Download Seborrheic Dermatitis: An Update

Acta Dermatovenerol Croat
2012;20(2):98-104
REVIEW
Seborrheic Dermatitis: An Update
Zrinka Bukvić Mokos1, Martina Kralj2, Aleksandra Basta-Juzbašić1,
Ines Lakoš Jukić1
University Hospital Center Zagreb, Department of Dermatology and Venereology,
School of Medicine University of Zagreb; 2Department of Dermatology, Karlovac
General Hospital, Karlovac, Croatia
1
Corresponding author:
Assist. Prof. Zrinka Bukvić Mokos, MD, PhD
University Hospital Center Zagreb
Department of Dermatology and Venereology
School of Medicine University of Zagreb
Šalata 4
HR-10000 Zagreb
Croatia
[email protected]
Received: October 25, 2011
Accepted: May 15, 2012
SUMMARY Seborrheic dermatitis is a chronic relapsing inflammatory
skin disorder clinically characterized by scaling and poorly defined
erythematous patches. The prevalence of adult seborrheic dermatitis
is estimated at 5%. Although the exact cause of seborrheic dermatitis
has yet to be understood, Malassezia yeasts, hormones (androgens),
sebum levels and immune response are known to play important roles
in its development. Additional factors including drugs, winter temperatures and stress may exacerbate seborrheic dermatitis. A variety of
treatment modalities are available, including antifungal agents, topical
low-potency steroids and calcineurin inhibitors (immunomodulators).
This review summarizes current knowledge on the etiopathogenesis
and therapy of adult seborrheic dermatitis.
Key words: seborrheic dermatitis, Malassezia yeast, sebum, antifungal agents
INTRODUCTION
Seborrheic dermatitis (SD) is a common chronic
relapsing inflammatory skin disorder clinically characterized by poorly defined erythematous patches
and scaling. SD primarily affects sebum rich areas, including scalp, face, upper chest and back (1).
The prevalence of adult SD is estimated at 5%
(2). This condition is more common in males than in
females. Among adults, the peak incidence is in the
third and fourth decades of life. Although the exact
cause of SD has yet to be understood, Malassezia
yeasts, hormones (androgens), sebum levels and immune response are known to play important roles in
its etiopathogenesis (3). Some researchers propose a
pivotal role for Malassezia yeasts (formerly called Pityrosporum ovale) in seborrheic dermatitis (4). Antifun-
98
gal therapy leads to decreased colonization with Malassezia spp. and concomitant disappearance of skin
lesions, which is probably the strongest evidence that
Malassezia spp. have momentous role in the development of SD (5). Other therapeutic options include
corticosteroids, immunomodulators and antibiotics.
ETIOLOGY AND PATHOGENESIS
Despite quite a high prevalence of this disorder,
the exact cause is poorly understood. However, several factors (Malassezia yeasts, hormones, sebum levels, immune response, neurogenic factors, external
factors) seem to be involved in SD etiopathogenesis,
but the exact pathogenetic mechanism still remains
controversial.
ACTA DERMATOVENEROLOGICA CROATICA
Bukvić Mokos et al.
Seborrheic dermatitis
Malassezia species
Growing evidence indicates that Malassezia spp.
are a major etiologic factor in SD development. The
number of Malassezia spp. decreases after antifungal therapy with disappearance of skin lesions. This
is probably the strongest evidence that Malassezia
spp. have an important role in the development of SD.
Malassezia spp. are lipophilic yeasts that are ubiquitous residents of the skin (8). They are predominantly
situated on lipid-rich anatomic areas. Whereas eleven
species have been identified, seven of them are associated with human skin flora and SD. Malassezia (M.)
furfur, M. restricta, M. sympodialis, M. globosa, M. obobtusa and M. slooffiae have been detected on affected
skin (9). However, M. globosa and M. restricta predominate in SD lesions, particularly on the scalp (10).
