Comorbidities

Psoriasis is a multisystem disorder, and diagnosed patients frequently experience substantial comorbidities. Although outwardly psoriasis appears to be limited to the skin and joints, the underlying immune and biochemical dysregulation associated with the disease links psoriasis to several medical disorders.1 Evidence of a genetic relationship between psoriasis and autoimmune diseases is accumulating.2 For example, the chance of being affected by Crohn's disease (CD) or psoriasis is greater in families affected by one of the diseases than would be expected if these diseases were not related in some way.2 One study found that 10% of patients with CD had a first-degree relative with psoriasis; the prevalence was less than 3% in control patients who had no such relationships.2 Furthermore, psoriasis and CD have been found to occur more often in the same person than would be anticipated if there were no association between the two diseases.2

Studies have also shown that patients with psoriasis may have a small but significantly higher relative risk of developing lymphomas, specifically cutaneous T-cell lymphoma (CTCL) and Hodgkin's lymphoma. Cutaneous T-cell lymphoma is the most common form of T-cell lymphoma, and because it is a lymphoma of the skin, it might be connected to the pathophysiology of psoriasis.3 In one study, patients classified as having severe psoriasis had the most strongly increased relative risk of CTCL; there was also a greater risk of Hodgkin's lymphoma in patients with mild and severe psoriasis.3 Patients with chronic plaque psoriasis also have a higher incidence of nonalcoholic steatohepatitis or nonalcoholic fatty liver disease (NAFLD). Psoriasis was found to be more severe in those patients with NAFLD and higher Psoriasis Area and Severity Index (PASI) scores.4 Some psoriasis treatments, such as methotrexate, have been shown to cause elevated liver enzymes. Consequently, liver function monitoring of this population is of great importance.5

Patients with psoriasis are more likely to smoke cigarettes and to be diagnosed with diabetes, hyperlipidemia and hypertension. They are also more likely to have a higher body mass index (BMI) and to have a history of myocardial infarction (MI).6 Moreover, even when these cardiovascular risk factors are controlled, patients with psoriasis appear to be at increased risk of MI.1,6 Additionally, studies have shown that individuals who require hospitalization for their psoriasis have a substantial increase in risk for cardiovascular death,7 and young hospitalized patients with severe psoriasis have an even higher risk for MI.6 The association between psoriasis and cardiovascular morbidity may also be related to the effects of chronic inflammatory changes leading to T-cell infiltration and subsequent cytokine secretion.8

Personal behaviors that have been found to have negative effects on patient health have been shown to be common among psoriasis patients, particularly smoking,9 as mentioned previously. Several studies have indicated that patients with psoriasis have an increased prevalence of smoking, which may explain the increased prevalence of chronic obstructive pulmonary disease (COPD) among these patients as well. 9 In one study, the prevalence of smoking among psoriasis patients participating in the Utah Psoriasis Initiative (UPI) (37%) was higher than in both the nonpsoriatic controls in the general Utah population (13%) and the nonpsoriatic patients in the UPI population (25%).10 The study also demonstrated that 22% of patients with psoriasis who smoked began to do so after the onset of psoriasis.10

Obesity is delineated by a BMI above 30 kg/m2; one study demonstrated that the average patient with psoriasis had a BMI of 30.6 kg/m2.9 The UPI study also found that smoking is more prevalent in obese patients with psoriasis who are members of the general Utah population (35% vs 9%, respectively).10 The UPI study also determined that the prevalence of obesity among patients with psoriasis is almost twice that of the general Utah population (34% and 18%, respectively), and that obesity correlated with the severity of psoriasis, such that obese individuals were more likely to have more severe forms of psoriasis.10 Metabolic syndrome, composed of obesity, impaired glucose regulation, reduced high-density lipoprotein and hypertension, is significantly more common in psoriasis patients.11 How obesity and metabolic syndrome are related to the pathogenesis of psoriasis is not well understood, however.

