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Available online at

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Original article

Age at disease onset may help to further characterize the disease

phenotype in psoriatic arthritis
Sara Alonso a , Patricia Tejón a , Cristina Sarasqueta b , Pablo Coto c , Mercedes Alperi a ,
Rubén Queiro a,∗
a
Rheumatology Division, Hospital Universitario Central de Asturias (HUCA), Avenida de Roma, C/Celestino Villamil s/n, 33011 Oviedo, Spain
b
Clinical Epidemiology Unit, Complejo Hospitalario Donostia, 20080 Donostia, Spain
c
Dermatology Division, Hospital Universitario Central de Asturias (HUCA), Avenida de Roma, C/Celestino Villamil s/n, 33011 Oviedo, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To evaluate whether the age of disease presentation helps to better characterize the disease
Accepted 7 September 2015 phenotype in PsA.
Available online xxx Methods: Retrospective cohort study that included 205 consecutive patients fulfilling the CASPAR criteria
for PsA. Study outcomes were assessed using univariate and multivariate analyses according to the age
Keywords: of onset of both skin and joint disease (cut off at 40 years).
Psoriasis Results: Early onset psoriasis (EOP) showed more extensive skin involvement (OR 2.3, P = 0.011), axial
Psoriatic arthritis
pattern as disease onset (OR 4.6, P = 0.009) and mixed pattern during evolution (OR 2.4, P = 0.019), family
Cardiovascular risk factors
Age at disease onset
history of both psoriasis (OR 3.1, P = 0.003) and PsA (OR 4.0, P = 0.021), higher prevalence of HLA-C*06
(OR 2.03, P = 0.03) and HLA-B*27 (OR 2.7, P = 0.02). Early onset arthritis (EOA) had more family history
of PsA (OR 2.9, P = 0.007), and HLA-B*27 positivity (OR 5.9, P < 0.0001). Patients with late onset arthritis
(LOA) were more likely to have DM (OR 4.0, P = 0.009), hypertension (OR 2.5, P = 0.004), dyslipidemia (OR
2.3, P = 0.011), and obesity (OR 1.7, P = 0.012). Late onset psoriasis (LOP) tended to have more obesity
(OR 1.9, P = 0.035), DM (OR 9.4, P < 0.0001), hypertension (OR 4.1, P < 0.0001), and ischemic heart disease
during follow-up (OR 5.9, P = 0.021). In multivariate analysis, LOP predicted DM development (OR 12.1,
P = 0.006). LOA was shown to be an independent risk factor for hypertension (OR 5.2, P = 0.039).
Conclusion: Age at disease onset exerts a strong influence on several domains of disease phenotype in
PsA. Therefore, this descriptor should be considered a good stratification option for epidemiological and
genetic studies in PsA.
© 2015 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Psoriasis is a chronic inflammatory skin disease that affects is unclear at present [3]. Similarly, a split between early and late
1%–3% of the general population, with the highest incidence and onset disease has been proposed in PsA [2,4].
prevalence observed in white populations [1]. Psoriatic arthritis Another interesting aspect in the study of psoriatic disease is the
(PsA) is also a common feature of what is now called psoriatic dis- fact that cardiovascular (CV) comorbidity seem to be more frequent
ease [2]. At present, HLA-C*06 and B*27 are the most important in subjects with age of onset over 40 years. In that sense, type 2 DM
genetic biomarkers in psoriatic disease since they establish marked appeared to be related to the presence of arthritis and an onset
traits that in turn allow phenotypic differentiations in both popu- age after 40 years in one psoriasis study [5]. Although psoriasis is
lations [2]. Since the seminal work by Henseler and Christophers, associated with a higher prevalence of CV risk factors in adults,
early onset psoriasis (EOP) or type I, refers to patients with onset the relationship between the age of onset and its influence on the
before 40 years, more extensive skin disease, strong family aggre- development of this kind of risk is not completely understood [5,6].
gation and HLA-C*06 positivity. On the contrary, late onset psoriasis Recently, a French study showed that the age of onset of psoriasis
(LOP) or type II, refers to an onset at or after 40 years, being more did not seem to confer an additional risk for the development of CV
sporadic and seldom family-inherited, and its genetic background and metabolic comorbidities during adulthood [7]. However, sev-
eral studies in psoriasis and PsA do suggest this association [8–12].
Although currently the division of psoriasis into two major types
(I and II) is a widely accepted descriptor of this condition, it is
∗ Corresponding author. unclear whether this division can also be applied to patients with
E-mail address: rubenque7@yahoo.es (R. Queiro). PsA. Nor do we know whether the stratification of psoriatic disease

