doi: 10.1111/1346-8138.

13806 Journal of Dermatology 2017; 44: 863872

REVIEW ARTICLE
Critical role of environmental factors in the pathogenesis of
psoriasis
Jinrong ZENG, Shuaihantian LUO, Yumeng HUANG, Qianjin LU
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital of Central South University,
Changsha, China

ABSTRACT
Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors,
such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between envi-
ronmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is
a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset
and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous
clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the
mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments
against environmental risk factors.

Key words: environmental factors, epigenetics, genetics, pathogenesis, psoriasis.

INTRODUCTION influenced by environmental factors.68 T cells have been

Psoriasis is a chronic and recurrent inflammatory skin disease
which is characterized by hyperproliferative keratinocytes and
infiltrating immune cells, including T cells, dendritic cells,
macrophages and neutrophils. The main clinical features of
psoriasis are a thick epidermis that expresses keratin 16 (K16)
in cells above the basal layer and consistent T-lymphocyte
(positive by CD3 staining) infiltration into both the epidermis
and dermis of lesions. The prevalence in adults ranges 0.51
11.43%, and in children 01.37% depending on age, geo-
graphic location and genetic background.13 Initially, psoriasis
was just considered a disease with hyperproliferation and
abnormal differentiation of keratinocytes, while current
researches confirm that psoriasis is an autoimmune skin dis-
ease characterized by T-cell-mediated responses. The imbal-
ance among CD4+ T-cell subsets contributes to hyperkeratosis
and parakeratosis.4,5 Various T-cell subsets, such as T-helper
(Th)1, Th2, Th17 and regulatory T cells (Treg), are involved in
the immunopathogenesis and chronic inflammation response
of psoriasis. The fact that Th1 and Th17 cells increase while
Th2 and Treg decrease has been found in patients with psoria-
sis. So, blockade of pathogenic T-cell activation contributes to
the improvement of both clinical and histopathological disease
condition, including abnormal K16 expression and excessive
T-cell infiltration.
Currently, psoriasis is believed to be triggered by the combi-
nation of genetic, epigenetic and environmental influences, and
its genetic diversity and epigenetic modifications can be
believed to be a key mediator in psoriasis. Environmental risk
factors trigger the immune response of the body, where naive
T cells are activated by antigen-presenting cells (APC) in the
epidermis, especially Langerhans cells. APC can also release
cytokines such as interleukin (IL)-12 and IL-23, which promote
naive T cells to differentiate into Th1 and Th17 cells.9 Then, the
activated T cells migrate from lymph nodes to skin, where they
are stimulated to produce plenty of cytokines. Therefore, these
cytokines interact with the resident epidermal and dermal cells
and then cause changes, including keratinocyte proliferation
and epidermal thickness. All the changes involved in the two
main pathways around T cells include: IL-2/Th1/interferon
(IFN)-c and IL-23/Th17/IL-17. In the first pathway, IFN-c pro-
duced by activated Th1 cells induces the expression of co-sti-
mulatory molecules on dendritic cells and intercellular adhesion
molecule (ICAM)-1 on keratinocytes, stimulates tumor necrosis
factor (TNF)-a release from macrophages, thus inhibiting ker-
atinocyte apoptosis.10 In the second pathway, Th17 cells
release the main effector cytokines IL-17 and IL- 22. IL-17 can
influence the expression of cytokines such as TNF-a and
ICAM-1, increase keratinocyte expression of chemokines and
reduce expression of cell adhesion molecules.11 IL-22 also pro-
motes the proliferation of keratinocytes.12 Both of them result
in the disruption of the skin barrier (Fig. 1).
Unfortunately, there is no cure for psoriasis at present, and
most of the current treatments just manage the symptoms by
drugs while omitting the importance of avoiding risk factors,
such as excess ultraviolet (UV) exposure, specific drugs,

Correspondence: Qianjin Lu, Ph.D., Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011,
China. Email: qianlu5860@gmail.com
Received 20 December 2016; accepted 22 January 2017.

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J. Zeng et al.

Table 1. Environmental risk factors in psoriasis

Main risk Critical role in the pathogenesis

factors of psoriasis References
UV exposure Immunoregulatory and 48
pro-apoptotic effects
Downregulates Th17/IL-23
response
Medications Interfering individual immune 56,57
system
Including signaling pathway
and cytokine expression
Smoking Toxins in cigarettes; interfere 65
Diet and with normal nervous system 7
obesity signaling and immune
cell signaling
Overexpression of
pro-inflammatory and
anti-inflammatory cytokines
Alcohol Sensitive to gluten; immunological 67,71
intake disorders
Infections Inducing autoimmunity response; 83,99
breakdown of immune tolerance
Stress Disturbing immune system 108
regulation and
abnormal T-cell activation

IL, interleukin; Th17, T-helper 17; UV, ultraviolet.