Since Malassezia spp. have the ability to produce
lipases, they can initiate inflammatory response by
releasing oleic and arachidonic acid from the sebum
lipids (11,12). Both of these unsaturated fatty acids
have direct irritative and desquamative effects on keratinocytes. Furthermore, arachidonic acid metabolized by cyclooxygenase serves as a source of proinflammatory eicosanoids (particularly prostaglandins),
leading to inflammation and consequent damage of
stratum corneum. Keratinocytes at affected areas are
stimulated to produce proinflammatory cytokines
that further enhance and maintain the inflammatory
response. Malassezia-driven pathogenetic “vicious
circle” closes owing to the fact that saturated fatty acids, released by Malassezia lipases, are used as a “proliferative fuel” for these yeasts.
Hormones and skin lipids
SD is not always associated with excessive secretion of sebum (13). However, 50% of patients have
oily, sebum rich skin. As mentioned above, sebum
lipids are essential for Malassezia proliferation and
synthesis of initial proinflammatory factors, so a certain amount of sebum is always required in order to
provide permissive conditions for SD development.
Therefore, SD lesions are predominantly located on
skin areas rich in sebaceous glands. SD is most common in puberty and adolescence, during periods of
highest sebum production. There is also a possible
hormonal link: not only does the disease occur in puberty, but SD is more common in males than in females, suggesting an influence of androgens on the
pilosebaceous unit (14).
Immune response
Since SD is an inflammatory condition, largely accompanied by the presence of Malassezia yeast, it is
ACTA DERMATOVENEROLOGICA CROATICA
Acta Dermatovenerol Croat
2012;20(2):98-104
reasonable to assume that inappropriate immune
response may contribute to the pathogenesis. Although the immunopathogenetic mechanism involved in the development of SD is not clearly understood, several studies indicate immune dysfunction
in SD patients. The strongest evidence for immunodeficiency as an etiologic factor comes from findings
that SD prevalence is significantly higher (34%-83%)
among HIV positive and AIDS patients compared to
general population (approximately 3%). Furthermore, in HIV positive patients, a more severe clinical
presentation of SD (often affecting even extremities) has been observed; hence, SD in these patients
is considered by some authors as a distinctive entity
(“seborrheic-like dermatitis of acquired immunodeficiency syndrome”). Studies conducted by Bergbrant
et al. have directly shown impaired function of T cells
and increased number of NK cells in peripheral blood
of SD patients compared to control group (15). The
same study showed increased levels of total serum
IgA and IgG antibodies in patients with SD, which was
also confirmed by several other studies. Interestingly,
despite the presence of hypergammaglobulinemia in
SD patients, there were no elevated titers of antibodies specific to Malassezia antigens, suggesting that
increased immunoglobulin production occurs as a
response to yeast toxins and lipase activity. Faergemann et al. found infiltration of NK cells and macrophages in SD affected skin areas, with concomitant
local activation of complement and proinflammatory
cytokine induction, which all together can result in
epidermal devastation (16). Considering the fact that
Malassezia may be present on the skin commensally,
without provoking any immune reaction or inflammation, it could be concluded that in SD patients
an abnormal immune reaction to the yeasts occurs,
which is influenced by the interplay of other pathogenetic factors that may govern and modulate an individual immune response.
Neurogenic factors
The frequent occurrence of SD in patients with
Parkinson’s disease has long been clinically observed,
particularly in those with prolonged and severe seborrhea, which provides permissive conditions for Malassezia proliferation (17). Since bilateral seborrhea occurs in patients with unilateral parkinsonism, it seems
that these changes in sebum level are provo­ked endocrinologically rather than neurologically (18). This
is supported by the findings of increased plasma αmelanocyte stimulating hormone (α-MSH) levels in
patients with Parkinson’s disease, probably due to
the lack of MSH-inhibiting factor as a consequence
of insufficient dopaminergic neuronal activity (19).
99
Bukvić Mokos et al.
