However, the same assistant enrolled and assigned the treatment of the participants, whereas the investigator was masked

Similarity of the study groups (selection bias)Low riskQuote: "The mean baseline score for erythema, pruritus and scaling did not differ significantly between the two treatment groups"

Blinding of participants (performance bias)High riskThe study was not blinded

Blinding of care providers (performance bias)Unclear riskThis was not reported

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "in an attempt to make the assessments investigator masked"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNone were identified

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: a standard randomisation sheet was used

Blinding: double-blind

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Not reported. Each had seborrhoeic dermatitis occurring primarily in the nasolabial folds


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 50 in total (the initial group assignment numbers have not been reported. By the end of the study, there were 24 participants in the fluocinolone group and 19 participants in the vehicle group)

Number of dropouts: 7 (14%)

Sex of those who completed (baseline was not reported): 21 males and 22 females

Age: not reported as mean, median, or range (reported as number of participants in 6 different age groups)

Country: USA


InterventionsTreatment

  • Fluocinolone acetonide solution 0.01%, applied on the face twice a day for 84 days (12 weeks)


Comparator/s

  • Propylene glycol solution, applied on the face twice daily for 84 days (12 weeks)


Each participant was instructed to shampoo the scalp once weekly with Drytergent®


Outcomes
  1. Clinical severity scores (erythema and scaling, scale 1+ to 3+) excluding scalp, clinical photographs


NotesOnly inpatients were included


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "standard randomization sheet"

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Unclear riskThis was not reported

Blinding of participants (performance bias)Low riskThe study was double-blind, but it was not reported specifically which parties were blinded. Nevertheless, the participants received the intervention and the comparison in identical containers

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe dropout rate was 24% in the control group. The initial group assignment numbers were not reported

Selective reporting (reporting bias)Unclear riskPrespecified outcomes were reported

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: no (open-label)

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • Allergic to the tested products
  • Other dermatosis of the scalp
  • Phototherapy during the month before enrolment
  • Use of other topical therapeutic drugs or shampoos during the 2 months before
  • Immunosuppressive treatment including systemic steroids during the 3 months before enrolment
  • Significant renal disease or liver disease
  • Chronic diseases like asthma, diabetes, and hypertension
  • Pregnancy or lactation


Number of randomised participants: 83 in total (tacrolimus N = 27, betamethasone N = 27, zinc pyrithione N = 29)

Number of dropouts: altogether, 27 at 8 weeks (33%). At week 4, the dropout rate was 23% in the treatment arm that received treatment for 4 weeks only. The dropout rate at 4 weeks was not reported for the group that continued the treatment for 8 weeks. The dropout rate for this group was 38% at week 8

Sex: not reported

Age (mean): tacrolimus arm = 38.0 years, betamethasone arm = 39.0 years, zinc pyrithione arm = 34.7 years

Country: Korea


InterventionsTreatment

  • Tacrolimus 0.1% ointment, applied to the scalp twice daily for 4 weeks


Comparator/s

  • Betamethasone lotion, applied to the scalp twice daily for 4 weeks
  • Zinc pyrithione 1% shampoo, applied to the scalp 3 times a week for 4 weeks


Outcomes
  1. Clinical severity scores (dandruff and lesional extent, scale 0 to 3) evaluated by investigator


Notes"At week 4, 53 patients continued the same treatment for an additional 4 weeks, but the other 30 patients stopped the treatments and were followed up at week 8." We only used the results from week 4 in this review because the only efficacy outcome that we could use was dandruff score, and the results for dandruff score were given at 4 weeks only. The dropout rate for those that used the interventions for 8 weeks was 38%. We requested and received additional data from the contact author


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "randomly allocated"

Allocation concealment (selection bias)Unclear riskQuote: "randomly allocated"

Similarity of the study groups (selection bias)Unclear riskThe differences in baseline clinical severity scores and dandruff scores were evaluated only for those who completed the 8-week follow-up-study. We used the results at 4 weeks

Blinding of participants (performance bias)High riskThis was an open-label study

Blinding of care providers (performance bias)High riskThis was an open-label study

Blinding of outcome assessment (detection bias)
All outcomes
High riskThis was an open-label study

Incomplete outcome data (attrition bias)
All outcomes
High riskThe dropout rate was 23% in the treatment arm that received treatment for 4 weeks only, but there was considerable variation between the groups (dropout rate was 50% in the betamethasone group, 0% in the tacrolimus group, and 20% in the zinc pyrithione group). The dropout rate at 4 weeks was not reported for the group that continued the treatment for 8 weeks. At 8 weeks, the dropout rates varied between 16% in the zinc pyrithione group, 24% in the betamethasone group, and 76% in the tacrolimus group. There were no intention-to-treat analyses

