By Daniel Zaghi, MD, MS, and Caitriona Ryan, MD
As dermatology residents, we are keenly aware of the many facets of psoriasis pathophysiology, quality of life impact, and treatment options. Residents likely already know that psoriasis is a Th1/Th17 immune-mediated disorder that targets the skin, joints, and nails, often culminating in a tremendous reduction in quality of life for patients. Residents may be less aware, however, of other recent developments in the world of psoriasis. Below we highlight three areas that deserve further attention and may improve the care we provide to our psoriasis patients.
Treatment options expanding
Treatment options for psoriasis have expanded tremendously over the past two decades. The first systemic agents for psoriasis were borrowed from other indications. Methotrexate was first used for psoriasis after it showed efficacy in oncology. Cyclosporine was adapted for use in psoriasis after serendipitous clearance of psoriasis was noted in patients taking the drug to prevent renal transplant rejection.
Many of the biologic treatments currently used to treat psoriasis, such as rituximab, adalimumab, and etanercept, were first introduced for rheumatoid arthritis or inflammatory bowel disease and later used in psoriasis. As understanding of the pathogenesis of psoriasis has grown, newer treatments more discriminately target the inflammatory milieu driving psoriasis. Ustekinumab, a monoclonal antibody to the p40 subunit of IL-12 and IL-23, is one such treatment, which has also recently been approved for psoriatic arthritis.
Though ustekinumab is the newest biologic on the block, it certainly will not be the last biologic treatment designed specifically for psoriasis. Other biologics targeting IL-23 are in development. Also, with the discovery of Th17 cells, newer biologic agents will now block either IL-17 cytokines or their receptor.
These biologic agents have demonstrated dramatic and often rapid improvements in plaque psoriasis above and beyond current biologics. Approval of these agents for clinical use is expected in late 2014 and 2015. New oral medicines, such as tofacitinib, a JAK inhibitor, and apremilast, a phosphodiesterase-4 inhibitor, are also currently being studied for use in psoriasis. As our understanding of the pathophysiology of psoriasis grows, we can expect that our treatment armamentarium will continue to expand.
A closer look at psoriasis and comorbidities
As residents who care for psoriasis patients in clinic and read psoriasis studies in journal club, we are likely familiar with the comorbidities associated with the disease. The list of comorbid conditions is exhaustive and continues to grow. Some of the comorbidities include an elevated risk of depression, anxiety, lymphoma, obesity, diabetes, hypertension, hyperlipidemia, obstructive sleep apnea, myocardial infarction, stroke, inflammatory bowel disease, emphysema, and metabolic syndrome. Of particular concern for patients with psoriasis is the elevated rate of cardiovascular disease.
A 2010 study demonstrated that patients with severe psoriasis die approximately four years younger than patients without psoriasis, with heart disease as the chief cause of increased mortality1. Another landmark prospective cohort study in JAMA demonstrated an increased risk of myocardial infarction even after controlling for traditional risk factors, concluding that psoriasis may be an independent cardiovascular risk factor2.
As the association between psoriasis and cardiovascular disease has been well established, attention has now shifted to the ability of treatment to mitigate this increase in cardiovascular risk. A large retrospective cohort study of veterans found that methotrexate reduced the risk of vascular disease among psoriasis patients by 27 percent and that concomitant folic acid further reduced the risk to 44 percent. A retrospective chart review of nearly 9,000 psoriasis patients at Kaiser Permanente of Southern California found reduction approximately 50 percent in the rate of myocardial infarction among patients treated with TNF-α inhibitors, phototherapy, or oral agents compared to patients treated with topical agents3.
In a 2014 position paper from the Medical Board of the National Psoriasis Foundation (NPF), recommendations for cardiovascular screening in psoriasis patients were set forth. The Board recommended following blood pressure, pulse, and BMI measurements every two years and fasting glucose and lipids every five years, or every two years if additional cardiovascular risk factors are present4. With a preponderance of evidence demonstrating an association with cardiovascular disease and the possibility of reducing that risk, it is imperative that we not only discuss with patients the existence of the many psoriasis comorbidities, but the potential for improvement with treatment.