Seborrheic dermatitis
Namely, treatment with L-dopa successfully restores
MSH-inhibiting factor synthesis and reduces sebum
secretion in parkinsonian patients. This sebostatic effect of L-dopa is limited exclusively to patients with
Parkinson’s disease, whereas in other seborrheic conditions such as acne, L-dopa has no effect on sebum
production (19). Furthermore, facial immobility of
Parkinson’s disease patients (mask-like face) can secondarily lead to the increased sebum accumulation,
thus additionally contributing to the tendency of SD
development.
Similar mechanisms may be, at least partially, responsible for the frequent occurrence of SD in patients treated with neuroleptic drugs, as well as in patients with tardive dyskinesia, central nervous system
trauma and facial nerve palsy.
Frequent occurrence of SD is also observed in depressive disorders, but this could be attributed to the
tendency of depressed patients to remain indoors, as
well as to altered hygiene habits.
Other factors
SD has a seasonal aspect; relapse of the disease is
more common in low fall and winter. The condition
can be triggered by emotional stress; a high rate of
seborrhea is reported among combat troops in war
times (20). Traditionally, diet is blamed for the development of SD. A severe zinc deficiency in patients
with acrodermatitis enteropathica and acrodermatitis-like conditions can produce a seborrheic dermatitis-like rash (20). Common SD does not respond to
supplementary zinc therapy.
CLINICAL FEATURES
Typical SD lesions are erythematous patches, with
greasy large scales. The disorder has a predilection for
areas with numerous sebaceous glands, such as scalp,
hairline, eyebrow, glabella, nasolabial folds, ears, upper chest, back, axillae, umbilicus and groins. Patients
often report pruritus, especially on the scalp and in
the ear canal. Scalp lesions may extend into the forehead skin and form scaly erythematous border called
“corona seborrheica“. Two forms of SD may occur on
the chest, a common petaloid type and quite rare pityriasiform type (6). The petaloid type starts with red
to brown follicular and perifollicular papules, which
develop to patches that resemble the shape of flower
petals or medallion. The pityriasiform type is probably an acute severe form of petaloid SD (7). This type
has generalized maculae and patches that follow the
skin lines mimicking pityriasis rosea. In some individuals, chronic dermatitis of the ear canal may be the
only manifestation of SD. Another common symptom
100
Acta Dermatovenerol Croat
2012;20(2):98-104
of SD is blepharitis with honey-colored crusts along
the rim of the eyelid. When only this manifestation is
present, the diagnosis is not simple. A serious variant
of this skin disorder is generalized exfoliative erythroderma (seborrheic erythroderma).
DIFFERENTIAL DIAGNOSIS
Although in everyday practice SD can usually
be diagnosed at the first sight, patients presenting
with skin lesions suspect of SD should be thoroughly
considered for the possible presence of other, more
serious dermatologic disorders, which are clinically
manifested with chronic eczematous and papulosquamous lesions. The patient’s age, gender, affected sites, presence of concomitant conditions and
diseases (especially immuno-compromising), family history as well as everyday habits must be taken
in consideration on differential diagnosis. A patient
with erythematous and scaling plaques in the areas
such as scalp, nasolabial folds, eyebrows and retroauricular regions has most likely SD, but these clinical
features of SD may be confused with psoriasis, leading to misdiagnosis. To facilitate distinction, findings
of sharply demarcated scalp plaques, nail pitting and
distal onycholysis may be helpful, as they are typically
present in psoriatic patients (21). The occurrence of
so-called seborrhiasis could be found, indicating a
condition with overlapping psoriasis and SD on the
face. Facial SD lesions may resemble skin changes
found in systemic lupus erythematosus (if suspected,
immunologic assessment is required) and in certain
photodermatoses. SD changes on the trunk sometimes may be misinterpreted as tinea versicolor that
can easily be distinguished with Wood light examination and presence of hyphae on scraped KOH cytologic preparation. Furthermore, differential diagnosis
also includes atopic and contact dermatitis, rosacea,
dermatophytosis, candidiasis, and, uncommonly, cutaneous lymphoma or Langerhans cell histiocytosis.