Selective reporting (reporting bias)Low riskNo selective reporting bias was identified

Other biasLow riskNo other bias was identified


MethodsStudy type: individual RCT

Randomisation method: not reported

Blinding: double-blind

Intention-to-treat analysis used: no


ParticipantsInclusion criteria of the trial

  • Seborrhoeic dermatitis


Exclusion criteria of the trial

  • Not reported


Number of randomised participants: 78 in total (6 participants were excluded because of a lack of treatment data. Finally, there were 36 participants in both groups.). The initial assignment numbers in each group were not reported

Number of dropouts: 6 (8%)

Sex: not reported

Mean age (range): hydrocortisone arm = 32.0 (18 to 73) years, ketoconazole arm = 34 (18 to 78 years)

Country: Greece


InterventionsTreatment

  • Hydrocortisone 1% cream, applied to the affected areas once daily for 4 weeks


Comparator/s

  • Ketoconazole 2% cream, applied once daily for 4 weeks


Outcomes
  1. Global evaluation (total clearing - good - fair - poor - not evaluable)
  2. Erythema, scaling, papules, and itching scores (scale 0 to 3)


NotesMost of the results were not given in numerical form. We have approximated the numbers from figures, where applicable. The location of SeD lesions was not mentioned as inclusion criteria, but the sites of interest were reported to include the scalp, retroauricular area, eyebrows, hairline, nasolabial folds, sternum, external ear canal, and bridge of the nose


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Allocation concealment (selection bias)Unclear riskThis was not reported

Similarity of the study groups (selection bias)Low riskQuote: "Both groups were comparable for age, weight, height, sex distribution, and duration of the infection"

Blinding of participants (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of care providers (performance bias)Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWhilst the study was reported to be double-blind, it was not clear who was blinded

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe dropout rate was acceptable. The initial number of participants in each group was not reported

Selective reporting (reporting bias)Low riskPredefined outcomes were reported

Other biasUnclear riskSome of the authors were affiliated to the pharmaceutical industry


MethodsStudy type: individual RCT

Randomisation method: not mentioned

Blinding: no (open-label trial)

Intention-to-treat analysis used: yes


ParticipantsInclusion criteria of the trial

  • Mild or moderate seborrhoeic dermatitis of the scalp


Exclusion criteria of the trial

  • People with plaques or severe crusts on the scalp or with signs suggestive of psoriasis
  • Any underlying condition or concomitant treatment that might interfere with or account for SeD
  • Use of systemic steroid during the 4 weeks preceding the study
  • Pregnant and breastfeeding women


Number of randomised participants: 69 in total (betamethasone N = 34, ketoconazole N = 35)

Number of dropouts: 0

Sex: 33 males, 36 females

Mean age (range): betamethasone arm = 45.6 (20 to 75) years, ketoconazole arm = 40.1 (18 to 73) years

Country: the Netherlands


InterventionsTreatment

  • Betamethasone 17-valerate 0.1% lotion, applied to the scalp twice daily for the first week, once daily in the second week, and twice weekly in the third and fourth weeks


Comparator/s

  • Ketoconazole 20 mg/g hydrogel, applied to the scalp twice weekly for 4 weeks


Outcomes
  1. Itching, scaling, and greasiness scores (scale 0 to 4)
  2. Overall improvement evaluated by participants and investigators (cured - markedly improved - improved - unchanged - worsened)
  3. Adverse events


Notes"72 patients gave written informed consent and entered the wash-out period, but 2 had spontaneous remission and 1 withdrew for a non-study-related reason leaving 69 patients randomized". The results were given in figures and not in exact numbers. We approximated the numbers from figures, where feasible


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThis was not reported in detail

Quote: "randomly allocated"

Allocation concealment (selection bias)Unclear riskThis was not reported in detail

Quote: "randomly allocated"

Similarity of the study groups (selection bias)Low riskQuote: "The groups were very well matched for demography and clinical characteristics"

Blinding of participants (performance bias)High riskThis was an open-label study

Blinding of care providers (performance bias)High riskThis was an open-label study

Blinding of outcome assessment (detection bias)
All outcomes
High riskThis was an open-label study

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskAll prespecified outcomes were reported, albeit not sufficiently enough for use in the meta-analysis

Other biasUnclear risk1 author was affiliated to Glaxo-Wellcome (The Netherlands) BV, and Glaxo-Wellcome provided all products

Quote: "Financial support for the study was generously provided by Glaxo-Wellcome (The Netherlands) BV"


