Optimizing Treatment Approaches in Seborrheic Dermatitis Goldenberg Gary, MD Additional article information Abstract Seborrheic dermatitis is a chronic, recurring, cutaneous condition that causes erythema and flaking, sometimes appearing as macules or plaues !ith dry !hite or moist oily scales" #n adults, it commonly occurs in areas !ith high concentrations of sebaceous glands" The face and scalp are the most freuently affected areas, and in$ol$ement of multiple sites is common" Dandruff is regarded as a mild noninflammatory form of seborrheic dermatitis" There is a high incidence of seborrheic dermatitis among persons !ith human immunodeficiency $irus infection or %arkinson&s disease" The cause of seborrheic dermatitis is not !ell understood, but appears to be related to the composition of the sebaceous gland secretions, the proliferation of Malessezia yeasts, and the host immune response" Treatment options for nonscalp and scalp seborrheic dermatitis include topical agents and shampoos containing antifungal agents, anti'inflammatory agents, keratolytic agents, and calcineurin inhibitors" (ecause multiple body sites are usually in$ol$ed, the physician should examine all commonly affected areas" %atients should be made a!are that seborrheic dermatitis is a chronic condition that !ill probably recur e$en after successful treatment" 1 Seborrheic dermatitis )SD*, a chronic, recurrent, inflammatory condition characteri+ed by erythema and skin flaking, may be resistant to treatment and often has a substantial negati$e impact on uality of life",-. #t affects approximately six million people in the /nited States and is associated !ith direct and indirect medical costs of approximately 01.2 million per year"3 Although the causes of SD are not completely understood, progress has been made in this area, and se$eral effecti$e treatment options are a$ailable" This article !ill re$ie! the clinical presentation of SD and the current understanding of its etiology and discuss currently a$ailable treatment options" 2 CLINICAL PRESENTATION Seborrheic dermatitis may appear as macules or thin plaues !ith a reddish or yello! appearance and dry !hite or moist oily scales"4 #n adults, it most often occurs in areas !ith a high concentration of sebaceous glands, including the face, scalp, ears, chest, and body folds"4 #t usually affects multiple body areas, occurring on the face in 55 percent of patients, the scalp in 62 percent, the chest in 16 percent, and the arms or legs in , to 1 percent". #n more than half of patients !ith facial SD, the scalp is affected as !ell". 7n the face, SD commonly occurs in the nasolabial folds, eyebro!s, anterior hairline, and glabella",,8 7n the scalp, the lesions may range from mild desuamation to bro!nish crusts affixed to the skin and hair"4 9esions on the central chest may ha$e a petaloid appearance"6 Some patients report pruritus, particularly if the scalp is affected"1,4,8 #t generally is not accompanied by papules or pustules"1Secondary bacterial infection may occur, aggra$ating erythema and exudate and causing local discomfort"4 #n adults, SD is a chronic, recurrent condition marked by periods of exacerbation occurring at $ariable inter$als"8 %atients may report that outbreaks are triggered by emotional stress, depression, fatigue, exposure to air conditioning or damp or dry conditions in the !orkplace, systemic infections, use of certain medications, or other factors". The infantile form of SD is a self'limited condition generally resol$ing by age three or four months"8 The adult form usually appears first around the time of puberty, !hen sebaceous glands become more acti$e, sometimes lasting until young 3 adulthood", The condition increases again in pre$alence after age 42", #t affects approximately , to 4 percent of immunocompetent adults and as many as 12 to 5. percent of human immunodeficiency $irus ):#;*'positi$e indi$iduals"4,8 7ther populations at risk include persons !ith %arkinson&s disease or other neurological disorders, mood disorders, significant life stress, or lo! exposure to sunlight"1 More men than !omen ha$e SD, but it sho!s no preference for any racial or ethnic group"8 #t may occur in association !ith atopic dermatitis or other skin disorders, complicating its diagnosis"5 Some contro$ersy has surrounded the relationship bet!een SD and dandruff" Most authors no! agree that dandruff is a mild, noninflammatory form of SD"1,8,< Dandruff