Association of Clinical and Demographic Factors
With the Severity of Palmoplantar Pustulosis
Natashia Benzian-Olsson, MSc; Nick Dand, PhD; Charlotte Chaloner, MSc; Zsuzsa Bata-Csorgo, MD;
Riccardo Borroni, MD; A. David Burden, MD; Hywel L. Cooper, BM; Victoria Cornelius, PhD; Suzie Cro, PhD;
Tejus Dasandi, BSc; ChristopherE . M. Griffiths, MD; Külli Kingo, MD, PhD; Sulev Koks, MD,PhD;
Helen Lachmann, MD; Helen McAteer, BSc; Freya Meynell, MSc; Ulrich Mrowietz, MD; Richard Parslew, MB, BS;
Prakash Patel, BSc; Andrew E. Pink, PhD, MBBS; Nick J. Reynolds, MD; Adrian Tanew, MD; Kaspar Torz,MD;
Hannes Trattner, MD; Shyamal Wahie, MD; Richard B. Warren,PhD, MD; Andrew Wright, MB, ChB;
Jonathan N. Barker, MD; Alexander A. Navarini,MD, PhD; Catherine H. Smith, MD; Francesca Capon, PhD; for the
ERASPEN consortium and the APRICOT and PLUM study team
IMPORTANCE Although palmoplantar pustulosis (PPP) can significantly impact quality of life,
the factors underlying disease severity have not been studied.
OBJECTIVE To examine the factors associated with PPP severity.
DESIGN, SETTING, AND PARTICIPANTS An observational, cross-sectional study of 2 cohorts was
conducted. A UK data set including 203 patients was obtained through the Anakinra in
Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study
Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European
cohort including 193 patients was independently ascertained by the European Rare and
Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or
tertiary dermatology referral centers. All patients were of European descent. The PPP
diagnosis was established by dermatologists, based on clinical examination and/or published
consensus criteria. The present study was conducted from October 1, 2014, to March 15,
2020.
MAIN OUTCOMES AND MEASURES Demographic characteristics, comorbidities, smoking
status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity
from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA),
measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).
RESULTS Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at
onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with
age of onset (r= −0.18, P= .01). Similarly, in the 159 Northern European patients who were
eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset,
45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to
severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild
PGA score (46.5 years [IQR, 35-55 years]) (P= .04). In the UK sample, the median PPPASI
score was higher in women (9.6 [IQR, 3.0-16.2]) vs men (4.0 [IQR, 1.0-11.7]) (P= .01).
Likewise, moderate to severe PPP was more prevalent among Northern European women (57
of 134 [43%]) compared with men (5 of 25 [20%]) (P= .03). In the UK cohort, the median
PPPASI score was increased in current smokers (10.7 [IQR, 4.2-17.5]) compared with former
smokers (7 [IQR, 2.0-14.4]) and nonsmokers (2.2 [IQR, 1-6]) (P= .003). Comparable
differences were observed in the Northern European data set, as the prevalence of moderate
to severe PPP was higher in former and current smokers (51 of 130 [39%]) compared with
nonsmokers (6 of 24 [25%]) (P= .14).
CONCLUSIONS AND RELEVANCE The findings of this study suggest that PPP severity is
associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation
intervention might be beneficial.
JAMA Dermatol. doi:10.1001/jamadermatol.2020.3275
Published online September 16, 2020.
Supplemental content
Author Affiliations: Author
affiliations are listed at the end of this
article.
Group Information: The ERASPEN
consortium and the APRICOT and
PLUM study team members appear at
the end of the article.
Corresponding Author: Catherine H.
Smith, MD, St John’s Instituteof
Dermatology, King’sCollege London,
London SE1 9RT, United Kingdom
(catherine.smith@kcl.ac.uk).
Research
JAMA Dermatology | Original Investigation
(Reprinted) E1
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Palmoplantar pustulosis (PPP) is an uncommon pustu-
lar eruption affecting the palms and/or soles. It is ob-
served in approximately 1:2000 individuals of Euro-
pean descent and 1:800 individuals of East Asian descent.
1
The
disease typically manifests in adulthood, with a median age
of onset older than 45 years reported in most studies.
2
Palmo-
plantar pustulosis shows a marked sex bias, with women ac-
counting for 60% to 90% of affected individuals.
2,3
The dis-
ease is also characterized by an association with cigarette
smoking, with up to 90% of patients self-identifying as smok-
ers at the time of diagnosis.
2,4-6
The disease manifests with the eruption of sterile, neu-
trophil-filled pustules on the palms and soles. The lesions,
which can occur on a background of normal or inflamed skin,
are persistent (>3 months), painful, and disabling, and can be
accompanied by fissures, pruritus, and a burning sensation.
