Received: 22 April 2019 | Revised: 7 February 2020 | Accepted: 27 February 2020

DOI: 10.1111/exd.14091

REVIEW ARTICLE

An update on the microbiology, immunology and genetics of

seborrheic dermatitis

Jonas A. Adalsteinsson1 | Shivani Kaushik2 | Sonal Muzumdar1 |

Emma Guttman-Yassky2 | Jonathan Ungar2

1
Department of Dermatology, University of
Connecticut, Farmington, Connecticut
2
Department of Dermatology, Icahn School
of Medicine at Mount Sinai, New York, New
York
Correspondence
Jonas Adalsteinsson, Department of
Dermatology, University of Connecticut,
Farmington, CT.
Email: adalsteinsson@uchc.edu
Abstract
The underlying mechanism of seborrheic dermatitis (SD) is poorly understood but
major scientific progress has been made in recent years related to microbiology, im-
munology and genetics. In light of this, the major goal of this article was to summarize
the most recent articles on SD, specifically related to underlying pathophysiology. SD
results from Malassezia hydrolysation of free fatty acids with activation of the im-
mune system by the way of pattern recognition receptors, inflammasome, IL-1β and
NF-kB. M. restricta and M. globosa are likely the most virulent subspecies, producing
large quantities of irritating oleic acids, leading to IL-8 and IL-17 activation. IL-17 and
IL-4 might play a big role in pathogenesis, but this needs to be further studied using
novel biologics. No clear genetic predisposition has been established; however, re-
cent studies implicated certain increased-risk human leucocyte antigen (HLA) alleles,
such as A*32, DQB1*05 and DRB1*01 as well as possible associations with psoriasis
and atopic dermatitis (AD) through the LCE3 gene cluster while SD, and SD-like syn-
dromes, shares genetic mutations that appear to impair the ability of the immune
system to restrict Malassezia growth, partially due to complement system dysfunc-
tion. A paucity of studies exists looking at the relationship between SD and systemic
disease. In HIV, SD is thought to be secondary to a combination of immune dysregu-
lation and disruption in skin microbiota with unhindered Malassezia proliferation. In
Parkinson's disease, SD is most likely secondary to parasympathetic hyperactivity
with increased sebum production as well as facial immobility which leads to sebum
accumulation.

KEYWORDS

inflammasome, Malassezia, sebaceous glands, seborrheic dermatitis, systemic disease

Abbreviations: AD, Atopic dermatitis; EGFR, Epidermal growth factor receptor; HIV, Human immunodeficiency virus; HLA, Human leucocyte antigen; PD, Parkinson's disease; SD,
Seborrheic dermatitis.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Experimental Dermatology. 2020;29:481–489.  wileyonlinelibrary.com/journal/exd | 481

