Evidence indicating the serious effects of psoriasis inflammation to the rest of the body and not just the skin, as once thought, is starting to accumulate, noted Dr. Jeffrey Sobell.
"We are just beginning to understand the impact of uncontrolled inflammation on the body, separate from the effects we're seeing in the skin and joints," Dr. Sobell, of the department of dermatology, Tufts University, Boston, said in an interview. This evidence has raised the question of whether conditions, such as cardiovascular disease (CVD), improve by "treating an individual's underlying psoriasis and controlling that tremendous inflammation" that characterizes the disease.
In addition to CVD, psoriasis patients are at an increased for depression and other conditions such as Crohn's disease, certain cancers, and chronic obstructive pulmonary disease. In a presentation at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation, Dr. Sobell focused on psoriatic arthritis (PsA), depression, and CVD.
PsA
PsA usually appears an average of 10 years after the onset of skin disease (QJ Med. 1987;62:127-41); about 70% of patients have skin manifestations initially, while 15% develop joint symptoms first, and 15% develop joint and skin symptoms simultaneously, he noted.
Dermatologists should screen for arthritis in their psoriasis patients because a prompt diagnosis is critical. Early intervention, particularly with a tumor necrosis factor (TNF) blocker, can reduce the potential for joint deformities and disability, in addition to helping alleviate the signs and symptoms of arthritis, he noted.The FDA-approved biologic treatments for PsA - etanercept, infliximab, adalimumab, and golimumab - are approved for reducing the signs and symptoms of active arthritis, including the progression of structural damage and improving physical function.
"I encourage dermatologists when seeing psoriasis patients to ask questions about arthritis symptoms," such as joint stiffness in the morning, and performing a physical examination that includes looking for asymmetric inflammatory arthritis and tender or swollen joints, said Dr. Sobell. Patients should also be asked about whether they have a family history of PsA, and, if they have joint pain, whether it fluctuates with psoriasis exacerbations, he said, noting that only about 35% of patients with PsA have simultaneous flares of skin and joints.
Depression
Depression affects about 25% of people with psoriasis, and it can be debilitating, sometimes leading to suicidal thoughts, particularly in younger patients, Dr. Sobell said. Although the disease itself has a psychological impact on patients, increased TNF levels are known to be elevated in depression. This "may be part of the pathogenesis of depression" in people with psoriasis, and therefore, TNF levels are a possible target of treatment, he said.
Evidence that treatment with an anti-TNF agent improves symptoms of depression and fatigue includes a phase III study evaluating the efficacy of etanercept, compared with placebo, in over 600 patients with moderate to severe psoriasis (Lancet 2006;367:29-35). At week 12, treatment was associated with improved symptoms of depression and fatigue. Improvements were not strongly correlated with improvements in Psoriasis Area and Severity Index scores and were also seen in patients with little improvement of psoriasis. This "may be a detectable effect of neutralization of TNF" on depression, Dr. Sobell said.
Although these results are intriguing, he added that more studies are needed to further investigate the relationship between TNF levels and depression, and that conclusions cannot be made about the impact of anti-TNF treatment and depression in the general population.
CVD
Psoriasis patients are more likely to have comorbid diseases that are CVD risk factors, such as obesity, hypertension, hyperlipidemia, and insulin resistance. However, psoriasis is also an independent risk factor for MI and CVD, which is thought to be related to the immune and inflammatory activity of skin disease, Dr. Sobell said.
He referred to evidence that TNF, which has a major role in the pathogenesis of RA and psoriasis, also plays a role in cardiovascular disease, including TNF effects on promoting insulin resistance. TNF also induces the cytokine interleukin-6, which increases C-reactive protein (CRP), an inflammatory biomarker that is associated with an increased CVD risk.
This type of evidence raises the issue of whether treatment with systemic psoriasis treatments can reduce cardiovascular risk in these patients, and whether biologic agents improve CVD risk factors and markers, Dr. Sobell said.
Most of the data that have found an association between anti-TNF therapy and improvements in CVD risk factors and markers have been in people with RA, he said. In a small study of RA patients, those treated with adalimumab had significant increases in HDL cholesterol and reduced CRP levels after 2 weeks, compared with those in the placebo group (Ann. Rheum. Dis. 2005; 64:303-5).