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Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis

Authors:

Abstract

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.
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
Downloaded From: https://jamanetwork.com/ by a University College London User on 09/21/2020
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.
Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis Original Investigation Research
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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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Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis Original Investigation Research
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... Our study revealed a female predominance for PPP and a mean age of onset of 42.38 years, similar to previous reports. 2,3,[5][6][7][8][9][10][11][12][13] We found that PPP onset is most common in palmar areas (41.1%); however, both palmar and plantar involvement was the most common presentation (60.1%) at the time of recruitment. Two previous reports 14,15 described a similar pattern, indicating that PPP typically starts on either palmar or plantar areas (64% and 72%, respectively) before involving both. ...
... 16 We also aimed to identify whether there is an association between obesity and disease severity, as few studies have examined this association. 3,9,17 Consistent with two previous studies, 3,9 we found no association between higher PPPASI and either mean BMI or frequency of overweight/obesity. However, Serizawa et al. 17 recently reported that BMI was a predictor for PPPASI, therefore this association warrants further investigation. ...
... 16 We also aimed to identify whether there is an association between obesity and disease severity, as few studies have examined this association. 3,9,17 Consistent with two previous studies, 3,9 we found no association between higher PPPASI and either mean BMI or frequency of overweight/obesity. However, Serizawa et al. 17 recently reported that BMI was a predictor for PPPASI, therefore this association warrants further investigation. ...
Article
Full-text available
Background Palmoplantar pustulosis (PPP) is a rare, chronic, inflammatory skin disease characterised by sterile pustules on palmar or plantar areas, and data on PPP are scarce. Objectives To investigate the PPP clinical characteristics and risk factors for disease severity amongst a large cohort of Turkish PPP patients. Methods We conducted a cross-sectional, multicentre study of PPP patients recruited from 21 tertiary centres across Turkey. Results A total of 263 patients (165 women, 98 men) were evaluated. Most patients (75.6%) were former or current smokers. The mean Palmoplantar Pustulosis Area and Severity Index (PPPASI) score was 8.70 ± 8.06, and the mean Dermatology Life Quality Index (DLQI) score was 6.87 ± 6.08, and these scores were significantly correlated (r = 0.524, p < 0.001). Regression analysis showed that current smoking was significantly associated with increased PPPASI scores (p = 0.028). Co-existing psoriasis vulgaris (PSV) was reported by 70 (26.6%) patients. The prevalence of male sex, palmar PPP onset incidence, disease duration, DLQI score, nail involvement, and psoriatic arthritis prevalence were significantly increased among PPP patients with PSV. Of the patients, 18 (6.8%) had biologic therapy-induced paradoxical PPP, and these patients had significantly increased mean DLQI scores and PSA prevalence (r = 0.026, p = 0.001). Conclusions Our data suggested that smoking is a risk factor for both PPP development and disease severity, PPP patients with PSV present distinct clinical features, and patients with biologic therapy-induced paradoxical PPP have reduced quality of life and are more likely to have PSA.
... We found four cohorts from three different studies in the literature reporting clinical characteristics of PPP; two were monocentric, and none had a study size larger than our cohort ( Table 2). [8][9][10] The proportion of females ranged from 59% to 83%, with the median age at disease onset of 44.2 to 51.1 years, which agrees with our data. In our cohort, the respective rates of hypertension, current/former smokers and thyroid disease were comparable with the literature, but the prevalence of diabetes was slightly less in our study (12.1% to 15% vs. 9.8% in our cohort). ...
... The 42.7% proportion of our patients with acral pustular disease showing an association with PV exceeded the highest prevalence rates from the literature, which ranged from 11% to 33%. [8][9][10] In the same way, the prevalence of arthritis was higher in our cohort than the literature (22.6% vs. 8.6% to 16.7% [8][9][10]). Several biases might account for these apparent discrepancies, especially the massive tertiary care centre recruitment in our study, which might affect patient profiles, including severity, as well as physician assessments. ...
... The 42.7% proportion of our patients with acral pustular disease showing an association with PV exceeded the highest prevalence rates from the literature, which ranged from 11% to 33%. [8][9][10] In the same way, the prevalence of arthritis was higher in our cohort than the literature (22.6% vs. 8.6% to 16.7% [8][9][10]). Several biases might account for these apparent discrepancies, especially the massive tertiary care centre recruitment in our study, which might affect patient profiles, including severity, as well as physician assessments. ...
