Skin disorders. Seborrhoeic dermatitis Search date February 2007 Juan Jorge Manriquez and Pablo Uribe ...

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1 Search date February 27 Juan Jorge Manriquez and Pablo Uribe ABSTRACT INTRODUCTION: affects at least 1 3% of the population. Malassezia (Pityrosporum) ovale is thought to be the causative organism, and causes inflammation involving T cells and complement. tends to relapse after treatment. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of topical treatments for seborrhoeic dermatitis of the scalp in adults? What are the effects of topical treatments for seborrhoeic dermatitis of the face and body in adults? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 26 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: bifonazole, emollients, ketoconazole, lithium succinate, selenium sulphide, tar shampoo, terbinafine, and topical steroids (betamethasone valerate, clobetasol propionate, clobetasone butyrate, hydrocortisone, mometasone furate). QUESTIONS What are the effects of topical treatments for seborrhoeic dermatitis of the scalp in adults? What are the effects of topical treatments for seborrhoeic dermatitis of the face and body in adults? TOPICAL TREATMENTS FOR SEBORRHOEIC DER- MATITIS OF SCALP Beneficial Ketoconazole Likely to be beneficial Bifonazole Corticosteroids (topical) (hydrocortisone, betamethasone valerate, clobetasone butyrate, mometasone furoate, clobetasol propionate)* Selenium sulphide Tar shampoo INTERVENTIONS Likely to be beneficial Bifonazole Corticosteroids (topical) (hydrocortisone, betamethasone valerate, clobetasone butyrate, mometasone furoate, clobetasol propionate; short term episodic treatment in adults)* Unknown effectiveness Emollients Lithium succinate Selenium sulphide Terbinafine Unknown effectiveness Terbinafine TOPICAL TREATMENTS FOR SEBORRHOEIC DER- MATITIS OF FACE OR BODY Beneficial Ketoconazole To be covered in future updates Combination agents Oral antifungal agents Topical calcineurin inhibitors Footnote *Based on consensus. Key points affects at least 1 3% of the population and causes red patches with greasy scales on the face, chest, skin flexures, and scalp. The cause of seborrhoeic dermatitis is unknown. Malassezia yeasts are considered to have an important role producing an inflammatory reaction involving T cells and complement. Known risk factors include immunodeficiency, neurological or cardiac disease, and alcoholic pancreatitis. In this review, however, we deal with treatment in immunocompetent adults who have no known predisposing conditions. tends to relapse after treatment. In adults with seborrhoeic dermatitis of the scalp, antifungal preparations containing ketoconazole improve symptoms compared with placebo. Bifonazole and selenium sulphide are also likely to be effective, but we don't know whether terbinafine is beneficial as no studies have been found. BMJ Publishing Group Ltd 27. All rights reserved Clinical Evidence 27;7:1713

2 There is consensus that topical corticosteroids are effective in treating seborrhoeic dermatitis of the scalp in adults, although no studies have been found. Tar shampoo may reduce scalp dandruff and redness compared with placebo. In adults with seborrhoeic dermatitis of the face and body, short courses of topical corticosteroids are considered to be effective if used episodically, although no studies have been found that assessed this. Ketoconazole cream or gel and bifonazole cream may improve skin symptoms compared with placebo. We don't know whether terbinafine or selenium sulphide are also beneficial as no studies have been found. We don't know whether emollients or topical lithium succinate improve lesions compared with no treatment. DEFINITION INCIDENCE/ PREVALENCE occurs in areas of the skin with a rich supply of sebaceous glands and manifests as red, sharply marginated lesions with greasy looking scales. On the face it mainly affects the medial aspect of the eyebrows, the area between the eyebrows, and the nasolabial folds. It may also affect the skin on the chest (commonly presternal) and the flexures. On the scalp it manifests as dry, flaking desquamation (dandruff) or yellow, greasy scaling with erythema. Dandruff is a lay term commonly used in the context of mild seborrhoeic dermatitis of the scalp. However, any scalp condition that produces scales could be labelled as dandruff. There is also an infantile variant, commonly