is extremely common, !ith a pre$alence as high as 42 percent of the population"1 CAUSES OF SEBORREIC DER!ATITIS Although the causes of SD are not completely understood, it appears to result from a combination of the follo!ing three factors= sebaceous gland secretion, presence ofMalassezia yeast, and the host immune response"8 Sebum is an important component of skin surface lipids and contains high amounts of sualene, !ax esters, and triglycerides",2 %ersons !ith SD do not necessarily ha$e excess sebaceous gland acti$ity, but the composition of their skin surface lipid may be altered, creating a more supporti$e en$ironment for gro!th of lipid' dependent micro'organisms",2 4 The role of Malassezia yeasts in SD is some!hat contro$ersial, although most researchers belie$e they play an important role"< Malassezia yeasts are normally commensal species found primarily in follicular infundibula and commonly isolated from sebum'rich areas of the body, such as the face, scalp, trunk, and back",, They produce abundant lipases that hydroly+e triglycerides and free saturated fatty acids on !hich the yeast is dependent",1 These fatty acids may ha$e irritant effects that induce scaling or may cause release of arachidonic acid, !hich promotes inflammation in skin"< There are se$en primary species= M. globosa, M. restricta, M. obtusa, M. sloojjiae, M. sympodialis, M. jurjur, and M. pachydermatis )the last occurs only on animals*"< M. globosa and M. restricta are thought to be the species most commonly associated !ith SD, although M. jurjur and other species ha$e also been implicated"<,,.,,3 Some studies ha$e found high numbers of Malassezia yeasts on the scalp of persons !ith SD, but others ha$e found no difference in the density of these yeasts bet!een the skin of persons !ith SD and that of persons !ithout it", Differing sampling methods may contribute to these contradictory findings" Malassezia exist not only on the skin surface, but also !ithin the layers of the stratum corneum, and a true count !ould reuire examining the full thickness of the skin suama", Support for the role of Malassezia in SD comes from studies demonstrating that use of $arious antifungal treatments results in reduction of Malassezia, !hich is accompanied by impro$ement in symptoms"8,< The role of the host immune response in the pathogenesis of SD is uncertain" Some researchers ha$e reported increased numbers of natural killer cells, CD,8 cells, and 5 inflammatory interleukins and acti$ation of complement in the lesional skin of patients !ith SD compared !ith their o!n nonlesional skin or the skin of healthy controls"8 >e$ertheless, total antibody le$els are no higher in SD patients than in controls and a host response specific to Malassezia yeasts has not been identified"<The pre$alence of SD in persons infected !ith :#; suggests that the condition is mediated by the immune system? ho!e$er, the response of SD to successful retro$iral therapy is $ariable"4 Thus, a definiti$e understanding of the pathophysiology of SD a!aits further research, but the role of Malassezia yeasts as causati$e or contributing agents appears to be !ell established" DIA"NOSIS The differential diagnosis of SD should include psoriasis, rosacea, Demodex dermatitis, atopic ec+ema, pityriasis $ersicolor, contact dermatitis, and tinea infections"1 SD may also resemble 9angerhans cell histiocytosis or secondary syphilis"1,4 The diagnosis is usually clinical, but candidiasis, tinea infection, and Demodex dermatitis may be ruled out !ith a negati$e potassium hydroxide test"1 #t should be kept in mind that SD may be accompanied by other dermatological disorders" Care should be taken to differentiate SD from psoriasis $ulgaris",4 @arly SD has a spongiform appearance that distinguishes it from psoriasis, but in later stages these conditions are more difficult to tell apart" Some patients present !ith sebopsoriasis, 6 !hich includes features of both disease states"1 9esions on the elbo!s or knees and nail pitting suggest psoriasis, !hich may spare the face",4 TREAT!ENT The primary goals of therapy for SD are to clear the $isible signs of disease and reduce bothersome symptoms, especially pruritus"8 (ecause the face and scalp are the most commonly affected areas, itching or redness on the scalp in a patient !ith facial SD indicates the need for treatment at both sites". %atients should be informed that SD is a chronic, relapsing condition and that