Epidemiologic studies have shown that, in patients with psoriatic arthritis (PsA), associated comorbidities may occur more frequently than expected. This article discusses related comorbidities in patients with PsA. Identifying these comorbidities may affect the management and treatment decisions for these patients to ensure an optimal clinical outcome. All health care providers caring for patients with PsA should be aware of the relevant comorbidities and should have an understanding of how these comorbidities affect management. The common comorbidities include cardiovascular disease, metabolic syndrome, obesity, diabetes, fatty liver disease, inflammatory bowel disease, ophthalmic disease, kidney disease, osteoporosis, depression, and anxiety.
Key points
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Providing comprehensive care of patients with psoriatic arthritis includes screening for related comorbidities and taking this into consideration for relevant treatment selection.
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The most common comorbidity among patients with psoriatic arthritis is cardiovascular disease, so there is an emphasis on traditional cardiovascular risk factors such as obesity and diabetes.
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Additional comorbidities include ophthalmic disease, liver disease, inflammatory bowel disease, depression and anxiety, osteoporosis, kidney disease, malignancy, and infection.
Introduction
Psoriatic arthritis (PsA) is well known to affect the skin and joints and emerging research has identified specific comorbidities related to PsA. More than half of patients with PsA have at least 1 comorbidity ( Table 1 ) and this has a significant negative impact on quality of life. Recognizing and addressing comorbidities are critical to safely and effectively treating patients with PsA because these comorbidities often have implications not only for impaired function and quality of life but also therapy selection. This article summarizes the knowledge to date regarding the most relevant comorbidities in patients with PsA and highlights therapy options for patients with PsA in the setting of comorbid conditions.
| No of Comorbid Conditions | Salaffi et al, 2009 (n = 101), Peripheral PsA, n (%) a | Salaffi et al, 2009 (n = 65), Axial PsA, n (%) a | Husted et al, 2013 (Total n = 631), PsA, n (%) b |
|---|---|---|---|
| 0 | 45 (44.6) | 19 (29.3) | — |
| 1 | 26 (25.7) | 12 (18.5) | — |
| 2 | 13 (12.9) | 21 (32.3) | — |
| <3 | 84 (83.2) | 52 (80.0) | 365 (57.8) |
| ≥3 | 17 (16.8) | 13 (20.0) | 266 (42.2) |
a Based on patient Self-Administered Comorbidity Questionnaire list of 13 comorbidities: heart disease, hypertension, lung disease, diabetes, ulcer or stomach disease, kidney and liver disease, anemia or other blood disease, cancer, depression, osteoarthritis, back pain, and rheumatoid arthritis.
b Based on a list of 15 comorbidities: CVD, hypertension, hyperlipidemia, type II diabetes, obesity, respiratory disease, gastrointestinal disease, neurologic disease, autoimmune disease, liver disease, depression/anxiety, cancer, other musculoskeletal conditions, infection, and fibromyalgia.
Important comorbidities shown to be associated with PsA disease include premature cardiovascular disease (CVD); metabolic syndrome (diabetes, obesity); ophthalmic, liver, kidney, and inflammatory bowel disease (IBD); depression; and anxiety ( Fig. 1 ). PsA comorbidities associated with both the disease and the treatments include infectious complications, malignancy risk, and osteoporosis. Recently published data on the incidence of specific comorbidities in patients with PsA are listed in Table 2 .
| Comorbidity | Husted et al, 2013 (n = 631), n (%) a | Kraishi et al, 2014 (n = 196), n (%) | Edson-Heredia et al, 2015 (n = 1952), n (%) | Feldman et al, 2015 (n = 1230), n (%) b | Ogdie et al, 2015 (n = 8706), n (%) |
|---|---|---|---|---|---|
| Obesity | 204 (32.3) | 117 (59.7) | — | — | — |
| Hypertension | 221 (35.0) | 64 (32.7) | 376 (19.3) | 440 (35.8) | — |
| Infection | 216 (34.2) | — | — | — | — |
| Depression/anxiety | 130 (20.6) | 27 (13.8) | 530 (27.2) | 185 (15.0) | — |
| Hyperlipidemia | 124 (19.7) | 98 (61.6) c | 157 (8.0) | 425 (34.6) | — |
| Diabetes | 72 (11.4) | 27 (13.8) | 98 (5.0) | 196 (15.9) | — |
| Cancer | 56 (8.9) | — | — | 80 (6.5) | — |
| CVD | 48 (7.6) | 17 (8.7) | 64 (3.3) | 118 (9.6) | 338 (3.9) |
| Gastrointestinal disease | 37 (5.9) | — | — | 16 (1.3) | — |
| Liver disease | 15 (2.4) | — | — | — | — |
a Based on a list of 15 comorbidities: CVD, hypertension, hyperlipidemia, type II diabetes, obesity, respiratory disease, gastrointestinal disease, neurologic disease, autoimmune disease, liver disease, depression/anxiety, cancer, other musculoskeletal conditions, infection, and fibromyalgia.
b Comorbidities in patients with PsA with moderate to severe PsO.