Obstructive sleep apnea (OSA) has also been shown to be more common in those with psoriasis: A preliminary study has revealed that the incidence of OSA is significantly higher in the psoriasis population (11%) than in a group of dermatologic controls (0%).9 This relationship between sleep apnea and psoriasis may be related to comorbidities common to the two conditions, or it may result from a shared pathogenesis rooted in the production of inflammatory mediators.9 There are other common causes of sleep disturbances in patients with psoriasis, including pruritus, psoriatic arthritis and pain associated with psoriatic lesions.12 Both direct and indirect evidence indicates that sleep quality in patients with psoriasis can be adversely affected by depression as well. In addition, cytokine and neuropeptide secretions may act to alter sleep physiology, leading to sleep difficulties. For example, tumor necrosis factor, interleukin-6 and substance P are mediators involved in several conditions, including psoriasis, pruritus, depression, pain and OSA, all of which may have adverse effects on sleep.12

Alcohol consumption and depression are also prevalent among patients with psoriasis, which may be attributable, at least in part, to the psychosocial morbidity associated with psoriasis.13,14 Liver biopsy abnormalities found in patients with psoriasis have led some to speculate that these patients might be abusing alcohol. Furthermore, studies have demonstrated that heavy drinking tends to be associated with more severe psoriasis.14 Psoriasis is more common than anticipated in patients diagnosed with alcoholic cirrhosis, and inpatients being treated for alcoholism were three times more likely to have psoriasis than expected.14 Other studies have found that those psoriasis inpatients with extensive disease (a mean affected total body surface area of approximately 50%) have the highest depression scores,15 and that suicidal ideation is increased substantially in patients with psoriasis.16 Consequently, assessment tools such as the Dermatology Life Quality Index, the Quality of Life 12-item instrument and the Carroll Rating Scale for Depression are essential to a thorough evaluation of disease burden and severity in all psoriasis patients.9

Thorough, comprehensive care of patients with psoriasis requires vigilant attention to signs and symptoms of psoriasis comorbidities, which depends on close cooperation among health care professionals charged with care of these patients, including dermatologists and primary care physicians, as well as allied subspecialists, including cardiologists, endocrinologists and hepatologists.9

References:
  1. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2009;58(5):826-850.
  2. Najarian DJ, Gottlieb AB. Connections between psoriasis and Crohn's disease. J Am Acad Dermatol. 2003;48(6):805-821.
  3. Gelfand JM, Shin DB, Neimann AL, et al. The risk of lymphoma in patients with psoriasis. J Invest Dermatol. 2006;126(10):2194-2201.
  4. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):758-764.
  5. Nyfors A. Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics. Acad Pathol Microb Scand A. 1977;85(4):511-518.
  6. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741.
  7. Mallibris L, Akre O, Granath F, et al. Increased risk for cardiovascular mortality in psoriasis in patients but not in outpatients. Eur J Epidemiol. 2004;19(3):225-230.
  8. Spah F. Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. Br J Dermatol. 2008;159(Suppl 2):10-17.
  9. Kim N, Thrash B, Menter A. Comorbidities in psoriasis patients. Semin Cutan Med Surg. 2010;29(1):10-15.
  10. Herron M, Hinckley M, Hoffman M, et al. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol. 2005;141(12):1527-1534.
  11. Gisondi P, Tessari G, Conti A, et al. Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based casecontrol study. Br J Dermatol. 2007;157(1):68-73.
  12. Gowda S, Goldblum OM, McCall VW, Feldman SR. Factors affecting sleep quality in patients with psoriasis. J Am Acad Dermatol. 2010;63(1):114-123.
  13. Esposito M, Saraceno R, Giunta A, et al. An Italian study on psoriasis and depression. Dermatology. 2006;212(2):123-127.
  14. Higgins E. Alcohol, smoking and psoriasis. Clin Exp Dermatol. 2000;25(2):107-110.
  15. Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol. 1998;139(5):846-850.
  16. Rapp SR, Exum ML, Reboussin DM, et al. The physical, psychological and social impact of psoriasis. J Health Psych. 1997;2(4):525-537.

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The Emerging Role of Vitamin D in Dermatology
Presented by Emil A. Tanghetti, MD
Center for Dermatology and Laser Surgery
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