BJD

S Y S TE M A T IC R E V IE W British Journal of Dermatology

Psychological stress and psoriasis: a systematic review and

meta-analysis*
I. Snast iD ,1 O. Reiter iD ,1 L. Atzmony iD ,1 Y.A. Leshem iD ,1,2 E. Hodak,1,2 D. Mimouni1,2 and L. Pavlovsky1
1
Department of Dermatology, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel
2
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Linked Comment: Dodoo-Schittko. Br J Dermatol 2018; 178:1002.

Summary

Correspondence Background Psychological stress has long been linked with the exacerbation/onset
Lev Pavlovsky. of psoriasis.
E-mail: levp@clalit.org.il Objectives To determine if antecedent psychological stress is associated with the
exacerbation/onset of psoriasis.
Accepted for publication
Methods A search of the PubMed, PsycINFO, Cochrane library and ClinicalTrials.gov
30 October 2017
databases was performed. Surveys evaluating beliefs about stress reactivity were
Funding analysed separately. Suitable studies were meta-analysed.
The study was funded by an unrestricted grant Results Thirty-nine studies (32 537 patients) were included: 19 surveys, seven
from Pfizer Inc. cross-sectional studies, 12 case–control studies and one cohort study. Forty-six
per cent of patients believed their disease was stress reactive and 54% recalled
Conflicts of interest
preceding stressful events. Case–control studies evaluating stressful events rates
None declared.
prior to the exacerbation (n = 6) or onset (n = 6) of psoriasis varied in time lag
I.S. and O.R. contributed equally to this to recollection (≤ 9 months to ≥ 5 years). Pooling five studies evaluating stress-
manuscript. D.M. and L.P. contributed ful events preceding onset of psoriasis gave an odds ratio (OR) of 3
4 [95% con-
equally to this manuscript. fidence interval (CI) 1
8–6
4; I2 = 87%]; the only study evaluating a documented
*Plain language summary available online
stress disorder diagnosis reported similar rates between patients and controls (OR
1
2, 95% CI 0
8–1
8). Four studies evaluating stressful events prior to psoriasis
DOI 10.1111/bjd.16116 exacerbation reported comparable rates with controls, whereas two found more
frequent/severe preceding events among patients with psoriasis. A small prospec-
tive cohort study reported a modest association between stress levels and exacer-
bation of psoriasis (r = 0
28, P < 0
05).
Conclusions The association between preceding stress and exacerbation/onset of
psoriasis is based primarily on retrospective studies with many limitations. No
convincing evidence exists that preceding stress is strongly associated with exac-
erbation/onset of psoriasis.

What’s already known about this topic?

• It is common knowledge among patients with psoriasis and their physicians that
psychological stress aggravates psoriasis.
• Numerous observational studies have suggested a link between preceding psycho-
logical stress and exacerbation and onset of psoriasis.

What does this study add?

• A review of the current literature revealed that the association between preceding
stress and psoriasis is built almost exclusively on retrospective studies with many
limitations. To date, no convincing evidence exists that stress is strongly associated
with psoriasis exacerbation and onset.
• This finding is psychologically beneficial for patients and has occupational and
therapeutic implications.