482 | ADALSTEINSSON et al.
1 | W H AT I S S E B O R R H E I C D E R M ATITI S ?
1.1 | Introduction
Seborrheic Dermatitis (SD) and dandruff are chronic skin disorders
on opposite ends of the same spectrum, with dandruff as a milder
form of SD, characterized by mild scaling of the scalp without vis-
[1,2]
ible inflammation. At least 50 million Americans are thought to
be affected, with $300 million spent annually on over-the-counter
products.[2,3] At the other end of the spectrum, SD typically presents
as a red scaly rash, affecting the sebaceous areas of the face, scalp,
upper chest and back; however, this presentation can be varied.[1,3]
It is estimated that, together, SD and dandruff affect half of the adult
[3]
population, yet their aetiology is not well understood. For more
than a century, Malassezia yeast has been implicated as a major fac-
tor in causing SD and dandruff with M. restricta and M. globosa likely
the predominant species.[1,3‒9] The complex interplay of Malassezia,
keratinocytes and the immune response against an altered lipid com-
position in the skin plays a crucial role in SD pathogenesis.
1.2 | Epidemiology
While SD affects all ages, it has a predominantly bimodal distribu-
tion, with a peak during infancy (2-12 months of age) and another
peak in early adulthood.[10‒13] Additionally, the incidence is higher
among human immunodeficiency virus (HIV)-infected and immu-
nocompromised patients ranging from 30% to 83%.[14‒17] There
are multiple factors that determine an individual's susceptibil-
ity to the development of disease such as gender, individual lipid
composition, immune status, neuropsychiatric factors (including
Parkinson's disease (PD) and other neuropsychiatric diseases) and
high environmental humidity and heat.[6,18] In recent years, studies
have suggested a genetic predisposition, although further study is
needed. While SD and dandruff have a strong relationship with HIV,
most patients with SD have no major abnormalities of the immune
system.[18‒21]
1.3 | Clinical features
Dandruff is the most common form of SD, with most individu-
als never seeking medical treatment. It presents as scales with-
out visible inflammation. While dandruff is often limited to the
scalp, it can also involve the chest, shoulders and back.[14,22] SD
is mainly a clinical diagnosis, but sometimes this is complicated by
atypical, varied presentation. SD can be mild, moderate or severe
based on the extent of inflammation and scaling. The character-
istic clinical findings include greasy yellow scales overlying well
[13,14,22]
defined erythematous patches. In patients with darker skin,
[23]
SD may present with hypopigmented, scaly patches. SD in in-
fants usually presents in 3rd-4th week of life with erythematous
plaques with fine greasy scales, often in the diaper or scalp areas.
In infants, cradle cap is the second most common clinical manifes-
tation. It may present on the scalp, face, retro-auricular area, body
folds and trunk; in rare instances, it may be generalized. Another
common presentation in infants is the “diaper” form.[3,13,18,24] The
most severe form of SD is usually seen in patients with an underly-
ing disease such as neuropsychiatric diseases, particularly PD or
HIV.[25‒33] Pruritus does not necessarily always accompany SD,
but is more prevalent in the more inflammatory forms, and espe-
cially with scalp involvement. The disease does not only affect the
skin, but it can also be accompanied by hair loss, which is often
transient and resolves upon disease improvement. In children, it
is usually self-limited, whereas it is more often a chronic condition
in adults.[1,2,13] A recent study concluded that the prevalence of
SD in their patient population was 14.3%, with the disease being
especially common in light-skinned populations during the winter.
The authors concluded that this was due to increased xerosis and
decreased barrier function in the winter, as well as possible UV
protective effects during the summer. Dark-skinned individuals
might be less likely to seek care due to seborrheic dermatitis, pos-
sibly due to less striking erythema or improved barrier function
compared with light-skinned individuals.[34]
1.4 | Differential diagnoses
Seborrheic dermatitis has a wide range of differential diagnoses, de-
pending both on age and distribution. During infancy, it is important
to differentiate SD from Langerhans cell histiocytosis as misdiagno-
sis can lead to delay in treatment. In adults with adult facial SD, the
differential diagnoses include rosacea and lupus erythematosus. As
it often presents as a malar rash, it is important to be mindful of SD
as the most common cause for malar rash in adults. Involvement of
the nasolabial fold and scaling favours the diagnosis of SD while pus-
tules favour rosacea. Worsening with sun exposure can favour both
rosacea and cutaneous lupus. The most common differentials for
scalp and truncal SD in adults include eczema, psoriasis, and tinea
versicolor.[3,20,35‒37]
2 | TH E PATH O PH YS I O LO G Y O F
S E B O R R H E I C D E R M ATITI S
While the order of events is unclear regarding the pathophysiology
of SD, it is agreed upon by most sources that the three main prereq-
uisites are as follows: Malassezia colonization, lipid secretion by seba-
ceous glands and an underlying immune system susceptibility.[1,5,7,38]