MethodsStudy type: individual RCT

Randomisation method: computer-generated blocks of 4

Blinding: double-blind

Intention-to-treat analysis used: Both ITT and PP analyses were used


ParticipantsInclusion criteria of the trial

  • Facial seborrhoeic dermatitis


Exclusion criteria of the trial

  • Pregnancy or nursing
  • Allergies to products
  • Acne vulgaris or rosacea
  • People with poorly controlled chronic conditions
  • Those with cancer, neurologic conditions, or HIV infection (or other immunosuppression)


Number of randomised participants: 96 in total (pimecrolimus N = 47, vehicle N = 49)

Number of dropouts: 2 (2%)

Sex: 85 males, 11 females

Mean age (range): pimecrolimus arm = 59.5 (27 to 84) years, placebo arm = 59.6 (20 to 88) years

Country: USA


InterventionsTreatment

  • Pimecrolimus 1% cream, applied to the face twice daily for 4 weeks


Comparator/s

  • Placebo (vehicle), applied to the face twice daily for 4 weeks


Outcomes
  1. Erythema and scaling score (scale 0 to 3)
  2. Total target area score (sum of erythema and scaling score)
  3. IGA score (Investigator's Global Assessment score, scale 0 to 4)
  4. Adverse events


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The computer-generated randomization assignment (blocks of 4) was only accessible to the research pharmacist during the study"

Allocation concealment (selection bias)Low riskQuote: "The computer-generated randomization assignment (blocks of 4) was only accessible to the research pharmacist during the study"

Similarity of the study groups (selection bias)Unclear riskQuote: "At baseline, both groups had similar demographics...with the exception that a higher percentage of participants in the pimecrolimus group (38%) had previously used medication to treat their seborrhoeic dermatitis, compared with participants in the vehicle group (29%). In addition, participants in the vehicle group had milder disease at baseline compared with those in the pimecrolimus group with regard to mean scale target area score...and with regard to mean facial IGA"

Blinding of participants (performance bias)Low riskThe study was double-blind

Quote: "The two creams were packaged in identical tubes"

Blinding of care providers (performance bias)Low riskQuote: "double-blind"

Blinded parties were not specified. Nevertheless, the research pharmacist was the only person that knew the participants' assignments

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "double-blind"

Blinded parties were not specified. Nevertheless, the research pharmacist was the only person that knew the participants' assignments

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe dropout rate was acceptable

Selective reporting (reporting bias)Low riskPrespecified outcomes were reported

Other biasUnclear riskQuote: "This investigator-initiated study was supported by Novartis Pharmaceuticals Corporation" Novartis Pharmaceuticals Corporation employed at least 2 of the authors

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aertgeerts 1985Only 1 of 161 participants had SeD

Albrecht 1986Only 9 of 383 participants had SeD

Alebiosu 2003Only 2 of the participants had dandruff; there was no mention about the proportion of SeD participants

Alexander 1967The intervention was not anti-inflammatory (tar)

Amos 1994The interventions were not anti-inflammatory (tar and ketoconazole)

Anonymous 1994aThis study was not a RCT, and the interventions were not anti-inflammatory

Anonymous 1994bThis was a review

Arenas 1999The intervention was not anti-inflammatory (ichthyol/octopirox/salicylic acid)

Attarzadeh 2013Allocation of treatment (emu oil or either clotrimazole or hyrocortisone) was not randomised as treatment 1 was always used on the right side, and treatment 2 was used on the left side of the face

Banerjee 1975The interventions were a combinations of drugs (a combination of nitrofurazone and hydrocortisone acetate compared with a combination of framycetin sulfate and dexamethasone acetate and a combination of neomycin, bacitracin, polymyxin B sulfate, and hydrocortisone)

Barbanoj 2005The intervention was not anti-inflammatory (eberconazole), and participants were healthy volunteers

Basak 1999This was a poster. The efficacy and safety results were not given in numerical form, and it was not possible to ensure that efficacy was assessed in ways relevant for the review

Bertamino 1975Less than 75% of participants had seborrhoeic dermatitis; randomisation was not explained clearly

Binder 1972Less than 75% of participants had seborrhoeic dermatitis; the affected area was not reported

Boyle 1986The intervention was a combination of lithium succinate and zinc

Camarasa 1975Only 1 participant out of 37 had SeD

Carboni 1982The comparison was between 2 formulas of clobetasol

Christodoulou 1983The intervention was in peroral form

Cuelenaere 1992The interventions was a combination of lithium succinate and zinc sulphate

Curley 1990The diagnosis of the participants was mainly psoriasis or eczema; only a few had SeD