they should anticipate future outbreaks",8 %atients should also be ad$ised to a$oid triggers of SD symptoms to the extent possible and not to irritate the lesions by excessi$e scratching or use of potent keratolytic preparations",8,,6 NONSCALP SEBORREIC DER!ATITIS Antifungal agents, anti'inflammatory agents, and keratolytic agents are a$ailable in a $ariety of formulations for treatment of SD on areas other than the scalp" Table , lists commonly used treatments for nonscalp SD and indicates the le$el of e$idence that supports their use" TA(9@ , Treatments for nonscalp seborrheic dermatitis 7 Antifungal agents. Aith the understanding of the role of Malassezia in SD, antifungal agents ha$e taken on an important role in its treatment" Betocona+ole 1C cream applied t!ice daily for four !eeks has been sho!n to be as effecti$e as hydrocortisone ,C cream in treatment of SD at multiple body sites",5 #n a randomi+ed, double'blind trial of 34< patients !ith SD treated !ith ketocona+ole 1C gel or $ehicle once daily for ,3 days, there !as a significantly higher rate of successful treatment )14".C $s" ,."<C,PD2"22,3* and significantly greater reductions in erythema, pruritus, and scaling in ketocona+ole'treated patients",< A 1C foam formulation of ketocona+ole has been sho!n to be significantly more effecti$e than $ehicle for treatment of SD on the face, scalp, and body, and eually as effecti$e as ketocona+ole 1C cream"12 Ciclopiroxolamine ,C cream, t!ice daily for 15 days follo!ed by once daily for 15 days, !as compared !ith $ehicle for the treatment of SD in a randomi+ed, doubleblind trial that enrolled ,1< patients"1, At the end of the maintenance phase, complete disappearance of erythema and scaling !as found in 8. percent of the ciclopiroxolamine'treated group and .3 percent of the $ehicle'treated group )PE2"226*"1, #n an open'label study of sertacona+ole nitrate 1C cream, 4< percent of 12 subFects !ith mild'to'se$ere SD !ere successfully treated, !ith impro$ements in scaling, erythema, induration, and pruritus"11 8 A randomi+ed, double'blind study demonstrated that metronida+ole 2"64C gel is as effecti$e as ketocona+ole 1C cream in treatment of facial SD, !ith a similar side effect profile"1. Gor patients !ith persistent SD resistant to topical agents, oral antifungals may be an option" 7ral itracona+ole gi$en in a dose of 122mgHday for one !eek, follo!ed by a maintenance dose, resulted in clinical impro$ement of SD symptoms in t!o open' label trials"13,14 Corticosteroids. :ydrocortisone and a !ide $ariety of other lo!' to mid'potency corticosteroids ha$e been used successfully in the treatment of SD" A double'blind study that compared hydrocortisone ,C cream !ith ketocona+ole 1C cream in 61 patients !ith mild'to'moderate SD found that the t!o agents produced similar rates of response and similar reductions in scaling, redness, itching, and papules"18 #n a ,1'!eek, single'blind, randomi+ed, comparati$e trial, hydrocortisone ,C ointment !as found to be eually as effecti$e as tacrolimus 2",C ointment in reducing the symptoms of facial SD by physician assessment, although tacrolimus !as superior by patient assessment"16 Combination antifungal/anti-inflammatory. %romisebI Topical Cream )%romius %harma, 99C, (ridge!ater, >e! Jersey* is a nonsteroidal prescription medical de$ice !ith anti'inflammatory and antifungal acti$ity appro$ed for treatment of SD"15 #n an in$estigator'blind, parallel'group study, 66 patients !ith mild or moderate SD of the face !ere randomi+ed to combination antifungalHanti' inflammatory cream or desonide 2"24C cream t!ice daily for up to 15 9 days"1< Se$erity of symptoms declined significantly from baseline to Day ,3 and Day 15 in both groups"1< Treatment !as successful )clear or almost clear* in 54 percent of patients using combination antifungalHanti'inflammatory cream and <1 percent of patients using desonide cream )PDnot significant* and the t!o products had similar safety profiles"1< Calcineurin inhibitors. Topical calcineurin inhibitors ha$e immunomodulatory and anti'inflammatory properties that make them useful in the treatment of SD"16 Tacrolimus 2",C ointment !as found to be as effecti$e as hydrocortisone ,C ointment in the treatment of SD, reuired fe!er applications during the ,1'!eek study period because of clearing of symptoms, and !as rated more fa$orably by patients"16 #n a randomi+ed, open'label trial, pimecrolimus ,C cream !as compared !ith