Dermatologic Clinics (Antifungal Therapy, Volume 21, Number 3, July 2003)

186 Pages·2003·2.35 MB·English

by  Aditya K. Gupta

DermatolClin21(2003)xi
Preface
Antifungal therapy
AdityaK.Gupta,MD,PhD,FRCP(C)
GuestEditor
The prevalence of fungal infections has been and other subgroups who may be immunocompro-
increasing over the past few decades, suggesting a mised. Treatment of onychomycosis begins with the
growing demand for antifungal therapy to treat proper diagnosis of the causative organism. Terbina-
such diseases. Fungal infections can be superficial, fine, itraconazole (pulse and continuous), and fluco-
cutaneous, or systemic, and may be caused by nazolehavebeeneffectiveoralantifungalagents.For
dermatophytes, nondermatophyte molds, or yeasts. some conditions, such as superficial white onycho-
Both topical and systemic antifungal agents are mycosis, a topical agent may be sufficient, while
being successfully used to treat these infections; other typesofonychomycosis (eg,dermatophytoma)
however, development of newer antifungal agents mayrequirecombinedtherapy(eg,surgicalortopical
is currently underway. andsystemic).Naillacquersmaybeeffectiveinmild
This issue of the Dermatologic Clinics discusses to moderate casesof onychomycosis.
the management of fungal infections with emphasis As biotechnology and mycology advances, new
on treatment—in particular, the treatment of various antifungal agents are also being developed to
tinea infections, seborrheic dermatitis, pityriasis ver- combat fungal infections. Developments include
sicolor,andonychomycosis. modified versions of standard antifungal agents
TheUSFoodandDrugAdministrationhasnotyet and the discovery of entirely new classes of agents
approvedterbinafine,itraconazole,orfluconazolefor for antifungal treatment.
the treatment of tinea capitis in children; however,
published literature demonstrates that these antifun- AdityaK.Gupta, MD, PhD,FRCP(C)
gals are effective and safe when used for fungal Division of Dermatology
infections and that physicians frequently use these Department of Medicine
agentsto treat pediatric patients. SunnybrookandWomen’s College
Studieshavereportedavarietyofchoicesforthe HealthScienceCenter (SunnybrookSite)
treatmentoftineapedis.Althoughoraltreatmentshave University of Toronto
generally demonstrated a greater ability to reach 2075Bayview Avenue
deeper layers of skin, topical agents have a lower Toronto, OntarioM4N3M5, Canada
potential for adverse events. Dermatophytosis com-
plex infections may require treatment for both the MediprobeLaboratories Inc.
fungalandbacterialcomponentsofaninfection. 490WonderlandRoadSouth, Suite6
The incidence of onychomycosis is increased in London,OntarioN6K 1L6, Canada
men, the elderly, diabetics, HIV-positive individuals, E-mail address: [email protected]
0733-8635/03/$ – seefrontmatterD2003ElsevierInc.Allrightsreserved.
doi:10.1016/S0733-8635(03)00041-X
DermatolClin21(2003)395–400
Tinea corporis, tinea cruris, tinea nigra, and piedra
Aditya K. Gupta, MD, PhD, FRCP(C)a,b,*, Maria Chaudhry, HBScb,
Boni Elewski, MDc
aDivisionofDermatology,DepartmentofMedicine,SunnybrookandWomen’sCollegeHealthScienceCenter(SunnybrookSite),
UniversityofToronto,2075BayviewAvenue,Toronto,Ontario M4N3M5,Canada
bMediprobeLaboratoriesInc.,490WonderlandRoadSouth,Suite6,London,OntarioN6K1L6,Canada
cDepartmentofDermatology,UniversityofAlabama,700EighteenthStreetSouth,Suite414,Birmingham,AL35233-0009,USA
Tinea infections are among the most common Tineacorporis andcruris
dermatologic conditions throughout the world. Skin
ringworminfections,suchastineacorporisandtinea Definition
cruris, are primarily caused by the dermatophytes
Trichophytonrubrum,Trichophytonmentagrophytes, Tinea corporis and tinea cruris are superficial
andMicrosporumcanis.Tineanigraisaninfectionof dermatophyteinfections,commonlyknownas‘‘ring-
the palms or soles, which may be associated with worm.’’ Tinea corporis includes all superficial der-
travel to endemic regions (eg, Southeast United matophyte infectionsofthe glabrousskin,excluding
StatesandCentralAmerica).Blackorwhitenodules the scalp, beard, face, hands, feet, and groin. Tinea
found along the shaft of the hair may be infections crurisincludesinfectionsofthegenitalia,pubicarea,
withPiedraiahortae,orTrichosporonspecies,better perineal skin,and perianal skin.
