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Research Updates

Joel M. Gelfand, MD

Comorbidities in Psoriasis: Part Two

Joel Gelfand

Tuesday, November 06, 2007

Psoriasis is a common chronic inflammatory disease of the skin that has been associated with a variety of comorbidities. More recent work has focused on how comorbid diseases and exposures can be risk factors for the development of psoriasis, as well as how chronic psoriasis can be a risk factor for the development of other diseases that share a common immune pathophysiology.

A risk factor is an exposure or characteristic that increases an individual's chance for developing a certain outcome, and by definition, the association is not explained by confounding (e.g. third factors that explain the association) or bias (e.g. systematic error in how patients are selected or information is collected). A risk factor may suggest a causal relationship based on strength of study design (randomized controlled trial is the gold standard), temporal relationship, strength of the association, consistency of studies, and biological plausibility.

In this review, I will summarize some of the major comorbidities associated with psoriasis, highlighting recent studies that evaluate risk factors for onset of psoriasis or exacerbation of psoriasis, and studies that evaluate psoriasis as a risk factor for developing diseases that share a similar immune pathophysiology.

This commentary will address cancer, cardiovascular and metabolic disease, psychiatric disease, and psoriatic arthritis. Part One addresses infection, body mass index (BMI), and smoking and alcohol.

Cancer

The immunologic nature of psoriasis, as well as therapies that are immunosuppressive or mutagenic, may predispose patients with psoriasis to an increased risk of cancer. A higher incidence of non-melanoma skin cancer (NMSC) has been reported in psoriasis patients, and there are conflicting findings regarding internal cancers such as lung, breast, colon and prostate.1-7 Lymphoma has been of special interest as inflammatory conditions may be associated with a higher risk of lymphoproliferative diseases. Studies of the risk of internal lymphoma in psoriasis patients have yielded inconsistent results.8-15 The largest study to date found no increased risk of non-Hodgkin's lymphoma but did observe an increased risk of Hodgkin's lymphoma and a markedly increased relative risk for cutaneous T-cell lymphoma (CTCL).16 The association of psoriasis with CTCL may be due to misdiagnosis of early CTCL as psoriasis or may be related to chronic lymphoproliferation leading to CTCL.16 Recently, the results of 30 years of follow-up of psoriasis patients treated with PUVA found that patients who received PUVA and were exposed to high levels of methotrexate (≥36 months) had an increased incidence of lymphoma compared to the general population (IRR 4.39, 95% CI 1.59-12.06).17 Patients who received >300 UVB treatments, were skin types 1 or 2, or received >200 PUVA treatments also had increased rates of lymphoma, but these were not statistically significant, possibly due to limitations of statistical power and incomplete ascertainment of outcomes.

Cardiovascular and Metabolic Disease

Epidemiologic studies in Sweden, Germany, and the Unites States have demonstrated an association between psoriasis and cardiovascular disease (CVD).18-20 Mallbris and colleagues found that a Swedish cohort of patients with a history of hospital admission for psoriasis had an overall increased risk of CV mortality compared to the general population (SMR 1.52; 95% CI: 1.44-1.60).20 However, this finding was not supported by Stern et al. who found no evidence of increased cardiovascular mortality in psoriasis patients receiving psoralen and long-wave ultraviolet radiation (PUVA) treatment compared to the general population (SMR 0.83, 90% 0.7-1.0).21 These studies are limited in that they are of highly selected patient populations, utilized an external comparison group (which can introduce bias), and did not control for other cardiac risk factors that may confound the relationship between psoriasis and CVD.

In addition to smoking and obesity, several studies suggest that cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia are more prevalent in psoriasis patients.18,19,22-28 In particular, diabetes has shown an association with severe psoriasis (OR 1.62, 95% CI 1.3-2.01) independent of other risk factors for diabetes such as obesity.7 Although evolving evidence suggests that psoriasis is associated with a variety of cardiovascular risk factors, recent studies suggest that psoriasis itself is an independent risk factor for developing coronary artery disease and myocardial infarction (MI), possibly due to shared immunologic pathways that function abnormally in both diseases.29-31 For example, a large cohort study of more than 130,000 patients with psoriasis demonstrated that psoriasis was associated with an increased risk of MI even when controlling for major cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, smoking, and BMI. The increased risk of MI attributable to severe psoriasis (N=3837) was similar in magnitude to the risk of MI conferred by other major risk factors such as diabetes.29 A smaller study of 32 severe psoriasis patients selected from a referral practice demonstrated a higher prevalence of coronary artery disease even when controlling for multiple risk factors for atherosclerosis.32