Skin biopsy is rarely needed to verify the diagnosis,
and associated histologic changes may vary from acanthosis and parakeratosis to spongiosis.
MANAGEMENT AND THERAPY
Since the key underlying pathogenetic mechanisms of SD include excessive Mallasezia spp. proliferation with consequent induction of local skin inflammatory response, today’s therapeutic approach
is commonly based on topical antifungal, antiinflammatory and immunomodulatory agents. Given that
desquamation is regularly present, keratolytics are
also highly effective. In some patients, significant improvement can also be achieved by antibiotics (met-
ACTA DERMATOVENEROLOGICA CROATICA
Bukvić Mokos et al.
Seborrheic dermatitis
ronidazole), tar and phototherapy. Systemic therapy
is rarely required, only in severe cases with strikingly
outspread lesions, as well as in cases unresponsive to
topical treatment. Some alternative therapeutic approaches have also been reported, such as tea tree oil
and 90% honey diluted in warm water.
TOPICAL THERAPY
Topical agents are effective and well tolerated in
the majority of SD cases, as shown and validated by
multiple randomized clinical trials, but today also empirically well-known from everyday clinical practice.
Antifungal medications
Although earlier treatment approaches were focused on antiinflammatory agents, today it is generally accepted that initial therapy for SD should be
based on topical antimycotics. Azole class of antifungal agents (lanosterol 14 α-demethylase inhibitors)
proved to be most effective in growth inhibition of
Malassezia spp., associated with the development of
SD.
Among the azoles, ketoconazole applied in various vehicles showed superior effects, and hence it is
the first-line treatment for SD.
Ketoconazole is available in different topical overthe-counter preparations, such as shampoos, creams
and gels. Ketoconazole shampoo 2% is effective in
treating scalp SD, used twice weekly. Intermittent use
of ketoconazole 2% shampoo (once weekly) has been
shown to have a significant prophylactic effect (22).
Ketoconazole 2% cream significantly improves SD
lesions of the face and chest used twice daily (effective as hydrocortisone 1% cream) and, intermittently
used, also effectively maintains remission (23). Ketoconazole also has slight antiinflammatory properties,
and it is principally well tolerated in all available formulations.
Bifonazole 1% cream, used once daily, is usually
effective in the treatment of SD of the scalp and face
(24,25). A combination ointment containing 1% bifonazole and 40% urea helps reduce the symptoms
of scalp SD (26).
Miconazole is an azole that can also be effectively
used in the treatment of SD as a monotherapy or in
combination with hydrocortisone (27).
Another topical antifungal agent, ciclopirox 1%
cream, is likewise effective and provides a reduction
of symptoms when used twice daily. Ciclopirox has
both antifungal and antiinflammatory properties (28).
Combinations of ciclopirox 1.5% shampoo with salicylic acid 3% or zinc pyrithione 1% are also effective
ACTA DERMATOVENEROLOGICA CROATICA
Acta Dermatovenerol Croat
2012;20(2):98-104
(29). Recent studies show statistical non-inferiority of
ciclopirox in comparison with ketoconazole (30).
Corticosteroids
In severe cases of SD, low to mild potency topical corticosteroids are effective in fast clearing of
visible signs and associated symptoms (31). Topical
corticosteroids can be used alone or in combination
with antifungal agents. Often and prolonged use is
not recommended because of their well-known side
effects such as atrophy, telangiectasias, hypertrichosis and perioral dermatitis. Antifungal agents are still
the first choice in the treatment of SD due to the fact
that ketoconazole 2% has been shown to be superior
to betamethasone diproprionate 0.05% in reducing
symptoms and lowering the number of Malassezia
spp. (32). There is a consensus that topical corticosteroids are useful in short term mainly to control erythema and itching.