Figure 1. Psoriasis pathogenesis. Psoriasis is believed to be
triggered by a combination of genetic, disordered immune sys-
tem and environmental influences, and its genetics and
immune system can be affected by environmental factors.
Naive T cells are activated by antigen-presenting cells (APC) in
the epidermis, which promote naive T cells to differentiate into
T-helper (Th)1 and Th17, so that Th1 and Th17 cells increase
while Th2 and regulatory T cells (Treg) decrease. Then, the
activated T cells migrate from lymph nodes to skin, where they
are stimulated to produce plenty of cytokines. So these cytoki-
nes interact with the resident epidermal and dermal cells and
then cause changes, including keratinocyte proliferation and
epidermal thickness. DC, dendritic cells; IFN, interferon; IL,
interleukin; TNF, tumor necrosis factor; UV, ultraviolet.
infections, smoking, alcohol abusing and stress, and the critical
role of them on psoriasis are summarized in Table 1.
PATHOGENESIS OF PSORIASIS
Genetic polymorphism and epigenetic modification
in psoriasis
The pathogenesis of psoriasis mainly relates to the combined
effect of multiple gene susceptibility loci, the disordered
immune system together with pervasive environmental risk fac-
tors. Genome-wide association studies (GWAS) have been
applied successfully in psoriasis to explore the genetic archi-
tecture. Large amounts of data indicate psoriasis-susceptibility
loci or candidate genes (showed in Table 2) among different
populations, such as PSORS1 that could account for 3540%
in psoriasis in heritability.1315 In brief, the gene variants
associated with psoriasis can generally be divided into two
categories: immune-specific and skin-specific genes.16 Among
them, it is worth mentioning that mutations of caspase recruit-
ment domain-containing protein 14 (CARD14) and IL36RN
genes have been recognized as responsible genetic factors of
generalized pustular psoriasis.17,18 The CARD14 gene encodes
a protein that promotes the activation of nuclear factor (NF)-jB
and upregulates the expression of pro-inflammatory pathway
genes.19 IL36RN encodes the IL-36 receptor antagonist (IL-
36Ra) which counteracts the inflammatory effect of IL-36
cytokines (IL-36a, IL-36b and IL-36c) by binding their receptor
(IL-1RL2) and prevents the downstream activation of NF-jB
signaling.20 Recent studies identified more than dozens of
gene locus mutations of CARD14 and IL36RN, which differed
depending on geography and race. Now, psoriasis is com-
monly described as a T-cell-mediated autoimmune disease, in
which IFN-c and TNF-a act as key pro-inflammatory players
influenced by environmental factors and susceptibility genes.
Several biologics targeting cytokines and T cells have been
approved by the US Food and Drug Administration (FDA)
applied in clinics to treat psoriasis. Psoriasis is a multigene dis-
order whose manifestation and severity are likely to depend on
the patients genetic background.21,22 The incidence of psoria-
sis increased significantly (P < 0.05) in the patients relatives
and the concordance rate was much higher between monozy-
gotic twins (6572%) than dizygotic twins (1530%), which
indicated that genetic linkage played the key role in psoria-
sis.2,2325 Family lineage studies suggest that psoriasis has two
different genetic subpopulations, one with multifactorial

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 Environmental factors on psoriasis

Table 2. Several susceptibility loci associated with psoriasis

Susceptibility loci SNP Function References

HLA-C rs10484554c Involve in the immune reactions 115
IL-12B rs3213094 Encode IL-12-p40 subunit and promote Th1 development 116
IL-23R rs11209026 Initiate a tumor necrosis factor-dependent epidermal hyperplasia 117
LCE3D rs4112788 Control epidermal terminal differentiation 117
TNFAIP3 rs610604 Act downstream of TNF-a and regulate NF-jB signaling 115
IL13 rs20541 Involve in the modulation of Th2 immune responses 115
TNIP1 rs1024995b Act downstream of TNF-a and regulate NF-jB signaling 115
IL23A rs2066808 Promote inflammation response 115
ZNF313 rs2235617d Regulate T-cell activation 118

Superscript indicates alleles. NF, nuclear factor; SNP, single nucleotide polymorphisms; Th1, T-helper 1; T-helper 2; TNF, tumor necrosis factor.