known as ‘‘black piedra’’ or ‘‘white piedra.’’ To
avoid a misdiagnosis, identification of dermatophyte Etiology andepidemiology
infections requires both a fungal culture on Sabour-
aud’s agar media, and a mycologic examination, Tineacorporisandtineacrurismaybecausedby
consisting of a 10% to 15% KOH preparation, from any of the dermatophytes making up the genera
skinscrapings.Topical antifungalsmay besufficient Trichophyton, Microsporum, and Epidermophyton
for treatment of tinea corporis and cruris and tinea [1]. Both conditions are common throughout the
nigra,andtheshavingofhairinfectedbypiedramay world, with men being affected by tinea cruris more
also be beneficial. Systemic therapy, however, may frequently than women. The causative organism can
be required when the infected areas are large, mac- invade both the stratum corneum and the terminal
eratedwithasecondaryinfection,orinimmunocom- hair of the affected areas [2]. Once infected, scales
promisedindividuals. Preventativemeasuresoftinea may be transmitted through direct contact between
infections include practicing good personal hygiene; individuals,orindirectlythroughcontactwithobjects
keeping the skin dry and cool at all times; and that carry the infected scales [3]. This transfer of
avoidingsharingtowels,clothing,orhairaccessories infection is thought to occur through arthroconidia
with infected individuals. that are shed by the infected host in skin scales [4].
Autoinfection by other dermatophytes elsewhere in
thebody,especiallythefoottothegroin,mayalsobe
amethod of contracting atinea infection[5].
* Correspondingauthor.Suite6,490WonderlandRoad, Children are frequently infected with M canis,
London,Ontario,N6K1L6,Canada. another causative organism of tinea corporis, espe-
E-mailaddress:[email protected](A.K.Gupta). cially those exposed to infected animals, such as
0733-8635/03/$ – seefrontmatterD2003ElsevierInc.Allrightsreserved.
doi:10.1016/S0733-8635(03)00031-7
396 A.K.Guptaetal/DermatolClin21(2003)395–400
cats, dogs, horses, or cattle. Infection may also be disease, and pemphigus vegetans may be mistaken
transmittedbytransferofsporesfromtheskinorhair for tinea cruris. Cutaneous candidiasis, which often
of a child to another host [6]. The most common affects women, may be distinguished from tinea
predisposingfactorformostdermatophyteinfections cruris of males. Satellite lesions and white pustules
inadultsisexcessiveperspiration.Inaddition,occlu- ofCandidamayaffectthescrotum,whereasdermato-
siveclothingmayprovideanenvironmentwherethe phytes do not. Erythrasma produces a coral fluores-
dermatophyte organisms can thrive. Individuals in- cenceunderWood’slight,whichisnotseenintinea
volvedincontactsports,suchaswrestling,football,or cruris [12].
rugby, may also be at risk of acquiring a tinea
infection[7]. Diagnosis andlaboratoryfindings
Clinicalmanifestation Because of the broad range of differential diag-
nosis of dermatophyte infections, it is important to
Tinea corporis and tinea cruris infections may perform a mycologic examination, consisting of a
present as an annular erythematous plaque with a 10% to 15% KOH preparation, from skin scrapings,
raised leading edge and scaling. Clearance occurs in andafungal culture onSabouraud’s agarmedia.