Article
Full-text available
Background: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. Objectives: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. Methods: In this multicenter national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. Results: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity, and higher median BMI (p=0.01, p=0.02 and p=0.05, respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years, respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1%, respectively). Conclusion: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.
... PPP shows a marked sex bias, with women accounting for 60-90% of affected individuals and is associated with smoking, with up to 90% of participants self-identifying as smokers at the time of diagnosis. 41 Higher prevalence rates have also been reported in white people than in other ethnic groups. 42 Currently validated outcome measures in PPP are lacking, and validation of end points is required. ...
... It has enabled and established a productive partnership with the European Rare And Severe Psoriasis Network (ERASPEN), leading to the publication of two research papers. 41,43 It has also enabled the identification of a novel disease gene that has been described in a recent article. 44 Since the inception of this trial, IL-36 per se has been further validated as a potential therapeutic target in pustular psoriasis, with the first proof-of-concept phase 1 study of the IL-36 receptor antagonist monoclonal antibody BI655130 showing efficacy in GPP in a series of seven participants. ...
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Background Palmoplantar pustulosis is a rare, debilitating, chronic skin disease involving the hands and feet, and there are limited treatment options. Mechanistic findings suggest that interleukin 1 may be a pathogenic driver. Objective To determine whether or not anakinra [Sobi (Swedish Orphan Biovitrum AB), Stockholm, Sweden], an interleukin 1 receptor antagonist, delivers therapeutic benefit in palmoplantar pustulosis. Design A Phase IV, randomised, double-blind, placebo-controlled study with two stages and an adaptive element (24 participants in stage 1, 64 participants in total) with an open-label extension. Setting Sixteen hospitals across England, Scotland and Wales. Participants Adults (aged ≥ 18 years) with a diagnosis of palmoplantar pustulosis and a disease duration of > 6 months and of sufficient impact and severity to require systemic therapy. Interventions Participants were randomised (1 : 1) to daily self-administered subcutaneous injection of either anakinra or a placebo for 8 weeks. Main outcome measures The primary outcome was the Palmoplantar Pustulosis Area and Severity Index score measured at 0, 1, 4, 8 and 12 weeks, with the primary end point at 8 weeks adjusted for baseline. Secondary outcomes included other investigator-assessed efficacy measures of disease severity, safety measures and participant-reported measures of efficacy and impact. Results A total of 64 participants (mean baseline Palmoplantar Pustulosis Area and Severity Index score of 17.8, standard deviation 10.5) received anakinra ( n = 31) or the placebo ( n = 33). In the primary intention-to-treat analysis, which estimated the effect of the treatment policy, the mean treatment group difference at 8 weeks after adjustment for baseline Palmoplantar Pustulosis Area and Severity Index score was –1.65 (95% confidence interval –4.77 to 1.47; p = 0.300), in favour of anakinra relative to placebo, but was not statistically significant. Similarly, secondary investigator-assessed outcomes did not show statistical superiority of anakinra: the baseline-adjusted mean difference in fresh pustule count (palms and soles) between the anakinra group and the placebo group was 2.94 (95% confidence interval –26.44 to 32.33), in favour of placebo, and the mean difference in total pustule count was –30.08 (95% confidence interval –83.20 to 23.05), in favour of anakinra. Participant-assessed outcomes were consistent with these objective findings: the baseline-adjusted mean difference in Dermatology Life Quality Index between the anakinra group and the placebo group was 0.52 (95% confidence interval –2.04 to 3.07), in favour of placebo, and the mean difference in Palmoplantar Quality-of-Life Index was 1.27 (95% confidence interval –3.04 to 5.57), in favour of placebo. However, the proportion of participants who strongly agreed that treatment was worthwhile was greater in the anakinra group (12/29, 41%) than in the placebo group (4/28, 14%), a difference in proportion of 27% (95% confidence interval 5% to 49%). In the complier-average causal effect analysis, the baseline-adjusted mean treatment group difference in the week 8 Palmoplantar Pustulosis Area and Severity Index score in individuals who received ≥ 50% of injections was –2.30 (95% confidence interval –6.54 to 1.93; p = 0.287) and in those who received ≥ 90% of injections was –3.80 (95% confidence interval –10.76 to 3.16; p = 0.285), in favour of anakinra. No serious infections, significant neutropenia or other serious adverse events occurred. Injection site reactions were more frequent for those receiving anakinra (19/31, 61%) than for those receiving placebo (1/33, 3%). Conclusions There was no evidence that anakinra was superior to placebo. For the treatment of palmoplantar pustulosis, interleukin 1 blockade is not a useful intervention. Limitations The sample size was calculated to detect a large effect size. Treatment adherence was lower than expected. It cannot be ruled out that there was some selection bias towards less severe or unstable participants entering the trial given that the trial was placebo controlled with a required washout period. Future work Palmoplantar pustulosis remains an area of high unmet need and further research is recommended to (1) identify new drug targets, (2) determine the contributory role of drug exposure (including pharmacokinetics and adherence) and (3) validate outcome measures in palmoplantar pustulosis. Trial registration This trial is registered as ISCRTN13127147 and EudraCT 2015-003600-23. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation ; Vol. 9, No. 2. See the NIHR Journals Library for further project information.