determination and one with multigenic inheritance, which also
strongly suggests the contribution of epigenetic or environmen-
tal factors in the pathogenesis of disease.26,27 Among these
researches there are even conflicting results obtained in differ-
ent populations. Recent studies indicate that epigenetic-regu-
lated networks may be the key causative elements in some
cases to explain the clinical manifestations. Epigenetic modifi-
cation is often seen in the psoriasis, which can change the
manifestations instead of altering DNA sequence but can be
passed on to offspring. Studies showed the fact that the gen-
ome-wide methylation level of peripheral blood mononuclear
cells (PBMC) in psoriatic skin lesions and peripheral blood
increased significantly; more interestingly, the expression of
DNMT1 increased while MBD2 and MeCP2 decreased in
PBMC and the acetylation level of histone H4 decreased signif-
icantly because of the downregulated expression of P300, CBP
and Sirt1, and the upregulated expression of HDAC1,
SUV39H1 and EZH2.28,29 However, it is still a challenge to
know the exact mechanism how the environmental factors
influence epigenetic changes in psoriasis.
Interaction between environmental factors and
genetics in psoriasis
Environmental factors appear to induce inflammatory diseases
in individuals with latent genetic susceptibility. Many alterations
could be triggered by environmental factors such as diet,
microbial infections (from bacteria, fungus and virus), chemical
irritants or UV radiation exposure,30 and bad habits (such as
smoking and drinking).31,32 Now, it is widely accepted that the
interplay between environmental and genetic factors con-
tributes to the onset, development and present clinical symp-
toms of psoriasis. Parisi et al.33 suggested that the prevalence
of psoriasis distribution differed between Europe (0.732.9%)
and the USA (0.72.6%), indicating that different races had
various genetic backgrounds. The author also discussed the
variability in psoriasis prevalence among distinct geographic
positions. Several studies of psoriasis and psoriatic arthritis
have demonstrated the interaction of genes and environment.
Wei et al.34 had verified that environmental elements (including
mental stress, infection, trauma, damp, drugs smoking and
drinking) were all the risk factors in the course of occurrence,
aggravation and recurrence of psoriasis and found that human
leukocyte antigen (HLA)-A26 had significant positive correlation
with psoriasis of no environmental exposure (P < 0.0001). In
their research, they illustrated that environmental factors had
significant interaction with HLA-A26. Jin et al. discovered the
joint effect of HLA-Cw6 and smoking, a wonderful explanation
to identify the susceptibly variant related to psoriasis. The risk
of psoriasis is 11-fold less for non-smokers without the HLA-
Cw6 gene in comparison with smokers carrying the HLA-Cw6
gene in the Chinese Han population.35 GWAS have verified
amounts of genes correlated with environmental risks of psori-
asis. As we all know, obesity is a common risk factor for psori-
asis, and the roles of genetic factors may be modified by
obesity in psoriasis development.3537 Li et al.38 demonstrated
the epigenetic modifying action of obesity in the relevance of
psoriasis and genetic variants, and they even affirmed the
increased risk of psoriasis related to the single nucleotide poly-
morphism in IL-12B. Although little is known about the mecha-
nism of geneenvironment interactions in psoriasis, we have
the opportunity to evaluate geneenvironment interactions in
cohort studies because plenty of published GWAS applied to
psoriasis since 2007.
Interaction between environmental factors and
epigenetics in psoriasis
Epidemiological studies have showed that environmental risk
factors may result in the susceptibility and severity of psoriasis
among isogenic lines by epigenetic changes.39 Recently, epi-
genetic modification changes including DNA methylation, his-
tone modification and non-coding RNA have been found to be
involved in many diseases, such as psoriasis. These epigenetic
changes can often been seen in the pathogenesis of psoriasis.
Secreted frizzled-related protein (SFRP)4, a negative regulator
of the Wnt signaling pathway, can directly inhibit pathological
keratinocyte proliferation induced by pro-inflammatory cytoki-
nes, and the high methylation level of the promoter has led to
epigenetic downregulation of SFRP4 in inflamed skin of psori-
atic patients and imiquimod mouse models, which contributed
to the hyperplasia of epidermis in psoriasis.40 In a study direc-
ted by Zhou et al.,41 the researchers found nine instances of
skin-specific DNA methylation of differentially methylated sites
associated with psoriasis by a three-stage epigenome-wide
association study, which were not obviously influenced by

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J. Zeng et al.