Davies 1999The intervention was tar or ciclopirox olamine, which are not relevant for this review

de la Brassine 1984Randomisation, site, and age were unclear

Dobrev 20031 intervention is a combination of drugs (salicylic acid, plant tar, and green microalgae), and others were not anti-inflammatory (selenium sulphide, zinc pyrithione, and a combination of ketoconazole, metronidazole, and sulphur)

Elewski 2009bThis was a review

Elie 1983Only 17 out of 40 participants had SeD

Eun 2009This was a poster, which did not contain enough data

Franz 2000Participants had psoriasis not SeD

Fredriksson 1975aThe study was not randomised

Fredriksson 1985The intervention was not anti-inflammatory (tar)

Freeman 2002Less than 75% of participants had seborrhoic dermatitis in the desonide group

Fritz 1995The intervention was a combination of lithium and zinc sulphate

Futterer 1981The comparison was irrelevant (piroctone olamine and zinc pyrithione)

Gayko 2006The intervention was a combination of ichthyol and ketoconazole

Gentry 1973Age and affected area are unknown

Goffin 1996The interventions were not anti-inflammatory (econazole nitrate, piroctone olamine, senium sulphide, and zinc pyrithione)

Gould 1988The reference was a summary of a paper. The used efficacy measures were not reported in detail. The results were not reported in numerical form

Grossman 1997The interventions were not anti-inflammatory (zinc pyrithione and ketoconazole)

High 2006The study was not randomised or controlled

Hochman 1988The interventions were combinations of non-anti-inflammatory agents (sulphur + salicylic acid)

Humke 2002The nature of the intervention was unclear: a new shampoo free of ketoconazole versus a ketoconazole-containing shampoo

Jacksonville 1969The age of the participants was unknown; randomisation was unclear; and the time-in-between was not reported

Jafferany 2008This was a review

Jaramillo 1992The intervention was not anti-inflammatory (zinc pyrithione)

Jensen 2009This was a poster. The age of the participants was not reported. The outcomes used were not in the interest of this review

Jensen 2010This was a poster. There was no information on the age of the participants or the affected/investigated site. The used outcomes were not reported, and the results of interest in this review were not reported in numerical form

Kaminester 2002The intervention was not anti-inflammatory (sulphacetamide)

Karsono 2010The intervention was not anti-inflammatory (zinc pyrithione)

Kim 2012This was a poster. The results of interest for this review were not reported in detail or in numerical form. No useful data could be added to the analyses

Kim 2013This study included an induction phase with an active treatment only (not controlled) and thereafter a controlled maintenance phase

Kircik 2009Participants were healthy volunteers, and the intervention was not anti-inflammatory

Levy 1974There was only 1 participant with SeD

Li 2000The interventions were irrelevant for the review (Triatop®, which is a ketoconazole-containing compound, and tar)

Lin 2010This was a review

Luo 1993The intervention was antifungal (bifonazole)

López Padilla 1996The interventions were not anti-inflammatory (ketoconazole and climbazole)

Marks 1974The outcomes used in the study were not relevant for the review. There were no useful data to be added to the analyses

Mensing 2008Only 10 out of 27 participants had SeD, and there was no control treatment

Nolting 1983Less than 75% of participants had SeD, and results were not reported separately for SeD participants

Nolting 1985Only 1 out of 80 participants had the diagnosis of SeD

Pierard-Franchimont 1995The interventions were not anti-inflammatory (econazole, ketoconazole, piroctone olamine, and selenium sulphide)

Pierard-Franchimont 1999The intervention was not anti-inflammatory (tar). This was a poster

Pierard-Franchimont 2000The intervention was not anti-inflammatory (tar)

Pierard-Franchimont 2002aThe interventions were a combination of non-anti-inflammatory agents (ketoconazole, piroctone olamine, and zinc pyrithione formulations)

Pierard-Franchimont 2002bThe intervention was a combination of antifungal and anti-inflammatory drugs (ketoconazole and desonide combination)

Pierard-Franchimont 2002cThe interventions were not anti-inflammatory (ketoconazole and zinc pyrithione)

Reiffenstuhl 1973Only 3 out of 54 participants had SeD, and there was no control intervention

Reinhard 1974Only 5 out of 122 participants had SeD

Sohn 1978This was a non-randomised study

Tomoka 1973Only 2 out of 84 participants had SeD

Turnbull 1982Less than 75% of participants had seborrhoeic dermatitis

Veien 1980The intervention was a combination of 2 non-anti-inflammatory agents (coal tar and zinc pyrithione)

Wacker 1989Randomisation and proportion of SeD participants was unclear

Weiss 2011The intervention was not anti-inflammatory (ketoconazole)

