Multiple Sclerosis and Related Disorders 13 (2017) 81–86

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Multiple Sclerosis and Related Disorders

journal homepage: www.elsevier.com/locate/msard

Increased incidence and prevalence of psoriasis in multiple sclerosis MARK

a,b,⁎ c d e b
Ruth Ann Marrie , Scott B. Patten , Helen Tremlett , Christina Wolfson , Stella Leung , John
D. Fiskf
a
Department of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba,
Winnipeg, Canada
b
Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
c
Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada
d
Department of Medicine (Neurology) and Centre for Brain Health, University of British Columbia, Vancouver, Canada
e
Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Montreal, Canada
f
Departments of Psychiatry, Psychology & Neuroscience, and Medicine, Dalhousie University, Halifax, Canada

A R T I C L E I N F O A BS T RAC T

Keywords: Background: Psoriasis and multiple sclerosis (MS) share some risk factors, and fumarates are effective disease-
Multiple sclerosis modifying therapies for both psoriasis and MS, suggesting a common pathogenesis. However, findings
Psoriasis regarding the occurrence of psoriasis in the MS population are inconsistent.
Incidence Objectives: We aimed to estimate the incidence and prevalence of psoriasis in the MS population versus a
Prevalence
matched cohort from the general population.
Validation
Methods: We used population-based administrative data from the Canadian province of Manitoba to identify
4911 persons with MS and 23,274 age-, sex- and geographically-matched controls aged 20 years and older. We
developed case definitions for psoriasis using ICD-9/10 codes and prescription claims. These case definitions
were compared to self-reported psoriasis diagnoses. The preferred definition was applied to estimate the
incidence and prevalence of psoriasis over the period 1998–2008. We used multivariable Cox regression to
estimate the risk of psoriasis in the MS population at the individual level, adjusting for sex, age at the index date,
socioeconomic status and physician visits.
Results: In 2008, the crude incidence of psoriasis per 100,000 person-years was 466.7 (95%CI: 266.8–758.0)
in the MS population, and 221.3 in the matched population (95%CI: 158.1–301.4). The crude prevalence of
psoriasis per 100,000 persons was 4666.1 (95%CI: 3985.2–5429.9) in the MS population, and 3313.5 (95%CI:
3057.4–3585.3) in the matched population. The incidence and prevalence of psoriasis rose slightly over time.
After adjusting for sex, age at the index date, socioeconomic status and physician visits, the risk of incident
psoriasis was 54% higher in the MS population (HR 1.54; 95%CI: 1.07–2.24).
Conclusion: Psoriasis incidence and prevalence are higher in the MS population than in the matched
population.

1. Introduction
The etiology of multiple sclerosis (MS) remains unknown but
insight may be gained by studying comorbidities that occur with
different frequency than expected in MS as compared to the general
population. In this regard, immune-mediated disorders have been of
particular interest. Psoriasis is an immune-mediated skin disorder
characterized by scaly erythematous plaques. It is common in the
general population with prevalence estimates ranging from 0.9% to
8.5% in adults depending on the region, and like MS, the prevalence
appears to increase with increasing distance from the equator.(Parisi,
Symmons et al., 2013) Psoriasis and MS share risk factors,(Setty,
Curhan et al., 2007; Cotsapas, Voight et al., 2011; Handel, Williamson
et al., 2011; Hedstrom, Olsson et al., 2012; Armstrong, Harskamp
et al., 2014) and fumarates are effective disease-modifying therapies
for both psoriasis and MS,(Gold, Kappos et al., 2012) suggesting a
common pathogenesis.
Findings regarding the occurrence of psoriasis in the MS population
are inconsistent, with the estimated incidence of psoriasis ranging from
0.17% to 1.63% while the estimated prevalence ranges from 0.39% to
7.74%.(Marrie, Reider et al., 2014) However, few prior studies were
population-based, and most were conducted in Europe. Whether
psoriasis occurs more often than expected in those with MS remains
uncertain.(Marrie, Reider et al., 2014) One Danish study found the