affecting the scalp, flexures, and genital area, but this infantile variant seems to have a different pathogenesis than adult seborrhoeic dermatitis. Common differential diagnoses for seborrhoeic dermatitis of the scalp are psoriasis, eczema (see review on atopic eczema), and tinea capitis (see table 1, p 9 ). is estimated to affect around 1 3% of the general population. [1] However, this is likely to be an underestimate because people do not tend to seek medical advice for mild dandruff. AETIOLOGY/ The cause of seborrhoeic dermatitis is unknown and seems to be a multifactorial disease. Malassezia RISK FACTORS yeasts, a genus classified in seven species, are considered to have an important role in seborrhoeic dermatitis producing an inflammatory reaction involving T cells and complement. Conditions that have been reported to predispose to seborrhoeic dermatitis include human immunodeficiency virus, [2] neurological conditions such as Parkinson's disease, neuronal damage such as facial nerve palsy, [3] spinal injury, [4] ischaemic heart disease, [5] and alcoholic pancreatitis. [6] In this review, we deal with treatment in immunocompetent adults who have no known predisposing conditions. PROGNOSIS is a chronic condition that tends to flare and remit spontaneously, and is [1] [7] prone to recurrence after treatment. AIMS OF To reduce the symptoms and signs of seborrhoeic dermatitis with minimal adverse effects. Most INTERVENTION therapeutic options aim to reduce colonisation with Malassezia spp and reduce inflammation, although they tend to palliate rather than cure. OUTCOMES METHODS Severity of symptoms, including itching, scale, and erythema; adverse effects of treatment. BMJ Clinical Evidence search and appraisal February 27. Most authors have used the term dandruff to mean seborrhoeic dermatitis of the scalp. If there was any doubt about the diagnosis the study was excluded. The following databases were used to identify studies for this systematic review: Medline 1966 to February 27, Embase 198 to February 27, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 27, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for evaluation in this review were: published systematic reviews and RCTs in any language. RCTs had to be double blinded and contain 2 or more individuals. Trials of less than 4 weeks' duration had to have at least 9% follow up; trials lasting 4 weeks or longer had to have at least 8% follow up. Trials of less than 1 week were excluded. We use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table, p 11 ). BMJ Publishing Group Ltd 27. All rights reserved

3 QUESTION What are the effects of topical treatments for seborrhoeic dermatitis of the scalp in adults? OPTION KETOCONAZOLE SCALP PREPARATIONS Compared with placebo Ketoconazole shampoo is more effective than placebo at improving scalp symptoms such as scaling, itching, redness, and dandruff at 4 weeks in people with seborrhoeic dermatitis of the scalp (moderatequality evidence). Ketoconazole shampoo versus placebo: We found no systematic reviews. We found five RCTs ranging in size from 2 to 246 participants. [8] [9] [1] [11] [12] All found improvements in symptoms with ketoconazole 2% shampoo after 4 weeks compared with placebo (see table 2, p 1 ). Ketoconazole shampoo versus placebo: Four of the five RCTs reported that there were no adverse effects of treatment. [8] [9] [1] [11] The fifth RCT reported one instance of scalp tenderness that was probably related to ketoconazole treatment. [12] OPTION BIFONAZOLE SCALP PREPARATIONS Compared with placebo Bifonazole shampoo may be more effective than placebo at improving symptoms such as scaling and pruritus, and overall symptom severity at six weeks in people with seborrhoea or seborrhoeic dermatitis of the scalp (low-quality evidence). Bifonazole shampoo versus placebo: We found no systematic review. We found one RCT which compared bifonazole 1% shampoo versus placebo. [13] It found that bifonazole 1% shampoo significantly improved scalp symptoms (severity of scaling, pruritus, and overall severity graded by a clinician on a 3 point scale from = none to 3 = severe) compared with placebo after 6 weeks (51 people with seborrhoea or seborrhoeic dermatitis of the scalp; scaling: P =.1; pruritus: P =.8; overall severity: P =.12). Bifonazole shampoo versus placebo: The RCT reported no major side effects. [13] OPTION SELENIUM SULPHIDE SCALP PREPARATIONS Compared