1044 British Journal of Dermatology (2018) 178, pp1044–1055 © 2017 British Association of Dermatologists

Psoriasis is a chronic inflammatory skin disorder with a com-
plex immune-mediated pathophysiology affecting between
0
9% and 8
5% of the general population.1 Descriptions of a
relationship between psychological stress and psoriasis date
back centuries. In a case history of a patient with outbreaks of
psoriasis written > 1200 years ago, a Persian physician sug-
gested that severe interpersonal conflicts may have been a con-
tributory factor.2
Psychological stress occurs when an individual perceives the
environmental demands tax or exceed their adaptive capacity.3
The operationalization of stress and the physiological mecha-
nisms mediating the interplay of stress and psoriasis are com-
plex.4 Early survey-based studies evaluated patients’ beliefs on
the role of emotional stress on the exacerbation and onset of
psoriasis.5 In the 1960s, the life event paradigm gained impe-
tus with the development of life event inventories that
included positive (e.g. marriage) or negative (e.g. the death of
a spouse) events, which were used as indicators of external
stressors.6 Later, life event checklists evolved to expand the
range of major events evaluated. A major milestone was the
development of structured life event interviews, which
allowed the researcher to gain insight into the context and
timing of events. Although many observational studies utiliz-
ing the aforementioned methodologies pointed to an associa-
tion between antecedent stress and the exacerbation and onset
of psoriasis, their results should be interpreted with caution,
given their retrospective nature, which is prone to multiple
biases. Notably, recall bias is a major threat to studies’ internal
validity, given that many patients with psoriasis preconceive
stress as a risk factor.7 Several physiological mechanisms have
been proposed to explain the relationship between stress and
psoriasis.8,9 Studies exploring the ‘brain–skin connection’ have
revealed that the skin is both a prominent target organ and a
factory for neuroendocrine, neurotransmitter and neuropep-
tide signals, which profoundly affect skin biology. Thus, upon
perception of stress, the skin may respond by releasing inflam-
matory cytokines. In turn, this may lead to mast cell activa-
tion, which promotes immune dysregulation and neurogenic
inflammation.8
Despite widespread belief of the association between pre-
ceding stress and the exacerbation and onset of psoriasis, no
systematic review has been conducted to date. Given the
important clinical and occupational implications of this topic
the aim of this systematic review and meta-analysis is to pro-
vide a comprehensive overview of the literature linking ante-
cedent psychological stress with exacerbation and onset of
psoriasis.10
Materials and methods
The systematic review and meta-analysis were conducted and
reported according to the Preferred Reporting Items for Sys-
tematic reviews and Meta-Analyses (PRISMA) statement and
registered with the PROSPERO international prospective regis-
ter (CRD42016044007).11
© 2017 British Association of Dermatologists
Psychological stress and psoriasis, I. Snast et al. 1045
Search strategy
A comprehensive database search was performed independently
using PubMed, the ongoing trials registry/database of the U.S.
National Institutes of Health (www.clinicaltrials.gov); Cochrane
Central Register of Controlled Trials; Cochrane Database of Sys-
tematic Reviews; PsycINFO; and the reference lists of included
articles. The following search terms were used: [“Psoriasis”
(medical subject heading; MeSH) OR psoriasis) AND [“stress,
psychological” (MeSH) OR Stress OR stressor OR stressors OR
psychological OR psychic OR life events]. We included only
studies published in or translated into English from inception
to May 2017. Reference lists from included studies were manu-
ally scanned to identify any additional results. Authors were
contacted for missing data and clarifications. Any disagreement
was resolved by discussion with a third author (L.P).
Eligibility criteria
Studies that met the following criteria were included: (i) rele-
vance – original study of any design analysing the association
between antecedent psychological stress (prospectively or by
patients’ recollection) and onset or clinical exacerbation of
psoriasis; (ii) participants – patients of all ages of either sex
with a clinical diagnosis of psoriasis. Controls in case–control
studies were healthy participants or participants with minor
skin disorders believed to be unrelated to stress (e.g. naevi
and fungal infections). Permissive criteria for the progression
of psoriasis was allowed, not contingent on the use of vali-
dated scales [e.g. Psoriasis Area and Severity Index (PASI)],
including self-description of an exacerbation.
We excluded: (i) studies with sample sizes < 10; (ii) stud-
ies assessing the effects of stress on treatment effectiveness
(e.g. psoriasis clearance); and (iii) nonplaque subtypes of pso-
riasis (studies were included if > 55% of patients had plaque-
type psoriasis).
Study selection and data extraction
Two reviewers (I.S. and O.R.) independently screened the
titles and abstracts of all retrieved articles followed by the full
text of articles considered to be potentially eligible for inclu-
sion. Subsequently, data were extracted into a predefined elec-
tronic extraction form, which included the following: (i)
study characteristics (country, year, design, setting); (ii) par-
ticipants’ characteristics (mean age, sex, number of cases and
controls, control definition); (iii) exposure and disease charac-
teristics, such as screening tools for stress, exposure character-
istics, disease definition, exposure–disease interval, outcome
recollection interval and effect estimates. Psychological stress
was assessed using different methods, including self-reported
diagnosis and various validated scales evaluating specific life
events, such as the Social Readjustment Rating Scale.
Two reviewers (I.S. and O.R.) independently assessed the