Wollina 2006This was a review

Wollina 2007This was a review

Yawalkar 1983Less than 75% of participants had SeD

 
Characteristics of studies awaiting assessment [ordered by study ID]

MethodsRandomised, controlled, double-blind study

Duration: 44 days with 3 phases (control, treatment, and follow-up period)

Participants
  • 20 adult men with severe seborrheic dermatitis of the scalp

Interventions
  • Dexamethasone 0.012% in an aerosol alcohol-isopropyl myristate formula
  • Fluocinolone acetonide 0.01%

OutcomesScored degree of seborrheic involvement (summary scores)

NotesThe participants were not blinded. Only the evaluating physician was blinded (single-blind). Side-effects were not reported


MethodsRandomised, controlled, double-blind study

Duration: not reported

Participants
  • 67 participants aged 15 to 60 years with seborrheic dermatitis of the face

Interventions
  • Fluocinolone acetonide solution (0.01%) in a propylene glycol base
  • Propylene glycol

OutcomesClinical effectiveness defined as test drug preferred and identified; improvement (either partial or complete decrease of redness, scaling and itching), side effects

Notes-

 
Characteristics of ongoing studies [ordered by study ID]

Trial name or titleClinical efficacy of pimecrolimus cream in seborrheic dermatitis. Efficacy of pimecrolimus in normalizing clinical symptoms, explorative study of barrier function, hydration, lipid content and differentiation in seborrheic dermatitis: a randomized, double-blind study in adults with seborrheic dermatitis treated with 1% pimecrolimus cream versus 2% ketoconazole cream as control

MethodsThis is a randomised, controlled, double-blind study

Duration: 4 weeks

Participants
  • 18 years or older with mild to severe seborrhoeic dermatitis

Interventions
  • Pimecrolimus cream 1%
  • Ketoconazole cream 2%

OutcomesPrimary outcome/s of the trial

  • Change of IGA scores in 1 week


Secondary outcome/s of the trial

  • Change in IGA scoring in relation to the face
  • Pruritus, erythema, and scaling scores
  • Cosmetic acceptability assessment
  • Epidermal effects
  • Changes in Malassezia counting at 4 weeks

Starting dateEntered into database: August 2006

Contact informationDepartment of Dermatology, University of Kiel, Germany

NotesOngoing. Database accessed on 17 December 2012


Trial name or titleA multicenter, randomized, double-blind, two-arm, vehicle-controlled, parallel-group, two stage study to evaluate and demonstrate the efficacy and to evaluate the safety of pimecrolimus 1% cream in the treatment of seborrhoeic dermatitis in patients 12 years of age and older

MethodsThis is a randomised, double-blind, parallel group, 2-stage study

Initial estimate of the duration of the trial: 9 months

Participants
  • People with seborrhoeic dermatitis aged 18 years or older

Interventions
  • Pimecrolimus 1% cream (Elidel®)
  • Placebo cream

OutcomesPrimary outcome/s of the trial

  • Overall clearance (IGA of 0) assessed at 1, 2, or 3 weeks. 1 of these assessment time points will be selected for the final analysis of the primary end point


Secondary outcome/s of the trial

  • Facial clearance
  • Time to overall clearance
  • Time to facial clearance
  • Change in pruritus
  • Severity of lesional erythema and scaling
  • Time to relapse
  • Safety
  • Health-related quality of life
  • Amount of study drug/participant/episode

Starting dateEntered into database: October 2006

Contact informationNovartis Pharma Services AG, Switzerland

NotesCompleted, but no publications provided in searched databases. In the title, the age of the participants is limited to 12 or older whereas in the inclusion criteria, the age limit is 18 or older. The trial has 2 stages, but these are not defined clearly. Database accessed on 17 December 2012


Trial name or titleEfficacy and tolerance of V0071 GM 01A in inflammatory seborrhoeic dermatitis of the scalp

MethodsThis is a randomised, open-label (investigator-masked in initiation therapy), parallel group study (phase II)

Initial estimate of the duration of the trial: 11 months

Participants
  • People aged 18 to 65 years with inflammatory seborrhoeic dermatitis of the scalp or with dandruff

Interventions
  • V0071 GM 01A (betamethasone dipropionate 0.05%) shampoo
  • Ketoconazole 2% foaming gel

OutcomesPrimary outcome/s of the trial

  • Erythema and scaling sum scores on each half head at 2 weeks


Secondary outcome/s of the trial

  • Efficacy of intervention on inflammatory seborrhoeic dermatitis
  • Local and global tolerance of the interventions

Starting dateEntered into database: January 2008

Contact informationPierre Fabre Dermatologie, France

NotesOngoing study. Database accessed on 17 December 2012


Trial name or titleEfficacité et tolérance du LBC 45 dans la dermite séborrhéique du cuir chevelu