with placebo Selenium sulphide shampoo is more effective than placebo at reducing dandruff, and at increasing response to treatment at 29 days, in people with moderate to severe dandruff (moderate-quality evidence). Selenium sulphide shampoo versus placebo: We found no systematic reviews. We found one RCT which compared three treatments randomised in a 2 : 2 : 1 ratio: selenium sulphide 2.5% shampoo (1 people); ketoconazole 2% shampoo (97 people); and placebo (49 people). [11] It found significantly greater reductions in mean adherent dandruff scores (determined by visual examination of six scalp areas, in which = none and 9 1 = severe/heavy) with selenium sulphide shampoo compared with placebo over 29 days (people with moderate to severe dandruff; percentage reduction in adherent dandruff scores from baseline: 66.7% with selenium sulphide v 44.5% with placebo; P value not reported). It also found that significantly more people responded to treatment (global improvement of completely cleared, excellent, or good) with selenium sulphide shampoo than with placebo at 29 days (AR for responding to treatment: 54.7% with selenium sulphide v 28.6% with placebo; P =.4). BMJ Publishing Group Ltd 27. All rights reserved.... 3

4 Selenium sulphide shampoo versus placebo: The RCT reported infrequent adverse events with selenium sulphide shampoo, including pruritus or burning sensation of the scalp (3 people), eruption near the hair line (1 person), psoriasis (1 person), lightening/bleaching of hair colour (2 people), orange staining of the scalp (1 person), and a chemical taste during shampooing (1 person). [11] OPTION TAR SHAMPOO Compared with placebo Tar shampoo is more effective than placebo at improving dandruff and redness at 29 days in people with seborrhoeic dermatitis or dandruff (moderate-quality evidence). For GRADE evaluation of seborrhoeic dermatitis, see table, p 11. OPTION Tar shampoo versus placebo: We found no systematic reviews. We found one RCT which compared tar shampoo (4% coal tar) versus placebo. [12] It found that, compared with placebo, tar shampoo significantly improved both dandruff (dandruff score, assessed by a technician by multiplying size of affected area by severity; size of affected area scored from = 1% to 4 = > 7%; severity scored from 1 = small flakes resembling a white powder to 5 = flakes adhering to the scalp as white or yellow plates) and redness (graded by a clinician on a 5 point scale from = none to 4 = very severe) after 29 days (111 people with seborrhoeic dermatitis or dandruff; mean reduction in dandruff score from baseline: 31 with tar shampoo v 19 with placebo, P <.1; mean difference in redness from baseline: 1.2 with tar shampoo v.6 with placebo, P <.5). There was no significant difference in scaling or area of seborrhoeic dermatitis after 29 days between tar shampoo and placebo. Tar shampoo versus placebo: The RCT reported no major adverse events. [12] TOPICAL CORTICOSTEROIDS (HYDROCORTISONE, BETAMETHASONE VALERATE, CLO- BETASONE BUTYRATE, MOMETASONE FUROATE, CLOBETASOL PROPIONATE) We found no direct information about whether topical corticosteroids (hydrocortisone, betamethasone valerate, clobetasone butyrate, mometasone furoate, or clobetasol propionate) are better than no active treatment for seborrhoeic dermatitis of the scalp in adults. There is consensus that topical corticosteroids are effective in treating seborrhoeic dermatitis of the scalp in adults. Topical corticosteroids versus placebo: We found no systematic review or RCTs comparing topical corticosteroids (hydrocortisone, betamethasone valerate, clobetasone butyrate, mometasone furoate, or clobetasol propionate) versus placebo for seborrhoeic dermatitis of the scalp in adults. Topical corticosteroids versus placebo: We found no RCTs. Although no systematic reviews or RCTs were identified, there is consensus that topical corticosteroids are effective in treating seborrhoeic dermatitis of the scalp in adults. Betamethasone valerate scalp application in a lotion or mousse is routinely used in practice by dermatologists. OPTION TERBINAFINE SCALP PREPARATIONS We found no direct information about whether terbinafine is better than no active treatment in adults with seborrhoeic dermatitis of the scalp. Terbinafine versus placebo: We found no systematic review or RCTs (see comment below). Terbinafine versus placebo: We found no RCTs (see comment below). BMJ Publishing Group Ltd 27. All rights reserved.... 4