⁎
Correspondence to: Health Sciences Centre, GF 543- 820 Sherbrook Street, Winnipeg MB, Canada R3A 1R9.

http://dx.doi.org/10.1016/j.msard.2017.02.012
Received 24 November 2016; Received in revised form 6 February 2017; Accepted 17 February 2017
2211-0348/ © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
R.A. Marrie et al.
incidence of psoriasis to be non-significantly higher in the MS
population than expected for the general population.(Nielsen, Frisch
et al., 2008) One English study also found the prevalence of psoriasis to
be higher than expected in the MS population based on the literature
for the general population, but five other studies have reported no
difference in prevalence.(Marrie, Reider et al. 2014)
Therefore, we developed and validated an administrative case
definition for psoriasis and determined the incidence and prevalence
of psoriasis in the MS population as compared to a matched cohort
drawn from the general population.
2. Materials and methods
2.1. Setting
We conducted this population-based study in the Canadian pro-
vince of Manitoba.
2.2. Administrative data
Manitoba Health delivers publicly funded health services to nearly
all provincial residents, and maintains electronic records of those
health services. Since 1984, each health service encounter includes a
unique personal health identification number (PHIN) identifying who
received the service. We linked the anonymized versions of the
population registry, hospital Discharge Abstract Database (DAD),
physician claims and Drug Program Information Network (DPIN)
datasets via scrambled PHIN (to protect confidentiality). The popula-
tion registry captures demographic information (dates of birth and
death, sex, postal code) and dates of insurance coverage. Hospital
abstracts include admission and discharge dates, and up to 25
discharge diagnoses recorded using the International Classification of
Disease (ICD)−9-CM or ICD-10-CA codes, depending on the year.
Physician claims include the date of service, and one diagnosis,
recorded using a three-digit ICD-9-CM code. The DPIN has captured
the date of dispensation, drug name and identification number (DIN)
for all outpatient prescriptions dispensed to Manitoba residents since
1996. Except for prescription claims, administrative data were avail-
able from 1984 to 2011.
2.3. Study populations
First, we identified all persons with MS in Manitoba who met a
validated administrative case definition for MS (Marrie, Yu et al., 2010)
between 1984 and 2011, and assigned the date of their first claim for
demyelinating disease as the date of MS diagnosis (index date). Next,
we identified a matched cohort from the general population by
excluding individuals with any diagnostic codes for demyelinating
disease and then matching up to 5 controls for each case on sex, exact
year of birth and region of residence (postal code) to the MS cohort.
Each control was assigned the same index date as their matched cases.
MS cases and matched controls were included in the analyses from the
index date until death, emigration, or end of the study, whichever came
first.
2.4. Case definitions for Psoriasis
Based on previous studies that employed administrative data, or
validated algorithms based on electronic medical records databases for
the identification of psoriasis,(Chang, Chen et al., 2009; Seminara,
Abuabara et al., 2011; Asgari, Wu et al., 2013; Lofvendahl, Theander
et al., 2014) we selected ICD-9/10 codes for psoriasis and psoriasis
with psoriatic arthritis (696.0, 696.1, L40.xx, M07.0, M07.2, M07.3)
for our candidate case definitions. We generated lists of prescription
medications available for treatment of psoriasis in Canada using the
Anatomic Therapeutic Chemical classification system. These included
82
Multiple Sclerosis and Related Disorders 13 (2017) 81–86
D05AC (antracen derivatives), D05AD (psoralens for topical use),
D05AX (other antipsoriatics for topical use), D05BA (psoralens for
systematic use), and D05BB (retinoids for treatment of psoriasis).
