To investigate the association between potential environmental exposures and the development of psoriatic arthritis (PsA) in patients with psoriasis.
To investigate the association between potential environmental exposures and the development of psoriatic arthritis (PsA) in patients with psoriasis.
In this case–control study, the cases were patients with recent-onset PsA. The controls were psoriasis patients without arthritis. The occurrence of the following environmental exposures was recorded through a standardized questionnaire: smoking, alcohol consumption, infections, injuries, physically demanding occupational tasks, stressful life events, vaccinations, and female hormonal exposures. The association between each exposure to environmental events and disease status was assessed through logistic regression after adjustment for age, sex, education level, and duration and severity of psoriasis.
There were 159 subjects in each group. The following exposures remained significantly associated with PsA following multivariate logistic regression: lifting cumulative loads of at least 100 pounds/hour (odds ratio [OR] 2.8, 95% confidence interval [95% CI] 1.51–5.05), infections that required antibiotics (OR 1.7, 95% CI 1.00–2.77), smoking (OR 0.6, 95% CI 0.36–0.89), and injuries (OR 2.1, 95% CI 1.11–4.01). The results were not appreciably changed with the inclusion of each of these factors in a single regression model; however, the level of significance for injuries had become borderline. No association was found between PsA and alcohol consumption, vaccination, stressful life events, and female hormonal exposures.
Lifting heavy loads and infections that required antibiotics were associated with the occurrence of arthritis among patients with psoriasis. There was an inverse association between smoking and PsA. Further studies are necessary to determine whether these and other environmental factors are moderated by predisposing genetic factors.
Psoriasis is an immune-mediated skin disease affecting 2–3% of the population. Psoriatic arthritis (PsA) is an inflammatory arthritis that affects approximately one-third of people with psoriasis (1). In the majority of the patients with PsA, inflammatory arthritis develops on average 7 years after the onset of the skin disease (2). PsA is a complex disease with genetic and environmental risk factors playing a major role in disease susceptibility (3). Genetic factors solely cannot account for all cases of PsA. One of the suggested pathogenic models for PsA is that psoriasis patients who carry susceptibility genes for arthritis develop PsA after exposure to triggering environmental factors (4). Suggested factors include physical and emotional trauma, infections, and hormonal changes (5). A few studies have systematically assessed environmental risk factors for PsA among patients with psoriasis and showed conflicting results (6, 7). In this case–control study, we aimed to investigate the association between several putative environmental risk factors and the occurrence of PsA among patients with psoriasis.
This group included adults with recent-onset PsA that satisfied the CASPAR (ClASsification criteria for Psoriatic ARthritis) classification criteria (8) selected from the University of Toronto PsA cohort. The patients are followed in the PsA clinic every 6–12 months, according to a standardized protocol. For the purpose of this study, we identified all patients with PsA of less than 7 years of duration since diagnosis. We attempted to contact all of the patients in the database that satisfied the study criteria, either during their followup visit in the clinic or by telephone or mail.
The control group included psoriasis patients without arthritis that were recruited from the recently established Toronto Psoriasis Cohort (9), which enrolls psoriasis patients uncomplicated by arthritis and aims to study risk factors for PsA. These patients are assessed by a rheumatologist initially to rule out the presence of inflammatory arthritis, and then annually for symptoms or signs of inflammatory arthritis. If inflammatory arthritis is diagnosed, the subject is considered to have developed the outcome of interest and is censored. This process ensures that all of the psoriasis cohort subjects are free of arthritis. In order to minimize selection bias, psoriasis patients were recruited from several sources: dermatology clinics at Toronto Western Hospital and Women's College Hospital, community dermatologists, family medicine clinics in Toronto, and the general public in the greater Toronto area by advertising in local newspapers. Most of the patients were recruited from dermatology clinics and phototherapy centers. For this study, the controls were recruited consecutively upon their visit to the clinic for their annual followup visit.
Demographic and clinical data were available from the cohorts' computerized databases. The severity of psoriasis was assessed by the highest Psoriasis Area and Severity Index (PASI) score in the first 3 years of followup. Severe psoriasis was defined as a PASI score of ≥10.