5 QUESTION Terbinafine versus placebo: Terbinafine is not manufactured as a scalp preparation in the UK and is not known to be available worldwide. What are the effects of topical treatments for seborrhoeic dermatitis of the face and body in adults? OPTION KETOCONAZOLE Compared with placebo Ketoconazole may be more effective than placebo at increasing the number of people successfully treated, and at improving symptoms such as erythema, scaling, papules, and pruritus, at 4 weeks (lowquality evidence). Ketoconazole versus placebo: We found no systematic review. We found two small RCTs that compared ketoconazole 2% cream versus placebo [8] [14] and one large RCT that compared ketoconazole 2% gel versus placebo. [15] The first small RCT found that ketoconazole 2% cream improved symptoms (according to a composite clinical score in which 8 sites were graded for erythema, scaling, papules, and pruritus; range not given) compared with placebo after 4 weeks (37 people with seborrhoeic dermatitis; reduction in approximate mean sum of symptom scores from baseline [see comment below]: 19 with ketoconazole cream v 13 with placebo; P value not reported). [14] The second small RCT compared ketoconazole 2% cream plus ketoconazole 2% shampoo versus placebo. [8] It found that ketoconazole 2% cream improved facial symptoms (severity of symptoms graded on a 4 point scale from = none to 3 = severe) compared with placebo after 4 weeks (2 people with seborrhoeic dermatitis of the face, with or without seborrhoeic dermatitis of the scalp, chest, or back [see comment below]; AR for improving by at least one symptom grade from baseline: 9% [9/1] with ketoconazole v % [/1] with placebo; P value not reported). [8]. The third large RCT compared a once daily 2 week course of ketoconazole 2% gel versus placebo (vehicle gel) in people with seborrhoeic dermatitis. [15] Successful treatment was defined as both an erythema and scaling score of (none) if the baseline score was 2 or less (moderate) or a score of 1 or less (mild) if the baseline score was 3 (severe) based on a 4 point scale for erythema and scaling, and an Investigator's Global Assessment score of (clear) or 1 (almost clear), based on a 5 point scale measured at day 28. The RCT found that a significantly greater proportion of subjects were successfully treated with ketoconazole 2% gel compared with placebo after 4 weeks (459 people with seborrhoeic dermatitis; percentage of subjects successfully treated, intention to treat analysis: 25.3% [58/229] with ketoconazole v 13.9% [32/23] with placebo; P value =.14). [15] Ketoconazole versus placebo: Two of the RCTs reported that there were no adverse effects of treatment. [8] [14] One RCT found that there were mild or moderate adverse effects similarly distributed between treatment groups. [15] The RCT reported that treatment related adverse effects in 1% or more of subjects were application site burning (2.6% with ketoconazole gel v 2.6% with placebo gel), erythema (1.7% v 1.3%), and application site reaction (.4% v 1.7%; between group statistical analysis not reported). [15] Ketoconazole versus placebo: Approximate mean scores were extracted from graphs because data were not tabulated. [14] Of the 2 people with seborrhoeic dermatitis of the face, 16 (8%) also had seborrhoeic dermatitis of the scalp, seven (35%) had chest involvement, and five (25%) had back involvement. [8] OPTION BIFONAZOLE Compared with placebo Bifonazole cream may be more effective than placebo at improving symptoms and response to treatment at 4 weeks in people with seborrhoeic dermatitis of the face (low-quality evidence). Bifonazole versus placebo: We found no systematic review. We found one RCT which compared bifonazole 1% cream versus placebo. [16] It found that significantly more people responded to treatment (global improvement graded on a 4 point scale from = no improvement or worsening to 3 = healing) with bifonazole compared with placebo at 4 weeks (1 people with seborrhoeic dermatitis of the face; AR for healing: 16/37 [43%] with bifonazole v 1/43 [23%] with placebo; AR for improvement: 2/37 [54%] BMJ Publishing Group Ltd 27. All rights reserved.... 5