The pathogenesis can be categorized into five different phases.
1. Sebaceous glands secrete lipids onto the skin surface.[7,39,40]
2. Malassezia colonizes areas that are covered with lipids.[5‒7,9]
3. Lipase is secreted by Malassezia, resulting in the generation of
free fatty acids (FFA) and lipid peroxides that activate the inflam-
matory response.[7,41,42]
ADALSTEINSSON et al.
4. The immune system generates cytokines, such as IL-1α, IL-1β, IL-2,
IL-4, IL-6, IL-8, IL-10, IL-12 and TNF-α. This stimulates keratinocyte
[19,20,43,44]
proliferation and differentiation.
5. Skin barrier disruption with resulting clinically evident erythema,
pruritus and scaling.[13,14,22]
The pathophysiology of SD is summarized in Figure 1. Several
endogenous and exogenous factors have been implicated in the
development of SD. Exogenous factors include the Malassezia
fungus and other microbiota, stress, poor skin and hair care prac-
tices, hot humid weather conditions and certain medications such
as antineoplastic agents and epidermal growth factor receptor
(EGFR) inhibitors.[6,18,42,45‒51] The role of diet is controversial but
a recent cross-sectional study examining dietary patterns and SD
concluded that a high fruit intake was associated with less SD,
whereas a “Western” dietary pattern in females was associated
with increased risk of SD.[52] Endogenous factors include male gen-
der, increased androgen activity, sebaceous gland activity and lipid
composition, with recent studies suggesting a highly likely role of
underlying genetics and the immune system, although this has
been debated upon in the past.[7,19,53] The increased prevalence of
SD in males is likely due to higher androgen levels compared with
females, with androgens affecting sebaceous gland activity and
lipid composition in a way that promotes Malassezia growth.[7,19,38]
Supporting an underlying genetic role includes certain genetic mu-
tations and syndromes such as Leiner disease, which are known
to produce a rash with an SD-like phenotype. Supporting an im-
portant role of the immune system is the fact that certain diseases
affecting the immune system such as HIV, lymphoma and bone
marrow suppression tend to predispose patients to develop SD.
Other endogenous factors such as the nervous system also seem
to play a role with PD patients and stroke patients being at an
increased risk of SD.[25‒33,46,54]
3 | M I C RO B I OTA , A M A J O R CU LPR IT
Formerly known as Pityrosporum, the Malassezia fungus is a lipophilic
budding yeast that has been consistently shown to be important in
[36,43]
the pathogenesis of SD.
Malassezia's virulence is thought to be due to its high cell wall
lipid content, which provides mechanical stability, promotes re-
sistance to osmosis and also protects it from phagocytosis[55,56]
M. restricta and M. globosa are the two most prevalent species of
Malassezia in SD in most studies, and it is suggested that they have a
significantly increased expression of lipase genes which contributes
to their virulence. It has been shown that the quantity of yeasts di-
rectly correlates with the severity of disease; however, some stud-
ies disagree with this finding.[57‒64] Therefore, it has been suggested
that an overgrowth of Malassezia organisms is important only in
those individuals who are immunologically predisposed towards the
development of SD. It remains unclear, why these organisms would
be pathogenic only in selected individuals but it might be due to
| 483
individual differences in sebaceous gland function, lipid composition
and immune function.[43,65]
The Malassezia genus includes over 14 species of fungi. The ones
most commonly associated with SD are M. globosa, M. restricta, M.
furfur, M. sympodialis, M. obtuse, M. slooffiae and most recently, M.
arunalkei[57‒64,66] In recent years, many studies have been conducted
looking at the differences between these fungi, including differ-
ences in body site distribution and geographical differences. The
prevalence of different Malassezia species seems to differ between
countries. According to Barac et al, M. globosa is the most prevalent
species in Canada, Iran and Greece.[19,60,67,68]M. restricta is the most
prevalent species in South Korea and Bosnia. In Serbia, it is M. sloof-
fiae.[19,69] Three recent studies conducted in India and China revealed
that M. restricta and M. globosa are the two most prevalent species
on the skin of patients with SD.[38] The reason for this difference be-
tween countries is not known. On the scalp and forehead, M. restricta
is the most common while M. globosa is the most common species
found on the chest and back. The differences in distribution of these
two species are attributed to different lipid content at different body
sites.[59,64,65,70‒73] Interestingly, gender does not seem to predispose
individuals to certain strains of Malassezia over others; however, age
does—M. globosa seems to be more common in individuals younger
than 14 years, and M. sympodialis seems to be more common in older
subjects. Young adults between 21-30 have been shown to have the
highest positive culture rate, with the chest having the highest and
the thighs having the lowest positive culture rates of all evaluated
body parts. This unequal representation of Malassezia among age
groups has been attributed to differences in sebum production at dif-
ferent ages.[1,19,38,43,47,65,74‒76]