Introduction
Psoriatic arthritis (PsA) is well known to affect the skin and joints and emerging research has identified specific comorbidities related to PsA. More than half of patients with PsA have at least 1 comorbidity ( Table 1 ) and this has a significant negative impact on quality of life. Recognizing and addressing comorbidities are critical to safely and effectively treating patients with PsA because these comorbidities often have implications not only for impaired function and quality of life but also therapy selection. This article summarizes the knowledge to date regarding the most relevant comorbidities in patients with PsA and highlights therapy options for patients with PsA in the setting of comorbid conditions.
| No of Comorbid Conditions | Salaffi et al, 2009 (n = 101), Peripheral PsA, n (%) a | Salaffi et al, 2009 (n = 65), Axial PsA, n (%) a | Husted et al, 2013 (Total n = 631), PsA, n (%) b |
|---|---|---|---|
| 0 | 45 (44.6) | 19 (29.3) | — |
| 1 | 26 (25.7) | 12 (18.5) | — |
| 2 | 13 (12.9) | 21 (32.3) | — |
| <3 | 84 (83.2) | 52 (80.0) | 365 (57.8) |
| ≥3 | 17 (16.8) | 13 (20.0) | 266 (42.2) |
a Based on patient Self-Administered Comorbidity Questionnaire list of 13 comorbidities: heart disease, hypertension, lung disease, diabetes, ulcer or stomach disease, kidney and liver disease, anemia or other blood disease, cancer, depression, osteoarthritis, back pain, and rheumatoid arthritis.
b Based on a list of 15 comorbidities: CVD, hypertension, hyperlipidemia, type II diabetes, obesity, respiratory disease, gastrointestinal disease, neurologic disease, autoimmune disease, liver disease, depression/anxiety, cancer, other musculoskeletal conditions, infection, and fibromyalgia.
Important comorbidities shown to be associated with PsA disease include premature cardiovascular disease (CVD); metabolic syndrome (diabetes, obesity); ophthalmic, liver, kidney, and inflammatory bowel disease (IBD); depression; and anxiety ( Fig. 1 ). PsA comorbidities associated with both the disease and the treatments include infectious complications, malignancy risk, and osteoporosis. Recently published data on the incidence of specific comorbidities in patients with PsA are listed in Table 2 .
| Comorbidity | Husted et al, 2013 (n = 631), n (%) a | Kraishi et al, 2014 (n = 196), n (%) | Edson-Heredia et al, 2015 (n = 1952), n (%) | Feldman et al, 2015 (n = 1230), n (%) b | Ogdie et al, 2015 (n = 8706), n (%) |
|---|---|---|---|---|---|
| Obesity | 204 (32.3) | 117 (59.7) | — | — | — |
| Hypertension | 221 (35.0) | 64 (32.7) | 376 (19.3) | 440 (35.8) | — |
| Infection | 216 (34.2) | — | — | — | — |
| Depression/anxiety | 130 (20.6) | 27 (13.8) | 530 (27.2) | 185 (15.0) | — |
| Hyperlipidemia | 124 (19.7) | 98 (61.6) c | 157 (8.0) | 425 (34.6) | — |
| Diabetes | 72 (11.4) | 27 (13.8) | 98 (5.0) | 196 (15.9) | — |
| Cancer | 56 (8.9) | — | — | 80 (6.5) | — |
| CVD | 48 (7.6) | 17 (8.7) | 64 (3.3) | 118 (9.6) | 338 (3.9) |
| Gastrointestinal disease | 37 (5.9) | — | — | 16 (1.3) | — |
| Liver disease | 15 (2.4) | — | — | — | — |
a Based on a list of 15 comorbidities: CVD, hypertension, hyperlipidemia, type II diabetes, obesity, respiratory disease, gastrointestinal disease, neurologic disease, autoimmune disease, liver disease, depression/anxiety, cancer, other musculoskeletal conditions, infection, and fibromyalgia.
b Comorbidities in patients with PsA with moderate to severe PsO.