6 OPTION with bifonazole v 26/43 [61%] with placebo; AR for treatment failure: 1/37 [3%] with bifonazole v 7/43 [16%] with placebo; overall P value =.44; P values for individual outcomes not reported). Bifonazole versus placebo: The RCT reported more minor adverse effects of treatment (including itch, burning, tightness, erythema, papules, and scaling) with bifonazole than with placebo (5/5 [1%] with bifonazole v 2/5 [4%] with placebo; P value not reported). [16]. TOPICAL CORTICOSTEROIDS (HYDROCORTISONE, BETAMETHASONE VALERATE, CLO- BETASONE BUTYRATE, MOMETASONE FUROATE, CLOBETASOL PROPIONATE) We found no direct information about whether topical corticosteroids (hydrocortisone, betamethasone valerate, clobetasone butyrate, mometasone furoate, or clobetasol propionate) are better than no active treatment for seborrhoeic dermatitis of the scalp in adults.there is consensus that short courses of topical corticosteroids used episodically are effective in treating seborrhoeic dermatitis of the face and body in adults. Topical corticosteroids versus placebo: We found no systematic review or RCTs comparing topical corticosteroids (hydrocortisone, betamethasone valerate, clobetasone butyrate, mometasone furoate, or clobetasol propionate) versus placebo in adults with seborrhoeic dermatitis of the face and body. Topical corticosteroids versus placebo: We found no RCTs. Although we found no RCTs of topical corticosteroids in adults with seborrhoeic dermatitis of the face or body, consensus regards their use as effective. It is current practice to use short courses of topical corticosteroids episodically in seborrhoeic dermatitis. Affected areas of the body are treated with short courses of potent topical corticosteroids (betamethasone valerate [.1%], mometasone furoate [.1%]) while the face is treated with short courses of moderate (clobetasone butyrate [.5%]) or low potency (hydrocortisone [1%]) corticosteroids. OPTION EMOLLIENTS We found no direct information about whether emollients are better than no active treatment in adults with seborrhoeic dermatitis of the face and body. Emollients versus no treatment: We found no systematic review or RCTs of sufficient quality comparing emollients versus no treatment in adults with seborrhoeic dermatitis of the face and body. Emollients versus no treatment: We found no RCTs. OPTION LITHIUM SUCCINATE Compared with placebo Lithium succinate cream may be more effective than placebo at improving overall clinical impression, severity of redness, scaling, and greasiness in adults with seborrhoeic dermatitis of the face and body (very low-quality evidence). Lithium succinate versus placebo: We found no systematic review or RCTs of sufficient quality comparing lithium succinate versus placebo in adults with seborrhoeic dermatitis of the face and body (see comment below). Lithium succinate versus placebo: We found no RCTs of sufficient quality. BMJ Publishing Group Ltd 27. All rights reserved.... 6

7 We found one crossover RCT (3 people with seborrhoeic dermatitis of the face and/or the trunk) which compared lithium succinate 8% cream versus placebo. [17] It found that lithium succinate significantly improved symptoms (graded on a 1 mm scale on severity of redness, scaling, greasiness, and overall clinical impression of the condition) compared with placebo (results not pre-crossover). However, these results should be interpreted with caution because of the potential for persistence of effects after crossover. The RCT also had a high withdrawal rate (37%) and it is not clear whether the analyses were conducted on an intention to treat basis. Withdrawals were due to non-compliance (2 people with lithium succinate, 3 with placebo), local stinging sensation and erythema (1 person with lithium succinate, 2 with placebo), worsening of acne vulgaris (1 person with lithium succinate, 1 with placebo), or resolution of lesions (1 person, group not reported). OPTION SELENIUM SULPHIDE We found no direct information about whether selenium sulphide is better than no active treatment in adults with seborrhoeic dermatitis of the face and body. Selenium sulphide versus placebo: We found no systematic review or RCTs. Selenium sulphide versus placebo: We found no RCTs. OPTION TERBINAFINE We found no direct information about whether terbinafine is better than no active treatment in adults with seborrhoeic dermatitis of the face and body. Terbinafine versus placebo: We found no systematic review or RCTs. Terbinafine versus placebo: We found no RCTs. GLOSSARY Low-quality evidence 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. Moderate-quality evidence Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Very