... Thus, PPP T cells showed a complex activation pattern [58]. The present results have indicated systemic abnormalities in PPP [59]. Th17/Th2 cells have been reported to be IL-4/IL-17-producing in peripheral blood and from BAL (Bronchoalveolar lavage) of asthmatic patients [60,61]. ...
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Palmoplantar pustulosis (PPP) is a disease that causes recurrent blisters and aseptic pustules on the palms and soles. It has been suggested that both innate and acquired immunity are involved. In particular, based on the tonsils and basic experiments, it has been assumed that T and B cells are involved in its pathogenesis. In addition, the results of clinical trials have suggested that IL-23 is closely related to the pathogenesis. This review describes PPP and the genetic background, the factors involved in the onset and exacerbation of disease and its relation to the molecular mechanism. In addition, we describe the usefulness of biological therapy and its implications in relation to the importance in pathology, the pathogenesis of PPP, the importance of the role of the IL-23–Th17 axis and IL-36 in PPP. Furthermore, we describe an animal experimental model of PPP, the efficacy and mechanism of action of guselkumab, an anti-IL-23 antibody, the latest research, and finally the possibility for it to be effective for other autoimmune diseases.
... Severe disease was found to be associated with female gender, earlier disease presenatiton and smoking. The disease severity decreases dramatically with the cessation of smoking [7]. ...
... 11 On the other hand, another systematic review reported cautiously that smoking may cause an increased prevalence and severity of HE, especially in high-risk occupations. 12 Several other chronic inflammatory skin diseases are linked to smoking, such as AD, 25 palmoplantar pustulosis, 26 and psoriasis. 27 Smoking has an immunomodulatory effect with elevated levels of immunoglobulin E (IgE), increased macrophage and dendritic cell activity, a release of pro-inflammatory cytokines, and a favored activity of the Th2 pathway. ...
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Background Several risk factors, among others lifestyle factors, have been suggested for hand eczema (HE). Objectives To investigate a possible association between HE and life style factors, including smoking, alcohol consumption, stress, body mass index (BMI), waist circumference, physical activity, diet and amount of sleep in the Dutch general population. Methods Data from the large population-based LifeLines Cohort Study was used. Individuals with HE in the past year were identified by a cross-sectional questionnaire in 2020. At baseline, information on lifestyle factors was collected. Results In total 57 046 individuals were included in the present analysis. Smoking ≥8 cigarettes/day, and smoking ≥15 pack years showed a positive association with HE in the past year. Also, chronic stress, a BMI > 30 kg/m2, and a waist circumference of >90 cm, were positively associated with HE in the past year. Conclusions The current study indicates that lifestyle factors are associated with HE. Advice regarding lifestyle factors might contribute to enhance overall health, of which HE might possibly benefit in conjunction. Further studies should also focus on the association between lifestyle factors and the severity and prognosis of HE rather than on occurrence alone. This article is protected by copyright. All rights reserved.