http://dx.doi.org/10.1016/j.jbspin.2015.09.004
1297-319X/© 2015 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Alonso S, et al. Age at disease onset may help to further characterize the disease phenotype in psoriatic
arthritis. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.09.004
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according to age at disease onset will be of help to better charac- than 140/90 mmHg during follow-up, chronic use of antihyper-
terize the clinical and CV risk profile in these patients. The aim of tensive treatment or diagnosis by medical specialist;
this study was to find out whether the stratification of psoriatic dis- • dyslipidemia: defined as the ongoing finding of cholesterol fig-
ease according to the age of onset helps to better define the disease ures above 240 mg/dL or triglycerides figures above 200 mg/dL
phenotype of these patients. during follow-up, chronic treatment with lipid-lowering drugs,
or diagnosis by medical specialist;
1. Methods • obesity: defined as the presence of a body mass index (BMI)
greater than 30 kg/m2 , whereas overweight involves a BMI
This was a retrospective cohort study including 205 consecutive between 25 and 29.9 kg/m2 ;
patients treated at a single university hospital who fulfilled the CAS- • smoking habit: we consider as active smokers, all those smoker
PAR classification criteria for PsA [13]. These patients were attended patients at the time of the study (irrespective of the number of
according to a standard protocol in a monographic PsA clinic within cigarettes); on the other hand, those patients with past smoking
our Rheumatology department. All demographic, clinical, labora- habit (at least five years), but not being active smokers at the time
tory, therapeutic and radiographic variables were collected in a of the study, are regarded as former smokers;
standardized manner as depicted below. Patients were informed • ischemic heart disease: defined as at least one cardiac event such
about the objectives of the study and consent informed sheets as acute myocardial infarction, stable or unstable angina, diag-
were signed by all participants. This study was conducted follow- nosed by medical specialist;
ing the rules of good clinical practice (Helsinki Declaration). An • cerebrovascular disease: any transient or permanent event as
institutional ethics committee of Hospital Universitario Central de a result of a disorder of cerebral circulation either ischemic or
Asturias approved the final version of this study. hemorrhagic diagnosed by medical specialist;
• peripheral vascular disease: defined as the presence of at least
1.1. Study population and study variables one episode of peripheral arterial ischemic disease diagnosed by
medical specialist.
The cohort was composed by 112 men and 93 women with a
mean age of 52.9 ± 13 years. The description of joint patterns was 1.3. Statistical analysis
made on the basis of the dominant pattern observed in the last
5 years of follow-up. Patients with 4 or less swollen joints were Descriptive statistics with mean and standard deviation for
labelled as oligoarthritis category; those who presented 5 or more quantitative variables and percentages for qualitative variables
were tagged under the polyarthritis category. Patients who pre- were included. Differences between qualitative variables were
sented radiographic sacroiliitis with inflammatory back pain (IBP), analysed by using Chi2 and Fisher’s exact tests. Differences between
irrespective of the presence of peripheral arthritis, conformed the quantitative variables were analysed by using Student’s t-test. To