genetic variations. Among them, the expression levels of

CYP2S1, ECE1, EIF2C2, MAN1C1 and DLGAP4 were nega-
tively related to DNA methylation. Recently, the technology of
using methylated DNA immunoprecipitation sequencing sug-
gested that DNA methylation may play an important role in the
epigenetic dysregulation of biological pathways in psoriasis.28
miRNA-31 induced by NF-jB is one of the most dynamic
miRNA identified in the skin of psoriatic patients and mouse
models, whose aberrant rise in keratinocytes will promote their
abnormal proliferation, increase acanthosis and inhibit the dis-
ease recovery in IL-23 mouse models. Study has confirmed
that the protein phosphatase 6 (ppp6c) acting as a targeted
molecular is a negative regulator that restricts the G1 to S
phase progression. The rise of miR-31 directly inhibits ppp6c
expression, thus enhancing keratinocyte proliferation.42
Recently, the emergence of long non-coding RNA (lncRNA) has
attracted our attention, defined as non-protein coding RNA
transcripts longer than 200 nucleotides, are acting as key regu-
lators of diverse cellular processes. Moreover, the expression
levels of various lncRNA are closely related to epidermal differ-
entiation and immunoregulation,43 such as PRINS, which is ele-
vated in non-lesional skin areas in patients with psoriasis while
deceased in the lesion. GIP3, which is increased in the lesional
skin areas, as its potential target gene, can reduce the sensitiv-
ity of keratinocytes to spontaneous apoptosis.44 All these find-
ings will benefit us in better understanding the molecular
mechanism of psoriasis (Fig. 2).

MECHANISMS OF ENVIRONMENTAL RISK

FACTORS IMPACT ON PSORIASIS
UV radiation exposure
Ultraviolet radiation from natural sunlight or artificial sources has
been actually exploited for treating psoriasis in recent decades.
The incidence of psoriasis may differ among various populations
owing to regional disparity with distinct UV distribution. A case
control study explored absolute latitude suggesting that there
was a wide variation in prevalence between 0% (in Samoa, aver-
age absolute latitude 13.35) and 3.3% (in Tanzania, average
absolute latitude 6).45 Moreover, sunscreen habits, altitude and
ground reflection of UV light may also result in differences in
average UV exposure. The mechanism of UV therapy mainly
includes three aspects. First, more vitamin D can be produced
by exposure to UV-B. Vitamin D is a hormone which plays a criti-
cal role in the treatment of psoriasis. Data shows that the optimal
concentration of vitamin D (25[OH]D) in serum circulating level
for maximum effect should be between 30 and 50 ng/mL (75
125 nmol/L).35. Therefore, if vitamin D is lower than 30 ng/mL,
UV-B exposure will benefit patients a lot. 25(OH)D plays a vital
role in the regulation of dendritic cells, the modulation of ker-
atinocytes and the proliferation of T cells.46,47 Second, UV-B has
pro-apoptotic effects leading to production of various pro- and
anti-inflammatory cytokines. It simultaneously suppresses the
differentiation of Th17 cells and inhibits IL-23/IL-17 expression.48
In addition, UV exposure can reduce immune cells migration to
skin, and lower psoriasis-related antimicrobial peptides, particu-
larly LL-37 and psoriasin which are visibly increased in
Figure 2. Epigenetic regulation in the pathogenesis of psoria-
sis. Environmental risk factors may lead to the high susceptibil-
ity and severity of psoriasis by epigenetic changes. Epigenetic
modification changes including DNA methylation, histone modi-
fication and non-coding RNA. The activation of nuclear factor
(NF)-jB and Wnt signaling pathways have been found to play
a vital role in the epigenetic mechanisms of the epidermal
hyperplasia in psoriasis. They activate the inflammation
response by targeting key molecular such as ppp6c, following
exposure to certain environmental triggers. M, methylation; IL,
interleukin; SFRP4, secreted frizzled-related protein 4. [Correc-
tion added on 6 June 2017, after first online publication: The
figure has been modified to remove the mention of STAT6.]
psoriasis.49 Studies showed that APC and autoreactive dermal T
cells with intense stimulation were considered to be primary initi-
ating factors contributing to the pathogenesis of this condi-
tion.45,50 UV-B is an excellent therapeutic option for moderate
psoriasis because of its high efficacy, relative safety and afford-
ability. Weatherhead et al.51 investigated whether UV-B has
higher efficacy in clearing psoriatic lesions and inducing remis-
sion. They also pointed out that only 311-nm UV-B could con-
tribute to fatal apoptosis in lesional epidermis, and the main
apoptotic cells were keratinocytes. What is more, they provided
a new insight into the use of keratinocyte apoptosis as a promis-
ing biomarker to further explore which wavelengths of UV-B
were most effective in curing psoriasis.52