Metronidazole
There are contradictory data on the effectiveness
of topical metronidazole 0.75% gel. In two trials, metronidazole showed better efficacy than placebo and
was as effective as ketoconazole 2% cream (33,34).
Conversely, Koca et al. found metronidazole not superior to placebo in patients with SD (35).
Calcineurin inhibitors
Topical calcineurin inhibitors, pimecrolimus 1%
cream and tacrolimus 0.03% and 0.1% ointment
decrease cutaneous inflammation by inhibiting Tlymphocyte driven cytokine production (36). These
agents are not associated with the side effect profile
of corticosteroids. In a randomized, double blind, vehicle-controlled 4-week efficacy trial of twice daily
pimecrolimus 1% cream in 96 patients, topical calcineurin inhibitor therapy was effective and well tolerated in the treatment of SD (37). In two randomized
clinical trials, pimecrolimus 1% proved to be as effective as topical corticosteroids (hydrocortisone acetate
1% cream or betamethasone 17-valerate 0.1% cream)
(1). However, rare cases of malignancy (e.g., skin and
lymphoma) have been reported in patients treated
with topical calcineurin inhibitors. Due to this fact,
long-term use is not recommended and application
should be limited to lesions of SD (38).
Zinc pyrithione
Zinc pyrithione is a common active ingredient in
most of the over-the-counter anti-dandruff shampoos and has both antifungal and antimicrobial effects (39). This agent is available in concentrations of
101
Bukvić Mokos et al.
Seborrheic dermatitis
1% and 2% in shampoos as well as a 1% cream formulation (40). Zinc pyrithione has shown inferior efficacy than ketoconazole in several trials, but it might
still be effective to clear visible signs of the disease
when used alone or in combination with ketoconazole (41).
Lithium salts
Topical lithium succinate and lithium gluconate
are effective agents in treating SD in the areas other
than scalp, probably due to their antiinflammatory
effects. In a randomized trial involving 12 patients,
lithium succinate 8% ointment showed greater efficacy than placebo in the treatment of visible signs
of the disease in HIV-positive patients (42). Lithium
gluconate 8% ointment, used twice daily, was shown
to be more effective than placebo in an 8-week trial
involving 129 patients with facial lesions (43). Also,
lithium gluconate 8% ointment is more effective than
ketoconazole 2%.
Selenium sulfide
In a randomized double-blind trial involving 246
patients with moderate to severe dandruff, selenium
sulfide 2.5% was tested against ketoconazole 2% and
placebo. Both medicated shampoos showed greater
efficacy than placebo, but ketoconazole was better
tolerated (44).
Phototherapy
Many patients notice improvement during the
summer. Phototherapy using UVB rays is sometimes
considered as an option for severe or recalcitrant SD.
In an open prospective study, 18 patients with severe SD were treated with narrow-band UVB three
times per week until the clearance or upon completing 2 months of therapy (45). The median number of
treatment sessions was 23 and the median cumulative UVB dose was 9.8 J/cm2. All patients showed improvement, especially those with severe disease, but
burning and itching may occur during phototherapy.
The biggest drawback of UVB irradiation is rapid disease relapse appearing 2-6 weeks after treatment.
Also, there are risks associated with exceeding the
maximum lifetime allowable cumulative dose and
carcinogenic effects on the skin.
SYSTEMIC THERAPY: ORAL ANTIFUNGAL
MEDICATIONS
Data on the effectiveness of systemic antifungal
therapy are not consistent. In a randomized, double
blind, placebo-controlled study, 174 patients with
SD received either 250 mg of terbinafine or placebo
102
Acta Dermatovenerol Croat
2012;20(2):98-104
for 6 weeks. Oral terbinafine was not more effective
than placebo in patients with facial SD, but in other
areas terbinafine showed greater efficacy than placebo (46). In another double blind study involving 63
patients, oral fluconazole in a 300 mg single weekly
dose showed no significant therapeutic effect (47). In
one trial involving 19 patients, ketoconazole (200 mg
daily dose for 4 weeks) showed significant improvement (48). On deciding on oral antimycotic therapy,
the cost-benefit ratio must be carefully considered
due to the possible hepatotoxic effect of systemic
antifungals.