Thereafter, we constructed candidate case definitions that varied the
number of physician, hospital and prescription claims required and the
number of years over which these were required, to classify a person as
having psoriasis.
As described elsewhere, we employed a validation cohort that
included 327 persons with MS who reported their MS history and
comorbidities using a questionnaire and consented to linkage of their
clinical information with their administrative data.(Marrie, Yu et al.,
2010) This cohort was constructed by asking Manitoba Health to
identify all hospital, physician and prescription claims for demyelinat-
ing disease between April 1, 1984 and March 31, 2007. (Marrie, Yu
et al., 2010) Manitoba Health then mailed questionnaires to 2000
randomly selected individuals from this cohort who were: ≥ 18 years
old as of January 1, 2007, alive and residing in Manitoba when the
study started and who had ≥ 3 hospital, physician or prescription
claims between 1984 and 2007; or ≥ 1 claim for persons resident in
2004 or later, where ≥ 1 claim was for MS or neuromyelitis optica. The
validation cohort for the present study comprised the individuals with
confirmed diagnoses of MS who responded. This questionnaire asked
“Has a doctor ever told you that you have any of the following
conditions?”, adding the condition of psoriasis to a validated ques-
tionnaire that listed multiple conditions.(Horton, Rudick et al., 2010)
The specificity of a self-reported diagnosis of psoriasis as compared to
medical records was 96%. Within this validation cohort, we compared
the performance of the candidate administrative case definitions for
psoriasis with self-report, using sensitivity, specificity, positive pre-
dictive value and negative predictive value. Also, we compared the
agreement between the two data sources using a kappa (κ) statistic
where neither was considered the reference standard. We interpreted κ
as: slight (0–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial
(0.61–0.80), and almost perfect agreement (0.81–1.0).(Landis and
Koch, 1977).
2.5. Incidence and prevalence of Psoriasis
Based on findings in the validation cohort, we selected and applied
a preferred case definition to both the MS and matched study
populations. Because psoriasis is chronic, once an individual met the
case definition, he/she was considered affected in all subsequent years
while alive and resident in Manitoba. We estimated the prevalence on
October 1 each year using the mid-year population figures as the
denominators. To estimate incidence after MS diagnosis (index date)
we used a 2-year run-in period preceding the first psoriasis claim to
enhance the likelihood that cases were truly incident. However, as the
preferred case definition included prescription claims which only
became available in 1996, the first incident case could only be
identified from 1998 onwards. Incidence may artificially drop at the
end of a study period when there is insufficient time to meet the case
definition. Thus, to reduce the likelihood of artefactual temporal trends
we limited our reporting of incidence and prevalence to the 10-year
period, 1998–2008.
Incidence and prevalence estimates were age-standardized to the
2001 Canadian population, the census population closest to the study
mid-point. Age-specific average annual incidence was reported using
age groups 20–44, 45–59, and ≥ 60 years, to ensure adequate cell sizes
to protect participant confidentiality and for consistency with prior
work regarding the burden of comorbidity in MS.(Marrie, Fisk et al.,
2015) Sex-specific estimates were also reported. We report 95%
confidence intervals (CI) for each parameter based on the binomial
distribution. We compared age-standardized incidence and prevalence
estimates between groups using negative binomial regression, to
account for overdispersion, adjusting for year. We report incidence
rate ratios (IRR), prevalence ratios (PR) and the corresponding 95%
R.A. Marrie et al. Multiple Sclerosis and Related Disorders 13 (2017) 81–86