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Background Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder, characterised by eruptions of painful, neutrophil-filled pustules on the palms and soles. While PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat. Objective We sought to investigate the immune pathways that underlie the pathogenesis of PPP. Methods We applied bulk- and single-cell RNA-sequencing methods to the analysis of skin biopsies and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy Results Bulk RNA-sequencing of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several Th2 genes typically upregulated in atopic dermatitis. To further explore these findings, we carried out single-cell RNA-sequencing in peripheral blood mononuclear cells of healthy and affected individuals. We found that the memory CD4+T-cells of PPP patients were skewed towards a Th17 phenotype, a phenomenon that was particularly significant among CLA+ skin-homing cells. We also identified a subset of memory CD4+ T-cells which expressed both Th17 (KLRB1/CD161) and Th2 (GATA3) markers, with pseudo-time analysis suggesting that the population was the result of Th17 to Th2 plasticity. Interestingly, the GATA3+/CD161+ cells were over-represented among the PBMCs of affected individuals, both in the scRNA-seq dataset and in independent flow-cytometry experiments. Dual positive cells were also detected in patient skin by means of immune fluorescence microscopy. Conclusions These observations demonstrate that PPP is associated with complex T-cell activation patterns and may explain why biologics that target individual T-helper populations have shown limited therapeutic efficacy. Clinical implications The simultaneous activation of Th17 and Th2 responses in PPP supports the therapeutic use of agents that inhibit multiple T-cell pathways.
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Importance: Palmoplantar pustulosis (PPP) has been reported to be accompanied by systemic conditions. However, the risks of comorbidities in patients with PPP have rarely been evaluated. Objective: To assess the risks of comorbidities in patients with PPP compared with patients with psoriasis vulgaris or pompholyx. Design, setting, and participants: This nationwide population-based cross-sectional study used data from the Korean National Health Insurance database and the National Health Screening Program collected from January 1, 2010, to December 31, 2019. Data were analyzed from July 1, 2020, to October 31, 2021. Korean patients diagnosed with PPP, psoriasis vulgaris, or pompholyx who visited a dermatologist between January 1, 2010, and December 31, 2019, were enrolled. Exposures: Presence of PPP. Main outcomes and measures: The risks of comorbidities among patients with PPP vs patients with psoriasis vulgaris or pompholyx were evaluated using a multivariable logistic regression model. Results: A total of 37 399 patients with PPP (mean [SD] age, 48.98 [17.20] years; 51.7% female), 332 279 patients with psoriasis vulgaris (mean [SD] age, 47.29 [18.34] years; 58.7% male), and 365 415 patients with pompholyx (mean [SD] age, 40.92 [17.63] years; 57.4% female) were included in the analyses. Compared with patients with pompholyx, those with PPP had significantly higher risks of developing psoriasis vulgaris (adjusted odds ratio [aOR], 72.96; 95% CI, 68.19-78.05; P < .001), psoriatic arthritis (aOR, 8.06; 95% CI, 6.55-9.92; P < .001), ankylosing spondylitis (aOR, 1.91; 95% CI, 1.61-2.27; P < .001), type 1 diabetes (aOR, 1.33; 95% CI, 1.16-1.52; P < .001), type 2 diabetes (aOR, 1.33; 95% CI, 1.29-1.38; P < .001), Graves disease (aOR, 1.25; 95% CI, 1.11-1.42; P < .001), Crohn disease (aOR, 1.63; 95% CI, 1.11-2.40; P = .01), and vitiligo (aOR, 1.87; 95% CI, 1.65-2.12; P < .001) after adjusting for demographic covariates. The risks of ankylosing spondylitis (aOR, 1.37; 95% CI, 1.16-1.62; P < .001) and Graves disease (aOR, 1.40; 95% CI, 1.23-1.58; P < .001) were significantly higher among patients with PPP vs psoriasis vulgaris. However, the risks of psoriatic arthritis (aOR, 0.54; 95% CI, 0.47-0.63; P < .001), systemic lupus erythematosus (aOR, 0.67; 95% CI, 0.46-0.97; P = .04), Sjögren syndrome (aOR, 0.70; 95% CI, 0.50-0.96; P = .03), systemic sclerosis (aOR, 0.29; 95% CI, 0.11-0.77; P = .01), vitiligo (aOR, 0.53; 95% CI, 0.47-0.60; P < .001), and alopecia areata (aOR, 0.88; 95% CI, 0.81-0.95; P = .001) were significantly lower among those with PPP vs psoriasis vulgaris. Conclusions and relevance: The results of this cross-sectional study suggest that patients with PPP have an overlapping comorbidity profile with patients with psoriasis vulgaris but not patients with pompholyx. However, the risks of comorbidities among patients with PPP may be substantially different from those among patients with psoriasis vulgaris.