axial pattern. For the purposes of this study, patients were strati- determine the strength of the association of each variable depend-
fied in early and late onset disease according to a cut off point of ing on the age of onset of psoriasis and PsA, an odds ratio (OR)
40 years. This cut off was applied for onset ages in both skin and of each variable (univariate analysis) was estimated, with its cor-
joint disease. responding confidence interval (CI) of 95%. To infer the value of
Family history of psoriasis and PsA was collected. Educational each variable in the occurrence estimation of each cardiovascular
level was assessed and classified under three categories accord- risk factor depending of the age of onset, significant variables in
ing to the achieved degree: primary, secondary (high-school), and the univariate analysis (including age) were introduced in a multi-
university studies. Data regarding skin disease included the main variate analysis with a backward stepwise approach. The statistical
type of psoriasis, location of lesions, nail disease and percentage analysis software package used was SPSS v.19.0.
of patients with involvement of three or more body areas. Psoriasis
was confirmed by a dermatologist. In relation to the clinical features
of arthritis, both the onset pattern of arthritis (oligoarticular, pol- 2. Results
yarticular, axial, mixed, distal interphalangeal (DIP) involvement,
enthesitis, or dactilitis) depending on the dominant pattern over We evaluated 205 patients, 112 (54.63%) males and 93 (45.37%)
the first six months of disease, as well as the main pattern dur- females. The mean age was 52.9 ± 13 years. The mean age at psoria-
ing follow-up were taken into account. Pelvic, lumbar and cervical sis onset was 30.5 ± 17.1 years and the mean age of onset of arthritis
lateral X-rays were included in the radiographic study to assess was 43.3 ± 14.2 years. The mean lag time between the onset of pso-
spinal involvement. X-rays of affected areas during follow-up were riasis and onset of arthritis was 14.6 ± 12.6 years.
also obtained. Laboratory data included the following routine tests: Educational level was distributed as follow: 52.7% of patients
blood and urine biochemistry, hemogram, ESR, HLA-B*27, HLA- had primary school education, 25.8% had secondary education and
C*06, RF and CRP. 21.6% had a university degree.
Glucocorticoid, NSAID, conventional as well as biologic DMARD Baseline demographic, clinical and cardiovascular characteris-
use was collected. tics of patients are shown in Table 1. During follow-up, men showed
more frequently nail disease [57.1% vs. 38.7; OR 2.1 (1.2–3.7)
1.2. Definition of cardiovascular risk factors and cardiovascular P = 0.009] and higher lipid levels [36.6% vs. 23.7%; OR 1.9 (1.1–3.4)
outcomes P = 0.045].
In 139 patients, psoriasis debuted before the age of 40 with an
The following variables were also collected: average age of onset of disease of 20.7 ± 9.7 years, versus 66 patients
with psoriasis after 40 years (average onset age 53.5 ± 7.6 years).
• diabetes mellitus (DM): defined by the analytical finding during A higher latency between the onset of skin psoriasis and arthri-
monitoring of glucose elevation of more than 126 mg/dL on two tis in patients with EOP was observed, specifically an average of
fasting determinations, chronic treatment with antidiabetic or 18 ± 7.6 years in patients with EOP versus 6.6 ± 5.6 years in patients
insulin, or diagnosis by medical specialist; with LOP (P < 0.0001).
• high blood pressure (hypertension): defined as finding at least Regarding the clinical features, EOP patients presented with
two determinations on different days of blood pressure greater more extensive skin disease (P = 0.011), greater family history of