CIs. Both the IR and PR have null values of 1, such that 95%Cis
excluding this value can be considered statistically significant at the
p=0.05 level.
2.6. Multivariable analysis
We used a multivariable Cox proportional hazards model to
compare the risk of incident psoriasis in the MS and matched
populations at the individual level. Zero time was the index date.
Model covariates were index year (1998–2000, 2001–2003, 2004–
2008), age at the index date (continuous), sex (male as reference),
socioeconomic status (SES) in quintiles (lowest as reference group),
comorbidity, and number of physician visits. SES was based on average
household income in the postal code of residence by linkage to census
data. Comorbidities of interest were those associated with psoriasis,
(Grozdev et al., 2014a,b) and for which there were validated admin-
istrative case definitions in the MS population.(Marrie, Yu et al., 2013;
Marrie, Fisk et al., 2014) These included chronic lung disease,
hypertension, inflammatory bowel disease, diabetes, hyperlipidemia,
ischemic heart disease and any mood disorder, each of which was
included in the model as a time-varying covariate as of the date of the
first claim for the comorbidity. We included the annual number of
physician visits other than those related to psoriasis as a time-varying
covariate in the model, to account for possible surveillance bias due to
increased contacts with the health system in the MS population. Model
assumptions were tested using standard methods.(Collett, 2003).
We obtained ethics approval from the University of Manitoba
Health Research Ethics Board, and approval to access administrative
data from the Manitoba Health Information Privacy Committee.
Statistical analyses were conducted using SAS 9.4 (SAS Institute Inc.,
Cary NC).
3. Results
3.1. Participants
Our study included 4911 persons identified with MS and 23,274
matched persons from the general population; over 70% were women
(Table 1).(Marrie, Fisk et al., 2015) The characteristics of the validation
cohort have been detailed previously.(Marrie, Yu et al., 2012) Most
participants (n=430) were white (91.6%) and female (77.0%), with a
mean age at MS symptom onset of 33.2 (11.1) years. The self-reported
prevalence of psoriasis in this validation cohort was 4.2%.(Horton,
Rudick et al., 2010; Marrie, Yu et al., 2012).
ing specificity. Adding prescription claims increased sensitivity without
reducing specificity. Adding more years of data increased sensitivity for
some definitions, and reduced specificity, although the declines in
specificity were less than the gains in sensitivity. The highest sensitivity
observed was 72.2%, for definitions requiring ≥ 1 hospital or ≥ 1
physician or ≥ 1 prescription claims, regardless of the number of years
of data used (1–5 years). Specificities of all case definitions were high,
ranging from 89.9% to 99%. The highest specificity observed (99%) was
for the definition that required ≥ 3 hospital or physician claims in any
combination over 1 year; specificity was similar (98.8%) for the
definition that required ≥ 3 hospital or physician or prescription claims
in any combination over 1 or 2 years. Agreement between medical
records and the administrative case definitions was highest (κ=0.49)
for the definitions that required ≥ 1 hospital or ≥ 2 physician or ≥ 2
prescription claims over two years or that required ≥ 2 hospital,
physician or prescription claims in any combination over two years.
Several other definitions reached similar levels of agreement.
We applied the case definition (Supplemental table 1, definition ‘N′)
that required ≥1 hospital or ≥ 2 physician or ≥ 2 prescription claims
over two years to determine the incidence and prevalence of psoriasis
as this definition had the highest agreement with self-report as well as
high specificity (97.3) and adequate sensitivity (55.5). Of the defini-
tions that did not use prescription claims ‘K′ had the highest agreement
with medical records (κ=0.42) although sensitivity was only 44.4%.
3.3. Incidence
In 1998, the crude incidence of psoriasis in the MS population was
80.6 (95%CI: 9.8, 291.1) per 100,000 person-years, and it was 466.7
(95%CI: 266.8, 758.0) in 2008. In the matched population, the crude
incidence of psoriasis per 100,000 person-years was 151.9 (95%CI:
90.0, 240.1) in 1998 and 221.3 (95%CI: 158.1, 301.4) in 2008. In the
MS population crude incidence rates were more variable than in the
matched population, with wider confidence intervals, reflecting the
small numbers of individuals affected by psoriasis. After age-standar-
dization, and adjustment for year the incidence of psoriasis remained
higher in the MS population than in the matched population (IRR 1.48;
95%CI: 1.09, 2.00). Adjusting for MS status, the incidence of psoriasis
rose slightly over time (IRR 1.05/year; 95%CI: 0.996, 1.10).
Over the 10-year study period, the average annual incidence in the
MS population was 268.9 (95%CI: 216.0, 330.9) while it was 174.2
(95%CI: 154.8, 195.3) in the matched population. The peak incidence
in both populations was at age ≥ 60 years (Table 2).