betamethasone 2",C cream in 12 patients !ith SD !ho !ere instructed to discontinue treatment !hen symptoms cleared".2 (y Day <, all patients had discontinued treatment".2 The t!o drugs !ere eually effecti$e at reducing symptoms of erythema, scaling, and pruritus, but symptom relief !as sustained longer in the pimecrolimus group".2 #n comparati$e trials, pimecrolimus ,C cream has been sho!n to be as effecti$e as hydrocortisone ,C cream and ketocona+ole 1C cream in the treatment of SD, !ith higher rates of ad$erse effects".,,.1 %imecrolimus ,C cream !as found to be significantly more effecti$e for treatment of facial SD than methylprednisolone 2",C cream or metronida+ole 2"64C 10 gel !hen applied t!ice daily for eight !eeks, !ith fe!er ad$erse effects and a lo!er rate of recurrence than metronida+ole".. SCALP SEBORREIC DER!ATITIS Seborrheic dermatitis of the scalp is most con$eniently treated !ith shampoos containing antifungal agents, corticosteroids, or keratolytic agents? products are also a$ailable that combine drugs from these different classes" Table 1 lists commonly used treatments for SD of the scalp and indicates the le$el of e$idence that supports their use" TA(9@ 1 Treatments for seborrheic dermatitis of the scalp Antifungal shampoos. Betocona+ole 1C shampoo !as compared !ith selenium sulfide 1"4C shampoo in a four'!eek, randomi+ed, double'blind trial of patients !ith moderate'to'se$ere dandruff".3 T!ice'!eekly use of either shampoo !as superior to placebo, but not significantly different from each other".3 There !as a significantly higher incidence of ad$erse effects among patients using selenium sulfide shampoo".3 Ciclopirox ,C shampoo used once or t!ice !eekly for four !eeks !as sho!n to be superior to $ehicle for treatment of SD in a randomi+ed, double'blind, controlled 11 study that recruited <3< patients".4 Subseuent prophylactic use of ciclopirox shampoo once !eekly or once e$ery t!o !eeks reduced the relapse rate".4 Ciclopirox shampoo and ketocona+ole shampoo !ere compared in a double'blind study of .42 patients !ith SD".8 The t!o treatments !ere eually effecti$e and both better than placebo, although patients rated the ciclopirox shampoo more fa$orably".8 Corticosteroid shampoos. #n a randomi+ed, single'blind study of .18 subFects !ith moderate'to'se$ere scalp SD, clobetasol propionate 2"24C shampoo t!ice !eekly for four !eeks produced a significantly greater reduction in symptoms than ketocona+ole 1C shampoo".6 Alternating use of clobetasol shampoo and ketocona+ole shampoo !as also superior to ketocona+ole shampoo alone".6 Combination products. %romisebI %lus Scalp Aash )%romius %harma, 99C* contains surfactants and skin conditioning agents, !hich remo$e excess sebum as !ell as lactoferrin and piroctone olamine, !hich may reduce the proliferation ofMalassezia".5 #n an open'label trial, 14 subFects !ith SD used this proprietary !ash an a$erage of t!ice !eekly for t!o !eeks".5 All 14 had a positi$e response and more than <2 percent reported impro$ement in seborrhea, dandruff, pruritus, and redness".5 #n a single'blind study, a shampoo containing ciclopiroxolamine ,"4C and salicylic acid .C !as sho!n to ha$e efficacy similar to that of ketocona+ole 1C shampoo for 12 the treatment of dandruffHSD".< Gor both groups, impro$ement !as sustained for ,3 days after treatment ended".< A shampoo containing ciclopiroxolamine ,"4C and +inc pyrithione ,C !as found to be as effecti$e as ketocona+ole 1C foaming gel in a single'blind study of ,5< patients !ith scalp SD, !ith a greater reduction in pruritus during the early treatment phase and more fa$orable ratings from patients"32 Keratolytic products. A randomi+ed, double'blind study compared a shampoo containing lipohydroxy acid 2",C and salicylic acid ,".C !ith a shampoo containing ciclopiroxolamine ,"4C and salicylic acid .C in ,22 subFects !ith scalp SD"3, After four !eeks of treatment, the tolerance, global efficacy, and cosmetic effects of the lipohydroxy acid shampoo !ere significantly superior to those of the ciclopiroxolamine shampoo"3, A topical solution of urea, propylene glycol, and lactic acid, applied daily for four !eeks then three times per !eek for four !eeks, !as compared !ith placebo for treatment of mild'to'se$ere SD of the scalp"31 @rythema and desuamation !ere impro$ed at Aeeks 1 and 3, but the impro$ements !ere not maintained at eight !eeks"31 CONCLUSION Seborrheic dermatitis is a common, chronic, inflammatory