Based on literature that has suggested that different environmental exposures are associated with PsA, we investigated a broad range of potential triggering factors. We designed a questionnaire for assessment of these exposures. The study population was asked to report whether they have had any of the environmental exposure events under investigation in the previous 10 years. Patients were asked to specify, for each event, the year of occurrence, whether they required medical consultation, or if they were admitted to the hospital. The following exposures were recorded: 1) physical trauma that included injuries, fractures, and road traffic accidents; 2) infections that required antibiotic treatment and infectious diarrhea; 3) vaccinations to hepatitis A and B, influenza, pneumococcus, rubella, and tetanus; 4) emotional stress, including death of a close family member, divorce or separation, moving house, change of job, becoming unemployed, and treatment for anxiety or depression; 5) female hormonal exposures, i.e., ages of first and last menstrual periods, use of hormonal contraception and hormone replacement therapy, fertility treatment, and pregnancies; 6) occupational exposures; 7) smoking status; and 8) alcohol consumption. For occupational exposures, we hypothesized that recurrent microtrauma that is related to certain occupations may be associated with PsA. The literature was searched for studies that assessed the association between several occupational tasks and musculoskeletal problems. The cutoff levels that were found to increase the risk of these problems were chosen (10). Only subjects that have been employed in the last 10 years were asked to report exposures to the following: prolonged standing of more than 30 minutes/hour, squatting for more than 5 minutes/hour, lifting cumulative heavy loads of more than 100 pounds/hour, pushing cumulative loads of more than 200 pounds/hour, using vibrating tools for more than 4 hours/day, frequent repetitive hand movements of more than 45 minutes/hour, forceful gripping of more than 4 hours/day, and bending of the wrist for more than 4 hours/day. For smoking status, a current smoker was defined as a person that has smoked at least 1 cigarette a day for at least 1 year at the time of the diagnosis of PsA or at the date of the first assessment for patients in the psoriasis group. A past smoker was defined as a person who had a history of smoking as defined above, but denied active smoking at the time of the diagnosis of PsA or at the date of the assessment for patients in the psoriasis group. The “ever smoker” group combined the current and past smokers. Alcohol consumption was categorized as social, daily, or nondrinker before the diagnosis of PsA or before the date of assessment for patients in the psoriasis group.
Recall bias is a potential problem in this type of study. We expected patients with arthritis to recall more environmental events, since patients may link these events to the onset of arthritis. In order to minimize this bias, the environmental events were not related explicitly to the onset of the arthritis, but the participants were simply asked to report events that occurred within the 10 years prior to the assessment date, and therefore a linkage between the onset of arthritis and exposure was avoided. Only exposures that occurred before the onset of arthritis were considered. In order to ensure that cases and controls had equal duration of time for potential exposures, we assigned a reference date for each control that was derived from the date of onset of arthritis for the corresponding case having a similar duration of psoriasis. Therefore, the matching ensured there was a similar time period at risk of exposure and thus potential confounding variables were controlled for through the regression analysis.
Baseline descriptive statistics were computed with continuous variables summarized by their means and SDs and categorical variables summarized by proportions. The proportions of patients that were exposed to the different types of environmental factors before the reference date were calculated. For several of the exposures, mostly in the vaccination section, a significant proportion of the responses was “don't know” or missing. Missing variables were assigned a distinct code. This process allowed us to avoid a selection bias by excluding those individuals from the full regression model. Since there were too many environmental factors for inclusion as covariates in the full regression model, we performed a “screening” step. This step aimed to detect the most significant exposures (P value less than 0.1) after adjusting for age, sex, level of education, and severity and duration of psoriasis, and included only those in the final logistic regression model. We then constructed a logistic regression model that included all of the exposures that were found to be significant in the “screening” step, adjusting for the same confounders. Logistic regression analysis was used to identify key factors predictive of PsA. Covariate effects were considered statistically significant if the P value from the 2-sided Wald's test was less than 0.05. This study was approved by the University Health Network Research Ethics Board.