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Medications
Studies have showed that many drugs, such as antiproliferative
agents (imiquimod), antivirals and antidepressants (lithium), anti-
hypertensives (beta-blockers), TNF-a, and many novel biologics
including anticytokine therapies used in the treatment of psoria-
sis (anti-TNF antibodies), have all been clinically associated with
initiation and exacerbation of psoriasis.53 The most widely
accepted hypothesis suggests there is an interaction between
TNF-a and IFN-a. IFN-a is an important cytokine that controls
natural immunity and is mainly produced from plasmacytoid
dendritic cells through stimuli such as infection or trauma. IFN-a
is also identified as a key element in the early phase of psoriatic
induction. TNF-a negatively regulates IFN-a production. There-
fore, anti-TNF-a therapy could increase IFN-a expression at the
tissue level and induce psoriasis.54 Vinter et al.55 induced a pso-
riasis-like inflammatory skin condition through applying Aldara
(Aldara 5%; Meda, Solna, Sweden) cream containing 5% imiqui-
mod, which may be because of its defective recruitment of
adaptive immune system and the strong stimulation of IL-10
counter-regulation. Imiquimod is a Toll-like receptor 7/8 agonist
used to treat genital warts and non-melanoma skin tumors. It
can activate the type I IFN-signaling pathway and has been con-
sidered as one of the best investigated triggers of psoriasis.56
Dalkilic et al.57 conducted a research involving 514 patients trea-
ted with anti-TNF-a and matched healthy controls in Turkey. The
incidence of anti-TNF-a-induced psoriasis was 1.16% (6/514
patients) which suggested that biological agents should be
restricted to an appropriate application field and physicians
should take full account of their indications. Sahuquillo-Torralba
et al.58 found that pembrolizumab, a new drug approved by the
FDA for cancer immunotherapy, could worsen the symptoms of
psoriasis. These drugs mainly aim at interfering with the individ-
uals immune system, resulting in psoriasis induction. The mech-
anisms by which the drugs trigger psoriasis are complicated, so
the clinical application of those drugs inevitably encounters
some difficulties.
Smoking
Smoking or secondhand smoke exposure is a possible risk
factor for psoriasis. However, controversial results are also
observed.59,60 The exact impact of smoking on disease activity
of psoriasis is not clearly known yet. Studies have showed that
smoking can increase the activity of spondyloarthritis and
rheumatoid arthritis, thus reducing quality of life.6163 Hojgaard
et al.64 conducted an observational research of 1388 psoriatic
patients to study the correlation between smoking and treat-
ment effect of TNF-a inhibitors. The result showed that heavy
smoking could decrease the treatment effect of TNF-a-targeted
drugs, and the impact seemed partially reversible. Naldi et al.36
directed an interesting comparative study and showed that
smoking expedited the occurrence of psoriatic arthritis in
patients without psoriasis, while it slowed down the recurrence
of psoriatic arthritis in patients with psoriasis. The reasons why
smoking is a possible risk factor of psoriasis are highly com-
plex due to a variety of unknown toxins contained in cigarettes.
However, one critical reason is the binding between nicotine
and nicotinic acetylcholine receptors (nAChR) leading to
2017 Japanese Dermatological Association
Environmental factors on psoriasis
disruptions of normal nervous system signaling. The nAChR-
mediated transduction pathway can regulate keratinocyte
function. Also, many immune cells including T cells, B cells
leukemic cell lines and thymocyte, have active nAChR and
nicotine binding to these receptors interferes with immune cell
signaling.65 What is more, it is believed that smoking is posi-
tively related to an increased risk of psoriatic comorbidity
including cardiovascular diseases.66
Alcohol intake
Even though the hypothesis that alcohol consumption is asso-
ciated with the increased risk of psoriasis onset and worsening
is not credible enough, studies showed that alcohol could
directly and indirectly enhance the production of pro-inflamma-
tory cytokines from many cell types, leading to persistent sys-
temic inflammation and promoting lymphocyte proliferation.
Moreover, alcohol and acetone could directly stimulate ker-
atinocyte proliferation and increase the mRNA levels of genes
characteristic of proliferating keratinocytes, such as a5 integrin,
cyclin D1 and keratinocyte growth factor receptor. In addition,
acetylcholine may also trigger psoriasis.67 Qureshi et al.31 sug-
gested that there was an obviously positive correlation
between heavy beer intake and risk of developing psoriasis
among women, whereas another survey showed that alcohol
intake may exacerbate psoriasis severity.68 The relationship
between psoriasis and alcohol intake is complicated, and dif-
ferent studies reached various conclusions. However, the con-
sensus is that patients with moderate to severe psoriasis have
a higher incidence and mortality of alcohol-associated dis-
eases, including cardiovascular diseases and tristimania.69 Bre-
naut et al. conducted a systematic published work review in
2013 using the Medline, Embase and Cochrane databases. He
found four of five studies showing that alcohol was a risk factor
for psoriasis.70 The possible mechanism is that beer and some