3.4. Prevalence
3.2. Case definitions

In 1998, the crude prevalence of psoriasis in the MS population was

We tested multiple case definitions, labelled A to AT (Supplemental
2285.3 (95%CI: 1735.3, 2954.2) per 100,000 persons, and it was
table 1). For any given number of years of data, requiring more
physician visits reduced the sensitivity of the definition while increas-
Table 2
Age and sex-specific average annual incidence rates (95% confidence intervals) of
Table 1 psoriasis per 100,000 population, 1998–2008.
Characteristics of the study population.
Age Matched population MS population
Characteristics Manitoba group
Female Male Both Female Male Both
Data Years 1984/85–2010/11a
MS cases, n 4911 20–44 157.3 132.2 152.0 201.0 124.6 184.8
Female, n (%) 3556 (72.4) (122.6, (75.5, (121.5, (119.2, (25.7, (114.4,
Age at index date, mean (SD) 43.6 (13.5) 1988) 214.7) 187.7) 317.6) 364.2) 282.5)
Matched controls, n 23,274
Female, n (%) 16,903 (71.4) 45–59 198.0 132.2 180.6 256.9 292.5 266.3
Age at index date, mean (SD) 43.5 (13.5) (161.6, (85.7, (150.6, (169.3, (146.0, (188.4,
240.2) 195.5) 214.7) 373.7) 523.5) 365.5)
a
To allow 2 year run-in period, to ensure that all cases were identified using all 3 data
sources (hospital, physician and prescription claims) and to avoid artifactual drops in ≥60 234.3 113.0 194.2 369.1 475.8 402.2
incidence at the end of the study period due to inadequate follow-up time for new cases to (180.0, (63.2, (153.5, (222.2, (237.5, (271.4,
quality, actual results are presented for 1998–2008, although all stated years of data were 299.7) 186.4) 242.4) 576.5) 851.3) 574.2)
accessed;

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R.A. Marrie et al. Multiple Sclerosis and Related Disorders 13 (2017) 81–86

Fig. 1. Crude prevalence of psoriasis in the multiple sclerosis and matched populations, 1998–2008.

4666.1 (95%CI: 3985.2, 5429.9) in 2008. The age-standardized pre- Table 4

valence of psoriasis in the MS population in 2008 was 3272.3 (95%CI: Multivariable association of MS with incident psoriasis.
2722.7, 3821.9). In the matched population, the crude prevalence of
Variable Adjusted HRa (95% Adjusted HRb (95%
psoriasis per 100,000 persons was 1491.4 (95%CI: 1268.6, 1742.1) in CI) CI)
1998 and 3313.5 (95%CI: 3057.4, 3585.3) in 2008. The age-standar-
dized prevalence of psoriasis in the matched population in 2008 was Population
Matched 1.0 1.0
2341.7 (95%CI: 2134.8, 2548.6). Over the study period, the age-
standardized prevalence of psoriasis was higher in the MS population MS 1.64 1.54
than the matched population (PR 1.31; 95%CI: 1.25, 1.37), and the (1.14, 2.37) (1.07, 2.24)
prevalence increased over time (PR 1.06; 95%CI: 1.05–1.07; Fig. 1).
Sex
Male 1.0 1.0
3.5. Risk factors
Female 1.55 1.50
The characteristics of the individuals with incident psoriasis in the (1.01, 2.35) (0.99, 2.29)
two cohorts did not differ with respect to sex, SES, or region of
Age at diagnosis 0.998 0.997
residence, at the index date (Table 3). Although the age at diagnosis of
(0.98, 1.01) (0.98, 1.01)
psoriasis averaged 2.7 years older in the MS population than in the
matched population, this difference was not statistically significant. Socioeconomic status
The populations also did not differ with respect to the prevalence of Quintile 1 1.0 1.0
specific individual comorbidities when psoriasis was diagnosed.
Quintile 2 2.06 2.08
In a univariate model, the risk of incident psoriasis was higher in
(1.16, 3.66) (1.17, 3.70)
the MS population than the matched population (HR 1.64; 95%CI:
1.14, 2.37). In a multivariable model, adjusting for index year, sex, age Quintile 3 1.84 1.84
(0.999, 3.40) (1.00, 3.70)
Table 3
Characteristics of incident psoriasis cases in the multiple sclerosis (MS) and matched Quintile 4 2.48 2.51
populations. (1.40, 4.38) (1.42, 4.44)