7
Comorbidities are also common, as affected individuals are at
increased risk of psoriasis vulgaris, psoriatic arthritis, and au-
toimmune thyroid disease.
8
While PPP can profoundly impact quality of life, the fac-
tors underlying variable disease severity have not been inves-
tigated. The rarity of the condition has hindered the ascertain-
ment and characterization of adequately powered data sets.
In this context, the objective of our study was 2-fold: to evalu-
ate the features of PPP in 2 independent patient cohorts and
to examine whether PPP severity is influenced by sex and
smoking status—the 2 most well-established risk factors for the
disease.
1
Given that symptoms typically manifest in adult-
hood, we also sought to examine whether the presentation of
PPP is more severe in early-onset cases.
Methods
Patients
This study was carried out in accordance with the principles
of the Declaration of Helsinki
9
and with the approval of the par-
ticipating institutions’ ethics committees. The present study
was approved by London Bridge Research ethics committee
(London, UK) and Kantonale Ethikkommission (Zurich, Swit-
zerland). All patients granted their informed consent in writ-
ing; participants did not receive financial compensation. This
study followed the Strengthening the Reporting of Observa-
tional Studies in Epidemiology (STROBE) reporting guideline
for cross-sectional studies. The present study was conducted
from October 1, 2014, to March 15, 2020.
The UK resource included 203 unrelated and prospec-
tively ascertained patients. Forty-two patients were re-
cruited between 2016 and 2019 through Anakinra in Pustular
Psoriasis, Response in a Controlled Trial (APRICOT).
10
The re-
maining 161 patients were enrolled between 2016 and 2020
through the sister research study Pustular Psoriasis, Elucidat-
ing Underlying Mechanisms (PLUM).
11
A total of 23 dermatol-
ogy centers located across the UK were involved in the recruit-
ment.
The Northern Europe resource included 193 unrelated pa-
tients. Affected individuals were mostly enrolled between 2014
and 2017 through 3 centers affiliated with the European Rare
and Severe Psoriasis Expert Network (ERASPEN). These cen-
ters were in the dermatology departments of the Medical Uni-
versity of Vienna, Austria (n = 100), Tartu University, Estonia
(n = 57), and University Medical Centre Schleswig-Holstein,
Campus Kiel, Germany (n = 31). The remaining 5 patients were
recruited outside the main reference centers by clinicians who
provided individual cases to the ERASPEN Consortium.
Pustular psoriasis was always diagnosed by a dermatolo-
gist, based on clinical examination and/or the ERASPEN con-
sensus criteria.
7
The observation of sterile, macroscopically vis-
ible pustules on palms or soles was the main inclusion criterion.
Conversely, the presence of pustules restricted to the edges of
psoriatic plaques represented an exclusionc riterion. Individu-
als with concomitant generalized pustular psoriasis or con-
comitant acrodermatitis continua of Hallopeau were also ex-
cluded from the study, given that lesions affecting nails or
nonacral skin are deemed incompatible with a diagnosis of
PPP.
12
Clinical information and key demographics were collated
using a standardized case report form, shared by all centers.
In the UK cohort, disease severity was measured using the Pal-
moplantar Pustulosis Area Severity Index (PPPASI)
13
and the
Dermatology Life Quality Index (DLQI) (eFigure 1 in the Supple-
ment). The PPPASI measures severityof the disease with scores
from 0 (no sign of disease) to 72 (very severe disease). The DLQI
measures quality of life with scores ranging from 0 to 30, with
higher scores indicating greater impairment. In the Northern
European cohort, patients were assessed with the Physician
Global Assessment (PGA), which has been shown to correlate
with the PPPASI.
14
The individuals who recorded clinical data
and measured disease severity (reporting dermatologists or
trained research nurses) were blinded to the study objec-
tives.
Statistical Analysis
Given that different scoring systems were used in the UK and
Northern European cohorts, the 2 data sets were analyzed sepa-
rately. The quantitative PPPASI and DLQI measures obtained
in the UK cohort were analyzed using the Mann-Whitney test
for binary variables, such as sex, or the Kruskal-Wallis test for
categorical variables, such as smoking status. The correlation
Key Points
Question Are clinical and demographic factors associated with
the severity of palmoplantar pustulosis?
Findings In a cross-sectional study of 203 patients in the UK, the
Palmoplantar Pustulosis Psoriasis Area Severity Index score was
significantly higher in women compared with men and in current
smokers vs former and never smokers. Both of these findings were
replicated in an independently ascertained, Northern European
cohort including 159 patients.
Meaning The findings of this study suggest that smoking
cessation interventions may be beneficial in patients with
palmoplantar pustulosis and should be investigated in clinical
studies.