alcoholic beverages are made with wheat or other products
containing gluten, so only those people who are sensitive to
gluten frequently have symptoms. In conclusion, smoking and
alcohol may induce the onset of psoriasis by various mecha-
nisms, including immunological disorders such as keratinocyte
hyperproliferation and overexpression of pro-inflammatory
cytokines.71 However, the exact mechanisms by which
tobacco and alcohol induce psoriasis still require further inves-
tigation to verify the relation between tobacco and alcohol con-
sumption and psoriasis.
Diet and obesity
Patients often wonder what they cannot eat and whether diet-
ary changes can improve their symptoms or prevent recur-
rence. Of course, this refers to whether weight loss can
contribute to their skin condition in this discussion. Association
of psoriasis severity and high body mass index (BMI) score
has been identified in several recent researches which suggest
that bodyweight loss can improve Psoriasis Area and Severity
Index score of the patients.72 In addition, it is certain that
healthy eating patterns would benefit psoriatic patients, includ-
ing the use of oral vitamin B12, vitamin D, selenium and
omega-3 fatty acids in fish oils.73 As stated earlier, the optimal
867
J. Zeng et al.
concentration of vitamin D (25[OH]D) in serum circulating level
is 3050 ng/mL; if obese and lean subjects take the same
dose, the circulating level of vitamin D in the obese subject
would be insufficient, leaving gradually less 25(OH)D in the
organism. However, more data about nutritional interventions is
needed for clinical physicians to manage psoriatic patients. A
meta-analysis performed by Millsop et al.73 found that fish oil
seemed to be the most useful to improve the condition of
patients in a randomized controlled trial. Recently, epidemio-
logical and clinical studies74 have provided a possible curative
effect of a gluten-free diet for psoriasis. It was reported that a
gluten-free diet seemed to be in certain psoriatic patients
favor according to some early evidence, but it also needed
more trials in different populations. Obesity has been proved
correlative with a pro-inflammatory state and numbers of study
results have showed that being overweight could worsen psori-
asis. Wolk et al.75 conducted a casecontrol study composed
of 373 psoriatic patients and matched healthy controls in 2009.
They showed that obese individuals had a twofold increased
risk to develop psoriasis in comparison with those of normal
bodyweight. Furthermore, they found that each unit increase in
BMI was associated with a 9% increase in the risk of psoriasis
onset and a 7% increase in the risk of psoriasis severity. How-
ever, it is unknown whether psoriasis outcome was influenced
by weight loss interventions, and still now none of any studies
can expound the problem clearly. Several studies7678 have
sought to establish the possible impact of diet change and
weight loss on the therapeutic effect of psoriasis. They also
showed a condition improvement in the process of psoriasis
treatment and disease severity index that declined obviously
after following a gluten-free diet for those anti-gliadin antibody
(AGA)-positive patients. There is an agreement that overex-
pression levels of pro-inflammatory and anti-inflammatory
cytokines is most important in the pathogenesis of psoriasis.
Interestingly, obese individuals bear more chronic inflamma-
tion, which increases the risk for psoriasis onset.79 A study
conducted by Edson-Heredia et al.80 explored which clinical
factors in psoriasis correlated with the response to biologic
therapy, and they found that BMI had the most intense
response to biologics in the whole studies. Ustekinumab was
mainly used for treating psoriasis and it was proved to be a
promising biologic agent. Its phase III clinical trial showed that
higher bodyweight was a potential predictor of worse response
to it at the 28th week (P < 0.0001).81 Based on the above stud-
ies, proper diet adjustment and healthy bodyweight may bene-
fit psoriatic patients in the process of treatment but more
clinical data is needed to confirm this conclusion.
Microbiota and psoriasis
Cutaneous microbiota and psoriasis
Skin and intestinal microbiota have been the focus of much
attention in all fields recently, especially immunology. A sum-
mary of studies of microorganisms in psoriasis is displayed in
Table 3. There is a peaceful coexistence among bacteria, fungi
and virus in a healthy body, which can develop an effective
first-line barrier defense against pathogens and other
868
environmental risk factors. The composition of the microbiome
is specific to each individual. Usually, the microbes and their
host interact with each other in a harmonious way.82 However,
disordered immune responses can cause inflammatory dis-
eases, and the exact etiology remains unknown. Hajishengallis
et al.83 assumed that microbes could induce autoimmunity in
those persons with a potential genetic susceptibility. Micro-
ecosystem disturbance induces infection when the host is in
poor condition because of drug abuse, complications and
undernutrition, together with other environmental factors such
as diet, stress, and tobacco and alcohol intake.84 Without the
impact of environmental factors, the composition of the micro-
biome would remain relatively stable over a whole lifetime but
change a little with aging.85 Th17 cells have been identified as
major constituents of psoriasis pathogenesis and many other