the center of the lesion; however, resolution is often When tinea corporis or tinea cruris infection is
incomplete, because nodules may be left scattered suspected,examinationoftheinfectedscalesfromthe
throughouttheinfectedarea[2].Theclearanceinthe leadingedgeofthelesionmayrevealseptatehyphae
center of the lesion may be the manifestation of an coursingthroughthesquamas[8].Culturesincubated
immune response of the host to the infecting orga- atroomtemperatureshouldgrowthecausativeorga-
nism [2]. Pruritus is a common symptom, and pain nism within 2 weeks.
may be present if the involved area is macerated or
secondarily infected [8]. The lesion of tinea cruris Treatment
extendsfromthegroindownthethighsandbackward
on the perineum or about the anus; the scrotum and As in many casesof cutaneous fungal infections,
labiamajoraaregenerallyexcluded[9].Tineacorpo- topicaltherapyissufficient,butsystemictreatmentis
riscanalsopresentinanon-ringwormfashion,where necessarywhenlargeareasofthebodyareinvolved,
itmaymanifestasanerythematouspapuleoraseries the incidence is chronic or recurrent, or when the
ofvesicles[4].Whenazoophilicdermatophyte,such infection is in immunocompromised patients [13].
as Trichophyton verrucosum, is the responsible or- Tinea corporis and tinea cruris respond satisfactorily
ganism, an intense inflammatory reaction can result to topical therapies, such as the azoles (sulconazole,
in large pustular lesions or a kerion [8]. In addition, oxiconazole, miconazole, clotrimazole, econazole,
occasionally frank bullae may appear as an expres- andketoconazole);theallylamines(naftifineandter-
sion of the inflammation, causing tinea corporis binafine); benzylamine derivatives (butenafine); and
bullosa [10]. When viable hyphae invade and track hydroxypyridones(ciclopiroxolamine).However,re-
down the hair shaft and into the dermis, perhaps peatedapplicationtolargeareasoftheskinmaynot
because of trauma caused by shaving, inflammatory alwaysbefeasibleorconvenientforthepatient.Thus,
papules and pustules may develop. In addition, ery- oral treatments may be preferred by the patient
thema and perifolliculitis may also be part of the (Table1)[14–19].
clinicalpicture of Majocchi’s granuloma [9]. Theuseoforalketoconazolehasbeenlimitedby
its rare association with hepatotoxicity [20]. Griseo-
Differential diagnosis fulvin has a rapid disappearance from the stratum
corneum after administration because it is not very
Other diseases closely resembling tinea corporis keratophilic with poor binding with keratin. Patients
areimpetigo,nummulardermatitis,andsecondaryand maybeatahigherriskofrelapse[21].Thedosageof
tertiarysyphilis[11].Atineacorporiseruptionthatis terbinafine is 250 mg/d given for 2 to 4 weeks. The
morepapulosquamousinpresentationmaybemistak- triazoles, fluconazole and itraconazole, are also safe
enfor psoriasis,lichen planus,seborrheic dermatitis, and effective treatments for tinea corporis and tinea
pityriasisrosea,orpityriasisrubrapilaris[8]. cruris [18,20]. Fluconazole has shown high clinical
The crural region may be infected by other der- and mycologic cure rates with once weekly therapy
matoses that present comparable clinical features as [22]. Itraconazole is effective when given a regimen
tineacruris.Psoriasis,seborrheicdermatitis,candidi- of 200 mg daily for 7 days [23]. Topical cortico-
asis, erythrasma, lichen simplex chronicus, Darier’s steroidapplicationisamistreatmentandmayleadto
A.K.Guptaetal/DermatolClin21(2003)395–400 397
Table1
Systemicantifungaltreatmentsfortineacorporisandtineacruris
Tineainfection Griseofulvin Terbinafine Itraconazole Fluconazole Ketoconazole
Tineacorporis 250mgtwicedailyuntil 250mg/dfor2to 200mg/d 150–300mg/wk 200mg/dfor4
andcruris cureisreached[14,15] 4weeks[16] for1wk[17] for2to4wk[18] to8weeks[19]
suppressionofphysicalsigns[2]andtothedevelop- thehostoccurs,causingthefungustoproliferatemore
mentof tinea incognito. rapidly [27]. The fungus adheres to the skin in a
hydrophobic manner and can survive for prolonged
Prevention andcontrol periodsintheenvironmentalconditionsprevailingon
theskinbecauseitisabletoendurehighsalinityand
Tineacorporisandcrurisaredermatophyteinfec- lowpH[28].