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The development of metabolic disorders occurs in psoriasis: insulin resistance, systemic inflammation, atherosclerosis, oxidative stress and obesity. The paper presents pathological biochemical pathways of metabolic disorders development which is caused by common cytokine profile chara-cteristic for psoriasis and obesity and they are tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). The following links play a role in the development of insulin resistance: insulin receptor (IRS-1) and insulin receptor substrate (SIR-1), glucose transporter protein (GLUT-4), also there is a decrease in the phosphatidylinositol 3-kinase pathway (PI3AKT) activity, and an increase in the mitogen activating protein kinase (MAPK) activity. Factors influencing the development of inflammation are discussed: IL-6, C-reactive protein, tissue plasminogen activator inhibitor (PAI-1), monocyte chemoattractant protein 1 (MCP-1), proinflammatory adipokines; processes of vascular inflammation development, atherosclerosis development and oxidative stress. This article discusses endocrine disruption of adipocytes in obesity and the influence of adipokines and inflammatory mediators synthesized by fat cells on psoriatic disease. Advanced glycation end products (AGEs), hyperhomocysteinemia (HHcy) due to vitamin B12 and folic acid deficiency, and a 5,10-methylfolate reductase (MTHFR) mutation are also important in the clinical manifestations of psoriasis. The possibility of assessing metabolic disorders and dysfunction of various organs by changes in the levels of metabolites in the blood and skin of patients with psoriasis is discussed.
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Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris. The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP. In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1β, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP. Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.
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Introduction: Generalized pustular psoriasis (GPP) is characterized by widespread erythema and edema, superficial sterile coalescing pustules, and lakes of pus. Although the impact of GPP is thought to be substantial, emerging literature on its clinical, humanistic, and economic burden has not previously been described in a structured way. Areas covered: A structured search focused on the identification of studies in GPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical, humanistic, and economic burden. Expert opinion: Despite its significant clinical, humanistic, and economic burden, GPP is poorly classified and inadequately studied. A recent European (ERASPEN) consensus classifies GPP into relapsing and persistent disease and classifies patients on the presence or absence of psoriasis vulgaris. Classification of GPP lesions involving >30% body surface area or use of hospitalization as a surrogate may be a way to identify significant flares. Given the frequency of flares, the impaired quality of life during the post-flare period, and safety/tolerability issues, it is clear that current treatment options are not sufficient. Long-term studies utilizing the European consensus statement with subclassifiers are required to supplement our current understanding of the burden of GPP.
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Introduction: Palmoplantar psoriasis (PPP) is a variant of psoriasis that affects the palms and/or soles. Although PPP is a disabling and therapeutically challenging condition, its epidemiology is poorly defined. Aim: To assess the prevalence of PPP locations (palms, soles or both), and to analyse epidemiological and clinical characteristics of the disease. Material and methods: Two bibliographic databases (MEDLINE and SCOPUS) were used as data sources searched from inception to October 2017. The selection of articles was limited to human subjects and English or French languages. Results: A search resulted in a total of 293 articles, out of which 24 were utilized for the current systematic review and 21 for meta-analysis. All listed studies comprised a total of 2083 patients with PPP, with more males than females. According to the results of meta-analysis, majority of patients had the highest prevalence of both palms and soles involvement (95% CI: 47-67), with an almost equal prevalence showing palmar (21%; 95% CI: 13-30) or plantar (20%; 95% CI: 12-29) involvement. The most prevalent type of PPP was plaque/hyperkeratotic, followed by the pustular type. Conclusions: Almost three-fifths (59%) of all PPP patients had involvement of both palms and soles, while exclusive palmar or plantar involvement was seen in 21% and 20% of patients, respectively. Future research should be performed to elucidate basic epidemiological and clinical characteristics of PPP, which would be helpful for proper consideration of this condition.
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Background: Palmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis. Methods/design: We will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2. Discussion: We have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatment in pustular psoriasis. Trial registration: ISRCTN13127147 . Registered on 1st August 2016. EudraCT, 2015-003600-23 . Registered on 1st April 2016.