Research Original Investigation Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis
E2 JAMA Dermatology Published online September 16, 2020 (Reprinted) jamadermatology.com
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between PPPASI or DLQI findings and age at onset was as-
sessed using the Spearman rank correlation coefficient. To ac-
count for the confounding effects of therapeutic interven-
tion, statistical significance was confirmed by regression
analysis. The PPPASI and DLQI values were normalized (square
root transformation) and analyzed vs sex, age of onset, or smok-
ing status, using treatment as a covariate.
To maximize statistical power,the c ategorical PGA scores
recorded in the Northern European data set were dichoto-
mized into clear to mild (including PGA-0 [clear], PGA-1 [al-
most clear], and PGA-2 [mild]) and moderate to severe (in-
cluding PGA-3 [moderate] and PGA-4 [severe]). The 2 groups
were then compared using the Fisher exact test. Given thatthe
purpose of the PGA analysis was to replicate results showing
statistical significance in the UK cohort, Pvalues were com-
puted based on a 1-tailed distribution. As the number of indi-
viduals receiving systemic treatment was relatively small
(n = 25 f romthe Medic al Universityof Vienna and 9 from Tartu
University), the confounding effect of therapeutic interven-
tion was addressed by excluding these cases from down-
stream analyses.
Individuals for whom information on smoking status or
age at onset was missing (Table) were excluded from the rel-
evant analyses. All statistical tests were implemented in R, ver-
sion 3.6.1 (R Project for Statistical Computing). Pvalues <.05
were considered statistically significant.
Results
Patient Cohorts
The features of the UK and Northern European cohorts are sum-
marized in the Table. Among the 203 UK patients (43 men
[21%]; 160 women [79%]; median age at onset, 48 [interquar-
tile range (IQR), 38-59] years). The Northern European cohort
comprised 193 patients (32 men [17%]; 161 women [83%]; me-
dian age at onset, 45 [IQR, 33-54] years). Of these, 159 pa-
tients were available for analysis (25 men [16%]; 134 women
[84%]; median age at onset, 45 [IQR, 34-53.3] years). All pa-
tients were of European descent. The percentage of women
(>75%), median age of onset (≥45years), and prevalence of cur-
rent and former smokers (>80%) werecomparable in the 2 data
sets. Prominent nail involvement was observed in both study
populations, with more than 30% of patients presenting with
at least 1 of the following: pustules involving the nail appara-
tus, subungual hyperkeratosis, permanent nail loss, and non-
pustular nail dystrophy.
Concurrent psoriasis vulgaris was observed in substan-
tial numbers of study participants (66/203 [33%] UK patients
and 22/193 [11%] Northern European cases), while psoriatic ar-
thritis was reported in fewer patients from both cohorts (20/
203 [10%] UK cases and 17/193 [9%] Northern European indi-
viduals).
Autoimmune thyroid disease was reported in several af-
fected individuals from both data sets (14 of 203 [7%] of UK
cases and 25 of 193 [13%] of Northern European patients). The
prevalence of obesity (60 of 150 [40%] in the UK data set and
51 of 193 [26%] in the Northern European sample) was com-
parable to that observed among the overall population of Brit-
ish (36%),
15
German (25%),
16
and Estonian (21%)
16
adults. In
keeping with this observation, no correlation between the body
Table. Featuresof Study Cohorts
Cohort
United
Kingdom
Northern
Europe
Demographic characteristics
a
Women, No. (%) 160/203 (79) 161/193 (83)
Men, No. (%) 43/203 (21) 32/193 (17)
Age at onset, median (IQR), y
b
48 (38-59) 45 (33-54)
Family history of psoriasis vulgaris,
No. (%)
65/203 (32) 33/193 (17)
Family history of pustular psoriasis,
No. (%)
9/203 (4)
c
10/93 (11)
d
Smoking status, No. (%)
Current 90/203 (44) 124/193 (64)
Former 88/203 (43) 36/193 (19)
Never 23/203 (11) 28/193 (15)
Unknown 2/203 (1) 5/193 (3)
Clinical presentation
Disease duration, median (IQR), y
b
6 (2-14) 16 (10-20)
d
Nail involvement, No. (%) 65/203 (32) 64/193 (33)
Concurrent psoriasis vulgaris, No. (%) 66/203 (33) 22/193 (11)
Concurrent psoriatic arthritis, No. (%) 20/203 (10) 17/193 (9)
Severity
PPPASI score, median (IQR)
e
8.2 (2.2-15.6) NA
DLQI score, median (IQR)
f,g
10 (3.3-16) NA
On systemic treatment, No. (%)
h
78/203 (38) 34/193 (18)
PGA score, No. (%)
i
NA
Clear/mild (0-2) 120/193 (62)
Moderate/severe (3-4) 73/193 (38)
Comorbid disease, No. (%)
Asthma 25/203 (12) 5/93 (5)
d
Depression 31/203 (15) 28/193 (15)
Diabetes 26/203 (13) 29/193 (15)
Hypertension 41/203 (20) 58/193 (30)
Autoimmune thyroid disease 14/203 (7) 25/193 (13)
Obesity
j
60/150 (40)
k
51/193 (26)
Abbreviations: DLQI, Dermatology Life Quality Index; IQR, interquartile range;
NA, not applicable; PGA, Physician Global Assessment; PPPASI, Palmoplantar
Pustular Psoriasis Area Severity Index.