Please cite this article in press as: Alonso S, et al. Age at disease onset may help to further characterize the disease phenotype in psoriatic
arthritis. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.09.004
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Table 1 Table 2
Demographic, clinical and cardiovascular risk factors of the study population. Univariate comparison between patients with early and late psoriasisa .

Variables Patients, n = 205 Variables Early psoriasis Late psoriasis P value

n = 139 (%) n = 66 (%)
Mean age, years (SD) 52.9 ± 13
Mean age of onset of psoriasis 30.5 ± 17.1 Pustular psoriasis 3 (2.2) 7 (10.6) P = 0.007
Mean age of onset of arthritis 43.3 ± 14.2 OR 5.6 (1.4–22.8)
Mean latency time psoriasis-arthritis 14.6 ± 12.6 ≥ 3 areas of psoriasis 74 (53.2) 23 (34.8) P = 0.011
Sex, number (%) OR 2.3 (1.2–4.5)
Male 112 (54.6%) Family history of 77 (55.4) 20 (30.3) P = 0.003
Female 93 (45.4%) psoriasis OR 3.1 (1.5–6.4)
Educational level (%) Family history of PsA 27 (19.4) 4 (6.1) P = 0.021
Primary school 52.7% OR 4 (1.1–14.1)
Secondary education 25.8% Spondylitis as onset 31 (22.3) 4 (6.1) P = 0.009
University degree 21.7% OR 4.6 (1.3–16.1)
Psoriasis onset, number (mean onset age ± SD) Oligoarthritis during 22 (15.8) 21 (31.8) P = 0.018
< 40 years 139 (20.7 ± 9.7) evolution OR 0.4 (0.2–0.9)
> 40 years 66 (53.5 ± 7.6) Mixed pattern during 54 (38.8) 13 (19.7) P = 0.019
PsA onset, number (mean onset age ± SD) evolution OR 2.4 (1.1–5.2)
< 40 years 82 (29 ± 7.2) HLA-B*27 34 (24.5) 7 (10.6) P = 0.02
> 40 years 123 (52.8 ± 8.6) OR 2.7 (1.1–6.5)
Plaque psoriasis 176 (85.9%) HLA-C*06 60 (43.2) 18 (27.3) P = 0.03
Nail disease 100 (48.8%) OR 2.03 (1.1–3.8)
≥ 3 areas of psoriasis 97 (47.3%) Diabetes Mellitus 6 (4.3) 19 (28.8) P < 0.0001
Family history of psoriasis 97 (47.3%) OR 9.4 (3.2–27.5)
Family history of PsA 31 (15.1%) Hypertension 29 (20.9) 34 (51.5) P < 0.0001
Oligoarthritis 43 (21%) OR 4.1 (2.0–8.1)
Polyarthritis 72 (35%) Obesity 27 (17.4) 22 (33.3) P = 0.035
Spondylitis 19 (9.3%) OR 1.9 (1.02–4.1)
Mixed pattern 67 (32.7%) Ischemic heart 3 (2.2) 6 (9.1) P = 0.021
Dactylitis 58 (28.3%) disease OR 5.9 (1.1–31.2)
DIP disease 48 (23.4%) a
Only significant differences are included.
Mutilating arthritis 2 (1%)
Erosive disease 30 (14.7%)
HLA-B*27 41 (20%)
HLA-C*06 78 (38%)
obesity (P = 0.012), and higher rate of former smoking habit
Diabetes mellitus 25 (12.2%)
Hypertension 63 (30.7%) (P = 0.002) (Table 3).
Dyslipidemia 63 (30.7%) Since the increased prevalence of CV comorbidity in late onset
Obesity 49 (24%) disease could be just due to the age factor per se, we performed a
Overweight 38 (18.5%) logistic regression analysis adjusting for age, sex and other covari-
Ischemic heart disease 9 (4.4%)
ables (including medications).
Cerebrovascular disease 9 (4.4%)
Peripheral vascular disease 6 (2.9%) With respect to DM, regardless of the age of subjects, the onset
Smokers 52 (25.4%) of psoriasis after 40 years was associated with its development (OR
Ex-smokers 53 (25.8%) 12.1; CI: 2–73.1, P = 0.006). Conversely, the age of onset of arthritis
NSAID use 86 (42%)
was not found linked to this outcome.
Glucocorticoid use 32 (15.6%)
Methotrexate use 133 (64.8%)
Regarding hypertension, regardless of age, onset of arthritis
Biologic use 70 (34.1%) after 40 years (OR 5.2, CI 1.09–25.02, P = 0.039) proved to be an
SD: standard deviation; PsA: psoriatic arthritis; DIP: distal interphalangeal joint;
independent risk factor for its development. By contrast, the age
NSAID: non-steroidal anti-inflammatory drugs. of onset of skin disease showed no association.
The remaining CV risk factors as well as CV outcomes showed
no association with age at onset of psoriatic disease.