One hundred ninety PsA patients that satisfied the study criteria were identified through a search in the computerized PsA database. We attempted to contact all of them; however, we were unable to contact 29 (6 deceased), and 2 were excluded due to poor English language skills. Overall, 159 PsA patients (83.6%) were included in the study. We then aimed to recruit a similar number of psoriasis patients. A total of 196 patients with psoriasis were approached for enrollment, of whom 159 (81.1%) completed the questionnaire.
The demographic and clinical characteristics of the study population are shown in Table 1. The cases and controls had a similar mean duration of psoriasis and male to female ratio. Level of education, often associated with socioeconomic status, was also similar in the 2 groups. The psoriasis group was slightly older than the PsA group (by a mean of 3.5 years). The mean ± SD duration of PsA at the time of the assessment was relatively short, 3.1 ± 2.2 years, which indicates the recent onset of the disease and minimizes problems due to recall. A mean ± SD time window of 6.9 ± 2.2 years prior to the onset of arthritis and a comparable time period for the controls were captured (range 2–10 years).
|PsA (n = 159)||Psoriasis (n = 159)|
|Age, mean ± SD years||44.9 ± 13.1||48.4 ± 13.3|
|Male sex||89 (55.9)||86 (54.1)|
|White ethnicity||124 (81.6)||137 (86.2)|
|Family history of psoriasis||70 (44.6)||71 (44.9)|
|Family history of PsA||13 (8.2)||5 (3.1)|
|College/university education status||122 (77.7)||127 (79.9)|
|Duration of psoriasis, mean ± SD years||17.2 ± 13||18.6 ± 14.5|
|Duration of PsA, mean ± SD years||3.1 ± 2.2||N/A|
|Pattern of arthritis at diagnosis||N/A|
|Spine + polyarthritis||22 (16.4)|
|Spine + oligoarthritis||12 (8.9)|
|Distal (DIP joints) only||3 (2.2)|
|Maximal PASI score (in the first 3 years of followup), mean ± SD||7.3 ± 9.6||7.1 ± 7.2|
|Severe psoriasis||33 (20.9)||34 (21.4)|
|Methotrexate||22 (14)||5 (3.1)|
|Biologics||10 (6.4)||2 (1.3)|
|Psoriatic nail lesions||109 (70.8)||69 (43.4)|
Surprisingly, there was not a significant difference in psoriasis severity between the PsA and psoriasis patients. This may be explained by the fact that many of the patients with psoriasis were reviewed after several phototherapy treatments that may have improved their skin scores, whereas many of the PsA patients were reviewed prior to starting therapy at a time when their PASI scores were higher.
The proportions of patients that were exposed to different environmental factors are shown in Table 2.
|Exposure†||PsA frequency, no. (%)||Psoriasis frequency, no. (%)||Univariate||Multivariate|
|OR||95% CI||P||OR||95% CI||P|
|Car accidents requiring medical treatment||6 (3.8)||5 (3.2)||1.2||0.32–4.04||0.76||1.1||0.32–3.74||0.89|
|Fractures||16 (10.1)||14 (8.9)||1.2||0.36–3.98||0.77||1.2||0.54–2.51||0.69|
|Any other injury‡||34 (21.4)||12 (10.7)||2.3||1.21–4.26||0.01||2.1||1.11–4.01||0.02|
|Infective diarrhea||20 (12.7)||11 (7)||1.9||0.88–4.16||0.10||1.7||0.76–3.79||0.19|