risk of bias in the included studies with the Newcastle–Ottawa
British Journal of Dermatology (2018) 178, pp1044–1055
1046 Psychological stress and psoriasis, I. Snast et al.
Scale (NOS).12 A modified NOS was used for cross-sectional
studies (Appendix S1; see Supporting Information). Grading
was categorized as follows: low < 4; moderate 4–6; high > 6.13
Any disagreement was resolved by discussion with a third
author (L.P).
Data analysis
All studies were classified according to their method of eval-
uating the relationship between stress and psoriasis as fol-
lows: (i) cross-sectional, (ii) case–control or (iii) cohort.
Surveys that evaluated patients’ beliefs about stress reactivity
were analysed separately. Patients’ beliefs were operational-
ized by questioning patients on whether stress was a trigger
of psoriasis or connected to psoriasis flare-ups. Data were
combined at the aggregate level and presented using descrip-
tive statistics. Patients’ beliefs regarding stress reactivity were
analysed by year of publication, using linear regression. The
result is presented as a correlation coefficient (r) with the
statistical significance set at P < 0
05. Publication bias was
not assessed owing to the small number of studies
included.14 For quantitative analysis, odds ratios (ORs) for
stressful events prior to the onset of psoriasis were calculated
with 95% confidence intervals (CIs). ORs were pooled using
statistical software (Comprehensive Meta-Analysis, Version
3
0). Analyses were performed using the random-effects
model of DerSimonian and Lard because we expected consid-
erable heterogeneity across stress screening tools. Hetero-
geneity was assessed by visually examining the forest plot
for nonoverlapping CIs using the v2-test, with P < 0
1 indi-
cating statistical significance and I2 > 50% indicating substan-
tial heterogeneity.
Results
Our initial search yielded 1526 results (Fig. 1). We excluded
57 duplicate studies. After examining the titles and abstracts
of the retrieved studies, 64 were selected based on the eligibil-
ity criteria. After reviewing the full-length articles, 25 were
excluded for the following reasons: lack of a temporal rela-
tionship between stress and psoriasis (n = 7), duplicates
(n = 8), nonplaque-type psoriasis (n = 4), evaluation of stress
on treatment effectiveness (n = 3), insufficient information
(n = 2) and sample size < 10 (n = 1).
Characteristics of the included studies
Thirty-nine studies, evaluating 32 537 patients, fulfilled the
eligibility criteria (19 surveys,7,15–32 seven cross-sectional
studies,33–39 12 case–control studies,40–51 one cohort study52).
The characteristics of the case–control and cohort studies are
presented in Table 1; the characteristics of the included sur-
veys and cross-sectional studies are presented in Tables S1 and
S2 (see Supporting Information). Studies were published
between 1964 and 2015. The studies were conducted in Eur-
ope (n = 26), Asia (n = 8), the U.S.A. (n = 4) and Africa
British Journal of Dermatology (2018) 178, pp1044–1055
(n = 1). Thirty studies were conducted in an outpatient setting
and nine in an inpatient setting. Participants’ mean age ranged
from 12 to 52 years. Studies used heterogeneous methodolo-
gies: surveys evaluated patients’ beliefs regarding stress reactiv-
ity; cross-sectional and case–control studies evaluated the
association between preceding stressful life events and exacer-
bation and onset of psoriasis; and one cohort study prospec-
tively evaluated the association between daily stress levels and
exacerbation of psoriasis. Disease definition varied (excluding
surveys): exacerbation (n = 10), psoriasis onset (n = 9),
mixed definition (n = 1). Only six studies reported on the
nature of events, four of which were related to family issues.
Stress–psoriasis time interval varied significantly among the
included studies: surveys and cross-sectional studies mostly
failed to report specific time frames; case–control studies
reported the interval to be within 12 months; a cohort study
reported a pre-emptive interval of 4 weeks. Only nine case–
control studies reported an outcome recollection time lag,
which varied substantially: ≤ 6 months (n = 5); within
9 months to more than 5 years (n = 4).
The quality of the studies based on the NOS is reported in
Tables S3 and S4 (see Supporting Information) and is summa-
rized in Table 1. Seven case–control studies were designated
as high quality, nine studies were of moderate quality (three
cross-sectional, five case–control, one cohort) and four cross-
sectional studies were designated as low quality. Points were
most often lost on the method of ascertaining exposure to
stress and on comparability. Overall, 12 studies ascertained
exposure to stress based on nonvalidated scales, including
questionnaires/clinical interviews (n = 7) and via validated
scales, yet were not blinded to case–control status (n = 5).
Only three cross-sectional, four case–control and one cohort
study adequately ascertained exposure to stress. Results were
not affected by a study’s quality.
Patients’ beliefs of reactivity to stress
Nineteen surveys, evaluating a total of 26 099 participants,
evaluated patients’ beliefs regarding stress and exacerbation
and onset of psoriasis. Forty-six per cent (range 27–88) of
patients believed their disease was reactive to stress. Using a
linear regression model, we calculated a correlation coefficient
of 0
44 (P < 0
05) between year of publication and belief
prevalence (Fig. 2).
Preceding stressful events and exacerbation and onset of
psoriasis in cross-sectional studies
Seven studies with 1275 patients and no control group were
included. Based on heterogeneous, mostly nonvalidated
screening tools, including psychiatric interviews, question-
naires and life events scales, 54% of participants recalled
stressful events preceding exacerbation and onset of psoriasis.
One study reported a correlation coefficient of 0
28
(P < 0
0001) between stressful events and exacerbation of
psoriasis.33
© 2017 British Association of Dermatologists
 Psychological stress and psoriasis, I. Snast et al. 1047