MethodsThis is a randomised, controlled, double-blind, parallel group, phase II study

Initial estimate of the duration of the trial: 70 days

Participants
  • 18 years or older with seborrhoeic dermatitis of the scalp of moderate to severe intensity
  • Disease for at least 2 months

Interventions
  • Lithium gluconate gel 8/100 g/g
  • Placebo gel

OutcomesPrimary outcome/s of the trial

  • The sum of erythema and scaling scores at day 56


Secondary outcome/s of the trial

  • None mentioned

Starting dateEntered into database: August 2009

Contact informationLABCATAL, France

NotesOngoing study. Database accessed on 17 December 2012


Trial name or titleConfirmation de l'efficacité et de la tolérance du LBC 45 dans la dermite séborrhéique du cuir chevelu

MethodsThis is a randomised, controlled, single-blind, parallel group, phase II study

Initial estimate of the duration of the trial: 70 days

Participants
  • 18 years or older
  • Moderate to severe seborrhoeic dermatitis of the scalp for at least 2 months

Interventions
  • Lithium gluconate gel 8%
  • Ciclopirox olamine shampoo 1.5% and placebo gel

OutcomesPrimary outcome/s of the trial

  • The efficacy of lithium gluconate compared with placebo after 8 weeks of treatment and assessed with sum scores (erythema and scaling)


Secondary outcome/s of the trial

  • The efficacy of lithium gluconate in moderate to severe seborrhoeic dermatitis of the scalp compared with ciclopirox olamine after 4 and 8 weeks of treatment
  • The efficacy of lithium gluconate compared with placebo after 4 weeks
  • The local and general tolerance to lithium gluconate after 4 and 8 weeks
  • Participants' preferences between lithium gluconate and ciclopirox olamine at 8 weeks
  • To compare the efficacy of different modes of application of lithium gluconate at 4 and 8 weeks

Starting dateEntered into database: October 2010

Contact informationLaboratoire LABCATAL, France

NotesOngoing study. Database accessed on 17 December 2012


Trial name or titleA 4 week randomized double-blind parallel group active comparator controlled study of Elidel for the treatment of seborrheic dermatitis

MethodsThis is a randomised, double-blind, parallel group study

Participants
  • 18 years or older with seborrhoeic dermatitis

Interventions
  • Pimecrolimus cream 1%
  • Ketoconazole cream 2%

OutcomesPrimary outcome/s of the trial

  • The change of IGA from baseline to week 1


Secondary outcome/s of the trial

  • Per cent of participants with facial clearance

Starting dateJanuary 2007

Contact informationJoseph F Fowler Jr, Dermatology Specialists Research

NotesCompleted in January 2009, but no publications provided. Database accessed on 17 December 2012


Trial name or titleComparative evaluation of the efficacy and tolerability of prednisolone acetate 0.5% cream versus betamethasone valerate 0.1% cream in the treatment of pediatric and adult dermatosis

MethodsThis is a randomised, open-label, parallel group phase III study

Participants
  • 12 to 60 year-old people with mild to moderate corticosensitive dermatosis (atopic dermatitis, contact dermatitis, seborrhoeic dermatitis, or psoriasis)

Interventions
  • 0.5% prednisolone acetate cream
  • 0.1% betamethasone valerate cream

OutcomesPrimary outcome/s of the trial

  • "Evaluate efficacy and safety" at 2 weeks


Secondary outcome/s of the trial

  • "Evaluate physicians' and patients' perception of the efficacy and tolerability of treatment" at 2 weeks

Starting dateFebruary 2010

Contact informationCláudia Domingues

cdomingues@mantecorp.com

NotesThe study is not yet open for participant recruitment. At this point, it is impossible to know if this study will be relevant for this review. Database accessed on 17 December 2012

 
Comparison 1. Steroid vs placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)3313Risk Ratio (M-H, Random, 95% CI)3.76 [1.22, 11.56]

   1.1 Mild steroids
147Risk Ratio (M-H, Random, 95% CI)1.57 [0.29, 8.53]

   1.2 Strong steroids
2266Risk Ratio (M-H, Random, 95% CI)5.92 [0.99, 35.52]

 2 Total clearance (over 4 weeks)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

   2.1 Strong steroids
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Mean change in erythema score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   3.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Erythema score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   4.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Mean change in scaling score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   5.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Scaling scores (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   6.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Mean change in pruritus score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   7.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Pruritus scores (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   8.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Any adverse effect (at 4 weeks or less)3508Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.29, 2.72]