a
All study participants were of European descent.
b
Data not available for 11 UK cases and 1 Northern European case.
c
One patient had a family history of both psoriasis vulgaris and pustular
psoriasis.
d
Information not available for the 100 patients recruited in Vienna, Austria.
e
PPPASI measures severity with scores from 0 (no sign of disease) to 72 (very
severe disease).
f
Data not available for 8 UK cases.
g
DLQI measures quality of life with scores from 0 to 30; higher scores indicate
greater impairment.
h
On systemic treatment at the time of recruitment or the preceding 4 weeks.
i
PGA measures severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate),
and 4 (severe).
j
Body mass index greater than 30 (calculated as weight in kilograms divided by
height in meters squared).
k
Data not available for 53 UK cases.
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mass index of patients with PPP and their PPPASI was noted
(Spearman r = 0.03, P= .61).
While different scoring systems were used in the 2 co-
horts, both included a substantial proportion of individuals
with severe PPP, reflecting ascertainment in hospital set-
tings. Specifically, 84 of 203 UK patients (41%) had a PPPASI
score greater than 10 and 73 of 193 of their Northern Euro-
pean counterparts (38%) had a PGA score greater than or equal
to 3 (Table).
Disease Severity
Among UK patients, age at onset was inverselycorrelated with
the PPPASI score (r= −0.18, P= .01) (Figure 1A), although not
with DLQI score (r= −0.08, P= .21). The association with the
PPPASI score remained significant when the confounding ef-
fect of systemic treatment was taken into accountby linear re-
gression (P= .04) (eTablein the Supplement). In keeping with
these findings, the analysis of the Northern European cohort
revealed that the median age at onset was lowerin patients with
moderate to severe PGA (41 [IQR, 30.5-52] years) compared
with those with clear to mild PGA (46.5 [IQR, 35.0-55.0] years)
(P= .04) (Figure 1B). Thus, severe PPP appeared to be associ-
ated with early disease onset.
In the UK sample, the median PPPASI score was higher in
women (9.6 [IQR, 3.0-16.2]) compared with men (4.0 [IQR, 1.0-
11.7]) (P= .01) (Figure 2A). The same applied to the median
DLQI (women: 10.5 [IQR, 4.3-17] vs men: 4 [IQR, 1-9];
P=8.2×10
−5
) (eFigure 2 in the Supplement). Both associa-
tions were confirmed when systemic treatment was included
in a linear regression model (P= .03 for PPPASI, P< .001 for
DLQI) (eTable in the Supplement). In agreement with these ob-
servations, analysis of the Northern European data set re-
vealed that moderate to severe PPP was moreprevalent among
women (57 of 134 [43%]) compared with men (5 of 25 [20%])
(P= .03) (Figure 2B). Thus, PPP severity appeared to be asso-
ciated with the sex of the patients in both the UK and North-
ern European study populations.
Among the UK patients, the median PPPASIscore was high-
est in current smokers (10.7 [IQR, 4.2-17.5]), intermediate in
former smokers (7 [IQR, 2.0-14.4]), and lowest among non-
smokers (2.2 [IQR, 1-6]) (P= .003) (Figure 3A). Comparable
findings were obtained when the median DLQI scores were ana-
lyzed (current smokers: 10 [IQR, 4.8-16.3] vs former smokers:
Figure 1. Association Between Disease Severity and Age of Onset
60
50
40
30
20
10
0
PPPASI score
Age at onset, y
UK cohort
A
Northern European cohort
B
900 10 20 30 40 50 60 70 80
80
70
60
50
40
30
20
10
0
Age at onset, y
Clear/mild Moderate/severe
A, In the UK cohort, the Palmoplantar Pustulosis Psoriasis Area Severity Index
(PPPASI) score was inversely correlated with age of onset (r= −0.18, P= .01).
Regression lines are plotted with their 95% CIs (gray areas). B, In the Northern
European sample, age of onset was significantly lower among patients with
moderate-to-severe disease. Data are presented as median (interquartile
range). P< .05 per Mann-Whitney test. PPPASI measures severitywith scores
from 0 (no sign of disease) to 72 (very severe disease).