Fig 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the systematic literature search.

© 2017 British Association of Dermatologists British Journal of Dermatology (2018) 178, pp1044–1055
1048 Psychological stress and psoriasis, I. Snast et al.

Table 1 Characteristics of case–control and cohort studies included in the systematic review

Stress screening
Mean age tool (validated/
Study Country Design Patients (years) not validated) Exposure characteristics
Al’Abadie et al. U.K. CC 67 outpatients with 36 vs. 34 Questionnaire 47 patients with psoriasis recalled
(1994)41 psoriasis, 67 (not validated) stressful events, of which 35%
controls with minor were related to family, 20% to
skin disorders personal illness, 19% to work
or school and 15% to hormonal
changes

Fava et al. Italy CC 20 inpatients with 32 vs. 40 Semi- structured 16 patients with psoriasis recalled
(1980)42 psoriasis (35% F) interview based stressful events
and 20 controls with on Paykel’s scale
fungal infections (validated)
(55% F)
Ozden et al. Turkey CC 537 paediatric 12 vs. 11 Questionnaire 299 paediatric patients had
(2011)43 outpatients (61% F) completed by stressful events, of which 32%
with psoriasis and mothers of were related to relationship
511 HCs (58% F) children (not problems and 15% to diagnosis
validated) of psychiatric disease
Manolache Romania CC 95 outpatients with Median age 48 SRRS (validated) 45 patients with psoriasis recalled
et al. psoriasis (66% F) vs. 46 stressful events of which 43%
(2010)44 and 169 controls were related to family, 32% to
with minor skin financial issues and 26% to
disorders personal issues
Huerta et al. U.K. Nested 3994 outpatients with NA Computerized 42 patients with psoriasis had a
(2007)45 CC psoriasis and 10 000 diagnosis of a stress disorder
healthy age- and stress disorder
sex-matched controls retrieved from
GP database
(validated)
Payne et al. U.K. CC 16 outpatients with Average age NA ALEICR Patients with psoriasis had
(1985)40 psoriasis and 16 12, > 60 years; (validated) comparable life event scores to
healthy age- and 10, 31– controls
sex-matched controls 59 years; 10,
16–30 years
Seville U.K. CC 132 inpatients with NA Questionnaire 51 patients with psoriasis recalled
(1977)46 psoriasis and 132 (not validated) stressful events of which 73%
HCs were related to family and 27%
to personal issues