SD may result from an immune reaction to Malassezia or its
by-products. Wikramanayake et al proposed that changes in the
host, such as epidermal dysfunction, cause an alteration in the skin
microbiome, leading to a proliferation of Malassezia. Metabolites of
Malassezia infiltrate the epidermal barrier leading to an inflammatory
response. Immune cells are recruited to the site of inflammation.
Their proinflammatory cytokines cause barrier dysfunction, result-
ing in increased alteration of the skin microbiota. As a result, more
Malassezia and its by-products are able to penetrate the epidermis,
resulting in a continual cycle of inflammation.[77]
In addition to Malassezia species, it is suggested that certain bac-
teria also contribute to the pathogenesis of SD by their ability to
hydrolyse sebum and supply nutrients that promote the growth of
Malassezia. A recent study done by Tanaka et al analysed bacterial
microbiota on non-lesional and lesional sites of 24 patients with SD
using pyrosequencing and quantitative real-time polymerase chain
reaction. The results showed a predominance of Acinetobacter,
Staphylococcus and Streptococcus on lesional skin.[46] Additional
bacteria that have been implicated include Corynebacterium and
Propionibacterium. One study found a higher colonization rate of
S. epidermidis in both HIV-positive and HIV-negative patients with
SD.[46,78] Another recent study reported that S. aureus was the most
common bacterial member of the skin flora in patients with SD, pro-
posing an etiological role for S. aureus.[79]
484 | ADALSTEINSSON et al.
FIGURE 1 Our updated understanding behind the pathophysiology of seborrheic dermatitis
Park et al compared the scalp microbiome of patients with dan-
druff and SD to patients without the disease. They found that bacte-
rial and fungal communities were different between the two groups.
Staphylococcus species and M. restricta were associated with an in-
creased incidence of scalp disease. Propionobacterium species and M.
globosa were associated with a normal scalp. In addition, the balance
of M. restricta with other bacterial and fungal organisms was found
to be important in the development of dandruff and seborrheic
dermatitis.[80]
4 | S E BAC EO U S G L A N DS A N D LI PI DS
Sebaceous glands are holocrine glands, widely distributed in all areas
of the body except for the palms, soles and back of the feet. They
have the greatest concentration on the face, followed by the back
and the chest.[7] The role of sebaceous glands in SD is strongly impli-
cated by the predilection of SD in these areas and high prevalence of
SD during periods of high sebaceous activity, such as infancy and ad-
olescence/young adulthood. Sebaceous gland activity is stimulated
by androgens and adrenal corticosteroids.[7] High sebum activity has
a direct correlation with SD and acne, and an inverse relationship
with atopic dermatitis (AD). Moreover, it has been shown that pa-
tients with acne and SD are less likely to suffer from AD compared
with the general population.[38,46,81] Androgens play an important
role in the regulation of sebaceous gland activity and, therefore, SD
is more common in males.[7] However, some studies have reported
higher prevalence in women which has been attributed to more fre-
quent use of cosmetics.[19,53]
The skin surface lipid film is composed of both sebocyte and
keratinocyte derived lipids. Keratinocyte lipids are incorporated
within the layers of the stratum corneum, while sebocyte lipids are
secreted onto the skin surface. Sebum lipid composition differs from
keratinocyte lipids. Squalene is present only in sebum lipids and is
used as a marker to differentiate sebaceous from keratinocyte lip-
ids.[81‒84] Malassezia lipases and phosphates hydrolyse sebaceous lip-
ids, resulting in decreased triglycerides and a corresponding increase
in free fatty acids. Malassezia uses saturated fatty acids, leaving be-
hind irritating unsaturated fatty acids such as oleic acids. Oleic acid
is believed to be the main trigger for inflammation in SD, and an indi-
vidual's sensitivity to this irritating free fatty acid is thought to play a
crucial role in the pathogenesis of disease. When oleic acid is applied
ADALSTEINSSON et al.
topically, patients with SD experience more extensive skin desqua-
mation than non-SD subjects, displaying their underlying increased
sensitivity to fatty acid–induced skin barrier disruption.[7,41,46,81,85]
5 | M A J O R A DVA N C E S I N I M M U N O LO G Y
A N D M O LEC U L A R B I O LO G Y
In recent years, there has been great advancement in our under-
standing of many immunological and biomolecular pathways and
techniques. Malassezia yeast are thought to induce the maturation
of dendritic cells with further inflammasome assembly, Th2 stimula-
tion and the stimulation of a great number of inflammatory pathways
and secretion of different cytokines with disruption of the skin bar-
[20]
rier A large number of inflammatory markers have been noted to
be increased in SD, including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10,
IL-12, TNF-α, beta-defensins, IFN-γ, nitric oxide and histamine.[20]
Recently, it was shown by Wikramanayake et al that Mpzl3 knock-
out mice, which have an SD-like phenotype, had increased levels of
IL-17 expressing γδ T cells. This is the first time that Il-17 has been
implicated in SD.[86] There also seems to be a disruption in structural