|Infections requiring antibiotics‡||53 (34.4)||37 (23.7)||1.7||1.03–2.77||0.04||1.7||1.00–2.77||0.05|
|Infections that required hospitalization‡||11 (7.2)||0 (0)|
|Hepatitis A||3 (2.5)||4 (3.6)||0.7||0.15–3.16||0.63||0.7||0.14–2.99||0.58|
|Hepatitis B||29 (22.6)||19 (16.2)||1.5||0.79–2.87||0.21||1.5||0.76–2.81||0.25|
|Pneumococcus||30 (23.6)||20 (17.1)||1.5||0.80–2.82||0.21||1.4||0.75–2.72||0.28|
|Flu||59 (41.5)||60 (44.7)||0.9||0.54–1.42||0.58||1.0||0.58–1.57||0.87|
|Rubella||4 (2.9)||5 (3.9)||0.8||0.20–2.88||0.68||0.8||0.22–3.32||0.81|
|Tetanus||6 (4.8)||4 (3.7)||1.3||0.36–4.81||0.67||1.1||0.29–4.24||0.87|
|Death in the family||41 (26.8)||44 (28.9)||0.9||0.54–1.48||0.67||1.1||0.63–1.79||0.82|
|Divorce/separation||17 (10.9)||12 (7.7)||1.5||0.67–3.18||0.33||1.5||0.69–3.35||0.29|
|Move house||74 (50)||64 (43)||1.3||0.83–2.07||0.24||1.1||0.67–1.82||0.68|
|Changed job||70 (46.7)||56 (40)||1.3||0.82–2.09||0.25||1.2||0.73–2.07||0.44|
|Becoming employed||34 (22.7)||35 (22.8)||1.0||0.57–1.69||0.96||1.0||0.54–1.66||0.85|
|Treated for anxiety/depression||21 (13.9)||26 (16.8)||0.8||0.43–1.46||0.47||0.8||0.39–1.45||0.41|
|Squatting (>5 minutes/hour)||45 (30.8)||32 (21.9)||1.5||0.92–2.59||0.10||1.6||0.92–2.66||0.10|
|Prolonged standing (>30 minutes/hour)||95 (65.7)||85 (58.2)||1.3||0.80–2.05||0.29||1.3||0.77–2.05||0.22|
|Lifting heavy weights (>100 pounds/hour)‡||44 (30.1)||19 (13)||2.9||1.61–5.27||0.0004||2.8||1.51–5.05||0.001|
|Pushing heavy weights (>200 pounds/hour)||29 (19.8)||18 (12.3)||1.7||0.91–3.27||0.08||1.59||0.83–3.06||0.16|
|Using vibrating tools (>4 hours/day)||7 (4.8)||8 (5.5)||0.9||0.30–2.43||0.77||0.8||0.27–2.32||0.66|
|Repetitive hand movements (>45 minutes/hour)||88 (6)||85 (5.8)||1.1||0.66–1.66||0.72||1.1||0.65–1.69||0.83|
|Forceful gripping (>4 hours/day)||28 (19.2)||21 (14.4)||1.3||0.71–2.42||0.38||1.0||0.64–2.27||0.56|
|Bending the wrist (>4 hours/day)||65 (44.5)||65 (44.5)||1.0||0.60–1.50||0.83||1.0||0.59–1.53||0.84|
|Smoking: never vs. ever‡||64 (40.2)||89 (56)||0.5||0.34–0.82||0.005||0.6||0.36–0.89||0.01|
|Social vs. none||85 (55.6)||88 (56.4)||0.9||0.59–1.53||0.82||0.9||0.56–1.50||0.73|
|Daily vs. none||12 (7.8)||13 (8.3)||0.9||0.38–2.16||0.82||1.0||0.42–2.51||0.96|
The proportion of smokers (current and past) was lower in the PsA group compared to the psoriasis group (40.2% versus 56%), leading to a significant inverse association between smoking and PsA (odds ratio [OR] 0.6, 95% confidence interval [95% CI] 0.36–0.89). The ORs for past smokers (OR 0.52, 95% CI 0.31–0.88; P = 0.015) and current smokers (OR 0.54, 95% CI 0.31–0.96; P = 0.038) compared to those who never smoked were similar.
The proportions of social, daily, and nondrinkers were found to be similar in the PsA and psoriasis groups.
Steroid treatment has been reported to be associated with an increased risk of developing PsA among patients with psoriasis (6). However, in our study, none of the psoriasis patients had a history of oral corticosteroid treatment, while only 1 PsA patient had been treated with steroids in the exposure time window prior to the diagnosis of PsA.