tionsparticularly common in areasof excessiveheat Tinea nigra typically occurs in children and
and moisture. A dry, cool environment may play a young adults with female predominance [25]. It is
role in reducing infection [9]. In addition, avoiding commonly observed in patients living in warm
contact with farm animals and other individuals countries or in those who have lived in or visited
infected with tinea corporis and cruris may help in the tropics or subtropics and brought the infection
preventing infection. In individuals with onychomy- back to North America [27]. Infection with tinea
cosis, it has been observed that there is a higher nigra has been reported from South Africa, Brazil,
prevalence of tinea cruris; this may be the result of Panama,Cuba,andPuertoRicoandmanycaseshave
autoinfection acquired when the individual brushes been reported from the coastal areas of southeastern
fungalorganismsontotheunderwear followingcon- United States [29].
tact with the infected feet and toenails. In such
an instance it may be prudent to cover the infected Clinical manifestation
toenails by first putting on socks, followed by
the undergarment. Hortaea werneckii presents as a brownish black,
velvety macular lesion that is neither elevated nor
scaly, and occasionally pruritic. The lesion may
Tineanigra darken, especially at the borders, while it gradually
spreads at an uneven rate, producing an irregular
Definition outline [2,8].
Tinea nigra is an asymptomatic mycotic skin Differentialdiagnosis
infectionaffectingthestratumcorneum[8].Itoccurs
mainlyonthepalms,butmayalsoinvolvethesoles. Because of the similarity in color and growth of
Tinea nigra infection has also been reported on the the lesion, tinea nigra is most frequently misdiag-
neckandtrunk. nosedwith pigmented junctionalnevusor malignant
melanoma[30].Anaccuratediagnosisoftineanigra
Etiology andepidemiology is important to prevent the diagnostic and excisional
surgery [31] and concomitant scarring associated
Theorganismresponsiblefortineanigra,Hortaea with treatment of nevomelanocytic lesions. Tinea
werneckii (formally known as Phaeoannellomyces nigra can also be mistaken for a lentigo, pityriasis
werneckii, Exophiala werneckii, and Cladospo- (tinea)versicolor,drugeruption,chromhidrosis,con-
riumwerneckii),isadematiaceousfunguscommonly tact dermatitis, syphilis, pinta, or staining from a
foundinnature.Ithasbeenisolatedfromsuperficial variety of chemical or dyes[8,31].
dermallesionsinhumans,suchasinflammatoryscalp
lesions; macerated interdigital lesions; and environ- Diagnosis andlaboratory findings
mentalsources(suchassalteddriedfish,soilsamples,
andhousedust)[24,25].InfectionwithHwerneckiiis Culture of tinea nigra grows readily at room
thoughttooccurbyinoculationthroughtrauma[26]. temperature,butsometimesslowlyonprimaryisola-
Incubation times may range from a few weeks to tion averaging 2 to 4 weeks before identification is
20 years, and is thought to produce clinical disease possible [31]. Microscopic examination of scrapings
whenachangeinthebalancebetweenthefungusand of the stratum corneum reveals numerous dark-col-
398 A.K.Guptaetal/DermatolClin21(2003)395–400
ored branching septate hyphae and round to oval nodulesalongthehairshaftcharacterizeblackpiedra,
spores withsome budding.The coloniesareinitially withthefungalactivitylimitedtothecuticleandwith
moist, shiny,black,andyeast-like [30]. nopenetrationofthehairshaft.Blackpiedraismore
frequent andlesssporadic than white piedra.