Lyketsos et al. Greece CC 26 inpatients (46% F) NA SRRS (validated) NA

(1985)49 with psoriasis and
38 patients (61% F)
with minor skin
disorders

ßSahiner et al. Turkey CC 31 inpatients (55% F) 42 vs. 35 Life events NA

(2014)51 with psoriasis and inventory by
50 HCs (58% F) Sorias (validated)

British Journal of Dermatology (2018) 178, pp1044–1055 © 2017 British Association of Dermatologists
 Psychological stress and psoriasis, I. Snast et al. 1049

Outcome definition Outcome–

Exposure– [self-report (SR)/ recollection
disease interval physician] time lag Effect estimates Quality (NOS) Remarks
Within 4 weeks, Psoriasis onset (SR) NA OR 12 (95% CI 5–27, Moderate An initial sample of 113
38%; within P < 0
001) for stressful events patients with psoriasis
4–10 weeks, prior to disease onset and 128 patients with
35%; beyond minor skin disorders
10 weeks, 27% were age-matched,
resulting in 67 patients
in each group
Within Psoriasis onset Within 1 year, OR 4 (95% CI 1–16; P = 0
05) Moderate
6 months (physician) 30%; within for stressful events prior to
1–5 years, 40%; disease onset
beyond 5 years,
30%
Within Psoriasis onset On average, OR 2
9 (95% CI 2
3–3
8; High
12 months (physician) 3
2 years P < 0
001) for stressful events
prior to disease onset

Within Psoriasis onset Within 9 months OR 3
7 (95% CI 2
1–6
5; High

12 months (physician) P < 0
001) for stressful events
prior to disease onset

Within Psoriasis onset No recollection OR 1
2 (95% CI 0
8–1
8; High

12 months (physician) P > 0
05) for stress disorder
prior to disease onset

Within Psoriasis Short period Comparable life event scores Moderate

12 months exacerbation (SR) (absolute values (sum, 2557 vs. 2442, Mann–
NA) Whitney U-test = 126,
P = 0
96) prior to disease
exacerbation
Within 1 month Psoriasis NA OR 5
8 (95% CI 3–11; Moderate Patients were asked a
exacerbation (SR) P < 0
001) for stressful event suggestive question
prior to disease exacerbation for a possible
association between
stress and psoriasis
(‘What upset or illness
was there just before
onset of the rash?’)
Within Psoriasis NA Patients with psoriasis scored High
12 months exacerbation (SR) significantly higher, i.e. more
stress (median score 539 vs.
58; P < 0
001, Mann–Whitney
U-test) prior to disease
exacerbation
Within Psoriasis onset Within 1 year, Psoriatics scored higher, i.e. High
6 months (physician) 10%; within 1– more stress prior to disease
5 years, 16%; onset (Cohen’s d = 3
9, 95% CI
beyond 5 years, 3
2–4
7)
74%;

© 2017 British Association of Dermatologists British Journal of Dermatology (2018) 178, pp1044–1055
1050 Psychological stress and psoriasis, I. Snast et al.

Table 1 Continued

Stress screening tool

Mean age (validated/not
Study Country Design Patients (years) validated) Exposure characteristics
Picardi et al. Italy CC 33 inpatients (39%) 43 vs. 37 PIRLE (validated) On average, each patient had
(2005)47 with psoriasis and 1
6 stressful events and
73 patients (56%) 0
2 major AEs
with minor skin
disorders

Picardi et al. Italy CC 40 outpatients (48% 35 vs. 34 PIRLE (validated) On average, each patient had
(2003)48 F) with psoriasis and 2
8 stressful events and
116 patients (62% 0
3 major AEs
F) with minor skin
disorders

Jankovi
c et al. Montenegro CC 110 outpatients 45 vs. 46 PIRLE (validated) On average, each patient had
(2009)50 (53%) with psoriasis 1
7 stressful events and
and 200 patients 0
21 major AEs
(59%) with minor
skin disorders
Verhoeven The Cohort 62 outpatients (27%) 52 Short 49-item On average, maximum stress
et al. Netherlands with psoriasis version of values of 17 and minimum
(2009)52 Everyday Problem of 5 (t = 13
6, P < 0
001)
Checklist
(validated)