Only the 148 PsA patients and 146 psoriasis patients who were employed during the 10 years prior to the assessment date were evaluated. Lifting cumulative heavy loads of at least 100 pounds/hour was more common in the PsA group (30.1% versus 13%; OR 2.8, 95% CI 1.51–5.05). The following occupational tasks were more common in the PsA group: squatting for at least 5 minutes/hour (30.8% versus 21.9%; 95% CI 0.92–2.66, P = 0.1) and pushing cumulative heavy weights of more than 200 pounds/hour (19.8% versus 12.3%; 95% CI 0.83–3.06, P = 0.16). However, as noted by the P values, none of these differences reached statistical significance at the 5% level. No particular pattern of joint involvement was associated with carrying heavy loads.
A history of infectious diarrhea in the exposure time window under study was more common in the PsA group. However, this did not reach statistical significance (12.7% versus 7%; P = 0.19). Other infections that required antibiotic treatment were significantly associated with PsA (OR 1.7, 95% CI 1.00–2.77). In addition, the proportion of severe infections that required hospitalization was significantly higher in the PsA group during the exposure time window under study (7.2% versus 0%; P < 0.001). The types of infections reported in the PsA group included lower respiratory tract infection (11%), upper respiratory tract infection (22.2%), urinary tract infection (8.3%), skin and soft tissue infections (25%), sinus infection (8.3%), sepsis (2.8%), hepatitis B or C (8.3%), and other types of infections (13.9%). There was no significant difference in the types of infection between the psoriasis and PsA groups. A polyarticular pattern of arthritis was more common among patients with a history of infection (74%) compared to those without (58.6%). There was a trend for an association between a history of infection and a polyarticular pattern at presentation (OR 2, 95% CI 0.95–4.25; P = 0.06). Therefore, it is unlikely that there was a significant misclassification with reactive arthritis, as the typical pattern of this type of arthritis is oligoarticular.
There was no significant difference between the case and control groups in the proportions of subjects that had road traffic accidents and fractures in the exposure time window under study. However, more PsA patients reported having other types of injuries (21.4% versus 10.7%; OR 2.1, 95% CI 1.11–4.01). The types of injuries in the PsA group were very variable and included cuts, falls, burns, and blunt and penetrating trauma, and affected all body areas, often several body parts at once. Therefore, it was difficult to analyze the correlation between the site of the injury and the joint of onset of the arthritis.
Since vaccinations were reported to be associated with PsA in a previous study (6), we included this exposure in the analysis, although up to 30% of the information was missing. The proportion of patients with missing information was similar in the cases and controls. We analyzed the data twice, first by excluding the patients with the missing information from the analysis, and again by considering the missing data as “no exposure” to the particular vaccination. There were no significant changes in the OR of the 2 analyses. The following vaccinations were assessed: those for hepatitis A and B, pneumococcus, flu, rubella, and tetanus. There were no statistically significant differences in the proportions of exposures to the different types of vaccinations in the 2 groups during the exposure time window under study after adjusting for potential confounders.
Exposures to the following potential emotional stressful events were assessed: death of a close family member, divorce or separation, moving house, changing job, becoming unemployed, and treatment for depression or anxiety. None of these exposures was significantly associated with PsA in the univariate or multivariate analyses.
The following events were investigated: age at first menstrual period, age at onset of menopause, use of oral contraceptive pills, use of hormone replacement therapy, pregnancy, and fertility treatment. The results are shown in Table 3. None of these exposures was significantly associated with PsA in the univariate or multivariate analyses.