Treatment Whitepiedraischaracterizedbywhite-to-tannod-
ules along the shafts of hair in the scalp, beard,
Tinea nigra responds to treatments with kerato- eyebrows, eyelashes, and groin, genital and perigen-
lytics (Whitfield’s ointment) and simple abrasion; ital area [37]. Numerous discrete, soft nodules that
however,topicalimidazoles,suchas2%miconazole are barely visible to the naked eye are attached to
creamand2%ketoconazolecream,aremorepopular the hair shaft, and produce a gritty sensation when
[32]. Topical thiabendazole and ciclopirox olamine palpated [44]. The nodules may be detached easily,
may also be effective [33,34]. Topical tolnaftate and and the affected hairs may be split or broken [36].
oral griseofulvin are usually ineffective, and topical T asahii and T inkin can behave as opportunistic
undecylenicacid gives variable results [35]. pathogens, particularly in immunosuppressed
patients,wheretheycancauseseriousandlife-threat-
eningsymptoms[45].
Piedra
Differentialdiagnosis
Definition
Clinically, many hair disorders can be confused
Piedra,meaningstoneinSpanish,islimitedtothe with piedra [36]. White and black piedra should be
hair shaft without involvement of the adjacent skin distinguished from each other and nits, hair casts,
[36]. Two varieties of piedra may be seen: black developmental defects of the hair shaft, and tricho-
piedra andwhitepiedra. mycosis axillaris [8]. Infections can co-exist with
dermatophyte or Candidainfections, anderythrasma
Etiology andepidemiology [9]. White piedra should be differentiated from pe-
diculosis [46].
Thecausativeorganismofblackpiedra,Phortae,
and Trichosporon ovoides, T inkin and T asahii, of Diagnosis andlaboratoryfindings
white piedra have a worldwide distribution. Black
piedraoccursfrequentlyinhumid,wettropicalareas Infection with P hortae (black piedra) reveals
and is common in certain tropical areas of central tightly packed, darkly pigmented hyphae, asci, and
South America and Southeast Asia, whereas white ascospores attached to the hair shaft, whereas infec-
piedraoccursinsemitropicalandtemperatecountries tion with Trichosporon species (white piedra) shows
[37].Phortaehasbeenfoundonthehairsofanimals, loosely arranged hyphae, blastoconidia, and arthro-
including primates, and stagnant water, soil, and conidia attached to the hair shaft [37]. Fungal
vegetables [38]. It has been suggested that for some culturesareperformedonSabouraud’sdextroseagar.
native populations, black piedra may have cosmetic SomeTrichosporonspecies involvedinwhitepiedra
importance[39]. (eg, T ovoides) are inhibited by cycloheximide,
The natural habitats of Trichosporon species are whichisfoundindermatophytetestmedium,Myco-
soil, lake water, and plants, and such fungi are sel, and Mycobiotic [37].
occasionally seen as normal flora of the human skin
and mouth [40]. White piedra has been found on Treatment
animal hairs, including monkeys, horses, and lower
mammals [41]. Infection with piedra does not seem Shaving or clipping the infected hair is the treat-
relatedtopersonalhygieneorexposuretoaninfected mentofchoiceforbothtypesofpiedra;however,this
person,nordoeswhitepiedraofthepubichairseem methodmaynotbeestheticallypleasingtoallpatents,
tospread bysexual contact [42]. especially women. Antifungal therapy may be initi-
ated in conjunction with shaving [8]. Black piedra
Clinicalmanifestation may be treated with oral terbinafine [43]. Effective
therapies against white piedra include imidazoles,
Black piedra is a condition that presents as a ciclopiroxolamine,2%seleniumsulfide,6%precip-
stone-hard black nodule on the scalp, beard, mous- itatedsulfurinpetrolatum,chlorhexidinesolution,and
tache, and pubic hair shaft [43]. Brown-black hard zinc pyrithione [37]. In the older literature other
A.K.Guptaetal/DermatolClin21(2003)395–400 399
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DermatolClin21(2003)401–412
Seborrheic dermatitis
Aditya K. Gupta, MD, PhD, FRCP(C)a,b,*,
Robyn Bluhm, HBSc (Hons), BA, MAb,c, Elizabeth A. Cooper, BSc, BEScb,
Richard C. Summerbell, PhDd, Roma Batra, PhD, MSc, MPhilb
aDivisionofDermatology,DepartmentofMedicine,SunnybrookandWomen’sCollegeHealthScienceCenter(SunnybrookSite),
UniversityofToronto,2075BayviewAvenue,Toronto,Ontario,M4N3M5,Canada
bMediprobeLaboratoriesInc.,490WonderlandRoadSouth,Suite6,London,OntarioN6K1L6,Canada
cUniversityofWesternOntario,London,Ontario,Canada
dCentraalbureauvoorSchimmelcultures,Uppsalalaan8,3584CT,Utrecht,TheNetherlands
Seborrheic dermatitis presents as red, flaking, may develop seborrheic dermatitis subsequent to
greasy-looking patches of skin that are located most psoralen plus type Aultraviolet lighttherapy [7].