CONCLUSION
Seborrheic dermatitis is a chronic, relapsing, papulosquamous inflammatory skin disorder, which must
be strictly distinguished from seborrhea. The etiology is still not completely understood, but among
the many identified etiopathogenetic factors, Malassezia yeast has certainly a pivotal role. In the majority
of cases, satisfactory therapeutic results are achieved
by topical antifungal agents of the azole class that are
principally well tolerated without significant side effects, and therefore today are considered as the firstchoice treatment for SD. Local glucocorticoids are
also effective, but long-term use should be avoided
because of their well-known side effects. Although
SD per se does not seriously disrupt the patient’s
quality of life, it should be kept in mind that its occurrence, particularly in severe, therapy-resistant form,
can be a predictor of some serious conditions such
as HIV infection.
References
1.Stefanaki I, Katsambas A. Therapeutic update on
sebborheic dermatitis. Skin Ther Lett 2010;15:1-4.
2.Fritsch PO, Reider N. Other eczematous eruptions.
In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology. New York: Mosby; 2003. pp. 215-8.
3.Picardo M, Camelli N. Seborrheic dermatitis. In:
Williams H, editor. Evidence-Based Dermatology.
Blackwell Publishing; 2008. pp. 164-70.
4.Gupta AK, Bluhm R, Cooper EA, Summerbell RC,
Batra R. Seborrheic dermatitis. Dermatol Clin
2003;21:401-12.
5.Del Rosso JQ, Kim GK. Seborrheic dermatitis and
Malassezia species: how are they related? J Clin
Aesth Dermatol 2009;111:14-7.
6.Janniger CK, Shwartz RA. Seborrheic dermatitis.
Am Fam Physician 1995;52:149-55, 159-60.
7.Beiber T. Other types of dermatitis. In: Burgdorf
WHC, Plewig G, Wolff HH, Landhalter M, editors.
ACTA DERMATOVENEROLOGICA CROATICA
Bukvić Mokos et al.
Seborrheic dermatitis
Braun Falco’s Dermatology. Springer; 2009. pp.
425-33.
8.Gupta AK, Batra R, Bluhm R, Boekhout T, Dawson
TL Jr. Skin disease associated with Malassezia species. J Am Acad Dermatol 2004;54:785-98.
9.Nakabayashi A, Sei Y, Gulliot J. Identification of
Malassezia species isolated from patients with
seborrheic dermatitis, atopic dermatitis, pityriasis versicolor and normal subjects. Med Mycol
2000;38:337-41.
10.Dawson TL. Malassezia globosa and restricta:
breakthrough understanding of the etiology and
treatment of dandruff and seborrheic dermatitis
through whole-genome analysis. J Invest Dermatol 2007;12:15-9.
11. Greaves MV, Camp RDR. Prostaglandins, leukotrienes, phospholipase, platelet activating factor and
cytokines: an integrated approach to inflammation
of human skin. Arch Dermatol Res 1988;280:S33-41.
12.Riciputo RM, Oliveri S, Micali G, Sapuppo A.
Phospholipase activity in Malassezia furfur pathogenic strains. Mycoses 1996;39:233-5.
13.Naldi L, Rebora A. Seborrheic dermatitis. N Engl J
Med 2009;360:387-96.
14.Gupta AK, Bluhm R. Seborrheic dermatitis. J Eur
Acad Dermatol Venereol 2004;18:13-26.
15.Bergbrant IM, Johansson S, Robbins D, Scheynius
A, Faergemann J, Södeström T. An immunological
study in patients with seborrhoeic dermatitis. Clin
Exp Dermatol 1991;16:331-8.