|Exposure†||PsA (n = 68)‡||Psoriasis (n = 73)||Univariate||Multivariate|
|OR||95% CI||P||OR||95% CI||P|
|Age at first period, mean ± SD years||12.5 ± 1.6||12.7 ± 1.6||0.85|
|Becoming postmenopausal, no./total (%)||13/19 (68.4)||12/20 (60)||0.7||0.19–2.58||0.58||1.8||0.31–11.49||0.50|
|Using oral contraceptive treatment||24 (35.3)||26 (35.6)||1.0||0.51–2.02||0.96||1.7||0.71–4.23||0.23|
|Using hormone replacement therapy||9 (13.2)||10 (13.7)||1.0||0.48–2.16||0.95||1.1||0.50–2.39||0.83|
|Pregnancy||13 (19.1)||13 (17.8)||0.9||0.39–2.15||0.84||1.2||0.47–2.09||0.73|
|Fertility treatment||5 (7.5)||7 (9.6)||0.7||0.23–2.48||0.63||0.9||0.26–2.98||0.83|
The exposures that were found to be associated with PsA after adjustment for age, sex, level of education, and severity and duration of psoriasis were included in a full logistic regression model to test their independent effect. The results of the analysis are shown in Table 4. The following variables remained significantly associated with PsA: smoking (OR 0.47, 95% CI 0.29–0.77), occupations that required lifting heavy weights (OR 2.92, 95% CI 1.56–5.46), and infections that required antibiotic treatment (OR 1.72, 95% CI 1.01–2.95). Having a history of an injury was of borderline significance after inclusion in the full logistic regression model (OR 1.98, P = 0.054).
|Smoking status: never vs. ever†||0.47||0.29–0.77||0.003|
|Occupational task: lifting heavy weight†||2.92||1.56–5.46||0.0008|
|Infection that required antibiotic treatment†||1.72||1.01–2.95||0.046|
|Duration of psoriasis (1-year increase)||0.99||0.98–1.01||0.63|
|Age (1-year increase)||0.99||0.97–1.01||0.29|
|Severe psoriasis (PASI score ≥10)||0.89||0.49–1.61||0.70|
|College/university level of education||1.18||0.66–2.13||0.56|
In this study we investigated the association between a number of a priori chosen environmental factors and PsA among patients with psoriasis. Our results suggest that there is an association between PsA and infections, physical trauma including physically demanding occupational tasks, and smoking.
Only a limited number of studies have investigated environmental risk factors for PsA. Pattison et al compared the prevalence of environmental exposures among 98 British PsA and 163 psoriasis patients over a window of exposure that ranged from 5–10 years prior to the onset of arthritis. Information about environmental exposures was collected through questionnaires. In their study, physical trauma, rubella vaccination, oral ulcers, and moving house were found to be associated with PsA (6). Another study by Thumboo et al used an administrative database from Rochester, Minnesota, and retrospectively evaluated exposure to several environmental risk factors among 60 PsA and 120 psoriasis patients (7). They did not define a specific window of exposure. In that study, pregnancy was found to be protective of PsA, while steroid use was associated with a higher risk of the disease. These studies had several limitations; first, their small sample size precluded identifying important associations due to reduced power. The use of an administrative database as a source of information may have led to underestimation of events that are often not coded or are coded incorrectly. The study by Pattison et al included controls from a dermatology clinic, while the PsA patients were recruited from their rheumatologists or by advertisement (6). The controls were not evaluated to exclude the presence of PsA. It has been shown that PsA is underestimated among psoriasis patients, as approximately 18% of the psoriasis patients that were found to have inflammatory arthritis were unaware of their condition and had never been seen by a rheumatologist (11). The problem of misclassification of patients and controls may significantly affect the results in case–control studies where the outcome (in this case, PsA) is not rare among the control group. Misclassification can decrease the power of the study to detect significant associations. In our study, we aimed to minimize the misclassification of cases and controls by having a rheumatologist evaluate all of the controls to rule out clinical inflammatory arthritis. The cases and controls were recruited from the same program, and were evaluated according to the same protocol.
Several case reports and case series have highlighted the potential role of local trauma in the pathogenesis of PsA (12, 13). However, only a few studies have systematically assessed its role in PsA. Scarpa et al (14) reported more acute medical events, including injuries that occurred less than 10 days before the onset of the arthritis, in patients with PsA compared to the group with rheumatoid arthritis. Pattison et al (6) found that the occurrence of an injury was more common in patients with PsA compared to patients with psoriasis. However, Thumboo et al did not find an association between trauma and PsA (7). In our study, patients with PsA had double the risk of experiencing injuries in the time window under study compared to patients with psoriasis. However, that association has become of borderline significance and there was a small reduction in the effect size after the inclusion of injuries in the full regression model, suggesting that injuries were related to one of the other risk factors in the model. The most likely candidate is physically demanding occupations that involved lifting heavy weights, because when that covariate was excluded from the model, injuries were found to be associated with PsA (data not shown).