Cardiovascular disease
Inflammation and Atherosclerosis
Understanding of atherosclerosis has recently evolved from simply cholesterol deposition to a more complex process that may be a manifestation of a chronic inflammatory disease. It has been shown that systemic inflammation, involving low-grade inflammatory activity in the vascular wall, is pivotal in the pathogenesis of atherosclerosis. Many of the inflammatory cells and cytokines, including tumor necrosis factor (TNF) alpha, that play an active role in synovitis and psoriatic diseases are also active in atherosclerosis. This inflammatory burden is thought to lead to increased insulin resistance, oxidative stress, endothelial cell dysfunction, and the development of atherosclerosis, which may ultimately result in myocardial infarction (MI) or cerebrovascular accidents (CVAs).
The concept of a common pathogenic mechanism for atherosclerosis and systemic rheumatic diseases has resulted in the increasing importance of a multidisciplinary integrated approach to optimize screening and therapy for patients with PsA, with active coordination between primary care and cardiology colleagues. Patients with chronic inflammatory states may interact synergistically with cardiovascular (CV) risk factors or independently to augment vascular dysfunction leading to accelerated atherosclerosis.
Cardiovascular Risk
CVDs, such as an increased prevalence of ischemic heart disease, cerebrovascular disease, diastolic dysfunction, left ventricular dysfunction, abnormal carotid intimal thickness, and CV death, represent a major source of morbidity for patients with PsA. Patients with PsA have a higher prevalence and incidence of MI and stroke than the general population. Patients with PsA have an increased prevalence of traditional CV risk factors, such as a history of diabetes, hypertension, obesity, dyslipidemia, and smoking. However, this increased prevalence may not fully explain CV risk in PsA. Recent studies have found that up to 30% to 50% of patients with PsA with atherosclerosis do not have these traditional CV risk factors. In several studies this increased risk has been attributed not only to increased traditional risk factors but also to chronic systemic inflammation. In addition to an increased prevalence of traditional CV risk factors, patients with PsA also have an increased prevalence of metabolic syndrome, which is a combination of hypertension and hyperlipidemia risk factors and comorbidities such as obesity and diabetes. Metabolic syndrome has been associated with increased severity of PsA and increased CVD.
Recent studies have suggested that patients with PsA with metabolic syndrome have the highest overall maximum carotid artery intima-media thickness and prevalence of carotid plaques compared with other patients with psoriatic disease. Studies have suggested that the length of disease and exposure to chronic inflammation may play a role in increased carotid plaque burden over time. These observations support the hypothesis that incremental increases in inflammatory pathways in PsA may contribute to an even higher CV risk and metabolic syndrome compared with psoriasis alone.
In a recent controlled study by Han and colleagues prevalence ratios for CVD and their risk factors in 3066 patients with PsA compared with matched controls were increased for the following CVDs: ischemic heart disease (1.3), congestive heart failure (CHF) (1.5), cerebrovascular disease (1.3), atherosclerosis (1.4), peripheral vascular disease (1.6), type II diabetes (1.5), hyperlipidemia (1.2), and hypertension (1.3). Similar increased prevalence ratios were also found in rheumatoid arthritis (RA) (n = 28,208) and ankylosing spondylitis (AS) (n = 1843) cohorts. An increased risk of CVD compared with controls was reported for a large prospective study of 648 patients with PsA followed at The University of Toronto Psoriatic Arthritis Clinic. Of these patients, 23.9% (n = 155) developed at least 1 of the following conditions: hypertension (n = 122), MI (n = 38), angina (n = 21), CHF (n = 11), or a CVA (n = 5). The standardized prevalence ratios (SPRs) for MI (2.57; 95% confidence interval [CI], 1.73–3.80), angina (1.97; 95% CI, 1.24–3.12), and hypertension (1.90; 95% CI, 1.59–2.27) were statistically significant, whereas the SPRs for CHF (1.19; 95% CI, 0.50–2.86) and CVA (0.91; 95% CI, 0.34–2.43) were not.