Psychiatric Disease

Multiple studies, the majority of which are descriptive, have examined psychological characteristics of patients with psoriasis.33-35 A wide range of problems have been described, such as depression, anxiety, obsessive behavior, sexual dysfunction, and suicidal ideation.36-41 Suicidal ideation was found to be present in 7.2% of patients hospitalized for psoriasis, 2.5% of psoriasis outpatients and 2.4-3.3% of general medical patients, suggesting that patients with more severe disease may have greater emotional impairment.33 Psychological distresses may also impair response to psoriasis therapies. For example, in a cohort of psoriasis patients treated with PUVA, pathological or high-level worry was a significant predictor of time taken for PUVA to clear psoriasis, whereas clinical severity of psoriasis, skin phenotype, alcohol intake, anxiety, and depression were not.42

Psoriatic Arthritis

Joint diseases are common among patients with psoriasis.43  Psoriatic arthritis is defined as a rheumatoid factor-negative inflammatory arthritis associated with psoriasis.44  Estimates of the prevalence of psoriatic arthritis among patients with psoriasis vary from 6% up to 30%.43,45  Population-based studies, which are broadly representative of all patients with psoriasis, have found a prevalence of psoriatic arthritis in patients with psoriasis to be 6.25% in Olmstead County, Minnesota, and 11% in the continental US population.8 Additionally, the population-based studies and clinic-based studies have indicated that the prevalence of psoriatic arthritis increases significantly based on the BSA affected by psoriasis.8,9

In general, psoriatic arthritis tends to appear several years after the onset of skin lesions in the majority of patients; however, it can precede the skin disease in approximately 13-17% of cases.10 Nail lesions may help to identify those patients with psoriasis who are at higher risk of developing arthritis as these lesions occur in 80-90% of patients with psoriatic arthritis compared to 46% in those with psoriasis uncomplicated by arthritis.11 Although the severity of skin psoriasis predicts the prevalence of psoriatic arthritis, it does not reliably correlate with the severity of psoriatic arthritis symptoms and signs.11 Broadly representative population-based studies suggest that the incidence of structural damage in psoriatic arthritis is low (<10%) and that the disease does not impact mortality.45 Studies from tertiary care centers, which are skewed toward patients with more severe disease, have shown a higher risk of mortality for patients with psoriatic arthritis and have found higher overall frequencies of destructive joint changes.10,12 Several HLA types have been associated with psoriatic arthritis, suggesting a genetic predisposition to developing this disease.13, 14, 46

Conclusions

Psoriasis is associated with a variety of comorbidities and adverse health behaviors such as smoking and alcohol use. Evolving data suggests that some conditions and behaviors may increase a patient's risk of developing psoriasis (such as smoking and obesity). For patients with psoriasis, evolving data suggests that smoking, alcohol, and excessive worry may result in more severe skin disease, treatment non-compliance, and treatment resistance, respectively, and that psoriasis itself may be an independent risk factor for having diabetes and atherosclerosis and for developing a subsequent MI. The cumulative impact of severe chronic psoriasis and its associated comorbidities is demonstrated by recent data showing that severe psoriasis is associated with a 50% increased risk in all-cause mortality and that these patients die approximately 3-4 years younger than patients without psoriasis.15

The emerging data highlight the importance of comprehensive medical care for patients with psoriasis. Patients should be counseled on the importance of maintaining a healthy body weight, not smoking, and not drinking alcohol to excess. Furthermore, screening for symptoms of psoriatic arthritis and risk factors for cardiovascular disease in psoriasis patients and appropriate treatment of these conditions when identified is encouraged. Additional studies are necessary to determine if treating psoriasis will result in a decrease in the incidence of adverse health outcomes (e.g. MI), as well as to more clearly determine how psoriasis skin severity and treatment relate to morbidity rates.

References

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  3. Hannuksela-Svahn A, Sigurgeirsson B, Pukkala E, et al. Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis. Br J Dermatol. 1999;141:497-501.
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