Figure 2. Disease Severity Scores in Women and Men
100
80
60
40
20
0
PPP cases, %
Northern European cohort
B
UK cohort
A
60
50
40
30
20
10
0
PPPASI score
WomenWomen Men Men
Moderate/severe PGA
Clear/mild PGA
A, In the UK cohort, Palmoplantar Pustulosis Psoriasis Area Severity Index
(PPPASI) scores were significantly higher in women than men. Data are
presented as median (interquartile range). P< .01 per Mann-Whitney test. B, In
the Northern European sample, the proportion of individuals with moderate to
severe disease was significantly elevated in women compared with men. P<.05
per Fisher exact test. Physician Global Assessment (PGA) measures severity as
0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). PPPASI
measures severity with scores from 0 (no sign of disease) to 72 (very severe
disease). PPP indicates palmoplantar pustulosis.
Research Original Investigation Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis
E4 JAMADermatology Published online September 16,2020 (Reprinted) jamadermatology.com
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9 [IQR, 3-17] vs nonsmokers: 5 [IQR, 1-10.8]) (P= .04) (eFig-
ure 3 in the Supplement). Both associations could be repli-
cated when the effects of systemic treatment were incorpo-
rated into a linear model (P= .005 for PPPASI, P= .04 for DLQI)
(eTable in the Supplement). The percentage of current smok-
ers (men: 18/43 [42%] and women: 72/160 [45%]) and former
smokers (men: 19/43 [44%] and women: 69/160 [43%]) was
comparable in the 2 sexes. Moreover, multivariable regres-
sion modeling found no evidence that the effect of smoking
differed by sex (data available from the authors).
While the analysis of the smaller Northern European data
set did not yield statistically significant results, we observed
a similar trend toward increased disease severity in smokers.
Moderate to severe PPP was more frequent amongc urrentand
former smokers (51 of 130 [39%]) than nonsmokers (6 of 24
[25%]) (P= .14) (Figure 3B).
Discussion
To our knowledge, this is the first systematic study of the fac-
tors associated with PPP severity. This study builds on previ-
ous work from our network, which enabled the definition of
consensus diagnostic criteria for PPP
7
and suggested that the
disease is genetically different from other forms of pustular
psoriasis.
2
Our investigation noted key epidemiologic features of
PPP, such as the late age of onset and sex bias (male-female
ratios were >1:3.5 in both cohorts). Psoriasis vulgaris con-
currence, which is frequently reported in PPP, was also
observed in the 2 data sets. While the prevalence of psoria-
sis vulgaris in the 2 cohorts was consistent with published
estimates (14%-61%),
17
the number of individuals with both
PPP and psoriasis vulgaris was too small for subgroup analy-
ses, and the use of different scoring systems prevented us
from merging the UK and Northern European data sets.
Conversely, the study of the entire resource highlighted
aspects of PPP that, to our knowledge, had not been system-
atically investigated before.
We observed nail involvement in approximately one-
third of affected individuals. Subungual pustulation was re-
ported in a similar fraction of cases in a small UK study,
18
sug-
gesting that nail abnormalities are a consistent featureof PPP.
We also report substantial comorbidity with psoriatic ar-
thritis, which was present in both cohorts at a frequency greater
than 9%. This percentage exceeds the prevalence of the dis-
ease in the general population (0.1%-0.3%).
19
Obesity was relatively uncommon, affecting only one-
third of all study participants. This level contrasts with find-
ings obtained in psoriasis vulgaris studies, where the associa-
tion with obesity is well established
20
and up to 42% of
individuals with severe disease have a body mass index greater
than 30.
21
Overall, these findings suggest that PPP is part of the pso-
riasis spectrum because the substantial comorbidity with pso-
riasis vulgaris and psoriatic arthritis points to shared patho-
genic pathways. Atthe same time, the distinctive demographics
of PPP suggest the involvement of risk factors that are spe-
cific to this disease. For example, the female bias that charac-
terizes PPP is not observed in palmoplantar psoriasis.
22
Like-
wise, psoriasis vulgaris affects both sexes equally
23
and
occurred with comparable frequency in the male (15/28 [35%])
and female (51/160 [32%]) patients examined in this study
(P= .72).
Our analysis of PPPASI and PGA scores suggests that
PPP severity is higher in women vs men. Further experi-
mental studies will be required to dissect the causes of this
phenomenon. These sources may involve genetic modifiers
or hormonal imbalances that could be targeted for disease
treatment.
Our study also noted an association between cigarette
smoking and disease severity that was statistically signifi-
cant in the UK cohort (P< .01), where PPPASIvalues were high-
est in smokers, intermediate in former smokers, and lowestin
nonsmokers. This observation suggests a clinically relevant
dosage effect that may be validated and refined by analyzing
pack-year data in further patient resources.
Smoking cessation is sometimes applied to the manage-
ment of PPP and was found to be beneficial in a pilot study.
24,25
In this context, our findings suggest that smoking cessation
should be systematically investigated in adequately powered
trials.