Characteristic Matched MS population p-value Quintile 5 1.98 2.01

population (n=89) (1.10, 3.56) (1.12, 3.62)
(n=292)
Index Year
Age at psoriasis 51.6 (13.3) 54.3 (13.7) 0.097 1998–2000 1.0 1.0
diagnosis, mean (SD)
Female sex, n (%) 236 (80.8) 64 (71.9) 0.07 2001–2003 0.93 0.93
Urban, n (%) 207 (70.9) 70 (78.6) 0.15 (0.62, 1.40) (0.62, 1.40)

Socioeconomic status, n 0.76 2004–2009 0.88 0.88

(%) (0.53, 1.46) (0.53, 1.47)
Quintile 1 43 (14.7) 11 (12.4)
Quintile 2 60 (20.5) 18 (20.2) Number of physician visits – 1.02
Quintile 3 56 (19.2) 22 (24.7) (1.00, 1.03)
Quintile 4 65 (22.3) 21 (23.6)
a
Quintile 5 68 (23.3) 17 (19.1) Multivariable model not adjusted for physician visits;
b
Inflammatory bowel 0 (0) 0 (0) – multivariable model adjusted for physician visits
disease, n (%)
Chronic lung disease, n 31 (10.6) 7 (7.9) 0.45 at the index date, and SES, this increased risk of incident psoriasis
(%)
remained unchanged (Table 4). Women and those of higher SES were
Diabetes, n (%) 24 (8.2) 9 (10.1) 0.58
Hypertension, n (%) 57 (19.5) 13 (14.6) 0.29 at greater risk for psoriasis. After adjustment for physician visits, the
Hyperlipidemia, n (%) 33 (11.3) 8 (9.0) 0.54 risk of incident psoriasis in the MS was attenuated slightly (HR 1.54;
Ischemic heart disease, 15 (51.1) 9 (10.1) 0.09 95%CI: 1.07, 2.24; Table 4). Additional adjustment for the presence of
n (%) specific comorbidities did not affect the association between MS and
Any mood disorder, n 34 (11.6) 11 (12.4) 0.85
(%)
psoriasis, and these comorbidities were not associated with the risk of
psoriasis (data not shown). We did not identify any interactions