   9.1 Mild steroids
147Risk Ratio (M-H, Fixed, 95% CI)0.35 [0.01, 8.11]

   9.2 Strong steroids
2461Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.31, 3.58]

 
Comparison 2. Steroid vs calcineurin inhibitor

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)260Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.88, 1.32]

   1.1 Mild steroids
140Risk Ratio (M-H, Fixed, 95% CI)1.13 [0.83, 1.55]

   1.2 Strong steroids
120Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.83, 1.20]

 2 Erythema score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   2.1 Mild steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Scaling score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   3.1 Mild steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Mean change in dandruff score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   4.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Any adverse effects at 4 weeks or less260Risk Ratio (M-H, Fixed, 95% CI)0.22 [0.05, 0.89]

   5.1 Mild steroids
140Risk Ratio (M-H, Fixed, 95% CI)0.14 [0.02, 1.06]

   5.2 Strong steroids
120Risk Ratio (M-H, Fixed, 95% CI)0.41 [0.05, 3.28]

 6 Any adverse effects (at 4 weeks or more)272Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.26, 1.47]

   6.1 Mild steroids
272Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.26, 1.47]

 
Comparison 3. Steroid vs azole

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)8464Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.94, 1.32]

   1.1 Mild steroids
5310Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.87, 1.28]

   1.2 Strong steroids
3154Risk Ratio (M-H, Fixed, 95% CI)1.29 [0.88, 1.90]

 2 Total clearance (at 4 weeks or less, evaluated by participant)2Risk Ratio (M-H, Random, 95% CI)Totals not selected

   2.1 Mild steroids
1Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

   2.2 Strong steroids
1Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 3 Erythema score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   3.1 Strong steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Mean change in erythema score at 4 weeks or less1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   4.1 Mild steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Scaling score (at 4 weeks or less)2Std. Mean Difference (IV, Fixed, 95% CI)Subtotals only

   5.1 Strong steroids
2118Std. Mean Difference (IV, Fixed, 95% CI)-2.72 [-3.24, -2.21]

 6 Mean change in scaling score at 4 weeks or less1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   6.1 Mild steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Pruritus score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   7.1 Mild steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Mean change in pruritus score at 4 weeks or less1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   8.1 Mild steroids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Any adverse effects at 4 weeks or less6381Risk Ratio (M-H, Fixed, 95% CI)1.45 [0.74, 2.85]

   9.1 Mild steroids
4263Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.44, 2.26]

   9.2 Strong steroids
2118Risk Ratio (M-H, Fixed, 95% CI)3.25 [0.86, 12.36]

 10 Any adverse effects at 4 weeks or more2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

   10.1 Mild steroids
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   10.2 Strong steroids
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Mild steroid vs strong steroid

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)293Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.65, 1.40]

 2 Total clearance (at 4 weeks or less, evaluated by participant)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Total clearance at 4 weeks or more1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Erythema score (at 4 weeks or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 Scaling score (at 4 weeks or less)263Std. Mean Difference (IV, Fixed, 95% CI)-0.05 [-0.55, 0.45]

 6 Pruritus score (at 4 weeks or less)3114Std. Mean Difference (IV, Fixed, 95% CI)0.13 [-0.24, 0.50]

 7 Any adverse effects (at 4 weeks or less)3118Risk Ratio (M-H, Fixed, 95% CI)1.37 [0.32, 5.93]

 8 Any adverse effects (at 4 weeks or more)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 5. Steroid vs zinc pyrithione

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Scaling score (< 4 weeks)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 6. Desonide (mild steroid) vs Promiseb®

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 7. Steroid vs calcipotriol

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Any adverse effects (at 4 weeks or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 8. Calcineurin inhibitor vs placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (at 4 weeks or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Mean change in erythema score at 4 weeks or less1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Mean change in scaling score at 4 weeks or less1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 Outcome: any adverse effects1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 9. Calcineurin inhibitor vs azole

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Erythema score (over 4 weeks)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 2 Scaling score (over 4 weeks)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Any adverse effects (over 4 weeks)2Risk Ratio (M-H, Random, 95% CI)Totals not selected

 
Comparison 10. Calcineurin inhibitor vs zinc pyrithione

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Dandruff score (< 4 weeks)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 11. Lithium vs placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (over 4 weeks)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Any adverse effects at 4 weeks or more1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 12. Lithium vs azole

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total clearance (< 4 weeks)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Total clearance (at 4 weeks or more)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Summary of findings for the main comparison. Calcineurin inhibitor compared with steroid for seborrhoeic dermatitis of the scalp or face

Steroid compared with calcineurin inhibitor for seborrhoeic dermatitis of the scalp or face

Patient or population: people with seborrhoeic dermatitis
Settings: community setting implied from context but not stated
Intervention: steroid
Comparison: calcineurin inhibitor

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Calcineurin inhibitorSteroid

Total clearance (at 4 weeks or less)
Investigator's assessment
Follow up: ≦ 2 weeks
839 per 1000906 per 1000
(738 to 1000)
RR 1.08
(0.88 to 1.32)
60
(2 studies)
⊕⊕⊝⊝
low¹,²
-

*The basis for the assumed risk is the risk in the control groups of the relevant trials. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 ¹Participants were not blinded.
²Small number of participants in studies.
 