Limitations
This study has limitations. The setting was exclusively
based in secondary and tertiary referral centers, where the
proportion of patients with severe PPP and the burden of
comorbid disease may be higher than in other settings.
Figure 3. Disease Severity Scores in Current, Former, and Never Smokers
100
80
60
40
20
0
PPP cases, %
Northern European cohort
B
UK cohort
A
60
50
40
30
20
10
0
PPPASI score
SmokerCurrent
smoker
Former
smoker
Never
smoker
Never smoker
Moderate/severe PGA
Clear/mild PGA
A, In the UK cohort, Palmoplantar Pustulosis Psoriasis Area Severity Index
(PPPASI) scores are highest in current smokers, intermediate in former smokers
and lowest in never smokers. Data are presented as median (interquartile
range). P< .01 per Kruskal-Walliste st. B, In the Northern Europeansample, the
proportion of individuals with moderate to severe disease was elevated in
current and former smokers compared with never smokers. Physician Global
Assessment (PGA) measures severity as 0 (clear), 1 (almost clear), 2 (mild), 3
(moderate), and 4 (severe). PPPASI measures severitywith score s from 0 (no
sign of disease) to 72 (very severe disease). PPP indicates palmoplantar
pustulosis.
Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis Original Investigation Research
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Thus, the potential for ascertainment bias limits the gener-
alizability of our findings.
Different measures of disease severity were used in the UK
(DLQI and PPPASI) and Northern European cohorts (PGA). Al-
though these scales are widely used in clinical practice, our re-
sults suggest that the categorical nature of the PGA tool af-
fected the statistical power of the Northern European cohort
and limited our ability to apply correlation-based methods.
Thus, quantitative measurements,such as the PPPASI, or even
more-sensitive methods, such as machine-learning–based pus-
tule counts, should be considered the standard for studies of
PPP severity.
Conclusions
The findings from this cross-sectional study note the ben-
efits of multicenter collaboration and standardized data col-
lection in the analysis of rare skin diseases. The study also sug-
gests that PPP symptoms are particularly severe in patients with
early-onset disease, women, and current smokers. The asso-
ciation between the severity of the disease and smoking will
need to be replicated in further data sets; however, the in-
creased severity suggests that smoking cessation interven-
tions may benefit the treatment of PPP.
ARTICLE INFORMATION
Accepted for Publication: June 19, 2020.
Published Online: September 16, 2020.
doi:10.1001/jamadermatol.2020.3275
Open Access: This is an open access article
distributed under the terms of the CC-BY License.
© 2020 Benzian-Olsson N et al. JAMA
Dermatology.
Author Affiliations: Department of Medical and
Molecular Genetics, King's College London, London,
United Kingdom (Benzian-Olsson, Dand, Chaloner,
Capon); Health Data Research UK, London, United
Kingdom (Dand); Department of Dermatology and
Allergology, Universityof Szeged, Szeged, Hungary
(Bata-Csorgo); Humanitas Clinical and Research
Center, IRCCS, Milan, Italy (Borroni); Department of
Biomedical Sciences, Humanitas University,Milan,
Italy (Borroni); Institute of Infection, Immunity and
Inflammation, University of Glasgow,Glasgow,
United Kingdom (Burden); Portsmouth
Dermatology Unit, Portsmouth Hospitals Trust,
Portsmouth, United Kingdom (Cooper); Imperial
Clinical Trials Unit, School of Public Health, Imperial
College London, London, United Kingdom
(Cornelius, Cro); St John's Institute of Dermatology,
King's College London, London, United Kingdom
(Dasandi, Meynell, Patel, Pink, Barker,Smith);
Dermatology Centre, National Institute for Health
Research Manchester Biomedical Research Centre,
University of Manchester,Manche ster, United
Kingdom (Griffiths); Dermatology Clinic, Tartu
University Hospital, Department of Dermatology,
University of Tartu, Tartu, Estonia (Kingo); Centre
for Molecular Medicine and Innovative
Therapeutics, Murdoch and Perron Institute for
Neurological and Translational Science, Murdoch
University,Nedlands, Western Australia, Australia
(Koks); National Amyloidosis Centre, University
College London, Royal FreeCampus, London,
United Kingdom (Lachmann); The Psoriasis
Association, Northampton, United Kingdom
(McAteer); Psoriasis Center at the Department of
Dermatology, UniversityMedical Center,
Schleswig-Holstein, Campus Kiel, Kiel, Germany
(Mrowietz, Torz); Department of Dermatology,
Royal Liverpool Hospitals, Liverpool, United
Kingdom (Parslew); Translationaland Clinical
Research Institute, Newcastle University, Newcastle
upon Tyne, United Kingdom (Reynolds);
Department of Dermatology and National Institute
for Health Research Newcastle Biomedical
Research Centre, Newcastle Hospitals NHS
Foundation Trust,Newcastle upon Tyne, United
Kingdom (Reynolds); Department of Dermatology,
Medical University of Vienna, Austria (Tanew,
Trattner);Depar tment of Dermatology, University
Hospital of North Durham, Durham (Wahie); The
Dermatology Centre, Salford Royal NHS Foundation
Trust, University of Manchester, Manchester
Academic Health Science Centre, Manchester,
United Kingdom (Warren); Department of
Dermatology, St LukesHospital, Bradford, United
Kingdom (Wright); Department of Dermatology &
Allergy, UniversityHospital of Basel, Basel,
Switzerland (Navarini).