cutaneous condition characteri+ed by erythema and skin flaking that tends to recur e$en after successful treatment and has a significant negati$e impact on uality of life" #ts occurrence 13 appears to be related to the proliferation of commensal Malassezia species" 7ccurrence at multiple body sites is common? the face and scalp are the most freuently affected areas" >umerous antifungal, anti'inflammatory, keratolytic, and immunomodulatory agents ha$e been sho!n to be effecti$e in the treatment of SD, but patients should be informed that recurrence is common and that ongoing treatment may be necessary" Footnotes DISCLOSURE: Dr# "o$%enberg reports no re$e&ant con'$icts o' interest# !an(script %e&e$opment )as s(pporte% b* Promi(s Pharma+ LLC# Artic$e in'ormation , C$in Aesthet Dermato$# Feb -./01 23-45 66768# P!CID5 P!C09:86;; "o$%enberg "ar*+ !D !o(nt Sinai Schoo$ o' !e%icine+ Department o' Dermato$og*+ Ne) <or=+ Ne) <or= Correspon%ing a(thor# ADDRESS CORRESPONDENCE TO: "ar* "o$%enberg+ !D+ 9 East 8;th St+ Bo> /.6;+ Ne) <or=+ N< /..-81 E?mai$5 "ar*go$%enbergm%@at@gmai$#com Cop*right notice Artic$es 'rom The ,o(rna$ o' C$inica$ an% Aesthetic Dermato$og* are pro&i%e% here co(rtes* o' Matrix Medical Communications REFERENCES ," (iko!ski J" Gacial seborrheic dermatitis= a report on current status and therapeutic hori+ons" J Drugs Dermatol" 122<?5)1*=,14-,.." 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J%ubMedK .2" Ligopoulos D, #oannides D, Balogeromitros D, et al" %imecrolimus cream ,C $s" betamethasone ,6'$alerate 2",C cream in the treatment of seborrhoeic dermatitis" A randomi+ed open'label clinical trial" (r J Dermatol" 1223?,4,=,26,-,264" J%ubMedK .," Giroo+ A, Solhpour A, Gorouhi G, et al" %imecrolimus cream, ,C, $s" hydrocortisone acetate cream, ,C, in the treatment of facial seborrheic dermatitis= a randomi+ed, in$estigator'blind, clinical trial" Arch Dermatol" 1228?,31)5*=,284- ,258" J%ubMedK .1" Boc @, Arca @, Bose 7, Akar A" An open, randomi+ed, prospecti$e, comparati$e study of topical pimecrolimus ,C cream and topical ketocona+ole 1C cream in the treatment of seborrheic dermatitis" J Dermatol Treat" 122<?12),*=3-<" J%ubMedK 16 .." Cicek D, Bandi (, (akar S, Turgut D" %imecrolimus ,C cream, methylprednisolone aceponate 2",C cream and metronida+ole 2"64C gel in the treatment of seborrheic dermatitis= a randomi+ed clinical study" J Dermatol Treat" 122<?12=.33-.3<" J%ubMedK .3" Danby GA, Maddin AS, Margesson 9J, Losenthal D" A randomi+ed, double' blind, placebo'controlled trial of ketocona+ole 1C shampoo $ersus selenium sulfide 1"4C shampoo in the treatment of moderate to se$ere dandruff" J Am Acad Dermatol",<<.?1<=,225-,2,1" J%ubMedK .4" Shuster S, Meynadier J, Berl :, >olting S" Treatment and prophylaxis of seborrheic dermatitis of the scalp !ith antipityrosporal ,C ciclopirox shampoo" Arch Dermatol"1224?,3,=36-41" J%ubMedK .8" Latna$el LC, Suire LA, (oorman GC" Clinical efficacies of shampoos containing ciclopirox olamine ),"4C* and ketocona+ole )1"2C* in the treatment of seborrhoeic dermatitis" J Dermatol Treat" 1226?,5=55-<8" J%ubMedK .6" 7rtonne J'%, >ikkels AG, Leich B, et al" @fficacious and safe management of moderate to se$ere scalp seborrhoeic dermatitis using clobetasol propionate shampoo 2"24C combined !ith ketocona+ole shampoo 1C= a randomi+ed, controlled study" (r J Dermatol"12,,?,84=,6,-,68" J%ubMedK .5" Bircik 9" SubFect e$aluation of the treatment of seborrheic dermatitis of the scalp !ith a non'steroidal scalp !ash" %oster presented at= 12,1 Ainter Clinical Dermatology Conference? January ,3',<, 12,1? Baanapali, :a!aii" .<" Suire LA, Goode B" A randomised, single'blind, single'centre clinical trial to e$aluate comparati$e clinical efficacy of shampoos containing ciclopirox olamine ),"4C* and salicylic acid ).C*, or ketocona+ole )1C, >i+oralI* for the treatment of dandruffHseborrhoeic dermatitis" J Dermatol Treat" 1221?,.=4,-82" J%ubMedK 32" 9orette G, @rmosilla ;" Study #n$estigators Group" Clinical efficacy of a ne! ciclopiroxolamineH+inc pyrithione shampoo in scalp seborrheic dermatitis treatment" @ur J Dermatol" 1228?,8)4*=445-483" J%ubMedK 3," Seite S, Lougier A, Talarico S" Landomi+ed study comparing the efficacy and tolerance of a llipohydroxy acid shampoo to a ciclopiroxolamine shampoo in the treatment of scalp seborrheic dermatitis" J Cosmet Dermatol" 122<?5=13<- 14." 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