autoimmune diseases. Cutaneous microbiota was revealed
100 years ago and accumulated evidences confirmed the rela-
tion between skin microorganisms and psoriatic lesions, such
as streptococcal b-hemolytic group A throat infections linked
to guttate psoriasis.85 Drago et al.86 also suggested that the
type of microorganisms resides at different skin locations could
influence the onset and the progression of cutaneous diseases.
Studies showed that antibiotics targeting Gram-negative and
Gram-positive bacteria could ameliorate psoriasiform dermatitis
induced by imiquimod, and it inhibited the differentiation of T
cells and the production of pro-inflammatory IL-17 and IL-22.87
Importantly, T cells detected from psoriatic lesions react to
streptococcal and staphylococcal peptidoglycan in an antigen-
specific way.88 Surprisingly, the deterioration of the skin inflam-
mation is not related to the rise in IL-17-producing b+ or cd+ T
cells. Instead, the severity of skin inflammation was mainly
ascribed to prominent increase in skin T-cell-derived IL-22,
especially T-cell receptor cd+ IL-22+ cells. So, they suggested
that IL-22-producing T cells, particularly cd+ T cells, play the
most vital role in the aggravation of skin inflammation.87 Other
microorganisms including Staphylococcus aureus, Malassezia
and Candida are also involved in the pathogenesis of psoria-
sis.89,90 Staphylococcus and Streptococcus are commonly
seen in all levels of skin.90 Propionibacterium acnes are the
main microorganisms located in a normal individuals skin but
not in those influenced by psoriasis,86,91,92 which may be a
predictor of a disordered microbial system that induces the
onset of psoriasis. A disordered micro-ecosystem probably
plays a critical role in the pathogenesis of psoriasis or may be
engaged in the disease exacerbation.
Intestinal microbiota and psoriasis
The intestinal microbiome plays a vital role in maintaining our
intestinal mucosal barrier and normal immune function which
exerts extra-intestinal regulation function at remote individual
body sites.93 There is a well-known correlation between
Crohns disease (CD) and psoriasis. Patients with CD have a
fivefold higher risk of developing psoriasis than those without
CD. On the contrary, patients with psoriasis are more likely to
suffer from CD.94 More importantly, it has been reported that
the innate immune system is active in psoriasis. Recently,
studies have suggested that the mechanism of intestinal tract
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Table 3. Main microorganisms in psoriasis
Species Most common genus in psoriasis
Bacteria Streptococcus and Staphylococcus
Dermal layers Corynebacterium
Pseudomonas and Escherichia
Bacteroides and Clostridium
Proteus
Fungi Malassezia
Candida
infection was similar to skin infection. Bacteroides fragilis can
promote Treg differentiation via producing polysaccharide A
and regulating the balance of Th1/Th2,95,96 while segmented
filamentous bacteria direct Th17 cell differentiation,97 and
Clostridium species promote Treg development.98 Danese
et al. proposed that a breakdown of immune tolerance affected
by disordered microbiota of the intestinal tract may contribute
to the onset of psoriasis.99 However, the exact etiology of the
activation has not been entirely clear. In fact, the presence of
intestinal inflammation in psoriatic arthritis has been showed in
multiple studies.100102 An obvious correlation is apparent
between psoriasis and inflammatory bowel disease (IBD), and
they have similarities in genetic factors and pathogene-
sis.103,104 Evidence showed that guttate psoriasis was com-
monly triggered by streptococcal infection, which even
presented in the blood of psoriasis.105 What is more, emotion-
induced skin inflammation is related to dysbiosis in the intesti-
nal microbiome. A hypothesis of the presence of the gut
brainskin axis in normal individuals may be possible.106 Stud-
ies have suggested that Streptococcus in the tonsils may con-
tribute to the onset of chronic plaque psoriasis,107 and bacteria
in the intestinal tract would initiate and maintain psoriasis.107
The microbiome may be the director, or a mediator at least,
often involved in the common inflammatory pathways in
autoimmune diseases. These explanations may also refer to
other extra-intestinal clinical manifestations such as IBD and
extracutaneous clinical manifestations such as psoriasis.84
However, not all clinical data is consistent. This phenomenon
may be concerned with susceptibility genes, which embody
the interaction between environmental factors and genetics.
The relationship between organism infection and psoriasis
seems to be a vital and potentially promising field for future
research.
Psychiatric factors
Psoriatic patients often feel nervous and great pressure
because of their appearance. So, they are not willing to take
daily physical activities or join in social activities, even fall into
depression, the prevalence of which varies 1062% according
to different studies. In turn, depression can worsen psoriasis,
forming a vicious circle. Stress in daily life is related to the new
onset of psoriasis and will worsen the symptoms of psoria-
sis.107 Park and Youn109 also found that mental stress played
a critical role in the occurrence, development and aggravation
of psoriasis (P < 0.01). Psychological stress is known to impact
psoriasis through immune system regulation and abnormal T-