Given that systemic inflammation has been implicated in accelerated atherosclerosis in patients with rheumatic disease, decreasing inflammation through the use of disease-modifying antirheumatic drugs (DMARDs) has been hypothesized to attenuate CV risk. However 2 recent studies report results that contradict this rationale. Chen and colleagues described a comparable incidence of ischemic heart disease in patients with psoriasis treated with methotrexate (MTX) and those treated with other nonbiologic antipsoriatic drugs. Similarly, recently published data by Ogdie and colleagues on risk of major adverse CV events (MACE) among 8706 patients with PsA from a UK population-based longitudinal cohort study (1994–2010) showed conflicting results on the effects of DMARDs on the incidence of MACE. After adjustment for traditional risk factors, they showed an increased risk for incident MI for both non–DMARD-treated and DMARD-treated patients with PsA (hazard ratio [HR], 1.36; 95% CI, 1.04–1.77; and HR, 1.36; 95% CI, 1.01–1.84 respectively). However, the risk of incident stroke and the composite MACE outcome were significantly increased only in non–DMARD-treated patients with PsA (HR, 1.33; 95% CI, 1.03–1.71; and HR, 1.24; 95% CI, 1.03–1.49 respectively). In addition, CV death was not significantly increased in either non–DMARD-treated or DMARD-treated cohorts (HR, 1.07; 95% CI, 0.79–1.44; and HR, 0.96; 95% CI, 0.64–1.43). These studies stress the need to better understand the mechanism underlying increased CVD in patients with psoriasis and PsA given conflicting results.
The study by Ogdie and colleagues also showed that high Psoriasis Area and Severity Index score was an important factor associated with CVD. Several other studies have supported the increased predictive value of the severity of skin lesions in PsA. A large retrospective cohort study of the General Practice Research Database in the United Kingdom used psoriasis diagnostic codes and any history of systemic therapy to identify patients with mild and severe psoriasis from 1987 to 2002 with the objective of determining the risk of mortality in patients with psoriasis alone and in those with psoriasis and associated inflammatory arthropathies. The investigators reported no overall effect of mild psoriasis on mortality (HR, 1.0; 95% CI, 0.97–1.02), whereas patients with severe psoriasis showed an increased overall mortality risk (HR, 1.5; 95%CI, 1.3–1.7). The association of severe psoriasis with mortality persisted after exclusion of patients with inflammatory arthropathy (HR, 1.5; 95% CI, 1.3–1.8). Male and female patients with severe psoriasis died 3.5 years (95% CI, 1.2–5.8) and 4.4 (95% CI, 2.2–6.6) years younger, respectively, than patients without psoriasis ( P <.001). Risk of mortality relative to age was greatest in younger patients with severe psoriasis in this study, and this is supported by another study, which indicated that younger patients (<40 years old) with severe psoriasis had the highest relative risk of CV mortality. These findings point to skin disease severity and age of onset as a tools for predicting increased incidence and severity of CVD in psoriasis and PsA. Some studies report less comparable risks for CV events and CV mortality in psoriasis compared with the general population, which may suggest a need for further investigation, but nonetheless most data advocate screening and management of CV risk factors in patients with psoriasis.
Cardiovascular Screening and Management
Patients with PsA should be screened at least annually for traditional CV risk factors, such as blood pressure and serum lipids, and more often in patients with added risks. Screening considerations for CVD and the other comorbidities seen in patients with PsA are listed in Table 3 . It is important to be aware that typical risk stratification scores for CVD in the general population (eg, Framingham Risk Score and the Systematic Coronary Risk Evaluation algorithm) often underestimate the risk for CV events. Identification and subsequent management of traditional risk factors (eg, hypertension, diabetes, hyperlipidemia, and smoking) are important for these patients. Thus, CV risk factor management should be the same as for the general population in primary prevention CV care.
| Comorbidity | Screening Considerations |
|---|---|
| CVD | Check blood pressure. Check fasting lipid panel (or high-density lipoprotein and total cholesterol). Encourage patients to follow up with primary care physician or preventive cardiologist for management of CV risk factors. Calculate risk score (ie, Framingham or SCORE), recognizing that the 10-year event rate estimate is likely to be an underestimate of the patient’s true propensity for CVD. Encourage smoking cessation when applicable. Educate patients about the increased risk for CVD in psoriasis and PsA |
| Obesity | Measure weight and calculate BMI. Counsel patients on the benefits of weight loss for improvement in CV health and joint health. Normal BMI is associated with achieving disease remission and improved response to therapy |
| Diabetes | Refer patients with increased random glucose levels of more than 200 mg/dL on routine tests to primary care for diagnosis and management of diabetes. Check fasting glucose or hemoglobin A1c level at least once in patients more than 45 y of age or if symptoms of hyperglycemia occur |
| IBD | Ask about gastrointestinal symptoms in the review of systems. Refer early to a gastroenterologist if symptoms of IBD are present (eg, hematochezia, chronic diarrhea) |
| Ophthalmic disease | Ask about ophthalmic symptoms (eg, dryness, redness, pain, vision loss) in the review of systems. Refer early for evaluation |
| Osteoporosis | Follow general screening recommendations for general population. Calculate a FRAX score based on DEXA results (if applicable). If prescribing glucocorticoids, refer to ACR recommendations for when to consider preventive therapy |
| Malignancy | Follow screening recommendations for general population. Consider yearly/periodic skin check for patients with a UV light therapy history |
| Liver and kidney disease | Check liver function tests and creatinine level before initiating therapy. Consider checking HCV Ab, HBV antigen, HBV core antibody, HBV surface antibody |
| Depression and anxiety | Ask about symptoms of depression and anxiety in the review of systems and refer for management if identified |
To date, no prospective studies have specifically examined the effect of aggressive PsA treatment on risk of CV events. Prior studies investigating the hypothesis that CV risk can be attenuated by decreasing inflammation through the use of DMARD therapy have produced conflicting results, as reported earlier. The risk of CV outcomes associated with chronic corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use in patients with PsA has not been studied in a controlled clinical trial. The future results of an ongoing PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen) trial (clinical trials.gov ) investigating the CVD outcomes of 3 different NSAIDs in the treatment of arthritis may help clarify these differential CV risks. In summary, current clinical practice has no definitive pharmacologic treatment recommendations to address future CV risk in patients with PsA or for other systemic rheumatic diseases.