low-quality evidence Any estimate of effect is very uncertain. SUBSTANTIVE CHANGES Ketoconazole (under question on topical treatments for seborrhoeic dermatitis of the face and body in adults) One large RCT added comparing ketoconazole gel versus placebo; [15] benefits and harms data enhanced, recategorised from Unknown effectiveness to Beneficial. Selenium sulphide (under question on topical treatments for seborrhoeic dermatitis of the scalp in adults) Evidence re-evaluated, recategorised from Beneficial to Likely to be beneficial. REFERENCES 1. Gupta AK, Bluhm R, Cooper EA.. Dermatol Clin 23;21: [PubMed] 2. Berger RS. Cutaneous manifestations of early human immunodeficiency virus exposure. J Am Acad Dermatol 1988;19: [PubMed] 3. Bettley FR, Marten RH. Unilateral seborrhoeic dermatitis following a nerve lesion. Arch Dermatol 1956;73: Wilson CL, Walshe M. Incidence of seborrhoeic dermatitis in spinal injury patients. Br J Dermatol 1988;119(suppl 33): Tager A. in acute cardiac disease. Br J Dermatol 1964;76: [PubMed] 6. Barba A, Piubello W, Vantini I, et al. Skin lesions in chronic alcoholic pancreatitis. Dermatologica 1982;164: [PubMed] 7. Rook et al. Textbook of Dermatology, 6th ed. Blackwell and Synergy: Green CA, Farr PM, Shuster S. Treatment of seborrhoeic dermatitis with ketoconazole: II. Response of seborrhoeic dermatitis of the face, scalp and trunk to topical ketoconazole. Br J Dermatol 1987;116: [PubMed] 9. Carr MM, Pryce DM, Ive FA. Treatment of seborrhoeic dermatitis with ketoconazole: I. Response of seborrhoeic dermatitis of the scalp to topical ketoconazole. Br J Dermatol 1987;116: [PubMed] 1. Berger R, Mills OH. Double blind placebo-controlled trial of ketoconazole 2% shampoo in the treatment of moderate to severe dandruff. Adv Ther 199;7: Danby FW, Maddin WS, Margesson LJ. A randomised, double-blind, placebocontrolled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of moderate to severe dandruff. J Am Acad Dermatol 1993;29: [PubMed] BMJ Publishing Group Ltd 27. All rights reserved.... 7

8 12. Davies DB, Boorman GC, Shuttleworth D. Comparative efficacy of shampoos containing coal tar (4.% w/w; Tarmed TM ), coal tar (4.% w/w) plus ciclopirox olamine (1.% w/w; Tarmed TM AF) and ketoconazole (2.% w/w; Nizoral ) for the treatment of dandruff/seborrhoeic dermatitis. J Dermatol Treat 1999;1: Segal R, David A, Ingber R, et al. Treatment with bifonazole shampoo for seborrhoea and seborrhoeic dermatitis: a randomised, double blind study. Acta Derm Venereol (Stockh) 1992;72: Skinner RB, Noah PW, Taylor RM, et al. Double-blind treatment of seborrheic dermatitis cream with 2% ketoconazole cream. J Am Acad Dermatol 1985;12: [PubMed] 15. Elewski B, Ling MR, Phillips TJ. Efficacy and safety of a new once-daily topical ketoconazole 2% gel in the treatment of seborrheic dermatitis: a phase III trial. J Drugs Dermatol 26;5: [PubMed] 16. Zienicke H, Korting HC, Braun-Falco O, et al. Comparative efficacy and safety of bifonazole 1% cream and the corresponding base preparation in the treatment of seborrhoeic dermatitis. Mycoses 1993;36: [PubMed] 17. Cuelenaere C, De Bersaques J, Kint A. Use of topical lithium succinate in the treatment of seborrhoeic dermatitis. Dermatology 1992;184: [PubMed] Juan Jorge Manríquez Unidad Docente Asociada de Dermatologia School of Medicine, Pontificia Universidad Catolica de Chile Santiago Chile Pablo Uribe Unidad Docente Asociada de Dermatologia School of Medicine, Pontificia Universidad Catolica de Chile Santiago Chile Competing interests: JM and PU declare that they have no competing interests. Disclaimer The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication. BMJ Publishing Group Ltd 27. All rights reserved.... 8

9 TABLE 1 Differential diagnoses for seborrhoeic dermatitis of the scalp (see text). Diagnosis Psoriasis Eczema (atopic and contact dermatitis) Tinea capitis Distinguishing features Prominent erythema Tendency for hair line involvement More prominent silver scale Presence of psoriasis elsewhere (skin, nails, joints) Atopic dermatitis: General skin examination History Contact dermatitis: Distribution of eczema History Microscopy Fungal culture of scalp scrapings BMJ Publishing Group Ltd 27. All rights reserved