Biologic treatments and skin cancer
With the immunosuppression of the biologic therapies comes the potential for an increase in malignancy, in particular, the development of nonmelanoma skin cancer (NMSC) and melanoma — both have been the subject of intensive investigation. Several high-quality studies have found an increased risk of NMSC among psoriasis patients treated with biologic agents compared with biologic-naïve psoriasis patients. A possible association between biologic therapies and melanoma, on the other hand, is less established.
One study found a non-statistically significant increase in melanomas among psoriasis patients treated with biologics. A December 2013 study in the Journal of the American Academy of Dermatology (JAAD), however, found that while biologic-naïve psoriasis patients had lower numbers of melanocytic nevi than patients without psoriasis, the odds of a higher nevus count increased by 35 percent for each biologic therapy administered.5
Interestingly, this finding was independent of psoriasis disease severity. How much of this is confounded by surveillance bias, previous immunosuppressant therapies, or phototherapy remains to be determined. Nonetheless, this emerging body of evidence should not be ignored with some psoriasis experts and studies suggesting regular skin examinations for psoriasis patients on biologic therapies.
The three areas discussed above are just a sample of recent developments in psoriasis. The NPF also helps providers stay current with research, advancements, and treatments by offering an electronic newsletter called CURE. You can sign up for the free newsletter on the NPF website
Also recommended for residents is the article “Research gaps in psoriasis: Opportunities for future studies,” published last year in JAAD and available online.
Keeping connected, staying up to date, and advocating for our psoriasis patients will ensure that we continue to offer the best possible care for them.
AAD psoriasis app
The Academy’s psoriasis app
is designed to help users develop the skills required to manage patients with psoriasis and psoriatic arthritis. The content, which is drawn from the AAD’s comprehensive psoriasis guidelines of care, emphasizes decision-making criteria that enable the clinician to individualize therapy based upon disease type, extent, response to previous treatments, quality of life issues, and comorbidities. It enables clinicians to recognize and diagnose challenging cases and formulate appropriate evidence-based treatment for patients.
1. Arch Dermatol
. 2007 Dec; 143(12):1493-9. The risk of mortality in patients with psoriasis: results from a population-based study. Gelfand JM, Troxel AB, Lewis JD, Kurd SK, Shin DB, Wang X, Margolis DJ, Strom BL.
. 2006;296(14):1735-1741.Risk of Myocardial Infarction in Patients with Psoriasis. Joel M. Gelfand, MD, MSCE; Andrea L. Neimann, MD; Daniel B. Shin, BA; Xingmei Wang, MS; David J. Margolis, MD, PhD; Andrea B. Troxel, ScD. doi:10.1001/jama.296.14.1735
3. Arch Dermatol
. 2012 Nov; 148(11):1244-50. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Wu JJ, Poon KY, Channual JC, Shen AY. doi: 10.1001/archdermatol.2012.2502
4. From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies. Hugh J, Van Voorhees AS, Nijhawan RI, Bagel J, Lebwohl M, Blauvelt A, Hsu S, Weinberg JM.
5. J Am Acad Dermatol
. 2013 Dec; 69(6):947-53. Frequency of melanocytic nevi in psoriatic patients is related to treatment and not to disease severity. Di Cesare A, Riitano A, Suppa M, Fidanza R, Zangrilli A, Esposito M, Fargnoli MC, Chimenti S, Peris K. doi: 10.1016/j.jaad.2013.08.017. Epub 2013 Oct 2.
Dr. Zaghi completed a two-year research fellowship in psoriasis, led original investigative research in psoriasis, and was one of 12 residents awarded a stipend for psoriasis research by the National Psoriasis Foundation (NPF). He is currently a PGY-3 dermatology resident at Baylor University Medical Center in Dallas.
Dr. Ryan has published extensively in psoriasis with the majority of her publications focusing on the immunobiology of psoriasis and pharmogenomics of psoriasis treatment. She commenced her dermatology training in Ireland and is now a PGY-4 dermatology resident at Baylor University Medical Center in Dallas.