Summary of findings 2. Steroid compared with azole for seborrhoeic dermatitis of the scalp or face

Steroid compared with azole for seborrhoeic dermatitis of the scalp or face

Patient or population: people with seborrhoeic dermatitis of the scalp or face
Settings: community setting implied from context but not stated
Intervention: steroid
Comparison: azole

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

AzoleSteroid

Total clearance (at 4 weeks or less)
Investigator's assessment
Follow up: 3 to 4 weeks
474 per 1000526 per 1000
(445 to 625)
RR 1.11
(0.94 to 1.32)
464
(8 studies)
⊕⊕⊕⊝
moderate¹
-

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 ¹Risk of bias considerable in all studies.
 
Summary of findings 3. Strong steroid (class III or IV) compared with mild steroid (class I or II) for seborrhoeic dermatitis of the scalp or face

Strong steroid (class III or IV) compared with mild steroid (class I or II) for seborrhoeic dermatitis

Patient or population: people with seborrhoeic dermatitis
Settings: community setting implied from context but not stated
Intervention: strong steroid (class III or IV)
Comparison: mild steroid (class I or II)

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Mild steroid (class I or II)Strong steroid (class III or IV)

Total clearance (at 4 weeks or less)
Investigator's assessment
Follow up: 3 to 4 weeks
413 per 1000397 per 1000
(268 to 578)
RR 0.96
(0.65 to 1.4)
93
(2 studies)
⊕⊕⊕⊝
moderate¹
-

Total clearance (more than 4 weeks)
Investigator's assessment
Follow up: 6 weeks
644 per 1000509 per 1000
(406 to 631)
RR 0.79
(0.63 to 0.98)
117
(1 study)
⊕⊕⊝⊝
low²
-

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 ¹Imprecision (two small studies).
²One study that was not blinded (patient and care provider not blinded; blinding of outcome assessment not reported).
 
Summary of findings 4. Lithium compared with azole for seborrhoeic dermatitis of the scalp or face

Lithium compared with azole for seborrhoeic dermatitis

Patient or population: people with seborrhoeic dermatitis
Settings: community setting
Intervention: lithium
Comparison: azole

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

AzoleLithium

Total clearance
Investigator's assessment
Follow up: 4 weeks
147 per 1000263 per 1000
(162 to 426)
RR 1.79
(1.1 to 2.9)
288
(1 study)
⊕⊕⊝⊝
low¹
-

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 ¹One study in which participants were not blinded and blinding of others was not reported.
 
Table 1. Reygagne 2007

The study investigated clobetasol propionate shampoo (0.05%) with three different application times (2.5 minutes, 5 minutes, and 10 minutes) and the comparisons included ketoconazole and vehicle. Each group included 11 participants. Some of the results are unobtainable from the figures in the report, and only results stated in the text could be used. The study lasted 4 weeks. The study has not been included in the meta-analyses as the mode of application was different from all other studies.

SteroidVehicleAzole

Total clearance18.2% to 45.5% (in different application groups)9.1%9.1%

Erythema scores¹0.1 in clobetasol 5-minute group; otherwise, not reported (P value = 0.024 for comparison with vehicle)0.70.1

Scaling scores (loose desquamation)²0.3 in clobetasol 10-minute group, and 0.4 in clobetasol 5-minute group; otherwise, not reported (P value = 0.027 for comparison between clobetasol 10-minute group and vehicle group)1.0Not reported

Pruritus score- 4.8 mm in clobetasol 5-minute group; otherwise, not reported (P value = 0.007 for comparison with vehicle)- 34 mm- not reported in text (8.9 mm approximated from figure)

Any adverse effects1 participant (9%) in all groups experienced burning. 1 participant in clobetasol 10-minute group reported dry skin. 1 participant in clobetasol 5-minute group reported folliculitis1 participant (9%) experienced burning. Eczema was reported in 1 person1 participant (9%) experienced burning

 ¹Outcome "erythema scores" refers to erythema scores at end of study. A lower score relates to a better treatment effect.
²Outcome "scaling scores" refers to scaling scores at end of study. A lower score relates to a better treatment effect.