10 [8] [9] [1] TABLE 2 RCTs comparing ketoconazole shampoo versus placebo for seborrhoeic dermatitis of the scalp (see antifungal scalp preparations, p 3 ). [11] [12] Trial details Ketoconazole (2% shampoo plus 2% cream) v placebo Crossover RCT comparing ketoconazole 2% shampoo v placebo (shampoo base without ketoconazole) Ketoconazole 2% shampoo v placebo (shampoo base without ketoconazole) Ketoconazole 2% shampoo v selenium sulphide 2.5% shampoo v placebo Ketoconazole 2% shampoo v coal tar 4.% plus ciclopirox olamine 1% shampoo v placebo VAS = visual analogue scale. Ref [8] [9] [1] [11] [12] Participants 2 people with seborrhoeic dermatitis of the face: 8% had seborrhoeic dermatitis of the scalp, 35% had chest involvement, and 25% had back involvement 2 people (16 male, 4 female) with either dandruff or seborrhoeic dermatitis (no distinction made between these; proportion with seborrhoeic dermatitis not reported) 53 people with moderate to severe dandruff, 28 [52.8%] of whom had seborrhoeic dermatitis 246 people with moderate to severe dandruff 163 people with seborrhoeic dermatitis or dandruff Outcome Clinician rated scalp scaling ( = none to 3 = severe): AR for improvement in scaling at 4 weeks: 86% (6/7) with ketoconazole v % (/9) with placebo (P value not reported) Participant rated scalp scaling (1 mm VAS from = none to 1 = severe): Scalp scaling improved significantly more at 4 weeks with ketoconazole than with placebo (scores shown graphically; P <.5) Participant rated scalp itching and scaling (1 mm VAS from = none to 1 = "worst ever"): Approximate median change in itch score at 4 weeks: 2 with ketoconazole v +8 with placebo (P value not reported) Approximate median change in scale score at 4 weeks: 2 with ketoconazole v +15 with placebo (P value not reported) (Median scores pre crossover approximated from graphs) Adherent dandruff score (six scalp areas assessed; = no scaling to 1 = extremely severe scaling): Mean change in score at day 15: 12 with ketoconazole v 7 with placebo (P <.5) Mean change in score at day 29: 19 with ketoconazole v 13 with placebo (P <.5) Response to treatment (global evaluation of completely cleared, excellent, or good): AR for responding to treatment at day 29: 78.6% (22/28) with ketoconazole v 37.5% (9/24) with placebo (P =.4) Adherent dandruff score (six scalp areas assessed; = none and 9 1 = severe/heavy): % Reduction in mean score from baseline at 29 days: 73.% with ketoconazole v 44.5% with placebo (P value not reported) Response to treatment (global evaluation of completely cleared, excellent, or good): AR for responding to treatment at day 29: 64.9% with ketoconazole v 28.6% with placebo (P <.1) Clinician rated scaling and redness ( = none to 4 = very severe): Mean reduction in scale score at 29 days: 1.2 with ketoconazole v.3 with placebo (P <.1) Mean reduction in redness score at 29 days: 1.3 with ketoconazole v.5 with placebo (P <.1) Area of scalp affected by seborrhoeic dermatitis: No significant difference between ketoconazole and placebo at 29 days (area and P value not reported). BMJ Publishing Group Ltd 27. All rights reserved.... 1

11 TABLE Important outcomes Number of studies (participants) GRADE evaluation of interventions for seborrhoeic dermatitis, adverse effects Outcome Comparison Type of evidence What are the effects of topical treatments for seborrhoeic dermatitis of the scalp in adults? [8] [9] [1] 5 (52) Ketoconazole shampoo v 4 1 [11] [12] placebo 1 (51) [13] Bifonazole v placebo (246) [11] 1 (111) [12] Selenium sulphide v placebo Tar shampoo v placebo 4 4 Quality 1 1 Consistency Directness Effect size GRADE Moderate Low Moderate Moderate Comment Quality point deducted for incomplete reporting of results Quality points deducted for sparse data and incomplete reporting of results Quality point deducted for incomplete reporting of results Quality point deducted for sparse data What are the effects of topical treatments for seborrhoeic dermatitis of the face and body in adults? [8] [14] 3 (516) Ketoconazole v placebo (1) [15] 1 (3) [17] Bifonazole cream v placebo Lithium succinate cream v placebo Low Low Very low Quality point deducted for incomplete reporting of results. Directness point deducted for no direct comparison between groups in two RCTs Quality points deducted for sparse data and incomplete reporting of results Quality points deducted for sparse data, incomplete reporting of results, no intention-to-treat analysis, poor follow-up, and uncertainty about results Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies. Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio. BMJ Publishing Group Ltd 27. All rights reserved