Author Contributions: Ms Benzian-Olsson and Dr
Capon had full access to all of the data in the study
and take responsibility for the integrity of the data
and the accuracy of the data analysis.
Concept and design: Benzian-Olsson, Chaloner,
Cornelius, Griffiths, Koks, McAteer,Barker, Smith,
Capon.
Acquisition, analysis, or interpretation of data:
Benzian-Olsson, Dand, Chaloner, Bata-Csorgo,
Borroni, Burden, Cooper, Cro,Dasandi, Griff iths,
Kingo, Koks, Lachmann, Meynell, Mrowietz,
Parslew, Patel,Pink, Reynolds, Tanew, Torz,
Trattner, Wahie, Warren, Wright, Barker, Navarini,
Smith, Capon.
Drafting of the manuscript: Benzian-Olsson, Dand,
Chaloner, Kingo,Barker, Smith, Capon.
Critical revision of the manuscript for important
intellectual content: Benzian-Olsson, Dand,
Bata-Csorgo, Borroni, Burden, Cooper,Cornelius,
Cro, Dasandi, Griffiths, Koks, Lachmann, McAteer,
Meynell, Mrowietz, Parslew,Patel, Pink, Reynolds,
Tanew, Torz,Trattner, Wahie, Warren,Wright,
Barker, Navarini,Smith.
Statistical analysis: Benzian-Olsson, Dand,
Chaloner, Patel.
Obtained funding: Cornelius, Griffiths, Koks, Smith,
Capon.
Administrative, technical, or material support:
Benzian-Olsson, Dand, Chaloner, Bata-Csorgo,
Borroni, Burden, Cooper, Dasandi, Koks,Lachmann,
McAteer, Meynell, Mrowietz, Parslew, Patel, Pink,
Tanew, Torz,Wright, Navarini.
Supervision: Koks, Pink, Warren, Barker, Smith,
Capon.
Conflict of Interest Disclosures: Dr Borroni
reported receiving grants from Celgene Research
Award and personal fees from AbbVie outside the
submitted work. Dr Burden reported receiving
personal fees from Boehringer Ingelheim, Novartis,
Celgene, Janssen, AbbVie, and Almirall outside the
submitted work. Dr Cro reported receiving grants
from the National Institute for Health Research
(NIHR) Efficacy and Mechanism Evaluation during
the conduct of the study. Dr Griffiths reported
receiving grants from the Medical Research Council
(MRC) NIHR during the conduct of the study.Dr
Koks reported receiving grants from Estonian
Research Council and grants from H2020 ERAchair
during the conduct of the study and Prion Ltd, a
member of the board and shareholder of the
company.Dr Mc Ateerrepor ted receivinggrants
from AbbVie, Almirral, Amgen, Celgene, Eli Lilly,
Janssen, LEO Pharma, UCB, and Thornton and Ross
Derma outside the submitted work. Dr Patel
reported receiving grants from Efficacy and
Mechanism Evaluation (EME) Programme during
the conduct of the study. Dr Pink reported receiving
personal fees from AbbVie, Lilly,Sanof i, Leo
Pharma, Novartis, Almirall, UCB, Janssen, and La
Roche-Posay outside the submitted work. Dr
Reynolds reported receiving lecture fees from
AbbVie (to Newcastle University), payment for
medical advisory board meeting and lectures fees
from Almirall (to Newcastle University),
contributing to a clinical trial from AnaptysBio (to
Newcastle upon TyneHospital), lec ture fees from
Celgene to Newcastle University), lecture fees from
Janssen (to Newcastle University), grants and
serving as a paid member of a medical advisory
board from Novartis, and lecture fees from UCB
Pharma Ltd (to Newcastle University) outside the
submitted work. Dr Wahie reported receiving
nonfinancial support from Janssen, AbbVie,
Novartis, and Almirall outside the submitted work.