NOS, Newcastle–Ottawa Scale; CC = case–control; NA, not available; OR, odds ratio; CI, confidence interval; F, female; HC, healthy control;
SRRS, Social Readjustment Rating Scale; GP, general practitioner; ALEICR, Adaptation of Life Events Inventory of Cochrane and Robertson;
PIRLE, Paykel’s Interview for Recent Life Events; AE, adverse events; EPC, Everyday Problem Checklist; PASI, Psoriasis Area and Severity Index.

Fig 2. Percentage of patients believing in reactivity to stress, as described by 19 surveys over time.

Preceding stressful events and psoriasis onset in
case–control studies
Six studies with 4744 patients with psoriasis and 10 817 controls
were included. Five studies provided rates of preceding stressful
event and stress disorder prior to onset of psoriasis, which were
included in a meta-analysis (Fig. 3). Rates were significantly
higher among patients with psoriasis compared with controls
(pooled OR 3
4, 95% CI 1
8–6
4; P < 0
001, I2 = 87%);41–45
however, the only study reporting documented stress disorder
rates found no difference between patients with psoriasis and

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 Psychological stress and psoriasis, I. Snast et al. 1051

Outcome–
Exposure– Outcome definition [self- recollection Quality
disease interval report (SR)/physician] time lag Effect estimates (NOS) Remarks
Within Psoriasis exacerbation Within Comparable mean total AEs (Cohen’s High
12 months (SR) 3 months d = –0
24, 95% CI –0
66 to
0
16) and major AEs (Cohen’s d
= –0
27, 95% CI –0
68 ot 0
14)
in multivariate logistic regression
prior disease to exacerbation
Within Psoriasis exacerbation Within Comparable mean total AEs (Cohen’s Moderate 6/40 patients had
12 months (SR) 3 months d = 0
15, 95% CI –2
1 to 5
1) and psoriasis onset
major AEs (Cohen’s d = 0, 95% CI
–0
36 to 0
36) in multivariate
logistic regression prior disease
exacerbation
Within Psoriasis exacerbation Within No significant difference in total/ High Patients with psoriasis
12 months (SR) 6 months major AEs in multivariate logistic had an OR of 2
regression (effect size not available) (95% CI 1
4–2
9;
prior disease exacerbation P < 0
001) for the
first 25 AEs
Within Psoriasis exacerbation No recollection Pearson’s correlation coefficient Moderate
4 weeks (physician). On average, +0
28 between stress and disease
an absolute change of 1 exacerbation (P < 0
05)
in PASI between
maximum and
minimum stress values

Fig 3. Odds ratios for stressful events preceding psoriasis onset. df, degrees of freedom. CI, confidence interval.

controls (OR 1
2, 95% CI 0
8–1
8).45 The substantial hetero-
geneity may be attributable to nonvalidated assessment of stress
and variability of time lag to recollection (five studies provided
data, ≤ 9 months to ≥ 5 years). One additional study, evaluating
patients > 5 years after disease onset, reported more severe events
among patients with psoriasis vs. controls.51
evaluating patients within 6 months of disease exacerbation
found comparable preceding stressful events rates between
patients with psoriasis and controls.40,47,48,50 Two studies fail-
ing to report on time lag to recollection found higher rates (OR
5
8, 95% CI 3–11) and more severe events among the patients
with psoriasis than in controls.46,49

Preceding stressful events and exacerbation of psoriasis Association between daily stress and exacerbation of
in case–control studies psoriasis in a cohort study
Six case–control studies with 357 patients with psoriasis and One prospective cohort study evaluated 62 patients with
595 controls without psoriasis were included. Four studies mild psoriasis.52 Patients were followed for 6 months with