84
R.A. Marrie et al.
between sex and population nor between sex and age.
4. Discussion
We evaluated the incidence and prevalence of psoriasis in the MS
population and a matched cohort from the general population using
population-based administrative health data over a 10-year period. In
2008, the prevalence of psoriasis in the matched population was 3.3%,
similar to the prevalence reported in the United States during a similar
time period (3.1%).(Helmick, Lee-Han et al., 2014) The incidence and
prevalence of psoriasis increased over time in the MS and matched
populations, also consistent with recent findings in the general
population globally.(Parisi, Symmons et al., 2013).
All case definitions for psoriasis that we tested had high specificity,
limiting the probability of false positives. Although sensitivity of the
definitions with the highest specificity was low, we achieved a
sensitivity of 72% while maintaining a relatively high specificity of
90%. Our literature review did not identify any previously validated
administrative case definitions for psoriasis in an MS cohort and
studies that have previously validated case definitions in the general
population have generally used different data sources, specifically
electronic medical records.(Seminara, Abuabara et al., 2011; Asgari,
Wu et al., 2013) One study in Sweden that used information from
computerized medical records and administrative data sources and
identified psoriasis using ICD-10 codes L40.1, L40.2, L40.4, L40.5,
L40.8, L40.9, found that the presence of one of these codes had a
positive predictive value of 81%.(Lofvendahl, Theander et al., 2014).
Two European studies estimated the incidence of psoriasis in the
MS population to range from 0.17% to 1.6%, lower than our estimate.
The latter study identified hospitalized persons with MS living in
Northern Greece, and captured psoriasis using a questionnaire fol-
lowed by medical records review.(Deretzi, Kountouras et al., 2010)
They reported an incidence of 1.6% over a mean follow-up of 7.1 years
though the annual incidence rate was not stated. The former study was
population-based and linked the Danish MS Register to a hospital
register but also did not report annual incidence rate.(Nielsen, Frisch
et al., 2008) This study required ≥ 2 hospital claims for psoriasis, and
found newly diagnosed psoriasis in 0.17% of their MS cases. However,
by virtue of being limited to hospital records, milder cases of psoriasis
diagnosed and treated by primary care providers or by specialists
practicing outside hospitals would not have been captured, potentially
leading to the lower estimate of incidence obtained.
A prior systematic review identified six studies in which the
prevalence of psoriasis in the MS population was reported, with
estimates ranging from 0.39% to 7.74%.(Marrie, Reider et al. 2014)
The highest of these was from the lone population-based study,
although the sample was relatively small, including only 155 definite,
probable and possible MS cases.(Midgard, Gronning et al., 1996) At
4.7%, our estimate of the prevalence of psoriasis falls within the range
of these prior estimates.
We found that the incidence and prevalence of psoriasis were
higher in the MS population than in the matched population. The
increased risk of incident psoriasis was nearly identical to that reported
in Denmark previously (HR 1.5; 95%CI: 0.95–2.4).(Nielsen, Frisch
et al., 2008) In another Danish study, the risk of incident MS was
increased among individuals with mild (IRR 1.84; 95%CI: 1.46, 2.30)
and severe psoriasis (IRR 2.61; 95%CI: 1.44, 4.74).(Egeberg, Mallbris
et al., 2016) After we adjusted for health care utilization the association
was attenuated slightly, but remained statistically significant, suggest-
ing that our observations do not simply reflect improved ascertainment
in the MS population due to increased contacts with the health system.
The later mean age at diagnosis of psoriasis in the MS cohort also
suggests that our findings are not due to ascertainment biases. The
increased prevalence of psoriasis was consistent with our findings of
increased incidence, and with the findings of one English study which
reported a two-fold increase in prevalence.(Edwards and
85
Multiple Sclerosis and Related Disorders 13 (2017) 81–86
Constantinescu, 2004) However, other studies have reported no
difference in prevalence.(Cendrowski, 1989; Midgard, Gronning
et al., 1996; Henderson, Bain et al., 2000; Laroni, Calabrese et al.,
2006; Ramagopalan, Dyment et al., 2007) The differences in our
findings and those earlier studies may reflect prior limitations which
included small samples with few individuals affected by psoriasis in
either population, the use of hospital-based controls, or the use of
spousal controls which may lead to overmatching and attenuation of
associations.
Female sex and higher SES were associated with increased risk of
psoriasis in the MS and matched populations. A prior systematic review
found the association between sex and incidence of psoriasis in the
general population to be inconsistent, with some studies reporting the
incidence to be higher in women and others reporting the opposite.
(Parisi, Symmons et al., 2013) Reported findings differed by age too.
(Parisi, Symmons et al., 2013) Differences in immunological responses