psoriasis (P = 0.003), increased frequency of family history of PsA

(P = 0.021) and increased presence of axial pattern as a form of debut Table 3
(P = 0.009). Meanwhile, LOP patients showed greater presence of Univariate comparison between patients with early and late psoriatic arthritisa .
pustular psoriasis (P = 0.007) and oligoarticular disease during evo- Variables Early PsA Late PsA P value
lution (P = 0.018). Likewise, patients with EOP, presented more n = 82 (%) n = 123 (%)
frequently a mixed pattern of axial plus peripheral disease during Family history of PsA 19 (23.2) 12 (9.8) P = 0.007
follow-up (P = 0.019) and increased HLA-B*27 positivity (P = 0.035). OR 2.9 (1.3–6.4)
In terms of cardiovascular risk factors, patients with LOP were HLA-B*27 30 (36.6) 11 (8.9) P < 0.0001
more prone to have obesity (P = 0.035), DM (P < 0.0001) and hyper- OR 5.9 (2.7–12.6)
Diabetes mellitus 4 (5) 21 (17.1) P = 0.009
tension (P < 0.0001), as well as a higher rate of ischemic heart
OR 4.0 (1.3–12.2)
disease during follow-up (P = 0.021) (Table 2). Hypertension 16 (19.5) 47 (38.2) P = 0.004
In 82 patients, arthritis began before 40 years (mean onset age OR 2.5 (1.3–4.9)
29 ± 7.2 years) while in 123 patients arthritis started after this age Dyslipidemia 17 (20.7) 46 (37.4) P = 0.011
OR 2.3 (1.2–4.4)
limit (mean onset age 52.8 ± 8.6 years).
Obesity 15 (18.3) 34 (27.6) P = 0.012
In terms of clinical characteristics, patients with EOA were more OR 1.7 (1.1–3.4)
likely to have family history of PsA (P = 0.007), as well as HLA- Smokers 28 (41.8) 24 (21.8) P = 0.005
B*27 positivity (P = 0.041). Regarding cardiovascular risk factors, OR 2.6 (1.3–5)
patients with EOA were more likely to be smokers (P = 0.005), in Ex-smokers 11 (16.4) 42 (38.2) P = 0.002
OR 3.3 (1.6–7.0)
comparison to patients with LOA that showed higher frequency of
a
DM (P = 0.009), hypertension (P = 0.004), dyslipidemia (P = 0.011), Only significant differences are included.

Please cite this article in press as: Alonso S, et al. Age at disease onset may help to further characterize the disease phenotype in psoriatic
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3. Discussion Robust evidence suggests that patients with psoriatic disease