Obesity
Most patients with PsA are overweight (body mass index [BMI] >25) or obese (BMI>30). Several studies have suggested that obese BMI may be a risk factor for psoriasis (PsO) and PsA. An analysis of the CORRONA (Consortium of Rheumatology Researchers of North America) database found patients with PsA to be heavier than patients with RA by an average of 7.7 kg (17 pounds). In a large study comparing BMI in PsA (n = 644), PsO (n = 448), RA (n = 350), and the general population, the percentages with obesity were 37%, 29%, 27%, and 18% respectively and the odds of obesity were 61% higher for patients with PsA than for patients with PsO (95% CI, 1.10, 2.37).
Research is needed on the link between PsA and obesity to further examine its relationship with psoriatic disease onset and to determine whether it is a consequence of the disease. Other potential mechanisms linking PsA obesity and CV risk, including dyslipidemia, hypertension, insulin resistance, and smoking, have not been well-defined.
Effect of Body Weight on Therapy
It has been reported that obesity and metabolic syndrome may negatively affect PsA disease activity and response to therapy. Eder and colleagues found that obesity was associated with a lower probability of achieving sustained remission, irrespective of therapy used. di Minno and colleagues similarly showed that obesity was an independent risk factor (after multivariable adjustment) for not achieving minimal disease activity (MDA) over 24 months of follow-up (HR, 4.90; 95% CI, 3.04 to 7.87). In patients who achieved MDA at 12 months, obesity was a significant risk factor for relapse at 24 months. The investigators extended this work to examine the rate of achievement of MDA in overweight/obese patients with PsA who initiated TNF inhibitors. Successful weight loss of 5% or more of total body weight was associated with a higher likelihood of achieving MDA (odds ratio [OR], 4.20; 95% CI, 1.82 to 9.66). In addition, the presence of metabolic syndrome was also a risk factor for not achieving MDA. Therefore, patients who are overweight and/or obese should be encouraged to lose weight, not only for potential increased benefit from therapy but also for decreased risk for other comorbidities associated with obesity, including diabetes and CVD.
Diabetes
PsA has been associated with an increased prevalence and incidence of diabetes mellitus (DM). Specifically, type II DM has been observed in 12% to 18.6% of patients with PsA. This finding may be partially explained by increased obesity and unhealthy lifestyles, and possibly related to insulin resistance associated with PsA inflammation. DM should always be a consideration when monitoring therapy and appropriate testing should be undertaken when an increased blood glucose level is identified.
There are no studies to address management of patients with PsA and diabetes and limited data exist on the effect of therapy on development of DM. Glucocorticoids should naturally be avoided and, when needed, managed carefully in combination with the patient’s primary care physician or endocrinologist. The use of oral and topical corticosteroids in an observational study increased the risk of developing DM by 30% in patients with psoriatic disease, whereas the use of a TNF inhibitor was associated with a reduced risk of developing DM (OR, 0.62) compared with the use of other nonbiologic DMARDs (excluding MTX).
Related posts:
The Epidemiology of Psoriatic Arthritis
Clinical Features and Diagnostic Considerations in Psoriatic Arthritis
Natural History, Prognosis, and Socioeconomic Aspects of Psoriatic Arthritis
Genetic, Epigenetic and Pharmacogenetic Aspects of Psoriasis and Psoriatic Arthritis
Outcome Measures in Psoriatic Arthritis
Biologic Therapy for Psoriatic Arthritis
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