epidermal biomarkers such as keratins 1, 10 and 11 as well as cera-
mides and sphingoid lipids, which are important for the integrity of
the skin barrier.[20,87] With successful treatment of SD, it has been
shown that ceramides and sphingoid bases return to their normal
levels, keratins increase and inflammatory markers such as IL-1, IL-8
and histamine return to normal.[19,20,43,44]
The innate immune system plays a key role in SD by mounting
the first immune response against Malassezia; however, there has
[44]
been limited research on this topic. When Malassezia interacts
with epidermal cells in susceptible individuals, antigen-presenting
cells are stimulated through pattern recognition receptor activa-
tion. There are many different types of pattern recognition recep-
tors that get stimulated in this process such as toll-like receptor-2,
NOD-like receptors and C-type lectin receptors.[44,88] Certain Nod-
like receptors are a part of an intracellular protein complex called
an inflammasome. With stimulation of NOD, the inflammasome gets
assembled, the protease caspase-1 is activated and it cleaves pro
IL-1β. Active IL-1β is a powerful inflammatory cytokine involved in
the pathogenesis of many diseases, including SD.[89‒92] This has been
suggested to be a key pathway in the innate immune response to
[93‒95]
fungi such as candida, aspergillus and Malassezia. In addition,
the stimulation of extracellular toll-like receptor-2 has also been
shown to be an important mechanism, mainly through an increase
in IL-8 production by keratinocytes which further leads to migration
[96]
of neutrophils and lymphocytes and activation of NF-kB. In par-
ticular, the most prevalent Malassezia species in SD, M. globosa and
M. restricta, have been shown to elicit a greater IL-8 response than
other species. Other immunomodulary effects of Malassezia include
inhibition of IL-1 secretions in vitro, which seems to play a role in
limiting the inflammation seen in other Malassezia associated dis-
eases, such as pityriasis versicolor, which has minimal inflammation
despite a high fungal load.[38] SD appears to share some common
| 485
immunological pathophysiology with other inflammatory dermato-
ses, including psoriasis and AD, but differs from each in associated
triggering factors.[20,38,44]
6 | TH E U N C LE A R RO LE O F G E N E TI C S
To date, the study of genetic predisposition for SD has been limited,
but recent studies have shown that genetic susceptibility likely plays
a role as certain human leucocyte antigen (HLA) subtypes tend to
increase risk of developing SD. Even though psoriasis and AD each
share several clinical and pathologic features with SD, a recent study
failed to find robust evidence for a shared genetic background be-
tween these diseases.[97,98]
In 2014, an observational case-control study comparing HLA
alleles in individuals with SD and healthy volunteers reported that
fourteen haplotypes appeared twice or more in individuals with SD
and four haplotypes with frequencies <0.0010 were found in two pa-
tients with SD. They found three alleles that had not been previously
reported in association with SD—A*32, DQB1*05 and DRB1*01.[98]
Sanders et al did a cross-sectional study using a candidate gene ap-
proach to investigate whether genetic variants previously associated
with AD and psoriasis are also associated with an increased risk of
SD. In addition, they conducted a genome-wide associate study to
identify variants associated with SD. They did not find a significant
locus for SD after correcting for multiple testing although the LCE3
gene cluster, known to be important in psoriasis and AD, did show
suggestive associations with SD. They concluded that their findings
suggested an overlap between SD, psoriasis and AD although this
needs to be further studied.[97]
In 2018, Mills et al proposed a set of genes, called the “unhealthy
skin signature” which were found to be dysregulated in a number of
cutaneous diseases including SD, psoriasis, AD and acne. In this gene
cluster, genes that were associated with the immune response were
upregulated. Genes controlling regulation of the Wnt/B-catenin
pathway and actin-filament based processes were downregulated.[99]
So far 11 gene mutations or protein deficiencies have been
identified that can induce SD or an SD-like rash. Most of these
mutations play a role in either the immune response or epidermal
differentiation. These mutations were summarized in a review done
by Karakadze et al in 2017.[21] Mutations associated with impaired
cutaneous immunity in humans include ACT1, C5, IKBKG and STK4,
summarized in Table 1. The ACT1 mutation leads to defects in cu-
taneous immunity by abolishing IL-17, leading to an SD-like inflam-
mation in response to cutaneous fungi.[100] C5 complement defects
can present with diarrhoea, recurrent infections, generalized SD and
wasting in infants, better known as Leiner's disease. C5 is important
for both opsonization and formation of the membrane attack com-
plex. These deficiencies lead to a decreased innate immune response
against Malassezia, leading to increased Malassezia counts on the
skin.[101‒103] IKBKG encodes nuclear factor kB essential modulator
(NEMO) which is essential for NK-kB signalling. This pathway plays
a vital role in the regulation of the innate and adaptive immunity,
486 | ADALSTEINSSON et al.