Work-related physical activity can lead to musculoskeletal disorders and specific occupational tasks can lead to osteoarthritis (15, 16). The role of occupation-related physical activities in the pathogenesis of PsA has not been thoroughly investigated. In ankylosing spondylitis, occupations that require recurrent bending, twisting, and stretching are associated with more functional limitation and higher radiographic spinal scores (17). In our study, occupations that were associated with lifting heavy weights were more common in the PsA group and recurrent squatting and pushing heavy weights also tended to be more common in the PsA group. Recurrent microtrauma that is associated with these physically demanding occupations may lead to greater susceptibility to PsA.
It has been suggested that infections play a role in the pathogenesis of PsA. The role of infection as a triggering event for arthritis is well established in reactive arthritis, which has some common features with PsA (18). Infections of the gastrointestinal and urogenital tracts are most commonly associated with reactive arthritis. While the frequency of urogenital tract infection was similar in the 2 groups, infectious diarrhea tended to be more common in the PsA group. Human immunodeficiency virus infection that has been linked to severe psoriasis and PsA (19) was found only in the psoriasis group.
An interesting finding was the inverse association between smoking and PsA. While smoking is a well-established risk factor for psoriasis (20, 21), in our study it was found to be significantly less common among the PsA cases. A similar trend was reported by Pattison et al, who found a trend of fewer smokers among the PsA patients (6). In their study, the OR (0.68) was similar to the OR in our study (0.5) but was not significant, possibly due to a smaller sample size. Rakkhit et al reported that the time to development of PsA decreases with smoking prior to psoriasis onset and increases with smoking after psoriasis onset (22). Smoking was also found to have a protective effect on the pathogenesis of ulcerative colitis, a disorder that bears some clinical and genetic similarities to PsA (23–25). The mechanisms underlying these observations are unknown, but suggested explanations include decreased expression of interleukin-1β (IL-1β), IL-8, and altered response of the Toll-like receptor pathway to infectious agents among smokers (26, 27). Another mechanism that may explain the protective effect of smoking is through the activation of the nicotinic receptor. Nicotine can activate the α7 nicotinic acetylcholine receptor that inhibits intracellular proinflammatory pathways that are associated with the development of arthritis (28, 29). This pathway is a target for novel therapeutic agents for the treatment of arthritis.
There are several limitations to our study. Its retrospective nature may have led to a recall bias that stems from the tendency of the cases to recall more events that preceded the onset of arthritis than the controls. We have tried to minimize that problem in several ways. By approaching patients with a recent onset of arthritis, our study population had a short interval from the onset of PsA of approximately 3 years. We also avoided linking environmental exposures and arthritis in the questionnaire, and requested information about events that occurred in the past 10 years. We have also assessed recall bias by comparing the reported information about exposure to infections and injuries with available data from a computerized database that stores medical records from 6 medical centers and outpatient clinics in Toronto. Our aim was to assess whether there has been underreporting of events by psoriasis patients. Overall, 3 of 3 patients with psoriasis reported a previous injury and 0 of 2 reported an infection. In the PsA group, only 1 of 3 reported an injury and 1 of 6 reported an infection. Therefore, although these figures are small, it seems that recall bias is not a threat to the validity of the study, as the rates of reporting were not lower in the psoriasis group.
In summary, in this study we investigated the association between several environmental exposures and PsA. We have found that infections that required antibiotic treatment, injuries, and occupations that involved lifting heavy weights were associated with PsA, while there was an inverse association with smoking. These results need to be confirmed by a prospective study among patients with psoriasis.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Gladman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Eder, Chandran, Shanmugarajah, Shen, Rosen, Cook, Gladman.
Acquisition of data. Eder, Law, Chandran, Shanmugarajah, Gladman.
Analysis and interpretation of data. Eder, Law, Chandran, Shanmugarajah, Shen, Rosen, Cook, Gladman.
We would like to thank Gideon Kalman-Lamb for his help in preparing this manuscript.