between men and women are well-recognized (Klein and Flanagan,
2016) and women are at increased risk of most autoimmune diseases,
(Voskuhl, 2011) although psoriasis may also be more likely to remain
undiagnosed among men than among women.(Kurd and Gelfand,
2009) Under-diagnosis is also more common among those who are
less educated,(Kurd and Gelfand, 2009) a finding that may explain the
higher incidence of psoriasis among participants with higher SES.
Several comorbidities have been reported to be associated with
psoriasis, (Grozdev et al., 2014a,b) but we did not observe these
associations in our study populations. This may reflect several factors.
First, we had lower power to detect such associations due to the
relatively small number of individuals affected by both psoriasis and
these comorbidities. Second, while several of these comorbidities have
been reported to be more common among individuals with a current
diagnosis of psoriasis,(Grozdev et al., 2014a,b) we evaluated these
associations before the onset of psoriasis.
The population-based design of this study and 10-year study period
are strengths. Limitations of the study should be noted as well. The
validation cohort may not fully represent the MS population. As we
lacked access to the complete medical record for the validation cohort,
we compared the administrative case definitions to self-reported
diagnoses of psoriasis. Although a recent study suggests that self-
report is valid for assessing psoriasis, (Modalsli, Snekvik et al., 2016) it
may not capture undiagnosed scalp psoriasis. While specificity of the
definition we used for psoriasis was high, sensitivity was modest,
therefore we likely underestimated the true burden of psoriasis in both
populations.
5. Conclusions
The incidence and prevalence of psoriasis are higher in MS than in
a matched cohort from the general population. This association may
reflect shared genetic factors between psoriasis and MS and shared
environmental factors such as smoking that can be targets for inter-
vention.(Cotsapas, Voight et al., 2011; Handel, Williamson et al., 2011;
Armstrong, Harskamp et al., 2014) Since fumarates are effective in
both conditions, further investigation of this association may yield
etiologic insights into MS. Regardless, given that psoriasis affects
nearly 5% of the MS population, and is itself associated with increased
comorbidity and lowered quality of life,(Grozdev et al., 2014a,b) this
condition warrants attention in the context of comprehensive MS care.
Acknowledgement/Funding source
This study was supported (in part) by operating and Don Paty
Career Development grants from the Multiple Sclerosis Society of
Canada, CIHR (CBG 101829), and the Waugh Family Chair in Multiple
Sclerosis. The funding source(s) had no role in the study design,
collection, analysis or interpretation of the data, nor in the decision to
submit the article for publication. The results and conclusions pre-
R.A. Marrie et al.
sented are those of the authors. No official endorsement by Manitoba
Health is intended or should be inferred.
Disclosures
Ruth Ann Marrie receives research funding from: Canadian
Institutes of Health Research, Public Health Agency of Canada,
Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific
Foundation, Rx & D Health Research Foundation, National Multiple
Sclerosis Society, Crohn's and Colitis Canada, the Consortium of MS
Centers, and has conducted clinical trials funded by Sanofi-Aventis.
Christina Wolfson receives research funding from the Multiple
Sclerosis Society of Canada, Canadian Institutes of Health Research,
Canada Foundation for Innovation, the National MS Society and has
received one speaking honorarium from Novartis.
Helen Tremlett is the Canada Research Chair for
Neuroepidemiology and Multiple Sclerosis. She currently receives
research support from the National Multiple Sclerosis Society, the
Canadian Institutes of Health Research, the Multiple Sclerosis Society
of Canada and the Multiple Sclerosis Scientific Research Foundation.
In addition, in the last five years she has received research support
from the Multiple Sclerosis Society of Canada (Don Paty Career
Development Award); the Michael Smith Foundation for Health
Research (Scholar Award) and the UK MS Trust; speaker honoraria
and/or travel expenses to attend conferences from the Consortium of
MS Centers (2013), the National MS Society (2012, 2014, 2016), Teva
Pharmaceuticals (2011), ECTRIMS (2011, 2012, 2013, 2014, 2015,
2016), UK MS Trust (2011), the Chesapeake Health Education
Program, US Veterans Affairs (2012), Novartis Canada (2012),
Biogen Idec (2014), American Academy of Neurology (2013, 2014,
2015, 2016). All speaker honoraria are either declined or donated to an
MS charity or to an unrestricted grant for use by her research group.
John Fisk receives research funding from the Canadian Institutes of
Health Research, Rx & D Health Research Foundation MS Society of
Canada, National Multiple Sclerosis Society, and the Dalhousie Medical
Research Foundation.
Stella Leung reports no disclosures.
Scott Patten reports no disclosures.
Appendix A. Supplementary material
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.msard.2017.02.012.
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