2017 Japanese Dermatological Association
Environmental factors on psoriasis
Main distribution levels References
Epithelial and 90
Epithelial layer
Outer epithelial layer
Subdermal layer
Dermal layer
Epithelial layer 119,120
Epithelial layer
cell activation.84 The most common psychiatric troubles related
to dermatological conditions in general are depression, anxiety
and suicidal thoughts. The biological links between psoriasis
and depression are now well-established, and the psychiatric
comorbidity is estimated to be approximately 30%.110 Cha-
moun et al.110 suggested that psoriasis has an important
impact on the formation of a patients personality in their child-
hood or adolescence. Conversely, personality will have an
influence on the morbidity of psoriasis. Martn-Brufau et al.111
evaluated the relationship between emotional condition and
skin lesions in a study of 823 psoriatic patients. Their data sup-
ported the association and also explained the association
between the specific kind of emotions and psoriatic lesions.
Therefore, it is essential to take care of the emotion of psoriatic
patients. Sometimes, disease prevention is more important
than the treatment of the disease in the clinic.
ENVIRONMENTAL FACTORS IN TREATMENT
OF PSORIASIS
Treatment of psoriasis has been a long process, from the very
first using coal tar, until now the classic treatment methods
emerge, which involve methotrexate, cyclosporin, vitamin D
derivatives, calcineurin inhibitors and newer biologic agents.
However, most psoriatic patients are increasingly taking medi-
cine to manage their symptoms clinically; some patients even
have to take long-term drugs to maintain the condition while
ignoring the important role of environmental factors in the
development and prognosis of their diseases. Once their con-
dition gets better, they continue to smoke, drink and eat
extravagantly. What is worse, some of them are so ashamed
of their bad appearance that they fall into depression, leading
to recurrence. Therefore, psychological interventions including
psychological counseling and relaxation therapy combined
with related medications can offer benefits to most patients
with psoriasis. Physicians should pay more attention to psy-
chological comfort of their patients, encourage them to acquire
confidence and teach them how to prevent psoriasis. Above
all, prospective and casecontrol studies have certified that
higher BMI, alcohol intake, smoking, drugs and infection are
connected with a high risk of psoriasis. So, high BMI or AGA-
positive patients should adopt dietotherapy, which is eating
more food containing rich vitamin D, losing weight and avoid-
ing gluten in food, especially AGA-positive patients. Recently,
studies have found the link between microbiota and psoriasis,
so topical treatment takes anti-infection into consideration.
869
J. Zeng et al.
More interestingly, a womens health study found that women
who exercised regularly were less likely to have psoriasis than
women who did not like to participate in regular physical activ-
ities.112 Frankel et al.113 also carried out a large cohort study
to demonstrate that running and performing aerobic exercise
or calisthenics could reduce risk of psoriasis, and the real
effectiveness of physical activity would be impacted by the
patients mood. Exercise can relieve stress, reduce anxiety
and tension, improve emotional well-being and help maintain
an ideal weight. So, it may be a potentially promising treat-
ment option for depression.114 Moreover, outdoor sports
encouraging optimal UV radiation exposure is an effective
treatment for psoriasis plaque, which can replenish more vita-
min D made in the skin regularly. Above all, the physicians
final goal is to supervise patients maintaining a healthy, body
free of infection, depression, obesity, alcohol and cigarettes.
All the above environmental factors are interrelated and func-
tion together in the onset, development and recurrence of pso-
riasis. Therefore, the management of psoriasis should
emphasize avoiding recurrence and improving the prognosis of
psoriasis instead of only depending on drug therapy, especially
for those who have high risk of family history or susceptibility
genes.
CONCLUSION
Psoriasis is believed to be triggered by a combination of
genetic, disordered immune system and environmental influ-
ences. Recently, numbers of studies showed that the environ-
mental risk factors include UV, drugs, smoking and alcohol,
infection and mental stress, all of which play a critical role in
the pathogenesis of psoriasis. Currently, studies have showed
that environmental risk factors affect the occurrence, progres-
sion and recurrence of psoriasis mainly via disturbing its genet-
ics and immune system; as part of this process, the
mechanisms of epigenetic modifications cannot be ignored.
However, the exact evidence needs to be investigated more
deeply and more risk factors wait to be discovered. Therefore,
this review suggests that doctors should provide patients more
recommendations on how to prevent the onset or recurrence
of psoriasis as part of their daily lives.
ACKNOWLEDGMENTS: This work is supported by the Key
Project of National Natural Science Foundation of China (no. 81430074)
and Major International Cooperation Project of National Natural Science
Foundation of China (no. 81220108017).
CONFLICT OF INTEREST: None declared.
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