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Importance Palmoplantar pustulosis (PPP) is a recalcitrant skin disease with no biologics currently approved for treatment. The involvement of interleukin 23 (IL-23) and cytokines of the type 17 helper T cell lineage in the pathogenesis of PPP has been recently postulated. Objective To evaluate the efficacy and safety of guselkumab, an anti–IL-23 monoclonal antibody, in Japanese patients with PPP. Design, Setting, and Participants This double-blind, randomized, placebo-controlled, parallel-group, 24-week trial was conducted between May 14, 2013, and September 27, 2014, at 11 centers in Japan. Participants were patients with moderate to severe PPP that did not respond adequately to conventional treatments. Interventions Patients were randomized 1:1 to receive guselkumab, 200 mg, by subcutaneous injection or matching placebo at weeks 0 and 4. Main Outcomes and Measures Changes in total scores of skin-related outcomes from baseline at the end of week 16 (primary clinical cutoff) and through week 24 were measured. Serum biomarker analyses were performed at baseline, week 4, and week 16, and safety was monitored through week 24. Results Of 49 randomized patients (35 [71%] women; median [range] age, 52 [28-77] years), 41 completed the study at week 24. Mean (SD) PPP severity index total scores (primary end point) improved significantly from baseline in guselkumab-treated patients (−3.3 [2.43]) vs placebo (−1.8 [2.09]) (least squares mean difference, −1.5; 95% CI, –2.9 to –0.2; P = .03). At week 16, PPP area and severity index scores (least squares mean difference, −5.65; 95% CI, −9.80 to −1.50; P = .009) and proportion of patients achieving 50% reduction in these scores (difference in proportion, 39.2; 95% CI, 14.0-64.3; P = .009) improved significantly. A numerically higher proportion of patients had a physician’s global assessment score of 1 or less in the guselkumab group vs placebo. Improvement in efficacy scores was maintained through week 24 in the guselkumab group. Significant reductions from baseline in serum IL-17A and IL-17F cytokine levels were observed at weeks 4 and 16. Frequency of treatment-emergent adverse events was comparable between the guselkumab group (19 of 25 patients [76%]) and the placebo group (18 of 24 patients [75%]). Frequent adverse effects included nasopharyngitis (14 patients [29%]), headache (3 patients [6%]), contact dermatitis (3 patients [6%]), and injection site erythema (3 patients [6%]). No major safety concerns emerged during the study. Conclusions and Relevance Targeting IL-23 and its associated immune cascade with guselkumab may be a safe and useful therapeutic option for treatment of PPP. Trial Registration clinicaltrials.gov Identifier: NCT01845987
Article
Background Palmoplantar pustulosis (PPP) is a chronic pustular skin condition on palms and soles. The disease is often seen in combination with plaque psoriasis, and whether PPP is a variant of psoriasis has been debated. The disease prevalence of PPP and co‐occurring psoriasis is not yet established and the patient group remains understudied. Objectives To estimate the prevalence of PPP and co‐occurring psoriasis in three population‐based cohorts and provide information on patient demographics and characteristics. Methods Administrative healthcare registries and insurance databases from the US, Denmark and Germany were used as data sources. Patients with PPP were defined by a single ICD‐10 code for PPP during a one‐year period. Information regarding co‐occurring plaque psoriasis and other comorbidities were extracted. Furthermore, use of anti‐psoriatic medication was identified. Results A total of 1435, 751 and 1832 patients with PPP were identified in the US, Danish and German populations, with an estimated one‐year prevalence of 0.009%, 0.005%, and 0.08%, respectively. Plaque psoriasis was prevalent in 14.2% to 61.3% of patients with PPP. Patients with co‐occurring psoriasis had an overall higher prevalence of psoriatic arthritis. Similarly, medication use was more prevalent in PPP patients with co‐occurring psoriasis, especially pronounced was the use of biologic therapies. Conclusions This large observational study on patients with PPP provides detailed information regarding patient demographics, comorbidities, and medication use. The one‐year prevalence of PPP varied in the three studied populations, possibly due to differences in diagnostics and recording practices. Psoriasis was frequently co‐occurring in patients with PPP. This article is protected by copyright. All rights reserved.