TA B L E 1 Gene mutations or protein

Gene mutation Function
deficiencies in humans that can lead to an
ACT1 Adaptor molecule that interacts with IL-17 receptors SD-like rash[21]
to activate NF-kB. This leads to an abnormal
immune response to cutaneous fungi[100]
Biotinidase Enzyme deficiency which results in decreased free
biotin for cellular use[110]
C5 complement Required for opsonization of pathogens and
formation of membrane attack complex for
phagocytosis. Can present as Leiner's disease[101‒103]
IKBKG Encodes NEMO, a regulatory subunit of the
IKK complex. Leading to a disruption of NK-kB
signalling[104]
STK4 A kinase which is critical for maintenance of
lymphocytes[105‒107]
ZNF750 Transcription factor that regulates keratinocyte
terminal differentiation[107‒109]

cytokine production, infection, and inflammation.[104] STK4 mu-
tation leads to CD4 lymphopenia, low serum C4 level and various
combined immunodeficiencies.[105‒107] ZNF750 mutation resulted in
a defected zinc finger transcription factor. It is a key regulator for
[107‒109]
keratinocyte terminal differentiation. Abnormal host immu-
nity may allow Malassezia to multiply with the resulting increase in
oleic acid causing skin irritation and defective epidermal differenti-
ation. The exact mechanism of SD rash is unknown but mutations
in mice have led to development of an SD-like phenotype includ-
ing the 2C T-cell receptor, rough coat and myelin protein zero-like
3, which are important for normal immune function and epidermal
differentiation.[21]
7 | A CO M PLE X R E L ATI O N S H I P W ITH
S YS TE M I C D I S E A S E S
Seborrheic dermatitis has been associated with several different dis-
eases. While a myriad of neurological, immunosuppressive, genetic
and psychiatric conditions have also been associated with SD, the
two most strongly associated are HIV and PD. The paucity of studies
examining the association between these diseases and SD has left
the connection between these entities and SD unexplained.[25‒33]
Seborrheic dermatitis has a 20%-83% prevalence in HIV-infected
patients. It is speculated that immune dysregulation leads to a dis-
ruption in skin microbiota and the inflammatory response in these
patients, leading to SD. CD4 lymphopenia may allow for unhindered
proliferation of Malassezia organisms on the skin.[111] Clinical pre-
sentation of SD in HIV can be different than in non-HIV patients.
HIV patients tend to have more severe and generalized inflamma-
tion and a yellower, thicker and greasier scale. It has a similar dis-
tribution but tends to be more generalized and can spread to areas
considered to be atypical. It is thus considered by some dermatol-
ogists to be a distinct disease. Several studies have challenged the
role of Malassezia in SD in HIV-infected patients. One study done
in HIV-positive patients showed either negative or limited growth
of Malassezia.[43,78,112‒114] On the other hand, a significantly higher
number of Malassezia was cultured from HIV-negative patients with
SD. These studies suggest that HIV-positive patients may have a dif-
ferent pathogenic mechanism than SD in individuals with an intact
immune system. These patients are also often refractory to standard
SD treatments, requiring prolonged courses of topicals and systemic
antifungals, and treatment failure is common.[43,78,114]
Parkinson’s disease is another common entity with highly increased
prevalence of SD, which can be seen in approximately 60% of patients
with PD.[115] Malassezia yeast density has been shown to almost double
in SD lesional skin in patients with PD compared with SD lesional skin
in non-PD patients. This is most likely due to parasympathetic system
hyperactivity, leading to increased sebum production. Facial immo-
bility is also thought to play a role as it may lead to increased sebum
accumulation. This may also explain the higher SD prevalence in other