have a high burden of CV comorbidity. Our data add support to
In this study, the importance of age at symptoms onset in pso- this view. However, this increased burden of comorbidity has been
riatic disease has been investigated in order to better characterize studied in large populations of patients with psoriasis and PsA
the disease phenotype of this condition. The cut off point of 40 years regardless of the stratification proposed in our study. Therefore,
was chosen according to the proposal by Henseler and Christophers an important part of this burden might be attributed to age factor
[3]. Many of our findings confirm the usefulness of this stratification per se and not to the disease itself. As a novelty, we found these
point as this was associated to marked traits of psoriatic disease. comorbidities among late onset cases, both numerically and sta-
The novelty of our study is that this kind of stratification had not tistically. After adjusting for several confusion factors, late onset
been previously used in PsA to characterize this condition from the disease has proven to be an independent risk factor for DM and
clinical and CV standpoint. hypertension in this cohort. Thus, patients with psoriasis starting
In line with previous work, we found that EOP was associated after 40 years had a higher risk for diabetes development, while
with more family history of psoriasis, more extended skin disease those with arthritis onset above this age limit were more prone to
and HLA-C*06 positivity [5,14,15]. However, some striking findings hypertension. Both findings suggest that both phenotypes (skin and
had not been emphasized before. For example, late onset cases had joint) of psoriatic disease are associated with a differential cardio-
higher prevalence of pustular psoriasis when compared to early vascular risk. So that psoriasis is linked to an increased risk of DM
onset cases. Likewise, age at psoriasis onset seemed to influence while arthritis is associated with an increased risk of hypertension.
some characteristics of the joint disease. Thus, spondylitis as onset This latter finding has also been noted by others [9]. In this study,
pattern or oligoarthritis during follow-up, were more commonly the other cardiovascular outcomes may likely be attributed to age
seen in EOP and LOP, respectively. Another striking feature was the per se.
association of HLA-B*27 with EOP, although this finding might obey Finally, this study has certain limitations such as its retrospec-
more to an association with EOA, something recently highlighted in tive and cross-sectional nature, the relatively small number of
the literature [16]. However, a possible relationship between this patients included, and the fact of dealing with a single-centre series
allele and an earlier onset age for psoriasis was already mentioned (inclusion bias). It is important to consider that the fact of working
years ago [17]. with an arbitrary cut off point in 40 years involves in the majority of
As for the population stratification by age of onset of arthritis, cases that we are studying two normally-distributed populations
this distinction seems equally operative because we found a statis- with two overlapped tails; i.e., patients with type I psoriasis will fall
tically significant association between HLA-B*27 and early forms into the distribution curve of the type II and vice versa, although
of PsA. Indeed, the strength of the association between HLA-B*27 we will see that as patients move away from that age point, they
and disease risk was more clearly demonstrated among EOA (OR keep conforming more homogeneous groups from the clinical and
5.9) than in those with EOP (2.73). On the other hand, HLA-C*06 CV standpoint [22].
cases were equally distributed among EOA and LOA. These find- In summary, by means of the stratification of the age of onset
ings support the notion that two separate principal patterns of HLA either of psoriasis or arthritis, we can observe a major relevance
effect will result in the psoriasis phenotype as it has been sug- of the genetic component in the early onset disease, and a greater
gested recently. The first involves the classic psoriasis susceptibility penetrance of CV risk factors in patients with late onset disease.
gene C*06, and is characterized by more penetrant skin disease Greater etiological involvement of environmental factors with a
with less prevalent and more time-dependent development of the dose-response relationship would translate into shorter psoriasis-
musculoskeletal manifestations. The second appears to be medi- arthritis latencies in the late onset case. Therefore, this work shows
ated by alleles of the HLA–B locus, including B*27 and B*39. This that the stratification of this population-based on age at disease
latter pattern includes a musculoskeletal phenotype nearly equiv- onset is suitable to better characterize this pathology and should
alent in penetrance to that of the skin disease, and, in the case of be one more element to take into account in future epidemiological,
B*27, occurs temporally much more coincident with musculoskele- clinical and genetic risk studies for this condition.
tal involvement [16]. We also found a greater family history of PsA
in the EOA subgroup, which again emphasizes the importance of
Disclosure of interest
genetic factors in early onset disease.
Some epidemiological studies have pointed towards a higher
The authors declare that they have no competing interest.
risk of PsA among psoriasis with more than 3 body areas affected
or in those patients with involvement of scalp or intergluteal fold
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Please cite this article in press as: Alonso S, et al. Age at disease onset may help to further characterize the disease phenotype in psoriatic
arthritis. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.09.004