Chapter
Psoriasis is a common inflammatory skin disorder that is classified into multiple disease subtypes. The pustular variants, which are characterized by neutrophilic infiltrates, present with acute, potentially-life threatening episodes of pustulation and systemic upset (generalised pustular psoriasis, GPP) or with chronic and disabling pustulation of the hands and feet (palmar plantar pustulosis, PPP and acrodermatitis continua of Hallopeau, ACH). These are very severe conditions that are extremely difficult to treat.
Article
Background: The term pustular psoriasis indicates a group of severe skin disorders characterised by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris (PV), can have an acute systemic (generalised pustular psoriasis, GPP) or chronic localised presentation (palmoplantar pustulosis, PPP; acrodermatitis continua of Hallopeau, ACH). While mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. Objective: We sought to characterise clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. Methods: We ascertained a dataset of unprecedented size, including 863 unrelated patients (251 GPP, 560 PPP, 28 ACH, 24 multiple diagnoses). We undertook mutation screening in 473 cases. Results: PV concurrence was lowest in PPP (15.8% vs. 54.4% in GPP and 46.2% in ACH, P<0.0005 for both), whereas mean age of onset was earliest in GPP (31.0 years vs. 43.7 in PPP and 51.8 in ACH, P<0.0001 for both). The percentage of females was higher in PPP (77.0%) than GPP (62.5%) (P=5.8x10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P<10-15). While AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in PPP (0.03) than GPP (0.19) and ACH (0.16) (P=1.9x10-14 and 0.002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset, in all forms of pustular psoriasis (P=0.003). Conclusions: The analysis of an unparalleled patient resource revealed key clinical and genetic differences between PPP and GPP.
Article
Background: Palmoplantar pustulosis (PPP) is a recalcitrant chronic inflammatory skin disease. Data relevant for the medical care of patients with PPP are scarce. Thus, the aim of this work was to investigate the disease burden, clinical characteristics, and comorbidity of PPP patients in Germany. Patients and methods: PPP patients were examined in a crosssectional study at seven specialized psoriasis centers in Germany. Results: Of the 172 included patients with PPP, 79.1% were female and 69.8% were smokers.In addition, 25.0% suffered from psoriasis vulgaris, 28.2% had documented psoriatic arthritis, and 30.2% had a family history of psoriasis. In 77 patients the mean Dermatology Life Quality Index (DLQI) was 12.2 ± 7.7 (mean ± SD). The mean Psoriasis Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 12.6 ± 8.6. Mean body mass index was above average at 27.1 ± 5.5. The PPP patients had previously received an average of 2.6 ± 2.1 different anti-psoriatic systemic drugs or UV-therapies. The systemic drugs that had been used most frequently were corticosteroids in 40.1% of patients, followed by acitretin (37.8%), and methotrexate (27.9%). The PPPASI was 13.4 ± 8.9 in patients without current systemic therapy and 10.4 ± 7.9 in patients with systemic therapy. Conclusion: Many PPP patients had a concomitant diagnosis of psoriasis vulgaris and/or psoriatic arthritis or had a family history of psoriasis. Despite the fact that many of the patients were using anti-psoriatic therapies, there was still a high burden of disease within this PPP cohort. This insufficient control of symptoms demonstrates the urgent need for new PPP treatments.
Article
Background: Association of palmoplantar pustulosis (PPP) with metabolic and autoimmune diseases has been reported in mostly small case series or anecdotal cases. Objective: To assess health-related quality of life and prevalence of comorbidities in a large cohort of PPP patients. Methods: We conducted a cross-sectional study on patients with either active or past PPP. Disease severity was measured by the Palmoplantar Pustulosis Area and Severity Index (ppPASI). Quality of life was assessed by the Dermatology Life Quality Index (DLQI). Comorbidities were evaluated by medical history, blood examination, stool testing for Helicobacter pylori antigen and screening tools for depression and psoriatic arthritis. Results: A total of 102 patients (87 women, 15 men) with a mean age of 52.6 ± 14.1 years were evaluated. The mean DLQI was 7 ± 6. Comorbidities were frequent and consisted of hypercholesterolemia (38%), hypertension (32%), obesity (27%), metabolic syndrome (26%), depression (24%), diabetes (19%), autoimmune thyroiditis (16%) and psoriatic arthritis (16%). Conclusion: Patients with PPP have an impaired quality of life and a broad range of comorbidities. Contrary to other reports our investigation failed to show an association between PPP and coeliac disease or H. pylori infection. This article is protected by copyright. All rights reserved.