Dr Navarini reported receiving grants from EADV
during the conduct of the study; grants and
personal fees from AbbVie; personal fees from
Almirall, Amgen, Eli Lilly,Galderma, Leo Pharma,
Novartis, Sanofi, UCB, and Biomed; grants and
personal fees from Boehringer Ingelheim; and
nonfinancial support from Janssen-Cilag outside
the submitted work. Dr Smith reported receiving
grants from National Institute for Health Research
and nonfinancial support from SOBI during the
conduct of the study; grants from Medical Research
Council, grants from Boehringer Ingelheim GmbH,
grants from Innovative Medicines Initiative Horizon
2020, and grants from Medical Research Council
outside the submitted work; and serving as an
unpaid guideline committee member for UK and
European guidelines for psoriasis, including
pustular psoriasis. Dr Capon reported receiving
grants from the European Academy of Dermatology
and Venereology and MRC/NIHR during the
conduct of the study; and grants from
Boehringer-Ingelheim and personal fees from
AnaptysBio outside the submitted work. No other
disclosures were reported.
Funding/Support: Support for the study was
received from the Department of Health via the
NIHR BioResource Clinical Research Facility and
comprehensive Biomedical Research Centre awards
Research Original Investigation Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis
E6 JAMADermatology Published online September 16,2020 (Reprinted) jamadermatology.com
Downloaded From: https://jamanetwork.com/ by a University College London User on 09/21/2020
to Guy’s and St Thomas’ NHS Foundation Trust in
partnership with King’s College London and King’s
College Hospital NHS Foundation Trust
(guysbrc-2012-1).Suppor t wasalso received from
the Newcastle NIHR Biomedical Research Centre.
The APRICOT trial and the PLUM study were
funded by the EME Programme, an MRC and NIHR
partnership (grant EME 13/50/17 to Drs Smith,
Capon, Barker, and Griffiths). This work was
supported by the European Academy of
Dermatology and Venereology (grant
PPRC-2018-25to Drs Barker, Capon, and Navarini,
and grant PPRC-2012-11 to Drs Navarini and Barker).
Ms Benzian-Olsson was funded by an NIHR
predoctoral fellowship (grant NIHR300473). Dr
Dand was funded by Health Data Research UK
(MR/S003126/1). Dr Griffiths was funded in part by
the NIHR Manchester Biomedical Research Centre
and is an NIHR Emeritus Senior Investigator.Dr
Reynolds is an NIHR Senior Investigator and
receives support from the Newcastle MRC/EPSRC
Molecular Pathology Node and the Newcastle NIHR
Medtech and In Vitro Diagnostic Co-operative. Dr
Warren is supported by the Manchester NIHR
Biomedical Research Centre.
Role of the Funder/Sponsor:The funding
organizations had no role in the design and conduct
of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Membership of the PLUM and APRICOT Study
Team: Thefollowing members of the PLUM and
APRICOT study team contributed to this work:
Mahmud Ali, Worthing Hospital; Nisha Arujuna,
Kingston Hospital; Suzannah August, Poole
Hospital; David Baudry,Guy’s Hospital, London; A.
David Burden, Glasgow Western Infirmary; Hywel
Cooper, St Marys Hospital, Portsmouth; Victoria
Cornelius, Imperial College London; Suzie Cro,
Imperial College London; Giles Dunnill, University
Hospitals Bristol; Christopher Griffiths, University of
Manchester; John Ingram, University Hospital of
Wales; Helen Lachmann, Royal FreeHospital,
London; Effie Ladoyanni, Russell’s Hall Hospital,
Dudley; Nick Levell, Norfolk & Norwich University
Hospital; Areti Makrygeorgou, West Glasgow
Ambulatory Care Hospital; Helen McAteer, The
Psoriasis Association, Northampton; John
McKenna, Leicester RoyalInf irmary;Freya Meynell,
Guy’s Hospital, London; Richard Parslew, Royal
Liverpool; Prakash Patel, Guy’s Hospital, London;
Andrew Pink, Guy’s Hospital, London; Angela
Pushparajah, Guy’s Hospital, London; Nick
Reynolds, Newcastle Hospitals; Catherine Smith,
Guy’s Hospital, London; Shyamal Wahie,University
Hospital of North Durham and Darlington Memorial
Hospital; Richard Warren, Salford Royal Infirmary;
Rosemary Wilson, Guy’s Hospital, London; Andrew
Wright, St Lukes Hospital, Bradford.
Membership of the ERASPEN Study Team:The
following members of the ERASPEN study team
contributed to this work: Zsuzsa Bata-Csorgo,
University of Szeged; Riccardo Borroni, Humanitas
University,Milan; Ulrich Mrowietz, University
Medical Centre Schleswig-Holstein, Campus Kiel,
Germany; Raquel Rivera, Hospital Universitario 12
Octubre; Noemi Eiris Salvado, Complejo Asistencial
Universitario de Leon; Hannes Trattner,
Spezialambulanz für Psoriasis, Vienna.
Disclaimer: The views expressed in this publication
are those of the authors and not necessarily those
of the MRC, NHS, NIHR, or the Department of
Health.
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