16.Faergemann J, Bergbrant IM, Dohsé M. Seborrhoeic dermatitis and Pityrosporum (Malassezia)
folliculitis: characterization of inflammatory
cells and mediators in the skin by immunohistochemistry. Br J Dermatol 2001;144:549-56.
17.Cowley NC, Farr RM, Shuster S. The permissive effect of sebum in seborrhoeic dermatitis: an explanation of the rash in neurological disorders. Br J
Dermatol 1990;122:71-6.
18.Burton JL, Shuster S. Effect of L-dopa on seborrhoea of parkinsonism. Lancet 1970;2:19-20.
19.Burton JL, Cartlidge M, Shuster S. Effect of L-dopa
on the seborrhoea of parkinsonism. Br J Dermatol
1973;88:475-9.
20.Plewig G, Jansen T. Seborrheic dermatitis. In: Wolff
K, Goldsmith L, Katz SI, Glichrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick’s Dermatology in General Medicine. McGraw-Hill Companies, Inc.; 2008.
pp. 219-25.
21.Kaszuba A, Schwartz RA, Seneczko F. Diagnosis,
clinical types and treatment of psoriasis. Nowa
Klinika 2001;8:762-8.
ACTA DERMATOVENEROLOGICA CROATICA
Acta Dermatovenerol Croat
2012;20(2):98-104
22.Peter RU, Richarz-Barthauer U. Successful treatment and prophylaxis of scalp seborrhoeic dermatitis and dandruff with 2% ketoconazole shampoo: results of a multicentre, double-blind, placebo-controlled trial. Br J Dermatol 1995;132:441-5.
23.Stratigos JD, Antoniou C, Katsambas A, Böhler K,
Fritsch P, Schmöl A, et al. Ketoconazole 2% cream
versus hydrocortisone 1% cream in the treatment
of seborrheic dermatitis: a double-blind comparative study. J Am Acad Dermatol 1988;19:850-3.
24.Segal R, David M, Ingber A. Treatment with bifonazole shampoo for seborrhea and seborrheic
dermatitis: a randomized, double-blind study.
Acta Derm Venerol 1992;72:454-5.
25.Zienicke H, Korting HC, Braun-Falco O, Effendy I,
Hagedorn M, Küchmeister B, et al. Comparative efficacy and safety of bifonazole 1% cream and the
corresponding base preparation in the treatment
of seborrheic dermatitis. Mycoses 1993;36:32531.
26.Shemer A, Nathanson N, Kaplan B, Weiss G,
Newman N, Trau H. Treatment of scalp seborrheic dermatitis and psoriasis with and ointment
of 40% urea and 1% bifonazole. Int J Dermatol
2000;39:521-38.
27.Faergemann J. Seborrhoeic dermatitis and Pityrosporum orbiculare: treatment of seborrhoeic dermatitis of the scalp with miconazole hydrocortisone (Daktacort), miconazole and hydrocortisone.
Br J Dermatol 1986;114:695-700.
28. Gupta AK, Bluhm R. Ciclopirox (Loprox) gel for superficial fungal infections. Skin Ther Lett 2004;9:4-5.
29.Lorette G, Ermosilla V. Clinical efficacy of a new
ciclopiroxolamine/zinc pyrithione shampoo in
scalp seborrheic dermatitis treatment. Eur J Dermatol 2006;6:558-64.
30.Ratnavel RC, Squire RA, Boorman GC. Clinical efficacies of shampoos containing ciclopiroxolamine (1.5%) and ketoconazole (2.0%) in the treatment of seborrhoeic dermatitis. J Dermatol Treat
2007;18:88-96.
31.Del Rosso JQ. Adult seborrheic dermatitis: a status report on practical topical management. J Clin
Aesthet Dermatol 2011;4:32-8.
32.Ortonne JP, Lacour JP, Vitetta A, Le Fichoux Y. Comparative study of ketoconazole 2% foaming gel
and betamethasone dipropionate 0.05% lotion in
the treatment of seborrheic dermatitis in adults.