© 2017 British Association of Dermatologists British Journal of Dermatology (2018) 178, pp1044–1055
1052 Psychological stress and psoriasis, I. Snast et al.
monthly clinical evaluation by a dermatologist, including
assessment of daily stress levels using a validated scale. A
modest, albeit statistically significant, correlation coefficient
of 0
28 (P < 0
05) was found between stress levels and
exacerbation of psoriasis 4 weeks later. An absolute PASI
worsening of 1 was reported between minimum and maxi-
mum levels of stress.
Discussion
The results of this comprehensive systematic review indicate
that there is no high-quality evidence to support the notion
that preceding psychological stress is strongly associated with
exacerbation and onset of psoriasis. As stress is a general con-
cept with psychological, behavioural and biological determi-
nants,53 we pre-emptively decided to focus on the broad
definition of psychological stress. Accordingly, studies’
descriptions of stress ranged from a general, nonspecific type
to definitive stressful events. In all, we included 39 heteroge-
neous studies published in the last 50 years from across the
globe with conflicting findings and heterogeneous methodolo-
gies.
Nineteen studies surveyed 26 099 patients with psoria-
sis regarding their beliefs in the role of stress in their
disease.7,15–32 On average, 46% of patients believed their
disease was reactive to stress. Berg et al. noted that the per-
centage of patients believing psoriasis was stress-related was
low in studies prior to 1990 but increased thereafter.54 To
further investigate this finding, we performed a linear
regression analysis confirming a growing positive trend over
time (Fig. 2). The increase may be at least partly attributa-
ble to greater patient accessibility to medical services, which
commonly accept stress as a well-established risk factor in
psoriasis.55 Additionally, five cross-sectional studies revealed
that, on average, 54% of patients could recall major life
events preceding the exacerbation and onset of psoriasis.34–
38
Patients’ perceptions are of limited validity in proving the
association between preceding stress and exacerbation and
onset of psoriasis, given that many patients describe stress to
be a consequence of psoriasis.56 Additionally, dermatologists –
many of whom believe that stress plays a significant role in
psoriasis57 – may inadvertently contribute to the tendency of
their patients to associate stress with psoriasis by questioning
or informing them about the aggravating role of stress. Over-
all, as all cross-sectional studies lacked control groups and
failed to report on time lag to event recollection, they add lit-
tle value in supporting the association between preceding
stress and exacerbation and onset of psoriasis.
Case–control studies evaluated the occurrence of stressful
events preceding exacerbation (n = 6) and onset (n = 6) of
psoriasis vs. controls without psoriasis, yielding inconsistent
results. Accordingly, the pooled ORs of five studies evaluat-
ing stressful events preceding the onset of psoriasis,41–45
with considerable heterogeneity and under-reporting of time
lag to recollection, found higher rates among patients with
British Journal of Dermatology (2018) 178, pp1044–1055
psoriasis vs. controls (OR 3
4, 95% CI 1
8–6
4; I2 = 87%).
Likewise, two studies failing to report the time lag to recol-
lection found more frequent (OR 5
8, 95% CI 3–11) and
severe life events among patients with psoriasis prior to dis-
ease exacerbation.46,49 In contrast, the only study that was
not based on patient recollection reported comparable stress
disorder rates (OR 1
2, 95% CI 0
8–1
8),45 and four studies
evaluating patients with a recent exacerbation of psoriasis (≤
6 months) reported comparable life events rates between
patients and controls,40,47,48,50 highlighting the importance
of adequate reporting of the time lag to recollection in
future studies.
The significant amount of heterogeneity can also be attribu-
ted to nonvalidated measurement of stress. For instance, in
one study, patients were first questioned about their belief
concerning the stress–psoriasis relationship before undergoing
life events evaluation.41 This might have amplified patients’
recollection of events, culminating in a significant OR of 12
(95% CI 5–27; P < 0
001). In all, the weight of evidence of
case–control studies increases toward a limited association
between antecedent stress and onset and exacerbation of psori-
asis. Nonetheless, as studies evaluated primarily major life
events while neglecting daily and chronic stressors, unequivo-
cal conclusions cannot be drawn.
Because cohort studies measure events in a chronological
order and can make a distinction between cause and effect,
they may be the best study design for the topic of interest.58
Unfortunately, only one cohort study with 62 patients was
retrieved, indicating that antecedent stress has only a modest
association with exacerbation of onset and exacerbation
(r = 0
28; P < 0
05), thus supporting case–control studies
with a higher quality of evidence.52 Similarly, two small
prospective studies not meeting our eligibility criteria found
no, or only a modest, association (r = 0
31; P < 0
01)
between antecedent stress levels and subsequent exacerbation
of onset and exacerbation.54,59
Finally, the mechanisms underlying the interplay between
stress and psoriasis are not fully understood, and a study of
the interaction between psychology and the nervous and
immune systems is in order. Classically, neurochemical and
hormonal mechanisms, including activation of the innate
immune system, have been proposed to explain the pathologi-
cal effect of stress on the exacerbation and onset of psoriasis.60
Yet, more recent studies have focused on the potential adap-
tive function of stress, including stress-induced immunosup-
pression.9 The net outcome of these contrasting effects is yet
to be determined.
Our study has some methodological limitations. Firstly, it
is possible that pertinent studies were missed because the
search was restricted to articles published in English.61 Sec-
ondly, we primarily evaluated plaque-type psoriasis, yet it is
possible that certain subtypes are more strongly associated
with stress. Thirdly, several studies have shown that psycho-
logical stress may reduce the efficacy of psoriasis treatment,62
whereas simple stress-alleviating interventions may be advan-
tageous.63,64 As the effect of stress on treatment effectiveness
© 2017 British Association of Dermatologists