neurological diseases as well, such as stroke.[28,115] Higher sebum leads
to higher Malassezia virulence potential because of increased free
fatty acid production such as oleic acid. The most effective species of
Malassezia to hydrolyse the sebum, M. globosa, has been shown to be
the most prevalent species in patients with PD.[115] Additionally, pa-
tients with PD have increased levels of melanocyte-stimulating hor-
mone, which has been shown to have a positive relationship with SD.
As a result, increased seborrhoea and SD may be signs of impending
autonomic dysfunction in parkinsonian patients.[116,117] The effect of
L-dopa has been shown to reduce sebum secretion in these patients
with eventual improvement in SD. Finally, the high yeast density in PD
patients, with high lipase activity and high prevalence of SD, supports
the importance of an infectious role in the pathophysiology of SD, es-
pecially Malassezia.[43,115]
8 | FU T U R E D I R EC TI O N S
While SD is often considered a minor disease by many practi-
tioners, its high prevalence and significant impact on patients’
quality of life makes it an important disease to understand and
ADALSTEINSSON et al.
treat. Many studies in recent years have helped to elucidate the
pathophysiology of SD. However, there is still much that is un-
known, and further rigorous research is needed to better under-
stand its pathogenesis, especially when it comes to novel biologic
treatments.
We still do not fully understand fully how SD will respond to
different types of interleukin blockade, such as IL-4 (mainly dup-
ilumab), IL-17 and IL-23 blockade. Despite IL-4 levels being re-
ported to be increased in some cases of SD, IL-4 blockade might
actually worsen SD. It has been proposed that specifically head
and neck dermatitis, a well-known side effect of dupilumab, might
be due to increased levels of IL-17 in lesional skin.[118] In 2018,
Wikramanayake et al demonstrated increased levels of IL-17 ex-
pressing γδ T cells in Mpzl3 knockout mice. This was the first time
IL-17 had been shown to be increased in SD.[86] Th17 activity might
be increased in SD at baseline, which could be worsened further
with IL-4 blockade.[118] This is supported further by the fact that
head and neck dermatitis responds to fluconazole in many cases.
Future studies should aim to look at IL-17 levels in lesional skin
of human subjects with SD, before and after treatment with IL-17
blockers such as Ixekizumab, Secukinumab and Brodaliumab, as
well as clinical response. When it comes to IL-4, there have been
conflicting reports. Faergemann et al found increased levels of IL-4
in the skin of patients with SD when compared to normal con-
trols.[119] However, Trznadel-Grodzka et al found that IL-4 levels
were similar between patients with SD and normal controls.[120]
Further studies are needed to determine the role of interleukins
and novel biologic therapies in SD, as that might dramatically in-
crease our understanding of SD pathophysiology.
C O N FL I C T O F I N T E R E S T
The authors have no conflicts of interest to report.
AU T H O R C O N T R I B U T I O N
All authors have read and approved the final manuscript. JA con-
ducted the literature review and wrote the main manuscript. SK and
SM assisted with literature review and writing the manuscript. EG
contributed to quality control and served as content advisor for the
manuscript. JU served as primary content decision maker and wrote
the manuscript.
ORCID
Jonas A. Adalsteinsson https://orcid.org/0000-0002-1159-6159
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How to cite this article: Adalsteinsson JA, Kaushik S,
Muzumdar S, Guttman-Yassky E, Ungar J. An update on the
microbiology, immunology and genetics of seborrheic
dermatitis. Exp Dermatol. 2020;29:481–489. https://doi.
org/10.1111/exd.14091