Dermatology 1992;184:275-80.
33.Prasad D, Pandhi R, Negi KS, Kumar B. Topical metronidazole in seborrheic dermatitis – a doubleblind study. Dermatology 2001;202:35-7.
103
Bukvić Mokos et al.
Seborrheic dermatitis
34.Seckin D, Gurbuz O, Akin O. Metronidazole 0.75%
gel vs. ketoconazole 2% cream in the treatment
of facial seborrheic dermatitis: a randomized,
double-blind study. J Eur Acad Dermatol Venereol
2007;21:345-50.
35.Koca R, Altinyazar HC, Eştürk E. Is topical metronidazole effective in seborrheic dermatitis? A double-blind study. Int J Dermatol 2003;42:632-5.
36.Cook BA, Warshaw EM. Role of topical calcineurin
inhibitors in the treatment of seborrheic dermatitis: a review of pathophysiology, safety, and efficacy. Am J Clin Dermatol 2009;10:105-16.
37.Warshaw EM, Wohlhuter RJ, Liu A, Zeller SA, Wenner RA, Bowers S, et al. Results of a randomized,
double-blind, vehicle-controlled efficacy trial of
pimecrolimus cream 1% for the treatment of moderate to severe facial seborrheic dermatitis. J Am
Acad Dermatol 2007;57:257-64.
38.Berk T, Scheinfeld N. Seborrheic dermatitis. P T
2010;35:348-52.
39.Opdyke DL, Burnett CM, Brauer EW. Anti­-seborrheic qualities of zinc pyrithione in a cream vehicle: II Safety evaluation. Food Cosmet Toxicol
1967;5:321-6.
40.Marks R, Pearse AD, Walker AP. The effects of a
shampoo containing zinc pyrithione on the control of dandruff. Br J Dermatol 1985;112:415-22.
41.Pierard-Franchimont C, Goffin V, Decroix J, Pierard
GE. A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe
dandruff and seborrheic dermatitis. Skin Pharmacol Appl Skin Physiol 2002;15:434-41.
104
Acta Dermatovenerol Croat
2012;20(2):98-104
42.Langtry JA, Rowland Payne CM, Staughton RC,
Stewart JC, Horrobin DF. Topical lithium succinate
ointment (Efalith) in the treatment of AIDS-related seborrhoeic dermatitis. Clin Exp Dermatol
1997;22:216-9.
43.Dreno B, Moyse D. Lithium gluconate in the treatment of seborrhoeic dermatitis: a multicenter,
randomised, double blind study versus placebo.
Eur J Dermatol 2002;12:549-52.
44.Danby FW, Maddin WS, Margesson LJ, Rosenthal
D. A randomized, double blind, placebo controlled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of
moderate to severe dandruff. J Am Acad Dermatol
1993;29:1008-12.
45.Pirkhammer D, Seeber A, Hönigsmann H, Tanew
A. Narrow-band ultraviolet B (ATL-01) phototherapy is an effective and safe treatment option for
patients with severe seborrhoeic dermatitis. Br J
Dermatol 2000;143:964-8.
46.Vena GA, Micali G, Santoianni P, Cassano N, Peruzzi E. Oral terbinafine in the treatment of multi-site
seborrheic dermatitis: a multicenter, double-blind
placebo-controlled study. Int J Immunopathol
Pharmacol 2005;18:745-53.
47.Cömert A, Bekiroglu N, Gürbüz O, Ergun T. Efficacy
of oral fluconazole in the treatment of seborrheic
dermatitis: a placebo controlled study. Am J Clin
Dermatol 2007;8:235-8.
48.Ford GP, Farr PM, Ive FA, Shuster S. The response
of seborrheic dermatitis to ketoconazole. Br J Dermatol 1984;111:603-7.
ACTA DERMATOVENEROLOGICA CROATICA