was beyond the scope of this work, further research is
recommended.
The literature on the association between antecedent psy-
chological stress and exacerbation and onset of psoriasis is
built almost exclusively on retrospective studies with many
limitations. Although surveys and cross-sectional studies have
shown that most patients with psoriasis believe they are
reactive to psychological stress and can recall major events
preceding disease, this cannot be interpreted as evidence of a
causal relation. Case–control studies assessing the occurrence
of major events have yielded inconsistent results with signifi-
cant heterogeneity and under-reporting of the time lag to
recollection. Given that only one small prospective cohort
study was retrieved, concluding stress levels were only mod-
estly associated with exacerbation of psoriasis, no convincing
evidence exists that antecedent stress is strongly associated
with exacerbation and onset of psoriasis. As previous studies
have found that a clear relationship could only be established
under extreme states of stress, further prospective studies
evaluating the full spectrum of psychological stress are
needed.31,61
Our study has major implications in several clinical
spheres. Although a recent systematic review set out to assess
the risk for suicidal ideation/suicidality among patients with
psoriasis concluded no association existed,13 previous studies
have shown that the mere belief that stress causes psoriasis is
associated with higher levels of anxiety, stress and depres-
sion.20,65 Thus, our study may have psychological signifi-
cance for patients with psoriasis. From the occupational
perspective, on the basis of personal experience and beliefs,
stress is commonly regarded as a well-established trigger of
psoriasis. Consequently, our conclusion has implications for
disability and pension entitlement,10 and highlights the need
for evidence-based consensus standards. This study can guide
the design of future studies in terms of validated stress mea-
surement, reporting the time lag to recollection and paying
attention to daily/chronic stressors. Finally, from a therapeu-
tic aspect, patients with psoriasis should be carefully assessed
for known trigger factors before attributing disease exacerba-
tion and onset to psychological stress.
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Supporting Information
Additional Supporting Information may be found in the online
version of this article at the publisher’s website:
Table S1 Characteristics of cross-sectional studies included
in the systematic review.
Table S2 Surveys evaluating patients’ belief of reactivity to
stress.
© 2017 British Association of Dermatologists
 Psychological stress and psoriasis, I. Snast et al. 1055

Table S3 Quality assessment of cross-sectional studies, includ- Appendix S1 Adapted Newcastle–Ottawa Quality Assessment
ing adapted Newcastle–Ottawa Scale and recall bias risk. Scale for cross-sectional studies.
Table S4 Quality assessment of case–control and cohort stud- Video S1 Author video.
ies including Newcastle–Ottawa Scale and recall bias risk. Powerpoint S1 Journal Club Slide Set.

© 2017 British Association of Dermatologists British Journal of Dermatology (2018) 178, pp1044–1055