commonly on the scalp, nasolabial folds, eyebrows, The relationship between seborrheic dermatitis
ears, and chest. In some patients, flexural areas may anddandruffisalsocontroversial.Someinvestigators
alsobeinvolved.Moreover,theextentofflakingand regard a diagnosis of ‘‘seborrheic dermatitis of the
erythemamayvary.Althoughseborrheicdermatitisin scalp’’ as a way of describing severe dandruff,
adultsmaybeclinicallysimilartoinfantileseborrheic whereas others believe that the term ‘‘dandruff’’
dermatitis (including cradle cap), the former is not shouldbeusedforanyflakingofthescalp,regardless
commoninchildren.Rather,ittendstomakeitsfirst ofetiology[8–12].Therecentresurgenceofinterest
appearance around the time of puberty, with the intheroleofMalasseziayeastsinthedevelopmentof
increase in skin lipids that occurs at this time. It is seborrheic dermatitis has provided additional evi-
particularlycommoninadolescentsandyoungadults, dence that, in most cases, dandruff is a mild form
and is relatively rare in the middle aged. In patients of seborrheic dermatitis. Some authors believe that
overtheageof50years,however,seborrheicderma- dandruff is a noninflammatory form of seborrheic
titis again becomes quite common [1,2]. It is more dermatitis[13,14].Seborrheicdermatitisisoftenseen
common in men than in women. Overall, its preva- in conjunction with other skin diseases, including
lence in immunocompetent adults is estimated to be rosacea, blepharitis or ocular irritation, and acne
between1%and3%[3].Theincidenceofseborrheic vulgaris[15–19].Itisalsocommoninpatientswith
dermatitis is unusually high among patients with other skin diseases associated with Malassezia spe-
AIDS, ranging from 30% to 83% [3–5]. In patients cies, such as pityriasis versicolor and Malassezia
with chronic seborrheic dermatitis, the lesions often folliculitis [20,21].
worseninthewinter;however,theeffectofincreased
sunlightonseborrheicdermatitisisunclear.Although
there is some evidence that exposure to sunlight can Malassezia yeasts
improvetheclinicalappearanceofseborrheicderma-
titis [6], it has also been reported that some patients Seven of the nine known Malassezia yeast spe-
cies are normal commensals of adult human skin.
These species are Malassezia furfur, M sympodialis,
* Correspondingauthor.Suite6,490WonderlandRoad, M dermatis, M restricta, M slooffiae, M obtusa, and
London,Ontario,N6K1L6,Canada. Mglobosa[22–24].Mpachydermatisisnotconsid-
E-mailaddress:[email protected](A.K.Gupta). ered to be a normal human commensal because it is
0733-8635/03/$ – seefrontmatterD2003ElsevierInc.Allrightsreserved.
doi:10.1016/S0733-8635(03)00028-7
402 A.K.Guptaetal/DermatolClin21(2003)401–412
primarily zoophilic. The new species M equi has difficult.Thirdly,ithasalsobeensuggestedbyGupta
been detected in horses [25]. The species that have et al [23] that the use of synthetic detergents and
beencommonlyassociatedwithseborrheicdermatitis shampoosmightreflectartifactualpatientfactorsthat
are M globosa and M restricta [3,26]. Other inves- might be associated with reduced colony counts.
tigators, however, have also found M furfur, M Despitethiscomplexity,andthecontroversythathas
sympodialis, M obtusa, and M slooffiae [26]. These ensued from it, there is increasing acceptance of the
commensalsrequireanexogenoussourceoflipidsto proposition that Malassezia yeasts play some role in
grow, and tend to appear on the skin at around the the development of seborrheic dermatitis. Further
time of puberty. Moreover, their distribution on the evidence for this is that ketoconazole, an antifungal
skin (most commonly on the face, scalp, and trunk) agent,significantlydecreasesthenumberofMalasse-
occurs on lipid-rich areas of the body. Further ziayeastsinseborrheicdermatitispatients,andthere-
evidence that these yeasts require lipids comes from byimprovestheclinicalappearanceofthedisease.
the fact they have the ability to produce lipases
[27,28]. The lipases are involved in the release of Immune responsein seborrheic dermatitis
arachidonicacid,whichisinvolvedintheinflamma-
tion of skin [29]. Because there are no clear differences in yeast
carriagelevelsbetweenseborrheicdermatitispatients
and healthy controls, it has been suggested that a
Seborrheicdermatitis and Malasseziayeasts: predisposition to this disease involves some sort of
causalrelationship? immune or inflammatory reaction. T-cell function
maybedepressedinpatientswithseborrheicderma-
Early researchers believed that Malassezia yeasts titis and there may be an increase in the number of
played a causative role in seborrheic dermatitis; natural killer cells, or in the levels of IgA and IgG
however, a causal mechanism was not found antibodies found in serum [40]. Two studies have
[30,31]. In view of this, and because Malassezia shown,however,thatpatientswithseborrheicderma-
yeasts occur on healthy skin of people both with titisdonotseemtohaveelevatedIgGantibodytiters
and without seborrheic dermatitis lesions, the sug- against the yeasts [40,41]. The authors of these
gestion that Malassezia yeasts were responsible for studies suggest that seborrheic dermatitis is caused
this disease lost popularity. Instead, investigators by an abnormal reaction of the skin to the yeasts
viewed seborrheic dermatitis as primarily being a themselvesortosometoxinthattheyproduce.There
disorder causedbyhyperproliferation. is evidence that there is a strong inflammatory
Theefficacyoftheantifungalagentketoconazole reaction involved in seborrheic dermatitis, including
in the treatment of seborrheic dermatitis has revived an increase in NK1+ and CD16+ cells, activation of
interest in the potential role of Malassezia yeasts in complement, and an increased production of inflam-
this disease [32,33]. Some researchers believe that matory interleukins in lesional skin, compared with
Malassezia yeasts are present in unusually high levelsfoundinnonlesionalskininthesepatientsand
numbers on the scalp of patients with dandruff or in the skinof healthy controls [42].
seborrheic dermatitis [34,35]. There are others who Seborrheic dermatitis is also associated with im-
haveshownthattherearenosignificantdifferencesin mune deficiency, most notably in HIV-positive and
the number of Malasseziacounts onlesional skin of AIDS patients. In this population, seborrheic derma-
seborrheic dermatitis patients compared with nonle- titishasbeenreportedtooccurmuchmorecommonly
sional skin in healthy subjects [36,37]. Some inves- thanitdoesinthegeneralpopulation[43].Reported
tigators have found that in seborrheic dermatitis, the figures range from 34% to 83% [44,45]. Seborrheic
densityofMalasseziaspeciesislowerinlesionalskin dermatitis in HIV-positive and AIDS patients is
compared with nonlesional skin [23]. A number of relatively severe and lesions of the extremities are
factors may explain the variability of results found common[45–48].Astheimmunedeficiencyinthese
when measuring the fungal load. Firstly, Malassezia patients becomes progressively worse, so do the
arenotonlyrestrictedtotheskinsurfacebutarealso lesionsofseborrheicdermatitis[47,49].Thesediffer-
presentwithinthelayersofthestratumcorneum[38]. ences in the clinical presentation of seborrheic der-
Ideally, the full thickness of skin squama should be matitisinHIV-positiveandAIDSpatientshaveledto
examinedtogiveatruepictureofMalasseziacounts the suggestion that the ‘‘seborrheic-like’’ dermatitis
[29,39].Secondly,thevarietyofsamplingtechniques associatedwithAIDSshouldberegardedasadistinct
usedbyvariousauthorsfurthercomplicatestheprob- clinical condition that is secondary to the immune
lem and makes comparison between studies very deficiency [48].